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Sample records for comparative transduction mechanisms

  1. Comparative transduction mechanisms of hair cells in the bullfrog utriculus. 1: Responses to intracellular current

    NASA Technical Reports Server (NTRS)

    Baird, Richard A.

    1994-01-01

    Hair cells in the bullfrog sacculus are specifically adapted to sense small-amplitude, high-frequency linear accelerations. These hair cells display many properties that are undesirable or inappropriate for hair cells that must provide static gravity sensitivity. This study resulted in part due to an interest in seeing how the transduction mechanisms of hair cells in a gravity-sensing otolith endorgan would differ from those in the bullfrog sacculus. The bullfrog utriculus is an appropriate model for these studies, because its structure is representative of higher vertebrates in general and its function as a sensor of static gravity and dynamic linear acceleration is well known. Hair cells in the bullfrog utriculus, classifiable as Type 2 by cell body and synapse morphology, differ markedly in hair bundle morphology from those in the bullfrog sacculus. Moreover, the hair bundle morphologies of utricular hair cells, unlike those in the sacculus, differ in different membrane regions.

  2. Comparative transduction mechanisms of hair cells in the bullfrog uticulus. 2: Sensitivity and response dynamics to hair bundle displacement

    NASA Technical Reports Server (NTRS)

    Baird, Richard A.

    1994-01-01

    The present study was motivated by an interest in seeing whether hair cell types in the bullfrog utriculus might differ in their voltage responses to hair bundle displacement. Particular interest was in assessing the contributions of two factors to the responses of utricular hair cells. First, interest in examining the effect of hair bundle morphology on the sensitivity of hair cells to natural stimulation was motivated by the observation that vestibular hair cells, unlike many auditory hair cells, are not free-standing but rather linked to an accessory cupular or otolithic membrane via the tip of their kinocilium. Interest also laid in examining the contribution, if any, of adaptation to the response properties of utricular hair cells. Hair cells in auditory and vibratory inner ear endorgans adapt to maintained displacements of their hair bundles, sharply limiting their low frequency sensitivity. This adaptation is mediated by a shift in the displacement-response curve (DRC) of the hair cell along the displacement axis. Observations suggest that the adaptation process occurs within the hair bundle and precedes mechanoelectric transduction. Recent observations of time-dependent changes in hair bundle stiffness are consistent with this conclusion. Adaptation would be expected to be most useful in inner ear endorgans in which hair cells are subject to large static displacements that could potentially saturate their instantaneous response and compromise their sensitivity to high frequency stimulation. The adaptation process also permits hair cells to maintain their sensory hair bundle in the most sensitive portion of their DRC. In vestibular otolith organs in which static sensitivity is desirable, any adaptation process in the hair cells may be undesirable. The rate and extent of the decline of the voltage responses was measured of utricular hair cells to step and sinusoidal hair bundle displacements. Then for similar resting potentials and response amplitudes, the

  3. Comparative transduction mechanisms of hair cells in the bullfrog utriculus. II. Sensitivity and response dynamics to hair bundle displacement

    NASA Technical Reports Server (NTRS)

    Baird, R. A.

    1994-01-01

    lever arm between kinociliary and stereociliary displacement; 2) tip link extension/linear displacement, largely a function of stereociliary height and separation; and 3) stereociliary number, an estimate of the number of transduction channels, were considered in this analysis. The first of these factors was quantitatively more important than the latter two factors and their total contribution was largest in Type B and Type C cells. Theoretical models were also used to calculate the relation between rotary and linear displacement.(ABSTRACT TRUNCATED AT 400 WORDS).

  4. Signal transduction mechanisms in plants: an overview

    NASA Technical Reports Server (NTRS)

    Clark, G. B.; Thompson, G. Jr; Roux, S. J.

    2001-01-01

    This article provides an overview on recent advances in some of the basic signalling mechanisms that participate in a wide variety of stimulus-response pathways. The mechanisms include calcium-based signalling, G-protein-mediated-signalling and signalling involving inositol phospholipids, with discussion on the role of protein kinases and phosphatases interspersed. As a further defining feature, the article highlights recent exciting findings on three extracellular components that have not been given coverage in previous reviews of signal transduction in plants, extracellular calmodulin, extracellular ATP, and integrin-like receptors, all of which affect plant growth and development.

  5. Novel mechanisms of endothelial mechano-transduction

    PubMed Central

    Abe, Jun-ichi; Berk, Bradford C

    2014-01-01

    Atherosclerosis is a focal disease that develops preferentially where non-laminar, disturbed blood flow (d-flow) occurs such as branches, bifurcations, and curvatures of large arteries. Endothelial cells sense and respond differently to d-flow compared to steady laminar flow (s-flow). D-flow that occurs in so-called athero-prone areas activates pro-inflammatory and apoptotic signaling, and this results in endothelial dysfunction and leads to subsequent development of atherosclerosis. In contrast, s-flow as “athero-protective flow” promotes expression of many anti-inflammatory genes such as Kruppel-like factor 2 (KLF2) and endothelial nitric oxide synthase (eNOS) and inhibits endothelial inflammation and athrogenesis. Here we will discuss that d-flow and s-flow induce pro- and anti-atherogenic events via flow type-specific “mechanotransduction” pathways. We will focus on five mechano-sensitive pathways: MEK5 (MAPK/ERK kinase 5)-ERK5-KLF2 signaling, ERK5-PPAR (peroxisome proliferator-activated receptor) signaling, and mechano-signaling pathways involving SUMOylation, protein kinase C-ζ, (PKCζ), and p90 ribosomal S6 kinase (p90RSK). We believe that clarifying regulation mechanisms between these two flow types will provide new insights into therapeutic approaches for the prevention and treatment of atherosclerosis. PMID:25301843

  6. Cell-penetrating peptides: Possible transduction mechanisms and therapeutic applications

    PubMed Central

    GUO, ZHENGRONG; PENG, HUANYAN; KANG, JIWEN; SUN, DIANXING

    2016-01-01

    Cell-penetrating peptides (CPPs), also known as protein transduction domains, are a class of diverse peptides with 5–30 amino acids. CPPs are divided into cationic, amphipathic and hydrophobic CPPs. They are able to carry small molecules, plasmid DNA, small interfering RNA, proteins, viruses, imaging agents and other various nanoparticles across the cellular membrane, resulting in internalization of the intact cargos. However, the mechanisms of CPP internalization remain to be elucidated. Recently, CPPs have received considerable attention due to their high transduction efficiency and low cytotoxicity. These peptides have a significant potential for diagnostic and therapeutic applications, such as delivery of fluorescent or radioactive compounds for imaging, delivery of peptides and proteins for therapeutic application, and delivery of molecules into induced pluripotent stem cells for directing differentiation. The present study reviews the classifications and transduction mechanisms of CPPs, as well as their potential applications. PMID:27123243

  7. Mechanism and evolution of cytosolic Hedgehog signal transduction

    PubMed Central

    Wilson, Christopher W.; Chuang, Pao-Tien

    2010-01-01

    Hedgehog (Hh) signaling is required for embryonic patterning and postnatal physiology in invertebrates and vertebrates. With the revelation that the primary cilium is crucial for mammalian Hh signaling, the prevailing view that Hh signal transduction mechanisms are conserved across species has been challenged. However, more recent progress on elucidating the function of core Hh pathway cytosolic regulators in Drosophila, zebrafish and mice has confirmed that the essential logic of Hh transduction is similar between species. Here, we review Hh signaling events at the membrane and in the cytosol, and focus on parallel and divergent functions of cytosolic Hh regulators in Drosophila and mammals. PMID:20530542

  8. Electro-optical transduction via a mechanical membrane

    NASA Astrophysics Data System (ADS)

    Stambaugh, Corey; Lawall, John

    2013-03-01

    Both cavity opto-mechanics and cavity electro-mechanics have been studied as means to achieve ground state cooling of mechanical systems. Recent focus has turned to hybrid systems that attempt to convert photons between microwave and optical frequencies through mechanical transduction. This should allow quantum information stored in an electrical cavity to be transferred optically over longer distances. In this talk we describe our hybrid system, a silicon nitride membrane that is coupled to a piezoelectric element and placed within a high finesse Fabry-Perot cavity. This setup allows us to both sense and perturb the mechanical motion of the membrane. Results regarding the coupling between the different domains and the design strategies to optimize these couplings will be discussed.

  9. Molecular mechanisms in signal transduction at the membrane

    PubMed Central

    Groves, Jay T; Kuriyan, John

    2013-01-01

    Signal transduction originates at the membrane, where the clustering of signaling proteins is a key step in transmitting a message. Membranes are difficult to study, and their influence on signaling is still only understood at the most rudimentary level. Recent advances in the biophysics of membranes, surveyed in this review, have highlighted a variety of phenomena that are likely to influence signaling activity, such as local composition heterogeneities and long-range mechanical effects. We discuss recent mechanistic insights into three signaling systems—Ras activation, Ephrin signaling and the control of actin nucleation—where the active role of membrane components is now appreciated and for which experimentation on the membrane is required for further understanding. PMID:20495561

  10. PRDM Proteins: Molecular Mechanisms in Signal Transduction and Transcriptional Regulation.

    PubMed

    Di Zazzo, Erika; De Rosa, Caterina; Abbondanza, Ciro; Moncharmont, Bruno

    2013-01-01

    PRDM (PRDI-BF1 and RIZ homology domain containing) protein family members are characterized by the presence of a PR domain and a variable number of Zn-finger repeats. Experimental evidence has shown that the PRDM proteins play an important role in gene expression regulation, modifying the chromatin structure either directly, through the intrinsic methyltransferase activity, or indirectly through the recruitment of chromatin remodeling complexes. PRDM proteins have a dual action: they mediate the effect induced by different cell signals like steroid hormones and control the expression of growth factors. PRDM proteins therefore have a pivotal role in the transduction of signals that control cell proliferation and differentiation and consequently neoplastic transformation. In this review, we describe pathways in which PRDM proteins are involved and the molecular mechanism of their transcriptional regulation. PMID:24832654

  11. PRDM Proteins: Molecular Mechanisms in Signal Transduction and Transcriptional Regulation

    PubMed Central

    Di Zazzo, Erika; De Rosa, Caterina; Abbondanza, Ciro; Moncharmont, Bruno

    2013-01-01

    PRDM (PRDI-BF1 and RIZ homology domain containing) protein family members are characterized by the presence of a PR domain and a variable number of Zn-finger repeats. Experimental evidence has shown that the PRDM proteins play an important role in gene expression regulation, modifying the chromatin structure either directly, through the intrinsic methyltransferase activity, or indirectly through the recruitment of chromatin remodeling complexes. PRDM proteins have a dual action: they mediate the effect induced by different cell signals like steroid hormones and control the expression of growth factors. PRDM proteins therefore have a pivotal role in the transduction of signals that control cell proliferation and differentiation and consequently neoplastic transformation. In this review, we describe pathways in which PRDM proteins are involved and the molecular mechanism of their transcriptional regulation. PMID:24832654

  12. Nonreciprocal Radio Frequency Transduction in a Parametric Mechanical Artificial Lattice.

    PubMed

    Huang, Pu; Zhang, Liang; Zhou, Jingwei; Tian, Tian; Yin, Peiran; Duan, Changkui; Du, Jiangfeng

    2016-07-01

    Generating nonreciprocal radio frequency transduction plays important roles in a wide range of research and applications, and an aspiration is to integrate this functionality into microcircuits without introducing a magnetic field, which, however, remains challenging. By designing a 1D artificial lattice structure with a neighbor interaction engineered parametrically, we predicted a nonreciprocity transduction with a large unidirectionality. We then experimentally demonstrated the phenomenon on a nanoelectromechanical chip fabricated by conventional complementary metal-silicon processing. A unidirectionality with isolation as high as 24 dB is achieved, and several different transduction schemes are realized by programing the control voltage topology. Apart from being used as a radio frequency isolator, the system provides a way to build a practical on-chip programmable device for broad research and applications in the radio frequency domain. PMID:27419591

  13. Nonreciprocal Radio Frequency Transduction in a Parametric Mechanical Artificial Lattice

    NASA Astrophysics Data System (ADS)

    Huang, Pu; Zhang, Liang; Zhou, Jingwei; Tian, Tian; Yin, Peiran; Duan, Changkui; Du, Jiangfeng

    2016-07-01

    Generating nonreciprocal radio frequency transduction plays important roles in a wide range of research and applications, and an aspiration is to integrate this functionality into microcircuits without introducing a magnetic field, which, however, remains challenging. By designing a 1D artificial lattice structure with a neighbor interaction engineered parametrically, we predicted a nonreciprocity transduction with a large unidirectionality. We then experimentally demonstrated the phenomenon on a nanoelectromechanical chip fabricated by conventional complementary metal-silicon processing. A unidirectionality with isolation as high as 24 dB is achieved, and several different transduction schemes are realized by programing the control voltage topology. Apart from being used as a radio frequency isolator, the system provides a way to build a practical on-chip programmable device for broad research and applications in the radio frequency domain.

  14. MOLECULAR MECHANISMS OF RECEPTOR KINASE ACTION IN BRASSINOSTEROID SIGNAL TRANSDUCTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Brassinosteroids (BRs) regulate multiple aspects of plant growth and development and require an active BRASSINOSTEROID INSENSITIVE 1 (BRI1) and BRI1-ASSOCIATED RECEPTOR KINASE 1 (BAK1) for hormone perception and signal transduction. To examine early events in BR signaling, we used co-immunoprecipita...

  15. Phage Transduction.

    PubMed

    Goh, Shan

    2016-01-01

    Bacteriophages mediate horizontal gene transfer through a mechanism known as transduction. Phage transduction carried out in the laboratory involves a bacterial donor and a recipient, both of which are susceptible to infection by the phage of interest. Phage is propagated in the donor, concentrated, and exposed transiently to recipient at different multiplicity of infection ratios. Transductants are selected for the desired phenotype by culture on selective medium. Here we describe transduction of ermB conferring resistance to erythromycin by the C. difficile phage ϕC2. PMID:27507341

  16. Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity.

    PubMed

    Elosegui-Artola, Alberto; Oria, Roger; Chen, Yunfeng; Kosmalska, Anita; Pérez-González, Carlos; Castro, Natalia; Zhu, Cheng; Trepat, Xavier; Roca-Cusachs, Pere

    2016-05-01

    Cell function depends on tissue rigidity, which cells probe by applying and transmitting forces to their extracellular matrix, and then transducing them into biochemical signals. Here we show that in response to matrix rigidity and density, force transmission and transduction are explained by the mechanical properties of the actin-talin-integrin-fibronectin clutch. We demonstrate that force transmission is regulated by a dynamic clutch mechanism, which unveils its fundamental biphasic force/rigidity relationship on talin depletion. Force transduction is triggered by talin unfolding above a stiffness threshold. Below this threshold, integrins unbind and release force before talin can unfold. Above the threshold, talin unfolds and binds to vinculin, leading to adhesion growth and YAP nuclear translocation. Matrix density, myosin contractility, integrin ligation and talin mechanical stability differently and nonlinearly regulate both force transmission and the transduction threshold. In all cases, coupling of talin unfolding dynamics to a theoretical clutch model quantitatively predicts cell response. PMID:27065098

  17. Molecular mechanisms of gravity perception and signal transduction in plants.

    PubMed

    Kolesnikov, Yaroslav S; Kretynin, Serhiy V; Volotovsky, Igor D; Kordyum, Elizabeth L; Ruelland, Eric; Kravets, Volodymyr S

    2016-07-01

    Gravity is one of the environmental cues that direct plant growth and development. Recent investigations of different gravity signalling pathways have added complexity to how we think gravity is perceived. Particular cells within specific organs or tissues perceive gravity stimulus. Many downstream signalling events transmit the perceived information into subcellular, biochemical, and genomic responses. They are rapid, non-genomic, regulatory, and cell-specific. The chain of events may pass by signalling lipids, the cytoskeleton, intracellular calcium levels, protein phosphorylation-dependent pathways, proteome changes, membrane transport, vacuolar biogenesis mechanisms, or nuclear events. These events culminate in changes in gene expression and auxin lateral redistribution in gravity response sites. The possible integration of these signalling events with amyloplast movements or with other perception mechanisms is discussed. Further investigation is needed to understand how plants coordinate mechanisms and signals to sense this important physical factor. PMID:26215561

  18. Structural mechanism for signal transduction in RXR nuclear receptor heterodimers

    PubMed Central

    Kojetin, Douglas J.; Matta-Camacho, Edna; Hughes, Travis S.; Srinivasan, Sathish; Nwachukwu, Jerome C.; Cavett, Valerie; Nowak, Jason; Chalmers, Michael J.; Marciano, David P.; Kamenecka, Theodore M.; Shulman, Andrew I.; Rance, Mark; Griffin, Patrick R.; Bruning, John B.; Nettles, Kendall W.

    2015-01-01

    A subset of nuclear receptors (NRs) function as obligate heterodimers with retinoid X receptor (RXR), allowing integration of ligand-dependent signals across the dimer interface via an unknown structural mechanism. Using nuclear magnetic resonance (NMR) spectroscopy, x-ray crystallography and hydrogen/deuterium exchange (HDX) mass spectrometry, here we show an allosteric mechanism through which RXR co-operates with a permissive dimer partner, peroxisome proliferator-activated receptor (PPAR)-γ, while rendered generally unresponsive by a non-permissive dimer partner, thyroid hormone (TR) receptor. Amino acid residues that mediate this allosteric mechanism comprise an evolutionarily conserved network discovered by statistical coupling analysis (SCA). This SCA network acts as a signalling rheostat to integrate signals between dimer partners, ligands and coregulator-binding sites, thereby affecting signal transmission in RXR heterodimers. These findings define rules guiding how NRs integrate two ligand-dependent signalling pathways into RXR heterodimer-specific responses. PMID:26289479

  19. In search of the cochlear amplifier: New mechanical and molecular tools to probe transduction channel function

    NASA Astrophysics Data System (ADS)

    Karavitaki, K. Domenica; Indzhykulian, Artur A.; Zhang, Duan-Sun; Corey, David P.

    2015-12-01

    The study of mechanotransduction in cochlear hair cells requires stimulus methods that mimic the in-vivo stimulation. We have developed a new mechanical probe to better mimic the physiological stimulus delivered to cochlear hair cells through the overlying tectorial membrane. We combine these new probes with electroporation to study the contribution of different components of the transduction apparatus.

  20. Cerebral Artery Signal Transduction Mechanisms: Developmental Changes in Dynamics and Ca2+ Sensitivity

    PubMed Central

    Longo, Lawrence D.; Goyal, Ravi

    2012-01-01

    As compared to the adult, the developing fetus and newborn infant are at much greater risk for dysregulation of cerebral blood flow (CBF), with complications such as intraventricular and germinal matrix hemorrhage with resultant neurologic sequelae. To minimize this dysregulation and its consequences presents a major challenge. Although in many respects the fundamental signal transduction mechanisms that regulate relaxation and contraction pathways, and thus cerebrovascular tone and CBF in the immature organism are similar to those of the adult, the individual elements, pathways, and roles differ greatly. Here, we review aspects of these maturational changes of relaxation/contraction mechanisms in terms of both electro-mechanical and pharmaco-mechanical coupling, their biochemical pathways and signaling networks. In contrast to the adult cerebrovasculature, in addition to attenuated structure with differences in multiple cytoskeletal elements, developing cerebrovasculature of fetus and newborn differs in many respects, such as a strikingly increased sensitivity to [Ca2+]i and requirement for extracellular Ca2+ for contraction. In essence, the immature cerebrovasculature demonstrates both “hyper-relaxation” and “hypo-contraction”. A challenge is to unravel the manner in which these mechanisms are integrated, particularly in terms of both Ca2+-dependent and Ca2+-independent pathways to increase Ca2+ sensitivity. Gaining an appreciation of these significant age-related differences in signal mechanisms also will be critical to understanding more completely the vulnerability of the developing cerebral vasculature to hypoxia and other stresses. Of vital importance, a more complete understanding of these mechanisms promises hope for improved strategies for therapeutic intervention and clinical management of intensive care of the premature newborn. PMID:24063382

  1. Cerebral artery signal transduction mechanisms: developmental changes in dynamics and Ca2+ sensitivity.

    PubMed

    Longo, Lawrence D; Goyal, Ravi

    2013-09-01

    As compared to the adult, the developing fetus and newborn infant are at much greater risk for dysregulation of cerebral blood flow (CBF), with complications such as intraventricular and germinal matrix hemorrhage with resultant neurologic sequelae. To minimize this dysregulation and its consequences presents a major challenge. Although in many respects the fundamental signal transduction mechanisms that regulate relaxation and contraction pathways, and thus cerebrovascular tone and CBF in the immature organism are similar to those of the adult, the individual elements, pathways, and roles differ greatly. Here, we review aspects of these maturational changes of relaxation/contraction mechanisms in terms of both electro-mechanical and pharmaco-mechanical coupling, their biochemical pathways and signaling networks. In contrast to the adult cerebrovasculature, in addition to attenuated structure with differences in multiple cytoskeletal elements, developing cerebrovasculature of fetus and newborn differs in many respects, such as a strikingly increased sensitivity to [Ca(2+)]i and requirement for extracellular Ca(2+) for contraction. In essence, the immature cerebrovasculature demonstrates both "hyper-relaxation" and "hypo-contraction". A challenge is to unravel the manner in which these mechanisms are integrated, particularly in terms of both Ca(2+)-dependent and Ca(2+)-independent pathways to increase Ca(2+) sensitivity. Gaining an appreciation of these significant age-related differences in signal mechanisms also will be critical to understanding more completely the vulnerability of the developing cerebral vasculature to hypoxia and other stresses. Of vital importance, a more complete understanding of these mechanisms promises hope for improved strategies for therapeutic intervention and clinical management of intensive care of the premature newborn. PMID:24063382

  2. Mechanical code comparator

    DOEpatents

    Peter, Frank J.; Dalton, Larry J.; Plummer, David W.

    2002-01-01

    A new class of mechanical code comparators is described which have broad potential for application in safety, surety, and security applications. These devices can be implemented as micro-scale electromechanical systems that isolate a secure or otherwise controlled device until an access code is entered. This access code is converted into a series of mechanical inputs to the mechanical code comparator, which compares the access code to a pre-input combination, entered previously into the mechanical code comparator by an operator at the system security control point. These devices provide extremely high levels of robust security. Being totally mechanical in operation, an access control system properly based on such devices cannot be circumvented by software attack alone.

  3. Comparative Transduction Mechanisms of Vestibular Otolith Hair Cells

    NASA Technical Reports Server (NTRS)

    Baird, Richard A.

    1994-01-01

    Hair cells in the bullfrog vestibular otolith organs regenerate following aminoglycoside ototoxicity. Hair cells in these organs are differentially sensitive to gentamicin, with saccular hair cells and hair cells in the utricular striola being damaged at lower gentamicin concentrations than hair cells in the utricular extrastriola. Regenerating hair cells in these organs have short hair bundles and can be classified into a number of phenotypes using the same morphological criteria used to identify their mature counterparts. Our studies suggest that some supporting cells can convert, or transdifferentiate,into hair cells without an intervening cell division. By stimulating these processes in humans, clinicians may be able to alleviate human deafness and peripheral vestibular disorders by regenerating and replacing lost hair cells. In vivo and in vitro studies were done on cell proliferation and hair cell regeneration.

  4. Keratinocyte galvanotaxis in combined DC and AC electric fields supports an electromechanical transduction sensing mechanism.

    PubMed

    Hart, Francis X; Laird, Mhairi; Riding, Aimie; Pullar, Christine E

    2013-02-01

    Sedentary keratinocytes at the edge of a skin wound migrate into the wound, guided by the generation of an endogenous electric field (EF) generated by the collapse of the transepithelial potential. The center of the wound quickly becomes more negative than the surrounding tissue and remains the cathode of the endogenous EF until the wound is completely re-epithelialized. This endogenous guidance cue can be studied in vitro. When placed in a direct current (DC) EF of physiological strength, 100 V/m, keratinocytes migrate directionally toward the cathode in a process known as galvanotaxis. Although a number of membrane-bound (e.g., epidermal growth factor receptor (EGFR), integrins) and cytosolic proteins (cAMP, ERK, PI3K) are known to play a role in the downstream signaling mechanisms underpinning galvanotaxis, the initial sensing mechanism for this response is not understood. To investigate the EF sensor, we studied the migration of keratinocytes in a DC EF of 100 V/m, alternating current (AC) EFs of 40 V/m at either 1.6 or 160 Hz, and combinations of DC and AC EFs. In the AC EFs alone, keratinocytes migrated randomly. The 1.6 Hz AC EF combined with the DC EF suppressed the direction of migration but had no effect on speed. In contrast, the 160 Hz AC EF combined with the DC EF did not affect the direction of migration but increased the migration speed compared to the DC EF alone. These results can be understood in terms of an electromechanical transduction model, but not an electrodiffusion/osmosis or a voltage-gated channel model. PMID:22907479

  5. External Mechanical Work and Pendular Energy Transduction of Overground and Treadmill Walking in Adolescents with Unilateral Cerebral Palsy

    PubMed Central

    Zollinger, Marie; Degache, Francis; Currat, Gabriel; Pochon, Ludmila; Peyrot, Nicolas; Newman, Christopher J.; Malatesta, Davide

    2016-01-01

    Purpose: Motor impairments affect functional abilities and gait in children and adolescents with cerebral palsy (CP). Improving their walking is an essential objective of treatment, and the use of a treadmill for gait analysis and training could offer several advantages in adolescents with CP. However, there is a controversy regarding the similarity between treadmill and overground walking both for gait analysis and training in children and adolescents. The aim of this study was to compare the external mechanical work and pendular energy transduction of these two types of gait modalities at standard and preferred walking speeds in adolescents with unilateral cerebral palsy (UCP) and typically developing (TD) adolescents matched on age, height and body mass. Methods: Spatiotemporal parameters, external mechanical work and pendular energy transduction of walking were computed using two inertial sensors equipped with a triaxial accelerometer and gyroscope and compared in 10 UCP (14.2 ± 1.7 year) and 10 TD (14.1 ± 1.9 year) adolescents during treadmill and overground walking at standard and preferred speeds. Results: The treadmill induced almost identical mechanical changes to overground walking in TD adolescents and those with UCP, with the exception of potential and kinetic vertical and lateral mechanical works, which are both significantly increased in the overground-treadmill transition only in UCP (P < 0.05). Conclusions: Adolescents with UCP have a reduced adaptive capacity in absorbing and decelerating the speed created by a treadmill (i.e., dynamic stability) compared to TD adolescents. This may have an important implication in rehabilitation programs that assess and train gait by using a treadmill in adolescents with UCP. PMID:27148062

  6. Novel optical methodologies in studying mechanical signal transduction in mammalian cells

    NASA Technical Reports Server (NTRS)

    Stamatas, G. N.; McIntire, L. V.

    1999-01-01

    For the last 3 decades evidence has been accumulating that some types of mammalian cells respond to their mechanically active environment by altering their morphology, growth rate, and metabolism. The study of such responses is very important in understanding, physiological and pathological conditions ranging from bone formation to atherosclerosis. Obtaining this knowledge has been the goal for an active research area in bioengineering termed cell mechanotransduction. The advancement of optical methodologies used in cell biology research has given the tools to elucidate cellular mechanisms that would otherwise be impossible to visualize. Combined with molecular biology techniques, they give engineers invaluable tools in understanding the chemical pathways involved in mechanotransduction. Herein we briefly review the current knowledge on mechanical signal transduction in mammalian cells, focusing on the application of novel optical techniques in the ongoing research.

  7. Lessons in Fundamental Mechanisms and Diverse Adaptations from the 2015 Bacterial Locomotion and Signal Transduction Meeting

    PubMed Central

    Prüβ, Birgit M.; Liu, Jun; Higgs, Penelope I.

    2015-01-01

    In response to rapid changes in their environment, bacteria control a number of processes, including motility, cell division, biofilm formation, and virulence. Research presented in January 2015 at the biennial Bacterial Locomotion and Signal Transduction (BLAST) meeting in Tucson, AZ, illustrates the elegant complexity of the nanoarrays, nanomachines, and networks of interacting proteins that mediate such processes. Studies employing an array of biophysical, genetic, cell biology, and mathematical methods are providing an increasingly detailed understanding of the mechanisms of these systems within well-studied bacteria. Furthermore, comparisons of these processes in diverse bacterial species are providing insight into novel regulatory and functional mechanisms. This review summarizes research presented at the BLAST meeting on these fundamental mechanisms and diverse adaptations, including findings of importance for applications involving bacteria of medical or agricultural relevance. PMID:26195592

  8. Global Transcription Profiling Reveals Multiple Sugar Signal Transduction Mechanisms in ArabidopsisW⃞

    PubMed Central

    Price, John; Laxmi, Ashverya; St. Martin, Steven K.; Jang, Jyan-Chyun

    2004-01-01

    Complex and interconnected signaling networks allow organisms to control cell division, growth, differentiation, or programmed cell death in response to metabolic and environmental cues. In plants, it is known that sugar and nitrogen are critical nutrient signals; however, our understanding of the molecular mechanisms underlying nutrient signal transduction is very limited. To begin unraveling complex sugar signaling networks in plants, DNA microarray analysis was used to determine the effects of glucose and inorganic nitrogen source on gene expression on a global scale in Arabidopsis thaliana. In whole seedling tissue, glucose is a more potent signal in regulating transcription than inorganic nitrogen. In fact, other than genes associated with nitrate assimilation, glucose had a greater effect in regulating nitrogen metabolic genes than nitrogen itself. Glucose also regulated a broader range of genes, including genes associated with carbohydrate metabolism, signal transduction, and metabolite transport. In addition, a large number of stress responsive genes were also induced by glucose, indicating a role of sugar in environmental responses. Cluster analysis revealed significant interaction between glucose and nitrogen in regulating gene expression because glucose can modulate the effects of nitrogen and vise versa. Intriguingly, cycloheximide treatment appeared to disrupt glucose induction more than glucose repression, suggesting that de novo protein synthesis is an intermediary event required before most glucose induction can occur. Cross talk between sugar and ethylene signaling may take place on the transcriptional level because several ethylene biosynthetic and signal transduction genes are repressed by glucose, and the repression is largely unaffected by cycloheximide. Collectively, our global expression data strongly support the idea that glucose and inorganic nitrogen act as both metabolites and signaling molecules. PMID:15273295

  9. The Clickable Guard Cell, Version II: Interactive Model of Guard Cell Signal Transduction Mechanisms and Pathways.

    PubMed

    Kwak, June M; Mäser, Pascal; Schroeder, Julian I

    2008-01-01

    Guard cells are located in the leaf epidermis and pairs of guard cells surround and form stomatal pores, which regulate CO(2) influx from the atmosphere into leaves for photosynthetic carbon fixation. Stomatal guard cells also regulate water loss of plants via transpiration to the atmosphere. Signal transduction mechanisms in guard cells integrate a multitude of different stimuli to modulate stomatal apertures. Stomata open in response to light. Stomata close in response to drought stress, elevated CO(2), ozone and low humidity. In response to drought, plants synthesize the hormone abscisic acid (ABA) that triggers closing of stomatal pores. Guard cells have become a highly developed model system for dissecting signal transduction mechanisms in plants and for elucidating how individual signaling mechanisms can interact within a network in a single cell. Many new findings have been made in the last few years. This chapter is an update of an electronic interactive chapter in the previous edition of The Arabidopsis Book (Mäser et al. 2003). Here we focus on mechanisms for which genes and mutations have been characterized, including signaling components for which there is substantial signaling, biochemical and genetic evidence. Ion channels have been shown to represent targets of early signal transduction mechanisms and provide functional signaling and quantitative analysis points to determine where and how mutations affect branches within the guard cell signaling network. Although a substantial number of genes and proteins that function in guard cell signaling have been identified in recent years, there are many more left to be identified and the protein-protein interactions within this network will be an important subject of future research. A fully interactive clickable electronic version of this publication can be accessed at the following web site: http://www-biology.ucsd.edu/labs/schroeder/clickablegc2/. The interactive clickable version includes the following

  10. Preliminary evaluation of nanoscale biogenic magnetite-based ferromagnetic transduction mechanisms for mobile phone bioeffects.

    PubMed

    Cranfield, Charles; Wieser, Heinz Gregor; Al Madan, Jaffar; Dobson, Jon

    2003-03-01

    Ferromagnetic transduction models have been proposed as a potential mechanism for mobile phone bioeffects. These models are based on the coupling of RF and pulsed electromagnetic emissions to biogenic magnetite (Fe3O4) present in the human brain via either ferromagnetic resonance or mechanical activation of cellular ion channels. We have tested these models experimentally for the first time using a bacterial analogue (Magnetospirillum magnetotacticum) which produces intracellular biogenic magnetite similar to that present in the human brain. Experimental evaluation revealed that exposure to mobile phone emissions resulted in a consistent and significantly higher proportion of cell death in exposed cultures versus sham exposure (p = 0.037). Though there appears to be a repeatable trend toward higher cell mortality in magnetite-producing bacteria exposed to mobile phone emissions, it is not yet clear that this would extrapolate to a deleterious health effect in humans. PMID:15382422

  11. Rhizobium nod factor signaling. Evidence for a g protein-mediated transduction mechanism

    PubMed Central

    Pingret, JL; Journet, EP; Barker, DG

    1998-01-01

    Rhizobium nodulation (Nod) factors are lipochitooligosaccharide signals that elicit key symbiotic developmental responses in the host legume root. In this study, we have investigated Nod factor signal transduction in the Medicago root epidermis by using a pharmacological approach in conjunction with transgenic plants expressing the Nod factor-responsive reporter construct pMtENOD12-GUS. Evidence for the participation of heterotrimeric G proteins in Nod factor signaling has come from three complementary observations: (1) the amphiphilic peptides mastoparan and Mas7, known G protein agonists, are able to mimic Nod factor-induced epidermal MtENOD12 expression; (2) growth of plants in nodulation-inhibiting conditions (10 mM NH4NO3) leads to a dramatic reduction in both Nod factor- and mastoparan-elicited gene expression; and (3) bacterial pertussis toxin, a well-characterized G protein antagonist, blocks the activities of both the Nod factor and mastoparan. In addition, we have found that antagonists that interfere with phospholipase C activity (neomycin and U73122) and Ca2+ influx/release (EGTA, La3+, and ruthenium red) block Nod factor/mastoparan activity. Taken together, these results are consistent with a Nod factor signal transduction mechanism involving G protein mediation coupled to the activation of both phosphoinositide and Ca2+ second messenger pathways. PMID:9596628

  12. TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction.

    PubMed

    Kwan, Kelvin Y; Allchorne, Andrew J; Vollrath, Melissa A; Christensen, Adam P; Zhang, Duan-Sun; Woolf, Clifford J; Corey, David P

    2006-04-20

    TRPA1, a member of the transient receptor potential (TRP) family of ion channels, is expressed by dorsal root ganglion neurons and by cells of the inner ear, where it has proposed roles in sensing sound, painful cold, and irritating chemicals. To test the in vivo roles of TRPA1, we generated a mouse in which the essential exons required for proper function of the Trpa1 gene were deleted. Knockout mice display behavioral deficits in response to mustard oil, to cold ( approximately 0 degrees C), and to punctate mechanical stimuli. These mice have a normal startle reflex to loud noise, a normal sense of balance, a normal auditory brainstem response, and normal transduction currents in vestibular hair cells. TRPA1 is apparently not essential for hair-cell transduction but contributes to the transduction of mechanical, cold, and chemical stimuli in nociceptor sensory neurons. PMID:16630838

  13. Calcium specificity signaling mechanisms in abscisic acid signal transduction in Arabidopsis guard cells.

    PubMed

    Brandt, Benjamin; Munemasa, Shintaro; Wang, Cun; Nguyen, Desiree; Yong, Taiming; Yang, Paul G; Poretsky, Elly; Belknap, Thomas F; Waadt, Rainer; Alemán, Fernando; Schroeder, Julian I

    2015-01-01

    A central question is how specificity in cellular responses to the eukaryotic second messenger Ca(2+) is achieved. Plant guard cells, that form stomatal pores for gas exchange, provide a powerful system for in depth investigation of Ca(2+)-signaling specificity in plants. In intact guard cells, abscisic acid (ABA) enhances (primes) the Ca(2+)-sensitivity of downstream signaling events that result in activation of S-type anion channels during stomatal closure, providing a specificity mechanism in Ca(2+)-signaling. However, the underlying genetic and biochemical mechanisms remain unknown. Here we show impairment of ABA signal transduction in stomata of calcium-dependent protein kinase quadruple mutant plants. Interestingly, protein phosphatase 2Cs prevent non-specific Ca(2+)-signaling. Moreover, we demonstrate an unexpected interdependence of the Ca(2+)-dependent and Ca(2+)-independent ABA-signaling branches and the in planta requirement of simultaneous phosphorylation at two key phosphorylation sites in SLAC1. We identify novel mechanisms ensuring specificity and robustness within stomatal Ca(2+)-signaling on a cellular, genetic, and biochemical level. PMID:26192964

  14. Calcium specificity signaling mechanisms in abscisic acid signal transduction in Arabidopsis guard cells

    PubMed Central

    Brandt, Benjamin; Munemasa, Shintaro; Wang, Cun; Nguyen, Desiree; Yong, Taiming; Yang, Paul G; Poretsky, Elly; Belknap, Thomas F; Waadt, Rainer; Alemán, Fernando; Schroeder, Julian I

    2015-01-01

    A central question is how specificity in cellular responses to the eukaryotic second messenger Ca2+ is achieved. Plant guard cells, that form stomatal pores for gas exchange, provide a powerful system for in depth investigation of Ca2+-signaling specificity in plants. In intact guard cells, abscisic acid (ABA) enhances (primes) the Ca2+-sensitivity of downstream signaling events that result in activation of S-type anion channels during stomatal closure, providing a specificity mechanism in Ca2+-signaling. However, the underlying genetic and biochemical mechanisms remain unknown. Here we show impairment of ABA signal transduction in stomata of calcium-dependent protein kinase quadruple mutant plants. Interestingly, protein phosphatase 2Cs prevent non-specific Ca2+-signaling. Moreover, we demonstrate an unexpected interdependence of the Ca2+-dependent and Ca2+-independent ABA-signaling branches and the in planta requirement of simultaneous phosphorylation at two key phosphorylation sites in SLAC1. We identify novel mechanisms ensuring specificity and robustness within stomatal Ca2+-signaling on a cellular, genetic, and biochemical level. DOI: http://dx.doi.org/10.7554/eLife.03599.001 PMID:26192964

  15. Mechanical basis of osmosensory transduction in magnocellular neurosecretory neurones of the rat supraoptic nucleus.

    PubMed

    Prager-Khoutorsky, M; Bourque, C W

    2015-06-01

    Rat magnocellular neurosecretory cells (MNCs) release vasopressin and oxytocin to promote antidiuresis and natriuresis at the kidney. The osmotic control of oxytocin and vasopressin release at the neurohypophysis is required for osmoregulation in these animals, and this release is mediated by a modulation of the action potential firing rate by the MNCs. Under basal (isotonic) conditions, MNCs fire action potentials at a slow rate, and this activity is inhibited by hypo-osmotic conditions and enhanced by hypertonicity. The effects of changes in osmolality on MNCs are mediated by a number of different factors, including the involvement of synaptic inputs, the release of taurine by local glial cells and regulation of ion channels expressed within the neurosecretory neurones themselves. We review recent findings that have clarified our understanding of how osmotic stimuli modulate the activity of nonselective cation channels in MNCs. Previous studies have shown that osmotically-evoked changes in membrane potential and action potential firing rate in acutely isolated MNCs are provoked mainly by a modulation of nonselective cation channels. Notably, the excitation of isolated MNCs during hypertonicity is mediated by the activation of a capsaicin-insensitive cation channel that MNCs express as an N-terminal variant of the transient receptor potential vanilloid 1 (Trpv1) channel. The activation of this channel during hypertonicity is a mechanical process associated with cell shrinking. The effectiveness of this mechanical process depends on the presence of a thin layer of actin filaments (F-actin) beneath the plasma membrane, as well as a densely interweaved network of microtubules (MTs) occupying the bulk of the cytoplasm of MNCs. Although the mechanism by which F-actin contributes to Trpv1 activation remains unknown, recent data have shown that MTs interact with Trpv1 channels via binding sites on the C-terminus, and that the force mediated through this complex is

  16. Studies on the Mechanism of Transduction by Bacteriophage ϕ_entitystart_#947_entit I. Genetic Characterization of the Transducing Segment

    PubMed Central

    Gratia, Jean-Pierre

    1976-01-01

    The bacteriophage Φγ, though related to the lambdoid phage ϕ80, has unusual features in its specialized transduction and is being investigated to determine the mechanism of the transduction process. Genetic analysis of the transducing element gives evidence for a relatively long and uniform linear segment, up to about 1% of the E. coli chromosome, extending in either direction from the prophage attachment site, e.g., on the right side: att80-tonB-trpABCDE-cysB-pryF. The att end includes a variable amount of phage genome, probably very short in most particles. In a small fraction of the transducing particles the phage segment may be more extensive and, conversely, the bacterial segment is shorter, ending around cysB. The transducing segment from modificationless bacteria carries a site susceptible to the K-restriction system which affects the efficiency of transduction. PMID:795713

  17. The condensed chromatin fiber: an allosteric chemo-mechanical machine for signal transduction and genome processing

    NASA Astrophysics Data System (ADS)

    Lesne, Annick; Bécavin, Christophe; Victor, Jean–Marc

    2012-02-01

    Allostery is a key concept of molecular biology which refers to the control of an enzyme activity by an effector molecule binding the enzyme at another site rather than the active site (allos = other in Greek). We revisit here allostery in the context of chromatin and argue that allosteric principles underlie and explain the functional architecture required for spacetime coordination of gene expression at all scales from DNA to the whole chromosome. We further suggest that this functional architecture is provided by the chromatin fiber itself. The structural, mechanical and topological features of the chromatin fiber endow chromosomes with a tunable signal transduction from specific (or nonspecific) effectors to specific (or nonspecific) active sites. Mechanical constraints can travel along the fiber all the better since the fiber is more compact and regular, which speaks in favor of the actual existence of the (so-called 30 nm) chromatin fiber. Chromatin fiber allostery reconciles both the physical and biochemical approaches of chromatin. We illustrate this view with two supporting specific examples. Moreover, from a methodological point of view, we suggest that the notion of chromatin fiber allostery is particularly relevant for systemic approaches. Finally we discuss the evolutionary power of allostery in the context of chromatin and its relation to modularity.

  18. Development of a CMOS MEMS pressure sensor with a mechanical force-displacement transduction structure

    NASA Astrophysics Data System (ADS)

    Cheng, Chao-Lin; Chang, Heng-Chung; Chang, Chun-I.; Fang, Weileun

    2015-12-01

    This study presents a capacitive pressure sensor with a mechanical force-displacement transduction structure based on the commercially available standard CMOS process (the TSMC 0.18 μm 1P6M CMOS process). The pressure sensor has a deformable diaphragm to support a movable plate with an embedded sensing electrode. As the diaphragm is deformed by the ambient pressure, the movable plate and its embedded sensing electrode are displaced. Thus, the pressure is detected from the capacitance change between the movable and fixed electrodes. The undeformed movable electrode will increase the effective sensing area between the sensing electrodes, thereby improving the sensitivity. Experimental results show that the proposed pressure sensor with a force-displacement transducer will increase the sensitivity by 126% within the 20 kPa-300 kPa absolute pressure range. Moreover, this study extends the design to add pillars inside the pressure sensor to further increase its sensing area as well as sensitivity. A sensitivity improvement of 117% is also demonstrated for a pressure sensor with an enlarged sensing electrode (the overlap area is increased two fold).

  19. Mechanisms of Cardiovascular Homeostasis and Pathophysiology--From Gene Expression, Signal Transduction to Cellular Communication.

    PubMed

    Akazawa, Hiroshi

    2015-01-01

    During embryogenesis, progenitor cells are specified and differentiated into mature cardiomyocytes. Soon after birth, the ability of cardiomyocytes to proliferate is strongly restrained, and thereafter, they grow in size without cell division. Under pathological conditions, cardiomyocytes show adaptive and maladaptive responses through complex intracellular signaling pathways and cross-talking networks of intercellular and inter-tissue communications, but ultimately, they become dysfunctional and undergo cell death or degeneration. Cardiovascular diseases remain the most prevalent, costly, disabling, and deadly medical conditions. To develop novel therapies for them, it is important to elucidate the underlying mechanisms that govern gene expression, signal transduction to cellular communication. In this review article for the 2014 SATO Memorial Award, an approach to uncover molecular and cellular pathophysiology is summarized, focusing on homeobox transcription factor Nkx2-5 in the transcriptional regulation of the cardiac gene program, 3-phosphoinositide-dependent kinase-1, in the regulation of postnatal cardiomyocyte growth, survival, and function, angiotensin II type 1 receptor in the development of pathological hypertrophy and remodeling, and mast cell infiltration in the pathogenesis of atrial remodeling and fibrillation. PMID:26538467

  20. Endothelin receptors and their cellular signal transduction mechanism in human cultured prostatic smooth muscle cells.

    PubMed

    Saita, Y; Koizumi, T; Yazawa, H; Morita, T; Takenaka, T; Honda, K

    1997-06-01

    1. Endothelin (ET) receptors, and their cellular signal transduction mechanism, were characterized in a primary culture of human prostatic smooth muscle cells (HP cell). 2. [125I]-ET-1 and [125I]-ET-3 binding studies revealed that both ETA and ETB receptors were present in the HP cells, and the ratio of ETA to ETB receptors was 1.4:1. 3. Analysis of ET receptor mRNA by reverse transcription-polymerase chain reaction also demonstrated that HP cells express both ETA and ETB receptors. 4. ET-1 and ET-3 increased intracellular free Ca2+ concentration ([Ca2+]i) in the HP cells in a concentration-dependent manner. Use of subtype selective antagonists BQ-123 and BQ-788, indicated that both ETA and ETB receptors were coupled to an increase in [Ca2+]i. 5. Pretreatment of the cells with pertussis toxin resulted in a significant but partial attenuation of the [Ca2+]i increase mediated through the ETA and ETB receptors. However, sensitivity to pertussis toxin (PTX) was significantly different between them. 6. In conclusion, HP cells possess ETA and ETB receptors. Further, these two endothelin receptor subtypes evoke an increase in [Ca2+]i possibly via the action of different GTP-binding proteins. PMID:9208135

  1. Endothelin receptors and their cellular signal transduction mechanism in human cultured prostatic smooth muscle cells

    PubMed Central

    Saita, Yuji; Koizumi, Tomonobu; Yazawa, Hidenori; Morita, Takashi; Takenaka, Toichi; Honda, Kazuo

    1997-01-01

    Endothelin (ET) receptors, and their cellular signal transduction mechanism, were characterized in a primary culture of human prostatic smooth muscle cells (HP cell). [125I]-ET-1 and [125I]-ET-3 binding studies revealed that both ETA and ETB receptors were present in the HP cells, and the ratio of ETA to ETB receptors was 1.4:1. Analysis of ET receptor mRNA by reverse transcription-polymerase chain reaction also demonstrated that HP cells express both ETA and ETB receptors. ET-1 and ET-3 increased intracellular free Ca2+ concentration ([Ca2+]i) in the HP cells in a concentration-dependent manner. Use of subtype selective antagonists BQ-123 and BQ-788, indicated that both ETA and ETB receptors were coupled to an increase in [Ca2+]i. Pretreatment of the cells with pertussis toxin resulted in a significant but partial attenuation of the [Ca2+]i increase mediated through the ETA and ETB receptors. However, sensitivity to pertussis toxin (PTX) was significantly different between them. In conclusion, HP cells possess ETA and ETB receptors. Further, these two endothelin receptor subtypes evoke an increase in [Ca2+]i possibly via the action of different GTP-binding proteins. PMID:9208135

  2. Mechanisms of regulation of olfactory transduction and adaptation in the olfactory cilium.

    PubMed

    Antunes, Gabriela; Sebastião, Ana Maria; Simoes de Souza, Fabio Marques

    2014-01-01

    Olfactory adaptation is a fundamental process for the functioning of the olfactory system, but the underlying mechanisms regulating its occurrence in intact olfactory sensory neurons (OSNs) are not fully understood. In this work, we have combined stochastic computational modeling and a systematic pharmacological study of different signaling pathways to investigate their impact during short-term adaptation (STA). We used odorant stimulation and electroolfactogram (EOG) recordings of the olfactory epithelium treated with pharmacological blockers to study the molecular mechanisms regulating the occurrence of adaptation in OSNs. EOG responses to paired-pulses of odorants showed that inhibition of phosphodiesterases (PDEs) and phosphatases enhanced the levels of STA in the olfactory epithelium, and this effect was mimicked by blocking vesicle exocytosis and reduced by blocking cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and vesicle endocytosis. These results suggest that G-coupled receptors (GPCRs) cycling is involved with the occurrence of STA. To gain insights on the dynamical aspects of this process, we developed a stochastic computational model. The model consists of the olfactory transduction currents mediated by the cyclic nucleotide gated (CNG) channels and calcium ion (Ca(2+))-activated chloride (CAC) channels, and the dynamics of their respective ligands, cAMP and Ca(2+), and it simulates the EOG results obtained under different experimental conditions through changes in the amplitude and duration of cAMP and Ca(2+) response, two second messengers implicated with STA occurrence. The model reproduced the experimental data for each pharmacological treatment and provided a mechanistic explanation for the action of GPCR cycling in the levels of second messengers modulating the levels of STA. All together, these experimental and theoretical results indicate the existence of a mechanism of regulation of STA by signaling pathways that control

  3. Mechanisms of Regulation of Olfactory Transduction and Adaptation in the Olfactory Cilium

    PubMed Central

    Antunes, Gabriela; Sebastião, Ana Maria; Simoes de Souza, Fabio Marques

    2014-01-01

    Olfactory adaptation is a fundamental process for the functioning of the olfactory system, but the underlying mechanisms regulating its occurrence in intact olfactory sensory neurons (OSNs) are not fully understood. In this work, we have combined stochastic computational modeling and a systematic pharmacological study of different signaling pathways to investigate their impact during short-term adaptation (STA). We used odorant stimulation and electroolfactogram (EOG) recordings of the olfactory epithelium treated with pharmacological blockers to study the molecular mechanisms regulating the occurrence of adaptation in OSNs. EOG responses to paired-pulses of odorants showed that inhibition of phosphodiesterases (PDEs) and phosphatases enhanced the levels of STA in the olfactory epithelium, and this effect was mimicked by blocking vesicle exocytosis and reduced by blocking cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and vesicle endocytosis. These results suggest that G-coupled receptors (GPCRs) cycling is involved with the occurrence of STA. To gain insights on the dynamical aspects of this process, we developed a stochastic computational model. The model consists of the olfactory transduction currents mediated by the cyclic nucleotide gated (CNG) channels and calcium ion (Ca2+)-activated chloride (CAC) channels, and the dynamics of their respective ligands, cAMP and Ca2+, and it simulates the EOG results obtained under different experimental conditions through changes in the amplitude and duration of cAMP and Ca2+ response, two second messengers implicated with STA occurrence. The model reproduced the experimental data for each pharmacological treatment and provided a mechanistic explanation for the action of GPCR cycling in the levels of second messengers modulating the levels of STA. All together, these experimental and theoretical results indicate the existence of a mechanism of regulation of STA by signaling pathways that control GPCR

  4. New perspectives on photosynthetic phosphorylation in the light of a torsional mechanism of energy transduction and ATP synthesis.

    PubMed

    Nath, Sunil; Elangovan, Ravikrishnan

    2011-12-01

    New perspectives on photophosphorylation have been offered from the standpoint of the torsional mechanism of energy transduction and ATP synthesis. New experimental data on the involvement of malate anions in ATP synthesis in an acid-base malate bath procedure has been reported on spinach chloroplast thylakoids as the model system. The data cannot be reconciled with the chemiosmotic theory but has been shown to be naturally explained by the torsional mechanism. The path of malic acid in the acid and base stages of the experiment has been traced, offering further strong support to the new paradigm. Classical observations in the field have been re-interpreted in the light of these findings. A new concept of ion translocation, energy transduction and coupling at the overall physiological level in photophosphorylation has been presented and a large number of novel experimentally testable predictions have been made and shown to arise as logical consequences of the new perspectives. PMID:22083127

  5. Real-time PCR monitoring of signal transduction related genes involved in water stress tolerance mechanism of sunflower.

    PubMed

    Roche, Jane; Hewezi, Tarek; Bouniols, Andrée; Gentzbittel, Laurent

    2009-02-01

    The study deals with the quantitative expression pattern of genes involved in signaling transduction pathways in response to water stress in leaves and embryos of a water stress tolerant genotype compared to a non-tolerant genotype using real-time quantitative PCR. The experiment was conducted in the field. The results showed a high quantitative up-regulation of genes belonging to protein kinase, phosphatase and transcription factor pathways (from two to 70 fold) only in leaves of the tolerant genotype compared to the non-tolerant genotype. Moreover, genes related to the protein kinase pathway were down-regulated in leaves of the non-tolerant genotype. On the contrary, in seeds, our study showed that the positive regulation of genes related to the signal transduction pathway observed in leaves of the tolerant genotype is turned off, suggesting different transcriptional control of signaling water stress in reproductive organs compared to vegetative organs. PMID:19054682

  6. An investigation into membrane bound redox carriers involved in energy transduction mechanism in Brevibacterium linens DSM 20158 with unsequenced genome.

    PubMed

    Shabbiri, Khadija; Botting, Catherine H; Adnan, Ahmad; Fuszard, Matthew; Naseem, Shahid; Ahmed, Safeer; Shujaat, Shahida; Syed, Quratulain; Ahmad, Waqar

    2014-04-01

    Brevibacterium linens (B. linens) DSM 20158 with an unsequenced genome can be used as a non-pathogenic model to study features it has in common with other unsequenced pathogens of the same genus on the basis of comparative proteome analysis. The most efficient way to kill a pathogen is to target its energy transduction mechanism. In the present study, we have identified the redox protein complexes involved in the electron transport chain of B. linens DSM 20158 from their clear homology with the shot-gun genome sequenced strain BL2 of B. linens by using the SDS-Polyacrylamide gel electrophoresis coupled with nano LC-MS/MS mass spectrometry. B. linens is found to have a branched electron transport chain (Respiratory chain), in which electrons can enter the respiratory chain either at NADH (Complex I) or at Complex II level or at the cytochrome level. Moreover, we are able to isolate, purify, and characterize the membrane bound Complex II (succinate dehydrogenase), Complex III (menaquinone cytochrome c reductase cytochrome c subunit, Complex IV (cytochrome c oxidase), and Complex V (ATP synthase) of B. linens strain DSM 20158. PMID:24573306

  7. Signal transduction mechanism of a peptide mimetic of interferon-gamma.

    PubMed

    Subramaniam, Prem S; Flowers, Lawrence O; Haider, S Mohammed I; Johnson, Howard M

    2004-05-11

    The C-terminus of interferon-gamma (IFNgamma) contains a nuclear localization sequence (NLS) required for the activation and nuclear translocation of the transcription factor STAT1alpha and induction of IFNgamma-activated genes. On the basis of this and other studies, we developed a peptide mimetic of IFNgamma that possesses the IFNgamma functions of antiviral activity and upregulation of MHC class II molecules. The mimetic also shares with IFNgamma the ability to induce the activation and nuclear translocation of STAT1alpha and the IFNgamma receptor (IFNGR)-1 subunit. The mimetic, IFNgamma(95-132), is a peptide that consists of the C-terminal residues 95-132 of murine IFNgamma and contains a required alpha-helical domain and the NLS of IFNgamma. In this study, we determined the mechanism of the intracellular action of the mimetic at the level of signal transduction. We show that the mimetic mediates the nuclear transport of IFNGR-1 through its interaction with IFNGR-1 cytoplasmic region 253-287 via both the helical region and the NLS of IFNgamma(95-132). Alanine substitutions of the NLS of the mimetic showed that the NLS was required for nuclear translocation and that the nuclear transport properties of the mimetic correlated with its ability to bind IFNGR-1. These data also show that the NLS of IFNgamma(95-132) can interact simultaneously with IFNGR-1 and the nuclear import machinery. We found that in in vitro nuclear transport assays tyrosine-phosphorylated STAT1alpha failed to undergo nuclear translocation in the presence of nuclear import factors, but was transported to nucleus in the presence of IFNgamma(95-132) and JAK2-phosphorylated IFNGR-1, to which STAT1alpha binds, as a complex of IFNgamma(95-132)/IFNGR-1/STAT1alpha. Thus, the mimetic, which possesses IFNgamma function, is directly involved as a chaperone in the nuclear transport of STAT1alpha and shares this mechanism of action with that previously described for IFNgamma. The mimetic, like IFNgamma, is

  8. Mechanisms of signal transduction by ethylene: overlapping and non-overlapping signalling roles in a receptor family

    PubMed Central

    Shakeel, Samina N.; Wang, Xiaomin; Binder, Brad M.; Schaller, G. Eric

    2013-01-01

    The plant hormone ethylene regulates growth and development as well as responses to biotic and abiotic stresses. Over the last few decades, key elements involved in ethylene signal transduction have been identified through genetic approaches, these elements defining a pathway that extends from initial ethylene perception at the endoplasmic reticulum to changes in transcriptional regulation within the nucleus. Here, we present our current understanding of ethylene signal transduction, focusing on recent developments that support a model with overlapping and non-overlapping roles for members of the ethylene receptor family. We consider the evidence supporting this model for sub-functionalization within the receptor family, and then discuss mechanisms by which such a sub-functionalization may occur. To this end, we consider the importance of receptor interactions in modulating their signal output and how such interactions vary in the receptor family. In addition, we consider evidence indicating that ethylene signal output by the receptors involves both phosphorylation-dependent and phosphorylation-independent mechanisms. We conclude with a current model for signalling by the ethylene receptors placed within the overall context of ethylene signal transduction. PMID:23543258

  9. Alteration of membrane transductive mechanisms induced by ethanol in human lymphocyte cultures.

    PubMed

    Fanò, G; Belia, S; Mariggiò, M A; Antonica, A; Agea, E; Spinozzi, F

    1993-03-01

    Ethanol, in millimolar concentrations, significantly modifies different transductive systems in human lymphocyte cultures. In particular, the presence of alcohol in the medium more than doubles the [Ca2+]i (from 70-90 to 200-250 nM), increasing Ca2+ fluxes from outside, and inhibits the active transport carried out by the calcium pump. The Ca2+ release from intracellular stores is not involved because 10 mM EGTA in the medium completely abolished the rise of [Ca2+]i. Since IP3 levels and cAMP concentrations are also involved in ethanol events (although with opposite effects), it seems that the alcohol may have a specific target on cell membranes (G-proteins) which influence many transductive pathways. PMID:8388700

  10. TRPV Ion Channels and Sensory Transduction of Osmotic and Mechanical Stimuli in Mammals

    NASA Astrophysics Data System (ADS)

    Liedtke, Wolfgang

    In signal transduction in metazoan cells, ion channels of the transient receptor potential (TRP) family have been identified as responding to diverse external and internal stimuli, amongst them osmotic stimuli. This chapter will highlight findings on the TRP vanilloid (TRPV) subfamily - both vertebrate and invertebrate members. Of the six mammalian TRPV channels, TRPV1, 2 and 4 have been demonstrated to function in transduction of osmotic stimuli. TRPV channels have been found to function in cellular as well as systemic osmotic homeostasis in vertebrates. Invertebrate TRPV channels - five in Caenorhabditis elegans and two in Drosophila - have been shown to play a role in mechanosensation such as hearing and proprioception in Drosophila and nose touch in C. elegans, and in the response to osmotic stimuli in C. elegans. In a striking example of evolutionary conservation of function, mammalian TRPV4 has been found to rescue osmo- and mechano-sensory deficits of the TRPV mutant strain osm-9 in C. elegans, despite the fact that the respective proteins share not more than 26% orthology.

  11. Comparative RNA-sequencing analysis of mthl1 functions and signal transductions in Tribolium castaneum.

    PubMed

    Li, Chengjun; Wu, Wei; Sang, Ming; Liu, Xing; Hu, Xingxing; Yun, Xiaopei; Li, Bin

    2014-09-01

    Methuselah-like 1 of Tribolium castaneum (TcMthl1) has been reported to play crucial roles in development, lifespan, stress resistance and reproduction. However, the signaling system of TcMthl1 is unknown. Thus, we compare the transcriptome profile of RNAi treated larvae (ds-Tcmthl1) and control larvae of T. castaneum by RNA-sequencing, and obtained 14,613,514 sequence reads aligned with 13,533 genes; 812 differentially expressed genes (DEGs) were identified. These DEGs were classified into 47 GO functional groups, including such functions as the immune system process, the response to stimulus, the developmental process and reproduction. Interestingly, knock-down of Tcmthl1 suppressed both of Toll and IMD immunity pathways which most likely modulated the effects of Tcmthl1 on lifespan and stress resistance. Additionally, the DEGs encoding Blimp-1, Ftz-F1, E74 and Timeless may participate in the development and reproduction of ds-Tcmthl1 insects. The findings of these DEGs and pathways will provide valuable insight into TcMthl1 signaling and regulation system. PMID:24992031

  12. Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus

    PubMed Central

    Ji, Quanjiang; Chen, Peter J.; Qin, Guangrong; Deng, Xin; Hao, Ziyang; Wawrzak, Zdzislaw; Yeo, Won-Sik; Quang, Jenny Winjing; Cho, Hoonsik; Luo, Guan-Zheng; Weng, Xiaocheng; You, Qiancheng; Luan, Chi-Hao; Yang, Xiaojing; Bae, Taeok; Yu, Kunqian; Jiang, Hualiang; He, Chuan

    2016-01-01

    Most low GC Gram-positive bacteria possess an essential walKR two-component system (TCS) for signal transduction involved in regulating cell wall homoeostasis. Despite the well-established intracellular regulatory mechanism, the role of this TCS in extracellular signal recognition and factors that modulate the activity of this TCS remain largely unknown. Here we identify the extracellular receptor of the kinase ‘WalK' (erWalK) as a key hub for bridging extracellular signal input and intracellular kinase activity modulation in Staphylococcus aureus. Characterization of the crystal structure of erWalK revealed a canonical Per-Arnt-Sim (PAS) domain for signal sensing. Single amino-acid mutation of potential signal-transduction residues resulted in severely impaired function of WalKR. A small molecule derived from structure-based virtual screening against erWalK is capable of selectively activating the walKR TCS. The molecular level characterization of erWalK will not only facilitate exploration of natural signal(s) but also provide a template for rational design of erWalK inhibitors. PMID:26987594

  13. Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus

    DOE PAGESBeta

    Ji, Quanjiang; Chen, Peter J.; Qin, Guangrong; Deng, Xin; Hao, Ziyang; Wawrzak, Zdzislaw; Yeo, Won -Sik; Quang, Jenny Winjing; Cho, Hoonsik; Luo, Guan -Zheng; et al

    2016-03-18

    Most low GC Gram-positive bacteria possess an essential walKR two-component system (TCS) for signal transduction involved in regulating cell wall homoeostasis. Despite the well-established intracellular regulatory mechanism, the role of this TCS in extracellular signal recognition and factors that modulate the activity of this TCS remain largely unknown. Here we identify the extracellular receptor of the kinase ‘WalK’ (erWalK) as a key hub for bridging extracellular signal input and intracellular kinase activity modulation in Staphylococcus aureus. Characterization of the crystal structure of erWalK revealed a canonical Per-Arnt-Sim (PAS) domain for signal sensing. Single amino-acid mutation of potential signal-transduction residues resultedmore » in severely impaired function of WalKR. A small molecule derived from structure-based virtual screening against erWalK is capable of selectively activating the walKR TCS. Lastly, the molecular level characterization of erWalK will not only facilitate exploration of natural signal(s) but also provide a template for rational design of erWalK inhibitors.« less

  14. Potential insight for drug discovery from high fidelity receptor-mediated transduction mechanisms in insects

    PubMed Central

    Raffa, Robert B.; Raffa, Kenneth F.

    2011-01-01

    Introduction There is a pervasive and growing concern about the small number of new pharmaceutical agents. There are many proposed explanations for this trend that do not involve the drug-discovery process per se, but the discovery process itself has also come under scrutiny. If the current paradigms are indeed not working, where are novel ideas to come from? Perhaps it is time to look to novel sources. Areas covered The receptor-signaling and 2nd-messenger transduction processes present in insects are quite similar to those in mammals (involving G proteins, ion channels, etc.). However, a review of these systems reveals an unprecedented degree of high potency and receptor selectivity to an extent greater than that modeled in most current drug-discovery approaches. Expert opinion A better understanding of insect receptor pharmacology could stimulate novel theoretical and practical ideas in mammalian pharmacology (drug discovery) and, conversely, the application of pharmacology and medicinal chemistry principles could stimulate novel advances in entomology (safer and more targeted control of pest species). PMID:21984882

  15. Toward Quantifying the Electrostatic Transduction Mechanism in Carbon Nanotube Biomolecular Sensors

    NASA Astrophysics Data System (ADS)

    Lerner, Mitchell; Kybert, Nicholas; Mendoza, Ryan; Dailey, Jennifer; Johnson, A. T. Charlie

    2013-03-01

    Despite the great promise of carbon nanotube field-effect transistors (CNT FETs) for applications in chemical and biochemical detection, a quantitative understanding of sensor responses is lacking. To explore the role of electrostatics in sensor transduction, experiments were conducted with a set of similar compounds designed to adsorb onto the CNT FET via a pyrene linker group and take on a set of known charge states under ambient conditions. Acidic and basic species were observed to induce threshold voltage shifts of opposite sign, consistent with gating of the CNT FET by local charges due to protonation or deprotonation of the pyrene compounds by interfacial water. The magnitude of the gate voltage shift was controlled by the distance between the charged group and the CNT. Additionally, functionalization with an uncharged pyrene compound showed a threshold shift ascribed to its molecular dipole moment. This work illustrates a method for producing CNT FETs with controlled values of the turnoff gate voltage, and more generally, these results will inform the development of quantitative models for the response of CNT FET chemical and biochemical sensors. As an example, the results of an experiment detecting biomarkers of Lyme disease will be discussed in the context of this model.

  16. Radiative ion-ion neutralization: a new gas-phase atmospheric pressure ion transduction mechanism.

    PubMed

    Davis, Eric J; Siems, William F; Hill, Herbert H

    2012-06-01

    All atmospheric pressure ion detectors, including photo ionization detectors, flame ionization detectors, electron capture detectors, and ion mobility spectrometers, utilize Faraday plate designs in which ionic charge is collected and amplified. The sensitivity of these Faraday plate ion detectors are limited by thermal (Johnson) noise in the associated electronics. Thus approximately 10(6) ions per second are required for a minimal detection. This is not the case for ion detection under vacuum conditions where secondary electron multipliers (SEMs) can be used. SEMs produce a cascade of approximately 10(6) electrons per ion impinging on the conversion dynode. Similarly, photomultiplier tubes (PMTs) can generate approximately 10(6) electrons per photon. Unlike SEMs, however, PMTs are evacuated and sealed so that they are commonly used under atmospheric pressure conditions. This paper describes an atmospheric pressure ion detector based on coupling a PMT with light emitted from ion-ion neutralization reactions. The normal Faraday plate collector electrode was replaced with an electrode "needle" used to concentrate the anions as they were drawn to the tip of the needle by a strong focusing electric field. Light was emitted near the surface of the electrode when analyte ions were neutralized with cations produced from the anode. Although radiative-ion-ion recombination has been previously reported, this is the first time ions from separate ionization sources have been combined to produce light. The light from this radiative-ion-ion-neutralization (RIIN) was detected using a photon multiplier such that an ion mobility spectrum was obtained by monitoring the light emitted from mobility separated ions. An IMS spectrum of nitroglycerin (NG) was obtained utilizing RIIN for tranducing the mobility separated ions into an analytical signal. The implications of this novel ion transduction method are the potential for counting ions at atmospheric pressure and for obtaining ion

  17. Glucose and Stress Independently Regulate Source and Sink Metabolism and Defense Mechanisms via Signal Transduction Pathways Involving Protein Phosphorylation.

    PubMed Central

    Ehness, R.; Ecker, M.; Godt, D. E.; Roitsch, T.

    1997-01-01

    In higher plants, sugars are required not only to sustain heterotrophic growth but also to regulate the expression of a variety of genes. Environmental stresses, such as pathogen infection and wounding, activate a cascade of defense responses and may also affect carbohydrate metabolism. In this study, the relationship between sugar- and stress-activated signal transduction pathways and the underlying regulatory mechanism was analyzed. Photoautotrophically growing suspension culture cells of Chenopodium rubrum were used as a model system to study the effects of the metabolic regulator D-glucose and of different stress-related stimuli on photosynthesis, sink metabolism, and defense response by analyzing the regulation of mRNAs for representative enzymes of these pathways. Glucose as well as the fungal elicitor chitosan, the phosphatase inhibitor endothall, and benzoic acid were shown to result in a coordinated regulatory mechanism. The mRNAs for phenylalanine ammonia-lyase, a key enzyme of defense response, and for the sink-specific extracellular invertase were induced. In contrast, the mRNA for the Calvin cycle enzyme ribulose bisphosphate carboxylase was repressed. This inverse regulatory pattern was also observed in experiments with wounded leaves of C. rubrum plants. The differential effect of the protein kinase inhibitor staurosporine on mRNA regulation demonstrates that the carbohydrate signal and the stress-related stimuli independently activate different intracellular signaling pathways that ultimately are integrated to coordinately regulate source and sink metabolism and activate defense responses. The various stimuli triggered the transient and rapid activation of protein kinases that phosphorylate the myelin basic protein. The involvement of phosphorylation in signal transduction is further supported by the effect of the protein kinase inhibitor staurosporine on mRNA levels. PMID:12237349

  18. Phosphorylation in halobacterial signal transduction.

    PubMed Central

    Rudolph, J; Tolliday, N; Schmitt, C; Schuster, S C; Oesterhelt, D

    1995-01-01

    Regulated phosphorylation of proteins has been shown to be a hallmark of signal transduction mechanisms in both Eubacteria and Eukarya. Here we demonstrate that phosphorylation and dephosphorylation are also the underlying mechanism of chemo- and phototactic signal transduction in Archaea, the third branch of the living world. Cloning and sequencing of the region upstream of the cheA gene, known to be required for chemo- and phototaxis in Halobacterium salinarium, has identified cheY and cheB analogs which appear to form part of an operon which also includes cheA and the following open reading frame of 585 nucleotides. The CheY and CheB proteins have 31.3 and 37.5% sequence identity compared with the known signal transduction proteins CheY and CheB from Escherichia coli, respectively. The biochemical activities of both CheA and CheY were investigated following their expression in E.coli, isolation and renaturation. Wild-type CheA could be phosphorylated in a time-dependent manner in the presence of [gamma-32P]ATP and Mg2+, whereas the mutant CheA(H44Q) remained unlabeled. Phosphorylated CheA was dephosphorylated rapidly by the addition of wild-type CheY. The mutant CheY(D53A) had no effect on phosphorylated CheA. The mechanism of chemo- and phototactic signal transduction in the Archaeon H.salinarium, therefore, is similar to the two-component signaling system known from chemotaxis in the eubacterium E.coli. Images PMID:7556066

  19. Amiloride-Insensitive Salt Taste Is Mediated by Two Populations of Type III Taste Cells with Distinct Transduction Mechanisms

    PubMed Central

    Sukumaran, Sunil K.; Margolskee, Robert F.; Bachmanov, Alexander A.

    2016-01-01

    Responses in the amiloride-insensitive (AI) pathway, one of the two pathways mediating salty taste in mammals, are modulated by the size of the anion of a salt. This “anion effect” has been hypothesized to result from inhibitory transepithelial potentials (TPs) generated across the lingual epithelium as cations permeate through tight junctions and leave their larger and less permeable anions behind (Ye et al., 1991). We tested directly the necessity of TPs for the anion effect by measuring responses to NaCl and Na-gluconate (small and large anion sodium salts, respectively) in isolated taste cells from mouse circumvallate papillae. Using calcium imaging, we identified AI salt-responsive type III taste cells and demonstrated that they compose a subpopulation of acid-responsive taste cells. Even in the absence of TPs, many (66%) AI salt-responsive type III taste cells still exhibited the anion effect, demonstrating that some component of the transduction machinery for salty taste in type III cells is sensitive to anion size. We hypothesized that osmotic responses could explain why a minority of type III cells (34%) had AI salt responses but lacked anion sensitivity. All AI type III cells had osmotic responses to cellobiose, which were significantly modulated by extracellular sodium concentration, suggesting the presence of a sodium-conducting osmotically sensitive ion channel. However, these responses were significantly larger in AI type III cells that did not exhibit the anion effect. These findings indicate that multiple mechanisms could underlie AI salt responses in type III taste cells, one of which may contribute to the anion effect. SIGNIFICANCE STATEMENT Understanding the mechanisms underlying salty taste will help inform strategies to combat the health problems associated with NaCl overconsumption by humans. Of the two pathways underlying salty taste in mammals, the amiloride-insensitive (AI) pathway is the least understood. Using calcium imaging of

  20. Yifuning postpones ovarian aging through antioxidant mechanisms and suppression of the Rb/p53 signal transduction pathway.

    PubMed

    Liang, Lei; Zhang, Xu-Hui; Ji, Bo; Yao, Hui; Ling, Xiao-Mei; Guo, Zhi-Jian; Deng, Hong-Zhu; Wu, Xin-Rong

    2016-07-01

    Yifuning is a traditional Chinese medicine recipe that has been used for many years in China for its effects on treating climacteric syndrome in women. The present study aimed to demonstrate the effects and underlying molecular mechanism of Yifuning on the ovaries of aging rats. Selected aging rats were administered different doses of Yifuning (1.0 or 2.0 g/kg by lavage), and after 6 weeks the rats were sacrificed. The activit of indicators of oxidative stress in the serum were measured. The expression levels of 8-oxo-2'-deoxyguanosine (8-OHDG) and p53 in the ovaries were examined using immunohistochemistry. The expression levels of the corresponding genes and proteins were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting analyses, respectively. The results indicated that Yifuning significantly prevented ovarian failure, as indicated by improvements in estrous cycling, reproductive organ weights and sex hormone serum levels. Yifuning significantly increased the levels of superoxide dismutase, glutathione peroxidase, catalase and reduced malondialdehyde and hydrogen peroxide levels. Yifuning reduced DNA damage in the ovaries by reducing the expression of 8‑OHDG and p53. Treatment with Yifuning significantly reduced the age‑induced p19, p53, p21 and Rb activity in the ovaries. The present study demonstrates that Yifuning prevents ovarian failure and the mechanism involved is partly associated with antioxidants and suppression of the Rb/p53 signal transduction pathway. PMID:27222316

  1. Comparative advantages of mechanical biosensors

    PubMed Central

    Arlett, J.L.; Myers, E.B.; Roukes, M.L.

    2013-01-01

    Mechanical interactions are fundamental to biology. Mechanical forces of chemical origin determine motility and adhesion on the cellular scale, and govern transport and affinity on the molecular scale. Biological sensing in the mechanical domain provides unique opportunities to measure forces, displacements and mass changes from cellular and subcellular processes. Nanomechanical systems are particularly well matched in size with molecular interactions, and provide a basis for biological probes with single-molecule sensitivity. Here we review micro- and nanoscale biosensors, with a particular focus on fast mechanical biosensing in fluid by mass- and force-based methods, and the challenges presented by non-specific interactions. We explain the general issues that will be critical to the success of any type of next-generation mechanical biosensor, such as the need to improve intrinsic device performance, fabrication reproducibility and system integration. We also discuss the need for a greater understanding of analyte–sensor interactions on the nanoscale and of stochastic processes in the sensing environment. PMID:21441911

  2. Structure of Concatenated HAMP Domains Provides a Mechanism for Signal Transduction

    SciTech Connect

    Airola, Michael V.; Watts, Kylie J.; Bilwes, Alexandrine M.; Crane, Brian R.

    2010-08-23

    HAMP domains are widespread prokaryotic signaling modules found as single domains or poly-HAMP chains in both transmembrane and soluble proteins. The crystal structure of a three-unit poly-HAMP chain from the Pseudomonas aeruginosa soluble receptor Aer2 defines a universal parallel four-helix bundle architecture for diverse HAMP domains. Two contiguous domains integrate to form a concatenated di-HAMP structure. The three HAMP domains display two distinct conformations that differ by changes in helical register, crossing angle, and rotation. These conformations are stabilized by different subsets of conserved residues. Known signals delivered to HAMP would be expected to switch the relative stability of the two conformations and the position of a coiled-coil phase stutter at the junction with downstream helices. We propose that the two conformations represent opposing HAMP signaling states and suggest a signaling mechanism whereby HAMP domains interconvert between the two states, which alternate down a poly-HAMP chain.

  3. Emerging Molecular Mechanisms of Signal Transduction in Pentameric Ligand-Gated Ion Channels.

    PubMed

    Nemecz, Ákos; Prevost, Marie S; Menny, Anaïs; Corringer, Pierre-Jean

    2016-05-01

    Nicotinic acetylcholine, serotonin type 3, γ-amminobutyric acid type A, and glycine receptors are major players of human neuronal communication. They belong to the family of pentameric ligand-gated ion channels, sharing a highly conserved modular 3D structure. Recently, high-resolution structures of both open- and closed-pore conformations have been solved for a bacterial, an invertebrate, and a vertebrate receptor in this family. These data suggest that a common gating mechanism occurs, coupling neurotransmitter binding to pore opening, but they also pinpoint significant differences among subtypes. In this Review, we summarize the structural and functional data in light of these gating models and speculate about their mechanistic consequences on ion permeation, pathological mutations, as well as functional regulation by orthosteric and allosteric effectors. PMID:27151638

  4. Therapeutic effects of tyroservatide on metastasis of lung cancer and its mechanism affecting integrin–focal adhesion kinase signal transduction

    PubMed Central

    Huang, Yu-ting; Zhao, Lan; Fu, Zheng; Zhao, Meng; Song, Xiao-meng; Jia, Jing; Wang, Song; Li, Jin-ping; Zhu, Zhi-feng; Lin, Gang; Lu, Rong; Yao, Zhi

    2016-01-01

    Tyroservatide (YSV) can inhibit the growth and metastasis of mouse lung cancer significantly. This study investigated the therapeutic effects of tripeptide YSV on metastasis of human lung cancer cells and explored its possible mechanism that affects integrin–focal adhesion kinase (FAK) signal transduction in tumor cells. YSV significantly inhibited the adhesion and the invasion of highly metastatic human lung cancer cell lines 95D, A549, and NCI-H1299. In addition, YSV significantly inhibited phosphorylation of FAK Tyr397 and FAK Tyr576/577 in the 95D, A549, and NCI-H1299 human lung cancer cells in vitro. And the mRNA level and protein expression of FAK in these human lung cancer cells decreased at the same time. YSV also significantly inhibited mRNA and protein levels of integrin β1 and integrin β3 in the 95D, A549, and NCI-H1299 human lung cancer cells. Our research showed that YSV inhibited adhesion and invasion of human lung cancer cells and exhibited therapeutic effects on metastasis of lung cancer. PMID:27041993

  5. Experimental and theoretical investigation of the precise transduction mechanism in giant magnetoresistive biosensors

    PubMed Central

    Lee, Jung-Rok; Sato, Noriyuki; Bechstein, Daniel J. B.; Osterfeld, Sebastian J.; Wang, Junyi; Gani, Adi Wijaya; Hall, Drew A.; Wang, Shan X.

    2016-01-01

    Giant magnetoresistive (GMR) biosensors consisting of many rectangular stripes are being developed for high sensitivity medical diagnostics of diseases at early stages, but many aspects of the sensing mechanism remain to be clarified. Using e-beam patterned masks on the sensors, we showed that the magnetic nanoparticles with a diameter of 50 nm located between the stripes predominantly determine the sensor signals over those located on the sensor stripes. Based on computational analysis, it was confirmed that the particles in the trench, particularly those near the edges of the stripes, mainly affect the sensor signals due to additional field from the stripe under an applied field. We also demonstrated that the direction of the average magnetic field from the particles that contributes to the signal is indeed the same as that of the applied field, indicating that the particles in the trench are pivotal to produce sensor signal. Importantly, the same detection principle was validated with a duplex protein assay. Also, 8 different types of sensor stripes were fabricated and design parameters were explored. According to the detection principle uncovered, GMR biosensors can be further optimized to improve their sensitivity, which is highly desirable for early diagnosis of diseases. PMID:26728870

  6. An energy transduction mechanism used in bacterial flagellar type III protein export

    PubMed Central

    Minamino, Tohru; Morimoto, Yusuke V.; Hara, Noritaka; Namba, Keiichi

    2011-01-01

    Flagellar proteins of bacteria are exported by a specific export apparatus. FliI ATPase forms a complex with FliH and FliJ and escorts export substrates from the cytoplasm to the export gate complex, which is made up of six membrane proteins. The export gate complex utilizes proton motive force across the cytoplasmic membrane for protein translocation, but the mechanism remains unknown. Here we show that the export gate complex by itself is a proton–protein antiporter that uses the two components of proton motive force, Δψ and ΔpH, for different steps of the protein export process. However, in the presence of FliH, FliI and FliJ, a specific binding of FliJ with an export gate membrane protein, FlhA, is brought about by the FliH–FliI complex, which turns the export gate into a highly efficient, Δψ-driven protein export apparatus. PMID:21934659

  7. Sensing behaviors of polypyrrole nanotubes prepared in reverse microemulsions: effects of transducer size and transduction mechanism.

    PubMed

    Yoon, Hyeonseok; Chang, Mincheol; Jang, Jyongsik

    2006-07-27

    Polypyrrole (PPy) nanotubes with different diameters were readily fabricated using cylindrical micelle templates in sodium bis(2-ethylhexyl) sulfosuccinate (AOT) reverse microemulsions. Interestingly, Raman spectroscopy and ultraviolet (UV)-visible spectroscopy revealed that the PPy nanotubes with smaller diameters had a more extended conjugation length as well as a higher oxidation level. The PPy nanotubes were deposited onto a microelectrode array and were exposed to chemical vapor and electromagnetic radiation: typically, NH(3) vapor and UV light were chosen. The electrical response of PPy nanotubes to two different kinds of analytes was strongly dependent on their diameters. Moreover, since the small dimensions of PPy nanotubes facilitated the interaction between nanotubes and analytes, the PPy nanotube sensors showed conspicuously enhanced responses compared with conventional PPy. PMID:16854102

  8. Mechanism of 2-oxoglutarate signaling by the Synechococcus elongatus PII signal transduction protein

    PubMed Central

    Fokina, Oleksandra; Chellamuthu, Vasuki-Ranjani; Forchhammer, Karl; Zeth, Kornelius

    2010-01-01

    PII proteins control key processes of nitrogen metabolism in bacteria, archaea, and plants in response to the central metabolites ATP, ADP, and 2-oxoglutarate (2-OG), signaling cellular energy and carbon and nitrogen abundance. This metabolic information is integrated by PII and transmitted to regulatory targets (key enzymes, transporters, and transcription factors), modulating their activity. In oxygenic phototrophs, the controlling enzyme of arginine synthesis, N-acetyl-glutamate kinase (NAGK), is a major PII target, whose activity responds to 2-OG via PII. Here we show structures of the Synechococcus elongatus PII protein in complex with ATP, Mg2+, and 2-OG, which clarify how 2-OG affects PII–NAGK interaction. PII trimers with all three sites fully occupied were obtained as well as structures with one or two 2-OG molecules per PII trimer. These structures identify the site of 2-OG located in the vicinity between the subunit clefts and the base of the T loop. The 2-OG is bound to a Mg2+ ion, which is coordinated by three phosphates of ATP, and by ionic interactions with the highly conserved residues K58 and Q39 together with B- and T-loop backbone interactions. These interactions impose a unique T-loop conformation that affects the interactions with the PII target. Structures of PII trimers with one or two bound 2-OG molecules reveal the basis for anticooperative 2-OG binding and shed light on the intersubunit signaling mechanism by which PII senses effectors in a wide range of concentrations. PMID:21041661

  9. Mechanism of 2-oxoglutarate signaling by the Synechococcus elongatus PII signal transduction protein.

    PubMed

    Fokina, Oleksandra; Chellamuthu, Vasuki-Ranjani; Forchhammer, Karl; Zeth, Kornelius

    2010-11-16

    P(II) proteins control key processes of nitrogen metabolism in bacteria, archaea, and plants in response to the central metabolites ATP, ADP, and 2-oxoglutarate (2-OG), signaling cellular energy and carbon and nitrogen abundance. This metabolic information is integrated by P(II) and transmitted to regulatory targets (key enzymes, transporters, and transcription factors), modulating their activity. In oxygenic phototrophs, the controlling enzyme of arginine synthesis, N-acetyl-glutamate kinase (NAGK), is a major P(II) target, whose activity responds to 2-OG via P(II). Here we show structures of the Synechococcus elongatus P(II) protein in complex with ATP, Mg(2+), and 2-OG, which clarify how 2-OG affects P(II)-NAGK interaction. P(II) trimers with all three sites fully occupied were obtained as well as structures with one or two 2-OG molecules per P(II) trimer. These structures identify the site of 2-OG located in the vicinity between the subunit clefts and the base of the T loop. The 2-OG is bound to a Mg(2+) ion, which is coordinated by three phosphates of ATP, and by ionic interactions with the highly conserved residues K58 and Q39 together with B- and T-loop backbone interactions. These interactions impose a unique T-loop conformation that affects the interactions with the P(II) target. Structures of P(II) trimers with one or two bound 2-OG molecules reveal the basis for anticooperative 2-OG binding and shed light on the intersubunit signaling mechanism by which P(II) senses effectors in a wide range of concentrations. PMID:21041661

  10. Receptor subtypes and signal transduction mechanisms contributing to the estrogenic attenuation of cannabinoid-induced changes in energy homeostasis.

    PubMed

    Washburn, Neal; Borgquist, Amanda; Wang, Kate; Jeffery, Garrett S; Kelly, Martin J; Wagner, Edward J

    2013-01-01

    We examined the receptor subtypes and signal transduction mechanisms contributing to the estrogenic modulation of cannabinoid-induced changes in energy balance. Food intake and, in some cases, O2 consumption, CO2 production and the respiratory exchange ratio were evaluated in ovariectomized female guinea pigs treated s.c. with the cannabinoid receptor agonist WIN 55,212-2 or its cremephor/ethanol/0.9% saline vehicle, and either with estradiol benzoate (EB), the estrogen receptor (ER) α agonist PPT, the ERβ agonist DPN, the Gq-coupled membrane ER agonist STX, the GPR30 agonist G-1 or their respective vehicles. Patch-clamp recordings were performed in hypothalamic slices. EB, STX, PPT and G-1 decreased daily food intake. Of these, EB, STX and PPT blocked the WIN 55,212-2-induced increase in food intake within 1-4 h. The estrogenic diminution of cannabinoid-induced hyperphagia correlated with a rapid (within 15 min) attenuation of cannabinoid-mediated decreases in glutamatergic synaptic input onto arcuate neurons, which was completely blocked by inhibition of protein kinase C (PKC) and attenuated by inhibition of protein kinase A (PKA). STX, but not PPT, mimicked this rapid estrogenic effect. However, PPT abolished the cannabinoid-induced inhibition of glutamatergic neurotransmission in cells from animals treated 24 h prior. The estrogenic antagonism of this presynaptic inhibition was observed in anorexigenic proopiomelanocortin neurons. These data reveal that estrogens negatively modulate cannabinoid-induced changes in energy balance via Gq-coupled membrane ER- and ERα-mediated mechanisms involving activation of PKC and PKA. As such, they further our understanding of the pathways through which estrogens act to temper cannabinoid sensitivity in regulating energy homeostasis in females. PMID:22538462

  11. The HDAC Inhibitor FK228 Enhances Adenoviral Transgene Expression by a Transduction-Independent Mechanism but Does Not Increase Adenovirus Replication

    PubMed Central

    Danielsson, Angelika; Dzojic, Helena; Rashkova, Victoria; Cheng, Wing-Shing; Essand, Magnus

    2011-01-01

    The histone deacetylase inhibitor FK228 has previously been shown to enhance adenoviral transgene expression when cells are pre-incubated with the drug. Upregulation of the coxsackie adenovirus receptor (CAR), leading to increased viral transduction, has been proposed as the main mechanism. In the present study, we found that the highest increase in transgene expression was achieved when non-toxic concentrations of FK228 were added immediately after transduction, demonstrating that the main effect by which FK228 enhances transgene expression is transduction-independent. FK228 had positive effects both on Ad5 and Ad5/f35 vectors with a variety of transgenes and promoters, indicating that FK228 works mainly by increasing transgene expression at the transcriptional level. In some cases, the effects were dramatic, as demonstrated by an increase in CD40L expression by FK228 from 0.3% to 62% when the murine prostate cancer cell line TRAMP-C2 was transduced with Ad[CD40L]. One unexpected finding was that FK228 decreased the transgene expression of an adenoviral vector with the prostate cell-specific PPT promoter in the human prostate adenocarcinoma cell lines LNCaP and PC-346C. This is probably a consequence of alteration of the adenocarcinoma cell lines towards a neuroendocrine differentiation after FK228 treatment. The observations in this study indicate that FK228 enhances adenoviral therapy by a transduction-independent mechanism. Furthermore, since histone deacetylase inhibitors may affect the differentiation of cells, it is important to keep in mind that the activity and specificity of tissue- and tumor-specific promoters may also be affected. PMID:21379379

  12. Sensory Transduction in Caenorhabditis elegans

    NASA Astrophysics Data System (ADS)

    Brown, Austin L.; Ramot, Daniel; Goodman, Miriam B.

    The roundworm Caenorhabditis elegans has a well-defined and comparatively simple repertoire of sensory-guided behaviors, all of which rely on its ability to detect chemical, mechanical or thermal stimuli. In this chapter, we review what is known about the ion channels that mediate sensation in this remarkable model organism. Genetic screens for mutants defective in sensory-guided behaviors have identified genes encoding channel proteins, which are likely transducers of chemical, thermal, and mechanical stimuli. Such classical genetic approaches are now being coupled with molecular genetics and in vivo cellular physiology to elucidate how these channels are activated in specific sensory neurons. The ion channel superfamilies implicated in sensory transduction in C. elegans - CNG, TRP, and DEG/ENaC - are conserved across phyla and also appear to contribute to sensory transduction in other organisms, including vertebrates. What we learn about the role of these ion channels in C. elegans sensation is likely to illuminate analogous processes in other animals, including humans.

  13. Inhibition of Intracellular Antiviral Defense Mechanisms Augments Lentiviral Transduction of Human Natural Killer Cells: Implications for Gene Therapy

    PubMed Central

    Sutlu, Tolga; Nyström, Sanna; Gilljam, Mari; Stellan, Birgitta; Applequist, Steven E.

    2012-01-01

    Abstract Adoptive immunotherapy with genetically modified natural killer (NK) cells is a promising approach for cancer treatment. Yet, optimization of highly efficient and clinically applicable gene transfer protocols for NK cells still presents a challenge. In this study, we aimed at identifying conditions under which optimum lentiviral gene transfer to NK cells can be achieved. Our results demonstrate that stimulation of NK cells with interleukin (IL)-2 and IL-21 supports efficient transduction using a VSV-G pseudotyped lentiviral vector. Moreover, we have identified that inhibition of innate immune receptor signaling greatly enhances transduction efficiency. We were able to boost the efficiency of lentiviral genetic modification on average 3.8-fold using BX795, an inhibitor of the TBK1/IKKɛ complex acting downstream of RIG-I, MDA-5, and TLR3. We have also observed that the use of BX795 enhances lentiviral transduction efficiency in a number of human and mouse cell lines, indicating a broadly applicable, practical, and safe approach that has the potential of being applicable to various gene therapy protocols. PMID:22779406

  14. Molecular basis of mechanosensory transduction

    NASA Astrophysics Data System (ADS)

    Gillespie, Peter G.; Walker, Richard G.

    2001-09-01

    Mechanotransduction - a cell's conversion of a mechanical stimulus into an electrical signal - reveals vital features of an organism's environment. From hair cells and skin mechanoreceptors in vertebrates, to bristle receptors in flies and touch receptors in worms, mechanically sensitive cells are essential in the life of an organism. The scarcity of these cells and the uniqueness of their transduction mechanisms have conspired to slow molecular characterization of the ensembles that carry out mechanotransduction. But recent progress in both invertebrates and vertebrates is beginning to reveal the identities of proteins essential for transduction.

  15. beta3-Adrenergic-dependent and -independent mechanisms participate in cold-induced modulation of insulin signal transduction in brown adipose tissue of rats.

    PubMed

    Gasparetti, Alessandra L; Alvarez-Rojas, Fernanda; de Araujo, Eliana P; Hirata, Aparecida E; Saad, Mário J A; Velloso, Lício A

    2005-03-01

    During cold exposure, homeothermic animals mobilize glucose with higher efficiency than at thermoneutrality. An interaction between the insulin signal transduction machinery and high sympathetic tonus is thought to play an important role in this phenomenon. In the present study, rats were exposed to cold during 8 days and treated, or not, with a beta3-adrenergic agonist, BRL37344 sodium 4-2-2-(3-chlorophenyl)-2-hydroxyethyl amino propyl phenoxy-acetic acid sodium (BRL37344), or antagonist, SR59230A 3-(2-ethylphenoxy)-[(1S)-1,2,3,4-tetrahydronaphth-1-ylamino]-(2S)-2-propanol oxalate (SR59230A), to evaluate the cross-talk between insulin and beta3-adrenergic intracellular signaling in brown adipose tissue. The drugs did not modify food ingestion, body temperature, and body weight in control and cold-exposed rats. Treatment of control rats with BRL37344 led to higher insulin-induced tyrosine phosphorylation of the insulin receptors, insulin receptor substrate (IRS)-1 and ERK, higher insulin-induced IRS-1/PI3-kinase association, and higher [Ser(473)] phosphorylation of Akt. Cold exposure alone promoted higher insulin-induced tyrosine phosphorylation of the insulin receptors, IRS-1, IRS-2, and ERK, and higher insulin-induced IRS-1 and IRS-2/PI3-kinase association. Except for the regulation of ERK, SR59230A abolished all the cold-induced effects upon the insulin signal transduction pathway. However, this antagonist only partially inhibited the cold-induced increase of glucose uptake. Thus, the sympathetic tonus generated during cold-exposure acts, in brown adipose tissue, through the beta3-adrenergic receptor and modulates insulin signal transduction, with the exception of ERK. However, insulin-independent mechanisms other than beta3-adrenergic activation participate in cold-induced glucose uptake in brown adipose tissue of rats. PMID:15750837

  16. Comparative physiology of renal tubular transport mechanisms.

    PubMed Central

    Long, S.; Giebisch, G.

    1979-01-01

    This manuscript discusses current concepts of glomerular filtration and tubular transport of sodium, water, potassium, and urinary acidification by vertebrate kidneys in a comparative context. Work in mammalian and amphibian nephrons receives major emphasis due to our interest in application of new techniques for investigation of cellular mechanisms; when available, data from other vertebrate classes are discussed. Images FIG. 3 PMID:395765

  17. Comment on 'Comparative analysis of the isovolume calibration method for non-invasive respiratory monitoring techniques based on area transduction versus circumference transduction using the connected cylinders model' (2011 Physiol. Meas. 32 1265-74).

    PubMed

    Augousti, A T; Radosz, A

    2015-05-01

    An analysis introduced by the authors in 2011 examining the robustness of the isovolume method for the calibration of the respiratory inductive plethysmograph based on the connected cylinders particular model of Konno and Mead's generalized two-compartment model of respiration is extended. It is demonstrated that extending this to a more physically realistic geometrical model, termed the connected prismatic elliptical segments model, does not enhance the earlier analysis, and that the analysis can easily be proven to cover all area-based transduction sensors, irrespective of the actual geometry of the compartments. PMID:25903299

  18. Comparative studies of gene regulatory mechanisms.

    PubMed

    Pai, Athma A; Gilad, Yoav

    2014-12-01

    It has become increasingly clear that changes in gene regulation have played an important role in adaptive evolution both between and within species. Over the past five years, comparative studies have moved beyond simple characterizations of differences in gene expression levels within and between species to studying variation in regulatory mechanisms. We still know relatively little about the precise chain of events that lead to most regulatory adaptations, but we have taken significant steps towards understanding the relative importance of changes in different mechanisms of gene regulatory evolution. In this review, we first discuss insights from comparative studies in model organisms, where the available experimental toolkit is extensive. We then focus on a few recent comparative studies in primates, where the limited feasibility of experimental manipulation dictates the approaches that can be used to study gene regulatory evolution. PMID:25215415

  19. Quantitative phosphoproteomics of murine Fmr1-KO cell lines provides new insights into FMRP-dependent signal transduction mechanisms.

    PubMed

    Matic, Katarina; Eninger, Timo; Bardoni, Barbara; Davidovic, Laetitia; Macek, Boris

    2014-10-01

    Fragile X mental retardation protein (FMRP) is an RNA-binding protein that has a major effect on neuronal protein synthesis. Transcriptional silencing of the FMR1 gene leads to loss of FMRP and development of Fragile X syndrome (FXS), the most common known hereditary cause of intellectual impairment and autism. Here we utilize SILAC-based quantitative phosphoproteomics to analyze murine FMR1(-) and FMR1(+) fibroblastic cell lines derived from FMR1-KO embryos to identify proteins and phosphorylation sites dysregulated as a consequence of FMRP loss. We quantify FMRP-related changes in the levels of 5,023 proteins and 6,133 phosphorylation events and map them onto major signal transduction pathways. Our study confirms global downregulation of the MAPK/ERK pathway and decrease in phosphorylation level of ERK1/2 in the absence of FMRP, which is connected to attenuation of long-term potentiation. We detect differential expression of several key proteins from the p53 pathway, pointing to the involvement of p53 signaling in dysregulated cell cycle control in FXS. Finally, we detect differential expression and phosphorylation of proteins involved in pre-mRNA processing and nuclear transport, as well as Wnt and calcium signaling, such as PLC, PKC, NFAT, and cPLA2. We postulate that calcium homeostasis is likely affected in molecular pathogenesis of FXS. PMID:25168779

  20. Regulation of epidermal-growth-factor-receptor signal transduction by cis-unsaturated fatty acids. Evidence for a protein kinase C-independent mechanism.

    PubMed Central

    Casabiell, X; Pandiella, A; Casanueva, F F

    1991-01-01

    The effect of acute treatment with non-esterified fatty acids (NEFA) on transmembrane signalling has been investigated in three different cell lines. In EGFR T17 cells, pretreatment with cis-unsaturated (oleic and palmitoleic acids) NEFA, but not with saturated or trans-unsaturated NEFA, inhibited the epidermal-growth-factor (EGF)-induced increases in cytosolic [Ca2+], membrane potential and Ins(1,4,5)P3 generation. The blocking effect was found to be time- and dose-dependent and rapidly reversible after washout. However, oleic acid treatment did not block either binding of 125I-EGF to its receptor or EGF-induced autophosphorylation of the EGF receptor. The mechanism of action of NEFA could not be attributed to protein kinase C activation, since (i) down-regulation of the enzyme by long-term treatment with phorbol esters did not prevent blockade by oleic acid, and (ii) the effects of acutely administered phorbol ester and oleic acid were additive. In this cell line, signalling at bradykinin and bombesin receptors was also impaired by oleic acid. In A431 cells, oleic acid also blocked signal transduction at the EGF and B2 bradykinin receptors. Finally, in PC12 cells, oleic acid blocked the Ca2+ influx mediated by the activation of B2 bradykinin receptors. In conclusion: (1) NEFA block signal transduction by interfering with receptor-phospholipase C or phospholipase C-substrate interaction without preventing ligand binding; (2) NEFA do not act by a protein kinase C-mediated mechanism; (3) the effect of NEFA is dependent on their configuration rather than hydrophobicity or chain length; (4) this effect is evident in several different cell lines and receptor systems. Images Fig. 4. PMID:1898356

  1. Erythropoietin suppresses epithelial to mesenchymal transition and intercepts Smad signal transduction through a MEK-dependent mechanism in pig kidney (LLC-PK1) cell lines

    SciTech Connect

    Chen, Chien-Liang; Chou, Kang-Ju; Lee, Po-Tsang; Chen, Ying-Shou; Chang, Tsu-Yuan; Hsu, Chih-Yang; Huang, Wei-Chieh; Chung, Hsiao-Min; Fang, Hua-Chang

    2010-04-15

    Purpose: Tumor growth factor-{beta}1 (TGF-{beta}1) plays a pivotal role in processes like kidney epithelial-mesenchymal transition (EMT) and interstitial fibrosis, which correlate well with progression of renal disease. Little is known about underlying mechanisms that regulate EMT. Based on the anatomical relationship between erythropoietin (EPO)-producing interstitial fibroblasts and adjacent tubular cells, we investigated the role of EPO in TGF-{beta}1-mediated EMT and fibrosis in kidney injury. Methods: We examined apoptosis and EMT in TGF-{beta}1-treated LLC-PK1 cells in the presence or absence of EPO. We examined the effect of EPO on TGF-{beta}1-mediated Smad signaling. Apoptosis and cell proliferation were assessed with flow cytometry and hemocytometry. We used Western blotting and indirect immunofluorescence to evaluate expression levels of TGF-{beta}1 signal pathway proteins and EMT markers. Results: We demonstrated that ZVAD-FMK (a caspase inhibitor) inhibited TGF-{beta}1-induced apoptosis but did not inhibit EMT. In contrast, EPO reversed TGF-{beta}1-mediated apoptosis and also partially inhibited TGF-{beta}1-mediated EMT. We showed that EPO treatment suppressed TGF-{beta}1-mediated signaling by inhibiting the phosphorylation and nuclear translocation of Smad 3. Inhibition of mitogen-activated protein kinase kinase 1 (MEK 1) either directly with PD98059 or with MEK 1 siRNA resulted in inhibition of EPO-mediated suppression of EMT and Smad signal transduction in TGF-{beta}1-treated cells. Conclusions: EPO inhibited apoptosis and EMT in TGF-{beta}1-treated LLC-PK1 cells. This effect of EPO was partially mediated by a mitogen-activated protein kinase-dependent inhibition of Smad signal transduction.

  2. Comparing fluid mechanics models with experimental data.

    PubMed Central

    Spedding, G R

    2003-01-01

    The art of modelling the physical world lies in the appropriate simplification and abstraction of the complete problem. In fluid mechanics, the Navier-Stokes equations provide a model that is valid under most circumstances germane to animal locomotion, but the complexity of solutions provides strong incentive for the development of further, more simplified practical models. When the flow organizes itself so that all shearing motions are collected into localized patches, then various mathematical vortex models have been very successful in predicting and furthering the physical understanding of many flows, particularly in aerodynamics. Experimental models have the significant added convenience that the fluid mechanics can be generated by a real fluid, not a model, provided the appropriate dimensionless groups have similar values. Then, analogous problems can be encountered in making intelligible but independent descriptions of the experimental results. Finally, model predictions and experimental results may be compared if, and only if, numerical estimates of the likely variations in the tested quantities are provided. Examples from recent experimental measurements of wakes behind a fixed wing and behind a bird in free flight are used to illustrate these principles. PMID:14561348

  3. SENTRA, a database of signal transduction proteins.

    SciTech Connect

    D'Souza, M.; Romine, M. F.; Maltsev, N.; Mathematics and Computer Science; PNNL

    2000-01-01

    SENTRA, available via URL http://wit.mcs.anl.gov/WIT2/Sentra/, is a database of proteins associated with microbial signal transduction. The database currently includes the classical two-component signal transduction pathway proteins and methyl-accepting chemotaxis proteins, but will be expanded to also include other classes of signal transduction systems that are modulated by phosphorylation or methylation reactions. Although the majority of database entries are from prokaryotic systems, eukaroytic proteins with bacterial-like signal transduction domains are also included. Currently SENTRA contains signal transduction proteins in 34 complete and almost completely sequenced prokaryotic genomes, as well as sequences from 243 organisms available in public databases (SWISS-PROT and EMBL). The analysis was carried out within the framework of the WIT2 system, which is designed and implemented to support genetic sequence analysis and comparative analysis of sequenced genomes.

  4. Tetrodotoxin as a tool to elucidate sensory transduction mechanisms: the case for the arterial chemoreceptors of the carotid body.

    PubMed

    Rocher, Asuncion; Caceres, Ana Isabel; Obeso, Ana; Gonzalez, Constancio

    2011-12-01

    Carotid bodies (CBs) are secondary sensory receptors in which the sensing elements, chemoreceptor cells, are activated by decreases in arterial PO(2) (hypoxic hypoxia). Upon activation, chemoreceptor cells (also known as Type I and glomus cells) increase their rate of release of neurotransmitters that drive the sensory activity in the carotid sinus nerve (CSN) which ends in the brain stem where reflex responses are coordinated. When challenged with hypoxic hypoxia, the physiopathologically most relevant stimulus to the CBs, they are activated and initiate ventilatory and cardiocirculatory reflexes. Reflex increase in minute volume ventilation promotes CO(2) removal from alveoli and a decrease in alveolar PCO(2) ensues. Reduced alveolar PCO(2) makes possible alveolar and arterial PO(2) to increase minimizing the intensity of hypoxia. The ventilatory effect, in conjunction the cardiocirculatory components of the CB chemoreflex, tend to maintain an adequate supply of oxygen to the tissues. The CB has been the focus of attention since the discovery of its nature as a sensory organ by de Castro (1928) and the discovery of its function as the origin of ventilatory reflexes by Heymans' group (1930). A great deal of effort has been focused on the study of the mechanisms involved in O(2) detection. This review is devoted to this topic, mechanisms of oxygen sensing. Starting from a summary of the main theories evolving through the years, we will emphasize the nature and significance of the findings obtained with veratridine and tetrodotoxin (TTX) in the genesis of current models of O(2)-sensing. PMID:22363245

  5. Tetrodotoxin as a Tool to Elucidate Sensory Transduction Mechanisms: The Case for the Arterial Chemoreceptors of the Carotid Body

    PubMed Central

    Rocher, Asuncion; Caceres, Ana Isabel; Obeso, Ana; Gonzalez, Constancio

    2011-01-01

    Carotid bodies (CBs) are secondary sensory receptors in which the sensing elements, chemoreceptor cells, are activated by decreases in arterial PO2 (hypoxic hypoxia). Upon activation, chemoreceptor cells (also known as Type I and glomus cells) increase their rate of release of neurotransmitters that drive the sensory activity in the carotid sinus nerve (CSN) which ends in the brain stem where reflex responses are coordinated. When challenged with hypoxic hypoxia, the physiopathologically most relevant stimulus to the CBs, they are activated and initiate ventilatory and cardiocirculatory reflexes. Reflex increase in minute volume ventilation promotes CO2 removal from alveoli and a decrease in alveolar PCO2 ensues. Reduced alveolar PCO2 makes possible alveolar and arterial PO2 to increase minimizing the intensity of hypoxia. The ventilatory effect, in conjunction the cardiocirculatory components of the CB chemoreflex, tend to maintain an adequate supply of oxygen to the tissues. The CB has been the focus of attention since the discovery of its nature as a sensory organ by de Castro (1928) and the discovery of its function as the origin of ventilatory reflexes by Heymans group (1930). A great deal of effort has been focused on the study of the mechanisms involved in O2 detection. This review is devoted to this topic, mechanisms of oxygen sensing. Starting from a summary of the main theories evolving through the years, we will emphasize the nature and significance of the findings obtained with veratridine and tetrodotoxin (TTX) in the genesis of current models of O2-sensing. PMID:22363245

  6. Second messenger/signal transduction pathways in major mood disorders: moving from membrane to mechanism of action, part I: major depressive disorder

    PubMed Central

    Niciu, Mark J.; Ionescu, Dawn F.; Mathews, Daniel C.; Richards, Erica M.; Zarate, Carlos A.

    2016-01-01

    The etiopathogenesis and treatment of major mood disorders have historically focused on modulation of monoaminergic (serotonin, norepinephrine, dopamine) and amino acid [γ-aminobutyric acid (GABA), glutamate] receptors at the plasma membrane. Although the activation and inhibition of these receptors acutely alter local neurotransmitter levels, their neuropsychiatric effects are not immediately observed. This time lag implicates intracellular neuroplasticity as primary in the mechanism of action of antidepressants and mood stabilizers. The modulation of intracellular second messenger/signal transduction cascades affects neurotrophic pathways that are both necessary and sufficient for monoaminergic and amino acid–based treatments. In this review, we will discuss the evidence in support of intracellular mediators in the pathophysiology and treatment of preclinical models of despair and major depressive disorder (MDD). More specifically, we will focus on the following pathways: cAMP/PKA/CREB, neurotrophin-mediated (MAPK and others), p11, Wnt/Fz/Dvl/GSK3β, and NFκB/ΔFosB. We will also discuss recent discoveries with rapidly acting antidepressants, which activate the mammalian target of rapamycin (mTOR) and release of inhibition on local translation via elongation factor stimulation. Throughout this discourse, we will highlight potential intracellular targets for therapeutic intervention. Finally, future clinical implications are discussed. PMID:23462230

  7. Pheromone Transduction in Moths

    PubMed Central

    Stengl, Monika

    2010-01-01

    Calling female moths attract their mates late at night with intermittent release of a species-specific sex-pheromone blend. Mean frequency of pheromone filaments encodes distance to the calling female. In their zig-zagging upwind search male moths encounter turbulent pheromone blend filaments at highly variable concentrations and frequencies. The male moth antennae are delicately designed to detect and distinguish even traces of these sex pheromones amongst the abundance of other odors. Its olfactory receptor neurons sense even single pheromone molecules and track intermittent pheromone filaments of highly variable frequencies up to about 30 Hz over a wide concentration range. In the hawkmoth Manduca sexta brief, weak pheromone stimuli as encountered during flight are detected via a metabotropic PLCβ-dependent signal transduction cascade which leads to transient changes in intracellular Ca2+ concentrations. Strong or long pheromone stimuli, which are possibly perceived in direct contact with the female, activate receptor-guanylyl cyclases causing long-term adaptation. In addition, depending on endogenous rhythms of the moth's physiological state, hormones such as the stress hormone octopamine modulate second messenger levels in sensory neurons. High octopamine levels during the activity phase maximize temporal resolution cAMP-dependently as a prerequisite to mate location. Thus, I suggest that sliding adjustment of odor response threshold and kinetics is based upon relative concentration ratios of intracellular Ca2+ and cyclic nucleotide levels which gate different ion channels synergistically. In addition, I propose a new hypothesis for the cyclic nucleotide-dependent ion channel formed by insect olfactory receptor/coreceptor complexes. Instead of being employed for an ionotropic mechanism of odor detection it is proposed to control subthreshold membrane potential oscillation of sensory neurons, as a basis for temporal encoding of odors. PMID:21228914

  8. Pathway to the piezoelectronic transduction logic device.

    PubMed

    Solomon, P M; Bryce, B A; Kuroda, M A; Keech, R; Shetty, S; Shaw, T M; Copel, M; Hung, L-W; Schrott, A G; Armstrong, C; Gordon, M S; Reuter, K B; Theis, T N; Haensch, W; Rossnagel, S M; Miyazoe, H; Elmegreen, B G; Liu, X-H; Trolier-McKinstry, S; Martyna, G J; Newns, D M

    2015-04-01

    The piezoelectronic transistor (PET) has been proposed as a transduction device not subject to the voltage limits of field-effect transistors. The PET transduces voltage to stress, activating a facile insulator-metal transition, thereby achieving multigigahertz switching speeds, as predicted by modeling, at lower power than the comparable generation field effect transistor (FET). Here, the fabrication and measurement of the first physical PET devices are reported, showing both on/off switching and cycling. The results demonstrate the realization of a stress-based transduction principle, representing the early steps on a developmental pathway to PET technology with potential to contribute to the IT industry. PMID:25793915

  9. Protein Regulation in Signal Transduction.

    PubMed

    Lee, Michael J; Yaffe, Michael B

    2016-01-01

    SUMMARYCells must respond to a diverse, complex, and ever-changing mix of signals, using a fairly limited set of parts. Changes in protein level, protein localization, protein activity, and protein-protein interactions are critical aspects of signal transduction, allowing cells to respond highly specifically to a nearly limitless set of cues and also to vary the sensitivity, duration, and dynamics of the response. Signal-dependent changes in levels of gene expression and protein synthesis play an important role in regulation of protein levels, whereas posttranslational modifications of proteins regulate their degradation, localization, and functional interactions. Protein ubiquitylation, for example, can direct proteins to the proteasome for degradation or provide a signal that regulates their interactions and/or location within the cell. Similarly, protein phosphorylation by specific kinases is a key mechanism for augmenting protein activity and relaying signals to other proteins that possess domains that recognize the phosphorylated residues. PMID:27252361

  10. Signal Transduction of Fertilization in Frog Eggs and Anti-Apoptotic Mechanism in Human Cancer Cells: Common and Specific Functions of Membrane Microdomains

    PubMed Central

    Sato, Ken-Ichi

    2008-01-01

    Membrane microdomains or lipid/membrane rafts are distinct areas on the plasma membranes, where a specific subset of lipids (e.g. cholesterol, sphingolipids) and proteins (e.g. glycosylphosphatidylinositol-anchored proteins, growth factor receptor/kinases) are getting together and functioning for several aspects of cellular functions. Our recent investigation has revealed that fertilization of African clawed frog, Xenopus laevis, requires cholesterol-dependent nature of egg membrane microdomains. Moreover, fertilization of Xenopus eggs involves proteolytic cleavage of the extracellular part and subsequent phosphorylation of a cytoplasmic tyrosine residue of uroplakin III, an egg membrane microdomain-associated protein. Protease activity toward uroplakin III seems to be derived from fertilizing sperm, while phosphorylation of uroplakin III seems to be catalyzed by the egg tyrosine kinase Src, whose activation is required for cytoplasmic rearrangement of fertilized eggs; so-called ‘egg activation’. Therefore, it is assumed that uroplakin III serves an integral part of signal transduction in fertilization of Xenopus. Our more recent study on human cancer cells has revealed that a similar but distinct scheme of signal transduction operates in anti-apoptotic growth of cells. Namely, in human bladder carcinoma cells, cooperation of uroplakin III and Src, both of which localize to the membrane microdomains, allows cells to escape from apoptotic cell death and proliferate under culture conditions deprived of serum. In this review, I briefly introduce about biology of fertilization and cancer, and then present and discuss our experimental data on general importance and specific features of membrane microdomains in Xenopus fertilization and anti-apoptosis in human bladder carcinoma cells. PMID:18949075

  11. Investigation of the Mechanoelectrical Transduction at Single Stereocilia by Afm

    NASA Astrophysics Data System (ADS)

    Langer, M. G.; Fink, S.; Löffler, K.; Koitschev, A.; Zenner, H.-P.

    2003-02-01

    The transduction of sound into an electrical signal in the inner ear is closely related to the mechanical properties of the hair bundles cytoskeleton and cross-linkage. In this study the effect of lateral cross-links on hair bundle mechanics and the transduction current response is demonstrated on the level of individual stereocilia. For experiments stereocilia of outer hair cells of postnatal rats (P3 - P8) were scanned with a sharp AFM tip at nanometerscale. Transduction currents were simultaneously recorded in the whole-cell-recording mode with patch clamp. AFM was used as a nanotool for local mechanical stimulation and force measurement at stereocilia whereas patch clamp serves as a detector for the electrical response of the cell. In a first experiment force transmission between adjacent stereocilia of the V- and W- shaped hair bundles of outer hair cells was investigated. Results showed that a force exerted to a single stereocilium declined to 36 % at the nearest adjacent stereocilium of the same row. This result supposes AFM to be convenient for local displacement of single stereocilia. For control, the local response of transduction channels was measured at single stereocilia of the same hair bundle. Measured transduction current amplitudes ranged from 9 to 49 pA supposing an opening of one to five transduction channels. Both, weak force transmission by lateral cross-links and small transduction current amplitudes indicate a weak mechanical interaction between individual stereocilia of the tallest row of stereocilia of outer hair cells from postnatal rats.

  12. Separate TRP channels mediate amplification and transduction in drosophila

    NASA Astrophysics Data System (ADS)

    Lehnert, Brendan P.; Baker, Allison E.; Wilson, Rachel I.

    2015-12-01

    Auditory receptor cells rely on mechanically-gated channels to transform sound stimuli into neural activity. Several TRP channels have been implicated in Drosophila auditory transduction, but mechanistic studies have been hampered by the inability to record subthreshold signals from receptor neurons. We developed a non-invasive method for measuring these signals by recording from a central neuron that is electrically coupled to a genetically-defined population of auditory receptors. We find that the TRPN family member NompC, which is necessary for the active amplification of motion by the auditory organ, is not required for transduction. Instead, NompC sensitizes the transduction complex to movement and precisely regulates the static forces on the complex. In contrast, the TRPV channels Nanchung and Inactive are required for responses to sound, suggesting they are components of the transduction complex. Thus, transduction and active amplification are genetically separable processes in Drosophila hearing.

  13. Peptide-mediated interference with baculovirus transduction.

    PubMed

    Mäkelä, Anna R; Närvänen, Ale; Oker-Blom, Christian

    2008-03-20

    Baculovirus represents a multifunctional platform with potential for biomedical applications including disease therapies. The importance of F3, a tumor-homing peptide, in baculovirus transduction was previously recognized by the ability of F3 to augment viral binding and gene delivery to human cancer cells following display on the viral envelope. Here, F3 was utilized as a molecular tool to expand understanding of the poorly characterized baculovirus-mammalian cell interactions. Baculovirus-mediated transduction of HepG2 hepatocarcinoma cells was strongly inhibited by coincubating the virus with synthetic F3 or following incorporation of F3 into viral nucleocapsid by genetic engineering, the former suggesting direct interaction of the soluble peptide with the virus particles. Since internalization and nuclear accumulation of the virus were significantly inhibited or delayed, but the kinetics of viral binding, initial uptake, and endosomal release were unaffected, F3 likely interferes with cytoplasmic trafficking and subsequent nuclear transport of the virus. A polyclonal antibody raised against nucleolin, the internalizing receptor of F3, failed to inhibit cellular binding, but considerably reduced viral transduction efficiency, proposing the involvement of nucleolin in baculovirus entry. Together, these results render the F3 peptide a tool for elucidating the mechanism and molecular details conferring to baculovirus-mediated gene transduction in mammalian cells. PMID:18294718

  14. Mechanoelectric transduction in ionic polymer-metal composite

    NASA Astrophysics Data System (ADS)

    Tiwari, Rashi; Kim, Kwang J.

    2013-03-01

    The ability of ionic polymer-metal composite (IPMC) to generate current on mechanical deformation, defined as mechanoelectric transduction, can be exploited for design and development of numerous sensors and energy harvesters. However, sensor application of IPMC is currently limited due to the lack of understanding of the transduction mechanism. This paper presents a physics-based mechanoelectric model that takes into account material properties, electrostatic phenomenon, and ion transport in the IPMC. Experimental verification of the model predictions is also reported.

  15. Advances in Targeting Signal Transduction Pathways

    PubMed Central

    McCubrey, James A.; Steelman, Linda S.; Chappell, William H.; Sun, Lin; Davis, Nicole M.; Abrams, Stephen L.; Franklin, Richard A.; Cocco, Lucio; Evangelisti, Camilla; Chiarini, Francesca; Martelli, Alberto M.; Libra, Massimo; Candido, Saverio; Ligresti, Giovanni; Malaponte, Grazia; Mazzarino, Maria C.; Fagone, Paolo; Donia, Marco; Nicoletti, Ferdinando; Polesel, Jerry; Talamini, Renato; Bäsecke, Jörg; Mijatovic, Sanja; Maksimovic-Ivanic, Danijela; Milella, Michele; Tafuri, Agostino; Dulińska-Litewka, Joanna; Laidler, Piotr; D'Assoro, Antonio B.; Drobot, Lyudmyla; Umezawa, Kazuo; Montalto, Giuseppe; Cervello, Melchiorre; Demidenko, Zoya N.

    2012-01-01

    Over the past few years, significant advances have occurred in both our understanding of the complexity of signal transduction pathways as well as the isolation of specific inhibitors which target key components in those pathways. Furthermore critical information is being accrued regarding how genetic mutations can affect the sensitivity of various types of patients to targeted therapy. Finally, genetic mechanisms responsible for the development of resistance after targeted therapy are being discovered which may allow the creation of alternative therapies to overcome resistance. This review will discuss some of the highlights over the past few years on the roles of key signaling pathways in various diseases, the targeting of signal transduction pathways and the genetic mechanisms governing sensitivity and resistance to targeted therapies. PMID:23455493

  16. Mechanisms Underlying Language Acquisition: Benefits from a Comparative Approach

    ERIC Educational Resources Information Center

    Weiss, Daniel J.; Newport, Elissa L.

    2006-01-01

    One of the longstanding issues in language research has been the extent to which the mechanisms underlying language acquisition are uniquely human. The primary goal of this article is to introduce the reader to some of the recent developments in comparative language research that have shed new light on this issue. To appreciate the significance of…

  17. Generalized Transduction in CAULOBACTER CRESCENTUS

    PubMed Central

    Ely, Bert; Johnson, Reid C.

    1977-01-01

    Two closely related bacteriophage, ϕCr30 and ϕCr35, are the first bacteriophage shown to mediate generalized transduction in Caulobacter crescentus. Unlike most other transducing phage, they are virulent and do not form any sort of lysogenic relationship with their host. However, they are rather inefficient at adsorption, so that transductants have a good chance of survival. The phage particles have a head 80 nm in diameter and a contractile tail 140 nm in length. Procedures for growth and transduction with ϕCr30 are relatively simple; thus, it will be of great value for the genetic analysis of C. crescentus. PMID:17248770

  18. Comparing Chemical Mechanisms using Tagged Ozone Production Potentials

    NASA Astrophysics Data System (ADS)

    Coates, J.; Butler, T. M.

    2013-12-01

    Tropospheric ozone (O3) is a short-lived climate forcing pollutant that is detrimental to human health and crop growth. It is produced by reactions of volatile organic compounds (VOCs) and nitrogen oxides (NOx) in the presence of sunlight [Atkinson,2000]. The chemistry of intermediate species formed during VOC degradation show a time dependence and impacts the amount of O3 produced by the VOC [Butler et al., 2011]. Representing the intricacies of these reactions is not viable for chemical mechanisms used in global and regional models due to the computational resources available. Thus, chemical mechanisms reduce the amount of reactions either by lumping chemical species together as a model species, reducing the number of reaction pathways or both. As different chemical mechanisms use varying reduction techniques and assumptions especially with respect to the intermediate degradation species, it is important to compare the temporal evolution of ozone production obtained from differing chemical mechanisms. In this study, chemical mechanisms are compared using Tagged Ozone Production Potentials (TOPP) [Butler et al.,2011]. TOPPs measure the effect of a VOC on the odd oxygen family (Ox), which includes O3, nitrogen dioxide (NO2) and other species whose cycling effect O3 and NO2 production. TOPP values are obtained via a boxmodel run lasting seven diurnal cycles and tagging all species produced during VOC degradation; this enables the Ox production to be attributed to the VOC. This technique enables the temporal evolution of a VOCs' Ox production to be compared between the mechanisms. Comparing the TOPP profiles of the VOCs obtained using different mechanisms shows the effect of reduction techniques implemented by the mechanism and also allows a comparison of the tropospheric chemistry represented in the mechanisms. [Atkinson,2000] Atkinson, R. (2000). Atmospheric chemistry of VOCs and NOx. Atmospheric Environment, 34:2063-2101 [Butler et al., 2011] Butler, T. M

  19. RCY1, an Arabidopsis thaliana RPP8/HRT family resistance gene, conferring resistance to cucumber mosaic virus requires salicylic acid, ethylene and a novel signal transduction mechanism.

    PubMed

    Takahashi, Hideki; Miller, Jennifer; Nozaki, Yukine; Takeda, Megumi; Shah, Jyoti; Hase, Shu; Ikegami, Masato; Ehara, Yoshio; Dinesh-Kumar, S P

    2002-12-01

    The dominant locus, RCY1, in the Arabidopsis thaliana ecotype C24 confers resistance to the yellow strain of cucumber mosaic virus (CMV-Y). The RCY1 locus was mapped to a 150-kb region on chromosome 5. Sequence comparison of this region from C24 and a CMV-Y-susceptible C24 mutant predicts that the RCY1 gene encodes a 104-kDa CC-NBS-LRR-type protein. The RCY1 gene from C24, when expressed in the susceptible ecotype Wassilewskija (Ws), restricted the systemic spread of virus. RCY1 is allelic to the resistance genes RPP8 from the ecotype Landsberg erecta and HRT from the ecotype Dijon-17, which confer resistance to Peronospora parasitica biotype Emco5 and turnip crinkle virus (TCV), respectively. Examination of RCY1 plants defective in salicylic acid (SA), jasmonic acid (JA) and ethylene signaling revealed a requirement for SA and ethylene signaling in mounting a resistance response to CMV-Y. The RCY1 nahG etr1 double mutants exhibited an intermediate level of susceptibility to CMV-Y, compared to the resistant ecotype C24 and the susceptible ecotypes Columbia and Nossen. This suggests that in addition to SA and ethylene, a novel signaling mechanism is associated with the induction of resistance in CMV-Y-infected C24 plants. Moreover, our results suggest that the signaling pathways downstream of the RPP8, HRT, and RCY1 have evolved independently. PMID:12472683

  20. Mechanical Properties Comparing Composite Fiber Length to Amalgam

    PubMed Central

    Petersen, Richard C.; Liu, Perng-Ru

    2016-01-01

    Photocure fiber-reinforced composites (FRCs) with varying chopped quartz-fiber lengths were incorporated into a dental photocure zirconia-silicate particulate-filled composite (PFC) for mechanical test comparisons with a popular commercial spherical-particle amalgam. FRC lengths included 0.5-mm, 1.0 mm, 2.0 mm, and 3.0 mm all at a constant 28.2 volume percent. Four-point fully articulated fixtures were used according to American Standards Test Methods with sample dimensions of 2×2×50 mm3 across a 40 mm span to provide sufficient Euler flexural bending and prevent top-load compressive shear error. Mechanical properties for flexural strength, modulus, yield strength, resilience, work of fracture, critical strain energy release, critical stress intensity factor, and strain were obtained for comparison. Fiber length subsequently correlated with increasing all mechanical properties, p < 1.1×10−5. Although the modulus was significantly statistically higher for amalgam than all composites, all FRCs and even the PFC had higher values than amalgam for all other mechanical properties. Because amalgams provide increased longevity during clinical use compared to the standard PFCs, modulus would appear to be a mechanical property that might sufficiently reduce margin interlaminar shear stress and strain-related microcracking that could reduce failure rates. Also, since FRCs were tested with all mechanical properties that statistically significantly increased over the PFC, new avenues for future development could be provided toward surpassing amalgam in clinical longevity.

  1. Gravitational Effects on Signal Transduction

    NASA Technical Reports Server (NTRS)

    Sytkowski, Arthur J.

    1999-01-01

    An understanding of the mechanisms by which individual cells perceive gravity and how these cells transduce and respond to gravitational stimuli is critical for the development of long-term manned space flight experiments. We now propose to use a well-characterized model erythroid cell system and to investigate gravitational perturbations of its erythropoietin (Epo) signaling pathway and gene regulation. Cells will be grown at 1-G and in simulated microgravity in the NASA Rotating Wall Vessel bioreactor (RWV). Cell growth and differentiation, the Epo-receptor, the protein kinase C pathway to the c-myc gene, and the protein phosphatase pathway to the c-myb gene will be studied and evaluated as reporters of gravitational stimuli. The results of these experiments will have impact on the problems of 1) gravitational sensing by individual cells, and 2) the anemia of space flight. This ground-based study also will serve as a Space Station Development Study in gravitational effects on intracellular signal transduction.

  2. Nuclear Technology. Course 27: Metrology. Module 27-3, Gage Blocks, Mechanical Comparators and Electronic Comparators.

    ERIC Educational Resources Information Center

    Selleck, Ben; Espy, John

    This third in a series of eight modules for a course titled Metrology describes gage blocks and mechanical and electronic comparators. The module follows a typical format that includes the following sections: (1) introduction, (2) module prerequisites, (3) objectives, (4) notes to instructor/student, (5) subject matter, (6) materials needed, (7)…

  3. Confocal Scanner for Highly Sensitive Photonic Transduction of Nanomechanical Resonators

    NASA Astrophysics Data System (ADS)

    Diao, Zhu; Losby, Joseph E.; Sauer, Vincent T. K.; Westwood, Jocelyn N.; Freeman, Mark R.; Hiebert, Wayne K.

    2013-06-01

    We show that a simple confocal laser scanning system can be used to couple light through grating couplers into nanophotonic circuits. The coupling efficiency is better than 15% per coupler. Our technique avoids using multi-axis fibre stages and is especially advantageous when the nanophotonic circuit is kept in vacuum, e.g., for nanomechanical resonator displacement transduction. This was demonstrated by recording the resonant response of a nanomechanical doubly clamped beam embedded in a race-track optical cavity. The nanophotonic transduction offers an increase of two orders of magnitude in transduction responsivity compared with conventional free-space optical interferometry.

  4. Graviperception in ciliates: steps in the transduction chain

    NASA Astrophysics Data System (ADS)

    Hemmersbach, R.; Krause, M.; Bräucker, R.; Ivanova, K.

    Due to their clear gravity-induced behavioural responses (gravitaxis and gravikinesis) ciliates represent suitable model systems to study the mechanisms of gravity perception and signal transduction. While the development of distinct gravisensory organelles is the exception in ciliates (e.g. mueller organelles in Loxodes), a common strategy seems to be that the whole cytoplasm acts as statolith stimulating mechanosensitive ion channels in the cell membrane. In order to test this hypothesis, electrophysiological studies were performed, revealing the proposed changes (de- or hyperpolarizations) depending on the cell's (Stylonychia mytilus) spatial orientation. In order to test the involvement of second messengers in the gravity-signal transduction-chain, cAMP levels of Paramecium were measured under altered gravitational stimulation (TEXUS 37; centrifuge). We found a decrease in cAMP in microgravity and an increase in hypergravity (5 x g) compared to the 1 x g controls. Furthermore, the behaviour of Paramecium and Stylonychia was analyzed during the variable acceleration conditions of parabolic flights (5th German Parabolic Flight Campaign) and compared to data already known from TEXUS, MAXUS, and drop facilities (ZARM, JAMIC). The feasibility of parabolic flights with respect to threshold determination will be discussed.

  5. Comparing Ultrasound and Mechanical Steering in a Biodiesel Production Process

    NASA Astrophysics Data System (ADS)

    Costa-Felix, Rodrigo P. B.; Ferreira, Jerusa R. L.

    The analysis of the kinetics of the transesterification reaction is crucial to compare different routes or routes with different catalysts or reaction accelerators. The use of ultrasound is considereda method for accelerating the biodiesel production. However, little effort has been done and is reported in the literature about how and under what conditions the use of ultrasound really speeds up the process, or the conditions under which its use is unnecessary or even harmful, burdening the process. Two dissimilar energy injections into a typical route were tested: ultrasound (@ 1 MHz and no heating) and mechanical steering (with heating), both applied in an 8:1 ratio of soybean oil and methanol, adding 1% of KOH as catalyzer. As results, during the first 10 minutes of reaction ultrasound showed unbearable effect on the transesterification, whilst mechanical steering and heating achieved almost 70% of conversion ratio. However, during the following 10 minutes, the mechanical steering and heating got nothing more than 80% of conversion, a considerable less efficient process than ultrasound assisted one, which achieved more than 90%. The straightforward explanation is that ultrasound continually inserts energy in a slower rate, what can result in a more stable conversion scenario. On the other hand, mechanical steering and heating provides more energy at a glance, but cannot push the final conversion rate beyond a limit, as the transesterification is a double-way chemical process. The instability mechanical steering and heating settles in the reaction medium pulls the components back to their original states more than pushes than to the converted equilibrium state of the matter.

  6. mTOR Signal Transduction Pathways Contribute to TN-C FNIII A1 Overexpression by Mechanical Stress in Osteosarcoma Cells

    PubMed Central

    Zheng, Lianhe; Zhang, Dianzhong; Zhang, Yunfei; Wen, Yanhua; Wang, Yucai

    2014-01-01

    Osteosarcoma is the most common primary malignant bone tumor with a very poor prognosis. Treating osteosarcoma remains a challenge due to its high transitivity. Tenascin-C, with large molecular weight variants including different combinations of its alternative spliced FNIII repeats, is specifically over expressed in tumor tissues. This study examined the expression of Tenascin-C FNIIIA1 in osteosarcoma tissues, and estimated the effect of mechanical stimulation on A1 expression in MG-63 cells. Through immunohistochemical analysis, we found that the A1 protein was expressed at a higher level in osteosarcoma tissues than in adjacent normal tissues. By cell migration assay, we observed that there was a significant correlation between A1 expression and MG-63 cell migra-tion. The relation is that Tenascin-C FNIIIA1 can promote MG-63 cell migration. According to our further study into the effect of mechanical stimulation on A1 expression in MG-63 cells, the mRNA and protein levels of A1 were significantly up-regulated under mechanical stress with the mTOR molecule proving indispensable. Meanwhile, 4E-BP1 and S6K1 (downstream molecule of mTOR) are necessary for A1 normal expression in MG-63 cells whether or not mechanical stress has been encountered. We found that Tenascin-C FNIIIA1 is over-expressed in osteosar-coma tissues and can promote MG-63 cell migration. Furthermore, mechanical stress can facilitate MG-63 cell migration though facilitating A1 overexpression with the necessary molecules (mTOR, 4E-BP1 and S6K1). In con-clusion, high expression of A1 may promote the meta-stasis of osteosarcoma by facilitating MG-63 cell migration. Tenascin-C FNIIIA1 could be used as an indicator in metastatic osteosarcoma patients. PMID:24598996

  7. Signal transduction pathways involved in mechanotransduction in bone cells

    SciTech Connect

    Liedert, Astrid . E-mail: astrid.liedert@uni-ulm.de; Kaspar, Daniela; Blakytny, Robert; Claes, Lutz; Ignatius, Anita

    2006-10-13

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

  8. Cavity optoelectromechanical system combining strong electrical actuation with ultrasensitive transduction

    SciTech Connect

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

    2010-08-15

    A cavity optoelectromechanical system is reported which combines the ultrasensitive transduction of cavity optomechanical systems with the electrical actuation of nanoelectromechanical systems. Ultrasensitive mechanical transduction is achieved via optomechanical coupling. Electrical gradient forces as large as 0.40 {mu}N are realized, facilitating strong actuation with ultralow dissipation. A scanning probe microscope is implemented, capable of characterizing the mechanical modes. The integration of electrical actuation into optomechanical devices is an enabling step toward the regime of quantum nonlinear dynamics and provides capabilities for quantum control of mechanical motion.

  9. The sensory transduction pathways in bacterial chemotaxis

    NASA Technical Reports Server (NTRS)

    Taylor, Barry L.

    1989-01-01

    Bacterial chemotaxis is a useful model for investigating in molecular detail the behavioral response of cells to changes in their environment. Peritrichously flagellated bacteria such as coli and typhimurium swim by rotating helical flagella in a counterclockwise direction. If flagellar rotation is briefly reversed, the bacteria tumble and change the direction of swimming. The bacteria continuously sample the environment and use a temporal sensing mechanism to compare the present and immediate past environments. Bacteria respond to a broad range of stimuli including changes in temperature, oxygen concentration, pH and osmotic strength. Bacteria are attracted to potential sources of nutrition such as sugars and amino acids and are repelled by other chemicals. In the methylation-dependent pathways for sensory transduction and adaptation in E. coli and S. typhimurium, chemoeffectors bind to transducing proteins that span the plasma membrane. The transducing proteins are postulated to control the rate of autophosphorylation of the CheA protein, which in turn phosphorylates the CheY protein. The phospho-CheY protein binds to the switch on the flagellar motor and is the signal for clockwise rotation of the motor. Adaptation to an attractant is achieved by increasing methylation of the transducing protein until the attractant stimulus is cancelled. Responses to oxygen and certain sugars involve methylation-independent pathways in which adaption occurs without methylation of a transducing protein. Taxis toward oxygen is mediated by the electron transport system and changes in the proton motive force. Recent studies have shown that the methylation-independent pathway converges with the methylation-dependent pathway at or before the CheA protein.

  10. Gravitational sensory transduction chain in flagellates

    NASA Astrophysics Data System (ADS)

    Häder, D.-P.; Richter, P.; Ntefidou, M.; Lebert, M.

    Earlier hypotheses have assumed that gravitactic orientation in flagellates, such as the photosynthetic unicell Euglena gracilis, is brought about by passive alignment of the cells in the water column by being tail heavy. A recent experiment on a sounding rocket (TEXUS 40) comparing immobilized cells with mobile cells demonstrated that the passive buoy effect can account for approximately 20% of the orientation of the cells in a gravity field. The cells show either positive or negative gravitaxis depending on other external or internal factors. Shortly after inoculation, the tendency of young cells to swim downward in the water column can be readily reverted by adding micromolar concentrations of some heavy metal ions including copper, cadmium or lead. The negative gravitaxis of older cells is converted into a positive one by stress factors such as increasing salinity or exposure to excessive visible or UV radiation. The mechanism for this switch seems to involve reactive oxygen species since the gravitactic sign change was suppressed when oxygen was removed by flushing the cell suspension with nitrogen. Also, the addition of radical scavengers (Trolox, ascorbic acid or potassium cyanide) abolished or reduced the gravitactic sign change. Addition of hydrogen peroxide induced a gravitactic sign change in the absence of external stress factors. The primary reception for the gravity vector seems to involve mechanosensitive ion channels which specifically gate calcium ions inward. We have identified several gene sequences for putative mechanosensory channels in Euglena and have applied RNAi to identify which of these channels are involved in graviperception. The influx of Ca 2+ activates calmodulin (CaM) which has been shown to be involved in the sensory transduction chain of graviorientation. It is known that an adenylyl cyclase is bound to the flagellar membrane in Euglena which is activated by CaM. This enzyme produces cAMP which has also been shown to be the key

  11. Meeting Report: Teaching Signal Transduction

    ERIC Educational Resources Information Center

    Kramer, IJsbrand; Thomas, Geraint

    2006-01-01

    In July, 2005, the European Institute of Chemistry and Biology at the campus of the University of Bordeaux, France, hosted a focused week of seminars, workshops, and discussions around the theme of "teaching signal transduction." The purpose of the summer school was to offer both junior and senior university instructors a chance to reflect on the…

  12. Girdin/GIV is upregulated by cyclic tension, propagates mechanical signal transduction, and is required for the cellular proliferation and migration of MG-63 cells

    SciTech Connect

    Hu, Jiang-Tian; Li, Yan; Yu, Bing; Gao, Guo-Jie; Zhou, Ting; Li, Song

    2015-08-21

    To explore how Girdin/GIV is regulated by cyclic tension and propagates downstream signals to affect cell proliferation and migration. Human osteoblast-like MG-63 cells were exposed to cyclic tension force at 4000 μstrain and 0.5 Hz for 6 h, produced by a four-point bending system. Cyclic tension force upregulated Girdin and Akt expression and phosphorylation in cultured MG-63 cells. Girdin and Akt each promoted the phosphorylation of the other under stimulated tension. In vitro MTT and transwell assays showed that Girdin and Akt are required for cell proliferation and migration during cellular quiescence. Moreover, STAT3 was determined to be essential for Girdin expression under stimulated tension force in the physiological condition, as well as for osteoblast proliferation and migration during quiescence. These findings suggest that the STAT3/Girdin/Akt pathway activates in osteoblasts in response to mechanical stimulation and may play a significant role in triggering osteoblast proliferation and migration during orthodontic treatment. - Highlights: • Tension force upregulates Girdin and Akt expression and phosphorylation. • Girdin and Akt promotes the phosphorylation of each other under tension stimulation. • Girdin and Akt are required for MG-63 cell proliferation and migration. • STAT3 is essential for Girdin expression after application of the tension forces.

  13. The YfiBNR Signal Transduction Mechanism Reveals Novel Targets for the Evolution of Persistent Pseudomonas aeruginosa in Cystic Fibrosis Airways

    PubMed Central

    Manfredi, Pablo; Dötsch, Andreas; Blanka, Andrea; Bos, Raphael; Cornelis, Guy R.; Häussler, Susanne; Jenal, Urs

    2012-01-01

    The genetic adaptation of pathogens in host tissue plays a key role in the establishment of chronic infections. While whole genome sequencing has opened up the analysis of genetic changes occurring during long-term infections, the identification and characterization of adaptive traits is often obscured by a lack of knowledge of the underlying molecular processes. Our research addresses the role of Pseudomonas aeruginosa small colony variant (SCV) morphotypes in long-term infections. In the lungs of cystic fibrosis patients, the appearance of SCVs correlates with a prolonged persistence of infection and poor lung function. Formation of P. aeruginosa SCVs is linked to increased levels of the second messenger c-di-GMP. Our previous work identified the YfiBNR system as a key regulator of the SCV phenotype. The effector of this tripartite signaling module is the membrane bound diguanylate cyclase YfiN. Through a combination of genetic and biochemical analyses we first outline the mechanistic principles of YfiN regulation in detail. In particular, we identify a number of activating mutations in all three components of the Yfi regulatory system. YfiBNR is shown to function via tightly controlled competition between allosteric binding sites on the three Yfi proteins; a novel regulatory mechanism that is apparently widespread among periplasmic signaling systems in bacteria. We then show that during long-term lung infections of CF patients, activating mutations invade the population, driving SCV formation in vivo. The identification of mutational “scars” in the yfi genes of clinical isolates suggests that Yfi activity is both under positive and negative selection in vivo and that continuous adaptation of the c-di-GMP network contributes to the in vivo fitness of P. aeruginosa during chronic lung infections. These experiments uncover an important new principle of in vivo persistence, and identify the c-di-GMP network as a valid target for novel anti-infectives directed

  14. Reliable Signal Transduction

    NASA Astrophysics Data System (ADS)

    Wollman, Roy

    Stochasticity inherent to biochemical reactions (intrinsic noise) and variability in cellular states (extrinsic noise) degrade information transmitted through signaling networks. We analyzed the ability of temporal signal modulation - that is dynamics - to reduce noise-induced information loss. In the extracellular signal-regulated kinase (ERK), calcium (Ca(2 +)) , and nuclear factor kappa-B (NF- κB) pathways, response dynamics resulted in significantly greater information transmission capacities compared to nondynamic responses. Theoretical analysis demonstrated that signaling dynamics has a key role in overcoming extrinsic noise. Experimental measurements of information transmission in the ERK network under varying signal-to-noise levels confirmed our predictions and showed that signaling dynamics mitigate, and can potentially eliminate, extrinsic noise-induced information loss. By curbing the information-degrading effects of cell-to-cell variability, dynamic responses substantially increase the accuracy of biochemical signaling networks.

  15. Striatal Signal Transduction and Drug Addiction

    PubMed Central

    Philibin, Scott D.; Hernandez, Adan; Self, David W.; Bibb, James A.

    2011-01-01

    Drug addiction is a severe neuropsychiatric disorder characterized by loss of control over motivated behavior. The need for effective treatments mandates a greater understanding of the causes and identification of new therapeutic targets for drug development. Drugs of abuse subjugate normal reward-related behavior to uncontrollable drug-seeking and -taking. Contributions of brain reward circuitry are being mapped with increasing precision. The role of synaptic plasticity in addiction and underlying molecular mechanisms contributing to the formation of the addicted state are being delineated. Thus we may now consider the role of striatal signal transduction in addiction from a more integrative neurobiological perspective. Drugs of abuse alter dopaminergic and glutamatergic neurotransmission in medium spiny neurons of the striatum. Dopamine receptors important for reward serve as principle targets of drugs abuse, which interact with glutamate receptor signaling critical for reward learning. Complex networks of intracellular signal transduction mechanisms underlying these receptors are strongly stimulated by addictive drugs. Through these mechanisms, repeated drug exposure alters functional and structural neuroplasticity, resulting in transition to the addicted biological state and behavioral outcomes that typify addiction. Ca2+ and cAMP represent key second messengers that initiate signaling cascades, which regulate synaptic strength and neuronal excitability. Protein phosphorylation and dephosphorylation are fundamental mechanisms underlying synaptic plasticity that are dysregulated by drugs of abuse. Increased understanding of the regulatory mechanisms by which protein kinases and phosphatases exert their effects during normal reward learning and the addiction process may lead to novel targets and pharmacotherapeutics with increased efficacy in promoting abstinence and decreased side effects, such as interference with natural reward, for drug addiction. PMID

  16. Signal Transduction to the Permeability Transition Pore

    PubMed Central

    Rasola, Andrea; Sciacovelli, Marco; Pantic, Boris; Bernardi, Paolo

    2010-01-01

    The permeability transition pore (PTP) is an inner mitochondrial membrane channel that has been thoroughly characterized functionally, yet remains an elusive molecular entity. The best characterized PTP-regulatory component, cyclophilin (CyP) D, is a matrix protein that favors pore opening. CyP inhibitors, CyPD null animals, and in situ PTP readouts have established the role of PTP as an effector mechanism of cell death, and the growing definition of PTP signaling mechanisms. This review briefly covers the functional features of the PTP and the role played by its dysregulation in disease pathogenesis. Recent progress on PTP modulation by kinase/phosphatase signal transduction is discussed, with specific emphasis on hexokinase and on the Akt-ERK-GSK3 axis, which might modulate the PTP through CyPD phosphorylation. PMID:20153328

  17. Effects of Electrode Surface Morphology on the Transduction of Ionic Polymer-Metal Composites

    NASA Astrophysics Data System (ADS)

    Palmre, Viljar

    Ionic polymer-metal composites (IPMCs) are innovative smart materials that exhibit electromechanical and mechanoelectrical transduction (conversion of electrical input into mechanical deformation and vice versa). Due to low driving voltage (< 5 V) and ability to operate in aqueous environment, IPMCs are attractive for developing soft actuators and sensors for underwater robots and medical devices. This dissertation focuses on investigating the effects of electrode surface morphology in the transduction of Pt and Pd-Pt electrodes-based IPMCs, with the aim to improve the electrode surface design and thereby enhance the transduction performance of the material. Firstly, the synthesis techniques are developed to control and manipulate the surface structure of the mentioned electrodes through the electroless plating process. Using these techniques, IPMCs with different electrode surface structures are fabricated. The changes in the electrode surface morphology and the resulting effects on the material's electromechanical, mechanoelectrical, electrochemical and mechanical properties area examined and analyzed. This study shows that increasing the impregnation-reduction cycles under appropriate conditions leads to the formation and growth of platinum nanoparticles with sharp tips and edges---called Pt nanothorn assemblies---at the polymer-electrode interface. IPMCs designed with such nanostructured Pt electrodes are first to be reported. The experiments demonstrate that the formation and growth of Pt nanothorn assemblies at the electrode interface increases considerably the total transported charge during the transduction, thereby increasing significantly the displacement and blocking force output of IPMC. The improvement of the mentioned electromechanical properties was 3--5 times, depending on the input voltage and frequency used. Also, the peak mechanoelectrically induced voltage increased somewhat, although the overall effect of the surface structure was relatively

  18. Signal transduction by the growth hormone receptor

    SciTech Connect

    Waters, M.J.; Rowlinson, S.W.; Clarkson, R.W.

    1994-12-31

    It has been proposed that dimerization of identical receptor subunits by growth hormone (GH) is the mechanism of signal transduction across the cell membrane. We present here data with analogs of porcine GH (pGH), with GH receptors (GHR) mutated in the dimerization domain and with monoclonal antibodies to the GHR which indicate that dimerization is necessary but not sufficient for transduction. We also report nuclear uptake of GH both in vivo and in vitro, along with nuclear localization of the receptor and GH-binding protein (GHBP). This suggests that GH acts directly at the nucleus, and one possible target for this action is a rapid increase in transcription of C/EBP delta seen in 3T3-F442A cells in response to GH. This tyrosine kinase-dependent event may be an archetype for induction of other immediate early gene transcription factors which then interact to determine the programming of the subsequent transcriptional response to GH. 29 refs., 1 fig., 1 tab.

  19. Studying Cellular Signal Transduction with OMIC Technologies.

    PubMed

    Landry, Benjamin D; Clarke, David C; Lee, Michael J

    2015-10-23

    In the gulf between genotype and phenotype exists proteins and, in particular, protein signal transduction systems. These systems use a relatively limited parts list to respond to a much longer list of extracellular, environmental, and/or mechanical cues with rapidity and specificity. Most signaling networks function in a highly non-linear and often contextual manner. Furthermore, these processes occur dynamically across space and time. Because of these complexities, systems and "OMIC" approaches are essential for the study of signal transduction. One challenge in using OMIC-scale approaches to study signaling is that the "signal" can take different forms in different situations. Signals are encoded in diverse ways such as protein-protein interactions, enzyme activities, localizations, or post-translational modifications to proteins. Furthermore, in some cases, signals may be encoded only in the dynamics, duration, or rates of change of these features. Accordingly, systems-level analyses of signaling may need to integrate multiple experimental and/or computational approaches. As the field has progressed, the non-triviality of integrating experimental and computational analyses has become apparent. Successful use of OMIC methods to study signaling will require the "right" experiments and the "right" modeling approaches, and it is critical to consider both in the design phase of the project. In this review, we discuss common OMIC and modeling approaches for studying signaling, emphasizing the philosophical and practical considerations for effectively merging these two types of approaches to maximize the probability of obtaining reliable and novel insights into signaling biology. PMID:26244521

  20. Automated modelling of signal transduction networks

    PubMed Central

    2002-01-01

    Background Intracellular signal transduction is achieved by networks of proteins and small molecules that transmit information from the cell surface to the nucleus, where they ultimately effect transcriptional changes. Understanding the mechanisms cells use to accomplish this important process requires a detailed molecular description of the networks involved. Results We have developed a computational approach for generating static models of signal transduction networks which utilizes protein-interaction maps generated from large-scale two-hybrid screens and expression profiles from DNA microarrays. Networks are determined entirely by integrating protein-protein interaction data with microarray expression data, without prior knowledge of any pathway intermediates. In effect, this is equivalent to extracting subnetworks of the protein interaction dataset whose members have the most correlated expression profiles. Conclusion We show that our technique accurately reconstructs MAP Kinase signaling networks in Saccharomyces cerevisiae. This approach should enhance our ability to model signaling networks and to discover new components of known networks. More generally, it provides a method for synthesizing molecular data, either individual transcript abundance measurements or pairwise protein interactions, into higher level structures, such as pathways and networks. PMID:12413400

  1. A comparative review of four formulations of noncommutative quantum mechanics

    NASA Astrophysics Data System (ADS)

    Gouba, Laure

    2016-07-01

    Four formulations of quantum mechanics on noncommutative Moyal phase spaces are reviewed. These are the canonical, path-integral, Weyl-Wigner and systematic formulations. Although all these formulations represent quantum mechanics on a phase space with the same deformed Heisenberg algebra, there are mathematical and conceptual differences which we discuss.

  2. Morphogengineering roots: comparing mechanisms of morphogen gradient formation

    PubMed Central

    2012-01-01

    Background In developmental biology, there has been a recent focus on the robustness of morphogen gradients as possible providers of positional information. It was shown that functional morphogen gradients present strong biophysical constraints and lack of robustness to noise. Here we explore how the details of the mechanism which underlies the generation of a morphogen gradient can influence those properties. Results We contrast three gradient-generating mechanisms, (i) a source-decay mechanism; and (ii) a unidirectional transport mechanism; and (iii) a so-called reflux-loop mechanism. Focusing on the dynamics of the phytohormone auxin in the root, we show that only the reflux-loop mechanism can generate a gradient that would be adequate to supply functional positional information for the Arabidopsis root, for biophysically reasonable kinetic parameters. Conclusions We argue that traits that differ in spatial and temporal time-scales can impose complex selective pressures on the mechanism of morphogen gradient formation used for the development of the particular organism. PMID:22583698

  3. Signal Transduction in Histidine Kinases: Insights from New Structures

    PubMed Central

    Bhate, Manasi P.; Molnar, Kathleen S.; Goulian, Mark; DeGrado, William F.

    2015-01-01

    Histidine kinases (HKs) are major players in bacterial signaling. There has been an explosion of new HK crystal structures in the last five years. We globally analyze the structures of HKs to yield insights into the mechanisms by which signals are transmitted to and across protein structures in this family. We interpret known enzymological data in the context of new structural data to show how asymmetry across the dimer interface is a key feature of signal transduction in HKs, and discuss how different HK domains undergo asymmetric-to-symmetric transitions during signal transduction and catalysis. A thermodynamic framework for signaling that encompasses these various properties is presented and the consequences of weak thermodynamic coupling are discussed. The synthesis of observations from enzymology, structural biology, protein engineering and thermodynamics paves the way for a deeper molecular understanding of histidine kinase signal transduction. PMID:25982528

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

    PubMed Central

    Yoshioka, Tohru; Sakakibara, Manabu

    2013-01-01

    What is the general principle of sensory transduction? Sensory transduction is defined as energy transformation from the external world to the internal world. The energy of the external world, such as thermal energy (heat), electro-magnetic energy (light), mechanical energy (sound) and the energy from molecules (chemicals), is converted into electrochemical events in the animal nervous system. The following five classes of special sense receptors are utilized for energy conversion: vision (photo); audition (sound); taste and smell (chemo); and tactile (mechano). There are also other special sense receptors, including thermo and noxious receptors. The focus of this study is on photoreceptors, sound-receptors and odorant-receptors because the transduction mechanisms of these receptors are explained biochemically and understood by a common physical principle; these biochemical models are well known in neuroscience. The following notable problems are inherent in these biochemical models: the cGMP ionophore model of the vertebrate photoreceptor cannot explain the fast photo-response (∼msec); the tip links connection model of stereocilia in the basilar membrane for opening the K+ channel on the tip of a hair has difficulty explaining the high frequency vibration of hair cells without a damping of the oscillation, and the odorant shape-specific receptor model for olfactory transduction has difficulty in discriminating the minute differences among similar fragrant smells of essential oils with different molecular shapes. These difficulties might arise from a lack of the physical sense when the transduction models were proposed. This article will reconsider these problems and propose rational models for visual, olfactory and auditory transduction. PMID:27493557

  5. Theory and modeling of cylindrical thermo-acoustic transduction

    NASA Astrophysics Data System (ADS)

    Tong, Lihong; Lim, C. W.; Zhao, Xiushao; Geng, Daxing

    2016-06-01

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

  6. Epigenetic mechanisms and memory strength: a comparative study.

    PubMed

    Federman, Noel; Zalcman, Gisela; de la Fuente, Verónica; Fustiñana, Maria Sol; Romano, Arturo

    2014-01-01

    Memory consolidation requires de novo mRNA and protein synthesis. Transcriptional activation is controlled by transcription factors, their cofactors and repressors. Cofactors and repressors regulate gene expression by interacting with basal transcription machinery, remodeling chromatin structure and/or chemically modifying histones. Acetylation is the most studied epigenetic mechanism of histones modifications related to gene expression. This process is regulated by histone acetylases (HATs) and histone deacetylases (HDACs). More than 5 years ago, we began a line of research about the role of histone acetylation during memory consolidation. Here we review our work, presenting evidence about the critical role of this epigenetic mechanism during consolidation of context-signal memory in the crab Neohelice granulata, as well as during consolidation of novel object recognition memory in the mouse Mus musculus. Our evidence demonstrates that histone acetylation is a key mechanism in memory consolidation, functioning as a distinctive molecular feature of strong memories. Furthermore, we found that the strength of a memory can be characterized by its persistence or its resistance to extinction. Besides, we found that the role of this epigenetic mechanism regulating gene expression only in the formation of strongest memories is evolutionarily conserved. PMID:24978317

  7. Comparative transcriptome and metabolome provides new insights into the regulatory mechanisms of accelerated senescence in litchi fruit after cold storage.

    PubMed

    Yun, Ze; Qu, Hongxia; Wang, Hui; Zhu, Feng; Zhang, Zhengke; Duan, Xuewu; Yang, Bao; Cheng, Yunjiang; Jiang, Yueming

    2016-01-01

    Litchi is a non-climacteric subtropical fruit of high commercial value. The shelf life of litchi fruit under ambient conditions (AC) is approximately 4-6 days. Post-harvest cold storage prolongs the life of litchi fruit for up to 30 days with few changes in pericarp browning and total soluble solids. However, the shelf life of litchi fruits at ambient temperatures after pre-cold storage (PCS) is only 1-2 days. To better understand the mechanisms involved in the rapid fruit senescence induced by pre-cold storage, a transcriptome of litchi pericarp was constructed to assemble the reference genes, followed by comparative transcriptomic and metabolomic analyses. Results suggested that the senescence of harvested litchi fruit was likely to be an oxidative process initiated by ABA, including oxidation of lipids, polyphenols and anthocyanins. After cold storage, PCS fruit exhibited energy deficiency, and respiratory burst was elicited through aerobic and anaerobic respiration, which was regulated specifically by an up-regulated calcium signal, G-protein-coupled receptor signalling pathway and small GTPase-mediated signal transduction. The respiratory burst was largely associated with increased production of reactive oxygen species, up-regulated peroxidase activity and initiation of the lipoxygenase pathway, which were closely related to the accelerated senescence of PCS fruit. PMID:26763309

  8. Comparative transcriptome and metabolome provides new insights into the regulatory mechanisms of accelerated senescence in litchi fruit after cold storage

    PubMed Central

    Yun, Ze; Qu, Hongxia; Wang, Hui; Zhu, Feng; Zhang, Zhengke; Duan, Xuewu; Yang, Bao; Cheng, Yunjiang; Jiang, Yueming

    2016-01-01

    Litchi is a non-climacteric subtropical fruit of high commercial value. The shelf life of litchi fruit under ambient conditions (AC) is approximately 4–6 days. Post-harvest cold storage prolongs the life of litchi fruit for up to 30 days with few changes in pericarp browning and total soluble solids. However, the shelf life of litchi fruits at ambient temperatures after pre-cold storage (PCS) is only 1–2 days. To better understand the mechanisms involved in the rapid fruit senescence induced by pre-cold storage, a transcriptome of litchi pericarp was constructed to assemble the reference genes, followed by comparative transcriptomic and metabolomic analyses. Results suggested that the senescence of harvested litchi fruit was likely to be an oxidative process initiated by ABA, including oxidation of lipids, polyphenols and anthocyanins. After cold storage, PCS fruit exhibited energy deficiency, and respiratory burst was elicited through aerobic and anaerobic respiration, which was regulated specifically by an up-regulated calcium signal, G-protein-coupled receptor signalling pathway and small GTPase-mediated signal transduction. The respiratory burst was largely associated with increased production of reactive oxygen species, up-regulated peroxidase activity and initiation of the lipoxygenase pathway, which were closely related to the accelerated senescence of PCS fruit. PMID:26763309

  9. Calcium and signal transduction in plants

    NASA Technical Reports Server (NTRS)

    Poovaiah, B. W.; Reddy, A. S.

    1993-01-01

    Environmental and hormonal signals control diverse physiological processes in plants. The mechanisms by which plant cells perceive and transduce these signals are poorly understood. Understanding biochemical and molecular events involved in signal transduction pathways has become one of the most active areas of plant research. Research during the last 15 years has established that Ca2+ acts as a messenger in transducing external signals. The evidence in support of Ca2+ as a messenger is unequivocal and fulfills all the requirements of a messenger. The role of Ca2+ becomes even more important because it is the only messenger known so far in plants. Since our last review on the Ca2+ messenger system in 1987, there has been tremendous progress in elucidating various aspects of Ca(2+) -signaling pathways in plants. These include demonstration of signal-induced changes in cytosolic Ca2+, calmodulin and calmodulin-like proteins, identification of different Ca2+ channels, characterization of Ca(2+) -dependent protein kinases (CDPKs) both at the biochemical and molecular levels, evidence for the presence of calmodulin-dependent protein kinases, and increased evidence in support of the role of inositol phospholipids in the Ca(2+) -signaling system. Despite the progress in Ca2+ research in plants, it is still in its infancy and much more needs to be done to understand the precise mechanisms by which Ca2+ regulates a wide variety of physiological processes. The purpose of this review is to summarize some of these recent developments in Ca2+ research as it relates to signal transduction in plants.

  10. High-sensitivity linear piezoresistive transduction for nanomechanical beam resonators.

    PubMed

    Sansa, Marc; Fernández-Regúlez, Marta; Llobet, Jordi; San Paulo, Álvaro; Pérez-Murano, Francesc

    2014-01-01

    Highly sensitive conversion of motion into readable electrical signals is a crucial and challenging issue for nanomechanical resonators. Efficient transduction is particularly difficult to realize in devices of low dimensionality, such as beam resonators based on carbon nanotubes or silicon nanowires, where mechanical vibrations combine very high frequencies with miniscule amplitudes. Here we describe an enhanced piezoresistive transduction mechanism based on the asymmetry of the beam shape at rest. We show that this mechanism enables highly sensitive linear detection of the vibration of low-resistivity silicon beams without the need of exceptionally large piezoresistive coefficients. The general application of this effect is demonstrated by detecting multiple-order modes of silicon nanowire resonators made by either top-down or bottom-up fabrication methods. These results reveal a promising approach for practical applications of the simplest mechanical resonators, facilitating its manufacturability by very large-scale integration technologies. PMID:25000256

  11. Scleral mechanics: comparing whole globe inflation and uniaxial testing.

    PubMed

    Lari, David R; Schultz, David S; Wang, Aaron S; Lee, On-Tat; Stewart, Jay M

    2012-01-01

    The purpose of this study was to assess fundamental differences between the mechanics of the posterior sclera in paired eyes using uniaxial and whole globe inflation testing, with an emphasis on the relationship between testing conditions and observed tissue behavior. Twenty porcine eyes, consisting of matched pairs from 10 pigs, were used in this study. Within pairs, one eye was tested with 10 cycles of globe pressurization to 150 mmHg (∼10× normal IOP) while biaxial strains were tracked via an optical system at the posterior sclera. An excised posterior strip from the second eye was subjected to traditional uniaxial testing in which mechanical hysteresis was recorded from 10 cycles to a peak stress of 0.13 MPa (roughly equivalent to the circumferential wall stress produced by an IOP of 150 mmHg under the thin-walled pressure vessel assumption). For approximately equivalent loads, peak strains were more than twice as high in uniaxial tests than in inflation tests. Different trends in the load-deformation plots were seen between the tests, including an extended "toe" region in the uniaxial test, a generally steeper curve in the inflation tests, and reduced variability in the inflation tests. The unique opportunity of being able to mechanically load a whole globe under near physiologic conditions alongside a standard uniaxially tested specimen reveals the effects of testing artifacts relevant to most uniaxially tested soft tissues. Whole globe inflation offers testing conditions that significantly alter load-deformation behavior relative to uniaxial testing; consequently, laboratory studies of interventions or conditions that alter scleral mechanics may greatly benefit from these findings. PMID:22155444

  12. Scleral Mechanics: Comparing Whole Globe Inflation and Uniaxial Testing

    PubMed Central

    Lari, David R.; Schultz, David S.; Wang, Aaron S.; Lee, On-Tat; Stewart, Jay M.

    2012-01-01

    The purpose of this study was to assess fundamental differences between the mechanics of the posterior sclera in paired eyes using uniaxial and whole globe inflation testing, with an emphasis on the relationship between testing conditions and observed tissue behavior. Twenty porcine eyes, consisting of matched pairs from 10 pigs, were used in this study. Within pairs, one eye was tested with 10 cycles of globe pressurization to 150 mmHg (~10x normal IOP) while biaxial strains were tracked via an optical system at the posterior sclera. An excised posterior strip from the second eye was subjected to traditional uniaxial testing in which mechanical hysteresis was recorded from 10 cycles to a peak stress of 0.13 MPa (roughly equivalent to the circumferential wall stress produced by an IOP of 150 mmHg under the thin-walled pressure vessel assumption). For approximately equivalent loads, peak strains were more than twice as high in uniaxial tests than in inflation tests. Different trends in the load-deformation plots were seen between the tests, including an extended “toe” region in the uniaxial test, a generally steeper curve in the inflation tests, and reduced variability in the inflation tests. The unique opportunity of being able to mechanically load a whole globe under near physiologic conditions alongside a standard uniaxially tested specimen reveals the effects of testing artifacts relevant to most uniaxially tested soft tissues. Whole globe inflation offers testing conditions that significantly alter load-deformation behavior relative to uniaxial testing; consequently, laboratory studies of interventions or conditions that alter scleral mechanics may greatly benefit from these findings. PMID:22155444

  13. Hypergravity signal transduction and gene expression in cultured mammalian cells

    NASA Technical Reports Server (NTRS)

    Kumei, Y.; Whitson, P. A.

    1994-01-01

    A number of studies have been conducted during space flight and with clinostats and centrifuges, suggesting that gravity effects the proliferation and differentiation of mammalian cells in vitro. However, little is known about the mechanisms by which mammalian cells respond to changes in gravitational stress. This paper summarizes studies designed to clarify the effects of hypergravity on the cultured human HeLa cells and to investigate the mechanism of hypergravity signal transduction in these cells.

  14. A mechanical diode: Comparing numerical and experimental characterizations

    SciTech Connect

    Simmermacher, T.; Segalman, D.; Sagartz, M.

    1997-12-01

    The predictive modeling of vibration of many structural systems is crippled by an inability to predictively model the mechanics of joints. The lack of understanding of joint dynamics is evidenced by the substantial uncertainty of joint compliances in the numerical models and by the complete inability to predict joint damping. The lore is that at low amplitudes, joint mechanics are associated with Coulomb friction and stick-slip phenomena and that at high amplitudes, impact processes result in dissipation as well as shift of energy to other frequencies. Inadequate understanding of the physics precludes reliable predictions. In this introductory work, joint compliance is studied in both a numerical and experimental setting. A simple bolted interface is used as the test article and compliance is measured for the joint in both compression and in tension. This simple interface is shown to exhibit a strong non-linearity near the transition from compression to tension (or vice-versa). Modeling issues pertaining to numerically solving for the compliance are addressed. It is shown that the model predicts the experimental strains and compliance fairly well. It will be seen that the joint behavior is a mechanical analogy to a diode. In compression, the joint is very stiff, acting almost as a rigid link, while in tension the joint is soft, acting as a soft spring. Although there have been many other studies performed on bolted joints, the variety of joint geometries has demonstrated large variations in behavior. This study is an attempt to quantify the behavior of typical joints found in today`s weapon systems.

  15. Carbon acquisition by Cyanobacteria: Mechanisms, Comparative Genomics and Evolution

    SciTech Connect

    Kaplan, Aaron; Hagemann, Martin; Bauwe, Hermann; Kahlon, Shira; Ogawa, Teruo

    2008-01-01

    In this chapter we mainly focus on the mechanisms of inorganic carbon uptake, photorespiration, and the regulation between the metabolic fluxes involved in photoautotrophic, photomixotrophic and heterotrophic growth. We identify the genes involved, their regulation and phylogeny. Living in an environment where the CO₂ concentration is considerably lower than required to saturate their carboxylating enzyme, ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco), cyanobacteria acquired the CO₂ concentrating mechanism (CCM) that enables them to accumulate CO₂ at the carboxylation site. All the cyanobacteria examined to date are able to fix CO₂ into carbohydrates. However, in addition to variance in the range of physical growth conditions, cyanobacteria also vary substantially in their ability to consume organic carbon from their surroundings. Many strains are obligate photoautotrophs where the sole carbon source is CO₂, while others are able to perform photomixotrophic or even heterotrophic growth using a wide variety of organic substances (c.f. Rippka et al., 1979; Stal and Moezelaar, 1997b). Cyanobacteria constitute a unique case where the anabolic and catabolic carbohydrate metabolisms function in the same cellular compartment. In addition, the photosynthetic and respiratory electron transport pathways share components in the thylakoid membranes. Despite its importance to our understanding of cyanobacterial metabolism, little is known about the mechanisms involved in the shifts between photoautotrophic, heterotrophic and photomixotrophic modes of growth, and their regulation; between the different pathways of carbohydrate breakdown- glycolysis, fermentation, the oxidative pentose phosphate, the Krebs cycle and the photorespiratory pathways. In this chapter we shall briefly focus on recent advances in our understanding of the CCM and carbon metabolism in cyanobacteria.

  16. Carbon Acquisition by Cyanobacteria: Mechanisms, Comparative Genomics, and Evolution

    SciTech Connect

    Kaplan, Aaron; Hagemann, Martin; Bauwe, Hermann; Kahlon, Shira; Ogawa, Teruo

    2008-01-01

    In this chapter we mainly focus on the mechanisms of inorganic carbon uptake, photorespiration, and the regulation between the metabolic fluxes involved in photoautotrophic, photomixotrophic and heterotrophic growth. We identify the genes involved, their regulation and phylogeny. Living in an environment where the CO₂ concentration is considerably lower than required to saturate their carboxylating enzyme, ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco), cyanobacteria acquired the CO₂ concentrating mechanism (CCM) that enables them to accumulate CO₂ at the carboxylation site. All the cyanobacteria examined to date are able to fix CO₂ into carbohydrates. However, in addition to variance in the range of physical growth conditions, cyanobacteria also vary substantially in their ability to consume organic carbon from their surroundings. Many strains are obligate photoautotrophs where the sole carbon source is CO₂, while others are able to perform photomixotrophic or even heterotrophic growth using a wide variety of organic substances (c.f. Rippka et al., 1979; Stal and Moezelaar, 1997b). Cyanobacteria constitute a unique case where the anabolic and catabolic carbohydrate metabolisms function in the same cellular compartment. In addition, the photosynthetic and respiratory electron transport pathways share components in the thylakoid membranes. Despite its importance to our understanding of cyanobacterial metabolism, little is known about the mechanisms involved in the shifts between photoautotrophic, heterotrophic and photomixotrophic modes of growth, and their regulation; between the different pathways of carbohydrate breakdown- glycolysis, fermentation, the oxidative pentose phosphate, the Krebs cycle and the photorespiratory pathways. In this chapter we shall briefly focus on recent advances in our understanding of the CCM and carbon metabolism in cyanobacteria.

  17. Vocal mechanisms in birds and bats: a comparative view.

    PubMed

    Suthers, Roderick A

    2004-06-01

    Vocal signals play a very important role in the life of both birds and echolocating bats, but these two unrelated groups of flying vertebrates have very different vocal systems. They nevertheless must solve many of the same problems in producing sound. This brief review examines avian and microchiropteran motor mechanisms for: 1) coordinating the timing of phonation with the vocal motor pattern that controls its acoustic properties, and 2) achieving respiratory strategies that provide adequate ventilation for pulmonary gas exchange, while also facilitating longer duration songs or trains of sonar pulses. PMID:15258634

  18. A comparative evaluation of mechanical properties of nanofibrous materials

    NASA Astrophysics Data System (ADS)

    Lyubun, German P.; Bessudnova, Nadezda O.

    2014-01-01

    Restoration or replacement of lost or damaged hard tooth tissues remain a reconstructive clinical dentistry challenge. One of the most promising solutions to this problem is the development of novel concepts and methodologies of tissue engineering for the synthesis of three-dimensional graft constructs that are equivalent to original organs and tissues. This structural and functional compatibility can be reached by producing ultra-thin polymer filament scaffolds. This research aims through a series of studies to examine different methods of polymer filament material special preparation and test mechanical properties of the produced materials subjected to a tensile strain. Nanofibrous material preparation using chemically pure acetone and mixtures of ethanol/water has shown no significant changes in sample surface morphology. The high temperature impact on material morphology has resulted in the modification of fiber structure. In the course of mechanical tests it has been revealed the dependence of the material strength on the spinning solution compositions. The results achieved point to the possibility to develop nanofibrous materials with required parameters changing the methodology of spinning solution production.

  19. Kinetics of lentiviral vector transduction in human CD34(+) cells.

    PubMed

    Uchida, Naoya; Green, Rashidah; Ballantine, Josiah; Skala, Luke P; Hsieh, Matthew M; Tisdale, John F

    2016-02-01

    Unlike cell lines, human hematopoietic stem cells (HSCs) are less efficiently transduced with HIV-1 vectors, potentially limiting this approach. To investigate which step (internalization, reverse transcription, nuclear transport, and integration) limits lentiviral transduction, we evaluated the kinetics of lentiviral transduction in human CD34(+) cells. We transduced HeLa and CD34(+) cells with self-inactivating HIV-1 vector at low and tenfold higher multiplicity of infection (MOI) and evaluated vector amounts at various time points based on the rationale that if a given step was not limiting, tenfold greater vector amounts would be obtained at the tenfold higher MOI. We observed slower internalization (>60 min), a peak in reverse transcription at 24 hours, and completion of integration at 3 days in CD34(+) cells. In HeLa cells, there were approximately tenfold greater amounts at high MOI at all time points. When compared with HeLa cells, CD34(+) cells exhibited larger differences in vector amounts between high and low MOIs at 2-6 hours and a smaller difference at 12 hours to 10 days, revealing a limitation in human CD34(+) cell transduction around 12 hours, which corresponds to reverse transcription. In serial measurements of reverse transcription at 24 hours, vector amounts did not decrease once detected among CD34(+) cells. When using an HSC expansion medium, we observed less limitation for starting reverse transcription and more efficient transduction among CD34(+) cells in vitro and in xenografted mice. These data suggest that it is the initiation of reverse transcription that limits lentiviral transduction of human CD34(+) cells. Our findings provide an avenue for optimizing human CD34(+) cell transduction. PMID:26499040

  20. Comparing potential copper chelation mechanisms in Parkinson's disease protein

    NASA Astrophysics Data System (ADS)

    Rose, Frisco; Hodak, Miroslav; Bernholc, Jerry

    2011-03-01

    We have implemented the nudged elastic band (NEB) as a guided dynamics framework for our real-space multigrid method of DFT-based quantum simulations. This highly parallel approach resolves a minimum energy pathway (MEP) on the energy hypersurface by relaxing intermediates in a chain-of-states. As an initial application we present an investigation of chelating agents acting on copper ion bound to α -synuclein, whose misfolding is implicated in Parkinson's disease (PD). Copper ions are known to act as highly effective misfolding agents in a-synuclein and are thus an important target in understanding PD. Furthermore, chelation therapy has shown promise in the treatment of Alzheimer's and other neuro-degenerative diseases with similar metal-correlated pathologies. At present, our candidate chelating agents include nicotine, curcumin and clioquinol. We examine their MEP activation barriers in the context of a PD onset mechanism to assess the viability of various chelators for PD remediation.

  1. Meeting Report: Teaching Signal Transduction

    PubMed Central

    Kramer, IJsbrand; Thomas, Geraint

    2006-01-01

    In July, 2005, the European Institute of Chemistry and Biology at the campus of the University of Bordeaux, France, hosted a focused week of seminars, workshops, and discussions around the theme of “teaching signal transduction.” The purpose of the summer school was to offer both junior and senior university instructors a chance to reflect on the development and delivery of their teaching activities in this area. This was achieved by combining open seminars with restricted access workshops and discussion events. The results suggest ways in which systems biology, information and communication technology, Web-based investigations, and high standard illustrations might be more effectively and efficiently incorporated into modern cell biology courses. PMID:17012185

  2. Bleached pigment activates transduction in salamander cones

    PubMed Central

    1995-01-01

    We have used suction electrode recording together with rapid steps into 0.5 mM IBMX solution to investigate changes in guanylyl cyclase velocity produced by pigment bleaching in isolated cones of the salamander Ambystoma tigrinum. Both backgrounds and bleaches accelerate the time course of current increase during steps into IBMX. We interpret this as evidence that the velocity of the guanylyl cyclase is increased in background light or after bleaching. Our results indicate that cyclase velocity increases nearly linearly with increasing percent pigment bleached but nonlinearly (and may saturate) with increasing back-ground intensity. In cones (as previously demonstrated for rods), light-activated pigment and bleached pigment appear to have somewhat different effects on the transduction cascade. The effect of bleaching on cyclase rate is maintained for at least 15-20 min after the light is removed, much longer than is required after a bleach for circulating current and sensitivity to stabilize in an isolated cone. The effect on the cyclase rate can be completely reversed by treatment with liposomes containing 11-cis retinal. The effects of bleaching can also be partially reversed by beta-ionone, an analogue of the chromophore 11- cis-retinal which does not form a covalent attachment to opsin. Perfusion of a bleached cone with beta-ionone produces a rapid increase in circulating current and sensitivity, which rapidly reverses when the beta-ionone is removed. Perfusion with beta-ionone also causes a partial reversal of the bleach-induced acceleration of cyclase velocity. We conclude that bleaching produces an "equivalent background" excitation of the transduction cascade in cones, perhaps by a mechanism similar to that in rods. PMID:8786347

  3. Comparing mechanisms of host manipulation across host and parasite taxa

    USGS Publications Warehouse

    Lafferty, Kevin D.; Shaw, Jenny C.

    2013-01-01

    Parasites affect host behavior in several ways. They can alter activity, microhabitats or both. For trophically transmitted parasites (the focus of our study), decreased activity might impair the ability of hosts to respond to final-host predators, and increased activity and altered microhabitat choice might increase contact rates between hosts and final-host predators. In an analysis of trophically transmitted parasites, more parasite groups altered activity than altered microhabitat choice. Parasites that infected vertebrates were more likely to impair the host’s reaction to predators, whereas parasites that infected invertebrates were more likely to increase the host’s contact with predators. The site of infection might affect how parasites manipulate their hosts. For instance, parasites in the central nervous system seem particularly suited to manipulating host behavior. Manipulative parasites commonly occupy the body cavity, muscles and central nervous systems of their hosts. Acanthocephalans in the data set differed from other taxa in that they occurred exclusively in the body cavity of invertebrates. In addition, they were more likely to alter microhabitat choice than activity. Parasites in the body cavity (across parasite types) were more likely to be associated with increased host contact with predators. Parasites can manipulate the host through energetic drain, but most parasites use more sophisticated means. For instance, parasites target four physiological systems that shape behavior in both invertebrates and vertebrates: neural, endocrine, neuromodulatory and immunomodulatory. The interconnections between these systems make it difficult to isolate specific mechanisms of host behavioral manipulation.

  4. Energy implications of mechanical and mechanical-biological treatment compared to direct waste-to-energy.

    PubMed

    Cimpan, Ciprian; Wenzel, Henrik

    2013-07-01

    Primary energy savings potential is used to compare five residual municipal solid waste treatment systems, including configurations with mechanical (MT) and mechanical-biological (MBT) pre-treatment, which produce waste-derived fuels (RDF and SRF), biogas and/or recover additional materials for recycling, alongside a system based on conventional mass burn waste-to-energy and ash treatment. To examine the magnitude of potential savings we consider two energy efficiency levels (state-of-the-art and best available technology), the inclusion/exclusion of heat recovery (CHP vs. PP) and three different background end-use energy production systems (coal condensing electricity and natural gas heat, Nordic electricity mix and natural gas heat, and coal CHP energy quality allocation). The systems achieved net primary energy savings in a range between 34 and 140 MJprimary/100 MJinput waste, in the different scenario settings. The energy footprint of transportation needs, pre-treatment and reprocessing of recyclable materials was 3-9.5%, 1-18% and 1-8% respectively, relative to total energy savings. Mass combustion WtE achieved the highest savings in scenarios with CHP production, nonetheless, MBT-based systems had similarly high performance if SRF streams were co-combusted with coal. When RDF and SRF was only used in dedicated WtE plants, MBT-based systems totalled lower savings due to inherent system losses and additional energy costs. In scenarios without heat recovery, the biodrying MBS-based system achieved the highest savings, on the condition of SRF co-combustion. As a sensitivity scenario, alternative utilisation of SRF in cement kilns was modelled. It supported similar or higher net savings for all pre-treatment systems compared to mass combustion WtE, except when WtE CHP was possible in the first two background energy scenarios. Recovery of plastics for recycling before energy recovery increased net energy savings in most scenario variations, over those of full

  5. Protein phosphorylation and its role in archaeal signal transduction.

    PubMed

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

    2016-09-01

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

  6. Protein phosphorylation and its role in archaeal signal transduction

    PubMed Central

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

    2016-01-01

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

  7. Sentra, a database of signal transduction proteins.

    SciTech Connect

    Maltsev, N.; Marland, E.; Yu, G. X.; Bhatnagar, S.; Lusk, R.; Mathematics and Computer Science

    2002-01-01

    Sentra (http://www-wit.mcs.anl.gov/sentra) is a database of signal transduction proteins with the emphasis on microbial signal transduction. The database was updated to include classes of signal transduction systems modulated by either phosphorylation or methylation reactions such as PAS proteins and serine/threonine kinases, as well as the classical two-component histidine kinases and methyl-accepting chemotaxis proteins. Currently, Sentra contains signal transduction proteins from 43 completely sequenced prokaryotic genomes as well as sequences from SWISS-PROT and TrEMBL. Signal transduction proteins are annotated with information describing conserved domains, paralogous and orthologous sequences, and conserved chromosomal gene clusters. The newly developed user interface supports flexible search capabilities and extensive visualization of the data.

  8. Parallel Transduction of Nanomechanical Motion Using Plasmonic Resonators

    PubMed Central

    2014-01-01

    We demonstrate parallel transduction of thermally driven mechanical motion of an array of gold-coated silicon nitride nanomechanical beams, by using near-field confinement in plasmonic metal–insulator–metal resonators supported in the gap between the gold layers. The free-space optical readout, enabled by the plasmonic resonances, allows for addressing multiple mechanical resonators in a single measurement. Light absorbed in the metal layer of the beams modifies their mechanical properties, allowing photothermal tuning of the eigenfrequencies. The appearance of photothermally driven parametric amplification indicates the possibility of plasmonic mechanical actuation. PMID:25642442

  9. Blood Pressure Increases in OSA due to Maintained Neurovascular Sympathetic Transduction: Impact of CPAP

    PubMed Central

    Tamisier, Renaud; Tan, Can Ozan; Pepin, Jean-Louis; Levy, Patrick; Taylor, J. Andrew

    2015-01-01

    Study Objectives: To test the hypothesis that greater resting sympathetic activity in obstructive sleep apnea (OSA) syndrome would not induce a lesser sympathetic neurovascular transduction. Design: Case-controlled cohort study. Participants: 33 patients with newly diagnosed OSA without comorbidities and 14 healthy controls. Interventions: 6 months of continuous positive airway pressure (CPAP) treatment for OSA patients and follow-up for 9 healthy controls. Measurements and Results: We assessed resting sympathetic outflow and sympathetic neurovascular transduction. Sympathetic activity was directly measured (microneurography) at rest and in response to sustained isometric handgrip exercise. Neurovascular transduction was derived from the relationship of sympathetic activity and blood pressure to leg blood flow during exercise. Despite an elevated sympathetic activity of ∼50% in OSA compared to controls, neurovascular transduction was not different (i.e., absence of tachyphylaxis). After six months of CPAP, there were significant declines in diastolic pressure, averaging ∼4 mm Hg, and in sympathetic activity, averaging ∼20% with no change in transduction. Conclusions: Greater sympathetic activity in obstructive sleep apnea does not appear to be associated with lesser neurovascular transduction. Hence, elevated sympathetic outflow without lesser transduction may underlie the prevalent development of hypertension in this population that is well controlled by continuous positive airway pressure treatment. Citation: Tamisier R, Tan CO, Pepin JL, Levy P, Taylor JA. Blood pressure increases in OSA due to maintained neurovascular sympathetic transduction: impact of CPAP. SLEEP 2015;38(12):1973–1980. PMID:26039959

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

    NASA Astrophysics Data System (ADS)

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

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

  11. Tuning piezoresistive transduction in nanomechanical resonators by geometrical asymmetries

    SciTech Connect

    Llobet, J.; Sansa, M.; Lorenzoni, M.; Pérez-Murano, F.; Borrisé, X.; San Paulo, A.

    2015-08-17

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

  12. Tuning piezoresistive transduction in nanomechanical resonators by geometrical asymmetries

    NASA Astrophysics Data System (ADS)

    Llobet, J.; Sansa, M.; Lorenzoni, M.; Borrisé, X.; San Paulo, A.; Pérez-Murano, F.

    2015-08-01

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

  13. Hair-bundle friction from transduction channels' gating forces

    NASA Astrophysics Data System (ADS)

    Bormuth, Volker; Barral, Jérémie; Joanny, Jean-François; Jülicher, Frank; Martin, Pascal

    2015-12-01

    Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. We have shown recently that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle and thus provide a major source of damping [2]. We develop here a physical theory of passive hair-bundle mechanics that explains the origin of channel friction. We show that channel friction can be understood quantitatively by coupling the dynamics of the conformational change associated with channel gating to tip-link tension. As a result, varying channel properties affects friction, with faster channels producing smaller friction. The analysis emphasizes the dual role of transduction channels' gating forces, which affect both hair-bundle stiffness and drag. Friction originating from gating of ion channels is a general concept that is relevant to all mechanosensitive channels.

  14. Generalized transduction: new aspects of the events in the water column

    NASA Astrophysics Data System (ADS)

    Velimirov, B.; Chiura, H. X.; Kogure, K.

    2003-04-01

    Virus mediated transfer of genetic elements among bacteria in nature has become a major research topic in the last decade. Along with conjugation and transformation, transduction is a well-known mechanism resulting in horizontal gene transfer in procaryotic organisms. In the case of generalized transduction, all regions of the procaryotic chromosome or other genetic elements in the donor cell are transferred with nearly the same frequency to the recipient. The injection of this DNA induces the generation of stable transductants. Both virulent and temperate phages have the capability to induce general transduction.Within the frame of a study on intergeneric phage-mediated gene transfer between marine bacteria and enteric bacteria, namely an auxotrophic mutant of Escherichia coli (AB1157) we used virus like particles (VLPs) from an oligotrophic marine environment (Mediterranean Sea, West coast of Corsica) and obtained gene transfer frequencies ranging between 10-2 to 10-6 per viral particle. Consequently we had to assume that an important fraction of the VLPs obtained via ultrafiltration (Minitan Ultrafiltration System, Millipore, USA. 30 kDA cut-off filter) from surface seawater have the capability to induce general transduction. In the process of this investigation we made a number of new observations which were not compatible with the concept of general transduction. The obtained transductants were able to produce new VLPs, which had again the capability to induce transduction. In an attempt to characterize these particles we show that their appearance in the experiment was neither related to plaque formation nor to cell lysis and we discuss the concept of transduction in the light of new experimental evidence concerning transducing particles. Furthermore, a preliminary numerical model allowing an estimation of the transduction events, taking place in the water column within a year is presented.

  15. Generalized Transduction of Small Yersinia enterocolitica Plasmids

    PubMed Central

    Hertwig, Stefan; Popp, Andreas; Freytag, Barbara; Lurz, Rudi; Appel, Bernd

    1999-01-01

    To study phage-mediated gene transfer in Yersinia, the ability of Yersinia phages to transduce naturally occurring plasmids was investigated. The transduction experiments were performed with a temperate phage isolated from a pathogenic Yersinia enterocolitica strain and phage mixtures isolated from sewage. Small plasmids (4.3 and 5.8 kb) were transduced at a frequency of 10−5 to 10−7/PFU. However, we could not detect the transduction of any indigenous virulence plasmid (ca. 72 kb) in pathogenic Yersinia strains. Transductants obtained by infection with the temperate phage were lysogenic and harbored the phage genome in their chromosomes. PMID:10473387

  16. Perturbation in T cell signal transduction pathway in microgravity

    NASA Astrophysics Data System (ADS)

    Kulkarni, A.; Yamauchi, K.; Taga, M.; Odle, J.; Sundaresan, A.; Pellis, N.

    T lymphocytes are regulatory and effector components of the immune system. It has been documented that T cell function is down regulated in microgravity of space flight and also in microgravity analogs. Lymphocyte signal transduction and the function of its effector elements are essential for proper functioning of T cells in any environment. We have shown that T cell mediated responses are down regulated in the microgravity analogs; in vivo antiorthostatic suspension mouse model as well as the in vitro culture system of Bioreactor (BIO). One of the postulated mechanisms for this effect is perturbation in signal transduction mechanisms via disruption of cytoskeleton due to the tensile force acting on cell membranes. Using BIO cultured mouse splenocytes we analyzed T cell signaling molecules associated with T cell receptor (TcR) and essential in signal transduction and cellular function. ZAP-70, a protein tyrosine kinase, is unaltered in 1g, however, is decreased 50% in the BIO at 96 hrs. SLP-76 levels drop more than 50% early in Bio samples at 24 and 48 hrs. LAT was unchanged. Once activated, ZAP-70 interacts with and phosphorylates Vav, SLP-76 and LAT proteins resulting in one of the complexs, namely SLP- 76/Vav, which putatively plays a regulatory role in TcR signal transduction pathway, perhaps via the actin cytoskeleton. Thus the decrease in SLP -76 at earlier time point could lead to ineffective recruitment and activation of cytoskeleton. Further studies are underway to delineate the mechanisms of T cell down regulation in microgravity. (Supported by NASA NCC8-168 grant, ADK)

  17. Gravitational Effects on Signal Transduction

    NASA Technical Reports Server (NTRS)

    Sytkowski, Arthur J.

    1999-01-01

    The purpose of this study was to investigate in ground-based experiments, the effect of microgravity on in vitro erythroid differentiation triggered by the hematopoietic growth factor erythropoietin (Epo) and to begin to determine whether this is associated with the anemia of space flight. We chose to use a model cell culture system with which we have had a long and successful experience. These cells, designated Rauscher murine erythroleukemia, grow independently in suspension culture. We first compared the growth rate of Rauscher cells under conditions of simulated microgravity with that of cells grown at 1XG in standard tissue culture flasks. Therefore, since there were fewer cells in the RWV at each specified time, glucose consumption per cell was increased in simulated microgravity. We next began to study the effect of simulated microgravity on erythropoietin induced differentiation of these cells. In another experiment, we allow the cells to grown in flasks or in the RWV for 24 hours prior to the addition of Epo. We initiated studies of c-myb, a proto-oncogene the down-regulation of which is necessary for erythroid differentiation. These preliminary results suggest that simulated microgravity interferes with the signal to c-myb. This may be part of the mechanism that blocks differentiation. A flight experiment is planned within the next 18- 24 months.

  18. Signal transduction and information processing in mammalian taste buds

    PubMed Central

    2013-01-01

    The molecular machinery for chemosensory transduction in taste buds has received considerable attention within the last decade. Consequently, we now know a great deal about sweet, bitter, and umami taste mechanisms and are gaining ground rapidly on salty and sour transduction. Sweet, bitter, and umami tastes are transduced by G-protein-coupled receptors. Salty taste may be transduced by epithelial Na channels similar to those found in renal tissues. Sour transduction appears to be initiated by intracellular acidification acting on acid-sensitive membrane proteins. Once a taste signal is generated in a taste cell, the subsequent steps involve secretion of neurotransmitters, including ATP and serotonin. It is now recognized that the cells responding to sweet, bitter, and umami taste stimuli do not possess synapses and instead secrete the neurotransmitter ATP via a novel mechanism not involving conventional vesicular exocytosis. ATP is believed to excite primary sensory afferent fibers that convey gustatory signals to the brain. In contrast, taste cells that do have synapses release serotonin in response to gustatory stimulation. The postsynaptic targets of serotonin have not yet been identified. Finally, ATP secreted from receptor cells also acts on neighboring taste cells to stimulate their release of serotonin. This suggests that there is important information processing and signal coding taking place in the mammalian taste bud after gustatory stimulation. PMID:17468883

  19. [Cyclic Guanosine Monophosphate as a Mediator in Processes of Stress Signaling Transduction in Higher Plants].

    PubMed

    Dubovskaya, L V; Bakakina, Y S; Volotovski, I D

    2015-01-01

    Currently, biophysical mechanisms of stress signaling transduction became an object of consideration of researchers in connection with the urgent necessity to develop new techniques to enhance the sustainability and productivity of agricultural crops. The development of sensitive methods for the determination of cyclic guanosine monophosphate (cGMP) and comparative analysis of cGMP-dependent events in biological systems has contributed to progress in the understanding of the functioning of cGMP in plant cells. Currently, it is shown that cGMP as a secondary mediator is involved in such vital processes of growth and development of plants as seed germination, cell division, development of chloroplasts, flowering and regulation of stomatal movements. This review summarizes the available data in the literature about the role of cGMP in the responses of plant organisms to the action of stress factors of abiotic and biotic nature and its interaction with other intracellular mediators. With the use of existing ideas about the biophysical mechanisms of stress in plants, the basic elements of cGMP-dependent signal transduction system in a plant cell are considered. PMID:26394467

  20. EDITORIAL: Special section on signal transduction Special section on signal transduction

    NASA Astrophysics Data System (ADS)

    Shvartsman, Stanislav

    2012-08-01

    This special section of Physical Biology focuses on multiple aspects of signal transduction, broadly defined as the study of the mechanisms by which cells communicate with their environment. Mechanisms of cell communication involve detection of incoming signals, which can be chemical, mechanical or electromagnetic, relaying these signals to intracellular processes, such as cytoskeletal networks or gene expression systems, and, ultimately, converting these signals to responses such as cell differentiation or death. Given the multiscale nature of signal transduction systems, they must be studied at multiple levels, from the identities and structures of molecules comprising signal detection and interpretation networks, to the systems-level properties of these networks. The 11 papers in this special section illustrate some of the most exciting aspects of signal transduction research. The first two papers, by Marie-Anne Félix [1] and by Efrat Oron and Natalia Ivanova [2], focus on cell-cell interactions in developing tissues, using vulval patterning in worm and cell fate specification in mammalian embryos as prime examples of emergent cell behaviors. Next come two papers from the groups of Julio Saez-Rodriguez [3] and Kevin Janes [4]. These papers discuss how the causal relationships between multiple components of signaling systems can be inferred using multivariable statistical analysis of empirical data. An authoritative review by Zarnitsyna and Zhu [5] presents a detailed discussion of the sequence of signaling events involved in T-cell triggering. Once the structure and components of the signaling systems are determined, they can be modeled using approaches that have been successful in other physical sciences. As two examples of such approaches, reviews by Rubinstein [6] and Kholodenko [7], present reaction-diffusion models of cell polarization and thermodynamics-based models of gene regulation. An important class of models takes the form of enzymatic networks

  1. Comparative Proteomic Analysis of Cultured Suspension Cells of the Halophyte Halogeton glomeratus by iTRAQ Provides Insights into Response Mechanisms to Salt Stress

    PubMed Central

    Wang, Juncheng; Yao, Lirong; Li, Baochun; Meng, Yaxiong; Ma, Xiaole; Lai, Yong; Si, Erjing; Ren, Panrong; Yang, Ke; Shang, Xunwu; Wang, Huajun

    2016-01-01

    Soil salinity severely threatens land use capability and crop yields worldwide. An analysis of the molecular mechanisms of salt tolerance in halophytes will contribute to the development of salt-tolerant crops. In this study, a combination of physiological characteristics and iTRAQ-based proteomic approaches was conducted to investigate the molecular mechanisms underlying the salt response of suspension cell cultures of halophytic Halogeton glomeratus. These cells showed halophytic growth responses comparable to those of the whole plant. In total, 97 up-regulated proteins and 192 down-regulated proteins were identified as common to both 200 and 400 mM NaCl concentration treatments. Such salinity responsive proteins were mainly involved in energy, carbohydrate metabolism, stress defense, protein metabolism, signal transduction, cell growth, and cytoskeleton metabolism. Effective regulatory protein expression related to energy, stress defense, and carbohydrate metabolism play important roles in the salt-tolerance of H. glomeratus suspension cell cultures. However, known proteins regulating Na+ efflux from the cytoplasm and its compartmentalization into the vacuole did not change significantly under salinity stress suggesting our existing knowledge concerning Na+ extrusion and compartmentalization in halophytes needs to be evaluated further. Such data are discussed in the context of our current understandings of the mechanisms involved in the salinity response of the halophyte, H. glomeratus. PMID:26904073

  2. Comparative Proteomic Analysis of Cultured Suspension Cells of the Halophyte Halogeton glomeratus by iTRAQ Provides Insights into Response Mechanisms to Salt Stress.

    PubMed

    Wang, Juncheng; Yao, Lirong; Li, Baochun; Meng, Yaxiong; Ma, Xiaole; Lai, Yong; Si, Erjing; Ren, Panrong; Yang, Ke; Shang, Xunwu; Wang, Huajun

    2016-01-01

    Soil salinity severely threatens land use capability and crop yields worldwide. An analysis of the molecular mechanisms of salt tolerance in halophytes will contribute to the development of salt-tolerant crops. In this study, a combination of physiological characteristics and iTRAQ-based proteomic approaches was conducted to investigate the molecular mechanisms underlying the salt response of suspension cell cultures of halophytic Halogeton glomeratus. These cells showed halophytic growth responses comparable to those of the whole plant. In total, 97 up-regulated proteins and 192 down-regulated proteins were identified as common to both 200 and 400 mM NaCl concentration treatments. Such salinity responsive proteins were mainly involved in energy, carbohydrate metabolism, stress defense, protein metabolism, signal transduction, cell growth, and cytoskeleton metabolism. Effective regulatory protein expression related to energy, stress defense, and carbohydrate metabolism play important roles in the salt-tolerance of H. glomeratus suspension cell cultures. However, known proteins regulating Na(+) efflux from the cytoplasm and its compartmentalization into the vacuole did not change significantly under salinity stress suggesting our existing knowledge concerning Na(+) extrusion and compartmentalization in halophytes needs to be evaluated further. Such data are discussed in the context of our current understandings of the mechanisms involved in the salinity response of the halophyte, H. glomeratus. PMID:26904073

  3. Ion channels and the transduction of light signals

    NASA Technical Reports Server (NTRS)

    Spalding, E. P.; Evans, M. L. (Principal Investigator)

    2000-01-01

    Studies of biological light-sensing mechanisms are revealing important roles for ion channels. Photosensory transduction in plants is no exception. In this article, the evidence that ion channels perform such signal-transducing functions in the complex array of mechanisms that bring about plant photomorphogenesis will be reviewed and discussed. The examples selected for discussion range from light-gradient detection in unicellular algae to the photocontrol of stem growth in Arabidopsis. Also included is some discussion of the technical aspects of studies that combine electrophysiology and photobiology.

  4. The meridian system and mechanism of acupuncture: a comparative review. Part 3: Mechanisms of acupuncture therapies.

    PubMed

    Chang, Shyang

    2013-06-01

    The human body is a hierarchical organism containing many levels of mutually interacting oscillatory systems. From the viewpoint of traditional Chinese medicine, health is a state of harmony emergent from the interactions of these systems and disease is a state of discord. Hence, human diseases are considered as disturbed functions rather than changed structures. Indeed, the change from normal to abnormal structure may be beneficent rather than maleficent. For example, when one kidney becomes twice the normal size following the destruction of the other kidney, it is good and not bad for us because we might be dead otherwise. Therefore, in Part 3 of this three-part series, emphasis is mainly laid on the acupuncture mechanisms of treating disturbed physiological functions rather than disordered structures. At first, the basic tenets of conventional neuroscience and cardiology are reevaluated so that clear understanding of how nervous and cardiovascular systems work together can be obtained. Then, the general principles of diagnosis and treatment in traditional Chinese medicine from the integrative perspective of complex dynamic systems are proposed. Finally, mechanisms of acupuncture therapies for treating 14 different categories of disorders will be elucidated via the magneto-electric inductive effects of the meridian system. PMID:23915848

  5. Effects of dynamic compression on lentiviral transduction in an in vitro airway wall model.

    PubMed

    Tomei, Alice A; Choe, Melanie M; Swartz, Melody A

    2008-01-01

    Asthmatic patients are more susceptible to viral infection, and we asked whether dynamic strain on the airway wall (such as that associated with bronchoconstriction) would influence the rate of viral infection of the epithelial and subepithelial cells. To address this, we characterized the barrier function of a three-dimensional culture model of the bronchial airway wall mucosa, modified the culture conditions for optimization of ciliogenesis, and compared epithelial and subepithelial green fluorescent protein (GFP) transduction by a pWpts-GFP lentivirus, pseudotyped with VSV-G, under static vs. dynamic conditions. The model consisted of human lung fibroblasts, bronchial epithelial cells, and a type I collagen matrix, and after 21 days of culture at air liquid interface, it exhibited a pseudostratified epithelium comprised of basal cells, mucus-secreting cells, and ciliated columnar cells with beating cilia. Microparticle tracking revealed partial coordination of mucociliary transport among groups of cells. Slow dynamic compression of the airway wall model (15% strain at 0.1 Hz over 3 days) substantially enhanced GFP transduction of epithelial cells and underlying fibroblasts. Fibroblast-only controls showed a similar degree of transduction enhancement when undergoing dynamic strain, suggesting enhanced transport through the matrix. Tight junction loss in the epithelium after mechanical stress was observed by immunostaining. We conclude that dynamic compressive strain such as that associated with bronchoconstriction may promote transepithelial transport and enhance viral transgene delivery to epithelial and subepithelial cells. This finding has significance for asthma pathophysiology as well as for designing delivery strategies of viral gene therapies to the airways. PMID:18024723

  6. An Electrokinetic Model of Transduction in the Semicircular Canal

    PubMed Central

    O'Leary, Dennis P.

    1970-01-01

    Transduction in the semicircular canal was studied by focusing an infrared beam on either side of exposed ampullae from the posterior canals of Rana pipiens. The direction of fluid movement resulting from a stimulus was inferred by observing the polarity of the change in afferent impulse mean rate relative to the spontaneous value. On the basis of the accepted functional polarization of this receptor, the results indicate that fluid moved toward the warmer side of the ampulla. Convection and thermal reception were shown to be unlikely explanations for these results. Morover, cupular displacements toward the warmer side would not be expected. Because thermo-osmosis can cause fluid to move toward the warmer side in a gelatin membrane, the results can be interpreted as evidence that thermo-osmosis occurred in the gelatinous cupula and influenced the transduction mechanism. Thermo-osmosis of liquids appears to be due to an electric field that is set up in a charged membrane; hence, the hair cells might have detected an electric field that occurred in the cupula during thermo-osmosis. Electroreception might be an important link in the transduction of physiological stimuli also. Rotational stimuli could result in weak electric fields in the cupula by the mechanoelectric effect. Cupular displacements could be important for large stimuli, but extrapolations to threshold stimuli suggest displacements of angstrom amplitudes. Therefore, electroreception by the hair cells could be an explanation of the great sensitivity that has been observed in the semicircular canal and other labyrinthine receptors. PMID:5496906

  7. An electrokinetic model of transduction in the semicircular canal.

    PubMed

    O'Leary, D P

    1970-09-01

    Transduction in the semicircular canal was studied by focusing an infrared beam on either side of exposed ampullae from the posterior canals of Rana pipiens. The direction of fluid movement resulting from a stimulus was inferred by observing the polarity of the change in afferent impulse mean rate relative to the spontaneous value. On the basis of the accepted functional polarization of this receptor, the results indicate that fluid moved toward the warmer side of the ampulla. Convection and thermal reception were shown to be unlikely explanations for these results. Morover, cupular displacements toward the warmer side would not be expected. Because thermo-osmosis can cause fluid to move toward the warmer side in a gelatin membrane, the results can be interpreted as evidence that thermo-osmosis occurred in the gelatinous cupula and influenced the transduction mechanism. Thermo-osmosis of liquids appears to be due to an electric field that is set up in a charged membrane; hence, the hair cells might have detected an electric field that occurred in the cupula during thermo-osmosis. Electroreception might be an important link in the transduction of physiological stimuli also. Rotational stimuli could result in weak electric fields in the cupula by the mechanoelectric effect. Cupular displacements could be important for large stimuli, but extrapolations to threshold stimuli suggest displacements of angstrom amplitudes. Therefore, electroreception by the hair cells could be an explanation of the great sensitivity that has been observed in the semicircular canal and other labyrinthine receptors. PMID:5496906

  8. Soliton growth-signal transduction in topologically quantized T cells

    NASA Astrophysics Data System (ADS)

    Matsson, Leif

    1993-09-01

    A model for growth-signal transduction of the T cell and its growth factor, interleukin-2, is presented. It is obtained as a generalization of the usual rate equation and is founded on the observation that a definite number of receptor occupations must take place in order to promote transition to the S phase and subsequent DNA replication. The generalized rate equation is identified as the equation of motion of a Lagrangian field theory of Ginzburg-Landau (Goldstone) type. However it is not an ad hoc model but is a microscopic theory of the interaction of interleukin-2 and its receptor. The topological quantum number of the model is related to the observed definite number of receptor occupations required to elicit growth-signal transduction. Individual receptor quanta, up to this limit, are subjected to a type of Bose condensation. This collective excitation constitutes the growth signal in the form of a topological kink soliton which is then launched by the next potential receptor occupation that makes the interaction repulsive. The model provides a possible long-absent explanation of the triggering mechanism for growth-signal transduction by means of the ambivalent interaction, which switches sign after a definite number of receptor occupations. Moreover, it offers an explanation of how Nature screens out fractional signals in the growth-signal-transduction process of T cells. Although the model is derived for assumed point-like cells and certain other restrictions, the obtained dose-response curves are in striking agreement with proliferation data from studies of both the leukemic T cell line MLA-144 from gibbon ape and normal human T cells in, and without, the presence of monoclonal anti-Tac antibodies.

  9. Meeting report: Signal transduction meets systems biology

    PubMed Central

    2012-01-01

    In the 21st century, systems-wide analyses of biological processes are getting more and more realistic. Especially for the in depth analysis of signal transduction pathways and networks, various approaches of systems biology are now successfully used. The EU FP7 large integrated project SYBILLA (Systems Biology of T-cell Activation in Health and Disease) coordinates such an endeavor. By using a combination of experimental data sets and computational modelling, the consortium strives for gaining a detailed and mechanistic understanding of signal transduction processes that govern T-cell activation. In order to foster the interaction between systems biologists and experimentally working groups, SYBILLA co-organized the 15th meeting “Signal Transduction: Receptors, Mediators and Genes” together with the Signal Transduction Society (STS). Thus, the annual STS conference, held from November 7 to 9, 2011 in Weimar, Germany, provided an interdisciplinary forum for research on signal transduction with a major focus on systems biology addressing signalling events in T-cells. Here we report on a selection of ongoing projects of SYBILLA and how they were discussed at this interdisciplinary conference. PMID:22546078

  10. The transduction properties of intercostal muscle mechanoreceptors

    PubMed Central

    Holt, Gregory A; Johnson, Richard D; Davenport, Paul W

    2002-01-01

    Background Intercostal muscles are richly innervated by mechanoreceptors. In vivo studies of cat intercostal muscle have shown that there are 3 populations of intercostal muscle mechanoreceptors: primary muscle spindles (1°), secondary muscle spindles (2°) and Golgi tendon organs (GTO). The purpose of this study was to determine the mechanical transduction properties of intercostal muscle mechanoreceptors in response to controlled length and velocity displacements of the intercostal space. Mechanoreceptors, recorded from dorsal root fibers, were localized within an isolated intercostal muscle space (ICS). Changes in ICS displacement and the velocity of ICS displacement were independently controlled with an electromagnetic motor. ICS velocity (0.5 – 100 μm/msec to a displacement of 2,000 μm) and displacement (50–2,000 μm at a constant velocity of 10 μm/msec) parameters encompassed the full range of rib motion. Results Both 1° and 2° muscle spindles were found evenly distributed within the ICS. GTOs were localized along the rib borders. The 1° spindles had the greatest discharge frequency in response to displacement amplitude followed by the 2° afferents and GTOs. The 1° muscle spindles also possessed the greatest discharge frequency in response to graded velocity changes, 3.0 spikes·sec-1/μm·msec-1. GTOs had a velocity response of 2.4 spikes·sec-1/μm·msec-1 followed by 2° muscle spindles at 0.6 spikes·sec-1/μm·msec-1. Conclusion The results of this study provide a systematic description of the mechanosenitivity of the 3 types of intercostal muscle mechanoreceptors. These mechanoreceptors have discharge properties that transduce the magnitude and velocity of intercostal muscle length. PMID:12392601

  11. P2CS: a two-component system resource for prokaryotic signal transduction research

    PubMed Central

    Barakat, Mohamed; Ortet, Philippe; Jourlin-Castelli, Cécile; Ansaldi, Mireille; Méjean, Vincent; Whitworth, David E

    2009-01-01

    Background With the escalation of high throughput prokaryotic genome sequencing, there is an ever-increasing need for databases that characterise, catalogue and present data relating to particular gene sets and genomes/metagenomes. Two-component system (TCS) signal transduction pathways are the dominant mechanisms by which micro-organisms sense and respond to external as well as internal environmental changes. These systems respond to a wide range of stimuli by triggering diverse physiological adjustments, including alterations in gene expression, enzymatic reactions, or protein-protein interactions. Description We present P2CS (Prokaryotic 2-Component Systems), an integrated and comprehensive database of TCS signal transduction proteins, which contains a compilation of the TCS genes within 755 completely sequenced prokaryotic genomes and 39 metagenomes. P2CS provides detailed annotation of each TCS gene including family classification, sequence features, functional domains, as well as genomic context visualization. To bypass the generic problem of gene underestimation during genome annotation, we also constituted and searched an ORFeome, which improves the recovery of TCS proteins compared to searches on the equivalent proteomes. Conclusion P2CS has been developed for computational analysis of the modular TCSs of prokaryotic genomes and metagenomes. It provides a complete overview of information on TCSs, including predicted candidate proteins and probable proteins, which need further curation/validation. The database can be browsed and queried with a user-friendly web interface at . PMID:19604365

  12. Piezotransistive transduction of femtoscale displacement for photoacoustic spectroscopy

    PubMed Central

    Talukdar, Abdul; Faheem Khan, M.; Lee, Dongkyu; Kim, Seonghwan; Thundat, Thomas; Koley, Goutam

    2015-01-01

    Measurement of femtoscale displacements in the ultrasonic frequency range is attractive for advanced material characterization and sensing, yet major challenges remain in their reliable transduction using non-optical modalities, which can dramatically reduce the size and complexity of the transducer assembly. Here we demonstrate femtoscale displacement transduction using an AlGaN/GaN heterojunction field effect transistor-integrated GaN microcantilever that utilizes piezoelectric polarization-induced changes in two-dimensional electron gas to transduce displacement with very high sensitivity. The piezotransistor demonstrated an ultra-high gauge factor of 8,700 while consuming an extremely low power of 1.36 nW, and transduced external excitation with a superior noise-limited resolution of 12.43 fm Hz−1/2 and an outstanding responsivity of 170 nV fm−1, which is comparable to the optical transduction limits. These extraordinary characteristics, which enabled unique detection of nanogram quantity of analytes using photoacoustic spectroscopy, can be readily exploited in realizing a multitude of novel sensing paradigms. PMID:26258983

  13. Piezotransistive transduction of femtoscale displacement for photoacoustic spectroscopy

    NASA Astrophysics Data System (ADS)

    Talukdar, Abdul; Faheem Khan, M.; Lee, Dongkyu; Kim, Seonghwan; Thundat, Thomas; Koley, Goutam

    2015-08-01

    Measurement of femtoscale displacements in the ultrasonic frequency range is attractive for advanced material characterization and sensing, yet major challenges remain in their reliable transduction using non-optical modalities, which can dramatically reduce the size and complexity of the transducer assembly. Here we demonstrate femtoscale displacement transduction using an AlGaN/GaN heterojunction field effect transistor-integrated GaN microcantilever that utilizes piezoelectric polarization-induced changes in two-dimensional electron gas to transduce displacement with very high sensitivity. The piezotransistor demonstrated an ultra-high gauge factor of 8,700 while consuming an extremely low power of 1.36 nW, and transduced external excitation with a superior noise-limited resolution of 12.43 fm Hz-1/2 and an outstanding responsivity of 170 nV fm-1, which is comparable to the optical transduction limits. These extraordinary characteristics, which enabled unique detection of nanogram quantity of analytes using photoacoustic spectroscopy, can be readily exploited in realizing a multitude of novel sensing paradigms.

  14. Sympathetic vascular transduction is augmented in young normotensive blacks

    NASA Technical Reports Server (NTRS)

    Ray, Chester A.; Monahan, Kevin D.

    2002-01-01

    The purpose of the present study was to determine sympathetic vascular transduction in young normotensive black and white adults. We hypothesized that blacks would demonstrate augmented transduction of muscle sympathetic nerve activity (MSNA) into vascular resistance. To test this hypothesis, MSNA, forearm blood flow, heart rate, and arterial blood pressure were measured during lower body negative pressure (LBNP). At rest, no differences existed in arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance (FVR). Likewise, LBNP elicited comparable responses of these variables for blacks and whites. Baseline MSNA did not differ between blacks and whites, but whites demonstrated greater increases during LBNP (28 +/- 7 vs. 55 +/- 18%, 81 +/- 21 vs. 137 +/- 42%, 174 +/- 81 vs. 556 +/- 98% for -5, -15, and -40 mmHg LBNP, respectively; P < 0.001). Consistent with smaller increases in MSNA but similar FVR responses during LBNP, blacks demonstrated greater sympathetic vascular transduction (%FVR/%MSNA) than whites (0.95 +/- 0.07 vs. 0.82 +/- 0.07 U; 0.82 +/- 0.11 vs. 0.64 +/- 0.09 U; 0.95 +/- 0.37 vs. 0.35 +/- 0.09 U; P < 0.01). In summary, young whites demonstrate greater increases in MSNA during baroreceptor unloading than age-matched normotensive blacks. However, more importantly, for a given increase in MSNA, blacks demonstrate greater forearm vasoconstriction than whites. This finding may contribute to augmented blood pressure reactivity in blacks.

  15. Probing visual transduction in a plant cell

    PubMed Central

    Uhl, Rainer; Hegemann, Peter

    1990-01-01

    Light scattering studies of vertebrate rod cells have greatly aided our understanding of the visual transduction process. This technique has now been successfully applied to study visual transduction in a unicellular alga. Flash-induced light scattering changes have been recorded which are repeatable, graded with photon exposure, and adaptive. They appear on a timescale of 15-1,000 ms and correlate kinetically with flash-induced movement responses. The responsible photoreceptor is a rhodopsin. Evidence is provided for the ability of the organism to count single photons. PMID:19431775

  16. Effects of electrode surface structure on the mechanoelectrical transduction of IPMC sensors

    NASA Astrophysics Data System (ADS)

    Palmre, Viljar; Pugal, David; Kim, Kwang

    2014-03-01

    This study investigates the effects of electrode surface structure on the mechanoelectrical transduction of IPMC sensors. A physics-based mechanoelectrical transduction model was developed that takes into account the electrode surface profile (shape) by describing the polymer-electrode interface as a Koch fractal structure. Based on the model, the electrode surface effects were experimentally investigated in case of IPMCs with Pd-Pt electrodes. IPMCs with different electrode surface structures were fabricated through electroless plating process by appropriately controlling the synthesis parameters and conditions. The changes in the electrode surface morphology and the corresponding effects on the IPMC mechanoelectrical transduction were examined. Our experimental results indicate that increasing the dispersion of Pd particles near the membrane surface, and thus the polymer-electrode interfacial area, leads to a higher peak mechanoelectrically induced voltage of IPMC. However, the overall effect of the electrode surface structure is relatively low compared to the electromechanical transduction, which is in good agreement with theoretical prediction.

  17. Changes in gene expression and signal transduction in microgravity

    NASA Technical Reports Server (NTRS)

    Hughes-Fulford, M.

    2001-01-01

    Studies from space flights over the past three decades have demonstrated that basic physiological changes occur in humans during space flight. These changes include cephalic fluid shifts, loss of fluid and electrolytes, loss of muscle mass, space motion sickness, anemia, reduced immune response, and loss of calcium and mineralized bone. The cause of most of these manifestations is not known and until recently, the general approach was to investigate general systemic changes, not basic cellular responses to microgravity. This laboratory has recently studied gene growth and activation of normal osteoblasts (MC3T3-El) during spaceflight. Osteoblast cells were grown on glass coverslips and loaded in the Biorack plunger boxes. The osteoblasts were launched in a serum deprived state, activated in microgravity and collected in microgravity. The osteoblasts were examined for changes in gene expression and signal transduction. Approximately one day after growth activation significant changes were observed in gene expression in 0-G flight samples. Immediate early growth genes/growth factors cox-2, c-myc, bcl2, TGF beta1, bFGF and PCNA showed a significant diminished mRNA induction in microgravity FCS activated cells when compared to ground and 1-G flight controls. Cox-1 was not detected in any of the samples. There were no significant differences in the expression of reference gene mRNA between the ground, 0-G and 1-G samples. The data suggest that quiescent osteoblasts are slower to enter the cell cycle in microgravity and that the lack of gravity itself may be a significant factor in bone loss in spaceflight. Preliminary data from our STS 76 flight experiment support our hypothesis that a basic biological response occurs at the tissue, cellular, and molecular level in 0-G. Here we examine ground-based and space flown data to help us understand the mechanism of bone loss in microgravity.

  18. Transduction of nanovolt signals: Limits of electric-field detection

    NASA Astrophysics Data System (ADS)

    Kalmijn, J.

    1989-11-01

    Life scientists discussed the extreme electrical sensitivity of marine sharks, skates, and rays. After reviewing the results of earlier studies on the electric sense at the animal and system levels, the participants discussed the basic process of signal transduction in terms of voltage-sensitive ionic channels. Struck by the small charge displacements needed for excitation, they strongly recommended that sensory biologists, physiologists, and biophysicists join in a concerted effort to initiate new research on the ionic mechanisms of electric field detection. To obtain detailed information on the electroreceptive membrane and its ionic channels, high resolution recording techniques will be mandatory.

  19. Spatial organization and signal transduction at intercellular junctions

    PubMed Central

    Manz, Boryana N.; Groves, Jay T.

    2013-01-01

    The coordinated organization of cell membrane receptors into diverse micrometre-scale spatial patterns is emerging as an important theme of intercellular signalling, as exemplified by immunological synapses. Key characteristics of these patterns are that they transcend direct protein–protein interactions, emerge transiently and modulate signal transduction. Such cooperativity over multiple length scales presents new and intriguing challenges for the study and ultimate understanding of cellular signalling. As a result, new experimental strategies have emerged to manipulate the spatial organization of molecules inside living cells. The resulting spatial mutations yield insights into the interweaving of the spatial, mechanical and chemical aspects of intercellular signalling. PMID:20354536

  20. Fluorescence polarization assays in signal transduction discovery.

    PubMed

    Sportsman, J Richard; Daijo, Janet; Gaudet, Elizabeth A

    2003-05-01

    Fluorescence polarization (FP) has become widely employed for high throughput screening used in pharmaceutical drug discovery. Assays of important signal transduction targets are now adapted to FP. In this review we examine assays for cyclic adenosine monophosphate, phosphodiesterases, and protein kinases and phosphatases using FP competitive immunoassays and a direct enzymatic method called IMAP. PMID:12678698

  1. In-plane photonic transduction for microcantilever sensor arrays

    NASA Astrophysics Data System (ADS)

    Nordin, Gregory P.; Noh, Jong Wok; Kim, Seunghyun

    2007-02-01

    Microcantilevers show significant promise in sensing minute quantities of chemical and biological analytes in vapor and liquid media. Much of the reported work on microcantilever sensors has made use of single functionalized microcantilevers, usually derived from commercially available atomic force microscope (AFM) cantilevers. However, arrays with hundreds to thousands of microcantilevers on a single chip are required to create sophisticated, broad spectrum chemical and biological sensors in which individual microcantilevers have different bio- or chemoselective coatings. Unfortunately, the most sensitive microcantilever readout mechanisms (such as laser beam reflection as used in atomic force microscopy) are not readily scalable to large arrays. We therefore introduce a new microcantilever transduction mechanism for silicon-on-insulator (SOI) microcantilevers that is designed to scale to large arrays while maintaining a very compact form factor and high sensitivity. This mechanism is based on in-plane photonic transduction of microcantilever deflection in which the microcantilever itself forms a single mode rib waveguide. Light from the end of the microcantilever is directed across a small gap to an asymmetric receiving waveguide with two outputs that enables differential detection of microcantilever deflection. Initial noise and optical power budget calculations indicate that deflection sensitivities in the 10's of picometer range should be achievable.

  2. Abscisic acid perception and signaling transduction in strawberry

    PubMed Central

    Li, Chunli; Jia, Haifeng; Chai, Yemao; Shen, Yuanyue

    2011-01-01

    On basis of fruit differential respiration and ethylene effects, climacteric and non-climacteric fruits have been classically defined. Over the past decades, the molecular mechanisms of climacteric fruit ripening were abundantly described and found to focus on ethylene perception and signaling transduction. In contrast, until our most recent breakthroughs, much progress has been made toward understanding the signaling perception and transduction mechanisms for abscisic acid (ABA) in strawberry, a model for non-climacteric fruit ripening. Our reports not only have provided several lines of strong evidences for ABA-regulated ripening of strawberry fruit, but also have demonstrated that homology proteins of Arabidopsis ABA receptors, including PYR/PYL/RCAR and ABAR/CHLH, act as positive regulators of ripening in response to ABA. These receptors also trigger a set of ABA downstream signaling components, and determine significant changes in the expression levels of both sugar and pigment metabolism-related genes that are closely associated with ripening. Soluble sugars, especially sucrose, may act as a signal molecular to trigger ABA accumulation through an enzymatic action of 9-cis-epoxycarotenoid dioxygenase 1 (FaNCED1). This mini-review offers an overview of these processes and also outlines the possible, molecular mechanisms for ABA in the regulation of strawberry fruit ripening through the ABA receptors. PMID:22095148

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

    SciTech Connect

    Zaro, Jennica L.; Shen Weichiang . E-mail: weishen@usc.edu

    2005-07-01

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

  4. Strong cortical and spinal cord transduction after AAV7 and AAV9 delivery into the cerebrospinal fluid of nonhuman primates.

    PubMed

    Samaranch, Lluis; Salegio, Ernesto A; San Sebastian, Waldy; Kells, Adrian P; Bringas, John R; Forsayeth, John; Bankiewicz, Krystof S

    2013-05-01

    The present study builds on previous work showing that infusion of adeno-associated virus type 9 (AAV9) into the cisterna magna (CM) of nonhuman primates resulted in widespread transduction throughout cortex and spinal cord. Transduction efficiency was severely limited, however, by the presence of circulating anti-AAV antibodies. Accordingly, we compared AAV9 to a related serotype, AAV7, which has a high capsid homology. CM infusion of either AAV7 or AAV9 directed high level of cell transduction with similar patterns of distribution throughout brain cortex and along the spinal cord. Dorsal root ganglia and corticospinal tracts were also transduced. Both astrocytes and neurons were transduced. Interestingly, little transduction was observed in peripheral organs. Our results indicate that intrathecal delivery of either AAV7 or AAV9 directs a robust and widespread cellular transduction in the central nervous system and other peripheral neural structures. PMID:23517473

  5. CD46-Mediated Transduction of a Species D Adenovirus Vaccine Improves Mucosal Vaccine Efficacy

    PubMed Central

    Camacho, Zenaido T.; Turner, Mallory A.; Barry, Michael A.

    2014-01-01

    Abstract The high levels of preexisting immunity against Adenovirus type 5 (Ad5) have deemed Ad5 unusable for translation as a human vaccine vector. Low seroprevalent alternative viral vectors may be less impacted by preexisting immunity, but they may also have significantly different phenotypes from that of Ad5. In this study we compare species D Ads (26, 28, and 48) to the species C Ad5. In vitro transduction studies show striking differences between the species C and D viruses. Most notably, Ad26 transduced human dendritic cells much more effectively than Ad5. In vivo imaging studies showed strikingly different transgene expression profiles. The Ad5 virus was superior to the species D viruses in BALB/c mice when delivered intramuscularly. However, the inverse was true when the viruses were delivered mucosally via the intranasal epithelia. Intramuscular transduction was restored in mice that ubiquitously expressed human CD46, the primary receptor for species D viruses. We analyzed both species C and D Ads for their ability to induce prophylactic immunity against influenza in the CD46 transgenic mouse model. Surprisingly, the species D vaccines again failed to induce greater levels of protective immunity as compared with the species C Ad5 when delivered intramuscularly. However, the species D Ad vaccine vector, Ad48, induced significantly greater protection as compared with Ad5 when delivered mucosally via the intranasal route in CD46 transgenic mice. These data shed light on the complexities between the species and types of Ad. Our findings indicate that more research will be required to identify the mechanisms that play a key role in the induction of protective immunity induced by species D Ad vaccines. PMID:24635714

  6. CD46-mediated transduction of a species D adenovirus vaccine improves mucosal vaccine efficacy.

    PubMed

    Camacho, Zenaido T; Turner, Mallory A; Barry, Michael A; Weaver, Eric A

    2014-04-01

    The high levels of preexisting immunity against Adenovirus type 5 (Ad5) have deemed Ad5 unusable for translation as a human vaccine vector. Low seroprevalent alternative viral vectors may be less impacted by preexisting immunity, but they may also have significantly different phenotypes from that of Ad5. In this study we compare species D Ads (26, 28, and 48) to the species C Ad5. In vitro transduction studies show striking differences between the species C and D viruses. Most notably, Ad26 transduced human dendritic cells much more effectively than Ad5. In vivo imaging studies showed strikingly different transgene expression profiles. The Ad5 virus was superior to the species D viruses in BALB/c mice when delivered intramuscularly. However, the inverse was true when the viruses were delivered mucosally via the intranasal epithelia. Intramuscular transduction was restored in mice that ubiquitously expressed human CD46, the primary receptor for species D viruses. We analyzed both species C and D Ads for their ability to induce prophylactic immunity against influenza in the CD46 transgenic mouse model. Surprisingly, the species D vaccines again failed to induce greater levels of protective immunity as compared with the species C Ad5 when delivered intramuscularly. However, the species D Ad vaccine vector, Ad48, induced significantly greater protection as compared with Ad5 when delivered mucosally via the intranasal route in CD46 transgenic mice. These data shed light on the complexities between the species and types of Ad. Our findings indicate that more research will be required to identify the mechanisms that play a key role in the induction of protective immunity induced by species D Ad vaccines. PMID:24635714

  7. A comparative study of mineralized biocomposites: Hierarchical structure, quasi-static and dynamic mechanical behavior, and toughening mechanisms

    NASA Astrophysics Data System (ADS)

    Chen, Po-Yu

    Antlers have a primary function in combat and are designed for sustaining high impact loading and bending moment without fracture. Learning from antler may shed a new light on traumatic bone fracture prevention and development of novel fracture-resistant, impact-absorbent materials. Antlers have a similar microstructure as bones, composed mainly of type-I collagen fibrils and carbonated apatite crystals, arranged in osteons in the compact bone and trabeculae in the cancellous bone. However, antlers have lower mineral content and consist mainly of primary osteons. The structure of antler at various hierarchical levels was thoroughly characterized and examined using various techniques and compared with bovine femur. Quasi-static mechanical tests (three-point bending, compression, and nanoindentation) were conducted on elk antlers and the results were compared to reported data. The flexural strength and elastic modulus are similar to other antlers but lower than bovine femur. However, the antler has much higher work of fracture and fracture toughness compared with bone. Dynamic behavior of antler was investigated using a split-Hopkinson pressure bar system. Results showed that antler can sustain large amount of deformation without catastrophic fracture. In situ mechanical testing under ESEM was performed to examine crack propagation in the longitudinal and transverse orientations in compact antler. Nonlinear-elastic fracture mechanics were applied to determine R-curves. The fracture toughness in the transverse orientation is much higher than that in the longitudinal orientation due to crack deflections/twists at the hypermineralized interface and the rising R-curve behavior was observed. Synchrotron X-ray computed tomography and SEM images showed toughening mechanisms, including crack deflections/twists, uncracked ligament and collagen fiber bridging. The structure and compressive mechanical properties of the mineral and protein constituents in cancellous antler and

  8. The Physiology of Mechanoelectrical Transduction Channels in Hearing

    PubMed Central

    Fettiplace, Robert; Kim, Kyunghee X.

    2014-01-01

    Much is known about the mechanotransducer (MT) channels mediating transduction in hair cells of the vertrbrate inner ear. With the use of isolated preparations, it is experimentally feasible to deliver precise mechanical stimuli to individual cells and record the ensuing transducer currents. This approach has shown that small (1–100 nm) deflections of the hair-cell stereociliary bundle are transmitted via interciliary tip links to open MT channels at the tops of the stereocilia. These channels are cation-permeable with a high selectivity for Ca2+; two channels are thought to be localized at the lower end of the tip link, each with a large single-channel conductance that increases from the low- to high-frequency end of the cochlea. Ca2+ influx through open channels regulates their resting open probability, which may contribute to setting the hair cell resting potential in vivo. Ca2+ also controls transducer fast adaptation and force generation by the hair bundle, the two coupled processes increasing in speed from cochlear apex to base. The molecular intricacy of the stereocilary bundle and the transduction apparatus is reflected by the large number of single-gene mutations that are linked to sensorineural deafness, especially those in Usher syndrome. Studies of such mutants have led to the discovery of many of the molecules of the transduction complex, including the tip link and its attachments to the stereociliary core. However, the MT channel protein is still not firmly identified, nor is it known whether the channel is activated by force delivered through accessory proteins or by deformation of the lipid bilayer. PMID:24987009

  9. Mechanical characteristics of optical coatings prepared by various techniques: a comparative study.

    PubMed

    Klemberg-Sapieha, Jolanta E; Oberste-Berghaus, Jörg; Martinu, Ludvik; Blacker, Richard; Stevenson, Ian; Sadkhin, George; Morton, Dale; McEldowney, Scott; Klinger, Robert; Martin, Phil J; Court, Nadia; Dligatch, Svetlana; Gross, Mark; Netterfield, Roger P

    2004-05-01

    Good performance of optical coatings depends on the appropriate combination of optical and mechanical properties. Therefore, successful applications require good understanding of the relationship between optical microstructural and mechanical characteristics and film stability. In addition, there is a lack of standard mechanical tests that allow one to compare film properties measured in different laboratories. We give an overview of the methodology of mechanical measurements suitable for optical coatings; this includes depth-sensing indentation, scratch resistance, friction, abrasion and wear testing, and stress and adhesion evaluation. We used the techniques mentioned above in the same laboratory to systematically compare the mechanical behavior of frequently used high- and low-index materials, namely, TiO2, Ta2O5, and SiO2, prepared by different complementary techniques. They include ion-beam-assisted deposition by electron-beam evaporation, magnetron sputtering, dual-ion-beam sputtering, plasma-enhanced chemical-vapor deposition, and filtered cathodic arc deposition. The mechanical properties are correlated with the film microstructure that is inherently related to energetic conditions during film growth. PMID:15130006

  10. Feeding Behavior of Aplysia: A Model System for Comparing Cellular Mechanisms of Classical and Operant Conditioning

    ERIC Educational Resources Information Center

    Baxter, Douglas A.; Byrne, John H.

    2006-01-01

    Feeding behavior of Aplysia provides an excellent model system for analyzing and comparing mechanisms underlying appetitive classical conditioning and reward operant conditioning. Behavioral protocols have been developed for both forms of associative learning, both of which increase the occurrence of biting following training. Because the neural…

  11. The ethylene signal transduction pathway in Arabidopsis

    NASA Technical Reports Server (NTRS)

    Kieber, J. J.; Evans, M. L. (Principal Investigator)

    1997-01-01

    The gaseous hormone ethylene is an important regulator of plant growth and development. Using a simple response of etiolated seedlings to ethylene as a genetic screen, genes involved in ethylene signal transduction have been identified in Arabidopsis. Analysis of two of these genes that have been cloned reveals that ethylene signalling involves a combination of a protein (ETR1) with similarity to bacterial histidine kinases and a protein (CTR1) with similarity to Raf-1, a protein kinase involved in multiple signalling cascades in eukaryotic cells. Several lines of investigation provide compelling evidence that ETR1 encodes an ethylene receptor. For the first time there is a glimpse of the molecular circuitry underlying the signal transduction pathway for a plant hormone.

  12. Targeting Signaling Transduction Pathways in Bladder Cancer.

    PubMed

    Abbosh, Phillip H; McConkey, David J; Plimack, Elizabeth R

    2015-12-01

    Systemic therapy for urothelial carcinoma (UC) of the bladder has largely revolved around cytotoxic chemotherapy regimens. However, several recent clinical trials have explored the roles of targeted therapies which specifically inhibit signal transduction pathways. Simultaneously, a rationale for such therapies has come to the forefront of management of this disease because an overabundance of signaling pathways are genetically deranged as a result of point mutation or copy number alteration (CNA) as identified by several recent next generation sequencing (NGS) studies. Importantly, these derangements are found in all stages of disease, and therefore targeted therapies hold promise as a next step in the evolution of the medical management of both localized and metastatic UCC. We review the rationale for and progress in studying inhibition of signal transduction as a means of treatment of UCC. PMID:26472299

  13. Analysis of 4070A envelope levels in retroviral preparations and effect on target cell transduction efficiency.

    PubMed

    Slingsby, J H; Baban, D; Sutton, J; Esapa, M; Price, T; Kingsman, S M; Kingsman, A J; Slade, A

    2000-07-01

    A number of stable producer cell lines for high-titer Mo-MuLV vectors have been constructed. Development has previously centered on increasing end-point titers by producing maximal levels of Mo-MuLV Gag/Pol, envelope glycoproteins, and retroviral RNA genomes. We describe the production yields and transduction efficiency characteristics of two Mo-MuLV packaging cell lines, FLYA13 and TEFLYA. Although they both produce 4070A-pseudotyped retroviral vectors reproducibly at >1 x 10(6) LFU ml(-1), the transduction efficiency of unconcentrated and concentrated virus from FLYA13 lines is poor compared with vector preparations from TEFLYA lines. A powerful inhibitor of retroviral transduction is secreted by FLYA13 packaging cells. We show that the inhibitory factor does not affect transduction of target cells by RD114-pseudotyped vectors. This suggests that the inhibitory factor functions at the level of envelope-receptor interactions. Phosphate starvation of target cells shows a two-fold increase in Pit2 receptor mRNA and causes some improvement in FLYA13 virus transduction efficiency. Western blots show that FLYA13 viral samples contain an eight-fold higher ratio of 4070A envelope to p30gag than that of virus produced by TEFLYA producer cell lines. This study correlates overexpression of 4070A envelope glycoprotein in retroviral preparations with a reduction of transduction efficiency at high multiplicities of infection. We suggest that TEFLYA packaging cells express preferable levels of 4070A compared with FLYA13, which not only enables high-titer stocks to be generated, but also facilitates a high efficiency of transduction of target cells. PMID:10910141

  14. Signal transduction in T lymphocytes in microgravity

    NASA Technical Reports Server (NTRS)

    Cogoli, A.

    1997-01-01

    More than 120 experiments conducted in space in the last 15 years have shown that dramatic changes are occurring in several types of single cells during their exposure to microgravity. One focus of today's research on cells in space is on signal transduction, especially those steps involving the cytoskeleton and cell-cell interactions. Signal transduction is often altered in microgravity as well as in hypergravity. This leads to changes in cell proliferation, genetic expression and differentiation. Interesting examples are leukocytes, HeLa cells, epidermoid cells and osteoblastic cells. Signalling pathways were studied in T lymphocytes in microgravity by several investigators after the discovery that mitogenic activation in vitro is virtually nil at 0g. T cells are a good model to study signal transduction because three extracellular signals (mitogen, IL-1 and IL-2) are required for full activation, and two classical pathways (via proteins G and PKC) are activated within the cell. In addition, low molecular weight GTP-binding proteins (Ras and Rap) are interacting with the cytoskeleton. The data at 0g support the notion that the expression of IL-2 receptor is inhibited at 0g, while mitogen binding and the transmission of IL-1 by accessory cells occur normally. In addition, alterations of the cytoskeleton suggest that the interaction with Rap proteins is disturbed. Data obtained with phorbol esters indicate that the function of PKC is changed in microgravity. Similar conclusions are drawn from the results with epidermoid cells A431.

  15. Protein transduction method for cerebrovascular disorders.

    PubMed

    Ogawa, Tomoyuki; Ono, Shigeki; Ichikawa, Tomotsugu; Arimitsu, Seiji; Onoda, Keisuke; Tokunaga, Koji; Sugiu, Kenji; Tomizawa, Kazuhito; Matsui, Hideki; Date, Isao

    2009-02-01

    Many studies have shown that a motif of 11 consecutive arginines (11R) is one of the most effective protein transduction domains (PTD) for introducing proteins into the cell membrane. By conjugating this "11R", all sorts of proteins can effectively and harmlessly be transferred into any kind of cell. We therefore examined the transduction efficiency of 11R in cerebral arteries and obtained results showing that 11R fused enhanced green fluorescent protein (11R-EGFP) immediately and effectively penetrated all layers of the rat basilar artery (BA), especially the tunica media. This method provides a revolutionary approach to cerebral arteries and ours is the first study to demonstrate the successful transductionof a PTD fused protein into the cerebral arteries. In this review, we present an outline of our studies and other key studies related to cerebral vasospasm and 11R, problems to be overcome, and predictions regarding future use of the 11R protein transduction method for cerebral vasospasm (CV). PMID:19247417

  16. A Comparative Mechanical Analysis of Plant and Animal Cells Reveals Convergence across Kingdoms

    PubMed Central

    Durand-Smet, Pauline; Chastrette, Nicolas; Guiroy, Axel; Richert, Alain; Berne-Dedieu, Annick; Szecsi, Judit; Boudaoud, Arezki; Frachisse, Jean-Marie; Bendhamane, Mohammed; Hamant, Oliver; Asnacios, Atef

    2014-01-01

    Plant and animals have evolved different strategies for their development. Whether this is linked to major differences in their cell mechanics remains unclear, mainly because measurements on plant and animal cells relied on independent experiments and setups, thus hindering any direct comparison. In this study we used the same micro-rheometer to compare animal and plant single cell rheology. We found that wall-less plant cells exhibit the same weak power law rheology as animal cells, with comparable values of elastic and loss moduli. Remarkably, microtubules primarily contributed to the rheological behavior of wall-less plant cells whereas rheology of animal cells was mainly dependent on the actin network. Thus, plant and animal cells evolved different molecular strategies to reach a comparable cytoplasmic mechanical core, suggesting that evolutionary convergence could include the internal biophysical properties of cells. PMID:25418292

  17. The meridian system and mechanism of acupuncture--a comparative review. Part 2: mechanism of acupuncture analgesia.

    PubMed

    Chang, Shyang

    2013-03-01

    In traditional Chinese medicine (TCM), pain is never merely a sign of discomfort. It is usually an integral part of a particular disease or physiological malfunction. Thus pain should not be treated in isolation since it will disappear as soon as its cause is identified and removed. Hence, in this Part 2 of a three-part series, initially, clinical pathologies in modern medicine and TCM are compared. Then, the pain pathophysiologies of these two schools of thought are reviewed. In addition, certain unique features of acupuncture effects that any valid mechanism must account for are outlined. Finally, various mechanisms of acupuncture analgesia are reviewed. One plausible mechanism based on the meridian system of Part 1, i.e., the chaotic wave theory of fractal continuum in terms of the neurovascular network, is also proposed. It contends that the injury current due to acupuncture at an acupoint will trigger electromagnetic inductive effects so that the impedances of correlated neurovascular bundles are drastically changed. Two consequent scenarios are possible. (1) If the impedance of the meridian hugely mismatches with that of the brain after acupuncture, then the traveling wave of pain signal will be largely reflected back and only partially transmitted to the brain, hence pain relief can be achieved. (2) If the impedance of the meridian entirely matches that of the pain source after acupuncture, then the pain source would appear to be nonexistent to the brain, hence analgesia can be achieved. The former mechanism can be used to explain the relief for chronic pain and the latter one for acute pain. It is believed that the proposed mechanisms via match or mismatch of the impedances can explain how the acupuncture works not only in the treatment of pain, but also in various other therapies of Part 3. PMID:23548213

  18. Reduced modeling of signal transduction – a modular approach

    PubMed Central

    Koschorreck, Markus; Conzelmann, Holger; Ebert, Sybille; Ederer, Michael; Gilles, Ernst Dieter

    2007-01-01

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

  19. Insect mandibles—comparative mechanical properties and links with metal incorporation

    NASA Astrophysics Data System (ADS)

    Cribb, Bronwen W.; Stewart, Aaron; Huang, Han; Truss, Rowan; Noller, Barry; Rasch, Ronald; Zalucki, Myron P.

    2008-01-01

    A number of arthropod taxa contain metals in their mandibles (jaws), such as zinc, manganese, iron, and calcium. The occurrence of zinc and its co-located halogen chlorine have been studied in relation to the mechanical properties and shown to be linked in a direct fashion with increasing concentration. Hardness along with elastic modulus (stiffness) has also been linked to zinc and halogen concentration in some marine polychaete worms. The metal appears to be incorporated within the biological matrix, possibly bonding with proteins. However, the comparative advantage of metal inclusion has not been tested. It is possible that without metals, alternative mechanisms are used to achieve hardness of equal value in similar ‘tools’ such as mandibles. This question has direct bearing on the significance of metal hardening. In the present article, we compare across mandibles from six termite species, including samples with major zinc concentration, minor manganese, and no metals. Nanoindentation, electron microscopy, and electron microanalysis are used to assess metal concentration, form, and mechanical properties. The data demonstrate that termite mandibles lacking metals when fully developed have lower values for hardness and elastic modulus. Zinc is linked to a relative 20% increase in hardness when compared with mandibles devoid of metals. The similar transition metal, manganese, found in minor concentrations, is not linked to any significant increase in these mechanical properties. This raises the question of the function of manganese, which is as commonly found in insect mandibles as zinc and often located in the same mandibles.

  20. Insect mandibles--comparative mechanical properties and links with metal incorporation.

    PubMed

    Cribb, Bronwen W; Stewart, Aaron; Huang, Han; Truss, Rowan; Noller, Barry; Rasch, Ronald; Zalucki, Myron P

    2008-01-01

    A number of arthropod taxa contain metals in their mandibles (jaws), such as zinc, manganese, iron, and calcium. The occurrence of zinc and its co-located halogen chlorine have been studied in relation to the mechanical properties and shown to be linked in a direct fashion with increasing concentration. Hardness along with elastic modulus (stiffness) has also been linked to zinc and halogen concentration in some marine polychaete worms. The metal appears to be incorporated within the biological matrix, possibly bonding with proteins. However, the comparative advantage of metal inclusion has not been tested. It is possible that without metals, alternative mechanisms are used to achieve hardness of equal value in similar 'tools' such as mandibles. This question has direct bearing on the significance of metal hardening. In the present article, we compare across mandibles from six termite species, including samples with major zinc concentration, minor manganese, and no metals. Nanoindentation, electron microscopy, and electron microanalysis are used to assess metal concentration, form, and mechanical properties. The data demonstrate that termite mandibles lacking metals when fully developed have lower values for hardness and elastic modulus. Zinc is linked to a relative 20% increase in hardness when compared with mandibles devoid of metals. The similar transition metal, manganese, found in minor concentrations, is not linked to any significant increase in these mechanical properties. This raises the question of the function of manganese, which is as commonly found in insect mandibles as zinc and often located in the same mandibles. PMID:17646951

  1. A comparative study between axial and radial fluxfocusing magnetic gear topologies and mechanical gearboxes

    NASA Astrophysics Data System (ADS)

    Calvin, Matthew

    A variety of magnetic gear topologies have been investigated in recent years as alternatives to traditional mechanical gearboxes. In general these magnetic gears offer advantages in the non-contact transmission of torque including inherent overload protection, reduced acoustic emissions, and a reduction in the number of contacting components subject to wear. The earliest magnetic gear designs however suffered from low volumetric torque densities, which limited their utility for industrial applications. Research into flux focusing magnetic gearbox topologies has resulted in increased volumetric torque densities by actively engaging all of the magnets in the transmission of torque throughout the process. This research compared the volumetric torque density of axial and radial flux focusing magnetic gearbox designs and prototypes to planetary, cycloidal, and harmonic mechanical gearboxes. The rare earth scaled up radial and axial flux focusing topologies were found to have consistently higher volumetric torque densities than planetary gearboxes of comparable diameter. The cycloidal and harmonic gearboxes had comparable volumetric torque densities, with greater volumetric torque densities for some models and lesser volumetric torque densities for others. The expectation is that further improvements in volumetric torque density are possible for flux focusing magnetic gears with additional refinement and optimization of the designs. The current study does show that flux focusing magnetic gear topologies are a plausible future alternative to mechanical gearboxes in applications where their unique torque transmission mechanism would be advantageous.

  2. Energy transduction in surface photonic crystals

    NASA Astrophysics Data System (ADS)

    Yang, Fuchyi

    2011-12-01

    This dissertation is a detailed investigation of the fabrication, design, characterization, and understanding of physical principles of energy transduction in surface photonic crystals which are engineered for various applications. One-dimensional photonic crystals are engineered as optically tunable reflectance filters for lambda = 632.8 nm wavelength light by incorporating azobenzene liquid crystal dye molecules into the photonic crystal structure. Optical energy is transduced to accomplish mechanical work by exciting the dye molecules into different physical configurations, leading to changes in the optical properties of the dye molecules, namely their refractive index. This mechanism is used to tune the reflection resonance of the photonic crystal filter. The spectral and temporal optical tuning response of the photonic crystal filter due to excitation light at lambda = 532 nm is characterized. Modulation of the transmitted and reflected lambda = 632.8 nm light is achieved at microsecond time response. Two-dimensional photonic crystals are also investigated as reflectance filters for lambda = 532 nm wavelength light. Both optically tunable and static reflectance filters are studied. Again, azobenzene liquid crystal molecules are incorporated into the photonic crystal to achieve optical tuning of the reflectance wavelength. In this case, the lambda = 532 nm wavelength light is used for self-modulation. That is, the light serves both to optically tune the photonic crystal filter as well as to modulate its own reflection efficiency through the photonic crystal filter. Moreover, stacking of multiple photonic crystals into a single filter is studied for both static and optically tunable photonic crystal filters. It is shown that this approach improves the performance of the photonic crystal reflectance filter by increasing its optical density and its angular tolerance at the reflection wavelength of lambda = 532 nm. Additionally, surface photonic crystals are

  3. Perspective: Adhesion Mediated Signal Transduction in Bacterial Pathogens

    PubMed Central

    Moorthy, Sudha; Keklak, Julia; Klein, Eric A.

    2016-01-01

    During the infection process, pathogenic bacteria undergo large-scale transcriptional changes to promote virulence and increase intrahost survival. While much of this reprogramming occurs in response to changes in chemical environment, such as nutrient availability and pH, there is increasing evidence that adhesion to host-tissue can also trigger signal transduction pathways resulting in differential gene expression. Determining the molecular mechanisms of adhesion-mediated signaling requires disentangling the contributions of chemical and mechanical stimuli. Here we highlight recent work demonstrating that surface attachment drives a transcriptional response in bacterial pathogens, including uropathogenic Escherichia coli (E. coli), and discuss the complexity of experimental design when dissecting the specific role of adhesion-mediated signaling during infection. PMID:26901228

  4. Determinants of specificity in two-component signal transduction.

    PubMed

    Podgornaia, Anna I; Laub, Michael T

    2013-04-01

    Maintaining the faithful flow of information through signal transduction pathways is critical to the survival and proliferation of organisms. This problem is particularly challenging as many signaling proteins are part of large, paralogous families that are highly similar at the sequence and structural levels, increasing the risk of unwanted cross-talk. To detect environmental signals and process information, bacteria rely heavily on two-component signaling systems comprised of sensor histidine kinases and their cognate response regulators. Although most species encode dozens of these signaling pathways, there is relatively little cross-talk, indicating that individual pathways are well insulated and highly specific. Here, we review the molecular mechanisms that enforce this specificity. Further, we highlight recent studies that have revealed how these mechanisms evolve to accommodate the introduction of new pathways by gene duplication. PMID:23352354

  5. Perspective: Adhesion Mediated Signal Transduction in Bacterial Pathogens.

    PubMed

    Moorthy, Sudha; Keklak, Julia; Klein, Eric A

    2016-01-01

    During the infection process, pathogenic bacteria undergo large-scale transcriptional changes to promote virulence and increase intrahost survival. While much of this reprogramming occurs in response to changes in chemical environment, such as nutrient availability and pH, there is increasing evidence that adhesion to host-tissue can also trigger signal transduction pathways resulting in differential gene expression. Determining the molecular mechanisms of adhesion-mediated signaling requires disentangling the contributions of chemical and mechanical stimuli. Here we highlight recent work demonstrating that surface attachment drives a transcriptional response in bacterial pathogens, including uropathogenic Escherichia coli (E. coli), and discuss the complexity of experimental design when dissecting the specific role of adhesion-mediated signaling during infection. PMID:26901228

  6. Spatial Regulation and the Rate of Signal Transduction Activation

    PubMed Central

    Batada, Nizar N; Shepp, Larry A; Siegmund, David O; Levitt, Michael

    2006-01-01

    Of the many important signaling events that take place on the surface of a mammalian cell, activation of signal transduction pathways via interactions of cell surface receptors is one of the most important. Evidence suggests that cell surface proteins are not as freely diffusible as implied by the classic fluid mosaic model and that their confinement to membrane domains is regulated. It is unknown whether these dynamic localization mechanisms function to enhance signal transduction activation rate or to minimize cross talk among pathways that share common intermediates. To determine which of these two possibilities is more likely, we derive an explicit equation for the rate at which cell surface membrane proteins interact based on a Brownian motion model in the presence of endocytosis and exocytosis. We find that in the absence of any diffusion constraints, cell surface protein interaction rate is extremely high relative to cytoplasmic protein interaction rate even in a large mammalian cell with a receptor abundance of a mere two hundred molecules. Since a larger number of downstream signaling events needs to take place, each occurring at a much slower rate than the initial activation via association of cell surface proteins, we conclude that the role of co-localization is most likely that of cross-talk reduction rather than coupling efficiency enhancement. PMID:16699596

  7. Olfactory Signal Transduction in the Mouse Septal Organ

    PubMed Central

    Ma, Minghong; Grosmaitre, Xavier; Iwema, Carrie L.; Baker, Harriet; Greer, Charles A.; Shepherd, Gordon M.

    2008-01-01

    The septal organ, a distinct chemosensory organ observed in the mammalian nose, is essentially a small island of olfactory neuroepithelium located bilaterally at the ventral base of the nasal septum. Virtually nothing is known about its physiological properties and function. To understand the nature of the sensory neurons in this area, we studied the mechanisms underlying olfactory signal transduction in these neurons. The majority of the sensory neurons in the septal organ express olfactory-specific G-protein and adenylyl cyclase type III, suggesting that the cAMP signaling pathway plays a critical role in the septal organ as in the main olfactory epithelium (MOE). This is further supported by patch-clamp recordings from individual dendritic knobs of the sensory neurons in the septal organ. Odorant responses can be mimicked by an adenylyl cyclase activator and a phosphodiesterase inhibitor, and these responses can be blocked by an adenylyl cyclase inhibitor. There is a small subset of cells in the septal organ expressing a cGMP-stimulated phosphodiesterase (phosphodiesterase 2), a marker for the guanylyl cyclase-D subtype sensory neurons identified in the MOE. The results indicate that the septal organ resembles the MOE in major olfactory signal transduction pathways, odorant response properties, and projection to the main olfactory bulb. Molecular and functional analysis of the septal organ, which constitutes ~1% of the olfactory epithelium, will provide new insights into the organization of the mammalian olfactory system and the unique function this enigmatic organ may serve. PMID:12514230

  8. Gravity perception and signal transduction in single cells

    NASA Astrophysics Data System (ADS)

    Block, I.; Wolke, A.; Briegleb, W.; Ivanova, K.

    Cellular signal processing in multi-, as well as in unicellular organisms, has to rely on fundamentally similar mechanisms. Free-living single cells often use the gravity vector for their spatial orientation (gravitaxis) and show distinct gravisensitivities. In this investigation the gravisensitive giant ameboid cell Physarum polycephalum (Myxomycetes, acellular slime molds) is used. Its gravitaxis and the modulation of its intrinsic rhythmic contraction activity by gravity was demonstrated in 180 °turn experiments and in simulated, as well as in actual, near-weightlessness studies (fast-rotating clinostat; Spacelab D1, IML-1). The stimulus perception was addressed in an IML-2 experiment, which provided information on the gravireceptor itself by the determination of the cell's acceleration-sensitivity threshold. Ground-based experiments designed to elucidate the subsequent steps in signal transduction leading to a motor response, suggest that an acceleration stimulus induces changes in the level of second messenger, adenosine 3',5'-cyclic monophosphate (cAMP), indicating also that the acceleration-stimulus signal transduction chain of Physarum uses an ubiquitous second messenger pathway.

  9. Differentially piezoresistive transduction of high-Q encapsulated SOI-MEMS resonators with sub-100 nm gaps.

    PubMed

    Li, Cheng-Syun; Li, Ming-Huang; Li, Sheng-Shian

    2015-01-01

    A differentially piezoresistive (piezo-R) readout proposed for single-crystal-silicon (SCS) microelectromechanical systems (MEMS) resonators is implemented in a foundrybased resonator platform, demonstrating effective feedthrough cancellation using just simple piezoresistors from the resonator supports while maximizing their capacitively transduced driving areas. The SCS resonators are fabricated by a CMOS foundry using an SOI-MEMS technology together with a polysilicon refill process. A high electromechanical coupling coefficient is attained by the use of 50-nm transducer gap spacing. Moreover, a vacuum package of the fabricated resonators is carried out through wafer-level bonding process. In this work, the corner supporting beams of the resonator serve not only mechanical supports but also piezoresistors for detecting the motional signal, hence substantially simplifying the overall resonator design to realize the piezo-R sensing. In addition, the fabricated resonators are capable of either capacitive sensing or piezo-R detection under the same capacitive drive. To mitigate feedthrough signals from parasitics, a differential measurement configuration of the piezo-R transduction is implemented in this work, featuring more than 30-dB improvement on the feedthrough level as compared with the single-ended piezo-R counterpart and purely capacitive sensing readout. Furthermore, the high-Q design of the mechanical supports is also investigated, offering Q more than 10 000 with efficient piezo-R transduction for MEMS resonators. PMID:25585404

  10. A transductive neuro-fuzzy controller: application to a drilling process.

    PubMed

    Gajate, Agustín; Haber, Rodolfo E; Vega, Pastora I; Alique, José R

    2010-07-01

    Recently, new neuro-fuzzy inference algorithms have been developed to deal with the time-varying behavior and uncertainty of many complex systems. This paper presents the design and application of a novel transductive neuro-fuzzy inference method to control force in a high-performance drilling process. The main goal is to study, analyze, and verify the behavior of a transductive neuro-fuzzy inference system for controlling this complex process, specifically addressing the dynamic modeling, computational efficiency, and viability of the real-time application of this algorithm as well as assessing the topology of the neuro-fuzzy system (e.g., number of clusters, number of rules). A transductive reasoning method is used to create local neuro-fuzzy models for each input/output data set in a case study. The direct and inverse dynamics of a complex process are modeled using this strategy. The synergies among fuzzy, neural, and transductive strategies are then exploited to deal with process complexity and uncertainty through the application of the neuro-fuzzy models within an internal model control (IMC) scheme. A comparative study is made of the adaptive neuro-fuzzy inference system (ANFIS) and the suggested method inspired in a transductive neuro-fuzzy inference strategy. The two neuro-fuzzy strategies are evaluated in a real drilling force control problem. The experimental results demonstrated that the transductive neuro-fuzzy control system provides a good transient response (without overshoot) and better error-based performance indices than the ANFIS-based control system. In particular, the IMC system based on a transductive neuro-fuzzy inference approach reduces the influence of the increase in cutting force that occurs as the drill depth increases, reducing the risk of rapid tool wear and catastrophic tool breakage. PMID:20659865

  11. Comparative study of key exchange and authentication methods in application, transport and network level security mechanisms

    NASA Astrophysics Data System (ADS)

    Fathirad, Iraj; Devlin, John; Jiang, Frank

    2012-09-01

    The key-exchange and authentication are two crucial elements of any network security mechanism. IPsec, SSL/TLS, PGP and S/MIME are well-known security approaches in providing security service to network, transport and application layers; these protocols use different methods (based on their requirements) to establish keying materials and authenticates key-negotiation and participated parties. This paper studies and compares the authenticated key negotiation methods in mentioned protocols.

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

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

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

  13. The SUMOylation Pathway Restricts Gene Transduction by Adeno-Associated Viruses

    PubMed Central

    Henrich, Katharina; Chen, Qingxin; Beneke, Jürgen; Matula, Petr; Rohr, Karl; Kaderali, Lars; Beil, Nina; Erfle, Holger; Kleinschmidt, Jürgen A.; Müller, Martin

    2015-01-01

    Adeno-associated viruses are members of the genus dependoviruses of the parvoviridae family. AAV vectors are considered promising vectors for gene therapy and genetic vaccination as they can be easily produced, are highly stable and non-pathogenic. Nevertheless, transduction of cells in vitro and in vivo by AAV in the absence of a helper virus is comparatively inefficient requiring high multiplicity of infection. Several bottlenecks for AAV transduction have previously been described, including release from endosomes, nuclear transport and conversion of the single stranded DNA into a double stranded molecule. We hypothesized that the bottlenecks in AAV transduction are, in part, due to the presence of host cell restriction factors acting directly or indirectly on the AAV-mediated gene transduction. In order to identify such factors we performed a whole genome siRNA screen which identified a number of putative genes interfering with AAV gene transduction. A number of factors, yielding the highest scores, were identified as members of the SUMOylation pathway. We identified Ubc9, the E2 conjugating enzyme as well as Sae1 and Sae2, enzymes responsible for activating E1, as factors involved in restricting AAV. The restriction effect, mediated by these factors, was validated and reproduced independently. Our data indicate that SUMOylation targets entry of AAV capsids and not downstream processes of uncoating, including DNA single strand conversion or DNA damage signaling. We suggest that transiently targeting SUMOylation will enhance application of AAV in vitro and in vivo. PMID:26625259

  14. Cationic Liposomes Enhance the Rate of Transduction by a Recombinant Retroviral Vector In Vitro and In Vivo

    PubMed Central

    Porter, Colin D.; Lukacs, Katalin V.; Box, Gary; Takeuchi, Yasuhiro; Collins, Mary K. L.

    1998-01-01

    Cationic liposomes enhanced the rate of transduction of target cells with retroviral vectors. The greatest effect was seen with the formulation DC-Chol/DOPE, which gave a 20-fold increase in initial transduction rate. This allowed an efficiency of transduction after brief exposure of target cells to virus plus liposome that could be achieved only after extensive exposure to virus alone. Enhancement with DC-Chol/DOPE was optimal when stable virion-liposome complexes were preformed. The transduction rate for complexed virus, as for virus used alone or with the polycation Polybrene, showed first-order dependence on virus concentration. Cationic liposomes, but not Polybrene, were able to mediate envelope-independent transduction, but optimal efficiency required envelope-receptor interaction. When virus complexed with DC-Chol/DOPE was used to transduce human mesothelioma xenografts, transduction was enhanced four- to fivefold compared to that for virus alone. Since the efficacy of gene therapy is dependent on the number of cells modified, which is in turn dependent upon the balance between transduction and biological clearance of the vector, the ability of cationic liposomes to form stable complexes with retroviral vectors and enhance their rate of infection is likely to be important for in vivo application. PMID:9573249

  15. Recombinant Adeno-Associated Virus Utilizes Cell-Specific Infectious Entry Mechanisms

    PubMed Central

    Weinberg, Marc S.; Nicolson, Sarah; Bhatt, Aadra P.; McLendon, Michael; Li, Chengwen

    2014-01-01

    ABSTRACT Understanding the entry and trafficking mechanism(s) of recombinant adeno-associated virus (rAAV) into host cells can lead to evolution in capsid and vector design and delivery methods, resulting in enhanced transduction and therapeutic gene expression. Variability of findings regarding the early entry pathway of rAAV supports the possibility that rAAV, like other viruses, can utilize more than one infectious entry pathway. We tested whether inhibition of macropinocytosis impacted rAAV transduction of HeLa cells compared to hepatocellular carcinoma cell lines. We found that macropinocytosis inhibitor cytochalasin D blocked rAAV transduction of HeLa cells (>2-fold) but enhanced (10-fold) transduction in HepG2 and Huh7 lines. Similar results were obtained with another macropinocytosis inhibitor, 5-(N-ethyl-N-isopropyl) amiloride (EIPA). The augmented transduction was due to neither viral binding nor promoter activity, affected multiple rAAV serotypes (rAAV2, rAAV2-R585E, and rAAV8), and influenced single-stranded and self-complementary virions to comparable extents. Follow-up studies using CDC42 inhibitor ML141 and p21-activated kinase 1 (PAK1) siRNA knockdown also resulted in enhanced HepG2 transduction. Microscopy revealed that macropinocytosis inhibition correlated with expedited nuclear entry of the rAAV virions into HepG2 cells. Enhancement of hepatocellular rAAV transduction extended to the mouse liver in vivo (4-fold enhancement) but inversely blocked heart tissue transduction (13-fold). This evidence of host cell-specific rAAV entry pathways confers a potent means for controlling and enhancing vector delivery and could help unify the divergent accounts of rAAV cellular entry mechanisms. IMPORTANCE There is a recognized need for improved rAAV vector targeting strategies that result in delivery of fewer total particles, averting untoward toxicity and/or an immune response against the vector. A critical step in rAAV transduction is entry and early

  16. Signal Transduction Model of Magnetic Sensing in Cryptochrome Mediated Photoreception

    NASA Astrophysics Data System (ADS)

    Todd, Phillise Tiffeny

    While migratory birds have long been known to use the Earth's magnetic field for navigation, the precise biophysical mechanism behind this magnetic sense remains unconfirmed. A leading theory of magnetoreception suggests a chemical compass model with a yet undetermined molecular reaction site and unknown magnetically sensitive reactants. The cryptochrome photoreceptor has emerged as a promising candidate site. This investigation numerically models the first order kinetics of cryptochrome mediated photoreception, in order to evaluate its ability to function as a magnetic sensor and transduce orientation information along a neural pathway. A signal-to-noise ratio is defined to quantify the threshold for the functioning of a cryptochrome-based chemical compass. The model suggests that a flavin-superoxide radical pair in cryptochrome functions as the chemical reactants for magnetoreception. Such a cryptochrome-based signal transduction model reasonably predicts the general light intensity and wavelength effects that have been experimentally observed in migratory birds.

  17. Graviperception in ciliates: Steps in the transduction chain

    NASA Astrophysics Data System (ADS)

    Hemmersbach, R.; Krause, M.; Bräucker, R.; Ivanova, K.

    Ciliates represent suitable model systems to study the mechanisms of graviperception and signal transduction as they show clear gravity-induced behavioural responses (gravitaxis and gravikinesis). The cytoplasm seems to act as a "statolith" stimulating mechanosensitive ion channels in the cell membrane. In order to test this hypothesis, electrophysiological studies with Stylonychia mytilus were performed, revealing the proposed changes (de- or hyperpolarization) depending on the cell's spatial orientation. The behaviour of Paramecium and Stylonychia was also analyzed during variable acceleration conditions of parabolic flights (5th German Parabolic Flight Campaign, 2003). The corresponding data confirm the relaxation of the graviresponses in microgravity as well as the existence of thresholds of graviresponses, which are found to be in the range of 0.4× g (gravikinesis) and 0.6× g (gravitaxis).

  18. Supporting sensory transduction: cochlear fluid homeostasis and the endocochlear potential

    PubMed Central

    Wangemann, Philine

    2006-01-01

    The exquisite sensitivity of the cochlea, which mediates the transduction of sound waves into nerve impulses, depends on the endocochlear potential and requires a highly specialized environment that enables and sustains sensory function. Disturbance of cochlear homeostasis is the cause of many forms of hearing loss including the most frequently occurring syndromic and non-syndromic forms of hereditary hearing loss, Pendred syndrome and Cx26-related deafness. The occurrence of these and other monogenetic disorders illustrates that cochlear fluid homeostasis and the generation of the endocochlear potential are poorly secured by functional redundancy. This review summarizes the most prominent aspects of cochlear fluid homeostasis. It covers cochlear fluid composition, the generation of the endocochlear potential, K+ secretion and cycling and its regulation, the role of gap junctions, mechanisms of acid–base homeostasis, and Ca2+ transport. PMID:16857713

  19. Genetic Analysis of Gravity Signal Transduction in Arabidopsis Roots

    NASA Astrophysics Data System (ADS)

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

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

  20. Excitation and Adaptation in Bacteria–a Model Signal Transduction System that Controls Taxis and Spatial Pattern Formation

    PubMed Central

    Othmer, Hans G.; Xin, Xiangrong; Xue, Chuan

    2013-01-01

    The machinery for transduction of chemotactic stimuli in the bacterium E. coli is one of the most completely characterized signal transduction systems, and because of its relative simplicity, quantitative analysis of this system is possible. Here we discuss models which reproduce many of the important behaviors of the system. The important characteristics of the signal transduction system are excitation and adaptation, and the latter implies that the transduction system can function as a “derivative sensor” with respect to the ligand concentration in that the DC component of a signal is ultimately ignored if it is not too large. This temporal sensing mechanism provides the bacterium with a memory of its passage through spatially- or temporally-varying signal fields, and adaptation is essential for successful chemotaxis. We also discuss some of the spatial patterns observed in populations and indicate how cell-level behavior can be embedded in population-level descriptions. PMID:23624608

  1. Activity Dependent Signal Transduction in Skeletal Muscle

    NASA Technical Reports Server (NTRS)

    Hamilton, Susan L.

    1999-01-01

    The overall goals of this project are: 1) to define the initial signal transduction events whereby the removal of gravitational load from antigravity muscles, such as the soleus, triggers muscle atrophy, and 2) to develop countermeasures to prevent this from happening. Our rationale for this approach is that, if countermeasures can be developed to regulate these early events, we could avoid having to deal with the multiple cascades of events that occur downstream from the initial event. One of our major findings is that hind limb suspension causes an early and sustained increase in intracellular Ca(2+) concentration ([Ca (2+)](sub i)). In most cells the consequences of changes in ([Ca (2+)](sub i))depend on the amplitude, frequency and duration of the Ca(2+) signal and on other factors in the intracellular environment. We propose that muscle remodeling in microgravity represents a change in the balance among several CA(2+) regulated signal transduction pathways, in particular those involving the transcription factors NFAT and NFkB and the pro-apoptotic protein BAD. Other Ca(2+) sensitive pathways involving PKC, ras, rac, and CaM kinase II may also contribute to muscle remodeling.

  2. A Comparative Data-Based Modeling Study on Respiratory CO2 Gas Exchange during Mechanical Ventilation

    PubMed Central

    Kim, Chang-Sei; Ansermino, J. Mark; Hahn, Jin-Oh

    2016-01-01

    The goal of this study is to derive a minimally complex but credible model of respiratory CO2 gas exchange that may be used in systematic design and pilot testing of closed-loop end-tidal CO2 controllers in mechanical ventilation. We first derived a candidate model that captures the essential mechanisms involved in the respiratory CO2 gas exchange process. Then, we simplified the candidate model to derive two lower-order candidate models. We compared these candidate models for predictive capability and reliability using experimental data collected from 25 pediatric subjects undergoing dynamically varying mechanical ventilation during surgical procedures. A two-compartment model equipped with transport delay to account for CO2 delivery between the lungs and the tissues showed modest but statistically significant improvement in predictive capability over the same model without transport delay. Aggregating the lungs and the tissues into a single compartment further degraded the predictive fidelity of the model. In addition, the model equipped with transport delay demonstrated superior reliability to the one without transport delay. Further, the respiratory parameters derived from the model equipped with transport delay, but not the one without transport delay, were physiologically plausible. The results suggest that gas transport between the lungs and the tissues must be taken into account to accurately reproduce the respiratory CO2 gas exchange process under conditions of wide-ranging and dynamically varying mechanical ventilation conditions. PMID:26870728

  3. Mechanical reliability of microstructured optical fibers: a comparative study of tensile and bending strength

    NASA Astrophysics Data System (ADS)

    Sonnenfeld, C.; Sulejmani, S.; Geernaert, T.; Eve, S.; Gomina, M.; Makara, M.; Skorupski, K.; Mergo, P.; Berghmans, F.; Thienpont, H.

    2012-04-01

    Microstructured optical fibers are increasingly used in optical fiber sensing applications such as for example optical fiber based structural health monitoring. In such an application the fiber may experience substantial mechanical loads and has to remain functional during the entire lifetime of the structure to be monitored. The resistance to different types of mechanical loads has therefore to be characterized in order to assess the maximum stress and strain that a fiber can sustain. In this paper we therefore report on the extensive set of tensile tests and bending experiments that we have conducted both on microstructured optical fibers with an hexagonal air hole lattice and on standard optical fibers. We use Weibull statistics to model the strength distribution of the fibers and we follow a fracture mechanics approach in conjunction with microscopic observations of the fractured end faces to study crack initiation and propagation in both types of fibers. We show that the failure strain of microstructured fibers is about 4.3% as obtained with tensile tests, compared to 6.7% for reference fibers. Although the mechanical strength of microstructured optical fibers is lower than that of the standard fibers it is still adequate for these fibers to be used in many applications.

  4. A quantum mechanical study on phosphotyrosyl peptide binding to the SH2 domain of p56lck tyrosine kinase with insights into the biochemistry of intracellular signal transduction events.

    PubMed

    Pichierri, Fabio

    2004-05-01

    A study on the interaction between a phosphotyrosyl peptide with the SH2 domain of Lck kinase has been undertaken with the aid of semiempirical linear-scaling quantum mechanical methods. The structure of this complex has been solved at atomic resolution and, hence, it represents the ideal candidate for studying the charge deformation effects induced by the phosphopeptide on the binding site. Substantial changes in the charge of amino acid residues located in the binding pocket of the protein are observed upon ligand binding. More specifically, our quantum chemical calculations indicate that H-bonds involving charged side-chains are subject to consistent charge deformation effects whereas those forming salt bridges are unaffected by ligand binding. Furthermore, ligand binding has the effect of changing both the magnitude and direction of the protein's macrodipole, which rotates approximately 150 degrees with respect that of the unliganded protein. This suggests that a change in the polarization state of the protein might acts as a switch during the transmission of intracellular signals. The binding energy calculated with the aid of the COSMO solvation model corresponds to about -200 kcal/mol, most of which is attributed to the interaction of the phosphotyrosine head with the amino acid chains located in the binding site of the SH2 domain. PMID:15110947

  5. Effects of electromagnetic field stimulation on cellular signal transduction mechanisms: Analyses of the effects of low frequency electromagnetic fields on calcium spiking in ROS 17/2.8 cells. Final report

    SciTech Connect

    Sisken, B.F.; Sisken, J.E.

    1997-12-01

    The general goals of this work were to determine whether resting levels of cellular second messengers, especially calcium, are affected by low-level electromagnetic fields and the mechanisms that could lead to such changes. The work performed was directed at (1) verifying the report of McLeod et al (1990) that low frequency sinusoidal EMF can alter basal calcium fluctuations in cultured ROS 17/2.8 osteoblast-like cells and (2) reproducing the findings of Luben et al (1982) that pulsed electromagnetic fields can affect PTH-stimulated adenylate cyclase activity in osteoblasts. Initially a system was constructed so that cells could be exposed to sinusoidal electric fields using platinum electrodes. In this system, the electrodes were separated from the cells and culture medium by agar barriers. A series of experiments indicated that this system was subject to a significant, though little-known artifact in which a not well understood interaction between the electrodes and sodium ions in the medium or in plain salt solutions led to frequency and amplitude dependent emission of photons that are recorded by the detection system. They therefore designed and constructed an air gap reactor system that utilizes a ferromagnetic core to direct the magnetic flux generated by a sinusoidal coil. Studies on the effects of a 15 Hz pulsed electromagnetic field (PEMF) on cyclic AMP metabolism were performed on ROS 17/2.8 and MC3T3 cells.

  6. Comparative study of the mechanical behaviour of a cyanoacrylate and a bioadhesive.

    PubMed

    García Páez, J M; Jorge Herrero, E; Rocha, A; Maestro, M; Castillo-Olivares, J L; Millan, I; Carrera Sanmartin, A; Cordon, A

    2004-02-01

    We compared the mechanical resistance of 18 samples of calf pericardium bonded with a 100 mm2 overlap, by two types of glues: a cyanoacrylate (Loctite 4011) and a bioadhesive (BioGlue). Comparative tensile testing was also carried out in 40 paired samples, 20 bonded with the cyanoacrylate and 20 unbonded controls. The findings at rupture showed a greater resistance of the calf pericardium glued with cyanoacrylate, with a mean tensile strength of 0.15 MPa vs. 0.04 MPa for the biological glue (p= 0.000). They also demonstrated a loss of resistance of the samples bonded with cyanoacrylate when compared with that of the unbonded other halves of the pairs: 0.20 MPa and 0.27 MPa vs. 19.47 MPa and 24.44 MPa (p < 0.001). The method of selection by means of paired samples made it possible to establish the equations that relate the stress and strain, or deformation, with excellent coefficients of determination (R2). These equations demonstrate the marked elastic behaviour of the bonded samples. Moreover, these findings show the cyanoacrylate to be superior to the biological glue, leading to the examination of the compatibility, inalterability over time and mechanical behaviour of the cyanoacrylate in sutured samples, as well as the study of the anisotropy of the biomaterial when bonded with a bioadhesive. PMID:15330043

  7. In search of cellular control: signal transduction in context

    NASA Technical Reports Server (NTRS)

    Ingber, D.

    1998-01-01

    The field of molecular cell biology has experienced enormous advances over the last century by reducing the complexity of living cells into simpler molecular components and binding interactions that are amenable to rigorous biochemical analysis. However, as our tools become more powerful, there is a tendency to define mechanisms by what we can measure. The field is currently dominated by efforts to identify the key molecules and sequences that mediate the function of critical receptors, signal transducers, and molecular switches. Unfortunately, these conventional experimental approaches ignore the importance of supramolecular control mechanisms that play a critical role in cellular regulation. Thus, the significance of individual molecular constituents cannot be fully understood when studied in isolation because their function may vary depending on their context within the structural complexity of the living cell. These higher-order regulatory mechanisms are based on the cell's use of a form of solid-state biochemistry in which molecular components that mediate biochemical processing and signal transduction are immobilized on insoluble cytoskeletal scaffolds in the cytoplasm and nucleus. Key to the understanding of this form of cellular regulation is the realization that chemistry is structure and hence, recognition of the the importance of architecture and mechanics for signal integration and biochemical control. Recent work that has unified chemical and mechanical signaling pathways provides a glimpse of how this form of higher-order cellular control may function and where paths may lie in the future.

  8. Structural insights of homotypic interaction domains in the ligand-receptor signal transduction of tumor necrosis factor (TNF)

    PubMed Central

    Park, Young-Hoon; Jeong, Mi Suk; Jang, Se Bok

    2016-01-01

    Several members of tumor necrosis factor receptor (TNFR) superfamily that these members activate caspase-8 from death-inducing signaling complex (DISC) in TNF ligand-receptor signal transduction have been identified. In the extrinsic pathway, apoptotic signal transduction is induced in death domain (DD) superfamily; it consists of a hexahelical bundle that contains 80 amino acids. The DD superfamily includes about 100 members that belong to four subfamilies: death domain (DD), caspase recruitment domain (CARD), pyrin domain (PYD), and death effector domain (DED). This superfamily contains key building blocks: with these blocks, multimeric complexes are formed through homotypic interactions. Furthermore, each DD-binding event occurs exclusively. The DD superfamily regulates the balance between death and survival of cells. In this study, the structures, functions, and unique features of DD superfamily members are compared with their complexes. By elucidating structural insights of DD superfamily members, we investigate the interaction mechanisms of DD domains; these domains are involved in TNF ligand-receptor signaling. These DD superfamily members play a pivotal role in the development of more specific treatments of cancer. [BMB Reports 2016; 49(3): 159-166] PMID:26615973

  9. A comparative analysis of three self-balancing wheelchair balancing mechanisms.

    PubMed

    Olson, Zachery L; Van Moorhem, William K; Roemer, Robert B

    2006-12-01

    In the last 20 years, three different basic, dynamic balancing designs have been proposed for a self-balancing wheelchair (SBW) that allows the wheelchair user to transition from driving on all four wheels to driving while balanced on the two large rear wheels. The dynamic performance of these three SBW designs, the hanging pendulum counterweight (HPC), the single inverted pendulum (SIP), and the double inverted pendulum (DIP), are compared when controlled by a common state space controller. The four dynamic performance considerations of stability, driver dynamic stress, maneuverability and technical requirements were used to compare these designs while performing the following five tests: 1) transition from four-wheel to two-wheel, balancing mode; 2) stationary, self-balancing stability when subjected to an impact disturbance; 3) movement initiation, and stopping while balancing; 4) response to impact disturbances while moving; and 5) stability on low traction surfaces. In addition, the movement initiation and stopping test was repeated with increased chair mass and inertia to investigate the sensitivity of model performance to changes in model parameters. After comparing the three models it was determined that the HPC mechanism is the best choice for further development based on the criteria of stability, driver dynamic stress, maneuverability, and technical requirements. The HPC ranked equal or better compared to the SIP and DIP on 15 of 29 stability and performance factors. It was also the only design that was stable for all normally expected driving conditions. PMID:17190039

  10. Sensory Transduction of the CO2 Response of Guard Cells

    SciTech Connect

    Dr. Eduardo Zeiger

    2003-06-30

    Stomata have a key role in the regulation of gas exchange and intercellular CO2 concentrations of leaves. Guard cells sense internal and external signals in the leaf environment and transduce these signals into osmoregulatory processes that control stomatal apertures. This research proposal addresses the characterization of the sensory transduction of the CO2 signal in guard cells. Recent studies have shown that in Vicia leaves kept at constant light and temperature in a growth chamber, changes in ambient CO2 concentrations cause large changes in guard cell zeaxanthin that are linear with CO2-dependent changes in stomatal apertures. Research proposed here will test the hypothesis that zeaxanthin function as a transducer of CO2 signals in guard cells. Three central aspects of this hypothesis will be investigated: CO2 sensing by the carboxylation reaction of Rubisco in the guard cell chloroplast, which would modulate zeaxanthin concentrations via changes in lumen pH; transduction of the CO2 signal by zeaxanthin via a transducing cascade that controls guard cell osmoregulation; and blue light dependence of the CO2 signal transduction by zeaxanthin, required for the formation of an isomeric form of zeaxanthin that is physiologically active as a transducer. The role of Rubisco in CO2 sensing will be investigated in experiments characterizing the stomatal response to CO2 in the Arabidopsis mutants R100 and rca-, which have reduced rates of Rubisco-dependent carboxylation. The role of zeaxanthin as a CO2 transducer will be studied in npq1, a zeaxanthin-less mutant. The blue light-dependence of CO2 sensing will be studied in experiments characterizing the stomatal response to CO2 under red light. Arabidopsis mutants will also be used in further studies of an acclimation of the stomatal response to CO2, and a possible role of the xanthophyll cycle of the guard cell chloroplast in acclimations of the stomatal response to CO2. Studies on the osmoregulatory role of sucrose in

  11. Comparative sequence analysis suggests a conserved gating mechanism for TRP channels

    PubMed Central

    Palovcak, Eugene; Delemotte, Lucie; Klein, Michael L.

    2015-01-01

    The transient receptor potential (TRP) channel superfamily plays a central role in transducing diverse sensory stimuli in eukaryotes. Although dissimilar in sequence and domain organization, all known TRP channels act as polymodal cellular sensors and form tetrameric assemblies similar to those of their distant relatives, the voltage-gated potassium (Kv) channels. Here, we investigated the related questions of whether the allosteric mechanism underlying polymodal gating is common to all TRP channels, and how this mechanism differs from that underpinning Kv channel voltage sensitivity. To provide insight into these questions, we performed comparative sequence analysis on large, comprehensive ensembles of TRP and Kv channel sequences, contextualizing the patterns of conservation and correlation observed in the TRP channel sequences in light of the well-studied Kv channels. We report sequence features that are specific to TRP channels and, based on insight from recent TRPV1 structures, we suggest a model of TRP channel gating that differs substantially from the one mediating voltage sensitivity in Kv channels. The common mechanism underlying polymodal gating involves the displacement of a defect in the H-bond network of S6 that changes the orientation of the pore-lining residues at the hydrophobic gate. PMID:26078053

  12. Comparative study on graphene growth mechanism using Ni films, Ni/Mo sheets, and Pt substrates

    NASA Astrophysics Data System (ADS)

    Lee, Byeong-Joo; Jeong, Goo-Hwan

    2014-07-01

    We demonstrate a comparative study on graphene growth mechanism using various catalytic metal substrates such as Ni thin films, Ni-deposited Mo (Ni/Mo) sheets, and Pt sheets during chemical vapor deposition (CVD). Depending on the substrates, two kinds of graphene growth mechanisms that involve either precipitation or surface adsorption of carbon have been reported. We synthesized graphene, focusing especially on the initial growth stage during CVD, by varying synthesis parameters such as synthesis time, amount of feedstock, and cooling rate after synthesis. We concluded that precipitation-driven synthesis is dominant in the case of Ni substrates whereas adsorption-driven growth is dominant in the Ni/Mo system. In the case of the Pt substrate, which is generally believed to grow by carbon precipitation, graphene growth by adsorption was found to be dominant. We believe that our results will contribute to a clearer understanding of the graphene synthesis mechanism, and development of manufacturing routes for controllable synthesis of high-quality graphenes.

  13. In vitro comparative study of manual and mechanical rotary instrumentation of root canals using computed tomography.

    PubMed

    Limongi, Orlando; de Albuquerque, Diana Santana; Baratto Filho, Flares; Vanni, José Roberto; de Oliveira, Elias P Motcy; Barletta, Fernando Branco

    2007-01-01

    This in vitro study compared, using computed tomography (CT), the amount of dentin removed from root canal walls by manual and mechanical rotary instrumentation techniques. Forty mandibular incisors with dental crown and a single canal were selected. The teeth were randomly assigned to two groups, according to the technique used for root canal preparation: Group I - manual instrumentation with stainless steel files; Group II - mechanical instrumentation with RaCe rotary nickel-titanium instruments. In each tooth, root dentin thickness of the buccal, lingual, mesial and distal surfaces in the apical, middle and cervical thirds of the canal was measured (in mm) using a multislice CT scanner (Siemens Emotion, Duo). Data were stored in the SPSS v. 11.5 and SigmaPlot 2001 v. 7.101 softwares. After crown opening, working length was determined, root canals were instrumented and new CT scans were taken for assessment of root dentin thickness. Pre- and post-instrumentation data were compared and analyzed statistically by ANOVA and Tukey's post-hoc test for significant differences (p=0.05). Based on the findings of this study, it may be concluded that regarding dentin removal from root canal walls during instrumentation, neither of the techniques can be considered more effective than the other. PMID:19031646

  14. Comparing large lecture mechanics curricula using the Force Concept Inventory: A five thousand student study

    NASA Astrophysics Data System (ADS)

    Caballero, Marcos D.; Greco, Edwin F.; Murray, Eric R.; Bujak, Keith R.; Jackson Marr, M.; Catrambone, Richard; Kohlmyer, Matthew A.; Schatz, Michael F.

    2012-07-01

    The performance of over 5000 students in introductory calculus-based mechanics courses at the Georgia Institute of Technology was assessed using the Force Concept Inventory (FCI). Results from two different curricula were compared: a traditional mechanics curriculum and the Matter & Interactions (M&I) curriculum. Both were taught with similar interactive pedagogy. Post-instruction FCI averages were significantly higher for the traditional curriculum than for the M&I curriculum; the differences between curricula persist after accounting for factors such as pre-instruction FCI scores, grade point averages, and SAT scores. FCI performance on categories of items organized by concepts was also compared; traditional averages were significantly higher in each concept. We examined differences in student preparation between the curricula and found that the relative fraction of homework and lecture topics devoted to FCI force and motion concepts correlated with the observed performance differences. Concept inventories, as instruments for evaluating curricular reforms, are generally limited to the particular choice of content and goals of the instrument. Moreover, concept inventories fail to measure what are perhaps the most interesting aspects of reform: the non-overlapping content and goals that are not present in courses without reform.

  15. The mechanical properties of various chemical vapor deposition diamond structures compared to the ideal single crystal

    NASA Astrophysics Data System (ADS)

    Hess, Peter

    2012-03-01

    The structural and electronic properties of the diamond lattice, leading to its outstanding mechanical properties, are discussed. These include the highest elastic moduli and fracture strength of any known material. Its extreme hardness is strongly connected with the extreme shear modulus, which even exceeds the large bulk modulus, revealing that diamond is more resistant to shear deformation than to volume changes. These unique features protect the ideal diamond lattice also against mechanical failure and fracture. Besides fast heat conduction, the fast vibrational movement of carbon atoms results in an extreme speed of sound and propagation of crack tips with comparable velocity. The ideal mechanical properties are compared with those of real diamond films, plates, and crystals, such as ultrananocrystalline (UNC), nanocrystalline, microcrystalline, and homo- and heteroepitaxial single-crystal chemical vapor deposition (CVD) diamond, produced by metastable synthesis using CVD. Ultrasonic methods have played and continue to play a dominant role in the determination of the linear elastic properties, such as elastic moduli of crystals or the Young's modulus of thin films with substantially varying impurity levels and morphologies. A surprising result of these extensive measurements is that even UNC diamond may approach the extreme Young's modulus of single-crystal diamond under optimized deposition conditions. The physical reasons for why the stiffness often deviates by no more than a factor of two from the ideal value are discussed, keeping in mind the large variety of diamond materials grown by various deposition conditions. Diamond is also known for its extreme hardness and fracture strength, despite its brittle nature. However, even for the best natural and synthetic diamond crystals, the measured critical fracture stress is one to two orders of magnitude smaller than the ideal value obtained by ab initio calculations for the ideal cubic lattice. Currently

  16. How realistic are flat-ramp-flat fault kinematic models? Comparing mechanical and kinematic models

    NASA Astrophysics Data System (ADS)

    Cruz, L.; Nevitt, J. M.; Hilley, G. E.; Seixas, G.

    2015-12-01

    Rock within the upper crust appears to deform according to elasto-plastic constitutive rules, but structural geologists often employ kinematic descriptions that prescribe particle motions irrespective of these physical properties. In this contribution, we examine the range of constitutive properties that are approximately implied by kinematic models by comparing predicted deformations between mechanical and kinematic models for identical fault geometric configurations. Specifically, we use the ABAQUS finite-element package to model a fault-bend-fold geometry using an elasto-plastic constitutive rule (the elastic component is linear and the plastic failure occurs according to a Mohr-Coulomb failure criterion). We varied physical properties in the mechanical model (i.e., Young's modulus, Poisson ratio, cohesion yield strength, internal friction angle, sliding friction angle) to determine the impact of each on the observed deformations, which were then compared to predictions of kinematic models parameterized with identical geometries. We found that a limited sub-set of physical properties were required to produce deformations that were similar to those predicted by the kinematic models. Specifically, mechanical models with low cohesion are required to allow the kink at the bottom of the flat-ramp geometry to remain stationary over time. Additionally, deformations produced by steep ramp geometries (30 degrees) are difficult to reconcile between the two types of models, while lower slope gradients better conform to the geometric assumptions. These physical properties may fall within the range of those observed in laboratory experiments, suggesting that particle motions predicted by kinematic models may provide an approximate representation of those produced by a physically consistent model under some circumstances.

  17. Influence of Unweighting on Insulin Signal Transduction in Muscle

    NASA Technical Reports Server (NTRS)

    Tischler, Marc E.

    2002-01-01

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

  18. The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part II: signal transduction.

    PubMed

    Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

    2015-02-01

    The unique mechanoelectrochemical environment of cartilage has motivated researchers to investigate the effect of multiple biophysical cues, including mechanical, magnetic, and electrical stimulation, on chondrocyte biology. It is well established that biophysical stimuli promote chondrocyte proliferation, differentiation, and maturation within "biological windows" of defined dose parameters, including mode, frequency, magnitude, and duration of stimuli (see companion review Part I: Cellular Response). However, the underlying molecular mechanisms and signal transduction pathways activated in response to multiple biophysical stimuli remain to be elucidated. Understanding the mechanisms of biophysical signal transduction will deepen knowledge of tissue organogenesis, remodeling, and regeneration and aiding in the treatment of pathologies such as osteoarthritis. Further, this knowledge will provide the tissue engineer with a potent toolset to manipulate and control cell fate and subsequently develop functional replacement cartilage. The aim of this article is to review chondrocyte signal transduction pathways in response to mechanical, magnetic, and electrical cues. Signal transduction does not occur along a single pathway; rather a number of parallel pathways appear to be activated, with calcium signaling apparently common to all three types of stimuli, though there are different modes of activation. Current tissue engineering strategies, such as the development of "smart" functionalized biomaterials that enable the delivery of growth factors or integration of conjugated nanoparticles, may further benefit from targeting known signal transduction pathways in combination with external biophysical cues. PMID:25065615

  19. Comparing the mechanical properties of the porcine knee meniscus when hydrated in saline versus synovial fluid.

    PubMed

    Lakes, Emily H; Kline, Courtney L; McFetridge, Peter S; Allen, Kyle D

    2015-12-16

    As research progresses to find a suitable knee meniscus replacement, accurate in vitro testing becomes critical for feasibility and comparison studies of mechanical integrity. Within the knee, the meniscus is bathed in synovial fluid, yet the most common hydration fluid in laboratory testing is phosphate buffered saline (PBS). PBS is a relatively simple salt solution, while synovial fluid is a complex non-Newtonian fluid with multiple lubricating factors. As such, PBS may interact with meniscal tissue differently than synovial fluid, and thus, the hydration fluid may be an important factor in obtaining accurate results during in vitro testing. To evaluate these effects, medial porcine menisci were used to evaluate tissue mechanics in tension (n=11) and compression (n=15). In all tests, two samples from the same meniscus were taken, where one sample was hydrated in PBS and the other was hydrated in synovial fluid. Statistical analysis revealed no significant differences between the mean mechanical properties of samples tested in PBS compared to synovial fluid; however, compressive testing revealed the variability between samples was significantly reduced if samples were tested in synovial fluid. For example, the compressive Young׳s Modulus was 12.69±7.49MPa in PBS versus 12.34±4.27MPa in synovial fluid. These results indicate testing meniscal tissue in PBS will largely not affect the mean value of the mechanical properties, but performing compression testing in synovial fluid may provide more consistent results between samples and assist in reducing sample numbers in some experiments. PMID:26592438

  20. Exercise-Induced Signal Transduction and Gene Regulation In Skeletal Muscle

    PubMed Central

    Wackerhage, Henning; Woods, Niall M.

    2002-01-01

    Skeletal muscle adapts to various forms of exercise depending on the force, speed and duration characteristics of the contraction pattern. The stresses and signals associated with each contraction pattern are likely to specifically activate a network of signal transduction pathways that integrate this information. These pathways include the calcineurin, Calcium/calmodulin-dependent protein kinase (CaMK), mitogen-activated protein kinase (MAPK), protein kinase C (PKC), nuclear factor kappa B (NF-κB), AMP-dependent protein kinase (AMPK), insulin signalling and developmental pathways. Activated signal transduction pathways activate or increase the expression of transcription factors via various mechanisms. Skeletal muscle genes are usually regulated by combinatorial control exerted by several transcription factors and possibly other mechanisms. In addition, adaptations such as an increase in mitochondrial biogenesis or the activation of satellite cell proliferation involve distinct regulatory mechanisms. PMID:24748841

  1. In Vitro Comparative Assessment of Mechanical Blood Damage Induced by Different Hemodialysis Treatments.

    PubMed

    Sakota, Ranko; Lodi, Carlo Alberto; Sconziano, Sara Antonia; Beck, Werner; Bosch, Juan P

    2015-12-01

    Gradual deterioration of red blood cells (RBCs) due to mechanical stress (chronic hemolysis) is unavoidable during treatments that involve extracorporeal blood circulation, such as hemodialysis (HD). This effect is generally undetectable and does not generate any acute symptoms, but it leads to an increase in plasma free hemoglobin (fHb). There are no absolute safety levels for fHb increase, indicating the need for an empirical evaluation using comparative testing. The increase in fHb levels was investigated in vitro by applying double-needle double-pump HD (HD-DNDP), a new modality in which arterial and venous pumps both run continuously. fHb was measured during typical and worst-case simulated dialysis treatments (double-needle single-pump HD [HD-DNSP], hemodiafiltration [HDF-DN], single-needle double-pump HD [HD-SNDP], and HD-DNDP) performed in vitro using bovine blood for 4 h. Hemolysis-related indices (fHb%; index of hemolysis, IH; and normalized IH) were calculated and used for comparison. The increase in fHb during either HDF-DN or HD-SNDP with Artis and AK200 dialysis machines was similar, while the fHb at the maximum real blood flow rate (Qbreal ) at the completion of the HD-DNDP treatment on Artis was higher than that for HD-DNSP using a Phoenix dialysis machine (fHb% = 1.24 ± 0.13 and 0.92 ± 0.12 for the Artis machine with HD-DNDP at Qbreal  = 450 mL/min and Phoenix with HD-DNSP at Qbreal  = 500 mL/min, respectively). However, the fHb levels increased linearly, and no steep changes were observed. The increases observed during HD-DNDP were the same order of magnitude as those for widely used bloodlines and treatment modes for delivering dialysis treatments. The observed results matched literature findings, and thus the measured fHb trends are not predicted to have clinical side effects. HD-DNDP treatment with Artis does not merit any additional concern regarding mechanical stress to RBCs compared with that observed for

  2. Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans

    PubMed Central

    Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley; Lee, Kristy; Robinson, Rosann; Campbell, Michael S.; Kiso, Wendy K.; Schmitt, Dennis L.; Waddell, Peter J; Bhaskara, Srividya; Jensen, Shane T.; Maley, Carlo C.; Schiffman, Joshua D.

    2016-01-01

    IMPORTANCE Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. OBJECTIVE To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). DESIGN, SETTING, AND PARTICIPANTS A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. EXPOSURES Ionizing radiation and doxorubicin. MAIN OUTCOMES AND MEASURES Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. RESULTS Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95%CI, 0%–5%]; African wild dog, 8%[95%CI, 0%–16%]; lion, 2%[95%CI, 0% –7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95%CI, 3.14%–6.49%), compared with humans, who have 11% to 25%cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain

  3. Mechanical Signal Transduction in Countermeasures to Muscle Atrophy

    NASA Technical Reports Server (NTRS)

    Tidball, James G.; Chu, Amy (Technical Monitor)

    2002-01-01

    We have shown that modifications in muscle use result in changes in the expression and activity of calpains and nitric oxide synthase (NOS). Although muscle unloading for 10 days produced no change in the concentrations of calpain 1 or 2 and no change in calpain activation, muscle reloading produced a 90% increase in calpain 2 concentration. We developed an in vitro model to test our hypothesis that nitric oxide can inhibit cytoskeletal breakdown in skeletal muscle cells by inhibiting calpain cleavage of talin. Talin was selected because it is a well-characterized calpain substrate and it is codistributed with calpain in muscle cells. We found that intermittant loading during hindlimb suspension that is sufficient to prevent muscle mass loss that occurs during muscle unloading is also sufficient to prevent the decrease in NOS expression that normally occurs during hindlimb unloading. These findings indicate that therapeutics directed toward regulating the calpain/calpastatin system may be beneficial in preventing muscle mass loss in muscle injury, unloading and disease.

  4. On the mechanism of energy transduction in myosin subfragment 1.

    PubMed Central

    Botts, J; Takashi, R; Torgerson, P; Hozumi, T; Muhlrad, A; Mornet, D; Morales, M F

    1984-01-01

    It is proposed that the myosin subfragment 1 moiety of the muscle contractile apparatus is a self-contained "engine" whose operational plan is based on the interactive nature of ATP (or degradation intermediate) binding and actin binding, made possible by an intersite communication system. It is suggested that the spatial information required for examining this engine can, at least provisionally, be derived from fluorescence resonance energy transfer measurements interpreted by the Förster equation and that the existence of an intersite communication system can be deduced from piece-wise detection of interacting pairs of points. PMID:6585786

  5. Comparing Student Learning in Mechanics Using Simulations and Hands-on Activities

    NASA Astrophysics Data System (ADS)

    Carmichael, Adrian; Chini, Jacquelyn J.; Rebello, N. Sanjay; Puntambekar, Sadhana

    2010-10-01

    Often computer simulation environments present students with an idealized version of the real world which can affect students' conceptual understanding. In this study we investigate the effects of completing an experiment in mechanics using this ideal world as compared to an identical experiment in the real world. Students in three of five conceptual physics laboratory sections completed the physical experiment while the other two sections performed the virtual experiment. The experiments were part of a unit on simple machines from the CoMPASS curriculum [1] which integrates hypertext-based concept maps in a design-based context. There was no statistically significant difference between the pre and post data of the students in the two groups. Students who performed the virtual experiment were able to answer questions dealing with work and potential energy more correctly, though neither group was able to offer sound reasoning to support their answers.

  6. A comparative approach to the principal mechanisms of different memory systems

    NASA Astrophysics Data System (ADS)

    Rensing, Ludger; Koch, Michael; Becker, Annette

    2009-12-01

    The term “memory” applies not only to the preservation of information in neuronal and immune systems but also to phenomena observed for example in plants, single cells, and RNA viruses. We here compare the different forms of information storage with respect to possible common features. The latter may be characterized by (1) selection of pre-existing information, (2) activation of memory systems often including transcriptional, and translational, as well as epigenetic and genetic mechanisms, (3) subsequent consolidation of the activated state in a latent form ( standby mode), and (4) reactivation of the latent state of memory systems when the organism is exposed to the same (or conditioned) signal or to previous selective constraints. These features apparently also exist in the “evolutionary memory,” i.e., in evolving populations which have highly variable mutant spectra.

  7. Comparative investigation of diagnosis media for induction machine mechanical unbalance fault.

    PubMed

    Salah, Mohamed; Bacha, Khmais; Chaari, Abdelkader

    2013-11-01

    For an induction machine, we suggest a theoretical development of the mechanical unbalance effect on the analytical expressions of radial vibration and stator current. Related spectra are described and characteristic defect frequencies are determined. Moreover, the stray flux expressions are developed for both axial and radial sensor coil positions and a substitute diagnosis technique is proposed. In addition, the load torque effect on the detection efficiency of these diagnosis media is discussed and a comparative investigation is performed. The decisive factor of comparison is the fault sensitivity. Experimental results show that spectral analysis of the axial stray flux can be an alternative solution to cover effectiveness limitation of the traditional stator current technique and to substitute the classical vibration practice. PMID:23938005

  8. Chemical Modulation of Endocytic Sorting Augments Adeno-associated Viral Transduction.

    PubMed

    Berry, Garrett E; Asokan, Aravind

    2016-01-01

    Intracellular trafficking of viruses can be influenced by a variety of inter-connected cellular sorting and degradation pathways involving endo-lysosomal vesicles, the ubiquitin-proteasome system, and autophagy-based or endoplasmic reticulum-associated machinery. In the case of recombinant adeno-associated viruses (AAV), proteasome inhibitors are known to prevent degradation of ubiquitinated AAV capsids, thereby leading to increased nuclear accumulation and transduction. However, the impact of other cellular degradation pathways on AAV trafficking is not well understood. In the current study, we screened a panel of small molecules focused on modulating different cellular degradation pathways and identified eeyarestatin I (EerI) as a novel reagent that enhances AAV transduction. EerI improved AAV transduction by an order of magnitude regardless of vector dose, genome architecture, cell type, or serotype. This effect was preceded by sequestration of AAV within enlarged vesicles that were dispersed throughout the cytoplasm. Specifically, EerI treatment redirected AAV particles toward large vesicles positive for late endosomal (Rab7) and lysosomal (LAMP1) markers. Notably, MG132 and EerI (proteasomal and endoplasmic reticulum-associated degradation inhibitors, respectively) appear to enhance AAV transduction by increasing the intracellular accumulation of viral particles in a mutually exclusive fashion. Taken together, our results expand on potential strategies to redirect recombinant AAV vectors toward more productive trafficking pathways by deregulating cellular degradation mechanisms. PMID:26527686

  9. Exploring signal transduction in heteromultimeric protein based on energy dissipation model.

    PubMed

    Ma, Cheng-Wei; Xiu, Zhi-Long; Zeng, An-Ping

    2015-01-01

    Dynamic intersubunit interactions are key elements in the regulation of many biological systems. A better understanding of how subunits interact with each other and how their interactions are related to dynamic protein structure is a fundamental task in biology. In this paper, a heteromultimeric allosteric protein, Corynebacterium glutamicum aspartokinase, is used as a model system to explore the signal transduction involved in intersubunit interactions and allosteric communication with an emphasis on the intersubunit signaling process. For this purpose, energy dissipation simulation and network construction are conducted for each subunit and the whole protein. Comparison with experimental results shows that the new approach is able to predict all the mutation sites that have been experimentally proved to desensitize allosteric regulation of the enzyme. Additionally, analysis revealed that the function of the effector threonine is to facilitate the binding of the two subunits without contributing to the allosteric communication. During the allosteric regulation upon the binding of the effector lysine, signals can be transferred from the β-subunit to the catalytic site of the α-subunit through both a direct way of intersubunit signal transduction, and an indirect way: first, to the regulatory region of the α-subunit by intersubunit signal transduction and then to the catalytic region by intramolecular signal transduction. Therefore, the new approach is able to illustrate the diversity of the underlying mechanisms when the strength of feedback inhibition by the effector(s) is modulated, providing useful information that has potential applications in engineering heteromultimeric allosteric regulation. PMID:24279729

  10. Comparative Study of Transcriptome Profiles of Mechanical- and Skin-Transformed Schistosoma mansoni Schistosomula

    PubMed Central

    Protasio, Anna V.; Dunne, David W.; Berriman, Matthew

    2013-01-01

    Schistosome infection begins with the penetration of cercariae through healthy unbroken host skin. This process leads to the transformation of the free-living larvae into obligate parasites called schistosomula. This irreversible transformation, which occurs in as little as two hours, involves casting the cercaria tail and complete remodelling of the surface membrane. At this stage, parasites are vulnerable to host immune attack and oxidative stress. Consequently, the mechanisms by which the parasite recognises and swiftly adapts to the human host are still the subject of many studies, especially in the context of development of intervention strategies against schistosomiasis infection. Because obtaining enough material from in vivo infections is not always feasible for such studies, the transformation process is often mimicked in the laboratory by application of shear pressure to a cercarial sample resulting in mechanically transformed (MT) schistosomula. These parasites share remarkable morphological and biochemical similarity to the naturally transformed counterparts and have been considered a good proxy for parasites undergoing natural infection. Relying on this equivalency, MT schistosomula have been used almost exclusively in high-throughput studies of gene expression, identification of drug targets and identification of effective drugs against schistosomes. However, the transcriptional equivalency between skin-transformed (ST) and MT schistosomula has never been proven. In our approach to compare these two types of schistosomula preparations and to explore differences in gene expression triggered by the presence of a skin barrier, we performed RNA-seq transcriptome profiling of ST and MT schistosomula at 24 hours post transformation. We report that these two very distinct schistosomula preparations differ only in the expression of 38 genes (out of ∼11,000), providing convincing evidence to resolve the skin vs. mechanical long-lasting controversy. PMID

  11. Intraoral laser welding: ultrastructural and mechanical analysis to compare laboratory laser and dental laser.

    PubMed

    Fornaini, Carlo; Passaretti, Francesca; Villa, Elena; Rocca, Jean-Paul; Merigo, Elisabetta; Vescovi, Paolo; Meleti, Marco; Manfredi, Maddalena; Nammour, Samir

    2011-07-01

    The Nd:YAG laser has been used since 1970 in dental laboratories to weld metals on dental prostheses. Recently in several clinical cases, we have suggested that the Nd:YAG laser device commonly utilized in the dental office could be used to repair broken fixed, removable and orthodontic prostheses and to weld metals directly in the mouth. The aim of this work was to evaluate, using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and dynamic mechanical analysis (DMA), the quality of the weld and its mechanical strength, comparing a device normally used in dental laboratory and a device normally used in the dental office for oral surgery, the same as that described for intraoral welding. Metal plates of a Co-Cr-Mo dental alloy and steel orthodontic wires were subjected to four welding procedures: welding without filler metal using the laboratory laser, welding with filler metal using the laboratory laser, welding without filler metal using the office laser, and welding with filler metal using the office laser. The welded materials were then analysed by SEM, EDS and DMA. SEM analysis did not show significant differences between the samples although the plates welded using the office laser without filler metal showed a greater number of fissures than the other samples. EDS microanalysis of the welding zone showed a homogeneous composition of the metals. Mechanical tests showed similar elastic behaviours of the samples, with minimal differences between the samples welded with the two devices. No wire broke even under the maximum force applied by the analyser. This study seems to demonstrate that the welds produced using the office Nd:YAG laser device and the laboratory Nd:YAG laser device, as analysed by SEM, EDS and DMA, showed minimal and nonsignificant differences, although these findings need to be confirmed using a greater number of samples. PMID:20437262

  12. 4-Amino-2-chlorophenol: Comparative in vitro nephrotoxicity and mechanisms of bioactivation.

    PubMed

    Rankin, Gary O; Sweeney, Adam; Racine, Christopher; Ferguson, Travis; Preston, Deborah; Anestis, Dianne K

    2014-10-19

    Chlorinated anilines are nephrotoxicants both in vivo and in vitro. The mechanism of chloroaniline nephrotoxicity may occur via more than one mechanism, but aminochlorophenol metabolites appear to contribute to the adverse in vivo effects. The purpose of this study was to compare the nephrotoxic potential of 4-aminophenol (4-AP), 4-amino-2-chlorophenol (4-A2CP), 4-amino-3-chlorophenol (4-A3CP) and 4-amino-2,6-dichlorophenol (4-A2,6DCP) using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the model and to explore renal bioactivation mechanisms for 4-A2CP. For these studies, IRCC (∼4×10(6)cells/ml) were incubated with an aminophenol (0.5 or 1.0mM) or vehicle for 60min at 37°C with shaking. In some experiments, cells were pretreated with an antioxidant or cytochrome P450 (CYP), flavin-containing monooxygenase (FMO), peroxidase or cyclooxygenase inhibitor prior to 4-A2CP (1.0mM). Lactate dehydrogenase (LDH) release served as a measure of cytotoxicity. The order of decreasing nephrotoxic potential in IRCC was 4-A2,6-DCP>4-A2CP>4-AP>4-A3CP. The cytotoxicity induced by 4-A2CP was reduced by pretreatment with the peroxidase inhibitor mercaptosuccinic acid, and some antioxidants (ascorbate, glutathione, N-acetyl-l-cysteine) but not by others (α-tocopherol, DPPD). In addition, pretreatment with the iron chelator deferoxamine, several CYP inhibitors (except for the general CYP inhibitor piperonyl butoxide), FMO inhibitors or indomethacin (a cyclooxygenase inhibitor) failed to attenuate 4-A2CP cytotoxicity. These results demonstrate that the number and ring position of chloro groups can influence the nephrotoxic potential of 4-aminochlorophenols. In addition, 4-A2CP may be bioactivated by cyclooxygenase and peroxidases, and free radicals appear to play a role in 4-A2CP cytotoxicity. PMID:25446496

  13. 4-Amino-2-chlorophenol: Comparative In Vitro Nephrotoxicity and Mechanisms of Bioactivation

    PubMed Central

    Rankin, Gary O.; Sweeney, Adam; Racine, Christopher; Ferguson, Travis; Preston, Deborah; Anestis, Dianne K.

    2014-01-01

    Chlorinated anilines are nephrotoxicants both in vivo and in vitro. The mechanism of chloroaniline nephrotoxicity may occur via more than one mechanism, but aminochlorophenol metabolites appear to contribute to the adverse in vivo effects. The purpose of this study was to compare the nephrotoxic potential of 4-aminophenol (4-AP), 4-amino-2-chlorophenol (4-A2CP), 4-amino-3-chlorophenol (4-A3CP) and 4-amino-2,6-dichlorophenol (4-A2,6DCP) using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the model and to explore renal bioactivation mechanisms for 4-A2CP. For these studies, IRCC (~4×106 cells/ml) were incubated with an aminophenol (0.5 or 1.0 mM) or vehicle for 60 min at 37° C with shaking. In some experiments, cells were pretreated with an antioxidant or cytochrome P450 (CYP), flavin monooxygenase (FMO), peroxidase or cyclooxygenase inhibitor prior to 4-A2CP (1.0 mM). Lactate dehydrogenase (LDH) release served as a measure of cytotoxicity. The order of decreasing nephrotoxic potential in IRCC was 4-A2,6-DCP > 4-A2CP > 4-AP > 4-A3CP. The cytotoxicity induced by 4-A2CP was reduced by pretreatment with the peroxidase inhibitor mercaptosuccinic acid, and some antioxidants (ascorbate, glutathione, N-acetyl-L-cysteine) but not by others (α-tocopherol, DPPD). In addition, pretreatment with the iron chelator deferoxamine, several CYP inhibitors (except for the general CYP inhibitor piperonyl butoxide), FMO inhibitors or indomethacin (a cyclooxygenase inhibitor) failed to attenuate 4-A2CP cytotoxicity. These results demonstrate that the number and ring position of chloro groups can influence the nephrotoxic potential of 4-aminochlorophenols. In addition, 4-A2CP may be bioactivated by cyclooxygenase and peroxidases, and free radicals appear to play a role in 4-A2CP cytotoxicity. PMID:25446496

  14. Comparative anatomy of gall development on Gypsophila paniculata induced by bacteria with different mechanisms of pathogenicity.

    PubMed

    Chalupowicz, L; Barash, I; Schwartz, M; Aloni, R; Manulis, S

    2006-07-01

    Galls induced on Gypsophila paniculata by Pantoea agglomerans pv. gypsophilae (Pag) and Agrobacterium tumefaciens (At), bacteria with different mechanisms of pathogenicity, were compared morphologically and anatomically. The pathogenicity of Pag is dependent on the presence of an indigenous plasmid that harbors hrp gene cluster, genes encoding Hop virulence proteins and biosynthetic genes for auxin (IAA) and cytokinins (CKs), whereas that of At involves host transformation. The Pag-induced gall was rough, brittle and exhibited limited growth, in contrast to the smooth, firm appearance and continuous growth of the At-induced gall. Anatomical analysis revealed the presence of cells with enlarged nuclei and multiple nucleoli, giant cells and suberin deposition in Pag that were absent from At-induced galls. Although circular vessels were observed in both gall types, they were more numerous and the vascular system was more organized in At. An aerenchymal tissue was observed in the upper part of the galls. Ethylene emission from Pag galls, recorded 6 days after inoculation, was eight times as great as that from non-infected controls. In contrast, a significant decrease in ethylene production was observed in Gypsophila cuttings infected with Pag mutants deficient in IAA and CK production. The results presented are best accounted for by the two pathogens having distinct pathogenicity mechanisms that lead to their differential recognition by the host as non-self (Pag) and self (At). PMID:16477460

  15. Comparative study of mechanical properties of direct core build-up materials

    PubMed Central

    Kumar, Girish; Shivrayan, Amit

    2015-01-01

    Background and Objectives: The strength greatly influences the selection of core material because core must withstand forces due to mastication and para-function for many years. This study was conducted to evaluate certain mechanical properties of commonly used materials for direct core build-up, including visible light cured composite, polyacid modified composite, resin modified glass ionomer, high copper amalgam, and silver cermet cement. Materials and Methods: All the materials were manipulated according to the manufacturer's recommendations and standard test specimens were prepared. A universal testing machine at different cross-head speed was used to determine all the four mechanical properties. Mean compressive strength, diametral tensile strength, flexural strength, and elastic modulus with standard deviations were calculated. Multiple comparisons of the materials were also done. Results: Considerable differences in compressive strength, diametral tensile strength, and flexural strength were observed. Visible light cured composite showed relatively high compressive strength, diametral tensile strength, and flexural strength compared with the other tested materials. Amalgam showed the highest value for elastic modulus. Silver cermet showed less value for all the properties except for elastic modulus. Conclusions: Strength is one of the most important criteria for selection of a core material. Stronger materials better resist deformation and fracture provide more equitable stress distribution, greater stability, and greater probability of clinical success. PMID:25684905

  16. Comparative analysis of scintillation characteristics derived from different emission mechanisms in BaCl2

    NASA Astrophysics Data System (ADS)

    Fukabori, Akihiro

    2015-04-01

    Crack-free La3+-substituted BaCl2 single crystals without and with Eu2+ as an activator were successfully grown using the micro-pulling-down method. Luminescence bands from BaCl2 without and with the Eu2+ activator were assigned as mainly intrinsic and extrinsic, respectively. Therefore, BaCl2 as a host material is suitable for investigating the effects of the emission mechanism on the non-proportionality curves and energy resolution plots. First, the scintillation characteristics of BaCl2:La3+(11 at. %) and BaCl2:La3+(7.7 at. %):Eu2+(0.5 at. %) single crystals were determined along with those of BaCl2 and BaCl2:Eu2+(0.5 at. %) crystals. Second, the non-proportionality curves from the different emission origins in BaCl2 were confirmed to be consistent with phenomenological models. Third, the non-proportionality curves and energy resolution plots originating from intrinsic (without Eu2+) and extrinsic (with Eu2+) luminescence were compared. The results experimentally demonstrated that the emission mechanism influenced scintillator non-proportionality curves.

  17. The transduction channel of hair cells from the bull-frog characterized by noise analysis.

    PubMed

    Holton, T; Hudspeth, A J

    1986-06-01

    Receptor currents in response to mechanical stimuli were recorded from hair cells in the excised epithelium of the bull-frog sacculus by the whole-cell, gigohm-seal voltage-clamp technique. The stimulus-dependent transduction current was separated from the cell's stimulus-independent K+ and Ca2+ currents; the K+ currents were blocked with an internal solution containing Cs+ while the Ca2+ current was reduced by holding the membrane potential below -70 mV. The temperature of the preparation was maintained at about 10 degrees C to slow the kinetics of the cells' transduction channels. Calibrated displacements of hair bundles of individual hair cells were made with a probe coupled by suction to the kinociliary bulb and moved with a piezoelectricbimorph stimulator. The root mean square noise of probe motion was less than 2 nm. The mean, I, and the variance, sigma 2, of the receptor current were measured from the response to saturating (+/- 0.5 micron) displacements of the hair bundle. I was corrected for current offsets and sigma 2 for the transduction-independent background variance. The relation between sigma 2 and I is consistent with the predictions of a two-conductance-state model of the transduction channel, a model having only one non-zero conductance state. The relation between sigma 2 and I was fitted by the equation sigma 2 = Ii-I2/N, where N is the number of transduction channels in the cell and i is the current through a single open channel. The conductance of the transduction channel is approximately ohmic with a reversal potential near 0 mV. The estimated conductance of a single transduction channel, gamma, is 12.7 +/- 2.7 pS (mean +/- S.D.; n = 18) at 10 degrees C. gamma is independent of the maximum transduction conductance of the cell, Gmax. The number of transduction channels, N, is proportional to Gmax. N ranges from 7 to 280 in cells with Gmax ranging from 0.08 to 2.48 nS. The largest values of N correspond to a few, perhaps four, active

  18. Verhulst and stochastic models for comparing mechanisms of MAb productivity in six CHO cell lines.

    PubMed

    Shirsat, Nishikant; Avesh, Mohd; English, Niall J; Glennon, Brian; Al-Rubeai, Mohamed

    2016-08-01

    The present study validates previously published methodologies-stochastic and Verhulst-for modelling the growth and MAb productivity of six CHO cell lines grown in batch cultures. Cytometric and biochemical data were used to model growth and productivity. The stochastic explanatory models were developed to improve our understanding of the underlying mechanisms of growth and productivity, whereas the Verhulst mechanistic models were developed for their predictability. The parameters of the two sets of models were compared for their biological significance. The stochastic models, based on the cytometric data, indicated that the productivity mechanism is cell specific. However, as shown before, the modelling results indicated that G2 + ER indicate high productivity, while G1 + ER indicate low productivity, where G1 and G2 are the cell cycle phases and ER is Endoplasmic Reticulum. In all cell lines, growth proved to be inversely proportional to the cumulative G1 time (CG1T) for the G1 phase, whereas productivity was directly proportional to ER. Verhulst's rule, "the lower the intrinsic growth factor (r), the higher the growth (K)," did not hold for growth across all cell lines but held good for the cell lines with the same growth mechanism-i.e., r is cell specific. However, the Verhulst productivity rule, that productivity is inversely proportional to the intrinsic productivity factor (r x ), held well across all cell lines in spite of differences in their mechanisms for productivity-that is, r x is not cell specific. The productivity profile, as described by Verhulst's logistic model, is very similar to the Michaelis-Menten enzyme kinetic equation, suggesting that productivity is more likely enzymatic in nature. Comparison of the stochastic and Verhulst models indicated that CG1T in the cytometric data has the same significance as r, the intrinsic growth factor in the Verhulst models. The stochastic explanatory and the Verhulst logistic models can explain the

  19. The Membrane and Lipids as Integral Participants in Signal Transduction: Lipid Signal Transduction for the Non-Lipid Biochemist

    ERIC Educational Resources Information Center

    Eyster, Kathleen M.

    2007-01-01

    Reviews of signal transduction have often focused on the cascades of protein kinases and protein phosphatases and their cytoplasmic substrates that become activated in response to extracellular signals. Lipids, lipid kinases, and lipid phosphatases have not received the same amount of attention as proteins in studies of signal transduction.…

  20. Role of functionality in two-component signal transduction: A stochastic study

    NASA Astrophysics Data System (ADS)

    Maity, Alok Kumar; Bandyopadhyay, Arnab; Chaudhury, Pinaki; Banik, Suman K.

    2014-03-01

    We present a stochastic formalism for signal transduction processes in a bacterial two-component system. Using elementary mass action kinetics, the proposed model takes care of signal transduction in terms of a phosphotransfer mechanism between the cognate partners of a two-component system, viz., the sensor kinase and the response regulator. Based on the difference in functionality of the sensor kinase, the noisy phosphotransfer mechanism has been studied for monofunctional and bifunctional two-component systems using the formalism of the linear noise approximation. Steady-state analysis of both models quantifies different physically realizable quantities, e.g., the variance, the Fano factor (variance/mean), and mutual information. The resultant data reveal that both systems reliably transfer information of extracellular environment under low external stimulus and in a high-kinase-and-phosphatase regime. We extend our analysis further by studying the role of the two-component system in downstream gene regulation.

  1. Role of functionality in two-component signal transduction: a stochastic study.

    PubMed

    Maity, Alok Kumar; Bandyopadhyay, Arnab; Chaudhury, Pinaki; Banik, Suman K

    2014-03-01

    We present a stochastic formalism for signal transduction processes in a bacterial two-component system. Using elementary mass action kinetics, the proposed model takes care of signal transduction in terms of a phosphotransfer mechanism between the cognate partners of a two-component system, viz., the sensor kinase and the response regulator. Based on the difference in functionality of the sensor kinase, the noisy phosphotransfer mechanism has been studied for monofunctional and bifunctional two-component systems using the formalism of the linear noise approximation. Steady-state analysis of both models quantifies different physically realizable quantities, e.g., the variance, the Fano factor (variance/mean), and mutual information. The resultant data reveal that both systems reliably transfer information of extracellular environment under low external stimulus and in a high-kinase-and-phosphatase regime. We extend our analysis further by studying the role of the two-component system in downstream gene regulation. PMID:24730880

  2. The MiST2 database: a comprehensive genomics resource on microbial signal transduction

    PubMed Central

    Ulrich, Luke E.; Zhulin, Igor B.

    2010-01-01

    The MiST2 database (http://mistdb.com) identifies and catalogs the repertoire of signal transduction proteins in microbial genomes. Signal transduction systems regulate the majority of cellular activities including the metabolism, development, host-recognition, biofilm production, virulence, and antibiotic resistance of human pathogens. Thus, knowledge of the proteins and interactions that comprise these communication networks is an essential component to furthering biomedical discovery. These are identified by searching protein sequences for specific domain profiles that implicate a protein in signal transduction. Compared to the previous version of the database, MiST2 contains a host of new features and improvements including the following: draft genomes; extracytoplasmic function (ECF) sigma factor protein identification; enhanced classification of signaling proteins; novel, high-quality domain models for identifying histidine kinases and response regulators; neighboring two-component genes; gene cart; better search capabilities; enhanced taxonomy browser; advanced genome browser; and a modern, biologist-friendly web interface. MiST2 currently contains 966 complete and 157 draft bacterial and archaeal genomes, which collectively contain more than 245 000 signal transduction proteins. The majority (66%) of these are one-component systems, followed by two-component proteins (26%), chemotaxis (6%), and finally ECF factors (2%). PMID:19900966

  3. A comparative behavioural study of mechanical hypersensitivity in 2 pain models in rats and humans.

    PubMed

    Reitz, Marie-Céline; Hrncic, Dragan; Treede, Rolf-Detlef; Caspani, Ombretta

    2016-06-01

    The assessment of pain sensitivity in humans has been standardized using quantitative sensory testing, whereas in animals mostly paw withdrawal thresholds to diverse stimuli are measured. This study directly compares tests used in quantitative sensory testing (pinpricks, pressure algometer) with tests used in animal studies (electronic von Frey test: evF), which we applied to the dorsal hind limbs of humans after high frequency stimulation and rats after tibial nerve transection. Both experimental models induce profound mechanical hypersensitivity. At baseline, humans and rats showed a similar sensitivity to evF with 0.2 mm diameter tips, but significant differences for other test stimuli (all P < 0.001). When expressed as force divided by circumference, baseline thresholds for 0.8 mm probes were higher than for 0.2 mm in both species (both P < 0.001) suggesting spatial summation. At similar probe diameters, ramped stimuli showed higher baseline thresholds than stepped stimuli (P < 0.01) but similar sensitivity to change. For ramped stimuli sensitivity to change was higher with small probe tips than large blunt tips in both pain models (P < 0.01 in rat, P < 0.05 in humans). These data show that rat paw withdrawal threshold to punctate stimuli (0.2 mm diameter) can be used as surrogate parameters for human mechanical pain sensitivity, but probe size and shape should be standardized. Hypersensitivity to blunt pressure-the leading positive sensory sign after peripheral nerve injury in humans-is a novel finding in the tibial nerve transection model. By testing outside the primary zone of nerve damage (rat) or activation (humans), our methods likely involve effects of central sensitization in both species. PMID:26859819

  4. TMC function in hair cell transduction.

    PubMed

    Holt, Jeffrey R; Pan, Bifeng; Koussa, Mounir A; Asai, Yukako

    2014-05-01

    Transmembrane channel-like (TMC) proteins 1 and 2 are necessary for hair cell mechanotransduction but their precise function is controversial. A growing body of evidence supports a direct role for TMC1 and TMC2 as components of the transduction complex. However, a number of important questions remain and alternate hypotheses have been proposed. Here we present an historical overview of the identification and cloning of Tmc genes, a discussion of mutations in TMC1 that cause deafness in mice and humans and a brief review of other members of the Tmc gene superfamily. We also examine expression of Tmc mRNAs and localization of the protein products. The review focuses on potential functions of TMC proteins and the evidence from Beethoven mice that suggests a direct role for TMC1 in hair cell mechanotransduction. Data that support alternate interpretations are also considered. The article concludes with a discussion of outstanding questions and future directions for TMC research. This article is part of a Special Issue entitled . PMID:24423408

  5. Equivalent body-force model for magnetostrictive transduction in EMATs

    NASA Astrophysics Data System (ADS)

    Nagy, Peter B.; Ribichini, Remo

    2015-03-01

    Electromagnetic Acoustic Transducers (EMATs) are an attractive alternative to standard piezoelectric probes in those applications where couplant fluid cannot be used, i.e. high speed or high temperature testing, or when specific wave-modes have to be excited. When used on ferromagnetic samples, EMATs generate elastic waves through three different transduction mechanisms: the Lorentz force, the magnetization force and magnetostriction. The modeling of such phenomena has drawn the attention of several researchers, leading to different physical formalizations, especially for magnetostriction, being the most complex mechanism. This work presents a physics-based model for tangential bias field magnetostrictive EMATs employing surface tractions equivalent to the inertia body forces caused by magnetostrictive strains. This type of modeling had been previously used to validate a Finite Element model for normal bias field EMATs and here is extended to the tangential bias field configuration. Moreover, it is shown that the proposed model is equivalent to a recently developed method using the spatial convolution integral of body forces with Green's tensor to model elastic wave generation in a solid half-space.

  6. Reading Abilities of College Senior Industrial Arts Majors with Emphasis in Power Mechanics Compared with Readability of Power Mechanics Textbooks.

    ERIC Educational Resources Information Center

    Rose, Phillip Allen

    The purpose of this study was to determine the compatibility of the reading level of students with the required power-mechanics textbooks used by senior industrial arts majors in the California State University and Colleges System. The data for this study were obtained from responses to the Schrammel-Gray High School and College Reading Test…

  7. Comparative study of the mechanical properties of nanostructured thin films on stretchable substrates

    SciTech Connect

    Djaziri, S.; Renault, P.-O.; Le Bourhis, E.; Goudeau, Ph.; Faurie, D.; Geandier, G.; Mocuta, C.; Thiaudière, D.

    2014-09-07

    Comparative studies of the mechanical behavior between copper, tungsten, and W/Cu nanocomposite based on copper dispersoïd thin films were performed under in-situ controlled tensile equi-biaxial loadings using both synchrotron X-ray diffraction and digital image correlation techniques. The films first deform elastically with the lattice strain equal to the true strain given by digital image correlation measurements. The Cu single thin film intrinsic elastic limit of 0.27% is determined below the apparent elastic limit of W and W/Cu nanocomposite thin films, 0.30% and 0.49%, respectively. This difference is found to be driven by the existence of as-deposited residual stresses. Above the elastic limit on the lattice strain-true strain curves, we discriminate two different behaviors presumably footprints of plasticity and fracture. The Cu thin film shows a large transition domain (0.60% true strain range) to a plateau with a smooth evolution of the curve which is associated to peak broadening. In contrast, W and W/Cu nanocomposite thin films show a less smooth and reduced transition domain (0.30% true strain range) to a plateau with no peak broadening. These observations indicate that copper thin film shows some ductility while tungsten/copper nanocomposites thin films are brittle. Fracture resistance of W/Cu nanocomposite thin film is improved thanks to the high compressive residual stress and the elimination of the metastable β-W phase.

  8. Comparative study of chemo-electro-mechanical transport models for an electrically stimulated hydrogel

    NASA Astrophysics Data System (ADS)

    Elshaer, S. E.; Moussa, W. A.

    2014-07-01

    The main objective of this work is to introduce a new expression for the hydrogel’s hydration for use within the Poisson Nernst-Planck chemo electro mechanical (PNP CEM) transport models. This new contribution to the models support large deformation by considering the higher order terms in the Green-Lagrangian strain tensor. A detailed discussion of the CEM transport models using Poisson Nernst-Planck (PNP) and Poisson logarithmic Nernst-Planck (PLNP) equations for chemically and electrically stimulated hydrogels will be presented. The assumptions made to simplify both CEM transport models for electric field application in the order of 0.833 kV m-1 and a highly diluted electrolyte solution (97% is water) will be explained. This PNP CEM model has been verified accurately against experimental and numerical results. In addition, different definitions for normalizing the parameters are used to derive the dimensionless forms of both the PNP and PLNP CEM. Four models, PNP CEM, PLNP CEM, dimensionless PNP CEM and dimensionless PNLP CEM transport models were employed on an axially symmetric cylindrical hydrogel problem with an aspect ratio (diameter to thickness) of 175:3. The displacement and osmotic pressure obtained for the four models are compared against the variation of the number of elements for finite element analysis, simulation duration and solution rate when using the direct numerical solver.

  9. Comparative studies on the mechanisms of action of four polysaccharides on arterial restenosis.

    PubMed

    Deux, Jean-François; Meddahi-Pellé, Anne; Bree, Françoise; Bataille, Isabelle; Michel, Jean-Baptiste; Letourneur, Didier

    2009-01-01

    Percutaneous coronary interventions play a major role in the management of patients affected by coronary artery diseases. However, their efficiency is impaired by restenosis, defined as a reduction of the vessel lumen, occurring a few months after the procedure. A low-molecular-weight fraction of fucoidan, a vegetal heparin-like sulphated polysaccharide, was recently shown to greatly reduce in-stent restenosis after angioplasty in rabbits. To better understand the in vivo anti-restenotic effects of this polymer, we used fractions of fucoidan and compared to heparin and dextran of different sizes. We carried out in vitro growth inhibition experiments on vascular smooth muscle cells, performed an in vivo pharmacokinetic study, and locally delivered fluorescently-labeled polysaccharides in rabbit iliac arteries after angioplasty with a non-occlusive catheter. The results indicated that (i) preparation of well-characterized fractions from natural fucoidan is compulsory for in vitro and in vivo studies, (ii) antiproliferative activity of sulphated polysaccharides on cultured smooth muscle cells is not a major predictive factor for the reduction of restenosis in vivo and (iii) pharmacokinetic parameters and binding of low-molecular-weight fucoidan on angioplasty-induced injured vascular walls are important local and general factors controlling its mechanisms of action. PMID:19323884

  10. A field experiment comparing mechanical demands of two pruners for flower cutting.

    PubMed

    Berrio, S; Barrero, L H; Quintana, L A

    2012-01-01

    Manual flower cutting requires repetitive forceful movements that may explain the high incidence of upper-extremity MSDs among workers of the Colombian flower industry. Force demands may be caused by the use of pruners that have not been designed for Colombian workers. We conducted a repeated measures field experimental study (n=16, 69% women, 20 to 60 years old) to compare the mechanical demands during rose cutting of two different pruners (Traditional vs. alternative pruner) at two different cutting heights (elbow vs. over-shoulder). Demands included the perceived comfort, perceived effort and upper limb's muscular activity and posture. Workers perceived their traditional pruner as more comfortable but requiring more effort than the prototype tool. No benefits were observed regarding ulnar deviation with the alternative pruner. The wrist extension and related muscular activity of the wrist extensors were higher with the prototype pruner. The prototype pruner resulted in reduced muscular load of the wrist flexors; the biceps when working at the elbow height; and the deltoids when working at the shoulder height. However, Moderate results may be explained by the lack of time for workers' adaptation to the alternative tool. New design developments must focus on reducing extension and ulnar deviation of the wrist. PMID:22316904

  11. Comparing the mechanical influence of vinculin, focal adhesion kinase and p53 in mouse embryonic fibroblasts

    SciTech Connect

    Klemm, Anna H.; Diez, Gerold; Alonso, Jose-Luis

    2009-02-13

    Cytoskeletal reorganization is an ongoing process when cells adhere, move or invade extracellular substrates. The cellular force generation and transmission are determined by the intactness of the actomyosin-(focal adhesion complex)-integrin connection. We investigated the intracellular course of action in mouse embryonic fibroblasts deficient in the focal adhesion proteins vinculin and focal adhesion kinase (FAK) and the nuclear matrix protein p53 using magnetic tweezer and nanoparticle tracking techniques. Results show that the lack of these proteins decrease cellular stiffness and affect cell rheological behavior. The decrease in cellular binding strength was higher in FAK- to vinculin-deficient cells, whilst p53-deficient cells showed no effect compared to wildtype cells. The intracellular cytoskeletal activity was lowest in wildtype cells, but increased in the following order when cells lacked FAK+p53 > p53 > vinculin. In summary, cell mechanical processes are differently affected by the focal adhesion proteins vinculin and FAK than by the nuclear matrix protein, p53.

  12. Energy implications of mechanical and mechanical–biological treatment compared to direct waste-to-energy

    SciTech Connect

    Cimpan, Ciprian Wenzel, Henrik

    2013-07-15

    Highlights: • Compared systems achieve primary energy savings between 34 and 140 MJ{sub primary}/100 MJ{sub input} {sub waste.} • Savings magnitude is foremost determined by chosen primary energy and materials production. • Energy consumption and process losses can be upset by increased technology efficiency. • Material recovery accounts for significant shares of primary energy savings. • Direct waste-to-energy is highly efficient if cogeneration (CHP) is possible. - Abstract: Primary energy savings potential is used to compare five residual municipal solid waste treatment systems, including configurations with mechanical (MT) and mechanical–biological (MBT) pre-treatment, which produce waste-derived fuels (RDF and SRF), biogas and/or recover additional materials for recycling, alongside a system based on conventional mass burn waste-to-energy and ash treatment. To examine the magnitude of potential savings we consider two energy efficiency levels (state-of-the-art and best available technology), the inclusion/exclusion of heat recovery (CHP vs. PP) and three different background end-use energy production systems (coal condensing electricity and natural gas heat, Nordic electricity mix and natural gas heat, and coal CHP energy quality allocation). The systems achieved net primary energy savings in a range between 34 and 140 MJ{sub primary}/100 MJ{sub input} {sub waste}, in the different scenario settings. The energy footprint of transportation needs, pre-treatment and reprocessing of recyclable materials was 3–9.5%, 1–18% and 1–8% respectively, relative to total energy savings. Mass combustion WtE achieved the highest savings in scenarios with CHP production, nonetheless, MBT-based systems had similarly high performance if SRF streams were co-combusted with coal. When RDF and SRF was only used in dedicated WtE plants, MBT-based systems totalled lower savings due to inherent system losses and additional energy costs. In scenarios without heat

  13. Transduction, Tropism, and Biodistribution of AAV Vectors in the Lacrimal Gland

    PubMed Central

    Di Pasquale, Giovanni; Riveros, Paola Perez; Quinn, Kathrina; Handelman, Beverly; Chiorini, John A.

    2011-01-01

    Purpose. The lacrimal gland (LG) delivers defensive and metabolic factors to the ocular surface. These functions may be disrupted in several diseases, and for most of them there is no cure. The aim of this study is to investigate conditions and limitations for using adeno-associated virus (AAV) vectors as gene transfer agents to LG. Methods. Eight-week-old Balb/c mice were used to investigate route, gene expression, and time course of AAV gene vector transfer to LG. AAV vectors encoding firefly luciferase were administered to the LG and luciferase expression was evaluated in vivo by immunohistochemistry. Ocular surface and neutralizing antibodies were also evaluated. Results. The present work revealed that AAV vectors are able to delivery DNA to the LGs of mice. Direct injection had the highest level of transduction, and topical ocular drops the lowest. Overall, the AAV strain with highest transduction activity as measured by both luminescence and immunohistochemistry was AAV9, followed by AAV 5w8 and AAV5. Transduction was not different between sexes, could be detected as soon as 24 hours after injection, and lasted for at least 30 days (study termination). No tissue damage was observed when compared with controls. All vectors with detectable LG transduction induced neutralizing antibodies. Conclusions. LG gene delivery by AAV vectors appears to be both safe and well tolerated. The choice of vector influences both the overall transduction activity, as well as the spread of vector to other organs. This work supports the use of AAV-mediated gene therapy for dry eye. PMID:22110082

  14. Signal transduction by guanine nucleotide binding proteins.

    PubMed

    Spiegel, A M

    1987-01-01

    High affinity binding of guanine nucleotides and the ability to hydrolyze bound GTP to GDP are characteristics of an extended family of intracellular proteins. Subsets of this family include cytosolic initiation and elongation factors involved in protein synthesis, and cytoskeletal proteins such as tubulin (Hughes, S.M. (1983) FEBS Lett. 164, 1-8). A distinct subset of guanine nucleotide binding proteins is membrane-associated; members of this subset include the ras gene products (Ellis, R.W. et al. (1981) Nature 292, 506-511) and the heterotrimeric G-proteins (also termed N-proteins) (Gilman, A.G. (1984) Cell 36, 577-579). Substantial evidence indicates that G-proteins act as signal transducers by coupling receptors (R) to effectors (E). A similar function has been suggested but not proven for the ras gene products. Known G-proteins include Gs and Gi, the G-proteins associated with stimulation and inhibition, respectively, of adenylate cyclase; transducin (TD), the G-protein coupling rhodopsin to cGMP phosphodiesterase in rod photoreceptors (Bitensky, M.W. et al. (1981) Curr. Top. Membr. Transp. 15, 237-271; Stryer, L. (1986) Annu. Rev. Neurosci. 9, 87-119), and Go, a G-protein of unknown function that is highly abundant in brain (Sternweis, P.C. and Robishaw, J.D. (1984) J. Biol. Chem. 259, 13806-13813; Neer, E.J. et al. (1984) J. Biol. Chem. 259, 14222-14229). G-proteins also participate in other signal transduction pathways, notably that involving phosphoinositide breakdown. In this review, I highlight recent progress in our understanding of the structure, function, and diversity of G-proteins. PMID:2435586

  15. Polymeric microspheres as protein transduction reagents.

    PubMed

    Nagel, David; Behrendt, Jonathan M; Chimonides, Gwen F; Torr, Elizabeth E; Devitt, Andrew; Sutherland, Andrew J; Hine, Anna V

    2014-06-01

    Discovering the function of an unknown protein, particularly one with neither structural nor functional correlates, is a daunting task. Interaction analyses determine binding partners, whereas DNA transfection, either transient or stable, leads to intracellular expression, though not necessarily at physiologically relevant levels. In theory, direct intracellular protein delivery (protein transduction) provides a conceptually simpler alternative, but in practice the approach is problematic. Domains such as HIV TAT protein are valuable, but their effectiveness is protein specific. Similarly, the delivery of intact proteins via endocytic pathways (e.g. using liposomes) is problematic for functional analysis because of the potential for protein degradation in the endosomes/lysosomes. Consequently, recent reports that microspheres can deliver bio-cargoes into cells via a non-endocytic, energy-independent pathway offer an exciting and promising alternative for in vitro delivery of functional protein. In order for such promise to be fully exploited, microspheres are required that (i) are stably linked to proteins, (ii) can deliver those proteins with good efficiency, (iii) release functional protein once inside the cells, and (iv) permit concomitant tracking. Herein, we report the application of microspheres to successfully address all of these criteria simultaneously, for the first time. After cellular uptake, protein release was autocatalyzed by the reducing cytoplasmic environment. Outside of cells, the covalent microsphere-protein linkage was stable for ≥90 h at 37 °C. Using conservative methods of estimation, 74.3% ± 5.6% of cells were shown to take up these microspheres after 24 h of incubation, with the whole process of delivery and intracellular protein release occurring within 36 h. Intended for in vitro functional protein research, this approach will enable study of the consequences of protein delivery at physiologically relevant levels, without recourse to

  16. Polymeric Microspheres as Protein Transduction Reagents*

    PubMed Central

    Nagel, David; Behrendt, Jonathan M.; Chimonides, Gwen F.; Torr, Elizabeth E.; Devitt, Andrew; Sutherland, Andrew J.; Hine, Anna V.

    2014-01-01

    Discovering the function of an unknown protein, particularly one with neither structural nor functional correlates, is a daunting task. Interaction analyses determine binding partners, whereas DNA transfection, either transient or stable, leads to intracellular expression, though not necessarily at physiologically relevant levels. In theory, direct intracellular protein delivery (protein transduction) provides a conceptually simpler alternative, but in practice the approach is problematic. Domains such as HIV TAT protein are valuable, but their effectiveness is protein specific. Similarly, the delivery of intact proteins via endocytic pathways (e.g. using liposomes) is problematic for functional analysis because of the potential for protein degradation in the endosomes/lysosomes. Consequently, recent reports that microspheres can deliver bio-cargoes into cells via a non-endocytic, energy-independent pathway offer an exciting and promising alternative for in vitro delivery of functional protein. In order for such promise to be fully exploited, microspheres are required that (i) are stably linked to proteins, (ii) can deliver those proteins with good efficiency, (iii) release functional protein once inside the cells, and (iv) permit concomitant tracking. Herein, we report the application of microspheres to successfully address all of these criteria simultaneously, for the first time. After cellular uptake, protein release was autocatalyzed by the reducing cytoplasmic environment. Outside of cells, the covalent microsphere–protein linkage was stable for ≥90 h at 37 °C. Using conservative methods of estimation, 74.3% ± 5.6% of cells were shown to take up these microspheres after 24 h of incubation, with the whole process of delivery and intracellular protein release occurring within 36 h. Intended for in vitro functional protein research, this approach will enable study of the consequences of protein delivery at physiologically relevant levels, without recourse

  17. Comparative study of mechanical properties of dental restorative materials and dental hard tissues in compressive loads.

    PubMed

    Chun, Keyoung Jin; Lee, Jong Yeop

    2014-01-01

    There are two objectives. One is to show the differences in the mechanical properties of various dental restorative materials compared to those of enamel and dentin. The other is to ascertain which dental restorative materials are more suitable for clinical treatments. Amalgam, dental ceramic, gold alloy, dental resin, zirconia, and titanium alloy were processed as dental restorative material specimens. The specimens (width, height, and length of 1.2, 1.2, and 3.0 mm, respectively) were compressed at a constant loading speed of 0.1 mm/min. The maximum stress (115.0 ± 40.6, 55.0 ± 24.8, 291.2 ± 45.3, 274.6 ± 52.2, 2206.0 ± 522.9, and 953.4 ± 132.1 MPa), maximum strain (7.8% ± 0.5%, 4.0% ± 0.1%, 12.7% ± 0.8%, 32.8% ± 0.5%, 63.5% ± 14.0%, and 45.3% ± 7.4%), and elastic modulus (1437.5 ± 507.2, 1548.4 ± 583.5, 2323.4 ± 322.4, 833.1 ± 92.4, 3895.2 ± 202.9, and 2222.7 ± 277.6 MPa) were evident for amalgam, dental ceramic, gold alloy, dental resin, zirconia, and titanium alloy, respectively. The reference hardness value of amalgam, dental ceramic, gold alloy, dental resin, zirconia, and titanium alloy was 90, 420, 130-135, 86.6-124.2, 1250, and 349, respectively. Since enamel grinds food, its abrasion resistance is important. Therefore, hardness value should be prioritized for enamel. Since dentin absorbs bite forces, mechanical properties should be prioritized for dentin. The results suggest that gold alloy simultaneously has a hardness value lower than enamel (74.8 ± 18.1), which is important in the wear of the opposing natural teeth, and higher maximum stress, maximum strain, and elastic modulus than dentin (193.7 ± 30.6 MPa, 11.9% ± 0.1%, 1653.7 ± 277.9 MPa, respectively), which are important considering the rigidity to absorb bite forces. PMID:25352921

  18. Comparative study of mechanical properties of dental restorative materials and dental hard tissues in compressive loads

    PubMed Central

    Lee, Jong Yeop

    2014-01-01

    There are two objectives. One is to show the differences in the mechanical properties of various dental restorative materials compared to those of enamel and dentin. The other is to ascertain which dental restorative materials are more suitable for clinical treatments. Amalgam, dental ceramic, gold alloy, dental resin, zirconia, and titanium alloy were processed as dental restorative material specimens. The specimens (width, height, and length of 1.2, 1.2, and 3.0 mm, respectively) were compressed at a constant loading speed of 0.1 mm/min. The maximum stress (115.0 ± 40.6, 55.0 ± 24.8, 291.2 ± 45.3, 274.6 ± 52.2, 2206.0 ± 522.9, and 953.4 ± 132.1 MPa), maximum strain (7.8% ± 0.5%, 4.0% ± 0.1%, 12.7% ± 0.8%, 32.8% ± 0.5%, 63.5% ± 14.0%, and 45.3% ± 7.4%), and elastic modulus (1437.5 ± 507.2, 1548.4 ± 583.5, 2323.4 ± 322.4, 833.1 ± 92.4, 3895.2 ± 202.9, and 2222.7 ± 277.6 MPa) were evident for amalgam, dental ceramic, gold alloy, dental resin, zirconia, and titanium alloy, respectively. The reference hardness value of amalgam, dental ceramic, gold alloy, dental resin, zirconia, and titanium alloy was 90, 420, 130–135, 86.6–124.2, 1250, and 349, respectively. Since enamel grinds food, its abrasion resistance is important. Therefore, hardness value should be prioritized for enamel. Since dentin absorbs bite forces, mechanical properties should be prioritized for dentin. The results suggest that gold alloy simultaneously has a hardness value lower than enamel (74.8 ± 18.1), which is important in the wear of the opposing natural teeth, and higher maximum stress, maximum strain, and elastic modulus than dentin (193.7 ± 30.6 MPa, 11.9% ± 0.1%, 1653.7 ± 277.9 MPa, respectively), which are important considering the rigidity to absorb bite forces. PMID:25352921

  19. Sparse graph-based transduction for image classification

    NASA Astrophysics Data System (ADS)

    Huang, Sheng; Yang, Dan; Zhou, Jia; Huangfu, Lunwen; Zhang, Xiaohong

    2015-03-01

    Motivated by the remarkable successes of graph-based transduction (GT) and sparse representation (SR), we present a classifier named sparse graph-based classifier (SGC) for image classification. In SGC, SR is leveraged to measure the correlation (similarity) of every two samples and a graph is constructed for encoding these correlations. Then the Laplacian eigenmapping is adopted for deriving the graph Laplacian of the graph. Finally, SGC can be obtained by plugging the graph Laplacian into the conventional GT framework. In the image classification procedure, SGC utilizes the correlations which are encoded in the learned graph Laplacian, to infer the labels of unlabeled images. SGC inherits the merits of both GT and SR. Compared to SR, SGC improves the robustness and the discriminating power of GT. Compared to GT, SGC sufficiently exploits the whole data. Therefore, it alleviates the undercomplete dictionary issue suffered by SR. Four popular image databases are employed for evaluation. The results demonstrate that SGC can achieve a promising performance in comparison with the state-of-the-art classifiers, particularly in the small training sample size case and the noisy sample case.

  20. A scalable, high resolution strain sensing matrix suitable for tactile transduction.

    PubMed

    Scibelli, Anthony E; Krans, Jacob L

    2016-02-01

    The integration of tactile information, such as contact area, displacement magnitude, velocity, and acceleration, is paramount to the optimization of robotics in human-centric environments. Cost effective embeddable sensors with scalable receptive field size and strain sensitivity are not readily commercially available and would benefit investigations of in situ tissue mechanics. We describe the design and performance of a scalable sensor matrix that transduces fine parameters of strain and is made of combinable "modules". The sensors transduce static and dynamic strains of both uniaxial and multi-dimensional nature. Modules consist of three silicon wafers placed on top of and three on the bottom of a hexagonal collar, wafers are thus positioned 120° to one another to facilitate force vector extrapolation. Analog signals from each sensor can be easily compared to neighboring sensor output to determine mechanical phenomena such as slip or shear. The smallest of our prototype multiunit matrices consisted of seven hexes in a honeycomb orientation of 4.1mm diameter (containing 42 silicon gauges). Unamplified, unshielded output from this embodiment (3 Vexc button cell) yielded 1 mV from 5 μm displacement. Transduction linearity was high (R>0.99 nearest displacement) and exhibited nominal hysteresis. Modules may be placed upon or embedded into a multitude of materials and the size of individual hexagons may be scaled for favorable stiffness to strain ratio and to scale receptive field. Given the scalability of matrix size and resolution, we believe the sensor matrices could benefit the fields of prosthetics, robotics, and physiologic investigation of tissue mechanics. PMID:26710986

  1. MiR-10a improves hepatic fibrosis by regulating the TGFβl/Smads signal transduction pathway

    PubMed Central

    Zhou, Guangyao; Lin, Wei; Fang, Peipei; Lin, Xiuzhen; Zhuge, Lu; Hu, Zhiqiu; Jin, Lingxiang

    2016-01-01

    The aim of the present study was to examine the expression variation of the mouse hepatic fibrosis tissue transforming growth factor (TGF)-βl/Smads signal transduction pathway and its correlation with progression of hepatic fibrosis. The promotion effect of microRNA (miR)-10a on hepatic fibrosis and its possible mechanism was also assessed. Forty healthy female 8-week-old C57BL6/J mice were randomly divided into the control group (intraperitoneal injection of 5 µl/g normal saline, twice per week for 8 weeks) and the hepatic fibrosis group (intraperitoneal injection of 5 µl/g 10% CCI4 olive oil, twice per week for 8 weeks), with 20 mice per group. RT-PCR was used to test miR-10a expression in cells in the control and hepatic fibrosis groups. Cell culture and transfection of miR-10a mimics were conducted in the two groups and a Cell Counting Kit-8 was used to test the expression of TGF-β1 and Smad7 in hepatic fibroblasts. It was found that in comparison with the control group, miR-10a expression was significantly increased in the hepatic fibrosis group compared with the control group (P<0.05). The expression quantity of miR-10a was significantly increased in the transfection group compared with the control group (P<0.05). A high expression of miR-10a significantly improved TGF-β1 expression and reduced Smad7 expression in the hepatic fibrosis group (P<0.05). In conclusion, miR-10a expression was high in mouse hepatic tissues, transfection of miR-10a mimics significantly promoted the cell proliferation of hepatic fibrosis, and miR-10a improved hepatic fibrosis by regulating the TGF-βl/Smads signal transduction pathway. PMID:27602086

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

    PubMed Central

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

    2013-01-01

    Rehmannia is a commonly used Chinese herb, which improves learning and memory. However, the crucial components of the signal transduction pathway associated with this effect remain elusive. Pri-mary hippocampal neurons were cultured in vitro, insulted with high-concentration (1 × 10−4 mol/L) cor-ticosterone, and treated with 1 × 10−4 mol/L mannotriose. Thiazolyl blue tetrazolium bromide assay and western blot analysis showed that hippocampal neuron survival rates and protein levels of glucocorti-coid receptor, serum and glucocorticoid-regulated protein kinase, and brain-derived neurotrophic factor were all dramatically decreased after high-concentration corticosterone-induced injury. This effect was reversed by mannotriose, to a similar level as RU38486 and donepezil. Our findings indicate that mannotriose could protect hippocampal neurons from high-concentration corticosterone-induced injury. The mechanism by which this occurred was associated with levels of glucocorticoid receptor protein, serum and glucocorticoid-regulated protein kinase, and brain-derived neurotrophic factor. PMID:25206622

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

    PubMed Central

    Druwe, Ingrid L.

    2010-01-01

    Arsenic has been a recognized contaminant and toxicant, as well as a medicinal compound throughout human history. Populations throughout the world are exposed to arsenic and these exposures have been associated with a number of human cancers. Not much is known about the role of arsenic as a human carcinogen and more recently its role in non-cancerous diseases, such as cardiovascular disease, hypertension and diabetes mellitus have been uncovered. The health effects associated with arsenic are numerous and the association between arsenic exposure and human disease has intensified the search for molecular mechanisms that describe the biological activity of arsenic in humans and leads to the aforementioned disease states. Arsenic poses a human health risk due in part to the regulation of cellular signal transduction pathways and over the last few decades, some cellular mechanisms that account for arsenic toxicity, as well as, signal transduction pathways have been discovered. However, given the ubiquitous nature of arsenic in the environment, making sense of all the data remains a challenge. This review will focus on our knowledge of signal transduction pathways that are regulated by arsenic. PMID:20502880

  4. Transduction channels’ gating can control friction on vibrating hair-cell bundles in the ear

    PubMed Central

    Bormuth, Volker; Barral, Jérémie; Joanny, Jean-François; Jülicher, Frank; Martin, Pascal

    2014-01-01

    Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. Friction is generally thought to result mainly from viscous drag by the surrounding fluid. We demonstrate here that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle. We characterized friction by analyzing hysteresis in the force–displacement relation of single hair-cell bundles in response to periodic triangular stimuli. For bundle velocities high enough to outrun adaptation, we found that frictional forces were maximal within the narrow region of deflections that elicited significant channel gating, plummeted upon application of a channel blocker, and displayed a sublinear growth for increasing bundle velocity. At low velocity, the slope of the relation between the frictional force and velocity was nearly fivefold larger than the hydrodynamic friction coefficient that was measured when the transduction machinery was decoupled from bundle motion by severing tip links. A theoretical analysis reveals that channel friction arises from coupling the dynamics of the conformational change associated with channel gating to tip-link tension. Varying channel properties affects friction, with faster channels producing smaller friction. We propose that this intrinsic source of friction may contribute to the process that sets the hair cell’s characteristic frequency of responsiveness. PMID:24799674

  5. Transduction channels' gating can control friction on vibrating hair-cell bundles in the ear.

    PubMed

    Bormuth, Volker; Barral, Jérémie; Joanny, Jean-François; Jülicher, Frank; Martin, Pascal

    2014-05-20

    Hearing starts when sound-evoked mechanical vibrations of the hair-cell bundle activate mechanosensitive ion channels, giving birth to an electrical signal. As for any mechanical system, friction impedes movements of the hair bundle and thus constrains the sensitivity and frequency selectivity of auditory transduction. Friction is generally thought to result mainly from viscous drag by the surrounding fluid. We demonstrate here that the opening and closing of the transduction channels produce internal frictional forces that can dominate viscous drag on the micrometer-sized hair bundle. We characterized friction by analyzing hysteresis in the force-displacement relation of single hair-cell bundles in response to periodic triangular stimuli. For bundle velocities high enough to outrun adaptation, we found that frictional forces were maximal within the narrow region of deflections that elicited significant channel gating, plummeted upon application of a channel blocker, and displayed a sublinear growth for increasing bundle velocity. At low velocity, the slope of the relation between the frictional force and velocity was nearly fivefold larger than the hydrodynamic friction coefficient that was measured when the transduction machinery was decoupled from bundle motion by severing tip links. A theoretical analysis reveals that channel friction arises from coupling the dynamics of the conformational change associated with channel gating to tip-link tension. Varying channel properties affects friction, with faster channels producing smaller friction. We propose that this intrinsic source of friction may contribute to the process that sets the hair cell's characteristic frequency of responsiveness. PMID:24799674

  6. Engineering key components in a synthetic eukaryotic signal transduction pathway

    PubMed Central

    Antunes, Mauricio S; Morey, Kevin J; Tewari-Singh, Neera; Bowen, Tessa A; Smith, J Jeff; Webb, Colleen T; Hellinga, Homme W; Medford, June I

    2009-01-01

    Signal transduction underlies how living organisms detect and respond to stimuli. A goal of synthetic biology is to rewire natural signal transduction systems. Bacteria, yeast, and plants sense environmental aspects through conserved histidine kinase (HK) signal transduction systems. HK protein components are typically comprised of multiple, relatively modular, and conserved domains. Phosphate transfer between these components may exhibit considerable cross talk between the otherwise apparently linear pathways, thereby establishing networks that integrate multiple signals. We show that sequence conservation and cross talk can extend across kingdoms and can be exploited to produce a synthetic plant signal transduction system. In response to HK cross talk, heterologously expressed bacterial response regulators, PhoB and OmpR, translocate to the nucleus on HK activation. Using this discovery, combined with modification of PhoB (PhoB-VP64), we produced a key component of a eukaryotic synthetic signal transduction pathway. In response to exogenous cytokinin, PhoB-VP64 translocates to the nucleus, binds a synthetic PlantPho promoter, and activates gene expression. These results show that conserved-signaling components can be used across kingdoms and adapted to produce synthetic eukaryotic signal transduction pathways. PMID:19455134

  7. Inquiry into Chemotherapy-Induced P53 Activation in Cancer Cells as a Model for Teaching Signal Transduction

    ERIC Educational Resources Information Center

    Srougi, Melissa C.; Carson, Susan

    2013-01-01

    Intracellular and extracellular communication is conducted through an intricate and interwoven network of signal transduction pathways. The mechanisms for how cells speak with one another are of significant biological importance to both basic and industrial scientists from a number of different disciplines. We have therefore developed and…

  8. Intracellular transduction in the regulation of pheromone biosynthesis of the silkworm, Bombyx mori: suggested involvement of calmodulin and phosphoprotein phosphatase.

    PubMed

    Matsumoto, S; Ozawa, R; Nagamine, T; Kim, G H; Uchiumi, K; Shono, T; Mitsui, T

    1995-03-01

    We have tested the effects of chemicals on bombykol production in vitro in the silkworm, Bombyx mori, to probe the biochemical steps as well as underlying mechanisms regulated by PBAN. These results suggest the involvement of calmodulin and phosphoprotein phosphatase in the intracellular signal transduction of PBAN action. PMID:7766202

  9. Market Mechanisms in Education: School Choice in the Netherlands, England and Scotland in a Comparative Perspective.

    ERIC Educational Resources Information Center

    Teelken, Christine

    1999-01-01

    Analyzes differences in the availability of school choice in the Netherlands, England, and Scotland, focusing on trends in 10 choice-related variables. Concludes that all three countries are moving toward an increased market mechanism but exhibit extensive differences, with the Netherlands approaching the market mechanism most closely. Contains 61…

  10. Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication.

    PubMed

    Corrochano, Luis M; Kuo, Alan; Marcet-Houben, Marina; Polaino, Silvia; Salamov, Asaf; Villalobos-Escobedo, José M; Grimwood, Jane; Álvarez, M Isabel; Avalos, Javier; Bauer, Diane; Benito, Ernesto P; Benoit, Isabelle; Burger, Gertraud; Camino, Lola P; Cánovas, David; Cerdá-Olmedo, Enrique; Cheng, Jan-Fang; Domínguez, Angel; Eliáš, Marek; Eslava, Arturo P; Glaser, Fabian; Gutiérrez, Gabriel; Heitman, Joseph; Henrissat, Bernard; Iturriaga, Enrique A; Lang, B Franz; Lavín, José L; Lee, Soo Chan; Li, Wenjun; Lindquist, Erika; López-García, Sergio; Luque, Eva M; Marcos, Ana T; Martin, Joel; McCluskey, Kevin; Medina, Humberto R; Miralles-Durán, Alejandro; Miyazaki, Atsushi; Muñoz-Torres, Elisa; Oguiza, José A; Ohm, Robin A; Olmedo, María; Orejas, Margarita; Ortiz-Castellanos, Lucila; Pisabarro, Antonio G; Rodríguez-Romero, Julio; Ruiz-Herrera, José; Ruiz-Vázquez, Rosa; Sanz, Catalina; Schackwitz, Wendy; Shahriari, Mahdi; Shelest, Ekaterina; Silva-Franco, Fátima; Soanes, Darren; Syed, Khajamohiddin; Tagua, Víctor G; Talbot, Nicholas J; Thon, Michael R; Tice, Hope; de Vries, Ronald P; Wiebenga, Ad; Yadav, Jagjit S; Braun, Edward L; Baker, Scott E; Garre, Victoriano; Schmutz, Jeremy; Horwitz, Benjamin A; Torres-Martínez, Santiago; Idnurm, Alexander; Herrera-Estrella, Alfredo; Gabaldón, Toni; Grigoriev, Igor V

    2016-06-20

    Plants and fungi use light and other signals to regulate development, growth, and metabolism. The fruiting bodies of the fungus Phycomyces blakesleeanus are single cells that react to environmental cues, including light, but the mechanisms are largely unknown [1]. The related fungus Mucor circinelloides is an opportunistic human pathogen that changes its mode of growth upon receipt of signals from the environment to facilitate pathogenesis [2]. Understanding how these organisms respond to environmental cues should provide insights into the mechanisms of sensory perception and signal transduction by a single eukaryotic cell, and their role in pathogenesis. We sequenced the genomes of P. blakesleeanus and M. circinelloides and show that they have been shaped by an extensive genome duplication or, most likely, a whole-genome duplication (WGD), which is rarely observed in fungi [3-6]. We show that the genome duplication has expanded gene families, including those involved in signal transduction, and that duplicated genes have specialized, as evidenced by differences in their regulation by light. The transcriptional response to light varies with the developmental stage and is still observed in a photoreceptor mutant of P. blakesleeanus. A phototropic mutant of P. blakesleeanus with a heterozygous mutation in the photoreceptor gene madA demonstrates that photosensor dosage is important for the magnitude of signal transduction. We conclude that the genome duplication provided the means to improve signal transduction for enhanced perception of environmental signals. Our results will help to understand the role of genome dynamics in the evolution of sensory perception in eukaryotes. PMID:27238284

  11. The emerging role of phosphoinositide clustering in intracellular trafficking and signal transduction

    PubMed Central

    Picas, Laura; Gaits-Iacovoni, Frederique; Goud, Bruno

    2016-01-01

    Phosphoinositides are master regulators of multiple cellular processes: from vesicular trafficking to signaling, cytoskeleton dynamics, and cell growth. They are synthesized by the spatiotemporal regulated activity of phosphoinositide-metabolizing enzymes. The recent observation that some protein modules are able to cluster phosphoinositides suggests that alternative or complementary mechanisms might operate to stabilize the different phosphoinositide pools within cellular compartments. Herein, we discuss the different known and potential molecular players that are prone to engage phosphoinositide clustering and elaborate on how such a mechanism might take part in the regulation of intracellular trafficking and signal transduction. PMID:27092250

  12. Adenylate cyclase mediates olfactory transduction for a wide variety of odorants.

    PubMed Central

    Lowe, G; Nakamura, T; Gold, G H

    1989-01-01

    An odor-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] is thought to mediate olfactory transduction in vertebrates. However, it is not known whether the adenylate cyclase serves this function for all odorants or for only certain classes of odorants. To investigate this question, we have compared the abilities of 35 odorants to stimulate the adenylate cyclase and to elicit an electrophysiological response. We report a strong positive correlation between the magnitude of adenylate cyclase stimulation and the summated electrical response of the olfactory epithelium (electro-olfactogram) evoked by individual odorants. We also show that the adenylate cyclase stimulator forskolin equally attenuates the electro-olfactogram response for all odorants tested. These data provide evidence that the adenylate cyclase mediates transduction for a wide variety of odorants. PMID:2787513

  13. Prediction of Enzyme Mutant Activity Using Computational Mutagenesis and Incremental Transduction

    PubMed Central

    Basit, Nada; Wechsler, Harry

    2011-01-01

    Wet laboratory mutagenesis to determine enzyme activity changes is expensive and time consuming. This paper expands on standard one-shot learning by proposing an incremental transductive method (T2bRF) for the prediction of enzyme mutant activity during mutagenesis using Delaunay tessellation and 4-body statistical potentials for representation. Incremental learning is in tune with both eScience and actual experimentation, as it accounts for cumulative annotation effects of enzyme mutant activity over time. The experimental results reported, using cross-validation, show that overall the incremental transductive method proposed, using random forest as base classifier, yields better results compared to one-shot learning methods. T2bRF is shown to yield 90% on T4 and LAC (and 86% on HIV-1). This is significantly better than state-of-the-art competing methods, whose performance yield is at 80% or less using the same datasets. PMID:22007208

  14. Microgravity-induced alterations in signal transduction in cells of the immune system

    NASA Astrophysics Data System (ADS)

    Paulsen, Katrin; Thiel, Cora; Timm, Johanna; Schmidt, Peter M.; Huber, Kathrin; Tauber, Svantje; Hemmersbach, Ruth; Seibt, Dieter; Kroll, Hartmut; Grote, Karl-Heinrich; Zipp, Frauke; Schneider-Stock, Regine; Cogoli, Augusto; Hilliger, Andre; Engelmann, Frank; Ullrich, Oliver

    2010-11-01

    Since decades it is known that the activity of cells of the immune system is severely dysregulated in microgravity, however, the underlying molecular aspects have not been elucidated yet. The identification of gravity-sensitive molecular mechanisms in cells of the immune system is an important and indispensable prerequisite for the development of counteractive measures to prevent or treat disturbed immune cell function of astronauts during long-term space missions. Moreover, their sensitivity to altered gravity renders immune cells an ideal model system to understand if and how gravity on Earth is required for normal mammalian cell function and signal transduction. We investigated the effect of simulated weightlessness (2D clinostat) and of real microgravity (parabolic flights) on key signal pathways in a human monocytic and a T lymphocyte cell line. We found that cellular responses to microgravity strongly depend on the cell-type and the conditions in which the cells are subjected to microgravity. In Jurkat T cells, enhanced phosphorylation of the MAP kinases ERK-1/2, MEK and p38 and inhibition of nuclear translocation of NF-kB were the predominant responses to simulated weightlessness, in either stimulated or non-stimulated cells. In contrast, non-stimulated monocytic U937 cells responded to simulated weightlessness with enhanced overall tyrosine-phosphorylation and activation of c-jun, whereas PMA-stimulated U937 cells responded the opposite way with reduced tyrosine-phosphorylation and reduced activation of c-jun, compared with PMA-stimulated 1 g controls. P53 protein was phosphorylated rapidly in microgravity. The identification of gravi-sensitive mechanisms in cells of the immune system will not only enable us to understand and prevent the negative effects of long time exposure to microgravity on Astronauts, but could also lead to novel therapeutic targets in general.

  15. Postsynaptic Signal Transduction Models for Long-Term Potentiation and Depression

    PubMed Central

    Manninen, Tiina; Hituri, Katri; Kotaleski, Jeanette Hellgren; Blackwell, Kim T.; Linne, Marja-Leena

    2010-01-01

    More than a hundred biochemical species, activated by neurotransmitters binding to transmembrane receptors, are important in long-term potentiation (LTP) and long-term depression (LTD). To investigate which species and interactions are critical for synaptic plasticity, many computational postsynaptic signal transduction models have been developed. The models range from simple models with a single reversible reaction to detailed models with several hundred kinetic reactions. In this study, more than a hundred models are reviewed, and their features are compared and contrasted so that similarities and differences are more readily apparent. The models are classified according to the type of synaptic plasticity that is modeled (LTP or LTD) and whether they include diffusion or electrophysiological phenomena. Other characteristics that discriminate the models include the phase of synaptic plasticity modeled (induction, expression, or maintenance) and the simulation method used (deterministic or stochastic). We find that models are becoming increasingly sophisticated, by including stochastic properties, integrating with electrophysiological properties of entire neurons, or incorporating diffusion of signaling molecules. Simpler models continue to be developed because they are computationally efficient and allow theoretical analysis. The more complex models permit investigation of mechanisms underlying specific properties and experimental verification of model predictions. Nonetheless, it is difficult to fully comprehend the evolution of these models because (1) several models are not described in detail in the publications, (2) only a few models are provided in existing model databases, and (3) comparison to previous models is lacking. We conclude that the value of these models for understanding molecular mechanisms of synaptic plasticity is increasing and will be enhanced further with more complete descriptions and sharing of the published models. PMID:21188161

  16. Reciprocity and gyrotropism in magnetic resonance transduction

    SciTech Connect

    Tropp, James

    2006-12-15

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

  17. Reciprocity and gyrotropism in magnetic resonance transduction

    NASA Astrophysics Data System (ADS)

    Tropp, James

    2006-12-01

    We give formulas for transduction in magnetic resonance—i.e., the appearance of an emf due to Larmor precession of spins—based upon the modified Lorentz reciprocity principle for gyrotropic (also called “nonreciprocal”) media, i.e., in which a susceptibility tensor is carried to its transpose by reversal of an external static field [cf., R. F. Harrington and A. T. Villeneuve IRE Trans. Microwave Theory and Technique MTT6, 308 (1958)]. Prior applications of reciprocity to magnetic resonance, despite much success, have ignored the gyrotropism which necessarily arises due to nuclear and/or unpaired electronic spins. For detection with linearly polarized fields, oscillating at the Larmor frequency, the emf is written in terms of a volume integral containing a product of two factors which we define as the antenna patterns, i.e., (H1x±iH1y) , where, e.g., for a single transceive antenna, the H ’s are just the spatially dependent oscillatory magnetic field strengths, per the application of some reference current at the antenna terminals, with the negative sign obtaining for transmission, and the positive for reception. Similar expressions hold for separate transmit and receive antennas; expressions are also given for circular polarization of the fields. We then exhibit a receive-only array antenna of two elements for magnetic resonance imaging of protons, which, due an intensity artifact arising from stray reactive coupling of the elements, produces, despite its own bilateral symmetry, asymmetric proton NMR images of a symmetric cylindrical phantom containing aqueous saline solution [J. Tropp and T. Schirmer, J. Magn. Reson. 151, 146 (2001)]. Modification of this two-port antenna, to function in transmit-receive mode, allows us to demonstrate highly nonreciprocal behavior: that is, to record images (of cylindrical test phantoms containing aqueous saline solution) whose appearance dramatically changes, when the roles of transmission and reception are swapped

  18. SR-A and SREC-I binding peptides increase HDAd-mediated liver transduction

    PubMed Central

    Piccolo, Pasquale; Annunziata, Patrizia; Mithbaokar, Pratibha; Brunetti-Pierri, Nicola

    2014-01-01

    Helper-dependent adenoviral (HDAd) vectors can mediate long-term, high-level transgene expression from transduced hepatocytes without inducing chronic toxicity. However, vector therapeutic index is narrow because of a toxic acute response with potentially lethal consequences elicited by high vector doses. Kupffer cells and liver sinusoidal endothelial cells (LSECs) are major barriers to efficient hepatocyte transduction. We investigated two small peptides (PP1 and PP2) developed by phage display to block scavenger receptor type A (SR-A) and scavenger receptor expressed on endothelial cells type I (SREC-I) respectively, for enhancement of HDAd-mediated hepatocyte transduction efficiency. Pre-incubation of J774A.1 macrophages with either PP1 or PP2 prior to HDAd infection significantly reduced viral vector uptake. In vivo, fluorochrome-conjugated PP1 and PP2 injected intravenously into mice co-localized with both CD68 and CD31 on Kupffer cells and LSECs, respectively. Compared to saline pre-treated animals, intravenous injections of both peptides prior to the injection of an HDAd resulted in up to 3.7- and 2.9-fold increase of hepatic transgene expression with PP1 and PP2, respectively. In addition to hepatocyte transduction, compared to control saline injected mice, pre-treatment with either peptide resulted in no increased levels of serum interleukin-6 (IL-6), the major marker of adenoviral vector acute toxicity. In summary, we developed small peptides that significantly increase hepatocyte transduction efficacy and improve HDAd therapeutic index with potential for clinical applications. PMID:25119377

  19. Phosphoproteomic analysis of induced resistance reveals activation of signal transduction processes by beneficial and pathogenic interaction in grapevine.

    PubMed

    Perazzolli, Michele; Palmieri, Maria Cristina; Matafora, Vittoria; Bachi, Angela; Pertot, Ilaria

    2016-05-20

    Protein phosphorylation regulates several key processes of the plant immune system. Protein kinases and phosphatases are pivotal regulators of defense mechanisms elicited by resistance inducers. However, the phosphorylation cascades that trigger the induced resistance mechanisms in plants have not yet been deeply investigated. The beneficial fungus Trichoderma harzianum T39 (T39) induces resistance against grapevine downy mildew (Plasmopara viticola), but its efficacy could be further improved by a better understanding of the cellular regulations involved. We investigated quantitative changes in the grapevine phosphoproteome during T39-induced resistance to get an overview of regulatory mechanisms of downy mildew resistance. Immunodetection experiments revealed activation of the 45 and 49kDa kinases by T39 treatment both before and after pathogen inoculation, and the phosphoproteomic analysis identified 103 phosphopeptides that were significantly affected by the phosphorylation cascades during T39-induced resistance. Peptides affected by T39 treatment showed comparable phosphorylation levels after P. viticola inoculation, indicating activation of the microbial recognition machinery before pathogen infection. Phosphorylation profiles of proteins related to photosynthetic processes and protein ubiquitination indicated a partial overlap of cellular responses in T39-treated and control plants. However, phosphorylation changes of proteins involved in response to stimuli, signal transduction, hormone signaling, gene expression regulation, and RNA metabolism were exclusively elicited by P. viticola inoculation in T39-treated plants. These results highlighted the relevance of phosphorylation changes during T39-induced resistance and identified key regulator candidates of the grapevine defense against downy mildew. PMID:27010348

  20. A comparative study of commercial lithium ion battery cycle life in electrical vehicle: Aging mechanism identification

    NASA Astrophysics Data System (ADS)

    Han, Xuebing; Ouyang, Minggao; Lu, Languang; Li, Jianqiu; Zheng, Yuejiu; Li, Zhe

    2014-04-01

    When lithium-ion batteries age with cycling, the battery capacity decreases and the resistance increases. The aging mechanism of different types of lithium-ion batteries differs. The loss of lithium inventory, loss of active material, and the increase in resistance may result in battery aging. Generally, analysis of the battery aging mechanism requires dismantling of batteries and using methods such as X-ray diffraction and scanning electron microscopy. These methods may permanently damage the battery. Therefore, the methods are inappropriate for the battery management system (BMS) in an electric vehicle. The constant current charging curves while charging the battery could be used to get the incremental capacity and differential voltage curves for identifying the aging mechanism; the battery state-of-health can then be estimated. This method can be potentially used in the BMS for online diagnostic and prognostic services. The genetic algorithm could be used to quantitatively analyze the battery aging offline. And the membership function could be used for onboard aging mechanism identification.

  1. Invaded grassland communities have altered stability-maintenance mechanisms but equal stability compared to native communities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Theory predicts that stability should increase with diversity via several mechanisms. We tested predictions in a five-year experiment with exotic and native plant mixtures under two irrigation treatments. Diversity declined faster after planting in exotic than native mixtures. Variation in biomas...

  2. Exploitation of host signal transduction pathways and cytoskeletal functions by invasive bacteria.

    PubMed

    Rosenshine, I; Finlay, B B

    1993-01-01

    Many bacteria that cause disease have the capacity to enter into and live within eukaryotic cells such as epithelial cells and macrophages. The mechanisms used by these organisms to achieve and maintain this intracellular lifestyle vary considerably, but most mechanisms involve subversion and exploitation of host cell functions. Entry into non-phagocytic cells involves triggering host signal transduction mechanisms to induce rearrangement of the host cytoskeleton, thereby facilitating bacterial uptake. Once inside the host cell, intracellular pathogens either remain within membrane bound inclusions or escape to the cytoplasm. Those living in the cytoplasm can further pirate the host actin system, using actin as a mechanism to facilitate movement within and between host cells. Organisms remaining within the vacuole have specialized mechanisms for intracellular survival and growth which involve additional communication with the host cell. Some of the processes involved in the various steps of facultative intracellular parasitism are discussed in the context of subverting the host cell cytoskeleton and signal transduction pathways for bacterial benefit. PMID:8466472

  3. Comparative study on nano-mechanics and thermodynamics of fish otoliths.

    PubMed

    Dongni, Ren; Yonghua, Gao; Qingling, Feng

    2013-01-01

    Fish otolith is a kind of typical natural biomineral, which is composed of calcium carbonate and organic matrix. In fresh water carp otolith, the inorganic phase of lapillus is pure aragonite, and for asteriscus it is pure vaterite. In this research, the phase composition, phase transformation, mechanical property and solubility of lapillus and asteriscus were studied. And results showed that, the organic content of lapillus was higher than that of asteriscus; the phase-transition temperature of lapillus (aragonite-calcite) and asteriscus (vaterite-calcite) both happened between 520 and 640 °C; the nano-mechanical property of lapillus was better than that of asteriscus; the solubility of asteriscus powder was higher than that of lapillus powder. PMID:25428035

  4. Cellular Mechanisms and Behavioral Outcomes in Blast-Induced Neurotrauma: Comparing Experimental Setups.

    PubMed

    Bailey, Zachary S; Hubbard, W Brad; VandeVord, Pamela J

    2016-01-01

    Blast-induced neurotrauma (BINT) has increased in incidence over the past decades and can result in cognitive issues that have debilitating consequences. The exact primary and secondary mechanisms of injury have not been elucidated and appearance of cellular injury can vary based on many factors, such as blast overpressure magnitude and duration. Many methodologies to study blast neurotrauma have been employed, ranging from open-field explosives to experimental shock tubes for producing free-field blast waves. While there are benefits to the various methods, certain specifications need to be accounted for in order to properly examine BINT. Primary cell injury mechanisms, occurring as a direct result of the blast wave, have been identified in several studies and include cerebral vascular damage, blood-brain barrier disruption, axonal injury, and cytoskeletal damage. Secondary cell injury mechanisms, triggered subsequent to the initial insult, result in the activation of several molecular cascades and can include, but are not limited to, neuroinflammation and oxidative stress. The collective result of these secondary injuries can lead to functional deficits. Behavioral measures examining motor function, anxiety traits, and cognition/memory problems have been utilized to determine the level of injury severity. While cellular injury mechanisms have been identified following blast exposure, the various experimental models present both concurrent and conflicting results. Furthermore, the temporal response and progression of pathology after blast exposure have yet to be detailed and remain unclear due to limited resemblance of methodologies. This chapter summarizes the current state of blast neuropathology and emphasizes the need for a standardized preclinical model of blast neurotrauma. PMID:27604716

  5. Mechanosensing and signal transduction in tendrils.

    PubMed

    Engelberth, Jürgen

    2003-01-01

    The perception of thigmic stimuli is a widespread phenomenon among plants with decisive meaning for the ability to survive. Beside a general sensitivity for mechanical stimuli many plants have evolved specialized organs with highly developed mechanisms to perceive and transduce the applied forces. Tendrils of Bryonia dioica and Pisum sativum have been chosen to study the effects of mechanical stimulation on plant physiology. Both types of tendrils, although exhibiting different morphology, respond to such a stimulus with a rapid coiling response to the dorsal side of the organ within minutes. The actual perception of the stimulus is most likely coupled to the cytoskeleton serving as the mediator between the physical stimulus and the biochemical response. Drugs affecting the status of the cytoskeleton were used to get more insights into this specific process. The results indicate that microtubuli (MT) play the most important role in the perception of thigmic stimuli in tendrils. Colchicine-mediated disruption of MT lead to total inhibition of the response to the thigmic stimulus in tendrils of Pisum and to a reduced response in Bryonia. Alamethicin, an ionophore that can mimic action potentials in membranes, was able to bypass this inhibition suggesting a direct involvement of MT in depolarization of the membranes. Auxin, however, which is also supposed to be involved in the regulation of the coiling response, failed to bypass colchicine-dependent inhibition. Vinblastine, another microtubule depolimerizing agent, did induce tendril coiling in Pisum without further stimulation. Application of taxol and other MT-stabilizing drugs as well as disruption of the actin network did not affect the coiling response of tendrils. In Pisum indole-3-acetic acid (IAA) is induced after mechanical stimulation during the coiling response, but not jasmonic acid. A further consequence of mechanical stimulation is the induction of an oxidative burst and an increase in soluble sugar. A

  6. A comparative study of the effects of constructional elements on the mechanical behaviour of dragonfly wings

    NASA Astrophysics Data System (ADS)

    Rajabi, H.; Rezasefat, M.; Darvizeh, A.; Dirks, J.-H.; Eshghi, Sh.; Shafiei, A.; Mostofi, T. Mirzababaie; Gorb, S. N.

    2016-01-01

    Although wings of insects show a large variation in morphology, they are all made from a network of irregular veins interconnected through membranous areas. Depending on their shape, size, and position, wing veins are usually divided into three different groups: longitudinal veins, cross-veins and ambient veins. The veins together with the membrane and some other elements such as spines, nodus and pterostigma can be considered as the wing's "constructional elements". In spite of rather extensive literature on dragonfly wing structure, the role of each of these elements in determining the wing's function remains mostly unknown. As this question is difficult to answer in vivo using biomechanical experiments on actual wings, this study was undertaken to reveal the effects of the constructional elements on the mechanical behaviour of dragonfly wings by applying numerical simulations. An image processing technique was used to develop 12 finite element models of the insect wings with different constructional elements. The mechanical behaviour of these models was then simulated under normal and shear stresses due to tension, bending and torsion. A free vibration analysis was also performed to determine the resonant frequencies and the mode shapes of the models. For the first time, a quantitative comparison was carried out between the mechanical effects selectively caused by different elements. Our results suggest that the complex interactions of veins, membranes and corrugations may considerably affect the dynamic deformation of the insect wings during flight.

  7. Comparative theoretical studies of the phosphomonoester hydrolysis mechanism by purple acid phosphatases.

    PubMed

    Retegan, M; Milet, A; Jamet, H

    2010-07-01

    We present here the first ONIOM (our own n-layered integrated molecular orbital + molecular mechanics method) studies of a purple acid phosphatase enzyme. Our study focused on the structures of the red kidney bean PAP (kbPAP) complexed with phosphate and with phenyl phosphate and on the mechanism of the phenyl phosphate hydrolysis by the enzyme. Density functional theory (DFT) calculations were also performed using models of different sizes for comparison purpose. Results show that the inclusion of three histidine residues, His202, His295, and His296, with their protein surrounding, is crucial to properly describe the coordination of the substrates. They induce a conformation with the substrate closer to the nucleophilic mu-hydroxyde bridge. In the mechanistic study, a transition state is stabilized by a strong hydrogen bond between His202 and the leaving group of the substrate. Consequently, a smaller value for the activation energy barrier is obtained from DFT calculations including this histidine to the same calculations without this histidine. Using the ONIOM method, this activation energy barrier is even more reduced. So the mechanism, which considers the hydroxo group bridging the two metal ions as nucleophile, becomes really convincing, contrary to the results obtained with a small model at the DFT level. PMID:20550096

  8. Depletion suspends the comparator mechanism in monitoring: The role of chronic self-consciousness in sequential self-regulation.

    PubMed

    Jia, Lile; Hirt, Edward R

    2016-08-01

    In 4 studies, we accumulated support for the prediction that depletion suspends the comparator mechanism of self-regulatory monitoring. We adopted an individual difference approach and designated chronic self-consciousness as a signature variable for the comparator mechanism. In the nondepletion condition, we found that self-consciousness predicted self-regulation by itself (Study 1), or by interacting synergistically with other motivational factors such as online goal focus (Study 2) and task motivation (Study 3). In the depletion condition, self-consciousness ceased to predict task performance, which suggested that the self-focused comparator mechanism is suspended by depletion. Instead, depleted participants' self-control was predicted by their implicit goal to rest (Study 3), indicating that depletion does not indiscriminately suspend all self-regulatory processes. In Study 4, we showed that when an effective comparator mechanism is counterproductive to task performance, depletion can actually increase task performance. Implications of our findings for the underlying process of depletion as well as models positing ultimate explanations for sequential self-regulation are discussed. (PsycINFO Database Record PMID:27442767

  9. Microstructure and compressive mechanical properties of cortical bone in children with osteogenesis imperfecta treated with bisphosphonates compared with healthy children.

    PubMed

    Imbert, Laurianne; Aurégan, Jean-Charles; Pernelle, Kélig; Hoc, Thierry

    2015-06-01

    Osteogenesis imperfecta (OI) is a genetic disorder characterized by a change in bone tissue quality, but little data are available to describe the factors involved at the macroscopic scale. To better understand the effect of microstructure alterations on the mechanical properties at the sample scale, we studied the structural and mechanical properties of six cortical bone samples from children with OI treated with bisphosphonates and compared them to the properties of three controls. Scanning electron microscopy, high resolution computed tomography and compression testing were used to assess these properties. More resorption cavities and a higher osteocyte lacunar density were observed in OI bone compared with controls. Moreover, a higher porosity was measured for OI bones along with lower macroscopic Young's modulus, yield stress and ultimate stress. The microstructure was impaired in OI bones; the higher porosity and osteocyte lacunar density negatively impacted the mechanical properties and made the bone more prone to fracture. PMID:25828157

  10. Biomechanical Origins of Muscle Stem Cell Signal Transduction.

    PubMed

    Morrissey, James B; Cheng, Richard Y; Davoudi, Sadegh; Gilbert, Penney M

    2016-04-10

    Skeletal muscle, the most abundant and widespread tissue in the human body, contracts upon receiving electrochemical signals from the nervous system to support essential functions such as thermoregulation, limb movement, blinking, swallowing and breathing. Reconstruction of adult muscle tissue relies on a pool of mononucleate, resident muscle stem cells, known as "satellite cells", expressing the paired-box transcription factor Pax7 necessary for their specification during embryonic development and long-term maintenance during adult life. Satellite cells are located around the myofibres in a niche at the interface of the basal lamina and the host fibre plasma membrane (i.e., sarcolemma), at a very low frequency. Upon damage to the myofibres, quiescent satellite cells are activated and give rise to a population of transient amplifying myogenic progenitor cells, which eventually exit the cell cycle permanently and fuse to form new myofibres and regenerate the tissue. A subpopulation of satellite cells self-renew and repopulate the niche, poised to respond to future demands. Harnessing the potential of satellite cells relies on a complete understanding of the molecular mechanisms guiding their regulation in vivo. Over the past several decades, studies revealed many signal transduction pathways responsible for satellite cell fate decisions, but the niche cues driving the activation and silencing of these pathways are less clear. Here we explore the scintillating possibility that considering the dynamic changes in the biophysical properties of the skeletal muscle, namely stiffness, and the stretch and shear forces to which a myofibre can be subjected to may provide missing information necessary to gain a full understanding of satellite cell niche regulation. PMID:26004541

  11. Second-Chance Signal Transduction Explains Cooperative Flagellar Switching

    PubMed Central

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

    2012-01-01

    The reversal of flagellar motion (switching) results from the interaction between a switch complex of the flagellar rotor and a torque-generating stationary unit, or stator (motor unit). To explain the steeply cooperative ligand-induced switching, present models propose allosteric interactions between subunits of the rotor, but do not address the possibility of a reaction that stimulates a bidirectional motor unit to reverse direction of torque. During flagellar motion, the binding of a ligand-bound switch complex at the dwell site could excite a motor unit. The probability that another switch complex of the rotor, moving according to steady-state rotation, will reach the same dwell site before that motor unit returns to ground state will be determined by the independent decay rate of the excited-state motor unit. Here, we derive an analytical expression for the energy coupling between a switch complex and a motor unit of the stator complex of a flagellum, and demonstrate that this model accounts for the cooperative switching response without the need for allosteric interactions. The analytical result can be reproduced by simulation when (1) the motion of the rotor delivers a subsequent ligand-bound switch to the excited motor unit, thereby providing the excited motor unit with a second chance to remain excited, and (2) the outputs from multiple independent motor units are constrained to a single all-or-none event. In this proposed model, a motor unit and switch complex represent the components of a mathematically defined signal transduction mechanism in which energy coupling is driven by steady-state and is regulated by stochastic ligand binding. Mathematical derivation of the model shows the analytical function to be a general form of the Hill equation (Hill AV (1910) The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves. J Physiol 40: iv–vii). PMID:22844429

  12. Antitumor Activity of Tenacissoside H on Esophageal Cancer through Arresting Cell Cycle and Regulating PI3K/Akt-NF-κB Transduction Cascade

    PubMed Central

    Jia, Yong-sen; Hu, Xue-qin; Gabriella, Hegyi; Qin, Li-juan; Meggyeshazi, Nora

    2015-01-01

    Objective. The purpose of the study was to elucidate the molecular mechanism of tenacissoside H (TDH) inhibiting esophageal carcinoma infiltration and proliferation. Methods. In vitro, EC9706 cells were treated with TDH. Cells proliferation and cell cycle were assayed. PI3K and NF-κB mRNAs expression were determined by real time PCR. In vivo, model of nude mice with tumor was established. Mice were treated with TDH. Inhibition ratio of tumor volume was calculated. PCNA expression was examined. Protein expression in PI3K/Akt-NF-κB signaling pathway was determined. Results. In vitro, TDH significantly inhibited cells proliferation in a time-and-dose-dependent manner. TDH arrested the cell cycle in S phase and significantly inhibited PI3K and NF-κB mRNA expression, compared with blank controlled group (P < 0.05). In vivo, TDH strongly inhibits tumor growth and volume. PCNA expression was significantly decreased after treatment of TDH. TDH downregulated proteins expression in PI3K/Akt-NF-κB transduction cascade (P < 0.05). Conclusion. TDH inhibited esophageal carcinoma infiltration and proliferation both in vitro and in vivo. The anticancer activity has relation to arresting the cell cycle at the S phase, inhibited the PCNA expression of transplanted tumors in nude mice, and regulated the protein expression in the PI3K/Akt-NF-κB transduction cascade. PMID:26495015

  13. Gene transduction efficiency in cells of different species by HIV and EIAV vectors.

    PubMed

    Ikeda, Y; Collins, M K L; Radcliffe, P A; Mitrophanous, K A; Takeuchi, Y

    2002-07-01

    The ability of human immunodeficiency virus (HIV)- and equine infectious anaemia virus (EIAV)-based vectors to transduce cell lines from a range of species was compared. Both vectors carried the vesicular stomatitis virus G (VSV-G) envelope protein and encoded an enhanced green fluorescent protein (eGFP) gene driven by a human cytomegalovirus (CMV) early promoter. Immunostaining for viral core proteins and VSV-G was used to demonstrate that the HIV and EIAV vector preparations contained similar numbers of virus particles. Various cell lines were transduced with these vectors and the transduction efficiency was estimated by measuring eGFP expression. Efficient transduction by both vectors was observed in human, hamster, pig, horse, cat and dog cell lines, although EIAV vector was about 10-fold less efficient in human, hamster and pig cells normalised to the total number of viral particles. This could be partly explained by the lower RNA genome levels per particle for EIAV as measured by real-time RT-PCR. Rodent cells appeared to be transduced inefficiently with both vectors, but when the CMV promoter was substituted with the EF1alpha promoter in the HIV vectors, the expression level increased leading to an increase in the measurable level of transduction. PMID:12085241

  14. Ex Vivo and In Vivo Lentivirus-Mediated Transduction of Airway Epithelial Progenitor Cells.

    PubMed

    Leoni, Giulia; Wasowicz, Marguerite Y; Chan, Mario; Meng, Cuixiang; Farley, Raymond; Brody, Steven L; Inoue, Makoto; Hasegawa, Mamoru; Alton, Eric W F W; Griesenbach, Uta

    2015-01-01

    A key challenge in pulmonary gene therapy for cystic fibrosis is to provide long-term correction of the genetic defect. This may be achievable by targeting airway epithelial stem/progenitor cells with an integrating vector. Here, we evaluated the ability of a lentiviral vector, derived from the simian immunodeficiency virus and pseudotyped with F and HN envelope proteins from Sendai virus, to transduce progenitor basal cells of the mouse nasal airways. We first transduced basal cell-enriched cultures ex vivo and confirmed efficient transduction of cytokeratin-5 positive cells. We next asked whether progenitor cells could be transduced in vivo. We evaluated the transduction efficiency in mice pretreated by intranasal administration of polidocanol to expose the progenitor cell layer. Compared to control mice, polidocanol treated mice demonstrated a significant increase in the number of transduced basal cells at 3 and 14 days post vector administration. At 14 days, the epithelium of treated mice contained clusters (4 to 8 adjacent cells) of well differentiated ciliated, as well as basal cells suggesting a clonal expansion. These results indicate that our lentiviral vector can transduce progenitor basal cells in vivo, although transduction required denudation of the surface epithelium prior to vector administration. PMID:26471068

  15. Receptor clustering affects signal transduction at the membrane level in the reaction-limited regime

    NASA Astrophysics Data System (ADS)

    Caré, Bertrand R.; Soula, Hédi A.

    2013-01-01

    Many types of membrane receptors are found to be organized as clusters on the cell surface. We investigate the potential effect of such receptor clustering on the intracellular signal transduction stage. We consider a canonical pathway with a membrane receptor (R) activating a membrane-bound intracellular relay protein (G). We use Monte Carlo simulations to recreate biochemical reactions using different receptor spatial distributions and explore the dynamics of the signal transduction. Results show that activation of G by R is severely impaired by R clustering, leading to an apparent blunted biological effect compared to control. Paradoxically, this clustering decreases the half maximal effective dose (ED50) of the transduction stage, increasing the apparent affinity. We study an example of inter-receptor interaction in order to account for possible compensatory effects of clustering and observe the parameter range in which such interactions slightly counterbalance the loss of activation of G. The membrane receptors’ spatial distribution affects the internal stages of signal amplification, suggesting a functional role for membrane domains and receptor clustering independently of proximity-induced receptor-receptor interactions.

  16. A Learning-Based CT Prostate Segmentation Method via Joint Transductive Feature Selection and Regression

    PubMed Central

    Shi, Yinghuan; Gao, Yaozong; Liao, Shu; Zhang, Daoqiang

    2015-01-01

    In1 recent years, there has been a great interest in prostate segmentation, which is a important and challenging task for CT image guided radiotherapy. In this paper, a learning-based segmentation method via joint transductive feature selection and transductive regression is presented, which incorporates the physician’s simple manual specification (only taking a few seconds), to aid accurate segmentation, especially for the case with large irregular prostate motion. More specifically, for the current treatment image, experienced physician is first allowed to manually assign the labels for a small subset of prostate and non-prostate voxels, especially in the first and last slices of the prostate regions. Then, the proposed method follows the two step: in prostate-likelihood estimation step, two novel algorithms: tLasso and wLapRLS, will be sequentially employed for transductive feature selection and transductive regression, respectively, aiming to generate the prostate-likelihood map. In multi-atlases based label fusion step, the final segmentation result will be obtained according to the corresponding prostate-likelihood map and the previous images of the same patient. The proposed method has been substantially evaluated on a real prostate CT dataset including 24 patients with 330 CT images, and compared with several state-of-the-art methods. Experimental results show that the proposed method outperforms the state-of-the-arts in terms of higher Dice ratio, higher true positive fraction, and lower centroid distances. Also, the results demonstrate that simple manual specification can help improve the segmentation performance, which is clinically feasible in real practice. PMID:26752809

  17. Physiological performance of warm-adapted marine ectotherms: Thermal limits of mitochondrial energy transduction efficiency.

    PubMed

    Martinez, Eloy; Hendricks, Eric; Menze, Michael A; Torres, Joseph J

    2016-01-01

    Thermal regimes in aquatic systems have profound implications for the physiology of ectotherms. In particular, the effect of elevated temperatures on mitochondrial energy transduction in tropical and subtropical teleosts may have profound consequences on organismal performance and population viability. Upper and lower whole-organism critical temperatures for teleosts suggest that subtropical and tropical species are not susceptible to the warming trends associated with climate change, but sub-lethal effects on energy transduction efficiency and population dynamics remain unclear. The goal of the present study was to compare the thermal sensitivity of processes associated with mitochondrial energy transduction in liver mitochondria from the striped mojarra (Eugerres plumieri), the whitemouth croaker (Micropogonias furnieri) and the palometa (Trachinotus goodei), to those of the subtropical pinfish (Lagodon rhomboides) and the blue runner (Caranx crysos). Mitochondrial function was assayed at temperatures ranging from 10 to 40°C and results obtained for both tropical and subtropical species showed a reduction in the energy transduction efficiency of the oxidative phosphorylation (OXPHOS) system in most species studied at temperatures below whole-organism critical temperature thresholds. Our results show a loss of coupling between O2 consumption and ATP production before the onset of the critical thermal maxima, indicating that elevated temperature may severely impact the yield of ATP production per carbon unit oxidized. As warming trends are projected for tropical regions, increasing water temperatures in tropical estuaries and coral reefs could impact long-term growth and reproductive performance in tropical organisms, which are already close to their upper thermal limit. PMID:26297983

  18. Elucidation of Cross-Talk and Specificity of Early Response Mechanisms to Salt and PEG-Simulated Drought Stresses in Brassica napus Using Comparative Proteomic Analysis

    PubMed Central

    Luo, Junling; Tang, Shaohua; Peng, Xiaojue; Yan, Xiaohong; Zeng, Xinhua; Li, Jun; Li, Xiaofei; Wu, Gang

    2015-01-01

    To understand the cross-talk and specificity of the early responses of plants to salt and drought, we performed physiological and proteome analyses of Brassica napus seedlings pretreated with 245 mM NaCl or 25% polyethylene glycol (PEG) 6000 under identical osmotic pressure (-1.0 MPa). Significant decreases in water content and photosynthetic rate and excessive accumulation of compatible osmolytes and oxidative damage were observed in response to both stresses. Unexpectedly, the drought response was more severe than the salt response. We further identified 45 common differentially expressed proteins (DEPs), 143 salt-specific DEPs and 160 drought-specific DEPs by isobaric tags for relative and absolute quantitation (iTRAQ) analysis. The proteome quantitative data were then confirmed by multiple reaction monitoring (MRM). The differences in the proteomic profiles between drought-treated and salt-treated seedlings exceeded the similarities in the early stress responses. Signal perception and transduction, transport and membrane trafficking, and photosynthesis-related proteins were enriched as part of the molecular cross-talk and specificity mechanism in the early responses to the two abiotic stresses. The Ca2+ signaling, G protein-related signaling, 14-3-3 signaling pathway and phosphorylation cascades were the common signal transduction pathways shared by both salt and drought stress responses; however, the proteins with executive functions varied. These results indicate functional specialization of family proteins in response to different stresses, i.e., CDPK21, TPR, and CTR1 specific to phosphorylation cascades under early salt stress, whereas STN7 and BSL were specific to phosphorylation cascades under early drought stress. Only the calcium-binding EF-hand family protein and ZKT were clearly identified as signaling proteins that acted as cross-talk nodes for salt and drought signaling pathways. Our study provides new clues and insights for developing strategies to

  19. Elucidation of Cross-Talk and Specificity of Early Response Mechanisms to Salt and PEG-Simulated Drought Stresses in Brassica napus Using Comparative Proteomic Analysis.

    PubMed

    Luo, Junling; Tang, Shaohua; Peng, Xiaojue; Yan, Xiaohong; Zeng, Xinhua; Li, Jun; Li, Xiaofei; Wu, Gang

    2015-01-01

    To understand the cross-talk and specificity of the early responses of plants to salt and drought, we performed physiological and proteome analyses of Brassica napus seedlings pretreated with 245 mM NaCl or 25% polyethylene glycol (PEG) 6000 under identical osmotic pressure (-1.0 MPa). Significant decreases in water content and photosynthetic rate and excessive accumulation of compatible osmolytes and oxidative damage were observed in response to both stresses. Unexpectedly, the drought response was more severe than the salt response. We further identified 45 common differentially expressed proteins (DEPs), 143 salt-specific DEPs and 160 drought-specific DEPs by isobaric tags for relative and absolute quantitation (iTRAQ) analysis. The proteome quantitative data were then confirmed by multiple reaction monitoring (MRM). The differences in the proteomic profiles between drought-treated and salt-treated seedlings exceeded the similarities in the early stress responses. Signal perception and transduction, transport and membrane trafficking, and photosynthesis-related proteins were enriched as part of the molecular cross-talk and specificity mechanism in the early responses to the two abiotic stresses. The Ca2+ signaling, G protein-related signaling, 14-3-3 signaling pathway and phosphorylation cascades were the common signal transduction pathways shared by both salt and drought stress responses; however, the proteins with executive functions varied. These results indicate functional specialization of family proteins in response to different stresses, i.e., CDPK21, TPR, and CTR1 specific to phosphorylation cascades under early salt stress, whereas STN7 and BSL were specific to phosphorylation cascades under early drought stress. Only the calcium-binding EF-hand family protein and ZKT were clearly identified as signaling proteins that acted as cross-talk nodes for salt and drought signaling pathways. Our study provides new clues and insights for developing strategies to

  20. A comparative study of mechanical alloying and mechanical milling of Nd{sub 8}Fe{sub 88}B{sub 4}

    SciTech Connect

    Zeng, Q.; Xiao, Y.F.; Liu, X.B.; Dong, S.Z.; Deng, Y.S.; Zhang, Z.Y.; Wang, R.

    1999-06-01

    A comparative study was made of structure and magnetic properties of Nd{sub 8}Fe{sub 88}B{sub 4} prepared by mechanical alloying (MA) using elemental powders as starting materials and by mechanical milling (MM) of the alloy, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) combined with transmission electron microscopic (TEM) studies revealed that both milling procedures resulted in a mixture of {alpha}-Fe and an amorphous phase. The thermal stability of the as-milled powders produced by MA was comparable to that of the as-milled powders produced by MM. Heat treatment of the milled powders above the crystallization temperature resulted in the formation of a nanocrystalline mixture of Nd{sub 2}Fe{sub 14}B and {alpha}-Fe, but annealed MA powders demonstrated a somewhat coarser structure in comparison with annealed MM powders. Therefore, higher remanences and coercivities were obtained by MM.

  1. Modelling protein functional domains in signal transduction using Maude

    NASA Technical Reports Server (NTRS)

    Sriram, M. G.

    2003-01-01

    Modelling of protein-protein interactions in signal transduction is receiving increased attention in computational biology. This paper describes recent research in the application of Maude, a symbolic language founded on rewriting logic, to the modelling of functional domains within signalling proteins. Protein functional domains (PFDs) are a critical focus of modern signal transduction research. In general, Maude models can simulate biological signalling networks and produce specific testable hypotheses at various levels of abstraction. Developing symbolic models of signalling proteins containing functional domains is important because of the potential to generate analyses of complex signalling networks based on structure-function relationships.

  2. Comparative analysis of disease pathogenesis and molecular mechanisms of New World and Old World arenavirus infections

    PubMed Central

    McLay, Lisa; Liang, Yuying

    2014-01-01

    Arenaviruses can cause fatal human haemorrhagic fever (HF) diseases for which vaccines and therapies are extremely limited. Both the New World (NW) and Old World (OW) groups of arenaviruses contain HF-causing pathogens. Although these two groups share many similarities, important differences with regard to pathogenicity and molecular mechanisms of virus infection exist. These closely related pathogens share many characteristics, including genome structure, viral assembly, natural host selection and the ability to interfere with innate immune signalling. However, members of the NW and OW viruses appear to use different receptors for cellular entry, as well as different mechanisms of virus internalization. General differences in disease signs and symptoms and pathological lesions in patients infected with either NW or OW arenaviruses are also noted and discussed herein. Whilst both the OW Lassa virus (LASV) and the NW Junin virus (JUNV) can cause disruption of the vascular endothelium, which is an important pathological feature of HF, the immune responses to these related pathogens seem to be quite distinct. Whereas LASV infection results in an overall generalized immune suppression, patients infected with JUNV seem to develop a cytokine storm. Additionally, the type of immune response required for recovery and clearance of the virus is different between NW and OW infections. These differences may be important to allow the viruses to evade host immune detection. Understanding these differences will aid the development of new vaccines and treatment strategies against deadly HF viral infections. PMID:24068704

  3. Comparative proteomics exploring the molecular mechanism of eutrophic water purification using water hyacinth (Eichhornia crassipes).

    PubMed

    Li, Xiong; Xi, Houcheng; Sun, Xudong; Yang, Yunqiang; Yang, Shihai; Zhou, Yanli; Zhou, Xinmao; Yang, Yongping

    2015-06-01

    Eutrophication is a serious threat to ecosystem stability and use of water resources worldwide. Accordingly, physical, chemical, and biological technologies have been developed to treat eutrophic water. Phytoremediation has attracted a great deal of attention, and water hyacinth (Eichhornia crassipes) is regarded as one of the best plants for purification of eutrophic water. Previous studies have shown that water hyacinths remove nitrogen (N) and phosphorus (P) via diverse processes and that they can inhibit the growth of algae. However, the molecular mechanisms responsible for these processes, especially the role of proteins, are unknown. In this study, we applied a proteomics approach to investigate the protein dynamics of water hyacinth under three eutrophication levels. The results suggested that proteins with various functions, including response to stress, N and P metabolic pathways, synthesis and secretion, photosynthesis, biosynthesis, and energy metabolism, were involved in regulating water hyacinth to endure the excess-nutrient environment, remove N and P, and inhibit algal growth. The results help us understand the mechanism of purification of eutrophic water by water hyacinth and supply a theoretical basis for improving techniques for phytoremediation of polluted water. PMID:25563831

  4. Genome-wide Comparative Analysis of Atopic Dermatitis and Psoriasis Gives Insight into Opposing Genetic Mechanisms

    PubMed Central

    Baurecht, Hansjörg; Hotze, Melanie; Brand, Stephan; Büning, Carsten; Cormican, Paul; Corvin, Aiden; Ellinghaus, David; Ellinghaus, Eva; Esparza-Gordillo, Jorge; Fölster-Holst, Regina; Franke, Andre; Gieger, Christian; Hubner, Norbert; Illig, Thomas; Irvine, Alan D.; Kabesch, Michael; Lee, Young A.E.; Lieb, Wolfgang; Marenholz, Ingo; McLean, W.H. Irwin; Morris, Derek W.; Mrowietz, Ulrich; Nair, Rajan; Nöthen, Markus M.; Novak, Natalija; O’Regan, Grainne M.; Schreiber, Stefan; Smith, Catherine; Strauch, Konstantin; Stuart, Philip E.; Trembath, Richard; Tsoi, Lam C.; Weichenthal, Michael; Barker, Jonathan; Elder, James T.; Weidinger, Stephan; Cordell, Heather J.; Brown, Sara J.

    2015-01-01

    Atopic dermatitis and psoriasis are the two most common immune-mediated inflammatory disorders affecting the skin. Genome-wide studies demonstrate a high degree of genetic overlap, but these diseases have mutually exclusive clinical phenotypes and opposing immune mechanisms. Despite their prevalence, atopic dermatitis and psoriasis very rarely co-occur within one individual. By utilizing genome-wide association study and ImmunoChip data from >19,000 individuals and methodologies developed from meta-analysis, we have identified opposing risk alleles at shared loci as well as independent disease-specific loci within the epidermal differentiation complex (chromosome 1q21.3), the Th2 locus control region (chromosome 5q31.1), and the major histocompatibility complex (chromosome 6p21–22). We further identified previously unreported pleiotropic alleles with opposing effects on atopic dermatitis and psoriasis risk in PRKRA and ANXA6/TNIP1. In contrast, there was no evidence for shared loci with effects operating in the same direction on both diseases. Our results show that atopic dermatitis and psoriasis have distinct genetic mechanisms with opposing effects in shared pathways influencing epidermal differentiation and immune response. The statistical analysis methods developed in the conduct of this study have produced additional insight from previously published data sets. The approach is likely to be applicable to the investigation of the genetic basis of other complex traits with overlapping and distinct clinical features. PMID:25574825

  5. Impact of Age at Administration, Lysosomal Storage, and Transgene Regulatory Elements on AAV2/8-Mediated Rat Liver Transduction

    PubMed Central

    Cotugno, Gabriella; Annunziata, Patrizia; Barone, Maria Vittoria; Karali, Marianthi; Banfi, Sandro; Auricchio, Alberto

    2012-01-01

    Liver-directed gene transfer is being investigated for the treatment of systemic or liver-specific diseases. Recombinant vectors based on adeno-associated virus serotype 8 (AAV2/8) efficiently transduce liver cells allowing long term transgene expression after a single administration in animal models and in patients. We evaluated the impact on AAV2/8-mediated rat liver transduction of the following variables: i) age at vector administration, ii) presence of lysosomal storage in liver cells, and iii) regulatory elements included in the transgene expression cassette. We found that systemic administration of AAV2/8 to newborn rats results in vector genome dilution and reduced transduction efficacy when compared to adult injected animals, presumably due to hepatocyte proliferation. Accumulation of glycosaminoglycans in lysosomes does not impact on levels and distribution of AAV2/8-mediated liver transduction. Transgene expression occurs in hepatocytes but not in Kupffer or liver endothelial cells when the liver-specific thyroxine-binding-globulin promoter is used. However, extra-hepatic transduction is observed in the spleen and kidney of animals injected at birth. The use of target sequences for the hematopoietic-specific microRNA miR142-3p does not improve liver transduction efficacy neither reduce immune responses to the lysosomal enzyme arylsulfatase B. The inclusion of a variant of the Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE-m) decreases AAV2/8-mediated liver transduction levels. As AAV2/8-mediated liver gene transfer is entering in the clinical arena, these data will provide relevant information to the design of efficient AAV2/8-based therapeutic strategies. PMID:22428010

  6. Microbial iron management mechanisms in extremely acidic environments: comparative genomics evidence for diversity and versatility

    PubMed Central

    Osorio, Héctor; Martínez, Verónica; Nieto, Pamela A; Holmes, David S; Quatrini, Raquel

    2008-01-01

    Background Iron is an essential nutrient but can be toxic at high intracellular concentrations and organisms have evolved tightly regulated mechanisms for iron uptake and homeostasis. Information on iron management mechanisms is available for organisms living at circumneutral pH. However, very little is known about how acidophilic bacteria, especially those used for industrial copper bioleaching, cope with environmental iron loads that can be 1018 times the concentration found in pH neutral environments. This study was motivated by the need to fill this lacuna in knowledge. An understanding of how microorganisms thrive in acidic ecosystems with high iron loads requires a comprehensive investigation of the strategies to acquire iron and to coordinate this acquisition with utilization, storage and oxidation of iron through metal responsive regulation. In silico prediction of iron management genes and Fur regulation was carried out for three Acidithiobacilli: Acidithiobacillus ferrooxidans (iron and sulfur oxidizer) A. thiooxidans and A. caldus (sulfur oxidizers) that can live between pH 1 and pH 5 and for three strict iron oxidizers of the Leptospirillum genus that live at pH 1 or below. Results Acidithiobacilli have predicted FeoB-like Fe(II) and Nramp-like Fe(II)-Mn(II) transporters. They also have 14 different TonB dependent ferri-siderophore transporters of diverse siderophore affinity, although they do not produce classical siderophores. Instead they have predicted novel mechanisms for dicitrate synthesis and possibly also for phosphate-chelation mediated iron uptake. It is hypothesized that the unexpectedly large number and diversity of Fe(III)-uptake systems confers versatility to this group of acidophiles, especially in higher pH environments (pH 4–5) where soluble iron may not be abundant. In contrast, Leptospirilla have only a FtrI-Fet3P-like permease and three TonB dependent ferri-dicitrate siderophore systems. This paucity of iron uptake systems could

  7. Mechanism of amorphous silica particles precipitation: simulation approach compared to experimental results

    NASA Astrophysics Data System (ADS)

    Noguera, Claudine; Fritz, Bertrand; Clement, Alain

    2015-04-01

    Despite its importance in numerous industrial and natural processes, many unsolved questions remain regarding the mechanism of silica precipitation in aqueous solutions: order of the reaction, role of silica oligomers, existence of an induction time and characteristics of the particle population. Beyond empirical approaches used in the past, we demonstrate that the classical nucleation theory associated to a size dependent growth law, as embedded in the NANOKIN code (1-3), allows a quantitative description of precipitation occurring under largely different experimental conditions : preexisting initial supersaturation in a large domain of temperature (5-150°C) and chemical composition (4), supersaturation reached by neutralization of a high pH silica solution (5) or by fast cooling (6). In that way, the mechanism of silica precipitation can be unraveled. We are able to discard the hypothesis of an induction time as an explanation for the plateaus observed in the saturation curves in these experiments. We challenge the role of oligomer incorporation at the growth stage to account for the observed rate laws and we stress the difference between the order of the growth law and the order of the total reaction rate. We also demonstrate that the characteristics of the particle population are strongly dependent on the way supersaturation is reached (7). Such a microscopic approach thus proves to be well suited to elucidate the mechanism of nanoparticle formation in natural and industrial contexts, involving silica, but also other mineral phases produced as nanoparticles (8). (1) Noguera C., Fritz B., Clément A. and Barronet A., J. Cryst. Growth, 2006, 297, 180. (2) Noguera C., Fritz B., Clément A. and Barronet A., J. Cryst. Growth, 2006, 297, 187. (3) Fritz B., Clément A., Amal Y. and Noguera C., Geochim. Cosmochim. Acta, 2009, 73, 1340. (4) Rothbaum, H.P. and Rohde A.G., J. Colloid Interf. Sci., 1979,71, 533. (5) Tobler D.J., Shaw S. and Benning L.G., Geochim

  8. Comparative Study Of Focal Mechanisms In South Central Chile Before And After The 2010 Maule Earthquake

    NASA Astrophysics Data System (ADS)

    Agurto, H.; Rietbrock, A.; Ryder, I. M.; Haberland, C. A.

    2011-12-01

    On 27 February 2010, a Mw=8.8 earthquake occurred off the coast of south central Chile rupturing nearly 500 km of the subduction zone plate interface. The earthquake also generated a tsunami and caused more than 500 fatalities. The largest earthquakes recorded have taken place along subduction margins (e.g. Chile 1960, 2010, Andaman-Sumatra 2004, Japan 2011) and understanding their rupture mechanisms and deformation regimes is therefore of vital importance. From November 2004 to October 2005, the TIPTEQ project ("From The Incoming Plate to megaThrust EarthQuake"; Rietbrock et al., 2007; Haberland et al., 2009) maintained a network of 120 seismic stations inland and 10 stations at sea between 37 and 39° lat. S., continuously-recording and monitoring the seismicity occurring in the area before the 2010 Maule earthquake. By using first motion polarities and moment tensor inversion we have computed and analyzed focal mechanisms for a subset of data from these records. We found thrust faulting along the subduction interface down to a depth of ~30 km, followed by a gap in the seismicity and then deeper earthquakes showing diverse faulting mechanisms more sparsely distributed within the subducting plate. We also see strike-slip crustal faulting occurring down to ~12 km depth within the area of the Lanalhue fault. The most striking observation is the presence of deep (40 km) normal faulting seismicity in the fore-arc, close to the trench. We have now started to analyze the International Maule Aftershocks Dataset (IMAD) of the 2010 earthquake in the southern rupture region. Again we observe thrust faulting in the subduction interface and a seismic gap between an upper and lower zone of seismicity along the interface. By comparison of the pre- and post-earthquake datasets we are investigating whether the Maule earthquake caused any changes in the style of deformation in this part of Chile. References Haberland, C., A. Rietbrock, D. Lange, K. Bataille, and T. Dahm (2009

  9. Matricellular signal transduction involving calmodulin in the social amoebozoan dictyostelium.

    PubMed

    O'Day, Danton H; Huber, Robert J

    2013-01-01

    The social amoebozoan Dictyostelium discoideum undergoes a developmental sequence wherein an extracellular matrix (ECM) sheath surrounds a group of differentiating cells. This sheath is comprised of proteins and carbohydrates, like the ECM of mammalian tissues. One of the characterized ECM proteins is the cysteine-rich, EGF-like (EGFL) repeat-containing, calmodulin (CaM)-binding protein (CaMBP) CyrA. The first EGFL repeat of CyrA increases the rate of random cell motility and cyclic AMP-mediated chemotaxis. Processing of full-length CyrA (~63 kDa) releases two major EGFL repeat-containing fragments (~45 kDa and ~40 kDa) in an event that is developmentally regulated. Evidence for an EGFL repeat receptor also exists and downstream intracellular signaling pathways involving CaM, Ras, protein kinase A and vinculin B phosphorylation have been characterized. In total, these results identify CyrA as a true matricellular protein comparable in function to tenascin C and other matricellular proteins from mammalian cells. Insight into the regulation and processing of CyrA has also been revealed. CyrA is the first identified extracellular CaMBP in this eukaryotic microbe. In keeping with this, extracellular CaM (extCaM) has been shown to be present in the ECM sheath where it binds to CyrA and inhibits its cleavage to release the 45 kDa and 40 kDa EGFL repeat-containing fragments. The presence of extCaM and its role in regulating a matricellular protein during morphogenesis extends our understanding of CaM-mediated signal transduction in eukaryotes. PMID:24705101

  10. Similar Mechanisms? A Comparative Longitudinal Study of Adolescent Violence and Victimization.

    PubMed

    Sullivan, Christopher J; Ousey, Graham C; Wilcox, Pamela

    2016-05-01

    This study analyzes the extent to which there are similar patterns of violent offending and victimization in a panel of adolescents. Three explanatory perspectives are assessed: population heterogeneity, state dependence, and a mixed model. Data are drawn from a four-wave panel study of 3,976 adolescents. The main study measures comprise self-report indices for victimization and delinquency. Theoretical perspectives are specified through three distinct statistical approaches-latent growth curve, autoregressive simplex, and autoregressive latent trajectory (ALT) models. The analysis then incorporates the effects of relevant time-stable and time-varying influences. A mixed perspective, represented by the ALT model, best fits the data for both violent victimization and offending. Covariates drawn from the two perspectives have similar effects as well. The findings provide some support for a similar mechanisms hypothesis. PMID:25604970

  11. Comparative role of disc degeneration and ligament failure on functional mechanics of the lumbar spine.

    PubMed

    Ellingson, Arin M; Shaw, Miranda N; Giambini, Hugo; An, Kai-Nan

    2016-07-01

    Understanding spinal kinematics is essential for distinguishing between pathological conditions of spine disorders, which ultimately lead to low back pain. It is of high importance to understand how changes in mechanical properties affect the response of the lumbar spine, specifically in an effort to differentiate those associated with disc degeneration from ligamentous changes, allowing for more precise treatment strategies. To do this, the goals of this study were twofold: (1) develop and validate a finite element (FE) model of the lumbar spine and (2) systematically alter the properties of the intervertebral disc and ligaments to define respective roles in functional mechanics. A three-dimensional non-linear FE model of the lumbar spine (L3-sacrum) was developed and validated for pure moment bending. Disc degeneration and sequential ligament failure were modelled. Intersegmental range of motion (ROM) and bending stiffness were measured. The prediction of the FE model to moment loading in all three planes of bending showed very good agreement, where global and intersegmental ROM and bending stiffness of the model fell within one standard deviation of the in vitro results. Degeneration decreased ROM for all directions. Stiffness increased for all directions except axial rotation, where it initially increased then decreased for moderate and severe degeneration, respectively. Incremental ligament failure produced increased ROM and decreased stiffness. This effect was much more pronounced for all directions except lateral bending, which is minimally impacted by ligaments. These results indicate that lateral bending may be more apt to detect the subtle changes associated with degeneration, without being masked by associated changes of surrounding stabilizing structures. PMID:26404463

  12. Fluoride blocks an inactivation step of transduction in a locust photoreceptor

    PubMed Central

    Payne, Richard

    1982-01-01

    1. Photoreceptors in a superfused retina of a locust compound eye are treated with saline containing 10 mM-NaF, while their intracellular resting potential and responses are recorded using glass micropipettes. 2. Treatment for two minutes with 10 mM-NaF, followed by a series of brief, bright flashes of light, results in an irreversible, noisy depolarization of approximately 10 mV. The final, stable level of depolarization is reached through the summed effect of each of the noisy, depolarizing afterpotentials that follow every response of the cell to a light flash. If kept in darkness after treatment with NaF, the noisy depolarization still develops, but more gradually, over a period of 5 min. 3. The voltage noise induced by NaF mimics light-induced voltage noise when the two are compared at mean depolarizations of more than 15 mV. At very small depolarizations, however, fluoride-induced noise cannot be resolved into the large discrete events (bumps) that are typical of the response of a dark-adapted photoreceptor to a single photon. 4. The complete replacement of the superfusate sodium by choline reversibly reduces the fluoride-induced noise and depolarization to the same extent as it does the light-induced noise and depolarization of an illuminated cell. 5. Increasing the superfusate calcium concentration from 0·5 to 10 mM also reversibly reduces fluoride-induced noise and depolarization to the same extent as it does light-induced noise and depolarization. This action of calcium is accompanied by an increase in a cell's input resistance which opposes the reduction caused by light or fluoride treatment. 6. The results confirm the proposal (Payne, 1981) that anionic metabolic inhibitors cause spontaneous activity in sodium channels that are normally opened by light. A model is proposed in which fluoride acts by blocking the inactivation of a late stage in the transduction mechanism. PMID:6286940

  13. Regulation of Early Steps of GPVI Signal Transduction by Phosphatases: A Systems Biology Approach

    PubMed Central

    Dunster, Joanne L.; Mazet, Francoise; Fry, Michael J.; Gibbins, Jonathan M.; Tindall, Marcus J.

    2015-01-01

    We present a data-driven mathematical model of a key initiating step in platelet activation, a central process in the prevention of bleeding following Injury. In vascular disease, this process is activated inappropriately and causes thrombosis, heart attacks and stroke. The collagen receptor GPVI is the primary trigger for platelet activation at sites of injury. Understanding the complex molecular mechanisms initiated by this receptor is important for development of more effective antithrombotic medicines. In this work we developed a series of nonlinear ordinary differential equation models that are direct representations of biological hypotheses surrounding the initial steps in GPVI-stimulated signal transduction. At each stage model simulations were compared to our own quantitative, high-temporal experimental data that guides further experimental design, data collection and model refinement. Much is known about the linear forward reactions within platelet signalling pathways but knowledge of the roles of putative reverse reactions are poorly understood. An initial model, that includes a simple constitutively active phosphatase, was unable to explain experimental data. Model revisions, incorporating a complex pathway of interactions (and specifically the phosphatase TULA-2), provided a good description of the experimental data both based on observations of phosphorylation in samples from one donor and in those of a wider population. Our model was used to investigate the levels of proteins involved in regulating the pathway and the effect of low GPVI levels that have been associated with disease. Results indicate a clear separation in healthy and GPVI deficient states in respect of the signalling cascade dynamics associated with Syk tyrosine phosphorylation and activation. Our approach reveals the central importance of this negative feedback pathway that results in the temporal regulation of a specific class of protein tyrosine phosphatases in controlling the rate

  14. Regulation of Early Steps of GPVI Signal Transduction by Phosphatases: A Systems Biology Approach.

    PubMed

    Dunster, Joanne L; Mazet, Francoise; Fry, Michael J; Gibbins, Jonathan M; Tindall, Marcus J

    2015-11-01

    We present a data-driven mathematical model of a key initiating step in platelet activation, a central process in the prevention of bleeding following Injury. In vascular disease, this process is activated inappropriately and causes thrombosis, heart attacks and stroke. The collagen receptor GPVI is the primary trigger for platelet activation at sites of injury. Understanding the complex molecular mechanisms initiated by this receptor is important for development of more effective antithrombotic medicines. In this work we developed a series of nonlinear ordinary differential equation models that are direct representations of biological hypotheses surrounding the initial steps in GPVI-stimulated signal transduction. At each stage model simulations were compared to our own quantitative, high-temporal experimental data that guides further experimental design, data collection and model refinement. Much is known about the linear forward reactions within platelet signalling pathways but knowledge of the roles of putative reverse reactions are poorly understood. An initial model, that includes a simple constitutively active phosphatase, was unable to explain experimental data. Model revisions, incorporating a complex pathway of interactions (and specifically the phosphatase TULA-2), provided a good description of the experimental data both based on observations of phosphorylation in samples from one donor and in those of a wider population. Our model was used to investigate the levels of proteins involved in regulating the pathway and the effect of low GPVI levels that have been associated with disease. Results indicate a clear separation in healthy and GPVI deficient states in respect of the signalling cascade dynamics associated with Syk tyrosine phosphorylation and activation. Our approach reveals the central importance of this negative feedback pathway that results in the temporal regulation of a specific class of protein tyrosine phosphatases in controlling the rate

  15. Structure-function relationships in the IL-17 receptor: Implications for signal transduction and therapy

    PubMed Central

    Shen, Fang; Gaffen, Sarah L.

    2008-01-01

    IL-17 is the defining cytokine of a newly-described “Th17” population that plays critical roles in mediating inflammation and autoimmunity. The IL-17/IL-17 receptor superfamily is the most recent class of cytokines and receptors to be described, and until recently very little was known about its function or molecular biology. However, in the last year important new insights into the composition and dynamics of the receptor complex and mechanisms of downstream signal transduction have been made, which will be reviewed here. PMID:18178098

  16. Comparing residue clusters from thermophilic and mesophilic enzymes reveals adaptive mechanisms

    DOE PAGESBeta

    Sammond, Deanne W.; Kastelowitz, Noah; Himmel, Michael E.; Yin, Hang; Crowley, Michael F.; Bomble, Yannick J.

    2016-01-07

    Understanding how proteins adapt to function at high temperatures is important for deciphering the energetics that dictate protein stability and folding. While multiple principles important for thermostability have been identified, we lack a unified understanding of how internal protein structural and chemical environment determine qualitative or quantitative impact of evolutionary mutations. In this work we compare equivalent clusters of spatially neighboring residues between paired thermophilic and mesophilic homologues to evaluate adaptations under the selective pressure of high temperature. We find the residue clusters in thermophilic enzymes generally display improved atomic packing compared to mesophilic enzymes, in agreement with previous research.more » Unlike residue clusters from mesophilic enzymes, however, thermophilic residue clusters do not have significant cavities. In addition, anchor residues found in many clusters are highly conserved with respect to atomic packing between both thermophilic and mesophilic enzymes. As a result, the improvements in atomic packing observed in thermophilic homologues are not derived from these anchor residues but from neighboring positions, which may serve to expand optimized protein core regions.« less

  17. Comparing Residue Clusters from Thermophilic and Mesophilic Enzymes Reveals Adaptive Mechanisms

    PubMed Central

    Sammond, Deanne W.; Kastelowitz, Noah; Himmel, Michael E.; Yin, Hang; Crowley, Michael F.; Bomble, Yannick J.

    2016-01-01

    Understanding how proteins adapt to function at high temperatures is important for deciphering the energetics that dictate protein stability and folding. While multiple principles important for thermostability have been identified, we lack a unified understanding of how internal protein structural and chemical environment determine qualitative or quantitative impact of evolutionary mutations. In this work we compare equivalent clusters of spatially neighboring residues between paired thermophilic and mesophilic homologues to evaluate adaptations under the selective pressure of high temperature. We find the residue clusters in thermophilic enzymes generally display improved atomic packing compared to mesophilic enzymes, in agreement with previous research. Unlike residue clusters from mesophilic enzymes, however, thermophilic residue clusters do not have significant cavities. In addition, anchor residues found in many clusters are highly conserved with respect to atomic packing between both thermophilic and mesophilic enzymes. Thus the improvements in atomic packing observed in thermophilic homologues are not derived from these anchor residues but from neighboring positions, which may serve to expand optimized protein core regions. PMID:26741367

  18. Comparison of Transduction Efficiency of Recombinant AAV Serotypes 1, 2, 5, and 8 in the Rat Nigrostriatal System

    PubMed Central

    McFarland, Nikolaus R.; Lee, Jeng-Shin; Hyman, Bradley T.; McLean, Pamela J.

    2009-01-01

    Enhanced delivery and expression of genes in specific neuronal systems is critical for the development of genetic models of neurodegenerative disease and potential gene therapy. Recent discovery of new recombinant adeno-associated viral (rAAV) capsid serotypes has resulted in improved transduction efficiency, but expression levels, spread of transgene, and potential toxicity can differ depending on brain region and among species. We compared the transduction efficiency of titer-matched rAAV 2/1, 2/5 and 2/8 to the commonly used rAAV2/2 in the rat nigrostriatal system via expression of the reporter transgene, enhanced green fluorescent protein (EGFP). Newer rAAV serotypes 2/1, 2/5 and 2/8 demonstrated marked increase in transduction and spread of EGFP expression in dopaminergic nigrostriatal neurons and projections to the striatum and globus pallidus compared to rAAV2/2 at 2 weeks post injection. The number of nigral cells transduced was greatest for rAAV2/1, but for serotypes 2/5 and 2/8 was still 2 to 3-fold higher than that for 2/2. Enhanced transduction did not cause an increase in glial cell response or toxicity. New rAAV serotypes thus promise improved gene delivery to nigrostriatal system with the potential for better models and therapeutics for Parkinson disease and other neurodegenerative disorders. PMID:19250335

  19. Comparative Analysis of the Tour Jete and Aerial with Detailed Analysis of Aerial Takeoff Mechanics

    NASA Astrophysics Data System (ADS)

    Pierson, Mimi; Coplin, Kim

    2006-10-01

    Whether internally as muscle tension or from external sources, forces are necessary for all motion. This research focused on athletic rotations where conditions of flight are established during takeoff. By studying reaction forces that produce torques, moments of inertia, and linear and angular differences between distinct rotations around different principle axes of the body (tour jete in ballet - longitudinal axis; aerial in gymnastics - anteroposterior axis), and by looking at the values of angular momentum in the specific mechanics of aerial takeoff, we can gain insight into possible causes of injury, flaws in technique and limitations of athletes. Results showed significant differences in the horizontal and vertical components of takeoff between the tour jete and the aerial, and a realization that torque was produced in different biomechanical planes. Both rotations showed braking forces before takeoff to counteract forward momentum and increase vertical lift, but the angle of applied force varied, and the horizontal components of velocity and force and vertical velocity as well as moment of inertia throughout flight were consistently greater for the aerial. Breakdown of aerial takeoff highlighted the relative importance of the takeoff phases, showing that completion depends fundamentally upon the rotation of the rear foot and torso twisting during takeoff rather than the last foot in contact with the ground.

  20. Comparative population genetics of two invading ticks: Evidence of the ecological mechanisms underlying tick range expansions.

    PubMed

    Nadolny, Robyn; Gaff, Holly; Carlsson, Jens; Gauthier, David

    2015-10-01

    Two species of ixodid tick, Ixodes affinis Neumann and Amblyomma maculatum Koch, are simultaneously expanding their ranges throughout the mid-Atlantic region of the US. Although we have some understanding of the ecology and life history of these species, the ecological mechanisms governing where and how new populations establish and persist are unclear. To assess population connectivity and ancestry, we sequenced a fragment of the 16S mitochondrial rRNA gene from a representative sample of individuals of both species from populations throughout the eastern US. We found that despite overlapping host preferences throughout ontogeny, each species exhibited very different genetic and geographic patterns of population establishment and connectivity. I. affinis was of two distinct mitochondrial clades, with a clear geographic break separating northern and southern populations. Both I. affinis populations showed evidence of recent expansion, although the southern population was more genetically diverse, indicating a longer history of establishment. A. maculatum exhibited diverse haplotypes that showed no significant relationship with geographic patterns and little apparent connectivity between sites. Heteroplasmy was also observed in the 16S mitochondrial rRNA gene in 3.5% of A. maculatum individuals. Genetic evidence suggests that these species rely on different key life stages to successfully disperse into novel environments, and that host vagility, habitat stability and habitat connectivity all play critical roles in the establishment of new tick populations. PMID:26254575

  1. Comparative Transcriptional Profiling and Preliminary Study on Heterosis Mechanism of Super-Hybrid Rice

    PubMed Central

    Song, Gui-Sheng; Zhai, Hong-Li; Peng, Yong-Gang; Zhang, Lei; Wei, Gang; Chen, Xiao-Ying; Xiao, Yu-Guo; Wang, Lili; Wu, Bin; Zhang, Yu; Feng, Xiu-Jing; Gong, Wan-Kui; Liu, Yao; Yin, Zhi-Jie; Wang, Feng; Liu, Guo-Zhen; Xu, Hong-Lin; Wei, Xiao-Li; Zhao, Xiao-Ling; Ouwerkerk, Pieter B.F.; Hankemeier, Thomas; Reijmers, Theo; van der Heijden, Rob; Wang, Mei; van der Greef, Jan; Zhu, Zhen

    2010-01-01

    Heterosis is a biological phenomenon whereby the offspring from two parents show improved and superior performance than either inbred parental lines. Hybrid rice is one of the most successful apotheoses in crops utilizing heterosis. Transcriptional profiling of F1 super-hybrid rice Liangyou-2186 and its parents by serial analysis of gene expression (SAGE) revealed 1183 differentially expressed genes (DGs), among which DGs were found significantly enriched in pathways such as photosynthesis and carbon-fixation, and most of the key genes involved in the carbon-fixation pathway exhibited up-regulated expression in F1 hybrid rice. Moreover, increased catabolic activity of corresponding enzymes and photosynthetic efficiency were also detected, which combined to indicate that carbon fixation is enhanced in F1 hybrid, and might probably be associated with the yield vigor and heterosis in super-hybrid rice. By correlating DGs with yield-related quantitative trait loci (QTL), a potential relationship between differential gene expression and phenotypic changes was also found. In addition, a regulatory network involving circadian-rhythms and light signaling pathways was also found, as previously reported in Arabidopsis, which suggest that such a network might also be related with heterosis in hybrid rice. Altogether, the present study provides another view for understanding the molecular mechanism underlying heterosis in rice. PMID:20729474

  2. Neuropilins are positive regulators of Hedgehog signal transduction.

    PubMed

    Hillman, R Tyler; Feng, Brian Y; Ni, Jun; Woo, Wei-Meng; Milenkovic, Ljiljana; Hayden Gephart, Melanie G; Teruel, Mary N; Oro, Anthony E; Chen, James K; Scott, Matthew P

    2011-11-15

    The Hedgehog (Hh) pathway is essential for vertebrate embryogenesis, and excessive Hh target gene activation can cause cancer in humans. Here we show that Neuropilin 1 (Nrp1) and Nrp2, transmembrane proteins with roles in axon guidance and vascular endothelial growth factor (VEGF) signaling, are important positive regulators of Hh signal transduction. Nrps are expressed at times and locations of active Hh signal transduction during mouse development. Using cell lines lacking key Hh pathway components, we show that Nrps mediate Hh transduction between activated Smoothened (Smo) protein and the negative regulator Suppressor of Fused (SuFu). Nrp1 transcription is induced by Hh signaling, and Nrp1 overexpression increases maximal Hh target gene activation, indicating the existence of a positive feedback circuit. The regulation of Hh signal transduction by Nrps is conserved between mammals and bony fish, as we show that morpholinos targeting the Nrp zebrafish ortholog nrp1a produce a specific and highly penetrant Hh pathway loss-of-function phenotype. These findings enhance our knowledge of Hh pathway regulation and provide evidence for a conserved nexus between Nrps and this important developmental signaling system. PMID:22051878

  3. Beyond microarrays: Finding key transcription factors controlling signal transduction pathways

    PubMed Central

    Kel, Alexdander; Voss, Nico; Jauregui, Ruy; Kel-Margoulis, Olga; Wingender, Edgar

    2006-01-01

    Background Massive gene expression changes in different cellular states measured by microarrays, in fact, reflect just an "echo" of real molecular processes in the cells. Transcription factors constitute a class of the regulatory molecules that typically require posttranscriptional modifications or ligand binding in order to exert their function. Therefore, such important functional changes of transcription factors are not directly visible in the microarray experiments. Results We developed a novel approach to find key transcription factors that may explain concerted expression changes of specific components of the signal transduction network. The approach aims at revealing evidence of positive feedback loops in the signal transduction circuits through activation of pathway-specific transcription factors. We demonstrate that promoters of genes encoding components of many known signal transduction pathways are enriched by binding sites of those transcription factors that are endpoints of the considered pathways. Application of the approach to the microarray gene expression data on TNF-alpha stimulated primary human endothelial cells helped to reveal novel key transcription factors potentially involved in the regulation of the signal transduction pathways of the cells. Conclusion We developed a novel computational approach for revealing key transcription factors by knowledge-based analysis of gene expression data with the help of databases on gene regulatory networks (TRANSFAC® and TRANSPATH®). The corresponding software and databases are available at . PMID:17118134

  4. A Comparative Study of the Physical and Mechanical Properties of Hydrogen Using Data Mining Research Techniques

    NASA Astrophysics Data System (ADS)

    Settouti, Nadera; Aourag, Hafid

    2015-09-01

    Hydrogen was the first element to exist in the universe. It is the lightest and simplest element, but chemists do not agree about its placement in the periodic table; its position has given rise to much confusion. Metallization of hydrogen under high pressure influences its properties and its placement in the periodic table. The properties of groups I, IV, and VII are investigated, and are then compared to those of hydrogen. In this study, we present a data mining approach to determine models and discover the similarities included in the datasets. Principal component analysis and partial least squares regression were applied as data analysis techniques in order to explore multivariate data. Our results indicate that hydrogen shares some properties with certain elements and groups in the periodic table, such as carbon group elements, but not entirely, because hydrogen is still considered as an element that is special and apart.

  5. Coupled hydro-mechanical processes in crytalline rock and ininduratedand plastic clays: A comparative discussion

    SciTech Connect

    Tsang, Chin-Fu; Blumling, Peter; Bernier, Frederic

    2006-02-15

    This paper provides a comparative discussion of coupledhydromechanical processes in three different geological formations:crystalline rock, plastic clay, and indurated clay. First, the importantprocesses and associated property characteristics in the three rock typesare discussed. Then, one particular hydromechanical coupling is broughtup for detailed consideration, that of pore pressure changes in nearbyrock during tunnel excavation. Three field experiments in the three rocktypes are presented and their results are discussed. It is shown that themain physical processes are common to all three rock types, but with verydifferent time constants. The different issues raised by these cases arepointed out, and the transferable lessons learned are identified. Suchcross fertilization and simultaneous understanding of coupled processesin three very different rock types help to greatly enhance confidence inthe state of science in this field.

  6. Comparative study on the mechanisms of rotavirus inactivation by sodium dodecyl sulfate and ethylenediaminetetraacetate

    SciTech Connect

    Ward, R.L.; Ashley, C.S.

    1980-06-01

    This report describes a comparative study on the effects of the anionic detergent sodium dodecyl sulfate and the chelating agent ethylenediaminetetraacetate on purified rotavirus SA-11 particles. Both chemicals readily inactivated rotavirus at quite low concentrations and under very mild conditions. In addition, both agents modified the viral capsid and prevented the adsorption of inactivated virions to cells. Capsid damage by ethylenediaminetetraacetate caused a shift in the densities of rotavirions from about l.35 to about 1.37 g/ml and a reduction in their sedimentation coefficients. Sodium dodcyl sulfate, on the other hand, did not detectably alter either of these physical properties of rotavirions. Both agents caused some alteration of the isoelectric points of the virions. Finally, analysis of rotavirus proteins showed that ethylenediaminetetraacetate caused the loss of two protein peaks from the electrophoretic pattern of virions but sodium dodecyl sulfate caused the loss of only one of these same protein peaks.

  7. Transmembrane signal transduction by peptide hormones via family B G protein-coupled receptors

    PubMed Central

    Culhane, Kelly J.; Liu, Yuting; Cai, Yingying; Yan, Elsa C. Y.

    2015-01-01

    Although family B G protein-coupled receptors (GPCRs) contain only 15 members, they play key roles in transmembrane signal transduction of hormones. Family B GPCRs are drug targets for developing therapeutics for diseases ranging from metabolic to neurological disorders. Despite their importance, the molecular mechanism of activation of family B GPCRs remains largely unexplored due to the challenges in expression and purification of functional receptors to the quantity for biophysical characterization. Currently, there is no crystal structure available of a full-length family B GPCR. However, structures of key domains, including the extracellular ligand binding regions and seven-helical transmembrane regions, have been solved by X-ray crystallography and NMR, providing insights into the mechanisms of ligand recognition and selectivity, and helical arrangements within the cell membrane. Moreover, biophysical and biochemical methods have been used to explore functions, key residues for signaling, and the kinetics and dynamics of signaling processes. This review summarizes the current knowledge of the signal transduction mechanism of family B GPCRs at the molecular level and comments on the challenges and outlook for mechanistic studies of family B GPCRs. PMID:26594176

  8. Sodium-coupled energy transduction in the newly isolated thermoalkaliphilic strain LBS3.

    PubMed Central

    Prowe, S G; van de Vossenberg, J L; Driessen, A J; Antranikian, G; Konings, W N

    1996-01-01

    Strain LBS3 is a novel anaerobic thermoalkaliphilic bacterium that grows optimally at pH 9.5 and 50 degrees C. Since a high concentration of Na+ ions is required for growth, we have analyzed the primary bioenergetic mechanism of energy transduction in this organism. For this purpose, a method was devised for the isolation of right-side-out membrane vesicles that are functional for the energy-dependent uptake of solutes. A strict requirement for Na+ was observed for the uptake of several amino acids, and in the case of L-leucine, it was concluded that amino acid uptake occurs in symport with Na+ ions. Further characterization of the leucine transport system revealed that its pH and temperature optima closely match the conditions that support the growth of strain LBS3. The ATPase activity associated with inside-out membrane vesicles was found to be stimulated by both Na+ and Li+ ions. These data suggest that the primary mechanism of energy transduction in the anaerobic thermoalkaliphilic strain LBS3 is dependent on sodium cycling. The implications of this finding for the mechanism of intracellular pH regulation are discussed. PMID:8763937

  9. B cells from patients with systemic lupus erythematosus display abnormal antigen receptor-mediated early signal transduction events.

    PubMed Central

    Liossis, S N; Kovacs, B; Dennis, G; Kammer, G M; Tsokos, G C

    1996-01-01

    To understand the molecular mechanisms that are responsible for the B cell overactivity that is observed in patients with SLE, we have conducted experiments in which the surface immunoglobulin (sIg)-mediated early cell signaling events were studied. The anti-sIgM-mediated free intracytoplasmic calcium ([Ca2+]i) responses were significantly higher in SLE B cells compared with responses of normal individuals and to those of patients with other systemic autoimmune rheumatic diseases. The anti-IgD mAb induced [Ca2+]i responses were also higher in lupus B cells than in controls. The magnitude of anti-sIgM-mediated Ca2+ release from intracellular stores was also increased in B cells from SLE patients compared with normal controls. The amount of inositol phosphate metabolites produced upon crosslinking of sIgM was slightly higher in patients with lupus than in normal controls, although the difference was not statistically significant. In contrast, the degree of anti-sIgM-induced protein tyrosine phosphorylation was obviously increased in lupus patients. Our study demonstrates clearly for the first time that SLE B cells exhibit aberrant early signal transduction events, including augmented calcium responses after crosslinking of the B cell receptor and increased antigen-receptor-mediated phosphorylation of protein tyrosine residues. Because the above abnormalities did not correlate with disease activity or treatment status, we propose that they may have pathogenic significance. PMID:8958217

  10. Comparative Analysis of Latex Transcriptome Reveals Putative Molecular Mechanisms Underlying Super Productivity of Hevea brasiliensis

    PubMed Central

    Li, Heping; Fan, Yujie; Yang, Jianghua; Qi, Jiyan; Li, Huibo

    2013-01-01

    Increasing demand for natural rubber prompts studies into the mechanisms governing the productivity of rubber tree (Heveabrasiliensis). It is very interesting to notice that a rubber tree of clone PR107 in Yunnan, China is reported to yield more than 20 times higher than the average rubber tree. This super-high-yielding (SHY) rubber tree (designated as SY107), produced 4.12 kg of latex (cytoplasm of rubber producing laticifers, containing about 30% of rubber) per tapping, more than 7-fold higher than that of the control. This rubber tree is therefore a good material to study how the rubber production is regulated at a molecular aspect. A comprehensive cDNA-AFLP transcript profiling was performed on the latex of SY107 and its average counterparts by using the 384 selective primer pairs for two restriction enzyme combinations (ApoI/MseI and TaqI/MseI). A total of 746 differentially expressed (DE) transcript-derived fragments (TDFs) were identified, of which the expression patterns of 453 TDFs were further confirmed by RT-PCR. These RT-PCR confirmed TDFs represented 352 non-redundant genes, of which 215 had known or partially known functions and were grouped into 10 functional categories. The top three largest categories were transcription and protein synthesis (representing 24.7% of the total genes), defense and stress (15.3%), and primary and secondary metabolism (14.0%). Detailed analysis of the DE-genes suggests notable characteristics of SHY phenotype in improved sucrose loading capability, rubber biosynthesis-preferred sugar utilization, enhanced general metabolism and timely stress alleviation. However, the SHY phenotype has little correlation with rubber-biosynthesis pathway genes. PMID:24066172

  11. [Progress of studies on acu-moxibustion stimulation-induced cellular transmembrane signal transduction of the target-organs].

    PubMed

    Yi, Shou-Xiang; Peng, Yan

    2009-10-01

    Abundant research results have shown that multiple levels and links of cellular transmembrane signal transduction pathways in the target organs were involved in the efficacy of acupuncture. For instance, 1) various extra-cellular growth factors for initiating signal transduction by activating tyrosine protein kinase and non-receptor tyrosine kinase, 2) G protein-coupled protein kinase-second signal messengers, 3) ligands acting on intra-nuclear receptors to activate transduction pathway of nuclear transcription factors of the target genes, have been demonstrated in the favorable regulating process of acupuncture and moxibustion in different pathological animal models. In the present paper, the authors review the progress of studies on the abovementioned mechanism of acu-moxibustion underlying improving some disorders as 1) pain, cerebral ischemia, and senile dementia, 2) inflammation and tumor, and 3) myocardial ischemia. Moreover, the authors also analyze the extant problems and make a prospect on the future studies about the cellular transmembrane signal transduction pathways involving the effects of acupuncture and moxibustion. PMID:20128298

  12. Phosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma.

    PubMed

    Ge, Xuecai; Milenkovic, Ljiljana; Suyama, Kaye; Hartl, Tom; Purzner, Teresa; Winans, Amy; Meyer, Tobias; Scott, Matthew P

    2015-01-01

    Alterations in Hedgehog (Hh) signaling lead to birth defects and cancers including medulloblastoma, the most common pediatric brain tumor. Although inhibitors targeting the membrane protein Smoothened suppress Hh signaling, acquired drug resistance and tumor relapse call for additional therapeutic targets. Here we show that phosphodiesterase 4D (PDE4D) acts downstream of Neuropilins to control Hh transduction and medulloblastoma growth. PDE4D interacts directly with Neuropilins, positive regulators of Hh pathway. The Neuropilin ligand Semaphorin3 enhances this interaction, promoting PDE4D translocation to the plasma membrane and cAMP degradation. The consequent inhibition of protein kinase A (PKA) enhances Hh transduction. In the developing cerebellum, genetic removal of Neuropilins reduces Hh signaling activity and suppresses proliferation of granule neuron precursors. In mouse medulloblastoma allografts, PDE4D inhibitors suppress Hh transduction and inhibit tumor growth. Our findings reveal a new regulatory mechanism of Hh transduction, and highlight PDE4D as a promising target to treat Hh-related tumors. PMID:26371509

  13. Phosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma

    PubMed Central

    Ge, Xuecai; Milenkovic, Ljiljana; Suyama, Kaye; Hartl, Tom; Purzner, Teresa; Winans, Amy; Meyer, Tobias; Scott, Matthew P

    2015-01-01

    Alterations in Hedgehog (Hh) signaling lead to birth defects and cancers including medulloblastoma, the most common pediatric brain tumor. Although inhibitors targeting the membrane protein Smoothened suppress Hh signaling, acquired drug resistance and tumor relapse call for additional therapeutic targets. Here we show that phosphodiesterase 4D (PDE4D) acts downstream of Neuropilins to control Hh transduction and medulloblastoma growth. PDE4D interacts directly with Neuropilins, positive regulators of Hh pathway. The Neuropilin ligand Semaphorin3 enhances this interaction, promoting PDE4D translocation to the plasma membrane and cAMP degradation. The consequent inhibition of protein kinase A (PKA) enhances Hh transduction. In the developing cerebellum, genetic removal of Neuropilins reduces Hh signaling activity and suppresses proliferation of granule neuron precursors. In mouse medulloblastoma allografts, PDE4D inhibitors suppress Hh transduction and inhibit tumor growth. Our findings reveal a new regulatory mechanism of Hh transduction, and highlight PDE4D as a promising target to treat Hh-related tumors. DOI: http://dx.doi.org/10.7554/eLife.07068.001 PMID:26371509

  14. Ionic mechanisms limiting cardiac repolarization reserve in humans compared to dogs

    PubMed Central

    Jost, Norbert; Virág, László; Comtois, Philippe; Ördög, Balázs; Szuts, Viktória; Seprényi, György; Bitay, Miklós; Kohajda, Zsófia; Koncz, István; Nagy, Norbert; Szél, Tamás; Magyar, János; Kovács, Mária; Puskás, László G; Lengyel, Csaba; Wettwer, Erich; Ravens, Ursula; Nánási, Péter P; Papp, Julius Gy; Varró, András; Nattel, Stanley

    2013-01-01

    The species-specific determinants of repolarization are poorly understood. This study compared the contribution of various currents to cardiac repolarization in canine and human ventricle. Conventional microelectrode, whole-cell patch-clamp, molecular biological and mathematical modelling techniques were used. Selective IKr block (50–100 nmol l−1 dofetilide) lengthened AP duration at 90% of repolarization (APD90) >3-fold more in human than dog, suggesting smaller repolarization reserve in humans. Selective IK1 block (10 μmol l−1 BaCl2) and IKs block (1 μmol l−1 HMR-1556) increased APD90 more in canine than human right ventricular papillary muscle. Ion current measurements in isolated cardiomyocytes showed that IK1 and IKs densities were 3- and 4.5-fold larger in dogs than humans, respectively. IKr density and kinetics were similar in human versus dog. ICa and Ito were respectively ∼30% larger and ∼29% smaller in human, and Na+–Ca2+ exchange current was comparable. Cardiac mRNA levels for the main IK1 ion channel subunit Kir2.1 and the IKs accessory subunit minK were significantly lower, but mRNA expression of ERG and KvLQT1 (IKr and IKsα-subunits) were not significantly different, in human versus dog. Immunostaining suggested lower Kir2.1 and minK, and higher KvLQT1 protein expression in human versus canine cardiomyocytes. IK1 and IKs inhibition increased the APD-prolonging effect of IKr block more in dog (by 56% and 49%, respectively) than human (34 and 16%), indicating that both currents contribute to increased repolarization reserve in the dog. A mathematical model incorporating observed human–canine ion current differences confirmed the role of IK1 and IKs in repolarization reserve differences. Thus, humans show greater repolarization-delaying effects of IKr block than dogs, because of lower repolarization reserve contributions from IK1 and IKs, emphasizing species-specific determinants of repolarization and the limitations of animal models

  15. A comparative mechanical analysis of the pointe shoe toe box. An in vitro study.

    PubMed

    Cunningham, B W; DiStefano, A F; Kirjanov, N A; Levine, S E; Schon, L C

    1998-01-01

    Dancing en pointe requires the ballerina to stand on her toes, which are protected only by the pointe shoe toe box. This protection diminishes when the toe box loses its structural integrity. The objectives of this study were 1) to quantify the comparative structural static and fatigue properties of the pointe shoe toe box, and 2) to evaluate the preferred shoe characteristics as determined by a survey of local dancers. Five different pointe shoes (Capezio, Freed, Gaynor Minden, Leo's, and Grishko) were evaluated to quantify the static stiffness, static strength, and fatigue properties (cycles to failure) of the shoes. Under axial loading conditions, the Leo's shoe demonstrated the highest stiffness level, and the Freed shoe exhibited the least strength. Under vertical loading conditions, the Leo's and Freed shoes demonstrated the highest stiffness levels, and the Gaynor Minden and Freed shoes exhibited the highest strength. Fatigue testing highlighted the greatest differences among the five shoes, with the Gaynor Minden demonstrating the highest fatigue life. Dancers rated the top five shoe characteristics, in order of importance, as fit, comfort, box/platform shape, vamp shape, and durability and indicated that the "best" shoe is one that "feels right" and permits artistic maneuvers, not necessarily the strongest or most durable shoe. PMID:9689378

  16. [Mechanical changes in the femur induced by a joint prosthesis. Comparative extensometric studies].

    PubMed

    Delecrin, J; Royer, J; Passuty, N; Bainvel, J V

    1991-01-01

    This study using electrical extensometry is aimed at comparing the relative deformations of the same fresh femur before and after the successive implantation of the following titanium prostheses: a cement-free prosthesis with metaphyseal endocortical support, a cemented prosthesis with, then without collar, and finally a screwed titanium prosthesis. The 56 deformation measurement paths produce an overall exploration of the behavior of the femur. The results applied to the same straight section of the femur are different from those of earlier works. The density of the measurement areas has particularly been increased in the upper metaphysis by the use of bidirectional gages. The loading device ensures the absence of variations of the external stress torsion transmitted to the femur between the individual prostheses. The results recorded with the cement-free prosthesis with metaphyseal endocortical support and with the collar-free cemented prosthesis are very similar. The incidence of the "collar effect" is very low in spite of optimal in vitro implantation conditions ensuring good contact between the collar and the neck of the femur. The screwed prosthesis is the implant that most stiffens the upper end of the femur. The testing procedure chosen has allowed recording the deformations caused by the mere insertion of the implants and the bone. The importance of the upper metaphysea endocortical support of the cement-free, screwless implant contributes in ensuring a better primary anchorage, producing stresses that will then foster the secondary anchorage through endosteal osteogenesis. PMID:1843673

  17. Comparative Metagenomic Analysis Reveals Mechanisms for Stress Response in Hypoliths from Extreme Hyperarid Deserts.

    PubMed

    Le, Phuong Thi; Makhalanyane, Thulani P; Guerrero, Leandro D; Vikram, Surendra; Van de Peer, Yves; Cowan, Don A

    2016-01-01

    Understanding microbial adaptation to environmental stressors is crucial for interpreting broader ecological patterns. In the most extreme hot and cold deserts, cryptic niche communities are thought to play key roles in ecosystem processes and represent excellent model systems for investigating microbial responses to environmental stressors. However, relatively little is known about the genetic diversity underlying such functional processes in climatically extreme desert systems. This study presents the first comparative metagenome analysis of cyanobacteria-dominated hypolithic communities in hot (Namib Desert, Namibia) and cold (Miers Valley, Antarctica) hyperarid deserts. The most abundant phyla in both hypolith metagenomes were Actinobacteria, Proteobacteria, Cyanobacteria and Bacteroidetes with Cyanobacteria dominating in Antarctic hypoliths. However, no significant differences between the two metagenomes were identified. The Antarctic hypolithic metagenome displayed a high number of sequences assigned to sigma factors, replication, recombination and repair, translation, ribosomal structure, and biogenesis. In contrast, the Namib Desert metagenome showed a high abundance of sequences assigned to carbohydrate transport and metabolism. Metagenome data analysis also revealed significant divergence in the genetic determinants of amino acid and nucleotide metabolism between these two metagenomes and those of soil from other polar deserts, hot deserts, and non-desert soils. Our results suggest extensive niche differentiation in hypolithic microbial communities from these two extreme environments and a high genetic capacity for survival under environmental extremes. PMID:27503299

  18. Comparing the similarity of responses received from studies in Amazon's Mechanical Turk to studies conducted online and with direct recruitment.

    PubMed

    Bartneck, Christoph; Duenser, Andreas; Moltchanova, Elena; Zawieska, Karolina

    2015-01-01

    Computer and internet based questionnaires have become a standard tool in Human-Computer Interaction research and other related fields, such as psychology and sociology. Amazon's Mechanical Turk (AMT) service is a new method of recruiting participants and conducting certain types of experiments. This study compares whether participants recruited through AMT give different responses than participants recruited through an online forum or recruited directly on a university campus. Moreover, we compare whether a study conducted within AMT results in different responses compared to a study for which participants are recruited through AMT but which is conducted using an external online questionnaire service. The results of this study show that there is a statistical difference between results obtained from participants recruited through AMT compared to the results from the participant recruited on campus or through online forums. We do, however, argue that this difference is so small that it has no practical consequence. There was no significant difference between running the study within AMT compared to running it with an online questionnaire service. There was no significant difference between results obtained directly from within AMT compared to results obtained in the campus and online forum condition. This may suggest that AMT is a viable and economical option for recruiting participants and for conducting studies as setting up and running a study with AMT generally requires less effort and time compared to other frequently used methods. We discuss our findings as well as limitations of using AMT for empirical studies. PMID:25876027

  19. Gene amplification in thyroid cancer: A new mechanism defined by comparative genomic hybridization

    SciTech Connect

    Chen, X.N.; Lai, E.; Fagin, J.A.

    1994-09-01

    More than 12,000 new cases of thyroid cancer develop each year in the USA for which scant information is available on cytogenetic abnormalities. Comparative genomic hybridization (CGH) now permits the detection and mapping of amplified regions in DNAs without the need for metaphase tumor preparations. Using CGH, we have analyzed the DNA copy number changes in 10 human thyroid tumors. Further, the procedure of CGH was modified by using a chromomycin and sitamycin reverse-banding technique to provide a high resolution assignment of amplified regions. The results revealed a series of copy number changes including amplifications of chromosome bands 1p36, 1q42, 2p13, 2p21, 19q13.1 and losses of chromosome bands 16q12-13 and 16q22-23. The most striking regions of amplifications, band 2p21 and 2p13 were further analyzed by constructing a 90-member chromosome 2 BAC map and using 9 members of this to analyze WRO, a thyroid follicular carcinoma cell line containing double minutes (dm). Eight BACs revealed three copies of chromosome 2; one BAC mapping at the 2p21-22 border revealed significant and variable amplification in all of the metaphase dm`s suggesting a local amplification. Interphase analyses revealed about 40-70 signals per nucleus. The variable signals seen in the WRO cell population suggest the existence of a minor population with higher copy number and smaller amplicon size. In summary, high resolution CGH has been combined with BAC contig construction for the analysis of thyroid tumor to reveal a very specific region amplification on chromosome 2p21 likely to contain a new gene involved in thyroid cancer tumorigenesis.

  20. Comparative binding mechanism of lupeol compounds with plasma proteins and its pharmacological importance.

    PubMed

    Kallubai, Monika; Rachamallu, Aparna; Yeggoni, Daniel Pushparaju; Subramanyam, Rajagopal

    2015-04-01

    Lupeol, a triterpene, possesses beneficial effects like anti-inflammatory and anti-cancer properties. Binding of lupeol and its derivative (phytochemicals) to plasma proteins such as human serum albumin (HSA) and α-1-acid glycoprotein (AGP) is a major determinant in the disposition of drugs. Cytotoxic studies with mouse macrophages (RAW 246.7) and HeLa cell lines revealed anti-inflammatory and anti-cancer properties for both lupeol and lupeol derivative. Both molecules reduced the expression of pro-inflammatory cytokines in LPS induced macrophages. Further, apoptosis was observed in HeLa cell lines when they were incubated with these molecules for 24 h. The fluorescence quenching of HSA was observed upon titration with different concentrations of lupeol and lupeol derivative; their binding constants were found to be 3 ± 0.01 × 10(4) M(-1) and 6.2 ± 0.02 × 10(4) M(-1), with binding free energies of -6.59 kcal M(-1) and -7.2 kcal M(-1). With AGP, however, the lupeol and lupeol derivative showed binding constants of 0.9 ± 0.02 × 10(3) M(-1) and 2.7 ± 0.01 × 10(3) M(-1), with free energies of -4.6 kcal M(-1) and -5.1 kcal M(-1) respectively. Molecular displacement studies based on competition with site I-binding phenylbutazone (which binds site I of HSA) and ibuprofen (which binds site II) suggest that lupeol binds site II and the lupeol derivative site I. Molecular docking studies also confirmed that lupeol binds to the IIIA and the lupeol derivative to the IIA domain of HSA. Secondary structure changes were observed upon formation of HSA-lupeol/lupeol derivative complexes by circular dichroism spectroscopy. Molecular dynamics simulations support greater stability of HSA-lupeol and HSA-lupeol derivative complexes compared to that of HSA alone. PMID:25710711

  1. Evaluation of transtension and transpression within contractional fault steps: Comparing kinematic and mechanical models to field data

    NASA Astrophysics Data System (ADS)

    Nevitt, Johanna M.; Pollard, David D.; Warren, Jessica M.

    2014-03-01

    Rock deformation often is investigated using kinematic and/or mechanical models. Here we provide a direct comparison of these modeling techniques in the context of a deformed dike within a meter-scale contractional fault step. The kinematic models consider two possible shear plane orientations and various modes of deformation (simple shear, transtension, transpression), while the mechanical model uses the finite element method and assumes elastoplastic constitutive behavior. The results for the kinematic and mechanical models are directly compared using the modeled maximum and minimum principal stretches. The kinematic analysis indicates that the contractional step may be classified as either transtensional or transpressional depending on the modeled shear plane orientation, suggesting that these terms may be inappropriate descriptors of step-related deformation. While the kinematic models do an acceptable job of depicting the change in dike shape and orientation, they are restricted to a prescribed homogeneous deformation. In contrast, the mechanical model allows for heterogeneous deformation within the step to accurately represent the deformation. The ability to characterize heterogeneous deformation and include fault slip - not as a prescription, but as a solution to the governing equations of motion - represents a significant advantage of the mechanical model over the kinematic models.

  2. The discovery of signal transduction by G proteins. A personal account and an overview of the initial findings and contributions that led to our present understanding

    PubMed Central

    Birnbaumer, Lutz

    2007-01-01

    The realization that there existed a G-protein coupled signal transduction mechanism developed gradually and was initially the result of an ill fated quest for uncovering the mechanism of action of insulin, followed by a refocused research in many laboratories, including mine, on how GTP acted to increase hormonal stimulation of adenylyl cyclase. Independent research into how light-activated rhodopsin triggers a response in photoreceptor cells of the retina and the attendant biochemical studies joined midway and, without the left hand knowing well what the right hand was doing, preceded classical G protein research in identifying the molecular players responsible for signal transduction by G proteins. PMID:17141178

  3. Signal transduction of stress via ceramide.

    PubMed Central

    Mathias, S; Peña, L A; Kolesnick, R N

    1998-01-01

    The sphingomyelin (SM) pathway is a ubiquitous, evolutionarily conserved signalling system analogous to conventional systems such as the cAMP and phosphoinositide pathways. Ceramide, which serves as second messenger in this pathway, is generated from SM by the action of a neutral or acidic SMase, or by de novo synthesis co-ordinated through the enzyme ceramide synthase. A number of direct targets for ceramide action have now been identified, including ceramide-activated protein kinase, ceramide-activated protein phosphatase and protein kinase Czeta, which couple the SM pathway to well defined intracellular signalling cascades. The SM pathway induces differentiation, proliferation or growth arrest, depending on the cell type. Very often, however, the outcome of signalling through this pathway is apoptosis. Mammalian systems respond to diverse stresses with ceramide generation, and recent studies show that yeast manifest a form of this response. Thus ceramide signalling is an older stress response system than the caspase/apoptotic death pathway, and hence these two pathways must have become linked later in evolution. Signalling of the stress response through ceramide appears to play a role in the development of human diseases, including ischaemia/reperfusion injury, insulin resistance and diabetes, atherogenesis, septic shock and ovarian failure. Further, ceramide signalling mediates the therapeutic effects of chemotherapy and radiation in some cells. An understanding of the mechanisms by which ceramide regulates physiological and pathological events in specific cells may provide new targets for pharmacological intervention. PMID:9794783

  4. Signal transduction and chemotaxis in mast cells.

    PubMed

    Draber, Petr; Halova, Ivana; Polakovicova, Iva; Kawakami, Toshiaki

    2016-05-01

    Mast cells play crucial roles in both innate and adaptive arms of the immune system. Along with basophils, mast cells are essential effector cells for allergic inflammation that causes asthma, allergic rhinitis, food allergy and atopic dermatitis. Mast cells are usually increased in inflammatory sites of allergy and, upon activation, release various chemical, lipid, peptide and protein mediators of allergic reactions. Since antigen/immunoglobulin E (IgE)-mediated activation of these cells is a central event to trigger allergic reactions, innumerable studies have been conducted on how these cells are activated through cross-linking of the high-affinity IgE receptor (FcεRI). Development of mature mast cells from their progenitor cells is under the influence of several growth factors, of which the stem cell factor (SCF) seems to be the most important. Therefore, how SCF induces mast cell development and activation via its receptor, KIT, has been studied extensively, including a cross-talk between KIT and FcεRI signaling pathways. Although our understanding of the signaling mechanisms of the FcεRI and KIT pathways is far from complete, pharmaceutical applications of the knowledge about these pathways are underway. This review will focus on recent progresses in FcεRI and KIT signaling and chemotaxis. PMID:25941081

  5. The mechanism of action of endothelin-1 as compared with other agonists in vascular smooth muscle

    SciTech Connect

    Wallnoefer, A.W.; Weir, S.; Rueegg, U.C.; Cauvin, C. )

    1989-01-01

    The effects of endothelin-1 (ET-1) on tension and membrane potential in rat isolated mesenteric resistance vessels (MRVs) and on 45Ca influx, 45Ca efflux, inositol-1,4,5-triphosphate (IP3) production, and cytoplasmic Ca2+ concentration ((Ca2+)1) in cultured aortic smooth muscle cells were compared with those of other agonists. ET-1 induced contractions of the MRVs, which were slow in onset, but reached a similar maximum amplitude (at 10 nM ET-1) as that seen with norepinephrine (NE, 10 microM) or (arg8)vasopressin (AVP, 0.1 microM). The EC50 for ET-1 was 1.3 +/- 0.1 nM. Removal of extracellular Ca2+ reduced ET-1-induced contractions to 11 +/- 3% of those in Ca2+-containing medium. With NE, the same procedure reduced contractions to 47 +/- 7% of those in Ca2+-containing medium, while with AVP, the reduction was similar in magnitude to that induced by ET-1 (11 +/- 5% of those in Ca2+-containing medium). Relaxation of ET-1-induced and NE-induced contractions by diltiazem was not complete (maximal at 58 +/- 6% with 10 microM diltiazem after 6 nM ET-1, and at 70 +/- 3% after 0.1 microM NE), in contrast to that of 80 mM K+-induced contractions, which were potently (IC50 = 0.2 microM) and completely reversed (100% relaxation at 10 microM diltiazem). ET-1 (6 nM) caused a small but significant depolarization of the MRVs (approximately 7 mV), the magnitude of which was only about one-third of that induced by equieffective contractile concentrations of NE and AVP. The voltage-sensitive Ca2+ channel agonist Bay K 8644 (1 microM), in contrast to ET-1, NE, and AVP, produced a small contraction (30 +/- 2% of the maximum response to NE), but no further depolarization when added in the presence of 15 mM K+ (which elicited approximately 12 mV depolarization but no contraction).

  6. Comparative Transcriptomics of Sijung and Jumli Marshi Rice during Early Chilling Stress Imply Multiple Protective Mechanisms

    PubMed Central

    Lindlöf, Angelica; Chawade, Aakash; Sikora, Per; Olsson, Olof

    2015-01-01

    Introduction Low temperature is one of the major environmental factors that adversely affect plant growth and yield. Many cereal crops from tropical regions, such as rice, are chilling sensitive and, therefore, are affected already at <10°C. Interestingly, it has been demonstrated that chilling susceptibility varies greatly among rice varieties, which indicates differences in the underlying molecular responses. Understanding these differences is vital for continued development of rational breeding and transgenic strategies for more tolerant varieties. Thus, in this study, we conducted a comparative global gene expression profiling analysis of the chilling tolerant varieties Sijung and Jumli Marshi (spp. Japonica) during early chilling stress (<24 h, 10°C). Methods and Results Global gene expression experiments were conducted with Agilent Rice Gene Expression Microarray 4x44K. The analysed results showed that there was a relatively low (percentage or number) overlap in differentially expressed genes in the two varieties and that substantially more genes were up-regulated in Jumli Marshi than in Sijung but the number of down-regulated genes were higher in Sijung. In broad GO annotation terms, the activated response pathways in Sijung and Jumli Marshi were coherent, as a majority of the genes belonged to the catalytic, transcription regulator or transporter activity categories. However, a more detailed analysis revealed essential differences. For example, in Sijung, activation of calcium and phosphorylation signaling pathways, as well as of lipid transporters and exocytosis-related proteins take place very early in the stress response. Such responses can be coupled to processes aimed at strengthening the cell wall and plasma membrane against disruption. On the contrary, in Jumli Marshi, sugar production, detoxification, ROS scavenging, protection of chloroplast translation, and plausibly the activation of the jasmonic acid pathway were the very first response

  7. Two Component Signal Transduction in Desulfovibrio Species

    SciTech Connect

    Luning, Eric; Rajeev, Lara; Ray, Jayashree; Mukhopadhyay, Aindrila

    2010-05-17

    The environmentally relevant Desulfovibrio species are sulfate-reducing bacteria that are of interest in the bioremediation of heavy metal contaminated water. Among these, the genome of D. vulgaris Hildenborough encodes a large number of two component systems consisting of 72 putative response regulators (RR) and 64 putative histidinekinases (HK), the majority of which are uncharacterized. We classified the D. vulgaris Hildenborough RRs based on their output domains and compared the distribution of RRs in other sequenced Desulfovibrio species. We have successfully purified most RRs and several HKs as His-tagged proteins. We performed phospho-transfer experiments to verify relationships between cognate pairs of HK and RR, and we have also mapped a few non-cognate HK-RR pairs. Presented here are our discoveries from the Desulfovibrio RR categorization and results from the in vitro studies using purified His tagged D. vulgaris HKs and RRs.

  8. Signal transduction in mammalian oocytes during fertilization.

    PubMed

    Machaty, Zoltan

    2016-01-01

    Mammalian embryo development begins when the fertilizing sperm triggers a series of elevations in the oocyte's intracellular free Ca(2+) concentration. The elevations are the result of repeated release and re-uptake of Ca(2+) stored in the smooth endoplasmic reticulum. Ca(2+) release is primarily mediated by the phosphoinositide signaling system of the oocyte. The system is stimulated when the sperm causes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG); IP3 then binds its receptor on the surface of the endoplasmic reticulum that induces Ca(2+) release. The manner in which the sperm generates IP3, the Ca(2+) mobilizing second messenger, has been the subject of extensive research for a long time. The sperm factor hypothesis has eventually gained general acceptance, according to which it is a molecule from the sperm that diffuses into the ooplasm and stimulates the phosphoinositide cascade. Much evidence now indicates that the sperm-derived factor is phospholipase C-zeta (PLCζ) that cleaves PIP2 and generates IP3, eventually leading to oocyte activation. A recent addition to the candidate sperm factor list is the post-acrosomal sheath WW domain-binding protein (PAWP), whose role at fertilization is currently under debate. Ca(2+) influx across the plasma membrane is also important as, in the absence of extracellular Ca(2+), the oscillations run down prematurely. In pig oocytes, the influx that sustains the oscillations seems to be regulated by the filling status of the stores, whereas in the mouse other mechanisms might be involved. This work summarizes the current understanding of Ca(2+) signaling in mammalian oocytes. PMID:26453398

  9. Visual transduction in human rod photoreceptors.

    PubMed Central

    Kraft, T W; Schneeweis, D M; Schnapf, J L

    1993-01-01

    1. Photocurrents were recorded with suction electrodes from rod photoreceptors of seven humans. 2. Brief flashes of light evoked transient outward currents of up to 20 pA. With increasing light intensity the peak response amplitude increased along an exponential saturation function. A half-saturating peak response was evoked by approximately sixty-five photoisomerizations. 3. Responses to brief dim flashes rose to a peak in about 200 ms. The waveform was roughly like the impulse response of a series of four to five low-pass filters. 4. The rising phases of the responses to flashes of increasing strength were found to fit with a biochemical model of phototransduction with an 'effective delay time' and 'characteristic time' of about 2 and 800 ms, respectively. 5. Spectral sensitivities were obtained over a wavelength range from 380 to 760 nm. The action spectrum, which peaked at 495 nm, followed the template described for photoreceptors in the macaque retina. Variation between rods in the position of the spectrum on the wavelength axis was small. 6. The scotopic luminosity function derived from human psychophysical experiments was found to agree well with the measured rod action spectrum after adjustments were made for lens absorption and photopigment self-screening in the intact eye. 7. Responses to steps of light rose monotonically to a maintained level, showing little or no relaxation. Nevertheless, the relationship between light intensity and steady-state response amplitude was shallower than that expected from simple response saturation. This is consistent with an adaptation mechanism acting on a rapid time scale. 8. Flash sensitivity fell with increasing intensities of background light according to Weber's law. Sensitivity was reduced twofold by lights evoking about 120 photoisomerizations per second. Background lights decreased the time to peak and the integration time of the flash response by up to 20%. PMID:8229828

  10. Alterations in Energy Metabolism, Neuroprotection and Visual Signal Transduction in the Retina of Parkinsonian, MPTP-Treated Monkeys

    PubMed Central

    Bru-Martínez, Roque; Herrero, María Trinidad; Fernández-Villalba, Emiliano; Cuenca, Nicolás; Martín-Nieto, José

    2013-01-01

    Parkinson disease is mainly characterized by the degeneration of dopaminergic neurons in the central nervous system, including the retina. Different interrelated molecular mechanisms underlying Parkinson disease-associated neuronal death have been put forward in the brain, including oxidative stress and mitochondrial dysfunction. Systemic injection of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to monkeys elicits the appearance of a parkinsonian syndrome, including morphological and functional impairments in the retina. However, the intracellular events leading to derangement of dopaminergic and other retinal neurons in MPTP-treated animal models have not been so far investigated. Here we have used a comparative proteomics approach to identify proteins differentially expressed in the retina of MPTP-treated monkeys. Proteins were solubilized from the neural retinas of control and MPTP-treated animals, labelled separately with two different cyanine fluorophores and run pairwise on 2D DIGE gels. Out of >700 protein spots resolved and quantified, 36 were found to exhibit statistically significant differences in their expression levels, of at least ±1.4-fold, in the parkinsonian monkey retina compared with controls. Most of these spots were excised from preparative 2D gels, trypsinized and subjected to MALDI-TOF MS and LC-MS/MS analyses. Data obtained were used for protein sequence database interrogation, and 15 different proteins were successfully identified, of which 13 were underexpressed and 2 overexpressed. These proteins were involved in key cellular functional pathways such as glycolysis and mitochondrial electron transport, neuronal protection against stress and survival, and phototransduction processes. These functional categories underscore that alterations in energy metabolism, neuroprotective mechanisms and signal transduction are involved in MPTP-induced neuronal degeneration in the retina, in similarity to mechanisms thought to

  11. Two-Component Signal Transduction Systems of Desulfovibrio Vulgaris: Structural and Phylogenetic Analysis and Deduction of Putative Cognate Pairs

    SciTech Connect

    Zhang, Weiwen; Culley, David E.; Wu, Gang; Brockman, Fred J.

    2006-01-20

    ABSTRACT-Two-component signal transduction systems (TCSTS) composed of sensory histidine kinases (HK) and response regulators (RR), constitute a key element of the mechanism by which bacteria sense and respond to changes in environments. A large number of TCSTSs including 59 putative HKs and 55 RRs were identified from the Desulfovibrio vulgaris genome, indicating their important roles in regulation of cellular metabolism. In this study, the structural and phylogenetic analysis of all putative TCSTSs in D. vulgaris was performed. The results showed D. vulgaris contained an unexpectedly large number of hybrid-type HKs, implying that multiple-step phosphorelay may be a common signal transduction mechanism in D. vulgaris. Most TCSTS components of D. vulgaris were found clustered into several subfamilies previously recognized in other bacteria and extensive co-evolution between D. vulgaris HKs and RRs was observed, suggesting that the concordance of HKs and RRs in cognate phylogenetic groups could be indicative of cognate TCSTSs...

  12. Characterization and expression of genes involved in the ethylene biosynthesis and signal transduction during ripening of mulberry fruit.

    PubMed

    Liu, Changying; Zhao, Aichun; Zhu, Panpan; Li, Jun; Han, Leng; Wang, Xiling; Fan, Wei; Lü, Ruihua; Wang, Chuanhong; Li, Zhengang; Lu, Cheng; Yu, Maode

    2015-01-01

    Although ethylene is well known as an essential regulator of fruit development, little work has examined the role ethylene plays in the development and maturation of mulberry (Morus L.) fruit. To study the mechanism of ethylene action during fruit development in this species, we measured the ethylene production, fruit firmness, and soluble solids content (SSC) during fruit development and harvest. By comparing the results with those from other climacteric fruit, we concluded that Morus fruit are probably climacteric. Genes associated with the ethylene signal transduction pathway of Morus were characterized from M. notabilis Genome Database, including four ethylene receptor genes, a EIN2-like gene, a CTR1-like gene, four EIN3-like genes, and a RTE1-like gene. The expression patterns of these genes were analyzed in the fruit of M. atropurpurea cv. Jialing No.40. During fruit development, transcript levels of MaETR2, MaERS, MaEIN4, MaRTE, and MaCTR1 were lower at the early stages and higher after 26 days after full bloom (DAF), while MaETR1, MaEIL1, MaEIL2, and MaEIL3 remained constant. In ripening fruit, the transcripts of MaACO1 and MaACS3 increased, while MaACS1 and MaACO2 decreased after harvest. The transcripts of MaACO1, MaACO2, and MaACS3 were inhibited by ethylene, and 1-MCP (1-methylcyclopropene) upregulated MaACS3. The transcripts of the MaETR-like genes, MaRTE, and MaCTR1 were inhibited by ethylene and 1-MCP, suggesting that ethylene may accelerate the decline of MaETRs transcripts. No significant changes in the expression of MaEIN2, MaEIL1, and MaEIL3 were observed during ripening or in response to ethylene, while the expressions of MaEIL2 and MaEIL4 increased rapidly after 24 h after harvest (HAH) and were upregulated by ethylene. The present study provides insights into ethylene biosynthesis and signal transduction in Morus plants and lays a foundation for the further understanding of the mechanisms underlying Morus fruit development and ripening. PMID

  13. Characterization and Expression of Genes Involved in the Ethylene Biosynthesis and Signal Transduction during Ripening of Mulberry Fruit

    PubMed Central

    Liu, Changying; Zhao, Aichun; Zhu, Panpan; Li, Jun; Han, Leng; Wang, Xiling; Fan, Wei; Lü, Ruihua; Wang, Chuanhong; Li, Zhengang; Lu, Cheng; Yu, Maode

    2015-01-01

    Although ethylene is well known as an essential regulator of fruit development, little work has examined the role ethylene plays in the development and maturation of mulberry (Morus L.) fruit. To study the mechanism of ethylene action during fruit development in this species, we measured the ethylene production, fruit firmness, and soluble solids content (SSC) during fruit development and harvest. By comparing the results with those from other climacteric fruit, we concluded that Morus fruit are probably climacteric. Genes associated with the ethylene signal transduction pathway of Morus were characterized from M. notabilis Genome Database, including four ethylene receptor genes, a EIN2-like gene, a CTR1-like gene, four EIN3-like genes, and a RTE1-like gene. The expression patterns of these genes were analyzed in the fruit of M. atropurpurea cv. Jialing No.40. During fruit development, transcript levels of MaETR2, MaERS, MaEIN4, MaRTE, and MaCTR1 were lower at the early stages and higher after 26 days after full bloom (DAF), while MaETR1, MaEIL1, MaEIL2, and MaEIL3 remained constant. In ripening fruit, the transcripts of MaACO1 and MaACS3 increased, while MaACS1 and MaACO2 decreased after harvest. The transcripts of MaACO1, MaACO2, and MaACS3 were inhibited by ethylene, and 1-MCP (1–methylcyclopropene) upregulated MaACS3. The transcripts of the MaETR-like genes, MaRTE, and MaCTR1 were inhibited by ethylene and 1-MCP, suggesting that ethylene may accelerate the decline of MaETRs transcripts. No significant changes in the expression of MaEIN2, MaEIL1, and MaEIL3 were observed during ripening or in response to ethylene, while the expressions of MaEIL2 and MaEIL4 increased rapidly after 24 h after harvest (HAH) and were upregulated by ethylene. The present study provides insights into ethylene biosynthesis and signal transduction in Morus plants and lays a foundation for the further understanding of the mechanisms underlying Morus fruit development and ripening. PMID

  14. Developing a synthetic signal transduction system in plants.

    PubMed

    Morey, Kevin J; Antunes, Mauricio S; Albrecht, Kirk D; Bowen, Tessa A; Troupe, Jared F; Havens, Keira L; Medford, June I

    2011-01-01

    One area of focus in the emerging field of plant synthetic biology is the manipulation of systems involved in sensing and response to environmental signals. Sensing and responding to signals, including ligands, typically involves biological signal transduction. Plants use a wide variety of signaling systems to sense and respond to their environment. One of these systems, a histidine kinase (HK) based signaling system, lends itself to manipulation using the tools of synthetic biology. Both plants and bacteria use HKs to relay signals, which in bacteria can involve as few as two proteins (two-component systems or TCS). HK proteins are evolutionarily conserved between plants and bacteria and plant HK components have been shown to be functional in bacteria. We found that this conservation also applies to bacterial HK components which can function in plants. This conservation of function led us to hypothesize that synthetic HK signaling components can be designed and rapidly tested in bacteria. These novel HK signaling components form the foundation for a synthetic signaling system in plants, but typically require modifications such as codon optimization and proper targeting to allow optimal function. We describe the process and methodology of producing a synthetic signal transduction system in plants. We discovered that the bacterial response regulator (RR) PhoB shows HK-dependent nuclear translocation in planta. Using this discovery, we engineered a partial synthetic pathway in which a synthetic promoter (PlantPho) is activated using a plant-adapted PhoB (PhoB-VP64) and the endogenous HK-based cytokinin signaling pathway. Building on this work, we adapted an input or sensing system based on bacterial chemotactic binding proteins and HKs, resulting in a complete eukaryotic signal transduction system. Input to our eukaryotic signal transduction system is provided by a periplasmic binding protein (PBP), ribose-binding protein (RBP). RBP interacts with the membrane

  15. A comparative study of the mechanical performance of Glass and Glass/Carbon hybrid polymer composites at different temperature environments

    NASA Astrophysics Data System (ADS)

    Shukla, M. J.; Kumar, D. S.; Mahato, K. K.; Rathore, D. K.; Prusty, R. K.; Ray, B. C.

    2015-02-01

    Glass Fiber Reinforced Polymer (GFRP) composites have been widely accepted as high strength, low weight structural material as compared to their metallic counterparts. Some specific advanced high performance applications such as aerospace components still require superior specific strength and specific modulus. Carbon Fiber Reinforced Polymer (CFRP) composites exhibit superior specific strength and modulus but have a lower failure strain and high cost. Hence, the combination of both glass and carbon fiber in polymer composite may yield optimized mechanical properties. Further the in-service environment has a significant role on the mechanical performance of this class of materials. Present study aims to investigate the mechanical property of GFRP and Glass/Carbon (G/C hybrid) composites at room temperature, in-situ and ex-situ temperature conditions. In-situ testing at +70°C and +100°C results in significant loss in inter-laminar shear strength (ILSS) for both the composites as compared to room temperature. The ILSS was nearly equal for both the composite systems tested in-situ at +100°C and effect of fiber hybridisation was completely diminished there. At low temperature ex-situ conditioning significant reduction in ILSS was observed for both the systems. Further at -60°C G/C hybrid exhibited 32.4 % higher ILSS than GFRP. Hence this makes G/C hybrid a better choice of material in low temperature environmental applications.

  16. Evaluation of signal transduction pathways after transient cutaneous adenoviral gene delivery

    PubMed Central

    2011-01-01

    Background Adenoviral vectors have provided effective methods for in vivo gene delivery in therapeutic applications. However, these vectors can induce immune responses that may severely affect the ability of vector re-application. There is limited information about the mechanisms and signal transduction pathways involved in adenoviral recognition. For optimization of cutaneous gene therapy it is necessary to investigate molecular mechanisms of virus recognition in epidermal cells. The aim of this study was to investigate the signal transduction of the innate immunity after adenoviral DNA internalization in keratinocytes. Methods In vitro, keratinocytes were transfected with DNA, in the presence and absence of inhibitors for signalling molecules. In vivo, immunocompetent and athymic mice (n = 3 per group) were twice transduced with an Ad-vector. Results The results show an acute induction of type-I-interferon after in vitro transfection. Inhibition of PI3K, p38 MAPK, JNK and NFkappaB resulted in a decreased expression of type-I-interferon. In contrast to immunocompetent mice, athymic mice demonstrated a constant transgene expression and reduced inflammatory response in vivo. Conclusion The results suggest an induction of the innate immunity triggered by cytoplasm localised DNA which is mediated by PI3K-, p38 MAPK-, JNK-, NFkappaB-, JAK/STAT- and ERK1/2-dependent pathways. A stable transgene expression and a reduced inflammatory response in immunodeficient mice have been observed. These results provide potential for an effective adenoviral gene delivery into immunosupressed skin. PMID:21255430

  17. Genome-Wide RNAi Screening to Dissect the TGF-β Signal Transduction Pathway.

    PubMed

    Chen, Xiaochu; Xu, Lan

    2016-01-01

    The transforming growth factor-β (TGF-β) family of cytokines figures prominently in regulation of embryonic development and adult tissue homeostasis from Drosophila to mammals. Genetic defects affecting TGF-β signaling underlie developmental disorders and diseases such as cancer in human. Therefore, delineating the molecular mechanism by which TGF-β regulates cell biology is critical for understanding normal biology and disease mechanisms. Forward genetic screens in model organisms and biochemical approaches in mammalian tissue culture were instrumental in initial characterization of the TGF-β signal transduction pathway. With complete sequence information of the genomes and the advent of RNA interference (RNAi) technology, genome-wide RNAi screening emerged as a powerful functional genomics approach to systematically delineate molecular components of signal transduction pathways. Here, we describe a protocol for image-based whole-genome RNAi screening aimed at identifying molecules required for TGF-β signaling into the nucleus. Using this protocol we examined >90 % of annotated Drosophila open reading frames (ORF) individually and successfully uncovered several novel factors serving critical roles in the TGF-β pathway. Thus cell-based high-throughput functional genomics can uncover new mechanistic insights on signaling pathways beyond what the classical genetics had revealed. PMID:26520138

  18. Ca2+ Changes the Force Sensitivity of the Hair-Cell Transduction Channel

    PubMed Central

    Cheung, Eunice L. M.; Corey, David P.

    2006-01-01

    The mechanically gated transduction channels of vertebrate hair cells tend to close in ∼1 ms after their activation by hair bundle deflection. This fast adaptation is correlated with a quick negative movement of the bundle (a “twitch”), which can exert force and may mediate an active mechanical amplification of sound stimuli in hearing organs. We used an optical trap to deflect bullfrog hair bundles and to measure bundle movement while controlling Ca2+ entry with a voltage clamp. The twitch elicited by repolarization of the cell varied with force applied to the bundle, going to zero where channels were all open or closed. The force dependence is quantitatively consistent with a model in which a Ca2+-bound channel requires ∼3 pN more force to open, and rules out other models for the site of Ca2+ action. In addition, we characterized a faster, voltage-dependent “flick”, which requires intact tip links but not current through transduction channels. PMID:16214875

  19. A comparative study of the effects of vein-joints on the mechanical behaviour of insect wings: I. Single joints.

    PubMed

    Rajabi, H; Ghoroubi, N; Darvizeh, A; Dirks, J-H; Appel, E; Gorb, S N

    2015-10-01

    The flight performance of insects is strongly affected by the deformation of the wing during a stroke cycle. Many insects therefore use both active and passive mechanisms to control the deformation of their wings in flight. Several studies have focused on the wing kinematics, and plenty is known about the mechanism of their passive deformability. However, given the small size of the vein-joints, accurate direct mechanical experiments are almost impossible to perform. We therefore developed numerical models to perform a comparative and comprehensive investigation of the mechanical behaviour of the vein-joints under external loading conditions. The results illustrate the effect of the geometry and the presence of the rubberlike protein resilin on the flexibility of the joints. Our simulations further show the contribution of the spikes to the anisotropic flexural stiffness in the dorsal and ventral directions. In addition, our results show that the cross veins, only in one joint type, help to transfer the stress to the thicker longitudinal veins. The deformation pattern and the stress distribution in each vein-joint are discussed in detail. This study provides a strong background for further realistic modelling of the dragonfly wing deformation. PMID:26292260

  20. A Comparative Numerical Study on the Performances and Vortical Patterns of Two Bioinspired Oscillatory Mechanisms: Undulating and Pure Heaving

    PubMed Central

    Ebrahimi, Mohsen; Abbaspour, Madjid

    2015-01-01

    The hydrodynamics and energetics of bioinspired oscillating mechanisms have received significant attentions by engineers and biologists to develop the underwater and air vehicles. Undulating and pure heaving (or plunging) motions are two significant mechanisms which are utilized in nature to provide propulsive, maneuvering, and stabilization forces. This study aims to elucidate and compare the propulsive vortical signature and performance of these two important natural mechanisms through a systematic numerical study. Navier-Stokes equations are solved, by a pressure-based finite volume method solver, in an arbitrary Lagrangian-Eulerian (ALE) framework domain containing a 2D NACA0012 foil moving with prescribed kinematics. Some of the important findings are (1) the thrust production of the heaving foil begins at lower St and has a greater growing slope with respect to the St; (2) the undulating mechanism has some limitations to produce high thrust forces; (3) the undulating foil shows a lower power consumption and higher efficiency; (4) changing the Reynolds number (Re) in a constant St affects the performance of the oscillations; and (5) there is a distinguishable appearance of leading edge vortices in the wake of the heaving foil without observable ones in the wake of the undulating foil, especially at higher St. PMID:27057133

  1. A Comparative Numerical Study on the Performances and Vortical Patterns of Two Bioinspired Oscillatory Mechanisms: Undulating and Pure Heaving.

    PubMed

    Ebrahimi, Mohsen; Abbaspour, Madjid

    2015-01-01

    The hydrodynamics and energetics of bioinspired oscillating mechanisms have received significant attentions by engineers and biologists to develop the underwater and air vehicles. Undulating and pure heaving (or plunging) motions are two significant mechanisms which are utilized in nature to provide propulsive, maneuvering, and stabilization forces. This study aims to elucidate and compare the propulsive vortical signature and performance of these two important natural mechanisms through a systematic numerical study. Navier-Stokes equations are solved, by a pressure-based finite volume method solver, in an arbitrary Lagrangian-Eulerian (ALE) framework domain containing a 2D NACA0012 foil moving with prescribed kinematics. Some of the important findings are (1) the thrust production of the heaving foil begins at lower St and has a greater growing slope with respect to the St; (2) the undulating mechanism has some limitations to produce high thrust forces; (3) the undulating foil shows a lower power consumption and higher efficiency; (4) changing the Reynolds number (Re) in a constant St affects the performance of the oscillations; and (5) there is a distinguishable appearance of leading edge vortices in the wake of the heaving foil without observable ones in the wake of the undulating foil, especially at higher St. PMID:27057133

  2. Self-Complementary Adeno-Associated Virus Vectors Improve Transduction Efficiency of Corneal Endothelial Cells

    PubMed Central

    Gruenert, Anja K.; Czugala, Marta; Mueller, Chris; Schmeer, Marco; Schleef, Martin; Kruse, Friedrich E.; Fuchsluger, Thomas A.

    2016-01-01

    Transplantation of a donor cornea to restore vision is the most frequently performed transplantation in the world. Corneal endothelial cells (CEC) are crucial for the outcome of a graft as they maintain corneal transparency and avoid graft failure due to corneal opaqueness. Given the characteristic of being a monolayer and in direct contact with culture medium during cultivation in eye banks, CEC are specifically suitable for gene therapeutic approaches prior to transplantation. Recombinant adeno-associated virus 2 (rAAV2) vectors represent a promising tool for gene therapy of CEC. However, high vector titers are needed to achieve sufficient gene expression. One of the rate-limiting steps for transgene expression is the conversion of single-stranded (ss-) DNA vector genome into double-stranded (ds-) DNA. This step can be bypassed by using self-complementary (sc-) AAV2 vectors. Aim of this study was to compare for the first time transduction efficiencies of ss- and scAAV2 vectors in CEC. For this purpose AAV2 vectors containing enhanced green fluorescent protein (GFP) as transgene were used. Both in CEC and in donor corneas, transduction with scAAV2 resulted in significantly higher transgene expression compared to ssAAV2. The difference in transduction efficiency decreased with increasing vector titer. In most cases, only half the vector titer of scAAV2 was required for equal or higher gene expression rates than those of ssAAV2. In human donor corneas, GFP expression was 64.7±11.3% (scAAV) and 38.0±8.6% (ssAAV) (p<0.001), respectively. Furthermore, transduced cells maintained their viability and showed regular morphology. Working together with regulatory authorities, a translation of AAV2 vector-mediated gene therapy to achieve a temporary protection of corneal allografts during cultivation and transplantation could therefore become more realistic. PMID:27023329

  3. In situ patch-clamp recordings from Merkel cells in rat whisker hair follicles, an experimental protocol for studying tactile transduction in tactile-end organs.

    PubMed

    Ikeda, Ryo; Ling, Jennifer; Cha, Myeounghoon; Gu, Jianguo G

    2015-01-01

    Mammals use tactile end-organs to perform sensory tasks such as environmental exploration, social interaction, and tactile discrimination. However, cellular and molecular mechanisms underlying tactile transduction in tactile end-organs remain poorly understood. The patch-clamp recording technique may be the most valuable approach for detecting and studying tactile transduction in tactile end-organs, but it is technically challenging because tactile transduction elements in an end-organ are normally inaccessible by patch-clamp recording electrodes. Here we describe an in situ patch-clamp recording protocol for the study of tactile transduction in Merkel cells of rat whisker hair follicles, one of the most sensitive tactile end-organs in mammals. This technique offers an opportunity to explore the identities and properties of ion channels that are involved in tactile transduction in whisker hair follicles, and it may also lend a useful tool for researchers to study other tactile end-organs. The experimental protocol describes procedures for 1) tissue dissection and whisker hair follicle preparation, 2) device setup and steps for performing patch-clamp recordings from Merkel cells in a whisker hair follicle, 3) methods of delivering mechanical stimuli, and 4) intra-follicle microinjection for receptor knockdown in whisker hair follicles. The main procedures in this protocol, from tissue preparation to whole-cell patch-clamp recordings, can be completed in a few hours. PMID:25907165

  4. Modeling of power and energy transduction of embedded piezoelectric wafer active sensors for structural health monitoring

    NASA Astrophysics Data System (ADS)

    Lin, Bin; Giurgiutiu, Victor

    2010-04-01

    This paper presents a systematic investigation of power and energy transduction in piezoelectric wafer active sensors (PWAS) for structural health monitoring (SHM). After a literature review of the state of the art, the paper develops a simplified pitch-catch model of power and energy transduction of PWAS attached to structure. The model assumptions include: (a) 1-D axial and flexural wave propagation; (b) ideal bonding (pin-force) connection between PWAS and structure; (c) ideal excitation source at the transmitter PWAS and fully-resistive external load at the receiver PWAS. Frequency response functions are developed for voltage, current, complex power, active power, etc. First, we examined PWAS transmitter and determined the active power, reactive power, power rating of electrical requirement under harmonic voltage excitation. It was found that the reactive power is dominant and defines the power requirement for power supply / amplifier for PWAS applications. The electrical and mechanical power analysis at the PWAS structure interface indicates all the active electrical power provides the mechanical power at the interface. This provides the power and energy for the axial and flexural waves power and energy that propagate into the structure. The sum of forward and backward wave power equals the mechanical power PWAS applied to the structure. The parametric study of PWAS transmitter size shows the proper size and excitation frequency selection based on the tuning effects. Second, we studied the PWAS receiver structural interface acoustic and electrical energy transduction. The parametric study of receiver size, receiver impedance and external electrical load gives the PWAS design guideline for PWAS sensing and power harvesting applications. Finally we considered the power flow for a complete pitch-catch setup. In pitch-catch mode, the power flows from electrical source into piezoelectric power at the transmitter; the piezoelectric conduction converts the electrical

  5. Quantitative structure-activity relationships of insecticides and plant growth regulators: comparative studies toward understanding the molecular mechanism of action.

    PubMed Central

    Iwamura, H; Nishimura, K; Fujita, T

    1985-01-01

    Emphasis was put on the comparative quantitative structure-activity approaches to the exploration of action mechanisms of structurally different classes of compounds showing the same type of activity as well as those of the same type of compounds having different actions. Examples were selected from studies performed on insecticides and plant growth regulators, i.e., neurotoxic carbamates, phosphates, pyrethroids and DDT analogs, insect juvenile hormone mimics, and cytokinin agonistic and antagonistic compounds. Similarities and dissimilarities in structures required to elicit activity between compounds classes were revealed in terms of physicochemical parameters, provoking further exploration and evoking insights into the molecular mechanisms of action which may lead to the development of new structures having better qualities. PMID:3905379

  6. A Comparative Study of Information-Based Source Number Estimation Methods and Experimental Validations on Mechanical Systems

    PubMed Central

    Cheng, Wei; Zhang, Zhousuo; Cao, Hongrui; He, Zhengjia; Zhu, Guanwen

    2014-01-01

    This paper investigates one eigenvalue decomposition-based source number estimation method, and three information-based source number estimation methods, namely the Akaike Information Criterion (AIC), Minimum Description Length (MDL) and Bayesian Information Criterion (BIC), and improves BIC as Improved BIC (IBIC) to make it more efficient and easier for calculation. The performances of the abovementioned source number estimation methods are studied comparatively with numerical case studies, which contain a linear superposition case and a both linear superposition and nonlinear modulation mixing case. A test bed with three sound sources is constructed to test the performances of these methods on mechanical systems, and source separation is carried out to validate the effectiveness of the experimental studies. This work can benefit model order selection, complexity analysis of a system, and applications of source separation to mechanical systems for condition monitoring and fault diagnosis purposes. PMID:24776935

  7. Maxwell's demon in biochemical signal transduction with feedback loop.

    PubMed

    Ito, Sosuke; Sagawa, Takahiro

    2015-01-01

    Signal transduction in living cells is vital to maintain life itself, where information transfer in noisy environment plays a significant role. In a rather different context, the recent intensive research on 'Maxwell's demon'-a feedback controller that utilizes information of individual molecules-have led to a unified theory of information and thermodynamics. Here we combine these two streams of research, and show that the second law of thermodynamics with information reveals the fundamental limit of the robustness of signal transduction against environmental fluctuations. Especially, we find that the degree of robustness is quantitatively characterized by an informational quantity called transfer entropy. Our information-thermodynamic approach is applicable to biological communication inside cells, in which there is no explicit channel coding in contrast to artificial communication. Our result could open up a novel biophysical approach to understand information processing in living systems on the basis of the fundamental information-thermodynamics link. PMID:26099556

  8. A PKD Channel-based Biosensor for Taste Transduction

    NASA Astrophysics Data System (ADS)

    Wu, Chunsheng; Du, Liping; Hu, Liang; Zhang, Wei; Zhao, Luhang; Wang, Ping

    2011-09-01

    This study describes a micro electrode array (MEA)-based biosensor for taste transduction using heterologous expressed taste polycystic kidney disease-like (PKD) channels as molecular sensors. Taste PKD1L3/2L1 channels were expressed on the plasma membrane of human embryo kidney (HEK)-293 cells [1]. Then the cells were cultured on the surface of MEA chip [2] to record the responses of PKD channels to sour stimulations by monitoring membrane potential. The results indicate this MEA-based biosensor can record the special off-responses of PKD channels to sour stimulation in a non-invasive manner for a long term. It may provide an alternative tool for the research of taste transduction, especially for the characterization of taste ion channels.

  9. Maxwell's demon in biochemical signal transduction with feedback loop

    NASA Astrophysics Data System (ADS)

    Ito, Sosuke; Sagawa, Takahiro

    2015-06-01

    Signal transduction in living cells is vital to maintain life itself, where information transfer in noisy environment plays a significant role. In a rather different context, the recent intensive research on `Maxwell's demon'--a feedback controller that utilizes information of individual molecules--have led to a unified theory of information and thermodynamics. Here we combine these two streams of research, and show that the second law of thermodynamics with information reveals the fundamental limit of the robustness of signal transduction against environmental fluctuations. Especially, we find that the degree of robustness is quantitatively characterized by an informational quantity called transfer entropy. Our information-thermodynamic approach is applicable to biological communication inside cells, in which there is no explicit channel coding in contrast to artificial communication. Our result could open up a novel biophysical approach to understand information processing in living systems on the basis of the fundamental information-thermodynamics link.

  10. Pantropic retroviruses as a transduction tool for sea urchin embryos.

    PubMed

    Core, Amanda B; Reyna, Arlene E; Conaway, Evan A; Bradham, Cynthia A

    2012-04-01

    Sea urchins are an important model for experiments at the intersection of development and systems biology, and technical innovations that enhance the utility of this model are of great value. This study explores pantropic retroviruses as a transduction tool for sea urchin embryos, and demonstrates that pantropic retroviruses infect sea urchin embryos with high efficiency and genomically integrate at a copy number of one per cell. We successfully used a self-inactivation strategy to both insert a sea urchin-specific enhancer and disrupt the endogenous viral enhancer. The resulting self-inactivating viruses drive global and persistent gene expression, consistent with genomic integration during the first cell cycle. Together, these data provide substantial proof of principle for transduction technology in sea urchin embryos. PMID:22431628

  11. Mechanical properties and structure of Haliotis discus hannai Ino and Hemifusus tuba conch shells: a comparative study

    NASA Astrophysics Data System (ADS)

    Zhao, Jie; Chen, Chen; Liang, Yan; Wang, Jian

    2010-03-01

    Haliotis discus hannai Ino (abalone shell) and Hemifusus tuba conch shell have been studied for the purpose to comparatively investigate the mechanisms by which nature designs composites. It is shown that both shells are composed of aragonite and a small amount of proteins while the conch shell shows finer microstructure but lower strength than abalone shell. It is also shown that the fresh shells exhibits better property than those after heat-treatments. It is therefore supposed that the size of inorganic substance is not a dominant factor to improve strength, while both proteins in shells and the microstructure of inorganic matter also play important roles.

  12. Dynamic disorder and the energetic costs of information transduction

    SciTech Connect

    Thill, Peter

    2014-07-07

    We study a model of dynamic disorder relevant for signal transduction pathways in which enzymatic reaction rates fluctuate over several orders of magnitude. For the simple networks we consider, dynamic disorder drives the system far from equilibrium and imposes an energetic burden for high fidelity signaling capability. We study how the dynamics of the underlying stochastic behavior in the reaction rate process is related to the energetic cost of transmitting information through the network.

  13. Retroviral Transduction of T Cells and T Cell Precursors.

    PubMed

    Simmons, Amie; Alberola-Ila, José

    2016-01-01

    Transduction of lymphoid progenitors with retroviral or lentiviral vectors is a powerful experimental strategy to tease out the role of a gene or pathway in T cell development via gain-of-function or loss-of-function strategies. Here we discuss different approaches to use this powerful technology, and present some protocols that we use to transduce murine HSCs, thymocytes, and lymphoid cell lines with these viral vectors. PMID:26294401

  14. Dynamic disorder and the energetic costs of information transduction

    NASA Astrophysics Data System (ADS)

    Thill, Peter

    2014-07-01

    We study a model of dynamic disorder relevant for signal transduction pathways in which enzymatic reaction rates fluctuate over several orders of magnitude. For the simple networks we consider, dynamic disorder drives the system far from equilibrium and imposes an energetic burden for high fidelity signaling capability. We study how the dynamics of the underlying stochastic behavior in the reaction rate process is related to the energetic cost of transmitting information through the network.

  15. Protein transduction domain can enhance the humoral immunity and cross-protection of HPV16L2 peptide vaccines

    PubMed Central

    LI, LILI; GUO, YANTAO; LI, ZELIN; ZHOU, YUBAI; ZENG, YI

    2016-01-01

    Due to type-specificity, commercially available human papillomavirus (HPV) vaccines are only effective against homologous HPV serotypes, providing limited protection. Recent studies have highlighted the role of HPV minor capsid protein (known as L2) in inducing cross-protection. The N-terminal peptides of L2 contain conserved cross-response epitopes that can induce neutralizing antibodies against heterogeneous HPVs. However, when compared with L1, these peptides have lower immunogenicity, which limits the application of these vaccines. The protein transduction domain (PTD), located in the Tat protein of human immunodeficiency virus, facilitates delivery of DNA, peptides, proteins and virus particles into cells by unknown mechanisms, and has been reported to enhance immunogenicity of several antigens. In the present study, two peptides derived from the N-terminal of HPV16L2 were chosen as model antigens and constructed a series of L2 peptide vaccines by either fusing or mixing with PTD. Subsequently their immunogenicity was evaluated. The results indicated that the L2 peptides fused with PTD show considerably enhanced humoral immunity. In particular, they increased the titer of cross-neutralizing antibodies, while L2 peptides that had only been mixed with PTD induced only small cross-protection responses. Overall, the data suggest that fusion of L2 peptides with PTD significantly enhances their cross-protection and may be a promising strategy for the development of broad-spectrum HPV prophylactic vaccines. PMID:27284417

  16. Pluripotency transcription factor Sox2 is strongly adsorbed by heparin but requires a protein transduction domain for cell internalization

    SciTech Connect

    Albayrak, Cem; Yang, William C.; Swartz, James R.

    2013-02-15

    Highlights: ► Both R9Sox2 and Sox2 bind heparin with comparable affinity. ► Both R9Sox2 and Sox2 bind to fibroblasts, but only R9Sox2 is internalized. ► Internalization efficiency of R9Sox2 is 0.3% of the administered protein. ► Heparan sulfate adsorption may be part of a mechanism for managing cell death. -- Abstract: The binding of protein transduction domain (PTD)-conjugated proteins to heparan sulfate is an important step in cellular internalization of macromolecules. Here, we studied the pluripotency transcription factor Sox2, with or without the nonaarginine (R9) PTD. Unexpectedly, we observed that Sox2 is strongly adsorbed by heparin and by the fibroblasts without the R9 PTD. However, only the R9Sox2 fusion protein is internalized by the cells. These results collectively show that binding to heparan sulfate is not sufficient for cellular uptake, thereby supporting a recent hypothesis that other proteins play a role in cell internalization of PTD-conjugated proteins.

  17. Enhanced Central Nervous System Transduction with Lentiviral Vectors Pseudotyped with RVG/HIV-1gp41 Chimeric Envelope Glycoproteins

    PubMed Central

    Trabalza, Antonio; Eleftheriadou, Ioanna; Sgourou, Argyro; Liao, Ting-Yi; Patsali, Petros; Lee, Heyne

    2014-01-01

    ABSTRACT To investigate the potential benefits which may arise from pseudotyping the HIV-1 lentiviral vector with its homologous gp41 envelope glycoprotein (GP) cytoplasmic tail (CT), we created chimeric RVG/HIV-1gp41 GPs composed of the extracellular and transmembrane sequences of RVG and either the full-length gp41 CT or C terminus gp41 truncations sequentially removing existing conserved motifs. Lentiviruses (LVs) pseudotyped with the chimeric GPs were evaluated in terms of particle release (physical titer), biological titers, infectivity, and in vivo central nervous system (CNS) transduction. We report here that LVs carrying shorter CTs expressed higher levels of envelope GP and showed a higher average infectivity than those bearing full-length GPs. Interestingly, complete removal of GP CT led to vectors with the highest transduction efficiency. Removal of all C-terminal gp41 CT conserved motifs, leaving just 17 amino acids (aa), appeared to preserve infectivity and resulted in a significantly increased physical titer. Furthermore, incorporation of these 17 aa in the RVG CT notably enhanced the physical titer. In vivo stereotaxic delivery of LV vectors exhibiting the best in vitro titers into rodent striatum facilitated efficient transduction of the CNS at the site of injection. A particular observation was the improved retrograde transduction of neurons in connected distal sites that resulted from the chimeric envelope R5 which included the “Kennedy” sequence (Ken) and lentivirus lytic peptide 2 (LLP2) conserved motifs in the CT, and although it did not exhibit a comparable high titer upon pseudotyping, it led to a significant increase in distal retrograde transduction of neurons. IMPORTANCE In this study, we have produced novel chimeric envelopes bearing the extracellular domain of rabies fused to the cytoplasmic tail (CT) of gp41 and pseudotyped lentiviral vectors with them. Here we report novel effects on the transduction efficiency and physical titer

  18. Transduction patterns of pseudotyped lentiviral vectors in the nervous system.

    PubMed

    Wong, Liang-Fong; Azzouz, Mimoun; Walmsley, Lucy E; Askham, Zoe; Wilkes, Fraser J; Mitrophanous, Kyriacos A; Kingsman, Susan M; Mazarakis, Nicholas D

    2004-01-01

    We have developed a non-primate-based lentiviral vector based on the equine infectious anemia virus (EIAV) for efficient gene transfer to the central and peripheral nervous systems. Previously we have demonstrated that pseudotyping lentiviral vectors with the rabies virus glycoprotein confers retrograde axonal transport to these vectors. In the present study we have successfully produced high-titer EIAV vectors pseudotyped with envelope glycoproteins from Rhabdovirus vesicular stomatitis virus (VSV) serotypes (Indiana and Chandipura strains); rabies virus [various Evelyn-Rokitnicki-Abelseth ERA strains and challenge virus standard (CVS)]; Lyssavirus Mokola virus, a rabies-related virus; and Arenavirus lymphocytic choriomeningitis virus (LCMV). These vectors were delivered to the striatum or spinal cord of adult rats or muscle of neonatal mice by direct injection. We report that the lentiviral vectors pseudotyped with envelopes from the VSV Indiana strain, wild-type ERA, and CVS strains resulted in strong transduction in the striatum, while Mokola- and LCMV-pseudotyped vectors exhibited moderate and weak transduction, respectively. Furthermore ERA- and CVS-pseudotyped lentiviral vectors demonstrated retrograde transport and expression in distal neurons after injection in brain, spinal cord, and muscle. The differences in transduction efficiencies and retrograde transport conferred by these envelope glycoproteins present novel opportunities in designing therapeutic strategies for different neurological diseases. PMID:14741783

  19. Retinal transduction profiles by high-capacity viral vectors

    PubMed Central

    Puppo, Agostina; Cesi, Giulia; Marrocco, Elena; Piccolo, Pasquale; Jacca, Sarah; Shayakhmetov, Dmitry M.; Parks, Robin J.; Davidson, Beverly L.; Colloca, Stefano; Brunetti-Pierri, Nicola; Ng, Philip; Donofrio, Gaetano; Auricchio, Alberto

    2014-01-01

    Retinal gene therapy with adeno-associated viral (AAV) vectors is safe and effective in humans. However, the limited cargo capacity of AAV prevents their use for therapy of those inherited retinopathies (IRs) due to mutations in large (>5kb) genes. Viral vectors derived from Adenovirus (Ad), Lentivirus (LV) and Herpesvirus (HV) can package large DNA sequences but do not target efficiently retinal photoreceptors (PRs) where the majority of genes responsible for IRs are expressed. Here, we have evaluated the mouse retinal transduction profiles of vectors derived from 16 different Ad serotypes, 7 LV pseudotypes, and from a bovine HV. Most of the vectors tested transduced efficiently the retinal pigment epithelium (RPE). We found that LV-GP64 tends to transduce more PRs than the canonical LV-VSVG albeit this was restricted to a narrow region. We observed more extensive PR transduction with HdAd1, 2 and 5/F35++ than with LV, although none of them outperformed the canonical HdAd5 or matched the extension of PR transduction achieved with AAV2/8. PMID:24989814

  20. Mucopolysaccharidosis IIIB confers enhanced neonatal intracranial transduction by AAV8 but not by 5, 9 or rh10

    PubMed Central

    Gilkes, J A; Bloom, M D; Heldermon, C D

    2016-01-01

    Sanfilippo syndrome type B (mucopolysaccharidosis IIIB, MPS IIIB) is a lysosomal storage disease resulting from deficiency of N-acetyl-glucosaminidase (NAGLU) activity. To determine the possible therapeutic utility of recombinant adeno-associated virus (rAAV) in early gene therapy-based interventions, we performed a comprehensive assessment of transduction and biodistribution profiles of four central nervous system (CNS) administered rAAV serotypes, -5, -8, -9 and -rh10. To simulate optimal earliest treatment of the disease, each rAAV serotype was injected into the CNS of neonatal MPS IIIB and control animals. We observed marked differences in biodistribution and transduction profiles between the serotypes and this differed in MPS IIIB compared with healthy control mice. Overall, in control mice, all serotypes performed comparably, although some differences were observed in certain focal areas. In MPS IIIB mice, AAV8 was more efficient than AAV5, -9 and -rh10 for gene delivery to most structures analyzed, including the cerebral cortex, hippocampus and thalamus. Noteworthy, the pattern of biodistribution within the CNS varied by serotype and genotype. Interestingly, AAV8 also produced the highest green fluorescent protein intensity levels compared with any other serotype and demonstrated improved transduction in NAGLU compared with control brains. Importantly, we also show leakage of AAV8, -9 and -rh10, but not AAV5, from CNS parenchyma to systemic organs. Overall, our data suggest that AAV8 represents the best therapeutic gene transfer vector for early intervention in MPS IIIB. PMID:26674264

  1. Mucopolysaccharidosis IIIB confers enhanced neonatal intracranial transduction by AAV8 but not by 5, 9 or rh10.

    PubMed

    Gilkes, J A; Bloom, M D; Heldermon, C D

    2016-03-01

    Sanfilippo syndrome type B (mucopolysaccharidosis IIIB, MPS IIIB) is a lysosomal storage disease resulting from deficiency of N-acetyl-glucosaminidase (NAGLU) activity. To determine the possible therapeutic utility of recombinant adeno-associated virus (rAAV) in early gene therapy-based interventions, we performed a comprehensive assessment of transduction and biodistribution profiles of four central nervous system (CNS) administered rAAV serotypes, -5, -8, -9 and -rh10. To simulate optimal earliest treatment of the disease, each rAAV serotype was injected into the CNS of neonatal MPS IIIB and control animals. We observed marked differences in biodistribution and transduction profiles between the serotypes and this differed in MPS IIIB compared with healthy control mice. Overall, in control mice, all serotypes performed comparably, although some differences were observed in certain focal areas. In MPS IIIB mice, AAV8 was more efficient than AAV5, -9 and -rh10 for gene delivery to most structures analyzed, including the cerebral cortex, hippocampus and thalamus. Noteworthy, the pattern of biodistribution within the CNS varied by serotype and genotype. Interestingly, AAV8 also produced the highest green fluorescent protein intensity levels compared with any other serotype and demonstrated improved transduction in NAGLU compared with control brains. Importantly, we also show leakage of AAV8, -9 and -rh10, but not AAV5, from CNS parenchyma to systemic organs. Overall, our data suggest that AAV8 represents the best therapeutic gene transfer vector for early intervention in MPS IIIB. PMID:26674264

  2. Global insights into acetic acid resistance mechanisms and genetic stability of Acetobacter pasteurianus strains by comparative genomics

    PubMed Central

    Wang, Bin; Shao, Yanchun; Chen, Tao; Chen, Wanping; Chen, Fusheng

    2015-01-01

    Acetobacter pasteurianus (Ap) CICC 20001 and CGMCC 1.41 are two acetic acid bacteria strains that, because of their strong abilities to produce and tolerate high concentrations of acetic acid, have been widely used to brew vinegar in China. To globally understand the fermentation characteristics, acid-tolerant mechanisms and genetic stabilities, their genomes were sequenced. Genomic comparisons with 9 other sequenced Ap strains revealed that their chromosomes were evolutionarily conserved, whereas the plasmids were unique compared with other Ap strains. Analysis of the acid-tolerant metabolic pathway at the genomic level indicated that the metabolism of some amino acids and the known mechanisms of acetic acid tolerance, might collaboratively contribute to acetic acid resistance in Ap strains. The balance of instability factors and stability factors in the genomes of Ap CICC 20001 and CGMCC 1.41 strains might be the basis for their genetic stability, consistent with their stable industrial performances. These observations provide important insights into the acid resistance mechanism and the genetic stability of Ap strains and lay a foundation for future genetic manipulation and engineering of these two strains. PMID:26691589

  3. Global insights into acetic acid resistance mechanisms and genetic stability of Acetobacter pasteurianus strains by comparative genomics.

    PubMed

    Wang, Bin; Shao, Yanchun; Chen, Tao; Chen, Wanping; Chen, Fusheng

    2015-01-01

    Acetobacter pasteurianus (Ap) CICC 20001 and CGMCC 1.41 are two acetic acid bacteria strains that, because of their strong abilities to produce and tolerate high concentrations of acetic acid, have been widely used to brew vinegar in China. To globally understand the fermentation characteristics, acid-tolerant mechanisms and genetic stabilities, their genomes were sequenced. Genomic comparisons with 9 other sequenced Ap strains revealed that their chromosomes were evolutionarily conserved, whereas the plasmids were unique compared with other Ap strains. Analysis of the acid-tolerant metabolic pathway at the genomic level indicated that the metabolism of some amino acids and the known mechanisms of acetic acid tolerance, might collaboratively contribute to acetic acid resistance in Ap strains. The balance of instability factors and stability factors in the genomes of Ap CICC 20001 and CGMCC 1.41 strains might be the basis for their genetic stability, consistent with their stable industrial performances. These observations provide important insights into the acid resistance mechanism and the genetic stability of Ap strains and lay a foundation for future genetic manipulation and engineering of these two strains. PMID:26691589

  4. Comparative Analysis of Mechanical Properties of PWV, NO and Ascending Aorta between WHY Rats and SHR Rats

    PubMed Central

    Yu, Bo; Xu, De-Jun; Sun, Huan; Yang, Kun; Luo, Min

    2015-01-01

    Background The aim of this study was to compare and analyze the tensile mechanical properties of the ascending aorta (AA) in Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs), for the purpose of providing a biomechanical basis for hypertension prevention. Methods Pulse wave velocities (PWV) and serum nitric oxide (NO) concentrations were determined in 6-month-old WKY rats and SHRs (n = 21, n = 21, respectively). Then, 20 AAs from each group were obtained for longitudinal tensile testing. Results The maximum stress, maximum strain, and strain at a tensile stress of 16 Kpa were greater in WKY rats than in SHRs (p < 0.05). The aortic elastic modulus and PWV value were greater in SHRs than in WKY rats (p < 0.05 for both), while NO concentrations were lower in the SHR group than in the WKY group (p < 0.05). Conclusions The AA tensile mechanical properties differed between the WKY rats and SHRs, and the tensile mechanical properties of the SHR model had changed. PMID:27122902

  5. Global insights into acetic acid resistance mechanisms and genetic stability of Acetobacter pasteurianus strains by comparative genomics

    NASA Astrophysics Data System (ADS)

    Wang, Bin; Shao, Yanchun; Chen, Tao; Chen, Wanping; Chen, Fusheng

    2015-12-01

    Acetobacter pasteurianus (Ap) CICC 20001 and CGMCC 1.41 are two acetic acid bacteria strains that, because of their strong abilities to produce and tolerate high concentrations of acetic acid, have been widely used to brew vinegar in China. To globally understand the fermentation characteristics, acid-tolerant mechanisms and genetic stabilities, their genomes were sequenced. Genomic comparisons with 9 other sequenced Ap strains revealed that their chromosomes were evolutionarily conserved, whereas the plasmids were unique compared with other Ap strains. Analysis of the acid-tolerant metabolic pathway at the genomic level indicated that the metabolism of some amino acids and the known mechanisms of acetic acid tolerance, might collaboratively contribute to acetic acid resistance in Ap strains. The balance of instability factors and stability factors in the genomes of Ap CICC 20001 and CGMCC 1.41 strains might be the basis for their genetic stability, consistent with their stable industrial performances. These observations provide important insights into the acid resistance mechanism and the genetic stability of Ap strains and lay a foundation for future genetic manipulation and engineering of these two strains.

  6. A Comparative Study on the Mechanical, Thermal and Morphological Characterization of Poly(lactic acid)/Epoxidized Palm Oil Blend

    PubMed Central

    Giita Silverajah, V. S.; Ibrahim, Nor Azowa; Yunus, Wan Md Zin Wan; Hassan, Hazimah Abu; Woei, Chieng Buong

    2012-01-01

    In this work, poly(lactic acid) (PLA) a fully biodegradable thermoplastic polymer matrix was melt blended with three different epoxidized palm oil (EPO). The aim of this research was to enhance the flexibility, mechanical and thermal properties of PLA. The blends were prepared at various EPO contents of 1, 2, 3, 4 and 5 wt% and characterized. The SEM analysis evidenced successful modification on the neat PLA brittle morphology. Tensile tests indicate that the addition of 1 wt% EPO is sufficient to improve the strength and flexibility compared to neat PLA. Additionally, the flexural and impact properties were also enhanced. Further, DSC analysis showed that the addition of EPO results in a decrease in Tg, which implies an increase in the PLA chain mobility. In the presence of 1 wt% EPO, TGA results revealed significant increase in the thermal stability by 27%. Among the three EPOs used, EPO(3) showed the best mechanical and thermal properties compared to the other EPO’s, with an optimum loading of 1 wt%. Conclusively, EPO showed a promising outcome to overcome the brittleness and improve the overall properties of neat PLA, thus can be considered as a potential plasticizer. PMID:22754338

  7. A comparative study on the mechanical, thermal and morphological characterization of poly(lactic acid)/epoxidized Palm Oil blend.

    PubMed

    Giita Silverajah, V S; Ibrahim, Nor Azowa; Yunus, Wan Md Zin Wan; Hassan, Hazimah Abu; Woei, Chieng Buong

    2012-01-01

    In this work, poly(lactic acid) (PLA) a fully biodegradable thermoplastic polymer matrix was melt blended with three different epoxidized palm oil (EPO). The aim of this research was to enhance the flexibility, mechanical and thermal properties of PLA. The blends were prepared at various EPO contents of 1, 2, 3, 4 and 5 wt% and characterized. The SEM analysis evidenced successful modification on the neat PLA brittle morphology. Tensile tests indicate that the addition of 1 wt% EPO is sufficient to improve the strength and flexibility compared to neat PLA. Additionally, the flexural and impact properties were also enhanced. Further, DSC analysis showed that the addition of EPO results in a decrease in T(g), which implies an increase in the PLA chain mobility. In the presence of 1 wt% EPO, TGA results revealed significant increase in the thermal stability by 27%. Among the three EPOs used, EPO(3) showed the best mechanical and thermal properties compared to the other EPO's, with an optimum loading of 1 wt%. Conclusively, EPO showed a promising outcome to overcome the brittleness and improve the overall properties of neat PLA, thus can be considered as a potential plasticizer. PMID:22754338

  8. Comparative genomics analysis of the companion mechanisms of Bacillus thuringiensis Bc601 and Bacillus endophyticus Hbe603 in bacterial consortium

    PubMed Central

    Jia, Nan; Ding, Ming-Zhu; Gao, Feng; Yuan, Ying-Jin

    2016-01-01

    Bacillus thuringiensis and Bacillus endophyticus both act as the companion bacteria, which cooperate with Ketogulonigenium vulgare in vitamin C two-step fermentation. Two Bacillus species have different morphologies, swarming motility and 2-keto-L-gulonic acid productivities when they co-culture with K. vulgare. Here, we report the complete genome sequencing of B. thuringiensis Bc601 and eight plasmids of B. endophyticus Hbe603, and carry out the comparative genomics analysis. Consequently, B. thuringiensis Bc601, with greater ability of response to the external environment, has been found more two-component system, sporulation coat and peptidoglycan biosynthesis related proteins than B. endophyticus Hbe603, and B. endophyticus Hbe603, with greater ability of nutrients biosynthesis, has been found more alpha-galactosidase, propanoate, glutathione and inositol phosphate metabolism, and amino acid degradation related proteins than B. thuringiensis Bc601. Different ability of swarming motility, response to the external environment and nutrients biosynthesis may reflect different companion mechanisms of two Bacillus species. Comparative genomic analysis of B. endophyticus and B. thuringiensis enables us to further understand the cooperative mechanism with K. vulgare, and facilitate the optimization of bacterial consortium. PMID:27353048

  9. Comparative genomics analysis of the companion mechanisms of Bacillus thuringiensis Bc601 and Bacillus endophyticus Hbe603 in bacterial consortium.

    PubMed

    Jia, Nan; Ding, Ming-Zhu; Gao, Feng; Yuan, Ying-Jin

    2016-01-01

    Bacillus thuringiensis and Bacillus endophyticus both act as the companion bacteria, which cooperate with Ketogulonigenium vulgare in vitamin C two-step fermentation. Two Bacillus species have different morphologies, swarming motility and 2-keto-L-gulonic acid productivities when they co-culture with K. vulgare. Here, we report the complete genome sequencing of B. thuringiensis Bc601 and eight plasmids of B. endophyticus Hbe603, and carry out the comparative genomics analysis. Consequently, B. thuringiensis Bc601, with greater ability of response to the external environment, has been found more two-component system, sporulation coat and peptidoglycan biosynthesis related proteins than B. endophyticus Hbe603, and B. endophyticus Hbe603, with greater ability of nutrients biosynthesis, has been found more alpha-galactosidase, propanoate, glutathione and inositol phosphate metabolism, and amino acid degradation related proteins than B. thuringiensis Bc601. Different ability of swarming motility, response to the external environment and nutrients biosynthesis may reflect different companion mechanisms of two Bacillus species. Comparative genomic analysis of B. endophyticus and B. thuringiensis enables us to further understand the cooperative mechanism with K. vulgare, and facilitate the optimization of bacterial consortium. PMID:27353048

  10. A comparative study of sliding wear of nonmetallic dental restorative materials with emphasis on micromechanical wear mechanisms.

    PubMed

    Dupriez, Nataliya Deyneka; von Koeckritz, Ann-Kristin; Kunzelmann, Karl-Heinz

    2015-05-01

    The purpose of this study is to investigate the in vitro tribological behavior of modern nonmetallic restorative materials. Specimen prepared of IPS e.max Press lithium disilicate glass ceramic, IPS Empress Esthetic leucite-reinforced glass ceramic, Everest ZS Blanks yttria-stabilized zirconia and Lava Ultimate composite were subjected to wear using a wear machine designed to simulate occlusal loads. The wear of the investigated materials and antagonists were evaluated by a three-dimensional surface scanner. The quantitative wear test results were used to compare and rank the materials. Specimens were divided into two groups with steatite and alumina antagonists. For each antagonist material an analysis of variance was applied. As a post hoc test of the significant differences, Tukey's honest significant difference test was used. With steatite antagonist: wear of zirconia < wear of leucite-reinforced ceramic < wear of lithium disilicate ceramic < wear of Lava Ultimate composite. No significant wear difference was found for steatite antagonist. The wear of IPS e.max Press and Lava Ultimate against hard alumina was found to be twice lower as compared to their wear when opposing to steatite. The differences were associated with materials mechanical properties (hardness and fracture toughness) and with materials microstructure. Wear mechanisms are discussed. PMID:25303041

  11. Expression and functional analyses of the Arabidopsis QUA1 gene in light signal transduction.

    PubMed

    Zhaojin, Chen; Chuanyu, Ding; Yuan, Zheng

    2016-05-01

    Plants not only use light as an energy source for photosynthesis, but also have to monitor the light quality and quantity input to execute appropriate physiological and developmental responses, such as cell differentiation, structural and functional changes, as well as the formation of tissues and organs. The process is referred to as photomorphogenesis. Arabidopsis QUA1 (QUASIMODO1), which functions in pectin synthesis, is identified as a member of glycosyltransferases. Previously, the hypocotyl elongation of the qua1-1 mutant was shown to be inhibited under dark conditions. In this study, we used the qua1-1/cry1 and qua1-1/phyB double mutants as the materials to study the function of the QUA1 gene in light signal transduction. The results showed that QUA1 not only participated in hypocotyl elongation under dark conditions, but also in blue light, red light and far red light conditions. In qua1-1 mutant seedlings, both the cell length of hypocotyl and the light-regulated gene expression were affected. Compared with cry1 and phyB mutants, qua1-1/cry1 and qua1-1/phyB double mutants had the shorter hypocotyl. Light-regulated gene expression was also affected in the double mutants. These data indicated that QUA1 might participate in the light signal transduction regulated by CRY1 and PHYB. Hence, the QUA1 gene may play multiple roles in light signal transduction by regulating the cell elongation and light-regulated gene expression. PMID:27232492

  12. 'Advanced' generation lentiviruses as efficient vectors for cardiomyocyte gene transduction in vitro and in vivo.

    PubMed

    Bonci, D; Cittadini, A; Latronico, M V G; Borello, U; Aycock, J K; Drusco, A; Innocenzi, A; Follenzi, A; Lavitrano, M; Monti, M G; Ross, J; Naldini, L; Peschle, C; Cossu, G; Condorelli, G

    2003-04-01

    Efficient gene transduction in cardiomyocytes is a task that can be accomplished only by viral vectors. Up to now, the most commonly used vectors for this purpose have been adenoviral-derived ones. Recently, it has been demonstrated that lentiviral vectors can transduce growth-arrested cells, such as hematopoietic stem cells. Moreover, a modified form of lentiviral vector (the 'advanced' generation), containing an mRNA-stabilizer sequence and a nuclear import sequence, has been shown to significantly improve gene transduction in growth-arrested cells as compared to the third-generation vector. Therefore, we tested whether the 'advanced' generation lentivirus is capable of infecting and transducing cardiomyocytes both in vitro and in vivo, comparing efficacy in vitro against the third-generation of the same vector. Here we report that 'advanced' generation lentiviral vectors infected most (>80%) cardiomyocytes in culture, as demonstrated by immunofluorescence and FACS analyses: in contrast the percentage of cardiomyocytes infected by third-generation lentivirus was three- to four-fold lower. Moreover, 'advanced' generation lentivirus was also capable of infecting and inducing stable gene expression in adult myocardium in vivo. Thus, 'advanced' generation lentiviral vectors can be used for both in vitro and in vivo gene expression studies in the cardiomyocyte. PMID:12692591

  13. Unique interweaved microtubule scaffold mediates osmosensory transduction via physical interaction with TRPV1.

    PubMed

    Prager-Khoutorsky, Masha; Khoutorsky, Arkady; Bourque, Charles W

    2014-08-20

    The electrical activity of mammalian osmosensory neurons (ONs) is increased by plasma hypertonicity to command thirst, antidiuretic hormone release, and increased sympathetic tone during dehydration. Osmosensory transduction is a mechanical process whereby decreases in cell volume cause the activation of transient receptor potential vanilloid type-1 (TRPV1) channels to induce depolarization and increase spiking activity in ONs. However, it is not known how cell shrinking is mechanically coupled to channel activation. Using superresolution imaging, we found that ONs are endowed with a uniquely interweaved scaffold of microtubules throughout their somata. Microtubules physically interact with the C terminus of TRPV1 at the cell surface and provide a pushing force that drives channels activation during shrinking. Moreover, we found that changes in the density of these interactions can bidirectionally modulate osmosensory gain. Microtubules are thus an essential component of the vital neuronal mechanotransduction apparatus that allows the brain to monitor and correct body hydration. PMID:25123313

  14. Gadolinium inhibits mechanoelectrical transduction in rabbit carotid baroreceptors. Implication of stretch-activated channels.

    PubMed Central

    Hajduczok, G; Chapleau, M W; Ferlic, R J; Mao, H Z; Abboud, F M

    1994-01-01

    Gadolinium (Gd3+) has been shown to prevent mechanoelectrical transduction believed to be mediated through stretch-activated channels. We investigated the possible role of Gd(3+)-sensitive channels in mediating baroreceptor activity in the carotid sinus of rabbits. Baroreceptor activity induced by a ramp increase of carotid sinus pressure was reduced significantly during exposure to Gd3+. The inhibition was dose-related and reversible, and was not associated with alteration of carotid sinus wall mechanics as the pressure-strain relationship was unaffected. Veratrine triggered action potentials from single- and multiple-baroreceptor fibers when their response to pressure was inhibited by Gd3+. This suggests that the effect of Gd3+ on baroreceptors in the isolated carotid sinus was specific to their mechanical activation. The results suggest that stretch-activated ion channels sensitive to Gd3+ may be the mechanoelectrical transducers of rabbit carotid sinus baroreceptors. PMID:7527431

  15. Endocytosis of pro-inflammatory cytokine receptors and its relevance for signal transduction.

    PubMed

    Hermanns, Heike M; Wohlfahrt, Julia; Mais, Christine; Hergovits, Sabine; Jahn, Daniel; Geier, Andreas

    2016-08-01

    The pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6) are key players of the innate and adaptive immunity. Their activity needs to be tightly controlled to allow the initiation of an appropriate immune response as defense mechanism against pathogens or tissue injury. Excessive or sustained signaling of either of these cytokines leads to severe diseases, including rheumatoid arthritis, inflammatory bowel diseases (Crohn's disease, ulcerative colitis), steatohepatitis, periodic fevers and even cancer. Studies carried out in the last 30 years have emphasized that an elaborate control system for each of these cytokines exists. Here, we summarize what is currently known about the involvement of receptor endocytosis in the regulation of these pro-inflammatory cytokines' signaling cascades. Particularly in the last few years it was shown that this cellular process is far more than a mere feedback mechanism to clear cytokines from the circulation and to shut off their signal transduction. PMID:27071147

  16. Novel protective mechanisms of antidepressants against 3-nitropropionic acid induced Huntington's-like symptoms: a comparative study.

    PubMed

    Kumar, Puneet; Kalonia, Harikesh; Kumar, Anil

    2011-10-01

    Huntington's disease (HD) is characterized by progressive degeneration of neurons in the striatum, cortex and other parts of the brain, causing motor and cognitive dysfunction. 3-Nitropropionic acid (3-NP) is a well-known mycotoxin that significantly induces motor dysfunction in animals. Studies suggested the involvement of oxidative stress and nitric oxide mechanisms in HD pathogenesis. Clinical reports have also indicated the neuroprotective potential of antidepressants. Therefore, the present study has been designed to elucidate and compare the mechanistic role of different antidepressants (sertraline, venlafaxine, imipramine and trazodone) and their interaction with nitric oxide modulators if any, against 3-NP-induced neurotoxicity. Systemic 3-NP (10 mg/kg) administration for 14 days significantly reduced locomotor activity, body weight, motor coordination, oxidative defense and impaired mitochondrial complex enzyme activities in the striatum. Sertraline, venlafaxine, imipramine and trazodone treatments significantly improved behavioral, oxidative defense and mitochondrial complex enzyme activities as compared with the 3-NP-treated group. Systemic L-arginine (50 mg/kg) pretreatment with sub-effective dose of sertraline (10 mg/kg), venlafaxine (10 mg/kg), imipramine (10 mg/kg) and trazodone (10 mg/kg) for 14 days significantly attenuated their protective effect. Similarly, L-nitro-arginine methyl ester (L-NAME) (10 mg/kg) pretreatment with sub-effective dose of sertraline (10 mg/kg), venlafaxine (10 mg/kg), imipramine (10 mg/kg) and trazodone (10 mg/kg) for 14 days significantly potentiated their protective effects which were significant as compared with their effect alone, respectively. The results of the present study suggest that a nitric oxide mechanism might be involved in their protective effect against 3-NP-induced neurotoxicity. PMID:20305041

  17. Comparative Transcriptome Analysis of Latex Reveals Molecular Mechanisms Underlying Increased Rubber Yield in Hevea brasiliensis Self-Rooting Juvenile Clones

    PubMed Central

    Li, Hui-Liang; Guo, Dong; Zhu, Jia-Hong; Wang, Ying; Chen, Xiong-Ting; Peng, Shi-Qing

    2016-01-01

    Rubber tree (Hevea brasiliensis) self-rooting juvenile clones (JCs) are promising planting materials for rubber production. In a comparative trial between self-rooting JCs and donor clones (DCs), self-rooting JCs exhibited better performance in rubber yield. To study the molecular mechanism associated with higher rubber yield in self-rooting JCs, we sequenced and comparatively analyzed the latex of rubber tree self-rooting JCs and DCs at the transcriptome level. Total raw reads of 34,632,012 and 35,913,020 bp were obtained from the library of self-rooting JCs and DCs, respectively, by using Illumina HiSeq 2000 sequencing technology. De novo assemblies yielded 54689 unigenes from the library of self-rooting JCs and DCs. Among 54689 genes, 1716 genes were identified as differentially expressed between self-rooting JCs and DCs via comparative transcript profiling. Functional analysis showed that the genes related to the mass of categories were differentially enriched between the two clones. Several genes involved in carbohydrate metabolism, hormone metabolism and reactive oxygen species scavenging were up-regulated in self-rooting JCs, suggesting that the self-rooting JCs provide sufficient molecular basis for the increased rubber yielding, especially in the aspects of improved latex metabolisms and latex flow. Some genes encoding epigenetic modification enzymes were also differentially expressed between self-rooting JCs and DCs. Epigenetic modifications may lead to gene differential expression between self-rooting JCs and DCs. These data will provide new cues to understand the molecular mechanism underlying the improved rubber yield of H. brasiliensis self-rooting clones. PMID:27555864

  18. Comparative Transcriptome Analysis of Latex Reveals Molecular Mechanisms Underlying Increased Rubber Yield in Hevea brasiliensis Self-Rooting Juvenile Clones.

    PubMed

    Li, Hui-Liang; Guo, Dong; Zhu, Jia-Hong; Wang, Ying; Chen, Xiong-Ting; Peng, Shi-Qing

    2016-01-01

    Rubber tree (Hevea brasiliensis) self-rooting juvenile clones (JCs) are promising planting materials for rubber production. In a comparative trial between self-rooting JCs and donor clones (DCs), self-rooting JCs exhibited better performance in rubber yield. To study the molecular mechanism associated with higher rubber yield in self-rooting JCs, we sequenced and comparatively analyzed the latex of rubber tree self-rooting JCs and DCs at the transcriptome level. Total raw reads of 34,632,012 and 35,913,020 bp were obtained from the library of self-rooting JCs and DCs, respectively, by using Illumina HiSeq 2000 sequencing technology. De novo assemblies yielded 54689 unigenes from the library of self-rooting JCs and DCs. Among 54689 genes, 1716 genes were identified as differentially expressed between self-rooting JCs and DCs via comparative transcript profiling. Functional analysis showed that the genes related to the mass of categories were differentially enriched between the two clones. Several genes involved in carbohydrate metabolism, hormone metabolism and reactive oxygen species scavenging were up-regulated in self-rooting JCs, suggesting that the self-rooting JCs provide sufficient molecular basis for the increased rubber yielding, especially in the aspects of improved latex metabolisms and latex flow. Some genes encoding epigenetic modification enzymes were also differentially expressed between self-rooting JCs and DCs. Epigenetic modifications may lead to gene differential expression between self-rooting JCs and DCs. These data will provide new cues to understand the molecular mechanism underlying the improved rubber yield of H. brasiliensis self-rooting clones. PMID:27555864

  19. Structure analysis of the protein transduction domain of human Period1 and its mutant analogs.

    PubMed

    Yang, Xiao Lin; Xie, Jun; Niu, Bo; Hu, Xiao Nian; Gao, Yang; Xiang, Qian; Zhang, Yue Hong; Guo, Yong; Zhang, Zheng Guo

    2005-04-01

    Human Period1 (hPer1) has been proved to be able to translocate into cells in a protein transduction manner. The segment of amino acids 830-845 of hPer1 is its protein transduction domain (PTD). In order to explore the membrane penetrating mechanism of hPer1-PTD and the physico-chemical properties necessary in the process, Ala scanning mutation method was used to investigate the variation in the peptide internalization. To further investigate the related physico-chemical requirements, the three dimensional structures of hPer1-PTD and its mutant analogs were simulated by Rosetta method. The electrostatic potentials and energies of these structures were calculated using the Delphi algorithm to solve Poisson-Boltzman equation. The hydrophobicity was assessed by the percentage of the nonpolar area in SAS (solvent accessible surface (SAS)). It has been proved that the Arg836 was the key residue for peptide internalization. When this Arg mutated into Ala, the peptide could not cross the membrane. The large enough area with positive charge was the decisive factor for hPer1-PTD. The alpha-helical structure seemed to play an assistant role so as to enable the positive charge connected in spatial arrangement. PMID:15781181

  20. Amyloid beta-peptide disrupts carbachol-induced muscarinic cholinergic signal transduction in cortical neurons.

    PubMed Central

    Kelly, J F; Furukawa, K; Barger, S W; Rengen, M R; Mark, R J; Blanc, E M; Roth, G S; Mattson, M P

    1996-01-01

    Cholinergic pathways serve important functions in learning and memory processes, and deficits in cholinergic transmission occur in Alzheimer disease (AD). A subset of muscarinic cholinergic receptors are linked to G-proteins that activate phospholipase C, resulting in the liberation of inositol trisphosphate and Ca2+ release from intracellular stores. We now report that amyloid beta-peptide (Abeta), which forms plaques in the brain in AD, impairs muscarinic receptor activation of G proteins in cultured rat cortical neurons. Exposure of rodent fetal cortical neurons to Abeta25-35 and Abeta1-40 resulted in a concentration and time-dependent attenuation of carbachol-induced GTPase activity without affecting muscarinic receptor ligand binding parameters. Downstream events in the signal transduction cascade were similarly attenuated by Abeta. Carbachol-induced accumulation of inositol phosphates (IP, IP2, IP3, and IP4) was decreased and calcium imaging studies revealed that carbachol-induced release of calcium was severely impaired in neurons pretreated with Abeta. Muscarinic cholinergic signal transduction was disrupted with subtoxic levels of exposure to AP. The effects of Abeta on carbachol-induced GTPase activity and calcium release were attenuated by antioxidants, implicating free radicals in the mechanism whereby Abeta induced uncoupling of muscarinic receptors. These data demonstrate that Abeta disrupts muscarinic receptor coupling to G proteins that mediate induction of phosphoinositide accumulation and calcium release, findings that implicate Abeta in the impairment of cholinergic transmission that occurs in AD. PMID:8692890

  1. Extracellular vesicles including exosomes are mediators of signal transduction: Are they protective or pathogenic?

    PubMed Central

    Gangoda, Lahiru; Boukouris, Stephanie; Liem, Michael; Kalra, Hina; Mathivanan, Suresh

    2015-01-01

    Extracellular vesicles are signaling organelles that are released by many cell types and is highly conserved in both prokaryotes and eukaryotes. Based on the mechanism of biogenesis, these membranous vesicles can be classified as exosomes, shedding microvesicles and apoptotic blebs. It is becoming clearer that these extracellular vesicles mediate signal transduction in both autocrine and paracrine fashion by the transfer of proteins and RNA. Whilst the role of extracellular vesicles including exosomes in pathogenesis is well established, very little is known about their function in normal physiological conditions. Recent evidences allude that extracellular vesicles can mediate both protective and pathogenic effects depending on the precise state. In this review, we discuss the involvement of extracellular vesicle as mediators of signal transduction in neurodegenerative diseases and cancer. In addition, the role of extracellular vesicles in mediating Wnt and PI3K signaling pathways is also discussed. Additional findings on the involvement of extracellular vesicles in homeostasis and disease progression will promote a better biological understanding, advance future therapeutic and diagnostic applications. PMID:25307053

  2. Amyloid beta-peptide disrupts carbachol-induced muscarinic cholinergic signal transduction in cortical neurons.

    PubMed

    Kelly, J F; Furukawa, K; Barger, S W; Rengen, M R; Mark, R J; Blanc, E M; Roth, G S; Mattson, M P

    1996-06-25

    Cholinergic pathways serve important functions in learning and memory processes, and deficits in cholinergic transmission occur in Alzheimer disease (AD). A subset of muscarinic cholinergic receptors are linked to G-proteins that activate phospholipase C, resulting in the liberation of inositol trisphosphate and Ca2+ release from intracellular stores. We now report that amyloid beta-peptide (Abeta), which forms plaques in the brain in AD, impairs muscarinic receptor activation of G proteins in cultured rat cortical neurons. Exposure of rodent fetal cortical neurons to Abeta25-35 and Abeta1-40 resulted in a concentration and time-dependent attenuation of carbachol-induced GTPase activity without affecting muscarinic receptor ligand binding parameters. Downstream events in the signal transduction cascade were similarly attenuated by Abeta. Carbachol-induced accumulation of inositol phosphates (IP, IP2, IP3, and IP4) was decreased and calcium imaging studies revealed that carbachol-induced release of calcium was severely impaired in neurons pretreated with Abeta. Muscarinic cholinergic signal transduction was disrupted with subtoxic levels of exposure to AP. The effects of Abeta on carbachol-induced GTPase activity and calcium release were attenuated by antioxidants, implicating free radicals in the mechanism whereby Abeta induced uncoupling of muscarinic receptors. These data demonstrate that Abeta disrupts muscarinic receptor coupling to G proteins that mediate induction of phosphoinositide accumulation and calcium release, findings that implicate Abeta in the impairment of cholinergic transmission that occurs in AD. PMID:8692890

  3. Effects of low-energy electromagnetic fields (pulsed and DC) on membrane signal transduction processes in biological systems

    SciTech Connect

    Luben, R.A. )

    1991-07-01

    The vertebrate organism possesses a number of internal processes for signaling and communication between cell types. Hormones and neurotransmitters move from one cell type to another and carry chemical messages that modulate the metabolic responses of tissues to the environment. Interaction with these signaling systems is a potential mechanism by which very low-energy electromagnetic fields might produce metabolic responses in the body. Hormone and neurotransmitter receptors are specialized protein molecules that use a variety of biochemical activities to pass chemical signals from the outside of a cell across the plasma membrane to the interior of the cell. Since many low-energy electromagnetic fields have too little energy to directly traverse the membrane, it is possible that they may modify the existing signal transduction processes in cell membranes, thus producing both transduction and biochemical amplification of the effects of the field itself. As an example of the kinds of processes that may be involved in these interactions, one metabolic process in which the physiological effects of low-energy electromagnetic fields is well established is the healing of bone fractures. The process of regulation of bone turnover and healing is reviewed in the context of clinical applications of electromagnetic energy to the healing process, especially for persistent nonunion fractures. A hypothetical molecular mechanism is presented that might account for the observed effects of electromagnetic fields on bone cell metabolism in terms of the fields' interference with signal transduction events involved in the hormonal regulation of osteoblast function and differentiation. 88 refs.

  4. A comparative microbiological study to assess caries excavation by conventional rotary method and a chemo-mechanical method

    PubMed Central

    Anegundi, Rajesh T.; Patil, Shruthi B.; Tegginmani, Viresh; Shetty, Sheetal D.

    2012-01-01

    Aims: This study was aimed to determine the effectiveness of Papacárie® for caries removal as compared to the conventional method with respect to microbial flora, time, the amount of tissue removal, child's behavior, pain perception, and preference of treatment. Materials and Methods: Sixty primary molars of 30 children of age 4-9 years were selected randomly and divided into two groups of 30 teeth each: Group A treated by conventional method and group B with Papacárie® method. Results: Comparatively, no statistical difference was seen in microbial growth, total bacterial count, and lactobacilli count in both the groups (P = 0.36). The mean cavity entrance size with group A was 0.98133 mm and group B was 0.26083 mm (P < 0.001). The mean preparation time for group A was 4.7 Mins (minutes) and group B was 17.96 min s (P < 0.001). Majority of kids of both group A and B scored 3 (Frankl Behavior Rating Scale) before and after the treatment showing no statistical difference in their behavioral score (P = 1). In group A 50% of children experienced no pain as compared to 86.7% in group B (P = 0.01). There was no statistical difference in the preference of treatment (P = 0.12). Conclusion: Thus, the Chemo mechanical caries removal method can be considered as an effective method to control pain and preserve sound tooth structure during caries excavation. PMID:23633794

  5. The gravity persistent signal (gps) Mutants of Arabidopsis: Insights into Gravitropic Signal Transduction

    NASA Astrophysics Data System (ADS)

    Wyatt, S.

    The gravitropic response of Arabidopsis stems is rapid with a visible within 30 min and vertical reorientation within 2 h. However, horizontal gravistimulation for 3 h at 4°C does not cause curvature. When the stems are subsequently placed in the vertical position at RT, they bend in response to the previous, horizontal gravistimulation. These results indicate that the gravity perception step can occur at 4°C, but that part of the response is sensitive to cold. At 4°C, starch-containing amyloplasts in the endodermis of the inflorescence stems sedimented normally but auxin transport was abolished indicating that the cold treatment affected early events of the signal transduction pathway that occur after amyloplast sedimentation but prior to auxin transport. The gps mutants of Arabidopsis are a unique group of mutants that respond abnormally after gravistimulation at 4°C. gps1 shows no response to the cold gravistimulation, gps2 bends the wrong way as compared to wild type and gps3 over responds, bending past the anticipated curvature. The mutants were selected from a T-DNA tagged population. Cloning strategies based on the tag have been employed to identify the genes disrupted. GPS1 was cloned using TAIL PCR and is At3g20130, a cytochrome P450, CYP705A22, of unknown function. GPS1p::GFP fusions are being used to determine temporal and spatial expression of GPS1. The mutation in gps3 appears to disrupt a non-coding region downstream of At1g43950 No function has yet been determined for this region, but it appears that the mutation disrupts transcription of a transcription factor homologous to the DNA binding domain of an auxin response factor (ARF) 9-like protein. The identity of GPS2 is as yet unknown. The gps mutants represent potentially three independent aspects of signal transduction in the gravitropic response: perception or retention of the gravity signal (gps1), determination of the polarity of the response (gps2), and the tissue specificity of the

  6. Elucidating the Functional Roles of Spatial Organization in Cross-Membrane Signal Transduction by a Hybrid Simulation Method.

    PubMed

    Chen, Jiawen; Xie, Zhong-Ru; Wu, Yinghao

    2016-07-01

    The ligand-binding of membrane receptors on cell surfaces initiates the dynamic process of cross-membrane signal transduction. It is an indispensable part of the signaling network for cells to communicate with external environments. Recent experiments revealed that molecular components in signal transduction are not randomly mixed, but spatially organized into distinctive patterns. These patterns, such as receptor clustering and ligand oligomerization, lead to very different gene expression profiles. However, little is understood about the molecular mechanisms and functional impacts of this spatial-temporal regulation in cross-membrane signal transduction. In order to tackle this problem, we developed a hybrid computational method that decomposes a model of signaling network into two simulation modules. The physical process of binding between receptors and ligands on cell surfaces are simulated by a diffusion-reaction algorithm, while the downstream biochemical reactions are modeled by stochastic simulation of Gillespie algorithm. These two processes are coupled together by a synchronization framework. Using this method, we tested the dynamics of a simple signaling network in which the ligand binding of cell surface receptors triggers the phosphorylation of protein kinases, and in turn regulates the expression of target genes. We found that spatial aggregation of membrane receptors at cellular interfaces is able to either amplify or inhibit downstream signaling outputs, depending on the details of clustering mechanism. Moreover, by providing higher binding avidity, the co-localization of ligands into multi-valence complex modulates signaling in very different ways that are closely related to the binding affinity between ligand and receptor. We also found that the temporal oscillation of the signaling pathway that is derived from genetic feedback loops can be modified by the spatial clustering of membrane receptors. In summary, our method demonstrates the functional

  7. Hoxb4 transduction down-regulates Geminin protein, providing hematopoietic stem and progenitor cells with proliferation potential

    PubMed Central

    Ohno, Yoshinori; Yasunaga, Shin'ichiro; Ohtsubo, Motoaki; Mori, Sayaka; Tsumura, Miyuki; Okada, Satoshi; Ohta, Tomohiko; Ohtani, Kiyoshi; Kobayashi, Masao; Takihara, Yoshihiro

    2010-01-01

    Retrovirus-mediated transduction of Hoxb4 enhances hematopoietic stem cell (HSC) activity and enforced expression of Hoxb4 induces in vitro development of HSCs from differentiating mouse embryonic stem cells, but the underlying molecular mechanism remains unclear. We previously showed that the HSC activity was abrogated by accumulated Geminin, an inhibitor for the DNA replication licensing factor Cdt1 in mice deficient in Rae28 (also known as Phc1), which encodes a member of Polycomb-group complex 1. In this study we found that Hoxb4 transduction reduced accumulated Geminin in Rae28-deficient mice, despite increasing the mRNA, and restored the impaired HSC activity. Supertransduction of Geminin suppressed the HSC activity induced by Hoxb4 transduction, whereas knockdown of Geminin promoted the clonogenic and replating activities, indicating the importance of Geminin regulation in the molecular mechanism underlying Hoxb4 transduction-mediated enhancement of the HSC activity. This facilitated our investigation of how transduced Hoxb4 reduced Geminin. We showed in vitro and in vivo that Hoxb4 and the Roc1 (also known as Rbx1)-Ddb1-Cul4a ubiquitin ligase core component formed a complex designated as RDCOXB4, which acted as an E3 ubiquitin ligase for Geminin and down-regulated Geminin through the ubiquitin-proteasome system. Down-regulated Geminin and the resultant E2F activation may provide cells with proliferation potential by increasing a DNA prereplicative complex loaded onto chromatin. Here we suggest that transduced Hoxb4 down-regulates Geminin protein probably by constituting the E3 ubiquitin ligase for Geminin to provide hematopoietic stem and progenitor cells with proliferation potential. PMID:21098278

  8. Comparing the effect of open and closed endotracheal suctioning on pain and oxygenation in post CABG patients under mechanical ventilation

    PubMed Central

    Mohammadpour, Ali; Amini, Shahram; Shakeri, Mohammad Taghi; Mirzaei, Sahereh

    2015-01-01

    Background: The aim of this study was to compare changes in pain, oxygenation, and ventilation following endotracheal suctioning with open and closed suctioning systems in post coronary artery bypass grafting (CABG) patients. Materials and Methods: 130 post CABG mechanically ventilated patients were randomly allocated to undergo either open (n = 75) or closed (n = 55) endotracheal suctioning for 15 s. The patients received 100% oxygen for 1 min before and after suctioning. Pain score using critical-care pain objective tool (CPOT) was compared during suctioning between the two groups. Arterial oxygen pressure (PaO2), PaO2 to fraction of inspired oxygen (FiO2) (PF) ratio, and arterial carbon dioxide pressure (PaCO2) were compared at baseline and 5 min after suctioning. Peripheral oxygen saturation (SpO2) was compared at baseline, during suctioning, and at 1 min interval after suctioning for 5 min between the two groups. Results: The patients were the same with regard to CPOT scores, i.e. 3.21 (1.89) and 2.94 (1.56) in the open and closed suctioning systems, respectively. SpO2 did not change significantly between the two groups. Changes in PaO2 and PF ratio was more significant in the open than in the closed system (P = 0.007). Patients in the open group had a higher PaCO2 than those in the closed group, i.e. 40.54 (6.56) versus 38.02 (6.10), and the P value was 0.027. Conclusions: Our study revealed that patients’ pain and SpO2 changes are similar following endotracheal suctioning in both suctioning systems. However, oxygenation and ventilation are better preserved with closed suctioning system. PMID:25878695

  9. Comparative analysis of the mechanisms of sulfur anion oxidation and reduction by dsr operon to maintain environmental sulfur balance.

    PubMed

    Ghosh, Semanti; Bagchi, Angshuman

    2015-12-01

    Sulfur metabolism is one of the oldest known redox geochemical cycles in our atmosphere. These redox processes utilize different sulfur anions and the reactions are performed by the gene products of dsr operon from phylogenetically diverse sets of microorganisms. The operon is involved in the maintenance of environmental sulfur balance. Interestingly, the dsr operon is found to be present in both sulfur anion oxidizing and reducing microorganisms and in both types of organisms DsrAB protein complex plays a vital role. Though there are various reports regarding the genetics of dsr operon there are practically no reports dealing with the structural aspects of sulfur metabolism by dsr operon. In our present study, we tried to compare the mechanisms of sulfur anion oxidation and reduction by Allochromatium vinosum and Desulfovibrio vulgaris respectively through DsrAB protein complex. We analyzed the modes of bindings of sulfur anions to the DsrAB protein complex and observed that for sulfur anion oxidizers, sulfide and thiosulfate are the best substrates whereas for reducers sulfate and sulfite have the best binding abilities. We analyzed the binding interaction pattern of the DsrA and DsrB proteins while forming the DsrAB protein complexes in Desulfovibrio vulgaris and Allochromatium vinosum. To our knowledge this is the first report that analyzes the differences in binding patterns of sulfur substrates with DsrAB protein from these two microorganisms. This study would therefore be essential to predict the biochemical mechanism of sulfur anion oxidation and reduction by these two microorganisms i.e., Desulfovibrio vulgaris (sulfur anion reducer) and Allochromatium vinosum (sulfur anion oxidizer). Our observations also highlight the mechanism of sulfur geochemical cycle which has important implications in future study of sulfur metabolism as it has a huge application in waste remediation and production of industrial bio-products viz. vitamins, bio-polyesters and bio

  10. Understanding abiotic stress tolerance mechanisms in soybean: a comparative evaluation of soybean response to drought and flooding stress.

    PubMed

    Mutava, Raymond N; Prince, Silvas Jebakumar K; Syed, Naeem Hasan; Song, Li; Valliyodan, Babu; Chen, Wei; Nguyen, Henry T

    2015-01-01

    Many sources of drought and flooding tolerance have been identified in soybean, however underlying molecular and physiological mechanisms are poorly understood. Therefore, it is important to illuminate different plant responses to these abiotic stresses and understand the mechanisms that confer tolerance. Towards this goal we used four contrasting soybean (Glycine max) genotypes (PI 567690--drought tolerant, Pana--drought susceptible, PI 408105A--flooding tolerant, S99-2281--flooding susceptible) grown under greenhouse conditions and compared genotypic responses to drought and flooding at the physiological, biochemical, and cellular level. We also quantified these variations and tried to infer their role in drought and flooding tolerance in soybean. Our results revealed that different mechanisms contribute to reduction in net photosynthesis under drought and flooding stress. Under drought stress, ABA and stomatal conductance are responsible for reduced photosynthetic rate; while under flooding stress, accumulation of starch granules played a major role. Drought tolerant genotypes PI 567690 and PI 408105A had higher plastoglobule numbers than the susceptible Pana and S99-2281. Drought stress increased the number and size of plastoglobules in most of the genotypes pointing to a possible role in stress tolerance. Interestingly, there were seven fibrillin proteins localized within the plastoglobules that were up-regulated in the drought and flooding tolerant genotypes PI 567690 and PI 408105A, respectively, but down-regulated in the drought susceptible genotype Pana. These results suggest a potential role of Fibrillin proteins, FBN1a, 1b and 7a in soybean response to drought and flooding stress. PMID:25438143

  11. Comparative effects of dexamethasone and bergenin on chronic bronchitis and their anti-inflammatory mechanisms based on NMR metabolomics.

    PubMed

    Ren, Xiaolei; Ma, Shuangshuang; Wang, Juan; Tian, Simin; Fu, Xiaorui; Liu, Xinfeng; Li, Zhongfeng; Zhao, Baosheng; Wang, Xueyong

    2016-05-24

    In order to compare the effect of dexamethasone and bergenin on chronic bronchitis and to reveal their anti-inflammatory mechanisms, (1)H NMR-based metabolomics was performed to explore the potential biomarkers of the disease and study the therapeutic mechanisms of the drugs. In this study, 40 Sprague-Dawley male rats were randomly divided into 4 groups, namely control, model, dexamethasone and bergenin groups, with 10 rats in each group. Except for the control group, rats from the other three groups were exposed to tobacco smoke for 1 h d(-1) for 28 days. During the modeling, dexamethasone (0.2 mg kg(-1)) and bergenin (87 mg kg(-1)) were administered orally to dexamethasone or bergenin rats 3 h after exposure every day. On the other hand, control and model rats were intragastrically administered water. According to the results of morphometric analysis of the airway epithelium and the count of white blood cells in the bronchoalveolar lavage fluid (BALF), dexamethasone and bergenin could suppress the infiltration of inflammatory cells, inhibit the secretion of mucus, and reduce white blood cells in BALF. Serum samples from the rats' orbits were collected every week. The metabolic profiles of sera were analyzed by multivariate statistical analyses, including PCA, PLS-DA and OPLS-DA models, and 18 metabolites were identified. The dynamic fluctuations of these biomarkers in sera from different groups were detected. The results suggested that the anti-inflammatory mechanism of dexamethasone may be associated with BCAA metabolism and glycolysis while bergenin could change BCAA metabolism, glycine, serine and threonine metabolism, and glycolysis to treat chronic bronchitis. PMID:27098339

  12. A comparative fluid flow characterisation in a low frequency/high power sonoreactor and mechanical stirred vessel.

    PubMed

    Sajjadi, Baharak; Raman, Abdul Aziz Abdul; Ibrahim, Shaliza

    2015-11-01

    This study aims at analysing the jet-like acoustic streaming generated under low-frequency and high-power ultrasound irradiation and comparing it with fluid streaming generated by traditional mechanical mixing. The main characteristics of fluid flow, which include radial, axial and tangential terms of velocity and their effects on fluid flow pattern, pressure distribution, axial mixing time and turbulence intensity were considered at different power inputs. Both 3D CFD simulation and Particle Image Velocimetry (PIV) were used in this study. The CFD results indicated that the jet-like acoustic streaming reached the velocity magnitude of 145 cm/s at 400 W, which reduced the mixing time to 1.38 s. However, the minimum mixing time of 3.18 s corresponding to the impeller rotational speed of 800 RPM was observed for mechanical stirring. A uniform axial flow pattern was generated under ultrasound irradiation whereas the tangential flow pattern was more prominent in the stirred vessel. Besides, the highest turbulence was observed in the vicinity of the ultrasound transducer and impeller with the values of 138% and 82% for the ultrasonicator and stirred vessel, respectively. The predicted fluid flow pattern under ultrasound irradiation was in a reasonable agreement with that obtained from PIV, with a reasonable accuracy. PMID:26186855

  13. Comparative genomic analysis of carbon and nitrogen assimilation mechanisms in three indigenous bioleaching bacteria: predictions and validations

    PubMed Central

    Levicán, Gloria; Ugalde, Juan A; Ehrenfeld, Nicole; Maass, Alejandro; Parada, Pilar

    2008-01-01

    Background Carbon and nitrogen fixation are essential pathways for autotrophic bacteria living in extreme environments. These bacteria can use carbon dioxide directly from the air as their sole carbon source and can use different sources of nitrogen such as ammonia, nitrate, nitrite, or even nitrogen from the air. To have a better understanding of how these processes occur and to determine how we can make them more efficient, a comparative genomic analysis of three bioleaching bacteria isolated from mine sites in Chile was performed. This study demonstrated that there are important differences in the carbon dioxide and nitrogen fixation mechanisms among bioleaching bacteria that coexist in mining environments. Results In this study, we probed that both Acidithiobacillus ferrooxidans and Acidithiobacillus thiooxidans incorporate CO2 via the Calvin-Benson-Bassham cycle; however, the former bacterium has two copies of the Rubisco type I gene whereas the latter has only one copy. In contrast, we demonstrated that Leptospirillum ferriphilum utilizes the reductive tricarboxylic acid cycle for carbon fixation. Although all the species analyzed in our study can incorporate ammonia by an ammonia transporter, we demonstrated that Acidithiobacillus thiooxidans could also assimilate nitrate and nitrite but only Acidithiobacillus ferrooxidans could fix nitrogen directly from the air. Conclusion The current study utilized genomic and molecular evidence to verify carbon and nitrogen fixation mechanisms for three bioleaching bacteria and provided an analysis of the potential regulatory pathways and functional networks that control carbon and nitrogen fixation in these microorganisms. PMID:19055775

  14. Comparing apples and oranges-the influence of food mechanical properties on ingestive bite sizes in lemurs.

    PubMed

    Hartstone-Rose, Adam; Parkinson, Jennifer A; Criste, Taylor; Perry, Jonathan M G

    2015-07-01

    Previously we found that Maximum Ingested Bite Size (Vb )-the largest piece of food that an animal will ingest whole without biting first-scales isometrically with body size in 17 species of strepsirrhines at the Duke Lemur Center (DLC). However, because this earlier study focused on only three food types (two with similar mechanical properties), it did not yield results that were easily applied to describing the broad diets of these taxa. Expressing Vb in terms of food mechanical properties allows us to compare data across food types, including foods of wild lemurs, to better understand dietary adaptations in lemurs. To this end, we quantified Vb in five species of lemurs at the DLC representing large and small frugivores and folivores using ten types of food that vary widely in stiffness and toughness to determine how these properties relate to bite sizes. We found that although most species take smaller bites of stiffer foods, this negative relationship was not statistically significant across the whole sample. However, there is a significant relationship between bite size and toughness. All three of the more frugivorous taxa in our sample take significantly smaller bites of tougher foods. However, the two more folivorous lemurs do not. They take small bites for all foods. This suggests that the species most adapted to the consumption of tough foods do not modulate their ingestive sizes to accommodate larger pieces of weak foods. PMID:25727399

  15. Bioinformatics investigation of therapeutic mechanisms of Xuesaitong capsule treating ischemic cerebrovascular rat model with comparative transcriptome analysis

    PubMed Central

    Liao, Jiangquan; Wei, Benjun; Chen, Hengwen; Liu, Yongmei; Wang, Jie

    2016-01-01

    Background: Xuesaitong soft capsule (XST) which consists of panax notoginseng saponin (PNS) has been used to treat ischemic cerebrovascular diseases in China. The therapeutic mechanism of XST has not been elucidated yet from prospective of genomics and bioinformatics. Methods: A transcriptome analysis was performed to review series concerning middle cerebral artery occlusion (MCAO) rat model and XST intervention after MCAO from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were compared between blank group and model group, model group and XST group. Functional enrichment and pathway analysis were performed. Protein-Protein interaction network was constructed. The overlapping genes from two DEGs sets were screened out and profound analysis was performed. Results: Two series including 22 samples were obtained. 870 DEGs were identified between blank group and model group, and 1189 DEGs were identified between model group and XST group. GO terms and KEGG pathways of MCAO and XST intervention were significantly enriched. PPI networks were constructed to demonstrate the gene-gene interactions. The overlapping genes from two DEGs sets were highlighted. ANTXR2, FHL3, PRCP, TYROBP, TAF9B, FGFR2, BCL11B, RB1CC1 and MBNL2 were the pivotal genes and possible action sites of XST therapeutic mechanisms. Conclusion: MCAO is a pathological process with multiple. PMID:27347353

  16. Force transduction and lipid binding in MscL: A continuum-molecular approach

    SciTech Connect

    Vanegas, Juan M.; Arroyo, Marino; Fotiadis, Dimitrios

    2014-12-01

    The bacterial mechanosensitive channel MscL, a small protein mainly activated by membrane tension, is a central model system to study the transduction of mechanical stimuli into chemical signals. Mutagenic studies suggest that MscL gating strongly depends on both intra-protein and interfacial lipid-protein interactions. However, there is a gap between this detailed chemical information and current mechanical models of MscL gating. Here, we investigate the MscL bilayer-protein interface through molecular dynamics simulations, and take a combined continuum-molecular approach to connect chemistry and mechanics. We quantify the effect of membrane tension on the forces acting on the surface of the channel, and identify interactions that may be critical in the force transduction between the membrane and MscL. We find that the local stress distribution on the protein surface is largely asymmetric, particularly under tension, with the cytoplasmic side showing significantly larger and more localized forces, which pull the protein radially outward. The molecular interactions that mediate this behavior arise from hydrogen bonds between the electronegative oxygens in the lipid headgroup and a cluster of positively charged lysine residues on the amphipathic S1 domain and the C-terminal end of the second trans-membrane helix. We take advantage of this strong interaction (estimated to be 10–13 kT per lipid) to actuate the channel (by applying forces on protein-bound lipids) and explore its sensitivity to the pulling magnitude and direction. We conclude by highlighting the simple motif that confers MscL with strong anchoring to the bilayer, and its presence in various integral membrane proteins including the human mechanosensitive channel K2P1 and bovine rhodopsin.

  17. Force transduction and lipid binding in MscL: A continuum-molecular approach

    DOE PAGESBeta

    Vanegas, Juan M.; Arroyo, Marino; Fotiadis, Dimitrios

    2014-12-01

    The bacterial mechanosensitive channel MscL, a small protein mainly activated by membrane tension, is a central model system to study the transduction of mechanical stimuli into chemical signals. Mutagenic studies suggest that MscL gating strongly depends on both intra-protein and interfacial lipid-protein interactions. However, there is a gap between this detailed chemical information and current mechanical models of MscL gating. Here, we investigate the MscL bilayer-protein interface through molecular dynamics simulations, and take a combined continuum-molecular approach to connect chemistry and mechanics. We quantify the effect of membrane tension on the forces acting on the surface of the channel, andmore » identify interactions that may be critical in the force transduction between the membrane and MscL. We find that the local stress distribution on the protein surface is largely asymmetric, particularly under tension, with the cytoplasmic side showing significantly larger and more localized forces, which pull the protein radially outward. The molecular interactions that mediate this behavior arise from hydrogen bonds between the electronegative oxygens in the lipid headgroup and a cluster of positively charged lysine residues on the amphipathic S1 domain and the C-terminal end of the second trans-membrane helix. We take advantage of this strong interaction (estimated to be 10–13 kT per lipid) to actuate the channel (by applying forces on protein-bound lipids) and explore its sensitivity to the pulling magnitude and direction. We conclude by highlighting the simple motif that confers MscL with strong anchoring to the bilayer, and its presence in various integral membrane proteins including the human mechanosensitive channel K2P1 and bovine rhodopsin.« less

  18. Force transduction and lipid binding in MscL: a continuum-molecular approach.

    PubMed

    Vanegas, Juan M; Arroyo, Marino

    2014-01-01

    The bacterial mechanosensitive channel MscL, a small protein mainly activated by membrane tension, is a central model system to study the transduction of mechanical stimuli into chemical signals. Mutagenic studies suggest that MscL gating strongly depends on both intra-protein and interfacial lipid-protein interactions. However, there is a gap between this detailed chemical information and current mechanical models of MscL gating. Here, we investigate the MscL bilayer-protein interface through molecular dynamics simulations, and take a combined continuum-molecular approach to connect chemistry and mechanics. We quantify the effect of membrane tension on the forces acting on the surface of the channel, and identify interactions that may be critical in the force transduction between the membrane and MscL. We find that the local stress distribution on the protein surface is largely asymmetric, particularly under tension, with the cytoplasmic side showing significantly larger and more localized forces, which pull the protein radially outward. The molecular interactions that mediate this behavior arise from hydrogen bonds between the electronegative oxygens in the lipid headgroup and a cluster of positively charged lysine residues on the amphipathic S1 domain and the C-terminal end of the second trans-membrane helix. We take advantage of this strong interaction (estimated to be 10-13 kT per lipid) to actuate the channel (by applying forces on protein-bound lipids) and explore its sensitivity to the pulling magnitude and direction. We conclude by highlighting the simple motif that confers MscL with strong anchoring to the bilayer, and its presence in various integral membrane proteins including the human mechanosensitive channel K2P1 and bovine rhodopsin. PMID:25437007

  19. Force Transduction and Lipid Binding in MscL: A Continuum-Molecular Approach

    PubMed Central

    Vanegas, Juan M.; Arroyo, Marino

    2014-01-01

    The bacterial mechanosensitive channel MscL, a small protein mainly activated by membrane tension, is a central model system to study the transduction of mechanical stimuli into chemical signals. Mutagenic studies suggest that MscL gating strongly depends on both intra-protein and interfacial lipid-protein interactions. However, there is a gap between this detailed chemical information and current mechanical models of MscL gating. Here, we investigate the MscL bilayer-protein interface through molecular dynamics simulations, and take a combined continuum-molecular approach to connect chemistry and mechanics. We quantify the effect of membrane tension on the forces acting on the surface of the channel, and identify interactions that may be critical in the force transduction between the membrane and MscL. We find that the local stress distribution on the protein surface is largely asymmetric, particularly under tension, with the cytoplasmic side showing significantly larger and more localized forces, which pull the protein radially outward. The molecular interactions that mediate this behavior arise from hydrogen bonds between the electronegative oxygens in the lipid headgroup and a cluster of positively charged lysine residues on the amphipathic S1 domain and the C-terminal end of the second trans-membrane helix. We take advantage of this strong interaction (estimated to be 10–13 kT per lipid) to actuate the channel (by applying forces on protein-bound lipids) and explore its sensitivity to the pulling magnitude and direction. We conclude by highlighting the simple motif that confers MscL with strong anchoring to the bilayer, and its presence in various integral membrane proteins including the human mechanosensitive channel K2P1 and bovine rhodopsin. PMID:25437007

  20. A low-rank approximation-based transductive support tensor machine for semisupervised classification.

    PubMed

    Liu, Xiaolan; Guo, Tengjiao; He, Lifang; Yang, Xiaowei

    2015-06-01

    In the fields of machine learning, pattern recognition, image processing, and computer vision, the data are usually represented by the tensors. For the semisupervised tensor classification, the existing transductive support tensor machine (TSTM) needs to resort to iterative technique, which is very time-consuming. In order to overcome this shortcoming, in this paper, we extend the concave-convex procedure-based transductive support vector machine (CCCP-TSVM) to the tensor patterns and propose a low-rank approximation-based TSTM, in which the tensor rank-one decomposition is used to compute the inner product of the tensors. Theoretically, concave-convex procedure-based TSTM (CCCP-TSTM) is an extension of the linear CCCP-TSVM to tensor patterns. When the input patterns are vectors, CCCP-TSTM degenerates into the linear CCCP-TSVM. A set of experiments is conducted on 23 semisupervised classification tasks, which are generated from seven second-order face data sets, three third-order gait data sets, and two third-order image data sets, to illustrate the performance of the CCCP-TSTM. The results show that compared with CCCP-TSVM and TSTM, CCCP-TSTM provides significant performance gain in terms of test accuracy and training speed. PMID:25700447

  1. Identification of specific gravity sensitive signal transduction pathways in human A431 carcinoma cells

    NASA Astrophysics Data System (ADS)

    Rijken, P. J.; de Groot, R. P.; Kruijer, W.; de Laat, S. W.; Verkleij, A. J.; Boonstra, J.

    Epidermal growth factor (EGF) activates a well characterized signal transduction cascade in human A431 epidermoid carcinoma cells. The influence of gravity on EGF-induced EGF-receptor clustering and early gene expression as well as on actin polymerization and actin organization have been investigated. Different signalling pathways induced by the agents TPA, forskolin and A23187 that activate gene expression were tested for sensitivity to gravity. EGF-induced c-fos and c-jun expression were decreased in microgravity. However, constitutive β-2 microglobulin expression remained unaltered. Under simulated weightlessness conditions EGF- and TPA-induced c-fos expression was decreased, while forskolin- and A23187-induced c-fos expression was independent of the gravity conditions. These results suggest that gravity affects specific signalling pathways. Preliminary results indicate that EGF-induced EGF-receptor clustering remained unaltered irrespective of the gravity conditions. Furthermore, the relative filamentous actin content of steady state A431 cells was enhanced under microgravity conditions and actin filament organization was altered. Under simulated weightlessness actin filament organization in steady state cells as well as in EGF-treated cells was altered as compared to the 1 G reference experiment. Interestingly the microtubule and keratin organization in untreated cells showed no difference with the normal gravity samples. This indicates that gravity may affect specific components of the signal transduction circuitry.

  2. Overexpression of PGC-1α Influences Mitochondrial Signal Transduction of Dopaminergic Neurons.

    PubMed

    Ye, Qinyong; Huang, Wanling; Li, Dongzhu; Si, Erwang; Wang, Juhua; Wang, Yingqing; Chen, Chun; Chen, Xiaochun

    2016-08-01

    Parkinson's disease (PD) is a common neurodegenerative disease in the elderly. Mitochondrial dysfunction plays an important role in the pathogenesis of PD. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a powerful transcription factor, interacting with multiple transcription factors and widely involving in the regulation of mitochondrial biogenesis, oxidative stress, and other processes. The present study investigated the neuroprotective effects and signal transduction mechanisms of the overexpression of PGC-1α on N-methyl-4-phenylpyridinium ion (MPP(+))-induced mitochondrial damage in SH-SY5Y cell, establishing the cell model of overexpression of PGC-1α and the cell model of PD by using adenoviral vectors and MPP(+). 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide thiazolyl blue (MTT) assay was used to investigate the effects of MPP(+) and adenovirus on the cell viability of SH-SY5Y cells and the cell viability of experimental groups. Western blot and real-time PCR analysis were used to detect the expression of PGC-1α. Flow cytometry and ELISA were used to detect mitochondrial membrane potential and the level of cytochrome C, respectively. The level of intracellular ATP and H2O2 was measured by multifunctional fluorescence microplate. Western blot analysis and real-time PCR were used to observe the expression of estrogen-related receptor α (ERRα), peroxisome proliferator-activated receptor γ (PPARγ), nuclear respiratory factor (NRF)-1, and NRF-2. Confocal fluorescence analysis was used to observe subcellular localization of PGC-1α in SH-SY5Y cells under the intervention of MPP(+). The expression of PGC-1α messenger RNA and protein significantly increased in Adv-PGC-1α + GFP groups, compared with the control and Adv-GFP groups (P < 0.01). The overexpression of PGC-1α could increase mitochondrial membrane potential, reduce the release of mitochondrial cytochrome C, inhibit H2O2 production, and improve the

  3. Fanconi Anemia: A Signal Transduction and DNA Repair Pathway

    PubMed Central

    Kupfer, Gary M.

    2013-01-01

    Fanconi anemia (FA) is a fascinating, rare genetic disorder marked by congenital defects, bone marrow failure, and cancer susceptibility. Research in recent years has led to the elucidation of FA as a DNA repair disorder and involved multiple pathways as well as having wide applicability to common cancers, including breast, ovarian, and head and neck. This review will describe the clinical aspects of FA as well as the current state of its molecular pathophysiology. In particular, work from the Kupfer laboratory will be described that demonstrates how the FA pathway interacts with multiple DNA repair pathways, including the mismatch repair system and signal transduction pathway of the DNA damage response. PMID:24348213

  4. Deciphering Parameter Sensitivity in the BvgAS Signal Transduction

    PubMed Central

    Mapder, Tarunendu; Talukder, Srijeeta; Chattopadhyay, Sudip; Banik, Suman K.

    2016-01-01

    To understand the switching of different phenotypic phases of Bordetella pertussis, we propose an optimized mathematical framework for signal transduction through BvgAS two-component system. The response of the network output to the sensory input has been demonstrated in steady state. An analysis in terms of local sensitivity amplification characterizes the nature of the molecular switch. The sensitivity analysis of the model parameters within the framework of various correlation coefficients helps to decipher the contribution of the modular structure in signal propagation. Once classified, the model parameters are tuned to generate the behavior of some novel strains using simulated annealing, a stochastic optimization technique. PMID:26812153

  5. Signal transduction by the Wnt family of ligands.

    PubMed Central

    Dale, T C

    1998-01-01

    The Wnt genes encode a large family of secreted polypeptides that mediate cell-cell communication in diverse developmental processes. The loss or inappropriate activation of Wnt expression has been shown to alter cell fate, morphogenesis and mitogenesis. Recent progress has identified Wnt receptors and components of an intracellular signalling pathway that mediate Wnt-dependent transcription. This review will highlight this 'core' Wnt signal-transduction pathway, but also aims to reveal the potential diversity of Wnt signalling targets. Particular attention will be paid to the overlap between developmental biology and oncogenesis, since recent progress shows Wnt signalling forms a paradigm for an interdisciplinary approach. PMID:9425102

  6. Characterization of electrochemically deposited polypyrrole using magnetoelastic material transduction elements

    NASA Technical Reports Server (NTRS)

    Ersoz, Arzu; Ball, J. Christopher; Grimes, Craig A.; Bachas, Leonidas G.

    2002-01-01

    Magnetoelastic alloy films have been used as a working electrode in an electrochemical cell. This material allows magnetic interrogation of electrochemical deposition. This technique was used to monitor the electrochemical deposition of polypyrrole by multisweep (CV) and potentiostatic methods. Since the determination of the mass-sensitive magnetoelastic film's resonance frequency is based on magnetic transduction, an inherent advantage of this method is that it requires no electrical connections other than the working lead of the potentiostat. Increases in pyrrole deposition correlated with a decrease in the peak resonance frequency of the magnetoelastic alloy. This technique provides a novel approach by which one can monitor electrochemical processes.

  7. Suction among pickers: jaw mechanics, dietary breadth and feeding behaviour in beach-spawning Leuresthes spp. compared with their relatives.

    PubMed

    Higgins, B A; Horn, M H

    2014-06-01

    Jaw mechanics and dietary breadth in California grunion Leuresthes tenuis and Gulf grunion Leuresthes sardina were compared with three other members of the tribe Atherinopsini to test whether these two species have evolved a novel jaw protrusion that might be associated with feeding narrowly on abundant prey near spawning beaches. Quantitative comparison of cleared-and-stained specimens of five members of the atherinopsine clade showed that, compared with false grunion Colpichthys regis, topsmelt Atherinops affinis and jacksmelt Atherinopsis californiensis, L. tenuis and L. sardina have longer, more downwardly directed premaxillary protrusion, expanded dentary and premaxillary bones, greater lower jaw rotation and larger premaxilla-vomer separation. Leuresthes tenuis showed greater differences than L. sardina in these features. Comparison of the gut contents of L. tenuis and A. affinis with zooplankton samples collected simultaneously with these fishes in the water column within 1 km of shore showed that, as predicted, L. tenuis fed predominantly on mysid crustaceans and had a narrower diet than A. affinis. High-speed video analysis showed that L. tenuis exhibits a mean time to maximum jaw protrusion c. 2.5 times shorter than that of A. affinis. The grunion sister species, especially L. tenuis, have evolved suction feeding that may allow efficient feeding on common, evasive prey near spawning sites. The morphological traits seen in both species of Leuresthes signify a marked difference from their closest relatives in prey capture and suggest a type of jaw protrusion not yet seen in cyprinodontiforms or perciforms. PMID:24787078

  8. Rotaxanes and Photovoltaic Materials Based on Pi-Conjugated Donors and Acceptors: Toward Energy Transduction on the Nanoscale

    NASA Astrophysics Data System (ADS)

    Bruns, Carson J.

    The flow of energy between its various forms is central to our understanding of virtually all natural phenomena, from the origins and fate of the universe to the mechanisms that underpin Life. Therefore, a deeper fundamental understanding of how to manage energy processes at the molecular scale will open new doors in science and technology. This dissertation describes organic molecules and materials that are capable of transducing various forms of energy on the nanoscale, namely, a class of mechanically interlocked molecules known as rotaxanes for electrochemical-to-mechanical energy transduction (Part I), and a class of thin films known as organic photovoltaics (OPVs) for solar-to-electric energy transduction (Part II). These materials are all based on conjugated molecules with a capacity to donate or accept pi-electrons. A contemporary challenge in molecular nanotechnology is the development of artificial molecular machines (AMMs) that mimic the ability of motor proteins (e.g. myosin, kinesin) to perform mechanical work by leveraging a combination of energy sources and rich structural chemistry. Part I describes the synthesis, characterization, molecular dynamics, and switching properties of a series of `daisy chain' and oligorotaxane AMM prototypes. All compounds are templated by charge transfer and hydrogen bonding interactions between pi-associated 1,5-dioxynaphthlene donors appended with polyether groups and pi-acceptors of either neutral (naphthalenediimide) or charged (4,4´-bipyridinium) varieties, and are synthesized using efficient one-pot copper(I)-catalyzed azide-alkyne cycloaddition `click chemistry' protocols. The interlocked architectures of these rotaxanes enable them to express sophisticated secondary structures (i.e. foldamers) and mechanical motions in solution, which have been elucidated using dynamic 1H NMR spectroscopy. Furthermore, molecular dynamics simulations, cyclic voltammetry, and spectroelectrochemistry experiments have demonstrated

  9. Neuro-glial and systemic mechanisms of pathological responses in rat models of primary blast overpressure compared to "composite" blast.

    PubMed

    Svetlov, Stanislav I; Prima, Victor; Glushakova, Olena; Svetlov, Artem; Kirk, Daniel R; Gutierrez, Hector; Serebruany, Victor L; Curley, Kenneth C; Wang, Kevin K W; Hayes, Ronald L

    2012-01-01

    A number of experimental models of blast brain injury have been implemented in rodents and larger animals. However, the variety of blast sources and the complexity of blast wave biophysics have made data on injury mechanisms and biomarkers difficult to analyze and compare. Recently, we showed the importance of rat position toward blast generated by an external shock tube. In this study, we further characterized blast producing moderate traumatic brain injury and defined "composite" blast and primary blast exposure set-ups. Schlieren optics visualized interaction between the head and a shock wave generated by external shock tube, revealing strong head acceleration upon positioning the rat on-axis with the shock tube (composite blast), but negligible skull movement upon peak overpressure exposure off-axis (primary blast). Brain injury signatures of a primary blast hitting the frontal head were assessed and compared to damage produced by composite blast. Low to negligible levels of neurodegeneration were found following primary blast compared to composite blast by silver staining. However, persistent gliosis in hippocampus and accumulation of GFAP/CNPase in circulation was detected after both primary and composite blast. Also, markers of vascular/endothelial inflammation integrin alpha/beta, soluble intercellular adhesion molecule-1, and L-selectin along with neurotrophic factor nerve growth factor-beta were increased in serum within 6 h post-blasts and persisted for 7 days thereafter. In contrast, systemic IL-1, IL-10, fractalkine, neuroendocrine peptide Orexin A, and VEGF receptor Neuropilin-2 (NRP-2) were raised predominantly after primary blast exposure. In conclusion, biomarkers of major pathological pathways were elevated at all blast set-ups. The most significant and persistent changes in neuro-glial markers were found after composite blast, while primary blast instigated prominent systemic cytokine/chemokine, Orexin A, and Neuropilin-2 release

  10. Chemical Modification with High Molecular Weight Polyethylene Glycol Reduces Transduction of Hepatocytes and Increases Efficacy of Intravenously Delivered Oncolytic Adenovirus

    PubMed Central

    Doronin, Konstantin; Shashkova, Elena V.; May, Shannon M.; Hofherr, Sean E.

    2009-01-01

    Abstract Oncolytic adenoviruses are anticancer agents that replicate within tumors and spread to uninfected tumor cells, amplifying the anticancer effect of initial transduction. We tested whether coating the viral particle with polyethylene glycol (PEG) could reduce transduction of hepatocytes and hepatotoxicity after systemic (intravenous) administration of oncolytic adenovirus serotype 5 (Ad5). Conjugating Ad5 with high molecular weight 20-kDa PEG but not with 5-kDa PEG reduced hepatocyte transduction and hepatotoxicity after intravenous injection. PEGylation with 20-kDa PEG was as efficient at detargeting adenovirus from Kupffer cells and hepatocytes as virus predosing and warfarin. Bioluminescence imaging of virus distribution in two xenograft tumor models in nude mice demonstrated that PEGylation with 20-kDa PEG reduced liver infection 19- to 90-fold. Tumor transduction levels were similar for vectors PEGylated with 20-kDa PEG and unPEGylated vectors. Anticancer efficacy after a single intravenous injection was retained at the level of unmodified vector in large established prostate carcinoma xenografts, resulting in complete elimination of tumors in all animals and long-term tumor-free survival. Anticancer efficacy after a single intravenous injection was increased in large established hepatocellular carcinoma xenografts, resulting in significant prolongation of survival as compared with unmodified vector. The increase in efficacy was comparable to that obtained with predosing and warfarin pretreatment, significantly extending the median of survival. Shielding adenovirus with 20-kDa PEG may be a useful approach to improve the therapeutic window of oncolytic adenovirus after systemic delivery to primary and metastatic tumor sites. PMID:19469693

  11. Signal transduction in human pancreatic cancer: roles of transforming growth factor beta, somatostatin receptors, and other signal intermediates.

    PubMed

    Li, Min; Becnel, Lauren S; Li, Wei; Fisher, William E; Chen, Changyi; Yao, Qizhi

    2005-01-01

    Pancreatic cancer is a devastating disease because of the lack of early detection markers and effective treatments. It is the fourth leading cause of cancer-related death in western countries, including the United States. The mechanisms of pancreatic cancer progression remain unknown. Transforming growth factor beta (TGF-beta), a multifunctional cytokine, regulates cell growth and differentiation in healthy tissues, yet fails to do so in pancreatic cancer. Alterations of the TGF-beta and TGF-beta receptor/Smad signal transduction pathway have been implicated in pancreatic cancer. Furthermore, both the TGF-beta receptor and Smad proteins interact with a variety of cellular signal pathways, such as the somatostatin receptors (SSTRs), ERK1/2, and Wnt signal transduction cascades. This suggests that pancreatic cancer is a multi-gene-controlled malignancy and that effective treatments for pancreatic cancer should be aimed at multiple targets. In this review, we summarized the major signal intermediates involved in pancreatic cancer signal transduction pathways and specifically discussed how alterations in the regulatory functions of TGF-beta and Smad proteins allow for pancreatic carcinogenesis. PMID:16314822

  12. Heat-shock Treatment-mediated Increase in Transduction by Recombinant Adeno-associated Virus 2 Vectors Is Independent of the Cellular Heat-shock Protein 90*

    PubMed Central

    Zhong, Li; Qing, Keyun; Si, Yue; Chen, Linyuan; Tan, Mengqun; Srivastava, Arun

    2007-01-01

    Recombinant adeno-associated virus 2 (AAV) vectors transduction efficiency varies greatly in different cell types. We have described that a cellular protein, FKBP52, in its phosphorylated form interacts with the D-sequence in the viral inverted terminal repeat, inhibits viral second strand DNA synthesis, and limits transgene expression. Here we investigated the role of cellular heat-shock protein 90 (HSP90) in AAV transduction because FKBP52 forms a complex with HSP90, and because heat-shock treatment augments AAV transduction efficiency. Heat-shock treatment of HeLa cells resulted in tyrosine dephosphorylation of FKBP52, led to stabilization of the FKBP52-HSP90 complex, and resulted in ∼6-fold increase in AAV transduction. However, when HeLa cells were pre-treated with tyrphostin 23, a specific inhibitor of cellular epidermal growth factor receptor tyrosine kinase, which phosphorylates FKBP52 at tyrosine residues, heat-shock treatment resulted in a further 18-fold increase in AAV transduction. HSP90 was shown to be a part of the FKBP52-AAV D-sequence complex, but HSP90 by itself did not bind to the D-sequence. Geldanamycin treatment, which disrupts the HSP90-FKBP52 complex, resulted in >22-fold increase in AAV transduction in heat-shock-treated cells compared with heat shock alone. Deliberate overexpression of the human HSP90 gene resulted in a significant decrease in AAV-mediated transduction in tyrphostin 23-treated cells, whereas down-modulation of HSP90 levels led to a decrease in HSP90-FKBP52-AAV D-sequence complex formation, resulting in a significant increase in AAV transduction following pre-treatment with tyrphostin 23. These studies suggest that the observed increase in AAV transduction efficiency following heat-shock treatment is unlikely to be mediated by HSP90 alone and that increased levels of HSP90, in the absence of heat shock, facilitate binding of FKBP52 to the AAV D-sequence, thereby leading to inhibition of AAV-mediated transgene expression

  13. Nanomechanical transduction of molecular interactions on microcantilevers for biochemical detection and diagnostics

    NASA Astrophysics Data System (ADS)

    Tark, Soo-Hyun

    There is a strong demand for a reliable detection platform that can provide the benefits of enhanced sensitivity and selectivity with greater simplicity and cost-effectiveness. The new generations of biosensors also require microfabricated platforms with integrated biologically sensitive components for specific and quantitative detection of analytes in a miniaturized format as well as capabilities for label-free detection and massive parallelization. It has been unambiguously demonstrated that the molecular binding-induced surface stress can be used to monitor specific biochemical binding events and kinetics in real-time with high sensitivity, representing the promising potential for nanomechanical sensors. The fundamental validation of the receptor immobilization and target binding as well as the transduction and quantitative detection of such molecular recognition events taking place on microcantilevers are demonstrated utilizing the optical approach for monitoring the cantilever deflection. The label-free detection of cholera toxin using microcantilevers functionalized with ganglioside-Nanodiscs is demonstrated as a new strategy for immobilizing receptors on microcantilevers. The microcantilever-based sensors, however, require a new paradigm for signal transduction and detection beyond the optical method that supports the unique multiplexing capability by operating a large array of cantilevers with means for simple and accurate readout. Hence, a new electrical readout mechanism comprising a microcantilever array with MOSFETs embedded in the high stress region of the microcantilevers is developed, which provides label- and optics-free signal transduction mechanism. In this work, significant strides have been made towards the MOSFET-microcantilever detection approach. The process and device simulations for embedded-MOSFETs are performed to optimize process parameters and establish guidelines for device design and fabrication. Various designs of MOSFET

  14. Efficient magnetic torque transduction in biological environments using tunable nanomechanical resonators.

    PubMed

    Javaheri, Hooman; Barbiellini, Bernardo; Noubir, Guevara

    2011-01-01

    Electromagnetic interactions with biological systems promise new possibilities in medical applications and synthetic biology. Creating a controlled action in biological systems requires an efficient transduction of the electromagnetic energy to thermal or mechanical biosignals. In this paper, we present the design and optimization for a nano-scale magnetic torque transducer based on a tunable nanomechanical resonator. Operating in the resonance regime allows the presented system to efficiently absorb a large amount of energy from the source. In addition, systems tuned on well separated resonance frequencies may operate simultaneously without any interference. We describe the theoretical model of the system and show the possibility of achieving the resonance in biological settings for a system with reasonable dimensions. PMID:22254693

  15. Cyclopean gauge factor of the strain-resistance transduction of indium oxide films

    NASA Astrophysics Data System (ADS)

    Ivančo, J.; Halahovets, Y.; Végsö, K.; Klačková, I.; Kotlár, M.; Vojtko, A.; Micuśík, M.; Jergel, M.; Majková, E.

    2016-03-01

    The resistance of indium-oxide covered polyethylene terephthalate foils (IO-PET) shows an extreme sensitivity to tensile strain. In terms of the deformation-resistance transduction, the gauge factor as high as about 60 000 was recorded upon the relative elongation up to 1%. Except the onset of deformation, the nearly exponential dependence of the resistance on strain suggests that the conductivity of the strained films is governed by tunnelling mechanism; this notion is supported by the formation of scattered cracks in the IO- PET film. The cracks are oriented perpendicularly to the strain vector and are characterized by a rather similar and uniform width. Appropriateness of the standard definition of the gauge factor for strain sensors, which are governed by tunnelling conductance, is critically discussed.

  16. Structure-Function of CD36 and Importance of Fatty Acid Signal Transduction in Fat Metabolism

    PubMed Central

    Pepino, Marta Yanina; Kuda, Ondrej; Samovski, Dmitri; Abumrad, Nada A

    2015-01-01

    CD36 is a scavenger receptor that functions in high affinity tissue uptake of long chain fatty acids (FA) and contributes under excessive fat supply to lipid accumulation and metabolic dysfunction. This review describes recent evidence regarding the CD36 FA binding site and a potential mechanism for FA transfer. It also presents the view that CD36 and FA signaling coordinate fat utilization based on newly identified CD36 actions that involve oral fat perception, intestinal fat absorption, secretion of the peptides cholecystokinin and secretin, regulation of hepatic lipoprotein output, activation of beta oxidation by muscle and regulation of the production of the FA derived bioactive eicosanoids. Thus abnormalities of fat metabolism and the associated pathology might involve dysfunction of CD36-mediated signal transduction in addition to the changes of FA uptake. PMID:24850384

  17. Signal Transduction: From the Atomic Age to the Post-Genomic Era

    PubMed Central

    Thorner, Jeremy; Hunter, Tony; Cantley, Lewis C.; Sever, Richard

    2016-01-01

    SUMMARY We have come a long way in the 55 years since Edmond Fischer and the late Edwin Krebs discovered that the activity of glycogen phosphorylase is regulated by reversible protein phosphorylation. Many of the fundamental molecular mechanisms that operate in biological signaling have since been characterized and the vast web of interconnected pathways that make up the cellular signaling network has been mapped in considerable detail. Nonetheless, it is important to consider how fast this field is still moving and the issues at the current boundaries of our understanding. One must also appreciate what experimental strategies have allowed us to attain our present level of knowledge. We summarize here some key issues (both conceptual and methodological), raise unresolved questions, discuss potential pitfalls, and highlight areas in which our understanding is still rudimentary. We hope these wide-ranging ruminations will be useful to investigators who carry studies of signal transduction forward during the rest of the 21st century. PMID:25359498

  18. Dissecting single-molecule signal transduction in carbon nanotube circuits with protein engineering

    PubMed Central

    Choi, Yongki; Olsen, Tivoli J.; Sims, Patrick C.; Moody, Issa S.; Corso, Brad L.; Dang, Mytrang N.; Weiss, Gregory A.; Collins, Philip G.

    2013-01-01

    Single molecule experimental methods have provided new insights into biomolecular function, dynamic disorder, and transient states that are all invisible to conventional measurements. A novel, non-fluorescent single molecule technique involves attaching single molecules to single-walled carbon nanotube field-effective transistors (SWNT FETs). These ultrasensitive electronic devices provide long-duration, label-free monitoring of biomolecules and their dynamic motions. However, generalization of the SWNT FET technique first requires design rules that can predict the success and applicability of these devices. Here, we report on the transduction mechanism linking enzymatic processivity to electrical signal generation by a SWNT FET. The interaction between SWNT FETs and the enzyme lysozyme was systematically dissected using eight different lysozyme variants synthesized by protein engineering. The data prove that effective signal generation can be accomplished using a single charged amino acid, when appropriately located, providing a foundation to widely apply SWNT FET sensitivity to other biomolecular systems. PMID:23323846

  19. Prion-like Polymerization Underlies Signal Transduction in Antiviral Immune Defense and Inflammasome Activation

    PubMed Central

    Cai, Xin; Chen, Jueqi; Xu, Hui; Liu, Siqi; Jiang, Qiu-Xing; Halfmann, Randal; Chen, Zhijian J.

    2014-01-01

    SUMMARY Pathogens and cellular danger signals activate sensors such as RIG-I and NLRP3 to produce robust immune and inflammatory responses through respective adaptor proteins MAVS and ASC, which harbor essential N-terminal CARD and PYRIN domains, respectively. Here, we show that CARD and PYRIN function as bona fide prions in yeast and their prion forms are inducible by their respective upstream activators. Likewise, a yeast prion domain can functionally replace CARD and PYRIN in mammalian cell signaling. Mutations in MAVS and ASC that disrupt their prion activities in yeast also abrogate their ability to signal in mammalian cells. Furthermore, fibers of recombinant PYRIN can convert ASC into functional polymers capable of activating caspase-1. Remarkably, a conserved fungal NOD-like receptor and prion pair can functionally reconstitute signaling of NLRP3 and ASC PYRINs in mammalian cells. These results indicate that prion-like polymerization is a conserved signal transduction mechanism in innate immunity and inflammation. PMID:24630723

  20. Anomalous Brownian motion discloses viscoelasticity in the ear’s mechanoelectrical-transduction apparatus

    PubMed Central

    Kozlov, Andrei S.; Andor-Ardó, Daniel; Hudspeth, A. J.

    2012-01-01

    The ear detects sounds so faint that they produce only atomic-scale displacements in the mechanoelectrical transducer, yet thermal noise causes fluctuations larger by an order of magnitude. Explaining how hearing can operate when the magnitude of the noise greatly exceeds that of the signal requires an understanding both of the transducer’s micromechanics and of the associated noise. Using microrheology, we characterize the statistics of this noise; exploiting the fluctuation-dissipation theorem, we determine the associated micromechanics. The statistics reveal unusual Brownian motion in which the mean square displacement increases as a fractional power of time, indicating that the mechanisms governing energy dissipation are related to those of energy storage. This anomalous scaling contradicts the canonical model of mechanoelectrical transduction, but the results can be explained if the micromechanics incorporates viscoelasticity, a salient characteristic of biopolymers. We amend the canonical model and demonstrate several consequences of viscoelasticity for sensory coding. PMID:22328158

  1. The tip-link molecular complex of the auditory mechano-electrical transduction machinery.

    PubMed

    Pepermans, Elise; Petit, Christine

    2015-12-01

    Sound waves are converted into electrical signals by a process of mechano-electrical transduction (MET), which takes place in the hair bundle of cochlear hair cells. In response to the mechanical stimulus of the hair bundle, the tip-links, key components of the MET machinery, are tensioned and the MET channels open, which results in the generation of the cell receptor potential. Tip-links are composed of cadherin-23 (Cdh23) and protocadherin-15 (Pcdh15), both non-conventional cadherins, that form the upper and the lower part of these links, respectively. Here, we review the various Pcdh15 isoforms present in the organ of Corti, their localization in the auditory hair bundles, their involvement in the molecular complex forming the tip-link, and their interactions with transmembrane molecules that are components of the lower MET machinery. PMID:26049141

  2. Retroviral vectors for the transduction of autoregulated, bidirectional expression cassettes.

    PubMed

    Unsinger, J; Kröger, A; Hauser, H; Wirth, D

    2001-11-01

    Regulated transgene expression is increasingly used in research but is also needed for certain therapies. Regulatory systems are usually composed of two expression units, one bearing the gene of interest under control of a regulatable promoter and the other, a constitutively expressed transactivator that modulates the activity of the regulatable promoter. Because the cotransfer of two independent elements is not efficient in primary cells, single transduction step vectors conferring regulatable gene expression cassettes would be helpful. We have developed retroviral vectors containing an autoregulatory bidirectional expression cassette that encodes all components necessary for regulated expression of a gene of interest. The influence of the orientation of the reporter gene with respect to the viral long terminal repeat (LTR) and the effect of transcriptionally inactive LTRs were investigated using mouse leukemia virus (MLV) and self-inactivating (SIN)-based retroviral vectors. Strict regulation was observed when the reporter was inserted in antisense orientation with respect to the LTR, whereas a sense arrangement of the reporter resulted in a loss of regulation capacity. Expression and regulation of the antisense-orientated reporter gene were homogenous in infected cell pools and investigated cell clones. Long-term observations of infected cells over a period of 30 passages revealed stable expression and regulation. These autoregulated, bidirectional retroviral vectors combine the advantages of single-step transduction with strict regulation of the gene of interest in the infected target cells. PMID:11708885

  3. First realization of the piezoelectronic stress-based transduction device.

    PubMed

    Chang, Josephine B; Miyazoe, Hiroyuki; Copel, Matthew; Solomon, Paul M; Liu, Xiao-Hu; Shaw, Thomas M; Schrott, Alejandro G; Gignac, Lynne M; Martyna, Glenn J; Newns, Dennis M

    2015-09-18

    We present the first realization of a monolithically integrated piezoelectronic transistor (PET), a new transduction-based computer switch which could potentially operate conventional computer logic at 1/50 the power requirements of current Si-based transistors (Chen 2014 Proc. IEEE ICICDT pp 1-4; Mamaluy et al 2014 Proc. IWCE pp 1-2). In PET operation, an input gate voltage expands a piezoelectric element (PE), transducing the input into a pressure pulse which compresses a piezoresistive element (PR). The PR resistance goes down, transducing the signal back to voltage and turning the switch 'on'. This transduction physics, in principle, allows fast, low-voltage operation. In this work, we address the processing challenges of integrating chemically incompatible PR and PE materials together within a surrounding cage against which the PR can be compressed. This proof-of-concept demonstration of a fully integrated, stand-alone PET device is a key step in the development path toward a fast, low-power very large scale integration technology. PMID:26302818

  4. [Contractile proteins in chemical signal transduction in plant microspores].

    PubMed

    Roshchina, V V

    2005-01-01

    Involvement of contractile components in chemical signal transduction from the cell surface to the organelles was studied using unicellular systems. Neurotransmitters dopamine and serotonin as well as active forms of oxygen hydrogen peroxide and tert-butyl peroxide were used as chemical signals. Experiments were carried out on vegetative microspores of field horsetail Equisetum arvense and generative microspores (pollen) of amaryllis Hippeastrum hybridum treated with cytochalasin B (an inhibitor of actin polymerization in microfilaments), colchicine, and vinblastine (inhibitors of tubulin polymerization in microtubules). Both types of thus treated microspores demonstrated suppressed development, particularly, for cytochalasin B treatment. At the same time, an increased typical blue fluorescence of certain cell regions (along the cell wall and around nuclei and chloroplasts) where the corresponding contractile proteins could reside was observed. In contrast to anticontractile agents, dopamine, serotonin B, and the peroxides stimulated microspore germination. Microspore pretreatment with cytochalasin B and colchicine followed by the treatment with serotonin, dopamine, or the peroxides decreased the germination rate. Involvement of actin and tubulin in chemical signal transduction from the cell surface to the nucleus is proposed. PMID:16004258

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

    PubMed Central

    Jankovic-Raznatovic, Svetlana; Dragojevic-Dikic, Svetlana; Rakic, Snezana; Nikolic, Branka; Plesinac, Snezana; Tasic, Lidija; Perisic, Zivko; Sovilj, Mirjana; Adamovic, Tatjana; Koruga, Djuro

    2014-01-01

    Background. This experimental study evaluates fetal middle cerebral artery (MCA) circulation after the defined prenatal acoustical stimulation (PAS) and the role of cilia in hearing and memory and could explain signal transduction and memory according to cilia optical-acoustical properties. Methods. PAS was performed twice on 119 no-risk term pregnancies. We analyzed fetal MCA circulation before, after first and second PAS. Results. Analysis of the Pulsatility index basic (PIB) and before PAS and Pulsatility index reactive after the first PAS (PIR 1) shows high statistical difference, representing high influence on the brain circulation. Analysis of PIB and Pulsatility index reactive after the second PAS (PIR 2) shows no statistical difference. Cilia as nanoscale structure possess magnetic flux linkage that depends on the amount of charge that has passed between two-terminal variable resistors of cilia. Microtubule resistance, as a function of the current through and voltage across the structure, leads to appearance of cilia memory with the “memristor” property. Conclusion. Acoustical and optical cilia properties play crucial role in hearing and memory processes. We suggest that fetuses are getting used to sound, developing a kind of memory patterns, considering acoustical and electromagnetically waves and involving cilia and microtubules and try to explain signal transduction. PMID:24719851

  6. Analysis and logical modeling of biological signaling transduction networks

    NASA Astrophysics Data System (ADS)

    Sun, Zhongyao

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

  7. Dual-transduction-mode sensing approach for chemical detection

    SciTech Connect

    Wang, Liang; Swensen, James S.

    2012-11-01

    Smart devices such as electronic nose have been developed for application in many fields like national security, defense, environmental regulation, health care, pipeline monitoring and food analysis. Despite a large array of individual sensors, these devices still lack the ability to identify a target at a very low concentration out of a mixture of odors, limited by a single type of transduction as the sensing response to distinguish one odor from another. Here, we propose a new sensor architecture empowering each individual sensor with multi-dimensional transduction signals. The resolving power of our proposed electronic nose is thereby multiplied by a set of different and independent variables which synergistically will provide a unique combined fingerprint for each analyte. We demonstrate this concept using a Light Emitting Organic Field-Effect Transistor (LEOFET). Sensing response has been observed on both electrical and optical output signals from a green LEOFET upon exposure to an explosive taggant, with optical signal exhibiting much higher sensitivity. This new sensor architecture opens a field of devices for smart detection of chemical and biological targets.

  8. Gastrointestinal Congestion Dilates the Hepatic Artery Through the P38 MAPK Signal Transduction Pathway During Liver Transplantation.

    PubMed

    Cao, Zhongping; Tang, Xiaowen; Hou, Shike

    2016-01-01

    During the neohepatic stage of liver transplantation, hemodynamics change markedly. The current study aimed to investigate whether gastrointestinal congestion caused by inferior vena cava and hepatic portal vein clamping can dilate the hepatic artery and to determine the associated mechanisms. Ring segments of the hepatic artery were treated with the plasma from gastrointestinal congestion or the superior vena cava. The fractions in gastrointestinal congestion and the superior vena cava plasma were tested, and the effect of these fractions on the tone of the hepatic artery ring was examined. Different signal transduction blockers and different inhibitors were then used to determine the exact signal transduction pathway involved. In addition, endothelial cell structure was observed by transmission electron microscopy after treatment with the gastrointestinal congestion plasma or the superior vena cava plasma. Gastrointestinal congestion plasma contained more inflammatory cytokines than superior vena cava plasma, and these cytokines could cause hepatic artery ring dilatation. A P38 mitogen-activated protein kinase (P38 MAPK) signal transduction pathway blocker and nitric oxide (NO), prostaglandin (PGI2), nuclear factor-κB (NF-κB), and adenosine triphosphate (ATP)-sensitive K (KATP) channel inhibitors were able to significantly reverse the ring tension caused by gastrointestinal congestion plasma. The normal endothelium was also injured by treatment with gastrointestinal congestion plasma. The inflammatory cytokines in gastrointestinal congestion can cause hepatic artery ring dilatation through the P38 MAPK signal transduction pathway, and this phenomenon is also associated with NO, PGI2, NF-κB, and the KATP channel. These inflammatory cytokines can injure endothelial cells in the hepatic artery. PMID:26955003

  9. Aluminium-induced phospholipid signal transduction pathway in Coffea arabica suspension cells and its amelioration by silicic acid.

    PubMed

    Quintal-Tun, Fausto; Muñoz-Sánchez, J Armando; Ramos-Díaz, Ana; Escamilla-Bencomo, Armando; Martínez-Estévez, Manuel; Exley, Christopher; Hernández-Sotomayor, S M Teresa

    2007-02-01

    Coffee (Coffea arabica L.) is of economic importance worldwide. Its growth in organic-rich acidic soils is influenced by aluminium such that coffee yield may be impaired. Herein we have used the Al-sensitive C. arabica suspension cell line L2 to analyse the effect of two different Al species on the phosphoinositide signal transduction pathway. Our results have shown that the association of Al with coffee cells was affected by the pH and the form of Al in media. More Al was associated with cells at pH 4.3 than 5.8, whereas when Al was present as hydroxyaluminosilicates (HAS) the association was halved at pH 4.3 and unchanged at pH 5.8. Two signal transduction elements were also evaluated; phospholipase C (PLC) activity and phosphatidic acid (PA) formation. PLC was inhibited ( approximately 50%) when cells were incubated for 2 h in the presence of either AlCl(3) or Al in the form of HAS. PA formation was tested as a short-term response to Al. By way of contrast to what was found for PLC, incubation of cells for 15 min in the presence of AlCl(3) decreased the formation of PA whereas the same concentration of Al as HAS produced no effect upon its formation. These results suggest that Al is capable to exert its effects upon signal transduction as Al((aq))(3+) acting upon a mechanism linked to the phosphoinositide signal transduction pathway. PMID:17161461

  10. Genetic analysis of gravity signal transduction in roots

    NASA Astrophysics Data System (ADS)

    Masson, Patrick; Strohm, Allison; Baldwin, Katherine

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

  11. Generating Gene Ontology-Disease Inferences to Explore Mechanisms of Human Disease at the Comparative Toxicogenomics Database.

    PubMed

    Davis, Allan Peter; Wiegers, Thomas C; King, Benjamin L; Wiegers, Jolene; Grondin, Cynthia J; Sciaky, Daniela; Johnson, Robin J; Mattingly, Carolyn J

    2016-01-01

    Strategies for discovering common molecular events among disparate diseases hold promise for improving understanding of disease etiology and expanding treatment options. One technique is to leverage curated datasets found in the public domain. The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) manually curates chemical-gene, chemical-disease, and gene-disease interactions from the scientific literature. The use of official gene symbols in CTD interactions enables this information to be combined with the Gene Ontology (GO) file from NCBI Gene. By integrating these GO-gene annotations with CTD's gene-disease dataset, we produce 753,000 inferences between 15,700 GO terms and 4,200 diseases, providing opportunities to explore presumptive molecular underpinnings of diseases and identify biological similarities. Through a variety of applications, we demonstrate the utility of this novel resource. As a proof-of-concept, we first analyze known repositioned drugs (e.g., raloxifene and sildenafil) and see that their target diseases have a greater degree of similarity when comparing GO terms vs. genes. Next, a computational analysis predicts seemingly non-intuitive diseases (e.g., stomach ulcers and atherosclerosis) as being similar to bipolar disorder, and these are validated in the literature as reported co-diseases. Additionally, we leverage other CTD content to develop testable hypotheses about thalidomide-gene networks to treat seemingly disparate diseases. Finally, we illustrate how CTD tools can rank a series of drugs as potential candidates for repositioning against B-cell chronic lymphocytic leukemia and predict cisplatin and the small molecule inhibitor JQ1 as lead compounds. The CTD dataset is freely available for users to navigate pathologies within the context of extensive biological processes, molecular functions, and cellular components conferred by GO. This inference set should aid researchers, bioinformaticists, and pharmaceutical drug makers

  12. Cell-Type-Specific Characteristics Modulate the Transduction Efficiency of Adeno-Associated Virus Type 2 and Restrain Infection of Endothelial Cells

    PubMed Central

    Pajusola, Katri; Gruchala, Marcin; Joch, Hana; Lüscher, Thomas F.; Ylä-Herttuala, Seppo; Büeler, Hansruedi

    2002-01-01

    Adeno-associated viruses (AAVs) are promising vectors for various gene therapy applications due to their long-lasting transgene expression and wide spectrum of target cells. Recently, however, it has become apparent that there are considerable differences in the efficiencies of transduction of different cell types by AAVs. Here, we analyzed the efficiencies of transduction and the transport mechanisms of AAV type 2 (AAV-2) in different cell types, emphasizing endothelial cells. Expression analyses in both cultured cells and the rabbit carotid artery assay showed a remarkably low level of endothelial cell transduction in comparison to the highly permissive cell types. The study of the endosomal pathways of AAV-2 with fluorescently labeled virus showed clear targeting of the Golgi area in permissive cell lines, but this phenomenon was absent in the endothelial cell line EAhy-926. On the other hand, the response to the block of endosomal acidification by bafilomycin A1 also showed differences among the permissive cell types. We also analyzed the effect of proteasome inhibitors on endothelial cells, but their impact on the primary cells and in vivo was not significant. On the contrary, analysis of the expression pattern of heparan sulfate proteoglycans (HSPGs), the primary receptors of AAV-2, revealed massive deposits of HSPG in the extracellular matrix of endothelial cells. The matrix-associated receptors may therefore compete for virus binding and reduce transduction in endothelial cells. Accordingly, in endothelial cells detached from their matrix, AAV-2 transduction was significantly increased. Altogether, these results point to a more complex cell-type-specific mode of transduction of AAV-2 than previously appreciated. PMID:12388714

  13. Cell-type-specific characteristics modulate the transduction efficiency of adeno-associated virus type 2 and restrain infection of endothelial cells.

    PubMed

    Pajusola, Katri; Gruchala, Marcin; Joch, Hana; Lüscher, Thomas F; Ylä-Herttuala, Seppo; Büeler, Hansruedi

    2002-11-01

    Adeno-associated viruses (AAVs) are promising vectors for various gene therapy applications due to their long-lasting transgene expression and wide spectrum of target cells. Recently, however, it has become apparent that there are considerable differences in the efficiencies of transduction of different cell types by AAVs. Here, we analyzed the efficiencies of transduction and the transport mechanisms of AAV type 2 (AAV-2) in different cell types, emphasizing endothelial cells. Expression analyses in both cultured cells and the rabbit carotid artery assay showed a remarkably low level of endothelial cell transduction in comparison to the highly permissive cell types. The study of the endosomal pathways of AAV-2 with fluorescently labeled virus showed clear targeting of the Golgi area in permissive cell lines, but this phenomenon was absent in the endothelial cell line EAhy-926. On the other hand, the response to the block of endosomal acidification by bafilomycin A1 also showed differences among the permissive cell types. We also analyzed the effect of proteasome inhibitors on endothelial cells, but their impact on the primary cells and in vivo was not significant. On the contrary, analysis of the expression pattern of heparan sulfate proteoglycans (HSPGs), the primary receptors of AAV-2, revealed massive deposits of HSPG in the extracellular matrix of endothelial cells. The matrix-associated receptors may therefore compete for virus binding and reduce transduction in endothelial cells. Accordingly, in endothelial cells detached from their matrix, AAV-2 transduction was significantly increased. Altogether, these results point to a more complex cell-type-specific mode of transduction of AAV-2 than previously appreciated. PMID:12388714

  14. A Porcine Anterior Segment Perfusion and Transduction Model With Direct Visualization of the Trabecular Meshwork

    PubMed Central

    Loewen, Ralitsa T.; Roy, Pritha; Park, Daniel B.; Jensen, Adrianna; Scott, Gordon; Cohen-Karni, Devora; Fautsch, Michael P.; Schuman, Joel S.; Loewen, Nils A.

    2016-01-01

    Purpose To establish a consistent and affordable, high quality porcine anterior segment perfusion and transduction model that allows direct visualization of the trabecular meshwork. Methods Porcine anterior segments were cultured within 2 hours of death by removing lens and uvea and securing in a specially designed petri dish with a thin bottom to allow direct visualization of the trabecular meshwork with minimal distortion. Twenty-two control eyes (CO) with a constant flow rate were compared to eight gravity perfused eyes (COgr, 15 mm Hg). We established gene delivery to the TM using eGFP expressing feline immunodeficiency virus (FIV) vector GINSIN at 108 transducing units (TU) per eye (GINSIN_8, n = 8) and 107 TU (GINSIN_7, n = 8). Expression was assessed for 14 days before histology was obtained. Results Pig eyes were a reliable source for consistent and high quality anterior segment cultures with a low failure rate of 12%. Control eyes had an intraocular pressure (IOP) of 15.8 ± 1.9 mm Hg at fixed pump perfusion with 3 μL/min compared to gravity perfused COgr with imputed 3.7 ± 1.6 μL/min. Vector GINSIN_8 eyes experienced a transient posttransduction IOP increase of 44% that resolved at 48 hours; this was not observed in GINSIN_7 eyes. Expression was higher in GINSIN_8 than in GINSIN_7 eyes. Trabecular meshwork architecture was well preserved. Conclusions Compared with previously used human donor eyes, this inexpensive porcine anterior segment perfusion model is of sufficient, repeatable high quality to develop strategies of TM bioengineering. Trabecular meshwork could be observed directly. Despite significant anatomic differences, effects of transduction replicate the main aspects of previously explored human, feline and rodent models. PMID:27002293

  15. A Comparative Study of Iron Uptake Rates and Mechanisms amongst Marine and Fresh Water Cyanobacteria: Prevalence of Reductive Iron Uptake

    PubMed Central

    Lis, Hagar; Kranzler, Chana; Keren, Nir; Shaked, Yeala

    2015-01-01

    In this contribution, we address the question of iron bioavailability to cyanobacteria by measuring Fe uptake rates and probing for a reductive uptake pathway in diverse cyanobacterial species. We examined three Fe-substrates: dissolved inorganic iron (Fe') and the Fe-siderophores Ferrioxamine B (FOB) and FeAerobactin (FeAB). In order