Sample records for connexin40 gap junction

  1. Restricted distribution of connexin40, a gap junctional protein, in mammalian heart

    NARCIS (Netherlands)

    Gros, D.; Jarry-Guichard, T.; ten Velde, I.; de Maziere, A.; van Kempen, M. J.; Davoust, J.; Briand, J. P.; Moorman, A. F.; Jongsma, H. J.


    Connexin40 (Cx40) is a member of the connexin family of gap junction proteins. Its mRNA, abundant in lung, is also present in mammalian heart, although in lower amount. Rabbit antipeptide antibodies directed to the COOH terminus (residues 335 to 356) of rat Cx40 were characterized to investigate the

  2. Atrial fibrillation-linked germline GJA5/connexin40 mutants showed an increased hemichannel function.

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    Yiguo Sun

    Full Text Available Mutations in GJA5 encoding the gap junction protein connexin40 (Cx40 have been linked to lone atrial fibrillation. Some of these mutants result in impaired gap junction function due to either abnormal connexin localization or impaired gap junction channels, which may play a role in promoting atrial fibrillation. However, the effects of the atrial fibrillation-linked Cx40 mutants on hemichannel function have not been studied. Here we investigated two atrial fibrillation-linked germline Cx40 mutants, V85I and L221I. These two mutants formed putative gap junction plaques at cell-cell interfaces, with similar gap junction coupling conductance as that of wild-type Cx40. Connexin deficient HeLa cells expressing either one of these two mutants displayed prominent propidium iodide-uptake distinct from cells expressing wild-type Cx40 or other atrial fibrillation-linked Cx40 mutants, I75F, L229M, and Q49X. Propidium iodide-uptake was sensitive to [Ca2+]o and the hemichannel blockers, carbenoxolone, flufenamic acid and mefloquine, but was not affected by the pannexin 1 channel blocking agent, probenecid, indicating that uptake is most likely mediated via connexin hemichannels. A gain-of-hemichannel function in these two atrial fibrillation-linked Cx40 mutants may provide a novel mechanism underlying the etiology of atrial fibrillation.

  3. Hypoxic pulmonary vasoconstriction requires connexin 40–mediated endothelial signal conduction (United States)

    Wang, Liming; Yin, Jun; Nickles, Hannah T.; Ranke, Hannes; Tabuchi, Arata; Hoffmann, Julia; Tabeling, Christoph; Barbosa-Sicard, Eduardo; Chanson, Marc; Kwak, Brenda R.; Shin, Hee-Sup; Wu, Songwei; Isakson, Brant E.; Witzenrath, Martin; de Wit, Cor; Fleming, Ingrid; Kuppe, Hermann; Kuebler, Wolfgang M.


    Hypoxic pulmonary vasoconstriction (HPV) is a physiological mechanism by which pulmonary arteries constrict in hypoxic lung areas in order to redirect blood flow to areas with greater oxygen supply. Both oxygen sensing and the contractile response are thought to be intrinsic to pulmonary arterial smooth muscle cells. Here we speculated that the ideal site for oxygen sensing might instead be at the alveolocapillary level, with subsequent retrograde propagation to upstream arterioles via connexin 40 (Cx40) endothelial gap junctions. HPV was largely attenuated by Cx40-specific and nonspecific gap junction uncouplers in the lungs of wild-type mice and in lungs from mice lacking Cx40 (Cx40–/–). In vivo, hypoxemia was more severe in Cx40–/– mice than in wild-type mice. Real-time fluorescence imaging revealed that hypoxia caused endothelial membrane depolarization in alveolar capillaries that propagated to upstream arterioles in wild-type, but not Cx40–/–, mice. Transformation of endothelial depolarization into vasoconstriction involved endothelial voltage-dependent α1G subtype Ca2+ channels, cytosolic phospholipase A2, and epoxyeicosatrienoic acids. Based on these data, we propose that HPV originates at the alveolocapillary level, from which the hypoxic signal is propagated as endothelial membrane depolarization to upstream arterioles in a Cx40-dependent manner. PMID:23093775

  4. Gap junctions and connexin-interacting proteins

    NARCIS (Netherlands)

    Giepmans, Ben N G


    Gap junctions form channels between adjacent cells. The core proteins of these channels are the connexins. Regulation of gap junction communication (GJC) can be modulated by connexin-associating proteins, such as regulatory protein phosphatases and protein kinases, of which c-Src is the

  5. Increasing gap junctional coupling: a tool for dissecting the role of gap junctions

    DEFF Research Database (Denmark)

    Axelsen, Lene Nygaard; Haugan, Ketil; Stahlhut, Martin


    . In a number of cases, gap junctions have been implicated in the initiation and progress of disease, and experimental uncoupling has been used to investigate the exact role of coupling. The inverse approach, i.e., to increase coupling, has become possible in recent years and represents a new way of testing......Much of our current knowledge about the physiological and pathophysiological role of gap junctions is based on experiments where coupling has been reduced by either chemical agents or genetic modification. This has brought evidence that gap junctions are important in many physiological processes...... the role of gap junctions. The aim of this review is to summarize the current knowledge obtained with agents that selectively increase gap junctional intercellular coupling. Two approaches will be reviewed: increasing coupling by the use of antiarrhythmic peptide and its synthetic analogs...

  6. Gap junction diseases of the skin.

    NARCIS (Netherlands)

    Steensel, M.A.M. van


    Gap junctions are intercellular channels that allow the passage of water, ions, and small molecules. They are involved in quick, short-range messaging between cells and are found in skin, nervous tissue, heart, and muscle. An increasing number of hereditary skin disorders appear to be caused by

  7. Selective deletion of Connexin 40 in renin-producing cells impairs renal baroreceptor function and is associated with arterial hypertension (United States)

    Wagner, Charlotte; Jobs, Alexander; Schweda, Frank; Kurtz, Lisa; Kurt, Birguel; Sequeira Lopez, Maria L.; Gomez, R. Ariel; van Veen, Toon A.B.; de Wit, Cor; Kurtz, Armin


    Renin-producing juxtaglomerular cells are connected to each other and to endothelial cells of afferent arterioles by gap junctions containing Connexin 40 (Cx40), abundantly expressed by these two cell types. Here, we generated mice with cell-specific deletion of Cx40 in endothelial and in renin-producing cells, as its global deletion caused local dissociation of renin-producing cells from endothelial cells, renin hypersecretion, and hypertension. In mice lacking endothelial Cx40, the blood pressure, renin-producing cell distribution, and the control of renin secretion were similar to wild-type mice. In contrast, mice deficient for Cx40 in renin-producing cells were hypertensive and these cells were ectopically localized. Although plasma renin activity and kidney renin mRNA levels of these mice were not different from controls, the negative regulation of renin secretion by pressure was inverted to a positive feedback in kidneys lacking Cx40 in renin-producing cells. Thus, our findings show that endothelial Cx40 is not essential for the control of renin expression and/or release. Cx40 in renin-producing cells is required for their correct positioning in the juxtaglomerular area and the control of renin secretion by pressure. PMID:20686449

  8. Low prevalence of connexin-40 gene variants in atrial tissues and blood from atrial fibrillation subjects

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    Tchou Gregory D


    Full Text Available Abstract Background The atrial gap junction protein connexin-40 (Cx40 has been implicated to play an important role in atrial conduction and development of atrial fibrillation (AF. However, the frequency of Cx40 mutations in AF populations and their impact on Cx40 expression remains unclear. In this study, we sought to identify polymorphisms in the Cx40 gene GJA5, investigate the potential functional role of these polymorphisms, and determine their allelic frequencies. The prevalence of nonsynonymous Cx40 mutations in blood and atrial tissue was also compared to mutation frequencies reported in prior studies. Methods We conducted direct sequencing of the GJA5 coding and 3′ UTR regions in blood samples from 91 lone AF subjects and 67 atrial tissue-derived samples from a lone cohort, a mixed AF cohort, and several transplant donors. Reporter gene transfection and tissue allelic expression imbalance assays were used to assess the effects of a common insertion/deletion polymorphism on Cx40 mRNA stability and expression. Results We identified one novel synonymous SNP in blood-derived DNA from a lone AF subject. In atrial tissue-derived DNA from lone and mixed AF subjects, we observed one novel nonsynonymous SNP, one rare previously reported synonymous SNP, and one novel 3′ UTR SNP. A previously noted 25 bp insertion/deletion polymorphism in the 3′ UTR was found to be common (minor allele frequency = 0.45 but had no effect on Cx40 mRNA stability and expression. The observed prevalence of nonsynonymous Cx40 mutations in atrial tissues derived from lone AF subjects differed significantly (p = 0.03 from a prior atrial tissue study reporting a high mutation frequency in a group of highly selected young lone AF subjects. Conclusions Our results suggest that Cx40 coding SNPs are uncommon in AF populations, although rare mutations in this gene may certainly lead to AF pathogenesis. Furthermore, a common insertion/deletion polymorphism in the Cx40 3

  9. Ginsenoside Re prevents angiotensin II-induced gap-junction remodeling by activation of PPARγ in isolated beating rat atria. (United States)

    Zhang, Bo; Cui, Xun; Jin, Hong-Hua; Hong, Lan; Liu, Xia; Li, Xiang; Zhang, Qing-Gao; Liu, Li-Ping


    Ginsenoside Re (G-Re), a major ginsenoside in ginseng, has many beneficial pharmacological effects on negative cardiac contractility, electromechanical alternans, antiarrhythmia, angiogenic regeneration and cardiac electrophysiological function. However, effects of G-Re on gap-junction remodeling are unclear. Therefore, this study aimed to investigate the effect of G-Re on angiotensin II (Ang II)-induced downregulation of connexin-40 (CX40) and -43 (CX43) in beating rat left atria. In this study, the isolated perfused beating rat atrial model was used and atrial gap-junction remodeling was induced by Ang II. In vivo hemodynamic experiments were analyzed with a biological recorder. Changes in protein expression were analyzed by western blot. G-Re attenuated Ang II-induced abnormal changes in heart rate, MAP, LVESP, LVEDP, +dp/dt max, -dp/dt min, P wave amplitude, P-R interval and P wave length. This indicated a dose-dependent preventive role against Ang II-induced hyper hemodynamics in rats. Atrial activities of p38 mitogen-activated protein kinase (MAPK), nuclear factor kappa-B (NF-κB) and activator protein 1 (AP-1) were significantly increased by Ang II, as was expression of atrial collagen I and matrix metalloproteinase 2 (MMP2). Atrial CX40 and CX43 expression was downregulated by Ang II. These Ang II-induced atrial effects were blocked by G-Re, as well as rosiglitazone, an agonist of peroxisome proliferator-activated receptor γ (PPARγ), in a dose-dependent manner. However, this inhibition was abolished by the PPARγ inhibitor GW9662. G-Re may suppress Ang II-induced downregulation of CX40 and CX43, by activating PPARγ signaling, in isolated perfused beating rat atria. Copyright © 2017. Published by Elsevier Inc.

  10. Sex differences in endothelial function in porcine coronary arteries: a role for H2O2 and gap junctions? (United States)

    Wong, P S; Roberts, R E; Randall, M D


    Cardiovascular risk is higher in men and postmenopausal women compared with premenopausal women. This may be due to sex differences in endothelial function. Here, sex differences in endothelial function of porcine coronary arteries (PCAs) were investigated. Distal PCAs were studied under myographic conditions and after precontraction with U46619. Concentration-response curves to bradykinin were constructed in the presence of a range of inhibitors. In male and female PCAs, bradykinin produced comparable vasorelaxant responses. Inhibition of NO and prostanoid synthesis produced greater inhibition in males compared with females. Removing H2 O2 with PEG-catalase reduced the maximum relaxation in the absence, but not the presence of L-NAME and indomethacin in females, and had no effect in males. Blocking gap junctions with 100 µM carbenoxolone or 18α-glycyrrhetinic acid further inhibited the endothelium-derived hyperpolarization (EDH)-mediated response in females but not in males. In female PCAs, the maximum EDH-mediated response was reduced by inhibiting SKCa with apamin and by inhibiting IKCa with TRAM-34, or with both. In male PCAs, at maximum bradykinin concentration, the EDH-mediated response was reduced in the presence of apamin but not TRAM-34. Western blot did not detect any differences in connexins 40 or 43 or in IKCa expression between male and female PCAs. H2 O2 mediated some part of endothelium-dependent vasorelaxation in female PCAs and EDH was more important in females, with differences in the contribution of gap junctions and IKCa channels. These findings may contribute to understanding vascular protection in premenopausal women. © 2014 The British Pharmacological Society.

  11. Gap Junctions and Cancer: Communicating for 50 Years’ (United States)

    Aasen, Trond; Mesnil, Marc; Naus, Christian C.; Lampe, Paul D.; Laird, Dale W.


    Fifty years ago, tumour cells were found to lack electrical coupling, leading to the hypothesis that loss of direct intercellular communication is commonly associated with cancer onset and progression. Subsequent studies linked this phenomenon to gap junctions composed of connexin proteins. While many studies support the notion that connexins are tumour suppressors, recent evidence suggests that, in some tumour types, they may facilitate specific stages of tumour progression through both junctional and non-junctional signalling pathways. This Timeline article highlights the milestones connecting gap junctions to cancer, and underscores important unanswered questions, controversies and therapeutic opportunities in the field. PMID:27782134

  12. Microwave dependence of subharmonic gap structure in superconducting junctions

    DEFF Research Database (Denmark)

    Sørensen, O. Hoffman; Kofoed, Bent; Pedersen, Niels Falsig


    Experiments on both point-contact junctions (Nb-Nb) and on small area thin-film tunnel junctions (Sn-O-Sn) show that applied 4-mm radiation produces satellites associated with "subharmonic" gap structure as well as the familiar microwave-assisted tunneling structure associated with the supercondu...

  13. Gap-junctional coupling between neutrophils and endothelial cells


    Zahler, Stefan; Hoffmann, Anke; Gloe, Torsten; Pohl, Ulrich


    Communication between leukocytes and endothelial cells is crucial for inflammatory reactions. Paracrine cross-talk and outside-in signaling (via adhesion molecules) have been characterized as communication pathways to date. As leukocytes and endothelial cells express connexins, we considered intercellular communication via gap junctions an intriguing additional concept. We found that gap-junctional coupling between neutrophils and endothelium occurred in a time-dependent, bidirectional manner...

  14. Biosynthesis and structural composition of gap junction intercellular membrane channels. (United States)

    Falk, M M


    Gap junction channels assemble as dodecameric complexes, in which a hexameric connexon (hemichannel) in one plasma membrane docks end-to-end with a connexon in the membrane of a closely apposed cell to provide direct cell-to-cell communication. Synthesis, assembly, and trafficking of the gap junction channel subunit proteins referred to as connexins, largely appear to follow the general secretory pathway for membrane proteins. The connexin subunits can assemble into homo-, as well as distinct hetero-oligomeric connexons. Assembly appears to be based on specific signals located within the connexin polypeptides. Plaque formation by the clustering of gap junction channels in the plane of the membrane, as well as channel degradation are poorly understood processes that are topics of current research. Recently, we tagged connexins with the autofluorescent reporter green fluorescent protein (GFP), and its cyan (CFP), and yellow (YFP) color variants and combined this reporter technology with single, and dual-color, high resolution deconvolution microscopy, computational volume rendering, and time-lapse microscopy to examine the detailed organization, structural composition, and dynamics of gap junctions in live cells. This technology provided for the first time a realistic, three-dimensional impression of gap junctions as they appear in the plasma membranes of adjoining cells, and revealed an excitingly detailed structural organization of gap junctions never seen before in live cells. Here, I summarize recent progress in areas encompassing the synthesis, assembly and structural composition of gap junctions with a special emphasis on the recent results we obtained using cell-free translation/ membrane-protein translocation, and autofluorescent reporters in combination with live-cell deconvolution microscopy.

  15. PKCγ, role in lens differentiation and gap junction coupling. (United States)

    Das, Satyabrata; Wang, Huan; Molina, Samuel A; Martinez-Wittinghan, Francisco J; Jena, Snehalata; Bossmann, Leonie K; Miller, Kendra A; Mathias, Richard T; Takemoto, Dolores J


    To determine the role of PKCγ in the regulation of gap junction coupling in the normal lens, we have compared the properties of coupling in lenses from wild type (WT) and PKC-γ knockout (KO) mice. Western blotting, confocal immunofluorescence microscopy, immunoprecipitation, RT-PCR and quantitative real time PCR were used to study gap junction protein and message expression; gap junction coupling conductance and pH gating were measured in intact lenses using impedance studies. There were no gross differences in size, clarity, or expression of full-length Cx46 or Cx50 in lenses from WT and PKCγ KO mice. However, total Cx43 protein expression was ~150% higher in the KO lenses. In WT lenses, Cx43 was found only in epithelial cells whereas in KO lenses, its expression continued into the fiber cells. Gap junction coupling conductance in the differentiating fibers (DF) of PKCγ KO lenses was 34% larger than that of WT. In the mature fiber (MF), the effect was much larger with the KO lenses having an 82% increase in coupling over WT. pH gating of the DF fibers was not altered by the absence of PKCγ. PKCγ has a major role in the regulation of gap junction expression and coupling in the normal lens.

  16. Functional Gap Junctions in the Schwann Cell Myelin Sheath (United States)

    Balice-Gordon, Rita J.; Bone, Linda J.; Scherer, Steven S.


    The Schwann cell myelin sheath is a multilamellar structure with distinct structural domains in which different proteins are localized. Intracellular dye injection and video microscopy were used to show that functional gap junctions are present within the myelin sheath that allow small molecules to diffuse between the adaxonal and perinuclear Schwann cell cytoplasm. Gap junctions are localized to periodic interruptions in the compact myelin called Schmidt–Lanterman incisures and to paranodes; these regions contain at least one gap junction protein, connexin32 (Cx32). The radial diffusion of low molecular weight dyes across the myelin sheath was not interrupted in myelinating Schwann cells from cx32-null mice, indicating that other connexins participate in forming gap junctions in these cells. Owing to the unique geometry of myelinating Schwann cells, a gap junction-mediated radial pathway may be essential for rapid diffusion between the adaxonal and perinuclear cytoplasm, since this radial pathway is approximately one million times faster than the circumferential pathway. PMID:9722620

  17. Roles of gap junctions, connexins and pannexins in epilepsy

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    Shanthini eMylvaganam


    Full Text Available Enhanced gap junctional communication (GJC between neurons is considered a major factor underlying the neuronal synchrony driving seizure activity. In addition, the hippocampal sharp wave ripple complexes, associated with learning and seizures, are diminished by GJC blocking agents. Although gap junctional blocking drugs inhibit experimental seizures, they all have other nonspecific actions. Besides interneuronal GJC between dendrites, inter-axonal and inter-glial GJC is also considered important for seizure generation. Interestingly, in most studies of cerebral tissue from animal seizure models and from human patients with epilepsy, there is up-regulation of glial, but not neuronal gap junctional mRNA and protein. Significant changes in the expression and post-translational modification of the astrocytic connexin Cx43, and Panx1 were observed in an in vitro Co++ seizure model, further supporting a role for glia in seizure-genesis, although the reasons for this remain unclear. Further suggesting an involvement of astrocytic GJC in epilepsy, is the fact that the expression of astrocytic Cx mRNAs (Cxs 30 and 43 is several fold higher than that of neuronal Cx mRNAs (Cxs 36 and 45, and the number of glial cells outnumber neuronal cells in mammalian hippocampal and cortical tissue. Pannexin expression is also increased in both animal and human epileptic tissues. Specific Cx43 mimetic peptides, Gap 27 and SLS, inhibit the docking of astrocytic connexin Cx43 proteins from forming intercellular gap junctions, diminishing spontaneous seizures. Besides GJs, Cx membrane hemichannels in glia and Panx membrane channels in neurons and glia are also inhibited by gap junctional pharmacological blockers. Although there is no doubt that connexin-based gap junctions and hemichannels, and pannexin-based membrane channels are related to epilepsy, the specific details of how they are involved and how we can modulate their function for therapeutic purposes remain to

  18. Gap junction modulation by extracellular signaling molecules: the thymus model

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    Alves L.A.


    Full Text Available Gap junctions are intercellular channels which connect adjacent cells and allow direct exchange of molecules of low molecular weight between them. Such a communication has been described as fundamental in many systems due to its importance in coordination, proliferation and differentiation. Recently, it has been shown that gap junctional intercellular communication (GJIC can be modulated by several extracellular soluble factors such as classical hormones, neurotransmitters, interleukins, growth factors and some paracrine substances. Herein, we discuss some aspects of the general modulation of GJIC by extracellular messenger molecules and more particularly the regulation of such communication in the thymus gland. Additionally, we discuss recent data concerning the study of different neuropeptides and hormones in the modulation of GJIC in thymic epithelial cells. We also suggest that the thymus may be viewed as a model to study the modulation of gap junction communication by different extracellular messengers involved in non-classical circuits, since this organ is under bidirectional neuroimmunoendocrine control.

  19. [Gap junctions: A new therapeutic target in major depressive disorder?]. (United States)

    Sarrouilhe, D; Dejean, C


    Major depressive disorder is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and is associated with excess mortality, especially from cardiovascular diseases and through suicide. The treatments of this disease with tricyclic antidepressants and monoamine oxidase inhibitors are poorly tolerated and those that selectively target serotonin and norepinephrine re-uptake are not effective in all patients, showing the need to find new therapeutic targets. Post-mortem studies of brains from patients with major depressive disorders described a reduced expression of the gap junction-forming membrane proteins connexin 30 and connexin 43 in the prefrontal cortex and the locus coeruleus. The use of chronic unpredictable stress, a rodent model of depression, suggests that astrocytic gap junction dysfunction contributes to the pathophysiology of major depressive disorder. Chronic treatments of rats with fluoxetine and of rat cultured cortical astrocytes with amitriptyline support the hypothesis that the upregulation of gap junctional intercellular communication between brain astrocytes could be a novel mechanism for the therapeutic effect of antidepressants. In conclusion, astrocytic gap junctions are emerging as a new potential therapeutic target for the treatment of patients with major depressive disorder. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  20. Dynamically Active Compartments Coupled by a Stochastically Gated Gap Junction (United States)

    Bressloff, Paul C.; Lawley, Sean D.


    We analyze a one-dimensional PDE-ODE system representing the diffusion of signaling molecules between two cells coupled by a stochastically gated gap junction. We assume that signaling molecules diffuse within the cytoplasm of each cell and then either bind to some active region of the cell's membrane (treated as a well-mixed compartment) or pass through the gap junction to the interior of the other cell. We treat the gap junction as a randomly fluctuating gate that switches between an open and a closed state according to a two-state Markov process. This means that the resulting PDE-ODE is stochastic due to the presence of a randomly switching boundary in the interior of the domain. It is assumed that each membrane compartment acts as a conditional oscillator, that is, it sits below a supercritical Hopf bifurcation. In the ungated case (gap junction always open), the system supports diffusion-induced oscillations, in which the concentration of signaling molecules within the two compartments is either in-phase or anti-phase. The presence of a reflection symmetry (for identical cells) means that the stochastic gate only affects the existence of anti-phase oscillations. In particular, there exist parameter choices where the gated system supports oscillations, but the ungated system does not, and vice versa. The existence of oscillations is investigated by solving a spectral problem obtained by averaging over realizations of the stochastic gate.

  1. Gap junctions in developing thalamic and neocortical neuronal networks

    NARCIS (Netherlands)

    Niculescu, Dragos; Lohmann, C.


    The presence of direct, cytoplasmatic, communication between neurons in the brain of vertebrates has been demonstrated a long time ago. These gap junctions have been characterized in many brain areas in terms of subunit composition, biophysical properties, neuronal connectivity patterns, and

  2. The effect of gap junctional distribution on defibrillation (United States)

    Keener, James P.


    We summarize a mathematical theory for direct activation and defibrillation of cardiac tissue. We show that the direct stimulus and defibrillation thresholds are likely to be strongly affected by the gap junctional distribution and density, suggesting an indirect experimental test of the theory.

  3. Intracellular trafficking pathways of Cx43 gap junction channels. (United States)

    Epifantseva, Irina; Shaw, Robin M


    Gap Junction (GJ) channels, including the most common Connexin 43 (Cx43), have fundamental roles in excitable tissues by facilitating rapid transmission of action potentials between adjacent cells. For instance, synchronization during each heartbeat is regulated by these ion channels at the cardiomyocyte cell-cell border. Cx43 protein has a short half-life, and rapid synthesis and timely delivery of those proteins to particular subdomains are crucial for the cellular organization of gap junctions and maintenance of intracellular coupling. Impairment in gap junction trafficking contributes to dangerous complications in diseased hearts such as the arrhythmias of sudden cardiac death. Of recent interest are the protein-protein interactions with the Cx43 carboxy-terminus. These interactions have significant impact on the full length Cx43 lifecycle and also contribute to trafficking of Cx43 as well as possibly other functions. We are learning that many of the known non-canonical roles of Cx43 can be attributed to the recently identified six endogenous Cx43 truncated isoforms which are produced by internal translation. In general, alternative translation is a new leading edge for proteome expansion and therapeutic drug development. This review highlights recent mechanisms identified in the trafficking of gap junction channels, involvement of other proteins contributing to the delivery of channels to the cell-cell border, and understanding of possible roles of the newly discovered alternatively translated isoforms in Cx43 biology. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Experimental observation of subharmonic gap structures in long Josephson junctions

    DEFF Research Database (Denmark)

    Nordahn, M.A.; Manscher, Martin; Mygind, Jesper


    The subharmonic gap structure (SGS) in long-overlap Nb-AlOx-Nb Josephson tunnel junctions has been investigated. The experimental results show peaks in the differential conductance at both odd and even integer fractions of the gap voltage, VG Furthermore, the conductance peaks at V-G/2 has been...... observed to split into two peaks with different characteristics. At high magnetic fields, the I-V characteristics approach a single curve, while retaining the SGS conductance peaks. The gap structure and the SGS show the same temperature dependence. The SGS can be explained by a Josephson self...

  5. Gap junction coupling and calcium waves in the pancreatic islet. (United States)

    Benninger, Richard K P; Zhang, Min; Head, W Steven; Satin, Leslie S; Piston, David W


    The pancreatic islet is a highly coupled, multicellular system that exhibits complex spatiotemporal electrical activity in response to elevated glucose levels. The emergent properties of islets, which differ from those arising in isolated islet cells, are believed to arise in part by gap junctional coupling, but the mechanisms through which this coupling occurs are poorly understood. To uncover these mechanisms, we have used both high-speed imaging and theoretical modeling of the electrical activity in pancreatic islets under a reduction in the gap junction mediated electrical coupling. Utilizing islets from a gap junction protein connexin 36 knockout mouse model together with chemical inhibitors, we can modulate the electrical coupling in the islet in a precise manner and quantify this modulation by electrophysiology measurements. We find that after a reduction in electrical coupling, calcium waves are slowed as well as disrupted, and the number of cells showing synchronous calcium oscillations is reduced. This behavior can be reproduced by computational modeling of a heterogeneous population of beta-cells with heterogeneous levels of electrical coupling. The resulting quantitative agreement between the data and analytical models of islet connectivity, using only a single free parameter, reveals the mechanistic underpinnings of the multicellular behavior of the islet.

  6. Symposia for a Meeting on Ion Channels and Gap Junctions

    CERN Document Server

    Sáez, Juan


    Ion channels allow us to see nature in all its magnificence, to hear a Bach suite, to smell the aroma of grandmother's cooking, and, in this regard, they put us in contact with the external world. These ion channels are protein molecules located in the cell membrane. In complex organisms, cells need to communicate in order to know about their metabolic status and to act in a coordinate manner. The latter is also accomplished by a class of ion channels able to pierce the lipid bilayer membranes of two adjacent cells. These intercellular channels are the functional subunits of gap junctions. Accordingly, the book is divided in two parts: the first part is dedicated to ion channels that look to the external world, and the second part is dedicated to gap junctions found at cell interfaces. This book is based on a series of symposia for a meeting on ion channels and gap junctions held in Santiago, Chile, on November 28-30, 1995. The book should be useful to graduate students taking the first steps in this field as...

  7. Effect of thick barrier in a gapped graphene Josephson junction (United States)

    Suwannasit, Tatnatchai; Liewrian, Watchara


    We study the Josephson effect in a gapped graphene-based superconductor/barrier/superconductor junction using the Dirac-Bogoliubov de Gennes (DBdG) equation for theoretical prediction. A massive gap of this regime is induced by fabricating a monolayer graphene on substrate-induced bandgap and superconductivity is acquired by the proximity effect of conventional superconductor (s-wave superconductor) through top gate electrodes. This Josephson junction is investigated in case of thick barrier limit that is pointed out the effect of applying a gate voltage VG in the barrier. We find that the switching supercurrent can be controlled by the gate VG and the effect of thick barrier can influence the switching linear curve. When the barrier is adjusted to manner of a potential well which is inside the range of -m{v}F2≤ {V}G≤ 0, the supercurrent in the thick barrier case is examined to the same behavior as the thin barrier case. The controlling supercurrent through the electrostatic gate is suitable for alternative mechanism into experimental test.

  8. Role of Gap Junctions and Hemichannels in Parasitic Infections

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    José Luis Vega


    Full Text Available In vertebrates, connexins (Cxs and pannexins (Panxs are proteins that form gap junction channels and/or hemichannels located at cell-cell interfaces and cell surface, respectively. Similar channel types are formed by innexins in invertebrate cells. These channels serve as pathways for cellular communication that coordinate diverse physiologic processes. However, it is known that many acquired and inherited diseases deregulate Cx and/or Panx channels, condition that frequently worsens the pathological state of vertebrates. Recent evidences suggest that Cx and/or Panx hemichannels play a relevant role in bacterial and viral infections. Nonetheless, little is known about the role of Cx- and Panx-based channels in parasitic infections of vertebrates. In this review, available data on changes in Cx and gap junction channel changes induced by parasitic infections are summarized. Additionally, we describe recent findings that suggest possible roles of hemichannels in parasitic infections. Finally, the possibility of new therapeutic designs based on hemichannel blokers is presented.

  9. ATP- and gap junction-dependent intercellular calcium signaling in osteoblastic cells

    DEFF Research Database (Denmark)

    Jorgensen, N R; Geist, S T; Civitelli, R


    stores. In one model, IP3 traverses gap junctions and initiates the release of intracellular calcium stores in neighboring cells. Alternatively, calcium waves may be mediated not by gap junctional communication, but rather by autocrine activity of secreted ATP on P2 purinergic receptors. We studied...... mechanically induced calcium waves in two rat osteosarcoma cell lines that differ in the gap junction proteins they express, in their ability to pass microinjected dye from cell to cell, and in their expression of P2Y2 (P2U) purinergic receptors. ROS 17/2.8 cells, which express the gap junction protein...... connexin43 (Cx43), are well dye coupled, and lack P2U receptors, transmitted slow gap junction-dependent calcium waves that did not require release of intracellular calcium stores. UMR 106-01 cells predominantly express the gap junction protein connexin 45 (Cx45), are poorly dye coupled, and express P2U...

  10. Regulation of Cx43 gap junctions: the gatekeeper and the password. (United States)

    Hossain, M Z; Boynton, A L


    Gap junctions are regulatable pores that connect the cytoplasms of neighboring cells. Hossain and Boynton focus on connexin 43 gap junctions and their regulation by changing the phosphorylation status of the COOH-terminal domain of connexin 43 or by altering protein-protein interactions in this region. The COOH-terminal domain of connexin 43 appears to be a key player in regulating gap junctional communication (GJC) because many divergent signals in many different cell types modify this domain to inhibit GJC.

  11. Disruption of gap junctions attenuates aminoglycoside-elicited renal tubular cell injury (United States)

    Yao, Jian; Huang, Tao; Fang, Xin; Chi, Yuan; Zhu, Ying; Wan, Yigang; Matsue, Hiroyuki; Kitamura, Masanori


    BACKGROUND AND PURPOSE Gap junctions play important roles in the regulation of cell phenotype and in determining cell survival after various insults. Here, we investigated the role of gap junctions in aminoglycoside-induced injury to renal tubular cells. EXPERIMENTAL APPROACH Two tubular epithelial cell lines NRK-E52 and LLC-PK1 were compared for gap junction protein expression and function by immunofluorescent staining, Western blot and dye transfer assay. Cell viability after exposure to aminoglycosides was evaluated by WST assay. Gap junctions were modulated by transfection of the gap junction protein, connexin 43 (Cx43), use of Cx43 siRNA and gap junction inhibitors. KEY RESULTS NRK-E52 cells expressed abundant Cx43 and were functionally coupled by gap junctional intercellular communication (GJIC). Exposure of NRK-E52 cells to aminoglycosides, G418 and hygromycin, increased Cx43 phosphorylation and GJIC. The aminoglycosides also decreased cell viability that was prevented by gap junction inhibitors and Cx43 siRNA. LLC-PK1 cells were gap junction-deficient and resistant to aminoglycoside-induced cytotoxicity. Over-expression of a wild-type Cx43 converted LLC-PK1 cells to a drug-sensitive phenotype. The gap junction inhibitor α-glycyrrhetinic acid (α-GA) activated Akt in NRK-E52 cells. Inhibition of the Akt pathway enhanced cell toxicity to G418 and abolished the protective effects of α-GA. In addition, gentamycin-elicited cytotoxicity in NRK-E52 cells was also significantly attenuated by α-GA. CONCLUSION AND IMPLICATIONS Gap junctions contributed to the cytotoxic effects of aminoglycosides. Modulation of gap junctions could be a promising approach for prevention and treatment of aminoglycoside-induced renal tubular cell injury. PMID:20649601

  12. A history of gap junction structure: hexagonal arrays to atomic resolution. (United States)

    Grosely, Rosslyn; Sorgen, Paul L


    Gap junctions are specialized membrane structures that provide an intercellular pathway for the propagation and/or amplification of signaling cascades responsible for impulse propagation, cell growth, and development. Prior to the identification of the proteins that comprise gap junctions, elucidation of channel structure began with initial observations of a hexagonal nexus connecting apposed cellular membranes. Concomitant with technological advancements spanning over 50 years, atomic resolution structures are now available detailing channel architecture and the cytoplasmic domains that have helped to define mechanisms governing the regulation of gap junctions. Highlighted in this review are the seminal structural studies that have led to our current understanding of gap junction biology.

  13. Gap junction protein connexin43 exacerbates lung vascular permeability.

    Directory of Open Access Journals (Sweden)

    James J O'Donnell

    Full Text Available Increased vascular permeability causes pulmonary edema that impairs arterial oxygenation and thus contributes to morbidity and mortality associated with Acute Respiratory Distress Syndrome and sepsis. Although components of intercellular adhesive and tight junctions are critical for maintaining the endothelial barrier, there has been limited study of the roles of gap junctions and their component proteins (connexins. Since connexins can modulate inflammatory signaling in other systems, we hypothesized that connexins may also regulate pulmonary endothelial permeability. The relationships between connexins and the permeability response to inflammatory stimuli were studied in cultured human pulmonary endothelial cells. Prolonged treatment with thrombin, lipopolysaccharide, or pathological cyclic stretch increased levels of mRNA and protein for the major connexin, connexin43 (Cx43. Thrombin and lipopolysaccharide both increased intercellular communication assayed by transfer of microinjected Lucifer yellow. Although thrombin decreased transendothelial resistance in these cells, the response was attenuated by pretreatment with the connexin inhibitor carbenoxolone. Additionally, the decreases of transendothelial resistance produced by either thrombin or lipopolysaccharide were attenuated by reducing Cx43 expression by siRNA knockdown. Both carbenoxolone and Cx43 knockdown also abrogated thrombin-induced phosphorylation of myosin light chain. Taken together, these data suggest that increased lung vascular permeability induced by inflammatory conditions may be amplified via increased expression of Cx43 and intercellular communication among pulmonary endothelial cells.

  14. Ouabain Increases Gap Junctional Communication in Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Arturo Ponce


    Full Text Available Background/Aims: The finding that endogenous ouabain acts as a hormone prompted efforts to elucidate its physiological function. In previous studies, we have shown that 10 nM ouabain (i.e., a concentration within the physiological range modulates cell-cell contacts such as tight junctions and apical/basolateral polarity. In this study, we examined whether 10 nM ouabain affects another important cell-cell feature: gap junction communication (GJC. Methods: We employed two different approaches: 1 analysis of the cell-to-cell diffusion of neurobiotin injected into a particular MDCK cell (epithelial cells from dog kidneys in a confluent monolayer by counting the number of neighboring cells reached by the probe and 2 measurement of the electrical capacitance. Results: We found that 10 nM ouabain increase GJC by 475% within 1 hour. The Na+-K+-ATPase acts as a receptor of ouabain. In previous works we have shown that ouabain activates c-Src and ERK1/2 in 1 hour; in the present study we show that the inhibition of these proteins block the effect of ouabain on GJC. This increase in GJC does not require synthesis of new protein components, because the inhibitors cycloheximide and actinomycin D did not affect this phenomenon. Using silencing assays we also demonstrate that this ouabain-induced enhancement of GJC involves connexins 32 and 43. Conclusion: Ouabain 10 nM increases GJC in MDCK cells.

  15. Synchronization transition in gap-junction-coupled leech neurons (United States)

    Wang, Qingyun; Duan, Zhisheng; Feng, Zhaosheng; Chen, Guanrong; Lu, Qishao


    Real neurons can exhibit various types of firings including tonic spiking, bursting as well as silent state, which are frequently observed in neuronal electrophysiological experiments. More interestingly, it is found that neurons can demonstrate the co-existing mode of stable tonic spiking and bursting, which depends on initial conditions. In this paper, synchronization in gap-junction-coupled neurons with co-existing attractors of spiking and bursting firings is investigated as the coupling strength gets increased. Synchronization transitions can be identified by means of the bifurcation diagram and the correlation coefficient. It is illustrated that the coupled neurons can exhibit different types of synchronization transitions between spiking and bursting when the coupling strength increases. In the course of synchronization transitions, an intermittent synchronization can be observed. These results may be instructive to understand synchronization transitions in neuronal systems.

  16. Methamphetamine compromises gap junctional communication in astrocytes and neurons. (United States)

    Castellano, Paul; Nwagbo, Chisom; Martinez, Luis R; Eugenin, Eliseo A


    Methamphetamine (meth) is a central nervous system (CNS) stimulant that results in psychological and physical dependency. The long-term effects of meth within the CNS include neuronal plasticity changes, blood-brain barrier compromise, inflammation, electrical dysfunction, neuronal/glial toxicity, and an increased risk to infectious diseases including HIV. Most of the reported meth effects in the CNS are related to dysregulation of chemical synapses by altering the release and uptake of neurotransmitters, especially dopamine, norepinephrine, and epinephrine. However, little is known about the effects of meth on connexin (Cx) containing channels, such as gap junctions (GJ) and hemichannels (HC). We examined the effects of meth on Cx expression, function, and its role in NeuroAIDS. We found that meth altered Cx expression and localization, decreased GJ communication between neurons and astrocytes, and induced the opening of Cx43/Cx36 HC. Furthermore, we found that these changes in GJ and HC induced by meth treatment were mediated by activation of dopamine receptors, suggesting that dysregulation of dopamine signaling induced by meth is essential for GJ and HC compromise. Meth-induced changes in GJ and HC contributed to amplified CNS toxicity by dysregulating glutamate metabolism and increasing the susceptibility of neurons and astrocytes to bystander apoptosis induced by HIV. Together, our results indicate that connexin containing channels, GJ and HC, are essential in the pathogenesis of meth and increase the sensitivity of the CNS to HIV CNS disease. Methamphetamine (meth) is an extremely addictive central nervous system stimulant. Meth reduced gap junctional (GJ) communication by inducing internalization of connexin-43 (Cx43) in astrocytes and reducing expression of Cx36 in neurons by a mechanism involving activation of dopamine receptors (see cartoon). Meth-induced changes in Cx containing channels increased extracellular levels of glutamate and resulted in higher

  17. Ephaptic coupling rescues conduction failure in weakly coupled cardiac tissue with voltage-gated gap junctions (United States)

    Weinberg, S. H.


    Electrical conduction in cardiac tissue is usually considered to be primarily facilitated by gap junctions, providing a pathway between the intracellular spaces of neighboring cells. However, recent studies have highlighted the role of coupling via extracellular electric fields, also known as ephaptic coupling, particularly in the setting of reduced gap junction expression. Further, in the setting of reduced gap junctional coupling, voltage-dependent gating of gap junctions, an oft-neglected biophysical property in computational studies, produces a positive feedback that promotes conduction failure. We hypothesized that ephaptic coupling can break the positive feedback loop and rescue conduction failure in weakly coupled cardiac tissue. In a computational tissue model incorporating voltage-gated gap junctions and ephaptic coupling, we demonstrate that ephaptic coupling can rescue conduction failure in weakly coupled tissue. Further, ephaptic coupling increased conduction velocity in weakly coupled tissue, and importantly, reduced the minimum gap junctional coupling necessary for conduction, most prominently at fast pacing rates. Finally, we find that, although neglecting gap junction voltage-gating results in negligible differences in well coupled tissue, more significant differences occur in weakly coupled tissue, greatly underestimating the minimal gap junctional coupling that can maintain conduction. Our study suggests that ephaptic coupling plays a conduction-preserving role, particularly at rapid heart rates.

  18. Chemical Tumor Promoters, Oncogenes and Growth Factors: Modulators of Gap Junctional Intercellular Communication (United States)


    tives ( saccharin ), solvents (heptanol), pollutants (PCBs, PBBs), pesticides and herbicides (DDT, 2,3,5-T), nutritional factors (unsaturated fatty acids...acids and saccharin could inhibit gap junctional intercellular communication (41). Oncogenes as modulators of gap junctional intercellular communication...phosphorylation reactions, could (a) prepare the plasma membrane for active transport of regulatory ions and substrates for macromolecular synthesis


    GAP JUNCTION COMMUNICTION IN TRANSFECTED HUMAN CELL LINE: ACTION OF MELATONIN AND MAGNETIC FIELDS. OBJECTIVE: We previously showed that functional gap junction communication (GJC), as monitored by dye transfer (DT), could be enhanced in mouse C3H 10T112 cells and in mouse...

  20. Emergent Central Pattern Generator Behavior in Gap-Junction-Coupled Hodgkin-Huxley Style Neuron Model

    Directory of Open Access Journals (Sweden)

    Kyle G. Horn


    Full Text Available Most models of central pattern generators (CPGs involve two distinct nuclei mutually inhibiting one another via synapses. Here, we present a single-nucleus model of biologically realistic Hodgkin-Huxley neurons with random gap junction coupling. Despite no explicit division of neurons into two groups, we observe a spontaneous division of neurons into two distinct firing groups. In addition, we also demonstrate this phenomenon in a simplified version of the model, highlighting the importance of afterhyperpolarization currents ( to CPGs utilizing gap junction coupling. The properties of these CPGs also appear sensitive to gap junction conductance, probability of gap junction coupling between cells, topology of gap junction coupling, and, to a lesser extent, input current into our simulated nucleus.

  1. Analyzing the Effects of Gap Junction Blockade on Neural Synchrony via a Motoneuron Network Computational Model

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    Heraldo Memelli


    Full Text Available In specific regions of the central nervous system (CNS, gap junctions have been shown to participate in neuronal synchrony. Amongst the CNS regions identified, some populations of brainstem motoneurons are known to be coupled by gap junctions. The application of various gap junction blockers to these motoneuron populations, however, has led to mixed results regarding their synchronous firing behavior, with some studies reporting a decrease in synchrony while others surprisingly find an increase in synchrony. To address this discrepancy, we employ a neuronal network model of Hodgkin-Huxley-style motoneurons connected by gap junctions. Using this model, we implement a series of simulations and rigorously analyze their outcome, including the calculation of a measure of neuronal synchrony. Our simulations demonstrate that under specific conditions, uncoupling of gap junctions is capable of producing either a decrease or an increase in neuronal synchrony. Subsequently, these simulations provide mechanistic insight into these different outcomes.

  2. The role of gap junctions in inflammatory and neoplastic disorders (Review) (United States)

    Wong, Pui; Laxton, Victoria; Srivastava, Saurabh; Chan, Yin Wah Fiona; Tse, Gary


    Gap junctions are intercellular channels made of connexin proteins, mediating both electrical and biochemical signals between cells. The ability of gap junction proteins to regulate immune responses, cell proliferation, migration, apoptosis and carcinogenesis makes them attractive therapeutic targets for treating inflammatory and neoplastic disorders in different organ systems. Alterations in gap junction profile and expression levels are observed in hyperproliferative skin disorders, lymphatic vessel diseases, inflammatory lung diseases, liver injury and neoplastic disorders. It is now recognized that the therapeutic effects mediated by traditional pharmacological agents are dependent upon gap junction communication and may even act by influencing gap junction expression or function. Novel strategies for modulating the function or expression of connexins, such as the use of synthetic mimetic peptides and siRNA technology are considered. PMID:28098880

  3. Gap junctions between AII amacrine cells and calbindin-positive bipolar cells in the rabbit retina. (United States)

    Massey, S C; Mills, S L


    Electrical synapses or gap junctions occur between many retinal neurons. However, in most cases, the gap junctions have not been visualized directly. Instead, their presence has been inferred from tracer spread throughout the network of cells. Thus, tracer coupling is taken as a marker for the presence of gap junctions between coupled cells. AII amacrine cells are critical interneurons in the rod pathway of the mammalian retina. Rod bipolar cell output passes to AII amacrine cells, which in turn make conventional synapses with OFF cone bipolar cells and gap junctions with ON cone bipolar cells. Injections of biotinylated tracers into AII amacrine cells reveals coupling between the AII amacrine cell network and heterologous coupling with a variety of ON cone bipolar cells, including the calbindin-positive cone bipolar cell. To directly visualize gap junctions in this network, we prepared material for electron microscopy that was double labeled with antibodies to calretinin and calbindin to label AII amacrine cells and calbindin-positive cone bipolar cells, respectively. AII amacrine cells were postsynaptic to large vesicle-laden rod bipolar terminals, as previously reported. Gap junctions were identified between AII amacrine cells and calbindin-positive cone bipolar cell terminals identified by the presence of immunostaining and ribbon synapses. This represents direct confirmation of gap junctions between two different yet positively identified cells, which are tracer coupled, and provides additional evidence that tracer coupling with Neurobiotin indicates the presence of gap junctions. These results also definitively establish the presence of gap junctions between AII amacrine cells and calbindin bipolar cells which can therefore carry rod signals to the ON alpha ganglion cell.

  4. Bioglass promotes wound healing by affecting gap junction connexin 43 mediated endothelial cell behavior. (United States)

    Li, Haiyan; He, Jin; Yu, Hongfei; Green, Colin R; Chang, Jiang


    It is well known that gap junctions play an important role in wound healing, and bioactive glass (BG) has been shown to help healing when applied as a wound dressing. However, the effects of BG on gap junctional communication between cells involved in wound healing is not well understood. We hypothesized that BG may be able to affect gap junction mediated cell behavior to enhance wound healing. Therefore, we set out to investigate the effects of BG on gap junction related behavior of endothelial cells in order to elucidate the mechanisms through which BG is operating. In in vitro studies, BG ion extracts prevented death of human umbilical vein endothelial cells (HUVEC) following hypoxia in a dose dependent manner, possibly through connexin hemichannel modulation. In addition, BG showed stimulatory effects on gap junction communication between HUVECs and upregulated connexin43 (Cx43) expression. Furthermore, BG prompted expression of vascular endothelial growth factor and basic fibroblast growth factor as well as their receptors, and vascular endothelial cadherin in HUVECs, all of which are beneficial for vascularization. In vivo wound healing results showed that the wound closure of full-thickness excisional wounds of rats was accelerated by BG with reduced inflammation during initial stages of healing and stimulated angiogenesis during the proliferation stage. Therefore, BG can stimulate wound healing through affecting gap junctions and gap junction related endothelial cell behaviors, including prevention of endothelial cell death following hypoxia, stimulation of gap junction communication and upregulation of critical vascular growth factors, which contributes to the enhancement of angiogenesis in the wound bed and finally to accelerate wound healing. Although many studies have reported that BG stimulates angiogenesis and wound healing, this work reveals the relationship between BG and gap junction connexin 43 mediated endothelial cell behavior and elucidates

  5. Protein kinase C-dependent regulation of connexin43 gap junctions and hemichannels

    DEFF Research Database (Denmark)

    Alstrøm, Jette Skov; Stroemlund, Line Waring; Nielsen, Morten Schak


    Connexin43 (Cx43) generates intercellular gap junction channels involved in, among others, cardiac and brain function. Gap junctions are formed by the docking of two hemichannels from neighbouring cells. Undocked Cx43 hemichannels can upon different stimuli open towards the extracellular matrix...... and allow transport of molecules such as fluorescent dyes and ATP. A range of phosphorylated amino acids have been detected in the C-terminus of Cx43 and their physiological role has been intensively studied both in the gap junctional form of Cx43 and in its hemichannel configuration. We present the current...

  6. AII amacrine cells discriminate between heterocellular and homocellular locations when assembling connexin36-containing gap junctions. (United States)

    Meyer, Arndt; Hilgen, Gerrit; Dorgau, Birthe; Sammler, Esther M; Weiler, Reto; Monyer, Hannah; Dedek, Karin; Hormuzdi, Sheriar G


    Electrical synapses (gap junctions) rapidly transmit signals between neurons and are composed of connexins. In neurons, connexin36 (Cx36) is the most abundant isoform; however, the mechanisms underlying formation of Cx36-containing electrical synapses are unknown. We focus on homocellular and heterocellular gap junctions formed by an AII amacrine cell, a key interneuron found in all mammalian retinas. In mice lacking native Cx36 but expressing a variant tagged with enhanced green fluorescent protein at the C-terminus (KO-Cx36-EGFP), heterocellular gap junctions formed between AII cells and ON cone bipolar cells are fully functional, whereas homocellular gap junctions between two AII cells are not formed. A tracer injected into an AII amacrine cell spreads into ON cone bipolar cells but is excluded from other AII cells. Reconstruction of Cx36-EGFP clusters on an AII cell in the KO-Cx36-EGFP genotype confirmed that the number, but not average size, of the clusters is reduced - as expected for AII cells lacking a subset of electrical synapses. Our studies indicate that some neurons exhibit at least two discriminatory mechanisms for assembling Cx36. We suggest that employing different gap-junction-forming mechanisms could provide the means for a cell to regulate its gap junctions in a target-cell-specific manner, even if these junctions contain the same connexin.

  7. Nanostructured thin films for multiband-gap silicon triple junction solar cells

    NARCIS (Netherlands)

    Schropp, R.E.I.; Li, H. B. T.; Franken, R.H.; Rath, J.K.; van der Werf, C.H.M.; Schuttauf, J.A.; Stolk, R.L.


    By implementing nanostructure in multiband-gap proto-Si/proto-SiGe/nc-Si:H triple junction n–i–p solar cells, a considerable improvement in performance has been achieved. The unalloyed active layers in the top and bottom cell of these triple junction cells are deposited by Hot-Wire CVD. A

  8. Innexin gap junctions in nerve cells coordinate spontaneous contractile behavior in Hydra polyps (United States)

    Takaku, Yasuharu; Hwang, Jung Shan; Wolf, Alexander; Böttger, Angelika; Shimizu, Hiroshi; David, Charles N.; Gojobori, Takashi


    Nerve cells and spontaneous coordinated behavior first appeared near the base of animal evolution in the common ancestor of cnidarians and bilaterians. Experiments on the cnidarian Hydra have demonstrated that nerve cells are essential for this behavior, although nerve cells in Hydra are organized in a diffuse network and do not form ganglia. Here we show that the gap junction protein innexin-2 is expressed in a small group of nerve cells in the lower body column of Hydra and that an anti-innexin-2 antibody binds to gap junctions in the same region. Treatment of live animals with innexin-2 antibody eliminates gap junction staining and reduces spontaneous body column contractions. We conclude that a small subset of nerve cells, connected by gap junctions and capable of synchronous firing, act as a pacemaker to coordinate the contraction of the body column in the absence of ganglia.

  9. Gap junctional intercellular communication in hypoxia-ischemia-induced neuronal injury. (United States)

    Talhouk, Rabih S; Zeinieh, Michele P; Mikati, Mohamad A; El-Sabban, Marwan E


    Brain hypoxia-ischemia is a relatively common and serious problem in neonates and in adults. Its consequences include long-term histological and behavioral changes and reduction in seizure threshold. Gap junction intercellular communication is pivotal in the spread of hypoxia-ischemia related injury and in mediating its long-term effects. This review provides a comprehensive and critical review of hypoxia-ischemia and hypoxia in the brain and the potential role of gap junctions in the spread of the neuronal injury induced by these insults. It also presents the effects of hypoxia-ischemia and of hypoxia on the state of gap junctions in vitro and in vivo. Understanding the mechanisms involved in gap junction-mediated neuronal injury due to hypoxia will lead to the development of novel therapeutic strategies.

  10. Innexin gap junctions in nerve cells coordinate spontaneous contractile behavior in Hydra polyps

    KAUST Repository

    Takaku, Yasuharu


    Nerve cells and spontaneous coordinated behavior first appeared near the base of animal evolution in the common ancestor of cnidarians and bilaterians. Experiments on the cnidarian Hydra have demonstrated that nerve cells are essential for this behavior, although nerve cells in Hydra are organized in a diffuse network and do not form ganglia. Here we show that the gap junction protein innexin-2 is expressed in a small group of nerve cells in the lower body column of Hydra and that an anti-innexin-2 antibody binds to gap junctions in the same region. Treatment of live animals with innexin-2 antibody eliminates gap junction staining and reduces spontaneous body column contractions. We conclude that a small subset of nerve cells, connected by gap junctions and capable of synchronous firing, act as a pacemaker to coordinate the contraction of the body column in the absence of ganglia.

  11. Innexin gap junctions in nerve cells coordinate spontaneous contractile behavior in Hydra polyps. (United States)

    Takaku, Yasuharu; Hwang, Jung Shan; Wolf, Alexander; Böttger, Angelika; Shimizu, Hiroshi; David, Charles N; Gojobori, Takashi


    Nerve cells and spontaneous coordinated behavior first appeared near the base of animal evolution in the common ancestor of cnidarians and bilaterians. Experiments on the cnidarian Hydra have demonstrated that nerve cells are essential for this behavior, although nerve cells in Hydra are organized in a diffuse network and do not form ganglia. Here we show that the gap junction protein innexin-2 is expressed in a small group of nerve cells in the lower body column of Hydra and that an anti-innexin-2 antibody binds to gap junctions in the same region. Treatment of live animals with innexin-2 antibody eliminates gap junction staining and reduces spontaneous body column contractions. We conclude that a small subset of nerve cells, connected by gap junctions and capable of synchronous firing, act as a pacemaker to coordinate the contraction of the body column in the absence of ganglia.

  12. Gap junctional connections between hair cells, supporting cells and nerves in a vestibular organ. (United States)

    Mulroy, M J; Dempewolf, S A; Curtis, S; Iida, H C


    The pattern of gap-junctional connections between cells in the vestibular neuroepithelium of the posterior semicircular duct of the alligator lizard are described based upon the study of freeze fracture replicas and ultrathin sections with a transmission electron microscope. Both type I and type II hair cells are coupled to adjacent supporting cells by a series of small macular gap junctions located in a ring around the hair cell at the level of the apical circumferential belt of actin filaments. Adjacent supporting cells are extensively interconnected by gap junctions. A few cases of gap junctions between afferent dendrites and supporting cells, and between afferent dendrites and calyceal nerve endings were seen. These morphological observations together with data from other studies in the literature suggest a possible role for supporting cells in altering the micromechanical properties of the hair cell receptor organs during stimulation.

  13. Gap-junctional coupling between neutrophils and endothelial cells: a novel modulator of transendothelial migration. (United States)

    Zahler, Stefan; Hoffmann, Anke; Gloe, Torsten; Pohl, Ulrich


    Communication between leukocytes and endothelial cells is crucial for inflammatory reactions. Paracrine cross-talk and outside-in signaling (via adhesion molecules) have been characterized as communication pathways to date. As leukocytes and endothelial cells express connexins, we considered intercellular communication via gap junctions an intriguing additional concept. We found that gap-junctional coupling between neutrophils and endothelium occurred in a time-dependent, bidirectional manner and was facilitated by adhesion. After blockade of connexins, transmigration of neutrophils through the endothelial layer was enhanced, and the barrier function of cell monolayers was reduced during transmigration. Tumor necrosis factor alpha decreased coupling. In the presence of connexins, transmigration of neutrophils did not alter permeability. Thus, neutrophils couple to endothelium via gap junctions, functionally modulating transmigration and leakiness. Gap-junctional coupling may be a novel way of leukocyte-endothelial communication.

  14. Death of Neurons following Injury Requires Conductive Neuronal Gap Junction Channels but Not a Specific Connexin. (United States)

    Fontes, Joseph D; Ramsey, Jon; Polk, Jeremy M; Koop, Andre; Denisova, Janna V; Belousov, Andrei B


    Pharmacological blockade or genetic knockout of neuronal connexin 36 (Cx36)-containing gap junctions reduces neuronal death caused by ischemia, traumatic brain injury and NMDA receptor (NMDAR)-mediated excitotoxicity. However, whether Cx36 gap junctions contribute to neuronal death via channel-dependent or channel-independent mechanism remains an open question. To address this, we manipulated connexin protein expression via lentiviral transduction of mouse neuronal cortical cultures and analyzed neuronal death twenty-four hours following administration of NMDA (a model of NMDAR excitotoxicity) or oxygen-glucose deprivation (a model of ischemic injury). In cultures prepared from wild-type mice, over-expression and knockdown of Cx36-containing gap junctions augmented and prevented, respectively, neuronal death from NMDAR-mediated excitotoxicity and ischemia. In cultures obtained form from Cx36 knockout mice, re-expression of functional gap junction channels, containing either neuronal Cx36 or non-neuronal Cx43 or Cx31, resulted in increased neuronal death following insult. In contrast, the expression of communication-deficient gap junctions (containing mutated connexins) did not have this effect. Finally, the absence of ethidium bromide uptake in non-transduced wild-type neurons two hours following NMDAR excitotoxicity or ischemia suggested the absence of active endogenous hemichannels in those neurons. Taken together, these results suggest a role for neuronal gap junctions in cell death via a connexin type-independent mechanism that likely relies on channel activities of gap junctional complexes among neurons. A possible contribution of gap junction channel-permeable death signals in neuronal death is discussed.

  15. Gap junctions and epileptic seizures--two sides of the same coin?

    Directory of Open Access Journals (Sweden)

    Vladislav Volman

    Full Text Available Electrical synapses (gap junctions play a pivotal role in the synchronization of neuronal ensembles which also makes them likely agonists of pathological brain activity. Although large body of experimental data and theoretical considerations indicate that coupling neurons by electrical synapses promotes synchronous activity (and thus is potentially epileptogenic, some recent evidence questions the hypothesis of gap junctions being among purely epileptogenic factors. In particular, an expression of inter-neuronal gap junctions is often found to be higher after the experimentally induced seizures than before. Here we used a computational modeling approach to address the role of neuronal gap junctions in shaping the stability of a network to perturbations that are often associated with the onset of epileptic seizures. We show that under some circumstances, the addition of gap junctions can increase the dynamical stability of a network and thus suppress the collective electrical activity associated with seizures. This implies that the experimentally observed post-seizure additions of gap junctions could serve to prevent further escalations, suggesting furthermore that they are a consequence of an adaptive response of the neuronal network to the pathological activity. However, if the seizures are strong and persistent, our model predicts the existence of a critical tipping point after which additional gap junctions no longer suppress but strongly facilitate the escalation of epileptic seizures. Our results thus reveal a complex role of electrical coupling in relation to epileptiform events. Which dynamic scenario (seizure suppression or seizure escalation is ultimately adopted by the network depends critically on the strength and duration of seizures, in turn emphasizing the importance of temporal and causal aspects when linking gap junctions with epilepsy.

  16. Inter-band phase fluctuations in macroscopic quantum tunneling of multi-gap superconducting Josephson junctions

    Energy Technology Data Exchange (ETDEWEB)

    Asai, Hidehiro, E-mail: [Electronics and Photonics Research Institute (ESPRIT), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8568 (Japan); Ota, Yukihiro [CCSE, Japan Atomic Energy Agency, Kashiwa, Chiba 277-8587 (Japan); Kawabata, Shiro [Electronics and Photonics Research Institute (ESPRIT), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8568 (Japan); Nori, Franco [CEMS, RIKEN, Wako-shi, Saitama 351-0198 (Japan); Physics Department, University of Michigan, Ann Arbor, MI 48109-1040 (United States)


    Highlights: • We study MQT in Josephson junctions composed of multi-gap superconductors. • We derive a formula of the MQT escape rate for multiple phase differences. • We investigate the effect of inter-band phase fluctuation on MQT. • The MQT escape rate is significantly enhanced by the inter-band phase fluctuation. - Abstract: We theoretically investigate macroscopic quantum tunneling (MQT) in a hetero Josephson junction formed by a conventional single-gap superconductor and a multi-gap superconductor. In such Josephson junctions, phase differences for each tunneling channel are defined, and the fluctuation of the relative phase differences appear which is referred to as Josephson–Leggett’s mode. We take into account the effect of the fluctuation in the tunneling process and calculate the MQT escape rate for various junction parameters. We show that the fluctuation of relative phase differences drastically enhances the escape rate.

  17. Serotonergic transmission and gap junctional coupling in proventricular muscle cells in the American cockroach, Periplaneta americana. (United States)

    Yoshimura, Ryoichi; Suetsugu, Taeko; Endo, Yasuhisa


    The visceral muscle tissues of insects consist of striated muscle cells. The mechanisms responsible for delivering signals to the contractile muscles in the insect digestive tract remain unclear. We found that serotonergic nerves innervate the hemocoel surfaces of foregut and midgut muscles in the American cockroach. Electron microscopy of the neuromuscular junctions in the proventriculus (gizzard) revealed typical synaptic structures, the accumulation of large core/cored vesicles (neuropeptides) and small clear vesicle (neurotransmitter) at presynapses, and synaptic clefts. However, only a limited number of muscle cells, which were located in the outer part of the muscle layer, came into contact with synapses, which contained classical neurotransmitters, such as glutamate. A gap junction channel-permeable fluorescent dye, Lucifer yellow, was microinjected into single muscle cells, and it subsequently spread to several neighboring muscle cells. The dye movement occurred in the radial (hemocoel-lumen) direction rather than tangential directions. A gap junction blocker, octanol, reversibly inhibited the dye coupling. Messenger RNA for innexin 2, a gap junction-related protein, was detected in the proventriculus. These results suggest that motile signals in the insect digestive tract only reach the outermost part of the visceral muscles and are propagated to the inner muscle cells via gap junctions. Therefore, invertebrate gap junction-related proteins have potential as new targets for pest control. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Inducible deletion of connexin 40 in adult mice causes hypertension and disrupts pressure control of renin secretion

    NARCIS (Netherlands)

    Gerl, Melanie; Vöckl, Josef; Kurt, Birgül; van Veen, AAB; Kurtz, Armin; Wagner, Charlotte


    Genetic loss-of-function defects of connexin 40 in renal juxtaglomerular cells are associated with renin-dependent hypertension. The dysregulation of renin secretion results from an intrarenal displacement of renin cells and an interruption of the negative feedback control of renin secretion by

  19. Gap Junctions Contribute to Ictal/Interictal Genesis in Human Hypothalamic Hamartomas

    Directory of Open Access Journals (Sweden)

    Jie Wu


    Full Text Available Human hypothalamic hamartoma (HH is a rare subcortical lesion associated with treatment-resistant epilepsy. Cellular mechanisms responsible for epileptogenesis are unknown. We hypothesized that neuronal gap junctions contribute to epileptogenesis through synchronous activity within the neuron networks in HH tissue. We studied surgically resected HH tissue with Western-blot analysis, immunohistochemistry, electron microscopy, biocytin microinjection of recorded HH neurons, and microelectrode patch clamp recordings with and without pharmacological blockade of gap junctions. Normal human hypothalamus tissue was used as a control. Western blots showed increased expression of both connexin-36 (Cx36 and connexin-43 (Cx43 in HH tissue compared with normal human mammillary body tissue. Immunohistochemistry demonstrated that Cx36 and Cx43 are expressed in HH tissue, but Cx36 was mainly expressed within neuron clusters while Cx43 was mainly expressed outside of neuron clusters. Gap-junction profiles were observed between small HH neurons with electron microscopy. Biocytin injection into single recorded small HH neurons showed labeling of adjacent neurons, which was not observed in the presence of a neuronal gap-junction blocker, mefloquine. Microelectrode field recordings from freshly resected HH slices demonstrated spontaneous ictal/interictal-like discharges in most slices. Bath-application of gap-junction blockers significantly reduced ictal/interictal-like discharges in a concentration-dependent manner, while not affecting the action-potential firing of small gamma-aminobutyric acid (GABA neurons observed with whole-cell patch-clamp recordings from the same patient's HH tissue. These results suggest that neuronal gap junctions between small GABAergic HH neurons participate in the genesis of epileptic-like discharges. Blockade of gap junctions may be a new therapeutic strategy for controlling seizure activity in HH patients.

  20. Gap junctions in cells of the immune system: structure, regulation and possible functional roles

    Directory of Open Access Journals (Sweden)

    J.C. Sáez


    Full Text Available Gap junction channels are sites of cytoplasmic communication between contacting cells. In vertebrates, they consist of protein subunits denoted connexins (Cxs which are encoded by a gene family. According to their Cx composition, gap junction channels show different gating and permeability properties that define which ions and small molecules permeate them. Differences in Cx primary sequences suggest that channels composed of different Cxs are regulated differentially by intracellular pathways under specific physiological conditions. Functional roles of gap junction channels could be defined by the relative importance of permeant substances, resulting in coordination of electrical and/or metabolic cellular responses. Cells of the native and specific immune systems establish transient homo- and heterocellular contacts at various steps of the immune response. Morphological and functional studies reported during the last three decades have revealed that many intercellular contacts between cells in the immune response present gap junctions or "gap junction-like" structures. Partial characterization of the molecular composition of some of these plasma membrane structures and regulatory mechanisms that control them have been published recently. Studies designed to elucidate their physiological roles suggest that they might permit coordination of cellular events which favor the effective and timely response of the immune system.

  1. Regulation of gap junction channels by infectious agents and inflammation in the CNS

    Directory of Open Access Journals (Sweden)

    Paul eCastellano


    Full Text Available Gap junctions are conglomerates of intercellular channels that connect the cytoplasm of two or more cells, and facilitate the transfer of second messengers, small peptides and RNA resulting in metabolic and electrical coordination. In general, loss of gap junctional communication (GJC has been associated with cellular damage and inflammation resulting in compromise of physiological functions. Recently, it has become evident that gap junction channels also play a critical role in the pathogenesis of infectious diseases and associated inflammation. Several pathogens use the transfer of intracellular signals through GJ channels to spread infection and toxic signals that amplify inflammation to neighboring cells. Thus, identification of the mechanisms by which several infectious agents alter GJC could result in new potential therapeutic approaches to reduce inflammation and their pathogenesis.

  2. Effects of chronic gap junction conduction-enhancing antiarrhythmic peptide GAP-134 administration on experimental atrial fibrillation in dogs. (United States)

    Laurent, Gabriel; Leong-Poi, Howard; Mangat, Iqwal; Moe, Gordon W; Hu, Xudong; So, Petsy Pui-Sze; Tarulli, Emidio; Ramadeen, Andrew; Rossman, Eric I; Hennan, James K; Dorian, Paul


    Abnormal intercellular communication caused by connexin dysfunction may contribute to atrial fibrillation (AF). The present study assessed the effect of the gap junction conduction-enhancing antiarrhythmic peptide GAP-134 on AF inducibility and maintenance in a dog model of atrial cardiomyopathy. Twenty-four dogs subject to simultaneous atrioventricular pacing (220 bpm for 14 days) were randomly assigned to placebo treatment (PACED-CTRL; 12 dogs) or oral GAP-134 (2.9 mg/kg BID; PACED-GAP-134; 12 dogs) starting on day 0. UNPACED-CTRL (4 dogs) and UNPACED-GAP-134 (4 dogs) served as additional control groups. Change in left atrial (LA) systolic area from baseline to 14 days was calculated using transoesophageal echocardiography. At 14 days, animals underwent an open-chest electrophysiological study. PACED-CTRL dogs (versus UNPACED-CTRL) had a shorter estimated LA wavelength (8.0+/-1.4 versus 24.4+/-2.5 cm, P<0.05) and a greater AF vulnerability (mean AF duration, 1588+/-329 versus 25+/-34 seconds, P<0.05). Oral GAP-134 had no effect on AF vulnerability in UNPACED dogs. Compared with PACED-CTRL dogs, PACED-GAP-134 dogs had a longer estimated LA wavelength (10.2+/-2.8 versus 8.0+/-1.4 cm, respectively, P<0.05). Oral GAP-134 did not significantly reduce AF inducibility or maintenance in the entire group of 24 PACED dogs; in a subgroup of dogs (n=11) with less than 100% increase in LA systolic area, oral GAP-134 reduced AF induction from 100% to 40% and mean AF duration from 1737+/-120 to 615+/-280 seconds (P<0.05). Oral GAP-134 reduces pacing-induced decrease in LA wavelength and appears to attenuate AF vulnerability in dogs with less atrial mechanical remodeling. Gap junction modulation may affect AF in some circumstances.

  3. Targeted deletion of Aqp4 promotes the formation of astrocytic gap junctions. (United States)

    Katoozi, Shirin; Skauli, Nadia; Rahmani, Soulmaz; Camassa, Laura M A; Boldt, Henning B; Ottersen, Ole P; Amiry-Moghaddam, Mahmood


    Aquaporin-4 (AQP4) is the predominant water channel in the brain and is expressed in high density in astrocytes. By fluxing water along osmotic gradients, AQP4 contributes to brain volume and ion homeostasis. Here we ask whether deletion of Aqp4 leads to upregulation of the gap junctional proteins connexin-43 (Cx43) and connexin-30 (Cx30). These molecules couple adjacent astrocytes to each other and allow water and ions to redistribute within the astrocyte syncytium. Immunogold analysis of parietal cortex and hippocampus showed that the number of gap junctions per capillary profile is increased in AQP4 knockout (AQP4 KO) mice. The most pronounced changes were observed for Cx43 in hippocampus where the number of connexin labeled gap junctions increased by 100% following AQP4 KO. Western blot analysis of whole tissue homogenates showed no change in the amount of Cx43 or Cx30 protein after AQP4 KO. However, AQP4 KO led to a significant increase in the amount of Cx43 in a Triton X-100 insoluble fraction. This fraction is associated with connexin assembly into gap junctional plaques in the plasma membrane. In line with our immunoblot data, RT-qPCR showed no significant increase in Cx43 and Cx30 mRNA levels after AQP4 KO. Our findings suggest that AQP4 KO leads to increased aggregation of Cx43 into gap junctions and provide a putative mechanistic basis for the enhanced tracer coupling in hippocampi of AQP4 KO mice. The increased number of gap junctions in AQP4 deficient mice may explain why Aqp4 deletion has rather modest effects on brain volume and K+ homeostasis.

  4. Gap junction enhancer increases efficacy of cisplatin to attenuate mammary tumor growth.

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    Stephanie N Shishido

    Full Text Available Cisplatin treatment has an overall 19% response rate in animal models with malignant tumors. Increasing gap junction activity in tumor cells provides the targets to enhance antineoplastic therapies. Previously, a new class of substituted quinolines (PQs acts as gap junction enhancer, ability to increase the gap junctional intercellular communication, in breast cancer cells. We examined the effect of combinational treatment of PQs and antineoplastic drugs in an animal model, showing an increase in efficacy of antineoplastic drugs via the enhancement of gap junctions. Mice were implanted with estradiol-17ß (1.7 mg/pellet before the injection of 1×10⁷ T47D breast cancer cells subcutaneously into the inguinal region of mammary fat pad. Animals were treated intraperitoneally with DMSO (control, cisplatin (3.5 mg/kg, PQ (25 mg/kg, or a combining treatment of cisplatin and PQ. Cisplatin alone decreased mammary tumor growth by 85% while combinational treatment of cisplatin and PQ1 or PQ7 showed an additional reduction of 77% and 22% of tumor growth after 7 treatments at every 2 days, respectively. Histological results showed a significant increase of gap junction proteins, Cx43 and Cx26, in PQ-treated tissues compared to control or cisplatin. Furthermore, evidence of highly stained caspase 3 in tumors of combinational treatment (PQ and cisplatin was seen compared to cisplatin alone. We have showed for the first time an increase in the efficacy of antineoplastic drugs through a combinational treatment with PQs, a specific class of gap junction enhancers.

  5. Modulation of Asymmetric Flux in Heterotypic Gap Junctions by Pore Shape, Particle Size and Charge. (United States)

    Mondal, Abhijit; Sachse, Frank B; Moreno, Alonso P


    Gap junction channels play a vital role in intercellular communication by connecting cytoplasm of adjoined cells through arrays of channel-pores formed at the common membrane junction. Their structure and properties vary depending on the connexin isoform(s) involved in forming the full gap junction channel. Lack of information on the molecular structure of gap junction channels has limited the development of computational tools for single channel studies. Currently, we rely on cumbersome experimental techniques that have limited capabilities. We have earlier reported a simplified Brownian dynamics gap junction pore model and demonstrated that variations in pore shape at the single channel level can explain some of the differences in permeability of heterotypic channels observed in in vitro experiments. Based on this computational model, we designed simulations to study the influence of pore shape, particle size and charge in homotypic and heterotypic pores. We simulated dye diffusion under whole cell voltage clamping. Our simulation studies with pore shape variations revealed a pore shape with maximal flux asymmetry in a heterotypic pore. We identified pore shape profiles that match the in silico flux asymmetry results to the in vitro results of homotypic and heterotypic gap junction formed out of Cx43 and Cx45. Our simulation results indicate that the channel's pore-shape established flux asymmetry and that flux asymmetry is primarily regulated by the sizes of the conical and/or cylindrical mouths at each end of the pore. Within the set range of particle size and charge, flux asymmetry was found to be independent of particle size and directly proportional to charge magnitude. While particle charge was vital to creating flux asymmetry, charge magnitude only scaled the observed flux asymmetry. Our studies identified the key factors that help predict asymmetry. Finally, we suggest the role of such flux asymmetry in creating concentration imbalances of messenger

  6. Synopsis of the International Gap Junction Conference in Elsinore, Denmark August 5-9, 2007

    DEFF Research Database (Denmark)

    Willecke, Klaus; Nielsen, Morten Schak


    This synopsis covers the main results and conclusions from the platform presentations during the International Gap Junction Conference. More detailed information is provided in the mini reviews on controversial scientific issues, short reports of research results and conference abstracts published...... in this issue of Cell Communication and Adhesion....

  7. A unified framework for spiking and gap-junction interactions in distributed neuronal network simulations (United States)

    Hahne, Jan; Helias, Moritz; Kunkel, Susanne; Igarashi, Jun; Bolten, Matthias; Frommer, Andreas; Diesmann, Markus


    Contemporary simulators for networks of point and few-compartment model neurons come with a plethora of ready-to-use neuron and synapse models and support complex network topologies. Recent technological advancements have broadened the spectrum of application further to the efficient simulation of brain-scale networks on supercomputers. In distributed network simulations the amount of spike data that accrues per millisecond and process is typically low, such that a common optimization strategy is to communicate spikes at relatively long intervals, where the upper limit is given by the shortest synaptic transmission delay in the network. This approach is well-suited for simulations that employ only chemical synapses but it has so far impeded the incorporation of gap-junction models, which require instantaneous neuronal interactions. Here, we present a numerical algorithm based on a waveform-relaxation technique which allows for network simulations with gap junctions in a way that is compatible with the delayed communication strategy. Using a reference implementation in the NEST simulator, we demonstrate that the algorithm and the required data structures can be smoothly integrated with existing code such that they complement the infrastructure for spiking connections. To show that the unified framework for gap-junction and spiking interactions achieves high performance and delivers high accuracy in the presence of gap junctions, we present benchmarks for workstations, clusters, and supercomputers. Finally, we discuss limitations of the novel technology. PMID:26441628

  8. Intrinsic islet heterogeneity and gap junction coupling determine spatiotemporal Ca²⁺ wave dynamics. (United States)

    Benninger, Richard K P; Hutchens, Troy; Head, W Steven; McCaughey, Michael J; Zhang, Min; Le Marchand, Sylvain J; Satin, Leslie S; Piston, David W


    Insulin is released from the islets of Langerhans in discrete pulses that are linked to synchronized oscillations of intracellular free calcium ([Ca(2+)]i). Associated with each synchronized oscillation is a propagating calcium wave mediated by Connexin36 (Cx36) gap junctions. A computational islet model predicted that waves emerge due to heterogeneity in β-cell function throughout the islet. To test this, we applied defined patterns of glucose stimulation across the islet using a microfluidic device and measured how these perturbations affect calcium wave propagation. We further investigated how gap junction coupling regulates spatiotemporal [Ca(2+)]i dynamics in the face of heterogeneous glucose stimulation. Calcium waves were found to originate in regions of the islet having elevated excitability, and this heterogeneity is an intrinsic property of islet β-cells. The extent of [Ca(2+)]i elevation across the islet in the presence of heterogeneity is gap-junction dependent, which reveals a glucose dependence of gap junction coupling. To better describe these observations, we had to modify the computational islet model to consider the electrochemical gradient between neighboring β-cells. These results reveal how the spatiotemporal [Ca(2+)]i dynamics of the islet depend on β-cell heterogeneity and cell-cell coupling, and are important for understanding the regulation of coordinated insulin release across the islet. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. Intrinsic Islet Heterogeneity and Gap Junction Coupling Determine Spatiotemporal Ca2+ Wave Dynamics (United States)

    Benninger, Richard K.P.; Hutchens, Troy; Head, W. Steven; McCaughey, Michael J.; Zhang, Min; Le Marchand, Sylvain J.; Satin, Leslie S.; Piston, David W.


    Insulin is released from the islets of Langerhans in discrete pulses that are linked to synchronized oscillations of intracellular free calcium ([Ca2+]i). Associated with each synchronized oscillation is a propagating calcium wave mediated by Connexin36 (Cx36) gap junctions. A computational islet model predicted that waves emerge due to heterogeneity in β-cell function throughout the islet. To test this, we applied defined patterns of glucose stimulation across the islet using a microfluidic device and measured how these perturbations affect calcium wave propagation. We further investigated how gap junction coupling regulates spatiotemporal [Ca2+]i dynamics in the face of heterogeneous glucose stimulation. Calcium waves were found to originate in regions of the islet having elevated excitability, and this heterogeneity is an intrinsic property of islet β-cells. The extent of [Ca2+]i elevation across the islet in the presence of heterogeneity is gap-junction dependent, which reveals a glucose dependence of gap junction coupling. To better describe these observations, we had to modify the computational islet model to consider the electrochemical gradient between neighboring β-cells. These results reveal how the spatiotemporal [Ca2+]i dynamics of the islet depend on β-cell heterogeneity and cell-cell coupling, and are important for understanding the regulation of coordinated insulin release across the islet. PMID:25468351

  10. Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate

    NARCIS (Netherlands)

    van Zeijl, Leonie; Ponsioen, Bas; Giepmans, Ben N G; Ariaens, Aafke; Postma, Friso R; Várnai, Péter; Balla, Tamas; Divecha, Nullin; Jalink, Kees; Moolenaar, Wouter H


    Cell-cell communication through connexin43 (Cx43)-based gap junction channels is rapidly inhibited upon activation of various G protein coupled receptors; however, the mechanism is unknown. We show that Cx43-based cell-cell communication is inhibited by depletion of phosphatidylinositol

  11. Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Hideyuki eTakeuchi


    Full Text Available Microglia are macrophage-like resident immune cells that contribute to the maintenance of homeostasis in the central nervous system (CNS. Abnormal activation of microglia can cause damage in the CNS, and accumulation of activated microglia is a characteristic pathological observation in neurologic conditions such as trauma, stroke, inflammation, epilepsy, and neurodegenerative diseases. Activated microglia secrete high levels of glutamate, which damages CNS cells and has been implicated as a major cause of neurodegeneration in these conditions. Glutamate-receptor blockers and microglia inhibitors (e.g. minocycline have been examined as therapeutic candidates for several neurodegenerative diseases; however, these compounds exerted little therapeutic benefit because they either perturbed physiological glutamate signals or suppressed the actions of protective microglia. The ideal therapeutic approach would hamper the deleterious roles of activated microglia without diminishing their protective effects. We recently found that abnormally activated microglia secrete glutamate via gap-junction hemichannels on the cell surface. Moreover, administration of gap-junction inhibitors significantly suppressed excessive microglial glutamate release and improved disease symptoms in animal models of neurologic conditions such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer’s disease. Recent evidence also suggests that neuronal and glial communication via gap junctions amplifies neuroinflammation and neurodegeneration. Elucidation of the precise pathologic roles of gap junctions and hemichannels may lead to a novel therapeutic strategies that can slow and halt the progression of neurodegenerative diseases.

  12. Impact of Gap Junctional Intercellular Communication on MLO-Y4 Sclerostin and Soluble Factor Expression. (United States)

    York, S L; Sethu, P; Saunders, M M


    Bone remodeling is a continual process in which old bone is resorbed by osteoclasts and new bone is formed by osteoblasts, providing a mechanism for bones' ability to adapt to changes in its mechanical environment. While the role of osteoblasts and osteoclasts in bone remodeling is well understood, the cellular regulation of bone remodeling is unclear. One theory is that osteocytes, found within bone, play an important role in controlling the bone remodeling response. Osteocytes possess gap junctions, narrow channels that extend between nearby cells and allow communication between cells via the transfer of small molecules and ions. This work investigated the potential role of gap junctional intercellular communication in bone remodeling by exposing osteocyte-like MLO-Y4 cells to mechanical strains and quantifying the expression of soluble factors, including sclerostin, a protein closely associated with bone remodeling. The soluble factors and sclerostin expression were further examined after inhibiting gap junctional intercellular communication to study the impact of the communication. At supraphysiologic strains, the inhibition of gap junctional intercellular communication led to increases in sclerostin expression relative to cells in which communication was present, indicating that the communication may play a significant role in regulating bone remodeling.

  13. Increased phosphorylation of Cx36 gap junctions in the AII amacrine cells of RD retina. (United States)

    Ivanova, Elena; Yee, Christopher W; Sagdullaev, Botir T


    Retinal degeneration (RD) encompasses a family of diseases that lead to photoreceptor death and visual impairment. Visual decline due to photoreceptor cell loss is further compromised by emerging spontaneous hyperactivity in inner retinal cells. This aberrant activity acts as a barrier to signals from the remaining photoreceptors, hindering therapeutic strategies to restore light sensitivity in RD. Gap junctions, particularly those expressed in AII amacrine cells, have been shown to be integral to the generation of aberrant activity. It is unclear whether gap junction expression and coupling are altered in RD. To test this, we evaluated the expression and phosphorylation state of connexin36 (Cx36), the gap junction subunit predominantly expressed in AII amacrine cells, in two mouse models of RD, rd10 (slow degeneration) and rd1 (fast degeneration). Using Ser293-P antibody, which recognizes a phosphorylated form of connexin36, we found that phosphorylation of connexin36 in both slow and fast RD models was significantly greater than in wildtype controls. This elevated phosphorylation may underlie the increased gap junction coupling of AII amacrine cells exhibited by RD retina.

  14. Effect of gap junction distribution on impulse propagation in a monolayer of myocytes: a model study. (United States)

    Hubbard, Marjorie Letitia; Ying, Wenjun; Henriquez, Craig S


    To use microstructural computer models to study how four features of myocardial architecture affect propagation: brick wall tissue structures, jutting at cell ends, gap junction distribution and conductance along cell borders, and increased structural discontinuity. Simulations of longitudinal and transverse plane wave propagation and point propagation were performed in several two-dimensional (2D) microstructural models of adult cardiac tissue. Conduction velocities and maximum upstroke velocities were measured for a range of gap junction conductances and distributions. In tissue models with normal to low connectivity, brick wall architecture and jutting decrease cell-to-cell delay, increase longitudinal conduction velocity, and decrease longitudinal maximum upstroke velocity. Transverse conduction velocity also increases if the overlap or jutting introduces additional lateral (side-to-side) connections between myocytes. Both end-to-end and side-to-side interplicate gap junctions increase longitudinal and transverse conduction velocity; however, side-to-side interplicate gap junctions have the greatest influence on transverse conduction velocity and longitudinal and transverse maximum upstroke velocity. The complex structure of myocardium creates additional pathways of current flow that enhance both longitudinal and transverse propagation. These alternative pathways of current help to maintain conduction as connectivity between cells decreases.

  15. Chemopreventive agents attenuate rapid inhibition of gap junctional intercellular communication induced by environmental toxicants

    Czech Academy of Sciences Publication Activity Database

    Babica, Pavel; Čtveráčková, Lucie; Lenčešová, Zuzana; Trosko, J. E.; Upham, B. L.


    Roč. 68, č. 5 (2016), s. 827-837 ISSN 0163-5581 R&D Projects: GA MŠk LH12034 Institutional support: RVO:67985939 Keywords : gap junctional intercellular communication * chemopreventive agents * environmental toxicants Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.447, year: 2016

  16. Lack of biocytin transfer at gap junctions in the chicken vestibular nuclei. (United States)

    Arabshahi, A; Giaume, C; Peusner, K D


    In vivo experiments were designed to test for functional gap junctions at 'mixed' synapses that were morphologically characterized between the large-diameter, primary vestibular fibers and second-order vestibular neurons in the chicken, Gallus gallus. In previous intracellular recordings and dye injections into these neurons from brain slice preparations of chick embryos (E15/16) and also newborn hatchlings (HI-2), no evidence was obtained for functional gap junctions. Therefore, biocytin, a low molecular weight tracer that permeates gap junction channels, was extracellularly applied to either the ampullary nerves or to the vestibular ganglion of 3-6 day old hatchlings and adult chickens (9 months). This procedure resulted in the uptake of the dye and heavy staining of both the thick and thin fibers composing the vestibular nerve and in loading of vestibular efferent neurons. However, no dye transfer was observed between the large-diameter, primary vestibular fibers and second-order vestibular neurons. This observation, which was performed using a relatively non-invasive approach on intact animals, suggests that the gap junctions at these mixed synapses are probably not functional under the conditions of these experiments.


    OBJECTIVE: We have previously shown that gap junction communication (GJC) in mouse primary hepatocytes can be enhanced by treatment with physiological levels of melatonin, and that 45-Hz magnetic fields can eliminate this enhancement in a time-dependent manner. The objective of t...

  18. Interfering amino terminal peptides and functional implications for heteromeric gap junction formation

    Directory of Open Access Journals (Sweden)

    Richard David Veenstra


    Full Text Available Connexin43 (Cx43 is widely expressed in many different tissues of the human body. In cells of some organs, Cx43 is co-expressed with other connexins (Cx, including Cx46 and Cx50 in lens, Cx40 in atrium, Purkinje fibers, and the blood vessel wall, Cx45 in heart, and Cx37 in the ovary. Interactions with the co-expressed connexins may have profound functional implications. The abilities of Cx37, Cx45, Cx46, and Cx50 to function in heteromeric gap junction combinations with Cx43 are well documented. Different studies disagree regarding the ability of Cx43 and Cx40 to produce functional heteromeric gap junctions with each other. We review previous studies regarding the heteromeric interactions of Cx43. The possibility of negative functional interactions between the cytoplasmic pore-forming amino terminal (NT domains of these connexins was assessed using pentameric connexin sequence-specific NT domain (iNT peptides applied to cells expressing homomeric Cx40, Cx37, Cx45, Cx46, and Cx50 gap junctions. A Cx43 iNT peptide corresponding to amino acids 9 to 13 (Ac-KLLDK-NH2 specifically inhibited the electrical coupling of Cx40 gap junctions in a transjunctional (Vj voltage-dependent manner without affecting the function of homologous Cx37, Cx46, Cx50, and Cx45 gap junctions. A Cx40 iNT (Ac-EFLEE-OH peptide counteracted the Vj-dependent block of Cx40 gap junctions, whereas a similarly charged Cx50 iNT (Ac-EEVNE-OH peptide did not, suggesting that these NT domain interactions are not solely based on electrostatics. These data are consistent with functional Cx43 heteromeric gap junction formation with Cx37, Cx45, Cx46, and Cx50 and suggest that Cx40 uniquely experiences functional suppressive interactions with a Cx43 NT domain sequence. These findings present unique functional implications about the heteromeric interactions between Cx43 and Cx40 that may influence cardiac conduction in atrial myocardium and the specialized conduction system.

  19. Gap junctional regulatory mechanisms in the AII amacrine cell of the rabbit retina. (United States)

    Xia, Xiao-Bo; Mills, Stephen L


    Gap junctions are commonplace in retina, often between cells of the same morphological type, but sometimes linking different cell types. The strength of coupling between cells derives from the properties of the connexins, but also is regulated by the intracellular environment of each cell. We measured the relative coupling of two different gap junctions made by AII amacrine cells of the rabbit retina. Permeability to the tracer Neurobiotin was measured at different concentrations of the neuromodulators dopamine, nitric oxide, or cyclic adenosine monophosphate (cAMP) analogs. Diffusion coefficients were calculated separately for the gap junctions between pairs of AII amacrine cells and for those connecting AII amacrine cells with ON cone bipolar cells. Increased dopamine caused diffusion rates to decline more rapidly across the AII-AII gap junctions than across the AII-bipolar cell gap junctions. The rate of decline at these sites was well fit by a model proposing that dopamine modulates two independent gates in AII-AII channels, but only a single gate on the AII side of the AII-bipolar channel. However, a membrane-permeant cAMP agonist modulated both types of channel equally. Therefore, the major regulator of channel closure in this network is the local cAMP concentration within each cell, as regulated by dopamine, rather than different cAMP sensitivity of their respective gates. In contrast, nitric oxide preferentially reduced AII-bipolar cell permeabilities. Coupling from AII amacrine cells to the different bipolar cell subtypes was differentially affected by dopamine, indicating that light adaptation acting via dopamine release alters network coupling properties in multiple ways.

  20. Sustained inhibition of rat myometrial gap junctions and contractions by lindane

    Directory of Open Access Journals (Sweden)

    Grindatti Carmen M


    Full Text Available Abstract Background Gap junctions increase in size and abundance coincident with parturition, forming an intercellular communication network that permits the uterus to develop the forceful, coordinated contractions necessary for delivery of the fetus. Lindane, a pesticide used in the human and veterinary treatment of scabies and lice as well as in agricultural applications, inhibits uterine contractions in vitro, inhibits myometrial gap junctions, and has been associated with prolonged gestation length in rats. The aim of the present study was to investigate whether brief exposures to lindane would elicit sustained inhibition of rat uterine contractile activity and myometrial gap junction intercellular communication. Methods To examine effects on uterine contraction, longitudinal uterine strips isolated from late gestation (day 20 rats were exposed to lindane in muscle baths and monitored for changes in spontaneous phasic contractions during and after exposure to lindane. Lucifer yellow dye transfer between myometrial cells in culture was used to monitor gap junction intercellular communication. Results During a 1-h exposure, 10 micro M and 100 micro M lindane decreased peak force and frequency of uterine contraction but 1 micro M lindane did not. After removal of the exposure buffer, contraction force remained significantly depressed in uterine strips exposed to 100 micro M lindane, returning to less than 50% basal levels 5 h after cessation of lindane exposure. In cultured myometrial myocytes, significant sustained inhibition of Lucifer yellow dye transfer was observed 24 h after lindane exposures as brief as 10 min and as low as 0.1 micro M lindane. Conclusion Brief in vitro exposures to lindane have long-term effects on myometrial functions that are necessary for parturition, inhibiting spontaneous phasic contractions in late gestation rat uterus and gap junction intercellular communication in myometrial cell cultures.


    Directory of Open Access Journals (Sweden)

    S. Yu. Nikulina


    Full Text Available Aim. To study the association of hereditary sick sinus syndrome (SSS with connexin 40 gene (Cx40 polymorphism. Material and methods. 29 families with hereditary SSS were involved into prospective study. Probands were 20 women and 9 men (aged 58±0.15. Relatives, I-III degree of kinship, were 65 men and 68 women (aged 39±0.13. Clinical and instrumental examination was performed in all probands and their relatives. Diagnosis of SSS was verified by transesophageal atrial electrostimulation. Molecular genetic investigation of SSS patients and their relatives was carried out in laboratory of medical genetics of Research Institute of Therapy , Siberian Branch of Russian Academy of Medical Sciences. Results. 71 SSS patients, 44 their healthy relatives, I-III degree of kinship, 197 subjects of control group were genotyped for the polymorphism of 44G>A of gene Cx40. According to allele-specific polymerase chain reaction 3 types of genotypes ADRA2B (II — homozygous wild, ID — heterozygous, DD — homozygous mutant were found in SSS patients, their relatives and healthy subjects of control group. Conclusion. Significant predominance of the heterozygous genotype 44G>A was found in SSS (45,07±5,9% patients in comparison with subjects of the control group (29,44±3,2%.

  2. Above-gap conductance anomaly studied in superconductor-graphene-superconductor Josephson junctions

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jae-Hyun; Lee, Hu-Jong [Pohang University of Science and Technology, Pohang (Korea, Republic of); Doh, Yong-Joo [Korea University, Yeongigun (Korea, Republic of)


    We investigated the electrical transport properties of superconductor-graphene-superconductor (SGS) Josephson junctions. At low voltage bias, we observed the conventional proximity-coupled Josephson effect, such as supercurrent flow through graphene, a sub-gap structure of differential conductance due to Andreev reflection, and a periodic modulation of the critical current I{sub c} when a perpendicular magnetic field H is applied to the graphene. For high bias above the superconducting gap voltage, however, we observed an anomalous jump of the differential conductance, the voltage position of which is sensitive to the backgate voltage V{sub g}. Our extensive study with varying V{sub g}, temperature, and H reveals that the above-gap structure takes place at a characteristic power P{sup *}, irrespective of V{sub g}, for a given junction. The temperature and the H dependences of P{sup *} are well explained by an increase in the electron temperature in graphene.

  3. Connexin43 Mutation Causes Heterogeneous Gap Junction Loss and Sudden Infant Death (United States)

    Van Norstrand, David W.; Asimaki, Angeliki; Rubinos, Clio; Dolmatova, Elena; Srinivas, Miduturu; Tester, David J.; Saffitz, Jeffrey E.; Duffy, Heather S.; Ackerman, Michael J.


    Background An estimated 10-15% of sudden infant death syndrome (SIDS) may stem from channelopathy-mediated lethal arrhythmias. Loss of the GJA1-encoded gap junction channel protein connexin43 (Cx43) is known to underlie formation of lethal arrhythmias. GJA1 mutations have been associated with cardiac diseases including atrial fibrillation. Therefore, GJA1 is a plausible candidate gene for premature sudden death. Methods and Results GJA1 open reading frame mutational analysis was performed using PCR, DHPLC, and direct DNA sequencing on DNA from 292 SIDS cases. Immunofluorescence and dual whole cell patch-clamp studies were performed to determine functionality of mutant gap junctions. Immunostaining for gap junction proteins was performed on SIDS-associated paraffin-embedded cardiac tissue. Two rare, novel missense mutations, E42K and S272P, were detected in 2 of 292 SIDS cases, a 2-month-old white male and a 3-month-old white female, respectively. Analysis of the E42K victim’s parental DNA demonstrated a de novo mutation. Both mutations involved highly conserved residues and were absent in over 1000 ethnic-matched reference alleles. Immunofluorescence demonstrated no trafficking abnormalities for either mutation and S272P demonstrated wildtype junctional conductance. However, junctional conductance measurements for the E42K mutation demonstrated a loss-of-function not rescued by wildtype. Moreover, the E42K victim cardiac tissue demonstrated a mosaic immunostaining pattern for Cx43 protein. Conclusions This study provides the first molecular and functional evidence implicating a GJA1 mutation as a novel pathogenic substrate for SIDS. E42K-Cx43 demonstrated a trafficking-independent reduction in junctional coupling in vitro as well as demonstrating a mosaic pattern of mutational DNA distribution in deceased cardiac tissue, suggesting a novel mechanism of Cx43-associated sudden death. PMID:22179534

  4. The antiarrhythmic peptide analog rotigaptide (ZP123) stimulates gap junction intercellular communication in human osteoblasts and prevents decrease in femoral trabecular bone strength in ovariectomized rats

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne


    Gap junctions play an important role in bone development and function, but the lack of pharmacological tools has hampered the gap junction research. The antiarrhythmic peptides stimulate gap junction communication between cardiomyocytes, but effects in noncardiac tissue are unknown. The purpose o...

  5. Two classes of gap junction channels mediate soma-germline interactions essential for germline proliferation and gametogenesis in Caenorhabditis elegans. (United States)

    Starich, Todd A; Hall, David H; Greenstein, David


    In all animals examined, somatic cells of the gonad control multiple biological processes essential for germline development. Gap junction channels, composed of connexins in vertebrates and innexins in invertebrates, permit direct intercellular communication between cells and frequently form between somatic gonadal cells and germ cells. Gap junctions comprise hexameric hemichannels in apposing cells that dock to form channels for the exchange of small molecules. Here we report essential roles for two classes of gap junction channels, composed of five innexin proteins, in supporting the proliferation of germline stem cells and gametogenesis in the nematode Caenorhabditis elegans. Transmission electron microscopy of freeze-fracture replicas and fluorescence microscopy show that gap junctions between somatic cells and germ cells are more extensive than previously appreciated and are found throughout the gonad. One class of gap junctions, composed of INX-8 and INX-9 in the soma and INX-14 and INX-21 in the germ line, is required for the proliferation and differentiation of germline stem cells. Genetic epistasis experiments establish a role for these gap junction channels in germline proliferation independent of the glp-1/Notch pathway. A second class of gap junctions, composed of somatic INX-8 and INX-9 and germline INX-14 and INX-22, is required for the negative regulation of oocyte meiotic maturation. Rescue of gap junction channel formation in the stem cell niche rescues germline proliferation and uncovers a later channel requirement for embryonic viability. This analysis reveals gap junctions as a central organizing feature of many soma-germline interactions in C. elegans. Copyright © 2014 by the Genetics Society of America.

  6. Estimation of the effective intercellular diffusion coefficient in cell monolayers coupled by gap junctions

    DEFF Research Database (Denmark)

    Olesen, Niels Erik; Hofgaard, Johannes P; von Holstein-Rathlou, Niels-Henrik


    A recently developed dye-based assay to study gap junction permeability is analysed. The assay is based on electroporation of dye into a large number of connexin 43 expressing cells, grown to confluency on electrically conductive slides. The subsequent intercellular spread of dye to non-electropo......A recently developed dye-based assay to study gap junction permeability is analysed. The assay is based on electroporation of dye into a large number of connexin 43 expressing cells, grown to confluency on electrically conductive slides. The subsequent intercellular spread of dye to non......-electroporated parts of the monolayer enables estimation of the intercellular coupling. So far, the extent of dye spread has been analyzed in qualitative terms only and not in a manner based directly on the physics of the underlying diffusion process....

  7. Effect of sound on gap-junction-based intercellular signaling: Calcium waves under acoustic irradiation. (United States)

    Deymier, P A; Swinteck, N; Runge, K; Deymier-Black, A; Hoying, J B


    We present a previously unrecognized effect of sound waves on gap-junction-based intercellular signaling such as in biological tissues composed of endothelial cells. We suggest that sound irradiation may, through temporal and spatial modulation of cell-to-cell conductance, create intercellular calcium waves with unidirectional signal propagation associated with nonconventional topologies. Nonreciprocity in calcium wave propagation induced by sound wave irradiation is demonstrated in the case of a linear and a nonlinear reaction-diffusion model. This demonstration should be applicable to other types of gap-junction-based intercellular signals, and it is thought that it should be of help in interpreting a broad range of biological phenomena associated with the beneficial therapeutic effects of sound irradiation and possibly the harmful effects of sound waves on health.

  8. Central sensitization in medullary dorsal horn involves gap junctions and hemichannels


    Chiang, Chen Yu; Li, Zhaohui; Dostrovsky, Jonathan O.; Barry J Sessle


    Central sensitization is a fundamental mechanism contributing to acute and chronic pain conditions. Our previous studies have documented a glutamatergic-, purinergic- and glial-dependent central sensitization that can be induced in rat medullary dorsal horn (MDH) nociceptive neurons by mustard oil (MO) application to the tooth pulp. The present study demonstrated that carbenoxolone, a potent gap junction and hemichannel blocker, completely blocked all parameters of MO-induced central sensitiz...

  9. Robert Feulgen Prize Lecture. Distribution and role of gap junctions in normal myocardium and human ischaemic heart disease. (United States)

    Green, C R; Severs, N J


    In the heart, individual cardiac muscle cells are linked by gap junctions. These junctions form low resistance pathways along which the electrical impulse flows rapidly and repeatedly between all the cells of the myocardium, ensuring their synchronous contraction. To obtain probes for mapping the distribution of gap junctions in cardiac tissue, polyclonal antisera were raised to three synthetic peptides, each matching different cytoplasmically exposed portions of the sequence of connexin43, the major gap-junctional protein reported in the heart. The specificity of each antiserum for the peptide to which it was raised was established by dot blotting. New methods were developed for isolating enriched fractions of gap junctions from whole heart and from dissociated adult myocytes, in which detergent-treatment and raising the temperature (potentially damaging steps in previously described techniques) are avoided. Analysis of these fractions by SDS-polyacrylamide gel electrophoresis revealed major bands at 43 kDa (matching the molecular mass of connexin43) and at 70 kDa. Western blot experiments using our antisera indicated that both the 43-kDa and the 70-kDa bands represent cardiac gap-junctional proteins. Pre-embedding immunogold labelling of isolated gap junctions and post-embedding immunogold labelling of Lowicryl-embedded whole tissue demonstrated the specific binding of the antibodies to ultrastructurally defined gap junctions. One antiserum (raised to residues 131-142) was found to be particularly effective for cytochemical labelling. Using this antiserum for immunofluorescence labelling in combination with confocal scanning laser microscopy enabled highly sensitive detection and three-dimensional mapping of gap junctions through thick slices of cardiac tissue. By means of the serial optical sectioning ability of the confocal microscope, images of the entire gap junction population of complete en face-viewed disks were reconstructed. These reconstructions reveal

  10. NBT-II carcinoma behaviour is not dependent on cell-cell communication through gap junctions. (United States)

    Lesueur, F; Mesnil, M; Delouvée, A; Girault, J M; Yamasaki, H; Thiery, J P; Jouanneau, J


    To study the mechanism(s) underlying the proliferation of heterogeneous cell populations within a solid tumour, the NBT-II rat bladder carcinoma system was used. It has been first investigated whether the different cell populations are coupled through gap junctions (GJIC). Cells overexpressing the Cx43 were generated to test for any tumour suppressive activity in vivo. To determine whether GJIC is essential for tumour proliferation and the establishment of a cooperative community effect, NBT-II cells that are incompetent for cell coupling were generated. The data report that (i) carcinoma cells expressing or not FGF-1 are coupled through GJIC in vitro and in coculture and express the gap junction protein Cx43, (ii) overexpression of Cx43 in these cells does not affect their in vitro coupling capacities and in vivo tumourigenic growth properties, (iii) inhibition of GJIC through antisense strategy has no in vivo obvious consequence on the tumour growth properties of the carcinoma, and (iv) the community effect between two carcinoma cell populations does not critically involve cell coupling through gap junctions.

  11. Critical role of gap junction coupled KATP channel activity for regulated insulin secretion.

    Directory of Open Access Journals (Sweden)

    Jonathan V Rocheleau


    Full Text Available Pancreatic beta-cells secrete insulin in response to closure of ATP-sensitive K+ (KATP channels, which causes membrane depolarization and a concomitant rise in intracellular Ca2+ (Cai. In intact islets, beta-cells are coupled by gap junctions, which are proposed to synchronize electrical activity and Cai oscillations after exposure to stimulatory glucose (>7 mM. To determine the significance of this coupling in regulating insulin secretion, we examined islets and beta-cells from transgenic mice that express zero functional KATP channels in approximately 70% of their beta-cells, but normal KATP channel density in the remainder. We found that KATP channel activity from approximately 30% of the beta-cells is sufficient to maintain strong glucose dependence of metabolism, Cai, membrane potential, and insulin secretion from intact islets, but that glucose dependence is lost in isolated transgenic cells. Further, inhibition of gap junctions caused loss of glucose sensitivity specifically in transgenic islets. These data demonstrate a critical role of gap junctional coupling of KATP channel activity in control of membrane potential across the islet. Control via coupling lessens the effects of cell-cell variation and provides resistance to defects in excitability that would otherwise lead to a profound diabetic state, such as occurs in persistent neonatal diabetes mellitus.

  12. Gap junctional intercellular communication and cytoskeletal organization in chondrocytes in suspension in an ultrasound trap. (United States)

    Bazou, Despina; Dowthwaite, Gary P; Khan, Ilyas M; Archer, Charles W; Ralphs, James R; Coakley, W Terence


    Particles or cells suspended in an appropriately designed ultrasound standing wave field can be aggregated at a node to form a single monolayer in a plane that can be interrogated microscopically. The approach is applied here to investigate the temporal development of F-actin and Cx43 distribution and of gap junctional intercellular communication in 2-D chondrocyte aggregates (monolayers) rapidly and synchronously formed and held in suspension in an ultrasound trap. Development of the F-actin cytoskeleton in the confluent single layer of 'cuboidal' cells forming the aggregate was completed within 1 h. Chondrocytes levitated in the trap synchronously formed functional gap junctions (as assessed by CMFDA dye transfer assays) in less than 1 h of initiation of cell-cell contact in the trap. It was shown that Cx43 gene expression was retained in isolated chondrocytes in suspension. Preincubation of cells with the protein synthesis inhibitor cycloheximide caused a six-fold decrease in Cx43 accumulation (as assessed by immunofluorescence) at the interfaces of chondrocytes in the aggregate. It is shown that the ultrasound trap provides an approach to studying the early stages of cytoskeletal and gap junction development as cells progress from physical aggregation, through molecular adhesion, to display the intracellular consequences of receptor interactions.

  13. Inhibition of dye-coupling in Patella (mollusca) embryos by microinjection of antiserum against Nephrops (arthropoda) gap junctions

    NARCIS (Netherlands)

    Serras, F.; Buultjens, T.E.J.; Finbow, M.E.


    Antiserum raised against Nephrops gap junctions was injected into single cells of the 2-, 4-, 8-, 16-, and 32-cell stage of the Patella vulgata embryos. The pattern of junctional communication by iontophoresis of Lucifer Yellow CH was tested at the 32-cell stage. The results show that the normal

  14. Inhibition of dye-coupling in Patella (mollusca) embryos by microinjection of antiserum against Nephrops (arthropoda) gap junctions

    NARCIS (Netherlands)

    Serras, F.; Buultjens, T.E.J.; Finbow, M.E.

    Antiserum raised against Nephrops gap junctions was injected into single cells of the 2-, 4-, 8-, 16-, and 32-cell stage of the Patella vulgata embryos. The pattern of junctional communication by iontophoresis of Lucifer Yellow CH was tested at the 32-cell stage. The results show that the normal

  15. Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne


    The propagation of mechanically induced intercellular calcium waves (ICW) among osteoblastic cells occurs both by activation of P2Y (purinergic) receptors by extracellular nucleotides, resulting in "fast" ICW, and by gap junctional communication in cells that express connexin43 (Cx43), resulting...... in "slow" ICW. Human osteoblastic cells transmit intercellular calcium signals by both of these mechanisms. In the current studies we have examined the mechanism of slow gap junction-dependent ICW in osteoblastic cells. In ROS rat osteoblastic cells, gap junction-dependent ICW were inhibited by removal......43 (UMR/Cx43) we confirmed that nifedipine sensitivity of ICW required Cx43 expression. In human osteoblastic cells, gap junction-dependent ICW also required activation of L-type calcium channels and influx of extracellular calcium....

  16. Membrane integration of in vitro-translated gap junctional proteins: co- and post-translational mechanisms. (United States)

    Zhang, J T; Chen, M; Foote, C I; Nicholson, B J


    Connexins (Cx) are protein components of gap junction channels that permit the passage of small molecules between neighboring cells. cDNAs of a large family of connexins have been isolated and sequenced. A gap junction channel consists of two connexons, one from each cell in contact, composed of six connexin subunits. It has been suggested by Musil and coworkers that the oligomerization of formation of a connexon occurs at the level of the trans-Golgi network. In the present study, we initiated an analysis of the early stages of protein synthesis and membrane insertion of Cx32 and Cx26, two connexins that we have demonstrated are co-expressed in the same junctions in hepatocytes. Using an in vitro transcription and a coupled cell-free translation and translocation system, we observed that both Cx32 and Cx26 could insert into microsome membranes co-translationally, producing a topological structure indistinguishable from that in isolated gap junctions. To our surprise, Cx26 could also insert into membranes post-translationally with a native orientation. This post-translational membrane insertion process is dependent on nucleotides but not their hydrolysis. Cx32, on the other hand, could not insert into membranes post-translationally. These disparate properties of Cx32 and Cx26 are not due to the significant difference in the lengths of their C-terminal domains, but rather to their internal amino acid sequences. These observations raise the possibility that there may be another pathway for Cx26 to insert into membranes in cells and this feature may be important for the regulation of its functions. These findings may also lead us to a new approach to reconstitution without detergent extraction.

  17. Irsogladine maleate regulates gap junctional intercellular communication-dependent epithelial barrier in human nasal epithelial cells. (United States)

    Miyata, Ryo; Nomura, Kazuaki; Kakuki, Takuya; Takano, Ken-Ichi; Kohno, Takayuki; Konno, Takumi; Sawada, Norimasa; Himi, Tetsuo; Kojima, Takashi


    The airway epithelium of the human nasal mucosa acts as the first physical barrier that protects against inhaled substances and pathogens. Irsogladine maleate (IM) is an enhancer of gastric mucosal protective factors via upregulation of gap junctional intercellular communication (GJIC). GJIC is thought to participate in the formation of functional tight junctions. However, the effects of IM on GJIC and the epithelial barrier in human nasal epithelial cells (HNECs) remain unknown. To investigate the effects of IM on GJIC and the tight junctional barrier in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were treated with IM and the GJIC inhibitors oleamide and 18β-GA. Some cells were pretreated with IM before treatment with TLR3 ligand poly(I:C) to examine whether IM prevented the changes via TLR3-mediated signal pathways. In hTERT-HNECs, GJIC blockers reduced the expression of tight junction molecules claudin-1, -4, -7, occludin, tricellulin, and JAM-A. IM induced GJIC activity and enhanced the expression of claudin-1, -4, and JAM-A at the protein and mRNA levels with an increase of barrier function. GJIC blockers prevented the increase of the tight junction proteins induced by IM. Furthermore, IM prevented the reduction of JAM-A but not induction of IL-8 and TNF-α induced by poly(I:C). In conclusion, IM can maintain the GJIC-dependent tight junctional barrier via regulation of GJIC in upper airway nasal epithelium. Therefore, it is possible that IM may be useful as a nasal spray to prevent the disruption of the epithelial barrier by viral infections and exposure to allergens in human nasal mucosa.

  18. Gap junctions and other mechanisms of cell–cell communication regulate basal insulin secretion in the pancreatic islet (United States)

    Benninger, R K P; Head, W Steven; Zhang, Min; Satin, Leslie S; Piston, David W


    Abstract Cell–cell communication in the islet of Langerhans is important for the regulation of insulin secretion. Gap-junctions coordinate oscillations in intracellular free-calcium ([Ca2+]i) and insulin secretion in the islet following elevated glucose. Gap-junctions can also ensure that oscillatory [Ca2+]i ceases when glucose is at a basal levels. We determine the roles of gap-junctions and other cell–cell communication pathways in the suppression of insulin secretion under basal conditions. Metabolic, electrical and insulin secretion levels were measured from islets lacking gap-junction coupling following deletion of connexion36 (Cx36−/−), and these results were compared to those obtained using fully isolated β-cells. KATP loss-of-function islets provide a further experimental model to specifically study gap-junction mediated suppression of electrical activity. In isolated β-cells or Cx36−/− islets, elevations in [Ca2+]i persisted in a subset of cells even at basal glucose. Isolated β-cells showed elevated insulin secretion at basal glucose; however, insulin secretion from Cx36−/− islets was minimally altered. [Ca2+]i was further elevated under basal conditions, but insulin release still suppressed in KATP loss-of-function islets. Forced elevation of cAMP led to PKA-mediated increases in insulin secretion from islets lacking gap-junctions, but not from islets expressing Cx36 gap junctions. We conclude there is a redundancy in how cell–cell communication in the islet suppresses insulin release. Gap junctions suppress cellular heterogeneity and spontaneous [Ca2+]i signals, while other juxtacrine mechanisms, regulated by PKA and glucose, suppress more distal steps in exocytosis. Each mechanism is sufficiently robust to compensate for a loss of the other and still suppress basal insulin secretion. PMID:21930600

  19. Gap junctions and other mechanisms of cell-cell communication regulate basal insulin secretion in the pancreatic islet. (United States)

    Benninger, R K P; Head, W Steven; Zhang, Min; Satin, Leslie S; Piston, David W


    Cell-cell communication in the islet of Langerhans is important for the regulation of insulin secretion. Gap-junctions coordinate oscillations in intracellular free-calcium ([Ca(2+)](i)) and insulin secretion in the islet following elevated glucose. Gap-junctions can also ensure that oscillatory [Ca(2+)](i) ceases when glucose is at a basal levels. We determine the roles of gap-junctions and other cell-cell communication pathways in the suppression of insulin secretion under basal conditions. Metabolic, electrical and insulin secretion levels were measured from islets lacking gap-junction coupling following deletion of connexion36 (Cx36(-/-)), and these results were compared to those obtained using fully isolated β-cells. K(ATP) loss-of-function islets provide a further experimental model to specifically study gap-junction mediated suppression of electrical activity. In isolated β-cells or Cx36(-/-) islets, elevations in [Ca(2+)](i) persisted in a subset of cells even at basal glucose. Isolated β-cells showed elevated insulin secretion at basal glucose; however, insulin secretion from Cx36(-/-) islets was minimally altered. [Ca(2+)](i) was further elevated under basal conditions, but insulin release still suppressed in K(ATP) loss-of-function islets. Forced elevation of cAMP led to PKA-mediated increases in insulin secretion from islets lacking gap-junctions, but not from islets expressing Cx36 gap junctions. We conclude there is a redundancy in how cell-cell communication in the islet suppresses insulin release. Gap junctions suppress cellular heterogeneity and spontaneous [Ca(2+)](i) signals, while other juxtacrine mechanisms, regulated by PKA and glucose, suppress more distal steps in exocytosis. Each mechanism is sufficiently robust to compensate for a loss of the other and still suppress basal insulin secretion.

  20. Band-gaps in long Josephson junctions with periodic phase-shifts

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Saeed, E-mail: [Department of Mathematics, University of Malakand Chakdara, Dir(L), Pakhtunkhwa (Pakistan); Susanto, Hadi, E-mail: [Department of Mathematical Sciences, University of Essex, Colchester CO4 3SQ (United Kingdom); Wattis, Jonathan A.D. [School of Mathematical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom)


    We investigate analytically and numerically a long Josephson junction on an infinite domain, having arbitrary periodic phase shift of κ, that is, the so-called 0–κ long Josephson junction. The system is described by a one-dimensional sine-Gordon equation and has relatively recently been proposed as artificial atom lattices. We discuss the existence of periodic solutions of the system and investigate their stability both in the absence and presence of an applied bias current. We find critical values of the phase-discontinuity and the applied bias current beyond which static periodic solutions cease to exist. Due to the periodic discontinuity in the phase, the system admits regions of allowed and forbidden bands. We perturbatively investigate the Arnold tongues that separate the region of allowed and forbidden bands, and discuss the effect of an applied bias current on the band-gap structure. We present numerical simulations to support our analytical results. - Highlights: • A long Josephson junction on an infinite domain having arbitrary periodic phase shift has been proposed as artificial atom lattices recently. • We compute the band-gaps of the system asymptotically. • We show that the phase-shift and applied bias current can be used to control the band structures.

  1. Transient suppression of gap junctional intercellular communication after exposure to 100-nanosecond pulsed electric fields. (United States)

    Steuer, Anna; Schmidt, Anke; Labohá, Petra; Babica, Pavel; Kolb, Juergen F


    Gap junctional intercellular communication (GJIC) is an important mechanism that is involved and affected in many diseases and injuries. So far, the effect of nanosecond pulsed electric fields (nsPEFs) on the communication between cells was not investigated. An in vitro approach is presented with rat liver epithelial WB-F344 cells grown and exposed in a monolayer. In order to observe sub-lethal effects, cells were exposed to pulsed electric fields with a duration of 100ns and amplitudes between 10 and 20kV/cm. GJIC strongly decreased within 15min after treatment but recovered within 24h. Gene expression of Cx43 was significantly decreased and associated with a reduced total amount of Cx43 protein. In addition, MAP kinases p38 and Erk1/2, involved in Cx43 phosphorylation, were activated and Cx43 became hyperphosphorylated. Immunofluorescent staining of Cx43 displayed the disassembly of gap junctions. Further, a reorganization of the actin cytoskeleton was observed whereas tight junction protein ZO-1 was not significantly affected. All effects were field- and time-dependent and most pronounced within 30 to 60min after treatment. A better understanding of a possible manipulation of GJIC by nsPEFs might eventually offer a possibility to develop and improve treatments. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Analysis of longitudinal vibration band gaps in periodic carbon nanotube intramolecular junctions using finite element method

    Directory of Open Access Journals (Sweden)

    Jiaqian Li


    Full Text Available The longitudinal vibration band gaps in periodic (n, 0–(2n, 0 single-walled carbon nanotube(SWCNT intramolecular junctions(IMJs are investigated based on the finite element calculation. The frequency ranges of band gaps in frequency response functions(FRF simulated by finite element method (FEM show good agreement with those in band structure obtained by simple spring-mass model. Moreover, a comprehensive parametric study is also conducted to highlight the influences of the geometrical parameters such as the size of unit cell, component ratios of the IMJs and diameters of the CNT segments as well as geometric imperfections on the first band gap. The results show that the frequency ranges and the bandwidth of the gap strongly depend on the geometrical parameters. Furthermore, the influences of geometrical parameters on gaps are nuanced in IMJs with different topological defects. The existence of vibration band gaps in periodic IMJs lends a new insight into the development of CNT-based nano-devices in application of vibration isolation.

  3. Entrainment, retention, and transport of freely swimming fish in junction gaps between commercial barges operating on the Illinois Waterway (United States)

    Davis, Jeremiah J.; Jackson, P. Ryan; Engel, Frank; LeRoy, Jessica Z.; Neeley, Rebecca N.; Finney, Samuel T.; Murphy, Elizabeth A.


    Large Electric Dispersal Barriers were constructed in the Chicago Sanitary and Ship Canal (CSSC) to prevent the transfer of invasive fish species between the Mississippi River Basin and the Great Lakes Basin while simultaneously allowing the passage of commercial barge traffic. We investigated the potential for entrainment, retention, and transport of freely swimming fish within large gaps (> 50 m3) created at junction points between barges. Modified mark and capture trials were employed to assess fish entrainment, retention, and transport by barge tows. A multi-beam sonar system enabled estimation of fish abundance within barge junction gaps. Barges were also instrumented with acoustic Doppler velocity meters to map the velocity distribution in the water surrounding the barge and in the gap formed at the junction of two barges. Results indicate that the water inside the gap can move upstream with a barge tow at speeds near the barge tow travel speed. Water within 1 m to the side of the barge junction gaps was observed to move upstream with the barge tow. Observed transverse and vertical water velocities suggest pathways by which fish may potentially be entrained into barge junction gaps. Results of mark and capture trials provide direct evidence that small fish can become entrained by barges, retained within junction gaps, and transported over distances of at least 15.5 km. Fish entrained within the barge junction gap were retained in that space as the barge tow transited through locks and the Electric Dispersal Barriers, which would be expected to impede fish movement upstream.

  4. Sub-harmonic gap structure and Magneto-transport in suspended graphene -Superconductor ballistic junctions (United States)

    Kumaravadivel, Piranavan; Du, Xu


    Inducing superconductivity in graphene via the proximity effect enables to study the rich transport of the massless Dirac fermions at the Superconductor(S) - Graphene (G) interface. Some of the predictions are pseudo diffusive transport in Ballistic SGS junctions at low carrier densities and the unique specular and retro Andreev reflections in graphene. One of the challenges in observing these experimentally is to fabricate highly transparent ballistic SGS junctions that can be probed at low carrier densities near the Dirac point. In this talk we will present our recent results on suspended graphene- Niobium Josephson weak links. Our devices exhibit a mobility of ~ 350000 cm2V-1s-1 with a carrier density as low as 109 cm-2. Below the Superconducting transition temperature (Tc) ~ 9K, the devices show supercurrent and sub-harmonic gap structure due to Multiple Andreev reflections. In the vicinity of the Dirac point, the sub-harmonic gap structure becomes more pronounced, which as predicated, is indicative of pseudo-diffusive transport. With a fine scanning of gate voltage close to Dirac point we see emergence of some unusual sub- gap structures. We also report on our study of these samples below the upper critical field of Nb (~ 3.5T), where superconducting proximity effect coexists with Quantum Hall effect.

  5. Bovine connexin44, a lens gap junction protein: molecular cloning, immunologic characterization, and functional expression. (United States)

    Gupta, V K; Berthoud, V M; Atal, N; Jarillo, J A; Barrio, L C; Beyer, E C


    To identify, clone molecularly, characterize immunochemically, and express functionally a bovine lens gap junction protein (connexin). The methods used were polymerase chain reaction, genomic cloning, RNA and DNA blotting, bacterial expression of a fusion protein, immunoblotting, alkaline phosphatase treatment, Xenopus oocyte expression, and voltage clamp technique. A bovine genomic clone encoding a polypeptide of 44,424 d, termed connexin44 (Cx44), was isolated. Cx44 was most closely related to the lens connexins rat Cx46 and chicken Cx56. The Cx44 DNA hybridized to a 2.5 kb mRNA detected only in lens RNA. The carboxyl terminal 161 amino acids from Cx44 were expressed in bacteria fused to maltose binding protein (MBP). The Cx44/MBP fusion protein reacted in immunoblots with anti-rat Cx46(411 to 416) antibodies and with the monoclonal antibody 5H1, but not with a monoclonal antibody to MP70 nor with antibodies to other connexins. Cx44 translated in vitro from the cloned DNA showed a single band with an apparent electrophoretic mobility of approximately 50 kd on polyacrylamide gels containing sodium dodecyl sulfate. Multiple bands of 53 to 57 kd were detected by immunoblotting in homogenates of bovine lens; these bands were reduced to a broad band of approximately 50 kd by alkaline phosphatase treatment, suggesting that they represented phosphorylated forms of Cx44. Cx44 RNA injected in single oocytes induced a large and characteristic time- and voltage-dependent current. Overexpression of Cx44 produced depolarization and cell lysis. Junctional currents that could be regulated by transjunctional voltage were induced between paired oocytes injected with Cx44 RNA. Observations in paired oocytes suggested the assembly of hemichannels into junctional channels. Cx44 is a phosphoprotein component of bovine lens fiber gap junctions. Although it has a relatively distinct sequence, it shares sequence similarity, immunologic cross-reactivity, and electrophysiological

  6. Doping GaP core-shell nanowire pn-junctions

    DEFF Research Database (Denmark)

    Yazdi, Sadegh; Berg, Alexander; Borgström, Magnus T.


    The doping process in GaP core-shell nanowire pn-junctions using different precursors is evaluated by mapping the nanowires' electrostatic potential distribution by means of off-axis electron holography. Three precursors, triethyltin (TESn), ditertiarybutylselenide, and silane are investigated......, ditertiarybutylselenide and silane for n-type doping of the shell and that the concentration of p-type dopants is higher in the region of core grown parasitically by vapor-solid mechanism due to unintentional carbon doping from trimethylgallium precursor....

  7. Connexin 30 expression and frequency of connexin heterogeneity in astrocyte gap junction plaques increase with age in the rat retina.

    Directory of Open Access Journals (Sweden)

    Hussein Mansour

    Full Text Available We investigated age-associated changes in retinal astrocyte connexins (Cx by assaying Cx numbers, plaque sizes, protein expression levels and heterogeneity of gap junctions utilizing six-marker immunohistochemistry (IHC. We compared Wistar rat retinal wholemounts in animals aged 3 (young adult, 9 (middle-aged and 22 months (aged. We determined that retinal astrocytes have gap junctions composed of Cx26, -30, -43 and -45. Cx30 was consistently elevated at 22 months compared to younger ages both when associated with parenchymal astrocytes and vascular-associated astrocytes. Not only was the absolute number of Cx30 plaques significantly higher (P<0.05 but the size of the plaques was significantly larger at 22 months compared to younger ages (p<0.05. With age, Cx26 increased significantly initially, but returned to basal levels; whereas Cx43 expression remained low and stable with age. Evidence that astrocytes alter connexin compositions of gap junctions was demonstrated by the significant increase in the number of Cx26/Cx45 gap junctions with age. We also found gap junctions comprised of 1, 2, 3 or 4 Cx proteins suggesting that retinal astrocytes use various connexin protein combinations in their gap junctions during development and aging. These data provides new insight into the dynamic and extensive Cx network utilized by retinal astrocytes for communication within both the parenchyma and vasculature for the maintenance of normal retinal physiology with age. This characterisation of the changes in astrocytic gap junctional communication with age in the CNS is crucial to the understanding of physiological aging and age-related neurodegenerative diseases.

  8. Blockade of gap junction hemichannel suppresses disease progression in mouse models of amyotrophic lateral sclerosis and Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Hideyuki Takeuchi

    Full Text Available Glutamate released by activated microglia induces excitotoxic neuronal death, which likely contributes to non-cell autonomous neuronal death in neurodegenerative diseases, including amyotrophic lateral sclerosis and Alzheimer's disease. Although both blockade of glutamate receptors and inhibition of microglial activation are the therapeutic candidates for these neurodegenerative diseases, glutamate receptor blockers also perturbed physiological and essential glutamate signals, and inhibitors of microglial activation suppressed both neurotoxic/neuroprotective roles of microglia and hardly affected disease progression. We previously demonstrated that activated microglia release a large amount of glutamate specifically through gap junction hemichannel. Hence, blockade of gap junction hemichannel may be potentially beneficial in treatment of neurodegenerative diseases.In this study, we generated a novel blood-brain barrier permeable gap junction hemichannel blocker based on glycyrrhetinic acid. We found that pharmacologic blockade of gap junction hemichannel inhibited excessive glutamate release from activated microglia in vitro and in vivo without producing notable toxicity. Blocking gap junction hemichannel significantly suppressed neuronal loss of the spinal cord and extended survival in transgenic mice carrying human superoxide dismutase 1 with G93A or G37R mutation as an amyotrophic lateral sclerosis mouse model. Moreover, blockade of gap junction hemichannel also significantly improved memory impairments without altering amyloid β deposition in double transgenic mice expressing human amyloid precursor protein with K595N and M596L mutations and presenilin 1 with A264E mutation as an Alzheimer's disease mouse model.Our results suggest that gap junction hemichannel blockers may represent a new therapeutic strategy to target neurotoxic microglia specifically and prevent microglia-mediated neuronal death in various neurodegenerative diseases.

  9. Gap junction structure: unraveled, but not fully revealed [version 1; referees: 3 approved

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    Eric C. Beyer


    Full Text Available Gap junction channels facilitate the intercellular exchange of ions and small molecules, a process that is critical for the function of many different kinds of cells and tissues. Recent crystal structures of channels formed by one connexin isoform (connexin26 have been determined, and they have been subjected to molecular modeling. These studies have provided high-resolution models to gain insights into the mechanisms of channel conductance, molecular permeability, and gating. The models share similarities, but there are some differences in the conclusions reached by these studies. Many unanswered questions remain to allow an atomic-level understanding of intercellular communication mediated by connexin26. Because some domains of the connexin polypeptides are highly conserved (like the transmembrane regions, it is likely that some features of the connexin26 structure will apply to other members of the family of gap junction proteins. However, determination of high-resolution structures and modeling of other connexin channels will be required to account for the diverse biophysical properties and regulation conferred by the differences in their sequences.

  10. Activity-dependent neuronal control of gap-junctional communication in fibroblasts. (United States)

    Zeng, Yan; Lv, Xiaohua; Zeng, Shaoqun; Shi, Jing


    Intercellular communication through gap junctions plays an important role in fibroblast physiology. Here we report an activity-dependent neuronal control of gap-junctional communication (GJC) in rat dermal fibroblasts, which is associated with N-methyl-D-aspartate (NMDA) glutamate receptor-mediated elevations in intracellular Ca(2+). Both spontaneous and induced activation of dorsal root ganglion (DRG) neurons, manifested by action potentials and TTX-dependent inward currents, significantly reduced fibroblast GJC in Neuron/Fibroblast (N/F) cocultures. Reduced fibroblast GJC by DRG neurons was prevented by blockade of NMDA receptors and decrease of intra- and intercellular Ca(2+). Immunocytochemistry showed that the NR1 subunit of the NMDA receptor coexisted with CX43 at the plasma membrane of fibroblasts. Moreover, glutamate applied to fibroblast cultures triggered NMDA receptor-dependent intracellular Ca(2+) elevations and decrease of GJC. These data demonstrate that NMDA receptor activation contributes to downregulation of GJC in fibroblasts. Since fibroblasts have been shown to facilitate DRG neurite growth and survival, our findings provide a glimpse at the impact that neuronal activation has on fibroblast networks.

  11. Functional roles of the amino terminal domain in determining biophysical properties of Cx50 gap junction channels

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    Li eXin


    Full Text Available Communication through gap junction channels is essential for synchronized and coordinated cellular activities. The gap junction channel pore size, its switch control for opening/closing, and the modulations by chemicals can be different depending on the connexin subtypes that compose the channel. Recent structural and functional studies provide compelling evidence that the amino terminal (NT domains of several connexins line the pore of gap junction channels and play an important role in single channel conductance (γj and transjunctional voltage-dependent gating (Vj-gating. This article reviews recent studies conducted on a series of mutations/chimeras in the NT domain of connexin50 (Cx50. Functional examination of the gap junction channels formed by these mutants/chimeras shows the net charge number at the NT domain to be an important factor in γj and in Vj-gating. Furthermore, with an increase in the net negative charge at the NT domain, we observed an increase in the γj, as well as changes in the parameters of the Boltzmann fit of the normalized steady-state conductance and Vj relationship. Our data are consistent with a structural model where the NT domain of Cx50 lines the gap junction pore and plays an important role in sensing Vj and in the subsequent conformational changes leading to gating, as well as in limiting the rate of ion permeation.

  12. Genetic variation at the human connexin 43 locus but not at the connexin 40 locus is associated with left bundle branch block (United States)

    Ladenvall, Per; Andersson, Björn; Dellborg, Mikael; Hansson, Per-Olof; Eriksson, Henry; Thelle, Dag; Eriksson, Peter


    Background Bundle branch block (BBB) has been regarded as a disease of the conduction system, but occurs in mice lacking connexin 40 (expressed in atria, proximal conduction system) or connexin 43 (expressed in Purkinje cells, cardiomyocytes). Objective The aim of this paper is to explore whether BBB is heritable, and whether polymorphisms at connexin 40 and connexin 43 loci are associated with BBB. Methods To assess BBB heritability, we screened descendants of men with BBB in the population cohort ‘The Study of Men Born 1913’. DNA samples from 80-year-old men with extreme QRS-duration phenotypes were used to search for polymorphisms at connexin 40 and 43 loci. Associations between identified polymorphisms and BBB were evaluated in an independent cohort (INTERGENE). Results Seventy-seven men from ‘The Study of Men Born 1913’ with BBB had 116 descendants. Among the 76 participating descendants, 2 sons (6.4%) had BBB at 54 years of age. At the same age, 0.9% of men born in 1913 had BBB. We identified 6 single nucleotide polymorphisms (SNPs) in connexin 40 and 1 polymorphism in connexin 43. In the INTERGENE cohort, the connexin 43 polymorphism was associated with left BBB (LBBB) (4 of 35 LBBB vs 16 of 232 without BBB, χ2=7.4, p=0.03), but not with right BBB (RBBB) or overall BBB. None of the connexin 40 SNPs or haplotypes were associated with LBBB or RBBB. Conclusions These findings indicate that conduction by connexin 43 within the ventricular muscle distal to the specialised conduction system may be important for LBBB development. PMID:25893100

  13. Functional assessment of gap junctions in monolayer and three-dimensional cultures of human tendon cells using fluorescence recovery after photobleaching


    Kuzma-Kuzniarska, Maria; Yapp, Clarence; Pearson-Jones, Thomas W.; Jones, Andrew K; Hulley, Philippa A.


    Gap junction-mediated intercellular communication influences a variety of cellular activities. In tendons, gap junctions modulate collagen production, are involved in strain-induced cell death, and are involved in the response to mechanical stimulation. The aim of the present study was to investigate gap junction-mediated intercellular communication in healthy human tendon-derived cells using fluorescence recovery after photobleaching (FRAP). The FRAP is a noninvasive technique that allows qu...

  14. A Gap Junction Protein, Inx2, Modulates Calcium Flux to Specify Border Cell Fate during Drosophila oogenesis.

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    Aresh Sahu


    Full Text Available Intercellular communication mediated by gap junction (GJ proteins is indispensable during embryogenesis, tissue regeneration and wound healing. Here we report functional analysis of a gap junction protein, Innexin 2 (Inx2, in cell type specification during Drosophila oogenesis. Our data reveal a novel involvement of Inx2 in the specification of Border Cells (BCs, a migratory cell type, whose identity is determined by the cell autonomous STAT activity. We show that Inx2 influences BC fate specification by modulating STAT activity via Domeless receptor endocytosis. Furthermore, detailed experimental analysis has uncovered that Inx2 also regulates a calcium flux that transmits across the follicle cells. We propose that Inx2 mediated calcium flux in the follicle cells stimulates endocytosis by altering Dynamin (Shibire distribution which is in turn critical for careful calibration of STAT activation and, thus for BC specification. Together our data provide unprecedented molecular insights into how gap junction proteins can regulate cell-type specification.

  15. A Gap Junction Protein, Inx2, Modulates Calcium Flux to Specify Border Cell Fate during Drosophila oogenesis. (United States)

    Sahu, Aresh; Ghosh, Ritabrata; Deshpande, Girish; Prasad, Mohit


    Intercellular communication mediated by gap junction (GJ) proteins is indispensable during embryogenesis, tissue regeneration and wound healing. Here we report functional analysis of a gap junction protein, Innexin 2 (Inx2), in cell type specification during Drosophila oogenesis. Our data reveal a novel involvement of Inx2 in the specification of Border Cells (BCs), a migratory cell type, whose identity is determined by the cell autonomous STAT activity. We show that Inx2 influences BC fate specification by modulating STAT activity via Domeless receptor endocytosis. Furthermore, detailed experimental analysis has uncovered that Inx2 also regulates a calcium flux that transmits across the follicle cells. We propose that Inx2 mediated calcium flux in the follicle cells stimulates endocytosis by altering Dynamin (Shibire) distribution which is in turn critical for careful calibration of STAT activation and, thus for BC specification. Together our data provide unprecedented molecular insights into how gap junction proteins can regulate cell-type specification.

  16. Treatment with the gap junction modifier rotigaptide (ZP123) reduces infarct size in rats with chronic myocardial infarction

    DEFF Research Database (Denmark)

    Haugan, Ketil; Marcussen, Niels; Kjølbye, Anne Louise


    Treatment with non-selective drugs (eg, long-chain alcohols, halothane) that reduce gap junction intercellular communication (GJIC) is associated with reduced infarct size after myocardial infarction (MI). Therefore, it has been suggested that gap junction intercellular communication stimulating...... compounds may increase infarct size. The antiarrhythmic peptide analogue rotigaptide (ZP123) increases cardiac gap junction intercellular communication and the purpose of the present study was to examine the effects of rotigaptide treatment on infarct size. Myocardial infarction was induced in male rats...... by ligation of the left anterior descending artery (LAD). Rats (n = 156) were treated with rotigaptide at three dose levels or vehicle from the onset of ischemia and for 3 weeks following LAD occlusion. Infarct size was determined using histomorphometry after 3 weeks treatment. Rotigaptide treatment producing...

  17. Stochastic Model of Gap Junctions Exhibiting Rectification and Multiple Closed States of Slow Gates. (United States)

    Snipas, Mindaugas; Kraujalis, Tadas; Paulauskas, Nerijus; Maciunas, Kestutis; Bukauskas, Feliksas F


    Gap-junction (GJ) channels formed from connexin (Cx) proteins provide direct pathways for electrical and metabolic cell-cell communication. Earlier, we developed a stochastic 16-state model (S16SM) of voltage gating of the GJ channel containing two pairs of fast and slow gates, each operating between open (o) and closed (c) states. However, experimental data suggest that gates may in fact contain two or more closed states. We developed a model in which the slow gate operates according to a linear reaction scheme, o↔c1↔c2, where c1 and c2 are initial-closed and deep-closed states that both close the channel fully, whereas the fast gate operates between the open state and the closed state and exhibits a residual conductance. Thus, we developed a stochastic 36-state model (S36SM) of GJ channel gating that is sensitive to transjunctional voltage (Vj). To accelerate simulation and eliminate noise in simulated junctional conductance (gj) records, we transformed an S36SM into a Markov chain 36-state model (MC36SM) of GJ channel gating. This model provides an explanation for well-established experimental data, such as delayed gj recovery after Vj gating, hysteresis of gj-Vj dependence, and the low ratio of functional channels to the total number of GJ channels clustered in junctional plaques, and it has the potential to describe chemically mediated gating, which cannot be reflected using an S16SM. The MC36SM, when combined with global optimization algorithms, can be used for automated estimation of gating parameters including probabilities of c1↔c2 transitions from experimental gj-time and gj-Vj dependencies. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  18. Norepinephrine inhibits intercellular coupling in rat cardiomyocytes by ubiquitination of connexin43 gap junctions. (United States)

    Mollerup, Sarah; Hofgaard, Johannes P; Braunstein, Thomas H; Kjenseth, Ane; Leithe, Edward; Rivedal, Edgar; Holstein-Rathlou, Niels-Henrik; Nielsen, Morten Schak


    Gαq-stimulation reduces intercellular coupling within 10 min via a decrease in the membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP2), but the mechanism is unknown. Here we show that uncoupling in rat cardiomyocytes after stimulation of α-adrenergic Gαq-coupled receptors with norepinephrine is prevented by proteasomal and lysosomal inhibitors, suggesting that internalization and possibly degradation of connexin43 (Cx43) is involved. Uncoupling was accompanied by increased Triton X-100 solubility of Cx43, which is considered a measure of the non-junctional pool of Cx43. However, inhibition of the proteasome and lysosome further increased solubility while preserving coupling, suggesting that communicating gap junctions can be part of the soluble fraction. Ubiquitination of Cx43 was also increased, and Cx43 co-immunoprecipitated with the ubiquitin ligase Nedd4. Norepinephrine increases ubiquitination of Cx43 in cardiomyocytes, possibly via Nedd4. We suggest that Cx43 is subsequently internalized, which is preceded by acquired solubility in Triton X-100, which does not lead to uncoupling per se.

  19. Accessing gap-junction channel structure-function relationships through molecular modeling and simulations. (United States)

    Villanelo, F; Escalona, Y; Pareja-Barrueto, C; Garate, J A; Skerrett, I M; Perez-Acle, T


    Gap junction channels (GJCs) are massive protein channels connecting the cytoplasm of adjacent cells. These channels allow intercellular transfer of molecules up to ~1 kDa, including water, ions and other metabolites. Unveiling structure-function relationships coded into the molecular architecture of these channels is necessary to gain insight on their vast biological function including electrical synapse, inflammation, development and tissular homeostasis. From early works, computational methods have been critical to analyze and interpret experimental observations. Upon the availability of crystallographic structures, molecular modeling and simulations have become a valuable tool to assess structure-function relationships in GJCs. Modeling different connexin isoforms, simulating the transport process, and exploring molecular variants, have provided new hypotheses and out-of-the-box approaches to the study of these important channels. Here, we review foundational structural studies and recent developments on GJCs using molecular modeling and simulation techniques, highlighting the methods and the cross-talk with experimental evidence. By comparing results obtained by molecular modeling and simulations techniques with structural and functional information obtained from both recent literature and structural databases, we provide a critical assesment of structure-function relationships that can be obtained from the junction between theoretical and experimental evidence.

  20. Gap junctions suppress electrical but not [Ca(2+)] heterogeneity in resistance arteries

    DEFF Research Database (Denmark)

    Hald, Bjørn Olav; Welsh, Donald G; von Holstein-Rathlou, Niels-Henrik


    arises, a virtual arteriole was developed that introduces variation in the activities of ion-transport proteins between cells. By varying the level of heterogeneity and subpopulations of gap junctions (GJs), the resulting simulations shows that GJs suppress electrical variation but can only reduce......Despite stochastic variation in the molecular composition and morphology of individual smooth muscle and endothelial cells, the membrane potential along intact microvessels is remarkably uniform. This is crucial for coordinated vasomotor responses. To investigate how this electrical homogeneity...... cytosolic [Ca(2+)] variation. The process of electrical smoothing, however, introduces an energetic cost due to permanent currents, one which is proportional to the level of heterogeneity. This cost is particularly large when electrochemically different endothelial-cell and smooth-muscle-cell layers...

  1. Gap junction connexins in female reproductive organs: implications for women's reproductive health. (United States)

    Winterhager, Elke; Kidder, Gerald M


    Connexins comprise a family of ~20 proteins that form intercellular membrane channels (gap junction channels) providing a direct route for metabolites and signalling molecules to pass between cells. This review provides a critical analysis of the evidence for essential roles of individual connexins in female reproductive function, highlighting implications for women's reproductive health. No systematic review has been carried out. Published literature from the past 35 years was surveyed for research related to connexin involvement in development and function of the female reproductive system. Because of the demonstrated utility of genetic manipulation for elucidating connexin functions in various organs, much of the cited information comes from research with genetically modified mice. In some cases, a distinction is drawn between connexin functions clearly related to the formation of gap junction channels and those possibly linked to non-channel roles. Based on work with mice, several connexins are known to be required for female reproductive functions. Loss of connexin43 (CX43) causes an oocyte deficiency, and follicles lacking or expressing less CX43 in granulosa cells exhibit reduced growth, impairing fertility. CX43 is also expressed in human cumulus cells and, in the context of IVF, has been correlated with pregnancy outcome, suggesting that this connexin may be a determinant of oocyte and embryo quality in women. Loss of CX37, which exclusively connects oocytes with granulosa cells in the mouse, caused oocytes to cease growing without acquiring meiotic competence. Blocking of CX26 channels in the uterine epithelium disrupted implantation whereas loss or reduction of CX43 expression in the uterine stroma impaired decidualization and vascularization in mouse and human. Several connexins are important in placentation and, in the human, CX43 is a key regulator of the fusogenic pathway from the cytotrophoblast to the syncytiotrophoblast, ensuring placental growth

  2. Reactive Astrocytes Protect Melanoma Cells from Chemotherapy by Sequestering Intracellular Calcium through Gap Junction Communication Channels

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    Qingtang Lin


    Full Text Available Brain metastases are highly resistant to chemotherapy. Metastatic tumor cells are known to exploit the host microenvironment for their growth and survival. We report here that melanoma brain metastases are surrounded and infiltrated by activated astrocytes, and we hypothesized that these astrocytes can play a role similar to their established ability to protect neurons from apoptosis. In coculture experiments, astrocytes, but not fibroblasts, reduced apoptosis in human melanoma cells treated with various chemotherapeutic drugs. This chemoprotective effect was dependent on physical contact and gap junctional communication between astrocytes and tumor cells. Moreover, the protective effect of astrocytes resulted from their sequestering calcium from the cytoplasm of tumor cells. These data suggest that brain tumors can, in principle, harness the neuroprotective effects of reactive astrocytes for their own survival and implicate a heretofore unrecognized mechanism for resistance in brain metastasis that might be of relevance in the clinic.

  3. Sulforaphane counteracts aggressiveness of pancreatic cancer driven by dysregulated Cx43-mediated gap junctional intercellular communication (United States)

    Zhang, Yiyao; Isayev, Orkhan; Heilmann, Katharina; Schoensiegel, Frank; Liu, Li; Nessling, Michelle; Richter, Karsten; Labsch, Sabrina; Nwaeburu, Clifford C.; Mattern, Juergen; Gladkich, Jury; Giese, Nathalia; Werner, Jens; Schemmer, Peter; Gross, Wolfgang; Gebhard, Martha M.; Gerhauser, Clarissa; Schaefer, Michael; Herr, Ingrid


    The extreme aggressiveness of pancreatic ductal adenocarcinoma (PDA) has been associated with blocked gap junctional intercellular communication (GJIC) and the presence of cancer stem cells (CSCs). We examined whether disturbed GJIC is responsible for a CSC phenotype in established and primary cancer cells and patient tissue of PDA using interdisciplinary methods based in physiology, cell and molecular biology, histology and epigenetics. Flux of fluorescent dyes and gemcitabine through gap junctions (GJs) was intact in less aggressive cells but not in highly malignant cells with morphological dysfunctional GJs. Among several connexins, only Cx43 was expressed on the cell surface of less aggressive and GJIC-competent cells, whereas Cx43 surface expression was absent in highly malignant, E-cadherin-negative and GJIC-incompetent cells. The levels of total Cx43 protein and Cx43 phosphorylated at Ser368 and Ser279/282 were high in normal tissue but low to absent in malignant tissue. si-RNA-mediated inhibition of Cx43 expression in GJIC-competent cells prevented GJIC and induced colony formation and the expression of stem cell-related factors. The bioactive substance sulforaphane enhanced Cx43 and E-cadherin levels, inhibited the CSC markers c-Met and CD133, improved the functional morphology of GJs and enhanced GJIC. Sulforaphane altered the phosphorylation of several kinases and their substrates and inhibition of GSK3, JNK and PKC prevented sulforaphane-induced CX43 expression. The sulforaphane-mediated expression of Cx43 was not correlated with enhanced Cx43 RNA expression, acetylated histone binding and Cx43 promoter de-methylation, suggesting that posttranslational phosphorylation is the dominant regulatory mechanism. Together, the absence of Cx43 prevents GJIC and enhances aggressiveness, whereas sulforaphane counteracts this process, and our findings highlight dietary co-treatment as a viable treatment option for PDA. PMID:24742583

  4. Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction. (United States)

    Jabr, Rita I; Hatch, Fiona S; Salvage, Samantha C; Orlowski, Alejandro; Lampe, Paul D; Fry, Christopher H


    Cardiac arrhythmias are associated with raised intracellular [Ca 2+ ] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca 2+ -dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity. We investigated the role of the Ca 2+ -dependent phosphatase, calcineurin. Intracellular [Ca 2+ ] was raised in guinea-pig myocardium by a low-Na solution or increased stimulation. Conduction velocity and Gj were measured in multicellular strips. Phosphorylation of Cx43 serine residues (S365 and S368) and of the intermediary regulator I1 at threonine35 was measured by Western blot. Measurements were made in the presence and absence of inhibitors to calcineurin, I1 or protein phosphatase-1 and phosphatase-2.Raised [Ca 2 + ] i decreased Gj, reduced Cx43 phosphorylation at S365 and increased it at S368; these changes were reversed by calcineurin inhibitors. Cx43-S368 phosphorylation was reversed by the protein kinase C inhibitor chelerythrine. Raised [Ca 2+ ] i also decreased I1 phosphorylation, also prevented by calcineurin inhibitors, to increase activity of the Ca 2+ -independent phosphatase, PPI. The PP1 inhibitor, tautomycin, prevented Cx43-365 dephosphorylation, Cx43-S368 phosphorylation and Gj reduction in raised [Ca 2+ ] i . PP2A had no role. Conduction velocity was reduced by raised [Ca 2+ ] i and reversed by calcineurin inhibitors. Reduced action potential conduction and Gj in raised [Ca 2+ ] are regulated by calcineurin-dependent Cx43-S365 phosphorylation, leading to Cx43-S368 dephosphorylation. The calcineurin action is indirect, via I1 dephosphorylation and subsequent activation of PP1.

  5. Connexin domains relevant to the chemical gating of gap junction channels

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    C. Peracchia


    Full Text Available Most cells exchange ions and small metabolites via gap junction channels. These channels are made of two hemichannels (connexons, each formed by the radial arrangement of six connexin (Cx proteins. Connexins span the bilayer four times (M1-M4 and have both amino- and carboxy-termini (NT, CT at the cytoplasmic side of the membrane, forming two extracellular loops (E1, E2 and one inner (IL loop. The channels are regulated by gates that close with cytosolic acidification (e.g., CO2 treatment or increased calcium concentration, possibly via calmodulin activation. Although gap junction regulation is still unclear, connexin domains involved in gating are being defined. We have recently focused on the CO2 gating sensitivity of Cx32, Cx38 and various mutants and chimeras expressed in Xenopus oocytes and studied by double voltage clamp. Cx32 is weakly sensitive to CO2, whereas Cx38 is highly sensitive. A Cx32 chimera containing the second half of the inner loop (IL2 of Cx38 was as sensitive to CO2 as Cx38, indicating that this domain plays an important role. Deletion of CT by 84% did not affect CO2 sensitivity, but replacement of 5 arginines (R with sparagines (N at the beginning of CT (C1 greatly enhanced the CO2 sensitivity of Cx32. This suggests that whereas most of CT is irrelevant, positive charges of C1 maintain the CO2 sensitivity of Cx32 low. As a hypothesis we have proposed a model that involves charge interaction between negative residues of the beginning of IL1 and positive residues of either C1 or IL2. Open and closed channels would result from IL1-C1 and IL1-IL2 interactions, respectively

  6. Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles. (United States)

    Shuhaibar, Leia C; Egbert, Jeremy R; Norris, Rachael P; Lampe, Paul D; Nikolaev, Viacheslav O; Thunemann, Martin; Wen, Lai; Feil, Robert; Jaffe, Laurinda A


    Meiosis in mammalian oocytes is paused until luteinizing hormone (LH) activates receptors in the mural granulosa cells of the ovarian follicle. Prior work has established the central role of cyclic GMP (cGMP) from the granulosa cells in maintaining meiotic arrest, but it is not clear how binding of LH to receptors that are located up to 10 cell layers away from the oocyte lowers oocyte cGMP and restarts meiosis. Here, by visualizing intercellular trafficking of cGMP in real-time in live follicles from mice expressing a FRET sensor, we show that diffusion of cGMP through gap junctions is responsible not only for maintaining meiotic arrest, but also for rapid transmission of the signal that reinitiates meiosis from the follicle surface to the oocyte. Before LH exposure, the cGMP concentration throughout the follicle is at a uniformly high level of ∼2-4 μM. Then, within 1 min of LH application, cGMP begins to decrease in the peripheral granulosa cells. As a consequence, cGMP from the oocyte diffuses into the sink provided by the large granulosa cell volume, such that by 20 min the cGMP concentration in the follicle is uniformly low, ∼100 nM. The decrease in cGMP in the oocyte relieves the inhibition of the meiotic cell cycle. This direct demonstration that a physiological signal initiated by a stimulus in one region of an intact tissue can travel across many layers of cells via cyclic nucleotide diffusion through gap junctions could provide a general mechanism for diverse cellular processes.

  7. Phosphorylation on Ser-279 and Ser-282 of connexin43 regulates endocytosis and gap junction assembly in pancreatic cancer cells. (United States)

    Johnson, Kristen E; Mitra, Shalini; Katoch, Parul; Kelsey, Linda S; Johnson, Keith R; Mehta, Parmender P


    The molecular mechanisms regulating the assembly of connexins (Cxs) into gap junctions are poorly understood. Using human pancreatic tumor cell lines BxPC3 and Capan-1, which express Cx26 and Cx43, we show that, upon arrival at the cell surface, the assembly of Cx43 is impaired. Connexin43 fails to assemble, because it is internalized by clathrin-mediated endocytosis. Assembly is restored upon expressing a sorting-motif mutant of Cx43, which does not interact with the AP2 complex, and by expressing mutants that cannot be phosphorylated on Ser-279 and Ser-282. The mutants restore assembly by preventing clathrin-mediated endocytosis of Cx43. Our results also document that the sorting-motif mutant is assembled into gap junctions in cells in which the expression of endogenous Cx43 has been knocked down. Remarkably, Cx43 mutants that cannot be phosphorylated on Ser-279 or Ser-282 are assembled into gap junctions only when connexons are composed of Cx43 forms that can be phosphorylated on these serines and forms in which phosphorylation on these serines is abolished. Based on the subcellular fate of Cx43 in single and contacting cells, our results document that the endocytic itinerary of Cx43 is altered upon cell-cell contact, which causes Cx43 to traffic by EEA1-negative endosomes en route to lysosomes. Our results further show that gap-junctional plaques formed of a sorting motif-deficient mutant of Cx43, which is unable to be internalized by the clathrin-mediated pathway, are predominantly endocytosed in the form of annular junctions. Thus the differential phosphorylation of Cx43 on Ser-279 and Ser-282 is fine-tuned to control Cx43's endocytosis and assembly into gap junctions.

  8. First-principles spin-transfer torque in CuMnAs |GaP |CuMnAs junctions (United States)

    Stamenova, Maria; Mohebbi, Razie; Seyed-Yazdi, Jamileh; Rungger, Ivan; Sanvito, Stefano


    We demonstrate that an all-antiferromagnetic tunnel junction with current perpendicular to the plane geometry can be used as an efficient spintronic device with potential high-frequency operation. By using state-of-the-art density functional theory combined with quantum transport, we show that the Néel vector of the electrodes can be manipulated by spin-transfer torque. This is staggered over the two different magnetic sublattices and can generate dynamics and switching. At the same time the different magnetization states of the junction can be read by standard tunneling magnetoresistance. Calculations are performed for CuMnAs |GaP |CuMnAs junctions with different surface terminations between the antiferromagnetic CuMnAs electrodes and the insulating GaP spacer. We find that the torque remains staggered regardless of the termination, while the magnetoresistance depends on the microscopic details of the interface.

  9. Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus

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    Jinmi Koo


    Full Text Available BackgroundIn mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN. Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions.MethodsWe examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2 gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC knock-in mice using a real-time bioluminescence measurement system.ResultsAdministration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms.ConclusionThese findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock.

  10. Effect of Wenxin Granules on Gap Junction and MiR-1 in Rats with Myocardial Infarction

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    Aiming Wu


    Full Text Available Myocardial infarction (MI patients are at high risk of potential lethal arrhythmia. Gap junction and microRNA-1 (miR-1 are both arrhythmia generating conditions. The present study investigated whether Wenxin Granules (Wenxin-Keli, WXKL could prevent potential lethal arrhythmia by improving gap junctions and miR-1 following MI. Male Sprague-Dawley rats were divided randomly into control, model, metoprolol, low dose WXKL, and high dose WXKL groups. The MI rat model was created by coronary artery ligation. Treatments were administrated intragastrically to the rats for 4 weeks. Conventional transmission electron microscopy was performed to observe the ultrastructure of gap junctions. Quantitative real-time PCR and western blotting were used to detect the expression of miR-1, protein kinase C (PKC, and related proteins. Additionally, a programmatic electrophysiological stimulation test was performed to detect the ventricular fibrillation threshold (VFT. WXKL protected the ultrastructure of the gap junctions and their constituent Cx43 by regulating miR-1 and PKC mediated signal transduction and increased the VFT significantly in the rat MI model. The results suggested that WXKL is an effective alternative medicine to prevent potentially lethal arrhythmia following MI.

  11. Gap-junction coupling and ATP-sensitive potassium channels in human β -cell clusters: Effects on emergent dynamics (United States)

    Loppini, A.; Pedersen, M. G.; Braun, M.; Filippi, S.


    The importance of gap-junction coupling between β cells in pancreatic islets is well established in mouse. Such ultrastructural connections synchronize cellular activity, confine biological heterogeneity, and enhance insulin pulsatility. Dysfunction of coupling has been associated with diabetes and altered β -cell function. However, the role of gap junctions between human β cells is still largely unexplored. By using patch-clamp recordings of β cells from human donors, we previously estimated electrical properties of these channels by mathematical modeling of pairs of human β cells. In this work we revise our estimate by modeling triplet configurations and larger heterogeneous clusters. We find that a coupling conductance in the range 0.005 -0.020 nS/pF can reproduce experiments in almost all the simulated arrangements. We finally explore the consequence of gap-junction coupling of this magnitude between β cells with mutant variants of the ATP-sensitive potassium channels involved in some metabolic disorders and diabetic conditions, translating studies performed on rodents to the human case. Our results are finally discussed from the perspective of therapeutic strategies. In summary, modeling of more realistic clusters with more than two β cells slightly lowers our previous estimate of gap-junction conductance and gives rise to patterns that more closely resemble experimental traces.

  12. Influence of K+-channels and gap junctions on endothelium derived hyperpolarization-induced renal vasodilation in rats

    DEFF Research Database (Denmark)

    Rasmussen, Kasper Møller; Brasen, Jens Christian; Salomonsson, Max


    , involvement of renal myoendothelial gap junctions was evaluated in vitro. Because assessment of endothelial derived hyperpolarization-induced renal vasodilation in vivo is hampered by experimental limitations, we have combined in vivo and in vitro experiments. Isometric tension in rat renal interlobar...

  13. Down-regulation of membrana granulosa cell gap junctions is correlated with irreversible commitment to resume meiosis in golden Syrian hamster oocytes. (United States)

    Racowsky, C; Baldwin, K V; Larabell, C A; DeMarais, A A; Kazilek, C J


    One of the currently popular hypotheses for the regulation of meiotic resumption in mammalian oocytes proposes that the preovulatory surge of luteinizing hormone causes down-regulation of follicular gap junctions, which in turn disrupts transfer of a meiotic arrester from the somatic cells into the oocyte. The present study has investigated this hypothesis by examining the integrity of membrana granulosa cell gap junctions during the period of irreversible commitment to maturation of golden Syrian hamster oocytes in vivo. Our results have revealed a significant progressive decrease in the fractional area of cell surface occupied by gap junction membrane with increasing percentage of oocytes irreversibly committed to mature (1.946% and 0.921% fractional gap junction area at 0% and 100% oocytes irreversibly committed to mature, respectively, P less than 0.05). This net loss of membrana granulosa cell gap junctions from the cell surface was accompanied by a significant decrease in density of gap junction particles, whether they were arranged in rectilinear or non-rectilinear packing patterns. Furthermore, the number of gap junction particles per unit area of surface membrane scanned also underwent a significant progressive decrease with increasing percentage of oocytes irreversibly committed to mature. These data with the hamster are consistent with the hypothesis that down-regulation of membrana granulosa cell gap junctions may be of central importance in the regulation of gonadotropic stimulation of meiotic resumption in mammalian oocytes.

  14. Homotypic gap junctional communication associated with metastasis increases suppression increases with PKA kinase activity and is unaffected by P13K inhibition (United States)

    Loss of gap junctional intercellular communication (GJIC) between cancer cells is a common characteristic of malignant transformation. This communication is mediated by connexin proteins that make up the functional units of gap junctions. Connexins are highly regulated at the protein level and phosp...

  15. Adenosine receptors regulate gap junction coupling of the human cerebral microvascular endothelial cells hCMEC/D3 by Ca2+influx through cyclic nucleotide-gated channels. (United States)

    Bader, Almke; Bintig, Willem; Begandt, Daniela; Klett, Anne; Siller, Ina G; Gregor, Carola; Schaarschmidt, Frank; Weksler, Babette; Romero, Ignacio; Couraud, Pierre-Olivier; Hell, Stefan W; Ngezahayo, Anaclet


    Gap junction channels are essential for the formation and regulation of physiological units in tissues by allowing the lateral cell-to-cell diffusion of ions, metabolites and second messengers. Stimulation of the adenosine receptor subtype A 2B increases the gap junction coupling in the human blood-brain barrier endothelial cell line hCMEC/D3. Although the increased gap junction coupling is cAMP-dependent, neither the protein kinase A nor the exchange protein directly activated by cAMP were involved in this increase. We found that cAMP activates cyclic nucleotide-gated (CNG) channels and thereby induces a Ca 2+ influx, which leads to the increase in gap junction coupling. The report identifies CNG channels as a possible physiological link between adenosine receptors and the regulation of gap junction channels in endothelial cells of the blood-brain barrier. The human cerebral microvascular endothelial cell line hCMEC/D3 was used to characterize the physiological link between adenosine receptors and the gap junction coupling in endothelial cells of the blood-brain barrier. Expressed adenosine receptor subtypes and connexin (Cx) isoforms were identified by RT-PCR. Scrape loading/dye transfer was used to evaluate the impact of the A 2A and A 2B adenosine receptor subtype agonist 2-phenylaminoadenosine (2-PAA) on the gap junction coupling. We found that 2-PAA stimulated cAMP synthesis and enhanced gap junction coupling in a concentration-dependent manner. This enhancement was accompanied by an increase in gap junction plaques formed by Cx43. Inhibition of protein kinase A did not affect the 2-PAA-related enhancement of gap junction coupling. In contrast, the cyclic nucleotide-gated (CNG) channel inhibitor l-cis-diltiazem, as well as the chelation of intracellular Ca 2+ with BAPTA, or the absence of external Ca 2+ , suppressed the 2-PAA-related enhancement of gap junction coupling. Moreover, we observed a 2-PAA-dependent activation of CNG channels by a combination of

  16. Involvement of the adrenal glands and testis in gap junction formation via testosterone within the male rat anterior pituitary gland. (United States)

    Sakuma, Eisuke; Wada, Ikuo; Otsuka, Takanobu; Wakabayashi, Kenjiro; Ito, Kinya; Soji, Tsuyoshi; Herbert, Damon C


    We investigated the influence of testicular and adrenal androgens on the presence of gap junctions between folliculo-stellate cells in the anterior pituitary glands of 60-day-old Wistar-Imamichi strain male rats. The animals were separated into six groups: Group A served as the controls and had free access to a normal diet and water, Group B was given a normal diet and 0.9% NaCl for their drinking water as the controls of adrenalectomized groups, Group C was castrated, Group D was adrenalectomized, Group E was both castrated and adrenalectomized, and Group F was also both castrated and adrenalectomized. In addition, the animals of Group F were administered a dose of testosterone that is known to produce high physiological levels of the hormones in plasma. Five rats from each group were sacrificed 1, 2, 3, 4, 5, 6, and 7 days after their respective operation, and the anterior pituitary glands were removed and prepared for observation by transmission electron microscopy. We quantified the number of follicles and gap junctions and calculated the rate of occurrence as the ratio of the number of gap junctions existing between folliculo-stellate cells per intersected follicle profile. Simultaneous removal of adrenal glands with castration resulted in a significantly decrease in the number of gap junctions, whereas the administration of testosterone to these rats compensated for this change. These observations indicate that the preservation of gap junctions between folliculo-stellate cells is mainly dependent on androgens from both the testes and adrenal glands in adult male rats. Copyright © 2012 Wiley Periodicals, Inc.

  17. Heart Rate and Extracellular Sodium and Potassium Modulation of Gap Junction Mediated Conduction in Guinea Pigs

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    Michael eEntz


    Full Text Available Background: Recent studies suggested that cardiac conduction in murine hearts with narrow perinexi and 50% reduced connexin43 (Cx43 expression is more sensitive to relatively physiological changes of extracellular potassium ([K+]o and sodium ([Na+]o. Purpose: Determine whether similar [K+]o and [Na+]o changes alter conduction velocity (CV sensitivity to pharmacologic gap junction (GJ uncoupling in guinea pigs.Methods: [K+]o and [Na+]o were varied in Langendorff perfused guinea pig ventricles (Solution A: [K+]o=4.56 and [Na+]o=153.3 mM. Solution B: [K+]o=6.95 and [Na+]o=145.5 mM. Gap junctions were inhibited with carbenoxolone (CBX (15 and 30 μM. Epicardial CV was quantified by optical mapping. Perinexal width was measured with transmission electron microscopy. Total and phosphorylated Cx43 were evaluated by western blotting. Results: Solution composition did not alter CV under control conditions or with 15M CBX. Decreasing the basic cycle length (BCL of pacing from 300 to 160ms decreased CV uniformly with both solutions. At 30 M CBX, a change in solution did not alter CV either longitudinally or transversely at BCL=300ms. However, reducing BCL to 160ms caused CV to decrease more in hearts perfused with Solution B than A. Solution composition did not alter perinexal width, nor did it change total or phosphorylated serine 368 Cx43 expression. These data suggest that the solution dependent CV changes were independent of altered perinexal width or GJ coupling. Action potential duration was always shorter in hearts perfused with Solution B than A, independent of pacing rate and/or CBX concentration. Conclusions: Increased heart rate and GJ uncoupling can unmask small CV differences caused by changing [K+]o and [Na+]o. These data suggest that modulating extracellular ionic composition may be a novel anti-arrhythmic target in diseases with abnormal GJ coupling, particularly when heart rate cannot be controlled.

  18. Protein preconcentration using nanofractures generated by nanoparticle-assisted electric breakdown at junction gaps.

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    Chun-Ping Jen

    Full Text Available Sample preconcentration is an important step that increases the accuracy of subsequent detection, especially for samples with extremely low concentrations. Due to the overlapping of electrical double layers in the nanofluidic channel, the concentration polarization effect can be generated by applying an electric field. Therefore, a nonlinear electrokinetic flow is induced, which results in the fast accumulation of proteins in front of the induced ionic depletion zone, the so-called exclusion-enrichment effect. Nanofractures were created in this work to preconcentrate proteins via the exclusion-enrichment effect. The protein sample was driven by electroosmotic flow and accumulated at a specific location. The preconcentration chip for proteins was fabricated using simple standard soft lithography with a polydimethylsiloxane replica. Nanofractures were formed by utilizing nanoparticle-assisted electric breakdown. The proposed method for nanofracture formation that utilizes nanoparticle deposition at the junction gap between microchannels greatly decreases the required electric breakdown voltage. The experimental results indicate that a protein sample with an extremely low concentration of 1 nM was concentrated to 1.5×10(4-fold in 60 min using the proposed chip.

  19. Quantification of gap junctional intercellular communication based on digital image analysis. (United States)

    Hofgaard, Johannes P; Mollerup, Sarah; Holstein-Rathlou, Niels-Henrik; Nielsen, Morten Schak


    Intercellular communication via gap junction channels can be quantified by several methods based on diffusion of fluorescent dyes or metabolites. Given the variation in intercellular coupling of cells, even under untreated control conditions, it is of essence to quantify the coupling between numerous cells to obtain reliable estimates of metabolic coupling. Quantification is often based on manual counting of fluorescent cells, which is time consuming and may include some degree of subjectivity. In this report, we introduce a technique based on digital image analysis, and the software for the analysis is presented together with a detailed protocol in the online supplemental material ( Fluorescent dye was introduced in connexin 43-expressing C6 glioma cells by in situ electroporation, and fluorescence intensity was measured in the electroporated cells and in cells receiving dye by intercellular diffusion. The analysis performed is semiautomatic, and comparison with traditional cell counting shows that this method reliably determines the effect of uncoupling by several interventions. This new method of analysis yields a rapid and objective quantification process with a high degree of reproducibility.

  20. Extract from the zooxanthellate jellyfish Cotylorhiza tuberculata modulates gap junction intercellular communication in human cell cultures. (United States)

    Leone, Antonella; Lecci, Raffaella Marina; Durante, Miriana; Piraino, Stefano


    On a global scale, jellyfish populations in coastal marine ecosystems exhibit increasing trends of abundance. High-density outbreaks may directly or indirectly affect human economical and recreational activities, as well as public health. As the interest in biology of marine jellyfish grows, a number of jellyfish metabolites with healthy potential, such as anticancer or antioxidant activities, is increasingly reported. In this study, the Mediterranean "fried egg jellyfish" Cotylorhiza tuberculata (Macri, 1778) has been targeted in the search forputative valuable bioactive compounds. A medusa extract was obtained, fractionated, characterized by HPLC, GC-MS and SDS-PAGE and assayed for its biological activity on breast cancer cells (MCF-7) and human epidermal keratinocytes (HEKa). The composition of the jellyfish extract included photosynthetic pigments, valuable ω-3 and ω-6 fatty acids, and polypeptides derived either from jellyfish tissues and their algal symbionts. Extract fractions showed antioxidant activity and the ability to affect cell viability and intercellular communication mediated by gap junctions (GJIC) differentially in MCF-7 and HEKa cells. A significantly higher cytotoxicity and GJIC enhancement in MCF-7 compared to HEKa cells was recorded. A putative action mechanism for the anticancer bioactivity through the modulation of GJIC has been hypothesized and its nutraceutical and pharmaceutical potential was discussed.

  1. HPV16 E6 Controls the Gap Junction Protein Cx43 in Cervical Tumour Cells

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    Peng Sun


    Full Text Available Human papillomavirus type 16 (HPV16 causes a range of cancers including cervical and head and neck cancers. HPV E6 oncoprotein binds the cell polarity regulator hDlg (human homologue of Drosophila Discs Large. Previously we showed in vitro, and now in vivo, that hDlg also binds Connexin 43 (Cx43, a major component of gap junctions that mediate intercellular transfer of small molecules. In HPV16-positive non-tumour cervical epithelial cells (W12G Cx43 localised to the plasma membrane, while in W12T tumour cells derived from these, it relocated with hDlg into the cytoplasm. We now provide evidence that E6 regulates this cytoplasmic pool of Cx43. E6 siRNA depletion in W12T cells resulted in restoration of Cx43 and hDlg trafficking to the cell membrane. In C33a HPV-negative cervical tumour cells expressing HPV16 or 18 E6, Cx43 was located primarily in the cytoplasm, but mutation of the 18E6 C-terminal hDlg binding motif resulted in redistribution of Cx43 to the membrane. The data indicate for the first time that increased cytoplasmic E6 levels associated with malignant progression alter Cx43 trafficking and recycling to the membrane and the E6/hDlg interaction may be involved. This suggests a novel E6-associated mechanism for changes in Cx43 trafficking in cervical tumour cells.

  2. Formation of antiwaves in gap-junction-coupled chains of neurons. (United States)

    Urban, Alexander; Ermentrout, Bard


    Using network models consisting of gap-junction-coupled Wang-Buszaki neurons, we demonstrate that it is possible to obtain not only synchronous activity between neurons but also a variety of constant phase shifts between 0 and π. We call these phase shifts intermediate stable phase-locked states. These phase shifts can produce a large variety of wavelike activity patterns in one-dimensional chains and two-dimensional arrays of neurons, which can be studied by reducing the system of equations to a phase model. The 2π periodic coupling functions of these models are characterized by prominent higher order terms in their Fourier expansion, which can be varied by changing model parameters. We study how the relative contribution of the odd and even terms affects what solutions are possible, the basin of attraction of those solutions, and their stability. These models may be applicable to the spinal central pattern generators of the dogfish and also to the developing neocortex of the neonatal rat.

  3. Connexin expression and gap-junctional intercellular communication in ES cells and iPS cells. (United States)

    Oyamada, Masahito; Takebe, Kumiko; Endo, Aya; Hara, Sachiko; Oyamada, Yumiko


    Pluripotent stem cells, i.e., embryonic stem (ES) and induced pluripotent stem (iPS) cells, can indefinitely proliferate without commitment and differentiate into all cell lineages. ES cells are derived from the inner cell mass of the preimplantation blastocyst, whereas iPS cells are generated from somatic cells by overexpression of a few transcription factors. Many studies have demonstrated that mouse and human iPS cells are highly similar but not identical to their respective ES cell counterparts. The potential to generate basically any differentiated cell types from these cells offers the possibility to establish new models of mammalian development and to create new sources of cells for regenerative medicine. ES cells and iPS cells also provide useful models to study connexin expression and gap-junctional intercellular communication (GJIC) during cell differentiation and reprogramming. In 1996, we reported connexin expression and GJIC in mouse ES cells. Because a substantial number of papers on these subjects have been published since our report, this Mini Review summarizes currently available data on connexin expression and GJIC in ES cells and iPS cells during undifferentiated state, differentiation, and reprogramming.

  4. Barreloid Borders and Neuronal Activity Shape Panglial Gap Junction-Coupled Networks in the Mouse Thalamus. (United States)

    Claus, Lena; Philippot, Camille; Griemsmann, Stephanie; Timmermann, Aline; Jabs, Ronald; Henneberger, Christian; Kettenmann, Helmut; Steinhäuser, Christian


    The ventral posterior nucleus of the thalamus plays an important role in somatosensory information processing. It contains elongated cellular domains called barreloids, which are the structural basis for the somatotopic organization of vibrissae representation. So far, the organization of glial networks in these barreloid structures and its modulation by neuronal activity has not been studied. We have developed a method to visualize thalamic barreloid fields in acute slices. Combining electrophysiology, immunohistochemistry, and electroporation in transgenic mice with cell type-specific fluorescence labeling, we provide the first structure-function analyses of barreloidal glial gap junction networks. We observed coupled networks, which comprised both astrocytes and oligodendrocytes. The spread of tracers or a fluorescent glucose derivative through these networks was dependent on neuronal activity and limited by the barreloid borders, which were formed by uncoupled or weakly coupled oligodendrocytes. Neuronal somata were distributed homogeneously across barreloid fields with their processes running in parallel to the barreloid borders. Many astrocytes and oligodendrocytes were not part of the panglial networks. Thus, oligodendrocytes are the cellular elements limiting the communicating panglial network to a single barreloid, which might be important to ensure proper metabolic support to active neurons located within a particular vibrissae signaling pathway. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:

  5. Connexin Type and Fluorescent Protein Fusion Tag Determine Structural Stability of Gap Junction Plaques* (United States)

    Stout, Randy F.; Snapp, Erik Lee; Spray, David C.


    Gap junctions (GJs) are made up of plaques of laterally clustered intercellular channels and the membranes in which the channels are embedded. Arrangement of channels within a plaque determines subcellular distribution of connexin binding partners and sites of intercellular signaling. Here, we report the discovery that some connexin types form plaque structures with strikingly different degrees of fluidity in the arrangement of the GJ channel subcomponents of the GJ plaque. We uncovered this property of GJs by applying fluorescence recovery after photobleaching to GJs formed from connexins fused with fluorescent protein tags. We found that connexin 26 (Cx26) and Cx30 GJs readily diffuse within the plaque structures, whereas Cx43 GJs remain persistently immobile for more than 2 min after bleaching. The cytoplasmic C terminus of Cx43 was required for stability of Cx43 plaque arrangement. We provide evidence that these qualitative differences in GJ arrangement stability reflect endogenous characteristics, with the caveat that the sizes of the GJs examined were necessarily large for these measurements. We also uncovered an unrecognized effect of non-monomerized fluorescent protein on the dynamically arranged GJs and the organization of plaques composed of multiple connexin types. Together, these findings redefine our understanding of the GJ plaque structure and should be considered in future studies using fluorescent protein tags to probe dynamics of highly ordered protein complexes. PMID:26265468

  6. TLR2 mediates gap junctional intercellular communication through connexin-43 in intestinal epithelial barrier injury. (United States)

    Ey, Birgit; Eyking, Annette; Gerken, Guido; Podolsky, Daniel K; Cario, Elke


    Gap junctional intercellular communication (GJIC) coordinates cellular functions essential for sustaining tissue homeostasis; yet its regulation in the intestine is not well understood. Here, we identify a novel physiological link between Toll-like receptor (TLR) 2 and GJIC through modulation of Connexin-43 (Cx43) during acute and chronic inflammatory injury of the intestinal epithelial cell (IEC) barrier. Data from in vitro studies reveal that TLR2 activation modulates Cx43 synthesis and increases GJIC via Cx43 during IEC injury. The ulcerative colitis-associated TLR2-R753Q mutant targets Cx43 for increased proteasomal degradation, impairing TLR2-mediated GJIC during intestinal epithelial wounding. In vivo studies using mucosal RNA interference show that TLR2-mediated mucosal healing depends functionally on intestinal epithelial Cx43 during acute inflammatory stress-induced damage. Mice deficient in TLR2 exhibit IEC-specific alterations in Cx43, whereas administration of a TLR2 agonist protects GJIC by blocking accumulation of Cx43 and its hyperphosphorylation at Ser368 to prevent spontaneous chronic colitis in MDR1alpha-deficient mice. Finally, adding the TLR2 agonist to three-dimensional intestinal mucosa-like cultures of human biopsies preserves intestinal epithelial Cx43 integrity and polarization ex vivo. In conclusion, Cx43 plays an important role in innate immune control of commensal-mediated intestinal epithelial wound repair.

  7. Inhibition of gap junction communication at ectopic Eph/ephrin boundaries underlies craniofrontonasal syndrome.

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    Alice Davy


    Full Text Available Mutations in X-linked ephrin-B1 in humans cause craniofrontonasal syndrome (CFNS, a disease that affects female patients more severely than males. Sorting of ephrin-B1-positive and -negative cells following X-inactivation has been observed in ephrin-B1(+/- mice; however, the mechanisms by which mosaic ephrin-B1 expression leads to cell sorting and phenotypic defects remain unknown. Here we show that ephrin-B1(+/- mice exhibit calvarial defects, a phenotype autonomous to neural crest cells that correlates with cell sorting. We have traced the causes of calvarial defects to impaired differentiation of osteogenic precursors. We show that gap junction communication (GJC is inhibited at ectopic ephrin boundaries and that ephrin-B1 interacts with connexin43 and regulates its distribution. Moreover, we provide genetic evidence that GJC is implicated in the calvarial defects observed in ephrin-B1(+/- embryos. Our results uncover a novel role for Eph/ephrins in regulating GJC in vivo and suggest that the pleiotropic defects seen in CFNS patients are due to improper regulation of GJC in affected tissues.

  8. Low Level Pro-inflammatory Cytokines Decrease Connexin36 Gap Junction Coupling in Mouse and Human Islets through Nitric Oxide-mediated Protein Kinase Cδ* (United States)

    Farnsworth, Nikki L.; Walter, Rachelle L.; Hemmati, Alireza; Westacott, Matthew J.; Benninger, Richard K. P.


    Pro-inflammatory cytokines contribute to the decline in islet function during the development of diabetes. Cytokines can disrupt insulin secretion and calcium dynamics; however, the mechanisms underlying this are poorly understood. Connexin36 gap junctions coordinate glucose-induced calcium oscillations and pulsatile insulin secretion across the islet. Loss of gap junction coupling disrupts these dynamics, similar to that observed during the development of diabetes. This study investigates the mechanisms by which pro-inflammatory cytokines mediate gap junction coupling. Specifically, as cytokine-induced NO can activate PKCδ, we aimed to understand the role of PKCδ in modulating cytokine-induced changes in gap junction coupling. Isolated mouse and human islets were treated with varying levels of a cytokine mixture containing TNF-α, IL-1β, and IFN-γ. Islet dysfunction was measured by insulin secretion, calcium dynamics, and gap junction coupling. Modulators of PKCδ and NO were applied to determine their respective roles in modulating gap junction coupling. High levels of cytokines caused cell death and decreased insulin secretion. Low levels of cytokine treatment disrupted calcium dynamics and decreased gap junction coupling, in the absence of disruptions to insulin secretion. Decreases in gap junction coupling were dependent on NO-regulated PKCδ, and altered membrane organization of connexin36. This study defines several mechanisms underlying the disruption to gap junction coupling under conditions associated with the development of diabetes. These mechanisms will allow for greater understanding of islet dysfunction and suggest ways to ameliorate this dysfunction during the development of diabetes. PMID:26668311

  9. Expression of connexin32 and connexin43 gap junction proteins and E-cadherin in human lung cancer. (United States)

    Jinn, Y; Ichioka, M; Marumo, F


    We used immunohistochemical staining to examine the expression of the gap junction proteins connexin32 and connexin43 and of the intercellular adhesion molecule, E-cadherin, that is thought to be a prerequisite for gap junctional intercellular communication (GJIC), in 24 specimens of human lung cancer. Connexin32 was not found in cancer tissue and there were significantly fewer spots of connexin43 in the poorly differentiated versus the well differentiated (P = 0.0005) and moderately differentiated (P = 0.0002) adenocarcinomas and in the poorly differentiated versus the well differentiated (P = 0.0182) and moderately differentiated (P = 0.004) squamous cell carcinomas of the lung. E-Cadherin was expressed in all but three cases of poorly differentiated non-small cell lung cancer that showed a heterogeneously decreased expression of E-cadherin. These findings suggest that GJIC is decreased in poorly differentiated non-small cell lung cancer.

  10. Design and characterization of the first peptidomimetic molecule that prevents acidification-induced closure of cardiac gap junctions (United States)

    Verma, Vandana; Larsen, Bjarne Due; Coombs, Wanda; Lin, Xianming; Sarrou, Eliana; Taffet, Steven M.; Delmar, Mario


    Background Gap junctions are potential targets for pharmacological intervention. We have previously developed a series of peptide sequences that prevent closure of Cx43 channels, bind to cardiac Cx43 and prevent acidification-induced uncoupling of cardiac gap junctions. Objective We aimed to identify and validate the minimum core active structure in peptides containing an RR-N/Q-Y motif. Based on that information, we sought to generate a peptidomimetic molecule that acts on the chemical regulation of Cx43 channels. Methods Experiments were based on a combination of biochemical, spectroscopic and electrophysiological techniques, as well as molecular modeling of active pharmacophores with Cx43 activity. Results Molecular modeling analysis indicated that the functional elements of the side chains in the motif RRXY form a triangular structure. Experimental data revealed that compounds containing such a structure bind to Cx43 and prevent Cx43 chemical gating. These results provided us with the first platform for drug design targeted to the carboxyl terminal of Cx43. Using that platform, we designed and validated a peptidomimetic compound (ZP2519; molecular weight 619 Da) that prevented octanol-induced uncoupling of Cx43 channels, and pH gating of cardiac gap junctions. Conclusion Structure-based drug design can be applied to the development of pharmacophores that act directly on Cx43. Small molecules containing these pharmacophores can serve as tools to determine the role of gap junction regulation in the control of cardiac rhythm. Future studies will determine whether these compounds can function as pharmacological agents for the treatment of a selected subset of cardiac arrhythmias. PMID:20601149

  11. Decreased gap-junctional communication associated with segregation of the neuronal phenotype in the RT4 cell-line family. (United States)

    Donahue, L M; Webster, D R; Martinez, I; Spray, D C


    RT4 is a family of cell lines derived from a rat peripheral neurotumor. The RT4 family consists of a multipotential stem-cell line that spontaneously gives rise to three derivative cell types, one glial and two neuronal. The three derivative cell types are capable of further lineage-specific maturation under appropriate culture conditions. Gap-junctional communication is postulated to be important during nervous-system development by allowing and/or controlling the transmission of both electrical current and signaling molecules, which may affect growth and differentiation. Our characterization of gap-junctional communication in the RT4 cell line family revealed that: (1) the glial-derivative and the stem-cell line were extensively coupled, while the two neuronal derivatives were significantly less coupled, and (2) all of the RT4 cell lines, including the stem-cell line, expressed Cx43 mRNA and protein, and the levels were generally consistent with the observed degree of functional coupling. These observations are consistent with data from in vivo studies and establish the RT4 cell line family as a potentially useful in vitro model system for understanding the role(s) of gap-junctional communication during differentiation in the peripheral nervous system.

  12. Regulation of Gap Junctions in Porcine Cumulus-Oocyte Complexes: Contributions of Granulosa Cell Contact, Gonadotropins, and Lipid Rafts (United States)

    Sasseville, Maxime; Gagnon, Marie-Claude; Guillemette, Christine; Sullivan, Robert; Gilchrist, Robert B.; Richard, François J.


    Gap-junctional communication (GJC) plays a central role in oocyte growth. However, little is known about the regulation of connexin 43 (Cx43)-based gap-junction channels in cumulus-oocyte complexes (COCs) during in vitro maturation. We show that rupture of COCs from mural granulosa cells up-regulates Cx43-mediated GJC and that gonadotropins signal GJC breakdown by recruiting Cx43 to lipid rafts when oocyte meiosis resumes. Oocyte calcein uptake through gap junctions increases during early in vitro oocyte maturation and remains high until 18 h, when it falls simultaneously with the oocyte germinal vesicle breakdown. Immunodetection of Cx43 and fluorescence recovery after photobleaching assays revealed that the increase of GJC is independent of gonadotropins but requires RNA transcription, RNA polyadenylation, and translation. GJC rupture, in contrast, is achieved by a gonadotropin-dependent mechanism involving recruitment of Cx43 to clustered lipid rafts. These results show that GJC up-regulation in COCs in in vitro culture is independent of gonadotropins and transcriptionally regulated. However, GJC breakdown is gonadotropin dependent and mediated by the clustering of Cx43 in lipid raft microdomains. In conclusion, this study supports a functional role of lipid raft clustering of Cx43 in GJC breakdown in the COCs during in vitro maturation. PMID:19228792

  13. Gap junctional communication in osteocytes is amplified by low intensity vibrations in vitro.

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    Gunes Uzer

    Full Text Available The physical mechanism by which cells sense high-frequency mechanical signals of small magnitude is unknown. During exposure to vibrations, cell populations within a bone are subjected not only to acceleratory motions but also to fluid shear as a result of fluid-cell interactions. We explored displacements of the cell nucleus during exposure to vibrations with a finite element (FE model and tested in vitro whether vibrations can affect osteocyte communication independent of fluid shear. Osteocyte like MLO-Y4 cells were subjected to vibrations at acceleration magnitudes of 0.15 g and 1 g and frequencies of 30 Hz and 100 Hz. Gap junctional intracellular communication (GJIC in response to these four individual vibration regimes was investigated. The FE model demonstrated that vibration induced dynamic accelerations caused larger relative nuclear displacement than fluid shear. Across the four regimes, vibrations significantly increased GJIC between osteocytes by 25%. Enhanced GJIC was independent of vibration induced fluid shear; there were no differences in GJIC between the four different vibration regimes even though differences in fluid shear generated by the four regimes varied 23-fold. Vibration induced increases in GJIC were not associated with altered connexin 43 (Cx43 mRNA or protein levels, but were dependent on Akt activation. Combined, the in silico and in vitro experiments suggest that externally applied vibrations caused nuclear motions and that large differences in fluid shear did not influence nuclear motion (<1% or GJIC, perhaps indicating that vibration induced nuclear motions may directly increase GJIC. Whether the increase in GJIC is instrumental in modulating anabolic and anti-catabolic processes associated with the application of vibrations remains to be determined.

  14. Marine sponge depsipeptide increases gap junction length in HTC cells transfected with Cx43-GFP. (United States)

    Rangel, Marisa; Ionta, Marisa; Cristina Pfister, Sandra; Adolpho Sant'anna Ferreira, Raphael; Maria Machado-Santelli, Glaucia


    Connexins are membrane proteins that form GJ (gap junction) channels between adjacent cells. Cx43 (connexin 43), the most widely expressed member of the connexin family, has a rapid turnover rate, and its degradation involves both the lysosomal and ubiquitin-proteasome pathway. The goal of this work was to study the effects of geodiamolides, natural peptides from marine sponge that normally are involved with microfilament disruption, on connexin assembly or degradation in the plasma membrane. HTC (hepatocarcinoma cells) expressing Cx43-GFP (green fluorescent protein) were submitted to treatment with 200 nM geodiamolides A, B, H and I for 2 and 4 h. Microfilament distribution and the presence and size of GJ plaques were evaluated by laser scanning confocal microscopy. Among the four peptides tested, only Geo H (geodiamolide H) statistically enhanced the length of GJ plaques. Geodiamolide A also showed activity in the GJ plaque size; however, its effect was less pronounced. Treatment with Geo H could interfere with the delivery of connexins to the degradation structures, similar to proteasomal pathways, keeping the connexins assembled and accumulating GJ plaques. Further experiments, with the cells treated with Geo H, using the fungal antibiotic BFA (brefeldin A), were performed in order to uncouple events leading to GJ assembly from those related to GJ removal, since BFA is known to block protein trafficking within a fused ER (endoplasmic reticulum)/Golgi compartment. GJ plaques were drastically reduced after BFA/Geo H treatment, thus indicating that Geo H affects mainly the delivery pathway of Cx43 protein.

  15. Local oxidative stress expansion through endothelial cells--a key role for gap junction intercellular communication.

    Directory of Open Access Journals (Sweden)

    Ilan Feine

    Full Text Available BACKGROUND: Major circulation pathologies are initiated by oxidative insult expansion from a few injured endothelial cells to distal sites; this possibly involves mechanisms that are important to understanding circulation physiology and designing therapeutic management of myocardial pathologies. We tested the hypothesis that a localized oxidative insult of endothelial cells (ECs propagates through gap junction inter-cellular communication (GJIC. METHODOLOGY/PRINCIPAL FINDINGS: Cultures comprising the bEnd.3 cell line, that have been established and recognized as suitable for examining communication among ECs, were used to study the propagation of a localized oxidative insult to remote cells. Spatially confined near infrared illumination of parental or genetically modified bEnd.3 cultures, pretreated with the photosensitizer WST11, generated O(2•(- and •OH radicals in the illuminated cells. Time-lapse fluorescence microscopy, utilizing various markers, and other methods, were used to monitor the response of non-illuminated bystander and remote cells. Functional GJIC among ECs was shown to be mandatory for oxidative insult propagation, comprising de-novo generation of reactive oxygen and nitrogen species (ROS and RNS, respectively, activation and nuclear translocation of c-Jun N-terminal kinase, followed by massive apoptosis in all bystander cells adjacent to the primarily injured ECs. The oxidative insult propagated through GJIC for many hours, over hundreds of microns from the primary photogeneration site. This wave is shown to be limited by intracellular ROS scavenging, chemical GJIC inhibition or genetic manipulation of connexin 43 (a key component of GJIC. CONCLUSION/SIGNIFICANCE: Localized oxidative insults propagate through GJIC between ECs, while stimulating de-novo generation of ROS and RNS in bystander cells, thereby driving the insult's expansion.

  16. Evidence of involvement of neurone-glia/neurone-neurone communications via gap junctions in synchronised activity of KNDy neurones. (United States)

    Ikegami, K; Minabe, S; Ieda, N; Goto, T; Sugimoto, A; Nakamura, S; Inoue, N; Oishi, S; Maturana, A D; Sanbo, M; Hirabayashi, M; Maeda, K-I; Tsukamura, H; Uenoyama, Y


    Pulsatile secretion of gonadotrophin-releasing hormone (GnRH)/luteinising hormone is indispensable for the onset of puberty and reproductive activities at adulthood in mammalian species. A cohort of neurones expressing three neuropeptides, namely kisspeptin, encoded by the Kiss1 gene, neurokinin B (NKB) and dynorphin A, localised in the hypothalamic arcuate nucleus (ARC), so-called KNDy neurones, comprises a putative intrinsic source of the GnRH pulse generator. Synchronous activity among KNDy neurones is considered to be required for pulsatile GnRH secretion. It has been reported that gap junctions play a key role in synchronising electrical activity in the central nervous system. Thus, we hypothesised that gap junctions are involved in the synchronised activities of KNDy neurones, which is induced by NKB-NK3R signalling. We determined the role of NKB-NK3R signalling in Ca 2+ oscillation (an indicator of neuronal activities) of KNDy neurones and its synchronisation mechanism among KNDy neurones. Senktide, a selective agonist for NK3R, increased the frequency of Ca 2+ oscillations in cultured Kiss1-GFP cells collected from the mediobasal hypothalamus of the foetal Kiss1-green fluorescent protein (GFP) mice. The senktide-induced Ca 2+ oscillations were synchronised in the Kiss1-GFP and neighbouring glial cells. Confocal microscopy analysis of these cells, which have shown synchronised Ca 2+ oscillations, revealed close contacts between Kiss1-GFP cells, as well as between Kiss1-GFP cells and glial cells. Dye coupling experiments suggest cell-to-cell communication through gap junctions between Kiss1-GFP cells and neighbouring glial cells. Connexin-26 and -37 mRNA were found in isolated ARC Kiss1 cells taken from adult female Kiss1-GFP transgenic mice. Furthermore, 18β-glycyrrhetinic acids and mefloquine, which are gap junction inhibitors, attenuated senktide-induced Ca 2+ oscillations in Kiss1-GFP cells. Taken together, these results suggest that NKB-NK3R signalling


    Abstract Gap Junctional Intercellular Communication (GJIC) is the major pathway of intercellular signal transduction, and is, thus, important for normal cell growth and function. Recent studies have revealed a global distribution of some perfluorinated organic compounds e...

  18. Decreases in Gap Junction Coupling Recovers Ca2+ and Insulin Secretion in Neonatal Diabetes Mellitus, Dependent on Beta Cell Heterogeneity and Noise.

    Directory of Open Access Journals (Sweden)

    Aleena M Notary


    Full Text Available Diabetes is caused by dysfunction to β-cells in the islets of Langerhans, disrupting insulin secretion and glucose homeostasis. Gap junction-mediated electrical coupling between β-cells in the islet plays a major role in coordinating a pulsatile secretory response at elevated glucose and suppressing insulin secretion at basal glucose. Previously, we demonstrated that a critical number of inexcitable cells can rapidly suppress the overall islet response, as a result of gap junction coupling. This was demonstrated in a murine model of Neonatal Diabetes Mellitus (NDM involving expression of ATP-insensitive KATP channels, and by a multi-cellular computational model of islet electrical activity. Here we examined the mechanisms by which gap junction coupling contributes to islet dysfunction in NDM. We first verified the computational model against [Ca2+] and insulin secretion measurements in islets expressing ATP-insensitive KATP channels under different levels of gap junction coupling. We then applied this model to predict how different KATP channel mutations found in NDM suppress [Ca2+], and the role of gap junction coupling in this suppression. We further extended the model to account for stochastic noise and insulin secretion dynamics. We found experimentally and in the islet model that reductions in gap junction coupling allow progressively greater glucose-stimulated [Ca2+] and insulin secretion following expression of ATP-insensitive KATP channels. The model demonstrated good correspondence between suppression of [Ca2+] and clinical presentation of different NDM mutations. Significant recoveries in [Ca2+] and insulin secretion were predicted for many mutations upon reductions in gap junction coupling, where stochastic noise played a significant role in the recoveries. These findings provide new understanding how the islet functions as a multicellular system and for the role of gap junction channels in exacerbating the effects of decreased

  19. Gap junctions mediate large-scale Turing structures in a mean-field cortex driven by subcortical noise (United States)

    Steyn-Ross, Moira L.; Steyn-Ross, D. A.; Wilson, M. T.; Sleigh, J. W.


    One of the grand puzzles in neuroscience is establishing the link between cognition and the disparate patterns of spontaneous and task-induced brain activity that can be measured clinically using a wide range of detection modalities such as scalp electrodes and imaging tomography. High-level brain function is not a single-neuron property, yet emerges as a cooperative phenomenon of multiply-interacting populations of neurons. Therefore a fruitful modeling approach is to picture the cerebral cortex as a continuum characterized by parameters that have been averaged over a small volume of cortical tissue. Such mean-field cortical models have been used to investigate gross patterns of brain behavior such as anesthesia, the cycles of natural sleep, memory and erasure in slow-wave sleep, and epilepsy. There is persuasive and accumulating evidence that direct gap-junction connections between inhibitory neurons promote synchronous oscillatory behavior both locally and across distances of some centimeters, but, to date, continuum models have ignored gap-junction connectivity. In this paper we employ simple mean-field arguments to derive an expression for D2 , the diffusive coupling strength arising from gap-junction connections between inhibitory neurons. Using recent neurophysiological measurements reported by Fukuda [J. Neurosci. 26, 3434 (2006)], we estimate an upper limit of D2≈0.6cm2 . We apply a linear stability analysis to a standard mean-field cortical model, augmented with gap-junction diffusion, and find this value for the diffusive coupling strength to be close to the critical value required to destabilize the homogeneous steady state. Computer simulations demonstrate that larger values of D2 cause the noise-driven model cortex to spontaneously crystalize into random mazelike Turing structures: centimeter-scale spatial patterns in which regions of high-firing activity are intermixed with regions of low-firing activity. These structures are consistent with the

  20. High resolution, fluorescence deconvolution microscopy and tagging with the autofluorescent tracers CFP, GFP, and YFP to study the structural composition of gap junctions in living cells. (United States)

    Falk, M M; Lauf, U


    High-resolution, fluorescence deconvolution (DV) microscopy was implemented to obtain a detailed view of the organization and structural composition of gap junctions assembled from one or two different connexin isotypes in live and fixed cells. To visualize gap junctions, the structural protein components of gap junction channels, the connexin polypeptides alpha1(Cx43), beta1(Cx32), and beta2(Cx26), were tagged on their C-termini with the autofluorescent tracers green fluorescent protein (GFP), and its cyan (CFP), and yellow (YFP) color variants. Tagged connexins were expressed in transiently transfected HeLa cells. Comprehensive analysis including dye-transfer analysis demonstrated that the tagged connexins trafficked, assembled, and packed normally into functional gap junction channel plaques. Such gap junction plaques were examined by single, dual, and triple-color DV microscopy. High-resolution images and three-dimensional volume reconstructions of gap junction plaques were obtained by this technique, which revealed several new aspects of gap junction structure. Specifically, the studies demonstrated that the mode of channel distribution strictly depends on the connexin isotypes. Here we present such images, and volume reconstructions in context with images obtained by other light, and electron microscopic techniques, such as laser scanning confocal, conventional wide-field fluorescence, thin section, and freeze-fracture electron microscopy. In addition, we give a simple description of the principal mechanisms of DV microscopy, name advantages and disadvantages, and discuss issues such as dual-color imaging using CFP and YFP, spatial resolution, colocalization, and avoiding imaging artifacts.

  1. Optical modulation of nano-gap tunnelling junctions comprising self-assembled monolayers of hemicyanine dyes

    NARCIS (Netherlands)

    Pourhossein, Parisa; Vijayaraghavan, Ratheesh K; Meskers, Stefan C J; Chiechi, Ryan C


    Light-driven conductance switching in molecular tunnelling junctions that relies on photoisomerization is constrained by the limitations of kinetic traps and either by the sterics of rearranging atoms in a densely packed monolayer or the small absorbance of individual molecules. Here we demonstrate

  2. Role of Myoendothelial Gap Junctions in the Regulation of Human Coronary Artery Smooth Muscle Cell Differentiation by Laminar Shear Stress

    Directory of Open Access Journals (Sweden)

    Zongqi Zhang


    Full Text Available Background/Aims: Smooth muscle cells may dedifferentiate into the synthetic phenotype and promote atherosclerosis. Here, we explored the role of myoendothelial gap junctions in phenotypic switching of human coronary artery smooth muscle cells (HCASMCs co-cultured with human coronary artery endothelial cells (HCAECs exposed to shear stress. Methods: HCASMCs and HCAECs were seeded on opposite sides of Transwell inserts, and HCAECs were exposed to laminar shear stress of 12 dyn/cm2 or 5 dyn/cm2. The myoendothelial gap junctions were evaluated by using a multi-photon microscope. Results: In co-culture with HCAECs, HCASMCs exhibited a contractile phenotype, and maintained the expression of differentiation markers MHC and H1-calponin. HCASMCs and HCAECs formed functional intercellular junctions, as evidenced by colocalization of connexin(Cx40 and Cx43 on cellular projections inside the Transwell membrane and biocytin transfer from HCAECs to HCASMCs. Cx40 siRNA and 18-α-GA attenuated protein expression of MHC and H1-calponin in HCASMCs. Shear stress of 5 dyn/cm2 increased Cx43 and decreased Cx40 expression in HCAECs, and partly inhibited biocytin transfer from HCAECs to HCASMCs, which could be completely blocked by Cx43 siRNA or restored by Cx40 DNA transfected into HCAECs. The exposure of HCAECs to shear stress of 5 dyn/cm2 promoted HCASMC phenotypic switching, manifested by morphological changes, decrease in MHC and H1-calponin expression, and increase in platelet-derived growth factor (PDGF-BB release, which was partly rescued by Cx43 siRNA or Cx40 DNA or PDGF receptor signaling inhibitor. Conclusions: The exposure of HCAECs to shear stress of 5 dyn/cm2 caused the dysfunction of Cx40/Cx43 heterotypic myoendothelial gap junctions, which may be replaced by homotypic Cx43/Cx43 channels, and induced HCASMC transition to the synthetic phenotype associated with the activation of PDGF receptor signaling, which may contribute to shear stress

  3. Costimulation of N-methyl-D-aspartate and muscarinic neuronal receptors modulates gap junctional communication in striatal astrocytes. (United States)

    Rouach, N; Tencé, M; Glowinski, J; Giaume, C


    Cocultures of neurons and astrocytes from the rat striatum were used to determine whether the stimulation of neuronal receptors could affect the level of intercellular communication mediated by gap junctions in astrocytes. The costimulation of N-methyl-D-asparte (NMDA) and muscarinic receptors led to a prominent reduction of astrocyte gap junctional communication (GJC) in coculture. This treatment was not effective in astrocyte cultures, these cells being devoid of NMDA receptors. Both types of receptors contribute synergistically to this inhibitory response, as the reduction in astrocyte GJC was not observed after the blockade of either NMDA or muscarinic receptors. The involvement of a neuronal release of arachidonic acid (AA) in this inhibition was investigated because the costimulation of neuronal NMDA and muscarinic receptors markedly enhanced the release of AA in neuronal cultures and in cocultures. In addition, both the reduction of astrocyte GJC and the release of AA evoked by NMDA and muscarinic receptor costimulation were prevented by mepacrine, a phospholipase A(2) inhibitor, and this astrocyte GJC inhibition was mimicked by the exogenous application of AA. Metabolites of AA formed through the cyclooxygenase pathway seem to be responsible for the effects induced by either the costimulation of NMDA and muscarinic neuronal receptors or the application of exogenous AA because, in both cases, astrocyte GJC inhibition was prevented by indomethacin. Altogether, these data provide evidence for a neuronal control of astrocytic communication and open perspectives for the understanding of the modalities through which cholinergic interneurons and glutamatergic inputs affect local circuits in the striatum.

  4. Distinct molecular targets including SLO-1 and gap junctions are engaged across a continuum of ethanol concentrations in Caenorhabditis elegans (United States)

    Dillon, James; Andrianakis, Ioannis; Mould, Richard; Ient, Ben; Liu, Wei; James, Christopher; O'Connor, Vincent; Holden-Dye, Lindy


    Ethanol (alcohol) interacts with diverse molecular effectors across a range of concentrations in the brain, eliciting intoxication through to sedation. Invertebrate models including the nematode worm Caenorhabditis elegans have been deployed for molecular genetic studies to inform on key components of these alcohol signaling pathways. C. elegans studies have typically employed external dosing with high (>250 mM) ethanol concentrations: A careful analysis of responses to low concentrations is lacking. Using the C. elegans pharyngeal system as a paradigm, we report a previously uncharacterized continuum of cellular and behavioral responses to ethanol from low (10 mM) to high (300 mM) concentrations. The complexity of these responses indicates that the pleiotropic action of ethanol observed in mammalian brain is conserved in this invertebrate model. We investigated two candidate ethanol effectors, the calcium-activated K+ channel SLO-1 and gap junctions, and show that they contribute to, but are not sole determinants of, the low- and high-concentration effects, respectively. Notably, this study shows cellular and whole organismal behavioral responses to ethanol in C. elegans that directly equate to intoxicating through to supralethal blood alcohol concentrations in humans and provides an important benchmark for interpretation of paradigms that seek to inform on human alcohol use disorders.—Dillon, J., Andrianakis, I., Mould, R., Ient, B., Liu, W., James, C., O'Connor, V., Holden-Dye, L. Distinct molecular targets including SLO-1 and gap junctions are engaged across a continuum of ethanol concentrations in Caenorhabditis elegans. PMID:23882127

  5. Role of intramolecular interaction in connexin50: mediating the Ca2+-dependent binding of calmodulin to gap junction. (United States)

    Zhang, Xianrong; Qi, Yipeng


    Gap junction channels formed by connexin50 (Cx50) are critical for maintenance of eye lens transparency. Cleavage of the carboxyl terminus (CT) of Cx50 to produce truncated Cx50 (Cx50trunc) occurred naturally during maturation of lens fiber cells. The mechanism of its altered properties is under confirmation. It has been suggested that calmodulin (CaM) participates in gating some kinds of gap junction. Here, we performed confocal colocalization and co-immunoprecipitation experiments to study the relationships between Cx50 and CaM. Results exhibited that the CaM could colocalize Ca2+ dependently with CT in the linear area of cell-to-cell contact formed by Cx50trunc, while it could not localize in the linear area without expression of CT. Further study indicated that the CT could interact Ca2+ independently with the cytoplasmic loop (CL) of Cx50. These data put forward the importance of Ca2+-independent intramolecular interaction between CT and CL of Cx50, which mediate the Ca2+-dependent binding of CaM to Cx50. These intra- and intermolecular interactions may further improve our understanding of biological significance of the Cx50 in the eye lens.

  6. Intercellular calcium waves in the fire-diffuse-fire framework: Green's function for gap-junctional coupling. (United States)

    Harris, Jamie; Timofeeva, Yulia


    Calcium is a crucial component in a plethora of cellular processes involved in cell birth, life, and death. Intercellular calcium waves that can spread through multiple cells provide one form of cellular communication mechanism between various parts of cell tissues. Here we introduce a simple, yet biophysically realistic model for the propagation of intercellular calcium waves based on the fire-diffuse-fire type model for calcium dynamics. Calcium release sites are considered to be discretely distributed along individual linear cells that are connected by gap junctions and a solution of this model can be found in terms of the Green's function for this system. We develop the "sum-over-trips" formalism that takes into account the boundary conditions at gap junctions providing a generalization of the original sum-over-trips approach for constructing the response function for branched neural dendrites. We obtain the exact solution of the Green's function in the Laplace (frequency) domain for an infinite array of cells and show that this Green's function can be well approximated by its truncated version. This allows us to obtain an analytical traveling wave solution for an intercellular calcium wave and analyze the speed of solitary wave propagation as a function of physiologically important system parameters. Periodic and irregular traveling waves can be also sustained by the proposed model.

  7. Tunneling conductance in gapped graphene-based normal metal-insulator-superconductor junctions: Case of massive Dirac electrons

    Energy Technology Data Exchange (ETDEWEB)

    Goudarzi, H., E-mail: [Department of Physics, Faculty of Science, Urmia University, P.O. Box 165, Urmia (Iran, Islamic Republic of); Sedghi, H.; Khezerlou, M.; Mabhouti, Kh. [Department of Physics, Faculty of Science, Urmia University, P.O. Box 165, Urmia (Iran, Islamic Republic of)


    We study the quantum transport property in a gapped graphene-based normal metal-insulator-superconductor junctions (NG/IG/SG), in the limit of a thin barrier. The charged fermions in NG/IG/SG structure are treated as massive relativistic particles. Based on Andreev and normal reflections in normal-superconductor graphene-based junction and BTK formalism, the tunneling conductance's in terms of some different electrostatic superconductor, U{sub 0} and barrier, V{sub 0} potential are obtained. Using the experimental based values of the Fermi energy in the NG and SG (E{sub FN} and E{sub FN} + U{sub 0}, respectively), energy gap in graphene (2mv{sub F}{sup 2}) and superconducting order parameter, {Delta}, it is shown that the conductance spectra of such system represent a new behavior, i.e. if we take |E{sub FN}-mv{sub F}{sup 2}|{yields}0, it becomes as a step function of V{sub 0}. This behavior of charge transportation can be considered as a nano switch.

  8. Fluxes of lactate into, from, and among gap junction-coupled astrocytes and their interaction with noradrenaline

    Directory of Open Access Journals (Sweden)

    Leif eHertz


    Full Text Available Lactate is a versatile metabolite with important roles in modulation of brain glucose utilization rate (CMRglc, diagnosis of brain-injured patients, redox- and receptor-mediated signaling, memory, and alteration of gene transcription. Neurons and astrocytes release and accumulate lactate using equilibrative monocarboxylate transporters that carry out net transmembrane transport of lactate only until intra- and extracellular levels reach equilibrium. Astrocytes have much faster lactate uptake than neurons and shuttle more lactate among gap junction-coupled astrocytes than to nearby neurons. Lactate diffusion within syncytia can provide precursors for oxidative metabolism and glutamate synthesis and facilitate its release from endfeet to perivascular space to stimulate blood flow. Lactate efflux from brain during activation underlies the large underestimation of CMRglc with labeled glucose and fall in CMRO2/CMRglc ratio. Receptor-mediated effects of lactate on locus coeruleus neurons include noradrenaline release in cerebral cortex and c-AMP-mediated stimulation of astrocytic gap junctional coupling, thereby enhancing its dispersal and release from brain. Lactate transport is essential for its multifunctional roles.

  9. Integrating evolutionary game theory into an agent-based model of ductal carcinoma in situ: Role of gap junctions in cancer progression. (United States)

    Malekian, Negin; Habibi, Jafar; Zangooei, Mohammad Hossein; Aghakhani, Hojjat


    There are many cells with various phenotypic behaviors in cancer interacting with each other. For example, an apoptotic cell may induce apoptosis in adjacent cells. A living cell can also protect cells from undergoing apoptosis and necrosis. These survival and death signals are propagated through interaction pathways between adjacent cells called gap junctions. The function of these signals depends on the cellular context of the cell receiving them. For instance, a receiver cell experiencing a low level of oxygen may interpret a received survival signal as an apoptosis signal. In this study, we examine the effect of these signals on tumor growth. We make an evolutionary game theory component in order to model the signal propagation through gap junctions. The game payoffs are defined as a function of cellular context. Then, the game theory component is integrated into an agent-based model of tumor growth. After that, the integrated model is applied to ductal carcinoma in situ, a type of early stage breast cancer. Different scenarios are explored to observe the impact of the gap junction communication and parameters of the game theory component on cancer progression. We compare these scenarios by using the Wilcoxon signed-rank test. The Wilcoxon signed-rank test succeeds in proving a significant difference between the tumor growth of the model before and after considering the gap junction communication. The Wilcoxon signed-rank test also proves that the tumor growth significantly depends on the oxygen threshold of turning survival signals into apoptosis. In this study, the gap junction communication is modeled by using evolutionary game theory to illustrate its role at early stage cancers such as ductal carcinoma in situ. This work indicates that the gap junction communication and the oxygen threshold of turning survival signals into apoptosis can notably affect cancer progression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Impact of obesity on 7,12-dimethylbenz[a]anthracene-induced altered ovarian connexin gap junction proteins in female mice

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail:; Nteeba, Jackson, E-mail:; Keating, Aileen F., E-mail:


    The ovarian gap junction proteins alpha 4 (GJA4 or connexin 37; CX37), alpha 1 (GJA1 or connexin 43; CX43) and gamma 1 (GJC1 or connexin 45; CX45) are involved in cell communication and folliculogenesis. 7,12-dimethylbenz[a]anthracene (DMBA) alters Cx37 and Cx43 expression in cultured neonatal rat ovaries. Additionally, obesity has an additive effect on DMBA-induced ovarian cell death and follicle depletion, thus, we investigated in vivo impacts of obesity and DMBA on CX protein levels. Ovaries were collected from lean and obese mice aged 6, 12, 18, or 24 wks. A subset of 18 wk old mice (lean and obese) were dosed with sesame oil or DMBA (1 mg/kg; ip) for 14 days and ovaries collected 3 days thereafter. Cx43 and Cx45 mRNA and protein levels decreased (P < 0.05) after 18 wks while Cx37 mRNA and protein levels decreased (P < 0.05) after 24 wks in obese ovaries. Cx37 mRNA and antral follicle protein staining intensity were reduced (P < 0.05) by obesity while total CX37 protein was reduced (P < 0.05) in DMBA exposed obese ovaries. Cx43 mRNA and total protein levels were decreased (P < 0.05) by DMBA in both lean and obese ovaries while basal protein staining intensity was reduced (P < 0.05) in obese controls. Cx45 mRNA, total protein and protein staining intensity level were decreased (P < 0.05) by obesity. These data support that obesity temporally alters gap junction protein expression and that DMBA-induced ovotoxicity may involve reduced gap junction protein function. - Highlights: • Ovarian gap junction proteins are affected by ovarian aging and obesity. • DMBA exposure negatively impacts gap junction proteins. • Altered gap junction proteins may contribute to infertility.

  11. Gap Junction-Mediated Signaling from Motor Neurons Regulates Motor Generation in the Central Circuits of Larval Drosophila. (United States)

    Matsunaga, Teruyuki; Kohsaka, Hiroshi; Nose, Akinao


    In this study, we used the peristaltic crawling of Drosophila larvae as a model to study how motor patterns are regulated by central circuits. We built an experimental system that allows simultaneous application of optogenetics and calcium imaging to the isolated ventral nerve cord (VNC). We then investigated the effects of manipulating local activity of motor neurons (MNs) on fictive locomotion observed as waves of MN activity propagating along neuromeres. Optical inhibition of MNs with halorhodopsin3 in a middle segment (A4, A5, or A6), but not other segments, dramatically decreased the frequency of the motor waves. Conversely, local activation of MNs with channelrhodopsin2 in a posterior segment (A6 or A7) increased the frequency of the motor waves. Since peripheral nerves mediating sensory feedback were severed in the VNC preparation, these results indicate that MNs send signals to the central circuits to regulate motor pattern generation. Our results also indicate segmental specificity in the roles of MNs in motor control. The effects of the local MN activity manipulation were lost in shaking-B2 (shakB2 ) or ogre2 , gap-junction mutations in Drosophila, or upon acute application of the gap junction blocker carbenoxolone, implicating electrical synapses in the signaling from MNs. Cell-type-specific RNAi suggested shakB and ogre function in MNs and interneurons, respectively, during the signaling. Our results not only reveal an unexpected role for MNs in motor pattern regulation, but also introduce a powerful experimental system that enables examination of the input-output relationship among the component neurons in this system.SIGNIFICANCE STATEMENT Motor neurons are generally considered passive players in motor pattern generation, simply relaying information from upstream interneuronal circuits to the target muscles. This study shows instead that MNs play active roles in the control of motor generation by conveying information via gap junctions to the central

  12. Nonsynaptic NMDA receptors mediate activity-dependent plasticity of gap junctional coupling in the AII amacrine cell network. (United States)

    Kothmann, W Wade; Trexler, E Brady; Whitaker, Christopher M; Li, Wei; Massey, Stephen C; O'Brien, John


    Many neurons are coupled by electrical synapses into networks that have emergent properties. In the retina, coupling in these networks is dynamically regulated by changes in background illumination, optimizing signal integration for the visual environment. However, the mechanisms that control this plasticity are poorly understood. We have investigated these mechanisms in the rabbit AII amacrine cell, a multifunctional retinal neuron that forms an electrically coupled network via connexin 36 (Cx36) gap junctions. We find that presynaptic activity of glutamatergic ON bipolar cells drives increased phosphorylation of Cx36, indicative of increased coupling in the AII network. The phosphorylation is dependent on activation of nonsynaptic NMDA receptors that colocalize with Cx36 on AII amacrine cells, and is mediated by CaMKII. This activity-dependent increase in Cx36 phosphorylation works in opposition to dopamine-driven reduction of phosphorylation, establishing a local dynamic regulatory mechanism, and accounting for the nonlinear control of AII coupling by background illumination.

  13. Immunohistochemical localization of a gap junction protein (connexin43) in the muscularis externa of murine, canine, and human intestine

    DEFF Research Database (Denmark)

    Mikkelsen, H B; Huizinga, J D; Thuneberg, L


    Electron-microscopic studies have revealed a heterogeneous distribution of gap junctions in the muscularis externa of mammalian intestines. This heterogeneity is observed at four different levels: among species; between small and large intestines; between longitudinal and circular muscle layers...... also included the vascular smooth muscle of coronary arteries into our study. Two versions of the immunotechnique (peroxidase-antiperoxidase and fluorescence methods) were applied to frozen sections of murine, canine, and human small and large intestines, as well as to pig coronary artery. In the small...... intestine of all three species a very strong reactivity marked the outer main division of the circular muscle layer, while the longitudinal muscle layer as well as the inner thin division of the circular muscle layer were negative. In murine and human colon both muscle layers were negative, while in canine...

  14. Critical role of gap junction communication, calcium and nitric oxide signaling in bystander responses to focal photodynamic injury. (United States)

    Calì, Bianca; Ceolin, Stefano; Ceriani, Federico; Bortolozzi, Mario; Agnellini, Andrielly H R; Zorzi, Veronica; Predonzani, Andrea; Bronte, Vincenzo; Molon, Barbara; Mammano, Fabio


    Ionizing and nonionizing radiation affect not only directly targeted cells but also surrounding "bystander" cells. The underlying mechanisms and therapeutic role of bystander responses remain incompletely defined. Here we show that photosentizer activation in a single cell triggers apoptosis in bystander cancer cells, which are electrically coupled by gap junction channels and support the propagation of a Ca2+ wave initiated in the irradiated cell. The latter also acts as source of nitric oxide (NO) that diffuses to bystander cells, in which NO levels are further increased by a mechanism compatible with Ca(2+)-dependent enzymatic production. We detected similar signals in tumors grown in dorsal skinfold chambers applied to live mice. Pharmacological blockade of connexin channels significantly reduced the extent of apoptosis in bystander cells, consistent with a critical role played by intercellular communication, Ca2+ and NO in the bystander effects triggered by photodynamic therapy.

  15. Tunneling nanotubes (TNT) mediate long-range gap junctional communication: Implications for HIV cell to cell spread. (United States)

    Okafo, George; Prevedel, Lisa; Eugenin, Eliseo


    Cell-to-cell communication is essen for the development of multicellular systems and is coordinated by soluble factors, exosomes, gap junction (GJ) channels, and the recently described tunneling nanotubes (TNTs). We and others have demonstrated that TNT-like structures are mostly present during pathogenic conditions, including HIV infection. However, the nature, function, and communication properties of TNTs are still poorly understood. In this manuscript, we demonstrate that TNTs induced by HIV infection have functional GJs at the ends of their membrane extensions and that TNTs mediate long-range GJ communication during HIV infection. Blocking or reducing GJ communication during HIV infection resulted in aberrant TNT cell-to-cell contact, compromising HIV spread and replication. Thus, TNTs and associated GJs are required for the efficient cell-to-cell communication and viral spread. Our data indicate that targeting TNTs/GJs may provide new therapeutic opportunities for the treatment of HIV.

  16. Application of stochastic automata networks for creation of continuous time Markov chain models of voltage gating of gap junction channels. (United States)

    Snipas, Mindaugas; Pranevicius, Henrikas; Pranevicius, Mindaugas; Pranevicius, Osvaldas; Paulauskas, Nerijus; Bukauskas, Feliksas F


    The primary goal of this work was to study advantages of numerical methods used for the creation of continuous time Markov chain models (CTMC) of voltage gating of gap junction (GJ) channels composed of connexin protein. This task was accomplished by describing gating of GJs using the formalism of the stochastic automata networks (SANs), which allowed for very efficient building and storing of infinitesimal generator of the CTMC that allowed to produce matrices of the models containing a distinct block structure. All of that allowed us to develop efficient numerical methods for a steady-state solution of CTMC models. This allowed us to accelerate CPU time, which is necessary to solve CTMC models, ~20 times.

  17. Application of Stochastic Automata Networks for Creation of Continuous Time Markov Chain Models of Voltage Gating of Gap Junction Channels

    Directory of Open Access Journals (Sweden)

    Mindaugas Snipas


    Full Text Available The primary goal of this work was to study advantages of numerical methods used for the creation of continuous time Markov chain models (CTMC of voltage gating of gap junction (GJ channels composed of connexin protein. This task was accomplished by describing gating of GJs using the formalism of the stochastic automata networks (SANs, which allowed for very efficient building and storing of infinitesimal generator of the CTMC that allowed to produce matrices of the models containing a distinct block structure. All of that allowed us to develop efficient numerical methods for a steady-state solution of CTMC models. This allowed us to accelerate CPU time, which is necessary to solve CTMC models, ∼20 times.

  18. Modulatory effects of cAMP and PKC activation on gap junctional intercellular communication among thymic epithelial cells

    Directory of Open Access Journals (Sweden)

    Neves-dos-Santos Sandra


    Full Text Available Abstract Background We investigated the effects of the signaling molecules, cyclic AMP (cAMP and protein-kinase C (PKC, on gap junctional intercellular communication (GJIC between thymic epithelial cells (TEC. Results Treatment with 8-Br-cAMP, a cAMP analog; or forskolin, which stimulates cAMP production, resulted in an increase in dye transfer between adjacent TEC, inducing a three-fold enhancement in the mean fluorescence of coupled cells, ascertained by flow cytometry after calcein transfer. These treatments also increased Cx43 mRNA expression, and stimulated Cx43 protein accumulation in regions of intercellular contacts. VIP, adenosine, and epinephrine which may also signal through cyclic nucleotides were tested. The first two molecules did not mimic the effects of 8-Br-cAMP, however epinephrine was able to increase GJIC suggesting that this molecule functions as an endogenous inter-TEC GJIC modulators. Stimulation of PKC by phorbol-myristate-acetate inhibited inter-TEC GJIC. Importantly, both the enhancing and the decreasing effects, respectively induced by cAMP and PKC, were observed in both mouse and human TEC preparations. Lastly, experiments using mouse thymocyte/TEC heterocellular co-cultures suggested that the presence of thymocytes does not affect the degree of inter-TEC GJIC. Conclusions Overall, our data indicate that cAMP and PKC intracellular pathways are involved in the homeostatic control of the gap junction-mediated communication in the thymic epithelium, exerting respectively a positive and negative role upon cell coupling. This control is phylogenetically conserved in the thymus, since it was seen in both mouse and human TEC preparations. Lastly, our work provides new clues for a better understanding of how the thymic epithelial network can work as a physiological syncytium.

  19. Autophagy and gap junctional intercellular communication inhibition are involved in cadmium-induced apoptosis in rat liver cells

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    Zou, Hui [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China); Zhuo, Liling [College of Life Science, Zaozhuang University, Zaozhuang, Shandong, 277160 (China); Han, Tao; Hu, Di; Yang, Xiaokang; Wang, Yi; Yuan, Yan; Gu, Jianhong; Bian, Jianchun; Liu, Xuezhong [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China); Liu, Zongping, E-mail: [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China)


    Cadmium (Cd) is known to induce hepatotoxicity, yet the underlying mechanism of how this occurs is not fully understood. In this study, Cd-induced apoptosis was demonstrated in rat liver cells (BRL 3A) with apoptotic nuclear morphological changes and a decrease in cell index (CI) in a time- and concentration-dependent manner. The role of gap junctional intercellular communication (GJIC) and autophagy in Cd-induced apoptosis was investigated. Cd significantly induced GJIC inhibition as well as downregulation of connexin 43 (Cx43). The prototypical gap junction blocker carbenoxolone disodium (CBX) exacerbated the Cd-induced decrease in CI. Cd treatment was also found to cause autophagy, with an increase in mRNA expression of autophagy-related genes Atg-5, Atg-7, Beclin-1, and microtubule-associated protein light chain 3 (LC3) conversion from cytosolic LC3-I to membrane-bound LC3-II. The autophagic inducer rapamycin (RAP) prevented the Cd-induced CI decrease, while the autophagic inhibitor chloroquine (CQ) caused a further reduction in CI. In addition, CBX promoted Cd-induced autophagy, as well as changes in expression of Atg-5, Atg-7, Beclin-1 and LC3. CQ was found to block the Cd-induced decrease in Cx43 and GJIC inhibition, whereas RAP had opposite effect. These results demonstrate that autophagy plays a protective role during Cd-induced apoptosis in BRL 3A cells during 6 h of experiment, while autophagy exacerbates Cd-induced GJIC inhibition which has a negative effect on cellular fate. - Highlights: • GJIC and autophagy is crucial for biological processes. • Cd exposure causes GJIC inhibition and autophagy increase in BRL 3A cells. • Autophagy protects Cd induced BRL 3A cells apoptosis at an early stage. • Autophagy exacerbates Cd-induced GJIC inhibition. • GJIC plays an important role in autophagy induced cell death or survival.

  20. Investigation of the reciprocal relationship between the expression of two gap junction connexin proteins, connexin46 and connexin43. (United States)

    Banerjee, Debarshi; Das, Satyabrata; Molina, Samuel A; Madgwick, Dan; Katz, Melanie R; Jena, Snehalata; Bossmann, Leonie K; Pal, Debjani; Takemoto, Dolores J


    Connexins are the transmembrane proteins that form gap junctions between adjacent cells. The function of the diverse connexin molecules is related to their tissue-specific expression and highly dynamic turnover. Although multiple connexins have been previously reported to compensate for each other's functions, little is known about how connexins influence their own expression or intracellular regulation. Of the three vertebrate lens connexins, two connexins, connexin43 (Cx43) and connexin46 (Cx46), show reciprocal expression and subsequent function in the lens and in lens cell culture. In this study, we investigate the reciprocal relationship between the expression of Cx43 and Cx46. Forced depletion of Cx43, by tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate, is associated with an up-regulation of Cx46 at both the protein and message level in human lens epithelial cells. An siRNA-mediated down-regulation of Cx43 results in an increase in the level of Cx46 protein, suggesting endogenous Cx43 is involved in the regulation of endogenous Cx46 turnover. Overexpression of Cx46, in turn, induces the depletion of Cx43 in rabbit lens epithelial cells. Cx46-induced Cx43 degradation is likely mediated by the ubiquitin-proteasome pathway, as (i) treatment with proteasome inhibitors restores the Cx43 protein level and (ii) there is an increase in Cx43 ubiquitin conjugation in Cx46-overexpressing cells. We also present data that shows that the C-terminal intracellular tail domain of Cx46 is essential to induce degradation of Cx43. Therefore, our study shows that Cx43 and Cx46 have novel functions in regulating each other's expression and turnover in a reciprocal manner in addition to their conventional roles as gap junction proteins in lens cells.

  1. Neuronal differentiation requires a biphasic modulation of gap junctional intercellular communication caused by dynamic changes of connexin43 expression. (United States)

    Lemcke, Heiko; Nittel, Marie-Louise; Weiss, Dieter G; Kuznetsov, Sergei A


    It was suggested that gap junctional intercellular communication (GJIC) and connexin (Cx) proteins play a crucial role in cell proliferation and differentiation. However, the mechanisms of cell coupling in regulating cell fate during embryonic development are poorly understood. To study the role of GJIC in proliferation and differentiation, we used a human neural progenitor cell line derived from the ventral mesencephalon. Fluorescence recovery after photobleaching (FRAP) showed that dye coupling was extensive in proliferating cells but diminished after the induction of differentiation, as indicated by a 2.5-fold increase of the half-time of fluorescence recovery. Notably, recovery half-time decreased strongly (five-fold) in the later stage of differentiation. Western blot analysis revealed a similar time-dependent expression profile of Cx43, acting as the main gap junction-forming protein. Interestingly, large amounts of cytoplasmic Cx43 were retained mainly in the Golgi network during proliferation but decreased when differentiation was induced. Furthermore, down-regulation of Cx43 by small interfering RNA reduced functional cell coupling, which in turn resulted in a 50% decrease of both the proliferation rate and neuronal differentiation. Our findings suggest a dual function of Cx43 and GJIC in the neural development of ReNcell VM197 human progenitor cells. GJIC accompanied by high Cx43 expression is necessary (1) to maintain cells in a proliferative state and (2) to complete neuronal differentiation, including the establishment of a neural network. However, uncoupling of cells is crucial in the early stage of differentiation during cell fate commitment. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. Abrogation of Gap Junctional Communication in ES Cells Results in a Disruption of Primitive Endoderm Formation in Embryoid Bodies. (United States)

    Wörsdörfer, Philipp; Bosen, Felicitas; Gebhardt, Martina; Russ, Nicole; Zimmermann, Katrin; Komla Kessie, David; Sekaran, Thileepan; Egert, Angela; Ergün, Süleyman; Schorle, Hubert; Pfeifer, Alexander; Edenhofer, Frank; Willecke, Klaus


    Gap junctional intercellular communication (GJIC) has been suggested to be involved in early embryonic development but the actual functional role remained elusive. Connexin (Cx) 43 and Cx45 are co-expressed in embryonic stem (ES) cells, form gap junctions and are considered to exhibit adhesive function and/or to contribute to the establishment of defined communication compartments. Here, we describe the generation of Cx43/Cx45-double deficient mouse ES cells to achieve almost complete breakdown of GJIC. Cre-loxP induced deletion of both, Cx43 and Cx45, results in a block of differentiation in embryoid bodies (EBs) without affecting pluripotency marker expression and proliferation in ES cells. We demonstrate that GJIC-incompetent ES cells fail to form primitive endoderm in EB cultures, representing the inductive key step of further differentiation events. Lentiviral overexpression of either Cx43 or Cx45 in Cx43/45 mutants rescued the observed phenotype, confirming the specificity and indicating a partially redundant function of both connexins. Upon differentiation GJIC-incompetent ES cells exhibit a strikingly altered subcellular localization pattern of the transcription factor NFATc3. Control EBs exhibit significantly more activated NFATc3 in cellular nuclei than mutant EBs suggesting that Cx-mediated communication is needed for synchronized NFAT activation to induce orchestrated primitive endoderm formation. Moreover, pharmacological inhibition of NFATc3 activation by Cyclosporin A, a well-described inhibitor of calcineurin, phenocopies the loss of GJIC in control cells. Stem Cells 2017;35:859-871. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  3. Decreased levels of Cx43 gap junctions result in ameloblast dysregulation and enamel hypoplasia in Gja1Jrt/+ mice. (United States)

    Toth, K; Shao, Q; Lorentz, R; Laird, D W


    Coordinated differentiation of the ameloblast cell layer is essential to enamel matrix protein deposition and subsequent mineralization. It has been hypothesized that this process is governed by Cx43-based gap junctional intercellular communication as oculodentodigital dysplasia (ODDD) patients harboring autosomal-dominant mutations in Cx43 exhibit enamel defects typically resulting in early adulthood tooth loss. To assess the role of Cx43 in tooth development we employ a mouse model of ODDD that harbors a G60S Cx43 mutant, Gja1(Jrt)/+, and appears to exhibit tooth abnormalities that mimic the human disease. We found that total Cx43 plaques at all stages of ameloblast differentiation, as well as within the supporting cell layers, were greatly reduced in Gja1(Jrt)/+ incisors compared to wild-type littermate controls. To characterize the Gja1(Jrt)/+ mouse tooth phenotype, mice were sacrificed prior to tooth eruption (postnatal day 7), weaning (postnatal day 21), and adulthood (2 months postnatal). A severely disorganized Gja1(Jrt)/+ mouse ameloblast layer and abnormal accumulation of amelogenin were observed at stages when the cells were active in secretion and mineralization. Differences in enamel thickness became more apparent after tooth eruption and incisor exposure to the oral cavity suggesting that enamel integrity is compromised, leading to rapid erosion. Additional analysis of incisors from mutant mice revealed that they were longer with a thicker dentin layer than their wild-type littermates, which may reflect a mechanical stress response to the depleted enamel layer. Together, these data show that reduced levels of Cx43 gap junctions result in ameloblast dysregulation, enamel hypoplasia, and secondary tissue responses. (c) 2010 Wiley-Liss, Inc.

  4. S-diclofenac protects against doxorubicin-induced cardiomyopathy in mice via ameliorating cardiac gap junction remodeling.

    Directory of Open Access Journals (Sweden)

    Huili Zhang

    Full Text Available Hydrogen sulfide (H(2S, as a novel gaseous mediator, plays important roles in mammalian cardiovascular tissues. In the present study, we investigated the cardioprotective effect of S-diclofenac (2-[(2,6-dichlorophenylamino] benzeneacetic acid 4-(3H-1,2,dithiol-3-thione-5-ylphenyl ester, a novel H(2S-releasing derivative of diclofenac, in a murine model of doxorubicin-induced cardiomyopathy. After a single dose injection of doxorubicin (15 mg/kg, i.p., male C57BL/6J mice were given daily treatment of S-diclofenac (25 and 50 µmol/kg, i.p., diclofenac (25 and 50 µmol/kg, i.p., NaHS (50 µmol/kg, i.p., or same volume of vehicle. The cardioprotective effect of S-diclofenac was observed after 14 days. It showed that S-diclofenac, but not diclofenac, dose-dependently inhibited the doxorubicin-induced downregulation of cardiac gap junction proteins (connexin 43 and connexin 45 and thus reversed the remodeling of gap junctions in hearts. It also dose-dependently suppressed doxorubicin-induced activation of JNK in hearts. Furthermore, S-diclofenac produced a dose-dependent anti-inflammatory and anti-oxidative effect in this model. As a result, S-diclofenac significantly attenuated doxorubicin-related cardiac injury and cardiac dysfunction, and improved the survival rate of mice with doxorubicin-induced cardiomyopathy. These effects of S-diclofenac were mimicked in large part by NaHS. Therefore, we propose that H(2S released from S-diclofenac in vivo contributes to the protective effect in doxorubicin-induced cardiomyopathy. These data also provide evidence for a critical role of H(2S in the pathogenesis of doxorubicin-induced cardiomyopathy.

  5. Theory of large tunneling magnetoresistance in a gapped graphene-based ferromagnetic superconductor F/(FS) junction

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    Soodchomshom, Bumned [ThEP Center, Commission of Higher Education, 328 Si Ayuthaya Rd., Bangkok 10400 (Thailand); Department of Science and Mathematics (Physics), Faculty of Science and Technology, Pathumwan Institute of Technology, Bangkok 10330 (Thailand); Tang, I-Ming [ThEP Center, Commission of Higher Education, 328 Si Ayuthaya Rd., Bangkok 10400 (Thailand); Department of Physics, Faculty of Science, Mahidol University, Bangkok 10400 (Thailand); Hoonsawat, Rassmidara, E-mail: [ThEP Center, Commission of Higher Education, 328 Si Ayuthaya Rd., Bangkok 10400 (Thailand); Department of Physics, Faculty of Science, Mahidol University, Bangkok 10400 (Thailand); Mahidol University International College, Salaya Campus, Nakorn Pathom, 73170 (Thailand)


    Coexistence of superconductivity and ferromagnetism in a gapped graphene-based system (FS) is theoretically investigated. The center-of-mass momentum, P, of a Cooper pair in FS is found to be Papprox2E{sub ex}/(hv{sub F}sq root(1-(m/E{sub FS}){sup 2})), where m, E{sub ex}, E{sub FS} are the rest mass energy of the Dirac electron, exchange energy and the Fermi energy in the superconductor FS, respectively. It is unlike the nature in a conventional FFLO state where Papprox2E{sub ex}/hv{sub F}. This work studies the magneto effect on the transport property of a F/(FS) junction where F is a ferromagnetic gapless graphene. In this work, FS is achieved by depositing a conventional ferromagnetic s-wave superconductor on the top of gapped graphene sheet. The Zeeman splitting in FS induces spin-dependent Andreev resonance. The conductances effected by both spin-dependent specular Andreev reflections and spin-dependent Andreev resonances are investigated. The interplay between the spin-dependent specular Andreev reflection in the F region and the spin-dependent Andreev resonance in the FS region causes a very large tunneling magnetoresistance |TMR| approx 3000% for m -> E{sub FS}, possibly valuable in the graphene-based spintronic devices. This is because of the coexistence of the superconductivity and ferromagnetism in FS and the relativistic nature of electrons in graphene.

  6. Connexin-36 gap junctions regulate in vivo first- and second-phase insulin secretion dynamics and glucose tolerance in the conscious mouse. (United States)

    Head, W Steven; Orseth, Meredith L; Nunemaker, Craig S; Satin, Leslie S; Piston, David W; Benninger, Richard K P


    Insulin is secreted from the islets of Langerhans in coordinated pulses. These pulses are thought to lead to plasma insulin oscillations, which are putatively more effective in lowering blood glucose than continuous levels of insulin. Gap-junction coupling of β-cells by connexin-36 coordinates intracellular free calcium oscillations and pulsatile insulin release in isolated islets, however a role in vivo has not been shown. We test whether loss of gap-junction coupling disrupts plasma insulin oscillations and whether this impacts glucose tolerance. We characterized the connexin-36 knockout (Cx36(-/-)) mouse phenotype and performed hyperglycemic clamps with rapid sampling of insulin in Cx36(-/-) and control mice. Our results show that Cx36(-/-) mice are glucose intolerant, despite normal plasma insulin levels and insulin sensitivity. However, Cx36(-/-) mice exhibit reduced insulin pulse amplitudes and a reduction in first-phase insulin secretion. These changes are similarly found in isolated Cx36(-/-) islets. We conclude that Cx36 gap junctions regulate the in vivo dynamics of insulin secretion, which in turn is important for glucose homeostasis. Coordinated pulsatility of individual islets enhances the first-phase elevation and second-phase pulses of insulin. Because these dynamics are disrupted in the early stages of type 2 diabetes, dysregulation of gap-junction coupling could be an important factor in the development of this disease.

  7. The Display of Single-Domain Antibodies on the Surfaces of Connectosomes Enables Gap Junction-Mediated Drug Delivery to Specific Cell Populations. (United States)

    Gadok, Avinash K; Zhao, Chi; Meriwether, Amanda I; Ferrati, Silvia; Rowley, Tanner G; Zoldan, Janet; Smyth, Hugh D C; Stachowiak, Jeanne C


    Gap junctions, transmembrane protein channels that directly connect the cytoplasm of neighboring cells and enable the exchange of molecules between cells, are a promising new frontier for therapeutic delivery. Specifically, cell-derived lipid vesicles that contain functional gap junction channels, termed Connectosomes, have recently been demonstrated to substantially increase the effectiveness of small molecule chemotherapeutics. However, because gap junctions are present in nearly all tissues, Connectosomes have no intrinsic ability to target specific cell types, which potentially limits their therapeutic effectiveness. To address this challenge, here we display targeting ligands consisting of single-domain antibodies on the surfaces of Connectosomes. We demonstrate that these targeted Connectosomes selectively interact with cells that express a model receptor, promoting the selective delivery of the chemotherapeutic doxorubicin to this target cell population. More generally, our approach has the potential to boost cytoplasmic delivery of diverse therapeutic molecules to specific cell populations while protecting off-target cells, a critical step toward realizing the therapeutic potential of gap junctions.

  8. The lateral proximity effect and long-range energy-gap gradients in Ta/Al and Nb/Al Josephson junctions

    NARCIS (Netherlands)

    den Hartog, Ronald; Golubov, Alexandre Avraamovitch; Martin, D.; Verhoeve, P.; Poelaert, P.A.; Peacock, A.; Krumrey, M.


    We present two independent experiments, each of which suggests that the local energy gap in Ta (and Nb) has a lateral spatial variation on a scale of several μm. The first experiment is a series of current–voltage characterizations of Nb/Al/AlOx and Ta/Al/AlOx Josephson junctions, which reveals a

  9. Active response of a one-dimensional cardiac model with gap junctions to extracellular stimulation. (United States)

    Cartee, L A; Plonsey, R


    To study the response of cardiac tissue to electrical stimulation, a one-dimensional model of cardiac tissue has been developed using linear core-conductor theory and the DiFrancesco-Noble model of Purkinje tissue. The cable lies in a restricted extracellular medium and includes a representation of the junctional resistances known to interconnect cardiac cells. Two electrode geometries are considered: (a) a semi-infinite cable with a monopolar electrode at the end of the cable and (b) a terminated cable with one electrode at each end of the cable. In a series of simulations, stimuli of varying magnitude and polarity are applied at three different times during the plateau of the action potential. The results at the stimulus site show that the action potential duration may either decrease or increase in response to the stimulus, depending on the polarity and application time of the stimulus. The spatial behaviour of the cable in response to the stimulus indicates that sites greater than 200 cells from the stimulating electrode are not affected by the stimulus.

  10. Lack of connexin43-mediated Bergmann glial gap junctional coupling does not affect cerebellar long-term depression, motor coordination, or eyeblink conditioning

    Directory of Open Access Journals (Sweden)

    Mika Tanaka


    Full Text Available Bergmann glial cells are specialized astrocytes in the cerebellum. In the mature cerebellar molecular layer, Bergmann glial processes are closely associated with Purkinje cells, enclosing Purkinje cell dendritic synapses with a glial sheath. There is intensive gap junctional coupling between Bergmann glial processes, but their significance in cerebellar functions is not known. Connexin43 (Cx43, a major component of astrocytic gap junction channels, is abundantly expressed in Bergmann glial cells. To examine the role of Cx43-mediated gap junctions between Bergmann glial cells in cerebellar functions, we generated Cx43 conditional knockout mice with the S100b-Cre transgenic line (Cx43fl/fl:S100b-Cre, which exhibited a significant loss of Cx43 in the Bergmann glial cells and astrocytes in the cerebellum with a postnatal onset. The Cx43fl/fl:S100b-Cre mice had normal cerebellar architecture. Although gap junctional coupling between the Bergmann glial cells measured by spreading of microinjected Lucifer yellow was virtually abolished in Cx43fl/fl:S100b-Cre mice, electrophysiologic analysis revealed that cerebellar long-term depression could be induced and maintained normally in thier cerebellar slices. In addition, at the behavioral level, Cx43fl/fl:S100b-Cre mice had normal motor coordination in the rotarod task and normal conditioned eyelid response. Our findings suggest that Cx43-mediated gap junctional coupling between Bergmann glial cells is not necessary for the neuron-glia interactions required for cerebellum-dependent motor coordination and motor learning.

  11. Protein kinase A-mediated phosphorylation of connexin36 in mouse retina results in decreased gap junctional communication between AII amacrine cells. (United States)

    Urschel, Stephanie; Höher, Thorsten; Schubert, Timm; Alev, Cantas; Söhl, Goran; Wörsdörfer, Philipp; Asahara, Takayuki; Dermietzel, Rolf; Weiler, Reto; Willecke, Klaus


    Gap junctions in AII amacrine cells of mammalian retina participate in the coordination of the rod and cone signaling pathway involved in visual adaptation. Upon stimulation by light, released dopamine binds to D(1) receptors on AII amacrine cells leading to increased intracellular cAMP (cyclic adenosine monophosphate) levels. AII amacrine cells express the gap junctional protein connexin36 (Cx36). Phosphorylation of Cx36 has been hypothesized to regulate gap junctional activity of AII amacrine cells. However, until now in vivo phosphorylation of Cx36 has not been reported. Indeed, it had been concluded that Cx36 in bovine retina is not phosphorylated, but in vitro phosphorylation for Cx35, the bass ortholog of Cx36, had been shown. To clarify this experimental discrepancy, we examined protein kinase A (PKA)-induced phosphorylation of Cx36 in mouse retina as a possible mechanism to modulate the extent of gap junctional coupling. The cytoplasmic domains of Cx36 and the total Cx36 protein were phosphorylated in vitro by PKA. Mass spectroscopy revealed that all four possible PKA consensus motifs were phosphorylated; however, domains point mutated at the sites in question showed a prevalent usage of Ser-110 and Ser-293. Additionally, we demonstrated that Cx36 was phosphorylated in cultured mouse retina. Furthermore, activation of PKA increased the level of phosphorylation of Cx36. cAMP-stimulated, PKA-mediated phosphorylation of Cx36 protein was accompanied by a decrease of tracer coupling between AII amacrine cells. Our results link increased phosphorylation of Cx36 to down-regulation of permeability through gap junction channels mediating light adaptation in the retina.

  12. A novel role of dendritic gap junction and mechanisms underlying its interaction with thalamocortical conductance in fast spiking inhibitory neurons

    Directory of Open Access Journals (Sweden)

    Sun Qian-Quan


    Full Text Available Abstract Background Little is known about the roles of dendritic gap junctions (GJs of inhibitory interneurons in modulating temporal properties of sensory induced responses in sensory cortices. Electrophysiological dual patch-clamp recording and computational simulation methods were used in combination to examine a novel role of GJs in sensory mediated feed-forward inhibitory responses in barrel cortex layer IV and its underlying mechanisms. Results Under physiological conditions, excitatory post-junctional potentials (EPJPs interact with thalamocortical (TC inputs within an unprecedented few milliseconds (i.e. over 200 Hz to enhance the firing probability and synchrony of coupled fast-spiking (FS cells. Dendritic GJ coupling allows fourfold increase in synchrony and a significant enhancement in spike transmission efficacy in excitatory spiny stellate cells. The model revealed the following novel mechanisms: 1 rapid capacitive current (Icap underlies the activation of voltage-gated sodium channels; 2 there was less than 2 milliseconds in which the Icap underlying TC input and EPJP was coupled effectively; 3 cells with dendritic GJs had larger input conductance and smaller membrane response to weaker inputs; 4 synchrony in inhibitory networks by GJ coupling leads to reduced sporadic lateral inhibition and increased TC transmission efficacy. Conclusion Dendritic GJs of neocortical inhibitory networks can have very powerful effects in modulating the strength and the temporal properties of sensory induced feed-forward inhibitory and excitatory responses at a very high frequency band (>200 Hz. Rapid capacitive currents are identified as main mechanisms underlying interaction between two transient synaptic conductances.

  13. Analysis of trafficking, stability and function of human connexin 26 gap junction channels with deafness-causing mutations in the fourth transmembrane helix.

    Directory of Open Access Journals (Sweden)

    Cinzia Ambrosi

    Full Text Available Human Connexin26 gene mutations cause hearing loss. These hereditary mutations are the leading cause of childhood deafness worldwide. Mutations in gap junction proteins (connexins can impair intercellular communication by eliminating protein synthesis, mis-trafficking, or inducing channels that fail to dock or have aberrant function. We previously identified a new class of mutants that form non-functional gap junction channels and hemichannels (connexons by disrupting packing and inter-helix interactions. Here we analyzed fourteen point mutations in the fourth transmembrane helix of connexin26 (Cx26 that cause non-syndromic hearing loss. Eight mutations caused mis-trafficking (K188R, F191L, V198M, S199F, G200R, I203K, L205P, T208P. Of the remaining six that formed gap junctions in mammalian cells, M195T and A197S formed stable hemichannels after isolation with a baculovirus/Sf9 protein purification system, while C202F, I203T, L205V and N206S formed hemichannels with varying degrees of instability. The function of all six gap junction-forming mutants was further assessed through measurement of dye coupling in mammalian cells and junctional conductance in paired Xenopus oocytes. Dye coupling between cell pairs was reduced by varying degrees for all six mutants. In homotypic oocyte pairings, only A197S induced measurable conductance. In heterotypic pairings with wild-type Cx26, five of the six mutants formed functional gap junction channels, albeit with reduced efficiency. None of the mutants displayed significant alterations in sensitivity to transjunctional voltage or induced conductive hemichannels in single oocytes. Intra-hemichannel interactions between mutant and wild-type proteins were assessed in rescue experiments using baculovirus expression in Sf9 insect cells. Of the four unstable mutations (C202F, I203T, L205V, N206S only C202F and N206S formed stable hemichannels when co-expressed with wild-type Cx26. Stable M195T hemichannels

  14. Cytokine effects on gap junction communication and connexin expression in human bladder smooth muscle cells and suburothelial myofibroblasts.

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    Marco Heinrich

    Full Text Available BACKGROUND: The last decade identified cytokines as one group of major local cell signaling molecules related to bladder dysfunction like interstitial cystitis (IC and overactive bladder syndrome (OAB. Gap junctional intercellular communication (GJIC is essential for the coordination of normal bladder function and has been found to be altered in bladder dysfunction. Connexin (Cx 43 and Cx45 are the most important gap junction proteins in bladder smooth muscle cells (hBSMC and suburothelial myofibroblasts (hsMF. Modulation of connexin expression by cytokines has been demonstrated in various tissues. Therefore, we investigate the effect of interleukin (IL 4, IL6, IL10, tumor necrosis factor-alpha (TNFα and transforming growth factor-beta1 (TGFβ1 on GJIC, and Cx43 and Cx45 expression in cultured human bladder smooth muscle cells (hBSMC and human suburothelial myofibroblasts (hsMF. METHODOLOGY/PRINCIPAL FINDINGS: HBSMC and hsMF cultures were set up from bladder tissue of patients undergoing cystectomy. In cytokine stimulated cultured hBSMC and hsMF GJIC was analyzed via Fluorescence Recovery after Photo-bleaching (FRAP. Cx43 and Cx45 expression was assessed by quantitative PCR and confocal immunofluorescence. Membrane protein fraction of Cx43 and Cx45 was quantified by Dot Blot. Upregulation of cell-cell-communication was found after IL6 stimulation in both cell types. In hBSMC IL4 and TGFβ1 decreased both, GJIC and Cx43 protein expression, while TNFα did not alter communication in FRAP-experiments but increased Cx43 expression. GJ plaques size correlated with coupling efficacy measured, while Cx45 expression did not correlate with modulation of GJIC. CONCLUSIONS/SIGNIFICANCE: Our finding of specific cytokine effects on GJIC support the notion that cytokines play a pivotal role for pathophysiology of OAB and IC. Interestingly, the effects were independent from the classical definition of pro- and antiinflammatory cytokines. We conclude, that

  15. Up-regulation of gap junction in peripheral blood T lymphocytes contributes to the inflammatory response in essential hypertension. (United States)

    Ni, Xin; Wang, Ai; Zhang, Liang; Shan, Li-Ya; Zhang, Hai-Chao; Li, Li; Si, Jun-Qiang; Luo, Jian; Li, Xin-Zhi; Ma, Ke-Tao


    Inflammation has been shown to play an important role in the mechanisms involved in the pathogenesis of hypertension. Connexins (Cxs)-based gap junction channels (GJCs) or hemichannels (HCs) are involved in the maintenance of homeostasis in the immune system. However, the role of Cx43-based channels in T-lymphocytes in mediating the immune response in essential hypertension is not fully understand. The present study was designed to investigate the role of Cxs-based channels in T lymphocytes in the regulation of hypertension-mediated inflammation. The surface expressions of T lymphocyte subtypes, Cx40/Cx43, and inflammatory cytokines (IFN-γ (interferon-gamma) and TNF-ɑ (tumor necrosis factor alpha)) in T cells, as well as gap junction communication of peripheral blood lymphocytes from essential hypertensive patients (EHs) and normotensive healthy subjects (NTs) were detected by flow cytometry. Expression levels and phosphorylation of Cx43 protein in peripheral blood lymphocytes of EHs and NTs were analyzed by Western blot. The proliferation rate of peripheral blood mononuclear cells (PBMCs) after treatment with a Cxs inhibitor was examined by a CCK-8 assay. The levels of inflammatory cytokines were detected using ELISA. Within the CD3+ T cell subsets, we found a significant trend toward an increase in the percentage of CD4+ T cells and CD4+/CD8+ ratio as well as in serum levels of IFN-γ and TNF-ɑ in the peripheral blood of EHs compared with those in NTs. Moreover, the peripheral blood lymphocytes of EH patients exhibited enhanced GJCs formation, increased Cx43 protein level and Cx43 phosphorylation at Ser368, and a significant increase in Cx40/Cx43 surface expressions levels in CD4+ or CD8+ T lymphocytes. Cx43-based channel inhibition by a mimetic peptide greatly reduced the exchange of dye between lymphocytes, proliferation of stimulated lymphocytes and the pro-inflammatory cytokine levels of EHs and NTs. Our data suggest that Cx40/Cx43-based channels in

  16. Role of connexin (gap junction) genes in cell growth control and carcinogenesis; Role des jonctions intercellulaires dans la cancerogenese

    Energy Technology Data Exchange (ETDEWEB)

    Yamasaki, H.; Krutovskikh, V.; Mesnil, M.; Tanaka, T.; Zaidan-Dagli, M.L.; Omori, Y. [International Agency for Research on Cancer, Lyon (France). Unit of Multistage Carcinogenesis


    Gap junctional intercellular communication (GJIC) is considered to play a key role in the maintenance of tissue independence and homeostasis in multicellular organisms by controlling the growth of GJIC-connected cells. Gap junction channels are composed of connexin molecules and, so far, more than a dozen different connexin genes have been shown to be expressed in mammals. Reflecting the importance of GJIC in various physiological functions, deletion of different connexin genes from mice results in various disorders, including cancers, heart malformation or conduction abnormality, cataract, etc. The possible involvement of aberrant GJIC in abnormal cell growth and carcinogenesis has long been postulated and recent studies in our own and other laboratories have confirmed that expression and function of connexin genes play an important role in cell growth control. Thus, almost all malignant cells show altered homologous and/or heterologous GJIC and are often associated with aberrant expression or localization of connexins. Aberrant localization of connexins in some tumour cells is associated with lack of function of cell adhesion molecules, suggesting the importance of cell-cell recognition for GJIC. Transfection of connexin genes into tumorigenic cells restores normal cell growth, supporting the idea that connexins form a family of tumour-suppressor genes. Some studies also show that specific connexins may be necessary to control growth of specific cell types. We have produced various dominant-negative mutants of Cx26, Cx32 and Cx43 and showed that some of them prevent the growth control exerted by the corresponding wild-type genes. However, we have found that connexins 32, 37 and 43 genes are rarely mutated in tumours. In some of these studies, we noted that connexin expression per se, rather than GJIC level, is more closely related to growth control, suggesting that connexins may have a GJIC-independent function. We have recently created a transgenic mouse strain

  17. Sample preconcentration utilizing nanofractures generated by junction gap breakdown assisted by self-assembled monolayer of gold nanoparticles.

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    Chun-Ping Jen

    Full Text Available The preconcentration of proteins with low concentrations can be used to increase the sensitivity and accuracy of detection. A nonlinear electrokinetic flow is induced in a nanofluidic channel due to the overlap of electrical double layers, resulting in the fast accumulation of proteins, referred to as the exclusion-enrichment effect. The proposed chip for protein preconcentration was fabricated using simple standard soft lithography with a polydimethylsiloxane replica. This study extends our previous paper, in which gold nanoparticles were manually deposited onto the surface of a protein preconcentrator. In the present work, nanofractures were formed by utilizing the self-assembly of gold-nanoparticle-assisted electric breakdown. This reliable method for nanofracture formation, involving self-assembled monolayers of nanoparticles at the junction gap between microchannels, also decreases the required electric breakdown voltage. The experimental results reveal that a high concentration factor of 1.5×10(4 for a protein sample with an extremely low concentration of 1 nM was achieved in 30 min by using the proposed chip, which is faster than our previously proposed chip at the same conditions. Moreover, an immunoassay of bovine serum albumin (BSA and anti-BSA was carried out to demonstrate the applicability of the proposed chip.

  18. Doping GaP Core-Shell Nanowire pn-Junctions: A Study by Off-Axis Electron Holography. (United States)

    Yazdi, Sadegh; Berg, Alexander; Borgström, Magnus T; Kasama, Takeshi; Beleggia, Marco; Samuelson, Lars; Wagner, Jakob B


    The doping process in GaP core-shell nanowire pn-junctions using different precursors is evaluated by mapping the nanowires' electrostatic potential distribution by means of off-axis electron holography. Three precursors, triethyltin (TESn), ditertiarybutylselenide, and silane are investigated for n-type doping of nanowire shells; among them, TESn is shown to be the most efficient precursor. Off-axis electron holography reveals higher electrostatic potentials in the regions of nanowire cores grown by the vapor-liquid-solid (VLS) mechanism (axial growth) than the regions grown parasitically by the vapor-solid (VS) mechanism (radial growth), attributed to different incorporation efficiency between VLS and VS of unintentional p-type carbon doping originating from the trimethylgallium precursor. This study shows that off-axis electron holography of doped nanowires is unique in terms of the ability to map the electrostatic potential and thereby the active dopant distribution with high spatial resolution. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs

    DEFF Research Database (Denmark)

    Xing, Dezhi; Kjølbye, Anne Louise; Nielsen, Morten S


    demonstrated that 10 nM ZP123 improved gap junctional intercellular conductance by 69% +/- 20% in pairs of guinea pig ventricular myocytes. VT was induced by programmed stimulation in alpha-chloralose anaesthetized open chest dogs 1 to 4 hours after coronary artery occlusion. Three-dimensional activation...... mapping was done using six bipolar electrograms on each of 23 multipolar needles in the risk zone. When VT was reproducibly induced, dogs were randomly assigned to receive either saline or ZP123 cumulatively at three dose levels (intravenous bolus followed by 30-min infusion per dose). Attempts to induce...... VT were repeated in each infusion period. Mass spectrometry was used to measure ZP123 plasma concentrations. Twenty-six dogs with reentrant VT were included. ZP123 significantly prevented reentrant VT at all plasma concentrations vs saline: 1.0 +/- 0.2 nM: 6/12 vs 0/12; 7.7 +/- 0.6 nM: 7/13 vs 1...

  20. Segmental Bayesian estimation of gap-junctional and inhibitory conductance of inferior olive neurons from spike trains with complicated dynamics (United States)

    Hoang, Huu; Yamashita, Okito; Tokuda, Isao T.; Sato, Masa-aki; Kawato, Mitsuo; Toyama, Keisuke


    The inverse problem for estimating model parameters from brain spike data is an ill-posed problem because of a huge mismatch in the system complexity between the model and the brain as well as its non-stationary dynamics, and needs a stochastic approach that finds the most likely solution among many possible solutions. In the present study, we developed a segmental Bayesian method to estimate the two parameters of interest, the gap-junctional (gc) and inhibitory conductance (gi) from inferior olive spike data. Feature vectors were estimated for the spike data in a segment-wise fashion to compensate for the non-stationary firing dynamics. Hierarchical Bayesian estimation was conducted to estimate the gc and gi for every spike segment using a forward model constructed in the principal component analysis (PCA) space of the feature vectors, and to merge the segmental estimates into single estimates for every neuron. The segmental Bayesian estimation gave smaller fitting errors than the conventional Bayesian inference, which finds the estimates once across the entire spike data, or the minimum error method, which directly finds the closest match in the PCA space. The segmental Bayesian inference has the potential to overcome the problem of non-stationary dynamics and resolve the ill-posedness of the inverse problem because of the mismatch between the model and the brain under the constraints based, and it is a useful tool to evaluate parameters of interest for neuroscience from experimental spike train data. PMID:26052280

  1. Segmental Bayesian estimation of gap-junctional and inhibitory conductance of inferior olive neurons from spike trains with complicated dynamics

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    Huu eHoang


    Full Text Available The inverse problem for estimating model parameters from brain spike data is an ill-posed problem because of a huge mismatch in the system complexity between the model and the brain as well as its non-stationary dynamics, and needs a stochastic approach that finds the most likely solution among many possible solutions. In the present study, we developed a segmental Bayesian method to estimate the two parameters of interest, the gap-junctional (gc and inhibitory conductance (gi from inferior olive spike data. Feature vectors were estimated for the spike data in a segment-wise fashion to compensate for the non-stationary firing dynamics. Hierarchical Bayesian estimation was conducted to estimate the gc and gi for every spike segment using a forward model constructed in the principal component analysis (PCA space of the feature vectors, and to merge the segmental estimates into single estimates for every neuron. The segmental Bayesian estimation gave smaller fitting errors than the conventional Bayesian inference, which finds the estimates once across the entire spike data, or the minimum error method, which directly finds the closest match in the PCA space. The segmental Bayesian inference has the potential to overcome the problem of non-stationary dynamics and resolve the ill-posedness of the inverse problem because of the mismatch between the model and the brain under the constraints based, and it is a useful tool to evaluate parameters of interest for neuroscience from experimental spike train data.

  2. The Role of Gap Junction-Mediated Endothelial Cell–Cell Interaction in the Crosstalk between Inflammation and Blood Coagulation

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    Takayuki Okamoto


    Full Text Available Endothelial cells (ECs play a pivotal role in the crosstalk between blood coagulation and inflammation. Endothelial cellular dysfunction underlies the development of vascular inflammatory diseases. Recent studies have revealed that aberrant gap junctions (GJs and connexin (Cx hemichannels participate in the progression of cardiovascular diseases such as cardiac infarction, hypertension and atherosclerosis. ECs can communicate with adjacent ECs, vascular smooth muscle cells, leukocytes and platelets via GJs and Cx channels. ECs dynamically regulate the expression of numerous Cxs, as well as GJ functionality, in the context of inflammation. Alterations to either result in various side effects across a wide range of vascular functions. Here, we review the roles of endothelial GJs and Cx channels in vascular inflammation, blood coagulation and leukocyte adhesion. In addition, we discuss the relevant molecular mechanisms that endothelial GJs and Cx channels regulate, both the endothelial functions and mechanical properties of ECs. A better understanding of these processes promises the possibility of pharmacological treatments for vascular pathogenesis.

  3. Possible Mechanisms of Mercury Toxicity and Cancer Promotion: Involvement of Gap Junction Intercellular Communications and Inflammatory Cytokines

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    Roberto Zefferino


    Full Text Available A number of observations indicate that heavy metals are able to alter cellular metabolic pathways through induction of a prooxidative state. Nevertheless, the outcome of heavy metal-mediated effects in the development of human diseases is debated and needs further insights. Cancer is a well-established DNA mutation-linked disease; however, epigenetic events are perhaps more important and harmful than genetic alterations. Unfortunately, we do not have reliable screening methods to assess/validate the epigenetic (promoter effects of a physical or a chemical agent. We propose a mechanism of action whereby mercury acts as a possible promoter carcinogen. In the present contribution, we resume our previous studies on mercury tested at concentrations comparable with its occurrence as environmental pollutant. It is shown that Hg(II elicits a prooxidative state in keratinocytes linked to inhibition of gap junction-mediated intercellular communication and proinflammatory cytokine production. These combined effects may on one hand isolate cells from tissue-specific homeostasis promoting their proliferation and on the other hand tamper the immune system defense/surveillance checkmating the whole organism. Since Hg(II is not a mutagenic/genotoxic compound directly affecting gene expression, in a broader sense, mercury might be an example of an epigenetic tumor promoter or, further expanding this concept, a “metagenetic” effector.

  4. Enhanced gap junction intercellular communication inhibits catabolic and pro-inflammatory responses in tenocytes against heat stress. (United States)

    Maeda, Eijiro; Kimura, Shunsuke; Yamada, Masahiko; Tashiro, Masataka; Ohashi, Toshiro


    Elevation of tendon core temperature during severe activity is well known. However, its effects on tenocyte function have not been studied in detail. The present study tested a hypothesis that heat stimulation upregulates tenocyte catabolism, which can be modulated by the inhibition or the enhancement of gap junction intercellular communication (GJIC). Tenocytes isolated from rabbit Achilles tendons were subjected to heat stimulation at 37 °C, 41 °C or 43 °C for 30 min, and changes in cell viability, gene expressions and GJIC were examined. It was found that GJIC exhibited no changes by the stimulation even at 43 °C, but cell viability was decreased and catabolic and proinflammatory gene expressions were upregulated. Inhibition of GJIC demonstrated further upregulated catabolic and proinflammatory gene expressions. In contrast, enhanced GJIC, resulting from forced upregulation of connexin 43 gene, counteracted the heat-induced upregulation of catabolic and proinflammatory genes. These findings suggest that the temperature rise in tendon core could upregulate catabolic and proinflammatory activities, potentially leading to the onset of tendinopathy, and such upregulations could be suppressed by the enhancement of GJIC. Therefore, to prevent tendon injury at an early stage from becoming chronic injury, tendon core temperature and GJIC could be targets for post-activity treatments.

  5. Diverse pattern of gap junction beta-2 and gap junction beta-4 genes mutations and lack of contribution of DFNB21, DFNB24, DFNB29, and DFNB42 loci in autosomal recessive nonsyndromic hearing loss patients in Hormozgan, Iran

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    Masoud Akbarzadeh Laleh


    Full Text Available Background: We aimed to determine the contribution of four DFNB loci and mutation analysis of gap junction beta-2 (GJB2 and GJB4 genes in autosomal recessive nonsyndromic hearing loss (ARNSHL in South of Iran. Materials and Methods: A total of 36 large ARNSHL pedigrees with at least two affected subjects were enrolled in the current study. The GJB2 and GJB4 genes mutations were screened using direct sequencing method. The GJB2 and GJB4 negative families were analyzed for the linkage to DFNB21, DFNB24, DFNB29, and DFNB42 loci by genotyping the corresponding STR markers using polymerase chain reaction-PAGE method. Results: We found a homozygous nonsense mutation W77X and a homozygous missense mutation C169W in 5.55% of studied families in GJB2 and GJB4 genes, respectively. Five heterozygous mutations including V63G, A78T, and R127H in GJB2 gene, and R103C and R227W in GJB4 gene were detected. We identified two novel variations V63G in GJB2 and R227W in GJB4. In silico analysis predicted that both novel variations are deleterious mutations. We did not unveil any linkage between DFNB21, DFNB24, DFNB29, and DFNB42 loci and ARNSHL among studied families. Conclusion: This is the first report of GJB2 and GJB4 mutations from Hormozgan population. According to the previous publications regarding GJB2 and GJB4 mutations, the distribution of the mutations is different from other parts of Iran that should be considered in primary health-care programs. Further investigations are needed to evaluate the contribution of other loci in ARNSHL subjects in South of Iran.

  6. Role of gap junctional intercellular communication (GJIC) through p38 and ERK1/2 pathway in the differentiation of rat neuronal stem cells. (United States)

    Yang, Se-Ran; Cho, Sung-Dae; Ahn, Nam-Shik; Jung, Ji-Won; Park, Joon-Suk; Jo, Eun-Hye; Hwang, Jae-Woong; Jung, Ji-Youn; Kim, Tae-Yung; Yoon, Byoung-Su; Lee, Bong-Hee; Kang, Kyung-Sun; Lee, Yong-Soon


    Gap junctional intercellular communications (GJIC) contributes to neural function in development and differentiation of CNS. In this study, we have investigated the expression of GJIC during the differentiation of neuronal stem cells and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neuronal stem cell-derived cells from rat brain. During neuronal stem cell differentiation, expressions of Cx43 and 32 were increased for the duration of 72 hr, however the effect were decreased on the 7d. In the neuronal stem cell-derived cells, pretreatments with p38 MAP kinase inhibitor, SB203580, and MEK inhibitor, PD98059, could protect GJIC against TPA-induced inhibition of GJIC. Our data suggest that GJIC plays an important role during neuronal stem cell differentiation, and ERK1/2 and p38 MAP kinase signaling pathway may be closely related functionally to regulate gap junction in rat neuronal stem cell-derived cells.

  7. Akinesia and freezing caused by Na(+) leak-current channel (NALCN) deficiency corrected by pharmacological inhibition of K(+) channels and gap junctions. (United States)

    Kasap, Merve; Bonnett, Kendra; Aamodt, Eric J; Dwyer, Donard S


    The Na(+) leak-current channel (NALCN) regulates locomotion, respiration, and intellectual development. Previous work highlighted striking similarities between characteristic movement phenotypes of NALCN-deficient animals (Drosophila and Caenorhabditis elegans) and the major symptoms of Parkinson's disease and primary progressive freezing gait. We have discovered novel physiological connections between the NALCN, K(+) channels, and gap junctions that mediate regulation of locomotion in C. elegans. Drugs that block K(+) channels and gap junctions or that activate Ca(++) channels significantly improve movement of NALCN-deficient animals. Loss-of-function of the NALCN creates an imbalance in ions, including K(+) and Ca(++) , that interferes with normal cycles of depolarization-repolarization. This work suggests new therapeutic strategies for certain human movement disorders. J. Comp. Neurol. 525:1109-1121, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Gap junctions in the ovary of Drosophila melanogaster: localization of innexins 1, 2, 3 and 4 and evidence for intercellular communication via innexin-2 containing channels

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    Zimmermann Jennifer


    Full Text Available Abstract Background In the Drosophila ovary, germ-line and soma cells are interconnected via gap junctions. The main gap-junction proteins in invertebrates are members of the innexin family. In order to reveal the role that innexins play in cell-cell communication during oogenesis, we investigated the localization of innexins 1, 2, 3 and 4 using immunohistochemistry, and analyzed follicle development following channel blockade. Results We found innexin 1 predominantly localized to the baso-lateral domain of follicle cells, whereas innexin 2 is positioned apico-laterally as well as apically between follicle cells and germ-line cells. Innexin 3 was observed laterally in follicle cells and also in nurse cells, and innexin 4 was detected in the oolemma up to stage 8 and in nurse-cell membranes up to stage 12. In order to test whether innexins form channels suitable for intercellular communication, we microinjected innexin antibodies in combination with a fluorescent tracer into the oocyte of stage-10 follicles. We found that dye-coupling between oocyte and follicle cells was largely reduced by innexin-2 antibodies directed against the intracellular C-terminus as well as against the intracellular loop. Analyzing in vitro, between stages 10 and 14, the developmental capacities of follicles following microinjections of innexin-2 antibodies revealed defects in follicle-cell differentiation, nurse-cell regression, oocyte growth and choriogenesis. Conclusion Our results suggest that all analyzed innexins are involved in the formation of gap junctions in the ovary. While innexins 2 and 3 are colocalized between soma cells, innexins 2 and 4 are colocalized between soma and germ-line cells. Innexin 2 is participating in cell-cell communication via hemichannels residing in the oolemma. It is obvious that gap-junctional communication between germ-line and soma cells is essential for several processes during oogenesis.

  9. Tanshinone IIA increases the bystander effect of herpes simplex virus thymidine kinase/ganciclovir gene therapy via enhanced gap junctional intercellular communication.

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    Jianyong Xiao

    Full Text Available The bystander effect is an intriguing phenomenon by which adjacent cells become sensitized to drug treatment during gene therapy with herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV. This effect is reported to be mediated by gap junctional intercellular communication (GJIC, and therefore, we postulated that upregulation of genes that facilitate GJIC may enhance the HSV-tk/GCV bystander effect. Previous findings have shown Tanshinone IIA (Tan IIA, a chemical substance derived from a Chinese medicine herb, promotes the upregulation of the connexins Cx26 and Cx43 in B16 cells. Because gap junctions are formed by connexins, we hypothesized that Tan IIA might increase GJIC. Our results show that Tan IIA increased GJIC in B16 melanoma cells, leading to more efficient GCV-induced bystander killing in cells stably expressing HSV-tk. Additionally, in vivo experiments demonstrated that tumors in mice with 10% HSV-tk positive B16 cells and 90% wild-type B16 cells became smaller following treatment with the combination of GCV and Tan IIA as compared to GCV or Tan IIA alone. These data demonstrate that Tan IIA can augment the bystander effect of HSV-tk/GCV system through increased gap junction coupling, which adds strength to the promising strategy that develops connexins inducer to potentiate the effects of suicide gene therapy.

  10. Keratitis-Ichthyosis-Deafness syndrome-associated Cx26 mutants produce nonfunctional gap junctions but hyperactive hemichannels when co-expressed with wild type Cx43 (United States)

    García, Isaac E.; Maripillán, Jaime; Jara, Oscar; Ceriani, Ricardo; Palacios-Muñoz, Angelina; Ramachandran, Jayalakshimi; Olivero, Pablo; Pérez-Acle, Tomás; González, Carlos; Sáez, Juan C.; Contreras, Jorge E.; Martínez, Agustín D.


    Mutations in Cx26 gene are found in most cases of human genetic deafness. Some mutations produce syndromic deafness associated with skin disorders, like Keratitis Ichthyosis Deafness syndrome (KID). Because in the human skin Cx26 is co-expressed with other connexins, like Cx43 and Cx30, and since KID syndrome is inherited as autosomal dominant condition, it is possible that KID mutations change the way Cx26 interacts with other co-expressed connexins. Indeed, some Cx26 syndromic mutations showed gap junction dominant negative effect when co-expressed with wild type connexins, including Cx26 and Cx43. The nature of these interactions and the consequences on hemichannels and gap junction channels functions remain unknown. In this study we demonstrate that syndromic mutations at the N-terminus segment of Cx26, change connexin oligomerization compatibility, allowing aberrant interactions with Cx43. Strikingly, heteromeric oligomer formed by Cx43/Cx26 (syndromic mutants) show exacerbated hemichannel activity, but nonfunctional gap junction channels; this also occurs for those Cx26 KID mutants that do not show functional homomeric hemichannels. Heterologous expression of these hyperactive heteromeric hemichannels increases cell membrane permeability, favoring ATP release and Ca2+ overload. The functional paradox produced by oligomerization of Cx43 and Cx26 KID mutants could underlie the severe syndromic phenotype in human skin. PMID:25625422

  11. Tanshinone IIA increases the bystander effect of herpes simplex virus thymidine kinase/ganciclovir gene therapy via enhanced gap junctional intercellular communication. (United States)

    Xiao, Jianyong; Zhang, Guangxian; Qiu, Pengxiang; Liu, Xijuan; Wu, Yingya; Du, Biaoyan; Li, Jiefen; Zhou, Jing; Li, Jingjing; Tan, Yuhui


    The bystander effect is an intriguing phenomenon by which adjacent cells become sensitized to drug treatment during gene therapy with herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV). This effect is reported to be mediated by gap junctional intercellular communication (GJIC), and therefore, we postulated that upregulation of genes that facilitate GJIC may enhance the HSV-tk/GCV bystander effect. Previous findings have shown Tanshinone IIA (Tan IIA), a chemical substance derived from a Chinese medicine herb, promotes the upregulation of the connexins Cx26 and Cx43 in B16 cells. Because gap junctions are formed by connexins, we hypothesized that Tan IIA might increase GJIC. Our results show that Tan IIA increased GJIC in B16 melanoma cells, leading to more efficient GCV-induced bystander killing in cells stably expressing HSV-tk. Additionally, in vivo experiments demonstrated that tumors in mice with 10% HSV-tk positive B16 cells and 90% wild-type B16 cells became smaller following treatment with the combination of GCV and Tan IIA as compared to GCV or Tan IIA alone. These data demonstrate that Tan IIA can augment the bystander effect of HSV-tk/GCV system through increased gap junction coupling, which adds strength to the promising strategy that develops connexins inducer to potentiate the effects of suicide gene therapy.

  12. Characterization of a variant of gap junction protein α8 identified in a family with hereditary cataract.

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    Debbie S Kuo

    Full Text Available Congenital cataracts occur in isolation in about 70% of cases or are associated with other abnormalities such as anterior segment dysgenesis and microphthalmia. We identified a three-generation family in the University of California San Francisco glaucoma clinic comprising three individuals with congenital cataracts and aphakic glaucoma, one of whom also had microphthalmia. The purpose of this study was to identify a possible causative mutation in this family and to investigate its pathogenesis.We performed exome sequencing and identified a putative mutation in gap junction protein α8 (GJA8. We used PCR and DNA sequencing of GJA8 in affected and unaffected members of the pedigree to test segregation of the variant with the phenotype. We tested cellular distribution and function of the variant protein by immunofluorescence and intercellular transfer of Neurobiotin in transiently transfected HeLa cells.Exome sequencing revealed a variant in GJA8 (c.658A>G encoding connexin50 (Cx50 that resulted in a missense change (p.N220D in transmembrane domain 4. The variant was present in all three affected family members, but was also present in the proband's grandfather who was reported to be unaffected. The mutant protein localized to the plasma membrane and supported intercellular Neurobiotin transfer in HeLa cells.We identified a variant in transmembrane domain 4 of Cx50 in a family with autosomal dominant congenital cataracts. This variant has been previously identified in other cataract cohorts, but it is also present in unaffected individuals. Our study demonstrates that the mutant protein localized to the plasma membrane and formed functional intercellular channels. These data suggest that GJA8 c.658A>G is most likely a benign rare variant.

  13. Increased expression of gap junction protein--connexin 32 in lymph node metastases of human ductal breast cancer.

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    Mariola Sulkowska


    Full Text Available Gap junctions are specialized cell membrane channels composed of connexins (Cxs, which mediate the direct passage of small molecules between adjacent cells. They are involved in the regulation of cell cycle, cell signaling and differentiation as well as probably invasion and metastasis. Up to now, Cx32 status in human breast cancer has not been studied. Consequently, the aim of the present study was the evaluation of the expression of connexin 32 (Cx32 in primary breast tumors (PTs and matched-paired metastases to lymph nodes (MLNs in correlation with selected clinicopathological features. Tissue samples from 79 women were examined by immunohistochemistry, using the streptavidin-biotin-peroxidase complex technique for Cx32. Cytoplasmic expression of Cx32 was detected in 31 of 79 breast cancers (39.2%. Both epithelial and myoepithelial cells of normal ducts adjacent to the tumor did not express Cx32. Increased expression of studied Cx was observed in metastases to lymph nodes relative to primary tumors. Additionally, Cx32-negative primary tumors developed Cx32-positive metastases. Statistical comparisons of Cx32 expression in the matched pairs indicate that this protein significantly increased in lymph node metastases compared to primary tumors (p<0.001. The expression of Cx32 in primary breast cancer was not statistically associated with age of patients, tumor size, lymph node status, but we observed a tendency toward association between Cx32 expression and histological differentiation. In conclusion, transformed cells may have an ability to produce Cxs also atypical for normal cells. Increased expression of Cx32 in metastases to the lymph nodes might reflect alteration in connexin gene transcription during breast carcinogenesis and finally, it may be a sign of more malignant phenotype of cancerous cells.

  14. Experimental blunt chest trauma-induced myocardial inflammation and alteration of gap-junction protein connexin 43.

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    Miriam Kalbitz

    Full Text Available Severe blunt chest trauma in humans is associated with high mortality rates. Whereas lung tissue damage and lung inflammation after blunt chest trauma have extensively been investigated, the traumatic and posttraumatic effects on the heart remain poorly understood. Therefore, the purpose of this study was to define cardiac injury patterns in an experimental blunt chest trauma model in rats.Experimental blunt chest trauma was induced by a blast wave in rats, with subsequent analysis of its effects on the heart. The animals were subjected either to a sham or trauma procedure. Systemic markers for cardiac injury were determined after 24 h and 5 days. Postmortem analysis of heart tissue addressed structural injury and inflammation 24 h and 5 days after trauma.Plasma levels of extracellular histones were elevated 24 h and 5 days after blunt chest trauma compared to sham-treated animals. In the heart, up-regulation of interleukin-1β 24 h after trauma and increased myeloperoxidase activity 24 h and 5 days after trauma were accompanied by reduced complement C5a receptor-1 expression 24 h after trauma. Histological analysis revealed extravasation of erythrocytes and immunohistochemical analysis alteration of the pattern of the gap-junction protein connexin 43. Furthermore, a slight reduction of α-actinin and desmin expression in cardiac tissue was found after trauma together with a minor increase in sarcoplasmatic/endoplasmatic reticlulum calcium-ATPase (SERCA expression.The clinically highly relevant rat model of blast wave-induced blunt chest trauma is associated with cardiac inflammation and structural alterations in cardiac tissue.

  15. Experimental blunt chest trauma-induced myocardial inflammation and alteration of gap-junction protein connexin 43. (United States)

    Kalbitz, Miriam; Amann, Elisa Maria; Bosch, Belinda; Palmer, Annette; Schultze, Anke; Pressmar, Jochen; Weber, Birte; Wepler, Martin; Gebhard, Florian; Schrezenmeier, Hubert; Brenner, Rolf; Huber-Lang, Markus


    Severe blunt chest trauma in humans is associated with high mortality rates. Whereas lung tissue damage and lung inflammation after blunt chest trauma have extensively been investigated, the traumatic and posttraumatic effects on the heart remain poorly understood. Therefore, the purpose of this study was to define cardiac injury patterns in an experimental blunt chest trauma model in rats. Experimental blunt chest trauma was induced by a blast wave in rats, with subsequent analysis of its effects on the heart. The animals were subjected either to a sham or trauma procedure. Systemic markers for cardiac injury were determined after 24 h and 5 days. Postmortem analysis of heart tissue addressed structural injury and inflammation 24 h and 5 days after trauma. Plasma levels of extracellular histones were elevated 24 h and 5 days after blunt chest trauma compared to sham-treated animals. In the heart, up-regulation of interleukin-1β 24 h after trauma and increased myeloperoxidase activity 24 h and 5 days after trauma were accompanied by reduced complement C5a receptor-1 expression 24 h after trauma. Histological analysis revealed extravasation of erythrocytes and immunohistochemical analysis alteration of the pattern of the gap-junction protein connexin 43. Furthermore, a slight reduction of α-actinin and desmin expression in cardiac tissue was found after trauma together with a minor increase in sarcoplasmatic/endoplasmatic reticlulum calcium-ATPase (SERCA) expression. The clinically highly relevant rat model of blast wave-induced blunt chest trauma is associated with cardiac inflammation and structural alterations in cardiac tissue.

  16. Gap Junctional Blockade Stochastically Induces Different Species-Specific Head Anatomies in Genetically Wild-Type Girardia dorotocephala Flatworms

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    Maya Emmons-Bell


    Full Text Available The shape of an animal body plan is constructed from protein components encoded by the genome. However, bioelectric networks composed of many cell types have their own intrinsic dynamics, and can drive distinct morphological outcomes during embryogenesis and regeneration. Planarian flatworms are a popular system for exploring body plan patterning due to their regenerative capacity, but despite considerable molecular information regarding stem cell differentiation and basic axial patterning, very little is known about how distinct head shapes are produced. Here, we show that after decapitation in G. dorotocephala, a transient perturbation of physiological connectivity among cells (using the gap junction blocker octanol can result in regenerated heads with quite different shapes, stochastically matching other known species of planaria (S. mediterranea, D. japonica, and P. felina. We use morphometric analysis to quantify the ability of physiological network perturbations to induce different species-specific head shapes from the same genome. Moreover, we present a computational agent-based model of cell and physical dynamics during regeneration that quantitatively reproduces the observed shape changes. Morphological alterations induced in a genomically wild-type G. dorotocephala during regeneration include not only the shape of the head but also the morphology of the brain, the characteristic distribution of adult stem cells (neoblasts, and the bioelectric gradients of resting potential within the anterior tissues. Interestingly, the shape change is not permanent; after regeneration is complete, intact animals remodel back to G. dorotocephala-appropriate head shape within several weeks in a secondary phase of remodeling following initial complete regeneration. We present a conceptual model to guide future work to delineate the molecular mechanisms by which bioelectric networks stochastically select among a small set of discrete head morphologies

  17. Intercellular junctions in nerve-free hydra

    DEFF Research Database (Denmark)

    McDowall, A W; Grimmelikhuijzen, C J


    Epithelial cells of nerve-free hydra contain septate and gap junctions. In thin sections the gap junctions are characterized by a gap of 3-4 nm. Freeze-fracture demonstrates the presence of septate junctions and two further types of structures: (i) the "E-type" or "inverted" gap junctions...

  18. Competitive behavior of photons contributing to junction voltage jump in narrow band-gap semiconductor multi-quantum-well laser diodes at lasing threshold

    Directory of Open Access Journals (Sweden)

    Liefeng Feng


    Full Text Available The junction behavior of different narrow band-gap multi-quantum-well (MQW laser diodes (LDs confirmed that the jump in the junction voltage in the threshold region is a general characteristic of narrow band-gap LDs. The relative change in the 1310 nm LD is the most obvious. To analyze this sudden voltage change, the threshold region is divided into three stages by Ithl and Ithu, as shown in Fig. 2; Ithl is the conventional threshold, and as long as the current is higher than this threshold, lasing exists and the IdV/dI-I plot drops suddenly; Ithu is the steady lasing point, at which the separation of the quasi-Fermi levels of electron and holes across the active region (Vj is suddenly pinned. Based on the evolutionary model of dissipative structure theory, the rate equations of the photons in a single-mode LD were deduced in detail at Ithl and Ithu. The results proved that the observed behavior of stimulated emission suddenly substituting for spontaneous emission, in a manner similar to biological evolution, must lead to a sudden increase in the injection carriers in the threshold region, which then causes the sudden increase in the junction voltage in this region.

  19. On Biophysical Properties and Sensitivity to Gap Junction Blockers of Connexin 39 Hemichannels Expressed in HeLa Cells (United States)

    Vargas, Anibal A.; Cisterna, Bruno A.; Saavedra-Leiva, Fujiko; Urrutia, Carolina; Cea, Luis A.; Vielma, Alex H.; Gutierrez-Maldonado, Sebastian E.; Martin, Alberto J. M.; Pareja-Barrueto, Claudia; Escalona, Yerko; Schmachtenberg, Oliver; Lagos, Carlos F.; Perez-Acle, Tomas; Sáez, Juan C.


    Although connexins (Cxs) are broadly expressed by cells of mammalian organisms, Cx39 has a very restricted pattern of expression and the biophysical properties of Cx39-based channels [hemichannels (HCs) and gap junction channels (GJCs)] remain largely unknown. Here, we used HeLa cells transfected with Cx39 (HeLa-Cx39 cells) in which intercellular electrical coupling was not detected, indicating the absence of GJCs. However, functional HCs were found on the surface of cells exposed to conditions known to increase the open probability of other Cx HCs (e.g., extracellular divalent cationic-free solution (DCFS), extracellular alkaline pH, mechanical stimulus and depolarization to positive membrane potentials). Cx39 HCs were blocked by some traditional Cx HC blockers, but not by others or a pannexin1 channel blocker. HeLa-Cx39 cells showed similar resting membrane potentials (RMPs) to those of parental cells, and exposure to DCFS reduced RMPs in Cx39 transfectants, but not in parental cells. Under these conditions, unitary events of ~75 pS were frequent in HeLa-Cx39 cells and absent in parental cells. Real-time cellular uptake experiments of dyes with different physicochemical features, as well as the application of a machine-learning approach revealed that Cx39 HCs are preferentially permeable to molecules characterized by six categories of descriptors, namely: (1) electronegativity, (2) ionization potential, (3) polarizability, (4) size and geometry, (5) topological flexibility and (6) valence. However, Cx39 HCs opened by mechanical stimulation or alkaline pH were impermeable to Ca2+. Molecular modeling of Cx39-based channels suggest that a constriction present at the intracellular portion of the para helix region co-localizes with an electronegative patch, imposing an energetic and steric barrier, which in the case of GJCs may hinder channel function. Results reported here demonstrate that Cx39 form HCs and add to our understanding of the functional roles of Cx39 HCs

  20. Dysfunction in gap junction intercellular communication induces aberrant behavior of the inner cell mass and frequent collapses of expanded blastocysts in mouse embryos. (United States)

    Togashi, Kazue; Kumagai, Jin; Sato, Emiko; Shirasawa, Hiromitsu; Shimoda, Yuki; Makino, Kenichi; Sato, Wataru; Kumazawa, Yukiyo; Omori, Yasufumi; Terada, Yukihiro


    We investigated the role of gap junctions (GJs) in embryological differentiation, and observed the morphological behavior of the inner cell mass (ICM) by time-lapse movie observation (TLM) with gap junction inhibitors (GJis). ICR mouse embryos were exposed to two types of GJis in CZB medium: oleamide (0 to 50 μM) and 1-heptanol (0 to 10 mM). We compared the rate of blastocyst formation at embryonic day 4.5 (E4.5) with E5.5. We also observed and evaluated the times from the second cleavage to each embryonic developing stage by TLM. We investigated embryonic distribution of DNA, Nanog protein, and Connexin 43 protein with immunofluorescent staining. In the comparison of E4.5 with E5.5, inhibition of gap junction intercellular communication (GJIC) delayed embryonic blastocyst formation. The times from the second cleavage to blastocyst formation were significantly extended in the GJi-treated embryos (control vs with oleamide, 2224 ± 179 min vs 2354 ± 278 min, p = 0.013). Morphological differences were traced in control versus GJi-treated embryos until the hatching stage. Oleamide induced frequent severe collapses of expanded blastocysts (77.4 % versus 26.3 %, p = 0.0001) and aberrant ICM divisions connected to sticky strands (74.3 % versus 5.3 %, p = 0.0001). Immunofluorescent staining indicated Nanog-positive cells were distributed in each divided ICM. GJIC plays an important role in blastocyst formation, collapses of expanded blastocysts, and the ICM construction in mouse embryos.

  1. Amitriptyline up-regulates connexin43-gap junction in rat cultured cortical astrocytes via activation of the p38 and c-Fos/AP-1 signalling pathway. (United States)

    Morioka, N; Suekama, K; Zhang, F F; Kajitani, N; Hisaoka-Nakashima, K; Takebayashi, M; Nakata, Y


    Intercellular communication via gap junctions, comprised of connexin (Cx) proteins, allow for communication between astrocytes, which in turn is crucial for maintaining CNS homeostasis. The expression of Cx43 is decreased in post-mortem brains from patients with major depression. A potentially novel mechanism of tricyclic antidepressants is to increase the expression and functioning of gap junctions in astrocytes. The effect of amitriptyline on the expression of Cx43 and gap junction intercellular communication (GJIC) in rat primary cultured cortical astrocytes was investigated. We also investigated the role of p38 MAPK intracellular signalling pathway in the amitriptyline-induced expression of Cx43 and GJIC. Treatment with amitriptyline for 48 h significantly up-regulated Cx43 mRNA, protein and GJIC. The up-regulation of Cx43 was not monoamine-related since noradrenaline, 5-HT and dopamine did not induce Cx43 expression and pretreatment with α- and β-adrenoceptor antagonists had no effect. Intracellular signalling involved p38 MAPK, as amitriptyline significantly increased p38 MAPK phosphorylation and Cx43 expression and GJIC were significantly blocked by the p38 inhibitor SB 202190. Furthermore, amitriptyline-induced Cx43 expression and GJIC were markedly reduced by transcription factor AP-1 inhibitors (curcumin and tanshinone IIA). The translocation of c-Fos from the cytosol and the nucleus of cortical astrocytes was increased by amitriptyline, and this response was dependent on p38 activity. These findings indicate a novel mechanism of action of amitriptyline through cortical astrocytes, and further suggest that targeting this mechanism could lead to the development of a new class of antidepressants. © 2014 The British Pharmacological Society.

  2. The gap junction inhibitor 2-aminoethoxy-diphenyl-borate protects against acetaminophen hepatotoxicity by inhibiting cytochrome P450 enzymes and c-jun N-terminal kinase activation

    Energy Technology Data Exchange (ETDEWEB)

    Du, Kuo; Williams, C. David; McGill, Mitchell R.; Xie, Yuchao [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Farhood, Anwar [Department of Pathology, St. David' s North Austin Medical Center, Austin, TX 78756 (United States); Vinken, Mathieu [Department of Toxicology, Center for Pharmaceutical Sciences, Vrije Universiteit Brussels, 1090 Brussels (Belgium); Jaeschke, Hartmut, E-mail: [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)


    Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the US. Although many aspects of the mechanism are known, recent publications suggest that gap junctions composed of connexin32 function as critical intercellular communication channels which transfer cytotoxic mediators into neighboring hepatocytes and aggravate liver injury. However, these studies did not consider off-target effects of reagents used in these experiments, especially the gap junction inhibitor 2-aminoethoxy-diphenyl-borate (2-APB). In order to assess the mechanisms of protection of 2-APB in vivo, male C56Bl/6 mice were treated with 400 mg/kg APAP to cause extensive liver injury. This injury was prevented when animals were co-treated with 20 mg/kg 2-APB and was attenuated when 2-APB was administered 1.5 h after APAP. However, the protection was completely lost when 2-APB was given 4–6 h after APAP. Measurement of protein adducts and c-jun-N-terminal kinase (JNK) activation indicated that 2-APB reduced both protein binding and JNK activation, which correlated with hepatoprotection. Although some of the protection was due to the solvent dimethyl sulfoxide (DMSO), in vitro experiments clearly demonstrated that 2-APB directly inhibits cytochrome P450 activities. In addition, JNK activation induced by phorone and tert-butylhydroperoxide in vivo was inhibited by 2-APB. The effects against APAP toxicity in vivo were reproduced in primary cultured hepatocytes without use of DMSO and in the absence of functional gap junctions. We conclude that the protective effect of 2-APB was caused by inhibition of metabolic activation of APAP and inhibition of the JNK signaling pathway and not by blocking connexin32-based gap junctions. - Highlights: • 2-APB protected against APAP-induced liver injury in mice in vivo and in vitro • 2-APB protected by inhibiting APAP metabolic activation and JNK signaling pathway • DMSO inhibited APAP metabolic activation as the solvent of 2-APB

  3. Participation of gap junction communication in potentially lethal damage repair and DNA damage in human fibroblasts exposed to low- or high-LET radiation (United States)

    Autsavapromporn, Narongchai; Suzuki, Masao; Plante, Ianik; Liu, Cuihua; Uchihori, Yukio; Hei, Tom K.; Azzam, Edouard I.; Murakami, Takeshi


    Existing research has not fully explained how different types of ionizing radiation (IR) modulate the responses of cell populations or tissues. In our previous work, we showed that gap junction intercellular communication (GJIC) mediates the propagation of stressful effects among irradiated cells exposed to high linear energy transfer (LET) radiations, in which almost every cells is traversed by an IR track. In the present study, we conducted an in-depth study of the role of GJIC in modulating the repair of potentially lethal damage (PLDR) and micronuclei formation in cells exposed to low- or high-LET IR. Confluent human fibroblasts were exposed in the presence or absence of a gap junction inhibitor to 200 kV X rays (LET ∼ 1.7 keV/µm), carbon ions (LET ∼ 76 keV/µm), silicon ions (LET ∼ 113 keV/µm) or iron ions (LET ∼ 400 keV/µm) that resulted in isosurvival levels. The fibroblasts were incubated for various times at 37 °C. As expected, high-LET IR were more effective than were low-LET X rays at killing cells and damaging DNA shortly after irradiation. However, when cells were held in a confluent state for several hours, PLDR associated with a reduction in DNA damage, occurred only in cells exposed to X rays. Interestingly, inhibition of GJIC eliminated the enhancement of toxic effects, which resulted in an increase of cell survival and reduction in the level of micronucleus formation in cells exposed to high, but not in those exposed to low-LET IR. The experiment shows that gap-junction communication plays an important role in the propagation of stressful effects among irradiated cells exposed to high-LET IR while GJIC has only a minimal effect on PLDR and DNA damage following low-LET irradiation. Together, our results show that PLDR and induction of DNA damage clearly depend on gap-junction communication and radiation quality. PMID:23867854

  4. Evolution of Microbial Quorum Sensing to Human Global Quorum Sensing: An Insight into How Gap Junctional Intercellular Communication Might Be Linked to the Global Metabolic Disease Crisis (United States)

    Trosko, James E.


    The first anaerobic organism extracted energy for survival and reproduction from its source of nutrients, with the genetic means to ensure protection of its individual genome but also its species survival. While it had a means to communicate with its community via simple secreted molecules (“quorum sensing”), the eventual shift to an aerobic environment led to multi-cellular metazoan organisms, with evolutionary-selected genes to form extracellular matrices, stem cells, stem cell niches, and a family of gap junction or “connexin” genes. These germinal and somatic stem cells responded to extracellular signals that triggered intra-cellular signaling to regulate specific genes out of the total genome. These extra-cellular induced intra-cellular signals also modulated gap junctional intercellular communication (GJIC) in order to regulate the new cellular functions of symmetrical and asymmetrical cell division, cell differentiation, modes of cell death, and senescence. Within the hierarchical and cybernetic concepts, differentiated by neurons organized in the brain of the Homo sapiens, the conscious mind led to language, abstract ideas, technology, myth-making, scientific reasoning, and moral decision–making, i.e., the creation of culture. Over thousands of years, this has created the current collision between biological and cultural evolution, leading to the global “metabolic disease” crisis. PMID:27314399

  5. Rescue of Notch signaling in cells incapable of GDP-L-fucose synthesis by gap junction transfer of GDP-L-fucose in Drosophila. (United States)

    Ayukawa, Tomonori; Matsumoto, Kenjiroo; Ishikawa, Hiroyuki O; Ishio, Akira; Yamakawa, Tomoko; Aoyama, Naoki; Suzuki, Takuya; Matsuno, Kenji


    Notch (N) is a transmembrane receptor that mediates cell-cell interactions to determine many cell-fate decisions. N contains EGF-like repeats, many of which have an O-fucose glycan modification that regulates N-ligand binding. This modification requires GDP-L-fucose as a donor of fucose. The GDP-L-fucose biosynthetic pathways are well understood, including the de novo pathway, which depends on GDP-mannose 4,6 dehydratase (Gmd) and GDP-4-keto-6-deoxy-D-mannose 3,5-epimerase/4-reductase (Gmer). However, the potential for intercellularly supplied GDP-L-fucose and the molecular basis of such transportation have not been explored in depth. To address these points, we studied the genetic effects of mutating Gmd and Gmer on fucose modifications in Drosophila. We found that these mutants functioned cell-nonautonomously, and that GDP-L-fucose was supplied intercellularly through gap junctions composed of Innexin-2. GDP-L-fucose was not supplied through body fluids from different isolated organs, indicating that the intercellular distribution of GDP-L-fucose is restricted within a given organ. Moreover, the gap junction-mediated supply of GDP-L-fucose was sufficient to support the fucosylation of N-glycans and the O-fucosylation of the N EGF-like repeats. Our results indicate that intercellular delivery is a metabolic pathway for nucleotide sugars in live animals under certain circumstances.

  6. Extremely Low-Frequency Electromagnetic Fields Affect Myogenic Processes in C2C12 Myoblasts: Role of Gap-Junction-Mediated Intercellular Communication

    Directory of Open Access Journals (Sweden)

    Caterina Morabito


    Full Text Available Extremely low-frequency electromagnetic fields (ELF-EMFs can interact with biological systems. Although they are successfully used as therapeutic agents in physiatrics and rehabilitative practice, they might represent environmental pollutants and pose a risk to human health. Due to the lack of evidence of their mechanism of action, the effects of ELF-EMFs on differentiation processes in skeletal muscle were investigated. C2C12 myoblasts were exposed to ELF-EMFs generated by a solenoid. The effects of ELF-EMFs on cell viability and on growth and differentiation rates were studied using colorimetric and vital dye assays, cytomorphology, and molecular analysis of MyoD and myogenin expression, respectively. The establishment of functional gap junctions was investigated analyzing connexin 43 expression levels and measuring cell permeability, using microinjection/dye-transfer assays. The ELF-EMFs did not affect C2C12 myoblast viability or proliferation rate. Conversely, at ELF-EMF intensity in the mT range, the myogenic process was accelerated, through increased expression of MyoD, myogenin, and connexin 43. The increase in gap-junction function suggests promoting cell fusion and myotube differentiation. These data provide the first evidence of the mechanism through which ELF-EMFs may provide therapeutic benefits and can resolve, at least in part, some conditions of muscle dysfunction.

  7. Evolution of Microbial Quorum Sensing to Human Global Quorum Sensing: An Insight into How Gap Junctional Intercellular Communication Might Be Linked to the Global Metabolic Disease Crisis. (United States)

    Trosko, James E


    The first anaerobic organism extracted energy for survival and reproduction from its source of nutrients, with the genetic means to ensure protection of its individual genome but also its species survival. While it had a means to communicate with its community via simple secreted molecules ("quorum sensing"), the eventual shift to an aerobic environment led to multi-cellular metazoan organisms, with evolutionary-selected genes to form extracellular matrices, stem cells, stem cell niches, and a family of gap junction or "connexin" genes. These germinal and somatic stem cells responded to extracellular signals that triggered intra-cellular signaling to regulate specific genes out of the total genome. These extra-cellular induced intra-cellular signals also modulated gap junctional intercellular communication (GJIC) in order to regulate the new cellular functions of symmetrical and asymmetrical cell division, cell differentiation, modes of cell death, and senescence. Within the hierarchical and cybernetic concepts, differentiated by neurons organized in the brain of the Homo sapiens, the conscious mind led to language, abstract ideas, technology, myth-making, scientific reasoning, and moral decision-making, i.e., the creation of culture. Over thousands of years, this has created the current collision between biological and cultural evolution, leading to the global "metabolic disease" crisis.

  8. Extremely Low-Frequency Electromagnetic Fields Affect Myogenic Processes in C2C12 Myoblasts: Role of Gap-Junction-Mediated Intercellular Communication. (United States)

    Morabito, Caterina; Steimberg, Nathalie; Rovetta, Francesca; Boniotti, Jennifer; Guarnieri, Simone; Mazzoleni, Giovanna; Mariggiò, Maria A


    Extremely low-frequency electromagnetic fields (ELF-EMFs) can interact with biological systems. Although they are successfully used as therapeutic agents in physiatrics and rehabilitative practice, they might represent environmental pollutants and pose a risk to human health. Due to the lack of evidence of their mechanism of action, the effects of ELF-EMFs on differentiation processes in skeletal muscle were investigated. C2C12 myoblasts were exposed to ELF-EMFs generated by a solenoid. The effects of ELF-EMFs on cell viability and on growth and differentiation rates were studied using colorimetric and vital dye assays, cytomorphology, and molecular analysis of MyoD and myogenin expression, respectively. The establishment of functional gap junctions was investigated analyzing connexin 43 expression levels and measuring cell permeability, using microinjection/dye-transfer assays. The ELF-EMFs did not affect C2C12 myoblast viability or proliferation rate. Conversely, at ELF-EMF intensity in the mT range, the myogenic process was accelerated, through increased expression of MyoD, myogenin, and connexin 43. The increase in gap-junction function suggests promoting cell fusion and myotube differentiation. These data provide the first evidence of the mechanism through which ELF-EMFs may provide therapeutic benefits and can resolve, at least in part, some conditions of muscle dysfunction.

  9. What roles do colon stem cells and gap junctions play in the left and right location of origin of colorectal cancers? (United States)

    Trosko, James E; Lenz, Heinz-Josef


    This "Commentary" examines an important clinical observation that right-sided colorectal cancers appear less treatable than the left-sided cancers. The concepts of (a) the "initiation/promotion/progression" process, (b) the stem cell hypothesis, (c) the role gap junctional intercellular communication, (d) cancer cells lacking GJIC either because of the non-expression of connexin genes or of non-functional gap junction proteins, and (e) the role of the microbiome in promoting initiated colon stem cells to divide symmetrically or asymmetrically are examined to find an explanation. It has been speculated that "embryonic-like" lesions in the ascending colon are initiated stem cells, promoted via symmetrical cell division, while the polyp-type lesions in the descending colon are initiated stem cells stimulated to divide asymmetrically. To test this hypothesis, experiments could be designed to examine if right-sided lesions might express Oct4A and ABCG2 genes but not any connexin genes, whereas the left-sided lesions might express a connexin gene, but not Oct4A or the ABCG2 genes. Treatment of the right sided lesions might include transcriptional regulators, whereas the left-sided lesions would need to restore the posttranslational status of the connexin proteins.

  10. Mono-Heteromeric Configurations of Gap Junction Channels Formed by Connexin43 and Connexin45 Reduce Unitary Conductance and Determine both Voltage Gating and Metabolic Flux Asymmetry

    Directory of Open Access Journals (Sweden)

    Guoqiang Zhong


    Full Text Available In cardiac tissues, the expression of multiple connexins (Cx40, Cx43, Cx45, and Cx30.2 is a requirement for proper development and function. Gap junctions formed by these connexins have distinct permeability and gating mechanisms. Since a single cell can express more than one connexin isoform, the formation of hetero-multimeric gap junction channels provides a tissue with an enormous repertoire of combinations to modulate intercellular communication. To study further the perm-selectivity and gating properties of channels containing Cx43 and Cx45, we studied two monoheteromeric combinations in which a HeLa cell co-transfected with Cx43 and Cx45 was paired with a cell expressing only one of these connexins. Macroscopic measurements of total conductance between cell pairs indicated a drastic reduction in total conductance for mono-heteromeric channels. In terms of Vj dependent gating, Cx43 homomeric connexons facing heteromeric connexons only responded weakly to voltage negativity. Cx45 homomeric connexons exhibited no change in Vj gating when facing heteromeric connexons. The distributions of unitary conductances (γj for both mono-heteromeric channels were smaller than predicted, and both showed low permeability to the fluorescent dyes Lucifer yellow and Rhodamine123. For both mono-heteromeric channels, we observed flux asymmetry regardless of dye charge: flux was higher in the direction of the heteromeric connexon for MhetCx45 and in the direction of the homomeric Cx43 connexon for MhetCx43. Thus, our data suggest that co-expression of Cx45 and Cx43 induces the formation of heteromeric connexons with greatly reduced permeability and unitary conductance. Furthermore, it increases the asymmetry for voltage gating for opposing connexons, and it favors asymmetric flux of molecules across the junction that depends primarily on the size (not the charge of the crossing molecules.

  11. Solution to the inverse problem of estimating gap-junctional and inhibitory conductance in inferior olive neurons from spike trains by network model simulation. (United States)

    Onizuka, Miho; Hoang, Huu; Kawato, Mitsuo; Tokuda, Isao T; Schweighofer, Nicolas; Katori, Yuichi; Aihara, Kazuyuki; Lang, Eric J; Toyama, Keisuke


    The inferior olive (IO) possesses synaptic glomeruli, which contain dendritic spines from neighboring neurons and presynaptic terminals, many of which are inhibitory and GABAergic. Gap junctions between the spines electrically couple neighboring neurons whereas the GABAergic synaptic terminals are thought to act to decrease the effectiveness of this coupling. Thus, the glomeruli are thought to be important for determining the oscillatory and synchronized activity displayed by IO neurons. Indeed, the tendency to display such activity patterns is enhanced or reduced by the local administration of the GABA-A receptor blocker picrotoxin (PIX) or the gap junction blocker carbenoxolone (CBX), respectively. We studied the functional roles of the glomeruli by solving the inverse problem of estimating the inhibitory (gi) and gap-junctional conductance (gc) using an IO network model. This model was built upon a prior IO network model, in which the individual neurons consisted of soma and dendritic compartments, by adding a glomerular compartment comprising electrically coupled spines that received inhibitory synapses. The model was used in the forward mode to simulate spike data under PIX and CBX conditions for comparison with experimental data consisting of multi-electrode recordings of complex spikes from arrays of Purkinje cells (complex spikes are generated in a one-to-one manner by IO spikes and thus can substitute for directly measuring IO spike activity). The spatiotemporal firing dynamics of the experimental and simulation spike data were evaluated as feature vectors, including firing rates, local variation, auto-correlogram, cross-correlogram, and minimal distance, and were contracted onto two-dimensional principal component analysis (PCA) space. gc and gi were determined as the solution to the inverse problem such that the simulation and experimental spike data were closely matched in the PCA space. The goodness of the match was confirmed by an analysis of variance

  12. Tuning of optical and electrical properties of wide band gap Fe:SnO2/Li:NiO p- n junctions using 80 MeV oxygen ion beam (United States)

    Mistry, Bhaumik V.; Avasthi, D. K.; Joshi, U. S.


    Electrical and optical properties of pristine and swift heavy ion (SHI) irradiated p- n junction diode have been investigated for advanced electronics application. Fe:SnO2/Li:NiO p- n junction was fabricated by using pulsed laser deposition on c-sapphire substrate. The optical band gaps of Fe:SnO2 and Li:NiO films were obtained to be 3.88 and 3.37 eV, respectively. The current-voltage characteristics of the oxide-based p- n junction showed a rectifying behaviour with turn-on voltage of 0.95 V. The oxide-based p- n junction diode was irradiated to 80 MeV O+6 ions with 1 × 1012 ions/cm2 fluence. Decrease in grain size due to SHI irradiation is confirmed by the grazing angle X-ray diffraction and atomic force microscopy. In comparison with the pristine p- n junction diode, O+6 ion irradiated p-n junction diode shows the increase of surface roughness and decrease of percentage transmittance in visible region. For irradiated p- n junction diode, current-voltage curve has still rectifying behaviour but exhibits lower turn-on voltage than that of virgin p- n junction diode.

  13. Tuning of optical and electrical properties of wide band gap Fe:SnO{sub 2}/Li:NiO p-n junctions using 80 MeV oxygen ion beam

    Energy Technology Data Exchange (ETDEWEB)

    Mistry, Bhaumik V.; Joshi, U.S. [Gujarat University, Department of Physics, School of Sciences, Ahmedabad (India); Avasthi, D.K. [Inter University Accelerator Centre, New Delhi (India)


    Electrical and optical properties of pristine and swift heavy ion (SHI) irradiated p-n junction diode have been investigated for advanced electronics application. Fe:SnO{sub 2}/Li:NiO p-n junction was fabricated by using pulsed laser deposition on c-sapphire substrate. The optical band gaps of Fe:SnO{sub 2} and Li:NiO films were obtained to be 3.88 and 3.37 eV, respectively. The current-voltage characteristics of the oxide-based p-n junction showed a rectifying behaviour with turn-on voltage of 0.95 V. The oxide-based p-n junction diode was irradiated to 80 MeV O{sup +6} ions with 1 x 10{sup 12} ions/cm{sup 2} fluence. Decrease in grain size due to SHI irradiation is confirmed by the grazing angle X-ray diffraction and atomic force microscopy. In comparison with the pristine p-n junction diode, O{sup +6} ion irradiated p-n junction diode shows the increase of surface roughness and decrease of percentage transmittance in visible region. For irradiated p-n junction diode, current-voltage curve has still rectifying behaviour but exhibits lower turn-on voltage than that of virgin p-n junction diode. (orig.)

  14. Recovery effect of onion peel extract against H2 O2 -induced inhibition of gap-junctional intercellular communication is mediated through quercetin. (United States)

    Kim, Young-Jun; Seo, Sang Gwon; Choi, Keunhwa; Kim, Jong Eun; Kang, Heerim; Chung, Min-Yu; Lee, Ki Won; Lee, Hyong Joo


    Cellular oxidative damage mediated by reactive oxygen species has been reported to inhibit gap-junctional intercellular communication (GJIC). In turn, the inhibition of GJIC can be attenuated by functional food compounds with antioxidant properties. In this study, we compared the protective effects of onion peel extract (OPE) and onion flesh extract (OFE) on oxidative stress-mediated GJIC inhibition, and investigated the mechanisms of action responsible. OPE restored H2 O2 -induced GJIC inhibition to a higher degree than OFE in WB-F344 rat liver epithelial cells. OPE was found to inhibit H2 O2 -induced phosphorylation of ERK1/2 and Cx43. A radical scavenging assay demonstrated superiority of OPE over OFE, suggesting that the observed effects might be mediated via an antioxidant mechanism. Quercetin is the major compound that is likely to be responsible for the protective effect against H2 O2 -mediated GJIC inhibition. This study suggests that OPE, a material often discarded, may be of value for the future development of functional food products. This study demonstrates that onion peel extract (OPE) exhibits a protective effect against the inhibition of gap-junctional intercellular communication (GJIC) mediated by H2 O2 , which is likely to occur via its antioxidant activity. OPE contains significant concentrations of bioactive phenolic compounds. Reductions in oxidative stress can lead to recovery of GJIC, which has been reported to be implicated in the prevention and treatment of cancers. These findings suggest that onion peel, a common waste product, could be used as potential resources for functional food development. Onion peel could be processed into a quercetin-rich powder or a pill for the prevention of cancer and other oxidative stress-related diseases. © 2014 Institute of Food Technologists®

  15. Gap junctional connexin messenger RNA expression in the ovine uterus and placenta: effects of estradiol-17β-treatment, early pregnancy stages, and embryo origin. (United States)

    Johnson, M L; Redmer, D A; Reynolds, L P; Grazul-Bilska, A T


    Gap junctions play a major role in direct, contact-dependent cell-cell communication, and they have been implicated in the regulation of cellular metabolism and the coordination of cellular functions during growth and differentiation of organs and tissues. Gap junctional channels, composed of connexin (Cx) proteins, have been detected and shown to be influenced by hormones (eg, estrogen and progesterone) in uterine and placental tissues in several species. We hypothesized that (1) the messenger RNA (mRNA) for Cx26, Cx32, Cx37, and Cx43 is expressed in the uterus of ovariectomized sheep treated with estradiol-17β (E2) and in ovine placenta during early pregnancy, (2) E2-treatment of ovariectomized ewes would cause time-specific changes in Cx26, Cx32, Cx37, and Cx43 mRNA expression (experiment 1), and (3) expression of these 4 Cx would vary across the days of early pregnancy (experiment 2) and will be affected by embryo origin (ie, after application of assisted reproductive technologies [ARTs]; experiment 3). Thus, we collected uterine tissues at 0 to 24 h after E2 treatments (experiment 1), and placental tissues during days 14 to 30 of early pregnancy after natural (NAT) breeding (experiment 2) and on day 22 of early pregnancy established after transfer of embryos generated through natural breeding (NAT-ET), in vitro fertilization (IVF), or in vitro activation (IVA, parthenotes; experiment 3). In experiment 1, the expression of Cx26, Cx37, and Cx43 mRNA increased (P early pregnancy, there were significant changes (P early gestation both after natural mating and with application of ART. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Beyond Gap Junction Channel Function: the Expression of Cx43 Contributes to Aldosterone-Induced Mesangial Cell Proliferation via the ERK1/2 and PKC Pathways

    Directory of Open Access Journals (Sweden)

    Aiqing Zhang


    Full Text Available Aims: This study aimed to explore the precise mechanism and signaling pathways of mesangial cell (MC proliferation from a new point of view considering Connexin 43 (Cx43. Methods: MC proliferation was measured by the incorporation of 3H-thymidine (3H-TdR. Cx43 was over-expressed in MC cells using lipofectamine 2000, and the expression level was tested with reverse transcription-polymerase chain reaction (RT-PCR and Western blot analyses. The gap junction channel function was explored by Lucifer Yellow scrape loading and dye transfer (SLDT, and the intracellular calcium concentrations ([Ca2+]i were characterized by confocal microscopy on cells loaded with Fura-3/AM. Results: There was an inverse correlation between Cx43 expression and MC proliferation (P0.05. Our data also showed that the mineralcorticoid receptor (MR antagonist spironolactone, ERK1/2 inhibitor PD98059 and PKC inhibitor GF109203X could attenuate the down-regulation of Cx43 expression in Aldo-induced MC proliferation; however, the PI3K inhibitor LY294002 could block MC proliferation without affecting Cx43 expression at either the mRNA or protein level. In addition, Aldo promoted MC proliferation in parallel with increasing [Ca2+]i (PConclusions: Our study provides preliminary evidence that Cx43 is an important regulator of Aldo-promoted MC proliferation. Furthermore, reduced Cx43 expression promoted MC proliferation independent of the gap junction channel function, and this process might be mediated through the ERK1/2- and PKC-dependent pathways.

  17. [Influence of acupuncture of "Changqiang" (GV 1) on learning-memory ability and gap junction-related protein expression in the prefrontal cortex in autism rats]. (United States)

    Hong, Yu-Zhu; Zhang, Xue-Jun; Hong, Lin; Huang, Qian-Ru; Wu, Qiang


    To observe the effect of acupuncture stimulation of "Changqiang" (GV 1) on learning-memory ability and gap junction-related protein expression in the prefrontal cortex in autism rats. Forty Wistar rats were equally randomized into control, model, GV 1 and non-acupoint groups. For establishing autism model, Valproate acid (VPA) sodium (600 mg/kg) was given (i. p.) to pregnancy rats whose intimate filial generation was confirmed to be successful autism by eye-open tests, swimming test and Morris water maze swimming tasks. GV 1 or non-acupoint (the spot below the costal region, i.e., 2 cm superior to the posterior superior iliac spine and about 3 cm lateral to the spine) was punctured and stimulated for about 1 min by using a filiform needle, once daily for 30 days except the weekends. The rats' learning-memory ability was detected by Morris water maze tasks. The expression of gap junction-related proteins connexin 43 (CX 43), CX 32 and CX 36 in the frontal cortex tissue was detected by immunohistochemistry. After modeling, the postnatal rats' eye-open time on day 14, 15 and 16 was significantly later (P swimming ability on postnatal day 13 and 15 was obviously lower in comparison with that of the control group (P swimming velocity of the autism rats were obviously suppressed in the GV 1 group, rather than in the non-acupoint group (P autism rats, which may be closely related to its effects in up-regulating expression levels of CX 43, CX 32 and CX 36 in the frontal cortex.

  18. Abnormal Conduction in the Diseased Heart - Enhanced fibrosis due to reduced gap junction and sodium channel expression

    NARCIS (Netherlands)

    Jansen, J.A.


    The velocity with which the impulse is conducted is dependent on three different factors: excitability, cell-to-cell coupling and tissue characteristics. Excitability is mainly determined by Nav1.5 channels, determining the upstroke-velocity of the action potential, but also by Kir2.1 channels. Gap

  19. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model.

    Directory of Open Access Journals (Sweden)

    Iva Sovadinova

    Full Text Available Dysregulation of gap junctional intercellular communication (GJIC has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Dysregulation of GJIC by perfluorooctanoic acid and R59022 required both MEK1/2 and PC-PLC; while benzoylperoxide, arachidonic acid, 18β-glycyrrhetinic acid, perfluorooctane sulfonic acid, 1-monolaurin, pentachlorophenol and alachlor required neither MEK1/2 nor PC-PLC. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways, which indicated at least two other, yet unidentified, pathways that are involved in the regulation of GJIC.the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap

  20. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model (United States)

    Sovadinova, Iva; Babica, Pavel; Böke, Hatice; Kumar, Esha; Wilke, Andrew; Park, Joon-Suk; Trosko, James E.; Upham, Brad L.


    Dysregulation of gap junctional intercellular communication (GJIC) has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK)-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Dysregulation of GJIC by perfluorooctanoic acid and R59022 required both MEK1/2 and PC-PLC; while benzoylperoxide, arachidonic acid, 18β-glycyrrhetinic acid, perfluorooctane sulfonic acid, 1-monolaurin, pentachlorophenol and alachlor required neither MEK1/2 nor PC-PLC. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways, which indicated at least two other, yet unidentified, pathways that are involved in the regulation of GJIC. In conclusion: the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap

  1. Non-dioxin-like organic toxicant PCB153 modulates sphingolipid metabolism in liver progenitor cells: its role in Cx43-formed gap junction impairment. (United States)

    Pierucci, F; Frati, A; Squecco, R; Lenci, E; Vicenti, C; Slavik, J; Francini, F; Machala, M; Meacci, E


    The non-dioxin-like environmental toxicant 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153), member of a group of persistent organic pollutants wide-spread throughout the environment, reduces gap junction intercellular communication (GJIC), an event possibly associated with tumor promotion. Since very few studies have investigated the signaling effectors and mode(s) of action of PCB153, and it is known that the gap junction (GJ) protein Cx43 can be regulated by the bioactive sphingolipid (SL) sphingosine 1-phosphate (S1P), this in vitro study mainly addresses whether SL metabolism is affected by PCB153 in rat liver epithelial WB-F344 cells. PCB153 treatment obtained significant changes in the S1P/ceramide (Cer) ratio, known to be crucial in determining cell fate. In particular, an increase in S1P at 30 min and a decrease of the bioactive lipid at 3 h were observed, whereas Cer level increased at 1 h and 24 h. Notably, a time-dependent modulation of sphingosine kinase (SphK), the enzyme responsible for S1P synthesis, and of its regulators, ERK1/2 and protein phosphatase PP2A, supports the involvement of these signaling effectors in PCB153 toxicity. Electrophysiological analyses, furthermore, indicated that the lipophilic environmental toxicant significantly reduced GJ biophysical properties, affecting both voltage-dependent (such as those formed by Cx43 and/or Cx32) and voltage-independent channels, thereby demonstrating that PCB153 may act differently on GJs formed by distinct Cx isoforms. SphK down-regulation alone induced GJIC impairment, and, when combined with PCB153, the acute effect on GJ suppression was additive. Moreover, after enzyme-specific gene silencing, the SphK1 isoform appears to be responsible for down-regulating Cx43 expression, while being the target of PCB153 at short-term exposure. In conclusion, we provide the first evidence of novel effectors in PCB153 toxic action in rat liver stem-like cells, leading us to consider SLs as potential markers

  2. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model. (United States)

    Sovadinova, Iva; Babica, Pavel; Böke, Hatice; Kumar, Esha; Wilke, Andrew; Park, Joon-Suk; Trosko, James E; Upham, Brad L


    Dysregulation of gap junctional intercellular communication (GJIC) has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK)-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Dysregulation of GJIC by perfluorooctanoic acid and R59022 required both MEK1/2 and PC-PLC; while benzoylperoxide, arachidonic acid, 18β-glycyrrhetinic acid, perfluorooctane sulfonic acid, 1-monolaurin, pentachlorophenol and alachlor required neither MEK1/2 nor PC-PLC. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways, which indicated at least two other, yet unidentified, pathways that are involved in the regulation of GJIC. the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap junction channels

  3. Relating proton pumps with gap junctions: colocalization of ductin, the channel-forming subunit c of V-ATPase, with subunit a and with innexins 2 and 3 during Drosophila oogenesis. (United States)

    Lautemann, Julia; Bohrmann, Johannes


    Ion-transport mechanisms and gap junctions are known to cooperate in creating bioelectric phenomena, like pH gradients, voltage gradients and ion fluxes within single cells, tissues, organs, and whole organisms. Such phenomena have been shown to play regulatory roles in a variety of developmental and regenerative processes. Using Drosophila oogenesis as a model system, we aim at characterizing in detail the mechanisms underlying bioelectric phenomena in order to reveal their regulatory functions. We, therefore, investigated the stage-specific distribution patterns of V-ATPase components in relation to gap-junction proteins. We analysed the localization of the V-ATPase components ductin (subunit c) and subunit a, and the gap-junction components innexins 2 and 3, especially in polar cells, border cells, stalk cells and centripetally migrating cells. These types of follicle cells had previously been shown to exhibit characteristic patterns of membrane channels as well as membrane potential and intracellular pH. Stage-specifically, ductin and subunit a were found either colocalized or separately enriched in different regions of soma and germ-line cells. While ductin was often more prominent in plasma membranes, subunit a was more prominent in cytoplasmic and nuclear vesicles. Particularly, ductin was enriched in polar cells, stalk cells, and nurse-cell membranes, whereas subunit a was enriched in the cytoplasm of border cells, columnar follicle cells and germ-line cells. Comparably, ductin and both innexins 2 and 3 were either colocalized or separately enriched in different cellular regions. While ductin often showed a continuous membrane distribution, the distribution of both innexins was mostly punctate. Particularly, ductin was enriched in polar cells and stalk cells, whereas innexin 2 was enriched in the oolemma, and innexin 3 in centripetally migrating follicle cells. In lateral follicle-cell membranes, the three proteins were found colocalized as well as

  4. The ouabain-sensitive isoform of Na+-pump regulates vascular gap junctions via interaction with the Na+/Ca2+-exchanger in membrane microdomain

    DEFF Research Database (Denmark)

    Matchkov, Vladimir; Nilsson, Holger; Aalkjær, Christian

    Ouabain, an inhibitor of the Na+-pump, has been shown to inhibit intercellular communication. We have recently shown that gap junctions between vascular smooth muscle cells (SMCs) are regulated through an interaction between a ouabain-sensitive isoform of the Na+-pump and the Na+/Ca2+-exchanger...... leading to increases in [Ca2+]i in discrete areas near the plasma membrane. This suggests close association of these transport proteins in microdomains. Using PCR and co-immunoprecipitation we aimed to test this hypothesis in SMCs from mesenteric small arteries and in A7r5 cell line. Intercellular...... the uncoupling. Ten mM ouabain evoked spatially restricted [Ca2+]i transients along the cell periphery but not in the center of the cell. mRNA for all three isoforms of the Na+-pump α subunit were found in SMCs but only ouabain-sensitive α2 subunit was specifically co-immunoprecipitated with the Na+/Ca2...

  5. 17β estradiol regulation of connexin 43-based gap junction and mechanosensitivity through classical estrogen receptor pathway in osteocyte-like MLO-Y4 cells.

    KAUST Repository

    Ren, Jian


    Connexin 43 (Cx43) plays an essential role in osteocyte mechanotransduction. Although estrogen involves in the adaptive responses of bone cells to mechanical loadings, its effects on osteocytic Cx43-based gap junction intercellular communication (GJIC) remain obscure. We found that 17β estradiol (E2) up-regulated Cx43, and enhanced GJIC in osteocyte-like MLO-Y4 cells in fluorescence recovery after photobleaching (FRAP) assay. Combination of E2 pre-treatment and oscillating fluid flow (OFF) further enhanced Cx43 expression and mitogen-activated protein kinase (MAPK) phosphorylation, comparing to E2 or OFF treatment alone. Both blocking of classical estrogen receptors (ERα/β) by fulvestrant and ERα knockdown by small interfering RNA inhibited E2-mediated Cx43 increase, while a GPR30-specific agonist G-1 failed to promote Cx43 expression. Our results suggest that the presence of E2 enhanced Cx43-based GJIC mainly via ERα/β pathway, and sensitized osteocytes to mechanical loading. © 2012 Elsevier Inc. All rights reserved.

  6. 17β estradiol regulation of connexin 43-based gap junction and mechanosensitivity through classical estrogen receptor pathway in osteocyte-like MLO-Y4 cells. (United States)

    Ren, Jian; Wang, Xu-Hui; Wang, Guang-Chao; Wu, Jun-Hua


    Connexin 43 (Cx43) plays an essential role in osteocyte mechanotransduction. Although estrogen involves in the adaptive responses of bone cells to mechanical loadings, its effects on osteocytic Cx43-based gap junction intercellular communication (GJIC) remain obscure. We found that 17β estradiol (E2) up-regulated Cx43, and enhanced GJIC in osteocyte-like MLO-Y4 cells in fluorescence recovery after photobleaching (FRAP) assay. Combination of E2 pre-treatment and oscillating fluid flow (OFF) further enhanced Cx43 expression and mitogen-activated protein kinase (MAPK) phosphorylation, comparing to E2 or OFF treatment alone. Both blocking of classical estrogen receptors (ERα/β) by fulvestrant and ERα knockdown by small interfering RNA inhibited E2-mediated Cx43 increase, while a GPR30-specific agonist G-1 failed to promote Cx43 expression. Our results suggest that the presence of E2 enhanced Cx43-based GJIC mainly via ERα/β pathway, and sensitized osteocytes to mechanical loading. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Point correlation dimension can reveal functional changes caused by gap junction blockers in the 4-aminopyridine in vivo rat epilepsy model

    Energy Technology Data Exchange (ETDEWEB)

    Jardanhazy, Anett [Department of Neurology, University of Szeged, Semmelweis u. 6, Szeged H-6725 (Hungary); Molnar, Mark [Department of Psychophysiology, Institute for Psychology of the Hungarian Academy of Sciences, P.O. Box 398, Budapest H-1394 (Hungary)], E-mail:; Jardanhazy, Tamas [Department of Neurology, University of Szeged, Semmelweis u. 6, Szeged H-6725 (Hungary)], E-mail:


    The contribution of gap junction (GJ) blockers to seizure initiation was reexamined by means of an analysis on nonlinear dynamics with point correlation dimension (PD2i) at as well as around the primary focus, and mirror focus in an already active 4-aminopyridine-induced in vivo epilepsy model. From the data base of the ECoGs of anesthetized adult rats treated with quinine, a selective blocker of Cx36, and in combination with an additional broad-spectrum GJ blocker, carbenoxolone, 14 cases of each condition were reexamined with a stationarity insensitive nonlinear PD2i method. The blockade of the Cx36 channels decreased the usual drop of the point correlation dimension at the beginning of the seizures, and this was enhanced by the additional use of the global blocker carbenoxolone. The so-called characteristic DC shift just prior to seizure onset denotes a low dimensional seizure event and the recognizable seizures display very variable, rapidly changing dynamics, as revealed by the PD2i analysis. This nonlinear PD2i analysis demonstrated that the different GJ blockers in the already active epileptic model helped seizure initiation, but exerted inhibitory effects on the seizure onset itself, acting differently on the local components of the network organization generating seizure discharges, possibly changing the coupling strengths and time delays in the GJ-s.

  8. Inhibition of gap junctional Intercellular communication in WB-F344 rat liver epithelial cells by triphenyltin chloride through MAPK and PI3-kinase pathways

    Directory of Open Access Journals (Sweden)

    Tsai Ming-Che


    Full Text Available Abstract Background Organotin compounds (OTCs have been widely used as stabilizers in the production of plastic, agricultural pesticides, antifoulant plaints and wood preservation. The toxicity of triphenyltin (TPT compounds was known for their embryotoxic, neurotoxic, genotoxic and immunotoxic effects in mammals. The carcinogenicity of TPT was not well understood and few studies had discussed the effects of OTCs on gap junctional intercellular communication (GJIC of cells. Method In the present study, the effects of triphenyltin chloride (TPTC on GJIC in WB-F344 rat liver epithelial cells were evaluated, using the scrape-loading dye transfer technique. Results TPTC inhibited GJIC after a 30-min exposure in a concentration- and time-dependent manner. Pre-incubation of cells with the protein kinase C (PKC inhibitor did not modify the response, but the specific MEK 1 inhibitor PD98059 and PI3K inhibitor LY294002 decreased substantially the inhibition of GJIC by TPTC. After WB-F344 cells were exposed to TPTC, phosphorylation of Cx43 increased as seen in Western blot analysis. Conclusions These results show that TPTC inhibits GJIC in WB-F344 rat liver epithelial cells by altering the Cx43 protein expression through both MAPK and PI3-kinase pathways.

  9. Identification of marker genes for pars tuberalis morphogenesis in chick embryo: expression of Cytokine-like 1 and Gap junction protein alpha 5 in pars tuberalis. (United States)

    Aizawa, Sayaka; Higaki, Yuriko; Dudaui, Amrita; Nagasaka, Mai; Takahashi, Sumio; Sakata, Ichiro; Sakai, Takafumi


    The adenohypophysis is formed from the oral ectoderm and consists of the pars distalis (PD), pars intermedia, and pars tuberalis (PT). The mechanisms of PD development have been extensively studied, and the cellular differentiation of the PD is well understood. However, the morphogenesis and differentiation of the PT are still unclear, and the genes expressed during PT development remain largely unknown. We have explored genes specifically expressed in the PT during embryonic development and analyzed their spatiotemporal expression patterns. Microarray analysis of laser-captured PT and PD tissues obtained from chick embryos on embryonic day 10 (E10.0) has shown high expression of Cytokine-like 1 (CYTL1) and Gap junction protein alpha 5 (GJA5) genes in the PT. Detailed analysis of these spatiotemporal expression patterns during chick embryo development by in situ hybridization has revealed that CYTL1 mRNA first appears in the lateral head ectoderm and ventral head ectoderm at E1.5. The expression of CYTL1 moves into Rathke's pouch at E2.5 and is then localized in the PT primordium where it is continuously expressed until E12.0. GJA5 mRNA is transiently detected in the PT primordium from E6.0 to E12.0, whereas its expression is not detected in the PD during development. Thus, these genes might be involved in the regulation mechanisms of PT development and could be useful markers for PT development.

  10. Inhibition of gap-junctional intercellular communication and activation of mitogen-activated protein kinases by cyanobacterial extracts - indications of novel tumor promoting cyanotoxins? (United States)

    Bláha, Luděk; Babica, Pavel; Hilscherová, Klára; Upham, Brad L.


    Toxicity and liver tumor promotion of cyanotoxins microcystins have been extensively studied. However, recent studies document that other metabolites present in the complex cyanobacterial water blooms may also have adverse health effects. In this study we used rat liver epithelial stem-like cells (WB-F344) to examine the effects of cyanobacterial extracts on two established markers of tumor promotion, inhibition of gap-junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) – ERK1/2. Extracts of cyanobacteria (laboratory cultures of Microcystis aeruginosa and Aphanizomenon flos-aquae and water blooms dominated by these species) inhibited GJIC and activated MAPKs in a dose-dependent manner (effective concentrations ranging 0.5 - 5 mg d.w./mL). Effects were independent of the microcystin content and the strongest responses were elicited by the extracts of Aphanizomenon sp. Neither pure microcystin-LR nor cylindrospermopsin inhibited GJIC or activated MAPKs. Modulations of GJIC and MAPKs appeared to be specific to cyanobacterial extracts since extracts from green alga Chlamydomonas reinhardtii, heterotrophic bacterium Klebsiella terrigena, and isolated bacterial lipopolysaccharides had no comparable effects. Our study provides the first evidence on the existence of unknown cyanobacterial toxic metabolites that affect in vitro biomarkers of tumor promotion, i.e. inhibition of GJIC and activation of MAPKs. PMID:19619572

  11. Antiproliferative Action of Conjugated Linoleic Acid on Human MCF-7 Breast Cancer Cells Mediated by Enhancement of Gap Junctional Intercellular Communication through Inactivation of NF-κB

    Directory of Open Access Journals (Sweden)

    Md. Abdur Rakib


    Full Text Available The major conjugated linoleic acid (CLA isomers, c9,t11-CLA and t10,c12-CLA, have anticancer effects; however, the exact mechanisms underlying these effects are unknown. Evidence suggests that reversal of reduced gap junctional intercellular communication (GJIC in cancer cells inhibits cell growth and induces cell death. Hence, we determined that CLA isomers enhance GJIC in human MCF-7 breast cancer cells and investigated the underlying molecular mechanisms. The CLA isomers significantly enhanced GJIC of MCF-7 cells at 40 μM concentration, whereas CLA inhibited cell growth and induced caspase-dependent apoptosis. CLA increased connexin43 (Cx43 expression both at the transcriptional and translational levels. CLA inhibited nuclear factor-κB (NF-κB activity and enhanced reactive oxygen species (ROS generation. No significant difference was observed in the efficacy of c9,t11-CLA and t10,c12-CLA. These results suggest that the anticancer effect of CLA is associated with upregulation of GJIC mediated by enhanced Cx43 expression through inactivation of NF-κB and generation of ROS in MCF-7 cells.

  12. All-trans retinoic acid restores gap junctional intercellular communication between oral cancer cells with upregulation of Cx32 and Cx43 expressions in vitro. (United States)

    Wang, Juan; Dai, Yaohui; Huang, Yulei; Chen, Xiaohua; Wang, Hong; Hong, Yun; Xia, Juan; Cheng, Bin


    All-trans retinoic acid (ATRA) has been demonstrated to inhibit tumor growth by restoration of gap junctional intercellular communication (GJIC) via upregulation of connexin (Cx) expression in some solid tumors. However, the relationship between ATRA and GJIC remains unclear in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the effect of ATRA on the GJIC function of OSCC. We measured the effects of ATRA on the viability and cell cycle distribution of SCC9 and Tca8113 OSCC cells. The GJIC function was observed using the scrape-loading dye transfer technique, and the mRNA and protein levels of Cx32 and Cx43 were detected by qRT-PCR, Western blot, and immunofluorescence assays. ATRA inhibited the growth of OSCC cells in a dose- and time-dependent manner (P <0.05) and caused cell cycle arrest. ATRA-treated cells showed a 2.69-fold and 2.06-fold enhancement of GJIC in SCC9 and Tca8113 cells, respectively (P <0.05). Moreover, ATRA induced upregulation of Cx32 and Cx43 at both the mRNA and protein levels in OSCC cells. Our results indicated that restoration of GJIC via enhanced Cx32 and Cx43 expression might serve as a novel mechanism for the anti-tumor effect of ATRA in OSCC.

  13. Neuropeptide Y, substance P, and human bone morphogenetic protein 2 stimulate human osteoblast osteogenic activity by enhancing gap junction intercellular communication

    Energy Technology Data Exchange (ETDEWEB)

    Ma, W.H.; Liu, Y.J.; Wang, W.; Zhang, Y.Z. [The Third Hospital of Hebei Medical University, The Provincial Key Laboratory for Orthopedic Biomechanics of Hebei, Shijiazhuang, Hebei Province (China)


    Bone homeostasis seems to be controlled by delicate and subtle “cross talk” between the nervous system and “osteo-neuromediators” that control bone remodeling. The purpose of this study was to evaluate the effect of interactions between neuropeptides and human bone morphogenetic protein 2 (hBMP2) on human osteoblasts. We also investigated the effects of neuropeptides and hBMP2 on gap junction intercellular communication (GJIC). Osteoblasts were treated with neuropeptide Y (NPY), substance P (SP), or hBMP2 at three concentrations. At various intervals after treatment, cell viability was measured by the MTT assay. In addition, cellular alkaline phosphatase (ALP) activity and osteocalcin were determined by colorimetric assay and radioimmunoassay, respectively. The effects of NPY, SP and hBMP on GJIC were determined by laser scanning confocal microscopy. The viability of cells treated with neuropeptides and hBMP2 increased significantly in a time-dependent manner, but was inversely associated with the concentration of the treatments. ALP activity and osteocalcin were both reduced in osteoblasts exposed to the combination of neuropeptides and hBMP2. The GJIC of osteoblasts was significantly increased by the neuropeptides and hBMP2. These results suggest that osteoblast activity is increased by neuropeptides and hBMP2 through increased GJIC. Identification of the GJIC-mediated signal transduction capable of modulating the cellular activities of bone cells represents a novel approach to studying the biology of skeletal innervation.

  14. Conserved glycine at position 45 of major cochlear connexins constitutes a vital component of the Ca²⁺ sensor for gating of gap junction hemichannels. (United States)

    Zhang, Yanping; Hao, Hongxia


    Mutations in gap junction (GJ) family of proteins, especially in the connexin (Cx) 26, are responsible for causing severe congenital hearing loss in a significant portion of patients (30-50% in various ethnic groups). Substitution of glycine at the position 45 of Cx26 to glutamic acid (p.G45E mutation) causes the Keratitis-ichthyosis-deafness (KID) syndrome. Previous studies have suggested that this point mutation caused a gain-of-function defect. However, the molecular mechanism of KID syndrome remains unclear. Since glycine at this position is conserved in many Cxs expressed in the cochlea, we tested the hypothesis that glycine at position 45 is an important component of the sensor regulating the Ca(2+) gating of GJ hemichannels. Using reconstituted Cx30, 32 and 43 expressed in the HEK 293 cells, we compared the functions of wild type and p.G45E mutant Cxs. We found that G45E in Cx30 resulted in similar deleterious cellular effects as Cx26 did. Cell death occurred within 24h of transfection, which was rescued by increasing extracellular Ca(2+) concentration ([Ca(2+)]o). Dye loading assay showed that Cx30 G45E, similar to Cx26 G45E, had leaky hemichannels at physiological [Ca(2+)]o (1.2 mM). Higher [Ca(2+)]o reduced the dye loading in a dose-dependent manner. Whole cell membrane current recordings also indicated that G45E caused increased hemichannel activities. p.G45E mutations of Cx32 and 43 also resulted in leaky hemichannels compared to their respective wild types in lower [Ca(2+)]o. Our data in this study provided further support for the hypothesis that glycine at position 45 is a conserved Ca(2+) sensor for the gating of GJ hemichannels among multiple Cx subtypes expressed in the cochlea. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Lysophosphatidic acid inhibits gap-junctional communication and stimulates phosphorylation of connexin-43 in WB cells: possible involvement of the mitogen-activated protein kinase cascade. (United States)

    Hill, C S; Oh, S Y; Schmidt, S A; Clark, K J; Murray, A W


    Lysophosphatidic acid (LPA) was shown to be a powerful inhibitor of gap-junctional communication between cultured rat liver WB cells, as determined by the transfer of Lucifer Yellow, with 50% inhibition obtained at about 0.3 microM LPA. Inhibition of communication was rapid (5 min) and was maintained for at least 80 min. After incubation for 3 h with LPA, communication competence was partially restored and dye transfer was refractory to further addition of LPA. Communication in LPA-refractory cells retained sensitivity to inhibition by phorbol ester and by epidermal growth factor (EGF). LPA-induced inhibition was associated with phosphorylation of connexin-43 protein, as detected by slower migration of the protein detected on Western blots, which could be eliminated by incubation of samples with alkaline phosphatase. A close correspondence was observed between the time- and dose-dependency of LPA effects on communication and the induction of mitogen-activated protein kinase (MAP kinase). Activation of both the 42 kDa and 44 kDa subspecies were confirmed by mobility shifts on Western blots using an anti-(MAP kinase R1) (erk 1-III) antibody and by fractionation on Mono Q columns. Cells pretreated with phorbol ester for 24 h were insensitive to phorbol ester inhibition of communication or activation of MAP kinase, but retained their sensitivity to LPA. The results indicate that LPA initiates the activation of protein kinase cascades in WB cells that are probably independent of protein kinase C and identifies connexin-43 as one substrate for the activated kinases. Images Figure 1 Figure 3 Figure 6 PMID:7980407

  16. Regulation of gap junctions in melanoma and their impact on Melan-A/MART-1-specific CD8⁺ T lymphocyte emergence. (United States)

    Benlalam, Houssem; Carré, Thibault; Jalil, Abdelali; Noman, Zaeem; Caillou, Bernard; Vielh, Philippe; Tittarelli, Andrés; Robert, Caroline; Chouaib, Salem


    Gap junctions (GJs) enable intercellular communication between adjacent cells through channels of connexins. Using a three-dimensional construct, we previously showed that endothelial and tumor cells formed GJs, allowing melanoma-specific T lymphocytes to recognize and kill melanoma-derived endothelial cells. We demonstrate here on histological sections of melanoma biopsies that GJ formation occurs in vivo between tumor and endothelial cells and between T lymphocytes and target cells. We also show an in vitro increase of GJ formation in melanoma and endothelial cells following dacarbazin and interferon gamma (IFN-γ) treatment or hypoxic stress induction. Our data indicate that although connexin 43 (Cx43), the main GJ protein of the immune system, was localized at the immunological synapse between T lymphocyte and autologous melanoma cells, its over-expression or inhibition of GJs does not interfere with cytotoxic T lymphocyte (CTL) clone lytic function. In contrast, we showed that inhibition of GJs by oleamide during stimulation of resting PBMCs with Melan-A natural and analog peptides resulted in a decrease in antigen (Ag) specific CD8(+) T lymphocyte induction. These Ag-specific CD8(+) cells displayed paradoxically stronger reactivity as revealed by CD107a degranulation and IFN-γ secretion. These findings indicate that Cx43 does not affect lytic function of differentiated CTL, but reveal a major role for GJs in the regulation of antigen CD8(+)-naïve T lymphocyte activation. GJ formation occurs in vivo between T lymphocytes and tumor cells Cx43 localized at the immunological synapse between T and autologous melanoma cells Inhibition of GJs resulted in a decrease in Ag-specific CD8(+) T lymphocyte induction A role for GJs in the regulation of antigen CD8(+)-naïve T lymphocyte activation.

  17. A new singularity in the coherent coupling in Al/GaAs/Al SNS junctions at the bias voltage corresponding to the superconducting energy gap

    DEFF Research Database (Denmark)

    Taboryski, Rafael Jozef; Kutchinsky, Jonatan; Kuhn, Oliver


    Particularly high transmittivity superconductor-semiconductor barriers formed by MBE growth have been used to form short Josephson planar type Superconductor-Normal-metal-Superconductor (SNS) Josephson junctions with lengths down to 1 mu m. In these junctions the quasiparticles move diffusively a...... field was observed both at V-DC = 0 and V-DC = Delta/e = 163 mu V. At intermediate as well as higher voltages no oscillations were observed. (C) 1998 Elsevier Science B.V. All rights reserved....

  18. Hexavalent chromium at low concentration alters Sertoli cell barrier and connexin 43 gap junction but not claudin-11 and N-cadherin in the rat seminiferous tubule culture model

    Energy Technology Data Exchange (ETDEWEB)

    Carette, Diane [INSERM U 1065, Team 5 “Physiopathology of Germ Cell Control: Genomic and Non Genomic Mechanisms” C3M, University of Nice Sophia Antipolis, Nice (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Perrard, Marie-Hélène, E-mail: [Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon I, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon (France); Prisant, Nadia [University of Versailles/St Quentin-en-Yvelines (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Gilleron, Jérome; Pointis, Georges [INSERM U 1065, Team 5 “Physiopathology of Germ Cell Control: Genomic and Non Genomic Mechanisms” C3M, University of Nice Sophia Antipolis, Nice (France); Segretain, Dominique [University of Versailles/St Quentin-en-Yvelines (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Durand, Philippe [Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon I, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon (France); Kallistem SAS Ecole Normale Supérieure de Lyon, Lyon (France)


    Exposure to toxic metals, specifically those belonging to the nonessential group leads to human health defects and among them reprotoxic effects. The mechanisms by which these metals produce their negative effects on spermatogenesis have not been fully elucidated. By using the Durand's validated seminiferous tubule culture model, which mimics the in vivo situation, we recently reported that concentrations of hexavalent chromium, reported in the literature to be closed to that found in the blood circulation of men, increase the number of germ cell cytogenetic abnormalities. Since this metal is also known to affect cellular junctions, we investigated, in the present study, its potential influence on the Sertoli cell barrier and on junctional proteins present at this level such as connexin 43, claudin-11 and N-cadherin. Cultured seminiferous tubules in bicameral chambers expressed the three junctional proteins and ZO-1 for at least 12 days. Exposure to low concentrations of chromium (10 μg/l) increased the trans-epithelial resistance without major changes of claudin-11 and N-cadherin expressions but strongly delocalized the gap junction protein connexin 43 from the membrane to the cytoplasm of Sertoli cells. The possibility that the hexavalent chromium-induced alteration of connexin 43 indirectly mediates the effect of the toxic metal on the blood–testis barrier dynamic is postulated. - Highlights: ► Influence of Cr(VI) on the Sertoli cell barrier and on junctional proteins ► Use of cultured seminiferous tubules in bicameral chambers ► Low concentrations of Cr(VI) (10 μg/l) altered the trans-epithelial resistance. ► Cr(VI) did not alter claudin-11 and N-cadherin. ► Cr(VI) delocalized connexin 43 from the membrane to the cytoplasm of Sertoli cells.

  19. Mechanotransductive Regulation of Gap-Junction Activity Between MLO-Y4 Osteocyte-Like and MC3T3-E1 Osteoblast-Like Cells in Three-Dimensional Co-Culture. (United States)

    Juran, C. M.; Blaber, E. A.; Almeida, E. A. C.


    Cell and animal studies conducted onboard the International Space Station and formerly on Shuttle flights have provided groundbreaking data illuminating the deleterious biological response of bone to mechanical unloading. However the intercellular communicative mechanisms associated with the regulation of bone synthesis and bone resorption cells are still largely unknown. Connexin-43 (CX43), a gap junction protein, is hypothesized to play a significant role in osteoblast and osteocyte signaling. The purpose of this investigation was to evaluate within a novel three-dimensional microenvironment how the osteocyte-osteoblast gap-junction expression changes when cultures are exposed to exaggerated mechanical load. MLO-Y4 osteocyte-like cells were cultured on a 3D-Biotek polystyrene insert and placed in direct contact with an MC3T3-E1 pre-osteoblast co-cultured monolayer and exposed to 48 h of mechanical stimulation (pulsatile fluid flow (PFF) or monolayer cyclic stretch (MCS)) then evaluated for viability, proliferation, metabolism, and CX43 expression. Mono-cultured MLO-Y4 and MC3T3-E1 control experiments were conducted under PFF and MCS stimulation to observe how strain application stimuli (PFF cell membrane shear or MCS cell focal adhesion/attachment loading) initiates different signaling pathways or downstream regulatory controls. TotalLive cell count, viability and metabolic reduction (Trypan Blue, LIVEDead and Alamar Blue analysis respectively) indicate that mechanical activation of MC3T3-E1 cells inhibits proliferation while maintaining an average 1.04E4 reductioncell metabolic rate, *p0.05 n4. MLO-Y4s in monolayer culture increase in number when exposed to MCS loading but the percent of live cells within the population is low (46.3 total count, *p0.05 n4), these results may indicate an apoptotic signaling cascade. PFF stimulation of the three-dimensional co-cultures elicits a universal increase in CX43 in MLO-Y4 and MC3T3-E1 cells, illustrated by

  20. Nanotube junctions (United States)

    Crespi, Vincent Henry; Cohen, Marvin Lou; Louie, Steven Gwon Sheng; Zettl, Alexander Karlwalter


    The present invention comprises a new nanoscale metal-semiconductor, semiconductor-semiconductor, or metal-metal junction, designed by introducing topological or chemical defects in the atomic structure of the nanotube. Nanotubes comprising adjacent sections having differing electrical properties are described. These nanotubes can be constructed from combinations of carbon, boron, nitrogen and other elements. The nanotube can be designed having different indices on either side of a junction point in a continuous tube so that the electrical properties on either side of the junction vary in a useful fashion. For example, the inventive nanotube may be electrically conducting on one side of a junction and semiconducting on the other side. An example of a semiconductor-metal junction is a Schottky barrier. Alternatively, the nanotube may exhibit different semiconductor properties on either side of the junction. Nanotubes containing heterojunctions, Schottky barriers, and metal-metal junctions are useful for microcircuitry.

  1. Contribution of intracellular calcium and pH in ischemic uncoupling of cardiac gap junction channels formed of connexins 43, 40, and 45: a critical function of C-terminal domain.

    Directory of Open Access Journals (Sweden)

    Giriraj Sahu

    Full Text Available Ischemia is known to inhibit gap junction (GJ mediated intercellular communication. However the detail mechanisms of this inhibition are largely unknown. In the present study, we determined the vulnerability of different cardiac GJ channels formed of connexins (Cxs 43, 40, and 45 to simulated ischemia, by creating oxygen glucose deprived (OGD condition. 5 minutes of OGD decreased the junctional conductance (Gj of Cx43, Cx40 and Cx45 by 53±3%, 64±1% and 85±2% respectively. Reduction of Gj was prevented completely by restricting the change of both intracellular calcium ([Ca(2+]i and pH (pHi with potassium phosphate buffer. Clamping of either [Ca(2+]i or pHi, through BAPTA (2 mM or HEPES (80 mM respectively, offered partial resistance to ischemic uncoupling. Anti-calmodulin antibody attenuated the uncoupling of Cx43 and Cx45 significantly but not of Cx40. Furthermore, OGD could reduce only 26±2% of Gj in C-terminus (CT truncated Cx43 (Cx43-Δ257. Tethering CT of Cx43 to the CT-truncated Cx40 (Cx40-Δ249, and Cx45 (Cx45-Δ272 helped to resist OGD mediated uncoupling. Moreover, CT domain played a significant role in determining the junction current density and plaque diameter. Our results suggest; OGD mediated uncoupling of GJ channels is primarily due to elevated [Ca(2+]i and acidic pHi, though the latter contributes more. Among Cx43, Cx40 and Cx45, Cx43 is the most resistant to OGD while Cx45 is the most sensitive one. CT of Cx43 has major necessary elements for OGD induced uncoupling and it can complement CT of Cx40 and Cx45.

  2. Silver nanoparticles increase connexin43-mediated gap junctional intercellular communication in HaCaT cells through activation of reactive oxygen species and mitogen-activated protein kinase signal pathway

    DEFF Research Database (Denmark)

    Qin, Yu; Han, Limin; Yang, Di


    of Cx43 on GJIC were assessed. HaCaT cells exposed to non-coated AgNPs at different doses after a 24 hour exposure. To explore further the underlying mechanism, reactive oxygen species and mitogen-activated protein kinase pathway were evaluated after 2, 6, 12 and 24 hours. Our results revealed that non......-coated AgNP exposure at subcytotoxic doses increase GJIC partially via Cx43 upregulation. Reactive oxygen species and extracellular signal-regulated kinase and activation of c-Jun N-terminal kinase were involved in the AgNP-induced upregulation of Cx43. This study provides new insight into the potential......Silver nanoparticles (AgNPs) are widely used in health and consumer products that routinely contact skin. However, the biological effects and possible mechanisms of AgNPs on skin remain unclear. Gap junctional intercellular communication (GJIC) plays a critical role in multicellular organisms...

  3. Josephson junction (United States)

    Wendt, J.R.; Plut, T.A.; Martens, J.S.


    A novel method for fabricating nanometer geometry electronic devices is described. Such Josephson junctions can be accurately and reproducibly manufactured employing photolithographic and direct write electron beam lithography techniques in combination with aqueous etchants. In particular, a method is described for manufacturing planar Josephson junctions from high temperature superconducting material. 10 figs.

  4. Development of tight junctions between odontoblasts in early dentinogenesis as revealed by freeze-fracture


    Arana-Chavez, V.E.; Katchburian, Eduardo


    Background: Mature odontoblasts possess junctional structures constituted by adherens, gap, and tight junctions. Although adherens and gap junctions appear early between odontoblasts, there is no information on the appearance and development of tight junctions between odontoblasts. in this study, we have examined freeze-fracture replicas of early dentinogenesis to study the development of tight junctions between odontoblasts and to determine whether these junctions are of zonular or macular t...

  5. impairs gap junction function causing congenital cataract

    Indian Academy of Sciences (India)



    , Mudanjiang,. Heilongjiang Province, China. 2 Department of Genetics, National Research Institute for Family Planning, Beijing, China. 3 Department of immunology, Basic Medical College of Harbin Medical University, ...

  6. impairs gap junction function causing congenital cataract

    Indian Academy of Sciences (India)



    Dec 20, 2017 ... 1Department of Ophthalmology, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang 157000, Heilongjiang. Province, People's Republic of China. 2Department of Genetics, National Research Institute for Family Planning, Beijing 100081, People's Republic of China. 3Department of Immunology ...

  7. Graded junction termination extensions for electronic devices (United States)

    Merrett, J. Neil (Inventor); Isaacs-Smith, Tamara (Inventor); Sheridan, David C. (Inventor); Williams, John R. (Inventor)


    A graded junction termination extension in a silicon carbide (SiC) semiconductor device and method of its fabrication using ion implementation techniques is provided for high power devices. The properties of silicon carbide (SiC) make this wide band gap semiconductor a promising material for high power devices. This potential is demonstrated in various devices such as p-n diodes, Schottky diodes, bipolar junction transistors, thyristors, etc. These devices require adequate and affordable termination techniques to reduce leakage current and increase breakdown voltage in order to maximize power handling capabilities. The graded junction termination extension disclosed is effective, self-aligned, and simplifies the implementation process.

  8. GAP Analysis Program (GAP) (United States)

    Kansas Data Access and Support Center — The Kansas GAP Analysis Land Cover database depicts 43 land cover classes for the state of Kansas. The database was generated using a two-stage hybrid classification...

  9. Myoendothelial coupling through Cx40 contributes to EDH-induced vasodilation in murine renal arteries: evidence from experiments and modelling

    DEFF Research Database (Denmark)

    Brasen, Jens Christian; de Wit, Cynthia A.; Sorensen, C M


    Regulation of renal vascular resistance plays a major role in controlling arterial blood pressure. The endothelium participates in this regulation as endothelial derived hyperpolarization plays a significant role in smaller renal arteries and arterioles, but the exact mechanisms are still unknown...... of inward rectifier potassium channels (Kir) and Na+ /K+ -ATPases was evaluated as was the contribution from gap junctions. Mathematical models estimating diffusion of ions and electrical coupling in myoendothelial gap junctions were used to interpret the results. Lack of connexin40 significantly reduces...

  10. Intercellular junctions in the uterine epithelium of Salamandra salamandra (L.) (Amphibia, Urodela). A freeze-fracture study. (United States)

    Greven, H; Robenek, H


    Intercellular junctions in the uterine epithelium of the ovoviviparous urodele Salamandra salamandra were studied in pregnant and non-pregnant females by freeze-fracture technique. Junctional complexes consist of zonulae occludentes (tight junctions) and numerous maculae adhaerentes (desmosomes); z. adhaerentes and nexuses (gap junctions) could not be identified. Tight junctions are of the "flexible" type exhibiting loosely interconnected fibrils. The fibrillary network appears stretched more often in pregnant females possibly due to the mechanical stress of pregnancy. The structure and occurrence of the junctions identified, especially that of the tight junctions, is discussed with regard to the functions of the uterus during pregnancy.

  11. Interactive effects of inflammatory cytokine and abundant low-molecular-weight PAHs on inhibition of gap junctional intercellular communication, disruption of cell proliferation control, and the AhR-dependent transcription

    Czech Academy of Sciences Publication Activity Database

    Kabátková, Markéta; Svobodová, Jana; Pěnčíková, K.; Mohatad, D.S.; Šmerdová, Lenka; Kozubík, Alois; Machala, M.; Vondráček, Jan


    Roč. 232, č. 1 (2015), s. 113-121 ISSN 0378-4274 R&D Projects: GA ČR(CZ) GAP503/11/1227; GA ČR(CZ) GA13-07711S Institutional support: RVO:68081707 Keywords : PAHs * Inflammation * Cell proliferation Subject RIV: BO - Biophysics Impact factor: 3.522, year: 2015

  12. Molecular electronic junction transport

    DEFF Research Database (Denmark)

    Solomon, Gemma C.; Herrmann, Carmen; Ratner, Mark


    Whenasinglemolecule,oracollectionofmolecules,isplacedbetween two electrodes and voltage is applied, one has a molecular transport junction. We discuss such junctions, their properties, their description, and some of their applications. The discussion is qualitative rather than quantitative......, and focuses on mechanism, structure/function relations, regimes and mechanisms of transport, some molecular regularities, and some substantial challenges facing the field. Because there are many regimes and mechanisms in transport junctions, we will discuss time scales, geometries, and inelastic scattering...

  13. Proximity Effects in Superconductor-Graphene Junctions (United States)

    Cuellar, Fabian A.; Perconte, David; Martin, Marie-Blandine; Dlubak, Bruno; Piquemail, Maelis; Bernard, Rozenn; Trastoy, Juan; Moreau-Luchaire, Constance; Seneor, Pierre; Villegas, Javier E.; Kidambi, Piran; Hofmann, Stephan; Robertson, John


    Superconducting proximity effects are of particular interest in graphene: because of its band structure, an unconventional (specular) Andreev reflection is expected. In this context, high-Tc superconductor-graphene junctions are especially attractive. In these, the size of the superconducting energy-gap may exceed the graphene doping inhomogeneities around the Dirac point, which should favor the observation of the specular Andreev reflection. Yet, the fabrication of high-Tc superconductor-graphene junctions is challenging: the usual growth and lithography processes in both materials are incompatible. We report here on a fabrication method that allow us to fabricate planar cuprate superconductor-graphene junctions, which we characterize via conductance spectroscopy. We analyze the features in the conductance spectra as a function of graphene doping, and discuss them in the framework of the Andreev reflection. Work supported by Labex Nanosaclay.

  14. Malformation of junctional microdomains in cataract lens membranes from a type II diabetes patient. (United States)

    Mangenot, Stéphanie; Buzhynskyy, Nikolay; Girmens, Jean-François; Scheuring, Simon


    In eye core lens membranes, aquaporin-0 (AQP0) and connexins (Cx) form together well-structured supramolecular assemblies, the junctional microdomains, in which they assure water, ion, metabolite, and waste transport. Additionally, they mediate cell-cell adhesion-forming thin junctions (AQP0) and gap junctions (Cx). We have used atomic force microscopy and biochemical methods to analyze and compare the structure of junctional microdomains in human cataract lens membranes from a type II diabetes patient and healthy lens membranes from calf. A healthy intercellular junctional microdomain consists in average of approximately 150 tetragonally arranged (a = b = 65.5 A, gamma = 90 degrees) AQP0 tetramers surrounded by densely packed non-ordered connexon channels. Gap-junction connexons act as lineactants inside the membrane and confine AQP0 in the junctional microdomains. In the diabetic cataract lens, connexons were degraded, and AQP0 arrays are malformed. We conceptualize that absence of connexons lead to breakdown of cell nutrition.

  15. Development of tight junctions between odontoblasts in early dentinogenesis as revealed by freeze-fracture. (United States)

    Arana-Chavez, V E; Katchburian, E


    Mature odontoblasts possess junctional structures constituted by adherens, gap, and tight junctions. Although adherens and gap junctions appear early between odontoblasts, there is no information on the appearance and development of tight junctions between odontoblasts. In this study, we have examined freeze-fracture replicas of early dentinogenesis to study the development of tight junctions between odontoblasts and to determine whether these junctions are of zonular or macular type. Upper first molar tooth germs of Wistar rats between 1 and 3 days old were fixed in buffered 4% glutaraldehyde/4% formaldehyde and subsequently cryoprotected with cacodylate-buffered glycerol. Freeze-fracture replicas were obtained in a Balzers 301 apparatus, and early stages of dentinogenesis were examined in a Jeol 100 CX II electron microscope. In the stage of early dentine matrix prior to mineralization, odontoblasts exhibit only gap junctions. With the progression of development, the distal plasma membranes of odontoblasts show numerous short tight junctions formed by fused particles and grooves. In the stage of advanced mineralization, branched and continuous rows of fused particles or grooves constitute tight junctions of the focal or macular type. The present study shows that tight junctions of focal or macular type appear on distal plasma membrane of early odontoblasts during differentiation. Formation of tight junctions indicates the establishment of a distal membrane domain and maturation of odontoblasts. These events occur as mantle dentine formation ceases and circumpulpar dentine formation begins.

  16. No junctional communication between epithelial cells in hydra

    DEFF Research Database (Denmark)

    de Laat, S W; Tertoolen, L G; Grimmelikhuijzen, C J


    Diffusion gradients of morphogens have been inferred as a basis for the control of morphogenesis in hydra, and morphogenetic substances have been found which, on the basis of their molecular weight (MW), should be able to pass gap junctions. There have been several reports of the presence of gap...... junctions between epithelial cells of hydra. However, until now, there has been no report published on whether these junctions enable the epithelial cells to exchange molecules of small molecular weight, as has been described in other organisms. Therefore we decided to investigate the communicative...... properties of the junctional membranes by electrophysiological methods and by intracellular-dye iontophoresis. We report here that no electrotonic coupling is detectable between epithelial cells of Hydra attenuata in: (1) intact animals, (2) head-regenerating animals, (3) cell re-aggregates, and (4) hydra...

  17. Superconducting properties of lithographic lead break junctions (United States)

    Weber, David; Scheer, Elke


    We have fabricated mechanically controlled break junction samples made of lead (Pb) by means of state-of-the-art nanofabrication methods: electron beam lithography and physical vapour deposition. The electrical and magnetic properties were characterized in a {}3{He} cryostat and showed a hard superconducting gap. Temperature and magnetic field dependence of tunnel contacts were compared and quantitatively described by including either thermal broadening of the density of states or pair breaking in the framework of a Skalski model, respectively. We show point contact spectra of few-atom contacts and present tunneling spectra exhibiting a superconducting double-gap structure.

  18. Ballistic Graphene Josephson Junctions from the Short to the Long Junction Regimes: Part II- Critical current scaling of the Short and Long Junctions (United States)

    Ke, Chung-Ting; Borzenets, Ivan; Amet, Francois; Draelos, Anne; Wei, Ming-Tso; Seredinski, Andrew; Watanabe, Kenji; Taniguchi, Takashi; Bomze, Yuriy; Yamamoto, Michihisa; Tarucha, Seigo; Finkelstein, Gleb

    The Josephson effect describes the phenomenon of coupling a supercurrent between superconductors through a weak link. Using graphene as this weak link has seen much interest due to its tunable density and related Dirac fermion physics. Previously we have studied the critical current scaling in diffusive graphene samples with different junction lengths. For ballistic junctions, however, knowledge about transport properties remains scarce. With clean encapsulated graphene, studying the supercurrent transport mechanism in ballistic samples has now become feasible. We present measurements of ballistic graphene Josephson junctions from short to long junction limits. From their temperature dependence, we characterize the critical current in both the short and long junction cases by using the characteristic energies Δ and δE, where Δ is the superconducting gap and δE is the level spacing in the long junction case. At low temperatures, as KBT < Δ for short junctions and KBT < δE for long ones, we show that the critical current saturates at a level determined by the product of Δ (or δE) and the number of the junction's transversal modes.

  19. Shallow Junction Technology. (United States)

    Liu, Teyin Mark

    Shallow junction technology is a necessity to maintain the performance of the scaled integrated devices in VLSL. In this work, various approaches to the process design of shallow junctions in implantation/diffusion technology are explored. The high concentration shallow arsenic implant/diffusion profile is described by the Chebyshev polynomial model. Based on the model, the inter-relationships of four design parameters: sheet resistance, junction depth, effective surface concentration, and thermal cycle are analytically derived. A general design graph for shallow arsenic junctions is developed. A similar methodology is applied to describe the high concentration boron shallow junctions design. At very high concentration, arsenic clustering and boron precipitation limit the achievable lower bound of sheet resistance. The sheet resistance is experimentally characterized and modeled. The ultimate limitations on sheet resistance due to these effects are defined. Unintentional channeling in low energy ion-implantation of boron into silicon results in much deeper junctions than predicted by LSS theory, even for wafers tilted well off the channeling directions. The channeling tail imposes an unexpected limitation on the achievable shallow junction depth. This partial channeling effect caused by boron ions being randomly scattered into crystal channels is examined by a calculation of the angular spreading for boron ions in silicon. An empirical formula is found to describe the enhancement of junction depth. To prevent the boron channeling, two methods of dechanneling are explored. Dechanneling by surface oxide layers is found to be ineffective. As-implanted junction depths much deeper than the predictions of LSS theory cannot be avoided. Based on a "lucky" ion model, the as-implanted junction depth with the surface oxide can be predicted. Silicon pre-implantation is found very effective in reducing the junction depth. The amorphization process by the silicon pre

  20. Functional Molecular Junctions Derived from Double Self-Assembled Monolayers. (United States)

    Seo, Sohyeon; Hwang, Eunhee; Cho, Yunhee; Lee, Junghyun; Lee, Hyoyoung


    Information processing using molecular junctions is becoming more important as devices are miniaturized to the nanoscale. Herein, we report functional molecular junctions derived from double self-assembled monolayers (SAMs) intercalated between soft graphene electrodes. Newly assembled molecular junctions are fabricated by placing a molecular SAM/(top) electrode on another molecular SAM/(bottom) electrode by using a contact-assembly technique. Double SAMs can provide tunneling conjugation across the van der Waals gap between the terminals of each monolayer and exhibit new electrical functions. Robust contact-assembled molecular junctions can act as platforms for the development of equivalent contact molecular junctions between top and bottom electrodes, which can be applied independently to different kinds of molecules to enhance either the structural complexity or the assembly properties of molecules. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Quantum Junction Solar Cells

    KAUST Repository

    Tang, Jiang


    Colloidal quantum dot solids combine convenient solution-processing with quantum size effect tuning, offering avenues to high-efficiency multijunction cells based on a single materials synthesis and processing platform. The highest-performing colloidal quantum dot rectifying devices reported to date have relied on a junction between a quantum-tuned absorber and a bulk material (e.g., TiO 2); however, quantum tuning of the absorber then requires complete redesign of the bulk acceptor, compromising the benefits of facile quantum tuning. Here we report rectifying junctions constructed entirely using inherently band-aligned quantum-tuned materials. Realizing these quantum junction diodes relied upon the creation of an n-type quantum dot solid having a clean bandgap. We combine stable, chemically compatible, high-performance n-type and p-type materials to create the first quantum junction solar cells. We present a family of photovoltaic devices having widely tuned bandgaps of 0.6-1.6 eV that excel where conventional quantum-to-bulk devices fail to perform. Devices having optimal single-junction bandgaps exhibit certified AM1.5 solar power conversion efficiencies of 5.4%. Control over doping in quantum solids, and the successful integration of these materials to form stable quantum junctions, offers a powerful new degree of freedom to colloidal quantum dot optoelectronics. © 2012 American Chemical Society.

  2. Knowledge Gaps

    DEFF Research Database (Denmark)

    Lyles, Marjorie; Pedersen, Torben; Petersen, Bent


    , assimilating, and utilizing knowledge - are crucial determinants ofknowledge gap elimination. In contrast, the two factors deemed essential in traditionalinternationalization process theory - elapsed time of operations and experientiallearning - are found to have no or limited effect.Key words......: Internationalization, knowledge gap, absorptive capacity, learning box....

  3. Gap Resolution

    Energy Technology Data Exchange (ETDEWEB)


    Gap Resolution is a software package that was developed to improve Newbler genome assemblies by automating the closure of sequence gaps caused by repetitive regions in the DNA. This is done by performing the follow steps:1) Identify and distribute the data for each gap in sub-projects. 2) Assemble the data associated with each sub-project using a secondary assembler, such as Newbler or PGA. 3) Determine if any gaps are closed after reassembly, and either design fakes (consensus of closed gap) for those that closed or lab experiments for those that require additional data. The software requires as input a genome assembly produce by the Newbler assembler provided by Roche and 454 data containing paired-end reads.

  4. SUBMM heterodyne mixing using NbCN/Nb SIS tunnel junctions.

    NARCIS (Netherlands)

    vandeStadt, H; Mees, J; Barber, Z; Blamire, M; Dieleman, P; deGraauw, T

    We describe heterodyne mixing experiments with NbCN/Nb quasi-particle tunnel junctions at submillimeter wavelengths. In this wavelength range junctions with niobium nitride as superconducting material are promising because of the high gap voltage, about 5.7 mV, as compared to 3 mV for the more

  5. Junctional Epidermolysis Bullosa

    Directory of Open Access Journals (Sweden)

    Chuan-Hong Kao


    Full Text Available Epidermolysis bullosa (EB encompasses a heterogeneous group of genodermatoses, characterized by fragility and blistering of the skin, often associated with extracutaneous manifestations. The level of vesiculation within the skin defines 3 major subtypes of EB: EB simplex, junctional EB, and dystrophic EB. We present the case of a male neonate of 36 weeks' gestation, who was born with a few blisters with erosions and who rapidly developed extensive blistering of the skin. Histopathology revealed subepidermal blistering. Electron microscopy confirmed the cleavage of epidermis from dermis within the lamina lucida. Junctional EB was the diagnosis. The patient was discharged after hospitalization for 28 days. The development of new blisters with erosions were gradually improved after AQUACEL® Ag dressing, and the general condition was much better than at admission. The patient likely has a subtype of junctional EB termed generalized atrophic benign EB that clinically improves with age. He has the potential to father children and has a normal life expectancy.

  6. Kondo Effect in Bare Electromigrated Break Junctions (United States)

    Houck, Andrew; Labaziewicz, Jarek


    Electromigrated break junctions are one of only a very few systems currently available that provide sub-nanometer electrode gaps in a gated geometry. They have been used in several experiments over the past few years to measure transport through nanometer-scale objects such as single molecules. Our measurements show that the electromigrated electrode system--even by itself, without added nanoparticles-- is richer than previously thought. This talk will present gate- dependent transport measurements of Kondo impurities in bare gold break junctions, generated with high yield using an electromigration process that is actively controlled. An unexpected behavior of the splitting is observed in the crossover regime, where spin splitting is of the same order as the Kondo temperature. The Kondo resonances observed here may be due to atomic-scale metallic grains formed during electromigration.

  7. Tunable Nitride Josephson Junctions.

    Energy Technology Data Exchange (ETDEWEB)

    Missert, Nancy A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Henry, Michael David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Lewis, Rupert M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Howell, Stephen W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wolfley, Steven L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Brunke, Lyle Brent [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Wolak, Matthaeus [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    We have developed an ambient temperature, SiO2/Si wafer - scale process for Josephson junctions based on Nb electrodes and Ta x N barriers with tunable electronic properties. The films are fabricated by magnetron sputtering. The electronic properties of the TaxN barriers are controlled by adjusting the nitrogen flow during sputtering. This technology offers a scalable alternative to the more traditional junctions based on AlOx barriers for low - power, high - performance computing.

  8. Mythic gaps

    Directory of Open Access Journals (Sweden)

    William Hansen


    Full Text Available Different kinds of omissions sometimes occur, or are perceived to occur, in traditional narratives and in tradition-inspired literature. A familiar instance is when a narrator realizes that he or she does not fully remember the story that he or she has begun to tell, and so leaves out part of it, which for listeners may possibly result in an unintelligible narrative. But many instances of narrative gap are not so obvious. From straightforward, objective gaps one can distinguish less-obvious subjective gaps: in many cases narrators do not leave out anything crucial or truly relevant from their exposition, and yet readers perceive gaps and take steps to fill them. The present paper considers four examples of subjective gaps drawn from ancient Greek literature (the Pandora myth, ancient Roman literature (the Pygmalion legend, ancient Hebrew literature (the Joseph legend, and early Christian literature (the Jesus legend. I consider the quite varied ways in which interpreters expand the inherited texts of these stories, such as by devising names, manufacturing motives, creating backstories, and in general filling in biographical ellipses. Finally, I suggest an explanation for the phenomenon of subjective gaps, arguing that, despite their variety, they have a single cause.

  9. GAP Analysis Program (GAP) Raster (United States)

    Kansas Data Access and Support Center — The Kansas GAP Land Cover database depicts 43 land cover classes for the state of Kansas. The database was generated using a two-stage hybrid classification of...

  10. An unusual junctional scotoma. (United States)

    Milea, Dan; LeHoang, Phuc


    A 28-year-old woman presented with painful unilateral left visual loss, impaired color vision, left afferent pupillary defect, and normal ocular fundus. Although optic neuritis was first suspected, visual fields disclosed a junctional scotoma related to chiasmal demyelination, due to a probable multiple sclerosis.

  11. Doped semiconductor nanocrystal junctions

    Energy Technology Data Exchange (ETDEWEB)

    Borowik, Ł.; Mélin, T., E-mail: [Institut d’Electronique, de Microélectronique et de Nanotechnologie, CNRS-UMR8520, Avenue Poincaré, F-59652 Villeneuve d’Ascq (France); Nguyen-Tran, T.; Roca i Cabarrocas, P. [Laboratoire de Physique des Interfaces et des Couches Minces, CNRS-UMR7647, Ecole Polytechnique, F-91128 Palaiseau (France)


    Semiconductor junctions are the basis of electronic and photovoltaic devices. Here, we investigate junctions formed from highly doped (N{sub D}≈10{sup 20}−10{sup 21}cm{sup −3}) silicon nanocrystals (NCs) in the 2–50 nm size range, using Kelvin probe force microscopy experiments with single charge sensitivity. We show that the charge transfer from doped NCs towards a two-dimensional layer experimentally follows a simple phenomenological law, corresponding to formation of an interface dipole linearly increasing with the NC diameter. This feature leads to analytically predictable junction properties down to quantum size regimes: NC depletion width independent of the NC size and varying as N{sub D}{sup −1/3}, and depleted charge linearly increasing with the NC diameter and varying as N{sub D}{sup 1/3}. We thus establish a “nanocrystal counterpart” of conventional semiconductor planar junctions, here however valid in regimes of strong electrostatic and quantum confinements.

  12. Victory Junction Gang Camp (United States)

    Shell, Ryan


    This article describes the Victory Junction Gang Camp, a not-for-profit, NASCAR-themed camp for children with chronic medical conditions that serves 24 different disease groups. The mission of the camp is to give children life-changing camping experiences that are exciting, fun, and empowering in a safe and medically sound environment. While doing…

  13. Ballistic Graphene Josephson Junctions from the Short to the Long Junction Regimes: Part I- Governing Energy Scales of the Short and Long Junctions (United States)

    Borzenets, Ivan; Amet, Francois; Ke, Chung Ting; Draelos, Anne; Wei, Ming-Tso; Seredinski, Andrew; Watanabe, Kenji; Taniguchi, Takashi; Bomze, Yuriy; Yamamoto, Michihisa; Tarucha, Seigo; Finkelstein, Gleb

    We examine the behavior of the critical current, in ballistic Josephson junctions made of encapsulated graphene/boron-nitride heterostructures. The temperature dependence of the critical current allows us to identify and observe the crossover from the short to the long junction regimes. (The operational regime of a junction is defined by the ratio of the superconducting coherence length ξ to the junction length L). For each regime we extract the governing energy scales, which are found to be consistent with theory. In the short regime, the energy is consistent with the expected superconducting gap Δ. While in the long regime, the governing energy δE is independent of the carrier density and proportional to the level spacing of the ballistic cavity, as determined from Fabry-Perot oscillations of the junction normal resistance. However, in the intermediate regime, we find that junctions behave as if in the long regime, but with δE (which is typically a function of L) rescaled as L ->L + ξ .

  14. The role of remote closure in the perception of occlusion at junctions and illusory contours. (United States)

    Gillam, Barbara J; Grove, Philip M; Layden, Jessica


    Abstract. Perceived occlusion at T-junctions or illusory contours at implicit T-junctions are often modelled by using edge information without surface context. We explored the effect of closure on perceived occlusion at T-junctions. Two vertical lines separated by a gap each had six abutting horizontal lines on opposite sides forming T-junctions. These lines were either closed or not closed into pairs at the stem ends of the Ts. In experiment 1, closed T-junction stems gave a much stronger sense of occlusion at the vertical lines than unclosed ones, even though closure information was remote from the putative occlusion and local T-junction information remained constant. When the outer two T-junctions were converted to L-junctions, perceived occlusion considerably diminished. The effect of closure on illusory-contour strength for stimuli like those of experiment 1 but with the vertical lines omitted was explored in experiment 2. The two sets of horizontal lines, separated by a gap, were either closed or not closed into pairs at their outer ends. Illusory-contour strength along the vertical alignments was much greater for closed pairs. Line terminations on both sides of the gap enhanced illusory-contour strength, but whether they were collinear or not had little effect.

  15. GAP: A computer program for gene assembly

    Energy Technology Data Exchange (ETDEWEB)

    Eisnstein, J.R.; Uberbacher, E.C.; Guan, X.; Mural, R.J.; Mann, R.C.


    A computer program, GAP (Gene Assembly Program), has been written to assemble and score hypothetical genes, given a DNA sequence containing the gene, and the outputs of several other programs which analyze the sequence. These programs include the codign-recognition and splice-junction-recognition modules developed in this laboratory. GAP is a prototype of a planned system in which it will be integrated with an expert system and rule base. Initial tests of GAP have been carried out with four sequences, the exons of which have been determined by biochemcial methods. The highest-scoring hypothetical genes for each of the four sequences had percent correct splice junctions ranging from 50 to 100% (average 81%) and percent correct bases ranging from 92 to 100% (average 96%). 9 refs., 1 tab.

  16. Bifurcation transitions in gap-junction-coupled neurons (United States)

    Shaffer, Annabelle; Harris, Allison L.; Follmann, Rosangela; Rosa, Epaminondas


    Here we investigate transitions occurring in the dynamical states of pairs of distinct neurons electrically coupled, with one neuron tonic and the other bursting. Depending on the dynamics of the individual neurons, and for strong enough coupling, they synchronize either in a tonic or a bursting regime, or initially tonic transitioning to bursting via a period doubling cascade. Certain intrinsic properties of the individual neurons such as minimum firing rates are carried over into the dynamics of the coupled neurons affecting their ultimate synchronous state.

  17. A Model of Gap Junction Conductance and Ventricular Tachyarrhythmia

    National Research Council Canada - National Science Library

    Wu, X


    ... diseases, electrical coupling through GJ channels between cardiomyocytes is down regulated, We set up a mathematical model of a chain of myocardial fibers to study how changing the coupling affects...

  18. Do gap junctions regulate synchrony in the parkinsonian basal ganglia?

    NARCIS (Netherlands)

    Schwab, B.C.


    Patients with Parkinson’s disease (PD) typically suffer severely from different types of symptoms. Motor symptoms, restricting the patients’ ability to perform controlled movements in daily life, are of special clinical interest and have been related to neural activity in the basal ganglia.

  19. Structure modeling and mutational analysis of gap junction beta 2 ...

    African Journals Online (AJOL)

    The genome sequencing accomplishes complete genetic blue prints for hundreds of organisms, including humans. In the current era, we are trying to focus on analyzing, controlling and modifying functions of proteins encoded by these genomes. This task is attained by protein three dimensional structures.

  20. Tunneling transport in d-wave superconductor-silicene junction (United States)

    Hajati, Y.; Vosoughi nia, S.; Rashedi, G.


    We theoretically study the tunneling conductance of a normal/d-wave superconductor silicene junction using Blonder-Tinkham-Klapwijk (BTK) formalism. We discuss in detail how the conductances spectra are affected by inducing d-wave superconducting pairing symmetry in the buckled silicene. It is obtained that the amplitude of the spin/valley-dependent Andreev reflection and subgap conductance of the junction can be strongly modulated by the orientation angle of superconductive gap (β) and perpendicular electric field (EZ), suggesting that one may experimentally tune the transport properties of the junction through changing β and EZ. We demonstrate that the subgap conductance exhibits an oscillatory behavior as a function of the orientation angle of superconductive gap (β) with a period of π / 2 and by increasing the insulating gap of silicene, the charge conductance oscillations suppress. Remarkably, due to the buckled structure of silicene at the maximum orientation angle of the d-wave superconducting β = π / 4 , we found a very distinct behavior from the graphene-based NS junction where the charge conductance is insensitive to the bias energy. In addition, the Andreev reflection and subgap conductance can be switched on and off by applying electric field.

  1. Many-junction photovoltaic device performance under non-uniform high-concentration illumination (United States)

    Valdivia, Christopher E.; Wilkins, Matthew M.; Chahal, Sanmeet S.; Proulx, Francine; Provost, Philippe-Olivier; Masson, Denis P.; Fafard, Simon; Hinzer, Karin


    A parameterized 3D distributed circuit model was developed to calculate the performance of III-V solar cells and photonic power converters (PPC) with a variable number of epitaxial vertically-stacked pn junctions. PPC devices are designed with many pn junctions to realize higher voltages and to operate under non-uniform illumination profiles from a laser or LED. Performance impacts of non-uniform illumination were greatly reduced with increasing number of junctions, with simulations comparing PPC devices with 3 to 20 junctions. Experimental results using Azastra Opto's 12- and 20-junction PPC illuminated by an 845 nm diode laser show high performance even with a small gap between the PPC and optical fiber output, until the local tunnel junction limit is reached.

  2. Analysis of Waveguide Junction Discontinuities Using Finite Element Method (United States)

    Deshpande, Manohar D.


    A Finite Element Method (FEM) is presented to determine reflection and transmission coefficients of rectangular waveguide junction discontinuities. An H-plane discontinuity, an E-plane ridge discontinuity, and a step discontinuity in a concentric rectangular waveguide junction are analyzed using the FEM procedure. Also, reflection and transmission coefficients due to presence of a gap between two sections of a rectangular waveguide are determined using the FEM. The numerical results obtained by the present method are in excellent agreement with the earlier published results. The numerical results obtained by the FEM are compared with the numerical results obtained using the Mode Matching Method (MMM) and also with the measured data.

  3. Josephson junction analog and quasiparticle-pair current

    DEFF Research Database (Denmark)

    Bak, Christen Kjeldahl; Pedersen, Niels Falsig


    A close analogy exists between a Josephson junction and a phase-locked loop. A new type of electrical analog based on this principle is presented. It is shown that the inclusion in this analog of a low-pass filter gives rise to a current of the same form as the Josephson quasiparticle-pair curren....... A simple picture of the quasiparticle-pair current, which gives the right dependences, is obtained by assuming a junction cutoff frequency to be at the energy gap. ©1973 American Institute of Physics...

  4. Quasiparticle trapping, excitation, and tunneling times in Josephson junctions with spatially inhomogeneous electrodes (United States)

    Houwman, E. P.; Golubov, A. A.; Gijsbertsen, J. G.; Flokstra, J.; Rogalla, H.; Le Grand, J. B.; Bruijn, M. P.; de Korte, P. A. J.


    On the basis of a microscopic model of the proximity effect in an SS'-sandwich we have calculated effective trapping, excitation, and tunneling rates of the reduced gap region in an SS'IS″S junction as a function of temperature, voltage over the junction and strength of the proximity effect. We developed a simple model to describe the effect of magnetic fields on the gap of the superconductor, and calculated the trapping rate as function of the field. The experimentally determined gap reduction and quasiparticle loss times as function of the field were described in terms of this model.

  5. Cementoenamel junction: An insight

    Directory of Open Access Journals (Sweden)

    Kharidi Laxman Vandana


    Full Text Available The location and nature of cemento-enamel junction (CEJ are more than descriptive terms used simply to describe some aspects of tooth morphology; however, CEJ gains a lot of clinical significance due to various measurements dependent on it. It may be necessary to determine the location and pathological changes occurring at CEJ to make a diagnosis and treat diseases pertaining to epithelial attachment and gingival margin. However, the information related to CEJ is not discussed commonly. Hence, the present review paper provides an insight on CEJ in both primary and permanent dentition.

  6. NbN-AlN-NbN Josephson junctions on different substrates

    Energy Technology Data Exchange (ETDEWEB)

    Merker, Michael; Bohn, Christian; Voellinger, Marvin; Ilin, Konstantin; Siegel, Michael [KIT, Karlsruhe (Germany)


    Josephson junction technology is important for the realization of high quality cryogenic devices such as SQUIDs, RSFQ or SIS-mixers. The material system based on NbN/AlN/NbN tri-layer has gained a lot of interest, because it offers higher gap voltages and critical current densities compared to the well-established Nb/Al-AlOx/Nb technology. However, the realization of high quality Josephson junctions is more challenging. We developed a technology of Josephson junctions on a variety of substrates such as Silicon, Sapphire and Magnesium oxide and compared the quality parameters of these junctions at 4.2 K. The gap voltages achieved a range from 4 mV (for the junctions on Si) to 5.8 mV (in case of MgO substrates) which is considerably higher than those obtained from Nb based Josephson junctions. Another key parameter is the ratio of the subgap resistance to the normal state resistance. This so-called subgap ratio corresponds to the losses in a Josephson junction which have to be minimized. So far, subgap ratios of 26 have been achieved. Further careful optimization of the deposition conditions is required to maximize this ratio, The details of the optimization of technology and of characterization of NbN/AlN/NbN junctions will be presented and discussed.

  7. Regulation of cardiovascular connexins by mechanical forces and junctions. (United States)

    Meens, Merlijn J; Pfenniger, Anna; Kwak, Brenda R; Delmar, Mario


    Connexins form a family of transmembrane proteins that consists of 20 members in humans and 21 members in mice. Six connexins assemble into a connexon that can function as a hemichannel or connexon that can dock to a connexon expressed by a neighbouring cell, thereby forming a gap junction channel. Such intercellular channels synchronize responses in multicellular organisms through direct exchange of ions, small metabolites, and other second messenger molecules between the cytoplasms of adjacent cells. Multiple connexins are expressed in the cardiovascular system. These connexins not only experience the different biomechanical forces within this system, but may also act as effector proteins in co-ordinating responses within groups of cells towards these forces. This review discusses recent insights regarding regulation of cardiovascular connexins by mechanical forces and junctions. It specifically addresses effects of (i) shear stress on endothelial connexins, (ii) hypertension on vascular connexins, and (iii) changes in afterload and the composition of myocardial mechanical junctions on cardiac connexins.

  8. Tight Junctions Go Viral!

    Directory of Open Access Journals (Sweden)

    Jesús M. Torres-Flores


    Full Text Available Tight junctions (TJs are highly specialized membrane domains involved in many important cellular processes such as the regulation of the passage of ions and macromolecules across the paracellular space and the establishment of cell polarity in epithelial cells. Over the past few years there has been increasing evidence that different components of the TJs can be hijacked by viruses in order to complete their infectious cycle. Viruses from at least nine different families of DNA and RNA viruses have been reported to use TJ proteins in their benefit. For example, TJ proteins such as JAM-A or some members of the claudin family of proteins are used by members of the Reoviridae family and hepatitis C virus as receptors or co-receptors during their entry into their host cells. Reovirus, in addition, takes advantage of the TJ protein Junction Adhesion Molecule-A (JAM-A to achieve its hematogenous dissemination. Some other viruses are capable of regulating the expression or the localization of TJ proteins to induce cell transformation or to improve the efficiency of their exit process. This review encompasses the importance of TJs for viral entry, replication, dissemination, and egress, and makes a clear statement of the importance of studying these proteins to gain a better understanding of the replication strategies used by viruses that infect epithelial and/or endothelial cells.

  9. Topological Properties of Superconducting Junctions

    NARCIS (Netherlands)

    Pikulin, D.I.; Nazarov, Y.V.

    Motivated by recent developments in the field of one-dimensional topological superconductors, we investigate the topological properties of s-matrix of generic superconducting junctions where dimension should not play any role. We argue that for a finite junction the s-matrix is always topologically

  10. Mechanics of lithographically defined break junctions

    NARCIS (Netherlands)

    Vrouwe, SAG; van der Giessen, E; van der Molen, SJ; Dulic, D; Trouwborst, ML; van Wees, BJ

    We investigate the mechanics of lithographically defined mechanically controllable break junctions, both theoretically and experimentally. It is shown that the relationship between controlled deflection and junction opening depends on the details of the break junction geometry. As a result the

  11. Garlic (Allium sativum) feeding impairs Sertoli cell junctional proteins in male Wistar rat testis: microscopy study. (United States)

    Hammami, I; Nahdi, A; Atig, F; El May, A; El May, M V


    Sertoli cell junctions, such as adhesion junction (AJ), gap junction (GJ) and tight junction (TJ), are important for maintaining spermatogenesis. In previous studies, we showed the inhibitory effect of crude garlic (Allium sativum, As) on spermatogenesis and steroidogenesis. The aim of this work was to complete our investigation on the impact of this plant, especially on Sertoli cell junctional proteins (SCJPs). During 1 month, 24 male rats were divided into groups: group control (0% of As) and treated groups fed 5%, 10% and 15% of As. Light and electron microscopy observations were performed to localise junctional proteins: connexin-43, Zona Occluding-1 and N-cadherin (immunohistochemistry) and to describe junctions. We showed that the specific cells involved in the localisation of the SCJP were similar in both control and treated groups, but with different immunoreactivity intensity between them. The electron microscopy observation focused on TJs between Sertoli cells, constituting the blood-testis barrier, showed ultrastructural changes such as fragmentation of TJs between adjacent Sertoli cell membranes and dilatation of rough endoplasmic reticulum saccules giving an aspect of scale to these junctions. We concluded that crude garlic consumption during 1 month induces perturbations on Sertoli cell junctions. These alterations can explain apoptosis in testicular germ cells previously showed. © 2016 Blackwell Verlag GmbH.

  12. Thermoelectric transport properties in graphene connected molecular junctions


    Rodriguez, S. T.; Grosu, I.; Crisan, M.; Tifrea, I.


    We study the electronic contribution to the main thermoelectric properties of a molecular junction consisting of a single quantum dot coupled to graphene external leads. The system electrical conductivity (G), Seebeck coefficient ($S$), and the thermal conductivity ($\\kappa$), are numerically calculated based on a Green's function formalism that includes contributions up to the Hartree-Fock level. We consider the system leads to be made either of pure or gapped-graphene. To describe the free ...

  13. Ion bipolar junction transistors. (United States)

    Tybrandt, Klas; Larsson, Karin C; Richter-Dahlfors, Agneta; Berggren, Magnus


    Dynamic control of chemical microenvironments is essential for continued development in numerous fields of life sciences. Such control could be achieved with active chemical circuits for delivery of ions and biomolecules. As the basis for such circuitry, we report a solid-state ion bipolar junction transistor (IBJT) based on conducting polymers and thin films of anion- and cation-selective membranes. The IBJT is the ionic analogue to the conventional semiconductor BJT and is manufactured using standard microfabrication techniques. Transistor characteristics along with a model describing the principle of operation, in which an anionic base current amplifies a cationic collector current, are presented. By employing the IBJT as a bioelectronic circuit element for delivery of the neurotransmitter acetylcholine, its efficacy in modulating neuronal cell signaling is demonstrated.

  14. Graphene based superconducting junctions as spin sources for spintronics (United States)

    Emamipour, Hamidreza


    We investigate spin-polarized transport in graphene-based ferromagnet-superconductor junctions within the Blonder-Tinkham-Klapwijk formalism by using spin-polarized Dirac-Bogoliubov-de-Gennes equations. We consider superconductor in spin-singlet s-wave pairing state and ferromagnet is modeled by an exchange field with energy of Ex. We have found that graphene-based junctions can be used to produce highly spin-polarized current in different situations. For example, if we design a junction with high Ex and EF compared to order parameter of superconductor, then one can have a large spin-polarized current which is tunable in magnitude and sign by bias voltage and Ex. Therefore graphene-based superconducting junction can be used in spintronic devices in alternative to conventional junctions or half-metallic ferromagnets. Also, we have found that the calculated spin polarization can be used as a tool to distinguish specular Andreev reflection (SAR) from the conventional Andreev reflection (CAR) such that in the case of CAR, spin polarization in sub-gap region is completely negative which means that spin-down current is greater than spin-up current. When the SAR is dominated, the spin polarization is positive at all bias-voltages, which itself shows that spin-up current is greater than spin-down current.

  15. Morphology of the cemento-enamel junction in premolar teeth. (United States)

    Arambawatta, Kapila; Peiris, Roshan; Nanayakkara, Deepthi


    The present study attempted to describe the distribution of the mineralized tissues that compose the cemento-enamel junction, with respect to both the different types of permanent premolars of males and females and the various surfaces of individual teeth. The cervical region of ground sections of 67 premolars that had been extracted for orthodontic reasons were analyzed using transmitted light microscopy to identify which of the following tissue interrelationships was present at the cemento-enamel junction: cementum overlapping enamel; enamel overlapping cementum; edge-to-edge relationship between cementum and enamel; or the presence of gaps between the enamel and cementum with exposed dentin. An edge-to-edge interrelation between root cementum and enamel was predominant (55.1%). In approximately one-third of the sample, gaps between cementum and enamel with exposed dentin were observed. Cementum overlapping enamel was less prevalent than previously reported, and enamel overlapping cementum was seen in a very small proportion of the sample. In any one tooth, the distribution of mineralized tissues at the cemento-enamel junction was irregular and unpredictable. The frequency of gaps between enamel and cementum with exposure of dentin was higher than previously reported, which suggests that this region is fragile and strongly predisposed to pathological changes. Hence, this region should be protected and carefully managed during routine clinical procedures such as dental bleaching, orthodontic treatment, and placement of restorative materials.

  16. A self-aligned nano-fabrication process for vertical NbN-MgO-NbN Josephson junctions (United States)

    Grimm, A.; Jebari, S.; Hazra, D.; Blanchet, F.; Gustavo, F.; Thomassin, J.-L.; Hofheinz, M.


    We present a new process for fabricating vertical NbN-MgO-NbN Josephson junctions using self-aligned silicon nitride spacers. It allows for a wide range of junction areas from 0.02 to several 100 μm2. At the same time, it is suited for the implementation of complex microwave circuits with transmission line impedances ranging from 1 {{k}}{{Ω }}. The constituent thin films and the finished junctions are characterized. The latter are shown to have high gap voltages (> 4 {mV}) and low sub-gap leakage currents.

  17. Thermoelectric transport properties in graphene connected molecular junctions (United States)

    Rodriguez, S. T.; Grosu, I.; Crisan, M.; Ţifrea, I.


    We study the electronic contribution to the main thermoelectric properties of a molecular junction consisting of a single quantum dot coupled to graphene external leads. The system electrical conductivity (G), Seebeck coefficient (S), and the thermal conductivity (κ), are numerically calculated based on a Green's function formalism that includes contributions up to the Hartree-Fock level. We consider the system leads to be made either of pure or gapped-graphene. To describe the free electrons in the gapped-graphene electrodes we used two possible scenarios, the massive gap scenario, and the massless gap scenario, respectively. In all cases, the Fano effect is responsible for a strong violation of the Wiedemann-Franz law and we found a substantial increase of the system figure of merit ZT due to a drastic reduction of the system thermal coefficient. In the case of gapped-graphene electrodes, the system figure of merit presents a maximum at an optimal value of the energy gap of the order of Δ / D ∼ 0.002 (massive gap scenario) and Δ / D ∼ 0.0026 (massless gap scenario). Additionally, for all cases, the system figure of merit is temperature dependent.

  18. Molecular Diffusion through Cyanobacterial Septal Junctions

    Directory of Open Access Journals (Sweden)

    Mercedes Nieves-Morión


    Full Text Available Heterocyst-forming cyanobacteria grow as filaments in which intercellular molecular exchange takes place. During the differentiation of N2-fixing heterocysts, regulators are transferred between cells. In the diazotrophic filament, vegetative cells that fix CO2 through oxygenic photosynthesis provide the heterocysts with reduced carbon and heterocysts provide the vegetative cells with fixed nitrogen. Intercellular molecular transfer has been traced with fluorescent markers, including calcein, 5-carboxyfluorescein, and the sucrose analogue esculin, which are observed to move down their concentration gradient. In this work, we used fluorescence recovery after photobleaching (FRAP assays in the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120 to measure the temperature dependence of intercellular transfer of fluorescent markers. We find that the transfer rate constants are directly proportional to the absolute temperature. This indicates that the “septal junctions” (formerly known as “microplasmodesmata” linking the cells in the filament allow molecular exchange by simple diffusion, without any activated intermediate state. This constitutes a novel mechanism for molecular transfer across the bacterial cytoplasmic membrane, in addition to previously characterized mechanisms for active transport and facilitated diffusion. Cyanobacterial septal junctions are functionally analogous to the gap junctions of metazoans.

  19. The Gap Within the Gap

    Directory of Open Access Journals (Sweden)

    Katherine Michelmore


    Full Text Available Gaps in educational achievement between high- and low-income children are growing. Administrative data sets maintained by states and districts lack information about income but do indicate whether a student is eligible for subsidized school meals. We leverage the longitudinal structure of these data sets to develop a new measure of economic disadvantage. Half of eighth graders in Michigan are eligible for a subsidized meal, but just 14% have been eligible for subsidized meals in every grade since kindergarten. These children score 0.94 standard deviations below those who are never eligible for meal subsidies and 0.23 below those who are occasionally eligible. There is a negative, linear relationship between grades spent in economic disadvantage and eighth-grade test scores. This is not an exposure effect; the relationship is almost identical in third-grade, before children have been exposed to varying years of economic disadvantage. Survey data show that the number of years that a child will spend eligible for subsidized lunch is negatively correlated with her or his current household income. Years eligible for subsidized meals can therefore be used as a reasonable proxy for income. Our proposed measure can be used to estimate heterogeneous effects in program evaluations, to improve value-added calculations, and to better target resources.

  20. Imaging of cervicothoracic junction trauma

    Directory of Open Access Journals (Sweden)

    Wongwaisayawan S


    Full Text Available Sirote Wongwaisayawan,1 Ruedeekorn Suwannanon,2 Rathachai Kaewlai11Department of Radiology, Ramathibodi Hospital and Mahidol University, Bangkok, Thailand; 2Department of Radiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, ThailandAbstract: Cervicothoracic junction trauma is an important cause of morbidity and mortality in trauma patients. Imaging has played an important role in identifying injuries and guiding appropriate, timely therapy. Computed tomography is currently a method of choice for diagnosing cervicothoracic junction trauma, in which the pattern of injuries often suggests possible mechanisms and potential injuries. In this article, the authors describe and illustrate common and uncommon injuries that can occur in the cervicothoracic junction.Keywords: cervicothoracic junction, cervical spine, trauma, imaging, radiology

  1. Josephson junctions with ferromagnetic interlayer

    Energy Technology Data Exchange (ETDEWEB)

    Wild, Georg Hermann


    We report on the fabrication of superconductor/insulator/ferromagnetic metal/superconductor (Nb/AlO{sub x}/Pd{sub 0.82}Ni{sub 0.18}/Nb) Josephson junctions (SIFS JJs) with high critical current densities, large normal resistance times area products, and high quality factors. For these junctions, a transition from 0- to {pi}-coupling is observed for a thickness d{sub F}=6 nm of the ferromagnetic Pd{sub 0.82}Ni{sub 0.18} interlayer. The magnetic field dependence of the critical current of the junctions demonstrates good spatial homogeneity of the tunneling barrier and ferromagnetic interlayer. Magnetic characterization shows that the Pd{sub 0.82}Ni{sub 0.18} has an out-of-plane anisotropy and large saturation magnetization indicating negligible dead layers at the interfaces. A careful analysis of Fiske modes up to about 400 GHz provides valuable information on the junction quality factor and the relevant damping mechanisms. Whereas losses due to quasiparticle tunneling dominate at low frequencies, at high frequencies the damping is explained by the finite surface resistance of the junction electrodes. High quality factors of up to 30 around 200 GHz have been achieved. They allow to study the junction dynamics, in particular the switching probability from the zero-voltage into the voltage state with and without microwave irradiation. The experiments with microwave irradiation are well explained within semi-classical models and numerical simulations. In contrast, at mK temperature the switching dynamics without applied microwaves clearly shows secondary quantum effects. Here, we could observe for the first time macroscopic quantum tunneling in Josephson junctions with a ferromagnetic interlayer. This observation excludes fluctuations of the critical current as a consequence of an unstable magnetic domain structure of the ferromagnetic interlayer and affirms the suitability of SIFS Josephson junctions for quantum information processing.

  2. Time Dependent Tunneling in Laser Irradiated Scanning Tunneling Microscope Junction (United States)

    Park, Sookyung Hur

    A principal motivation for the studies reported in this thesis was to obtain a theoretical explanation for the experimental results obtained by Nguyen et al. (1989) to determine the traversal time of an electron tunneling through a quantum mechanical barrier in a laser irradiated STM junction. The work therefore focused on the calculation of tunneling in a time-dependent oscillating barrier, and more specifically on the inelastic contributions to the tunneling current. To do so the kinetic formalism for tunneling was modified and extended to calculate inelastic processes in an irradiated tunneling junction. Furthermore, there is significant absorption of power from the laser beam in the junction electrodes resulting in thermal effects which can influence the tunneling. Extensive analysis of the spatial and temporal temperature distributions was first done for a realistic model of the diode emitter and anode using the Green function method. Specifically we considered (i) thermal effects due to surface heating of the absorbed laser radiation, (ii) the thermoelectric emf produced in the junction due to differential heating, and (iii) resistive and Thomson heat produced in the junction by laser induced currents. Using first-order time-dependent perturbation theory we also (iv) calculated the inelastic tunneling current due to a time dependent oscillating barrier produced by the antenna geometry of the STM junction. Lastly, we (v) formulated photo-assisted tunneling due to the electron -photon interaction in the junction using the second-quantization formalism. Although quite significant results were obtained for the tunneling current density as a function of frequency, gap distance and other junction parameters which gave insights into important features of the Nguyen et al. experiment (and tunneling characteristics of an irradiated STM in general), no single expression was derived or calculated results obtained which explains or fits all their observed data, or

  3. Junction formation during desiccation cracking. (United States)

    Toga, K B; Alaca, B Erdem


    In order to provide a sound physical basis for the understanding of the formation of desiccation crack networks, an experimental study is presented addressing junction formation. Focusing on junctions, basic features of the network determining the final pattern, provides an elemental approach and imparts conceptual clarity to the rather complicated problem of the evolution of crack patterns. Using coffee-water mixtures a clear distinction between junction formation during nucleation and propagation is achieved. It is shown that for the same drying suspension, one can switch from the well-known symmetric triple junctions that are unique to the nucleation phase to propagation junctions that are purely dictated by the variations of the stress state. In the latter case, one can even manipulate the path of a propagating crack in a deterministic fashion by changing the stress state within the suspension. Clear microscopic evidence is provided for the formation of propagation junctions, and material inhomogeneity is observed to be reflected by a broad distribution of angles, in stark contrast to shrinkage cracks in homogeneous solid films.

  4. Improving the efficiency of GaP LED's which emit green light (United States)

    Ladany, I.; Kressel, H.


    A study of techniques for preparing n-type material and junctions which yield the most consistent high diode efficiency values high lighted the role that Ga vacancies and/or associated defects play in reducing the green luminescent efficiency of n-type GaP. A useful method for obtaining good quality material was developed. It is shown that junction formation at high temperatures in a process where the n to p transition occurs without removing the substrate from the furnace yields devices superior to those obtained by diffusion or double epitaxy in the conventional manner previously used for GaP junction formation.

  5. Morphology of the cementoenamel junction of primary teeth. (United States)

    Francischone, Leda Aparecida; Consolaro, Alberto


    The purpose of this study was to investigate anatomically the cementoenamel junctions (CEJs) of primary teeth by observation of the morphological relationship among enamel, cementum, and dentin. One hundred five human extracted primary teeth were analyzed by scanning electron microscopy. The teeth were divided into 7 groups, each with 15 primary teeth, as follows: maxillary central incisors (group 1); maxillary lateral incisors (group 2); maxillary canines (group 3); maxillary molars (group 4); mandibular incisors (group 5); mandibular canines (group 6); and mandibular molars (group 7). The entire cervical region was analyzed, especially concerning regularity of the CEJ, for establishment of the type of enamel-cementum relationship (cementum over enamel, the edge-to-edge relationship between cementum and enamel, and presence of gaps with exposure of dentinal tubuli). All circumferences represented by CEJs exhibit an interchange and combination of 3 types of relationships: (1) cementum over enamel; (2) enamel and cementum in the edge-to-edge relationship; and (3) the presence of a gap between the enamel and cementum with dentin exposure. There was no predominance as to the dental groups. All primary teeth exhibited the 3 morphological tissue interrelation types along the circumference of the cementoenamel junction. The irregularity and fragility of cementoenamel junction structures indicate that this region is weak and should be handled with care and protected during application of chemicals and utilization of clamps, dental instruments, and restorative materials.

  6. Modelling of Dual-Junction Solar Cells including Tunnel Junction

    Directory of Open Access Journals (Sweden)

    Abdelaziz Amine


    Full Text Available Monolithically stacked multijunction solar cells based on III–V semiconductors materials are the state-of-art of approach for high efficiency photovoltaic energy conversion, in particular for space applications. The individual subcells of the multi-junction structure are interconnected via tunnel diodes which must be optically transparent and connect the component cells with a minimum electrical resistance. The quality of these diodes determines the output performance of the solar cell. The purpose of this work is to contribute to the investigation of the tunnel electrical resistance of such a multi-junction cell through the analysis of the current-voltage (J-V characteristics under illumination. Our approach is based on an equivalent circuit model of a diode for each subcell. We examine the effect of tunnel resistance on the performance of a multi-junction cell using minimization of the least squares technique.

  7. Design of thin InGaAsN(Sb) n-i-p junctions for use in four-junction concentrating photovoltaic devices (United States)

    Wilkins, Matthew M.; Gupta, James; Jaouad, Abdelatif; Bouzazi, Boussairi; Fafard, Simon; Boucherif, Abderraouf; Valdivia, Christopher E.; Arès, Richard; Aimez, Vincent; Schriemer, Henry P.; Hinzer, Karin


    Four-junction solar cells for space and terrestrial applications require a junction with a band gap of ˜1 eV for optimal performance. InGaAsN or InGaAsN(Sb) dilute nitride junctions have been demonstrated for this purpose, but in achieving the 14 mA/cm2 short-circuit current needed to match typical GaInP and GaAs junctions, the open-circuit voltage (VOC) and fill factor of these junctions are compromised. In multijunction devices incorporating materials with short diffusion lengths, we study the use of thin junctions to minimize sensitivity to varying material quality and ensure adequate transmission into lower junctions. An n-i-p device with 0.65-μm absorber thickness has sufficient short-circuit current, however, it relies less heavily on field-aided collection than a device with a 1-μm absorber. Our standard cell fabrication process, which includes a rapid thermal anneal of the contacts, yields a significant improvement in diffusion length and device performance. By optimizing a four-junction cell around a smaller 1-sun short-circuit current of 12.5 mA/cm2, we produced an InGaAsN(Sb) junction with open-circuit voltage of 0.44 V at 1000 suns (1 sun=100 mW/cm2), diode ideality factor of 1.4, and sufficient light transmission to allow >12.5 mA/cm2 in all four subcells.

  8. The exon junction complex differentially marks spliced junctions. (United States)

    Saulière, Jérôme; Haque, Nazmul; Harms, Scot; Barbosa, Isabelle; Blanchette, Marco; Le Hir, Hervé


    The exon junction complex (EJC), which is deposited onto mRNAs as a consequence of splicing, is involved in multiple post-transcriptional events in metazoa. Here, using Drosophila melanogaster cells, we show that only some introns trigger EJC-dependent nonsense-mediated mRNA decay and that EJC association with particular spliced junctions depends on RNA cis-acting sequences. This study provides the first evidence to our knowledge that EJC deposition is not constitutive but instead is a regulated process.

  9. The Dissolution of Double Holliday Junctions

    DEFF Research Database (Denmark)

    Bizard, Anna H; Hickson, Ian D


    as "double Holliday junction dissolution." This reaction requires the cooperative action of a so-called "dissolvasome" comprising a Holliday junction branch migration enzyme (Sgs1/BLM RecQ helicase) and a type IA topoisomerase (Top3/TopoIIIα) in complex with its OB (oligonucleotide/oligosaccharide binding......Double Holliday junctions (dHJS) are important intermediates of homologous recombination. The separate junctions can each be cleaved by DNA structure-selective endonucleases known as Holliday junction resolvases. Alternatively, double Holliday junctions can be processed by a reaction known...

  10. Occluding junctions of invertebrate epithelia. (United States)

    Jonusaite, Sima; Donini, Andrew; Kelly, Scott P


    Invertebrate diversity and architecture is immense. This is achieved by the organization and function of four tissue types found in most metazoan phyla-epithelial, connective, muscle and nervous tissue. Epithelial tissue is found in all extant animals (parazoan and metazoan alike). Epithelial cells form cellular sheets that cover internal or external surfaces and regulate the passage of material between separated compartments. The transepithelial movement of biological material between compartments can occur across the transcellular pathway (i.e. across cells) or the paracellular pathway (i.e. between cells) and the latter is regulated by occluding junctions that typically link cells in a subapical domain. In this review, information on occluding junctions of invertebrate epithelia is consolidated and discussed in the context of morphology, ultrastructure and physiology. In addition, an overview of what is currently known about invertebrate occluding junction proteins and their role in maintaining the integrity of invertebrate epithelia and regulating the barrier properties of these tissues is presented.

  11. Transport properties of molecular junctions

    CERN Document Server

    Zimbovskaya, Natalya A


    A comprehensive overview of the physical mechanisms that control electron transport and the characteristics of metal-molecule-metal (MMM) junctions is presented. As far as possible, methods and formalisms presented elsewhere to analyze electron transport through molecules are avoided. This title introduces basic concepts—a description of the electron transport through molecular junctions—and briefly describes relevant experimental methods. Theoretical methods commonly used to analyze the electron transport through molecules are presented. Various effects that manifest in the electron transport through MMMs, as well as the basics of density-functional theory and its applications to electronic structure calculations in molecules are presented. Nanoelectronic applications of molecular junctions and similar systems are discussed as well. Molecular electronics is a diverse and rapidly growing field. Transport Properties of Molecular Junctions presents an up-to-date survey of the field suitable for researchers ...

  12. Method of making semiconductor junctions (United States)

    James, R. B.


    A p-n junction on a silicon substrate doped with boron ions (d-dopant) is made in the following manner. A shallow silicon surface layer including a n-type dopant is first obtained by ion implantation of the substrate with arsenic atoms. The arsenic-doped silicon layer at the surface has a relatively low initial reflectivity. Then, radiation from a pulsed carbon dioxide laser is directed onto the doped surface. A portion of the pulsed radiation causes melting of the thin arsenic-doped layer at the solid surface, giving the shallow melted surface a reflectivity greater than the initial reflectivity of the solid surface. The increased reflectivity of the melted surface prevents an additional portion of the pulsed radiation from causing further melting, thus controlling the depth of melting. The melted surface is then allowed to cool and solidify to form a p-n junction at a thin (less than 200A) junction depth.

  13. O tabagismo está associado com a remodelação de junções comunicantes no coração de ratos: explicação do paradoxo dos fumantes? Smoking is associated with remodeling of gap junction in the rat heart: smoker's paradox explanation?

    Directory of Open Access Journals (Sweden)

    Rosangela Novo


    reperfusion. OBJECTIVE: Thus, this study aimed to analyze the effects of exposure to tobacco smoke on intensity, distribution or phosphorylation of connexin 43 in the rat heart. METHODS: Wistar rats weighing 100 g were randomly allocated into 2 groups: 1 Control (n = 25; 2 Exposed to tobacco smoke (ETS, n = 23. After 5 weeks, left ventricular morphometric analysis, immunohisthochemistry and western blotting for connexin 43 (Cx43 were performed. RESULTS: Collagen volume fraction, cross-sectional areas, and ventricular weight were not statistically different between control and ETS. ETS showed lower stain intensity of Cx43 at intercalated disks (Control: 2.32 ± 0.19; ETS: 1.73 ± 0.18; p = 0.04. The distribution of CX43 at intercalated disks did not differ between the groups (Control: 3.73 ± 0.12; ETS: 3.20 ± 0.17; p = 0.18. ETS rats showed higher levels of dephosphorylated form of Cx43 (Control: 0.45 ± 0.11; ETS: 0.90 ± 0.11; p = 0.03. On the other hand, total Cx43 did not differ between control and ETS groups (Control: 0.75 ± 0.19; ETS: 0.93 ± 0.27; p = 0.58. CONCLUSION: Exposure to tobacco smoke resulted in cardiac gap junction remodeling, characterized by alterations in the quantity and phosphorylation of the Cx43, in rats hearts. This finding could explain the smoker's paradox observed in some studies.

  14. Self assembled silicon nanowire Schottky junction assisted by collagen (United States)

    Stievenard, Didier; Sahli, Billel; Coffinier, Yannick; Boukherroub, Rabah; Melnyk, Oleg


    We present results on self assembled silicon nanowire Schottky junction assisted by collagen fibrous. The collagen is the principle protein of connective human tissues. It presents the double interest to be a low cost biological material with the possibility to be combed as the DNA molecule. First, the collagen was combed on OTS modified surface with gold electrodes. Second, silicon nanowires were grown on silicon substrate by CVD of silane gas (SiH4) at high temperature (500 C) using a vapor-liquid-solid (VLS) process and gold particles as catalysts. In order to increase electrostatic interaction between the collagen and the nanowires, these latters were chemically modified by mercaptopropylmethoxysilane (MPTS), then chemically oxidized. Therefore, the nanowires were transferred from their substrate into water and a drop of it deposited on the surface. Nanowires are only bound to collagen and in particular, in electrode gaps. The formation of spontaneous Schotkty junction is demonstrated by current-voltage characteristics.

  15. Gravitation at the Josephson Junction

    Directory of Open Access Journals (Sweden)

    Victor Atanasov


    Full Text Available A geometric potential from the kinetic term of a constrained to a curved hyperplane of space-time quantum superconducting condensate is derived. An energy conservation relation involving the geometric field at every material point in the superconductor is demonstrated. At a Josephson junction the energy conservation relation implies the possibility of transforming electric energy into geometric field energy, that is, curvature of space-time. Experimental procedures to verify that the Josephson junction can act as a voltage-to-curvature converter are discussed.

  16. Voltage tunable differential heterodyne spectroscopy in the far-infrared with Josephson junctions (United States)

    Ulrich, B. T.


    The basic methods of differential heterodyne spectroscopy with Josephson junctions are described. A technique is outlined for bridging the gap between a local oscillator frequency and a signal frequency through the use of a voltage-tunable internal oscillation frequency in a Josephson junction structure. It is shown that an intermediate frequency can be converted to a conveniently low frequency by double frequency conversion carried out directly in a Josephson junction. The expected conversion efficiency is estimated qualitatively. Experiments are discussed in which the differential heterodyne frequency-conversion technique was demonstrated at a wavelength of 0.4 mm and a voltage-tunable oscillation in a double Josephson junction structure was observed, with oscillation line widths as narrow as 0.5 Hz, for a resistance of 3.3 nanohms and an estimated inductance of the order of 1 nH.

  17. Tunneling nanotubes and gap junctions–their role in long-range intercellular communication during development, health, and disease conditions

    NARCIS (Netherlands)

    Ariazi, J. (Jennifer); Benowitz, A. (Andrew); De Biasi, V. (Vern); M.L. den Boer (Monique); Cherqui, S. (Stephanie); Cui, H. (Haifeng); Douillet, N. (Nathalie); Eugenin, E.A. (Eliseo A.); Favre, D. (David); Goodman, S. (Spencer); Gousset, K. (Karine); Hanein, D. (Dorit); Israel, D.I. (David I.); Kimura, S. (Shunsuke); Kirkpatrick, R.B. (Robert B.); Kuhn, N. (Nastaran); Jeong, C. (Claire); Lou, E. (Emil); Mailliard, R. (Robbie); Maio, S. (Stephen); Okafo, G. (George); Osswald, M. (Matthias); Pasquier, J. (Jennifer); R. Polak (Roel); Pradel, G. (Gabriele); B. de Rooij (Bob); Schaeffer, P. (Peter); Skeberdis, V.A. (Vytenis A.); Smith, I.F. (Ian F.); Tanveer, A. (Ahmad); Volkmann, N. (Niels); Wu, Z. (Zhenhua); Zurzolo, C. (Chiara)


    textabstractCell-to-cell communication is essential for the organization, coordination, and development of cellular networks and multi-cellular systems. Intercellular communication is mediated by soluble factors (including growth factors, neurotransmitters, and cytokines/chemokines), gap junctions,

  18. Renormalization-group calculations of ground-state and transport properties of ultrasmall tunnel junctions

    DEFF Research Database (Denmark)

    Frota, H.O.; Flensberg, Karsten


    We have done a numerical renormalization-group calculation for a Hamiltonian modeling charging effect in ultrasmall tunnel junctions. We find that the conductance is enhanced by the quantum charge fluctuations allowing tunneling below the charging energy gap. However, in all cases the conductance...

  19. Tunneling Nanotubes and Gap Junctions–Their Role in Long-Range Intercellular Communication during Development, Health, and Disease Conditions


    Jennifer Ariazi; Andrew Benowitz; Vern De Biasi; den Boer, Monique L.; Stephanie Cherqui; Haifeng Cui; Nathalie Douillet; Eugenin, Eliseo A.; David Favre; Spencer Goodman; Karine Gousset; Dorit Hanein; Israel, David I.; Shunsuke Kimura; Kirkpatrick, Robert B.


    textabstractCell-to-cell communication is essential for the organization, coordination, and development of cellular networks and multi-cellular systems. Intercellular communication is mediated by soluble factors (including growth factors, neurotransmitters, and cytokines/chemokines), gap junctions, exosomes and recently described tunneling nanotubes (TNTs). It is unknown whether a combination of these communication mechanisms such as TNTs and gap junctions may be important, but further resear...

  20. Current noise in tunnel junctions

    Energy Technology Data Exchange (ETDEWEB)

    Frey, Moritz; Grabert, Hermann [Physikalisches Institut, Universitaet Freiburg, Hermann-Herder-Strasse 3, 79104, Freiburg (Germany)


    We study current fluctuations in tunnel junctions driven by a voltage source. The voltage is applied to the tunneling element via an impedance providing an electromagnetic environment of the junction. We use circuit theory to relate the fluctuations of the current flowing in the leads of the junction with the voltage fluctuations generated by the environmental impedance and the fluctuations of the tunneling current. The spectrum of current fluctuations is found to consist of three parts: a term arising from the environmental Johnson-Nyquist noise, a term due to the shot noise of the tunneling current and a third term describing the cross-correlation between these two noise sources. Our phenomenological theory reproduces previous results based on the Hamiltonian model for the dynamical Coulomb blockade and provides a simple understanding of the current fluctuation spectrum in terms of circuit theory and properties of the average current. Specific results are given for a tunnel junction driven through a resonator. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. Josephson tunnel junction microwave attenuator

    DEFF Research Database (Denmark)

    Koshelets, V. P.; Shitov, S. V.; Shchukin, A. V.


    A new element for superconducting electronic circuitry-a variable attenuator-has been proposed, designed, and successfully tested. The principle of operation is based on the change in the microwave impedance of a superconductor-insulator-superconductor (SIS) Josephson tunnel junction when dc bias...

  2. Dynamics of pi-junction interferometer circuits

    DEFF Research Database (Denmark)

    Kornkev, V.K.; Mozhaev, P.B.; Borisenko, I.V.


    The pi-junction superconducting circuit dynamics was studied by means of numerical simulation technique. Parallel arrays consisting of Josephson junctions of both 0- and pi-type were studied as a model of high-T-c grain-boundary Josephson junction. The array dynamics and the critical current...... dependence on magnetic field are discussed. Experimental results for dc interferometers with 0 and pi high-T-c bi-crystal Josephson junctions are reported and discussed in comparison with numerical simulation....

  3. delta-biased Josephson tunnel junctions

    DEFF Research Database (Denmark)

    Monaco, R.; Mygind, Jesper; Koshelet, V.


    Abstract: The behavior of a long Josephson tunnel junction drastically depends on the distribution of the dc bias current. We investigate the case in which the bias current is fed in the central point of a one-dimensional junction. Such junction configuration has been recently used to detect...

  4. Modelling and Analysis of Long Josephson Junctions

    NARCIS (Netherlands)

    Visser, T.P.P.


    For various reasons people have been interested in Josephson junctions. Ranging from "understanding nature" to building quantum computers. In this thesis we focus on a special type of junction (the long junction) and to a special type of problem fluxon dynamics.

  5. Stability of large-area molecular junctions

    NARCIS (Netherlands)

    Akkerman, Hylke B.; Kronemeijer, Auke J.; Harkema, Jan; van Hal, Paul A.; Smits, Edsger C. P.; de Leeuw, Dago M.; Blom, Paul W. M.

    The stability of molecular junctions is crucial for any application of molecular electronics. Degradation of molecular junctions when exposed to ambient conditions is regularly observed. In this report the stability of large-area molecular junctions under ambient conditions for more than two years

  6. Soliton bunching in annular Josephson junctions

    DEFF Research Database (Denmark)

    Vernik, I.V; Lazarides, Nickos; Sørensen, Mads Peter


    By studying soliton (fluxon) motion in long annular Josephson junctions it is possible to avoid the influence of the boundaries and soliton-soliton collisions present in linear junctions. A new experimental design consisting of a niobium coil placed on top of an annular junction has been used to ...

  7. All NbN tunnel junction fabrication (United States)

    Leduc, H. G.; Khanna, S. K.; Stern, J. A.


    The development of SIS tunnel junctions based on NbN for mixer applications in the submillimeter range is reported. The unique technological challenges inherent in the development of all refractory-compound superconductor-based tunnel junctions are highlighted. Current deposition and fabrication techniques are discussed, and the current status of all-NbN tunnel junctions is reported.

  8. Fabrication and properties of Nb/Al, Alox/Nb Josephson tunnel junctions with a double-oxide barrier (United States)

    Houwman, E. P.; Veldhuis, D.; Flokstra, J.; Rogalla, H.


    High-quality Nb/Al, Alox/Nb Josephson tunnel junctions using double-oxide layers as barriers have been fabricated. The critical current density is controlled by the thickness of the second Al layer. This layer has to be oxidized completely through in order to obtain high-quality junctions. Typically, gap voltages of 2.8-3.0 mV and Vm up to 70 mV at 4.2 K were obtained.

  9. Coherent quantum trasport in ferromagnet-superconductor-ferromagnet graphene junctions

    Directory of Open Access Journals (Sweden)

    M Salehi


    Full Text Available In this paper, we investigate the coherent quantum transport in grapheme-based ferromagnet-superconductor-ferromagent junctions within the framework of BCS theory using DBdG quasiparticles equation .The coherency with the finite size of superconductor region has two characteristic features subgap electron transport and oscillations of differential conductance. we show that periodic vanishing of the Andreev reflection at the energies called geometrical resonances above the superconducting gap is a striking consequence of quasiparticles interference. We suggest to make devices that produce polarized spin-current with possible applications in spintronics.

  10. Mechanics of Fluid-Filled Interstitial Gaps. II. Gap Characteristics in Xenopus Embryonic Ectoderm. (United States)

    Barua, Debanjan; Parent, Serge E; Winklbauer, Rudolf


    The ectoderm of the Xenopus embryo is permeated by a network of channels that appear in histological sections as interstitial gaps. We characterized this interstitial space by measuring gap sizes, angles formed between adjacent cells, and curvatures of cell surfaces at gaps. From these parameters, and from surface-tension values measured previously, we estimated the values of critical mechanical variables that determine gap sizes and shapes in the ectoderm, using a general model of interstitial gap mechanics. We concluded that gaps of 1-4 μm side length can be formed by the insertion of extracellular matrix fluid at three-cell junctions such that cell adhesion is locally disrupted and a tension difference between cell-cell contacts and the free cell surface at gaps of 0.003 mJ/m2 is generated. Furthermore, a cell hydrostatic pressure of 16.8 ± 1.7 Pa and an interstitial pressure of 3.9 ± 3.6 Pa, relative to the central blastocoel cavity of the embryo, was found to be consistent with the observed gap size and shape distribution. Reduction of cell adhesion by the knockdown of C-cadherin increased gap volume while leaving intracellular and interstitial pressures essentially unchanged. In both normal and adhesion-reduced ectoderm, cortical tension of the free cell surfaces at gaps does not return to the high values characteristic of the free surface of the whole tissue. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. Octagonal Defects at Carbon Nanotube Junctions

    Directory of Open Access Journals (Sweden)

    W. Jaskólski


    Full Text Available We investigate knee-shaped junctions of semiconductor zigzag carbon nanotubes. Two dissimilar octagons appear at such junctions; one of them can reconstruct into a pair of pentagons. The junction with two octagons presents two degenerate localized states at Fermi energy (EF. The reconstructed junction has only one state near EF, indicating that these localized states are related to the octagonal defects. The inclusion of Coulomb interaction splits the localized states in the junction with two octagons, yielding an antiferromagnetic system.

  12. Molecular series-tunneling junctions. (United States)

    Liao, Kung-Ching; Hsu, Liang-Yan; Bowers, Carleen M; Rabitz, Herschel; Whitesides, George M


    Charge transport through junctions consisting of insulating molecular units is a quantum phenomenon that cannot be described adequately by classical circuit laws. This paper explores tunneling current densities in self-assembled monolayer (SAM)-based junctions with the structure Ag(TS)/O2C-R1-R2-H//Ga2O3/EGaIn, where Ag(TS) is template-stripped silver and EGaIn is the eutectic alloy of gallium and indium; R1 and R2 refer to two classes of insulating molecular units-(CH2)n and (C6H4)m-that are connected in series and have different tunneling decay constants in the Simmons equation. These junctions can be analyzed as a form of series-tunneling junctions based on the observation that permuting the order of R1 and R2 in the junction does not alter the overall rate of charge transport. By using the Ag/O2C interface, this system decouples the highest occupied molecular orbital (HOMO, which is localized on the carboxylate group) from strong interactions with the R1 and R2 units. The differences in rates of tunneling are thus determined by the electronic structure of the groups R1 and R2; these differences are not influenced by the order of R1 and R2 in the SAM. In an electrical potential model that rationalizes this observation, R1 and R2 contribute independently to the height of the barrier. This model explicitly assumes that contributions to rates of tunneling from the Ag(TS)/O2C and H//Ga2O3 interfaces are constant across the series examined. The current density of these series-tunneling junctions can be described by J(V) = J0(V) exp(-β1d1 - β2d2), where J(V) is the current density (A/cm(2)) at applied voltage V and βi and di are the parameters describing the attenuation of the tunneling current through a rectangular tunneling barrier, with width d and a height related to the attenuation factor β.

  13. Valley and spin resonant tunneling current in ferromagnetic/nonmagnetic/ferromagnetic silicene junction

    Directory of Open Access Journals (Sweden)

    Yaser Hajati


    Full Text Available We study the transport properties in a ferromagnetic/nonmagnetic/ferromagnetic (FNF silicene junction in which an electrostatic gate potential, U, is attached to the nonmagnetic region. We show that the electrostatic gate potential U is a useful probe to control the band structure, quasi-bound states in the nonmagnetic barrier as well as the transport properties of the FNF silicene junction. In particular, by introducing the electrostatic gate potential, both the spin and valley conductances of the junction show an oscillatory behavior. The amplitude and frequency of such oscillations can be controlled by U. As an important result, we found that by increasing U, the second characteristic of the Klein tunneling is satisfied as a result of the quasiparticles chirality which can penetrate through a potential barrier. Moreover, it is found that for special values of U, the junction shows a gap in the spin and valley-resolve conductance and the amplitude of this gap is only controlled by the on-site potential difference, Δz. Our findings of high controllability of the spin and valley transport in such a FNF silicene junction may improve the performance of nano-electronics and spintronics devices.

  14. Mechanics of Fluid-Filled Interstitial Gaps. I. Modeling Gaps in a Compact Tissue. (United States)

    Parent, Serge E; Barua, Debanjan; Winklbauer, Rudolf


    Fluid-filled interstitial gaps are a common feature of compact tissues held together by cell-cell adhesion. Although such gaps can in principle be the result of weak, incomplete cell attachment, adhesion is usually too strong for this to occur. Using a mechanical model of tissue cohesion, we show that, instead, a combination of local prevention of cell adhesion at three-cell junctions by fluidlike extracellular material and a reduction of cortical tension at the gap surface are sufficient to generate stable gaps. The size and shape of these interstitial gaps depends on the mechanical tensions between cells and at gap surfaces, and on the difference between intracellular and interstitial pressures that is related to the volume of the interstitial fluid. As a consequence of the dependence on tension/tension ratios, the presence of gaps does not depend on the absolute strength of cell adhesion, and similar gaps are predicted to occur in tissues of widely differing cohesion. Tissue mechanical parameters can also vary within and between cells of a given tissue, generating asymmetrical gaps. Within limits, these can be approximated by symmetrical gaps. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  15. Seebeck effect in molecular junctions. (United States)

    Zimbovskaya, Natalya A


    Advances in the fabrication and characterization of nanoscale systems presently allow for a better understanding of their thermoelectric properties. As is known, the building blocks of thermoelectricity are the Peltier and Seebeck effects. In the present work we review results of theoretical studies of the Seebeck effect in single-molecule junctions and similar systems. The behavior of thermovoltage and thermopower in these systems is controlled by several factors including the geometry of molecular bridges, the characteristics of contacts between the bridge and the electrodes, the strength of the Coulomb interactions between electrons on the bridge, and of electron-phonon interactions. We describe the impact of these factors on the thermopower. Also, we discuss a nonlinear Seebeck effect in molecular junctions.

  16. Full range of proximity effect probed with superconductor/graphene/superconductor junctions (United States)

    Li, Chuan; Guéron, S.; Chepelianskii, A.; Bouchiat, H.


    The high tunability of the density of states of graphene makes it an ideal probe of quantum transport in different regimes. In particular, the supercurrent that can flow through a nonsuperconducting (N) material connected to two superconducting (S) electrodes, crucially depends on the length of the N relative to the superconducting coherence length. Using graphene as the N material we have investigated the full range of the superconducting proximity effect, from short to long diffusive junctions. By combining several S/graphene/S samples with different contacts and lengths, and measuring their gate-dependent critical currents (Ic) and normal state resistance RN, we compare the product e RNIc to the relevant energies, the Thouless energy in long junctions and the superconducting gap of the contacts in short junctions, over three orders of magnitude of Thouless energy. The experimental variations strikingly follow a universal law, close to the predictions of the proximity effect both in the long and short junction regime, as well as in the crossover region, thereby revealing the interplay of the different energy scales. Differences in the numerical coefficients reveal the crucial role played by the interfacial barrier between graphene and the superconducting electrodes, which reduces the supercurrent in both short and long junctions. Surprisingly, the reduction of supercurrent is independent of the gate voltage and of the nature of the electrodes. A reduced induced gap and Thouless energy are extracted, revealing the role played by the dwell time in the barrier in the short junction, and an effective increased diffusion time in the long junction. We compare our results to the theoretical predictions of Usadel equations and numerical simulations, which better reproduce experiments with imperfect NS interfaces.

  17. Dynamics of fractional vortices in long Josephson junctions; Dynamik fraktionaler Flusswirbel in langen Josephsonkontakten

    Energy Technology Data Exchange (ETDEWEB)

    Gaber, Tobias


    In this thesis static and dynamic properties of fractional vortices in long Josephson junctions are investigated. Fractional vortices are circulating supercurrents similar to the well-known Josephson fluxons. Yet, they show the distinguishing property of carrying only a fraction of the magnetic flux quantum. Fractional vortices are interesting non-linear objects. They spontaneously appear and are pinned at the phase discontinuity points of so called 0-{kappa} junctions but can be bend or flipped by external forces like bias currents or magnetic fields. 0-{kappa} junctions and fractional vortices are generalizations of the well-known 0-{pi} junctions and semifluxons, where not only phase jumps of pi but arbitrary values denoted by kappa are considered. By using so-called artificial 0-{kappa} junctions that are based on standard Nb-AlO{sub x}-Nb technology the classical dynamics of fractional vortices has been investigated experimentally for the very first time. Here, half-integer zero field steps could be observed. These voltage steps on the junction's current-voltage characteristics correspond to the periodic flipping/hopping of fractional vortices. In addition, the oscillatory eigenmodes of fractional vortices were investigated. In contrast to fluxons fractional vortices have an oscillatory eigenmode with a frequency within the plasma gap. Using resonance spectroscopy the dependence of the eigenmode frequency on the flux carried by the vortex and an applied bias current was determined. (orig.)

  18. Nanofluidic transport in branching nanochannels: a molecular sieve based on Y-junction nanotubes. (United States)

    Liu, Ling; Chen, Xi


    Using molecular dynamics (MD) simulations, we study the fundamental partitioning and screening behaviors of nanofluids confined in Y-junction nanochannels, and demonstrate their feasibility as efficient molecular sieves. A flow of gas or liquid molecules is partitioned at the junction and separated into the two side branches with different volume fractions. The opening gaps of the side branches are manipulated, and the sieve characteristics are explored as the gas phase, mixture composition/ratio, and opening dimensions are varied. The studies provide design principles for a molecular sieve with maximum probability passing one type of molecule into a screening branch, and meanwhile maximizing the rejection rate of other types of molecules.

  19. Efficient density matrix renormalization group algorithm to study Y junctions with integer and half-integer spin

    KAUST Repository

    Kumar, Manoranjan


    An efficient density matrix renormalization group (DMRG) algorithm is presented and applied to Y junctions, systems with three arms of n sites that meet at a central site. The accuracy is comparable to DMRG of chains. As in chains, new sites are always bonded to the most recently added sites and the superblock Hamiltonian contains only new or once renormalized operators. Junctions of up to N=3n+1≈500 sites are studied with antiferromagnetic (AF) Heisenberg exchange J between nearest-neighbor spins S or electron transfer t between nearest neighbors in half-filled Hubbard models. Exchange or electron transfer is exclusively between sites in two sublattices with NA≠NB. The ground state (GS) and spin densities ρr=⟨Szr⟩ at site r are quite different for junctions with S=1/2, 1, 3/2, and 2. The GS has finite total spin SG=2S(S) for even (odd) N and for MG=SG in the SG spin manifold, ρr>0(<0) at sites of the larger (smaller) sublattice. S=1/2 junctions have delocalized states and decreasing spin densities with increasing N. S=1 junctions have four localized Sz=1/2 states at the end of each arm and centered on the junction, consistent with localized states in S=1 chains with finite Haldane gap. The GS of S=3/2 or 2 junctions of up to 500 spins is a spin density wave with increased amplitude at the ends of arms or near the junction. Quantum fluctuations completely suppress AF order in S=1/2 or 1 junctions, as well as in half-filled Hubbard junctions, but reduce rather than suppress AF order in S=3/2 or 2 junctions.

  20. Simultaneous quasiparticle and Josephson tunneling in BSCCO-2212 break junctions.

    Energy Technology Data Exchange (ETDEWEB)

    Ozyuzer, L.


    Tunneling measurements are reported for superconductor-insulator-superconductor (SIS) break junctions on underdoped, optimally-doped, and overdoped single crystals of Bi{sub 2}Sr{sub 2}CaCu{sub 2}O{sub 8+{delta}} (Bi-2212). The junction I-V characteristics exhibit well-defined quasiparticle current jumps at eV = 2A as well as hysteretic Josephson currents. The quasiparticle branch has been analyzed in the framework of d{sub x{sup 2}-y{sup 2}} (d-wave) superconductivity and indicates that there is preferential tunneling along the lobe directions of the d-wave gap. For overdoped Bi-2212 with T{sub c} = 62 K, the Josephson current is measured as a function of junction resistance, R{sub n}, which varied by two orders of magnitude (1 k{Omega} to 100 k{Omega}). I{sub c}R{sub n} product is proportional to the 0.47 power of I{sub c} and displays a maximum of 7.0 mV. When the hole doping is decreased from overdoped (T{sub c} = 62 K) to the underdoped regime (T{sub c} = 70 K), the average I{sub c}R{sub n} product increases as does the quasiparticle gap. The maximum I{sub c}R{sub n} is {approximately} 40% of the {Delta}/e at each doping level, with a value as high as 25 mV in underdoped Bi-2212.

  1. Cavity syncronisation of underdamped Josephson junction arrays

    DEFF Research Database (Denmark)

    Barbara, P.; Filatrella, G.; Lobb, C.


    Our recent experiments show that arrays of underdamped Josephson junctions radiate coherently only above a threshold number of junctions switched onto the radiating state. For each junction, the radiating state is a resonant step in the current-voltage characteristics due to the interaction between...... the junctions in the array and an electromagnetic cavity. Here we show that a model of a one-dimensional array of Josephson junctions coupled to a resonator can produce many features of the coherent be havior above threshold, including coherent radiation of power and the shape of the array current......-voltage characteristic. The model also makes quantitative predictions about the degree of coherence of the junctions in the array. However, in this model there is no threshold; the experimental below-threshold region behavior could not be reproduced....

  2. Loss models for long Josephson junctions

    DEFF Research Database (Denmark)

    Olsen, O. H.; Samuelsen, Mogens Rugholm


    A general model for loss mechanisms in long Josephson junctions is presented. An expression for the zero-field step is found for a junction of overlap type by means of a perturbation method. Comparison between analytic solution and perturbation result shows good agreement.......A general model for loss mechanisms in long Josephson junctions is presented. An expression for the zero-field step is found for a junction of overlap type by means of a perturbation method. Comparison between analytic solution and perturbation result shows good agreement....

  3. Superconducting quantum interference devices with graphene junctions (United States)

    Thompson, Michael; Prance, Jonathan; Haley, Richard; Pashkin, Yuri; Ben Shalom, Moshe; Fal'Ko, Vladimir; Matthews, Anthony; White, Jeremy; Viznichenko, Roman; Melhem, Ziad

    We present measurements of DC superconducting quantum interference devices based on Nb/graphene/Nb Josephson junctions. The superconducting proximity effect in graphene can be used to build Josephson junctions whose critical current can be controlled by field-effect gates. These junctions combine the tunability of semiconductor Josephson junctions with the high critical currents and low contact resistances of metal SNS junctions. By using local gates, the SQUID junction critical currents can be modified individually and this allows the sensitivity and symmetry of the SQUID to be controlled in-situ. We compare the critical current of the SQUID with simulations that include a non-sinusoidal current phase relation in the junctions, as expected for ballistic graphene junctions. We also investigate the transfer function of the device in both symmetric and asymmetric configurations and find a highest transfer function of 300 μV/Φ0. Graphene Josephson junctions have the potential to add functionality to existing technologies; for example, to make SQUID magnetometers with tunable sensitivity or superconducting qubits with fast electrical control.

  4. Connexin40 correlates with oxidative stress in brains of traumatic brain injury rats. (United States)

    Chen, Wei; Guo, Yijun; Yang, Wenjin; Zheng, Ping; Zeng, Jinsong; Tong, Wusong


    Oxidative stress is an important factor in the pathophysiologic changes after traumatic brain injury (TBI). Connexin43 (Cx43) was reported to contribute to cerebral damage. However, the impacts of Cx40 have not been investigated in detail. In the present study, we hypothesized that Cx40 was involved in oxidative stress-induced brain injury after TBI. The controlled cortical impact (CCI) model was introduced to Wistar rats as a TBI model. Neurological deficits, oxidative stress and Cx40 were evaluated in TBI rats and N-acetylcysteine (NAC)-treated TBI rats. Neurological severity score (NSS) was used to assess neurological deficits. Brain infarction was measured by histo-staining. Brain edema was evaluated by measuring the brain water content. Cortex samples were collected to measure the tissue levels of malonyldialdehyde (MDA), nitric oxide (NO) and glutathione (GSH) and NADPH oxidase activity. Cx40 expression was determined by Western-blot. TBI-induced brain injuries gradually increased from 6 h to 24 h post CCI, and the severity remained till 72 h. The level of oxidative stress was consistent with the extent of neurological deficits. Cx40 was upregulated after TBI in a linear correlated manner with increased oxidative stress. With NAC intervention, both neurological deficits and oxidative stress were significantly attenuated. Meanwhile, elevated Cx40 expression in cortex was also prevented by NAC treatment. These studies revealed the relationship between levels of Cx40 and oxidative stress after TBI. The cortex Cx40 expression was positively correlated with the cerebral oxidative stress, indicating the involvement of Cx40 in the progress of brain damage.

  5. Role of Connexin40 in the autoregulatory response of the afferent arteriole

    DEFF Research Database (Denmark)

    Sørensen, Charlotte Mehlin; Giese, Isaiah; Braunstein, Thomas Hartig


    in the regulation of renin secretion. We investigated the effect of deleting the Cx40 gene on autoregulation of afferent arteriolar diameter in response to acute changes in renal perfusion pressure. The experiments were performed using the isolated blood perfused juxtamedullary nephron preparation in kidneys...... obtained from wild type or Cx40 knockout mice. Renal perfusion pressure was increased in steps from 75 mm Hg to 155 mm Hg and the response in afferent arteriolar diameter was measured. Hereafter a papillectomy was performed to inhibit TGF and the pressure steps were repeated. Conduction of intercellular Ca......(2+) changes in response to local electrical stimulation was examined in isolated interlobular arteries and afferent arterioles from wild type or Cx40 knockout mice. Cx40 knockout mice had an impaired autoregulatory response to acute changes in renal perfusion pressure compared to wild type mice...

  6. Influence of Connexin40 on the renal myogenic response in murine afferent arterioles

    DEFF Research Database (Denmark)

    Jacobsen, Jens Christian Brings; Sørensen, Charlotte Mehlin


    Renal autoregulation consists of two main mechanisms; the myogenic response and the tubuloglomerular feedback mechanism (TGF). Increases in renal perfusion pressure activate both mechanisms causing a reduction in diameter of the afferent arteriole (AA) resulting in stabilization of the glomerular...

  7. Gap and density theorems

    CERN Document Server

    Levinson, N


    A typical gap theorem of the type discussed in the book deals with a set of exponential functions { \\{e^{{{i\\lambda}_n} x}\\} } on an interval of the real line and explores the conditions under which this set generates the entire L_2 space on this interval. A typical gap theorem deals with functions f on the real line such that many Fourier coefficients of f vanish. The main goal of this book is to investigate relations between density and gap theorems and to study various cases where these theorems hold. The author also shows that density- and gap-type theorems are related to various propertie

  8. Bridging the Gap

    DEFF Research Database (Denmark)

    Kramer Overgaard, Majken; Broeng, Jes; Jensen, Monika Luniewska

    Bridging the Gap (BtG) is a 2-year project funded by The Danish Industry Foundation. The goal of Bridging the Gap has been to create a new innovation model which will increase the rate at which Danish universities can spinout new technology ventures.......Bridging the Gap (BtG) is a 2-year project funded by The Danish Industry Foundation. The goal of Bridging the Gap has been to create a new innovation model which will increase the rate at which Danish universities can spinout new technology ventures....

  9. Junction-temperature estimation in AlGaInP light-emitting diodes using the luminescence spectra method (United States)

    Jing, Wen; Yumei, Wen; Ping, Li; Sanshan, Wang


    This study proposes a practical method to estimate the junction temperature of AlGaInP LEDs using the luminescence spectra method. The peak wavelength shift of LEDs is due to the energy band gap shrinking. The temperature dependence of the bandgap of AlGaInP LEDs is derived from those of the underlying binary compounds AlP, GaP, and InP. Based on this, a theoretical model for the dependence of the peak wavelength on junction temperature is developed. Experimental results on the junction temperature of AlGaInP red light-emitting diodes are presented. Excellent agreement between the theoretical and experimental temperature dependence of the peak wavelength is found. Project supported by the National Natural Science Foundation of China (No. 61006053).

  10. Bridge the Gap

    DEFF Research Database (Denmark)

    Marselis, Randi Lorenz


    This article focuses on photo projects organised for teenage refugees by the Society for Humanistic Photography (Berlin, Germany). These projects, named Bridge the Gap I (2015), and Bridge the Gap II (2016), were carried out in Berlin and brought together teenagers with refugee and German...

  11. Multiplication in Silicon p-n Junctions

    DEFF Research Database (Denmark)

    Moll, John L.


    Multiplication values were measured in the collector junctions of silicon p-n-p and n-p-n transistors before and after bombardment by 1016 neutrons/cm2. Within experimental error there was no change either in junction fields, as deduced from capacitance measurements, or in multiplication values...

  12. Some properties of Cosmic String Junctions (United States)

    Karouby, Johanna


    Cosmic strings are linear concentrations of energy of macroscopic size. Since cosmic superstrings can form junctions, observing them would give some support to string theory. In the following, we study the lensing cosmic string junctions create, the shift in photons' wavelength passing through (leading to the Kaiser-Stebbins effect), and the gravitational radiation they emit.

  13. Coherent diffusive transport mediated by Andreev reflections at V=Delta/e in a mesoscopic superconductor/semiconductor/superconductor junction

    DEFF Research Database (Denmark)

    Kutchinsky, Jonatan; Taboryski, Rafael Jozef; Kuhn, Oliver


    We present experiments revealing a singularity in the coherent current across a superconductor/semiconductor/superconductor (SSmS) junction at the bias voltage corresponding to the superconducting energy gap V=Delta/e. The SSmS structure consists of highly doped GaAs with superconducting electrod...

  14. Josephson junctions and DC SQUIDS based on Nb/Al technology. (United States)

    Flokstra, J; Adelerhof, D J; Houwman, E P; Veldhuis, D; Rogalla, H


    A process for fabricating high-quality Josephson junctions and DC SQUIDs on basis of Nb/Al technology has been developed. DC magnetron sputtering is used for the deposition of the metal layers and the barrier is formed by thermal oxidation of the Al-layer. The junction area of 5 microns x 5 microns is obtained using anodisation. Three types of Josephson tunnel junctions have been prepared: standard Nb/Al, AlO kappa/Nb, symmetric Nb/Al, AlO kappa, Al/Nb and Nb/Al, AlO kappa/AlO kappa/Nb, the latter having a double oxide layer. We performed current-voltage and conductance-voltage measurements at different temperatures and special attention was paid to the noise behaviour. Gap and sub-gap parameters as well as barrier parameters are presented. Three different DC SQUID configurations were developed on basis of the Nb/Al Josephson junctions. The measured characteristics of the standard Tesche-Clarke DC SQUID, the resistively shunted SQUID and the inductively shunted SQUID are compared with special attention being paid to the noise properties. A 19-channel DC SQUID magnetometer with standard and/or resistively-shunted DC SQUIDs is under construction.

  15. Connexins and M3 Muscarinic Receptors Contribute to Heterogeneous Ca2+ Signaling in Mouse Aortic Endothelium

    Directory of Open Access Journals (Sweden)

    François-Xavier Boittin


    Full Text Available Background/Aims: Smooth muscle tone is controlled by Ca2+ signaling in the endothelial layer. Mouse endothelial cells are interconnected by gap junctions made of Connexin40 (Cx40 and Cx37, which allow the exchange of signaling molecules to coordinate their activity. Here, we investigated the role of Cx40 in the endothelial Ca2+ signaling of the mouse aorta. Methods: Ca2+ imaging was performed on intact aortic endothelium from both wild type (Cx40+/+ and Connexin40-deficient (Cx40 -/- mice. Results: Acetylcholine (ACh induced early fast and high amplitude Ca2+ transients in a fraction of endothelial cells expressing the M3 muscarinic receptors. Inhibition of intercellular communication using carbenoxolone or octanol fully blocked the propagation of ACh-induced Ca2+ transients toward adjacent cells in WT and Cx40-/- mice. As compared to WT, Cx40-/- mice displayed a reduced propagation of ACh-induced Ca2+ waves, indicating that Cx40 contributes to the spreading of Ca2+ signals. The propagation of those Ca2+ responses was not blocked by suramin, a blocker of purinergic ATP receptors, indicating that there is no paracrine effect of ATP release on the Ca2+ waves. Conclusions: Altogether our data show that Cx40 and Cx37 contribute to the propagation and amplification of the Ca2+ signaling triggered by ACh in endothelial cells expressing the M3 muscarinic receptors.

  16. An optimized efficient dual junction InGaN/CIGS solar cell: A numerical simulation (United States)

    Farhadi, Bita; Naseri, Mosayeb


    The photovoltaic performance of an efficient double junction InGaN/CIGS solar cell including a CdS antireflector top cover layer is studied using Silvaco ATLAS software. In this study, to gain a desired structure, the different design parameters, including the CIGS various band gaps, the doping concentration and the thickness of CdS layer are optimized. The simulation indicates that under current matching condition, an optimum efficiency of 40.42% is achieved.

  17. Solar energy converters based on multi-junction photoemission solar cells. (United States)

    Tereshchenko, O E; Golyashov, V A; Rodionov, A A; Chistokhin, I B; Kislykh, N V; Mironov, A V; Aksenov, V V


    Multi-junction solar cells with multiple p-n junctions made of different semiconductor materials have multiple bandgaps that allow reducing the relaxation energy loss and substantially increase the power-conversion efficiency. The choice of materials for each sub-cell is very limited due to the difficulties in extracting the current between the layers caused by the requirements for lattice- and current-matching. We propose a new vacuum multi-junction solar cell with multiple p-n junctions separated by vacuum gaps that allow using different semiconductor materials as cathode and anode, both activated to the state of effective negative electron affinity (NEA). In this work, the compact proximity focused vacuum tube with the GaAs(Cs,O) photocathode and AlGaAs/GaAs-(Cs,O) anode with GaAs quantum wells (QWs) is used as a prototype of a vacuum single-junction solar cell. The photodiode with the p-AlGaAs/GaAs anode showed the spectral power-conversion efficiency of about 1% at V bias  = 0 in transmission and reflection modes, while, at V bias  = 0.5 V, the efficiency increased up to 10%. In terms of energy conservation, we found the condition at which the energy cathode-to-anode transition was close to 1. Considering only the energy conservation part, the NEA-cell power-conversion efficiency can rich a quantum yield value which is measured up to more than 50%.

  18. Robustness of Majorana bound states in the short-junction limit (United States)

    Sticlet, Doru; Nijholt, Bas; Akhmerov, Anton


    We study the effects of strong coupling between a superconductor and a semiconductor nanowire on the creation of the Majorana bound states, when the quasiparticle dwell time in the normal part of the nanowire is much shorter than the inverse superconducting gap. This "short-junction" limit is relevant for the recent experiments using the epitaxially grown aluminum characterized by a transparent interface with the semiconductor and a small superconducting gap. We find that the small superconducting gap does not have a strong detrimental effect on the Majorana properties. Specifically, both the critical magnetic field required for creating a topological phase and the size of the Majorana bound states are independent of the superconducting gap. The critical magnetic field scales with the wire cross section, while the relative importance of the orbital and Zeeman effects of the magnetic field is controlled by the material parameters only: g factor, effective electron mass, and the semiconductor-superconductor interface transparency.

  19. Evaluation of the Electronic Structure of Single-Molecule Junctions Based on Current-Voltage and Thermopower Measurements: Application to C60Single-Molecule Junction. (United States)

    Komoto, Yuki; Isshiki, Yuji; Fujii, Shintaro; Nishino, Tomoaki; Kiguchi, Manabu


    The electronic structure of molecular junctions has a significant impact on their transport properties. Despite the decisive role of the electronic structure, a complete characterization of the electronic structure remains a challenge. This is because there is no straightforward way of measuring electron spectroscopy for an individual molecule trapped in a nanoscale gap between two metal electrodes. Herein, a comprehensive approach to obtain a detailed description of the electronic structure in single-molecule junctions based on the analysis of current-voltage (I-V) and thermoelectric characteristics is described. It is shown that the electronic structure of the prototypical C 60 single-molecule junction can be resolved by analyzing complementary results of the I-V and thermoelectric measurement. This combined approach confirmed that the C 60 single-molecule junction was highly conductive with molecular electronic conductances of 0.033 and 0.003 G 0 and a molecular Seebeck coefficient of -12 μV K -1 . In addition, we revealed that charge transport was mediated by a LUMO whose energy level was located 0.5≈0.6 eV above the Fermi level of the Au electrode. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Atomically Abrupt Topological p-n Junction. (United States)

    Kim, Sung Hwan; Jin, Kyung-Hwan; Kho, Byung Woo; Park, Byeong-Gyu; Liu, Feng; Kim, Jun Sung; Yeom, Han Woong


    Topological insulators (TI's) are a new class of quantum matter with extraordinary surface electronic states, which bear great potential for spintronics and error-tolerant quantum computing. In order to put a TI into any practical use, these materials need to be fabricated into devices whose basic units are often p-n junctions. Interesting electronic properties of a 'topological' p-n junction were proposed theoretically such as the junction electronic state and the spin rectification. However, the fabrication of a lateral topological p-n junction has been challenging because of materials, process, and fundamental reasons. Here, we demonstrate an innovative approach to realize a p-n junction of topological surface states (TSS's) of a three-dimensional (3D) topological insulator (TI) with an atomically abrupt interface. When a ultrathin Sb film is grown on a 3D TI of Bi2Se3 with a typical n-type TSS, the surface develops a strongly p-type TSS through the substantial hybridization between the 2D Sb film and the Bi2Se3 surface. Thus, the Bi2Se3 surface covered partially with Sb films bifurcates into areas of n- and p-type TSS's as separated by atomic step edges with a lateral electronic junction of as short as 2 nm. This approach opens a different avenue toward various electronic and spintronic devices based on well-defined topological p-n junctions with the scalability down to atomic dimensions.

  1. Wide-Gap Chalcopyrites

    CERN Document Server

    Siebentritt, Susanne


    Chalcopyrites, in particular those with a wide band gap, are fascinating materials in terms of their technological potential in the next generation of thin-film solar cells and in terms of their basic material properties. They exhibit uniquely low defect formation energies, leading to unusual doping and phase behavior and to extremely benign grain boundaries. This book collects articles on a number of those basic material properties of wide-gap chalcopyrites, comparing them to their low-gap cousins. They explore the doping of the materials, the electronic structure and the transport through interfaces and grain boundaries, the formation of the electric field in a solar cell, the mechanisms and suppression of recombination, the role of inhomogeneities, and the technological role of wide-gap chalcopyrites.

  2. Magnetotransport in La0.7Sr0.3MnO3/CuCr2O4/Fe3O4 magnetic junctions (United States)

    Iwata-Harms, Jodi M.; Chopdekar, Rajesh V.; Wong, Franklin J.; Nelson-Cheeseman, Brittany B.; Jenkins, Catherine A.; Arenholz, Elke; Suzuki, Yuri


    We demonstrate distinct magnetic and resistive switching with junction magnetoresistance up to -6% in magnetic tunnel junctions with a CuCr2O4 barrier. Junction magnetoresistance is inversely related to barrier thickness and reveals a maximum at a finite applied bias that converges to zero bias at low temperatures for all barrier thicknesses. The non-monotonic bias dependence is attributed to a charge gap from the Fe3O4 electrode and possible spin filtering from the spin-split conduction band of the ferrimagnetic CuCr2O4 barrier.

  3. The Gender Pay Gap


    Alan Manning


    Empirical research on gender pay gaps has traditionally focused on the role of gender-specific factors, particularly gender differences in qualifications and differences in the treatment of otherwise equally qualified male and female workers (i.e., labor market discrimination). This paper explores the determinants of the gender pay gap and argues for the importance of an additional factor, wage structure, the array of prices set for labor market skills and the rewards received for employment ...

  4. A method for cloning and sequencing long palindromic DNA junctions. (United States)

    Rattray, Alison J


    DNA sequences containing long adjacent inverted repeats (palindromes) are inherently unstable and are associated with many types of chromosomal rearrangements. The instability associated with palindromic sequences also creates difficulties in their molecular analysis: long palindromes (>250 bp/arm) are highly unstable in Escherichia coli, and cannot be directly PCR amplified or sequenced due to their propensity to form intra-strand hairpins. Here, we show that DNA molecules containing long palindromes (>900 bp/arm) can be transformed and stably maintained in Saccharomyces cerevisiae cells lacking a functional SAE2 gene. Treatment of the palindrome-containing DNA with sodium bisulfite at high temperature results in deamination of cytosine, converting it to uracil and thus reducing the propensity to form intra-strand hairpins. The bisulfite-treated DNA can then be PCR amplified, cloned and sequenced, allowing determination of the nucleotide sequence of the junctions. Our data demonstrates that long palindromes with either no spacer (perfect) or a 2 bp spacer can be stably maintained, recovered and sequenced from sae2Delta yeast cells. Since DNA sequences from mammalian cells can be gap repaired by their co-transformation into yeast cells with an appropriate vector, the methods described in this manuscript should provide some of the necessary tools to isolate and characterize palindromic junctions from mammalian cells.

  5. Carrier generation, recombination, trapping, and transport in semiconductors with position-dependent composition. [in junction solar cells (United States)

    Sah, C.-T.; Lindholm, F. A.


    The spatial variation of the chemical composition of a semiconductor modifies the ideal one-electron energy band model as well as the Shockley equations for carrier recombination and transport in two important ways. The random component of the spatial variation introduces localized states in the energy gap by perturbing the band states. The nonrandom component gives rise to the position dependences of the conduction and valence band edges or the electron affinity and the energy gap. This paper gives the modifications of the Shockley equations from these two effects as well as an example of the steady-state recombination rate from distributed gap states in junction solar cells

  6. Fluxon dynamics in three stacked Josephson junctions

    DEFF Research Database (Denmark)

    Gorria, Carlos; Christiansen, Peter Leth; Gaididei, Yuri Borisovich


    /sub -/, the coupling between junctions leads to a repulsion of the fluxons with the same polarity. Above this critical velocity a fluxon will induce radiation in the neighboring junctions, leading to a bunching of the fluxons in the stacked junctions. Using the Sakai-Bodin-Pedersen model, three coupled perturbed sine......-Gordon equations are numerically studied for different values of coupling, damping, and bias parameters. In a narrow range of velocities bunching occurs. Outside this interval the fluxons split and new fluxons may be created. I-V characteristics are presented...

  7. Switching effect in a gapped graphene d-wave superconductor structure

    Energy Technology Data Exchange (ETDEWEB)

    Soodchomshom, Bumned, E-mail: [Theoretical Physics of Advanced Technology Research, Department of Science and Mathematics (Physics), Faculty of Science and Technology, Pathumwan Institute of Technology, Bangkok 10330 (Thailand)


    By depositing a d-wave superconductor (using proximity method) on the top of graphene grown on a substrate-induced bandgap (such as a SiC substrate), a d-wave superconductor caused by the massive Dirac electrons can be fabricated. Using the BTK theory, the tunneling conductance in a gapped graphene N/d-wave superconductor junction, where N is a normal gapped graphene, is studied. This work focuses on the influence of d-wave pairing on the conductance of the junction. In this result, for conductance G/G{sub N} plotted versus either the biased voltage V or the d-wave superconducting orientation angular alpha, a sharp conductance peak like an impulse function can be observed due to increasing the Dirac energy gap. The maximum conductance peak G{sub max} is also enhanced by increasing the electrostatic potential U in superconductor-electrode, giving rise to G{sub max}/G{sub N}=2 for increasing U->infinity. This sharp conductance peak occurs related to the condition of eV=DELTAcos(2alpha). The unit step conductance in this junction, G/G{sub N}=2THETA(U), is found for alpha=pi/4 and eV/DELTA=0 when E{sub F}-mv{sub F}{sup 2}->0. This is unlike a unit step conductance in a gapped graphene N/s-wave superconductor junction which was recently observed for eV/DELTA=1.

  8. Current fluctuations in unconventional superconductor junctions with impurity scattering (United States)

    Burset, Pablo; Lu, Bo; Tamura, Shun; Tanaka, Yukio


    The order parameter of bulk two-dimensional superconductors is classified as nodal if it vanishes for a direction in momentum space, or gapful if it does not. Each class can be topologically nontrivial if Andreev bound states are formed at the edges of the superconductor. Nonmagnetic impurities in the superconductor affect the formation of Andreev bound states and can drastically change the tunneling spectra for small voltages. Here, we investigate the mean current and its fluctuations for two-dimensional tunnel junctions between normal-metal and unconventional superconductors by solving the quasiclassical Eilenberger equation self-consistently, including the presence of nonmagnetic impurities in the superconductor. As the impurity strength increases, we find that superconductivity is suppressed for almost all order parameters since (i) at zero applied bias, the effective transferred charge calculated from the noise-current ratio tends to the electron charge e , and (ii) for finite bias, the current-voltage characteristics follows that of a normal-state junction. There are notable exceptions to this trend. First, gapful nontrivial (chiral) superconductors are very robust against impurity scattering due to the linear dispersion relation of their surface Andreev bound states. Second, for nodal nontrivial superconductors, only px-wave pairing is almost immune to the presence of impurities due to the emergence of odd-frequency s -wave Cooper pairs near the interface. Due to their anisotropic dependence on the wave vector, impurity scattering is an effective pair-breaking mechanism for the remaining nodal superconductors. All these behaviors are neatly captured by the noise-current ratio, providing a useful guide to find experimental signatures for unconventional superconductivity.

  9. Electronic transport in molecular junctions (United States)

    Liu, Rui


    structured molecules could also show NDR. We show that molecular level crossing in a molecular double dot (MDD) system containing cobaltocene and ferrocene leads to NDR and hysteresis. Time-dependent transport properties of molecular junctions under external perturbation of a short time pulse or an alternative bias is studied by solving Green function in the time domain, combined with electronic structure information coming from ab initio density functional calculations. We found that the short time response depends on lead structure, bias voltage and barrier heights both at molecule-lead contacts and within molecules. Under an alternative current (AC) mode, the electron flow either lags (capacitive response) or leads (inductive response) the bias signal. The critical frequency for this transition is characteristic of a junction, depending on factors such as electronic structure of the leads and capacitance of the contacts.

  10. Effects of Intercellular Junction Protein Expression on Intracellular Ice Formation in Mouse Insulinoma Cells (United States)

    Higgins, Adam Z.; Karlsson, Jens O.M.


    The development of cryopreservation procedures for tissues has proven to be difficult in part because cells within tissue are more susceptible to intracellular ice formation (IIF) than are isolated cells. In particular, previous studies suggest that cell-cell interactions increase the likelihood of IIF by enabling propagation of ice between neighboring cells, a process thought to be mediated by gap junction channels. In this study, we investigated the effects of cell-cell interactions on IIF using three genetically modified strains of the mouse insulinoma cell line MIN6, each of which expressed key intercellular junction proteins (connexin-36, E-cadherin, and occludin) at different levels. High-speed video cryomicroscopy was used to visualize the freezing process in pairs of adherent cells, revealing that the initial IIF event in a given cell pair was correlated with a hitherto unrecognized precursor phenomenon: penetration of extracellular ice into paracellular spaces at the cell-cell interface. Such paracellular ice penetration occurred in the majority of cell pairs observed, and typically preceded and colocalized with the IIF initiation events. Paracellular ice penetration was generally not observed at temperatures >−5.65°C, which is consistent with a penetration mechanism via defects in tight-junction barriers at the cell-cell interface. Although the maximum temperature of paracellular penetration was similar for all four cell strains, genetically modified cells exhibited a significantly higher frequency of ice penetration and a higher mean IIF temperature than did wild-type cells. A four-state Markov chain model was used to quantify the rate constants of the paracellular ice penetration process, the penetration-associated IIF initiation process, and the intercellular ice propagation process. In the initial stages of freezing (>−15°C), junction protein expression appeared to only have a modest effect on the kinetics of propagative IIF, and even cell

  11. Parity measurement in topological Josephson junctions. (United States)

    Crépin, François; Trauzettel, Björn


    We study the properties of a topological Josephson junction made of both edges of a two-dimensional topological insulator. We show that, due to fermion parity pumping across the bulk, the global parity of the junction has a clear signature in the periodicity and critical value of the Josephson current. In particular, we find that the periodicity with the flux changes from 4π in a junction with an even number of quasiparticles to 2π in the odd sector. In the case of long junctions, we exhibit a rigorous mathematical connection between the spectrum of Andreev bound states and the fermion parity anomaly, through bosonization. Additionally, we discuss the rather quantitative effects of Coulomb interactions on the Josephson current.

  12. Current trends in salivary gland tight junctions (United States)

    Baker, Olga J.


    ABSTRACT Tight junctions form a continuous intercellular barrier between epithelial cells that is required to separate tissue spaces and regulate selective movement of solutes across the epithelium. They are composed of strands containing integral membrane proteins (e.g., claudins, occludin and tricellulin, junctional adhesion molecules and the coxsackie adenovirus receptor). These proteins are anchored to the cytoskeleton via scaffolding proteins such as ZO-1 and ZO-2. In salivary glands, tight junctions are involved in polarized saliva secretion and barrier maintenance between the extracellular environment and the glandular lumen. This review seeks to provide an overview of what is currently known, as well as the major questions and future research directions, regarding tight junction expression, organization and function within salivary glands. PMID:27583188

  13. Junction Point Detection Algorithm for SAR Image

    Directory of Open Access Journals (Sweden)

    Jun Zhang


    Full Text Available In this paper, we propose a novel junction point detector based on an azimuth consensus for remote sensing images. To eliminate the impact of noise and some noncorrelated edges of SAR image, an azimuth consensus constraint is developed. In addition to detecting the locations of junctions at the subpixel level, this operator recognizes their structures as well. A new formula that includes a minimization criterion for the total weighted distance is proposed to compute the locations of junction points accurately. Compared with other well-known detectors, including Forstner, JUDOCA, and CPDA, the experimental results indicate that our operator outperforms them both in location accuracy of junction points and in angle accuracy of branch edges. Moreover, our method possesses satisfying robustness to the impact of noise and changes of the SAR images. Our operator can be potentially used to solve a number of problems in computer vision, such as SAR image registration, wide-baseline matching, and UAV navigation system.

  14. Congenital right sided ureteropelvic junction obstructionin right ...

    African Journals Online (AJOL)

    Congenital right sided ureteropelvic junction obstructionin right crossed fused ectopia with extrarenal calycesmasquerading as massive retroperitoneal urinoma in acase of blunt trauma abdomen: A diagnostic enigma andnovel approach of management.

  15. Junction trees constructions in Bayesian networks (United States)

    Smail, Linda


    Junction trees are used as graphical structures over which propagation will be carried out through a very important property called the ruining intersection property. This paper examines an alternative method for constructing junction trees that are essential for the efficient computations of probabilities in Bayesian networks. The new proposed method converts a sequence of subsets of a Bayesian network into a junction tree, in other words, into a set of cliques that has the running intersection property. The obtained set of cliques and separators coincide with the junction trees obtained by the moralization and triangulation process, but it has the advantage of adapting to any computational task by adding links to the Bayesian network graph.

  16. New thermoelectric effect in tunnel junctions

    Energy Technology Data Exchange (ETDEWEB)

    Smith, A.D.; Tinkham, M.; Skocpol, W.J.


    A new type of thermoelectric current effect is derived for tunneling through oxide barriers between metals at different temperatures, for both superconducting and normal tunnel junctions. This effect was observed in both current and voltage measurements on Al-PbVb tunnel junctions in which one electrode was heated by laser irradiation. The existence of this thermoelectric effect may resolve long-standing discrepencies between experimental results and theoretical predictions for a series of point-contact experiments.

  17. Junction Parameter Extraction for Electronic Device Characterization


    Dib, S.; Salame, C.; Toufik, N.; Khoury, A; F. Pélanchon; Mialhe, P.


    A new method for the extraction of junction parameters from a description of the current–voltage characteristic is developed. A simulation is performed and a high accuracy is obtained for the determination of the singleexponential model parameters. The method is easy to implement in a control process for device characterization. An application, achieved to observe the degradation of the emitter–base junction of a bipolar transistor during an aging experiment, shows that the evolutions of t...

  18. Ferromagnetic Josephson junctions with niobium nitride (United States)

    Yamashita, Taro; Makise, Kazumasa; Kawakami, Akira; Terai, Hirotaka

    Recently, novel physics and device applications in hybrid structures of superconductor (SC) and ferromagnet (FM), e.g., spin injection into SC, long-range Josephson effect, cryogenic memory, have been studied actively. Among various interesting phenomena in SC/FM structures, a π state (π junction) emerged in ferromagnetic Josephson junctions (SC/FM/SC) is attractive as a superconducting phase shifter for superconducting devices. In the present work, we developed the ferromagnetic Josephson junction in order to realize a quiet superconducting flux qubit with a π junction. Contrary to conventional flux qubits, the qubit with a π junction can be operated without an external magnetic field which is a noise source, and thus good coherence characteristics is expected. As a superconducting material, we adopted niobium nitride (NbN) with high superconducting critical temperature of 16 K, which can be grown epitaxially on a magnesium oxide substrate. Regarding the ferromagnetic material we used copper nickel (CuNi), and fabricated the NbN/CuNi/NbN junctions and then evaluated the dependences of the Josephson critical current on the temperature, thickness and so on. This research was supported by JST, PRESTO.

  19. Fabrication and properties of Nb/Al, Al sub ox /Nb Josephson tunnel junctions with a double-oxide barrier

    Energy Technology Data Exchange (ETDEWEB)

    Houwman, E.P.; Veldhuis, D.; Flokstra, J.; Rogalla, H. (University of Twente, Faculty of Applied Physics, P.O.B. 217, 7500 AE Enschede, The Netherlands (NL))


    High-quality Nb/Al, Al{sub ox}/Nb Josephson tunnel junctions using double-oxide layers as barriers have been fabricated. The critical current density is controlled by the thickness of the second Al layer. This layer has to be oxidized completely through in order to obtain high-quality junctions. Typically, gap voltages of 2.8--3.0 mV and {ital V}{sub {ital m}} up to 70 mV at 4.2 K were obtained.

  20. Correlation between the graft–host junction of penetrating keratoplasty by anterior segment-optical coherence tomography and the magnitude of postoperative astigmatism

    Directory of Open Access Journals (Sweden)

    Ghada Azab Nassar


    Full Text Available Purpose: This study aimed to evaluate the alignment pattern of the graft–host junction after penetrating keratoplasty (PK by anterior segment-optical coherence tomography (AS-OCT and to correlate this pattern with the magnitude of postoperative astigmatism. Methods: This retrospective observational study was carried out on forty patients who underwent PK from February 2013 to August 2014. AS-OCT was performed, and the graft–host junctions were classified into well-apposed junction, malapposed junction, and equally apposed junction. Mal-apposition is subdivided into gap and protrusion. The correlations between clinical characteristics, wound profiles from the AS-OCT, and the magnitude of postoperative astigmatism by Sirius camera (Costruzione Strumenti Oftalmici [CSO], Florence, Italy (CSO, Sirius, were analyzed. Results: Graft–host junctions from forty patients were analyzed; 18 eyes had well-apposed junctions, ten eyes had malapposed junctions, and 12 had equally apposed junctions. The mean cylinder was −9.44 ± −4.00D in well-apposed group, −13.40 ± −5.01D in malapposed group, and −4.67 ± −0.94D in equally apposed group. Alignment pattern of the graft–host junction correlated significantly with the magnitude of astigmatism (P = 0.034. Preoperative corneal diseases did not have an effect on the magnitude of astigmatism (P = 0.123. Conclusion: The alignment pattern of the graft–host junction by AS-OCT can explain the postoperative astigmatism after PK where it correlates significantly with the magnitude of astigmatism.

  1. Pronounced Photovoltaic Response from Multilayered Transition-Metal Dichalcogenides PN-Junctions. (United States)

    Memaran, Shahriar; Pradhan, Nihar R; Lu, Zhengguang; Rhodes, Daniel; Ludwig, Jonathan; Zhou, Qiong; Ogunsolu, Omotola; Ajayan, Pulickel M; Smirnov, Dmitry; Fernández-Domínguez, Antonio I; García-Vidal, Francisco J; Balicas, Luis


    Transition metal dichalcogenides (TMDs) are layered semiconductors with indirect band gaps comparable to Si. These compounds can be grown in large area, while their gap(s) can be tuned by changing their chemical composition or by applying a gate voltage. The experimental evidence collected so far points toward a strong interaction with light, which contrasts with the small photovoltaic efficiencies η ≤ 1% extracted from bulk crystals or exfoliated monolayers. Here, we evaluate the potential of these compounds by studying the photovoltaic response of electrostatically generated PN-junctions composed of approximately 10 atomic layers of MoSe2 stacked onto the dielectric h-BN. In addition to ideal diode-like response, we find that these junctions can yield, under AM-1.5 illumination, photovoltaic efficiencies η exceeding 14%, with fill factors of ~70%. Given the available strategies for increasing η such as gap tuning, improving the quality of the electrical contacts, or the fabrication of tandem cells, our study suggests a remarkable potential for photovoltaic applications based on TMDs.

  2. Fabrication of TiN/AlN/TiN tunnel junctions

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Takeru; Naruse, Masato; Myoren, Hiroaki; Taino, Tohru, E-mail:


    Highlights: • We have fabricated TiN/AlN/TiN tunnel junctions with an epitaxial layer. • TiN and AlN films were deposited by dc and rf magnetron sputtering at ambient substrate temperatures. • The junctions have a V{sub g} = 1.1 mV, J{sub c} = 0.24 A/cm{sup 2}, R{sub sg}/R{sub n} of 7.2, and low subgap leakage current of 180 nA. - Abstract: We have fabricated TiN/AlN/TiN tunnel junctions with an epitaxial layer. The critical temperature of TiN can be changed in the range from 0.5 to 5.0 K. Therefore, it is easy to set 5.0 K as the target critical temperature. When a Superconducting Tunnel Junction (STJ) is operated as a photon detector, it is necessary to cool it to within 0.1 K of the critical temperature in consideration of the noise of the thermally stimulated currents. Because 0.3 K was desirable, as for the manufacture of general purpose photon detectors, the critical temperature 5.0 K. TiN and AlN films were deposited by dc and rf magnetron sputtering in a load-lock sputtering system at ambient substrate temperatures. The junctions have a gap voltage of V{sub g} = 1.1 mV, and critical current density of J{sub c} = 0.24 A/cm{sup 2}, and R{sub sg}/R{sub n} of 7.2, and low subgap leakage current (I{sub sub}@ 500 µV = 180 nA). We report our experiment system, the manufacture method and the junction properties in this paper.

  3. Mass gap without confinement (United States)

    Faedo, Antón F.; Mateos, David; Pravos, David; Subils, Javier G.


    We revisit a one-parameter family of three-dimensional gauge theories with known supergravity duals. We show that three infrared behaviors are possible. For generic values of the parameter, the theories exhibit a mass gap but no confinement, meaning no linear quark-antiquark potential; for one limiting value of the parameter the theory flows to an infrared fixed point; and for another limiting value it exhibits both a mass gap and confinement. Theories close to these limiting values exhibit quasi-conformal and quasi-confining dynamics, respectively. Eleven-dimensional supergravity provides a simple, geometric explanation of these features.

  4. The longevity gender gap

    DEFF Research Database (Denmark)

    Aviv, Abraham; Shay, Jerry; Christensen, Kaare


    resistant to the ravages of time. We discuss the interplay of these factors with telomere biology and oxidative stress and suggest that an explanation for the longevity gender gap may arise from a better understanding of the differences in telomere dynamics between men and women.......In this Perspective, we focus on the greater longevity of women as compared with men. We propose that, like aging itself, the longevity gender gap is exceedingly complex and argue that it may arise from sex-related hormonal differences and from somatic cell selection that favors cells more...

  5. Bridging the Emissions Gap


    Blok, K.


    The analyses in Chapters 2 and 3 of this report concluded that the emissions gap in 2020 will likely be between 8 and 13 GtCO2e. The chapters also estimated the difference between BaU emissions in 2020 and the emissions level consistent with a “likely” chance of staying within the 2°C target to be 14 GtCO2e. This chapter explores the potential for bridging this gap using a sector policy approach. Firstly, the chapter provides a summary and update of the estimated emission reduction potential ...

  6. Charge transport in nanoscale junctions. (United States)

    Albrecht, Tim; Kornyshev, Alexei; Bjørnholm, Thomas


    many particle excitations, new surface states in semiconductor electrodes, various mechanisms for single molecule rectification of the current, inelastic electron spectra and SERS spectroscopy. Three terminal architectures allowing (electrochemical) gating and transistor effects. Electrochemical nanojunctions and gating: intermolecular electron transfer in multi-redox metalloproteins, contact force modulation, characteristic current-noise patterns due to conformational fluctuations, resonance effects and electrocatalysis. Novel architectures: linear coupled quantum-dot-bridged junctions, electrochemical redox mediated transfer in two center systems leading to double maxima current-voltage plots and negative differential resistance, molecular-nanoparticle hybrid junctions and unexpected mesoscopic effects in polymeric wires. Device integration: techniques for creating stable metal/molecule/metal junctions using 'nano-alligator clips' and integration with 'traditional' silicon-based technology. The Guest Editors would like to thank all of the authors and referees of this special issue for their meticulous work in making each paper a valuable contribution to this research area, the early-bird authors for their patience, and Journal of Physics: Condensed Matter editorial staff in Bristol for their continuous support.

  7. Josephson tunnel junctions with ferromagnetic interlayer

    Energy Technology Data Exchange (ETDEWEB)

    Weides, M.P.


    Superconductivity and ferromagnetism are well-known physical properties of solid states that have been widely studied and long thought about as antagonistic phenomena due to difference in spin ordering. It turns out that the combination of both superconductor and ferromagnet leads to a very rich and interesting physics. One particular example, the phase oscillations of the superconducting order parameter inside the ferromagnet, will play a major role for the devices discussed in this work. In this thesis, I present Josephson junctions with a thin Al{sub 2}O{sub 3} tunnel barrier and a ferromagnetic interlayer, i.e. superconductor-insulator-ferromagnet-superconductor (SIFS) stacks. The fabrication of junctions was optimized regarding the insulation of electrodes and the homogeneity of the current transport. The junctions were either in the 0 or {pi} coupled ground state, depending on the thickness of the ferromagnetic layer and on temperature. The influence of ferromagnetic layer thickness on the transport properties and the coupling (0, {pi}) of SIFS tunnel junctions was studied. Furthermore, using a stepped ferromagnetic layer with well-chosen thicknesses, I obtained the so-called 0-{pi} Josephson junction. At a certain temperature this 0-{pi} junction can be made perfectly symmetric. In this case the ground state corresponds to a vortex of supercurrent creating a magnetic flux which is a fraction of the magnetic flux quantum {phi}{sub 0}. Such structures allow to study the physics of fractional vortices and to build various electronic circuits based on them. The SIFS junctions presented here have an exponentially vanishing damping at T {yields} 0. The SIFS technology developed within the framework of this work may be used to construct classical and quantum devices such as oscillators, memory cells and qubits. (orig.)

  8. Bridge the Gap. (United States)

    Klein, Mel; Cufaude, Jeffrey B.


    This document consists of two paired articles: the first, "Preparing Faculty Out of Class Experiences," by Mel Klein, and the second, "Help Advisers Be More Than Ghost Signatures," by Jeffrey B. Calfaude. Each article shares insights on how faculty advisers "bridge the gap" between students and faculty. When faculty members are asked to advise…

  9. Bridging the gap (United States)


    Astronomy is flourishing in China, with impressive achievements in instrument design and construction matched by a higher international research profile. Yet there remains a mismatch between the facilities available and those needed to progress. Sue Bowler wonders how the country will bridge the gap.

  10. Semantic Gaps Are Dangerous

    DEFF Research Database (Denmark)

    Ejstrup, Michael; le Fevre Jakobsen, Bjarne


    Semantic gaps are dangerous Language adapts to the environment where it serves as a tool to communication. Language is a social agreement, and we all have to stick to both grammaticalized and non-grammaticalized rules in order to pass information about the world around us. As such language develops...

  11. Bridging the Emissions Gap

    NARCIS (Netherlands)

    Blok, K.


    The analyses in Chapters 2 and 3 of this report concluded that the emissions gap in 2020 will likely be between 8 and 13 GtCO2e. The chapters also estimated the difference between BaU emissions in 2020 and the emissions level consistent with a “likely” chance of staying within the 2°C target to

  12. Estimating Gender Wage Gaps (United States)

    McDonald, Judith A.; Thornton, Robert J.


    Course research projects that use easy-to-access real-world data and that generate findings with which undergraduate students can readily identify are hard to find. The authors describe a project that requires students to estimate the current female-male earnings gap for new college graduates. The project also enables students to see to what…

  13. Model Building to Facilitate Understanding of Holliday Junction and Heteroduplex Formation, and Holliday Junction Resolution (United States)

    Selvarajah, Geeta; Selvarajah, Susila


    Students frequently expressed difficulty in understanding the molecular mechanisms involved in chromosomal recombination. Therefore, we explored alternative methods for presenting the two concepts of the double-strand break model: Holliday junction and heteroduplex formation, and Holliday junction resolution. In addition to a lecture and…

  14. Electronic transport through EuO spin-filter tunnel junctions

    KAUST Repository

    Jutong, Nuttachai


    Epitaxial spin-filter tunnel junctions based on the ferromagnetic semiconductor europium monoxide (EuO) are investigated by means of density functional theory. In particular, we focus on the spin transport properties of Cu(100)/EuO(100)/Cu(100) junctions. The dependence of the transmission coefficient and the current-voltage curves on the interface spacing and EuO thickness is explained in terms of the EuO density of states and the complex band structure. Furthermore, we also discuss the relation between the spin transport properties and the Cu-EuO interface geometry. The level alignment of the junction is sensitively affected by the interface spacing, since this determines the charge transfer between EuO and the Cu electrodes. Our calculations indicate that EuO epitaxially grown on Cu can act as a perfect spin filter, with a spin polarization of the current close to 100%, and with both the Eu-5d conduction-band and the Eu-4f valence-band states contributing to the coherent transport. For epitaxial EuO on Cu, a symmetry filtering is observed, with the Δ1 states dominating the transmission. This leads to a transport gap larger than the fundamental EuO band gap. Importantly, the high spin polarization of the current is preserved up to large bias voltages.

  15. Transport Properties of an Electron-Hole Bilayer in Contact with a Superconductor Hybrid Junction. (United States)

    Bercioux, D; Klapwijk, T M; Bergeret, F S


    We investigate the transport properties of a junction consisting of an electron-hole bilayer in contact with normal and superconducting leads. The electron-hole bilayer is considered as a semimetal with two electronic bands. We assume that in the region between the contacts the system hosts an exciton condensate described by a BCS-like model with a gap Γ in the quasiparticle density of states. We first discuss how the subgap electronic transport through the junction is mainly governed by the interplay between two kinds of reflection processes at the interfaces: the standard Andreev reflection at the interface between the superconductor and the exciton condensate, and a coherent crossed reflection at the semimetal-exciton-condensate interface that converts electrons from one layer into the other. We show that the differential conductance of the junction shows a minimum at voltages of the order of Γ/e. Such a minimum can be seen as a direct hallmark of the existence of the gapped excitonic state.

  16. Coherent quantum transport in hybrid Nb-InGaAs-Nb Josephson junctions (United States)

    Delfanazari, Kaveh; Puddy, R.; Ma, P.; Cao, M.; Yi, T.; Gul, Y.; Farrer, I.; Ritchie, D.; Joyce, H.; Kelly, M.; Smith, C.

    Because of the recently reported detection of Majorana fermions states at the superconductor-semiconductor (S-Sm) interface in InAs nanowire devices, the study of hybrid structures has received renewed interest. In this paper we present experimental results on proximity induced superconductivity in a high-mobility two-dimensional electron gas in InGaAs heterostructures. Eight symmetric S-Sm-S Josephson junctions were fabricated on a single InGaAs chip and each junction was measured individually using a lock-in measurement technique. The superconducting electrodes were made of Niobium (Nb). The measurements were carried out in a dilution fridge with a base temperature of 40 mK, and the quantum transport of junctions were measured below 800 mK. Owing to Andreev reflections at the S-Sm interfaces, the differential resistance (dV/dI) versus V curve shows the well-known subharmonic energy gap structure (SGS) at V = 2ΔNb/ne. The SGS features suppressed significantly with increasing temperature and magnetic field, leading to a shift of the SGSs toward zero bias. Our result paves the way for development of highly transparent hybrid S-Sm-S junctions and coherent circuits for quantum devices capable of performing quantum logic and processing functions.

  17. HfO2 and SiO2 as barriers in magnetic tunneling junctions (United States)

    Shukla, Gokaran; Archer, Thomas; Sanvito, Stefano


    SiO2 and HfO2 are both high-k, wide-gap semiconductors, currently used in the microelectronic industry as gate barriers. Here we investigate whether the same materials can be employed to make magnetic tunnel junctions, which in principle can be amenable for integration in conventional Si technology. By using a combination of density functional theory and the nonequilibrium Green's functions method for quantum transport we have studied the transport properties of Co [0001 ] /SiO2[001 ] /Co [0001 ] and Fe [001 ] /HfO2[001 ] /Fe [001 ] junctions. In both cases we found a quite large magnetoresistance, which is explained through the analysis of the real band structure of the magnets and the complex one of the insulator. We find that there is no symmetry spin filtering for the Co-based junction since the high transmission Δ2' band crosses the Fermi level, EF, for both spin directions. However, the fact that Co is a strong ferromagnet makes the orbital contribution to the two Δ2' spin subbands different, yielding magnetoresistance. In contrast for the Fe-based junction symmetry filtering is active for an energy window spanning between the Fermi level and 1 eV below EF, with Δ1 symmetry contributing to the transmission.

  18. Electrical properties of graphene tunnel junctions with high-κ metal-oxide barriers (United States)

    Feng, Ying; Trainer, Daniel J.; Chen, Ke


    An insulating barrier is one of the key components in electronic devices that makes use of quantum tunneling principles. Many metal-oxides have been used as a good barrier material in a tunnel junction for their large band gap, stable chemical properties and superb properties for forming a thin and pin-hole-free insulating layer. The reduced dimensions of transistors have led to the need for alternative, high dielectric constant (high-κ) oxides to replace conventional silicon-based dielectrics to reduce the leaking current induced by electron tunneling. On the other hand, a tunnel junction with one or both electrodes made of graphene may lead to novel applications due to the massless Dirac fermions from the graphene. Here we have fabricated sandwich-type graphene tunnel junctions with high-κ metal-oxides as barriers, including Al2O3, HfO2, ZrO2, and TiO2. Tunneling properties are investigated by observing the temperature and time dependences of the tunneling spectra. Our results show the potential for applications of high-κ oxides in graphene tunnel junctions and bringing new opportunities for memory and logic electronic devices.

  19. Proximity effect in superconductor-insulator-superconductor Josephson tunnel junctions: Theory and experiment (United States)

    Golubov, A. A.; Houwman, E. P.; Gijsbertsen, J. G.; Krasnov, V. M.; Flokstra, J.; Rogalla, H.; Kupriyanov, M. Yu.


    A microscopic model of the proximity effect in superconductor-insulator-superconductor (SS'IS''S) Josephson tunnel junctions has been developed for the general case of the finite critical temperature of the S' (S'') metal, arbitrary SS' (SS'') boundary transparency and the strength of the proximity effect between S and S' (respectively S and S''). The metals are assumed to be in the dirty limit and the thickness of the proximity layer is assumed to be small compared to its coherence length. The electrical properties of the SS'IS''S junction are calculated as a function of the strength of the proximity effect, boundary transparency, critical temperature ratio, and temperature. The experimentally determined electrical characteristics of a series of Nb/Al1, Al oxide, Al2/Nb junctions with varying thickness d1 of the Al1 layer were interpreted with this model. The current-voltage characteristics and the temperature dependence of the critical current and sum-gap voltage could be described quantitatively well without any other correction than the non-BCS ratio Δ0/kBTc~=1.93 of Nb. Deviations from the model for the junctions with the largest d1 are attributed to the fact that the Nb and Al are not fully in the dirty limit and d1 is not small compared to the coherence length.

  20. Proximity effect in Nb/Al, AlOxide, Al/Nb Josephson tunnel junctions (United States)

    Houwman, E. P.; Gijsbertsen, J. G.; Flokstra, J.; Rogalla, H.; Le Grand, J. B.; de Korte, P. A. J.; Golubov, A. A.


    Regions with reduced energy gap induced by the proximity effect give rise to quasi-particle loss in Josephson-junction X-ray detectors, but may also be used advantageously for quasi-particle collection. The influence of the thickness of the Al proximity layers in Nb/Al1,AlO(x),Al2/Nb Josephson tunnel junctions on the electrical characteristics has been investigated theoretically and experimentally. Theoretically it is found that the strength of the proximity effect is mainly determined by the proximity parameters gammaM1 (gammaM2) of the electrodes. Good fits of the measured I-V curves with theory were obtained for junctions with thicknesses dA11 ranging from 4 to 25 nm and dA12 = 3 nm, with gammaM2 about 0.12 and gammaM1/gammaM2 = dA11/dA12. For all junctions the proximity knee remains more pronounced than predicted.

  1. Inhomogeneous parallel arrays of Josephson junctions

    Energy Technology Data Exchange (ETDEWEB)

    Caputo, J.-G., E-mail: caputo@insa-rouen.f [Laboratoire de Mathematiques, INSA de Rouen, B.P. 8, Avenue de l' Universite, 76801 Saint-Etienne du Rouvray (France); Loukitch, L., E-mail: lionel.loukitch@insa-rouen.f [Laboratoire de Mathematiques, INSA de Rouen, B.P. 8, Avenue de l' Universite, 76801 Saint-Etienne du Rouvray (France)


    Highlights: {yields} New long wave model of an inhomogeneous parallel array of Josephson junctions. {yields} Adapted spectral problem giving resonances in the current-voltage characteristic. {yields} At resonances solution is described by two ordinary differential equations. {yields} Good agreement with the characteristic curve of a real five junction array. - Abstract: We model new inhomogeneous parallel arrays of small Josephson junctions by taking into account the time and space variations of the field in the cavity and the capacity miss-match at the junctions. The model consists in a wave equation with Dirac delta function sine nonlinearities. We introduce an adapted spectral problem whose spectrum gives the resonances in the current-voltage characteristic curve of any array. It is shown that at the resonances the solution is described by two simple ordinary differential equations. The resonances obtained by this approach are in good agreement with the characteristic curve of a real five junction array. This flexible approach is a first step towards building a device tailored for given purposes.

  2. Characterization of cytoskeletal and junctional proteins expressed by cells cultured from human arachnoid granulation tissue

    Directory of Open Access Journals (Sweden)

    Mehta Bhavya C


    the in vitro culture of arachnoidal cells grown from human AG tissue. We demonstrated that these cells in vitro continue to express some of the cytoskeletal and junctional proteins characterized previously in human AG tissue, such as proteins involved in the formation of gap junctions, desmosomes, epithelial specific adherens junctions, as well as tight junctions. These junctional proteins in particular may be important in allowing these arachnoidal cells to regulate CSF outflow.

  3. The limiting efficiency of band gap graded solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Rafat, Nadia H. [Faculty of Engineering, Cairo University, Giza (Egypt); Habib, S.E.D. [Faculty of electronics and communication, Cairo University, Giza (Egypt)


    Two fundamental mechanisms limit the maximum attainable efficiency of solar cells, namely the radiative recombination and Auger recombination. We show in this paper that proper band gap grading of the solar cell localizes the Auger recombination around the metallurgical junction. Two beneficial effects result from this Auger recombination localization; first the cell is less sensitive to the surface conditions, and second, the previous estimates for the limiting efficiency of solar cells by Shockley, Tiedje, and Green are revised upwardly. We calculate the optimum bandgap grading profile for several real material systems, including GaInAsP lattice matched to InP, and a-SiGe on a-Si substrate

  4. Tunnel junction based memristors as artificial synapses. (United States)

    Thomas, Andy; Niehörster, Stefan; Fabretti, Savio; Shepheard, Norman; Kuschel, Olga; Küpper, Karsten; Wollschläger, Joachim; Krzysteczko, Patryk; Chicca, Elisabetta


    We prepared magnesia, tantalum oxide, and barium titanate based tunnel junction structures and investigated their memristive properties. The low amplitudes of the resistance change in these types of junctions are the major obstacle for their use. Here, we increased the amplitude of the resistance change from 10% up to 100%. Utilizing the memristive properties, we looked into the use of the junction structures as artificial synapses. We observed analogs of long-term potentiation, long-term depression and spike-time dependent plasticity in these simple two terminal devices. Finally, we suggest a possible pathway of these devices toward their integration in neuromorphic systems for storing analog synaptic weights and supporting the implementation of biologically plausible learning mechanisms.

  5. Stability of DNA nanostructures by junction penalty. (United States)

    Lee, Jong Bum; Kim, Hyuncheol


    DNA nanostructures have been attracting much attention because of their well-controlled nanoarchitectural features. However, regulating the stability of DNA nanostructures is less well understood because of complexity. In this paper, the stability of DNA nanostructure was studied first in the form of simple building blocks. Since these DNA nanostructures have junctions on the center of the structures, the junctions were mainly investigated as a factor in the instability. In addition, regulation of the stability of complicated nanostructures based on these building blocks was achieved. Förster resonance energy transfer (FRET) methods were employed to monitor the conformation change with nano-scale sensitivity. The junction effect on DNA nanostructures was monitored with labeling FRET pairs at various conditions. DNA tile structures was also thoroughly studied by FRET.

  6. Neuromuscular Junction Dismantling in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Valentina Cappello


    Full Text Available Neuromuscular junction assembly and plasticity during embryonic, postnatal, and adult life are tightly regulated by the continuous cross-talk among motor nerve endings, muscle fibers, and glial cells. Altered communications among these components is thought to be responsible for the physiological age-related changes at this synapse and possibly for its destruction in pathological states. Neuromuscular junction dismantling plays a crucial role in the onset of Amyotrophic Lateral Sclerosis (ALS. ALS is characterized by the degeneration and death of motor neurons leading to skeletal muscle denervation, atrophy and, most often, death of the patient within five years from diagnosis. ALS is a non-cell autonomous disease as, besides motor neuron degeneration, glial cells, and possibly muscle fibers, play a role in its onset and progression. Here, we will review the recent literature regarding the mechanisms leading to neuromuscular junction disassembly and muscle denervation focusing on the role of the three players of this peripheral tripartite synapse.

  7. Josephson junctions with ferromagnetic alloy interlayer

    Energy Technology Data Exchange (ETDEWEB)

    Himmel, Nico


    Josephson junctions are used as active devices in superconducting electronics and quantum information technology. Outstanding properties are their distinct non-linear electrical characteristics and a usually sinusoidal relation between the current and the superconducting phase difference across the junction. In general the insertion of ferromagnetic material in the barrier of a Josephson junction is associated with a suppression of superconducting correlations. But also new phenomena can arise which may allow new circuit layouts and enhance the performance of applications. This thesis presents a systematic investigation for two concepts to fabricate Josephson junctions with a rather uncommon negative critical current. Such devices exhibit an intrinsic phase slip of π between the electrodes, so they are also known as π junctions. Both studies go well beyond existing experiments and in one system a π junction is shown for the first time. All the thin film junctions are based on superconducting Nb electrodes. In a first approach, barriers made from Si and Fe were investigated with respect to the realisation of π junctions by spin-flip processes. The distribution of Fe in the Si matrix was varied from pure layers to disperse compounds. The systematic fabrication of alloy barriers was facilitated by the development of a novel timing-based combinatorial sputtering technique for planetary deposition systems. An orthogonal gradient approach allowed to create binary layer libraries with independent variations of thickness and composition. Second, Nb vertical stroke AlO{sub x} vertical stroke Nb vertical stroke Ni{sub 60}Cu{sub 40} vertical stroke Nb (SIsFS) double barrier junctions were experimentally studied for the occurrence of proximity effect induced order parameter oscillations. Detailed dependencies of the critical current density on the thickness of s-layer and F-layer were acquired and show a remarkable agreement to existing theoretical predictions. Especially

  8. Bridge the Gap

    DEFF Research Database (Denmark)

    Marselis, Randi Lorenz


    This article focuses on photo projects organised for teenage refugees by the Society for Humanistic Photography (Berlin, Germany). These projects, named Bridge the Gap I (2015), and Bridge the Gap II (2016), were carried out in Berlin and brought together teenagers with refugee and German-majorit...... was produced – and sometimes not produced - within the projects. The importance of memory work in the context of refugee resettlement is often overlooked, but is particularly relevant when cultural encounters are organised in museums and exhibition galleries.......-majority backgrounds to experiment with digital photography and create joint exhibitions. Drawing on concepts from memory studies, such as travelling memory and multidirectional memory, the author examines the projects as interventions in German and Berlin memory cultures, and examines how multidirectional memory...

  9. Closing the Gap

    DEFF Research Database (Denmark)

    Tamke, Martin; Kobiella, Olaf


    The e4d design series is looking for an innovative use of digital technology in architectural education to overcome the gap between design development and the acquisition of digital skills. Digital design approaches include multimedia technology, the crossover of analogue and digital techniques, ...... architectural projects can be discussed; in addition, a competent monitoring of the process and outcome of innovative and efficient design strategies in architectural and pedagogical aspect is included.......The e4d design series is looking for an innovative use of digital technology in architectural education to overcome the gap between design development and the acquisition of digital skills. Digital design approaches include multimedia technology, the crossover of analogue and digital techniques......, rapid-prototyping, visualization, and the presentation in artistic movies. Over the past two years a problem- based design approach was developed, which enabled students to learn digital and architectural skills simultaneously and efficiently. The educational concept consisted generally of four steps...

  10. Minding the Gap

    Energy Technology Data Exchange (ETDEWEB)

    Firestone, Millicent Anne [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    Neutron & X-ray scattering provides nano- to meso-scale details of complex fluid structure; 1D electronic density maps dervied from SAXS yield molecular level insights; Neutron reflectivity provides substructure details of substrate supported complex fluids; Complex fluids composition can be optimized to support a wide variety of both soluble and membrane proteins; The water gap dimensions can be finely tuned through polymer component.

  11. 'Mind the Gap!'

    DEFF Research Database (Denmark)

    Persson, Karl Gunnar

    This paper challenges the widely held view that sharply falling real transport costs closed the transatlantic gap in grain prices in the second half of the 19th century. Several new results emerge from an analysis of a new data set of weekly wheat prices and freight costs from New York to UK mark...... convergence (or divergence) can appear if quality differences associated with allegedly homogeneous commodities like wheat are not controlled for....

  12. Mind the Gap


    Dorsett, R.; Rienzo, C.; Rolfe, H.; Burns, H.; Robertson, B-A.; Thorpe, B.; Wall, K.


    Mind the Gap sought to improve the metacognition and academic attainment of pupils in Year 4. There were two aspects to the intervention. The first involved training teachers in how to embed metacognitive approaches in their work, and how to continue to effectively and strategically involve parents. This training took place over a day and was provided by a consultant. The second component focused on parental engagement and offered families the opportunity to participate in a series of facilit...

  13. Position resolution of a double junction superconductive detector based on a single material (United States)

    Samedov, V. V.


    The Naples group from Istituto Nazionale di Fisica Nucleare presented the results of theoretical investigations of a new class of superconductive radiation detectors - double junction superconductive detector based on a single material [1]. In such detectors, the absorption of energy occurs in a long superconductive strip while two superconductive tunnel junctions positioned at the ends of the strip provide the readout of the signals. The main peculiarity of this type of detectors is that they are based on a single superconducting material, i.e., without trapping layers at the ends of the strip. In this paper, general approach to the position resolution of this type of detectors has been attempted. The formula for the position resolution is derived. It is shown that the application of the aluminium for the absorber may be the best possible way not only due to the small gap energy, but also mainly for STJ fabrication technology based on the aluminium oxide tunnel barrier.

  14. Proximity effect and Andreev reflection in single-C{sub 60} junctions

    Energy Technology Data Exchange (ETDEWEB)

    Brand, Jonathan; Neel, Nicolas; Kroeger, Joerg [Institut fuer Physik, Technische Universitaet Ilmenau, D-98693 Ilmenau (Germany)


    Single C{sub 60} molecules deposited on an ultrathin oxide film on Nb(110) were investigated using a low-temperature scanning tunnelling microscope. Spectroscopy of the differential conductance (dI/dV) in the tunnelling range indicates proximity-induced superconductivity in junctions comprising the oxide layer as well as single C{sub 60} molecules. Andreev reflection is enhanced upon controlled fabrication of tip-surface contacts. With decreasing electrode separation the Bardeen-Cooper-Schrieffer energy gap gradually evolves into a zero-bias peak in dI/dV spectra reflecting the spectroscopic signature of Andreev reflection. The current-voltage characteristics of the tunnelling and contact junctions are well described by the Blonder-Tinkham-Klapwijk theory. Our spectroscopic data evidence the influence of the electrodes' atomic-scale structure on electron transport across normal metal-superconductor interfaces.

  15. Self-heating in Josephson junction chains. New insight from old circuits

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Jared [Chemical and Quantum Physics, School of Applied Sciences, RMIT University, Melbourne, Victoria 3001 (Australia); Marthaler, Michael [Institute fuer Theoretische Festkoerperphysik, Karlsruhe Institute of Technology, 76128 Karlsruhe (Germany); Duty, Timothy [Centre for Engineered Quantum Systems (EQuS), School of Physics, University of New South Wales, Sydney, New South Wales 2052 (Australia)


    The conduction properties of arrays of Josephson junctions are been studied for decades, yet the experimental results never really match the predictions of the idealised theoretical models. Many reasons have been given for this, including imperfections in the measurement, in the fabrication process or in the theoretical models used. Recently, using a combination of systematic numerical and experimental studies, the gap between theory and experiment is closing. As an example of this, we discuss the role of self-heating in the transport properties of one-dimensional Josephson junction chains. We show tantalising experimental measurements and how these can be compared to various theoretical models for the self-heating processes within the chains.

  16. Seebeck Coefficient of a Single van der Waals Junction in Twisted Bilayer Graphene. (United States)

    Mahapatra, Phanibhusan S; Sarkar, Kingshuk; Krishnamurthy, H R; Mukerjee, Subroto; Ghosh, Arindam


    When two planar atomic membranes are placed within the van der Waals distance, the charge and heat transport across the interface are coupled by the rules of momentum conservation and structural commensurability, leading to outstanding thermoelectric properties. Here we show that an effective "interlayer phonon drag" determines the Seebeck coecient (S) across the van der Waals gap formed in twisted bilayer graphene (tBLG). The cross-plane thermovoltage, which is nonmonotonic in both temperature and density, is generated through scattering of electrons by the out-of-plane layer breathing (ZO'/ZA 2 ) phonon modes and differs dramatically from the expected Landauer-Buttiker formalism in conventional tunnel junctions. The tunability of the cross-plane Seebeck effect in van der Waals junctions may be valuable in creating a new genre of versatile thermoelectric systems with layered solids.


    Directory of Open Access Journals (Sweden)

    Ting-Chi Wei


    Full Text Available The existence of subordinate gaps in Mandarin Chinese casts doubt on analyses built on canonical coordinate gapping. We observe that the minimality of contrastive focus and the type of subordinate clause determine the acceptability of a missing gap in subordinate structure. Along this vein, we propose that a semantic-based deletion account can be used to interpret gapping in Mandarin. Such account relies on two violable constraints, AvoidF and Focus condition on gapping (Schwarzchild 1999, Merchant 2001 to compute the acceptability of a gap.

  18. Superconducting tunnel junctions on MgB{sub 2} using MgO and CaF{sub 2} as a barrier

    Energy Technology Data Exchange (ETDEWEB)

    Sakoda, Masahito, E-mail: [Department of Applied Physics, Tokyo University of Agriculture and Technology, 2-24-16, Koganei, Tokyo 184-8588 (Japan); Aibara, Masato; Mede, Kazuya; Kikuchi, Motoyuki; Naito, Michio [Department of Applied Physics, Tokyo University of Agriculture and Technology, 2-24-16, Koganei, Tokyo 184-8588 (Japan)


    Highlights: • We have revised the manuscript according to reviewer's comments. The details are in “Response to Reviewers”. • Superconducting junctions with MgO and CaF{sub 2} barrier were fabricated in order to improve the quality of junctions. • In SIN junctions with MgO barrier, clear superconducting gap was observed. (). • In SIS junctions with CaF2 barrier, Josephson current was observed over 30 K. (). • The compatibility of each barrier material at the upper and lower interfaces was clarified. (). - Abstract: We report the fabrication of superconducting tunnel junctions, both of superconductor–insulator-normal metal (SIN) and superconductor–insulator-superconductor (SIS), on MgB{sub 2} using MgO and CaF{sub 2} as a barrier. The SIN junctions fabricated using an MgO barrier showed excellent quasi-particle characteristics, including a large superconducting gap (Δ) of 2.5–3 meV and a low zero-bias conductance. We have also fabricated SIS junctions with an MgO barrier, but the quasi-particle characteristics of the SIS junctions are not as good as those of the SIN junctions, namely a reduced superconducting gap and a high zero-bias conductance. It appears that top MgB{sub 2} electrodes do not grow well on an MgO barrier, which is also suggested from in-situ RHEED observation. The SIN junctions fabricated using a CaF{sub 2} barrier showed less sharp quasi-particle characteristics than using an MgO barrier. However, the SIS junctions using a CaF{sub 2} barrier showed a fairly large I{sub c}R{sub N} value at 4.2 K over 1 mV and also exhibited finite Josephson current up to almost the film's T{sub c} (∼30 K). The RHEED observation revealed that top MgB{sub 2} electrodes grow well on a CaF{sub 2} barrier.

  19. Gender gaps and gains. (United States)

    Conly, S


    Findings from studies conducted worldwide indicate that educating girls allows them to gain more control over their lives, which, in turn, means that they have fewer, healthier children. In patriarchal societies, however, this education must last 6 or 7 years to be fully beneficial. Education of girls is also among the best economic investments a country can make because it leads to increased productivity and economic growth. However, women still suffer from a gender gap that has resulted in lower literacy among women and lower school attendance and duration of schooling among girls. However, gains have been made, and the gender gap in enrollment is narrowing in some regions, such as Latin America and East Asia. The gender gap continues its stranglehold, however, in the most populous and impoverished countries of sub-Saharan Africa. Enrollment rates in secondary schools have risen faster than for primary schools worldwide, with striking gains in East Asia. In some regions, such as Latin America, the secondary school enrollment rates are actually higher for girls than for boys. Strategies to improve girls' educational participation include 1) building more schools, 2) providing "girl-friendly" facilities, 3) increasing the number of women teachers, 4) improving the quality and relevance of the curriculum, 5) promoting education among parents, 6) providing sexual health education and services to reduce pregnancy-related drop-outs, and 7) making school hours flexible to accommodate girls' schedules.

  20. [Treatment of glottal gap]. (United States)

    Voigt-Zimmermann, S; Arens, C


    Glottal gaps can be either physiological or pathological. The latter are multifactorial, predominantly organic in origin and occasionally functional. Organic causes include vocal fold paralysis or scarring, as well as a deficiency or excess of tissue. In addition to loss of the mucosal wave, the degree of hoarseness is primarily determined by the circumferential area of the glottal gap. It is thus important to quantify the extent of glottal insufficiency. Although a patient's symptoms form the basis for treatment decisions, these may be subjective and inadequately reflected by the results of auditory-perceptual evaluation, voice analysis and voice performance tests. The therapeutic approach should always combine phonosurgery with conventional voice therapy methods. Voice therapy utilises all the resources made available by the sphincter model of the aerodigestive tract and knowledge on the mechanism of voice production. The aim of phonosurgery is medialization, reconstruction or reinnervation by injection laryngoplasty or larynx framework surgery. These different methods can be combined and often applied directly after vocal fold surgery (primary reconstruction). In conclusion, the techniques described here can be effectively employed to compensate for glottal gaps.

  1. Conductance Spectra in Graphene-Superconductor Junctions (United States)

    Tian, Jie; Zhou, Shi-Ping; Deng, Zhen-Yan


    The conductance spectra of a graphene ribbon and graphene-superconductor (G-S) junctions are investigated, using the tight-binding model and non-equilibrium Green' function formalism. It is found that the quantized conductance related to graphene' edge-states is robust against perturbations in the model parameters for a graphene monolayer ribbon with the zigzag boundary. With appropriate model parameter of the spin-orbit interaction strength, a new bound state with odd-frequency symmetry is found in the G-S junction. An enhancement in the zero-energy conductance amplitude is followed.

  2. GapBlaster-A Graphical Gap Filler for Prokaryote Genomes.

    Directory of Open Access Journals (Sweden)

    Pablo H C G de Sá

    Full Text Available The advent of NGS (Next Generation Sequencing technologies has resulted in an exponential increase in the number of complete genomes available in biological databases. This advance has allowed the development of several computational tools enabling analyses of large amounts of data in each of the various steps, from processing and quality filtering to gap filling and manual curation. The tools developed for gap closure are very useful as they result in more complete genomes, which will influence downstream analyses of genomic plasticity and comparative genomics. However, the gap filling step remains a challenge for genome assembly, often requiring manual intervention. Here, we present GapBlaster, a graphical application to evaluate and close gaps. GapBlaster was developed via Java programming language. The software uses contigs obtained in the assembly of the genome to perform an alignment against a draft of the genome/scaffold, using BLAST or Mummer to close gaps. Then, all identified alignments of contigs that extend through the gaps in the draft sequence are presented to the user for further evaluation via the GapBlaster graphical interface. GapBlaster presents significant results compared to other similar software and has the advantage of offering a graphical interface for manual curation of the gaps. GapBlaster program, the user guide and the test datasets are freely available at It requires Sun JDK 8 and Blast or Mummer.

  3. Relationship between Critical Current Fluctuation of Superconducting Bicrystal Junction and Junction Parameters (United States)

    Enpuku, Keiji; Minotani, Tadashi; Shiraishi, Fumio; Kandori, Atushi


    Critical current fluctuation of bicrystal junctions is estimated from the 1/f flux noise of the superconducting quantum interference device (SQUID) at T=77 K. The relationships between the current fluctuation and junction parameters, such as critical current Io and resistance R, are obtained. The obtained parameter dependence can be well explained by using the parameter dependence of the resistance fluctuation reported by Marx and Gross [Appl. Phys. Lett. 70, 120 (1997)] and the relationship between Io and R obtained for the present junctions. The agreement indicates that the critical current fluctuation is correlated with the resistance fluctuation through the relationship between Io and R.

  4. Superconducting quantum interference devices made with normal metal and insulator barrier Josephson junctions in Y-Ba-Cu-O directly written with a focused helium beam (United States)

    Cho, Ethan; Ma, Meng; Huynh, Chuong; Pratt, Kevin; Paulson, Doug; Glyantsev, Victor; Dynes, Robert; Cybart, Shane

    We will present electrical transport data for Y-Ba-Cu-O superconducting quantum interference devices (SQUIDs) with focused helium ion damage Josephson junctions. The junctions were directly written with a 30 keV focused helium ion beam, which locally creates disorder in Y-Ba-Cu-O that induces a superconducting-insulator transition. SQUIDs with Josephson junctions written with a dose of 4 ×1016 He+/cm2 have metallic barriers and show a current-voltage characteristic (I-V) well-described by the resistively shunted junction model. The spectral density of the flux noise is 10 μΦ0 / √ Hz at 10 Hz and the white noise at higher frequencies is 2 μΦ0 / √ Hz. SQUIDs with junctions written with higher ion doses (~ 9 ×1016 He+/cm2) have insulating Josephson barriers with a critical current of 22 μA and a resistance of 12 Ω at 4 K. The I-V for all of these devices is not hysteretic due to the small capacitance and the resistance. At higher voltage the junction I-V curve shows tunnel-junction behavior and a superconducting energy gap edge at 20 mV. We will discuss how these results are a promising step forward for sensitive magnetic sensors made from high temperature superconductors at various temperatures.

  5. Josephson junctions loaded by transmission lines: a revisited problem. (United States)

    Ranfagni, Anedio; Cacciari, Ilaria; Moretti, Paolo


    The problem of evaluating dissipative effects in Josephson junctions loaded by transmission lines is reexamined, for either the symmetric or the asymmetric case, with particular consideration of the time domain in which the interaction between junction and load system occurs.

  6. Long-range neural and gap junction protein-mediated cues control polarity during planarian regeneration

    NARCIS (Netherlands)

    Morokuma, Junji; Oviedo, Nestor J.; Walentek, Peter; Kema, Ido P.; Gu, Man Bock; Ahn, Joo-Myung; Hwang, Jung Shan; Gojobori, Takashi; Levin, Michael


    Having the ability to coordinate the behavior of stem cells to induce regeneration of specific large-scale structures would have far-reaching consequences in the treatment of degenerative diseases, acute injury, and aging. Thus, identifying and learning to manipulate the sequential steps that

  7. Role of gap junction protein connexin43 in astrogliosis induced by brain injury.

    Directory of Open Access Journals (Sweden)

    Nicolas Theodoric

    Full Text Available Astrogliosis is a process that involves morphological and biochemical changes associated with astrocyte activation in response to cell damage in the brain. The upregulation of intermediate filament proteins including glial fibrillary acidic protein (GFAP, nestin and vimentin are often used as indicators for astrogliosis. Although connexin43 (Cx43, a channel protein widely expressed in adult astrocytes, exhibits enhanced immunoreactivity in the peri-lesion region, its role in astrogliosis is still unclear. Here, we correlated the temporal and spatial expression of Cx43 to the activation of astrocytes and microglia in response to an acute needle stab wound in vivo. We found large numbers of microglia devoid of Cx43 in the needle wound at 3 days post injury (dpi while reactive astrocytes expressing Cx43 were present in the peripheral zone surrounding the injury site. A redistribution of Cx43 to the needle site, corresponding to the increased presence of GFAP-positive reactive astrocytes in the region, was only apparent from 6 dpi and sustained until at least 15 dpi. Interestingly, the extent of microglial activation and subsequent astrogliosis in the brain of Cx43 knockout mice was significantly larger than those of wild type, suggesting that Cx43 expression limits the degree of microgliosis. Although Cx43 is not essential for astrogliosis and microglial activation induced by a needle injury, our results demonstrate that Cx43 is a useful marker for injury induced astrogliosis due to its enhanced expression specifically within a small region of the lesion for an extended period. As a channel protein, Cx43 is a potential in vivo diagnostic tool of asymptomatic brain injury.

  8. Equilibrium analysis and phase synchronization of two coupled HR neurons with gap junction. (United States)

    Wang, Haixia; Wang, Qingyun; Lu, Qishao; Zheng, Yanhong


    The properties of equilibria and phase synchronization involving burst synchronization and spike synchronization of two electrically coupled HR neurons are studied in this paper. The findings reveal that in the non-delayed system the existence of equilibria can be turned into intersection of two odd functions, and two types of equilibria with symmetry and non-symmetry can be found. With the stability and bifurcation analysis, the bifurcations of equilibria are investigated. For the delayed system, the equilibria remain unchanged. However, the Hopf bifurcation point is drastically affected by time delay. For the phase synchronization, we focus on the synchronization transition from burst synchronization to spike synchronization in the non-delayed system and the effect of coupling strength and time delay on spike synchronization in delayed system. In addition, corresponding firing rhythms and spike synchronized regions are obtained in the two parameters plane. The results allow us to better understand the properties of equilibria, multi-time-scale properties of synchronization and temporal encoding scheme in neuronal systems.

  9. The connexin 46 mutant (V44M) impairs gap junction function ...

    Indian Academy of Sciences (India)

    Department of Ophthalmology, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang 157000, Heilongjiang Province, People's Republic of China; Department of Genetics, National Research Institute for Family Planning, Beijing 100081, People's Republic of China; Department of Immunology, Basic Medical College ...

  10. Quantification of gap junctional intercellular communication based on digital image analysis

    DEFF Research Database (Denmark)

    Hofgaard, Johannes P; Mollerup, Sarah; Holstein-Rathlou, Niels-Henrik


    numerous cells to obtain reliable estimates of metabolic coupling. Quantification is often based on manual counting of fluorescent cells, which is time consuming and may include some degree of subjectivity. In this report, we introduce a technique based on digital image analysis, and the software...... process with a high degree of reproducibility....

  11. Sphingosine-1-Phosphate reduces ischemia/reperfusion injury by phosphorylating the gap junction protein Connexin43

    DEFF Research Database (Denmark)

    Morel, Sandrine; Christoffersen, Christina; Axelsen, Lene N


    targets are largely unknown. Here, we investigate the pathways by which the Sphingosine-1-Phosphate (S1P) constituent of HDL limits cell death induced by cardiac ischemia/reperfusion (I/R). METHODS AND RESULTS: Apolipoprotein M (ApoM) transgenic (Apom-Tg) mice, in which plasma S1P is increased by 296...

  12. Managing the complexity of communication: regulation of gap junctions by post-translational modification

    DEFF Research Database (Denmark)

    Axelsen, Lene Nygaard; Callø, Kirstine; von Holstein-Rathlou, Niels-Henrik


    expression by transcription and translation is of great importance, the trafficking, channel activity and degradation are also under tight control. The function of connexins can be regulated by several post translational modifications, which affect numerous parameters; including number of channels, open...

  13. Voltage-Controlled Switching and Thermal Effects in VO2 Nano-Gap Junctions (United States)


    Driscoll, J. Quinn, M. Di Ventra, D. N. Basov, G. Seo, Y.-W. Lee, H.-T. Kim, and D. R. Smith, Phys. Rev. B 86, 094203 (2012). 35A. Zimmers , L. Aigouy...R. T. Han , S. D. Mahanti, P. M. Duxbury, F. Yuan, C.-Y. Ruan, K. Wang, and J. Wu, Phys. Rev. Lett. 109, 166406 (2012). 40C. Ko, Z. Yang, and S

  14. Stem cells can form gap junctions with cardiac myocytes and exert pro-arrhythmic effects

    Directory of Open Access Journals (Sweden)

    Nicoline Willemijn Smit


    Full Text Available Stem cell therapy has been suggested to be a promising option for regeneration of injured myocardium, for example following a myocardial infarction. For clinical use cell-based therapies have to be safe and applicable and are aimed to renovate the architecture of the heart. Yet for functional and coordinated activity synchronized with the host myocardium stem cells have to be capable of forming electrical connections with resident cardiomyocytes. In this paper we discuss whether stem cells are capable of establishing functional electrotonic connections with cardiomyocytes and whether these may generate a risk for arrhythmias. Application of stem cells in the clinical setting with outcomes concerning arrhythmogenic safety and future perspectives will also briefly be touched upon.

  15. Superconducting transport in single and parallel double InAs quantum dot Josephson junctions with Nb-based superconducting electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Baba, Shoji, E-mail:; Sailer, Juergen [Department of Applied Physics, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); Deacon, Russell S. [Center for Emergent Matter Science (CEMS), RIKEN, Wako, Saitama 351-0198 (Japan); RIKEN Advanced Science Laboratory, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Oiwa, Akira [The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047 (Japan); Shibata, Kenji [Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505 (Japan); Department of Electronics and Intelligent Systems, Tohoku Institute of Technology, Sendai 982-8577 (Japan); Hirakawa, Kazuhiko [Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505 (Japan); JST CREST, 4-1-8 Hon-cho, Kawaguchi-shi, Saitama 332-0012 (Japan); Tarucha, Seigo [Department of Applied Physics, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); Center for Emergent Matter Science (CEMS), RIKEN, Wako, Saitama 351-0198 (Japan); INQIE, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505 (Japan); QPEC, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 113-8656 (Japan)


    We report conductance and supercurrent measurements for InAs single and parallel double quantum dot Josephson junctions contacted with Nb or NbTiN superconducting electrodes. Large superconducting gap energy, high critical field, and large switching current are observed, all reflecting the features of Nb-based electrodes. For the parallel double dots, we observe an enhanced supercurrent when both dots are on resonance, which may reflect split Cooper pair tunneling.

  16. Epitaxial NbN/AlN/NbN tunnel junctions on Si substrates with TiN buffer layers

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Rui [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology (SIMIT), Chinese Academy of Sciences (CAS), Shanghai 200050 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Makise, Kazumasa; Terai, Hirotaka [Advanced ICT Research Institute, National Institute of Information and Communications Technology (Japan); Zhang, Lu [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology (SIMIT), Chinese Academy of Sciences (CAS), Shanghai 200050 (China); Wang, Zhen, E-mail: [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology (SIMIT), Chinese Academy of Sciences (CAS), Shanghai 200050 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Shanghai Tech University, Shanghai 201210 (China)


    We have developed epitaxial NbN/AlN/NbN tunnel junctions on Si (100) substrates with a TiN buffer layer. A 50-nm-thick (200)-oriented TiN thin film was introduced as the buffer layer for epitaxial growth of NbN/AlN/NbN trilayers on Si substrates. The fabricated NbN/AlN/NbN junctions demonstrated excellent tunneling properties with a high gap voltage of 5.5 mV, a large I{sub c}R{sub N} product of 3.8 mV, a sharp quasiparticle current rise with a ΔV{sub g} of 0.4 mV, and a small subgap leakage current. The junction quality factor R{sub sg}/R{sub N} was about 23 for the junction with a J{sub c} of 47 A/cm{sup 2} and was about 6 for the junction with a J{sub c} of 3.0 kA/cm{sup 2}. X-ray diffraction and transmission electron microscopy observations showed that the NbN/AlN/NbN trilayers were grown epitaxially on the (200)-orientated TiN buffer layer and had a highly crystalline structure with the (200) orientation.

  17. Epitaxial NbN/AlN/NbN tunnel junctions on Si substrates with TiN buffer layers

    Directory of Open Access Journals (Sweden)

    Rui Sun


    Full Text Available We have developed epitaxial NbN/AlN/NbN tunnel junctions on Si (100 substrates with a TiN buffer layer. A 50-nm-thick (200-oriented TiN thin film was introduced as the buffer layer for epitaxial growth of NbN/AlN/NbN trilayers on Si substrates. The fabricated NbN/AlN/NbN junctions demonstrated excellent tunneling properties with a high gap voltage of 5.5 mV, a large IcRN product of 3.8 mV, a sharp quasiparticle current rise with a ΔVg of 0.4 mV, and a small subgap leakage current. The junction quality factor Rsg/RN was about 23 for the junction with a Jc of 47 A/cm2 and was about 6 for the junction with a Jc of 3.0 kA/cm2. X-ray diffraction and transmission electron microscopy observations showed that the NbN/AlN/NbN trilayers were grown epitaxially on the (200-orientated TiN buffer layer and had a highly crystalline structure with the (200 orientation.

  18. Defect formation in long Josephson junctions

    DEFF Research Database (Denmark)

    Gordeeva, Anna; Pankratov, Andrey


    We study numerically a mechanism of vortex formation in a long Josephson junction within the framework of the one-dimensional sine-Gordon model. This mechanism is switched on below the critical temperature. It is shown that the number of fluxons versus velocity of cooling roughly scales according...

  19. Characterization of magnetic tunnel junction test pads

    DEFF Research Database (Denmark)

    Østerberg, Frederik Westergaard; Kjær, Daniel; Nielsen, Peter Folmer


    We show experimentally as well as theoretically that patterned magnetic tunnel junctions can be characterized using the current-in-plane tunneling (CIPT) method, and the key parameters, the resistance-area product (RA) and the tunnel magnetoresistance (TMR), can be determined. The CIPT method...

  20. Dismembered pyeloplasty for ureteropelvic junction syndrome ...

    African Journals Online (AJOL)

    Background: Open dismembered pyeloplasty remains the preferred surgical technique for ureteropelvic junction syndrome (UPJS) in most paediatric urology units. The authors present their experience of 230 patients and describe their form of presentation, treatment and early and long-term results. Materials and Methods: ...

  1. Two-dimensional bipolar junction transistors (United States)

    Gharekhanlou, Behnaz; Khorasani, Sina; Sarvari, Reza


    Recent development in fabrication technology of planar two-dimensional (2D) materials has introduced the possibility of numerous novel applications. Our recent analysis has revealed that by definition of p-n junctions through appropriate patterned doping of 2D semiconductors, ideal exponential I-V characteristics may be expected. However, the theory of 2D junctions turns out to be very different to that of standard bulk junctions. Based on this theory of 2D diodes, we construct for the first time a model to describe 2D bipolar junction transistors (2D-BJTs). We derive the small-signal equivalent model, and estimate the performance of a 2D-BJT device based on graphone as the example material. A current gain of about 138 and maximum threshold frequency of 77 GHz, together with a power-delay product of only 4 fJ per 1 μm lateral width is expected at an operating voltage of 5 V. In addition, we derive the necessary formulae and a new approximate solution for the continuity equation in the 2D configuration, which have been verified against numerical solutions.

  2. Craniocervical junction abnormalities with atlantoaxial subluxation ...

    African Journals Online (AJOL)

    Craniocervical junction abnormalities with atlantoaxial subluxation caused by ventral subluxation of C2 were diagnosed in a 6-month-old female Pomeranian with tetraplegia as a clinical sign. Lateral survey radiography of the neck with flexion revealed atlantoaxial subluxation with ventral subluxation of C2. Computed ...

  3. Intrinsically shunted Josephson junctions for electronics applications (United States)

    Belogolovskii, M.; Zhitlukhina, E.; Lacquaniti, V.; De Leo, N.; Fretto, M.; Sosso, A.


    Conventional Josephson metal-insulator-metal devices are inherently underdamped and exhibit hysteretic current-voltage response due to a very high subgap resistance compared to that in the normal state. At the same time, overdamped junctions with single-valued characteristics are needed for most superconducting digital applications. The usual way to overcome the hysteretic behavior is to place an external low-resistance normal-metal shunt in parallel with each junction. Unfortunately, such solution results in a considerable complication of the circuitry design and introduces parasitic inductance through the junction. This paper provides a concise overview of some generic approaches that have been proposed in order to realize internal shunting in Josephson heterostructures with a barrier that itself contains the desired resistive component. The main attention is paid to self-shunted devices with local weak-link transmission probabilities that are so strongly disordered in the interface plane that transmission probabilities are tiny for the main part of the transition region between two super-conducting electrodes, while a small part of the interface is well transparent. We discuss the possibility of realizing a universal bimodal distribution function and emphasize advantages of such junctions that can be considered as a new class of self-shunted Josephson devices promising for practical applications in superconducting electronics operating at 4.2 K.

  4. Gallium nitride junction field-effect transistor (United States)

    Zolper, John C.; Shul, Randy J.


    An all-ion implanted gallium-nitride (GaN) junction field-effect transistor (JFET) and method of making the same. Also disclosed are various ion implants, both n- and p-type, together with or without phosphorous co-implantation, in selected III-V semiconductor materials.

  5. Internal dynamics of long Josephson junction oscillators

    DEFF Research Database (Denmark)

    Christiansen, Peter Leth; Lomdahl, P. S.; Scott, Alwyn C.


    Numerical computations on a sine-Gordon model of the Josephson junction fluxon oscillator are compared with experimental measurements. Good agreement is found for the voltage current characteristic, oscillator power output, and range of current bias over which oscillation is observed. Our numerical...

  6. Holographic Josephson junction from massive gravity

    NARCIS (Netherlands)

    Hu, Ya-Peng; Li, Huai-Fan; Zeng, Hua-Bi; Zhang, H.


    We study the holographic superconductor-normal metal-superconductor (SNS) Josephson junction in de Rham-Gabadadze-Tolley massive gravity. If the boundary theory is independent of spatial directions, i.e., if the chemical potential is homogeneous in spatial directions, we find that the graviton mass

  7. The functional anatomy of the ureterovesical junction

    NARCIS (Netherlands)

    Thomson, A. S.; Dabhoiwala, N. F.; Verbeek, F. J.; Lamers, W. H.


    To obtain a new insight into the anti-reflux mechanism of the ureterovesical junction by studying the topographical anatomy of the juxta- and intravesical ureter and its relationship to the surrounding bladder musculature. Fresh pig bladders were fixed, frozen and serially sectioned. Enzyme

  8. Characterization of idiopathic esophagogastric junction outflow obstruction

    NARCIS (Netherlands)

    van Hoeij, F. B.; Smout, A. J. P. M.; Bredenoord, A. J.


    Esophagogastric junction (EGJ) outflow obstruction is a manometric diagnosis, characterized by an elevated relaxation pressure (IRP4) of the lower esophageal sphincter (LES) and intact or weak peristalsis. The etiology and preferred treatment remain unknown. We describe a large patient cohort in

  9. Anatomy of the human atrioventricular junctions revisited

    NARCIS (Netherlands)

    Anderson, R. H.; Ho, S. Y.; Becker, A. E.


    There have been suggestions made recently that our understanding of the atrioventricular junctions of the heart is less than adequate, with claims for several new findings concerning the arrangement of the ordinary working myocardium and the specialised pathways for atrioventricular conduction. In

  10. Microscopic tunneling theory of long Josephson junctions

    DEFF Research Database (Denmark)

    Grønbech-Jensen, N.; Hattel, Søren A.; Samuelsen, Mogens Rugholm


    We present a numerical scheme for solving a nonlinear partial integro-differential equation with nonlocal time dependence. The equation describes the dynamics in a long Josephson junction modeled by use of the microscopic theory for tunneling between superconductors. We demonstrate...

  11. Structural insights into the exon junction complex. (United States)

    Le Hir, Hervé; Andersen, Gregers Rom


    In higher eukaryotes, the exon junction complex is loaded onto spliced mRNAs at a precise position upstream of exon junctions, where it remains during nuclear export and cytoplasmic localisation until it is removed during the first translation round. The exon junction core complex consists of four proteins that form a dynamic binding platform for a variety of peripheral factors involved in mRNA metabolism. In the complex, mRNA binding is mediated by the DEAD-box protein eIF4AIII, and inhibition of its ATPase activity forms the mechanistic basis for the long-term stability of the complex. Recent crystal structures of the exon junction complex and eIF4AIII have provided the structural framework for investigating the function of the eIF4AIII ATPase and for localisation of surface patches involved in binding peripheral factors. Additionally, by comparison with the structure of a second DEAD-box protein also bound to RNA and ATP, general principles for the ATPase and unwinding/mRNP remodelling activities for this important group of enzymes can be proposed on the basis of atomic structures.

  12. Fluxon density waves in long Josephson junctions

    DEFF Research Database (Denmark)

    Olsen, O. H.; Ustinov, A. V.; Pedersen, Niels Falsig


    Numerical simulations of the multiple fluxon dynamics stimulated by an external oscillating force applied at a boundary of a long Josephson junction are presented. The calculated IV characteristics agree well with a recent experimental observation of rf-induced satellite flux-flow steps. The volt...... density waves....

  13. Closing the stop gap

    Energy Technology Data Exchange (ETDEWEB)

    Czakon, Michal [RWTH Aachen Univ. (Germany). Inst. fuer Theoretische Teilchnphysik und Kosmologie; Mitov, Alexander [Univ. of Cambridge (United Kingdom). Cavendish Lab.; Papucci, Michele [Lawrence Berkeley National Laboratory, CA (United States). Theoretical Physics Group; California Univ., Berkeley, CA (United States). Dept. of Physics; Ruderman, Joshua T. [Lawrence Berkeley National Laboratory, CA (United States). Theoretical Physics Group; California Univ., Berkeley, CA (United States). Dept. of Physics; New York Univ., NY (United States). Center for Cosmology and Particle Physics; Weiler, Andreas [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); CERN - European Organization for Nuclear Research, Geneva (Switzerland). Theory Div.


    Light stops are a hallmark of the most natural realizations of weak-scale supersymmetry. While stops have been extensively searched for, there remain open gaps around and below the top mass, due to similarities of stop and top signals with current statistics. We propose a new fast-track avenue to improve light stop searches for R-parity conserving supersymmetry, by comparing top cross section measurements to the theoretical prediction. Stop masses below ∝180 GeV can now be ruled out for a light neutralino. The possibility of a stop signal contaminating the top mass measurement is also briefly addressed.

  14. Addressing the innovation gap. (United States)

    Jeffrey, Phillip; Warne, Peter; Williams, Robert


    The 10 years since the mid-1990s have witnessed an unprecedented investment in Drug Discovery driven by both the unraveling of the human genome and the parallel introduction of various high-throughput technologies. During the same period, industry metrics describe a decline in the numbers of new molecular entities launched upon the global pharmaceutical markets. The Society for Medicines Research (SMR) meeting entitled "Addressing the Innovation Gap" brought together a program of expert speakers to comment upon the challenges currently facing the pharmaceutical industry and some of the measures being undertaken to enable future success.

  15. Tricellular junctions: how to build junctions at the TRICkiest points of epithelial cells (United States)

    Higashi, Tomohito; Miller, Ann L.


    Tricellular contacts are the places where three cells meet. In vertebrate epithelial cells, specialized structures called tricellular tight junctions (tTJs) and tricellular adherens junctions (tAJs) have been identified. tTJs are important for the maintenance of barrier function, and disruption of tTJ proteins contributes to familial deafness. tAJs have recently been attracting the attention of mechanobiologists because these sites are hot spots of epithelial tension. Although the molecular components, regulation, and function of tTJs and tAJs, as well as of invertebrate tricellular junctions, are beginning to be characterized, many questions remain. Here we broadly cover what is known about tricellular junctions, propose a new model for tension transmission at tAJs, and discuss key open questions. PMID:28705832

  16. Long Josephson Junction Stack Coupled to a Cavity

    DEFF Research Database (Denmark)

    Madsen, Søren Peder; Pedersen, Niels Falsig; Groenbech-Jensen, N.


    A stack of inductively coupled long Josephson junctions are modeled as a system of coupled sine-Gordon equations. One boundary of the stack is coupled electrically to a resonant cavity. With one fluxon in each Josephson junction, the inter-junction fluxon forces are repulsive. We look at a possible...

  17. Systematic study of shallow junction formation on germanium substrates

    DEFF Research Database (Denmark)

    Hellings, Geert; Rosseel, Erik; Clarysse, Trudo


    Published results on Ge junctions are benchmarked systematically using RS–XJ plots. The electrical activation level required to meet the ITRS targets is calculated. Additionally, new results are presented on shallow furnace-annealed B junctions and shallow laser-annealed As junctions. Co-implanti...

  18. Absolute migration and the evolution of the Rodriguez triple junction ...

    African Journals Online (AJOL)

    The Rodriguez Triple Junction (RTJ) is a junction connecting three mid-ocean ridges in the Indian Ocean: the Southwest Indian Ridge (SWIR), the Central Indian Ridge (CIR) and the Southeast Indian Ridge (SEIR). The evolution of the RTJ has been studied extensively for the past 10 Ma and the triple junction is believed to ...

  19. Tunneling Nanotubes and Gap Junctions–Their Role in Long-Range Intercellular Communication during Development, Health, and Disease Conditions

    Directory of Open Access Journals (Sweden)

    Jennifer Ariazi


    Full Text Available Cell-to-cell communication is essential for the organization, coordination, and development of cellular networks and multi-cellular systems. Intercellular communication is mediated by soluble factors (including growth factors, neurotransmitters, and cytokines/chemokines, gap junctions, exosomes and recently described tunneling nanotubes (TNTs. It is unknown whether a combination of these communication mechanisms such as TNTs and gap junctions may be important, but further research is required. TNTs are long cytoplasmic bridges that enable long-range, directed communication between connected cells. The proposed functions of TNTs are diverse and not well understood but have been shown to include the cell-to-cell transfer of vesicles, organelles, electrical stimuli and small molecules. However, the exact role of TNTs and gap junctions for intercellular communication and their impact on disease is still uncertain and thus, the subject of much debate. The combined data from numerous laboratories indicate that some TNT mediate a long-range gap junctional communication to coordinate metabolism and signaling, in relation to infectious, genetic, metabolic, cancer, and age-related diseases. This review aims to describe the current knowledge, challenges and future perspectives to characterize and explore this new intercellular communication system and to design TNT-based therapeutic strategies.

  20. Bisphosphonate osteo-necrosis of the jaws [BONJ], from defective function of oral epithelial intercellular junctions? (United States)

    Touyz, Louis Z G


    Bone osteonecrosis of the jaws (BONJ) is prevalent when diseases are treated with high bisphosphonate doses. The mouth is unique in that it has epithelial covered bony protuberances jutting into an infective environment. Should epithelium over these bony prominences be disrupted, abraded or ulcerated by trauma, extraction or therapy, not only will the mucosa not heal, but in vulnerable cases, where less-vital bone is present, there is development of BONJ. BONJ development is explained by BP's depleting available calcium ions from healthy functioning of epithelial gap junctions and disrupting the balance between osteogenesis and osteoclasis. Copyright © 2015. Published by Elsevier Ltd.

  1. Gap Task Force

    CERN Multimedia

    Lissuaer, D

    One of the more congested areas in the ATLAS detector is the GAP region (the area between the Barrel Calorimeter and the End Cap calorimeter) where Inner Detector services, LAr Services and some Tile services all must co-habitat in a very limited area. It has been clear for some time that the space in the GAP region is not sufficient to accommodate all that is needed. In the last few month additional problems of routing all the services to Z=0 have been encountered due to the very limited space between the Tile Calorimeter and the first layer of Muon chambers. The Technical Management Board (TMB) and the Executive Board (EB) decided in the middle of March to establish a Task Force to look at this problem and come up with a solution within well-specified guidelines. The task force consisted of experts from the ID, Muon, Liquid Argon and Tile systems in addition to experts from the Technical Coordination team and the Physics coordinator. The task force held many meetings and in general there were some very l...

  2. GAP-REACH (United States)

    Lewis-Fernández, Roberto; Raggio, Greer A.; Gorritz, Magdaliz; Duan, Naihua; Marcus, Sue; Cabassa, Leopoldo J.; Humensky, Jennifer; Becker, Anne E.; Alarcón, Renato D.; Oquendo, María A.; Hansen, Helena; Like, Robert C.; Weiss, Mitchell; Desai, Prakash N.; Jacobsen, Frederick M.; Foulks, Edward F.; Primm, Annelle; Lu, Francis; Kopelowicz, Alex; Hinton, Ladson; Hinton, Devon E.


    Growing awareness of health and health care disparities highlights the importance of including information about race, ethnicity, and culture (REC) in health research. Reporting of REC factors in research publications, however, is notoriously imprecise and unsystematic. This article describes the development of a checklist to assess the comprehensiveness and the applicability of REC factor reporting in psychiatric research publications. The 16-itemGAP-REACH© checklist was developed through a rigorous process of expert consensus, empirical content analysis in a sample of publications (N = 1205), and interrater reliability (IRR) assessment (N = 30). The items assess each section in the conventional structure of a health research article. Data from the assessment may be considered on an item-by-item basis or as a total score ranging from 0% to 100%. The final checklist has excellent IRR (κ = 0.91). The GAP-REACH may be used by multiple research stakeholders to assess the scope of REC reporting in a research article. PMID:24080673

  3. The Politics of Achievement Gaps

    DEFF Research Database (Denmark)

    Valant, J.; Newark, D. A.


    on achievement gaps have received little attention from researchers, despite playing an important role in shaping policymakers’ behaviors. Drawing on randomized experiments with a nationally representative sample of adults, we explore the public’s beliefs about test score gaps and its support for gap......For decades, researchers have documented large differences in average test scores between minority and White students and between poor and wealthy students. These gaps are a focal point of reformers’ and policymakers’ efforts to address educational inequities. However, the U.S. public’s views......-closing initiatives. We find that Americans are more concerned about—and more supportive of proposals to close—wealth-based achievement gaps than Black-White or Hispanic-White gaps. Americans also explain the causes of wealth-based gaps more readily. © 2016 AERA....

  4. Minding the gap

    Directory of Open Access Journals (Sweden)

    Mia Carlberg


    Full Text Available The plan for the Round table session was to focus on organizational and social/cultural differences between librarians and faculty with the aim to increase our awareness of the differences when we try to find ways to cooperate within the academy or school. This may help us to sort things out, experience acceptance and take adequate actions, saving energy and perhaps be less frustrated.  The questions that the workshop addressed were: What is in the gap between librarians and faculty when dealing with information literacy? How can we fill the gap? Participants discussed this in detail with the aim of together finding ways to understand it better and make it possible to find ways to fill this gap. By defining it and thereby making it easier to work out a strategy for future action to improve the teaching of information literacy, including listing possible, impossible or nearly impossible ways. The springboard to the discussion was extracted from some projects that the workshop leader has been engaged in since 2009. The first example is a research circle where Uppsala University Library used action research to observe and understand the process when we had the opportunity to implement information literacy classes with progression in an undergraduate program. What worked well? What did not? Why? This work was described together with other examples from Uppsala University to an international panel working with quality issues. What did they think of our work? May this change the ways we are working? How? Another example is an ongoing joint project where librarians and faculty members are trying to define ways to increase the cooperation between the library and faculty and make this cooperation sustainable. Recent experience from this was brought to the discussion.   There are an overwhelming number of papers written in this field. A few papers have inspired these ideas. One article in particular: Christiansen, L., Stombler, M. & Thaxton, L. (2004. A

  5. Small Multiples with Gaps. (United States)

    Meulemans, Wouter; Dykes, Jason; Slingsby, Aidan; Turkay, Cagatay; Wood, Jo


    Small multiples enable comparison by providing different views of a single data set in a dense and aligned manner. A common frame defines each view, which varies based upon values of a conditioning variable. An increasingly popular use of this technique is to project two-dimensional locations into a gridded space (e.g. grid maps), using the underlying distribution both as the conditioning variable and to determine the grid layout. Using whitespace in this layout has the potential to carry information, especially in a geographic context. Yet, the effects of doing so on the spatial properties of the original units are not understood. We explore the design space offered by such small multiples with gaps. We do so by constructing a comprehensive suite of metrics that capture properties of the layout used to arrange the small multiples for comparison (e.g. compactness and alignment) and the preservation of the original data (e.g. distance, topology and shape). We study these metrics in geographic data sets with varying properties and numbers of gaps. We use simulated annealing to optimize for each metric and measure the effects on the others. To explore these effects systematically, we take a new approach, developing a system to visualize this design space using a set of interactive matrices. We find that adding small amounts of whitespace to small multiple arrays improves some of the characteristics of 2D layouts, such as shape, distance and direction. This comes at the cost of other metrics, such as the retention of topology. Effects vary according to the input maps, with degree of variation in size of input regions found to be a factor. Optima exist for particular metrics in many cases, but at different amounts of whitespace for different maps. We suggest multiple metrics be used in optimized layouts, finding topology to be a primary factor in existing manually-crafted solutions, followed by a trade-off between shape and displacement. But the rich range of possible

  6. Shunted-Josephson-junction model. I. The autonomous case

    DEFF Research Database (Denmark)

    Belykh, V. N.; Pedersen, Niels Falsig; Sørensen, O. H.


    The shunted-Josephson-junction model: the parallel combination of a capacitance, a phase-dependent conductance, and an ideal junction element biased by a constant current, is discussed for arbitrary values of the junction parameters. The main objective is to provide a qualitative understanding...... of the junction behavior in different regions of the parameter space. Approximate formulas are given for the parameter-space decomposition into regions of qualitatively different junction behavior corroborated by the associated-phase plane portraits and also approximate expressions for the corresponding dc...

  7. Planar Josephson tunnel junctions in a transverse magnetic field

    DEFF Research Database (Denmark)

    Monacoa, R.; Aarøe, Morten; Mygind, Jesper


    demagnetization effects imposed by the tunnel barrier and electrodes geometry are important. Measurements of the junction critical current versus magnetic field in planar Nb-based high-quality junctions with different geometry, size, and critical current density show that it is advantageous to use a transverse......Traditionally, since the discovery of the Josephson effect in 1962, the magnetic diffraction pattern of planar Josephson tunnel junctions has been recorded with the field applied in the plane of the junction. Here we discuss the static junction properties in a transverse magnetic field where...

  8. Diluted II-VI oxide semiconductors with multiple band gaps. (United States)

    Yu, K M; Walukiewicz, W; Wu, J; Shan, W; Beeman, J W; Scarpulla, M A; Dubon, O D; Becla, P


    We report the realization of a new mult-band-gap semiconductor. Zn(1-y)Mn(y)OxTe1-x alloys have been synthesized using the combination of oxygen ion implantation and pulsed laser melting. Incorporation of small quantities of isovalent oxygen leads to the formation of a narrow, oxygen-derived band of extended states located within the band gap of the Zn(1-y)Mn(y)Te host. When only 1.3% of Te atoms are replaced with oxygen in a Zn0.88Mn0.12Te crystal the resulting band structure consists of two direct band gaps with interband transitions at approximately 1.77 and 2.7 eV. This remarkable modification of the band structure is well described by the band anticrossing model. With multiple band gaps that fall within the solar energy spectrum, Zn(1-y)Mn(y)OxTe1-x is a material perfectly satisfying the conditions for single-junction photovoltaics with the potential for power conversion efficiencies surpassing 50%.

  9. Bridging the gaps

    Directory of Open Access Journals (Sweden)

    Victoria Francis


    Full Text Available By the year 2020, the international eye care community hopes to have eliminated avoidable blindness as a public health problem. The global partnership, VISION 2020: The Right to Sight, has provided a focus for all concerned (from international policy makers to village level health workers, identified five priority eye conditions, and clarified the key components to achieve this purpose.1,2 However, as Daniel Etya’ale, co-ordinator for VISION 2020 in Africa points out, there is still a big gap between what needs to be done and what is being done and he estimates that currently hardly 20 per cent of the current needs in Africa are being met. On a more optimistic note, there has been a move towards closer and more functional partnerships between professional groups, governments, NGOs and industry.

  10. Unveiling the Gap

    DEFF Research Database (Denmark)

    Jensson, Pall; Rokkjær, Ole; Nørgaard, Bente

    needs, how universities decide what to teach, and how to bridge the gap. Do the university programs simply reflect the expertise of the faculty members? Is there need for increasing emphasis on continuing education? Is life-long education the answer, and has this been addressed by the CDIO community?......This paper describes a project in Europe called Industrial Engineering Standards in Europe (IESE). The project was collaboration between universities and organizations that offer Industrial Engineering (IE) education and/or continuing education in 6 European countries. The project was funded...... by the EU Leonardo da Vinci Partnership program. The project had two objectives. The first objective was to use the European Qualification Framework (EQF) as a benchmark against the National Qualification Framework (NQF) of the partner countries and the IE educations offered by the partner institutions...

  11. Bridging the Evaluation Gap

    Directory of Open Access Journals (Sweden)

    Paul Wouters


    Full Text Available Paul Wouters’ essay is concerned with bridging the gap between what we value in our academic work and how we are assessed in formal evaluation exercises. He reflects on the recent evaluation of his own center, and reminds us that it is productive to see evaluations not as the (obviously impossible attempt to produce a true representation of past work, but rather as the exploration and performance of “who one wants to be.” Reflecting on why STS should do more than just play along to survive in the indicator game, he suggests that our field should contribute to changing its very rules. In this endeavor, the attitude and sensibilities developed in our field may be more important than any specific theoretical concepts or methodologies.

  12. Bias dependence of the response of superconducting tunnel junctions used as photon detectors

    CERN Document Server

    Poelaert, A; Peacock, A; Kozorezov, A; Wigmore, J K


    In the last decade, several research groups have developed superconducting tunnel junctions (STJ) for photon detection in astronomy. Despite extensive studies, the behavior of multi-layered devices, subject to the superconducting proximity effect (proximized devices), has remained difficult to model. Recently, a new model has been presented, leading to a more realistic approach for the photon detection within an STJ. This model is based on the existence of local traps in the superconducting electrodes of the STJ. In this paper, we show that the new model is successful in predicting the bias dependence of the response of an STJ. The bias dependence also demonstrates that the quasiparticles, i.e. the charge carriers created as a result of the photon absorption process, cannot relax down to the superconducting energy gap. This result is important, since most theoretical developments to date (implicitly) assume that quasiparticle relax to the gap energy. crystal-structure; energy-levels; tantalum-; traps cooper-p...

  13. Junction conditions in extended Teleparallel gravities

    Energy Technology Data Exchange (ETDEWEB)

    De la Cruz-Dombriz, Álvaro [Departamento de Física Teórica I, Ciudad Universitaria, Universidad Complutense de Madrid, E-28040 Madrid (Spain); Dunsby, Peter K.S.; Sáez-Gómez, Diego, E-mail:, E-mail:, E-mail: [Astrophysics, Cosmology and Gravity Centre (ACGC), Department of Mathematics and Applied Mathematics, University of Cape Town, Rondebosch 7701, Cape Town (South Africa)


    In the context of extended Teleparallel gravity theories, we address the issue of junction conditions required to guarantee the correct matching of different regions of spacetime. In the absence of shells/branes, these conditions turn out to be more restrictive than their counterparts in General Relativity as in other extended theories of gravity. In fact, the general junction conditions on the matching hypersurfaces depend on the underlying theory and a new condition on the induced tetrads in order to avoid delta-like distributions in the field equations. This result imposes strict consequences on the viability of standard solutions such as the Einstein-Straus-like construction. We find that the continuity of the scalar torsion is required in order to recover the usual General Relativity results.

  14. Shot noise in YBCO bicrystal Josephson junctions

    DEFF Research Database (Denmark)

    Constantinian, K.Y.; Ovsyannikov, G.A.; Borisenko, I.V.


    We measured spectral noise density in YBCO symmetric bicrystal Josephson junctions on sapphire substrates at bias voltages up to 100 mV and T 4.2 K. Normal state resistance of the Josephson junctions, R-N = 20-90 Omega and ICRN up to 2.2 mV have been observed in the experimental samples. Noise...... measurements were carried out within frequency bands of 1-2 GHz and 0.3-300 kHz. At bias voltages 10 less than or equal to V less than or equal to 60 mV a linear voltage dependence of noise power has been registered, while at V less than or equal to 5 mV a noticeable noise rise has been observed. The latter...

  15. Non-Lagrangian theories from brane junctions

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Ling [Chalmers Univ. of Technology, Goeteborg (Sweden); Mitev, Vladimir [Humboldt Univ., Berlin (Germany). Inst. fuer Mathematik und Inst. fuer Physik; Pomoni, Elli [Deutsches Elektronen-Synchrotron DESY, Hamburg (Germany). Theory Group; Taki, Masato [RIKEN Nishina Center, Saitama (Japan). Mathematical Physics Lab.; Yagi, Futoshi [International School of Advanced Studies (SISSA), Trieste (Italy); INFN, Trieste (Italy); Korea Institute for Advanced Study (KIAS), Seoul (Korea, Republic of)


    In this article we use 5-brane junctions to study the 5D T{sub N} SCFTs corresponding to the 5D N=1 uplift of the 4D N=2 strongly coupled gauge theories, which are obtained by compactifying N M5 branes on a sphere with three full punctures. Even though these theories have no Lagrangian description, by using the 5-brane junctions proposed by Benini, Benvenuti and Tachikawa, we are able to derive their Seiberg-Witten curves and Nekrasov partition functions. We cross-check our results with the 5D superconformal index proposed by Kim, Kim and Lee. Through the AGTW correspondence, we discuss the relations between 5D superconformal indices and n-point functions of the q-deformed W{sub N} Toda theories.

  16. Electron transport in doped fullerene molecular junctions (United States)

    Kaur, Milanpreet; Sawhney, Ravinder Singh; Engles, Derick

    The effect of doping on the electron transport of molecular junctions is analyzed in this paper. The doped fullerene molecules are stringed to two semi-infinite gold electrodes and analyzed at equilibrium and nonequilibrium conditions of these device configurations. The contemplation is done using nonequilibrium Green’s function (NEGF)-density functional theory (DFT) to evaluate its density of states (DOS), transmission coefficient, molecular orbitals, electron density, charge transfer, current, and conductance. We conclude from the elucidated results that Au-C16Li4-Au and Au-C16Ne4-Au devices behave as an ordinary p-n junction diode and a Zener diode, respectively. Moreover, these doped fullerene molecules do not lose their metallic nature when sandwiched between the pair of gold electrodes.

  17. Charge Transport Phenomena in Peptide Molecular Junctions

    Directory of Open Access Journals (Sweden)

    Alessandra Luchini


    Full Text Available Inelastic electron tunneling spectroscopy (IETS is a valuable in situ spectroscopic analysis technique that provides a direct portrait of the electron transport properties of a molecular species. In the past, IETS has been applied to small molecules. Using self-assembled nanoelectronic junctions, IETS was performed for the first time on a large polypeptide protein peptide in the phosphorylated and native form, yielding interpretable spectra. A reproducible 10-fold shift of the I/V characteristics of the peptide was observed upon phosphorylation. Phosphorylation can be utilized as a site-specific modification to alter peptide structure and thereby influence electron transport in peptide molecular junctions. It is envisioned that kinases and phosphatases may be used to create tunable systems for molecular electronics applications, such as biosensors and memory devices.

  18. Gap Junction–mediated Cell–Cell Communication Modulates Mouse Neural Crest Migration


    Huang, G.Y.; Cooper, E.S.; Waldo, K.; Kirby, M L; Gilula, N B; Lo, C.W.


    Previous studies showed that conotruncal heart malformations can arise with the increase or decrease in α1 connexin function in neural crest cells. To elucidate the possible basis for the quantitative requirement for α1 connexin gap junctions in cardiac development, a neural crest outgrowth culture system was used to examine migration of neural crest cells derived from CMV43 transgenic embryos overexpressing α1 connexins, and from α1 connexin knockout (KO) mice and FC transgenic mice expressi...

  19. Josephson spin current in triplet superconductor junctions


    Asano, Yasuhiro


    This paper theoretically discusses the spin current in spin-triplet superconductor / insulator / spin-triplet superconductor junctions. At low temperatures, a midgap Andreev resonant state anomalously enhances not only the charge current but also the spin current. The coupling between the Cooper pairs and the electromagnetic fields leads to the Frounhofer pattern in the direct current spin flow in magnetic fields and the alternative spin current under applied bias-voltages.

  20. Decreased Vision and Junctional Scotoma from Pituicytoma

    Directory of Open Access Journals (Sweden)

    Nancy Huynh


    Full Text Available Pituicytomas are rare neoplasms of the sellar region. We report a case of vision loss and a junctional scotoma in a 43-year-old woman caused by compression of the optic chiasm by a pituitary tumor. The morphological and immunohistochemical characteristics of the tumor were consistent with the diagnosis of pituicytoma. The tumor was debulked surgically, and the patient’s vision improved.