Gap junctional communication modulates gene transcription by altering the recruitment of Sp1 and Sp3 to connexin-response elements in osteoblast promoters

NASA Technical Reports Server (NTRS)

Stains, Joseph P.; Lecanda, Fernando; Screen, Joanne; Towler, Dwight A.; Civitelli, Roberto

2003-01-01

Loss-of-function mutations of gap junction proteins, connexins, represent a mechanism of disease in a variety of tissues. We have shown that recessive (gene deletion) or dominant (connexin45 overexpression) disruption of connexin43 function results in osteoblast dysfunction and abnormal expression of osteoblast genes, including down-regulation of osteocalcin transcription. To elucidate the molecular mechanisms of gap junction-sensitive transcriptional regulation, we systematically analyzed the rat osteocalcin promoter for sensitivity to gap junctional intercellular communication. We identified an Sp1/Sp3 containing complex that assembles on a minimal element in the -70 to -57 region of the osteocalcin promoter in a gap junction-dependent manner. This CT-rich connexin-response element is necessary and sufficient to confer gap junction sensitivity to the osteocalcin proximal promoter. Repression of osteocalcin transcription occurs as a result of displacement of the stimulatory Sp1 by the inhibitory Sp3 on the promoter when gap junctional communication is perturbed. Modulation of Sp1/Sp3 recruitment also occurs on the collagen Ialpha1 promoter and translates into gap junction-sensitive transcriptional control of collagen Ialpha1 gene expression. Thus, regulation of Sp1/Sp3 recruitment to the promoter may represent a potential general mechanism for transcriptional control of target genes by signals passing through gap junctions.

Smad ubiquitination regulatory factor-2 controls gap junction intercellular communication by modulating endocytosis and degradation of connexin43.

PubMed

Fykerud, Tone Aase; Kjenseth, Ane; Schink, Kay Oliver; Sirnes, Solveig; Bruun, Jarle; Omori, Yasufumi; Brech, Andreas; Rivedal, Edgar; Leithe, Edward

2012-09-01

Gap junctions consist of arrays of intercellular channels that enable adjacent cells to communicate both electrically and metabolically. Gap junction channels are made of a family of integral membrane proteins called connexins, of which the best-studied member is connexin43. Gap junctions are dynamic plasma membrane domains, and connexin43 has a high turnover rate in most tissue types. However, the mechanisms involved in the regulation of connexin43 endocytosis and transport to lysosomes are still poorly understood. Here, we demonstrate by live-cell imaging analysis that treatment of cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) induces endocytosis of subdomains of connexin43 gap junctions. The internalized, connexin43-enriched vesicles were found to fuse with early endosomes, which was followed by transport of connexin43 to the lumen of early endosomes. The HECT E3 ubiquitin ligase smad ubiquitination regulatory factor-2 (Smurf2) was found to be recruited to connexin43 gap junctions in response to TPA treatment. Depletion of Smurf2 by small interfering RNA resulted in enhanced levels of connexin43 gap junctions between adjacent cells and increased gap junction intercellular communication. Smurf2 depletion also counteracted the TPA-induced endocytosis and degradation of connexin43. Collectively, these data identify Smurf2 as a novel regulator of connexin43 gap junctions.

Investigations To Characterize Multi-Junction Solar Cells In The Stratosphere Using Low-Cost Balloon And Communication Technologies

NASA Technical Reports Server (NTRS)

Bowe, Glenroy A.; Wang, Qianghua; Woodyard, James R.; Johnston, Richard R.; Brown, William J.

2005-01-01

The use of current balloon, control and communication technologies to test multi-junction solar sell in the stratosphere to achieve near AMO conditions have been investigated. The design criteria for the technologies are that they be reliable, low cost and readily available. Progress is reported on a program to design, launch, fly and retrieve payloads dedicated to testing multi-junction solar cells.

Dielectric properties of biological tissues in which cells are connected by communicating junctions

NASA Astrophysics Data System (ADS)

Asami, Koji

2007-06-01

The frequency dependence of the complex permittivity of biological tissues has been simulated using a simple model that is a cubic array of spherical cells in a parallel plate capacitor. The cells are connected by two types of communicating junctions: one is a membrane-lined channel for plasmodesmata in plant tissues, and the other is a conducting patch of adjoining plasma membranes for gap junctions in animal tissues. Both junctions provided similar effects on the dielectric properties of the tissue model. The model without junction showed a dielectric relaxation (called β-dispersion) that was expected from an interfacial polarization theory for a concentrated suspension of spherical cells. The dielectric relaxation was the same as that of the model in which neighbouring cells were connected by junctions perpendicular to the applied electric field. When neighbouring cells were connected by junctions parallel to the applied electric field or in all directions, a dielectric relaxation appeared at a lower frequency side in addition to the β-dispersion, corresponding to the so called α-dispersion. When junctions were randomly introduced at varied probabilities Pj, the low-frequency (LF) relaxation curve became broader, especially at Pj of 0.2-0.5, and its intensity was proportional to Pj up to 0.7. The intensity and the characteristic frequency of the LF relaxation both decreased with decreasing junction conductance. The simulations indicate that communicating junctions are important for understanding the LF dielectric relaxation in tissues.

INTEGRIN-MEDIATED CELL ATTACHMENT SHOWS TIME-DEPENDENT UPREGULATION OF GAP JUNCTION COMMUNICATION.

EPA Science Inventory

Integrin-mediated Cell Attachment Shows Time-Dependent Upregulation of Gap Junction
Communication

Rachel Grindstaff and Carl Blackman, National Health & Environmental Effects Research
Laboratory, Office of Research and Development, US EPA, Research Triang...

Molecular mechanisms regulating formation, trafficking and processing of annular gap junctions.

PubMed

Falk, Matthias M; Bell, Cheryl L; Kells Andrews, Rachael M; Murray, Sandra A

2016-05-24

Internalization of gap junction plaques results in the formation of annular gap junction vesicles. The factors that regulate the coordinated internalization of the gap junction plaques to form annular gap junction vesicles, and the subsequent events involved in annular gap junction processing have only relatively recently been investigated in detail. However it is becoming clear that while annular gap junction vesicles have been demonstrated to be degraded by autophagosomal and endo-lysosomal pathways, they undergo a number of additional processing events. Here, we characterize the morphology of the annular gap junction vesicle and review the current knowledge of the processes involved in their formation, fission, fusion, and degradation. In addition, we address the possibility for connexin protein recycling back to the plasma membrane to contribute to gap junction formation and intercellular communication. Information on gap junction plaque removal from the plasma membrane and the subsequent processing of annular gap junction vesicles is critical to our understanding of cell-cell communication as it relates to events regulating development, cell homeostasis, unstable proliferation of cancer cells, wound healing, changes in the ischemic heart, and many other physiological and pathological cellular phenomena.

Structure activity relationship of synaptic and junctional neurotransmission.

PubMed

Goyal, Raj K; Chaudhury, Arun

2013-06-01

Chemical neurotransmission may include transmission to local or remote sites. Locally, contact between 'bare' portions of the bulbous nerve terminal termed a varicosity and the effector cell may be in the form of either synapse or non-synaptic contact. Traditionally, all local transmissions between nerves and effector cells are considered synaptic in nature. This is particularly true for communication between neurons. However, communication between nerves and other effectors such as smooth muscles has been described as nonsynaptic or junctional in nature. Nonsynaptic neurotransmission is now also increasingly recognized in the CNS. This review focuses on the relationship between structure and function that orchestrate synaptic and junctional neurotransmissions. A synapse is a specialized focal contact between the presynaptic active zone capable of ultrafast release of soluble transmitters and the postsynaptic density that cluster ionotropic receptors. The presynaptic and the postsynaptic areas are separated by the 'closed' synaptic cavity. The physiological hallmark of the synapse is ultrafast postsynaptic potentials lasting milliseconds. In contrast, junctions are juxtapositions of nerve terminals and the effector cells without clear synaptic specializations and the junctional space is 'open' to the extracellular space. Based on the nature of the transmitters, postjunctional receptors and their separation from the release sites, the junctions can be divided into 'close' and 'wide' junctions. Functionally, the 'close' and the 'wide' junctions can be distinguished by postjunctional potentials lasting ~1s and tens of seconds, respectively. Both synaptic and junctional communications are common between neurons; however, junctional transmission is the rule at many neuro-non-neural effectors. Published by Elsevier B.V.

Structure activity relationship of synaptic and junctional neurotransmission

PubMed Central

Goyal, Raj K; Chaudhury, Arun

2013-01-01

Chemical neurotransmission may include transmission to local or remote sites. Locally, contact between ‘bare’ portions of the bulbous nerve terminal termed a varicosity and the effector cell may be in the form of either synapse or non-synaptic contact. Traditionally, all local transmissions between nerves and effector cells are considered synaptic in nature. This is particularly true for communication between neurons. However, communication between nerves and other effectors such as smooth muscles has been described as nonsynaptic or junctional in nature. Nonsynaptic neurotransmission is now also increasing recognized in the CNS. This review focuses on the relationship between structure and function that orchestrate synaptic and junctional neurotransmissions. A synapse is a specialized focal contact between the presynaptic active zone capable for ultrafast release of soluble transmitters and the postsynaptic density that cluster ionotropic receptors. The presynaptic and the postsynaptic areas are separated by the ‘closed’ synaptic cavity. The physiological hallmark of the synapse is ultrafast postsynaptic potentials lasting in milliseconds. In contrast, junctions are juxtapositions of nerve terminals and the effector cells without clear synaptic specializations and the junctional space is ‘open’ to the extracellular space. Based on the nature of the transmitters, postjunctional receptors and their separation from the release sites, the junctions can be divided into ‘close’ and ‘wide’ junctions. Functionally, the ‘close’ and the ‘wide’ junctions can be distinguished by postjunctional potentials lasting ~1 second and 10s of seconds, respectively. Both synaptic and junctional communications are common between neurons; however, junctional transmission is the rule at many neuro-non-neural effectors. PMID:23535140

Formation of functional gap junctions in amniotic fluid-derived stem cells induced by transmembrane co-culture with neonatal rat cardiomyocytes

PubMed Central

Connell, Jennifer Petsche; Augustini, Emily; Moise, Kenneth J; Johnson, Anthony; Jacot, Jeffrey G

2013-01-01

Amniotic fluid-derived stem cells (AFSC) have been reported to differentiate into cardiomyocyte-like cells and form gap junctions when directly mixed and cultured with neonatal rat ventricular myocytes (NRVM). This study investigated whether or not culture of AFSC on the opposite side of a Transwell membrane from NRVM, allowing for contact and communication without confounding factors such as cell fusion, could direct cardiac differentiation and enhance gap junction formation. Results were compared to shared media (Transwell), conditioned media and monoculture media controls. After a 2-week culture period, AFSC did not express cardiac myosin heavy chain or troponin T in any co-culture group. Protein expression of cardiac calsequestrin 2 was up-regulated in direct transmembrane co-cultures and media control cultures compared to the other experimental groups, but all groups were up-regulated compared with undifferentiated AFSC cultures. Gap junction communication, assessed with a scrape-loading dye transfer assay, was significantly increased in direct transmembrane co-cultures compared to all other conditions. Gap junction communication corresponded with increased connexin 43 gene expression and decreased phosphorylation of connexin 43. Our results suggest that direct transmembrane co-culture does not induce cardiomyocyte differentiation of AFSC, though calsequestrin expression is increased. However, direct transmembrane co-culture does enhance connexin-43-mediated gap junction communication between AFSC. PMID:23634988

Structural organization of intercellular channels II. Amino terminal domain of the connexins: sequence, functional roles, and structure.

PubMed

Beyer, Eric C; Lipkind, Gregory M; Kyle, John W; Berthoud, Viviana M

2012-08-01

The amino terminal domain (NT) of the connexins consists of their first 22-23 amino acids. Site-directed mutagenesis studies have demonstrated that NT amino acids are determinants of gap junction channel properties including unitary conductance, permeability/selectivity, and gating in response to transjunctional voltage. The importance of this region has also been emphasized by the identification of multiple disease-associated connexin mutants affecting amino acid residues in the NT region. The first part of the NT is α-helical. The structure of the Cx26 gap junction channel shows that the NT α-helix localizes within the channel, and lines the wall of the pore. Interactions of the amino acid residues in the NT with those in the transmembrane helices may be critical for holding the channel open. The predicted sites of these interactions and the applicability of the Cx26 structure to the NT of other connexins are considered. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics. Copyright © 2011. Published by Elsevier B.V.

LIMITATIONS IN THE USE OF MAGNETIC FIELDS TO EXAMINE GAP JUNCTION COMMUNICATION

EPA Science Inventory

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...

INFLUENCE OF SODIUM ARSENITE ON GAP JUNCTION COMMUNICATION IN RAT LIVER EPITHELIAL CELLS

EPA Science Inventory

Influence of sodium arsenite on gap junction communication in rat-Iiver epitheiial cells.

Arsenic is known to cause certain types of cancers, hepatitis, cirrhosis and neurological disorders as well as cardiovascular and reproductive effects and skin lesions. The mechanism...

Cut-loading: a useful tool for examining the extent of gap junction tracer coupling between retinal neurons.

PubMed

Choi, Hee Joo; Ribelayga, Christophe P; Mangel, Stuart C

2012-01-12

In addition to chemical synaptic transmission, neurons that are connected by gap junctions can also communicate rapidly via electrical synaptic transmission. Increasing evidence indicates that gap junctions not only permit electrical current flow and synchronous activity between interconnected or coupled cells, but that the strength or effectiveness of electrical communication between coupled cells can be modulated to a great extent(1,2). In addition, the large internal diameter (~1.2 nm) of many gap junction channels permits not only electric current flow, but also the diffusion of intracellular signaling molecules and small metabolites between interconnected cells, so that gap junctions may also mediate metabolic and chemical communication. The strength of gap junctional communication between neurons and its modulation by neurotransmitters and other factors can be studied by simultaneously electrically recording from coupled cells and by determining the extent of diffusion of tracer molecules, which are gap junction permeable, but not membrane permeable, following iontophoretic injection into single cells. However, these procedures can be extremely difficult to perform on neurons with small somata in intact neural tissue. Numerous studies on electrical synapses and the modulation of electrical communication have been conducted in the vertebrate retina, since each of the five retinal neuron types is electrically connected by gap junctions(3,4). Increasing evidence has shown that the circadian (24-hour) clock in the retina and changes in light stimulation regulate gap junction coupling(3-8). For example, recent work has demonstrated that the retinal circadian clock decreases gap junction coupling between rod and cone photoreceptor cells during the day by increasing dopamine D2 receptor activation, and dramatically increases rod-cone coupling at night by reducing D2 receptor activation(7,8). However, not only are these studies extremely difficult to perform on neurons with small somata in intact neural retinal tissue, but it can be difficult to adequately control the illumination conditions during the electrophysiological study of single retinal neurons to avoid light-induced changes in gap junction conductance. Here, we present a straightforward method of determining the extent of gap junction tracer coupling between retinal neurons under different illumination conditions and at different times of the day and night. This cut-loading technique is a modification of scrape loading(9-12), which is based on dye loading and diffusion through open gap junction channels. Scrape loading works well in cultured cells, but not in thick slices such as intact retinas. The cut-loading technique has been used to study photoreceptor coupling in intact fish and mammalian retinas(7, 8,13), and can be used to study coupling between other retinal neurons, as described here.

Connexin 43 expression on peripheral blood eosinophils: role of gap junctions in transendothelial migration.

PubMed

Vliagoftis, Harissios; Ebeling, Cory; Ilarraza, Ramses; Mahmudi-Azer, Salahaddin; Abel, Melanie; Adamko, Darryl; Befus, A Dean; Moqbel, Redwan

2014-01-01

Eosinophils circulate in the blood and are recruited in tissues during allergic inflammation. Gap junctions mediate direct communication between adjacent cells and may represent a new way of communication between immune cells distinct from communication through cytokines and chemokines. We characterized the expression of connexin (Cx)43 by eosinophils isolated from atopic individuals using RT-PCR, Western blotting, and confocal microscopy and studied the biological functions of gap junctions on eosinophils. The formation of functional gap junctions was evaluated measuring dye transfer using flow cytometry. The role of gap junctions on eosinophil transendothelial migration was studied using the inhibitor 18-a-glycyrrhetinic acid. Peripheral blood eosinophils express Cx43 mRNA and protein. Cx43 is localized not only in the cytoplasm but also on the plasma membrane. The membrane impermeable dye BCECF transferred from eosinophils to epithelial or endothelial cells following coculture in a dose and time dependent fashion. The gap junction inhibitors 18-a-glycyrrhetinic acid and octanol did not have a significant effect on dye transfer but reduced dye exit from eosinophils. The gap junction inhibitor 18-a-glycyrrhetinic acid inhibited eosinophil transendothelial migration in a dose dependent manner. Thus, eosinophils from atopic individuals express Cx43 constitutively and Cx43 may play an important role in eosinophil transendothelial migration and function in sites of inflammation.

Structural basis for the selective permeability of channels made of communicating junction proteins.

PubMed

Ek-Vitorin, Jose F; Burt, Janis M

2013-01-01

The open state(s) of gap junction channels is evident from their permeation by small ions in response to an applied intercellular (transjunctional/transchannel) voltage gradient. That an open channel allows variable amounts of current to transit from cell-to-cell in the face of a constant intercellular voltage difference indicates channel open/closing can be complete or partial. The physiological significance of such open state options is, arguably, the main concern of junctional regulation. Because gap junctions are permeable to many substances, it is sensible to inquire whether and how each open state influences the intercellular diffusion of molecules as valuable as, but less readily detected than current-carrying ions. Presumably, structural changes perceived as shifts in channel conductivity would significantly alter the transjunctional diffusion of molecules whose limiting diameter approximates the pore's limiting diameter. Moreover, changes in junctional permeability to some molecules might occur without evident changes in conductivity, either at macroscopic or single channel level. Open gap junction channels allow the exchange of cytoplasmic permeants between contacting cells by simple diffusion. The identity of such permeants, and the functional circumstances and consequences of their junctional exchange presently constitute the most urgent (and demanding) themes of the field. Here, we consider the necessity for regulating this exchange, the possible mechanism(s) and structural elements likely involved in such regulation, and how regulatory phenomena could be perceived as changes in chemical vs. electrical coupling; an overall reflection on our collective knowledge of junctional communication is then applied to suggest new avenues of research. This article is part of a Special Issue entitled: The Communicating junctions, roles and dysfunctions. Copyright © 2012 Elsevier B.V. All rights reserved.

INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION BY PERFLUORINATED COMPOUNDS IN RAT LIVER AND DOLPHIN KIDNEY EPITHELIAL CELL LINES IN VITRO AND SPRAGUE-DAWLEY RATS IN VIVO

EPA Science Inventory

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...

Live-cell imaging of ER-PM contact architecture by a novel TIRFM approach reveals extension of junctions in response to store-operated Ca2+-entry.

PubMed

Poteser, Michael; Leitinger, Gerd; Pritz, Elisabeth; Platzer, Dieter; Frischauf, Irene; Romanin, Christoph; Groschner, Klaus

2016-10-19

Nanometer-spaced appositions between endoplasmic reticulum and plasma membrane (ER-PM junctions) stabilized by membrane-joining protein complexes are critically involved in cellular Ca 2+ -handling and lipid trafficking. ER-PM junctional architecture and plasticity associated with inter-membrane communication are as yet barely understood. Here, we introduce a method to precisely characterize ER-PM junction morphology and dynamics with high temporal resolution and minimal disturbance of junctional intermembrane communication. We show that expression of soluble cytosolic fluorophores in combination with TIRFM enables to delineate ER and PM distance in the range of 10-150 nm. Live-cell imaging of sub-plasmalemmal structures in RBL-2H3 mast cells by this method, designated as fluorescence density mapping (FDM), revealed profound dynamics of ER-PM contact sites in response to store-depletion. We report the existence of a Ca 2+ -dependent process that expands the junctional ER to enlarge its contact surface with the PM, thereby promoting and stabilizing STIM1-Orai1 competent ER-PM junctions.

IJS: An Intelligent Junction Selection Based Routing Protocol for VANET to Support ITS Services.

PubMed

Bhoi, Sourav Kumar; Khilar, Pabitra Mohan

2014-01-01

Selecting junctions intelligently for data transmission provides better intelligent transportation system (ITS) services. The main problem in vehicular communication is high disturbances of link connectivity due to mobility and less density of vehicles. If link conditions are predicted earlier, then there is a less chance of performance degradation. In this paper, an intelligent junction selection based routing protocol (IJS) is proposed to transmit the data in a quickest path, in which the vehicles are mostly connected and have less link connectivity problem. In this protocol, a helping vehicle is set at every junction to control the communication by predicting link failures or network gaps in a route. Helping vehicle at the junction produces a score for every neighboring junction to forward the data to the destination by considering the current traffic information and selects that junction which has minimum score. IJS protocol is implemented and compared with GyTAR, A-STAR, and GSR routing protocols. Simulation results show that IJS performs better in terms of average end-to-end delay, network gap encounter, and number of hops.

IJS: An Intelligent Junction Selection Based Routing Protocol for VANET to Support ITS Services

PubMed Central

Khilar, Pabitra Mohan

2014-01-01

Selecting junctions intelligently for data transmission provides better intelligent transportation system (ITS) services. The main problem in vehicular communication is high disturbances of link connectivity due to mobility and less density of vehicles. If link conditions are predicted earlier, then there is a less chance of performance degradation. In this paper, an intelligent junction selection based routing protocol (IJS) is proposed to transmit the data in a quickest path, in which the vehicles are mostly connected and have less link connectivity problem. In this protocol, a helping vehicle is set at every junction to control the communication by predicting link failures or network gaps in a route. Helping vehicle at the junction produces a score for every neighboring junction to forward the data to the destination by considering the current traffic information and selects that junction which has minimum score. IJS protocol is implemented and compared with GyTAR, A-STAR, and GSR routing protocols. Simulation results show that IJS performs better in terms of average end-to-end delay, network gap encounter, and number of hops. PMID:27433485

Bi-directional gap junction-mediated soma-germline communication is essential for spermatogenesis.

PubMed

Smendziuk, Christopher M; Messenberg, Anat; Vogl, A Wayne; Tanentzapf, Guy

2015-08-01

Soma-germline interactions play conserved essential roles in regulating cell proliferation, differentiation, patterning and homeostasis in the gonad. In the Drosophila testis, secreted signalling molecules of the JAK-STAT, Hedgehog, BMP and EGF pathways are used to mediate soma-germline communication. Here, we demonstrate that gap junctions may also mediate direct, bi-directional signalling between the soma and germ line. When gap junctions between the soma and germ line are disrupted, germline differentiation is blocked and germline stem cells are not maintained. In the soma, gap junctions are required to regulate proliferation and differentiation. Localization and RNAi-mediated knockdown studies reveal that gap junctions in the fly testis are heterotypic channels containing Zpg (Inx4) and Inx2 on the germ line and the soma side, respectively. Overall, our results show that bi-directional gap junction-mediated signalling is essential to coordinate the soma and germ line to ensure proper spermatogenesis in Drosophila. Moreover, we show that stem cell maintenance and differentiation in the testis are directed by gap junction-derived cues. © 2015. Published by The Company of Biologists Ltd.

Kinase programs spatiotemporally regulate gap junction assembly and disassembly: effects on wound repair

PubMed Central

Solan, Joell L.; Lampe, Paul D.

2016-01-01

Gap junctions are highly ordered plasma membrane domains that are constantly assembled, remodeled and turned over due to the short half-life of connexins, the integral membrane proteins that form gap junctions. Connexin 43 (Cx43), by far the most widely expressed connexin, is phosphorylated at multiple serine residues in the cytoplasmic, C-terminal region allowing for exquisite cellular control over gap junctional communication. This is evident during epidermal wounding where spatiotemporal changes in connexin expression occur as cells are instructed whether to die, proliferate or migrate to promote repair. Early gap junctional communication is required for initiation of keratinocyte migration, but accelerated Cx43 turnover is also critical for proper wound healing at later stages. These events are controlled via a "kinase program" where sequential phosphorylation of Cx43 leads to reductions in Cx43’s half-life and significant depletion of gap junctions from the plasma membrane within several hours. The complex regulation of gap junction assembly and turnover affords several steps where intervention might speed wound healing. PMID:26706150

Kinase programs spatiotemporally regulate gap junction assembly and disassembly: Effects on wound repair.

PubMed

Solan, Joell L; Lampe, Paul D

2016-02-01

Gap junctions are highly ordered plasma membrane domains that are constantly assembled, remodeled and turned over due to the short half-life of connexins, the integral membrane proteins that form gap junctions. Connexin 43 (Cx43), by far the most widely expressed connexin, is phosphorylated at multiple serine residues in the cytoplasmic, C-terminal region allowing for exquisite cellular control over gap junctional communication. This is evident during epidermal wounding where spatiotemporal changes in connexin expression occur as cells are instructed whether to die, proliferate or migrate to promote repair. Early gap junctional communication is required for initiation of keratinocyte migration, but accelerated Cx43 turnover is also critical for proper wound healing at later stages. These events are controlled via a "kinase program" where sequential phosphorylation of Cx43 leads to reductions in Cx43's half-life and significant depletion of gap junctions from the plasma membrane within several hours. The complex regulation of gap junction assembly and turnover affords several steps where intervention might speed wound healing. Copyright © 2015 Elsevier Ltd. All rights reserved.

TEMPORAL CHANGE IN GAP JUNCTION FUNCTION IN PRIMARY HEPATOCYTES

EPA Science Inventory

TEMPORAL CHANGES IN GAP JUNCTION FUNCTION IN PRIMARY *

The objective of this study was to examine the reduction in gap junction communication (GJC) in primary hepatocytes due to coincident melatonin and magnetic field treatments to determine if these conditions could prov...

Gap-junction-mediated communication in human periodontal ligament cells.

PubMed

Kato, R; Ishihara, Y; Kawanabe, N; Sumiyoshi, K; Yoshikawa, Y; Nakamura, M; Imai, Y; Yanagita, T; Fukushima, H; Kamioka, H; Takano-Yamamoto, T; Yamashiro, T

2013-07-01

Periodontal tissue homeostasis depends on a complex cellular network that conveys cell-cell communication. Gap junctions (GJs), one of the intercellular communication systems, are found between adjacent human periodontal ligament (hPDL) cells; however, the functional GJ coupling between hPDL cells has not yet been elucidated. In this study, we investigated functional gap-junction-mediated intercellular communication in isolated primary hPDL cells. SEM images indicated that the cells were in contact with each other via dendritic processes, and also showed high anti-connexin43 (Cx43) immunoreactivity on these processes. Gap-junctional intercellular communication (GJIC) among hPDL cells was assessed by fluorescence recovery after a photobleaching (FRAP) analysis, which exhibited dye coupling between hPDL cells, and was remarkably down-regulated when the cells were treated with a GJ blocker. Additionally, we examined GJs under hypoxic stress. The fluorescence recovery and expression levels of Cx43 decreased time-dependently under the hypoxic condition. Exposure to GJ inhibitor or hypoxia increased RANKL expression, and decreased OPG expression. This study shows that GJIC is responsible for hPDL cells and that its activity is reduced under hypoxia. This is consistent with the possible role of hPDL cells in regulating the biochemical reactions in response to changes in the hypoxic environment.

Junction Propagation in Organometal Halide Perovskite-Polymer Composite Thin Films.

PubMed

Shan, Xin; Li, Junqiang; Chen, Mingming; Geske, Thomas; Bade, Sri Ganesh R; Yu, Zhibin

2017-06-01

With the emergence of organometal halide perovskite semiconductors, it has been discovered that a p-i-n junction can be formed in situ due to the migration of ionic species in the perovskite when a bias is applied. In this work, we investigated the junction formation dynamics in methylammonium lead tribromide (MAPbBr 3 )/polymer composite thin films. It was concluded that the p- and n- doped regions propagated into the intrinsic region with an increasing bias, leading to a reduced intrinsic perovskite layer thickness and the formation of an effective light-emitting junction regardless of perovskite layer thicknesses (300 nm to 30 μm). The junction propagation also played a major role in deteriorating the LED operation lifetime. Stable perovskite LEDs can be achieved by restricting the junction propagation after its formation.

Gap junction coupling is required for tumor cell migration through lymphatic endothelium.

PubMed

Karpinich, Natalie O; Caron, Kathleen M

2015-05-01

The lymphatic vasculature is a well-established conduit for metastasis, but the mechanisms by which tumor cells interact with lymphatic endothelial cells (LECs) to facilitate escape remain poorly understood. Elevated levels of the lymphangiogenic peptide adrenomedullin are found in many tumors, and we previously characterized that its expression is necessary for lymphatic vessel growth within both tumors and sentinel lymph nodes and for distant metastasis. This study used a tumor cell-LEC coculture system to identify a series of adrenomedullin-induced events that facilitated transendothelial migration of the tumor cells through a lymphatic monolayer. High levels of adrenomedullin expression enhanced adhesion of tumor cells to LECs, and further analysis revealed that adrenomedullin promoted gap junction coupling between LECs as evidenced by spread of Lucifer yellow dye. Adrenomedullin also enhanced heterocellular gap junction coupling as demonstrated by Calcein dye transfer from tumor cells into LECs. This connexin-mediated gap junction intercellular communication was necessary for tumor cells to undergo transendothelial migration because pharmacological blockade of this heterocellular communication prevented the ability of tumor cells to transmigrate through the lymphatic monolayer. In addition, treatment of LECs with adrenomedullin caused nuclear translocation of β-catenin, a component of endothelial cell junctions, causing an increase in transcription of the downstream target gene C-MYC. Importantly, blockade of gap junction intercellular communication prevented β-catenin nuclear translocation. Our findings indicate that maintenance of cell-cell communication is necessary to facilitate a cascade of events that lead to tumor cell migration through the lymphatic endothelium. © 2015 American Heart Association, Inc.

Structure and function of gap junction proteins: role of gap junction proteins in embryonic heart development.

PubMed

Ahir, Bhavesh K; Pratten, Margaret K

2014-01-01

Intercellular (cell-to-cell) communication is a crucial and complex mechanism during embryonic heart development. In the cardiovascular system, the beating of the heart is a dynamic and key regulatory process, which is functionally regulated by the coordinated spread of electrical activity through heart muscle cells. Heart tissues are composed of individual cells, each bearing specialized cell surface membrane structures called gap junctions that permit the intercellular exchange of ions and low molecular weight molecules. Gap junction channels are essential in normal heart function and they assist in the mediated spread of electrical impulses that stimulate synchronized contraction (via an electrical syncytium) of cardiac tissues. This present review describes the current knowledge of gap junction biology. In the first part, we summarise some relevant biochemical and physiological properties of gap junction proteins, including their structure and function. In the second part, we review the current evidence demonstrating the role of gap junction proteins in embryonic development with particular reference to those involved in embryonic heart development. Genetics and transgenic animal studies of gap junction protein function in embryonic heart development are considered and the alteration/disruption of gap junction intercellular communication which may lead to abnormal heart development is also discussed.

Role of the gut endoderm in relaying left-right patterning in mice.

PubMed

Viotti, Manuel; Niu, Lei; Shi, Song-Hai; Hadjantonakis, Anna-Katerina

2012-01-01

Establishment of left-right (LR) asymmetry occurs after gastrulation commences and utilizes a conserved cascade of events. In the mouse, LR symmetry is broken at a midline structure, the node, and involves signal relay to the lateral plate, where it results in asymmetric organ morphogenesis. How information transmits from the node to the distantly situated lateral plate remains unclear. Noting that embryos lacking Sox17 exhibit defects in both gut endoderm formation and LR patterning, we investigated a potential connection between these two processes. We observed an endoderm-specific absence of the critical gap junction component, Connexin43 (Cx43), in Sox17 mutants. Iontophoretic dye injection experiments revealed planar gap junction coupling across the gut endoderm in wild-type but not Sox17 mutant embryos. They also revealed uncoupling of left and right sides of the gut endoderm in an isolated domain of gap junction intercellular communication at the midline, which in principle could function as a barrier to communication between the left and right sides of the embryo. The role for gap junction communication in LR patterning was confirmed by pharmacological inhibition, which molecularly recapitulated the mutant phenotype. Collectively, our data demonstrate that Cx43-mediated communication across gap junctions within the gut endoderm serves as a mechanism for information relay between node and lateral plate in a process that is critical for the establishment of LR asymmetry in mice.

Intercellular communication via gap junctions affected by mechanical load in the bovine annulus fibrosus.

PubMed

Desrochers, Jane; Duncan, Neil A

2014-01-01

Cells in the intervertebral disc, as in other connective tissues including tendon, ligament and bone, form interconnected cellular networks that are linked via functional gap junctions. These cellular networks may be necessary to affect a coordinated response to mechanical and environmental stimuli. Using confocal microscopy with fluorescence recovery after photobleaching methods, we explored the in situ strain environment of the outer annulus of an intact bovine disc and the effect of high-level flexion on gap junction signalling. The in situ strain environment in the extracellular matrix of the outer annulus under high flexion load was observed to be non-uniform with the extensive cellular processes remaining crimped sometimes at flexion angles greater than 25°. A significant transient disruption of intercellular communication via functional gap junctions was measured after 10 and 20 min under high flexion load. This study illustrates that in healthy annulus fibrosus tissue, high mechanical loads can impede the functioning of the gap junctions. Future studies will explore more complex loading conditions to determine whether losses in intercellular communication can be permanent and whether gap junctions in aged and degenerated tissues become more susceptible to load. The current research suggests that cellular structures such as gap junctions and intercellular networks, as well as other cell-cell and cell-matrix interconnections, need to be considered in computational models in order to fully understand how macroscale mechanical signals are transmitted across scales to the microscale and ultimately into a cellular biosynthetic response in collagenous tissues.

Collective Calcium Signaling of Defective Multicellular Networks

NASA Astrophysics Data System (ADS)

Potter, Garrett; Sun, Bo

2015-03-01

A communicating multicellular network processes environmental cues into collective cellular dynamics. We have previously demonstrated that, when excited by extracellular ATP, fibroblast monolayers generate correlated calcium dynamics modulated by both the stimuli and gap junction communication between the cells. However, just as a well-connected neural network may be compromised by abnormal neurons, a tissue monolayer can also be defective with cancer cells, which typically have down regulated gap junctions. To understand the collective cellular dynamics in a defective multicellular network we have studied the calcium signaling of co-cultured breast cancer cells and fibroblast cells in various concentrations of ATP delivered through microfluidic devices. Our results demonstrate that cancer cells respond faster, generate singular spikes, and are more synchronous across all stimuli concentrations. Additionally, fibroblast cells exhibit persistent calcium oscillations that increase in regularity with greater stimuli. To interpret these results we quantitatively analyzed the immunostaining of purigenic receptors and gap junction channels. The results confirm our hypothesis that collective dynamics are mainly determined by the availability of gap junction communications.

Subsets of ATP-sensitive potassium channel (KATP) inhibitors increase gap junctional intercellular communication in metastatic cancer cell lines independent of SUR expression

USDA-ARS?s Scientific Manuscript database

Gap junctional intercellular communication (GJIC) is a process whereby cells share molecules and nutrients with each other by physical contact through cell membrane pores. In tumor cells, GJIC is often altered, suggesting that this process may be important in the context of cancer. Certain ion chan...

Analysis of gap junctional intercellular communications using a dielectrophoresis-based microchip.

PubMed

Tellez-Gabriel, Marta; Charrier, Céline; Brounais-Le Royer, Bénédicte; Mullard, Mathilde; Brown, Hannah K; Verrecchia, Franck; Heymann, Dominique

2017-03-01

Gap junctions are transmembrane structures that directly connect the cytoplasm of adjacent cells, making intercellular communications possible. It has been shown that the behaviour of several tumours - such as bone tumours - is related to gap junction intercellular communications (GJIC). Several methodologies are available for studying GJIC, based on measuring different parameters that are useful for multiple applications, such as the study of carcinogenesis for example. These methods nevertheless have several limitations. The present manuscript describes the setting up of a dielectrophoresis (DEP)-based lab-on-a-chip platform for the real-time study of Gap Junctional Intercellular Communication between osteosarcoma cells and the main cells accessible to their microenvironment. We conclude that using the DEParray technology for the GJIC assessment has several advantages comparing to current techniques. This methodology is less harmful for cells integrity; cells can be recovered after interaction to make further molecular analysis; it is possible to study GJIC in real time; we can promote cell interactions using up to five different populations. The setting up of this new methodology overcomes several difficulties to perform experiments for solving questions about GJIC process that we are not able to do with current technics. Copyright © 2017 Elsevier GmbH. All rights reserved.

Bioglass promotes wound healing by affecting gap junction connexin 43 mediated endothelial cell behavior.

PubMed

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

2016-04-01

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 one of the possible mechanisms through which BG stimulates wound healing. Copyright © 2016 Elsevier Ltd. All rights reserved.

HIV-tat alters Connexin43 expression and trafficking in human astrocytes: role in NeuroAIDS.

PubMed

Berman, Joan W; Carvallo, Loreto; Buckner, Clarisa M; Luers, Aimée; Prevedel, Lisa; Bennett, Michael V; Eugenin, Eliseo A

2016-03-02

HIV-associated neurocognitive disorders (HAND) are a major complication in at least half of the infected population despite effective antiretroviral treatment and immune reconstitution. HIV-associated CNS damage is not correlated with active viral replication but instead is associated with mechanisms that regulate inflammation and neuronal compromise. Our data indicate that one of these mechanisms is mediated by gap junction channels and/or hemichannels. Normally, gap junction channels shutdown under inflammatory conditions, including viral diseases. However, HIV infection upregulates Connexin43 (Cx43) expression and maintains gap junctional communication by unknown mechanism(s). Human primary astrocytes were exposed to several HIV proteins as well as to HIV, and expression and function of Connexin43- and Connexin30-containing channels were determined by western blot, immunofluorescence, microinjection of a fluorescent tracer and chromatin immunoprecipitation (ChIP). Here, we demonstrate that HIV infection increases Cx43 expression in vivo. HIV-tat, the transactivator of the virus, and no other HIV proteins tested, increases Cx43 expression and maintains functional gap junctional communication in human astrocytes. Cx43 upregulation is mediated by binding of the HIV-tat protein to the Cx43 promoter, but not to the Cx30 promoter, resulting in increased Cx43 messenger RNA (mRNA) and protein as well as gap junctional communication. We propose that HIV-tat contributes to the spread of intracellular toxic signals generated in a few HIV-infected cells into surrounding uninfected cells by upregulating gap junctional communication. In the current antiretroviral era, where HIV replication is often completely suppressed, viral factors such as HIV-tat are still produced and released from infected cells. Thus, blocking the effects of HIV-tat could result in new strategies to reduce the damaging consequences of HIV infection of the CNS.

Communication-dependent mineralization of osteoblasts via gap junctions.

PubMed

Hashida, Yukihiko; Nakahama, Ken-ichi; Shimizu, Kaori; Akiyama, Masako; Harada, Kiyoshi; Morita, Ikuo

2014-04-01

Connexin43 (Cx43) is a major gap junction (GJ) protein in bone and plays a critical role in osteoblast differentiation. Several studies show that osteoblast differentiation is delayed by Cx43 ablation. However, the precise mechanism underlying the role of Cx43 in osteoblast differentiation is not fully understood. Firstly, we analyzed the phenotype of a conditional knockout mouse, which was generated by mating of an osterix promoter-driven Cre expressing mouse with a Cx43-floxed mouse. As expected, delayed ossification was observed. Secondly, we demonstrated that the cell communication via gap junctions played an important role in osteoblast differentiation using a tamoxifen-inducible knockout system in vitro. Genetic ablation of Cx43 resulted in both the disruption of cell-communications and the attenuation of osteoblast mineralization induced by BMP-2, but not by ascorbic acid. Moreover, restoring full-length Cx43 (382aa) expression rescued the impairment of osteoblast cell-communication and osteoblast mineralization; however, the expression of the Cx43 N-terminal mutant (382aaG2V) did not rescue either of them. Comparing the gene expression profiles, the genes directly regulated by BMP-2 were attenuated by Cx43 gene ablation. These results suggested that the cell-communication mediated by gap junctions was indispensable for normal differentiation of osteoblast induced by BMP-2. Copyright © 2013 Elsevier Inc. All rights reserved.

InGaAlAsPN: A Materials System for Silicon Based Optoelectronics and Heterostructure Device Technologies

NASA Technical Reports Server (NTRS)

Broekaert, T. P. E.; Tang, S.; Wallace, R. M.; Beam, E. A., III; Duncan, W. M.; Kao, Y. -C.; Liu, H. -Y.

1995-01-01

A new material system is proposed for silicon based opto-electronic and heterostructure devices; the silicon lattice matched compositions of the (In,Ga,Al)-(As,P)N 3-5 compounds. In this nitride alloy material system, the bandgap is expected to be direct at the silicon lattice matched compositions with a bandgap range most likely to be in the infrared to visible. At lattice constants ranging between those of silicon carbide and silicon, a wider bandgap range is expected to be available and the high quality material obtained through lattice matching could enable applications such as monolithic color displays, high efficiency multi-junction solar cells, opto-electronic integrated circuits for fiber communications, and the transfer of existing 3-5 technology to silicon.

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

PubMed

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

2016-11-01

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.

Extract from the Zooxanthellate Jellyfish Cotylorhiza tuberculata Modulates Gap Junction Intercellular Communication in Human Cell Cultures

PubMed Central

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

2013-01-01

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-7and 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. PMID:23697954

Extract from the zooxanthellate jellyfish Cotylorhiza tuberculata modulates gap junction intercellular communication in human cell cultures.

PubMed

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

2013-05-22

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.

GAP JUNCTION COMMUNICATON IN A TRANSFECTED HUMAN CELL LINE: ACTION OF MELATONIN AND MAGNETIC FIELDS

EPA Science Inventory

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...

Meclofenamic acid blocks the gap junction communication between the retinal pigment epithelial cells.

PubMed

Ning, N; Wen, Y; Li, Y; Li, J

2013-11-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage the pain and inflammation. NSAIDs can cause serious side effects, including vision problems. However, the underlying mechanisms are still unclear. Therefore, we aimed to investigate the effect of meclofenamic acid (MFA) on retinal pigment epithelium (RPE). In our study, we applied image analysis and whole-cell patch clamp recording to directly measure the effect of MFA on the gap junctional coupling between RPE cells. Analysis of Lucifer yellow (LY) transfer revealed that the gap junction communication existed between RPE cells. Functional experiments using the whole-cell configuration of the patch clamp technique showed that a gap junction conductance also existed between this kind of cells. Importantly, MFA largely inhibited the gap junction conductance and induced the uncoupling of RPE cells. Other NSAIDs, like aspirin and flufenamic acid (FFA), had the same effect. The gap junction functionally existed in RPE cells, which can be blocked by MFA. These findings may explain, at least partially, the vision problems with certain clinically used NSAIDs.

Regulation of gap junctional charge selectivity in cells coexpressing connexin 40 and connexin 43.

PubMed

Heyman, Nathanael S; Kurjiaka, David T; Ek Vitorin, Jose F; Burt, Janis M

2009-07-01

Expression of connexin 40 (Cx40) and Cx43 in cardiovascular tissues varies as a function of age, injury, and development with unknown consequences on the selectivity of junctional communication and its acute regulation. We investigated the PKC-dependent regulation of charge selectivity in junctions composed of Cx43, Cx40, or both by simultaneous assessment of junctional permeance rate constants (B(dye)) for dyes of similar size but opposite charge, N,N,N-trimethyl-2-[methyl-(7-nitro-2,1,3-benzoxadiol-4-yl)amino]ethanaminium (NBD-M-TMA; +1) and Alexa 350 (-1). The ratio of dye rate constants (B(NBD-M-TMA)/B(Alexa 350)) indicated that Cx40 junctions are cation selective (10.7 +/- 0.5), whereas Cx43 junction are nonselective (1.22 +/- 0.14). In coexpressing cells, a broad range of junctional selectivities was observed with mean cation selectivity increasing as the Cx40 to Cx43 expression ratio increased. PKC activation reduced or eliminated dye permeability of Cx43 junctions without altering their charge selectivity, had no effect on either permeability or charge selectivity of Cx40 junctions, and significantly increased the cation selectivity of junctions formed by coexpressing cells (approaching charge selectivity of Cx40 junctions). Junctions composed of Cx43 truncated at residue 257 (Cx43tr) were also not charge selective, but when Cx43tr was coexpressed with Cx40, a broad range of junctional selectivities that was unaffected by PKC activation was observed. Thus, whereas the charge selectivities of homomeric/homotypic Cx43 and Cx40 junctions appear invariant, the selectivities of junctions formed by cells coexpressing Cx40 and Cx43 vary considerably, reflecting both their relative expression levels and phosphorylation-dependent regulation. Such regulation could represent a mechanism by which coexpressing cells such as vascular endothelium and atrial cells regulate acutely the selective intercellular communication mediated by their gap junctions.

Physiological and physiopathological aspects of connexins and communicating gap junctions in spermatogenesis

PubMed Central

Pointis, Georges; Gilleron, Jérome; Carette, Diane; Segretain, Dominique

2010-01-01

Spermatogenesis is a highly regulated process of germ cell proliferation and differentiation, starting from spermatogonia to spermatocytes and giving rise to spermatids, the future spermatozoa. In addition to endocrine regulation, testicular cell–cell interactions are essential for spermatogenesis. This precise control is mediated through paracrine/autocrine pathways, direct intercellular contacts and through intercellular communication channels, consisting of gap junctions and their constitutive proteins, the connexins. Gap junctions are localized between adjacent Leydig cells, between Sertoli cells and between Sertoli cells and specific germ cells. This review focuses on the distribution of connexins within the seminiferous epithelium, their participation in gap junction channel formation, the control of their expression and the physiological relevance of these junctions in both the Sertoli–Sertoli cell functional synchronization and the Sertoli–germ cell dialogue. In this review, we also discuss the potential implication of disrupted connexin in testis cancer, since impaired expression of connexin has been described as a typical feature of tumoral proliferation. PMID:20403873

Involvement of connexin 43 phosphorylation and gap junctional communication between smooth muscle cells in vasopressin-induced ROCK-dependent vasoconstriction after hemorrhagic shock.

PubMed

Yang, Guangming; Peng, Xiaoyong; Wu, Yue; Li, Tao; Liu, Liangming

2017-10-01

We examined the roles played by gap junctions (GJs) and the GJ channel protein connexin 43 (Cx43) in arginine vasopressin (AVP)-induced vasoconstriction after hemorrhagic shock and their relationship to Rho kinase (ROCK) and protein kinase C (PKC). The results showed that AVP induced an endothelium-independent contraction in rat superior mesenteric arteries (SMAs). Blocking the GJs significantly decreased the contractile response of SMAs and vascular smooth muscle cells (VSMCs) to AVP after shock and hypoxia. The selective Cx43-mimetic peptide inhibited the vascular contractile effect of AVP after shock and hypoxia. AVP restored hypoxia-induced decrease of Cx43 phosphorylation at Ser 262 and gap junctional communication in VSMCs. Activation of RhoA with U-46619 increased the contractile effect of AVP. This effect was antagonized by the ROCK inhibitor Y27632 and the Cx43-mimetic peptide. In contrast, neither an agonist nor an inhibitor of PKC had significant effects on AVP-induced contraction after hemorrhagic shock. In addition, silencing of Cx43 with siRNA blocked the AVP-induced increase of ROCK activity in hypoxic VSMCs. In conclusion, AVP-mediated vascular contractile effects are endothelium and myoendothelial gap junction independent. Gap junctions between VSMCs, gap junctional communication, and Cx43 phosphorylation at Ser 262 play important roles in the vascular effects of AVP. RhoA/ROCK, but not PKC, is involved in this process. Copyright © 2017 the American Physiological Society.

78 FR 47822 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-06

..., San Pedro, CA 90731. POLA seeks approval of the proposed discontinuance of Control Point (CP) Transfer Junction at Milepost 1.2 on the Pacific Harbor Line, San Pedro Subdivision. CP Transfer Junction will... discontinuance of CP Transfer Junction. A copy of the petition, as well as any written communications concerning...

Monolithic multi-color light emission/detection device

DOEpatents

Wanlass, Mark W.

1995-01-01

A single-crystal, monolithic, tandem, multi-color optical transceiver device is described, including (a) an InP substrate having upper and lower surfaces, (b) a first junction on the upper surface of the InP substrate, (c) a second junction on the first junction. The first junction is preferably GaInAsP of defined composition, and the second junction is preferably InP. The two junctions are lattice matched. The second junction has a larger energy band gap than the first junction. Additional junctions having successively larger energy band gaps may be included. The device is capable of simultaneous and distinct multi-color emission and detection over a single optical fiber.

Role of gap junction intercellular communication in testicular leydig cell apoptosis induced by oxaliplatin via the mitochondrial pathway.

PubMed

Tong, Xuhui; Han, Xi; Yu, Binbin; Yu, Meiling; Jiang, Guojun; Ji, Jie; Dong, Shuying

2015-01-01

Platinum agents are widely used in the chemotherapy of testicular cancer. However, adverse reactions and resistance to such agents have limited their application in antineoplastic treatment. The aim of the present study was to determine the role of gap junction intercellular communication (GJIC) composed of Cx43 on oxaliplatin‑induced survival/apoptosis in mouse leydig normal and cancer cells using MTT, Annexin V/PI double staining assays and western blot analysis. The results showed that GJIC exerted opposite effects on the mouse leydig cancer (I-10) and normal (TM3) cell apoptosis induced by oxaliplatin. In leydig cancer cells, survival of cells exposed to oxaliplatin was substantially reduced when gap junctions formed as compared to no gap junctions. Pharmacological inhibition of gap junctions by oleamide and 18-α-glycyrrhetinic acid resulted in enhanced survival/decreased apoptosis while enhancement of gap junctions by retinoic acid led to decreased survival/increased apoptosis. These effects occurred only in high‑density cultures (gap junction formed), while the pharmacological modulations had no effects when there was no opportunity for gap junction formation. Notably, GJIC played an opposite (protective) role in normal leydig cells survival/apoptosis following exposure to oxaliplatin. Furthermore, this converse oxaliplatin‑inducing apoptosis exerted through the functional gap junction was correlated with the mitochondrial pathway‑related protein Bcl-2/Bax and caspase‑3/9. These results suggested that in testicular leydig normal/cancer cells, GJIC plays an opposite role in oxaliplatin‑induced apoptosis via the mitochondrial pathway.

Prostate cancer cells specifically reorganize epithelial cell-fibroblast communication through proteoglycan and junction pathways.

PubMed

Suhovskih, Anastasia V; Kashuba, Vladimir I; Klein, George; Grigorieva, Elvira V

2017-01-02

Microenvironment and stromal fibroblasts are able to inhibit tumor cell proliferation both through secreted signaling molecules and direct cell-cell interactions but molecular mechanisms of these effects remain unclear. In this study, we investigated a role of cell-cell contact-related molecules (protein ECM components, proteoglycans (PGs) and junction-related molecules) in intercellular communications between the human TERT immortalized fibroblasts (BjTERT fibroblasts) and normal (PNT2) or cancer (LNCaP, PC3, DU145) prostate epithelial cells. It was shown that BjTERT-PNT2 cell coculture resulted in significant decrease of both BjTERT and PNT2 proliferation rates and reorganization of transcriptional activity of cell-cell contact-related genes in both cell types. Immunocytochemical staining revealed redistribution of DCN and LUM in PNT2 cells and significant increase of SDC1 at the intercellular contact zones between BjTERT and PNT2 cells, suggesting active involvement of the PGs in cell-cell contacts and contact inhibition of cell proliferation. Unlike to PNT2 cells, PC3 cells did not respond to BjTERT in terms of PGs expression, moderately increased transcriptional activity of junctions-related genes (especially tight junction) and failed to establish PC3-BjTERT contacts. At the same time, PC3 cells significantly down-regulated junctions-related genes (especially focal adhesions and adherens junctions) in BjTERT fibroblasts resulting in visible preference for homotypic PC3-PC3 over heterotypic PC3-BjTERT contacts and autonomous growth of PC3 clones. Taken together, the results demonstrate that an instructing role of fibroblasts to normal prostate epithelial cells is revoked by cancer cells through deregulation of proteoglycans and junction molecules expression and overall disorganization of fibroblast-cancer cell communication.

The Role of Gap Junction Communication and Oxidative Stress in the Propagation of Toxic Effects among High-Dose α-Particle-Irradiated Human Cells

PubMed Central

Autsavapromporn, Narongchai; de Toledo, Sonia M.; Little, John B.; Jay-Gerin, Jean-Paul; Harris, Andrew L.; Azzam, Edouard I.

2011-01-01

We investigated the roles of gap junction communication and oxidative stress in modulating potentially lethal damage repair in human fibroblast cultures exposed to doses of α particles or γ rays that targeted all cells in the cultures. As expected, α particles were more effective than γ rays at inducing cell killing; further, holding γ-irradiated cells in the confluent state for several hours after irradiation promoted increased survival and decreased chromosomal damage. However, maintaining α-particle-irradiated cells in the confluent state for various times prior to subculture resulted in increased rather than decreased lethality and was associated with persistent DNA damage and increased protein oxidation and lipid peroxidation. Inhibiting gap junction communication with 18-α-glycyrrhetinic acid or by knockdown of connexin43, a constitutive protein of junctional channels in these cells, protected against the toxic effects in α-particle-irradiated cell cultures during confluent holding. Upregulation of antioxidant defense by ectopic overexpression of glutathione peroxidase protected against cell killing by α particles when cells were analyzed shortly after exposure. However, it did not attenuate the decrease in survival during confluent holding. Together, these findings indicate that the damaging effect of α particles results in oxidative stress, and the toxic effects in the hours after irradiation are amplified by intercellular communication, but the communicated molecule(s) is unlikely to be a substrate of glutathione peroxidase. PMID:21388278

Gap junction blockage promotes cadmium-induced apoptosis in BRL 3A derived from Buffalo rat liver cells.

PubMed

Hu, Di; Zou, Hui; Han, Tao; Xie, Junze; Dai, Nannan; Zhuo, Liling; Gu, Jianhong; Bian, Jianchun; Yuan, Yan; Liu, Xuezhong; Liu, Zongping

2016-03-01

Gap junctions mediate direct communication between cells; however, toxicological cascade triggered by nonessential metals can abrogate cellular signaling mediated by gap junctions. Although cadmium (Cd) is known to induce apoptosis in organs and tissues, the mechanisms that underlie gap junction activity in Cd-induced apoptosis in BRL 3A rat liver cells has yet to be established. In this study, we showed that Cd treatment decreased the cell index (a measure of cellular electrical impedance) in BRL 3A cells. Mechanistically, we found that Cd exposure decreased expression of connexin 43 (Cx43), increased expression of p-Cx43 and elevated intracellular free Ca(2+) concentration, corresponding to a decrease in gap junctional intercellular communication. Gap junction blockage pretreatment with 18β-glycyrrhizic acid (GA) promoted Cd-induced apoptosis, involving changes in expression of Bax, Bcl-2, caspase-3 and the mitochondrial transmembrane electrical potential (Δψm). Additionally, GA was found to enhance ERK and p38 activation during Cd-induced activation of mitogen-activated protein kinases, but had no significant effect on JNK activation. Our results indicated the apoptosis-related proteins and the ERK and p38 signaling pathways may participate in gap junction blockage promoting Cd-induced apoptosis in BRL 3A cells.

Increase of gap junction activities in SW480 human colorectal cancer cells.

PubMed

Bigelow, Kristina; Nguyen, Thu A

2014-07-09

Colorectal cancer is one of the most common cancers in the United States with an early detection rate of only 39%. Colorectal cancer cells along with other cancer cells exhibit many deficiencies in cell-to-cell communication, particularly gap junctional intercellular communication (GJIC). GJIC has been reported to diminish as cancer cells progress. Gap junctions are intercellular channels composed of connexin proteins, which mediate the direct passage of small molecules from one cell to the next. They are involved in the regulation of the cell cycle, cell differentiation, and cell signaling. Since the regulation of gap junctions is lost in colorectal cancer cells, the goal of this study is to determine the effect of GJIC restoration in colorectal cancer cells. Gap Junction Activity Assay and protein analysis were performed to evaluate the effects of overexpression of connexin 43 (Cx43) and treatment of PQ1, a small molecule, on GJIC. Overexpression of Cx43 in SW480 colorectal cancer cells causes a 6-fold increase of gap junction activity compared to control. This suggests that overexpressing Cx43 can restore GJIC. Furthermore, small molecule like PQ1 directly targeting gap junction channel was used to increase GJIC. Gap junction enhancers, PQ1, at 200 nM showed a 4-fold increase of gap junction activity in SW480 cells. A shift from the P0 to the P2 isoform of Cx43 was seen after 1 hour treatment with 200 nM PQ1. Overexpression of Cx43 and treatment of PQ1 can directly increase gap junction activity. The findings provide an important implication in which restoration of gap junction activity can be targeted for drug development.

Septal Junctions in Filamentous Heterocyst-Forming Cyanobacteria.

PubMed

Flores, Enrique; Herrero, Antonia; Forchhammer, Karl; Maldener, Iris

2016-02-01

In the filaments of heterocyst-forming cyanobacteria, septal junctions that traverse the septal peptidoglycan join adjacent cells, allowing intercellular communication. Perforations in the septal peptidoglycan have been observed, and proteins involved in the formation of such perforations and putative protein components of the septal junctions have been identified, but their relationships are debated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Monolithic multi-color light emission/detection device

DOEpatents

Wanlass, M.W.

1995-02-21

A single-crystal, monolithic, tandem, multi-color optical transceiver device is described, including (a) an InP substrate having upper and lower surfaces, (b) a first junction on the upper surface of the InP substrate, (c) a second junction on the first junction. The first junction is preferably GaInAsP of defined composition, and the second junction is preferably InP. The two junctions are lattice matched. The second junction has a larger energy band gap than the first junction. Additional junctions having successively larger energy band gaps may be included. The device is capable of simultaneous and distinct multi-color emission and detection over a single optical fiber. 5 figs.

Connexin43 synthesis, phosphorylation, and degradation in regulation of transient inhibition of gap junction intercellular communication by the phorbol ester TPA in rat liver epithelial cells.

PubMed

Rivedal, Edgar; Leithe, Edward

2005-01-15

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induces transient inhibition of gap junction intercellular communication (GJIC) in several cell types. The initial block in GJIC has been attributed to protein kinase C (PKC) mediated phosphorylation of connexin gap junction proteins, including connexin43 (Cx43). Restoration of GJIC, associated with normalization of the Cx43 phosphorylation status, has been ascribed to different events, including dephosphorylation of Cx43 and de novo synthesis of Cx43 or other, non-gap junctional, proteins. The data presented suggest that restoration of GJIC during continuous TPA exposure in normal and transformed rat liver epithelial cells is dependent on synthesis of Cx43 protein, as well as the transport of already synthesized Cx43 from intracellular pools to the plasma membrane. Reactivation of inactivated Cx43 by dephosphorylation does not appear to be involved in the recovery of GJIC. Both PKC and MAP kinase is involved in TPA-induced degradation of Cx43 and inhibition of GJIC. We show that coincubation of TPA with the protein synthesis inhibitor cycloheximide or the transcription inhibitor actinomycin D results in synergistic enhancement of the level of activated ERK1/2. Together, the present data highlight Cx43 degradation and synthesis as critical determinants in TPA-induced modifications of cell-cell communication via gap junctions.

General anesthetics have differential inhibitory effects on gap junction channels and hemichannels in astrocytes and neurons.

PubMed

Liu, Xinhe; Gangoso, Ester; Yi, Chenju; Jeanson, Tiffany; Kandelman, Stanislas; Mantz, Jean; Giaume, Christian

2016-04-01

Astrocytes represent a major non-neuronal cell population actively involved in brain functions and pathologies. They express a large amount of gap junction proteins that allow communication between adjacent glial cells and the formation of glial networks. In addition, these membrane proteins can also operate as hemichannels, through which "gliotransmitters" are released, and thus contribute to neuroglial interaction. There are now reports demonstrating that alterations of astroglial gap junction communication and/or hemichannel activity impact neuronal and synaptic activity. Two decades ago we reported that several general anesthetics inhibited gap junctions in primary cultures of astrocytes (Mantz et al., (1993) Anesthesiology 78(5):892-901). As there are increasing studies investigating neuroglial interactions in anesthetized mice, we here updated this previous study by employing acute cortical slices and by characterizing the effects of general anesthetics on both astroglial gap junctions and hemichannels. As hemichannel activity is not detected in cortical astrocytes under basal conditions, we treated acute slices with the endotoxin LPS or proinflammatory cytokines to induce hemichannel activity in astrocytes, which in turn activated neuronal hemichannels. We studied two extensively used anesthetics, propofol and ketamine, and the more recently developed dexmedetomidine. We report that these drugs have differential inhibitory effects on gap junctional communication and hemichannel activity in astrocytes when used in their respective, clinically relevant concentrations, and that dexmedetomidine appears to be the least effective on both channel functions. In addition, the three anesthetics have similar effects on neuronal hemichannels. Altogether, our observations may contribute to optimizing the selection of anesthetics for in vivo animal studies. © 2015 Wiley Periodicals, Inc.

Gap junction- and hemichannel-independent actions of connexins.

PubMed

Jiang, Jean X; Gu, Sumin

2005-06-10

Connexins have been known to be the protein building blocks of gap junctions and mediate cell-cell communication. In contrast to the conventional dogma, recent evidence suggests that in addition to forming gap junction channels, connexins possess gap junction-independent functions. One important gap junction-independent function for connexins is to serve as the major functional component for hemichannels, the un-apposed halves of gap junctions. Hemichannels, as independent functional units, play roles that are different from that of gap junctions in the cell. The other functions of connexins appear to be gap junction- and hemichannel-independent. Published studies implicate the latter functions of connexins in cell growth, differentiation, tumorigenicity, injury, and apoptosis, although the mechanistic aspects of these actions remain largely unknown. In this review, gap junction- and hemichannel-independent functions of connexins are summarized, and the molecular mechanisms underlying these connexin functions are speculated and discussed.

Tight junctions and the modulation of barrier function in disease

PubMed Central

2008-01-01

Tight junctions create a paracellular barrier in epithelial and endothelial cells protecting them from the external environment. Two different classes of integral membrane proteins constitute the tight junction strands in epithelial cells and endothelial cells, occludin and members of the claudin protein family. In addition, cytoplasmic scaffolding molecules associated with these junctions regulate diverse physiological processes like proliferation, cell polarity and regulated diffusion. In many diseases, disruption of this regulated barrier occurs. This review will briefly describe the molecular composition of the tight junctions and then present evidence of the link between tight junction dysfunction and disease. PMID:18415116

The alpha2-adrenoreceptor agonist dexmedetomidine protects against lipopolysaccharide-induced apoptosis via inhibition of gap junctions in lung fibroblasts.

PubMed

Zhang, Yuan; Tan, Xiaoming; Xue, Lianfang

2018-01-01

The α2-adrenoceptor inducer dexmedetomidine protects against acute lung injury (ALI), but the mechanism of this effect is largely unknown. The present study investigated the effect of dexmedetomidine on apoptosis induced by lipopolysaccharide (LPS) and the relationship between this effect and gap junction intercellular communication in human lung fibroblast cell line. Flow cytometry was used to detect apoptosis induced by LPS. Parachute dye coupling assay was used to measure gap junction function, and western blot analysis was used to determine the expression levels of connexin43 (Cx43). The results revealed that exposure of human lung fibroblast cell line to LPS for 24 h increased the apoptosis, and pretreatment of dexmedetomidine and 18α-GA significantly reduced LPS-induced apoptosis. Dexmedetomidine exposure for 1 h inhibited gap junction function mainly via a decrease in Cx43 protein levels in human lung fibroblast cell line. These results demonstrated that the inhibition of gap junction intercellular communication by dexmedetomidine affected the LPS-induced apoptosis through inhibition of gap junction function by reducing Cx43 protein levels. The present study provides evidence of a novel mechanism underlying the effects of analgesics in counteracting ALI. Copyright © 2017 Elsevier Inc. All rights reserved.

Models and methods for in vitro testing of hepatic gap junctional communication.

PubMed

Maes, Michaël; Yanguas, Sara Crespo; Willebrords, Joost; Vinken, Mathieu

2015-12-25

Inherent to their pivotal roles in controlling all aspects of the liver cell life cycle, hepatocellular gap junctions are frequently disrupted upon impairment of the homeostatic balance, as occurs during liver toxicity. Hepatic gap junctions, which are mainly built up by connexin32, are specifically targeted by tumor promoters and epigenetic carcinogens. This renders inhibition of gap junction functionality a suitable indicator for the in vitro detection of nongenotoxic hepatocarcinogenicity. The establishment of a reliable liver gap junction inhibition assay for routine in vitro testing purposes requires a cellular system in which gap junctions are expressed at an in vivo-like level as well as an appropriate technique to probe gap junction activity. Both these models and methods are discussed in the current paper, thereby focusing on connexin32-based gap junctions. Copyright © 2015 Elsevier B.V. All rights reserved.

Regulation of osteoclastogenesis by gap junction communication.

PubMed

Matemba, Stephen F; Lie, Anita; Ransjö, Maria

2006-10-01

Receptor activator of NF-kappaB ligand (RANKL) is crucial in osteoclastogenesis but signaling events involved in osteoclast differentiation are far from complete and other signals may play a role in osteoclastogenesis. A more direct pathway for cellular crosstalk is provided by gap junction intercellular channel, which allows adjacent cells to exchange second messengers, ions, and cellular metabolites. Here we have investigated the role of gap junction communication in osteoclastogenesis in mouse bone marrow cultures. Immunoreactive sites for the gap junction protein connexin 43 (Cx43) were detected in the marrow stromal cells and in mature osteoclasts. Carbenoxolone (CBX) functionally blocked gap junction communication as demonstrated by a scrape loading Lucifer Yellow dye transfer technique. CBX caused a dose-dependent inhibition (significant > or = 90 microM) of the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells formed in 7- to 8-day marrow cultures stimulated by parathyroid hormone (PTH; 10 nM) or forskolin (FSK; 1 microM). Furthermore, CBX (100 microM) significantly inhibited prostaglandin E2 (PGE2; 10 microM) and 1,25(OH)2-vitamin D3 stimulated osteoclast differentiation in the mouse bone marrow cultures. Consequently, quantitative real-time polymerase chain reaction (PCR) analysis demonstrated that CBX downregulated the expression of osteoclast phenotypic markers, but without having any significant effects on RANK, RANKL, and osteoprotegerin (OPG) mRNA expression. However, the results demonstrated that CBX significantly inhibits RANKL-stimulated (100 ng/ml) osteoclastogenesis in the mouse bone marrow cultures. Taken together, our results suggests that gap junctional diffusion of messenger molecules interacts with signaling pathways downstream RANKL in osteoclast differentiation. Further studies are required to define the precise mechanisms and molecular targets involved. Copyright 2006 Wiley-Liss, Inc.

Nonlinear Gap Junctions Enable Long-Distance Propagation of Pulsating Calcium Waves in Astrocyte Networks

PubMed Central

Goldberg, Mati; De Pittà, Maurizio; Volman, Vladislav; Berry, Hugues; Ben-Jacob, Eshel

2010-01-01

A new paradigm has recently emerged in brain science whereby communications between glial cells and neuron-glia interactions should be considered together with neurons and their networks to understand higher brain functions. In particular, astrocytes, the main type of glial cells in the cortex, have been shown to communicate with neurons and with each other. They are thought to form a gap-junction-coupled syncytium supporting cell-cell communication via propagating Ca2+ waves. An identified mode of propagation is based on cytoplasm-to-cytoplasm transport of inositol trisphosphate (IP3) through gap junctions that locally trigger Ca2+ pulses via IP3-dependent Ca2+-induced Ca2+ release. It is, however, currently unknown whether this intracellular route is able to support the propagation of long-distance regenerative Ca2+ waves or is restricted to short-distance signaling. Furthermore, the influence of the intracellular signaling dynamics on intercellular propagation remains to be understood. In this work, we propose a model of the gap-junctional route for intercellular Ca2+ wave propagation in astrocytes. Our model yields two major predictions. First, we show that long-distance regenerative signaling requires nonlinear coupling in the gap junctions. Second, we show that even with nonlinear gap junctions, long-distance regenerative signaling is favored when the internal Ca2+ dynamics implements frequency modulation-encoding oscillations with pulsating dynamics, while amplitude modulation-encoding dynamics tends to restrict the propagation range. As a result, spatially heterogeneous molecular properties and/or weak couplings are shown to give rise to rich spatiotemporal dynamics that support complex propagation behaviors. These results shed new light on the mechanisms implicated in the propagation of Ca2+ waves across astrocytes and the precise conditions under which glial cells may participate in information processing in the brain. PMID:20865153

Design and demonstration of ultra-wide bandgap AlGaN tunnel junctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yuewei; Krishnamoorthy, Sriram; Akyol, Fatih

Ultra violet light emitting diodes (UV LEDs) face critical limitations in both the injection efficiency and the light extraction efficiency due to the resistive and absorbing p-type contact layers. In this work, we investigate the design and application of polarization engineered tunnel junctions for ultra-wide bandgap AlGaN (Al mole fraction >50%) materials towards highly efficient UV LEDs. We demonstrate that polarization-induced three dimensional charge is beneficial in reducing tunneling barriers especially for high composition AlGaN tunnel junctions. In addition, the design of graded tunnel junction structures could lead to low tunneling resistance below 10 –3 Ω cm 2 and lowmore » voltage consumption below 1 V (at 1 kA/cm 2) for high composition AlGaN tunnel junctions. Experimental demonstration of 292 nm emission was achieved through non-equilibrium hole injection into wide bandgap materials with bandgap energy larger than 4.7 eV, and detailed modeling of tunnel junctions shows that they can be engineered to have low resistance and can enable efficient emitters in the UV-C wavelength range.« less

Design and demonstration of ultra-wide bandgap AlGaN tunnel junctions

DOE PAGES

Zhang, Yuewei; Krishnamoorthy, Sriram; Akyol, Fatih; ...

2016-09-19

Ultra violet light emitting diodes (UV LEDs) face critical limitations in both the injection efficiency and the light extraction efficiency due to the resistive and absorbing p-type contact layers. In this work, we investigate the design and application of polarization engineered tunnel junctions for ultra-wide bandgap AlGaN (Al mole fraction >50%) materials towards highly efficient UV LEDs. We demonstrate that polarization-induced three dimensional charge is beneficial in reducing tunneling barriers especially for high composition AlGaN tunnel junctions. In addition, the design of graded tunnel junction structures could lead to low tunneling resistance below 10 –3 Ω cm 2 and lowmore » voltage consumption below 1 V (at 1 kA/cm 2) for high composition AlGaN tunnel junctions. Experimental demonstration of 292 nm emission was achieved through non-equilibrium hole injection into wide bandgap materials with bandgap energy larger than 4.7 eV, and detailed modeling of tunnel junctions shows that they can be engineered to have low resistance and can enable efficient emitters in the UV-C wavelength range.« less

Does rat granulation tissue maturation involve gap junction communications?

PubMed

Au, Katherine; Ehrlich, H Paul

2007-07-01

Wound healing, a coordinated process, proceeds by sequential changes in cell differentiation and terminates with the deposition of a new connective tissue matrix, a scar. Initially, there is the migratory fibroblast, followed by the proliferative fibroblast, then the synthetic fibroblast, which transforms into the myofibroblast, and finally the apoptotic fibroblast. Gap junction intercellular communications are proposed to coordinate the stringent control of fibroblast phenotypic changes. Does added oleamide, a natural fatty acid that blocks gap junction intercellular communications, alter the phenotypic progression of wound fibroblasts? Pairs of polyvinyl alcohol sponges attached to Alzet pumps, which constantly pumped either oleamide or vehicle solvent, were implanted subcutaneously into three rats. On day 8, implants were harvested and evaluated histologically and biochemically. The capsule of oleamide-treated sponge contained closely packed fibroblasts with little connective tissue between them. The birefringence intensity of that connective tissue was reduced, indicating a reduced density of collagen fiber bundles. Myofibroblasts, identified immunohistologically by alpha-smooth muscle actin-stained stress fibers, were reduced in oleamide-treated implants. Western blot analysis showing less alpha-smooth muscle actin confirmed the reduced density of myofibroblasts. It appears that oleamide retards the progression of wound repair, where less connective tissue is deposited, the collagen is less organized, and the appearance of myofibroblasts is impaired. These findings support the hypothesis that gap junction intercellular communications between wound fibroblasts in granulation tissue play a role in the progression of repair and the maturation of granulation tissue into scar.

Nanotechnology with Carbon Nanotubes: Mechanics, Chemistry, and Electronics

NASA Technical Reports Server (NTRS)

Srivastava, Deepak

2003-01-01

This viewgraph presentation reviews the Nanotechnology of carbon nanotubes. The contents include: 1) Nanomechanics examples; 2) Experimental validation of nanotubes in composites; 3) Anisotropic plastic collapse; 4) Spatio-temporal scales, yielding single-wall nanotubes; 5) Side-wall functionalization of nanotubes; 6) multi-wall Y junction carbon nanotubes; 7) Molecular electronics with Nanotube junctions; 8) Single-wall carbon nanotube junctions; welding; 9) biomimetic dendritic neurons: Carbon nanotube, nanotube electronics (basics), and nanotube junctions for Devices,

Structural basis for the selective permeability of channels made of communicating junction proteins

PubMed Central

Ek-Vitorin, Jose F.; Burt, Janis M.

2012-01-01

The open state(s) of gap junction channels is evident from their permeation by small ions in response to an applied intercellular (transjunctional/transchannel) voltage gradient. That an open channel allows variable amounts of current to transit from cell-to-cell in the face of a constant intercellular voltage difference indicates channel open/closing can be complete or partial. The physiological significance of such open state options is, arguably, the main concern of junctional regulation. Because gap junctions are permeable to many substances, it is sensible to inquire whether and how each open state influences the intercellular diffusion of molecules as valuable as, but less readily detected than current-carrying ions. Presumably, structural changes perceived as shifts in channel conductivity would significantly alter the transjunctional diffusion of molecules whose limiting diameter approximates the pore’s limiting diameter. Moreover, changes in junctional permeability to some molecules might occur without evident changes in conductivity, either at macroscopic or single channel level. Open gap junction channels allow the exchange of cytoplasmic permeants between contacting cells by simple diffusion. The identity of such permeants, and the functional circumstances and consequences of their junctional exchange presently constitute the most urgent (and demanding) themes of the field. Here, we consider the necessity for regulating this exchange, the possible mechanism(s) and structural elements likely involved in such regulation, and how regulatory phenomena could be perceived as changes in chemical vs. electrical coupling; an overall reflection on our collective knowledge of junctional communication is then applied to suggest new avenues of research. PMID:22342665

Dioscin augments HSV-tk-mediated suicide gene therapy for melanoma by promoting connexin-based intercellular communication

PubMed Central

Li, Bin; Wu, Yingya; Liu, Xijuan; Tan, Yuhui; Du, Biaoyan

2017-01-01

Suicide gene therapy is a promising strategy against melanoma. However, the low efficiency of the gene transfer technique can limit its application. Our preliminary data showed that dioscin, a glucoside saponin, could upregulate the expression of connexins Cx26 and Cx43, major components of gap junctions, in melanoma cells. We hypothesized that dioscin may increase the bystander effect of herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) through increasing the formation of gap junctions. Further analysis showed that dioscin indeed could increase the gap junctional intercellular communication in B16 melanoma cells, resulting in more efficient GCV-induced bystander killing in B16tk cells. By contrast, overexpression of dominant negative Cx43 impaired the cell-cell communication of B16 cells and subsequently weakened the bystander effect of HSV-tk/GCV gene therapy. In vivo, combination treatment with dioscin and GCV of tumor-bearing mice with 30% positive B16tk cells and 70% wild-type B16 cells caused a significant reduction in tumor volume and weight compared to treatment with GCV or dioscin alone. Taken together, these results demonstrated that dioscin could augment the bystander effect of the HSV-tk/GCV system through increasing connexin-mediated gap junction coupling. PMID:27903977

2',5'-Dihydroxychalcone down-regulates endothelial connexin43 gap junctions and affects MAP kinase activation.

PubMed

Lee, Yi-Nan; Yeh, Hung-I; Tian, Tin-Yi; Lu, Wen-Wei; Ko, Yu-Shien; Tsai, Cheng-Ho

2002-09-30

We examined the effect of 2',5'-dihydroxychalcone on connexin43 (Cx43) expression and gap-junctional communication in human umbilical vein endothelial cells (HUVEC). The result showed that expression of Cx43 is rapidly reduced by 2',5'-dihydroxychalcone in a dose-dependent manner, Concomitantly, the communication function, determined by fluorescence recovery after photobleaching (FRAP), is decreased. We further investigated whether the mitogen-activated protein (MAP) kinase and the degradation pathway of gap junctions are involved in these processes. Although the change of Cx43 is not affected by the level of fetal calf serum (FCS) used in the medium, activation of MAP kinase varies, depending on the FCS level. At a low level (0.5%), the chalcone inhibits the activation, like PD98059, a specific inhibitor of MAP kinase kinase. However, at a high level (20%), MAP kinase is activated. On the other hand, the chalcone's down-regulating effect on Cx43, while is totally blocked by protease inhibitors leupeptin and N-acetyl-leucyl-norleucinal (ALLN), persists in the presence of PD98059, We concluded that 2',5'-dihydroxychalcone down-regulates Cx43 expression and gap-junctional communication in the HUVEC via enhancement of the proteolysis pathway, and this compound possesses dual effects on MAP kinase activation.

Gap Junctional Communication in Morphogenesis

PubMed Central

Levin, Michael

2007-01-01

Gap junctions permit the direct passage of small molecules from the cytosol of one cell to that of its neighbor, and thus form a system of cell-cell communication that exists alongside familiar secretion/receptor signaling. Because of the rich potential for regulation of junctional conductance, and directional and molecular gating (specificity), gap junctional communication (GJC) plays a crucial role in many aspects of normal tissue physiology. However, the most exciting role for GJC is in the regulation of information flow that takes place during embryonic development, regeneration, and tumor progression. The molecular mechanisms by which GJC establishes local and long-range instructive morphogenetic cues are just beginning to be understood. This review summarizes the current knowledge of the involvement of GJC in the patterning of both vertebrate and invertebrate systems and discusses in detail several morphogenetic systems in which the properties of this signaling have been molecularly characterized. One model consistent with existing data in the fields of vertebrate left-right patterning and anterior-posterior polarity in flatworm regeneration postulates electrophoretically-guided movement of small molecule morphogens through long-range GJC paths. The discovery of mechanisms controlling embryonic and regenerative GJC-mediated signaling, and identification of the downstream targets of GJC-permeable molecules, represent exciting next areas of research in this fascinating field. PMID:17481700

Connexin composition in apposed gap junction hemiplaques revealed by matched double-replica freeze-fracture replica immunogold labeling.

PubMed

Rash, John E; Kamasawa, Naomi; Davidson, Kimberly G V; Yasumura, Thomas; Pereda, Alberto E; Nagy, James I

2012-06-01

Despite the combination of light-microscopic immunocytochemistry, histochemical mRNA detection techniques and protein reporter systems, progress in identifying the protein composition of neuronal versus glial gap junctions, determination of the differential localization of their constituent connexin proteins in two apposing membranes and understanding human neurological diseases caused by connexin mutations has been problematic due to ambiguities introduced in the cellular and subcellular assignment of connexins. Misassignments occurred primarily because membranes and their constituent proteins are below the limit of resolution of light microscopic imaging techniques. Currently, only serial thin-section transmission electron microscopy and freeze-fracture replica immunogold labeling have sufficient resolution to assign connexin proteins to either or both sides of gap junction plaques. However, freeze-fracture replica immunogold labeling has been limited because conventional freeze fracturing allows retrieval of only one of the two membrane fracture faces within a gap junction, making it difficult to identify connexin coupling partners in hemiplaques removed by fracturing. We now summarize progress in ascertaining the connexin composition of two coupled hemiplaques using matched double-replicas that are labeled simultaneously for multiple connexins. This approach allows unambiguous identification of connexins and determination of the membrane "sidedness" and the identities of connexin coupling partners in homotypic and heterotypic gap junctions of vertebrate neurons.

Highly-Sensitive Thin Film THz Detector Based on Edge Metal-Semiconductor-Metal Junction.

PubMed

Jeon, Youngeun; Jung, Sungchul; Jin, Hanbyul; Mo, Kyuhyung; Kim, Kyung Rok; Park, Wook-Ki; Han, Seong-Tae; Park, Kibog

2017-12-04

Terahertz (THz) detectors have been extensively studied for various applications such as security, wireless communication, and medical imaging. In case of metal-insulator-metal (MIM) tunnel junction THz detector, a small junction area is desirable because the detector response time can be shortened by reducing it. An edge metal-semiconductor-metal (EMSM) junction has been developed with a small junction area controlled precisely by the thicknesses of metal and semiconductor films. The voltage response of the EMSM THz detector shows the clear dependence on the polarization angle of incident THz wave and the responsivity is found to be very high (~2,169 V/W) at 0.4 THz without any antenna and signal amplifier. The EMSM junction structure can be a new and efficient way of fabricating the nonlinear device THz detector with high cut-off frequency relying on extremely small junction area.

GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks

PubMed Central

Mäkinen, Meeri Eeva-Liisa; Ylä-Outinen, Laura; Narkilahti, Susanna

2018-01-01

The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC)-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA) and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging) and temporal resolution microelectrode array (MEA). We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABAA mediated signaling. PMID:29559893

Such stuff as dreams are made on? Elaborative encoding, the ancient art of memory, and the hippocampus.

PubMed

Llewellyn, Sue

2013-12-01

This article argues that rapid eye movement (REM) dreaming is elaborative encoding for episodic memories. Elaborative encoding in REM can, at least partially, be understood through ancient art of memory (AAOM) principles: visualization, bizarre association, organization, narration, embodiment, and location. These principles render recent memories more distinctive through novel and meaningful association with emotionally salient, remote memories. The AAOM optimizes memory performance, suggesting that its principles may predict aspects of how episodic memory is configured in the brain. Integration and segregation are fundamental organizing principles in the cerebral cortex. Episodic memory networks interconnect profusely within the cortex, creating omnidirectional "landmark" junctions. Memories may be integrated at junctions but segregated along connecting network paths that meet at junctions. Episodic junctions may be instantiated during non-rapid eye movement (NREM) sleep after hippocampal associational function during REM dreams. Hippocampal association involves relating, binding, and integrating episodic memories into a mnemonic compositional whole. This often bizarre, composite image has not been present to the senses; it is not "real" because it hyperassociates several memories. During REM sleep, on the phenomenological level, this composite image is experienced as a dream scene. A dream scene may be instantiated as omnidirectional neocortical junction and retained by the hippocampus as an index. On episodic memory retrieval, an external stimulus (or an internal representation) is matched by the hippocampus against its indices. One or more indices then reference the relevant neocortical junctions from which episodic memories can be retrieved. Episodic junctions reach a processing (rather than conscious) level during normal wake to enable retrieval. If this hypothesis is correct, the stuff of dreams is the stuff of memory.

The Peptidoglycan-Binding Protein SjcF1 Influences Septal Junction Function and Channel Formation in the Filamentous Cyanobacterium Anabaena.

PubMed

Rudolf, Mareike; Tetik, Nalan; Ramos-León, Félix; Flinner, Nadine; Ngo, Giang; Stevanovic, Mara; Burnat, Mireia; Pernil, Rafael; Flores, Enrique; Schleiff, Enrico

2015-06-30

Filamentous, heterocyst-forming cyanobacteria exchange nutrients and regulators between cells for diazotrophic growth. Two alternative modes of exchange have been discussed involving transport either through the periplasm or through septal junctions linking adjacent cells. Septal junctions and channels in the septal peptidoglycan are likely filled with septal junction complexes. While possible proteinaceous factors involved in septal junction formation, SepJ (FraG), FraC, and FraD, have been identified, little is known about peptidoglycan channel formation and septal junction complex anchoring to the peptidoglycan. We describe a factor, SjcF1, involved in regulation of septal junction channel formation in the heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120. SjcF1 interacts with the peptidoglycan layer through two peptidoglycan-binding domains and is localized throughout the cell periphery but at higher levels in the intercellular septa. A strain with an insertion in sjcF1 was not affected in peptidoglycan synthesis but showed an altered morphology of the septal peptidoglycan channels, which were significantly wider in the mutant than in the wild type. The mutant was impaired in intercellular exchange of a fluorescent probe to a similar extent as a sepJ deletion mutant. SjcF1 additionally bears an SH3 domain for protein-protein interactions. SH3 binding domains were identified in SepJ and FraC, and evidence for interaction of SjcF1 with both SepJ and FraC was obtained. SjcF1 represents a novel protein involved in structuring the peptidoglycan layer, which links peptidoglycan channel formation to septal junction complex function in multicellular cyanobacteria. Nonetheless, based on its subcellular distribution, this might not be the only function of SjcF1. Cell-cell communication is central not only for eukaryotic but also for multicellular prokaryotic systems. Principles of intercellular communication are well established for eukaryotes, but the mechanisms and components involved in bacteria are just emerging. Filamentous heterocyst-forming cyanobacteria behave as multicellular organisms and represent an excellent model to study prokaryotic cell-cell communication. A path for intercellular metabolite exchange appears to involve transfer through molecular structures termed septal junctions. They are reminiscent of metazoan gap junctions that directly link adjacent cells. In cyanobacteria, such structures need to traverse the peptidoglycan layers in the intercellular septa of the filament. Here we describe a factor involved in the formation of channels across the septal peptidoglycan layers, thus contributing to the multicellular behavior of these organisms. Copyright © 2015 Rudolf et al.

ER-plasma membrane junctions: Why and how do we study them?

PubMed

Chang, Chi-Lun; Chen, Yu-Ju; Liou, Jen

2017-09-01

Endoplasmic reticulum (ER)-plasma membrane (PM) junctions are membrane microdomains important for communication between the ER and the PM. ER-PM junctions were first reported in muscle cells in 1957, but mostly ignored in non-excitable cells due to their scarcity and lack of functional significance. In 2005, the discovery of stromal interaction molecule 1 (STIM1) mediating a universal Ca 2+ feedback mechanism at ER-PM junctions in mammalian cells led to a resurgence of research interests toward ER-PM junctions. In the past decade, several major advancements have been made in this emerging topic in cell biology, including the generation of tools for labeling ER-PM junctions and the unraveling of mechanisms underlying regulation and functions of ER-PM junctions. This review summarizes early studies, recently developed tools, and current advances in the characterization and understanding of ER-PM junctions. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann. Copyright © 2017 Elsevier B.V. All rights reserved.

Terbinafine inhibits gap junctional intercellular communication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Ju Yeun, E-mail: whitewndus@naver.com

Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca{sup 2+} concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibitsmore » GJIC with a so far unknown mechanism of action. - Highlights: • In vitro pharmacological studies were performed on FRT-Cx43 and LN215 cells. • Terbinafine inhibits gap junctional intercellular communication in both cell lines. • The inhibitory effect of terbinafine is reversible and dose-dependent. • Treatment of terbinafine does not alter Cx43 phosphorylation or cytosolic Ca{sup 2+} concentration. • Inhibition of squalene epoxidase is not involved in this new effect of terbinafine.« less

Effects of vitamin D receptor knockout on cornea epithelium gap junctions.

PubMed

Lu, Xiaowen; Watsky, Mitchell A

2014-05-06

Gap junctions are present in all corneal cell types and have been shown to have a critical role in cell phenotype determination. Vitamin D has been shown to influence cell differentiation, and recent work demonstrates the presence of vitamin D in the ocular anterior segment. This study measured and compared gap junction diffusion coefficients among different cornea epithelium phenotypes and in keratocytes using a noninvasive technique, fluorescence recovery after photobleaching (FRAP), and examined the influence of vitamin D receptor (VDR) knockout on epithelial gap junction communication in intact corneas. Previous gap junction studies in cornea epithelium and keratocytes were performed using cultured cells or ex vivo invasive techniques. These invasive techniques were unable to measure diffusion coefficients and likely were disruptive to normal cell physiology. Corneas from VDR knockout and control mice were stained with 5(6)-carboxyfluorescein diacetate (CFDA). Gap junction diffusion coefficients of the corneal epithelium phenotypes and of keratocytes, residing in intact corneas, were detected using FRAP. Diffusion coefficients equaled 18.7, 9.8, 5.6, and 4.2 μm(2)/s for superficial squamous cells, middle wing cells, basal cells, and keratocytes, respectively. Corneal thickness, superficial cell size, and the superficial squamous cell diffusion coefficient of 10-week-old VDR knockout mice were significantly lower than those of control mice (P < 0.01). The superficial cell diffusion coefficient of heterozygous mice was significantly lower than control mice (P < 0.05). Our results demonstrate differences in gap junction dye spread among the epithelial cell phenotypes, mirroring the epithelial developmental axis. The VDR knockout influences previously unreported cell-to-cell communication in superficial epithelium.

Non-invasive microfluidic gap junction assay.

PubMed

Chen, Sisi; Lee, Luke P

2010-03-01

Gap junctions are protein channels between cells that allow direct electrical and metabolic coupling via the exchange of biomolecules and ions. Their expression, though ubiquitous in most mammalian cell types, is especially important for the proper functioning of cardiac and neuronal systems. Many existing methods for studying gap junction communication suffer from either unquantifiable data or difficulty of use. Here, we measure the extent of dye spread and effective diffusivities through gap junction connected cells using a quantitative microfluidic cell biology platform. After loading dye by hydrodynamic focusing of calcein/AM, dye transfer dynamics into neighboring, unexposed cells can be monitored via timelapse fluorescent microscopy. By using a selective microfluidic dye loading over a confluent layer of cells, we found that high expression of gap junctions in C6 cells transmits calcein across the monolayer with an effective diffusivity of 3.4 x 10(-13) m(2)/s, which are highly coupled by Cx43. We also found that the gap junction blocker 18alpha-GA works poorly in the presence of serum even at high concentrations (50 microM); however, it is highly effective down to 2.5 microM in the absence of serum. Furthermore, when the drug is washed out, dye spread resumes rapidly within 1 min for all doses, indicating the drug does not affect transcriptional regulation of connexins in these Cx43+ cells, in contrast to previous studies. This integrated microfluidic platform enables the in situ monitoring of gap junction communication, yielding dynamic information about intercellular molecular transfer and pharmacological inhibition and recovery.

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Rapid Changes in Connexin-43 in Response to Genotoxic Stress Stabilize Cell–Cell Communication in Corneal Endothelium

PubMed Central

Roh, Danny S.

2011-01-01

Purpose. To determine how corneal endothelial (CE) cells respond to acute genotoxic stress through changes in connexin-43 (Cx43) and gap junction intercellular communication (GJIC). Methods. Cultured bovine CE cells were exposed to mitomycin C or other DNA-damaging agents. Changes in the levels, stability, binding partners, and trafficking of Cx43 were assessed by Western blot analysis and immunostaining. Live-cell imaging of a Cx43–green fluorescent protein (GFP) fusion protein was used to evaluate internalization of cell surface Cx43. Dye transfer and fluorescent recovery after photobleaching (FRAP) assessed GJIC. Results. After genotoxic stress, Cx43 accumulated in large gap junction plaques, had reduced zonula occludens-1 binding, and displayed increased stability. Live-cell imaging of Cx43–GFP plaques in stressed CE cells revealed reduced gap junction internalization and degradation compared to control cells. Mitomycin C enhanced transport of Cx43 from the endoplasmic reticulum to the cell surface and formation of gap junction plaques. Mitomycin C treatment also protected GJIC from disruption after cytokine treatment. Discussion. These results show a novel CE cell response to genotoxic stress mediated by marked and rapid changes in Cx43 and GJIC. This stabilization of cell–cell communication may be an important early adaptation to acute stressors encountered by CE. PMID:21666237

Transient suppression of gap junctional intercellular communication after exposure to 100-nanosecond pulsed electric fields.

PubMed

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

2016-12-01

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.

Gap junction-mediated intercellular communication in the immune system.

PubMed

Neijssen, Joost; Pang, Baoxu; Neefjes, Jacques

2007-01-01

Immune cells are usually considered non-attached blood cells, which would exclude the formation of gap junctions. This is a misconception since many immune cells express connexin 43 (Cx43) and other connexins and are often residing in tissue. The role of gap junctions is largely ignored by immunologists as is the immune system in the field of gap junction research. Here, the current knowledge of the distribution of connexins and the function of gap junctions in the immune system is discussed. Gap junctions appear to play many roles in antibody productions and specific immune responses and may be important in sensing danger in tissue by the immune system. Gap junctions not only transfer electrical and metabolical but also immunological information in the form of peptides for a process called cross-presentation. This is essential for proper immune responses to viruses and possibly tumours. Until now only 40 research papers on gap junctions in the immune system appeared and this will almost certainly expand with the increased mutual interest between the fields of immunology and gap junction research.

Inter-Cellular Exchange of Cellular Components via VE-Cadherin-Dependent Trans-Endocytosis

PubMed Central

Sakurai, Takashi; Woolls, Melissa J.; Jin, Suk-Won

2014-01-01

Cell-cell communications typically involve receptor-mediated signaling initiated by soluble or cell-bound ligands. Here, we report a unique mode of endocytosis: proteins originating from cell-cell junctions and cytosolic cellular components from the neighboring cell are internalized, leading to direct exchange of cellular components between two adjacent endothelial cells. VE-cadherins form transcellular bridges between two endothelial cells that are the basis of adherence junctions. At such adherens junction sites, we observed the movement of the entire VE-cadherin molecule from one endothelial cell into the other with junctional and cytoplasmic components. This phenomenon, here termed trans-endocytosis, requires the establishment of a VE-cadherin homodimer in trans with internalization proceeding in a Rac1-, and actomyosin-dependent manner. Importantly, the trans-endocytosis is not dependent on any known endocytic pathway including clathrin-dependent endocytosis, macropinocytosis or phagocytosis. This novel form of cell-cell communications, leading to a direct exchange of cellular components, was observed in 2D and 3D-cultured endothelial cells as well as in the developing zebrafish vasculature. PMID:24603875

Effects of 18beta-glycyrrhetinic acid on the junctional complex and steroidogenesis in rat adrenocortical cells.

PubMed

Huang, Shih-Horng; Wu, Jiahn-Chun; Hwang, Ra-Der; Yeo, Hui-Lin; Wang, Seu-Mei

2003-09-01

Cellular junctions play important roles in cell differentiation, signal transduction, and cell function. This study investigated their function in steroid secretion by adrenal cells. Immunofluorescence staining revealed the presence of gap junctions and adherens junctions between adrenal cells. The major gap junction protein, connexin43, was seen as a linear dotted pattern of the typical gap junction plaques, in contrast to alpha-, beta-, and gamma-catenin, which were seen as continuous, linear staining of cell-cell adherens junction. Treatment with 18beta-glycyrrhetinic acid, a gap junction inhibitor, reduced the immunoreactivity of these proteins in a time- and dose-dependent manner, and caused the gap junction and adherens junction to separate longitudinally from the cell-cell contact sites, indicating the structural interdependency of these two junctions. Interestingly, 18beta-glycyrrhetinic acid stimulated a two- to three-fold increase in steroid production in these adrenal cells lacking intact cell junctions. These data raise the question of the necessity for cell communication for the endocrine function of adrenal cells. Pharmacological analyses indicated that the steroidogenic effect of 18beta-glycyrrhetinic acid was partially mediated by extracellular signal-related kinase and calcium/calmodulin-dependent kinase, a pathway distinct from the protein kinase A signaling pathway already known to mediate steroidogenesis in adrenal cells. Copyright 2003 Wiley-Liss, Inc.

Lovastatin inhibits gap junctional communication in cultured aortic smooth muscle cells.

PubMed

Shen, Jing; Wang, Li-Hong; Zheng, Liang-Rong; Zhu, Jian-Hua; Hu, Shen-Jiang

2010-09-01

Gap junctions, which serve as intercellular channels that allow the passage of ions and other small molecules between neighboring cells, play an important role in vital functions, including the regulation of cell growth, differentiation, and development. Statins, the 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase inhibitors, have been shown to inhibit the migration and proliferation of smooth muscle cells (SMCs) leading to an antiproliferative effect. Recent studies have shown that statins can reduce gap junction protein connexin43 (Cx43) expression both in vivo and in vitro. However, little work has been done on the effects of statins on gap junctional intercellular communication (GJIC). We hypothesized in this study that lovastatin inhibits vascular smooth muscle cells (VSMCs) migration through the inhibition of the GJIC. Rat aortic SMCs (RASMCs) were exposed to lovastatin. Vascular smooth muscle cells migration was then assessed with a Transwell migration assay. Gap junctional intercellular communication was determined by using fluorescence recovery after photobleaching (FRAP) analysis, which was performed with a laser-scanning confocal microscope. The migration of the cultured RASMCs were detected by Transwell system. Cell migration was dose-dependently inhibited with lovastatin. Compared with that in the control (110 ± 26), the number of migrated SMCs was significantly reduced to 72 ± 24 (P < .05), 62 ± 18 (P < .01), and 58 ± 19 (P < .01) at the concentration of 0.4, 2, and 10 umol/L, per field. The rate of fluorescence recovery (R) at 5 minutes after photobleaching was adopted as the functional index of GJIC. The R- value of cells exposed to lovastatin 10 umol/L for 48 hours was 24.38% ± 4.84%, whereas the cells in the control group had an R- value of 36.11% ± 10.53%, demonstrating that the GJIC of RASMCs was significantly inhibited by lovastatin (P < .01). Smaller concentrations of lovastatin 0.08 umol/L did not change gap junction coupling (P > .05). These results suggest that lovastatin inhibits migration in a dose-dependent manner by attenuating JIC. Suppression of gap junction function could add another explanation of statin-induced antiproliferative effect.

Blockade of brain stem gap junctions increases phrenic burst frequency and reduces phrenic burst synchronization in adult rat.

PubMed

Solomon, Irene C; Chon, Ki H; Rodriguez, Melissa N

2003-01-01

Recent investigations have examined the influence of gap junctional communication on generation and modulation of respiratory rhythm and inspiratory motoneuron synchronization in vitro using transverse medullary slice and en bloc brain stem-spinal cord preparations obtained from neonatal (1-5 days postnatal) mice. Gap junction proteins, however, have been identified in both neurons and glia in brain stem regions implicated in respiratory control in both neonatal and adult rodents. Here, we used an in vitro arterially perfused rat preparation to examine the role of gap junctional communication on generation and modulation of respiratory rhythm and inspiratory motoneuron synchronization in adult rodents. We recorded rhythmic inspiratory motor activity from one or both phrenic nerves before and during pharmacological blockade (i.e., uncoupling) of brain stem gap junctions using carbenoxolone (100 microM), 18alpha-glycyrrhetinic acid (25-100 microM), 18beta-glycyrrhetinic acid (25-100 microM), octanol (200-300 microM), or heptanol (200 microM). During perfusion with a gap junction uncoupling agent, we observed an increase in the frequency of phrenic bursts (~95% above baseline frequency; P < 0.001) and a decrease in peak amplitude of integrated phrenic nerve discharge (P < 0.001). The increase in frequency of phrenic bursts resulted from a decrease in both T(I) (P < 0.01) and T(E) (P < 0.01). In addition, the pattern of phrenic nerve discharge shifted from an augmenting discharge pattern to a "bell-shaped" or square-wave discharge pattern in most experiments. Spectral analyses using a fast Fourier transform (FFT) algorithm revealed a reduction in the peak power of both the 40- to 50-Hz peak (corresponding to the MFO) and 90- to 110-Hz peak (corresponding to the HFO) although spurious higher frequency activity (> or =130 Hz) was observed, suggesting an overall loss or reduction in inspiratory-phase synchronization. Although additional experiments are required to identify the specific brain stem regions and cell types (i.e., neurons, glia) mediating the observed modulations in phrenic motor output, these findings suggest that gap junction communication modulates generation of respiratory rhythm and inspiratory motoneuron synchronization in adult rodents in vitro.

The extracellular matrix component laminin promotes gap junction formation in the rat anterior pituitary gland.

PubMed

Horiguchi, Kotaro; Kouki, Tom; Fujiwara, Ken; Kikuchi, Motoshi; Yashiro, Takashi

2011-03-01

Folliculo-stellate (FS) cells in the anterior pituitary gland are believed to have multifunctional properties. FS cells connect to each other not only by mechanical means, but also by gap junctional cell-to-cell communication. Using transgenic rats that express green fluorescent protein (GFP) specifically in FS cells in the anterior pituitary gland (S100b-GFP rats), we recently revealed that FS cells in primary culture markedly change their shape, and form numerous interconnections with neighboring FS cells in the presence of laminin, an extracellular matrix (ECM) component of the basement membrane. Morphological and functional changes in cells are believed to be partly modified by matricrine signaling, by which ECM components function as cellular signals. In the present study, we examined whether gap junction formation between FS cells is affected by matricrine cues. A cell sorter was used to isolate FS cells from male S100b-GFP rat anterior pituitary for primary culture. We observed that mRNA and protein levels of connexin 43 in gap junction channels were clearly higher in the presence of laminin. In addition, we confirmed the formation of gap junctions between FS cells in primary culture by electron microscopy. Interestingly, we also observed that FS cells in the presence of laminin displayed well-developed rough endoplasmic reticulum and Golgi apparatus. Our findings suggest that, in anterior pituitary gland, FS cells may facilitate functional roles such as gap junctional cell-to-cell communication by matricrine signaling.

Berberine potentizes apoptosis induced by X-rays irradiation probably through modulation of gap junctions.

PubMed

Liu, Bing; Wang, Qin; Yuan, Dong-dong; Hong, Xiao-ting; Tao, Liang

2011-04-01

Clinical combination of some traditional Chinese medical herbs, including berberine, with irradiation is demonstrated to improve efficacy of tumor radiotherapy, yet the mechanisms for such effect remain largely unknown. The present study investigated the effect of berberine on apoptosis induced by X-rays irradiation and the relation between this effect and gap junction intercellular communication (GJIC). The role of gap junctions in the modulation of X-rays irradiation-induced apoptosis was explored by manipulation of connexin (Cx) expression, and gap junction function, using oleamide, a GJIC inhibitor, and berberine. In transfected HeLa cells, Cx32 expression increased apoptosis induced by X-rays irradiation, while inhibition of gap junction by oleamide reduced the irradiation responses, indicating the dependence of X-rays irradiation-induced apoptosis on GJIC. Berberine, at the concentrations without cytotoxicity, enhanced apoptosis induced by irradiation only in the presence of functional gap junctions. These results suggest that berberine potentizes cell apoptosis induced by X-rays irradiation, probably through enhancement of gap junction activity.

Gap junction plasticity as a mechanism to regulate network-wide oscillations

PubMed Central

Nicola, Wilten; Clopath, Claudia

2018-01-01

Cortical oscillations are thought to be involved in many cognitive functions and processes. Several mechanisms have been proposed to regulate oscillations. One prominent but understudied mechanism is gap junction coupling. Gap junctions are ubiquitous in cortex between GABAergic interneurons. Moreover, recent experiments indicate their strength can be modified in an activity-dependent manner, similar to chemical synapses. We hypothesized that activity-dependent gap junction plasticity acts as a mechanism to regulate oscillations in the cortex. We developed a computational model of gap junction plasticity in a recurrent cortical network based on recent experimental findings. We showed that gap junction plasticity can serve as a homeostatic mechanism for oscillations by maintaining a tight balance between two network states: asynchronous irregular activity and synchronized oscillations. This homeostatic mechanism allows for robust communication between neuronal assemblies through two different mechanisms: transient oscillations and frequency modulation. This implies a direct functional role for gap junction plasticity in information transmission in cortex. PMID:29529034

STIM proteins and the endoplasmic reticulum-plasma membrane junctions.

PubMed

Carrasco, Silvia; Meyer, Tobias

2011-01-01

Eukaryotic organelles can interact with each other through stable junctions where the two membranes are kept in close apposition. The junction that connects the endoplasmic reticulum to the plasma membrane (ER-PM junction) is unique in providing a direct communication link between the ER and the PM. In a recently discovered signaling process, STIM (stromal-interacting molecule) proteins sense a drop in ER Ca(2+) levels and directly activate Orai PM Ca(2+) channels across the junction space. In an inverse process, a voltage-gated PM Ca(2+) channel can directly open ER ryanodine-receptor Ca(2+) channels in striated-muscle cells. Although ER-PM junctions were first described 50 years ago, their broad importance in Ca(2+) signaling, as well as in the regulation of cholesterol and phosphatidylinositol lipid transfer, has only recently been realized. Here, we discuss research from different fields to provide a broad perspective on the structures and unique roles of ER-PM junctions in controlling signaling and metabolic processes.

Irsogladine maleate regulates gap junctional intercellular communication-dependent epithelial barrier in human nasal epithelial cells.

PubMed

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

2015-04-01

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.

Lipopolysaccharide effects on the proliferation of NRK52E cells via alternations in gap-junction function.

PubMed

Hei, Ziqing; Zhang, Ailan; Wei, Jing; Gan, Xiaoliang; Wang, Yanling; Luo, Gangjian; Li, Xiaoyun

2012-07-01

Gap junctions regulate proper kidney function by facilitating intercellular communication, vascular conduction, and tubular purinergic signaling. However, no clear relationship has been described between gap-junction function and acute kidney injury induced by the endotoxin lipopolysaccharide (LPS). Normal rat kidney epithelial cells (NRK52E cells) were seeded at high and low densities to promote or impede gap-junction formation, respectively, and establish distinctive levels of intercellular communication in culture. Cells were then challenged with LPS at various concentrations (10-1,000 ng/mL). LPS-induced formation and function of gap junctions were assessed by measuring changes in cell proliferation and colony-forming rates, fluorescent dye transmission to adjacent cells, expression levels of connexin43, and repositioning of confluent cells in response to the gap junction inhibitor oleamide or agonist retinoic acid. The cell proliferation rate and colony-forming rate of high- and low-density NRK52E cells were decreased upon LPS challenge, in a dose-dependent manner. The colony-forming rate of confluent high-density cells was significantly lower than that of low-density cells. Oleamide treatment raised the LPS-induced colony-forming rate of high-density cells, whereas retinoic acid decreased the rate. Neither oleamide nor retinoic acid significantly affected the LPS-induced colony-forming rate of low-density cells. Fluorescence transmission of high-density cells was reduced by LPS challenge, in a dose-dependent manner, but inclusion of retinoic acid increased the LPS-induced transmission of fluorescence. LPS challenge of either high- or low-density NRK52E cells resulted in down-regulated connexin43 expression. Gap-junction function plays an important role in concentration-dependent cytotoxic effect of LPS on normal rat kidney cells in vitro.

Inhibition of gap junction currents by the abused solvent toluene.

PubMed

Del Re, Angelo M; Woodward, John J

2005-05-09

Abused inhalants are a large class of compounds that are inhaled for their intoxicating and mood altering effects. They include chemicals with known therapeutic uses such as anesthetic gases as well as volatile organic solvents like toluene that are found in paint thinners and adhesives. Because of their widespread commercial use and availability, inhalants are often among the first drugs that children encounter and use of these compounds is often associated with adverse acute and long-term consequences. The cellular and molecular sites of action for abused inhalants is not well known although recent studies report that toluene and other organic solvents alter the activity of specific ligand- and voltage-gated ion channels that regulate cellular excitability. As part of an ongoing effort to define molecular sites of action for abused inhalants, this study examined the effect of toluene on the function of gap junction proteins endogenously expressed in human embryonic kidney (HEK 293) cells. Gap junctions allow cell-to-cell electrical communication as well as passage of small molecular weight substances and are critical for synchronizing cellular activity in certain tissues. Gap junction currents in HEK 293 cells were measured during brief voltage steps using patch-clamp electrophysiology and were blocked by known gap junction blockers confirming expression of connexin proteins in these cells. Toluene dose-dependently inhibited these conductances with threshold effects appearing at approximately 0.4 mM and near complete inhibition occurring at concentrations of 1 mM and higher. The estimated EC50 value for toluene inhibition of gap junction currents in HEK 293 cells was 0.57 mM. The results of these studies suggest that volatile solvents including toluene may produce some of their effects by disrupting inter-cellular communication mediated by gap junction proteins.

Dynamic current susceptibility as a probe of Majorana bound states in nanowire-based Josephson junctions

NASA Astrophysics Data System (ADS)

Trif, Mircea; Dmytruk, Olesia; Bouchiat, Hélène; Aguado, Ramón; Simon, Pascal

2018-02-01

We theoretically study a Josephson junction based on a semiconducting nanowire subject to a time-dependent flux bias. We establish a general density-matrix approach for the dynamical response of the Majorana junction and calculate the resulting flux-dependent susceptibility using both microscopic and effective low-energy descriptions for the nanowire. We find that the diagonal component of the susceptibility, associated with the dynamics of the Majorana state populations, dominates over the standard Kubo contribution for a wide range of experimentally relevant parameters. The diagonal term, explored, in this Rapid Communication, in the context of Majorana physics, allows probing accurately the presence of Majorana bound states in the junction.

High-efficiency inverted metamorphic 1.7/1.1 eV GaInAsP/GaInAs dual-junction solar cells

NASA Astrophysics Data System (ADS)

Jain, Nikhil; Schulte, Kevin L.; Geisz, John F.; Friedman, Daniel J.; France, Ryan M.; Perl, Emmett E.; Norman, Andrew G.; Guthrey, Harvey L.; Steiner, Myles A.

2018-01-01

Photovoltaic conversion efficiencies of 32.6 ± 1.4% under the AM1.5 G173 global spectrum, and 35.5% ± 1.2% at 38-suns concentration under the direct spectrum, are demonstrated for a monolithic, dual-junction 1.7/1.1 eV solar cell. The tandem cell consists of a 1.7 eV GaInAsP top-junction grown lattice-matched to a GaAs substrate, followed by a metamorphic 1.1 eV GaInAs junction grown on a transparent, compositionally graded metamorphic AlGaInAs buffer. This bandgap combination is much closer to the dual-junction optimum and offers headroom for absolute 3% improvement in efficiency, in comparison to the incumbent lattice-matched GaInP/GaAs (˜1.86/1.41 eV) solar cells. The challenge of growing a high-quality 1.7 eV GaInAsP solar cell is the propensity for phase separation in the GaInAsP alloy. The challenge of lattice-mismatched GaInAs solar cell growth is that it requires minimizing the residual dislocation density during the growth of a transparent compositionally graded buffer to enable efficient metamorphic tandem cell integration. Transmission electron microscopy reveals relatively weak composition fluctuation present in the 1.7 eV GaInAsP alloy, attained through growth control. The threading dislocation density of the GaInAs junction is ˜1 × 106 cm-2, as determined from cathodoluminescence measurements, highlighting the quality of the graded buffer. These material advances have enabled the performance of both junctions to reach over 80% of their Shockley-Queisser limiting efficiencies, with both the subcells demonstrating a bandgap-voltage offset, WOC (=Eg/q-VOC), of ˜0.39 V.

High-efficiency inverted metamorphic 1.7/1.1 eV GaInAsP/GaInAs dual-junction solar cells

DOE PAGES

Jain, Nikhil; Schulte, Kevin L.; Geisz, John F.; ...

2018-01-29

Photovoltaic conversion efficiencies of 32.6 +/- 1.4% under the AM1.5 G173 global spectrum, and 35.5 +/- 1.2% at 38-suns concentration under the direct spectrum, are demonstrated for a monolithic, dual-junction 1.7/1.1 eV solar cell. The tandem cell consists of a 1.7 eV GaInAsP top-junction grown lattice-matched to a GaAs substrate, followed by a metamorphic 1.1 eV GaInAs junction grown on a transparent, compositionally graded metamorphic AlGaInAs buffer. This bandgap combination is much closer to the dual-junction optimum and offers headroom for absolute 3% improvement in efficiency, in comparison to the incumbent lattice-matched GaInP/GaAs (~1.86/1.41 eV) solar cells. The challenge ofmore » growing a high-quality 1.7 eV GaInAsP solar cell is the propensity for phase separation in the GaInAsP alloy. The challenge of lattice-mismatched GaInAs solar cell growth is that it requires minimizing the residual dislocation density during the growth of a transparent compositionally graded buffer to enable efficient metamorphic tandem cell integration. Transmission electron microscopy reveals relatively weak composition fluctuation present in the 1.7 eV GaInAsP alloy, attained through growth control. The threading dislocation density of the GaInAs junction is ~1 x 10^6 cm-2, as determined from cathodoluminescence measurements, highlighting the quality of the graded buffer. These material advances have enabled the performance of both junctions to reach over 80% of their Shockley-Queisser limiting efficiencies, with both the subcells demonstrating a bandgap-voltage offset, WOC (=Eg/q-VOC), of ~0.39 V.« less

High-efficiency inverted metamorphic 1.7/1.1 eV GaInAsP/GaInAs dual-junction solar cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jain, Nikhil; Schulte, Kevin L.; Geisz, John F.

Photovoltaic conversion efficiencies of 32.6 +/- 1.4% under the AM1.5 G173 global spectrum, and 35.5 +/- 1.2% at 38-suns concentration under the direct spectrum, are demonstrated for a monolithic, dual-junction 1.7/1.1 eV solar cell. The tandem cell consists of a 1.7 eV GaInAsP top-junction grown lattice-matched to a GaAs substrate, followed by a metamorphic 1.1 eV GaInAs junction grown on a transparent, compositionally graded metamorphic AlGaInAs buffer. This bandgap combination is much closer to the dual-junction optimum and offers headroom for absolute 3% improvement in efficiency, in comparison to the incumbent lattice-matched GaInP/GaAs (~1.86/1.41 eV) solar cells. The challenge ofmore » growing a high-quality 1.7 eV GaInAsP solar cell is the propensity for phase separation in the GaInAsP alloy. The challenge of lattice-mismatched GaInAs solar cell growth is that it requires minimizing the residual dislocation density during the growth of a transparent compositionally graded buffer to enable efficient metamorphic tandem cell integration. Transmission electron microscopy reveals relatively weak composition fluctuation present in the 1.7 eV GaInAsP alloy, attained through growth control. The threading dislocation density of the GaInAs junction is ~1 x 10^6 cm-2, as determined from cathodoluminescence measurements, highlighting the quality of the graded buffer. These material advances have enabled the performance of both junctions to reach over 80% of their Shockley-Queisser limiting efficiencies, with both the subcells demonstrating a bandgap-voltage offset, WOC (=Eg/q-VOC), of ~0.39 V.« less

Atom-scale compositional distribution in InAlAsSb-based triple junction solar cells by atom probe tomography.

PubMed

Hernández-Saz, J; Herrera, M; Delgado, F J; Duguay, S; Philippe, T; Gonzalez, M; Abell, J; Walters, R J; Molina, S I

2016-07-29

The analysis by atom probe tomography (APT) of InAlAsSb layers with applications in triple junction solar cells (TJSCs) has shown the existence of In- and Sb-rich regions in the material. The composition variation found is not evident from the direct observation of the 3D atomic distribution and because of this a statistical analysis has been required. From previous analysis of these samples, it is shown that the small compositional fluctuations determined have a strong effect on the optical properties of the material and ultimately on the performance of TJSCs.

Broad spectrum solar cell

DOEpatents

Walukiewicz, Wladyslaw [Kensington, CA; Yu, Kin Man [Lafayette, CA; Wu, Junqiao [Richmond, CA; Schaff, William J [Ithaca, NY

2007-05-15

An alloy having a large band gap range is used in a multijunction solar cell to enhance utilization of the solar energy spectrum. In one embodiment, the alloy is In.sub.1-xGa.sub.xN having an energy bandgap range of approximately 0.7 eV to 3.4 eV, providing a good match to the solar energy spectrum. Multiple junctions having different bandgaps are stacked to form a solar cell. Each junction may have different bandgaps (realized by varying the alloy composition), and therefore be responsive to different parts of the spectrum. The junctions are stacked in such a manner that some bands of light pass through upper junctions to lower junctions that are responsive to such bands.

[The role of gap junction communication in metastatic B16 melanoma in C57BL mice].

PubMed

Fëdorov, E S; Manikhas, G M; Petrishchëv, N N; Dubina, M V

2006-01-01

The study is concerned with the effects of non-specific blocking gap junction communication with oleamide as well as genesis and spreading of melanoma B16 metastases to the lung in mice C57B1. The blocking exerted no distinct influence on primary tumorigenesis but had a marked effect on metastatic spread. Oleamide treatment during tumor growth led to an increase in area covered by metastases. A correlation was established between metastatic frequency and dosage: 1 mg/kg was followed by an upsurge in frequency of secondary lung tumors while 10 mg/kg--by a drop.

Low Connexin Channel-Dependent Intercellular Communication in Human Adult Hematopoietic Progenitor/Stem Cells: Probing Mechanisms of Autologous Stem Cell Therapy

PubMed Central

Yang, Jian; Darley, Richard L; Hallett, Maurice; Evans, W Howard

2009-01-01

Human bone marrow is a clinical source of autologous progenitor stem cells showing promise for cardiac repair following ischemic insult. Functional improvements following delivery of adult bone marrow CD34+ cells into heart tissue may require metabolic/electrical communication between participating cells. Since connexin43 (Cx43) channels are implicated in cardiogenesis and provide intercellular connectivity in the heart, the authors analyzed the expression of 20 connexins (Cx) in CD34+ cells and in monocytes and granulocytes in bone marrow and spinal cord. Reverse transcriptase-polymerase chain reaction (RT-PCR) detected only low expression of Cx43 and Cx37. Very low level dye coupling was detected by flow cytometry between CD34+ cells and other Cx43 expressing cells, including HL-1 cardiac cells, and was not inhibited by specific gap junction inhibitors. The results indicate that CD34+ cells are unlikely to communicate via gap junctions and the authors conclude that use of CD34+ cells to repair damaged hearts is unlikely to involve gap junctions. The results concur with the hypothesis that bone marrow cells elicit improved cardiac function through release of undefined paracrine mediators. PMID:20298144

Modulation of Brain Hemichannels and Gap Junction Channels by Pro-Inflammatory Agents and Their Possible Role in Neurodegeneration

PubMed Central

Sáez, Pablo J.; Shoji, Kenji F.; Schalper, Kurt A.; Palacios–Prado, Nicolás; Velarde, Victoria; Giaume, Christian; Bennett, Michael V.L.; Sáez, Juan C.

2009-01-01

Abstract In normal brain, neurons, astrocytes, and oligodendrocytes, the most abundant and active cells express pannexins and connexins, protein subunits of two families forming membrane channels. Most available evidence indicates that in mammals endogenously expressed pannexins form only hemichannels and connexins form both gap junction channels and hemichannels. Whereas gap junction channels connect the cytoplasm of contacting cells and coordinate electric and metabolic activity, hemichannels communicate the intra- and extracellular compartments and serve as a diffusional pathway for ions and small molecules. A subthreshold stimulation by acute pathological threatening conditions (e.g., global ischemia subthreshold for cell death) enhances neuronal Cx36 and glial Cx43 hemichannel activity, favoring ATP release and generation of preconditioning. If the stimulus is sufficiently deleterious, microglia become overactivated and release bioactive molecules that increase the activity of hemichannels and reduce gap junctional communication in astroglial networks, depriving neurons of astrocytic protective functions, and further reducing neuronal viability. Continuous glial activation triggered by low levels of anomalous proteins expressed in several neurodegenerative diseases induce glial hemichannel and gap junction channel disorders similar to those of acute inflammatory responses triggered by ischemia or infectious diseases. These changes are likely to occur in diverse cell types of the CNS and contribute to neurodegeneration during inflammatory process. Antiox. Redox Signal. 11, 369–399. PMID:18816186

A unified framework for spiking and gap-junction interactions in distributed neuronal network simulations.

PubMed

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

2015-01-01

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.

A unified framework for spiking and gap-junction interactions in distributed neuronal network simulations

PubMed Central

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

2015-01-01

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rivedal, Edgar; Leithe, Edward

Benzene is used at large volumes in many different human activities. Hematotoxicity and cancer-causation as a result of benzene exposure was recognized many years ago, but the mechanisms involved remain unclear. Aberrant regulation of gap junction intercellular communication (GJIC) has been linked to both cancer induction and interference with normal hematopoietic development. We have previously suggested that inhibition of GJIC may play a role in benzene toxicity since benzene metabolites were found to block GJIC, the ring-opened trans,trans-muconaldehyde (MUC) being the most potent metabolite. In the present work we have studied the molecular mechanisms underlying the MUC-induced inhibition of gapmore » junctional communication. We show that MUC induces cross-linking of the gap junction protein connexin43 and that this is likely to be responsible for the induced inhibition of GJIC, as well as the loss of connexin43 observed in Western blots. We also show that glutaraldehyde possesses similar effects as MUC, and we compare the effects to that of formaldehyde. The fact that glutaraldehyde and formaldehyde have been associated with induction of leukemia as well as disturbance of hematopoiesis, strengthens the possible link between the effect of MUC on gap junctions, and the toxic effects of benzene.« less

Diabetes Increases Cryoinjury Size with Associated Effects on Cx43 Gap Junction Function and Phosphorylation in the Mouse Heart.

PubMed

Palatinus, Joseph A; Gourdie, Robert G

2016-01-01

Diabetic patients develop larger myocardial infarctions and have an increased risk of death following a heart attack. The poor response to myocardial injury in the diabetic heart is likely related to the many metabolic derangements from diabetes that create a poor substrate in general for wound healing, response to injury and infection. Studies in rodents have implicated a role for the gap junction protein connexin 43 (Cx43) in regulating the injury response in diabetic skin wounds. In this study, we sought to determine whether diabetes alters Cx43 molecular interactions or intracellular communication in the cryoinjured STZ type I diabetic mouse heart. We found that epicardial cryoinjury size is increased in diabetic mice and this increase is prevented by preinjury insulin administration. Consistent with these findings, we found that intercellular coupling via gap junctions is decreased after insulin administration in diabetic and nondiabetic mice. This decrease in coupling is associated with a concomitant increase in phosphorylation of Cx43 at serine 368, a residue known to decrease channel conductance. Taken together, our results suggest that insulin regulates both gap junction-mediated intercellular communication and injury propagation in the mouse heart.

Epithelial junctions, cytoskeleton, and polarity.

PubMed

Pásti, Gabriella; Labouesse, Michel

2014-11-04

A distinctive feature of polarized epithelial cells is their specialized junctions, which contribute to cell integrity and provide platforms to orchestrate cell shape changes. This chapter discusses the composition, assembly and remodeling of C. elegans cell-cell (CeAJ) and hemidesmosome-like cell-extracellular matrix junctions (CeHD), proteins that anchor the cytoskeleton, and mechanisms involved in establishing epithelial polarity. Major recent progress in this area has come from the analysis of mechanisms that maintain cell polarity, which involve lipids and trafficking, and on the impact of mechanical forces on junction remodeling. This chapter focuses on cellular, rather than developmental, aspects of epithelial cells.

CMOS Image Sensor Using SOI-MOS/Photodiode Composite Photodetector Device

NASA Astrophysics Data System (ADS)

Uryu, Yuko; Asano, Tanemasa

2002-04-01

A new photodetector device composed of a lateral junction photodiode and a metal-oxide-semiconductor field-effect-transistor (MOSFET), in which the output of the diode is fed through the body of the MOSFET, has been investigated. It is shown that the silicon-on-insulator (SOI)-MOSFET amplifies the junction photodiode current due to the lateral bipolar action. It is also shown that the presence of the electrically floating gate enhances the current amplification factor of the SOI-MOSFET. The output current of this composite device linearly responds by four orders of illumination intensity. As an application of the composite device, a complementary-metal-oxide-semiconductor (CMOS) line sensor incorporating the composite device is fabricated and its operation is demonstrated. The output signal of the line sensor using the composite device was two times larger than that using the lateral photodiode.

Specificity of gap junction communication among human mammary cells and connexin transfectants in culture

PubMed Central

1993-01-01

In a previous paper (Lee et al., 1992), it was shown that normal human mammary epithelial cells (NMEC) express two connexin genes, Cx26 and Cx43, whereas neither gene is transcribed in a series of mammary tumor cell lines (TMEC). In this paper it is shown that normal human mammary fibroblasts (NMF) communicate and express Cx43 mRNA and protein. Transfection of either Cx26 or Cx43 genes into a tumor line, 21MT-2, induced the expression of the corresponding mRNAs and proteins as well as communication via gap junctions (GJs), although immunofluorescence demonstrated that the majority of Cx26 and Cx43 proteins present in transfected TMEC was largely cytoplasmic. Immunoblotting demonstrated that NMEC, NMF, and transfected TMEC each displayed a unique pattern of posttranslationally modified forms of Cx43 protein. The role of different connexins in regulating gap junction intercellular communication (GJIC) was examined using a novel two-dye method to assess homologous and heterologous communication quantitatively. The recipient cell population was prestained with a permanent non-toxic lipophilic dye that binds to membranes irreversibly (PKH26, Zynaxis); and the donor population is treated with a GJ-permeable dye Calcein, a derivative of fluorescein diacetate (Molecular Probes). After mixing the two cell populations under conditions promoting GJ formation, cells were analyzed by flow cytometry to determine the percentage of cells containing both dyes. It is shown here that Cx26 and Cx43 transfectants display strong homologous communication, as do NMEC and NMF. Furthermore, NMEC mixed with NMF communicate efficiently, Cx26 transfectants communicate with NMEC but not with NMF, and Cx43 transfectants communicate with NMF. Communication between Cx26 TMEC transfectants and NMEC was asymetrical with preferential movement of calcein from TMEC to NMEC. Despite the presence of Cx43 as well as Cx26 encoded proteins in the GJs of NMEC, few Cx43 transfectants communicated with NMEC. No heterologous GJIC was observed between Cx26- and Cx43-transfected TMEC suggesting that heterotypic GJs do not form or that Cx26/Cx43 channels do not permit dye transfer. PMID:8391000

FAST TRACK COMMUNICATION: Thermoelectric properties of graphene nanoribbons, junctions and superlattices

NASA Astrophysics Data System (ADS)

Chen, Y.; Jayasekera, T.; Calzolari, A.; Kim, K. W.; Buongiorno Nardelli, M.

2010-09-01

Using model interaction Hamiltonians for both electrons and phonons and Green's function formalism for ballistic transport, we have studied the thermal conductance and the thermoelectric properties of graphene nanoribbons (GNR), GNR junctions and periodic superlattices. Among our findings we have established the role that interfaces play in determining the thermoelectric response of GNR systems both across single junctions and in periodic superlattices. In general, increasing the number of interfaces in a single GNR system increases the peak ZT values that are thus maximized in a periodic superlattice. Moreover, we proved that the thermoelectric behavior is largely controlled by the width of the narrower component of the junction. Finally, we have demonstrated that chevron-type GNRs recently synthesized should display superior thermoelectric properties.

Investigations on rectifying behavior of Y{sub 0.95}Ca{sub 0.05}MnO{sub 3}/Si junction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhruv, Davit; V.V.P. Engineering College, Gujarat Technological University, Rajkot – 360 005; Joshi, Zalak

2016-05-06

In this communication, we report the rectifying properties observed across the junction, consists of Ca{sup +2} doped hexagonal YMnO{sub 3} manganite film, grown on n-type (100) Si single crystalline substrate. The junction was grown using cost effective chemical solution deposition (CSD) technique by employing spin coating method. Surface morphology of Y{sub 0.9}5Ca{sub 0.05}MnO{sub 3}/Si (YCMO/Si) film was carried out by atomic force microscopy and magnetic response of film was studied by magnetic force microscopy. Current – voltage characteristics of the junction was carried out by using Keithley source meter in current perpendicular to plane (CPP) mode at different temperatures. Rectificationmore » in I – V behavior has been observed for the junction at all the temperatures studied. With increase in temperature, rectification ratio, in the range of 10{sup 4}, increases across the junction. Results have been discussed in the context of thermal effects.« less

Thermoelectric metal comparator determines composition of alloys and metals

NASA Technical Reports Server (NTRS)

Stone, C. C.; Walker, D. E.

1967-01-01

Emf comparing device nondestructively inspects metals and alloys for conformance to a chemical specification. It uses the Seebeck effect to measure the difference in emf produced by the junction of a hot probe and the junction of a cold contact on the surface of an unknown metal.

Computer Aided Design of Ka-Band Waveguide Power Combining Architectures for Interplanetary Spacecraft

NASA Technical Reports Server (NTRS)

Vaden, Karl R.

2006-01-01

Communication systems for future NASA interplanetary spacecraft require transmitter power ranging from several hundred watts to kilowatts. Several hybrid junctions are considered as elements within a corporate combining architecture for high power Ka-band space traveling-wave tube amplifiers (TWTAs). This report presents the simulated transmission characteristics of several hybrid junctions designed for a low loss, high power waveguide based power combiner.

A new method to synthesize complicated multi-branched carbon nanotubes with controlled architecture and composition.

PubMed

Wei, Dacheng; Liu, Yunqi; Cao, Lingchao; Fu, Lei; Li, Xianglong; Wang, Yu; Yu, Gui; Zhu, Daoben

2006-02-01

Here we develop a simple method by using flow fluctuation to synthesize arrays of multi-branched carbon nanotubes (CNTs) that are far more complex than those previously reported. The architectures and compositions can be well controlled, thus avoiding any template or additive. A branching mechanism of fluctuation-promoted coalescence of catalyst particles is proposed. This finding will provide a hopeful approach to the goal of CNT-based integrated circuits and be valuable for applying branched junctions in nanoelectronics and producing branched junctions of other materials.

[Effects of Chinese herbal compound for supplementing qi and activating blood circulation on actin, Cx43 expressions and gap junctional intercellular communication functions of myocardial cells in patients with Coxsackie virus B 3 viral myocarditis].

PubMed

Zhang, Ming-xue; He, Wei; Gu, Ping

2010-08-01

To observe the effect of Chinese herbal compound for supplementing qi and activating blood circulation (CHC) on the gap junctional intercellular communication (GJIC) function of myocardial cells in patients with Coxsackie virus B 3 (CVB3) viral myocarditis. Expressions of actin and connexin43 (Cx43) in myocardial cells of patients arranged in three groups (the normal control group, the viral infected group and the CHC treated group) were detected by immunohistochemical method; the fluorescence photobleaching recovery rate of cells was detected by laser scanning confocal microscope. As compared with the viral infected group, the expressions of actin and Cx43 were increased and the GJIC function was improved in the CHC treated group. CHC could antagonize viral injury on skeleton protein, and repair the structure of gap junction channel to improve the GJIC function of myocardial cells after being attacked by CVB3.

Antidromic-rectifying gap junctions amplify chemical transmission at functionally mixed electrical-chemical synapses

PubMed Central

Liu, Ping; Chen, Bojun; Mailler, Roger; Wang, Zhao-Wen

2017-01-01

Neurons communicate through chemical synapses and electrical synapses (gap junctions). Although these two types of synapses often coexist between neurons, little is known about whether they interact, and whether any interactions between them are important to controlling synaptic strength and circuit functions. By studying chemical and electrical synapses between premotor interneurons (AVA) and downstream motor neurons (A-MNs) in the Caenorhabditis elegans escape circuit, we found that disrupting either the chemical or electrical synapses causes defective escape response. Gap junctions between AVA and A-MNs only allow antidromic current, but, curiously, disrupting them inhibits chemical transmission. In contrast, disrupting chemical synapses has no effect on the electrical coupling. These results demonstrate that gap junctions may serve as an amplifier of chemical transmission between neurons with both electrical and chemical synapses. The use of antidromic-rectifying gap junctions to amplify chemical transmission is potentially a conserved mechanism in circuit functions. PMID:28317880

Cross reactive arrays of three-way junction sensors for steroid determination

NASA Technical Reports Server (NTRS)

Stojanovic, Milan N. (Inventor); Nikic, Dragan B. (Inventor); Landry, Donald (Inventor)

2008-01-01

This invention provides analyte sensitive oligonucleotide compositions for detecting and analyzing analytes in solution, including complex solutions using cross reactive arrays of analyte sensitive oligonucleotide compositions.

Three-dimensional modeling and quantitative analysis of gap junction distributions in cardiac tissue.

PubMed

Lackey, Daniel P; Carruth, Eric D; Lasher, Richard A; Boenisch, Jan; Sachse, Frank B; Hitchcock, Robert W

2011-11-01

Gap junctions play a fundamental role in intercellular communication in cardiac tissue. Various types of heart disease including hypertrophy and ischemia are associated with alterations of the spatial arrangement of gap junctions. Previous studies applied two-dimensional optical and electron-microscopy to visualize gap junction arrangements. In normal cardiomyocytes, gap junctions were primarily found at cell ends, but can be found also in more central regions. In this study, we extended these approaches toward three-dimensional reconstruction of gap junction distributions based on high-resolution scanning confocal microscopy and image processing. We developed methods for quantitative characterization of gap junction distributions based on analysis of intensity profiles along the principal axes of myocytes. The analyses characterized gap junction polarization at cell ends and higher-order statistical image moments of intensity profiles. The methodology was tested in rat ventricular myocardium. Our analysis yielded novel quantitative data on gap junction distributions. In particular, the analysis demonstrated that the distributions exhibit significant variability with respect to polarization, skewness, and kurtosis. We suggest that this methodology provides a quantitative alternative to current approaches based on visual inspection, with applications in particular in characterization of engineered and diseased myocardium. Furthermore, we propose that these data provide improved input for computational modeling of cardiac conduction.

Transport and Junction Physics of Semiconductor-Metal Eutectic Composites

DTIC Science & Technology

1988-06-01

eutectic junction and includes the method for making contacts as well as current-voltage (I-V), capacitance- voltage (C-V), and electron-beam-induced current...junction was performed with another RTA at 8000C to 9000C for 10 s. This technique also worked well to provide the necessary ohmic contact. The necessary...solid state diffusion of Ta and Si. The diode is well behaved, with an ideality factor n = 1.10 ± 0.05. Deviation from the straight line forward

Disruption of gap junctions attenuates aminoglycoside-elicited renal tubular cell injury.

PubMed

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

2010-08-01

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. 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. 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 alpha-glycyrrhetinic acid (alpha-GA) activated Akt in NRK-E52 cells. Inhibition of the Akt pathway enhanced cell toxicity to G418 and abolished the protective effects of alpha-GA. In addition, gentamycin-elicited cytotoxicity in NRK-E52 cells was also significantly attenuated by alpha-GA. 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.

Dilute group III-V nitride intermediate band solar cells with contact blocking layers

DOEpatents

Walukiewicz, Wladyslaw; Yu, Kin Man

2015-02-24

An intermediate band solar cell (IBSC) is provided including a p-n junction based on dilute III-V nitride materials and a pair of contact blocking layers positioned on opposite surfaces of the p-n junction for electrically isolating the intermediate band of the p-n junction by blocking the charge transport in the intermediate band without affecting the electron and hole collection efficiency of the p-n junction, thereby increasing open circuit voltage (V.sub.OC) of the IBSC and increasing the photocurrent by utilizing the intermediate band to absorb photons with energy below the band gap of the absorber layers of the IBSC. Hence, the overall power conversion efficiency of a IBSC will be much higher than an conventional single junction solar cell. The p-n junction absorber layers of the IBSC may further have compositionally graded nitrogen concentrations to provide an electric field for more efficient charge collection.

Dilute Group III-V nitride intermediate band solar cells with contact blocking layers

DOEpatents

Walukiewicz, Wladyslaw [Kensington, CA; Yu, Kin Man [Lafayette, CA

2012-07-31

An intermediate band solar cell (IBSC) is provided including a p-n junction based on dilute III-V nitride materials and a pair of contact blocking layers positioned on opposite surfaces of the p-n junction for electrically isolating the intermediate band of the p-n junction by blocking the charge transport in the intermediate band without affecting the electron and hole collection efficiency of the p-n junction, thereby increasing open circuit voltage (V.sub.OC) of the IBSC and increasing the photocurrent by utilizing the intermediate band to absorb photons with energy below the band gap of the absorber layers of the IBSC. Hence, the overall power conversion efficiency of a IBSC will be much higher than an conventional single junction solar cell. The p-n junction absorber layers of the IBSC may further have compositionally graded nitrogen concentrations to provide an electric field for more efficient charge collection.

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.

PubMed

Trosko, James E

2016-06-15

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.

Analyzing phorbol ester effects on gap junctional communication: a dramatic inhibition of assembly

PubMed Central

1994-01-01

The effect of 12-O-tetradeconylphorbol-13-acetate (TPA) on gap junction assembly between Novikoff hepatoma cells was examined. Cells were dissociated with EDTA to single cells and then reaggregated to form new junctions. When TPA (25 nM) was added to the cells at the onset of the 60-min reaggregation, dye transfer was detected at only 0.6% of the cell-cell interfaces compared to 72% for the untreated control and 74% for 4-alpha TPA, an inactive isomer of TPA. Freeze-fracture electron microscopy of reaggregated control cells showed interfaces containing an average of more than 600 aggregated intramembranous gap junction particles, while TPA-treated cells had no gap junctions. However, Lucifer yellow dye transfer between nondissociated cells via gap junctions was unaffected by 60 min of TPA treatment. Therefore, TPA dramatically inhibited gap junction assembly but did not alter channel gating nor enhance disassembly of preexisting gap junction structures. Short term TPA treatment (< 30 min) increased phosphorylation of the gap junction protein molecular weight of 43,000 (Cx43), but did not change the cellular level of Cx43. Cell surface biotinylation experiments suggested that TPA did not substantially reduce the plasma membrane concentration of Cx43. Therefore, the simple presence of Cx43 in the plasma membrane is not sufficient for gap junction assembly, and protein kinase C probably exerts an effect on assembly of gap junctions at the plasma membrane level. PMID:7806568

Recto-anal junction (RAJ) microbiota composition in Escherichia coli O157:H7 shedding cattle

USDA-ARS?s Scientific Manuscript database

Introduction: Cattle are the asymptomatic reservoirs of Escherichia coli O157:H7 (O157) that tend to preferentially colonize the bovine recto-anal junction (RAJ). Therefore, understanding the taxonomic profile, microbial diversity, and microbiota-O157 interactions at the RAJ could give insights into...

76 FR 63919 - Whitestone Power and Communications; Notice of Technical Teleconference To Discuss Information...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-14

...). d. Name of Project: Microturbine Hydrokinetic River-In-Stream Energy Conversion Power Project (also.... Selvaggio, Whitestone Power and Communications, P.O. Box 1630, Delta Junction, Alaska 99737; (907) 895- 4938...: The proposed Microturbine Hydrokinetic River-In-Stream Energy Conversion Power Project would consist...

K-Band Latching Switches

NASA Technical Reports Server (NTRS)

Piotrowski, W. S.; Raue, J. E.

1984-01-01

Design, development, and tests are described for two single-pole-double-throw latching waveguide ferrite switches: a K-band switch in WR-42 waveguide and a Ka-band switch in WR-28 waveguide. Both switches have structurally simple junctions, mechanically interlocked without the use of bonding materials; they are impervious to the effects of thermal, shock, and vibration stresses. Ferrite material for the Ka-band switch with a proper combination of magnetic and dielectric properties was available and resulted in excellent low loss, wideband performance. The high power handling requirement of the K-band switch limited the choice of ferrite to nickel-zinc compositions with adequate magnetic properties, but with too low relative dielectric constant. The relative dielectric constant determines the junction dimensions for given frequency responses. In this case the too low value unavoidably leads to a larger than optimum junction volume, increasing the insertion loss and restricting the operating bandwidth. Efforts to overcome the materials-related difficulties through the design of a composite junction with increased effective dielectric properties efforts to modify the relative dielectric constant of nickel-zinc ferrite are examined.

Design and optimization of ARC less InGaP/GaAs single-/multi-junction solar cells with tunnel junction and back surface field layers

NASA Astrophysics Data System (ADS)

Chee, Kuan W. A.; Hu, Yuning

2018-07-01

There has always been an inexorable interest in the solar industry in boosting the photovoltaic conversion efficiency. This paper presents a theoretical and numerical simulation study of the effects of key design parameters on the photoelectric performance of single junction (InGaP- or GaAs-based) and dual junction (InGaP/GaAs) inorganic solar cells. The influence of base layer thickness, base doping concentration, junction temperature, back surface field layer composition and thickness, and tunnel junction material, were correlated with open circuit voltage, short-circuit current, fill factor and power conversion efficiency performance. The InGaP/GaAs dual junction solar cell was optimized with the tunnel junction and back surface field designs, yielding a short-circuit current density of 20.71 mAcm-2 , open-circuit voltage of 2.44 V and fill factor of 88.6%, and guaranteeing an optimal power conversion efficiency of at least 32.4% under 1 sun AM0 illumination even without an anti-reflective coating.

Cellular Interaction of Integrin α3β1 with Laminin 5 Promotes Gap Junctional Communication

PubMed Central

Lampe, Paul D.; Nguyen, Beth P.; Gil, Susana; Usui, Marcia; Olerud, John; Takada, Yoshikazu; Carter, William G.

1998-01-01

Wounding of skin activates epidermal cell migration over exposed dermal collagen and fibronectin and over laminin 5 secreted into the provisional basement membrane. Gap junctional intercellular communication (GJIC) has been proposed to integrate the individual motile cells into a synchronized colony. We found that outgrowths of human keratinocytes in wounds or epibole cultures display parallel changes in the expression of laminin 5, integrin α3β1, E-cadherin, and the gap junctional protein connexin 43. Adhesion of keratinocytes on laminin 5, collagen, and fibronectin was found to differentially regulate GJIC. When keratinocytes were adhered on laminin 5, both structural (assembly of connexin 43 in gap junctions) and functional (dye transfer) assays showed a two- to threefold increase compared with collagen and five- to eightfold over fibronectin. Based on studies with immobilized integrin antibody and integrin-transfected Chinese hamster ovary cells, the interaction of integrin α3β1 with laminin 5 was sufficient to promote GJIC. Mapping of intermediate steps in the pathway linking α3β1–laminin 5 interactions to GJIC indicated that protein trafficking and Rho signaling were both required. We suggest that adhesion of epithelial cells to laminin 5 in the basement membrane via α3β1 promotes GJIC that integrates individual cells into synchronized epiboles. PMID:9852164

Phylogenetic and bioinformatic analysis of gap junction-related proteins, innexins, pannexins and connexins.

PubMed

Fushiki, Daisuke; Hamada, Yasuo; Yoshimura, Ryoichi; Endo, Yasuhisa

2010-04-01

All multi-cellular animals, including hydra, insects and vertebrates, develop gap junctions, which communicate directly with neighboring cells. Gap junctions consist of protein families called connexins in vertebrates and innexins in invertebrates. Connexins and innexins have no homology in their amino acid sequence, but both are thought to have some similar characteristics, such as a tetra-membrane-spanning structure, formation of a channel by hexamer, and transmission of small molecules (e.g. ions) to neighboring cells. Pannexins were recently identified as a homolog of innexins in vertebrate genomes. Although pannexins are thought to share the function of intercellular communication with connexins and innexins, there is little information about the relationship among these three protein families of gap junctions. We phylgenetically and bioinformatically examined these protein families and other tetra-membrane-spanning proteins using a database and three analytical softwares. The clades formed by pannexin families do not belong to the species classification but do to paralogs of each member of pannexins. Amino acid sequences of pannexins are closely related to those of innexins but less to those of connexins. These data suggest that innexins and pannexins have a common origin, but the relationship between innexins/pannexins and connexins is as slight as that of other tetra-membrane-spanning members.

Intercellular Calcium Waves in HeLa Cells Expressing GFP-labeled Connexin 43, 32, or 26

PubMed Central

Paemeleire, Koen; Martin, Patricia E. M.; Coleman, Sharon L.; Fogarty, Kevin E.; Carrington, Walter A.; Leybaert, Luc; Tuft, Richard A.; Evans, W. Howard; Sanderson, Michael J.

2000-01-01

This study was undertaken to obtain direct evidence for the involvement of gap junctions in the propagation of intercellular Ca2+ waves. Gap junction-deficient HeLa cells were transfected with plasmids encoding for green fluorescent protein (GFP) fused to the cytoplasmic carboxyl termini of connexin 43 (Cx43), 32 (Cx32), or 26 (Cx26). The subsequently expressed GFP-labeled gap junctions rendered the cells dye- and electrically coupled and were detected at the plasma membranes at points of contact between adjacent cells. To correlate the distribution of gap junctions with the changes in [Ca2+]i associated with Ca2+ waves and the distribution of the endoplasmic reticulum (ER), cells were loaded with fluorescent Ca2+-sensitive (fluo-3 and fura-2) and ER membrane (ER-Tracker) dyes. Digital high-speed microscopy was used to collect a series of image slices from which the three-dimensional distribution of the gap junctions and ER were reconstructed. Subsequently, intercellular Ca2+ waves were induced in these cells by mechanical stimulation with or without extracellular apyrase, an ATP-degrading enzyme. In untransfected HeLa cells and in the absence of apyrase, cell-to-cell propagating [Ca2+]i changes were characterized by initiating Ca2+ puffs associated with the perinuclear ER. By contrast, in Cx–GFP-transfected cells and in the presence of apyrase, [Ca2+]i changes were propagated without initiating perinuclear Ca2+ puffs and were communicated between cells at the sites of the Cx–GFP gap junctions. The efficiency of Cx expression determined the extent of Ca2+ wave propagation. These results demonstrate that intercellular Ca2+ waves may be propagated simultaneously via an extracellular pathway and an intracellular pathway through gap junctions and that one form of communication may mask the other. PMID:10793154

Bioavailability and efficacy of a gap junction enhancer (PQ7) in a mouse mammary tumor model.

PubMed

Shishido, Stephanie N; Prasain, Keshar; Beck, Amanda; Nguyen, Thi D T; Hua, Duy H; Nguyen, Thu Annelise

2013-01-01

The loss of gap junctional intercellular communication is characteristic of neoplastic cells, suggesting that the restoration with a gap junction enhancer may be a new therapeutic treatment option with less detrimental effects than traditional antineoplastic drugs. A gap junction enhancer, 6-methoxy-8-[(2-furanylmethyl) amino]-4-methyl-5-(3-trifluoromethylphenyloxy) quinoline (PQ7), on the normal tissue was evaluated in healthy C57BL/6J mice in a systemic drug distribution study. Immunoblot analysis of the vital organs indicates a reduction in Cx43 expression in PQ7-treated animals with no observable change in morphology. Next the transgenic strain FVB/N-Tg(MMTV-PyVT) 634Mul/J (also known as PyVT) was used as a spontaneous mammary tumor mouse model to determine the biological and histological effects of PQ7 on tumorigenesis and metastasis at three stages of development: Pre tumor, Early tumor, and Late tumor formation. PQ7 was assessed to have a low toxicity through intraperitoneal administration, with the majority of the compound being detected in the heart, liver, and lungs six hours post injection. The treatment of tumor bearing animals with PQ7 had a 98% reduction in tumor growth, while also decreasing the total tumor burden compared to control mice during the Pre stage of development. PQ7 treatment increased Cx43 expression in the neoplastic tissue during Pre-tumor formation; however, this effect was not observed in Late stage tumor formation. This study shows that the gap junction enhancer, PQ7, has low toxicity to normal tissue in healthy C57BL/6J mice, while having clinical efficacy in the treatment of spontaneous mammary tumors of PyVT mice. Additionally, gap junctional intercellular communication and neoplastic cellular growth are shown to be inversely related, while treatment with PQ7 inhibits tumor growth through targeting gap junction expression.

Cell-specific expression of connexins and evidence of restricted gap junctional coupling between glial cells and between neurons.

PubMed

Rash, J E; Yasumura, T; Dudek, F E; Nagy, J I

2001-03-15

The transmembrane connexin proteins of gap junctions link extracellularly to form channels for cell-to-cell exchange of ions and small molecules. Two primary hypotheses of gap junction coupling in the CNS are the following: (1) generalized coupling occurs between neurons and glia, with some connexins expressed in both neurons and glia, and (2) intercellular junctional coupling is restricted to specific coupling partners, with different connexins expressed in each cell type. There is consensus that gap junctions link neurons to neurons and astrocytes to oligodendrocytes, ependymocytes, and other astrocytes. However, unresolved are the existence and degree to which gap junctions occur between oligodendrocytes, between oligodendrocytes and neurons, and between astrocytes and neurons. Using light microscopic immunocytochemistry and freeze-fracture replica immunogold labeling of adult rat CNS, we investigated whether four of the best-characterized CNS connexins are each present in one or more cell types, whether oligodendrocytes also share gap junctions with other oligodendrocytes or with neurons, and whether astrocytes share gap junctions with neurons. Connexin32 (Cx32) was found only in gap junctions of oligodendrocyte plasma membranes, Cx30 and Cx43 were found only in astrocyte membranes, and Cx36 was only in neurons. Oligodendrocytes shared intercellular gap junctions only with astrocytes, with each oligodendrocyte isolated from other oligodendrocytes except via astrocyte intermediaries. Finally, neurons shared gap junctions only with other neurons and not with glial cells. Thus, the different cell types of the CNS express different connexins, which define separate pathways for neuronal versus glial gap junctional communication.

Abundance and ultrastructural diversity of neuronal gap junctions in the OFF and ON sublaminae of the inner plexiform layer of rat and mouse retina.

PubMed

Kamasawa, N; Furman, C S; Davidson, K G V; Sampson, J A; Magnie, A R; Gebhardt, B R; Kamasawa, M; Yasumura, T; Zumbrunnen, J R; Pickard, G E; Nagy, J I; Rash, J E

2006-11-03

Neuronal gap junctions are abundant in both outer and inner plexiform layers of the mammalian retina. In the inner plexiform layer (IPL), ultrastructurally-identified gap junctions were reported primarily in the functionally-defined and anatomically-distinct ON sublamina, with few reported in the OFF sublamina. We used freeze-fracture replica immunogold labeling and confocal microscopy to quantitatively analyze the morphologies and distributions of neuronal gap junctions in the IPL of adult rat and mouse retina. Under "baseline" conditions (photopic illumination/general anesthesia), 649 neuronal gap junctions immunogold-labeled for connexin36 were identified in rat IPL, of which 375 were photomapped to OFF vs. ON sublaminae. In contrast to previous reports, the volume-density of gap junctions was equally abundant in both sublaminae. Five distinctive morphologies of gap junctions were identified: conventional crystalline and non-crystalline "plaques" (71% and 3%), plus unusual "string" (14%), "ribbon" (7%) and "reticular" (2%) forms. Plaque and reticular gap junctions were distributed throughout the IPL. However, string and ribbon gap junctions were restricted to the OFF sublamina, where they represented 48% of gap junctions in that layer. In string and ribbon junctions, curvilinear strands of connexons were dispersed over 5 to 20 times the area of conventional plaques having equal numbers of connexons. To define morphologies of gap junctions under different light-adaptation conditions, we examined an additional 1150 gap junctions from rats and mice prepared after 30 min of photopic, mesopic and scotopic illumination, with and without general anesthesia. Under these conditions, string and ribbon gap junctions remained abundant in the OFF sublamina and absent in the ON sublamina. Abundant gap junctions in the OFF sublamina of these two rodents with rod-dominant retinas revealed previously-undescribed but extensive pathways for inter-neuronal communication; and the wide dispersion of connexons in string and ribbon gap junctions suggests unique structural features of gap junctional coupling in the OFF vs. ON sublamina.

Ultrastructural demonstration of Cx43 gap junctions in induced pluripotent stem cells from human cord blood.

PubMed

Beckmann, Anja; Schubert, Madline; Hainz, Nadine; Haase, Alexandra; Martin, Ulrich; Tschernig, Thomas; Meier, Carola

2016-11-01

Gap junction proteins are essential for direct intercellular communication but also influence cellular differentiation and migration. The expression of various connexin gap junction proteins has been demonstrated in embryonic stem cells, with Cx43 being the most intensely studied. As Cx43 is the most prominent gap junction protein in the heart, cardiomyocyte-differentiated stem cells have been studied intensely. To date, however, little is known about the expression and the subcellular distribution of Cx43 in undifferentiated stem cells or about the structural arrangement of channels. We, therefore, here investigate expression of Cx43 in undifferentiated human cord-blood-derived induced pluripotent stem cells (hCBiPS2). For this purpose, we carried out quantitative real-time PCR and immunohistochemistry. For analysis of Cx43 ultrastructure and protein assembly, we performed freeze-fracture replica immunogold labeling (FRIL). Cx43 expression was detected at mRNA and protein level in hCBIPS2 cells. For the first time, ultrastructural data are presented on gap junction morphology in induced pluripotent stem (iPS) cells from cord blood: Our FRIL and electron microscopical analysis revealed the occurrence of gap junction plaques in undifferentiated iPS cells. In addition, these gap junctions were shown to contain the gap junction protein Cx43.

Disruption of gap junctions attenuates aminoglycoside-elicited renal tubular cell injury

PubMed Central

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

2010-01-01

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

Characterization of the column and autocellular junctions that define the vasculature of gill lamellae.

PubMed

Kato, Akira; Nakamura, Korefumi; Kudo, Hisayuki; Tran, Yen Ha; Yamamoto, Yoko; Doi, Hiroyuki; Hirose, Shigehisa

2007-09-01

Novel adhesion junctions have been characterized that are formed at the interface between pillar cells and collagen columns, both of which are essential constituents of the gill lamellae in fish. We termed these junctions the "column junction" and "autocellular junction" and determined their molecular compositions by immunofluorescence microscopy using pufferfish. We visualized collagen columns by concanavalin A staining and found that the components of integrin-mediated cell-matrix adhesion, such as talin, vinculin, paxillin, and fibronectin, were concentrated on plasma membranes surrounding collagen columns (column membranes). This connection is analogous to the focal adhesion of cultured mammalian cells, dense plaque of smooth muscle cells, and myotendinous junction of skeletal muscle cells. We named this connection the "column junction." In the cytoplasm near the column, actin fibers, actinin, and a phosphorylated myosin light chain of 20 kDa are densely located, suggesting the contractile nature of pillar cells. The membrane infoldings surrounding the collagen columns were found to be connected by the autocellular junction, whose components are highly tyrosine-phosphorylated and contain the tight junction protein ZO-1. This study represents the first molecular characterization and fluorescence visualization of the column and autocellular junctions involved in both maintaining structural integrity and the hemodynamics of the branchial lamellae.

Holding Tight: Cell Junctions and Cancer Spread.

PubMed

Knights, Alexander J; Funnell, Alister P W; Crossley, Merlin; Pearson, Richard C M

2012-01-01

Cell junctions are sites of intercellular adhesion that maintain the integrity of epithelial tissue and regulate signalling between cells. These adhesive junctions are comprised of protein complexes that serve to establish an intercellular cytoskeletal network for anchoring cells, in addition to regulating cell polarity, molecular transport and communication. The expression of cell adhesion molecules is tightly controlled and their downregulation is essential for epithelial-mesenchymal transition (EMT), a process that facilitates the generation of morphologically and functionally diverse cell types during embryogenesis. The characteristics of EMT are a loss of cell adhesion and increased cellular mobility. Hence, in addition to its normal role in development, dysregulated EMT has been linked to cancer progression and metastasis, the process whereby primary tumors migrate to invasive secondary sites in the body. This paper will review the current understanding of cell junctions and their role in cancer, with reference to the abnormal regulation of junction protein genes. The potential use of cell junction molecules as diagnostic and prognostic markers will also be discussed, as well as possible therapies for adhesive dysregulation.

Joint diseases: from connexins to gap junctions.

PubMed

Donahue, Henry J; Qu, Roy W; Genetos, Damian C

2017-12-19

Connexons form the basis of hemichannels and gap junctions. They are composed of six tetraspan proteins called connexins. Connexons can function as individual hemichannels, releasing cytosolic factors (such as ATP) into the pericellular environment. Alternatively, two hemichannel connexons from neighbouring cells can come together to form gap junctions, membrane-spanning channels that facilitate cell-cell communication by enabling signalling molecules of approximately 1 kDa to pass from one cell to an adjacent cell. Connexins are expressed in joint tissues including bone, cartilage, skeletal muscle and the synovium. Indicative of their importance as gap junction components, connexins are also known as gap junction proteins, but individual connexin proteins are gaining recognition for their channel-independent roles, which include scaffolding and signalling functions. Considerable evidence indicates that connexons contribute to the function of bone and muscle, but less is known about the function of connexons in other joint tissues. However, the implication that connexins and gap junctional channels might be involved in joint disease, including age-related bone loss, osteoarthritis and rheumatoid arthritis, emphasizes the need for further research into these areas and highlights the therapeutic potential of connexins.

Response of Fibroblasts MRC-5 to Flufenamic Acid-Grafted MCM-41 Nanoparticles.

PubMed

Lara, Giovanna Gomes; Cipreste, Marcelo Fernandes; Andrade, Gracielle Ferreira; Silva, Wellington Marcos da; Sousa, Edésia Martins Barros de

2018-01-09

Recently, flufenamic acid (FFA) was discovered among fenamates as a free radical scavenger and gap junction blocker; however, its effects have only been studied in cancer cells. Normal cells in the surroundings of a tumor also respond to radiation, although they are not hit by it directly. This phenomenon is known as the bystander effect, where response molecules pass from tumor cells to normal ones, through communication channels called gap junctions. The use of the enhanced permeability and retention effect, through which drug-loaded nanoparticles smaller than 200 nm may accumulate around a tumor, can prevent the local side effect upon controlled release of the drug. The present work, aimed at functionalizing MCM-41 (Mobil Composition of Matter No. 41) silica nanoparticles with FFA and determining its biocompatibility with human fibroblasts MRC-5 (Medical Research Council cell strain 5). MCM-41, was synthesized and characterized structurally and chemically, with multiple techniques. The biocompatibility assay was performed by Live/Dead technique, with calcein and propidium-iodide. MRC-5 cells were treated with FFA-grafted MCM-41 for 48 h, and 98% of cells remained viable, without signs of necrosis or morphological changes. The results show the feasibility of MCM-41 functionalization with FFA, and its potential protection of normal cells, in comparison to the role of FFA in cancerous ones.

Negative differential resistance in low Al-composition p-GaN/Mg-doped Al0.15Ga0.85N/n+-GaN hetero-junction grown by metal-organic chemical vapor deposition on sapphire substrate

NASA Astrophysics Data System (ADS)

Zhang, Kexiong; Liang, Hongwei; Shen, Rensheng; Wang, Dongsheng; Tao, Pengcheng; Liu, Yang; Xia, Xiaochuan; Luo, Yingmin; Du, Guotong

2014-02-01

Negative differential resistance (NDR) behavior was observed in low Al-composition p-GaN/Mg-doped-Al0.15Ga0.85N/n+-GaN hetero-junction grown by metal-organic chemical vapor deposition on sapphire substrate. The energy band and free carrier concentration of hetero-junction were studied by the model of the self-consistent solution of Schrödinger-Poisson equations combined with polarization engineering theory. At the forward bias of 0.95 V, the NDR effect has a high peak-to-valley current ratio of ˜9 with a peak current of 22.4 mA (˜current density of 11.4 A/cm2). An interesting phenomenon of NDR disappearance after consecutive scans and recurrence after electrical treatment was observed, which was associated with Poole-Frenkel effect.

Spin-transfer torque in multiferroic tunnel junctions with composite dielectric/ferroelectric barriers

NASA Astrophysics Data System (ADS)

Velev, Julian P.; Merodio, Pablo; Pollack, Cesar; Kalitsov, Alan; Chshiev, Mairbek; Kioussis, Nicholas

2017-12-01

Using model calculations, we demonstrate a very high level of control of the spin-transfer torque (STT) by electric field in multiferroic tunnel junctions with composite dielectric/ferroelectric barriers. We find that, for particular device parameters, toggling the polarization direction can switch the voltage-induced part of STT between a finite value and a value close to zero, i.e. quench and release the torque. Additionally, we demonstrate that under certain conditions the zero-voltage STT, i.e. the interlayer exchange coupling, can switch sign with polarization reversal, which is equivalent to reversing the magnetic ground state of the tunnel junction. This bias- and polarization-tunability of the STT could be exploited to engineer novel functionalities such as softening/hardening of the bit or increasing the signal-to-noise ratio in magnetic sensors, which can have important implications for magnetic random access memories or for combined memory and logic devices.

Terbinafine inhibits gap junctional intercellular communication.

PubMed

Lee, Ju Yeun; Yoon, Sei Mee; Choi, Eun Ju; Lee, Jinu

2016-09-15

Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca(2+) concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibits GJIC with a so far unknown mechanism of action. Copyright © 2016 Elsevier Inc. All rights reserved.

The beneficial effects of cumulus cells and oocyte-cumulus cell gap junctions depends on oocyte maturation and fertilization methods in mice.

PubMed

Zhou, Cheng-Jie; Wu, Sha-Na; Shen, Jiang-Peng; Wang, Dong-Hui; Kong, Xiang-Wei; Lu, Angeleem; Li, Yan-Jiao; Zhou, Hong-Xia; Zhao, Yue-Fang; Liang, Cheng-Guang

2016-01-01

Cumulus cells are a group of closely associated granulosa cells that surround and nourish oocytes. Previous studies have shown that cumulus cells contribute to oocyte maturation and fertilization through gap junction communication. However, it is not known how this gap junction signaling affects in vivo versus in vitro maturation of oocytes, and their subsequent fertilization and embryonic development following insemination. Therefore, in our study, we performed mouse oocyte maturation and insemination using in vivo- or in vitro-matured oocyte-cumulus complexes (OCCs, which retain gap junctions between the cumulus cells and the oocytes), in vitro-matured, denuded oocytes co-cultured with cumulus cells (DCs, which lack gap junctions between the cumulus cells and the oocytes), and in vitro-matured, denuded oocytes without cumulus cells (DOs). Using these models, we were able to analyze the effects of gap junction signaling on oocyte maturation, fertilization, and early embryo development. We found that gap junctions were necessary for both in vivo and in vitro oocyte maturation. In addition, for oocytes matured in vivo, the presence of cumulus cells during insemination improved fertilization and blastocyst formation, and this improvement was strengthened by gap junctions. Moreover, for oocytes matured in vitro, the presence of cumulus cells during insemination improved fertilization, but not blastocyst formation, and this improvement was independent of gap junctions. Our results demonstrate, for the first time, that the beneficial effect of gap junction signaling from cumulus cells depends on oocyte maturation and fertilization methods.

76 FR 54753 - Whitestone Power and Communications; Notice of Intent To File License Application, Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-02

... of Project: Microturbine Hydrokinetic River-In-Stream Energy Conversion Power Project (also known as... Contact: Steven M. Selvaggio, Whitestone Power and Communications, P.O. Box 1630, Delta Junction, Alaska... Hydrokinetic River-In-Stream Energy Conversion Power Project) and number (P-13305-002), and bear the heading...

Simvastatin-induced up-regulation of gap junctions composed of connexin 43 sensitize Leydig tumor cells to etoposide: an involvement of PKC pathway.

PubMed

Wang, Lingzhi; Fu, Yanni; Peng, Jianxin; Wu, Dengpan; Yu, Meiling; Xu, Chengfang; Wang, Qin; Tao, Liang

2013-10-04

Some of lipophilic statins have been reported to enhance toxicities induced by antineoplastic agents but the underling mechanism is unclear. The authors investigated the involvement of Cx43-mediated gap junction intercellular communication (GJIC) in the effect of simvastatin on the cellular toxicity induced by etoposide in this study. The results showed that a major component of the cytotoxicity of therapeutic levels of etoposide is mediated by gap junctions composed of connexin 43(Cx43) and simvastatin at the dosage which does not induce cytotoxicity enhances etoposide toxicity by increasing gap junction coupling. The augmentative effect of simvastatin on GJIC was related to the inhibition of PKC-mediated Cx43 phosphorylation at ser368 and subsequent enhancement of Cx43 membrane location induced by the agent. The present study suggests the possibility that upregulation of gap junctions may be utilized to increase the efficacy of anticancer chemotherapies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Connexin Communication Compartments and Wound Repair in Epithelial Tissue.

PubMed

Chanson, Marc; Watanabe, Masakatsu; O'Shaughnessy, Erin M; Zoso, Alice; Martin, Patricia E

2018-05-03

Epithelial tissues line the lumen of tracts and ducts connecting to the external environment. They are critical in forming an interface between the internal and external environment and, following assault from environmental factors and pathogens, they must rapidly repair to maintain cellular homeostasis. These tissue networks, that range from a single cell layer, such as in airway epithelium, to highly stratified and differentiated epithelial surfaces, such as the epidermis, are held together by a junctional nexus of proteins including adherens, tight and gap junctions, often forming unique and localised communication compartments activated for localised tissue repair. This review focuses on the dynamic changes that occur in connexins, the constituent proteins of the intercellular gap junction channel, during wound-healing processes and in localised inflammation, with an emphasis on the lung and skin. Current developments in targeting connexins as corrective therapies to improve wound closure and resolve localised inflammation are also discussed. Finally, we consider the emergence of the zebrafish as a concerted whole-animal model to study, visualise and track the events of wound repair and regeneration in real-time living model systems.

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

PubMed Central

Trosko, James E.

2016-01-01

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

Tanshinone IIA Increases the Bystander Effect of Herpes Simplex Virus Thymidine Kinase/Ganciclovir Gene Therapy via Enhanced Gap Junctional Intercellular Communication

PubMed Central

Liu, Xijuan; Wu, Yingya; Du, Biaoyan; Li, Jiefen; Zhou, Jing; Li, Jingjing; Tan, Yuhui

2013-01-01

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. PMID:23861780

FAST TRACK COMMUNICATION: Eight-logic memory cell based on multiferroic junctions

NASA Astrophysics Data System (ADS)

Yang, Feng; Zhou, Y. C.; Tang, M. H.; Liu, Fen; Ma, Ying; Zheng, X. J.; Zhao, W. F.; Xu, H. Y.; Sun, Z. H.

2009-04-01

A model is proposed for a device combining a multiferroic tunnel junction with a magnetoelectric (ME) film in which the magnetic configuration is controlled by the electric field. Calculations embodying the Green's function approach show that the magnetic polarization can be switched on and off by an electric field in the ME film due to the effect of elastic coupling interaction. Using a model including the spin-filter effect and screening of polarization charges, we have produced eight logic states of tunnelling resistance in the tunnel junction and have obtained corresponding laws that control them. The results provide some insights into the realization of an eight-logic memory cell.

Gap Junctions

PubMed Central

Nielsen, Morten Schak; Axelsen, Lene Nygaard; Sorgen, Paul L.; Verma, Vandana; Delmar, Mario; Holstein-Rathlou, Niels-Henrik

2013-01-01

Gap junctions are essential to the function of multicellular animals, which require a high degree of coordination between cells. In vertebrates, gap junctions comprise connexins and currently 21 connexins are known in humans. The functions of gap junctions are highly diverse and include exchange of metabolites and electrical signals between cells, as well as functions, which are apparently unrelated to intercellular communication. Given the diversity of gap junction physiology, regulation of gap junction activity is complex. The structure of the various connexins is known to some extent; and structural rearrangements and intramolecular interactions are important for regulation of channel function. Intercellular coupling is further regulated by the number and activity of channels present in gap junctional plaques. The number of connexins in cell-cell channels is regulated by controlling transcription, translation, trafficking, and degradation; and all of these processes are under strict control. Once in the membrane, channel activity is determined by the conductive properties of the connexin involved, which can be regulated by voltage and chemical gating, as well as a large number of posttranslational modifications. The aim of the present article is to review our current knowledge on the structure, regulation, function, and pharmacology of gap junctions. This will be supported by examples of how different connexins and their regulation act in concert to achieve appropriate physiological control, and how disturbances of connexin function can lead to disease. © 2012 American Physiological Society. Compr Physiol 2:1981-2035, 2012. PMID:23723031

Role of intercellular communications in breast cancer multicellular tumor spheroids after chemotherapy.

PubMed

Oktem, G; Bilir, A; Ayla, S; Yavasoglu, A; Goksel, G; Saydam, G; Uysal, A

2006-01-01

Tumor heterogeneity is an important feature that is especially involved in tumor aggressiveness. Multicellular tumor spheroids (MTS) may provide some benefits in different steps for investigation of the aggregation, organization, differentiation, and network formation of tumor cells in 3D space. This model offers a unique opportunity for improvements in the capability of a current strategy to detect the effect of an appropriate anticancer agent. The aim of this study was to investigate the cellular interactions and morphological changes following chemotherapy in a 3D breast cancer spheroid model. Distribution of the gap junction protein "connexin-43" and the tight junction protein "occludin" was investigated by immunohistochemistry. Cellular interactions were examined by using transmission and scanning electron microscopies as well as light microscopy with Giemsa staining after treating cells with doxorubicin, docetaxel, and doxorubicin/docetaxel combination. Statistical analyses showed significant changes and various alterations that were observed in all groups; however, the most prominent effect was detected in the doxorubicin/docetaxel combination group. Distinct composition as a vessel-like structure and a pseudoglandular pattern of control spheroids were detected in drug-administered groups. Immunohistochemical results were consistent with the ultrastructural changes. In conclusion, doxorubicin/docetaxel combination may be more effective than the single drug usage as shown in a 3D model. The MTS model has been found to be an appropriate and reliable method for the detection of the changes in the expression of cellular junction proteins as well as other cellular proteins occurring after chemotherapy. The MTS model can be used to validate the effects of various combinations or new chemotherapeutic agents as well as documentation of possible mechanisms of new drugs.

Two Classes of Gap Junction Channels Mediate Soma-Germline Interactions Essential for Germline Proliferation and Gametogenesis in Caenorhabditis elegans

PubMed Central

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

2014-01-01

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. PMID:25195067

An update on minding the gap in cancer.

PubMed

Mesnil, Marc; Aasen, Trond; Boucher, Jonathan; Chépied, Amandine; Cronier, Laurent; Defamie, Norah; Kameritsch, Petra; Laird, Dale W; Lampe, Paul D; Lathia, Justin D; Leithe, Edward; Mehta, Parmender P; Monvoisin, Arnaud; Pogoda, Kristin; Sin, Wun-Chey; Tabernero, Arantxa; Yamasaki, Hiroshi; Yeh, Elizabeth S; Dagli, Maria Lucia Zaidan; Naus, Christian C

2018-01-01

This article is a report of the "International Colloquium on Gap junctions: 50Years of Impact on Cancer" that was held 8-9 September 2016, at the Amphitheater "Pôle Biologie Santé" of the University of Poitiers (Poitiers, France). The colloquium was organized by M Mesnil (Université de Poitiers, Poitiers, France) and C Naus (University of British Columbia, Vancouver, Canada) to celebrate the 50th anniversary of the seminal work published in 1966 by Loewenstein and Kanno [Intercellular communication and the control of tissue growth: lack of communication between cancer cells, Nature, 116 (1966) 1248-1249] which initiated studies on the involvement of gap junctions in carcinogenesis. During the colloquium, 15 participants presented reviews or research updates in the field which are summarized below. Copyright © 2017 Elsevier B.V. All rights reserved.

ABUNDANCE AND ULTRASTRUCTURAL DIVERSITY OF NEURONAL GAP JUNCTIONS IN THE OFF AND ON SUBLAMINAE OF THE INNER PLEXIFORM LAYER OF RAT AND MOUSE RETINA

PubMed Central

KAMASAWA, N.; FURMAN, C. S.; DAVIDSON, K. G. V.; SAMPSON, J. A.; MAGNIE, A. R.; GEBHARDT, B. R.; KAMASAWA, M.; YASUMURA, T.; ZUMBRUNNEN, J. R.; PICKARD, G. E.; NAGY, J. I.; RASH, J. E.

2007-01-01

Neuronal gap junctions are abundant in both outer and inner plexiform layers of the mammalian retina. In the inner plexiform layer (IPL), ultrastructurally-identified gap junctions were reported primarily in the functionally-defined and anatomically-distinct ON sublamina, with few reported in the OFF sublamina. We used freeze-fracture replica immunogold labeling and confocal microscopy to quantitatively analyze the morphologies and distributions of neuronal gap junctions in the IPL of adult rat and mouse retina. Under “baseline” conditions (photopic illumination/general anesthesia), 649 neuronal gap junctions immunogold-labeled for connexin36 were identified in rat IPL, of which 375 were photomapped to OFF vs. ON sublaminae. In contrast to previous reports, the volume-density of gap junctions was equally abundant in both sublaminae. Five distinctive morphologies of gap junctions were identified: conventional crystalline and non-crystalline “plaques” (71% and 3%), plus unusual “string” (14%), “ribbon” (7%) and “reticular” (2%) forms. Plaque and reticular gap junctions were distributed throughout the IPL. However, string and ribbon gap junctions were restricted to the OFF sublamina, where they represented 48% of gap junctions in that layer. In string and ribbon junctions, curvilinear strands of connexons were dispersed over 5 to 20 times the area of conventional plaques having equal numbers of connexons. To define morphologies of gap junctions under different light-adaptation conditions, we examined an additional 1150 gap junctions from rats and mice prepared after 30 min of photopic, mesopic and scotopic illumination, with and without general anesthesia. Under these conditions, string and ribbon gap junctions remained abundant in the OFF sublamina and absent in the ON sublamina. Abundant gap junctions in the OFF sublamina of these two rodents with rod-dominant retinas revealed previously-undescribed but extensive pathways for inter-neuronal communication; and the wide dispersion of connexons in string and ribbon gap junctions suggests unique structural features of gap junctional coupling in the OFF vs. ON sublamina. PMID:17010526

Compositional grading of InxGa1-xAs/GaAs tunnel junctions enhanced by ErAs nanoparticles

NASA Astrophysics Data System (ADS)

Salas, R.; Krivoy, E. M.; Crook, A. M.; Nair, H. P.; Bank, S. R.

2011-10-01

We investigate the electrical conductivity of GaAs-based tunnel junctions enhanced with semimetallic ErAs nanoparticles. In particular, we examine the effects of digitally-graded InGaAs alloys on the n-type side of the tunnel junction, along with different p-type doping levels. Device characteristics of the graded structures indicate that the n-type Schottky barrier may not be the limiting factor in the tunneling current as initially hypothesized. Moreover, significantly improved forward and reverse bias tunneling currents were observed with increased p-type doping, suggesting p-side limitation.

Gap junctions and connexin hemichannels in the regulation of haemostasis and thrombosis.

PubMed

Vaiyapuri, Sakthivel; Flora, Gagan D; Gibbins, Jonathan M

2015-06-01

Platelets are involved in the maintenance of haemostasis but their inappropriate activation leads to thrombosis, a principal trigger for heart attack and ischaemic stroke. Although platelets circulate in isolation, upon activation they accumulate or aggregate together to form a thrombus, where they function in a co-ordinated manner to prevent loss of blood and control wound repair. Previous report (1) indicates that the stability and functions of a thrombus are maintained through sustained, contact-dependent signalling between platelets. Given the role of gap junctions in the co-ordination of tissue responses, it was hypothesized that gap junctions may be present within a thrombus and mediate intercellular communication between platelets. Therefore studies were performed to explore the presence and functions of connexins in platelets. In this brief review, the roles of hemichannels and gap junctions in the control of thrombosis and haemostasis and the future directions for this research will be discussed.

Semiconductor Lasers Containing Quantum Wells in Junctions

NASA Technical Reports Server (NTRS)

Yang, Rui Q.; Qiu, Yueming

2004-01-01

In a recent improvement upon In(x)Ga(1-x)As/InP semiconductor lasers of the bipolar cascade type, quantum wells are added to Esaki tunnel junctions, which are standard parts of such lasers. The energy depths and the geometric locations and thicknesses of the wells are tailored to exploit quantum tunneling such that, as described below, electrical resistances of junctions and concentrations of dopants can be reduced while laser performances can be improved. In(x)Ga(1-x)As/InP bipolar cascade lasers have been investigated as sources of near-infrared radiation (specifically, at wavelengths of about 980 and 1,550 nm) for photonic communication systems. The Esaki tunnel junctions in these lasers have been used to connect adjacent cascade stages and to enable transport of charge carriers between them. Typically, large concentrations of both n (electron-donor) and p (electron-acceptor) dopants have been necessary to impart low electrical resistances to Esaki tunnel junctions. Unfortunately, high doping contributes free-carrier absorption, thereby contributing to optical loss and thereby, further, degrading laser performance. In accordance with the present innovation, quantum wells are incorporated into the Esaki tunnel junctions so that the effective heights of barriers to quantum tunneling are reduced (see figure).

A Co-operative Regulation of Neuronal Excitability by UNC-7 Innexin and NCA/NALCN Leak Channel

PubMed Central

2011-01-01

Gap junctions mediate the electrical coupling and intercellular communication between neighboring cells. Some gap junction proteins, namely connexins and pannexins in vertebrates, and innexins in invertebrates, may also function as hemichannels. A conserved NCA/Dmα1U/NALCN family cation leak channel regulates the excitability and activity of vertebrate and invertebrate neurons. In the present study, we describe a genetic and functional interaction between the innexin UNC-7 and the cation leak channel NCA in Caenorhabditis elegans neurons. While the loss of the neuronal NCA channel function leads to a reduced evoked postsynaptic current at neuromuscular junctions, a simultaneous loss of the UNC-7 function restores the evoked response. The expression of UNC-7 in neurons reverts the effect of the unc-7 mutation; moreover, the expression of UNC-7 mutant proteins that are predicted to be unable to form gap junctions also reverts this effect, suggesting that UNC-7 innexin regulates neuronal activity, in part, through gap junction-independent functions. We propose that, in addition to gap junction-mediated functions, UNC-7 innexin may also form hemichannels to regulate C. elegans' neuronal activity cooperatively with the NCA family leak channels. PMID:21489288

Inhibition of gap junction intercellular communication is involved in silica nanoparticles-induced H9c2 cardiomyocytes apoptosis via the mitochondrial pathway.

PubMed

Du, Zhong-Jun; Cui, Guan-Qun; Zhang, Juan; Liu, Xiao-Mei; Zhang, Zhi-Hu; Jia, Qiang; Ng, Jack C; Peng, Cheng; Bo, Cun-Xiang; Shao, Hua

2017-01-01

Gap junction intercellular communication (GJIC) between cardiomyocytes is essential for synchronous heart contraction and relies on connexin-containing channels. Connexin 43 (Cx43) is a major component involved in GJIC in heart tissue, and its abnormal expression is closely associated with various cardiac diseases. Silica nanoparticles (SNPs) are known to induce cardiovascular toxicity. However, the mechanisms through which GJIC plays a role in cardiomyocytes apoptosis induced by SNPs remain unknown. The aim of the present study is to determine whether SNPs-decreased GJIC promotes apoptosis in rat cardiomyocytes cell line (H9c2 cells) via the mitochondrial pathway using CCK-8 Kit, scrape-loading dye transfer technique, Annexin V/PI double-staining assays, and Western blot analysis. The results showed that SNPs elicited cytotoxicity in H9c2 cells in a time- and concentration-dependent manner. SNPs also reduced GJIC in H9c2 cells in a concentration-dependent manner through downregulation of Cx43 and upregulation of P-Cx43. Inhibition of gap junctions by gap junction blocker carbenoxolone disodium resulted in decreased survival and increased apoptosis, whereas enhancement of the gap junctions by retinoic acid led to enhanced survival but decreased apoptosis. Furthermore, SNPs-induced apoptosis through the disrupted functional gap junction was correlated with abnormal expressions of the proteins involved in the mitochondrial pathway-related apoptosis such as Bcl-2/Bax, cytochrome C, Caspase-9, and Caspase-3. Taken together, our results provide the first evidence that SNPs-decreased GJIC promotes apoptosis in cardiomyocytes via the mitochondrial pathway. In addition, downregulation of GJIC by SNPs in cardiomyocytes is mediated through downregulation of Cx43 and upregulation of P-Cx43. These results suggest that in rat cardiomyocytes cell line, GJIC plays a protective role in SNPs-induced apoptosis and that GJIC may be one of the targets for SNPs-induced biological effects.

Communication: Finding destructive interference features in molecular transport junctions.

PubMed

Reuter, Matthew G; Hansen, Thorsten

2014-11-14

Associating molecular structure with quantum interference features in electrode-molecule-electrode transport junctions has been difficult because existing guidelines for understanding interferences only apply to conjugated hydrocarbons. Herein we use linear algebra and the Landauer-Büttiker theory for electron transport to derive a general rule for predicting the existence and locations of interference features. Our analysis illustrates that interferences can be directly determined from the molecular Hamiltonian and the molecule-electrode couplings, and we demonstrate its utility with several examples.

Improving cardiac gap junction communication as a new antiarrhythmic mechanism: the action of antiarrhythmic peptides.

PubMed

Dhein, Stefan; Hagen, Anja; Jozwiak, Joanna; Dietze, Anna; Garbade, Jens; Barten, Markus; Kostelka, Martin; Mohr, Friedrich-Wilhelm

2010-03-01

Co-ordinated electrical activation of the heart is maintained by intercellular coupling of cardiomyocytes via gap junctional channels located in the intercalated disks. These channels consist of two hexameric hemichannels, docked to each other, provided by either of the adjacent cells. Thus, a complete gap junction channel is made from 12 protein subunits, the connexins. While 21 isoforms of connexins are presently known, cardiomyocytes typically are coupled by Cx43 (most abundant), Cx40 or Cx45. Some years ago, antiarrhythmic peptides were discovered and synthesised, which were shown to increase macroscopic gap junction conductance (electrical coupling) and enhance dye transfer (metabolic coupling). The lead substance of these peptides is AAP10 (H-Gly-Ala-Gly-Hyp-Pro-Tyr-CONH(2)), a peptide with a horseshoe-like spatial structure as became evident from two-dimensional nuclear magnetic resonance studies. A stable D: -amino-acid derivative of AAP10, rotigaptide, as well as a non-peptide analogue, gap-134, has been developed in recent years. Antiarrhythmic peptides act on Cx43 and Cx45 gap junctions but not on Cx40 channels. AAP10 has been shown to enhance intercellular communication in rat, rabbit and human cardiomyocytes. Antiarrhythmic peptides are effective against ventricular tachyarrhythmias, such as late ischaemic (type IB) ventricular fibrillation, CaCl(2) or aconitine-induced arrhythmia. Interestingly, the effect of antiarrhythmic peptides is higher in partially uncoupled cells and was shown to be related to maintained Cx43 phosphorylation, while arrhythmogenic conditions like ischaemia result in Cx43 dephosphorylation and intercellular decoupling. It is still a matter of debate whether these drugs also act against atrial fibrillation. The present review outlines the development of this group of peptides and derivatives, their mode of action and molecular mechanisms, and discusses their possible therapeutic potential.

Gap junctions are essential for murine primordial follicle assembly immediately before birth.

PubMed

Teng, Zhen; Wang, Chao; Wang, Yijing; Huang, Kun; Xiang, Xi; Niu, Wanbao; Feng, Lizhao; Zhao, Lihua; Yan, Hao; Zhang, Hua

2016-02-01

The reserve of primordial follicles determines the reproductive ability of the female mammal over its reproductive life. The primordial follicle is composed of two types of cells: oocytes and surrounding pre-granulosa cells. However, the underlying mechanism regulating primordial follicle assembly is largely undefined. In this study, we found that gap junction communication (GJC) established between the ovarian cells in the perinatal mouse ovary may be involved in the process. First, gap junction structures between the oocyte and surrounding pre-granulosa cells appear at about 19.0 dpc (days post coitum). As many as 12 gap junction-related genes are upregulated at birth, implying that a complex communication may exist between ovarian cells, because specifically silencing the genes of individual gap junction proteins, such as Gja1, Gja4 or both, has no influence on primordial follicle assembly. On the other hand, non-specific blockers of GJC, such as carbenoxolone (CBX) and 18α-glycyrrhetinic acid (AGA), significantly inhibit mouse primordial follicle assembly. We proved that the temporal window for establishment of GJC in the fetal ovary is from 19.5 dpc to 1 dpp (days postpartum). In addition, the expression of ovarian somatic cell (OSC)-specific genes, such as Notch2, Foxl2 and Irx3, was negatively affected by GJC blockers, whereas oocyte-related genes, such as Ybx2, Nobox and Sohlh1, were hardly affected, implying that the establishment of GJC during this period may be more important to OSCs than to oocytes. In summary, our results indicated that GJC involves in the mouse primordial follicle assembly process at a specific temporal window that needs Notch signaling cross-talking. © 2016 Society for Reproduction and Fertility.

Drosophila Shaking-B protein forms gap junctions in paired Xenopus oocytes.

PubMed

Phelan, P; Stebbings, L A; Baines, R A; Bacon, J P; Davies, J A; Ford, C

1998-01-08

In most multicellular organisms direct cell-cell communication is mediated by the intercellular channels of gap junctions. These channels allow the exchange of ions and molecules that are believed to be essential for cell signalling during development and in some differentiated tissues. Proteins called connexins, which are products of a multigene family, are the structural components of vertebrate gap junctions. Surprisingly, molecular homologues of the connexins have not been described in any invertebrate. A separate gene family, which includes the Drosophila genes shaking-B and l(1)ogre, and the Caenorhabditis elegans genes unc-7 and eat-5, encodes transmembrane proteins with a predicted structure similar to that of the connexins. shaking-B and eat-5 are required for the formation of functional gap junctions. To test directly whether Shaking-B is a channel protein, we expressed it in paired Xenopus oocytes. Here we show that Shaking-B localizes to the membrane, and that its presence induces the formation of functional intercellular channels. To our knowledge, this is the first structural component of an invertebrate gap junction to be characterized.

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

NASA Technical Reports Server (NTRS)

Jorgensen, Niklas Rye; Teilmann, Stefan Cuoni; Henriksen, Zanne; Civitelli, Roberto; Sorensen, Ole Helmer; Steinberg, Thomas H.

2003-01-01

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 of extracellular calcium, plasma membrane depolarization by high extracellular potassium, and the L-type voltage-operated calcium channel inhibitor, nifedipine. In contrast, all these treatments enhanced the spread of P2 receptor-mediated ICW in UMR rat osteoblastic cells. Using UMR cells transfected to express Cx43 (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.

Role of Gap Junctions in Early Brain Injury Following Subarachnoid Hemorrhage

PubMed Central

Ayer, Robert; Chen, Wanqiu; Sugawara, Takashi; Suzuki, Hidenori; Zhang, John H.

2010-01-01

Gap junction inhibition has been demonstrated to reverse the vascular contraction that follows experimental subarachnoid hemorrhage. This study hypothesizes that the use of established gap junction inhibitors: octonal and carbenoxolone, to interrupt cell to cell communication will provide neuroprotection against early brain injury after SAH. The filament perforation model of SAH was performed in male Sprague–Dawley rats weighing between 300 and 380g. Octanol (260.46mg or 781.38 mg/kg), carbenoxolone (100 mg/kg), or vehicles were given via intraperitoneal injection 1 hour after SAH. Neurologic deficits and cerebral apoptosis were assessed 24 and 72 hours after SAH. In addition, Western blot analysis was performed to confirm the in vivo inhibition of CNS gap junctions. The administration of octanol and carbenoxolone both failed to attenuate the neurological deficits induced by SAH, and they did not reduce neuronal apoptosis. Additionally, carbenoloxone increased post SAH mortality and exacerbated SAH induced apoptosis. Despites previous studies that show gap junction inhibitors reverse vasospasm following experimental SAH, they failed to improve clinical outcomes or provide neuroprotection in this study. PMID:20018179

Inhibition of the gap junctional component of endothelium-dependent relaxations in rabbit iliac artery by 18-α glycyrrhetinic acid

PubMed Central

Taylor, Hannah J; Chaytor, Andrew T; Evans, W Howard; Griffith, Tudor M

1998-01-01

The gap junction inhibitor 18-α-glycyrrhetinic acid (α-GA, 100 μM) attenuated endothelium-dependent relaxations to acetylcholine and cyclopiazonic acid by ∼20% in rings of pre-constricted rabbit iliac artery. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 300 μM) inhibited relaxations to both agents by ∼65% and these were further attenuated by α-GA to <10% of control. In endothelium-denuded preparations, relaxations to sodium nitroprusside were not affected by α-GA. Heterocellular gap junctional communication may therefore account for nitric oxide-independent relaxations evoked both by receptor-dependent and -independent mechanisms in rabbit iliac artery. PMID:9776336

Death of Neurons following Injury Requires Conductive Neuronal Gap Junction Channels but Not a Specific Connexin

PubMed Central

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

2015-01-01

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. PMID:26017008

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

PubMed

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

2014-11-01

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.

Distal gap junctions and active dendrites can tune network dynamics.

PubMed

Saraga, Fernanda; Ng, Leo; Skinner, Frances K

2006-03-01

Gap junctions allow direct electrical communication between CNS neurons. From theoretical and modeling studies, it is well known that although gap junctions can act to synchronize network output, they can also give rise to many other dynamic patterns including antiphase and other phase-locked states. The particular network pattern that arises depends on cellular, intrinsic properties that affect firing frequencies as well as the strength and location of the gap junctions. Interneurons or GABAergic neurons in hippocampus are diverse in their cellular characteristics and have been shown to have active dendrites. Furthermore, parvalbumin-positive GABAergic neurons, also known as basket cells, can contact one another via gap junctions on their distal dendrites. Using two-cell network models, we explore how distal electrical connections affect network output. We build multi-compartment models of hippocampal basket cells using NEURON and endow them with varying amounts of active dendrites. Two-cell networks of these model cells as well as reduced versions are explored. The relationship between intrinsic frequency and the level of active dendrites allows us to define three regions based on what sort of network dynamics occur with distal gap junction coupling. Weak coupling theory is used to predict the delineation of these regions as well as examination of phase response curves and distal dendritic polarization levels. We find that a nonmonotonic dependence of network dynamic characteristics (phase lags) on gap junction conductance occurs. This suggests that distal electrical coupling and active dendrite levels can control how sensitive network dynamics are to gap junction modulation. With the extended geometry, gap junctions located at more distal locations must have larger conductances for pure synchrony to occur. Furthermore, based on simulations with heterogeneous networks, it may be that one requires active dendrites if phase-locking is to occur in networks formed with distal gap junctions.

Design of materials configurations for enhanced phononic and electronic properties

NASA Astrophysics Data System (ADS)

Daraio, Chiara

The discovery of novel nonlinear dynamic and electronic phenomena is presented for the specific cases of granular materials and carbon nanotubes. This research was conducted for designing and constructing optimized macro-, micro- and nano-scale structural configurations of materials, and for studying their phononic and electronic behavior. Variation of composite arrangements of granular elements with different elastic properties in a linear chain-of-sphere, Y-junction or 3-D configurations led to a variety of novel phononic phenomena and interesting physical properties, which can be potentially useful for security, communications, mechanical and biomedical engineering applications. Mechanical and electronic properties of carbon nanotubes with different atomic arrangements and microstructures were also investigated. Electronic properties of Y-junction configured carbon nanotubes exhibit an exciting transistor switch behavior which is not seen in linear configuration nanotubes. Strongly nonlinear materials were designed and fabricated using novel and innovative concepts. Due to their unique strongly nonlinear and anisotropic nature, novel wave phenomena have been discovered. Specifically, violations of Snell's law were detected and a new mechanism of wave interaction with interfaces between NTPCs (Nonlinear Tunable Phononic Crystals) was established. Polymer-based systems were tested for the first time, and the tunability of the solitary waves speed was demonstrated. New materials with transformed signal propagation speed in the manageable range of 10-100 m/s and signal amplitude typical for audible speech have been developed. The enhancing of the mitigation of solitary and shock waves in 1-D chains were demonstrated and a new protective medium was designed for practical applications. 1-D, 2-D and 3-D strongly nonlinear system have been investigated providing a broad impact on the whole area of strongly nonlinear wave dynamics and creating experimental basis for new theories and models. Potential applications include (1) designing of a sound scrambler/decoder for secure voice communications, (2) improving invisibility of submarine to acoustic detection signal, (3) noise and shock wave mitigation for protection of vibration sensitive devices such as head mounted vision devices, (4) drastic compression of acoustic signals into centimeter regime impulses for artificial ear implants, hearing aid and devices for ease of conversion to electronic signals and processing, and acoustic delay lines for communication applications.

Gap junctional intercellular communication dysfunction mediates the cognitive impairment induced by cerebral ischemia-reperfusion injury: PI3K/Akt pathway involved.

PubMed

Zhou, Shujun; Fang, Zheng; Wang, Gui; Wu, Song

2017-01-01

Cerebral ischemia/reperfusion (I/R) injury causes hippocampal apoptosis and cognitive impairment, and the dysfunction of gap junction intercellular communication (GJIC) may contribute to the cognitive impairment. We aim to examine the impact of cerebral I/R injury on cognitive impairment, the role of GJIC dysfunction in the rat hippocampus and the involvement of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway. Rats were subjected to a cerebral I/R procedure and underwent cognitive assessment with the novel object recognition and Morris Water Maze tasks. The distance of Lucifer Yellow dye transfer and the Cx43 protein were examined to measure GJIC. Neural apoptosis was assessed with the terminal deoxynucleotide-transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) method. After rats received inhibitors of the PI3K/Akt pathway, GJIC and cognitive ability were measured again. GJIC promotion by ZP123 significantly reversed cognitive impairment and hippocampal apoptosis induced by cerebral I/R, while the inhibition of GJIC by octanol significantly facilitated cognitive impairment and hippocampal apoptosis. The phosphorylation of Akt was enhanced by cerebral I/R and octanol but inhibited by ZP123. The inhibition of the PI3K/Akt pathway significantly suppressed GJIC and cognitive impairment. The PI3K/Akt pathway is involved in cognitive impairment caused by gap junctional communication dysfunction in the rat hippocampus after ischemia-reperfusion injury.

Response of Fibroblasts MRC-5 to Flufenamic Acid-Grafted MCM-41 Nanoparticles

PubMed Central

Lara, Giovanna Gomes; Andrade, Gracielle Ferreira; da Silva, Wellington Marcos

2018-01-01

Recently, flufenamic acid (FFA) was discovered among fenamates as a free radical scavenger and gap junction blocker; however, its effects have only been studied in cancer cells. Normal cells in the surroundings of a tumor also respond to radiation, although they are not hit by it directly. This phenomenon is known as the bystander effect, where response molecules pass from tumor cells to normal ones, through communication channels called gap junctions. The use of the enhanced permeability and retention effect, through which drug-loaded nanoparticles smaller than 200 nm may accumulate around a tumor, can prevent the local side effect upon controlled release of the drug. The present work, aimed at functionalizing MCM-41 (Mobil Composition of Matter No. 41) silica nanoparticles with FFA and determining its biocompatibility with human fibroblasts MRC-5 (Medical Research Council cell strain 5). MCM-41, was synthesized and characterized structurally and chemically, with multiple techniques. The biocompatibility assay was performed by Live/Dead technique, with calcein and propidium–iodide. MRC-5 cells were treated with FFA-grafted MCM-41 for 48 h, and 98% of cells remained viable, without signs of necrosis or morphological changes. The results show the feasibility of MCM-41 functionalization with FFA, and its potential protection of normal cells, in comparison to the role of FFA in cancerous ones. PMID:29315235

Depth profile composition studies of thin film CdS:Cu2S solar cells using XPS and AES

NASA Astrophysics Data System (ADS)

Bhide, V. G.; Salkalachen, S.; Rastogi, A. C.; Rao, C. N. R.; Hegde, M. S.

1981-09-01

Studies of the surface composition and depth profiles of thin film CdS:Cu2S solar cells based on the techniques of X-ray photoelectron spectroscopy (XPS) and Auger electron spectroscopy (AES) are reported. Specimens were fabricated by the thermal deposition of polycrystalline CdS films onto silver-backed electrodes predeposited on window glass substrates, followed by texturization in hot HCl and chemical plating in a hot CuCl(I) bath for a few seconds to achieve the topotaxial growth of CuS films. The XPS and AES studies indicate the junction to be fairly diffused in the as-prepared cell, with heat treatment in air at 210 C sharpening the junction, improving the stoichiometry of the Cu2S layer and thus improving cell performance. The top copper sulfide layer is found to contain impurities such as Cd, Cl, O and C, which may be removed by mild Ar(+) ion beam etching. The presence of copper deep in the junction is invariably detected, apparently in the grain boundary region in the form of CuS or Cu(2+) trapped in the lattice. It is also noted that the nominal valence state of copper changes abruptly from Cu(+) to Cu(2+) across the junction.

TC-PTP directly interacts with connexin43 to regulate gap junction intercellular communication

PubMed Central

Li, Hanjun; Spagnol, Gaelle; Naslavsky, Naava; Caplan, Steve; Sorgen, Paul L.

2014-01-01

ABSTRACT Protein kinases have long been reported to regulate connexins; however, little is known about the involvement of phosphatases in the modulation of intercellular communication through gap junctions and the subsequent downstream effects on cellular processes. Here, we identify an interaction between the T-cell protein tyrosine phosphatase (TC-PTP, officially known as PTPN2) and the carboxyl terminus of connexin43 (Cx43, officially known as GJA1). Two cell lines, normal rat kidney (NRK) cells endogenously expressing Cx43 and an NRK-derived cell line expressing v-Src with temperature-sensitive activity, were used to demonstrate that EGF and v-Src stimulation, respectively, induced TC-PTP to colocalize with Cx43 at the plasma membrane. Cell biology experiments using phospho-specific antibodies and biophysical assays demonstrated that the interaction is direct and that TC-PTP dephosphorylates Cx43 residues Y247 and Y265, but does not affect v-Src. Transfection of TC-PTP also indirectly led to the dephosphorylation of Cx43 S368, by inactivating PKCα and PKCδ, with no effect on the phosphorylation of S279 and S282 (MAPK-dependent phosphorylation sites). Dephosphorylation maintained Cx43 gap junctions at the plaque and partially reversed the channel closure caused by v-Src-mediated phosphorylation of Cx43. Understanding dephosphorylation, along with the well-documented roles of Cx43 phosphorylation, might eventually lead to methods to modulate the regulation of gap junction channels, with potential benefits for human health. PMID:24849651

Mixing at double-Tee junctions with unequal pipe sizes in ...

EPA Pesticide Factsheets

Pipe flow mixing with various solute concentrations and flow rates at pipe junctions is investigated. The degree of mixing affects the spread of contaminants in a water distribution system. Many studies have been conducted on the mixing at the cross junctions. Yet a few have focused on double-Tee junctions of unequal pipe sizes. To investigate the solute mixing at double-Tee junctions with unequal pipe sizes, a series of experiments were conducted in a turbulent regime (Re=12500–50000) with different Reynolds number ratios and connecting pipe lengths. It is shown that dimensionless outlet concentrations depended on mixing mechanism at the impinging interface of junctions. Junction with a larger pipe size ratio is associated with more complete mixing. The inlet Reynolds number ratio affects mixing more strongly than the outlet Reynolds number ratio. Furthermore, the dimensionless connecting pipe length in a double-Tee played an important and complicated role in the flow mixing. Based on these results, two-dimensional isopleth maps were developed for the calculation of normalized north outlet concentration. This journal article is to communicate the research results on pipe juncture mixing, a widespread and important phenomena in distribution system water quality analysis. The research outcome improves EPANET modeling capability for safe water supplies. In addition, the research is one of the outputs from the EPA-MOST bilateral cooperative research Project #1

The canonical WNT2 pathway and FSH interact to regulate gap junction assembly in mouse granulosa cells.

PubMed

Wang, Hong-Xing; Gillio-Meina, Carolina; Chen, Shuli; Gong, Xiang-Qun; Li, Tony Y; Bai, Donglin; Kidder, Gerald M

2013-08-01

WNTs are extracellular signaling molecules that exert their actions through receptors of the frizzled (FZD) family. Previous work indicated that WNT2 regulates cell proliferation in mouse granulosa cells acting through CTNNB1 (beta-catenin), a key component in canonical WNT signaling. In other cells, WNT signaling has been shown to regulate expression of connexin43 (CX43), a gap junction protein, as well as gap junction assembly. Since previous work demonstrated that CX43 is also essential in ovarian follicle development, the objective of this study was to determine if WNT2 regulates CX43 expression and/or gap-junctional intercellular communication (GJIC) in granulosa cells. WNT2 knockdown via siRNA markedly reduced CX43 expression and GJIC. CX43 expression, the extent of CX43-containing gap junction membrane, and GJIC were also reduced by CTNNB1 transient knockdown. CTNNB1 is mainly localized to the membranes between granulosa cells but disappeared from this location after WNT2 knockdown. Furthermore, CTNNB1 knockdown interfered with the ability of follicle-stimulating hormone (FSH) to promote the mobilization of CX43 into gap junctions. We propose that the WNT2/CTNNB1 pathway regulates CX43 expression and GJIC in granulosa cells by modulating CTNNB1 stability and localization in adherens junctions, and that this is essential for FSH stimulation of GJIC.

The E3 ubiquitin ligase NEDD4 induces endocytosis and lysosomal sorting of connexin 43 to promote loss of gap junctions.

PubMed

Totland, Max Z; Bergsland, Christian H; Fykerud, Tone A; Knudsen, Lars M; Rasmussen, Nikoline L; Eide, Peter W; Yohannes, Zeremariam; Sørensen, Vigdis; Brech, Andreas; Lothe, Ragnhild A; Leithe, Edward

2017-09-01

Intercellular communication via gap junctions has an important role in controlling cell growth and in maintaining tissue homeostasis. Connexin 43 (Cx43; also known as GJA1) is the most abundantly expressed gap junction channel protein in humans and acts as a tumor suppressor in multiple tissue types. Cx43 is often dysregulated at the post-translational level during cancer development, resulting in loss of gap junctions. However, the molecular basis underlying the aberrant regulation of Cx43 in cancer cells has remained elusive. Here, we demonstrate that the oncogenic E3 ubiquitin ligase NEDD4 regulates the Cx43 protein level in HeLa cells, both under basal conditions and in response to protein kinase C activation. Furthermore, overexpression of NEDD4, but not a catalytically inactive form of NEDD4, was found to result in nearly complete loss of gap junctions and increased lysosomal degradation of Cx43 in both HeLa and C33A cervical carcinoma cells. Collectively, the data provide new insights into the molecular basis underlying the regulation of gap junction size and represent the first evidence that an oncogenic E3 ubiquitin ligase promotes loss of gap junctions and Cx43 degradation in human carcinoma cells. © 2017. Published by The Company of Biologists Ltd.

Uterine Junctional Zone Thickness, Cervical Length and Bioelectrical Impedance Analysis of Body Composition in Women with Endometriosis

PubMed Central

Ayas, Selçuk; Bayraktar, Mesut; Gürbüz, Ayşe; Alkan, Akif; Eren, Sadiye

2012-01-01

Objective: We aimed to evaluate uterine junctional zone thickness, cervical length and bioelectrical impedance analysis of body composition in women with endometriosis. Material and Methods: This is a prospective study conducted in a tertiary teaching hospital. A total of 73 patients were included in the study. Endometriosis was surgically diagnosed in 36 patients (study group). The control group included 37 patients. Main outcome measure(s): Bioelectrical impedance analysis was used to measure body composition. Uterine junctional zone thickness and cervical length were measured by transvaginal ultrasonography. Results: Patients’ characteristics (age, gravida, parity, live baby, age of menarche, lengths of menstrual cycle, percentage of patients with dysmenorrhea, positive family history), body mass index (BMI) (kg/m2), amount of body fat (kg), percentage of body fat were not statistically different between the two groups (p>0.05). The length of menstruation and cervical length were longer in women with endometriosis. Similarly, the inner myometrium was thicker in women with endometriosis than the control group. Conclusion: The relation between endometriosis and demographic features such as age, gravida, parity, gravida, BMI, lengths of the menstrual cycle, age of menarche are controversial. Longer cervical length and thicker inner myometrial layer may be important in the etiopathogenesis of endometriosis. PMID:25207044

Hemichannel composition and electrical synaptic transmission: molecular diversity and its implications for electrical rectification

PubMed Central

Palacios-Prado, Nicolás; Huetteroth, Wolf; Pereda, Alberto E.

2014-01-01

Unapposed hemichannels (HCs) formed by hexamers of gap junction proteins are now known to be involved in various cellular processes under both physiological and pathological conditions. On the other hand, less is known regarding how differences in the molecular composition of HCs impact electrical synaptic transmission between neurons when they form intercellular heterotypic gap junctions (GJs). Here we review data indicating that molecular differences between apposed HCs at electrical synapses are generally associated with rectification of electrical transmission. Furthermore, this association has been observed at both innexin and connexin (Cx) based electrical synapses. We discuss the possible molecular mechanisms underlying electrical rectification, as well as the potential contribution of intracellular soluble factors to this phenomenon. We conclude that asymmetries in molecular composition and sensitivity to cellular factors of each contributing hemichannel can profoundly influence the transmission of electrical signals, endowing electrical synapses with more complex functional properties. PMID:25360082

Ohmic contact junction of carbon nanotubes fabricated by in situ electron beam deposition

NASA Astrophysics Data System (ADS)

Wang, Y. G.; Wang, T. H.; Lin, X. W.; Dravid, V. P.

2006-12-01

We present experimental evidence of in situ fabrication of multi-walled carbon nanotube junctions via electron beam induced deposition. The tip-to-tip interconnection of the nanotubes involves the alignment of two nanotubes via a piezodriven nanomanipulator and nano-welding by electron beam deposition. Hydrocarbon contamination from the pump oil vapour of the vacuum system of the TEM chamber was used as the solder; this is superior to the already available metallic solders because its composition is identical to the carbon nanotube. The hydrocarbon deposition, with perfect wettability, on the nanotubes establishes strong mechanical binding between the two nanotubes to form an integrated structure. Consequently, the nanotubes cross-linked by the hydrocarbon solder produce good electrical and mechanical connections. The joint dimension was determined by the size of the electron beam, which results in a sound junction with well-defined geometry and the smallest junction size obtained so far. In situ electric measurement showed a linear current-voltage property for the multi-walled nanotube junction.

Intercellular communication in the immune system: differential expression of connexin40 and 43, and perturbation of gap junction channel functions in peripheral blood and tonsil human lymphocyte subpopulations

PubMed Central

Oviedo‐orta, E; Hoy, T; Evans, W H

2000-01-01

The distribution and function of connexins (integral membrane proteins assembled into gap junction intercellular communication channels) were studied in human lymphocyte subpopulations. The expression of mRNA encoding connexins in peripheral blood and tonsil‐derived T, B and natural killer (NK) lymphocytes was examined. Connexin43 (Cx43) mRNA was expressed in peripheral blood and tonsil lymphocytes, but Cx40 mRNA expression was confined to tonsil‐derived T and B lymphocytes; Cx26, Cx32, Cx37 and Cx45 were not detected by reverse transcription–polymerase chain reaction (RT–PCR). Western blot analysis also demonstrated the presence of Cx40 and Cx43 proteins in T and B lymphocytes in a manner coincidental to the mRNA detection. Stimulation in vitro of T and B lymphocytes with phytohaemagglutinin (PHA) and lipopolysaccharide (LPS), respectively, increased Cx40 and Cx43 protein expression. Flow cytometric analysis, using antibodies to extracellular loop amino acid sequences of connexins, confirmed the surface expression of connexins in all lymphocyte subpopulations. Assembly of connexins into gap junctions providing direct intercellular channels linking attached lymphocytes was demonstrated by using a dye transfer technique. The exchange of dye between lymphocytes was inhibited by a connexin extracellular loop mimetic peptide and α‐glycyrrhetinic acid, two reagents that restrict intercellular communication across gap junctions. Dye coupling occurred between homologous and heterologous co‐cultures of T and B lymphocytes, and was not influenced by their stimulation with PHA and LPS. The connexin mimetic peptide caused a significant decrease in the in vitro synthesis of immunoglobulin M (IgM) by T‐ and B‐lymphocyte co‐cultured populations in the presence or absence of stimulation by PHA. The results identify connexins as important cell surface components that modulate immune processes. PMID:10792506

Interacting Network of the Gap Junction (GJ) Protein Connexin43 (Cx43) is Modulated by Ischemia and Reperfusion in the Heart.

PubMed

Martins-Marques, Tania; Anjo, Sandra Isabel; Pereira, Paulo; Manadas, Bruno; Girão, Henrique

2015-11-01

The coordinated and synchronized cardiac muscle contraction relies on an efficient gap junction-mediated intercellular communication (GJIC) between cardiomyocytes, which involves the rapid anisotropic impulse propagation through connexin (Cx)-containing channels, namely of Cx43, the most abundant Cx in the heart. Expectedly, disturbing mechanisms that affect channel activity, localization and turnover of Cx43 have been implicated in several cardiomyopathies, such as myocardial ischemia. Besides gap junction-mediated intercellular communication, Cx43 has been associated with channel-independent functions, including modulation of cell adhesion, differentiation, proliferation and gene transcription. It has been suggested that the role played by Cx43 is dictated by the nature of the proteins that interact with Cx43. Therefore, the characterization of the Cx43-interacting network and its dynamics is vital to understand not only the molecular mechanisms underlying pathological malfunction of gap junction-mediated intercellular communication, but also to unveil novel and unanticipated biological functions of Cx43. In the present report, we applied a quantitative SWATH-MS approach to characterize the Cx43 interactome in rat hearts subjected to ischemia and ischemia-reperfusion. Our results demonstrate that, in the heart, Cx43 interacts with proteins related with various biological processes such as metabolism, signaling and trafficking. The interaction of Cx43 with proteins involved in gene transcription strengthens the emerging concept that Cx43 has a role in gene expression regulation. Importantly, our data shows that the interactome of Cx43 (Connexome) is differentially modulated in diseased hearts. Overall, the characterization of Cx43-interacting network may contribute to the establishment of new therapeutic targets to modulate cardiac function in physiological and pathological conditions. Data are available via ProteomeXchange with identifier PXD002331. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Effect of intrinsic curvature and edge tension on the stability of binary mixed-membrane three-junctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gardner, Jasmine M.; Abrams, Cameron F.; Deserno, Markus

We use a combination of coarse-grained molecular dynamics simulations and theoretical modeling to examine three-junctions in mixed lipid bilayer membranes. These junctions are localized defect lines in which three bilayers merge in such a way that each bilayer shares one monolayer with one of the other two bilayers. The resulting local morphology is non-lamellar, resembling the threefold symmetric defect lines in inverse hexagonal phases, but it regularly occurs during membrane fission and fusion events. We realize a system of junctions by setting up a honeycomb lattice, which in its primitive cell contains two hexagons and four three-line junctions, permitting usmore » to study their stability as well as their line tension. We specifically consider the effects of lipid composition and intrinsic curvature in binary mixtures, which contain a fraction of negatively curved lipids in a curvature-neutral background phase. Three-junction stability results from a competition between the junction and an open edge, which arises if one of the three bilayers detaches from the other two. We show that the stable phase is the one with the lower defect line tension. The strong and opposite monolayer curvatures present in junctions and edges enhance the mole fraction of negatively curved lipids in junctions and deplete it in edges. This lipid sorting affects the two line tensions and in turn the relative stability of the two phases. It also leads to a subtle entropic barrier for the transition between junction and edge that is absent in uniform membranes.« less

Plant-derived triterpene celastrol ameliorates oxygen glucose deprivation-induced disruption of endothelial barrier assembly via inducing tight junction proteins.

PubMed

Luo, Dan; Zhao, Jia; Rong, Jianhui

2016-12-01

The integrity and functions of blood-brain barrier (BBB) are regulated by the expression and organization of tight junction proteins. The present study was designed to explore whether plant-derived triterpenoid celastrol could regulate tight junction integrity in murine brain endothelial bEnd3 cells. We disrupted the tight junctions between endothelial bEnd3 cells by oxygen glucose deprivation (OGD). We investigated the effects of celastrol on the permeability of endothelial monolayers by measuring transepithelial electrical resistance (TEER). To clarify the tight junction composition, we analyzed the expression of tight junction proteins by RT-PCR and Western blotting techniques. We found that celastrol recovered OGD-induced TEER loss in a concentration-dependent manner. Celastrol induced occludin, claudin-5 and zonula occludens-1 (ZO-1) in endothelial cells. As a result, celastrol effectively maintained tight junction integrity and inhibited macrophage migration through endothelial monolayers against OGD challenge. Further mechanistic studies revealed that celastrol induced the expression of occludin and ZO-1) via activating MAPKs and PI3K/Akt/mTOR pathway. We also observed that celastrol regulated claudin-5 expression through different mechanisms. The present study demonstrated that celastrol effectively protected tight junction integrity against OGD-induced damage. Thus, celastrol could be a drug candidate for the treatment of BBB dysfunction in various diseases. Copyright © 2016 Elsevier GmbH. All rights reserved.

A Computer-Automated Temperature Control System for Semiconductor Measurements.

DTIC Science & Technology

1979-11-01

Engineer: Jerry Silverman (RADC/ESE) temperature controller silicon devices data acquisition system mini-computer control application semiconductor dovice...characterization semiconductor materijals characterization silicon .’ AtlI EAC T 1 -fI I,,’-, *- s t ---v,.1.,,~ - d,f101h ir- IA i lr A computer...depends on the composition of the metals and the temperature of the junction. As the temperature of the junction increases so does the voltage at the

Nanostructured Solar Cells.

PubMed

Chen, Guanying; Ning, Zhijun; Ågren, Hans

2016-08-09

We are glad to announce the Special Issue "Nanostructured Solar Cells", published in Nanomaterials. This issue consists of eight articles, two communications, and one review paper, covering major important aspects of nanostructured solar cells of varying types. From fundamental physicochemical investigations to technological advances, and from single junction solar cells (silicon solar cell, dye sensitized solar cell, quantum dots sensitized solar cell, and small molecule organic solar cell) to tandem multi-junction solar cells, all aspects are included and discussed in this issue to advance the use of nanotechnology to improve the performance of solar cells with reduced fabrication costs.

FAST TRACK COMMUNICATION: Interlayer exchange coupling across a ferroelectric barrier

NASA Astrophysics Data System (ADS)

Zhuravlev, M. Ye; Vedyayev, A. V.; Tsymbal, E. Y.

2010-09-01

A new magnetoelectric effect is predicted originating from the interlayer exchange coupling between two ferromagnetic layers separated by an ultrathin ferroelectric barrier. It is demonstrated that ferroelectric polarization switching driven by an external electric field leads to a sizable change in the interlayer exchange coupling. The effect occurs in asymmetric ferromagnet/ferroelectric/ferromagnet junctions due to a change in the electrostatic potential profile across the junction affecting the interlayer coupling. The predicted phenomenon indicates the possibility of switching the magnetic configuration by reversing the polarization of the ferroelectric barrier layer.

Device Modeling and Characterization for CIGS Solar Cells

NASA Astrophysics Data System (ADS)

Song, Sang Ho

We studied the way to achieve high efficiency and low cost of CuIn1-xGaxSe2 (CIGS) solar cells. The Fowler-Nordheim (F-N) tunneling currents at low bias decreased the shunt resistances and degraded the fill factor and efficiency. The activation energies of majority traps were directly related with F-N tunneling currents by the energy barriers. Air anneals decreased the efficiency from 7.74% to 5.18% after a 150 °C, 1000 hour anneal. The decrease of shunt resistance due to F-N tunneling and the increase of series resistance degrade the efficiencies of solar cells. Air anneal reduces the free carrier densities by the newly generated Cu interstitial defects (Cui). Mobile Cui defects induce the metastability in CIGS solar cell. Since oxygen atoms are preferred to passivate the Se vacancies thus Cu interstitial defects explains well metastability of CIGS solar cells. Lattice mismatch and misfit stress between layers in CIGS solar cells can explain the particular effects of CIGS solar cells. The misfits of 35.08° rotated (220/204) CIGS to r-plane (102) MoSe2 layers are 1% ˜ -4% lower than other orientation and the lattice constants of two layers in short direction are matched at Ga composition x=0.35. This explains well the preferred orientation and the maximum efficiency of Ga composition effects. Misfit between CIGS and CdS generated the dislocations in CdS layer as the interface traps. Thermionic emission currents due to interface traps limit the open circuit voltage at high Ga composition. The trap densities were calculated by critical thickness and dislocation spacing and the numerical device simulation results were well matched with the experimental results. A metal oxide broken-gap p-n heterojunction is suggested for tunnel junction for multi-junction polycrystalline solar cells and we examined the characteristics of broken-gap tunnel junction by numerical simulation. Ballistic transport mechanism explains well I-V characteristics of broken-gap junction. P-type Cu2O and n-type In2O3 broken-gap heterojunction is effective with the CIGS tandem solar cells. The junction has linear I-V characteristics with moderate carrier concentration (2x1017 cm-3) and the resistance is lower than GaAs tunnel junction. The efficiency of a CGS/CIS tandem solar cells was 24.1% with buffer layers. And no significant degradations are expected due to broken gap junction.

Ballistic One-Dimensional InAs Nanowire Cross-Junction Interconnects.

PubMed

Gooth, Johannes; Borg, Mattias; Schmid, Heinz; Schaller, Vanessa; Wirths, Stephan; Moselund, Kirsten; Luisier, Mathieu; Karg, Siegfried; Riel, Heike

2017-04-12

Coherent interconnection of quantum bits remains an ongoing challenge in quantum information technology. Envisioned hardware to achieve this goal is based on semiconductor nanowire (NW) circuits, comprising individual NW devices that are linked through ballistic interconnects. However, maintaining the sensitive ballistic conduction and confinement conditions across NW intersections is a nontrivial problem. Here, we go beyond the characterization of a single NW device and demonstrate ballistic one-dimensional (1D) quantum transport in InAs NW cross-junctions, monolithically integrated on Si. Characteristic 1D conductance plateaus are resolved in field-effect measurements across up to four NW-junctions in series. The 1D ballistic transport and sub-band splitting is preserved for both crossing-directions. We show that the 1D modes of a single injection terminal can be distributed into multiple NW branches. We believe that NW cross-junctions are well-suited as cross-directional communication links for the reliable transfer of quantum information as required for quantum computational systems.

Genetic variants related to gap junctions and hormone secretion influence conception rates in cows

PubMed Central

Sugimoto, Mayumi; Sasaki, Shinji; Gotoh, Yusaku; Nakamura, Yuuki; Aoyagi, Yoshito; Kawahara, Takayoshi; Sugimoto, Yoshikazu

2013-01-01

The recent decline in fertility is a serious problem in the dairy industry. To overcome this problem, we performed a genome-wide association study using 384 Holsteins and identified four loci associated with conception rates. Two of them contained gap junction-related genes: PKP2 and CTTNBP2NL. Further analysis confirmed that PKP2 increased connexin 43, a gap junction protein, whereas CTTNBP2NL dephosphorylated connexin 43. Knockdown of PKP2 or overexpression of CTTNBP2NL inhibited embryo implantation in mice. The other two loci contained neuroendocrine-related genes: SETD6 and CACNB2. Additional experiments indicated that SETD6 is involved in the transcriptional regulation of gonadotropin-releasing hormone, whereas CACNB2 controlled the secretion of follicle-stimulating hormone in cattle. The total allele substitution effect of these genes on conception rate was 3.5%. Our findings reveal important roles for gap junction communication and the neuroendocrine system in conception and suggest unique selection methods to improve reproductive performance in the livestock industry. PMID:24218568

Gap Junction Inhibition Prevents Drug-induced Liver Toxicity and Fulminant Hepatic Failure

PubMed Central

Patel, Suraj J; Milwid, Jack M; King, Kevin R; Bohr, Stefan; Iracheta, Arvin; Li, Matthew; Vitalo, Antonia; Parekkadan, Biju; Jindal, Rohit; Yarmush, Martin L

2013-01-01

Drug-induced liver injury (DILI) limits the development and utilization of numerous therapeutic compounds, and consequently presents major challenges to the pharmaceutical industry and clinical medicine1, 2. Acetaminophen (APAP) containing compounds are among the most frequently prescribed drugs, and also the most common cause of DILI3. Here we describe a pharmacological strategy that targets gap junction communication to prevent amplification of fulminant hepatic failure and APAP-induced hepatotoxicity. We report that connexin 32 (Cx32), a key hepatic gap junction protein, is an essential mediator of DILI by showing that mice deficient in Cx32 are protected against liver damage, acute inflammation, and death. We identified a small molecule inhibitor of Cx32 as a novel hepatoprotectant that achieves the same result in wildtype mice when coadministered with known hepatotoxic drugs. These findings demonstrate that gap junction inhibition is an effective therapy for limiting DILI, and suggest a novel pharmaceutical strategy to improve drug safety. PMID:22252509

Genetic variants related to gap junctions and hormone secretion influence conception rates in cows.

PubMed

Sugimoto, Mayumi; Sasaki, Shinji; Gotoh, Yusaku; Nakamura, Yuuki; Aoyagi, Yoshito; Kawahara, Takayoshi; Sugimoto, Yoshikazu

2013-11-26

The recent decline in fertility is a serious problem in the dairy industry. To overcome this problem, we performed a genome-wide association study using 384 Holsteins and identified four loci associated with conception rates. Two of them contained gap junction-related genes: PKP2 and CTTNBP2NL. Further analysis confirmed that PKP2 increased connexin 43, a gap junction protein, whereas CTTNBP2NL dephosphorylated connexin 43. Knockdown of PKP2 or overexpression of CTTNBP2NL inhibited embryo implantation in mice. The other two loci contained neuroendocrine-related genes: SETD6 and CACNB2. Additional experiments indicated that SETD6 is involved in the transcriptional regulation of gonadotropin-releasing hormone, whereas CACNB2 controlled the secretion of follicle-stimulating hormone in cattle. The total allele substitution effect of these genes on conception rate was 3.5%. Our findings reveal important roles for gap junction communication and the neuroendocrine system in conception and suggest unique selection methods to improve reproductive performance in the livestock industry.

Redox-mediated regulation of connexin proteins; focus on nitric oxide.

PubMed

García, Isaac E; Sánchez, Helmuth A; Martínez, Agustín D; Retamal, Mauricio A

2018-01-01

Connexins are membrane proteins that form hemichannels and gap junction channels at the plasma membrane. Through these channels connexins participate in autocrine and paracrine intercellular communication. Connexin-based channels are tightly regulated by membrane potential, phosphorylation, pH, redox potential, and divalent cations, among others, and the imbalance of this regulation have been linked to many acquired and genetic diseases. Concerning the redox potential regulation, the nitric oxide (NO) has been described as a modulator of the hemichannels and gap junction channels properties. However, how NO regulates these channels is not well understood. In this mini-review, we summarize the current knowledge about the effects of redox potential focused in NO on the trafficking, formation and functional properties of hemichannels and gap junction channels. Copyright © 2017 Elsevier B.V. All rights reserved.

Ablation of atrial-ventricular junction tissues via the coronary sinus using cryo balloon technology.

PubMed

Avitall, Boaz; Lafontaine, Daniel; Rozmus, Grzegorz; Adoni, Naveed; Dehnee, Abed; Urbonas, Arvydas; Le, Khoi M; Aleksonis, Dinas

2005-04-01

The coronary sinus (CS) can provide access to targets across and within the atrioventricular (AV) junction. In 12 dogs (32 +/- 3 Kg), cryo balloons (10-19 mm) were applied to regions of the AV junction for 3 minutes at a temperature of -75.9( composite function) +/- 9(composite function)C (ranging -57 to -83). Electrical activity and pacing within the CS were assessed pre and post ablation and at least 3 months later in 9 dogs. In the 3 other dogs, hearts were examined immediately after cryo ablation. CS and circumflex angiography was performed pre and post ablation. The hearts, CS, and Cx were then examined for structural injury. The AV junction was sectioned and the hearts were immersed in Tetrazolium, and the lesions were inspected for transmurality across the AV groove. In 3/12 dogs the distal CS cryo lesions resulted in inferior ST segment depression that resolved within 5 minutes. There was no arrhythmia or hemodynamic changes. No CS electrical activity was noted post ablation. The pacing threshold increased from 2 +/- 2.3 mA to 7.4 +/- 3.6 mA (p < 0.001). Pathological examination of 3 acute hearts revealed hematomas. There was no pericardial effusion. No evidence of stenosis or thrombosis was seen within the CS and the circumflex artery. After 3 months of recovery, transmural lesions across the AV groove were present in all of the targeted AV regions. Intra-CS cryo balloon ablation is safe and can potentially replace endocardial RF ablation targeting the AV junction and the CS muscular sleeve.

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans.

PubMed

Jang, Heeun; Levy, Sagi; Flavell, Steven W; Mende, Fanny; Latham, Richard; Zimmer, Manuel; Bargmann, Cornelia I

2017-02-14

A hub-and-spoke circuit of neurons connected by gap junctions controls aggregation behavior and related behavioral responses to oxygen, pheromones, and food in Caenorhabditis elegans The molecular composition of the gap junctions connecting RMG hub neurons with sensory spoke neurons is unknown. We show here that the innexin gene unc-9 is required in RMG hub neurons to drive aggregation and related behaviors, indicating that UNC-9-containing gap junctions mediate RMG signaling. To dissect the circuit in detail, we developed methods to inhibit unc-9 -based gap junctions with dominant-negative unc-1 transgenes. unc-1(dn) alters a stomatin-like protein that regulates unc-9 electrical signaling; its disruptive effects can be rescued by a constitutively active UNC-9::GFP protein, demonstrating specificity. Expression of unc-1(dn) in RMG hub neurons, ADL or ASK pheromone-sensing neurons, or URX oxygen-sensing neurons disrupts specific elements of aggregation-related behaviors. In ADL, unc-1(dn) has effects opposite to those of tetanus toxin light chain, separating the roles of ADL electrical and chemical synapses. These results reveal roles of gap junctions in a complex behavior at cellular resolution and provide a tool for similar exploration of other gap junction circuits.

Dissection of neuronal gap junction circuits that regulate social behavior in Caenorhabditis elegans

PubMed Central

Jang, Heeun; Levy, Sagi; Flavell, Steven W.; Mende, Fanny; Latham, Richard; Zimmer, Manuel; Bargmann, Cornelia I.

2017-01-01

A hub-and-spoke circuit of neurons connected by gap junctions controls aggregation behavior and related behavioral responses to oxygen, pheromones, and food in Caenorhabditis elegans. The molecular composition of the gap junctions connecting RMG hub neurons with sensory spoke neurons is unknown. We show here that the innexin gene unc-9 is required in RMG hub neurons to drive aggregation and related behaviors, indicating that UNC-9–containing gap junctions mediate RMG signaling. To dissect the circuit in detail, we developed methods to inhibit unc-9–based gap junctions with dominant-negative unc-1 transgenes. unc-1(dn) alters a stomatin-like protein that regulates unc-9 electrical signaling; its disruptive effects can be rescued by a constitutively active UNC-9::GFP protein, demonstrating specificity. Expression of unc-1(dn) in RMG hub neurons, ADL or ASK pheromone-sensing neurons, or URX oxygen-sensing neurons disrupts specific elements of aggregation-related behaviors. In ADL, unc-1(dn) has effects opposite to those of tetanus toxin light chain, separating the roles of ADL electrical and chemical synapses. These results reveal roles of gap junctions in a complex behavior at cellular resolution and provide a tool for similar exploration of other gap junction circuits. PMID:28143932

Broad gap junction blocker carbenoxolone disrupts uterine preparation for embryo implantation in mice.

PubMed

Diao, Honglu; Xiao, Shuo; Howerth, Elizabeth W; Zhao, Fei; Li, Rong; Ard, Mary B; Ye, Xiaoqin

2013-08-01

Gap junctions have an important role in cell-to-cell communication, a process obviously required for embryo implantation. Uterine luminal epithelium (LE) is the first contact for an implanting embryo and is critical for the establishment of uterine receptivity. Microarray analysis of the LE from peri-implantation mouse uterus showed low-level expression of 19 gap junction proteins in preimplantation LE and upregulation of gap junction protein, beta 2 (GJB2, connexin 26, Cx26) in postimplantation LE. Time course study using in situ hybridization and immunofluorescence revealed upregulation of GJB2 in the LE surrounding the implantation site before decidualization. Similar dynamic expression of GJB2 was observed in the LE of artificially decidualized mice but not pseudopregnant mice. To determine the potential function of uterine gap junctions in embryo implantation, carbenoxolone (CBX), a broad gap junction blocker, was injected i.p. (100 mg/kg) or via local uterine fat pad (10 mg/kg) into pregnant mice on Gestation Day 3 at 1800 h, a few hours before embryo attachment to the LE. These CBX treatments disrupted embryo implantation, suggesting local effects of CBX in the uterus. However, i.p. injection of glycyrrhizic acid (100 mg/kg), which shares similar structure and multiple properties with CBX but is ineffective in blocking gap junctions, did not affect embryo implantation. Carbenoxolone also inhibited oil-induced artificial decidualization, concomitant with suppressed molecular changes and ultrastructural transformations associated with uterine preparation for embryo implantation, underscoring the adverse effect of CBX on uterine preparation for embryo implantation. These data demonstrate that uterine gap junctions are important for embryo implantation.

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

PubMed

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

2015-04-30

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.

Managing the complexity of communication: regulation of gap junctions by post-translational modification

PubMed Central

Axelsen, Lene N.; Calloe, Kirstine; Holstein-Rathlou, Niels-Henrik; Nielsen, Morten S.

2013-01-01

Gap junctions are comprised of connexins that form cell-to-cell channels which couple neighboring cells to accommodate the exchange of information. The need for communication does, however, change over time and therefore must be tightly controlled. Although the regulation of connexin protein 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 probability, single channel conductance or selectivity. The most extensively investigated post translational modifications are phosphorylations, which have been documented in all mammalian connexins. Besides phosphorylations, some connexins are known to be ubiquitinated, SUMOylated, nitrosylated, hydroxylated, acetylated, methylated, and γ-carboxyglutamated. The aim of the present review is to summarize our current knowledge of post translational regulation of the connexin family of proteins. PMID:24155720

P-n junction diodes with polarization induced p-type graded InxGa1-xN layer

NASA Astrophysics Data System (ADS)

Enatsu, Yuuki; Gupta, Chirag; Keller, Stacia; Nakamura, Shuji; Mishra, Umesh K.

2017-10-01

In this study, p-n junction diodes with polarization induced p-type layer are demonstrated on Ga polar (0001) bulk GaN substrates. A quasi-p-type region is obtained by linearly grading the indium composition in un-doped InxGa1-xN layers from 0% to 5%, taking advantage of the piezoelectric and spontaneous polarization fields which exist in group III-nitride heterostructures grown in the typical (0001) or c-direction. The un-doped graded InxGa1-xN layers needed to be capped with a thin Mg-doped InxGa1-xN layer to make good ohmic contacts and to reduce the on-resistance of the p-n diodes. The Pol-p-n junction diodes exhibited similar characteristics compared to reference samples with traditional p-GaN:Mg layers. A rise in breakdown voltage from 30 to 110 V was observed when the thickness of the graded InGaN layer was increased from 100 to 600 nm at the same grade composition.

Gap junctions favor normal rat kidney epithelial cell adaptation to chronic hypertonicity.

PubMed

Desforges, Bénédicte; Savarin, Philippe; Bounedjah, Ouissame; Delga, Stéphanie; Hamon, Loïc; Curmi, Patrick A; Pastré, David

2011-09-01

Upon hypertonic stress most often resulting from high salinity, cells need to balance their osmotic pressure by accumulating neutral osmolytes called compatible osmolytes like betaine, myo-inositol, and taurine. However, the massive uptake of compatible osmolytes is a slow process compared with other defense mechanisms related to oxidative or heat stress. This is especially critical for cycling cells as they have to double their volume while keeping a hospitable intracellular environment for the molecular machineries. Here we propose that clustered cells can accelerate the supply of compatible osmolytes to cycling cells via the transit, mediated by gap junctions, of compatible osmolytes from arrested to cycling cells. Both experimental results in epithelial normal rat kidney cells and theoretical estimations show that gap junctions indeed play a key role in cell adaptation to chronic hypertonicity. These results can provide basis for a better understanding of the functions of gap junctions in osmoregulation not only for the kidney but also for many other epithelia. In addition to this, we suggest that cancer cells that do not communicate via gap junctions poorly cope with hypertonic environments thus explaining the rare occurrence of cancer coming from the kidney medulla.

Gap Junctions and Connexin Hemichannels Underpin Haemostasis and Thrombosis

PubMed Central

Vaiyapuri, Sakthivel; Jones, Chris I.; Sasikumar, Parvathy; Moraes, Leonardo A.; Munger, Stephanie J.; Wright, Joy R.; Ali, Marfoua S.; Sage, Tanya; Kaiser, William J.; Tucker, Katherine L.; Stain, Christopher J.; Bye, Alexander P.; Jones, Sarah; Oviedo-Orta, Ernesto; Simon, Alexander M.; Mahaut-Smith, Martyn P.; Gibbins, Jonathan M.

2012-01-01

Background Connexins are a widespread family of membrane proteins that assemble into hexameric hemichannels, also known as connexons. Connexons regulate membrane permeability in individual cells or couple between adjacent cells to form gap junctions and thereby provide a pathway for regulated intercellular communication. We have now examined the role of connexins in platelets, blood cells that circulate in isolation, but upon tissue injury adhere to each other and the vessel wall to prevent blood loss and facilitate wound repair. Methods and Results We report the presence of connexins in platelets, notably connexin37, and that the formation of gap junctions within platelet thrombi is required for the control of clot retraction. Inhibition of connexin function modulated a range of platelet functional responses prior to platelet-platelet contact, and reduced laser induced thrombosis in vivo in mice. Deletion of the Cx37 gene (Gja4) in transgenic mice reduced platelet aggregation, fibrinogen binding, granule secretion and clot retraction indicating an important role for Cx37 hemichannels and gap junctions in platelet thrombus function. Conclusions Together, these data demonstrate that platelet gap junctions and hemichannels underpin the control of haemostasis and thrombosis and represent potential therapeutic targets. PMID:22528526

[Gap junctions: A new therapeutic target in major depressive disorder?].

PubMed

Sarrouilhe, D; Dejean, C

2015-11-01

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.

Role of gap junctional coupling in astrocytic networks in the determination of global ischaemia-induced oxidative stress and hippocampal damage.

PubMed

Perez Velazquez, Jose L; Kokarovtseva, Larisa; Sarbaziha, Raheleh; Jeyapalan, Zina; Leshchenko, Yevgen

2006-01-01

While there is evidence that gap junctions play important roles in the determination of cell injuries, there is not much known about mechanisms by which gap junctional communication may exert these functions. Using a global model of transient ischaemia in rats, we found that pretreatment with the gap junctional blockers carbenoxolone, 18alpha-glycyrrhetinic acid and endothelin, applied via cannulae implanted into the hippocampus in one hemisphere, resulted in decreased numbers of TUNEL-positive neurons, as compared with the contralateral hippocampus that received saline injection. Post-treatment with carbenoxolone for up to 30 min after the stroke injury still resulted in decreased cell death, but post-treatment at 90 min after the ischaemic insult did not result in differences in cell death. However, quinine, an inhibitor of Cx36-mediated gap junctional coupling, did not result in appreciable neuroprotection. Searching for a possible mechanism for the observed protective effects, possible actions of the gap junctional blockers in the electrical activity of the hippocampus during the ischaemic insult were assessed using intracerebral recordings, with no differences observed between the saline-injected and the contralateral drug-injected hippocampus. However, a significant reduction in lipid peroxides, a measure of free radical formation, in the hippocampus treated with carbenoxolone, revealed that the actions of gap junctional coupling during injuries may be causally related to oxidative stress. These observations suggest that coupling in glial networks may be functionally important in determining neuronal vulnerability to oxidative injuries.

Theoretical evaluation of two dimensional electron gas characteristics of quaternary AlxInyGa1-x-yN/GaN hetero-junctions

NASA Astrophysics Data System (ADS)

Rahbardar Mojaver, Hassan; Manouchehri, Farzin; Valizadeh, Pouya

2016-04-01

The two dimensional electron gas (2DEG) characteristics of gated metal-face wurtzite AlInGaN/GaN hetero-junctions including positions of subband energy levels, fermi energy level, and the 2DEG concentration as functions of physical and compositional properties of the hetero-junction (i.e., barrier thickness and metal mole-fractions) are theoretically evaluated using the variational method. The calculated values of the 2DEG concentration are in good agreement with the sparsely available experimental data reported in the literature. According to our simulation results, a considerable shift in the positive direction of threshold voltage of AlInGaN/GaN hetero-junction field-effect transistors can be achieved by engineering both the spontaneous and the piezoelectric polarizations using a quaternary AlInGaN barrier-layer of appropriate mole-fractions.

Propofol inhibits gap junctions by attenuating sevoflurane-induced cytotoxicity against rat liver cells in vitro.

PubMed

Huang, Fei; Li, Shangrong; Gan, Xiaoliang; Wang, Ren; Chen, Zhonggang

2014-04-01

Liver abnormalities are seen in a small proportion of patients following anaesthesia with sevoflurane. To investigate whether the cytotoxicity of sevoflurane against rat liver cells was mediated by gap junction intercellular communications, and the effect of propofol on sevoflurane-induced cytotoxicity. Experimental study. The study was carried out in the central laboratory of The Third Affiliated Hospital, Sun Yat-sen University. BRL-3A rat liver cells. Immortal rat liver cells BRL-3A were grown at low and high density. Colony-forming assays were performed to determine clonogenic growth of these cells. To investigate the effect of oleamide and propofol on gap junction function, we measured fluorescence transmission between cells using parachute dye-coupling assays. Immunoblotting assays were performed to determine connexin32 and connexin43 expression. Our colony formation assays revealed that, in low-density culture, sevoflurane caused no apparent inhibition of clonogenic growth of BRL-3A cells. In high-density culture, 2.2 to 4.4% sevoflurane markedly inhibited clonogenic growth of BRL-3A cells with 67.6 (0.34)% and 61.2 (0.17)% of the cells being viable, respectively (P = 0.003 vs. low-density culture), suggesting cell density dependency of sevoflurane-induced cytotoxicity. Our colony formation assays revealed that propofol markedly attenuated the suppression by sevoflurane of the clonogenic growth of BRL-3A cells (viability: propofol and sevoflurane, 91.5 (0.014)% vs. sevoflurane, 56.6 (0.019)%; P <0.01). Blocking gap junctions with 10 μmol l oleamide significantly attenuated 4.4% sevoflurane-induced suppression with a viability of 83.6 ± 0.138% (oleamide and sevoflurane vs. sevoflurane, P < 0.01). Immunoblotting assays further showed that propofol (3.2 μg ml) markedly reduced CX32 levels and significantly inhibited gap junctional intercellular communications as revealed by parachute dye-coupling assays. Values are mean (SD). This study provides the first direct evidence that sevoflurane-induced cytotoxicity, which is mediated through gap junctions, is attenuated by propofol, possibly by its action on Cx32 homomeric or heteromeric complexes.

Gap junction communication between uterine stromal cells plays a critical role in pregnancy-associated neovascularization and embryo survival.

PubMed

Laws, Mary J; Taylor, Robert N; Sidell, Neil; DeMayo, Francesco J; Lydon, John P; Gutstein, David E; Bagchi, Milan K; Bagchi, Indrani C

2008-08-01

In the uterus, the formation of new maternal blood vessels in the stromal compartment at the time of embryonic implantation is critical for the establishment and maintenance of pregnancy. Although uterine angiogenesis is known to be influenced by the steroid hormones estrogen (E) and progesterone (P), the underlying molecular pathways remain poorly understood. Here, we report that the expression of connexin 43 (Cx43), a major gap junction protein, is markedly enhanced in response to E in uterine stromal cells surrounding the implanted embryo during the early phases of pregnancy. Conditional deletion of the Cx43 gene in these stromal cells and the consequent disruption of their gap junctions led to a striking impairment in the development of new blood vessels within the stromal compartment, resulting in the arrest of embryo growth and early pregnancy loss. Further analysis of this phenotypical defect revealed that loss of Cx43 expression resulted in aberrant differentiation of uterine stromal cells and impaired production of several key angiogenic factors, including the vascular endothelial growth factor (Vegf). Ablation of CX43 expression in human endometrial stromal cells in vitro led to similar findings. Collectively, these results uncovered a unique link between steroid hormone-regulated cell-cell communication within the pregnant uterus and the development of an elaborate vascular network that supports embryonic growth. Our study presents the first evidence that Cx43-type gap junctions play a critical and conserved role in modulating stromal differentiation, and regulate the consequent production of crucial paracrine signals that control uterine neovascularization during implantation.

Implanted neural progenitor cells regulate glial reaction to brain injury and establish gap junctions with host glial cells.

PubMed

Talaverón, Rocío; Matarredona, Esperanza R; de la Cruz, Rosa R; Macías, David; Gálvez, Victoria; Pastor, Angel M

2014-04-01

Transplantation of neural stem/progenitor cells (NPCs) in the lesioned brain is able to restore morphological and physiological alterations induced by different injuries. The local microenvironment created at the site of grafting and the communication between grafted and host cells are crucial in the beneficial effects attributed to the NPC implants. We have previously described that NPC transplantation in an animal model of central axotomy restores firing properties and synaptic coverage of lesioned neurons and modulates their trophic factor content. In this study, we aim to explore anatomical relationships between implanted NPCs and host glia that might account for the implant-induced neuroprotective effects. Postnatal rat subventricular zone NPCs were isolated and grafted in adult rats after transection of the medial longitudinal fascicle. Brains were removed and analyzed eight weeks later. Immunohistochemistry for different glial markers revealed that NPC-grafted animals displayed significantly greater microglial activation than animals that received only vehicle injections. Implanted NPCs were located in close apposition to activated microglia and reactive astrocytes. The gap junction protein connexin43 was present in NPCs and glial cells at the lesion site and was often found interposed within adjacent implanted and glial cells. Gap junctions were identified between implanted NPCs and host astrocytes and less frequently between NPCs and microglia. Our results show that implanted NPCs modulate the glial reaction to lesion and establish the possibility of communication through gap junctions between grafted and host glial cells which might be involved in the restorative effects of NPC implants. Copyright © 2014 Wiley Periodicals, Inc.

Increase in gap junctional intercellular communication by high molecular weight hyaluronic acid associated with fibroblast growth factor 2 and keratinocyte growth factor production in normal human dermal fibroblasts.

PubMed

Park, Jeong Ung; Tsuchiya, Toshie

2002-07-01

The effects of different molecular weights of hyaluronic acid (HA), a major component of extracellular matrix, on gap junctional intercellular communication (GJIC) in normal human dermal fibroblasts (NHDF cells) were investigated. NHDF cells were cultured for 4 days with different molecular weights of HA and then the extent of GJIC was assessed by the scrape-loading dye transfer method, using Lucifer yellow. The area of dye transfer was greater in the dishes coated with HA than in those to which HA was added. Thus, NHDF cells cultured on surfaces coated with high molecular weight (HMW) HA (MW, 800 kDa) showed greatly enhanced GJIC. Furthermore, another aim of this study was to evaluate the effects of different molecular weights of HA on the production of FGF-2 and KGF, because both are important cytokines produced by NHDF cells. When FGF-2 and KGF cultured levels of cell extracts and media were determined by ELISA, both levels were significantly enhanced when cells were grown on plates coated with HMW HA. This finding indicated that the function of gap junction channels in NHDF cells grown on plates coated with HMW HA may promote the biosynthesis of growth factors such as FGF-2 and KGF.

Boldine Prevents Renal Alterations in Diabetic Rats

PubMed Central

Hernández-Salinas, Romina; Vielma, Alejandra Z.; Arismendi, Marlene N.; Boric, Mauricio P.; Sáez, Juan C.; Velarde, Victoria

2013-01-01

Diabetic nephropathy alters both structure and function of the kidney. These alterations are associated with increased levels of reactive oxygen species, matrix proteins, and proinflammatory molecules. Inflammation decreases gap junctional communication and increases hemichannel activity leading to increased membrane permeability and altering tissue homeostasis. Since current treatments for diabetic nephropathy do not prevent renal damage, we postulated an alternative treatment with boldine, an alkaloid obtained from boldo with antioxidant, anti-inflammatory, and hypoglycemic effects. Streptozotocin-induced diabetic and control rats were treated or not treated with boldine (50 mg/Kg/day) for ten weeks. In addition, mesangial cells were cultured under control conditions or in high glucose concentration plus proinflammatory cytokines, with or without boldine (100 µmol/L). Boldine treatment in diabetic animals prevented the increase in glycemia, blood pressure, renal thiobarbituric acid reactive substances and the urinary protein/creatinine ratio. Boldine also reduced alterations in matrix proteins and markers of renal damage. In mesangial cells, boldine prevented the increase in oxidative stress, the decrease in gap junctional communication, and the increase in cell permeability due to connexin hemichannel activity induced by high glucose and proinflammatory cytokines but did not block gap junction channels. Thus boldine prevented both renal and cellular alterations and could be useful for preventing tissue damage in diabetic subjects. PMID:24416726

Boldine prevents renal alterations in diabetic rats.

PubMed

Hernández-Salinas, Romina; Vielma, Alejandra Z; Arismendi, Marlene N; Boric, Mauricio P; Sáez, Juan C; Velarde, Victoria

2013-01-01

Diabetic nephropathy alters both structure and function of the kidney. These alterations are associated with increased levels of reactive oxygen species, matrix proteins, and proinflammatory molecules. Inflammation decreases gap junctional communication and increases hemichannel activity leading to increased membrane permeability and altering tissue homeostasis. Since current treatments for diabetic nephropathy do not prevent renal damage, we postulated an alternative treatment with boldine, an alkaloid obtained from boldo with antioxidant, anti-inflammatory, and hypoglycemic effects. Streptozotocin-induced diabetic and control rats were treated or not treated with boldine (50 mg/Kg/day) for ten weeks. In addition, mesangial cells were cultured under control conditions or in high glucose concentration plus proinflammatory cytokines, with or without boldine (100 µmol/L). Boldine treatment in diabetic animals prevented the increase in glycemia, blood pressure, renal thiobarbituric acid reactive substances and the urinary protein/creatinine ratio. Boldine also reduced alterations in matrix proteins and markers of renal damage. In mesangial cells, boldine prevented the increase in oxidative stress, the decrease in gap junctional communication, and the increase in cell permeability due to connexin hemichannel activity induced by high glucose and proinflammatory cytokines but did not block gap junction channels. Thus boldine prevented both renal and cellular alterations and could be useful for preventing tissue damage in diabetic subjects.

Endocochlear potential generation is associated with intercellular communication in the stria vascularis: structural analysis in the viable dominant spotting mouse mutant.

PubMed

Carlisle, L; Steel, K; Forge, A

1990-11-01

Deafness in the viable dominant spotting mouse mutant is due to a primary defect of the stria vascularis which results in absence of the positive endocochlear potential in scala media. Endocochlear potentials were measured and the structure of stria vascularis of mutants with potentials close to zero was compared with that in normal littermate controls by use of morphometric methods. The stria vascularis was significantly thinner in mutants. Marginal cells were not significantly different from controls in terms of volume density or intramembrane particle density but the network density of tight junctions was significantly reduced in the mutants. A virtual absence of gap junctions between basal cells and marginal or intermediate cells was observed, but intramembrane particle density and junctional complexes between adjacent basal cells were not different from controls. The volume density of basal cells was significantly greater in mutants. Intermediate cells accounted for a significantly smaller volume density of the stria vascularis in mutants and had a lower density of intramembrane particles than controls. Melanocytes were not identified in the stria vascularis of mutants. These results suggest that communication between marginal, intermediate and basal cells might be important to the normal function of the stria vascularis.

Heterotypic gap junctions at glutamatergic mixed synapses are abundant in goldfish brain

PubMed Central

Rash, John E.; Kamasawa, Naomi; Vanderpool, Kimberly G.; Yasumura, Thomas; O'Brien, John; Nannapaneni, Srikant; Pereda, Alberto E.; Nagy, James I.

2014-01-01

Gap junctions provide for direct intercellular electrical and metabolic coupling. The abundance of gap junctions at “large myelinated club ending” synapses on Mauthner cells of the teleost brain provided a convenient model to correlate anatomical and physiological properties of electrical synapses. There, presynaptic action potentials were found to evoke short-latency electrical “pre-potentials” immediately preceding their accompanying glutamate-induced depolarizations, making these the first unambiguously identified “mixed” (i.e., chemical plus electrical) synapses in the vertebrate CNS. We recently showed that gap junctions at these synapses exhibit asymmetric electrical resistance (i.e., electrical rectification), which we correlated with total molecular asymmetry of connexin composition in their apposing gap junction hemiplaques, with Cx35 restricted to axon terminal hemiplaques and Cx34.7 restricted to apposing Mauthner cell plasma membranes. We now show that similarly heterotypic neuronal gap junctions are abundant throughout goldfish brain, with labeling exclusively for Cx35 in presynaptic hemiplaques and exclusively for Cx34.7 in postsynaptic hemiplaques. Moreover, the vast majority of these asymmetric gap junctions occur at glutamatergic axon terminals. The widespread distribution of heterotypic gap junctions at glutamatergic mixed synapses throughout goldfish brain and spinal cord implies that pre- vs. postsynaptic asymmetry at electrical synapses evolved early in the chordate lineage. We propose that the advantages of the molecular and functional asymmetry of connexins at electrical synapses that are so prominently expressed in the teleost CNS are unlikely to have been abandoned in higher vertebrates. However, to create asymmetric coupling in mammals, where most gap junctions are composed of Cx36 on both sides, would require some other mechanism, such as differential phosphorylation of connexins on opposite sides of the same gap junction or on asymmetric differences in the complement of their scaffolding and regulatory proteins. PMID:25451276

Temperature excursions at the pulp-dentin junction during the curing of light-activated dental restorations.

PubMed

Jakubinek, Michael B; O'Neill, Catherine; Felix, Chris; Price, Richard B; White, Mary Anne

2008-11-01

Excessive heat produced during the curing of light-activated dental restorations may injure the dental pulp. The maximum temperature excursion at the pulp-dentin junction provides a means to assess the risk of thermal injury. In this investigation we develop and evaluate a model to simulate temperature increases during light-curing of dental restorations and use it to investigate the influence of several factors on the maximum temperature excursion along the pulp-dentin junction. Finite element method modeling, using COMSOL 3.3a, was employed to simulate temperature distributions in a 2D, axisymmetric model tooth. The necessary parameters were determined from a combination of literature reports and our measurements of enthalpy of polymerization, heat capacity, density, thermal conductivity and reflectance for several dental composites. Results of the model were validated using in vitro experiments. Comparisons with in vitro experiments indicate that the model provides a good approximation of the actual temperature increases. The intensity of the curing light, the curing time and the enthalpy of polymerization of the resin composite were the most important factors. The composite is a good insulator and the greatest risk occurs when using the light to cure the thin layer of bonding resin or in deep restorations that do not have a liner to act as a thermal barrier. The results show the importance of considering temperature increases when developing curing protocols. Furthermore, we suggest methods to minimize the temperature increase and hence the risk of thermal injury. The physical properties measured for several commercial composites may be useful in other studies.

Thermodynamic and achievable efficiencies for solar-driven electrochemical reduction of carbon dioxide to transportation fuels.

PubMed

Singh, Meenesh R; Clark, Ezra L; Bell, Alexis T

2015-11-10

Thermodynamic, achievable, and realistic efficiency limits of solar-driven electrochemical conversion of water and carbon dioxide to fuels are investigated as functions of light-absorber composition and configuration, and catalyst composition. The maximum thermodynamic efficiency at 1-sun illumination for adiabatic electrochemical synthesis of various solar fuels is in the range of 32-42%. Single-, double-, and triple-junction light absorbers are found to be optimal for electrochemical load ranges of 0-0.9 V, 0.9-1.95 V, and 1.95-3.5 V, respectively. Achievable solar-to-fuel (STF) efficiencies are determined using ideal double- and triple-junction light absorbers and the electrochemical load curves for CO2 reduction on silver and copper cathodes, and water oxidation kinetics over iridium oxide. The maximum achievable STF efficiencies for synthesis gas (H2 and CO) and Hythane (H2 and CH4) are 18.4% and 20.3%, respectively. Whereas the realistic STF efficiency of photoelectrochemical cells (PECs) can be as low as 0.8%, tandem PECs and photovoltaic (PV)-electrolyzers can operate at 7.2% under identical operating conditions. We show that the composition and energy content of solar fuels can also be adjusted by tuning the band-gaps of triple-junction light absorbers and/or the ratio of catalyst-to-PV area, and that the synthesis of liquid products and C2H4 have high profitability indices.

Thermodynamic and achievable efficiencies for solar-driven electrochemical reduction of carbon dioxide to transportation fuels

NASA Astrophysics Data System (ADS)

Singh, Meenesh R.; Clark, Ezra L.; Bell, Alexis T.

2015-11-01

Thermodynamic, achievable, and realistic efficiency limits of solar-driven electrochemical conversion of water and carbon dioxide to fuels are investigated as functions of light-absorber composition and configuration, and catalyst composition. The maximum thermodynamic efficiency at 1-sun illumination for adiabatic electrochemical synthesis of various solar fuels is in the range of 32-42%. Single-, double-, and triple-junction light absorbers are found to be optimal for electrochemical load ranges of 0-0.9 V, 0.9-1.95 V, and 1.95-3.5 V, respectively. Achievable solar-to-fuel (STF) efficiencies are determined using ideal double- and triple-junction light absorbers and the electrochemical load curves for CO2 reduction on silver and copper cathodes, and water oxidation kinetics over iridium oxide. The maximum achievable STF efficiencies for synthesis gas (H2 and CO) and Hythane (H2 and CH4) are 18.4% and 20.3%, respectively. Whereas the realistic STF efficiency of photoelectrochemical cells (PECs) can be as low as 0.8%, tandem PECs and photovoltaic (PV)-electrolyzers can operate at 7.2% under identical operating conditions. We show that the composition and energy content of solar fuels can also be adjusted by tuning the band-gaps of triple-junction light absorbers and/or the ratio of catalyst-to-PV area, and that the synthesis of liquid products and C2H4 have high profitability indices.

The tight junction protein ZO-2 and Janus kinase 1 mediate intercellular communications in vascular smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tkachuk, Natalia; Tkachuk, Sergey; Patecki, Margret

2011-07-08

Highlights: {yields} The tight junction protein ZO-2 associates with Jak1 in vascular smooth muscle cells via ZO-2 N-terminal fragment. {yields} Jak1 mediates ZO-2 tyrosine phosphorylation and ZO-2 localization to the sites of homotypic intercellular contacts. {yields} The urokinase receptor uPAR regulates ZO-2/Jak1 functional association. {yields} The ZO-2/Jak1/uPAR signaling complex is required for vascular smooth muscle cells functional network formation. -- Abstract: Recent evidence points to a multifunctional role of ZO-2, the tight junction protein of the MAGUK (membrane-associated guanylate kinase-like) family. Though ZO-2 has been found in cell types lacking tight junction structures, such as vascular smooth muscle cells (VSMC),more » little is known about ZO-2 function in these cells. We provide evidence that ZO-2 mediates specific homotypic cell-to-cell contacts between VSMC. Using mass spectrometry we found that ZO-2 is associated with the non-receptor tyrosine kinase Jak1. By generating specific ZO-2 constructs we further found that the N-terminal fragment of ZO-2 molecule is responsible for this interaction. Adenovirus-based expression of Jak1 inactive mutant demonstrated that Jak1 mediates ZO-2 tyrosine phosphorylation. By means of RNA silencing, expression of Jak1 mutant form and fluorescently labeled ZO-2 fusion protein we further specified that active Jak1, but not Jak1 inactive mutant, mediates ZO-2 localization to the sites of intercellular contacts. We identified the urokinase receptor uPAR as a pre-requisite for these cellular events. Functional requirement of the revealed signaling complex for VSMC network formation was confirmed in experiments using Matrigel and in contraction assay. Our findings imply involvement of the ZO-2 tight junction independent signaling complex containing Jak1 and uPAR in VSMC intercellular communications. This mechanism may contribute to vascular remodeling in occlusive cardiovascular diseases and in arteriogenesis.« less

Junctional and nonjunctional effects of heptanol and glycyrrhetinic acid derivates in rat mesenteric small arteries

PubMed Central

Matchkov, Vladimir V; Rahman, Awahan; Peng, Hongli; Nilsson, Holger; Aalkjær, Christian

2004-01-01

Heptanol, 18α-glycyrrhetinic acid (18αGA) and 18β-glycyrrhetinic acid (18βGA) are known blockers of gap junctions, and are often used in vascular studies. However, actions unrelated to gap junction block have been repeatedly suggested in the literature for these compounds. We report here the findings from a comprehensive study of these compounds in the arterial wall. Rat isolated mesenteric small arteries were studied with respect to isometric tension (myography), [Ca2+]i (Ca2+-sensitive dyes), membrane potential and – as a measure of intercellular coupling – input resistance (sharp intracellular glass electrodes). Also, membrane currents (patch-clamp) were measured in isolated smooth muscle cells (SMCs). Confocal imaging was used for visualisation of [Ca2+]i events in single SMCs in the arterial wall. Heptanol (150 μM) activated potassium currents, hyperpolarised the membrane, inhibited the Ca2+ current, and reduced [Ca2+]i and tension, but had little effect on input resistance. Only at concentrations above 200 μM did heptanol elevate input resistance, desynchronise SMCs and abolish vasomotion. 18βGA (30 μM) not only increased input resistance and desynchronised SMCs but also had nonjunctional effects on membrane currents. 18αGA (100 μM) had no significant effects on tension, [Ca2+]i, total membrane current and synchronisation in vascular smooth muscle. We conclude that in mesenteric small arteries, heptanol and 18βGA have important nonjunctional effects at concentrations where they have little or no effect on intercellular communication. Thus, the effects of heptanol and 18βGA on vascular function cannot be interpreted as being caused only by effects on gap junctions. 18αGA apparently does not block communication between SMCs in these arteries, although an effect on myoendothelial gap junctions cannot be excluded. PMID:15210581

SLO BK Potassium Channels Couple Gap Junctions to Inhibition of Calcium Signaling in Olfactory Neuron Diversification.

PubMed

Alqadah, Amel; Hsieh, Yi-Wen; Schumacher, Jennifer A; Wang, Xiaohong; Merrill, Sean A; Millington, Grethel; Bayne, Brittany; Jorgensen, Erik M; Chuang, Chiou-Fen

2016-01-01

The C. elegans AWC olfactory neuron pair communicates to specify asymmetric subtypes AWCOFF and AWCON in a stochastic manner. Intercellular communication between AWC and other neurons in a transient NSY-5 gap junction network antagonizes voltage-activated calcium channels, UNC-2 (CaV2) and EGL-19 (CaV1), in the AWCON cell, but how calcium signaling is downregulated by NSY-5 is only partly understood. Here, we show that voltage- and calcium-activated SLO BK potassium channels mediate gap junction signaling to inhibit calcium pathways for asymmetric AWC differentiation. Activation of vertebrate SLO-1 channels causes transient membrane hyperpolarization, which makes it an important negative feedback system for calcium entry through voltage-activated calcium channels. Consistent with the physiological roles of SLO-1, our genetic results suggest that slo-1 BK channels act downstream of NSY-5 gap junctions to inhibit calcium channel-mediated signaling in the specification of AWCON. We also show for the first time that slo-2 BK channels are important for AWC asymmetry and act redundantly with slo-1 to inhibit calcium signaling. In addition, nsy-5-dependent asymmetric expression of slo-1 and slo-2 in the AWCON neuron is necessary and sufficient for AWC asymmetry. SLO-1 and SLO-2 localize close to UNC-2 and EGL-19 in AWC, suggesting a role of possible functional coupling between SLO BK channels and voltage-activated calcium channels in AWC asymmetry. Furthermore, slo-1 and slo-2 regulate the localization of synaptic markers, UNC-2 and RAB-3, in AWC neurons to control AWC asymmetry. We also identify the requirement of bkip-1, which encodes a previously identified auxiliary subunit of SLO-1, for slo-1 and slo-2 function in AWC asymmetry. Together, these results provide an unprecedented molecular link between gap junctions and calcium pathways for terminal differentiation of olfactory neurons.

Quantification of gap junction selectivity.

PubMed

Ek-Vitorín, Jose F; Burt, Janis M

2005-12-01

Gap junctions, which are essential for functional coordination and homeostasis within tissues, permit the direct intercellular exchange of small molecules. The abundance and diversity of this exchange depends on the number and selectivity of the comprising channels and on the transjunctional gradient for and chemical character of the permeant molecules. Limited knowledge of functionally significant permeants and poor detectability of those few that are known have made it difficult to define channel selectivity. Presented herein is a multifaceted approach to the quantification of gap junction selectivity that includes determination of the rate constant for intercellular diffusion of a fluorescent probe (k2-DYE) and junctional conductance (gj) for each junction studied, such that the selective permeability (k2-DYE/gj) for dyes with differing chemical characteristics or junctions with differing connexin (Cx) compositions (or treatment conditions) can be compared. In addition, selective permeability can be correlated using single-channel conductance when this parameter is also measured. Our measurement strategy is capable of detecting 1) rate constants and selective permeabilities that differ across three orders of magnitude and 2) acute changes in that rate constant. Using this strategy, we have shown that 1) the selective permeability of Cx43 junctions to a small cationic dye varied across two orders of magnitude, consistent with the hypothesis that the various channel configurations adopted by Cx43 display different selective permeabilities; and 2) the selective permeability of Cx37 vs. Cx43 junctions was consistently and significantly lower.

Tuning the Rectification Ratio by Changing the Electronic Nature (Open-Shell and Closed-Shell) in Donor-Acceptor Self-Assembled Monolayers.

PubMed

Souto, Manuel; Yuan, Li; Morales, Dayana C; Jiang, Li; Ratera, Imma; Nijhuis, Christian A; Veciana, Jaume

2017-03-29

This Communication describes the mechanism of charge transport across self-assembled monolayers (SAMs) of two donor-acceptor systems consisting of a polychlorotriphenylmethyl (PTM) electron-acceptor moiety linked to an electron-donor ferrocene (Fc) unit supported by ultraflat template-stripped Au and contacted by a eutectic alloy of gallium and indium top contacts. The electronic and supramolecular structures of these SAMs were well characterized. The PTM unit can be switched between the nonradical and radical forms, which influences the rectification behavior of the junction. Junctions with nonradical units rectify currents via the highest occupied molecular orbital (HOMO) with a rectification ratio R = 99, but junctions with radical units have a new accessible state, a single-unoccupied molecular orbital (SUMO), which turns rectification off and drops R to 6.

RAPID COMMUNICATION: DC superconducting quantum interference devices fabricated using bicrystal grain boundary junctions in Co-doped BaFe2As2 epitaxial films

NASA Astrophysics Data System (ADS)

Katase, Takayoshi; Ishimaru, Yoshihiro; Tsukamoto, Akira; Hiramatsu, Hidenori; Kamiya, Toshio; Tanabe, Keiichi; Hosono, Hideo

2010-08-01

DC superconducting quantum interference devices (dc-SQUIDs) were fabricated in Co-doped BaFe2As2 epitaxial films on (La, Sr)(Al, Ta)O3 bicrystal substrates with 30° misorientation angles. The 18 × 8 µm2 SQUID loop with an estimated inductance of 13 pH contained two 3 µm wide grain boundary junctions. The voltage-flux characteristics clearly exhibited periodic modulations with ΔV = 1.4 µV at 14 K, while the intrinsic flux noise of dc-SQUIDs was 7.8 × 10 - 5 Φ0 Hz - 1/2 above 20 Hz. The rather high flux noise is mainly attributed to the small voltage modulation depth which results from the superconductor-normal-metal-superconductor junction nature of the bicrystal grain boundary.

Electrical characterization of ZnO/NiO p-n junction prepared by the sol-gel method

NASA Astrophysics Data System (ADS)

Merih Akyuzlu, A.; Dagdelen, Fethi; Gultek, Ahmet; Hendi, A. A.; Yakuphanoglu, Fahrettin

2017-04-01

ZnO and NiO films were synthesized on fluourine-doped tin oxide (FTO) glass substrate by the sol-gel method. The surface morphology of the films was investigated by atomic force microscopy. The optical band gaps of the ZnO and NiO films were found to be 3.198 and 3.827eV, respectively. A ZnO/NiO p-n junction diode was prepared and electrical charge transport mechanism of the diode was analyzed using thermionic emission and Norde functions. The ideality factor, barrier height and series resistance of the diode were determined to be 6.46, 1.036eV and 39.1 M {Ω} , respectively. The obtained results indicate that ZnO/NiO p-n junction can be used as transparent diode for optic communications.

Spontaneous and LH-induced maturation in Bufo arenarum oocytes: importance of gap junctions.

PubMed

Toranzo, G Sánchez; Oterino, J; Zelarayán, L; Bonilla, F; Bühler, M I

2007-02-01

It has been demonstrated in Bufo arenarum that fully grown oocytes are capable of meiotic resumption in the absence of a hormonal stimulus if they are deprived of their follicular envelopes. This event, called spontaneous maturation, only takes place in oocytes collected during the reproductive period, which have a metabolically mature cytoplasm. In Bufo arenarum, progesterone acts on the oocyte surface and causes modifications in the activities of important enzymes, such as a decrease in the activity of adenylate cyclase (AC) and the activation of phospholipase C (PLC). PLC activation leads to the formation of diacylglycerol (DAG) and inositol triphosphate (IP(3)), second messengers that activate protein kinase C (PKC) and cause an increase in intracellular Ca(2+). Recent data obtained from Bufo arenarum show that progesterone-induced maturation causes significant modifications in the level and composition of neutral lipids and phospholipids of whole fully grown ovarian oocytes and of enriched fractions in the plasma membrane. In amphibians, the luteinizing hormone (LH) is responsible for meiosis resumption through the induction of progesterone production by follicular cells. The aim of this work was to study the importance of gap junctions in the spontaneous and LH-induced maturation in Bufo arenarum oocytes. During the reproductive period, Bufo arenarum oocytes are capable of undergoing spontaneous maturation in a similar way to mammalian oocytes while, during the non-reproductive period, they exhibit the behaviour that is characteristic of amphibian oocytes, requiring progesterone stimulation for meiotic resumption (incapable oocytes). This different ability to mature spontaneously is coincident with differences in the amount and composition of the phospholipids in the oocyte membranes. Capable oocytes exhibit in their membranes higher quantities of phospholipids than incapable oocytes, especially of PC and PI, which are precursors of second messengers such as DAG and IP(3). The uncoupling of the gap junctions with 1-octanol or halothane fails to induce maturation in follicles from the non-reproductive period, whose oocytes are incapable of maturing spontaneously. However, if the treatment is performed during the reproductive period, with oocytes capable of undergoing spontaneous maturation, meiosis resumption occurs in high percentages, similar to those obtained by manual defolliculation. Interestingly, results show that LH is capable of inducing GVBD in both incapable oocytes and in oocytes capable of maturing spontaneously as long as follicle cells are present, which would imply the need for a communication pathway between the oocyte and the follicle cells. This possibility was analysed by combining LH treatment with uncoupling agents such as 1-octanol or halothane. Results show that maturation induction with LH requires a cell-cell coupling, as the uncoupling of the gap junctions decreases GVBD percentages. Experiments with LH in the presence of heparin, BAPTA/AM and theophylline suggest that the hormone could induce GVBD by means of the passage of IP(3) or Ca(2+) through the gap junctions, which would increase the Ca(2+) level in the oocyte cytoplasm and activate phosphodiesterase (PDE), thus contributing to the decrease in cAMP levels and allowing meiosis resumption.

Connexin36 localization to pinealocytes in the pineal gland of mouse and rat.

PubMed

Wang, S G; Tsao, D D; Vanderpool, K G; Yasumura, T; Rash, J E; Nagy, J I

2017-06-01

Several cell types in the pineal gland are known to establish intercellular gap junctions, but the connexin constituents of those junctions have not been fully characterized. Specifically, the expression of connexin36 (Cx36) protein and mRNA has been examined in the pineal, but the identity of cells that produce Cx36 and that form Cx36-containing gap junctions has not been determined. We used immunofluorescence and freeze fracture replica immunogold labelling (FRIL) of Cx36 to investigate the cellular and subcellular localization of Cx36 in the pineal gland of adult mouse and rat. Immunofluorescence labelling of Cx36 was visualized exclusively as puncta or short immunopositive strands that were distributed throughout the pineal, and which were absent in pineal sections from Cx36 null mice. By double immunofluorescence labelling, Cx36 was localized to tryptophan hydroxylase-positive and 5-hydroxytryptamine-positive pinealocyte cell bodies and their large initial processes, including at intersections of those processes and at sites displaying a confluence of processes. Labelling for the cell junction marker zonula occludens-1 (ZO-1) either overlapped or was closely associated with labelling for Cx36. Pinealocytes thus form Cx36-containing gap junctions that also incorporate the scaffolding protein ZO-1. FRIL revealed labelling of Cx36 at ultrastructurally defined gap junctions between pinealocytes, most of which was at gap junctions having reticular, ribbon or string configurations. The results suggest that the endocrine functions of pinealocytes and their secretion of melatonin is supported by their intercellular communication via Cx36-containing gap junctions, which may now be tested by the use of Cx36 null mice. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Mixed Electrical–Chemical Synapses in Adult Rat Hippocampus are Primarily Glutamatergic and Coupled by Connexin-36

PubMed Central

Hamzei-Sichani, Farid; Davidson, Kimberly G. V.; Yasumura, Thomas; Janssen, William G. M.; Wearne, Susan L.; Hof, Patrick R.; Traub, Roger D.; Gutiérrez, Rafael; Ottersen, Ole P.; Rash, John E.

2012-01-01

Dendrodendritic electrical signaling via gap junctions is now an accepted feature of neuronal communication in mammalian brain, whereas axodendritic and axosomatic gap junctions have rarely been described. We present ultrastructural, immunocytochemical, and dye-coupling evidence for “mixed” (electrical/chemical) synapses on both principal cells and interneurons in adult rat hippocampus. Thin-section electron microscopic images of small gap junction-like appositions were found at mossy fiber (MF) terminals on thorny excrescences of CA3 pyramidal neurons (CA3pyr), apparently forming glutamatergic mixed synapses. Lucifer Yellow injected into weakly fixed CA3pyr was detected in MF axons that contacted four injected CA3pyr, supporting gap junction-mediated coupling between those two types of principal cells. Freeze-fracture replica immunogold labeling revealed diverse sizes and morphologies of connexin-36-containing gap junctions throughout hippocampus. Of 20 immunogold-labeled gap junctions, seven were large (328–1140 connexons), three of which were consistent with electrical synapses between interneurons; but nine were at axon terminal synapses, three of which were immediately adjacent to distinctive glutamate receptor-containing postsynaptic densities, forming mixed glutamatergic synapses. Four others were adjacent to small clusters of immunogold-labeled 10-nm E-face intramembrane particles, apparently representing extrasynaptic glutamate receptor particles. Gap junctions also were on spines in stratum lucidum, stratum oriens, dentate gyrus, and hilus, on both interneurons and unidentified neurons. In addition, one putative GABAergic mixed synapse was found in thin-section images of a CA3pyr, but none were found by immunogold labeling, suggesting the rarity of GABAergic mixed synapses. Cx36-containing gap junctions throughout hippocampus suggest the possibility of reciprocal modulation of electrical and chemical signals in diverse hippocampal neurons. PMID:22615687

Connexins: Synthesis, Post-Translational Modifications, and Trafficking in Health and Disease

PubMed Central

Vidal-Brime, Laia; Lynn, K. Sabrina

2018-01-01

Connexins are tetraspan transmembrane proteins that form gap junctions and facilitate direct intercellular communication, a critical feature for the development, function, and homeostasis of tissues and organs. In addition, a growing number of gap junction-independent functions are being ascribed to these proteins. The connexin gene family is under extensive regulation at the transcriptional and post-transcriptional level, and undergoes numerous modifications at the protein level, including phosphorylation, which ultimately affects their trafficking, stability, and function. Here, we summarize these key regulatory events, with emphasis on how these affect connexin multifunctionality in health and disease. PMID:29701678

Enhanced Contacts for Inverted Metamorphic Multi-Junction Solar Cells Using Carbon Nanotube Metal Matrix Composites

DTIC Science & Technology

2018-01-18

to a variety solar energy markets. For instance, micro-cracks have been shown to cause decreased power output in single- and multi-crystalline Si PV ...fingers in silicon wafer solar cells and PV modules," Solar Energy Materials and Solar Cells, vol. 108, pp. 78-81, 1// 2013. [4] T. H. Reijenga and H...AFRL-RV-PS- AFRL-RV-PS- TR-2017-0125 TR-2017-0125 ENHANCED CONTACTS FOR INVERTED METAMORPHIC MULTI-JUNCTION SOLAR CELLS USING CARBON NANOTUBE METAL

Combined chemical and structural signals of biomaterials synergistically activate cell-cell communications for improving tissue regeneration.

PubMed

Xu, Yachen; Peng, Jinliang; Dong, Xin; Xu, Yuhong; Li, Haiyan; Chang, Jiang

2017-06-01

Biomaterials are only used as carriers of cells in the conventional tissue engineering. Considering the multi-cell environment and active cell-biomaterial interactions in tissue regeneration process, in this study, structural signals of aligned electrospun nanofibers and chemical signals of bioglass (BG) ionic products in cell culture medium are simultaneously applied to activate fibroblast-endothelial co-cultured cells in order to obtain an improved skin tissue engineering construct. Results demonstrate that the combined biomaterial signals synergistically activate fibroblast-endothelial co-culture skin tissue engineering constructs through promotion of paracrine effects and stimulation of gap junctional communication between cells, which results in enhanced vascularization and extracellular matrix protein synthesis in the constructs. Structural signals of aligned electrospun nanofibers play an important role in stimulating both of paracrine and gap junctional communication while chemical signals of BG ionic products mainly enhance paracrine effects. In vivo experiments reveal that the activated skin tissue engineering constructs significantly enhance wound healing as compared to control. This study indicates the advantages of synergistic effects between different bioactive signals of biomaterials can be taken to activate communication between different types of cells for obtaining tissue engineering constructs with improved functions. Tissue engineering can regenerate or replace tissue or organs through combining cells, biomaterials and growth factors. Normally, for repairing a specific tissue, only one type of cells, one kind of biomaterials, and specific growth factors are used to support cell growth. In this study, we proposed a novel tissue engineering approach by simply using co-cultured cells and combined biomaterial signals. Using a skin tissue engineering model, we successfully proved that the combined biomaterial signals such as surface nanostructures and bioactive ions could synergistically stimulate the cell-cell communication in co-culture system through paracrine effects and gap junction activation, and regulated expression of growth factors and extracellular matrix proteins, resulting in an activated tissue engineering constructs that significantly enhanced skin regeneration. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Polarization-induced Zener tunnel diodes in GaN/InGaN/GaN heterojunctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Xiaodong; Li, Wenjun; Islam, S. M.

By the insertion of thin In{sub x}Ga{sub 1−x}N layers into Nitrogen-polar GaN p-n junctions, polarization-induced Zener tunnel junctions are studied. The reverse-bias interband Zener tunneling current is found to be weakly temperature dependent, as opposed to the strongly temperature-dependent forward bias current. This indicates tunneling as the primary reverse-bias current transport mechanism. The Indium composition in the InGaN layer is systematically varied to demonstrate the increase in the interband tunneling current. Comparing the experimentally measured tunneling currents to a model helps identify the specific challenges in potentially taking such junctions towards nitride-based polarization-induced tunneling field-effect transistors.

Tight junction physiology of pleural mesothelium

PubMed Central

Markov, Alexander G.; Amasheh, Salah

2014-01-01

Pleura consists of visceral and parietal cell layers, producing a fluid, which is necessary for lubrication of the pleural space. Function of both mesothelial cell layers is necessary for the regulation of a constant pleural fluid volume and composition to facilitate lung movement during breathing. Recent studies have demonstrated that pleural mesothelial cells show a distinct expression pattern of tight junction proteins which are known to ubiquitously determine paracellular permeability. Most tight junction proteins provide a sealing function to epithelia, but some have been shown to have a paracellular channel function or ambiguous properties. Here we provide an in-depth review of the current knowledge concerning specific functional contribution of these proteins determining transport and barrier function of pleural mesothelium. PMID:25009499

Electrochemical characterization of bilayer lipid membrane-semiconductor junctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Xiao Kang; Baral, S.; Fendler, J.H.

Three different systems of glyceryl monooleate (GMO), bilayer lipid membrane (BLM) supported semiconductor particles have been prepared and characterized. A single composition of particulate semiconductor deposited only on one side of the BLM constituted system A, two different compositions of particulate semiconductors sequentially deposited on the same side of the BLM represented system B, and two different compositions of particulate semiconductors deposited on the opposite sides of the BLM made up system C.

Connexin 39.9 Protein Is Necessary for Coordinated Activation of Slow-twitch Muscle and Normal Behavior in Zebrafish*

PubMed Central

Hirata, Hiromi; Wen, Hua; Kawakami, Yu; Naganawa, Yuriko; Ogino, Kazutoyo; Yamada, Kenta; Saint-Amant, Louis; Low, Sean E.; Cui, Wilson W.; Zhou, Weibin; Sprague, Shawn M.; Asakawa, Kazuhide; Muto, Akira; Kawakami, Koichi; Kuwada, John Y.

2012-01-01

In many tissues and organs, connexin proteins assemble between neighboring cells to form gap junctions. These gap junctions facilitate direct intercellular communication between adjoining cells, allowing for the transmission of both chemical and electrical signals. In rodents, gap junctions are found in differentiating myoblasts and are important for myogenesis. Although gap junctions were once believed to be absent from differentiated skeletal muscle in mammals, recent studies in teleosts revealed that differentiated muscle does express connexins and is electrically coupled, at least at the larval stage. These findings raised questions regarding the functional significance of gap junctions in differentiated muscle. Our analysis of gap junctions in muscle began with the isolation of a zebrafish motor mutant that displayed weak coiling at day 1 of development, a behavior known to be driven by slow-twitch muscle (slow muscle). We identified a missense mutation in the gene encoding Connexin 39.9. In situ hybridization found connexin 39.9 to be expressed by slow muscle. Paired muscle recordings uncovered that wild-type slow muscles are electrically coupled, whereas mutant slow muscles are not. The further examination of cellular activity revealed aberrant, arrhythmic touch-evoked Ca2+ transients in mutant slow muscle and a reduction in the number of muscle fibers contracting in response to touch in mutants. These results indicate that Connexin 39.9 facilitates the spreading of neuronal inputs, which is irregular during motor development, beyond the muscle cells and that gap junctions play an essential role in the efficient recruitment of slow muscle fibers. PMID:22075003

Adipocytes in both brown and white adipose tissue of adult mice are functionally connected via gap junctions: implications for Chagas disease.

PubMed

Burke, Shoshana; Nagajyothi, Fnu; Thi, Mia M; Hanani, Menachem; Scherer, Philipp E; Tanowitz, Herbert B; Spray, David C

2014-11-01

Adipose tissue serves as a host reservoir for the protozoan Trypanosoma cruzi, the causative organism in Chagas disease. Gap junctions interconnect cells of most tissues, serving to synchronize cell activities including secretion in glandular tissue, and we have previously demonstrated that gap junctions are altered in various tissues and cells infected with T. cruzi. Herein, we examined the gap junction protein connexin 43 (Cx43) expression in infected adipose tissues. Adipose tissue is the largest endocrine organ of the body and is also involved in other physiological functions. In mammals, it is primarily composed of white adipocytes. Although gap junctions are a prominent feature of brown adipocytes, they have not been explored extensively in white adipocytes, especially in the setting of infection. Thus, we examined functional coupling in both white and brown adipocytes in mice. Injection of electrical current or the dye Lucifer Yellow into adipocytes within fat tissue spread to adjacent cells, which was reduced by treatment with agents known to block gap junctions. Moreover, Cx43 was detected in both brown and white fat tissue. At thirty and ninety days post-infection, Cx43 was downregulated in brown adipocytes and upregulated in white adipocytes. Gap junction-mediated intercellular communication likely contributes to hormone secretion and other functions in white adipose tissue and to nonshivering thermogenesis in brown fat, and modulation of the coupling by T. cruzi infection is expected to impact these functions. Copyright © 2014. Published by Elsevier Masson SAS.

Innexin2 gap junctions in somatic support cells are required for cyst formation and for egg chamber formation in Drosophila.

PubMed

Mukai, Masanori; Kato, Hirotaka; Hira, Seiji; Nakamura, Katsuhiro; Kita, Hiroaki; Kobayashi, Satoru

2011-01-01

Germ cells require intimate associations with surrounding somatic cells during gametogenesis. During oogenesis, gap junctions mediate communication between germ cells and somatic support cells. However, the molecular mechanisms by which gap junctions regulate the developmental processes during oogenesis are poorly understood. We have identified a female sterile allele of innexin2 (inx2), which encodes a gap junction protein in Drosophila. In females bearing this inx2 allele, cyst formation and egg chamber formation are impaired. In wild-type germaria, Inx2 is strongly expressed in escort cells and follicle cells, both of which make close contact with germline cells. We show that inx2 function in germarial somatic cells is required for the survival of early germ cells and promotes cyst formation, probably downstream of EGFR pathway, and that inx2 function in follicle cells promotes egg chamber formation through the regulation of DE-cadherin and Bazooka (Baz) at the boundary between germ cells and follicle cells. Furthermore, genetic experiments demonstrate that inx2 interacts with the zero population growth (zpg) gene, which encodes a germline-specific gap junction protein. These results indicate a multifunctional role for Inx2 gap junctions in somatic support cells in the regulation of early germ cell survival, cyst formation and egg chamber formation. Inx2 gap junctions may mediate the transfer of nutrients and signal molecules between germ cells and somatic support cells, as well as play a role in the regulation of cell adhesion. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

GnRH Episodic Secretion Is Altered by Pharmacological Blockade of Gap Junctions: Possible Involvement of Glial Cells.

PubMed

Pinet-Charvet, Caroline; Geller, Sarah; Desroziers, Elodie; Ottogalli, Monique; Lomet, Didier; Georgelin, Christine; Tillet, Yves; Franceschini, Isabelle; Vaudin, Pascal; Duittoz, Anne

2016-01-01

Episodic release of GnRH is essential for reproductive function. In vitro studies have established that this episodic release is an endogenous property of GnRH neurons and that GnRH secretory pulses are associated with synchronization of GnRH neuron activity. The cellular mechanisms by which GnRH neurons synchronize remain largely unknown. There is no clear evidence of physical coupling of GnRH neurons through gap junctions to explain episodic synchronization. However, coupling of glial cells through gap junctions has been shown to regulate neuron activity in their microenvironment. The present study investigated whether glial cell communication through gap junctions plays a role in GnRH neuron activity and secretion in the mouse. Our findings show that Glial Fibrillary Acidic Protein-expressing glial cells located in the median eminence in close vicinity to GnRH fibers expressed Gja1 encoding connexin-43. To study the impact of glial-gap junction coupling on GnRH neuron activity, an in vitro model of primary cultures from mouse embryo nasal placodes was used. In this model, GnRH neurons possess a glial microenvironment and were able to release GnRH in an episodic manner. Our findings show that in vitro glial cells forming the microenvironment of GnRH neurons expressed connexin-43 and displayed functional gap junctions. Pharmacological blockade of the gap junctions with 50 μM 18-α-glycyrrhetinic acid decreased GnRH secretion by reducing pulse frequency and amplitude, suppressed neuronal synchronization and drastically reduced spontaneous electrical activity, all these effects were reversed upon 18-α-glycyrrhetinic acid washout.

Neuronal Target Identification Requires AHA-1-Mediated Fine-Tuning of Wnt Signaling in C. elegans

PubMed Central

Zhang, Jingyan; Li, Xia; Jevince, Angela R.; Guan, Liying; Wang, Jiaming; Hall, David H.; Huang, Xun; Ding, Mei

2013-01-01

Electrical synaptic transmission through gap junctions is a vital mode of intercellular communication in the nervous system. The mechanism by which reciprocal target cells find each other during the formation of gap junctions, however, is poorly understood. Here we show that gap junctions are formed between BDU interneurons and PLM mechanoreceptors in C. elegans and the connectivity of BDU with PLM is influenced by Wnt signaling. We further identified two PAS-bHLH family transcription factors, AHA-1 and AHR-1, which function cell-autonomously within BDU and PLM to facilitate the target identification process. aha-1 and ahr-1 act genetically upstream of cam-1. CAM-1, a membrane-bound receptor tyrosine kinase, is present on both BDU and PLM cells and likely serves as a Wnt antagonist. By binding to a cis-regulatory element in the cam-1 promoter, AHA-1 enhances cam-1 transcription. Our study reveals a Wnt-dependent fine-tuning mechanism that is crucial for mutual target cell identification during the formation of gap junction connections. PMID:23825972

Semiconductor Lasers and Their Application in Optical Fiber Communication.

ERIC Educational Resources Information Center

Agrawal, Govind P.

1985-01-01

Working principles and operating characteristics of the extremely compact and highly efficient semiconductor lasers are explained. Topics include: the p-n junction; Fabry-Perot cavity; heterostructure semiconductor lasers; materials; emission characteristics; and single-frequency semiconductor lasers. Applications for semiconductor lasers include…

Calcium oxalate crystals induces tight junction disruption in distal renal tubular epithelial cells by activating ROS/Akt/p38 MAPK signaling pathway.

PubMed

Yu, Lei; Gan, Xiuguo; Liu, Xukun; An, Ruihua

2017-11-01

Tight junction plays important roles in regulating paracellular transports and maintaining cell polarity. Calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stones, have been demonstrated to be able to cause tight junction disruption to accelerate renal cell injury. However, the cellular signaling involved in COM crystal-induced tight junction disruption remains largely to be investigated. In the present study, we proved that COM crystals induced tight junction disruption by activating ROS/Akt/p38 MAPK pathway. Treating Madin-Darby canine kidney (MDCK) cells with COM crystals induced a substantial increasing of ROS generation and activation of Akt that triggered subsequential activation of ASK1 and p38 mitogen-activated protein kinase (MAPK). Western blot revealed a significantly decreased expression of ZO-1 and occludin, two important structural proteins of tight junction. Besides, redistribution and dissociation of ZO-1 were observed by COM crystals treatment. Inhibition of ROS by N-acetyl-l-cysteine (NAC) attenuated the activation of Akt, ASK1, p38 MAPK, and down-regulation of ZO-1 and occludin. The redistribution and dissociation of ZO-1 were also alleviated by NAC treatment. These results indicated that ROS were involved in the regulation of tight junction disruption induced by COM crystals. In addition, the down-regulation of ZO-1 and occludin, the phosphorylation of ASK1 and p38 MAPK were also attenuated by MK-2206, an inhibitor of Akt kinase, implying Akt was involved in the disruption of tight junction upstream of p38 MAPK. Thus, these results suggested that ROS-Akt-p38 MAPK signaling pathway was activated in COM crystal-induced disruption of tight junction in MDCK cells.

Physiological Role of Gap-Junctional Hemichannels

PubMed Central

Quist, Arjan Pieter; Rhee, Seung Keun; Lin, Hai; Lal, Ratneshwar

2000-01-01

Hemichannels in the overlapping regions of apposing cells plasma membranes join to form gap junctions and provide an intercellular communication pathway. Hemichannels are also present in the nonjunctional regions of individual cells and their activity is gated by several agents, including calcium. However, their physiological roles are unknown. Using techniques of atomic force microscopy (AFM), fluorescent dye uptake assay, and laser confocal immunofluorescence imaging, we have examined the extracellular calcium-dependent modulation of cell volume. In response to a change in the extracellular physiological calcium concentration (1.8 to ≤1.6 mM) in an otherwise isosmotic condition, real-time AFM imaging revealed a significant and reversible increase in the volume of cells expressing gap-junctional proteins (connexins). Volume change did not occur in cells that were not expressing connexins. However, after the transient or stable transfection of connexin43, volume change did occur. The volume increase was accompanied by cytochalasin D-sensitive higher cell stiffness, which helped maintain cell integrity. These cellular physical changes were prevented by gap-junctional blockers, oleamide and β-glycyrrhetinic acid, or were reversed by returning extracellular calcium to the normal level. We conclude that nongap-junctional hemichannels regulate cell volume in response to the change in extracellular physiological calcium in an otherwise isosmotic situation. PMID:10704454

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

PubMed

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

2015-06-01

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.

Molecular Diffusion through Cyanobacterial Septal Junctions.

PubMed

Nieves-Morión, Mercedes; Mullineaux, Conrad W; Flores, Enrique

2017-01-03

Heterocyst-forming cyanobacteria grow as filaments in which intercellular molecular exchange takes place. During the differentiation of N 2 -fixing heterocysts, regulators are transferred between cells. In the diazotrophic filament, vegetative cells that fix CO 2 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. Although bacteria are frequently considered just as unicellular organisms, there are bacteria that behave as true multicellular organisms. The heterocyst-forming cyanobacteria grow as filaments in which cells communicate. Intercellular molecular exchange is thought to be mediated by septal junctions. Here, we show that intercellular transfer of fluorescent markers in the cyanobacterial filament has the physical properties of simple diffusion. Thus, cyanobacterial septal junctions are functionally analogous to metazoan gap junctions, although their molecular components appear unrelated. Like metazoan gap junctions, the septal junctions of cyanobacteria allow the rapid intercellular exchange of small molecules, without stringent selectivity. Our finding expands the repertoire of mechanisms for molecular transfer across the plasma membrane in prokaryotes. Copyright © 2017 Nieves-Morión et al.

Planar heterostructures of single-layer transition metal dichalcogenides: Composite structures, Schottky junctions, tunneling barriers, and half metals

NASA Astrophysics Data System (ADS)

Aras, Mehmet; Kılıç, ćetin; Ciraci, S.

2017-02-01

Planar composite structures formed from the stripes of transition metal dichalcogenides joined commensurately along their zigzag or armchair edges can attain different states in a two-dimensional (2D), single-layer, such as a half metal, 2D or one-dimensional (1D) nonmagnetic metal and semiconductor. Widening of stripes induces metal-insulator transition through the confinements of electronic states to adjacent stripes, that results in the metal-semiconductor junction with a well-defined band lineup. Linear bending of the band edges of the semiconductor to form a Schottky barrier at the boundary between the metal and semiconductor is revealed. Unexpectedly, strictly 1D metallic states develop in a 2D system along the boundaries between stripes, which pins the Fermi level. Through the δ doping of a narrow metallic stripe one attains a nanowire in the 2D semiconducting sheet or narrow band semiconductor. A diverse combination of constituent stripes in either periodically repeating or finite-size heterostructures can acquire critical fundamental features and offer device capacities, such as Schottky junctions, nanocapacitors, resonant tunneling double barriers, and spin valves. These predictions are obtained from first-principles calculations performed in the framework of density functional theory.

RESPONSE TO KLAUNIG, J.E. ET AL, EPIGENETIC MECHANISMS OF CHEMICAL CARCINOGENESIS

EPA Science Inventory

The article by Klaunig et al. is a comprehensive review of the general principles underlying the induction of tumors by epigenetic mechanisms. The review describes the roles of cell proliferation, loss of apoptotic function, gap junctional intercellular communication, P450 induct...

Critical role of gap junction communication, calcium and nitric oxide signaling in bystander responses to focal photodynamic injury

PubMed Central

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

2015-01-01

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 Ca2+-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. PMID:25868859

Report on Project to Characterize Multi-Junction Solar Cells in the Stratosphere using Low-Cost Balloon and Communication Technologies

NASA Technical Reports Server (NTRS)

Mirza, Ali; Sant, David; Woodyard, James R.; Johnston, Richard R.; Brown, William J.

2002-01-01

Balloon, control and communication technologies are under development in our laboratory for testing multi-junction solar cells in the stratosphere to achieve near AM0 conditions. One flight, Suntracker I, has been carried out reported earlier. We report on our efforts in preparation for a second flight, Suntracker II, that was aborted due to hardware problems. The package for Suntracker I system has been modified to include separate electronics and battery packs for the 70 centimeter and 2 meter systems. The collimator control system and motor gearboxes have been redesigned to address problems with the virtual stops and backlash. Surface mount technology on a printed circuit board was used in place of the through-hole prototype circuit in efforts to reduce weight and size, and improve reliability. A mobile base station has been constructed that includes a 35' tower with a two axis rotator and multi-element yagi antennas. Modifications in Suntracker I and the factors that lead to aborting Suntracker II are discussed.

Pair-breaking mechanisms in superconductor—normal-metal—superconductor junctions

NASA Astrophysics Data System (ADS)

Yang, H. C.; Finnemore, D. K.

1984-08-01

The critical current density Jc has been measured for superconductor—normal-metal—superconductor (S-N-S) junctions over a wide range of temperature and composition in order to determine the depairing effects of magnetic impurities. Junctions, which are in a sandwich geometry with the N layer typically 600 nm thick, show well-defined diffraction patterns indicating that the junctions are of high quality. Below 4.2 K, the temperature dependence of Jc is found to follow a modified bridge theory based on the work of Makeev et al.

Thermodynamic and achievable efficiencies for solar-driven electrochemical reduction of carbon dioxide to transportation fuels

PubMed Central

Singh, Meenesh R.; Clark, Ezra L.; Bell, Alexis T.

2015-01-01

Thermodynamic, achievable, and realistic efficiency limits of solar-driven electrochemical conversion of water and carbon dioxide to fuels are investigated as functions of light-absorber composition and configuration, and catalyst composition. The maximum thermodynamic efficiency at 1-sun illumination for adiabatic electrochemical synthesis of various solar fuels is in the range of 32–42%. Single-, double-, and triple-junction light absorbers are found to be optimal for electrochemical load ranges of 0–0.9 V, 0.9–1.95 V, and 1.95–3.5 V, respectively. Achievable solar-to-fuel (STF) efficiencies are determined using ideal double- and triple-junction light absorbers and the electrochemical load curves for CO2 reduction on silver and copper cathodes, and water oxidation kinetics over iridium oxide. The maximum achievable STF efficiencies for synthesis gas (H2 and CO) and Hythane (H2 and CH4) are 18.4% and 20.3%, respectively. Whereas the realistic STF efficiency of photoelectrochemical cells (PECs) can be as low as 0.8%, tandem PECs and photovoltaic (PV)-electrolyzers can operate at 7.2% under identical operating conditions. We show that the composition and energy content of solar fuels can also be adjusted by tuning the band-gaps of triple-junction light absorbers and/or the ratio of catalyst-to-PV area, and that the synthesis of liquid products and C2H4 have high profitability indices. PMID:26504215

Thermodynamic and achievable efficiencies for solar-driven electrochemical reduction of carbon dioxide to transportation fuels

DOE PAGES

Singh, Meenesh R.; Clark, Ezra L.; Bell, Alexis T.

2015-10-26

Thermodynamic, achievable, and realistic efficiency limits of solar-driven electrochemical conversion of water and carbon dioxide to fuels are investigated as functions of light-absorber composition and configuration, and catalyst composition. The maximum thermodynamic efficiency at 1-sun illumination for adiabatic electrochemical synthesis of various solar fuels is in the range of 32–42%. Single-, double-, and triple-junction light absorbers are found to be optimal for electrochemical load ranges of 0–0.9 V, 0.9–1.95 V, and 1.95–3.5 V, respectively. Achievable solar-to-fuel (STF) efficiencies are determined using ideal double- and triple-junction light absorbers and the electrochemical load curves for CO 2 reduction on silver and coppermore » cathodes, and water oxidation kinetics over iridium oxide. The maximum achievable STF efficiencies for synthesis gas (H 2 and CO) and Hythane (H 2 and CH 4) are 18.4% and 20.3%, respectively. Whereas the realistic STF efficiency of photoelectrochemical cells (PECs) can be as low as 0.8%, tandem PECs and photovoltaic (PV)-electrolyzers can operate at 7.2% under identical operating conditions. Finally, we show that the composition and energy content of solar fuels can also be adjusted by tuning the band-gaps of triple-junction light absorbers and/or the ratio of catalyst-to-PV area, and that the synthesis of liquid products and C 2H 4 have high profitability indices.« less

Effects of multipurpose solutions (MPS) for hydrogel contact lenses on gap-junctional intercellular communication (GJIC) in rabbit corneal keratocytes.

PubMed

Sumide, Taizo; Tsuchiya, Toshie

2003-02-15

To ensure the effects of multipurpose solutions (MPS) for hydrogel contact lenses on the cornea, the inhibitory activity of three types of MPS on corneal cells has been evaluated with the use of scrape loading and dye transfer assay (SLDT assay) and Western blotting on rabbit corneal keratocytes (RC4). In SLDT assay, MPS-A and poloxamine showed dose-dependent inhibitory activity, suggesting the inhibitory action of MPS-A and poloxamine to gap junctional intercellular communication (GJIC) in the tested cells. Moreover, after treatment with MPS-A, the GJIC was initially inhibited within 4 h, and thereafter gradually turned to an approximately 60% level of the initial value. When MPS-A was removed from the incubation media after exposure of the cells, the recovery of GJIC was time dependent and returned to approximately initial levels at 8 h. Complete recovery was established after approximately 24 h. These findings suggested that the inhibitory action of MPS-A on corneal keratocytes was reversible. This inhibition was accompanied by a decrease in the quantity of connexin-43, which is a major protein constituting the gap junctional channel of these cells, and its change in the phosphorylation state. Taken together, it was suggested that MPS-A interacts with connexin-43, inducing an inhibitory action on GJIC. (c) 2002 Wiley Periodicals, Inc.

A Novel N14Y Mutation in Connexin26 in Keratitis-Ichthyosis-Deafness Syndrome

PubMed Central

Arita, Ken; Akiyama, Masashi; Aizawa, Tomoyasu; Umetsu, Yoshitaka; Segawa, Ikuo; Goto, Maki; Sawamura, Daisuke; Demura, Makoto; Kawano, Keiichi; Shimizu, Hiroshi

2006-01-01

Connexins (Cxs) are transmembranous proteins that connect adjacent cells via channels known as gap junctions. The N-terminal 21 amino acids of Cx26 are located at the cytoplasmic side of the channel pore and are thought to be essential for the regulation of channel selectivity. We have found a novel mutation, N14Y, in the N-terminal domain of Cx26 in a case of keratitis-ichthyosis-deafness syndrome. Reduced gap junctional intercellular communication was observed in the patient’s keratinocytes by the dye transfer assay using scrape-loading methods. The effect of this mutation on molecular structure was investigated using synthetic N-terminal peptides from both wild-type and mutated Cx26. Two-dimensional 1H nuclear magnetic resonance and circular dichroism measurements demonstrated that the secondary structures of these two model peptides are similar to each other. However, several novel nuclear Overhauser effect signals appeared in the N14Y mutant, and the secondary structure of the mutant peptide was more susceptible to induction of 2,2,2-trifluoroethanol than wild type. Thus, it is likely that the N14Y mutation induces a change in local structural flexibility of the N-terminal domain, which is important for exerting the activity of the channel function, resulting in impaired gap junctional intercellular communication. PMID:16877344

Transmembrane protein PERP is a component of tessellate junctions and of other junctional and non-junctional plasma membrane regions in diverse epithelial and epithelium-derived cells.

PubMed

Franke, Werner W; Heid, Hans; Zimbelmann, Ralf; Kuhn, Caecilia; Winter-Simanowski, Stefanie; Dörflinger, Yvette; Grund, Christine; Rickelt, Steffen

2013-07-01

Protein PERP (p53 apoptosis effector related to PMP-22) is a small (21.4 kDa) transmembrane polypeptide with an amino acid sequence indicative of a tetraspanin character. It is enriched in the plasma membrane and apparently contributes to cell-cell contacts. Hitherto, it has been reported to be exclusively a component of desmosomes of some stratified epithelia. However, by using a series of newly generated mono- and polyclonal antibodies, we show that protein PERP is not only present in all kinds of stratified epithelia but also occurs in simple, columnar, complex and transitional epithelia, in various types of squamous metaplasia and epithelium-derived tumors, in diverse epithelium-derived cell cultures and in myocardial tissue. Immunofluorescence and immunoelectron microscopy allow us to localize PERP predominantly in small intradesmosomal locations and in variously sized, junction-like peri- and interdesmosomal regions ("tessellate junctions"), mostly in mosaic or amalgamated combinations with other molecules believed, to date, to be exclusive components of tight and adherens junctions. In the heart, PERP is a major component of the composite junctions of the intercalated disks connecting cardiomyocytes. Finally, protein PERP is a cobblestone-like general component of special plasma membrane regions such as the bile canaliculi of liver and subapical-to-lateral zones of diverse columnar epithelia and upper urothelial cell layers. We discuss possible organizational and architectonic functions of protein PERP and its potential value as an immunohistochemical diagnostic marker.

Current-driven thermo-magnetic switching in magnetic tunnel junctions

NASA Astrophysics Data System (ADS)

Kravets, A. F.; Polishchuk, D. M.; Pashchenko, V. A.; Tovstolytkin, A. I.; Korenivski, V.

2017-12-01

We investigate switching of magnetic tunnel junctions (MTJs) driven by the thermal effect of the transport current through the junctions. The switching occurs in a specially designed composite free layer, which acts as one of the MTJ electrodes, and is due to a current-driven ferro-to-paramagnetic Curie transition with the associated exchange decoupling within the free layer leading to magnetic reversal. We simulate the current and heat propagation through the device and show how heat focusing can be used to improve the power efficiency. The Curie-switch MTJ demonstrated in this work has the advantage of being highly tunable in terms of its operating temperature range, conveniently to or just above room temperature, which can be of technological significance and competitive with the known switching methods using spin-transfer torques.

Flexible Lamination-Fabricated Ultra-High Frequency Diodes Based on Self-Supporting Semiconducting Composite Film of Silicon Micro-Particles and Nano-Fibrillated Cellulose.

PubMed

Sani, Negar; Wang, Xin; Granberg, Hjalmar; Andersson Ersman, Peter; Crispin, Xavier; Dyreklev, Peter; Engquist, Isak; Gustafsson, Göran; Berggren, Magnus

2016-06-30

Low cost and flexible devices such as wearable electronics, e-labels and distributed sensors will make the future "internet of things" viable. To power and communicate with such systems, high frequency rectifiers are crucial components. We present a simple method to manufacture flexible diodes, operating at GHz frequencies, based on self-adhesive composite films of silicon micro-particles (Si-μPs) and glycerol dispersed in nanofibrillated cellulose (NFC). NFC, Si-μPs and glycerol are mixed in a water suspension, forming a self-supporting nanocellulose-silicon composite film after drying. This film is cut and laminated between a flexible pre-patterned Al bottom electrode and a conductive Ni-coated carbon tape top contact. A Schottky junction is established between the Al electrode and the Si-μPs. The resulting flexible diodes show current levels on the order of mA for an area of 2 mm(2), a current rectification ratio up to 4 × 10(3) between 1 and 2 V bias and a cut-off frequency of 1.8 GHz. Energy harvesting experiments have been demonstrated using resistors as the load at 900 MHz and 1.8 GHz. The diode stack can be delaminated away from the Al electrode and then later on be transferred and reconfigured to another substrate. This provides us with reconfigurable GHz-operating diode circuits.

Flexible Lamination-Fabricated Ultra-High Frequency Diodes Based on Self-Supporting Semiconducting Composite Film of Silicon Micro-Particles and Nano-Fibrillated Cellulose

PubMed Central

Sani, Negar; Wang, Xin; Granberg, Hjalmar; Andersson Ersman, Peter; Crispin, Xavier; Dyreklev, Peter; Engquist, Isak; Gustafsson, Göran; Berggren, Magnus

2016-01-01

Low cost and flexible devices such as wearable electronics, e-labels and distributed sensors will make the future “internet of things” viable. To power and communicate with such systems, high frequency rectifiers are crucial components. We present a simple method to manufacture flexible diodes, operating at GHz frequencies, based on self-adhesive composite films of silicon micro-particles (Si-μPs) and glycerol dispersed in nanofibrillated cellulose (NFC). NFC, Si-μPs and glycerol are mixed in a water suspension, forming a self-supporting nanocellulose-silicon composite film after drying. This film is cut and laminated between a flexible pre-patterned Al bottom electrode and a conductive Ni-coated carbon tape top contact. A Schottky junction is established between the Al electrode and the Si-μPs. The resulting flexible diodes show current levels on the order of mA for an area of 2 mm2, a current rectification ratio up to 4 × 103 between 1 and 2 V bias and a cut-off frequency of 1.8 GHz. Energy harvesting experiments have been demonstrated using resistors as the load at 900 MHz and 1.8 GHz. The diode stack can be delaminated away from the Al electrode and then later on be transferred and reconfigured to another substrate. This provides us with reconfigurable GHz-operating diode circuits. PMID:27357006

Flexible Lamination-Fabricated Ultra-High Frequency Diodes Based on Self-Supporting Semiconducting Composite Film of Silicon Micro-Particles and Nano-Fibrillated Cellulose

NASA Astrophysics Data System (ADS)

Sani, Negar; Wang, Xin; Granberg, Hjalmar; Andersson Ersman, Peter; Crispin, Xavier; Dyreklev, Peter; Engquist, Isak; Gustafsson, Göran; Berggren, Magnus

2016-06-01

Low cost and flexible devices such as wearable electronics, e-labels and distributed sensors will make the future “internet of things” viable. To power and communicate with such systems, high frequency rectifiers are crucial components. We present a simple method to manufacture flexible diodes, operating at GHz frequencies, based on self-adhesive composite films of silicon micro-particles (Si-μPs) and glycerol dispersed in nanofibrillated cellulose (NFC). NFC, Si-μPs and glycerol are mixed in a water suspension, forming a self-supporting nanocellulose-silicon composite film after drying. This film is cut and laminated between a flexible pre-patterned Al bottom electrode and a conductive Ni-coated carbon tape top contact. A Schottky junction is established between the Al electrode and the Si-μPs. The resulting flexible diodes show current levels on the order of mA for an area of 2 mm2, a current rectification ratio up to 4 × 103 between 1 and 2 V bias and a cut-off frequency of 1.8 GHz. Energy harvesting experiments have been demonstrated using resistors as the load at 900 MHz and 1.8 GHz. The diode stack can be delaminated away from the Al electrode and then later on be transferred and reconfigured to another substrate. This provides us with reconfigurable GHz-operating diode circuits.

Cell-to-cell communication in plants, animals, and fungi: a comparative review.

PubMed

Bloemendal, Sandra; Kück, Ulrich

2013-01-01

Cell-to-cell communication is a prerequisite for differentiation and development in multicellular organisms. This communication has to be tightly regulated to ensure that cellular components such as organelles, macromolecules, hormones, or viruses leave the cell in a precisely organized way. During evolution, plants, animals, and fungi have developed similar ways of responding to this biological challenge. For example, in higher plants, plasmodesmata connect adjacent cells and allow communication to regulate differentiation and development. In animals, two main general structures that enable short- and long-range intercellular communication are known, namely gap junctions and tunneling nanotubes, respectively. Finally, filamentous fungi have also developed specialized structures called septal pores that allow intercellular communication via cytoplasmic flow. This review summarizes the underlying mechanisms for intercellular communication in these three eukaryotic groups and discusses its consequences for the regulation of differentiation and developmental processes.

Cell-to-cell communication in plants, animals, and fungi: a comparative review

NASA Astrophysics Data System (ADS)

Bloemendal, Sandra; Kück, Ulrich

2013-01-01

Cell-to-cell communication is a prerequisite for differentiation and development in multicellular organisms. This communication has to be tightly regulated to ensure that cellular components such as organelles, macromolecules, hormones, or viruses leave the cell in a precisely organized way. During evolution, plants, animals, and fungi have developed similar ways of responding to this biological challenge. For example, in higher plants, plasmodesmata connect adjacent cells and allow communication to regulate differentiation and development. In animals, two main general structures that enable short- and long-range intercellular communication are known, namely gap junctions and tunneling nanotubes, respectively. Finally, filamentous fungi have also developed specialized structures called septal pores that allow intercellular communication via cytoplasmic flow. This review summarizes the underlying mechanisms for intercellular communication in these three eukaryotic groups and discusses its consequences for the regulation of differentiation and developmental processes.

Cadmium disorganises the scaffolding of gap and tight junction proteins in the hepatic cell line WIF B9.

PubMed

Boucherie, Sylviane; Decaens, Catherine; Verbavatz, Jean-Marc; Grosse, Brigitte; Erard, Marie; Merola, Fabienne; Cassio, Doris; Combettes, Laurent

2013-12-01

Hepatocytes, which perform the main functions of the liver, are particularly vulnerable to toxic agents such as cadmium, an environmental pollutant. To identify the molecular targets for cadmium in hepatocytes, we have studied the effects of CdCl2 on the hybrid cell line WIF-B9 that exhibits stable structural and functional hepatocytic polarity. We showed that the toxicity of CdCl2 (1 µM, 24 h) resulted in a reduction in direct intercellular communication (via gap junctions) and in an increase in paracellular permeability (decrease in the sealing of tight junctions). These effects were not related to changes in the expression of the key proteins involved, Cx32 and claudin 2, the first being constitutive of gap junctions and the second of tight junctions in this cell line. Using immunofluorescence experiments, we observed a change in the location of Cx32 and claudin 2: these two proteins were less often found in the tight junction network that closes the bile canaliculi (BC). In control cells, 'Proximity Ligation Assay' (PLA Duolink®) has confirmed in situ that molecules of claudin 2 and Cx32 are very close to each other at the BC (probably less than 16 nm). This was no longer the case after treatment with CdCl2 . Localisation of occludin and Cx32 relative to each other was not modified by CdCl2 , but CdCl2 increased the PLA signal between molecules of JAM-A and Cx32. Finally, examination of freeze-fracture replicas obtained from cultures treated with CdCl2 showed the disruption of the network of tight junctions and the depletion or the disintegration of the junctional plaques associated with tight junctions. This study demonstrates in situ the changes induced by cadmium on the organisation of cell-cell junctions and points out the importance of the association Cx32/claudin 2 for the maintenance of normal hepatocyte functions. © 2013 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

MELATONIN ENHANCES JUNCTIONAL TRANSFER IN NORMAL C3H/1OT1/2 CELLS

EPA Science Inventory

There is strong evidence that pineal melatonin is involved in controlling neoplastic processes. e have reported that physiological, but not pharmacological or subphysiological, concentrations of melatonin enhance intercellular communication in normal C3H/1OT1/2 fibroblasts. ap ju...

Role of gap junctions in the contractile response to agonists in the mesenteric artery of spontaneously hypertensive rats.

PubMed

Ma, Ke-Tao; Li, Xin-Zhi; Li, Li; Jiang, Xue-Wei; Chen, Xin-Yan; Liu, Wei-Dong; Zhao, Lei; Zhang, Zhong-Shuang; Si, Jun-Qiang

2014-02-01

To investigate the effects of hypertension on the changes in gap junctions between vascular smooth muscle cells (VSMCs) in the mesenteric artery (MA) of spontaneously hypertensive rats (SHRs). Whole-cell patch clamp, pressure myography, real-time quantitative reverse transcription PCR (qRT-PCR), western blot analysis and transmission electron microscopy were used to examine the differences in expression and function of the gap junction between MA VSMCs of SHR and control normotensive Wistar-Kyoto (WKY) rats. (1) Whole-cell patch clamp measurements showed that the membrane capacitance and conductance of in-situ MA VSMCs of SHR were significantly greater than those of WKY rats (P<0.05), suggesting enhanced gap junction coupling between MA VSMCs of SHR. (2) The administration of phenylephrine (PE) and KCl (an endothelium-independent vasoconstrictor) initiated more pronounced vasoconstriction in SHR versus WKY rats (P<0.05). Furthermore, 2-APB (a gap junction inhibitor) attenuated PE- and KCl-induced vasoconstriction, and the inhibitory effects of 2-APB were significantly greater in SHR (P<0.05). (3) The expression of connexin 45 (Cx45) mRNA and protein in the MA was greater in SHR versus WKY rats (P<0.05). The level of phosphorylated Cx43 was significantly higher in SHR versus WKY rats (P<0.05), although the expression of total Cx43 mRNA and protein in the MA was equivalent between SHR and WKY rats. Electron microscopy revealed that the gap junctions were significantly larger in SHR versus WKY rats. Increases in the expression of Cx45 and phosphorylation of Cx43 may contribute to the enhancement of communication across gap junctions between MA VSMCs of SHR, which may increase the contractile response to agonists.

Tunneling studies of compositionally modulated PB/Fe films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wawro, A.; Witek, A.; Majewski, J.

1988-01-01

Preliminary results of preparation and investigation of compositionally modulated Pb/Fe films are reported. These films have been used as electrodes in Al/Al/sub 2/O/sub 3//{kappa}(Pb/Fe) tunnel junctions and the tunnelling characteristics I-V, dV/dI and d/sup 2/V/d/I/sup 2/ vs V have been studied in dependence on the modulation period.

The Importance of Connexin Hemichannels During Chondroprogenitor Cell Differentiation in Hydrogel Versus Microtissue Culture Models

PubMed Central

Schrobback, Karsten; Klein, Travis Jacob

2015-01-01

Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell–cell communication and differentiation. This is particularly important when choosing the appropriate culture platform as well as scaffold-based strategy for clinical translation, that is, hydrogel or microtissues, for investigating differentiation of chondroprogenitor cells in cartilage tissue engineering. We, therefore, studied the influence of gap junction-mediated cell–cell communication on chondrogenesis of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and articular chondrocytes. Expanded human chondrocytes and BM-MSCs were either (re-) differentiated in micromass cell pellets or encapsulated as isolated cells in alginate hydrogels. Samples were treated with and without the gap junction inhibitor 18-α glycyrrhetinic acid (18αGCA). DNA and glycosaminoglycan (GAG) content and gene expression levels (collagen I/II/X, aggrecan, and connexin 43) were quantified at various time points. Protein localization was determined using immunofluorescence, and adenosine-5′-triphosphate (ATP) was measured in conditioned media. While GAG/DNA was higher in alginate compared with pellets for chondrocytes, there were no differences in chondrogenic gene expression between culture models. Gap junction blocking reduced collagen II and extracellular ATP in all chondrocyte cultures and in BM-MSC hydrogels. However, differentiation capacity was not abolished completely by 18αGCA. Connexin 43 levels were high throughout chondrocyte cultures and peaked only later during BM-MSC differentiation, consistent with the delayed response of BM-MSCs to 18αGCA. Alginate hydrogels and microtissues are equally suited culture platforms for the chondrogenic (re-)differentiation of expanded human articular chondrocytes and BM-MSCs. Therefore, reducing direct cell–cell contacts does not affect in vitro chondrogenesis. However, blocking gap junctions compromises cell differentiation, pointing to a prominent role for hemichannel function in this process. Therefore, scaffold design strategies that promote an increasing distance between single chondroprogenitor cells do not restrict their differentiation potential in tissue-engineered constructs. PMID:25693425

The importance of connexin hemichannels during chondroprogenitor cell differentiation in hydrogel versus microtissue culture models.

PubMed

Schrobback, Karsten; Klein, Travis Jacob; Woodfield, Tim B F

2015-06-01

Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell-cell communication and differentiation. This is particularly important when choosing the appropriate culture platform as well as scaffold-based strategy for clinical translation, that is, hydrogel or microtissues, for investigating differentiation of chondroprogenitor cells in cartilage tissue engineering. We, therefore, studied the influence of gap junction-mediated cell-cell communication on chondrogenesis of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and articular chondrocytes. Expanded human chondrocytes and BM-MSCs were either (re-) differentiated in micromass cell pellets or encapsulated as isolated cells in alginate hydrogels. Samples were treated with and without the gap junction inhibitor 18-α glycyrrhetinic acid (18αGCA). DNA and glycosaminoglycan (GAG) content and gene expression levels (collagen I/II/X, aggrecan, and connexin 43) were quantified at various time points. Protein localization was determined using immunofluorescence, and adenosine-5'-triphosphate (ATP) was measured in conditioned media. While GAG/DNA was higher in alginate compared with pellets for chondrocytes, there were no differences in chondrogenic gene expression between culture models. Gap junction blocking reduced collagen II and extracellular ATP in all chondrocyte cultures and in BM-MSC hydrogels. However, differentiation capacity was not abolished completely by 18αGCA. Connexin 43 levels were high throughout chondrocyte cultures and peaked only later during BM-MSC differentiation, consistent with the delayed response of BM-MSCs to 18αGCA. Alginate hydrogels and microtissues are equally suited culture platforms for the chondrogenic (re-)differentiation of expanded human articular chondrocytes and BM-MSCs. Therefore, reducing direct cell-cell contacts does not affect in vitro chondrogenesis. However, blocking gap junctions compromises cell differentiation, pointing to a prominent role for hemichannel function in this process. Therefore, scaffold design strategies that promote an increasing distance between single chondroprogenitor cells do not restrict their differentiation potential in tissue-engineered constructs.

Gap Junction Intercellular Communication Mediates Ammonia-Induced Neurotoxicity.

PubMed

Bobermin, Larissa Daniele; Arús, Bernardo Assein; Leite, Marina Concli; Souza, Diogo Onofre; Gonçalves, Carlos-Alberto; Quincozes-Santos, André

2016-02-01

Astrocytes are important brain targets of ammonia, a neurotoxin implicated in the development of hepatic encephalopathy. During hyperammonemia, the pivotal role of astrocytes in brain function and homeostasis is impaired. These cells are abundantly interconnected by gap junctions (GJ), which are intercellular channels that allow the exchange of signaling molecules and metabolites. This communication may also increase cellular vulnerability during injuries, while GJ uncoupling could limit the extension of a lesion. Therefore, the current study was performed to investigate whether astrocyte coupling through GJ contributes to ammonia-induced cytotoxicity. We found that carbenoxolone (CBX), an effective GJ blocker, prevented the following effects induced by ammonia in astrocyte primary cultures: (1) decrease in cell viability and membrane integrity; (2) increase in reactive oxygen species production; (3) decrease in GSH intracellular levels; (4) GS activity; (5) pro-inflammatory cytokine release. On the other hand, CBX had no effect on C6 astroglial cells, which are poorly coupled via GJ. To our knowledge, this study provides the first evidence that GJ play a role in ammonia-induced cytotoxicity. Although more studies in vivo are required to confirm our hypothesis, our data suggest that GJ communication between astrocytes may transmit damage signals and excitotoxic components from unhealthy to normal cells, thereby contributing to the propagation of the neurotoxicity of ammonia.

Gap junctional intercellular communication is required to maintain embryonic stem cells in a non-differentiated and proliferative state.

PubMed

Todorova, Mariana G; Soria, Bernat; Quesada, Ivan

2008-02-01

Pluripotent embryonic stem (ES) cells are capable of maintaining a self-renewal state and have the potential to differentiate into derivatives of all three embryonic germ layers. Despite their importance in cell therapy and developmental biology, the mechanisms whereby ES cells remain in a proliferative and pluripotent state are still not fully understood. Here we establish a critical role of gap junctional intercellular communication (GJIC) and connexin43 (Cx43) in both processes. Pharmacological blockers of GJIC and Cx43 down-regulation by small interfering RNA (siRNA) caused a profound inhibitory effect on GJIC, as evidenced by experiments of fluorescence recovery after photobleaching. This deficient intercellular communication in ES cells induced a loss of their pluripotent state, which was manifested in morphological changes, a decrease in alkaline phosphatase activity, Oct-3/4 and Nanog expression, as well as an up-regulation of several differentiation markers. A decrease in the proliferation rate was also detected. Under these conditions, the formation of embryoid bodies from mouse ES cells was impaired, although this inhibition was reversible upon restoration of GJIC. Our findings define a major function of GJIC in the regulation of self-renewal and maintenance of pluripotency in ES cells. (c) 2007 Wiley-Liss, Inc.

Cell junction dynamics in the testis: Sertoli-germ cell interactions and male contraceptive development.

PubMed

Cheng, C Yan; Mruk, Dolores D

2002-10-01

Spermatogenesis is an intriguing but complicated biological process. However, many studies since the 1960s have focused either on the hormonal events of the hypothalamus-pituitary-testicular axis or morphological events that take place in the seminiferous epithelium. Recent advances in biochemistry, cell biology, and molecular biology have shifted attention to understanding some of the key events that regulate spermatogenesis, such as germ cell apoptosis, cell cycle regulation, Sertoli-germ cell communication, and junction dynamics. In this review, we discuss the physiology and biology of junction dynamics in the testis, in particular how these events affect interactions of Sertoli and germ cells in the seminiferous epithelium behind the blood-testis barrier. We also discuss how these events regulate the opening and closing of the blood-testis barrier to permit the timely passage of preleptotene and leptotene spermatocytes across the blood-testis barrier. This is physiologically important since developing germ cells must translocate across the blood-testis barrier as well as traverse the seminiferous epithelium during their development. We also discuss several available in vitro and in vivo models that can be used to study Sertoli-germ cell anchoring junctions and Sertoli-Sertoli tight junctions. An in-depth survey in this subject has also identified several potential targets to be tackled to perturb spermatogenesis, which will likely lead to the development of novel male contraceptives.

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

PubMed Central

Takeuchi, Hideyuki; Suzumura, Akio

2014-01-01

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. PMID:25228858

Role of Non-Myocyte Gap Junctions and Connexin Hemichannels in Cardiovascular Health and Disease: Novel Therapeutic Targets?

PubMed

Johnson, Robert D; Camelliti, Patrizia

2018-03-15

The heart is a complex organ composed of multiple cell types, including cardiomyocytes and different non-myocyte populations, all working closely together to determine the hearts properties and maintain normal cardiac function. Connexins are abundantly expressed proteins that form plasma membrane hemichannels and gap junctions between cells. Gap junctions are intracellular channels that allow for communication between cells, and in the heart they play a crucial role in cardiac conduction by coupling adjacent cardiomyocytes. Connexins are expressed in both cardiomyocytes and non-myocytes, including cardiac fibroblasts, endothelial cells, and macrophages. Non-myocytes are the largest population of cells in the heart, and therefore it is important to consider what roles connexins, hemichannels, and gap junctions play in these cell types. The aim of this review is to provide insight into connexin-based signalling in non-myocytes during health and disease, and highlight how targeting these proteins could lead to the development of novel therapies. We conclude that connexins in non-myocytes contribute to arrhythmias and adverse ventricular remodelling following myocardial infarction, and are associated with the initiation and development of atherosclerosis. Therefore, therapeutic interventions targeting these connexins represent an exciting new research avenue with great potential.

Low Al-composition p-GaN/Mg-doped Al0.25Ga0.75N/n+-GaN polarization-induced backward tunneling junction grown by metal-organic chemical vapor deposition on sapphire substrate

PubMed Central

Zhang, Kexiong; Liang, Hongwei; Liu, Yang; Shen, Rensheng; Guo, Wenping; Wang, Dongsheng; Xia, Xiaochuan; Tao, Pengcheng; Yang, Chao; Luo, Yingmin; Du, Guotong

2014-01-01

Low Al-composition p-GaN/Mg-doped Al0.25Ga0.75N/n+-GaN polarization-induced backward tunneling junction (PIBTJ) was grown by metal-organic chemical vapor deposition on sapphire substrate. A self-consistent solution of Poisson-Schrödinger equations combined with polarization-induced theory was used to model PIBTJ structure, energy band diagrams and free carrier concentrations distribution. The PIBTJ displays reliable and reproducible backward tunneling with a current density of 3 A/cm2 at the reverse bias of −1 V. The absence of negative differential resistance behavior of PIBTJ at forward bias can mainly be attributed to the hole compensation centers, including C, H and O impurities, accumulated at the p-GaN/Mg-doped AlGaN heterointerface. PMID:25205042

Low Al-composition p-GaN/Mg-doped Al0.25Ga0.75N/n+-GaN polarization-induced backward tunneling junction grown by metal-organic chemical vapor deposition on sapphire substrate.

PubMed

Zhang, Kexiong; Liang, Hongwei; Liu, Yang; Shen, Rensheng; Guo, Wenping; Wang, Dongsheng; Xia, Xiaochuan; Tao, Pengcheng; Yang, Chao; Luo, Yingmin; Du, Guotong

2014-09-10

Low Al-composition p-GaN/Mg-doped Al0.25Ga0.75N/n(+)-GaN polarization-induced backward tunneling junction (PIBTJ) was grown by metal-organic chemical vapor deposition on sapphire substrate. A self-consistent solution of Poisson-Schrödinger equations combined with polarization-induced theory was used to model PIBTJ structure, energy band diagrams and free carrier concentrations distribution. The PIBTJ displays reliable and reproducible backward tunneling with a current density of 3 A/cm(2) at the reverse bias of -1 V. The absence of negative differential resistance behavior of PIBTJ at forward bias can mainly be attributed to the hole compensation centers, including C, H and O impurities, accumulated at the p-GaN/Mg-doped AlGaN heterointerface.

Novel Photon-Counting Detectors for Free-Space Communication

NASA Technical Reports Server (NTRS)

Krainak, M. A.; Yang, G.; Sun, X.; Lu, W.; Merritt, S.; Beck, J.

2016-01-01

We present performance data for novel photon-counting detectors for free space optical communication. NASA GSFC is testing the performance of two types of novel photon-counting detectors 1) a 2x8 mercury cadmium telluride (HgCdTe) avalanche array made by DRS Inc., and a 2) a commercial 2880-element silicon avalanche photodiode (APD) array. We present and compare dark count, photon-detection efficiency, wavelength response and communication performance data for these detectors. We successfully measured real-time communication performance using both the 2 detected-photon threshold and AND-gate coincidence methods. Use of these methods allows mitigation of dark count, after-pulsing and background noise effects. The HgCdTe APD array routinely demonstrated photon detection efficiencies of greater than 50% across 5 arrays, with one array reaching a maximum PDE of 70%. We performed high-resolution pixel-surface spot scans and measured the junction diameters of its diodes. We found that decreasing the junction diameter from 31 micrometers to 25 micrometers doubled the e- APD gain from 470 for an array produced in the year 2010 to a gain of 1100 on an array delivered to NASA GSFC recently. The mean single-photon SNR was over 12 and the excess noise factors measurements were 1.2-1.3. The commercial silicon APD array exhibited a fast output with rise times of 300 ps and pulse widths of 600 ps. On-chip individually filtered signals from the entire array were multiplexed onto a single fast output.

Novel Photon-Counting Detectors for Free-Space Communication

NASA Technical Reports Server (NTRS)

Krainak, Michael A.; Yang, Guan; Sun, Xiaoli; Lu, Wei; Merritt, Scott; Beck, Jeff

2016-01-01

We present performance data for novel photon counting detectors for free space optical communication. NASA GSFC is testing the performance of three novel photon counting detectors 1) a 2x8 mercury cadmium telluride avalanche array made by DRS Inc. 2) a commercial 2880 silicon avalanche photodiode array and 3) a prototype resonant cavity silicon avalanche photodiode array. We will present and compare dark count, photon detection efficiency, wavelength response and communication performance data for these detectors. We discuss system wavelength trades and architectures for optimizing overall communication link sensitivity, data rate and cost performance. The HgCdTe APD array has photon detection efficiencies of greater than 50 were routinely demonstrated across 5 arrays, with one array reaching a maximum PDE of 70. High resolution pixel-surface spot scans were performed and the junction diameters of the diodes were measured. The junction diameter was decreased from 31 m to 25 m resulting in a 2x increase in e-APD gain from 470 on the 2010 array to 1100 on the array delivered to NASA GSFC. Mean single photon SNRs of over 12 were demonstrated at excess noise factors of 1.2-1.3.The commercial silicon APD array has a fast output with rise times of 300ps and pulse widths of 600ps. Received and filtered signals from the entire array are multiplexed onto this single fast output. The prototype resonant cavity silicon APD array is being developed for use at 1 micron wavelength.

Regulation of gap junction channels and hemichannels by phosphorylation and redox changes: a revision.

PubMed

Pogoda, Kristin; Kameritsch, Petra; Retamal, Mauricio A; Vega, José L

2016-05-24

Post-translational modifications of connexins play an important role in the regulation of gap junction and hemichannel permeability. The prerequisite for the formation of functional gap junction channels is the assembly of connexin proteins into hemichannels and their insertion into the membrane. Hemichannels can affect cellular processes by enabling the passage of signaling molecules between the intracellular and extracellular space. For the intercellular communication hemichannels from one cell have to dock to its counterparts on the opposing membrane of an adjacent cell to allow the transmission of signals via gap junctions from one cell to the other. The controlled opening of hemichannels and gating properties of complete gap junctions can be regulated via post-translational modifications of connexins. Not only channel gating, but also connexin trafficking and assembly into hemichannels can be affected by post-translational changes. Recent investigations have shown that connexins can be modified by phosphorylation/dephosphorylation, redox-related changes including effects of nitric oxide (NO), hydrogen sulfide (H2S) or carbon monoxide (CO), acetylation, methylation or ubiquitination. Most of the connexin isoforms are known to be phosphorylated, e.g. Cx43, one of the most studied connexin at all, has 21 reported phosphorylation sites. In this review, we provide an overview about the current knowledge and relevant research of responsible kinases, connexin phosphorylation sites and reported effects on gap junction and hemichannel regulation. Regarding the effects of oxidants we discuss the role of NO in different cell types and tissues and recent studies about modifications of connexins by CO and H2S.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zakhidov, A.A.; Yoshino, K.

Composites of fullerene C{sub 60} with conjugated polymers (CP) like polyalkylthiophene (PAT) and polyphenylene vinylene derivative (OO-PPV) have earlier demonstrated intensive charge transfer upon photoexcitation. Doping of CP/C{sub 60} composites by A metal vapors (A=K,Rb) is aimed at C{sub 60} induced SC, in which electrons of CP chains may participate in SC pairing, induced via hybridization with C{sub 60} molecules. We have found an SC phase experimentally both in PAT. (C{sub 60}) {sub y}K{sub x} and OO.PPV (C{sub 60}){sub y}K{sub x} by a sensitive method of low field microwave absorption (LFMA), and proved by SQUID. The SCT{sub c} ranges frommore » 12 to 17 K, depending on y and x. This SC phase shows a granular behavior in LFMA, and thus originates from SC A{sub 3}C{sub 60} clusters weakly linked by Josephson junctions. True C{sub 60} induced SC might be masked by granular A{sub 3}C{sub 60}. Anomalous LFMA and paramagnetic Meissner effects observed in SQUID, indicate the existence of Josephson {pi}-junctions. CP is apparently involved in SC via spin carrying polarons P in CP chains, which play a role of {pi}-junctions. Strategies for further search of C{sub 60} induced SC are discussed.« less

Current-voltage characteristics and electroresistance in LaMnO3-δ/La0.7Ca0.3MnO3/LaAlO3 thin film composites.

PubMed

Gadani, Keval; Keshvani, M J; Rajyaguru, Bhargav; Dhruv, Davit; Kataria, B R; Joshi, A D; Asokan, K; Shah, N A; Solanki, P S

2017-11-08

In this communication, we report results of the electrical transport properties across the interface of composites consisting of n-type LaMnO 3-δ (LMO) and p-type La 0.7 Ca 0.3 MnO 3 (LCMO) manganites grown on LaAlO 3 (LAO) single crystalline substrates using low cost wet chemical solution deposition (CSD) and sophisticated, well-controlled dry chemical vapor deposition (CVD) chemical techniques. The XRD ϕ-scan studies reveal the single crystalline nature of both bilayered composites, with parallel epitaxial growth of LMO and LCMO layers onto the LAO substrate. The valence states of Mn ions in both layers of both composites were identified by performing X-ray photoelectron spectroscopy (XPS). The I-V characteristics of the LMO/LCMO interfaces show strong backward diode-like behavior at higher applied voltages well above the crossover voltage (V NB ). Below V NB , the interfaces demonstrate normal diode-like characteristics throughout the studied temperature range. The electric field-induced modulation of the LMO/LCMO junction resistance of the interfaces has been observed. Electric field-dependent electroresistance (ER) modifications at different temperatures have also been studied. The electrical transport properties have been discussed in the context of various mechanisms, such as charge injection, tunneling, depletion region modification and thermal processes across the interface. The effects of structurally and chemically developed sharp interfaces between the LMO and LCMO layers on the transport properties of the presently studied bilayered thin film composites have been discussed on the basis of correlation between the physicochemical characterization and charge transport behavior. A comparison of different aspects of the transport properties has been presented in the context of the structural strain and crystallinity of the composites grown using both wet and dry chemical techniques.

Spatial nonuniformity in resistive-switching memory effects of NiO.

PubMed

Oka, Keisuke; Yanagida, Takeshi; Nagashima, Kazuki; Kanai, Masaki; Kawai, Tomoji; Kim, Jin-Soo; Park, Bae Ho

2011-08-17

Electrically driven resistance change phenomenon in metal/NiO/metal junctions, so-called resistive switching (RS), is a candidate for next-generation universal nonvolatile memories. However, the knowledge as to RS mechanisms is unfortunately far from comprehensive, especially the spatial switching location, which is crucial information to design reliable devices. In this communication, we demonstrate the identification of the spatial switching location of bipolar RS by introducing asymmetrically passivated planar NiO nanowire junctions. We have successfully identified that the bipolar RS in NiO occurs near the cathode rather than the anode. This trend can be interpreted in terms of an electrochemical redox model based on ion migration and p-type conduction.

Disruption of gap junctional intercellular communication by antibiotic gentamicin is associated with aberrant localization of occludin, N-cadherin, connexin 43, and vimentin in SerW3 Sertoli cells in vitro.

PubMed

Bekheet, Souad H M; Stahlmann, Ralf

2009-09-01

Spermatogenesis is a very complex process by which male germ cells differentiate into mature spermatozoa. The sophisticated communication network that controls spermatogenesis can be derailed so that dysfunction of one cell type propagates to all types as a cascade. This accounts for the particular vulnerability of the testis to environmental factors such as drugs and xenobiotics. Sertoli cells play an important role in protecting developing germ cells by forming a physiological barrier, limiting exposure to potentially toxic substrates, or conversely, facilitating uptake of xenobiotics within the testis. In this study, cells from the rat Sertoli line (SerW3) were incubated for 3, 6 and 9 subsequent days in serum free DMEM (SFDM) composed of DMEM supplemented with three different concentrations of antibiotic gentamicin (10, 30, and 100 μg). The effect of the three different concentrations of this antibiotic was determined on Sertoli cell-cell interaction through impaired expression of their constitutive tight junction proteins as early targets for different toxicants in vitro by immunochemistry analysis. The Sertoli SerW3 cell line illustrated the cytotoxicity of GS, as the intercellular junction proteins such as occludin, N-cadherin, connexin 43, and vimentin were delocalized from the membrane to the cytoplasmic compartment during exposure to the antibiotic. This study underlines the potential deleterious effects of the routine use of antibiotics during continuous cell culture.

Gap junction-mediated calcium waves define communication networks among murine postnatal neural progenitor cells.

PubMed

Lacar, Benjamin; Young, Stephanie Z; Platel, Jean-Claude; Bordey, Angélique

2011-12-01

In the postnatal neurogenic niche, two populations of astrocyte-like cells (B cells) persist, one acting as neural progenitor cells (NPCs, B1 cells) and one forming a structural boundary between the neurogenic niche and the striatum (B2 cells, niche astrocytes). Despite being viewed as two distinct entities, we found that B1 and B2 cells express the gap junction protein connexin 43 and display functional coupling involving 50-60 cells. Using neonatal electroporation to label slowly cycling radial glia-derived B1 cells, which send a basal process onto blood vessels, we further confirmed dye coupling between NPCs. To assess the functionality of the coupling, we used calcium imaging in a preparation preserving the three-dimensional architecture of the subventricular zone. Intercellular calcium waves were observed among B cells. These waves travelled bidirectionally between B1 and B2 cells and propagated on blood vessels. Inter-B-cell calcium waves were absent in the presence of a gap junction blocker but persisted with purinergic receptor blockers. These findings show that privileged microdomains of communication networks exist among NPCs and niche astrocytes. Such functional coupling between these two cell types suggests that niche astrocytes do not merely have a structural role, but may play an active role in shaping the behavior of NPCs. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Thermal cycling effects on adhesion of resin-bovine enamel junction among different composite resins.

PubMed

Chen, Wen-Cheng; Ko, Chia-Ling; Wu, Hui-Yu; Lai, Pei-Ling; Shih, Chi-Jen

2014-10-01

Thermal cycling is used to mimic the changes in oral cavity temperature experienced by composite resins when used clinically. The purpose of this study is to assess the thermal cycling effects of in-house produced composite resin on bonding strength. The dicalcium phosphate anhydrous filler surfaces are modified using nanocrystals and silanization (w/NP/Si). The resin is compared with commercially available composite resins Filtek Z250, Z350, and glass ionomer restorative material GIC Fuji-II LC (control). Different composite resins were filled into the dental enamel of bovine teeth. The bond force and resin-enamel junction graphical structures of the samples were determined after thermal cycling between 5 and 55°C in deionized water for 600 cycles. After thermal cycling, the w/NP/Si 30wt%, 50wt% and Filtek Z250, Z350 groups showed higher shear forces than glass ionomer GIC, and w/NP/Si 50wt% had the highest shear force. Through SEM observations, more of the fillings with w/NP/Si 30wt% and w/NP/Si 50wt% groups flowed into the enamel tubule, forming closed tubules with the composite resins. The push-out force is proportional to the resin flow depth and uniformity. The push-out tubule pore and resin shear pattern is the most uniform and consistent in the w/NP/Si 50wt% group. Accordingly, this developed composite resin maintains great mechanical properties after thermal cycling. Thus, it has the potential to be used in a clinical setting when restoring non-carious cervical lesions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Si-Ge-Sn alloys with 1.0 eV gap for CPV multijunction solar cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roucka, Radek, E-mail: radek@translucentinc.com; Clark, Andrew; Landini, Barbara

2015-09-28

Si-Ge-Sn ternary group IV alloys offer an alternative to currently used 1.0 eV gap materials utilized in multijunction solar cells. The advantage of Si-Ge-Sn is the ability to vary both the bandgap and lattice parameter independently. We present current development in fabrication of Si-Ge-Sn alloys with gaps in the 1.0 eV range. Produced material exhibits excellent structural properties, which allow for integration with existing III-V photovoltaic cell concepts. Time dependent room temperature photoluminescence data demonstrate that these materials have long carrier lifetimes. Absorption tunable by compositional changes is observed. As a prototype device set utilizing the 1 eV Si-Ge-Sn junction,more » single junction Si-Ge-Sn device and triple junction device with Si-Ge-Sn subcell have been fabricated. The resulting I-V and external quantum efficiency data show that the Si-Ge-Sn junction is fully functional and the performance is comparable to other 1.0 eV gap materials currently used.« less

Unveiling the composite structures of emissive consolidated p-i-n junction nanocells for white light emission.

PubMed

Lee, Kyu Seung; Shim, Jaeho; Lee, Hyunbok; Yim, Sang-Youp; Angadi, Basavaraj; Lim, Byungkwon; Son, Dong Ick

2018-06-08

Hybrid organic-Red-Green-Blue (RGB) color quantum dots were incorporated into consolidated p(polymer)-i(RGB quantum dots)-n(small molecules) junction structures to fabricate a single active layer for a light emitting diode device for white electroluminescence. The semiconductor RGB quantum dots, as an intrinsic material, were electrostatically bonded between functional groups of the p-type polymer organic material core surface and the n-type small molecular organic material shell surface. The ZnCdSe/ZnS and CdSe/ZnS quantum dots distributed uniformly and isotropically surrounding the polymer core which in turn was surrounded by small molecular organic materials. In the present study, we have identified the mechanisms of chemical synthesis and interactions of the p-i-n junction nanocell structure through modeling studies by DFT calculations. We have also investigated optical, structural and electrical properties along with the carrier transport mechanism of the light emitting diodes which have a single active layer of consolidated p-i-n junction nanocells for white electroluminescence.

Synthesis and photocatalytic activity of p–n junction CeO2/Co3O4 photocatalyst for the removal of various dyes from wastewater

NASA Astrophysics Data System (ADS)

Tang, Yuanzheng; Zhang, Meng; Wu, Zhengying; Chen, Zhigang; Liu, Chengbao; Lin, Yun; Chen, Feng

2018-04-01

CeO2, Co3O4, and Co3O4/CeO2 composites are successfully synthesized by a simple coprecipitation method. X-ray powder diffraction (XRD) and Fourier transform infrared (FTIR) results indicate that the CeO2, Co3O4, and Co3O4/CeO2 precursors sintered at 500 °C has good crystallization. The cerium nitrate introduced into cobalt nitrate precursor solution improved the surface morphology and photocatalytic activity of Co3O4 significantly. The photo-degradation of methylene blue (MB), xylenol orange (XO), methyl orange (MO), and methyl red (MR) catalyzed by prepared nanocomposites were studied under visible light irradiation. Photocatalytic experiment results indicate that the photocatalytic activity of Co3O4/CeO2 composites for degradation of various dyes highly depend on pH value. The optimum conditions for the photocatalytic experiments of Co3O4/CeO2 composites were determined to be as follows: dye concentration, 50 mg L‑1, and catalyst concentration, 50 mg L‑1. The excellent photocatalytic activity of the p–n junction Co3O4/CeO2 composites can be ascribed to the ·O2‑ radicals and h+.

Expression of gap junction protein connexin 43 in bovine urinary bladder tumours.

PubMed

Corteggio, A; Florio, J; Roperto, F; Borzacchiello, G

2011-01-01

The aetiopathogenesis of urinary bladder tumours in cattle involves prolonged ingestion of bracken fern and infection by bovine papillomavirus types 1 or 2 (BPV-1/2). The oncogenic activity of BPV is largely associated with the major oncoprotein E5. Gap junctions are the only communicating junctions found in animal tissues and are composed of proteins known as connexins. Alterations in connexin expression have been associated with oncogenesis. The present study investigated biochemically and immunohistochemically the expression of connexin 43 in samples of normal (n=2), dysplastic (n=3) and neoplastic (n=23) bovine urothelium. The tumours included 10 carcinomas in situ, five papillary urothelial carcinomas and eight invasive urothelial carcinomas. Normal and dysplastic urothelium had membrane expression of connexin 43, but this was reduced in samples of carcinoma in situ. Papillary urothelial carcinomas showed moderate cytoplasmic and membrane labelling, while invasive carcinoma showed loss of connexin 43 expression. Copyright © 2010 Elsevier Ltd. All rights reserved.

Gap junctional communication in the male reproductive system.

PubMed

Pointis, Georges; Fiorini, Céline; Defamie, Norah; Segretain, Dominique

2005-12-20

Male fertility is a highly controlled process that allows proliferation, meiosis and differentiation of male germ cells in the testis, final maturation in the epididymis and also requires functional male accessory glands: seminal vesicles, prostate and corpus cavernosum. In addition to classical endocrine and paracrine controls, mainly by gonadotropins LH and FSH and steroids, there is now strong evidence that all these processes are dependent upon the presence of homocellular or heterocellular junctions, including gap junctions and their specific connexins (Cxs), between the different cell types that structure the male reproductive tract. The present review is focused on the identification of Cxs, their distribution in the testis and in different structures of the male genital tract (epididymis, seminal vesicle, prostate, corpus cavernosum), their crucial role in the control of spermatogenesis and their implication in the function of the male accessory glands, including functional smooth muscle tone. Their potential dysfunctions in some testis (spermatogenic arrest, seminoma) and prostate (benign hyperplasia, adenocarcinoma) diseases and in the physiopathology of the human erectile function are also discussed.

An electrostatic mechanism for Ca2+-mediated regulation of gap junction channels

PubMed Central

Bennett, Brad C.; Purdy, Michael D.; Baker, Kent A.; Acharya, Chayan; McIntire, William E.; Stevens, Raymond C.; Zhang, Qinghai; Harris, Andrew L.; Abagyan, Ruben; Yeager, Mark

2016-01-01

Gap junction channels mediate intercellular signalling that is crucial in tissue development, homeostasis and pathologic states such as cardiac arrhythmias, cancer and trauma. To explore the mechanism by which Ca2+ blocks intercellular communication during tissue injury, we determined the X-ray crystal structures of the human Cx26 gap junction channel with and without bound Ca2+. The two structures were nearly identical, ruling out both a large-scale structural change and a local steric constriction of the pore. Ca2+ coordination sites reside at the interfaces between adjacent subunits, near the entrance to the extracellular gap, where local, side chain conformational rearrangements enable Ca2+chelation. Computational analysis revealed that Ca2+-binding generates a positive electrostatic barrier that substantially inhibits permeation of cations such as K+ into the pore. Our results provide structural evidence for a unique mechanism of channel regulation: ionic conduction block via an electrostatic barrier rather than steric occlusion of the channel pore. PMID:26753910

Mouse rods signal through gap junctions with cones.

PubMed

Asteriti, Sabrina; Gargini, Claudia; Cangiano, Lorenzo

2014-01-01

Rod and cone photoreceptors are coupled by gap junctions (GJs), relatively large channels able to mediate both electrical and molecular communication. Despite their critical location in our visual system and evidence that they are dynamically gated for dark/light adaptation, the full impact that rod-cone GJs can have on cone function is not known. We recorded the photovoltage of mouse cones and found that the initial level of rod input increased spontaneously after obtaining intracellular access. This process allowed us to explore the underlying coupling capacity to rods, revealing that fully coupled cones acquire a striking rod-like phenotype. Calcium, a candidate mediator of the coupling process, does not appear to be involved on the cone side of the junctional channels. Our findings show that the anatomical substrate is adequate for rod-cone coupling to play an important role in vision and, possibly, in biochemical signaling among photoreceptors. DOI: http://dx.doi.org/10.7554/eLife.01386.001.

An intercellular polyamine transfer via gap junctions regulates proliferation and response to stress in epithelial cells

PubMed Central

Desforges, Bénédicte; Curmi, Patrick A.; Bounedjah, Ouissame; Nakib, Samir; Hamon, Loic; De Bandt, Jean-Pascal; Pastré, David

2013-01-01

In the organism, quiescent epithelial cells have the potential to resume cycling as a result of various stimuli, including wound healing or oxidative stress. Because quiescent cells have a low polyamine level, resuming their growth requires an increase of their intracellular polyamine levels via de novo polyamine synthesis or their uptake from plasma. Another alternative, explored here, is an intercellular exchange with polyamine-rich cycling cells via gap junctions. We show that polyamines promote gap junction communication between proliferating cells by promoting dynamical microtubule plus ends at the cell periphery and thus allow polyamine exchange between cells. In this way, cycling cells favor regrowth in adjacent cells deprived of polyamines. In addition, intercellular interactions mediated by polyamines can coordinate the translational response to oxidative stress through the formation of stress granules. Some putative in vivo consequences of polyamine-mediated intercellular interactions are also discussed regarding cancer invasiveness and tissue regeneration. PMID:23515223

Mouse rods signal through gap junctions with cones

PubMed Central

Asteriti, Sabrina; Gargini, Claudia; Cangiano, Lorenzo

2014-01-01

Rod and cone photoreceptors are coupled by gap junctions (GJs), relatively large channels able to mediate both electrical and molecular communication. Despite their critical location in our visual system and evidence that they are dynamically gated for dark/light adaptation, the full impact that rod–cone GJs can have on cone function is not known. We recorded the photovoltage of mouse cones and found that the initial level of rod input increased spontaneously after obtaining intracellular access. This process allowed us to explore the underlying coupling capacity to rods, revealing that fully coupled cones acquire a striking rod-like phenotype. Calcium, a candidate mediator of the coupling process, does not appear to be involved on the cone side of the junctional channels. Our findings show that the anatomical substrate is adequate for rod–cone coupling to play an important role in vision and, possibly, in biochemical signaling among photoreceptors. DOI: http://dx.doi.org/10.7554/eLife.01386.001 PMID:24399457

Bibliography of Soviet Laser Developments, No. 18, October - December 1974

DTIC Science & Technology

1975-04-25

IIV Lasers, Laser Theory , Laser Biological Effects, Laser Communications, Laser Computer Technology, Holography, Laser Chemical Effects...spectros.copy of laser materials; ultrashort pulse generation; crystal growing; theoretical aspects of advanced lasers; and general laser theory Laser...Semiconductor: Mixed Junction 5 6. Semiconductor: Heterojunction ^ 7. Semiconductor: Theory 8. Nd:Glass B. Liquid Lasers 1

Cell-derived microparticles: new targets in the therapeutic management of disease.

PubMed

Roseblade, Ariane; Luk, Frederick; Rawling, Tristan; Ung, Alison; Grau, Georges E R; Bebawy, Mary

2013-01-01

Intercellular communication is essential to maintain vital physiological activities and to regulate the organism's phenotype. There are a number of ways in which cells communicate with one another. This can occur via autocrine signaling, endocrine signaling or by the transfer of molecular mediators across gap junctions. More recently communication via microvesicular shedding has gained important recognition as a significant pathway by which cells can coordinate the spread and dominance of selective traits within a population. Through this communication apparatus, cells can now acquire and secure a survival advantage, particularly in the context of malignant disease. This review aims to highlight some of the functions and implications of microparticles in physiology of various disease states, and present a novel therapeutic strategy through the regulation of microparticle production.

Development and evaluation of CAHPS survey items assessing how well healthcare providers address health literacy.

PubMed

Weidmer, Beverly A; Brach, Cindy; Hays, Ron D

2012-09-01

The complexity of health information often exceeds patients' skills to understand and use it. To develop survey items assessing how well healthcare providers communicate health information. Domains and items for the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Item Set for Addressing Health Literacy were identified through an environmental scan and input from stakeholders. The draft item set was translated into Spanish and pretested in both English and Spanish. The revised item set was field tested with a randomly selected sample of adult patients from 2 sites using mail and telephonic data collection. Item-scale correlations, confirmatory factor analysis, and internal consistency reliability estimates were estimated to assess how well the survey items performed and identify composite measures. Finally, we regressed the CAHPS global rating of the provider item on the CAHPS core communication composite and the new health literacy composites. A total of 601 completed surveys were obtained (52% response rate). Two composite measures were identified: (1) Communication to Improve Health Literacy (16 items); and (2) How Well Providers Communicate About Medicines (6 items). These 2 composites were significantly uniquely associated with the global rating of the provider (communication to improve health literacy: P<0.001, b=0.28; and communication about medicines composite: P=0.02, b=0.04). The 2 composites and the CAHPS core communication composite accounted for 51% of the variance in the global rating of the provider. A 5-item subset of the Communication to Improve Health Literacy composite accounted for 90% of the variance of the original 16-item composite. This study provides support for reliability and validity of the CAHPS Item Set for Addressing Health Literacy. These items can serve to assess whether healthcare providers have communicated effectively with their patients and as a tool for quality improvement.

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Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-13

...; Communicating Composite Scores in Direct-to-Consumer Advertising AGENCY: Food and Drug Administration, HHS... information entitled ``Communicating Composite Scores in Direct-to-Consumer (DTC) Advertising'' has been... ``Communicating Composite Scores in Direct-to-Consumer (DTC) Advertising'' to OMB for review and clearance under...

Hetero-junction photovoltaic device and method of fabricating the device

DOEpatents

Aytug, Tolga; Christen, David K; Paranthaman, Mariappan Parans; Polat, Ozgur

2014-02-10

A hetero-junction device and fabrication method in which phase-separated n-type and p-type semiconductor pillars define vertically-oriented p-n junctions extending above a substrate. Semiconductor materials are selected for the p-type and n-type pillars that are thermodynamically stable and substantially insoluble in one another. An epitaxial deposition process is employed to form the pillars on a nucleation layer and the mutual insolubility drives phase separation of the materials. During the epitaxial deposition process, the orientation is such that the nucleation layer initiates propagation of vertical columns resulting in a substantially ordered, three-dimensional structure throughout the deposited material. An oxidation state of at least a portion of one of the p-type or the n-type semiconductor materials is altered relative to the other, such that the band-gap energy of the semiconductor materials differ with respect to stoichiometric compositions and the device preferentially absorbs particular selected bands of radiation.

Ultralow-voltage-drop GaN/InGaN/GaN tunnel junctions with 12% indium content

NASA Astrophysics Data System (ADS)

Akyol, Fatih; Zhang, Yuewei; Krishnamoorthy, Sriram; Rajan, Siddharth

2017-12-01

We report a combination of highly doped layers and polarization engineering that achieves highly efficient blue-transparent GaN/InGaN/GaN tunnel junctions (In content = 12%). NPN diode structures with a low voltage drop of 4.04 V at 5 kA/cm2 and a differential resistance of 6.51 × 10-5 Ω·cm2 at 3 kA/cm2 were obtained. The tunnel junction design with n++-GaN (Si: 5 × 1020 cm-3)/3 nm p++-In0.12Ga0.88N (Mg: 1.5 × 1020 cm-3)/p++-GaN (Mg: 5 × 1020 cm-3) showed the best device performance. Device simulations agree well with the experimentally determined optimal design. The combination of low In composition and high doping can facilitate lower tunneling resistance for blue-transparent light-emitting diodes.

Scanning electron microscopic observations of fibrous structure of cemento-dentinal junction in healthy teeth.

PubMed

Pratebha, B; Jaikumar, N D; Sudhakar, R

2014-01-01

The cemento-dentinal junction (CDJ) is a structural and biologic link between cementum and dentin present in the roots of teeth. Conflicting reports about the origin, structure and composition of this layer are present in literature. The width of this junctional tissue is reported to be about 2-4 μm with adhesion of cementum and dentin by proteoglycans and by collagen fiber intermingling. The objective of this study is to observe and report the fibrous architecture of the CDJ of healthy tooth roots. A total of 15 healthy teeth samples were collected, sectioned into halves, demineralized in 5% ethylenediaminetetraacetic acid, processed using NaOH maceration technique and observed under a scanning electron microscope. The CDJ appeared to be a fibril poor groove with a width of 2-4 µm. Few areas of collagen fiber intermingling could be appreciated. A detailed observation of these tissues has been presented.

Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium

PubMed Central

Elzarrad, M Khair; Haroon, Abu; Willecke, Klaus; Dobrowolski, Radoslaw; Gillespie, Mark N; Al-Mehdi, Abu-Bakr

2008-01-01

Background The modulation of gap junctional communication between tumor cells and between tumor and vascular endothelial cells during tumorigenesis and metastasis is complex. The notion of a role for loss of gap junctional intercellular communication in tumorigenesis and metastasis has been controversial. While some of the stages of tumorigenesis and metastasis, such as uncontrolled cell division and cellular detachment, would necessitate the loss of intercellular junctions, other stages, such as intravasation, endothelial attachment, and vascularization, likely require increased cell-cell contact. We hypothesized that, in this multi-stage scheme, connexin-43 is centrally involved as a cell adhesion molecule mediating metastatic tumor attachment to the pulmonary endothelium. Methods Tumor cell attachment to pulmonary vasculature, tumor growth, and connexin-43 expression was studied in metastatic lung tumor sections obtained after tail-vein injection into nude mice of syngeneic breast cancer cell lines, overexpressing wild type connexin-43 or dominant-negatively mutated connexin-43 proteins. High-resolution immunofluorescence microscopy and Western blot analysis was performed using a connexin-43 monoclonal antibody. Calcein Orange Red AM dye transfer by fluorescence imaging was used to evaluate the gap junction function. Results Adhesion of breast cancer cells to the pulmonary endothelium increased with cancer cells overexpressing connexin-43 and markedly decreased with cells expressing dominant-negative connexin-43. Upregulation of connexin-43 was observed in tumor cell-endothelial cell contact areas in vitro and in vivo, and in areas of intratumor blood vessels and in micrometastatic foci. Conclusion Connexin-43 facilitates metastatic 'homing' by increasing adhesion of cancer cells to the lung endothelial cells. The marked upregulation of connexin-43 in tumor cell-endothelial cell contact areas, whether in preexisting 'homing' vessels or in newly formed tumor vessels, suggests that connexin-43 can serve as a potential marker of micrometastases and tumor vasculature and that it may play a role in the early incorporation of endothelial cells into small tumors as seeds for vasculogenesis. PMID:18647409

Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium.

PubMed

Elzarrad, M Khair; Haroon, Abu; Willecke, Klaus; Dobrowolski, Radoslaw; Gillespie, Mark N; Al-Mehdi, Abu-Bakr

2008-07-22

The modulation of gap junctional communication between tumor cells and between tumor and vascular endothelial cells during tumorigenesis and metastasis is complex. The notion of a role for loss of gap junctional intercellular communication in tumorigenesis and metastasis has been controversial. While some of the stages of tumorigenesis and metastasis, such as uncontrolled cell division and cellular detachment, would necessitate the loss of intercellular junctions, other stages, such as intravasation, endothelial attachment, and vascularization, likely require increased cell-cell contact. We hypothesized that, in this multi-stage scheme, connexin-43 is centrally involved as a cell adhesion molecule mediating metastatic tumor attachment to the pulmonary endothelium. Tumor cell attachment to pulmonary vasculature, tumor growth, and connexin-43 expression was studied in metastatic lung tumor sections obtained after tail-vein injection into nude mice of syngeneic breast cancer cell lines, overexpressing wild type connexin-43 or dominant-negatively mutated connexin-43 proteins. High-resolution immunofluorescence microscopy and Western blot analysis was performed using a connexin-43 monoclonal antibody. Calcein Orange Red AM dye transfer by fluorescence imaging was used to evaluate the gap junction function. Adhesion of breast cancer cells to the pulmonary endothelium increased with cancer cells overexpressing connexin-43 and markedly decreased with cells expressing dominant-negative connexin-43. Upregulation of connexin-43 was observed in tumor cell-endothelial cell contact areas in vitro and in vivo, and in areas of intratumor blood vessels and in micrometastatic foci. Connexin-43 facilitates metastatic 'homing' by increasing adhesion of cancer cells to the lung endothelial cells. The marked upregulation of connexin-43 in tumor cell-endothelial cell contact areas, whether in preexisting 'homing' vessels or in newly formed tumor vessels, suggests that connexin-43 can serve as a potential marker of micrometastases and tumor vasculature and that it may play a role in the early incorporation of endothelial cells into small tumors as seeds for vasculogenesis.

Homeostatic Regulation of the PI(4,5)P2-Ca2+ Signaling System at ER-PM Junctions

PubMed Central

Chang, Chi-Lun; Liou, Jen

2016-01-01

The phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-Ca2+ signaling system is important for cell activation in response to various extracellular stimuli. This signaling system is initiated by receptor-induced hydrolysis of PI(4,5)P2 in the plasma membrane (PM) to generate the soluble second messenger inositol 1,4,5-trisphosphate (IP3). IP3 subsequently triggers the release of Ca2+ from the endoplasmic reticulum (ER) store to the cytosol to activate Ca2+-mediated responses, such as secretion and proliferation. The consumed PM PI(4,5)P2 and ER Ca2+ must be quickly restored to sustain signaling responses, and to maintain the homeostasis of PI(4,5)P2 and Ca2+. Since phosphatidylinositol (PI), the precursor lipid for PM PI(4,5)P2, is synthesized in the ER membrane, and a Ca2+ influx across the PM is required to refill the ER Ca2+ store, efficient communications between the ER and the PM are critical for the homeostatic regulation of the PI(4,5)P2-Ca2+ signaling system. This review describes the major findings that established the framework of the PI(4,5)P2-Ca2+ signaling system, and recent discoveries on feedback control mechanisms at ER-PM junctions that sustain the PI(4,5)P2-Ca2+ signaling system. Particular emphasis is placed on the characterization of ER-PM junctions where efficient communications between the ER and the PM occurs, and the activation mechanisms of proteins that dynamically localize to ER-PM junctions to provide the feedback control during PI(4,5)P2-Ca2+ signaling, including the ER Ca2+ sensor STIM1, the extended synaptotagmin E-Syt1, and the PI transfer protein Nir2. This review is part of a Special Issue entitled The Cellular Lipid Landscape. PMID:26924250

Regulation of gap junction function and Connexin 43 expression by cytochrome P450 oxidoreductase (CYPOR)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Polusani, Srikanth R.; Kar, Rekha; Riquelme, Manuel A.

2011-08-05

Highlights: {yields} Humans with severe forms of cytochrome P450 oxidoreductase (CYPOR) mutations show bone defects as observed in Antley-Bixler Syndrome. {yields} First report showing knockdown of CYPOR in osteoblasts decreased Connexin 43 (Cx43) protein levels. Cx43 is known to play an important role in bone modeling. {yields} Knockdown of CYPOR decreased Gap Junctional Intercellular Communication and hemichannel activity. {yields} Knockdown of CYPOR decreased Cx43 in mouse primary calvarial osteoblasts. {yields} Decreased Cx43 expression was observed at the transcriptional level. -- Abstract: Cytochrome P450 oxidoreductase (CYPOR) is a microsomal electron-transferring enzyme containing both FAD and FMN as co-factors, which provides themore » reducing equivalents to various redox partners, such as cytochromes P450 (CYPs), heme oxygenase (HO), cytochrome b{sub 5} and squalene monooxygenase. Human patients with severe forms of CYPOR mutation show bone defects such as cranio- and humeroradial synostoses and long bone fractures, known as Antley-Bixler-like Syndrome (ABS). To elucidate the role of CYPOR in bone, we knocked-down CYPOR in multiple osteoblast cell lines using RNAi technology. In this study, knock-down of CYPOR decreased the expression of Connexin 43 (Cx43), known to play a critical role in bone formation, modeling, and remodeling. Knock-down of CYPOR also decreased Gap Junction Intercellular Communication (GJIC) and hemichannel activity. Promoter luciferase assays revealed that the decrease in expression of Cx43 in CYPOR knock-down cells was due to transcriptional repression. Primary osteoblasts isolated from bone specific Por knock-down mice calvariae confirmed the findings in the cell lines. Taken together, our study provides novel insights into the regulation of gap junction function by CYPOR and suggests that Cx43 may play an important role(s) in CYPOR-mediated bone defects seen in patients.« less

Intercellular diffusion of a fluorescent sucrose analog via the septal junctions in a filamentous cyanobacterium.

PubMed

Nürnberg, Dennis J; Mariscal, Vicente; Bornikoel, Jan; Nieves-Morión, Mercedes; Krauß, Norbert; Herrero, Antonia; Maldener, Iris; Flores, Enrique; Mullineaux, Conrad W

2015-03-17

Many filamentous cyanobacteria produce specialized nitrogen-fixing cells called heterocysts, which are located at semiregular intervals along the filament with about 10 to 20 photosynthetic vegetative cells in between. Nitrogen fixation in these complex multicellular bacteria depends on metabolite exchange between the two cell types, with the heterocysts supplying combined-nitrogen compounds but dependent on the vegetative cells for photosynthetically produced carbon compounds. Here, we used a fluorescent tracer to probe intercellular metabolite exchange in the filamentous heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120. We show that esculin, a fluorescent sucrose analog, is incorporated by a sucrose import system into the cytoplasm of Anabaena cells. The cytoplasmic esculin is rapidly and reversibly exchanged across vegetative-vegetative and vegetative-heterocyst cell junctions. Our measurements reveal the kinetics of esculin exchange and also show that intercellular metabolic communication is lost in a significant fraction of older heterocysts. SepJ, FraC, and FraD are proteins located at the intercellular septa and are suggested to form structures analogous to gap junctions. We show that a ΔsepJ ΔfraC ΔfraD triple mutant shows an altered septum structure with thinner septa but a denser peptidoglycan layer. Intercellular diffusion of esculin and fluorescein derivatives is impaired in this mutant, which also shows a greatly reduced frequency of nanopores in the intercellular septal cross walls. These findings suggest that FraC, FraD, and SepJ are important for the formation of junctional structures that constitute the major pathway for feeding heterocysts with sucrose. Anabaena and its relatives are filamentous cyanobacteria that exhibit a sophisticated form of prokaryotic multicellularity, with the formation of differentiated cell types, including normal photosynthetic cells and specialized nitrogen-fixing cells called heterocysts. The question of how heterocysts communicate and exchange metabolites with other cells in the filament is key to understanding this form of bacterial multicellularity. Here we provide the first information on the intercellular exchange of a physiologically important molecule, sucrose. We show that a fluorescent sucrose analog can be imported into the Anabaena cytoplasm by a sucrose import system. Once in the cytoplasm, it is rapidly and reversibly exchanged among all of the cells in the filament by diffusion across the septal junctions. Photosynthetically produced sucrose likely follows the same route from cytoplasm to cytoplasm. We identify some of the septal proteins involved in sucrose exchange, and our results indicate that these proteins form structures functionally analogous to metazoan gap junctions. Copyright © 2015 Nürnberg et al.

Re-establishment of gap junctional intercellular communication (GJIC) between human endometrial carcinomas by prostaglandin E(2).

PubMed

Schlemmer, Scott R; Kaufman, David G

2012-12-01

Reduced intercellular communication via gap junctions is correlated with carcinogenesis. Gap junctional intercellular communication (GJIC), between normal human endometrial epithelial cells is enhanced when endometrial stromal cells were present in culture. This enhancement of GJIC between normal epithelial cells also occurs when they are cultured in medium conditioned by stromal cells. This observation indicated that a soluble compound (or compounds) produced and secreted by stromal cells mediates GJIC in epithelial cells. Previous studies have shown that endometrial stromal cells release prostaglandin E(2) (PGE(2)) and prostaglandin F(2α) (PGF(2α)) under physiological conditions. When we evaluated the response of normal endometrial epithelial cells to various concentrations of PGE(2,) we found enhanced GJIC with 1nM PGE(2). This is a smaller increase in GJIC than that induced by medium conditioned by stromal cells. When the extracellular concentration of PGE(2) was measured after incubation with stromal cells, it was found to be similar to the concentrations showing maximal GJIC between the normal epithelial cells. When indomethacin was used to inhibit prostaglandin synthesis by stromal cells, GJIC was reduced but not eliminated between normal endometrial epithelial cells. These observations suggest that although PGE(2) secreted by stromal cells is an important mediator of GJIC between the epithelial cells, it is not the sole mediator. Transformed endometrial epithelial cells did not demonstrate GJIC even in the presence of stromal cells. However, we were able to re-establish GJIC in transformed epithelial cells when we added PGE(2) to the cells. Our findings show that PGE(2) may serve as an intercellular mediator between stromal and epithelial cells that regulates GJIC in normal and malignant epithelial cells. This suggests that maintenance of GJIC by preserving or replacing PGE(2) secretion by endometrial stromal cells may have the potential to suppress carcinogenesis in endometrial epithelial cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Methamphetamine compromises gap junctional communication in astrocytes and neurons.

PubMed

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

2016-05-01

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 sensitivity of neurons and astrocytes to apoptosis in response to HIV infection. © 2016 International Society for Neurochemistry.

Gap Junction Regulation of Vascular Tone: Implications of Modulatory Intercellular Communication During Gestation

PubMed Central

Ampey, Bryan C.; Morschauser, Timothy J.; Lampe, Paul D.

2017-01-01

In the vasculature, gap junctions (GJ) play a multifaceted role by serving as direct conduits for cell–cell intercellular communication via the facilitated diffusion of signaling molecules. GJs are essential for the control of gene expression and coordinated vascular development in addition to vascular function. The coupling of endothelial cells to each other, as well as with vascular smooth muscle cells via GJs, plays a relevant role in the control of vasomotor tone, tissue perfusion and arterial blood pressure. The regulation of cell-signaling is paramount to cardiovascular adaptations of pregnancy. Pregnancy requires highly developed cell-to-cell coupling, which is affected partly through the formation of intercellular GJs by Cx43, a gap junction protein, within adjacent cell membranes to help facilitate the increase of uterine blood flow (UBF) in order to ensure adequate perfusion for nutrient and oxygen delivery to the placenta and thus the fetus. One mode of communication that plays a critical role in regulating Cx43 is the release of endothelial-derived vasodilators such as prostacyclin (PGI2) and nitric oxide (NO) and their respective signaling mechanisms involving second messengers (cAMP and cGMP, respectively) that are likely to be important in maintaining UBF. Therefore, the assertion we present in this review is that GJs play an integral if not a central role in maintaining UBF by controlling rises in vasodilators (PGI2 and NO) via cyclic nucleotides. In this review, we discuss: (1) GJ structure and regulation; (2) second messenger regulation of GJ phosphorylation and formation; (3) pregnancy-induced changes in cell-signaling; and (4) the role of uterine arterial endothelial GJs during gestation. These topics integrate the current knowledge of this scientific field with interpretations and hypotheses regarding the vascular effects that are mediated by GJs and their relationship with vasodilatory vascular adaptations required for modulating the dramatic physiological rises in uteroplacental perfusion and blood flow observed during normal pregnancy. PMID:25015806

Highly Transparent Compositionally Graded Buffers for New Metamorphic Multijunction Solar Cell Designs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulte, Kevin L.; France, Ryan M.; Geisz, John F.

The development of compositionally graded buffer layers (CGBs) with enhanced transparency would enable novel five and six junction solar cells, with efficiencies approaching 50% under high concentration. Here, we demonstrate highly transparent grades between the GaAs and InP lattice constants on both A- and B-miscut GaAs substrates, employing Al xGayIn 1-x-yAs and highly Se-doped Burstein-Moss (BM) shifted Ga xIn 1-xP. Transparency to >810 and >890 nm wavelengths is demonstrated with BM-shifted Ga xIn 1-xP on B-miscut substrates and Al xGayIn 1-x-yAs/Ga xIn 1-xP(Se) combined grades on A-miscut substrates, respectively. 0.74 eV GaInAs solar cells grown on these transparent CGBs exhibitmore » Woc = 0.41 V at mA/ cm 2, performance comparable with the state-of-the-art Ga xIn 1-xP grade employed in the four-junction-inverted metamorphic multijunction (IMM) cell. A GaAs/0.74cV GaInAs tandem cell was grown with a transparent BM-shifted Ga xIn 1-xP CGB to verify the CGB performance in a multijunction device structure. Quantum efficiency measurements indicate that the CGB is completely transparent to photons below the GaAs bandedge, validating its use in 4-6 junction IMM devices with a single-graded buffer. Furthermore, this tandem represents a highly efficient two-junction band gap combination, achieving 29.6% ± 1.2% efficiency under the AM1.5 global spectrum, demonstrating how the additional transparency enables new device structures.« less

Highly Transparent Compositionally Graded Buffers for New Metamorphic Multijunction Solar Cell Designs

DOE PAGES

Schulte, Kevin L.; France, Ryan M.; Geisz, John F.

2016-11-11

The development of compositionally graded buffer layers (CGBs) with enhanced transparency would enable novel five and six junction solar cells, with efficiencies approaching 50% under high concentration. Here, we demonstrate highly transparent grades between the GaAs and InP lattice constants on both A- and B-miscut GaAs substrates, employing Al xGayIn 1-x-yAs and highly Se-doped Burstein-Moss (BM) shifted Ga xIn 1-xP. Transparency to >810 and >890 nm wavelengths is demonstrated with BM-shifted Ga xIn 1-xP on B-miscut substrates and Al xGayIn 1-x-yAs/Ga xIn 1-xP(Se) combined grades on A-miscut substrates, respectively. 0.74 eV GaInAs solar cells grown on these transparent CGBs exhibitmore » Woc = 0.41 V at mA/ cm 2, performance comparable with the state-of-the-art Ga xIn 1-xP grade employed in the four-junction-inverted metamorphic multijunction (IMM) cell. A GaAs/0.74cV GaInAs tandem cell was grown with a transparent BM-shifted Ga xIn 1-xP CGB to verify the CGB performance in a multijunction device structure. Quantum efficiency measurements indicate that the CGB is completely transparent to photons below the GaAs bandedge, validating its use in 4-6 junction IMM devices with a single-graded buffer. Furthermore, this tandem represents a highly efficient two-junction band gap combination, achieving 29.6% ± 1.2% efficiency under the AM1.5 global spectrum, demonstrating how the additional transparency enables new device structures.« less

IDENTIFICATION OF A PROTEIN-CONTAINING ENAMEL MATRIX LAYER WHICH BRIDGES WITH THE DENTIN-ENAMEL JUNCTION OF ADULT HUMAN TEETH1

PubMed Central

Dusevich, Vladimir; Xu, Changqi; Wang, Yong; Walker, Mary P.; Gorski, Jeff P.

2012-01-01

Objective To investigate the ultrastructure and chemical composition of the dentin-enamel junction and adjacent enamel of minimally processed third molar tooth sections. Design Undecalcified human third molar erupted teeth were sectioned and etched with 4% EDTA or 37% phosphoric acid prior to visualization by scanning electron microscopy. Confocal Raman spectroscopy was carried out at 50 μm and more than 400 μm away from the dentin-enamel junction before and after mild etching. Results A novel organic protein-containing enamel matrix layer was identified for the first time using scanning electron microscopy of etched bucco-lingual sections of crowns. This layer resembles a three-dimensional fibrous meshwork that is visually distinct from enamel “tufts”. Previous studies have generally used harsher solvent conditions which likely removed this layer and precluded its prior characterization. The shape of the organic enamel layer generally reflected that of sheath regions of enamel rods and extended from the dentin-enamel junction about 100–400 μm into the cuspal enamel. This layer exhibited a Raman C—H stretching peak at ~2931 cm−1 characteristic of proteins and this signal correlated directly with the presence and location of the matrix layer as identified by scanning electron microscopy. Conclusions The enamel protein layer was most prominent close to the dentin-enamel junction and was largely absent in cuspal enamel >400 μm away from the dentin enamel junction. We hypothesize that this protein containing matrix layer could provide an important biomechanical linkage between the enamel and the dentin-enamel junction and by extension, with the dentin, of the adult tooth. PMID:22609172

Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus

PubMed Central

Chen, Xiaodi; Threlkeld, Steven W.; Cummings, Erin E.; Juan, Ilona; Makeyev, Oleksandr; Besio, Walter G.; Gaitanis, John; Banks, William A.; Sadowska, Grazyna B.; Stonestreet, Barbara S.

2012-01-01

The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (Ki) and tight junction proteins by Western immunoblot in fetal sheep at 127 days-of-gestation without ischemia, and 4-, 24-, or 48-h after ischemia. The largest increase in Ki (P<0.05) was 4-h after ischemia. Occludin and claudin-5 expressions decreased at 4-h, but returned toward control levels 24- and 48-h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between Ki and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (Ki) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4-h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24- and 48- than 4-h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia. PMID:22986172

Minimal Effects of VEGF and Anti-VEGF Drugs on the Permeability or Selectivity of RPE Tight Junctions

PubMed Central

Peng, Shaomin; Adelman, Ron A.

2010-01-01

Purpose. Bevacizumab and ranibizumab are currently used to treat age-related macular degeneration by neutralizing vascular endothelial growth factor (VEGF). In this study, the potential side effects on the outer blood–retinal barrier were examined. Methods. Human fetal RPE (hfRPE) cells were used because they are highly differentiated in culture. The claudin composition of RPE tight junctions was determined by RT-PCR, immunoblot analysis, and immunofluorescence. ELISA assays monitored the secretion and trafficking of VEGF and a fluid-phase marker, methylpolyethylene glycol (mPEG). Tight junction functions were assessed by the conductance of K+ and Na+ (derived from the transepithelial electrical resistance, TER) and the flux of NaCl and mPEG. Results. Claudin-3, claudin-10, and claudin-19 were detected in RPE tight junctions. VEGF was secreted in equal amounts across the apical and basolateral membranes, but the apical membrane was more active in endocytosing and degrading VEGF. Exogenous VEGF and mPEG crossed the RPE monolayer by transcytosis, predominantly in the apical-to-basal direction. RPE tight junctions were selective for K+, but did not discriminate between Na+ and Cl−. VEGF, bevacizumab, and ranibizumab had minimal effects on TER, permeation of mPEG, and selectivity for K+, Na+, and Cl−. They had minimal effects on the expression and distribution of the claudins. Conclusions. RPE has mechanisms for maintaining low concentrations of VEGF in the subretinal space that include endocytosis and degradation and fluid-phase transcytosis in the apical-to-basal direction. RPE tight junctions are selective for K+ over Na+ and Cl−. Permeability and selectivity of the junctions are not affected by VEGF, bevacizumab, or ranibizumab. PMID:20042644

GaSb solar cells grown on GaAs via interfacial misfit arrays for use in the III-Sb multi-junction cell

NASA Astrophysics Data System (ADS)

Nelson, George T.; Juang, Bor-Chau; Slocum, Michael A.; Bittner, Zachary S.; Laghumavarapu, Ramesh B.; Huffaker, Diana L.; Hubbard, Seth M.

2017-12-01

Growth of GaSb with low threading dislocation density directly on GaAs may be possible with the strategic strain relaxation of interfacial misfit arrays. This creates an opportunity for a multi-junction solar cell with access to a wide range of well-developed direct bandgap materials. Multi-junction cells with a single layer of GaSb/GaAs interfacial misfit arrays could achieve higher efficiency than state-of-the-art inverted metamorphic multi-junction cells while forgoing the need for costly compositionally graded buffer layers. To develop this technology, GaSb single junction cells were grown via molecular beam epitaxy on both GaSb and GaAs substrates to compare homoepitaxial and heteroepitaxial GaSb device results. The GaSb-on-GaSb cell had an AM1.5g efficiency of 5.5% and a 44-sun AM1.5d efficiency of 8.9%. The GaSb-on-GaAs cell was 1.0% efficient under AM1.5g and 4.5% at 44 suns. The lower performance of the heteroepitaxial cell was due to low minority carrier Shockley-Read-Hall lifetimes and bulk shunting caused by defects related to the mismatched growth. A physics-based device simulator was used to create an inverted triple-junction GaInP/GaAs/GaSb model. The model predicted that, with current GaSb-on-GaAs material quality, the not-current-matched, proof-of-concept cell would provide 0.5% absolute efficiency gain over a tandem GaInP/GaAs cell at 1 sun and 2.5% gain at 44 suns, indicating that the effectiveness of the GaSb junction was a function of concentration.

Iron oxide nanoparticle-mediated development of cellular gap junction crosstalk to improve mesenchymal stem cells' therapeutic efficacy for myocardial infarction.

PubMed

Han, Jin; Kim, Bokyoung; Shin, Jung-Youn; Ryu, Seungmi; Noh, Myungkyung; Woo, Jongsu; Park, Jin-Sil; Lee, Youjin; Lee, Nohyun; Hyeon, Taeghwan; Choi, Donghoon; Kim, Byung-Soo

2015-03-24

Electrophysiological phenotype development and paracrine action of mesenchymal stem cells (MSCs) are the critical factors that determine the therapeutic efficacy of MSCs for myocardial infarction (MI). In such respect, coculture of MSCs with cardiac cells has windowed a platform for cardiac priming of MSCs. Particularly, active gap junctional crosstalk of MSCs with cardiac cells in coculture has been known to play a major role in the MSC modification through coculture. Here, we report that iron oxide nanoparticles (IONPs) significantly augment the expression of connexin 43 (Cx43), a gap junction protein, of cardiomyoblasts (H9C2), which would be critical for gap junctional communication with MSCs in coculture for the generation of therapeutic potential-improved MSCs. MSCs cocultured with IONP-harboring H9C2 (cocultured MSCs: cMSCs) showed active cellular crosstalk with H9C2 and displayed significantly higher levels of electrophysiological cardiac biomarkers and a cardiac repair-favorable paracrine profile, both of which are responsible for MI repair. Accordingly, significantly improved animal survival and heart function were observed upon cMSC injection into rat MI models compared with the injection of unmodified MSCs. The present study highlights an application of IONPs in developing gap junctional crosstalk among the cells and generating cMSCs that exceeds the reparative potentials of conventional MSCs. On the basis of our finding, the potential application of IONPs can be extended in cell biology and stem cell-based therapies.

Intercellular communication in sensory ganglia by purinergic receptors and gap junctions: implications for chronic pain.

PubMed

Hanani, Menachem

2012-12-03

Peripheral injury can cause abnormal activity in sensory neurons, which is a major factor in chronic pain. Recent work has shown that injury induces major changes not only in sensory neurons but also in the main type of glial cells in sensory ganglia-satellite glial cells (SGCs), and that interactions between sensory neurons and SGCs contribute to neuronal activity in pain models. The main functional changes observed in SGCs after injury are an increased gap junction-mediated coupling among these cells, and augmented sensitivity to ATP. There is evidence that the augmented gap junctions contribute to neuronal hyperexcitability in pain models, but the mechanism underlying this effect is not known. The changes in SGCs described above have been found following a wide range of injuries (both axotomy and inflammation) in somatic, orofacial and visceral regions, and therefore appear to be a general feature in chronic pain. We have found that in cultures of sensory ganglia calcium signals can spread from an SGC to neighboring cells by calcium waves, which are mediated by gap junctions and ATP acting on purinergic P2 receptors. A model is proposed to explain how augmented gap junctions and greater sensitivity to ATP can combine to produce enhanced calcium waves, which can lead to neuronal excitation. Thus this simple scheme can account for several major changes in sensory ganglia that are common to a great variety of pain models. Copyright © 2012 Elsevier B.V. All rights reserved.

Gap junction blockade induces apoptosis in human endometrial stromal cells.

PubMed

Yu, Jie; Berga, Sarah L; Zou, Wei; Sun, He-Ying; Johnston-MacAnanny, Erika; Yalcinkaya, Tamer; Sidell, Neil; Bagchi, Indrani C; Bagchi, Milan K; Taylor, Robert N

2014-07-01

One of the most dynamic adult human tissues is the endometrium. Through coordinated, cyclical proliferation, differentiation, leukocyte recruitment, apoptosis, and desquamation, the uterine lining is expanded and shed monthly, unless pregnancy is established. Errors in these steps potentially cause endometrial dysfunction, abnormal uterine bleeding, failed embryonic implantation, infertility, or endometrial carcinoma. Our prior studies showed that gap junctions comprised of Gap junction alpha-1 (GJA1) protein, also known as connexin 43 (CX43), subunits are critical to endometrial stromal cell differentiation. The current studies were undertaken to explore the mechanism of endometrial dysfunction when gap junction intercellular communication (GJIC) is disrupted. Gap junction blockade by two distinct GJIC inhibitors, 18α-glycyrrhetinic acid (AGA) and octanol (OcOH), suppressed proliferation and induced apoptosis in endometrial stromal cells, as manifested by reduced biomarkers of cell viability, increased TUNEL staining, caspase-3 activation, sub-G1 chromosomal DNA complement, as well as shortened telomere length. Unexpectedly, we also observed that the chemical inhibitors blocked CX43 gene expression. Moreover, when endometrial stromal cells were induced to undergo hormonal decidualization, following a 7-day exposure to 10 nM 17β-estradiol + 100 nM progesterone + 0.5 mM dibutyryl cAMP, characteristic epithelioid changes in cell shape and secretion of prolactin were blunted in the presence of AGA or OcOH, recapitulating effects of RNA interference of CX43. Our findings indicate that endometrial stromal cell proliferation and maintenance of decidualized endometrial function are GJIC-dependent, and that disruption of gap junctions induces endometrial stromal cell apoptosis. These observations may have important implications for several common clinical endometrial pathologies. © 2014 Wiley Periodicals, Inc.

Silicon modulators with optimized vertical PN junctions for high-modulation-efficiency and low-loss in the O-band

NASA Astrophysics Data System (ADS)

Ang, Thomas Y. L.; Png, Ching Eng; Lim, Soon Thor; Ong, Jun Rong

2018-02-01

Silicon modulators based on the carrier depletion mechanism are extensively used in recent years for high-speed data transmission. Lateral PN junctions are the most common electro-optical phase shifters for silicon Mach-Zehnder modulators (MZMs) due to its ease of fabrication. They have a relatively high DC VπLπ of around 2.5 V.cm in the Oband. An alternative approach is to design and optimize vertical PN junctions for lower DC VπLπ, which is currently lacking in the literature for silicon MZMs that operates using carrier depletion mechanism in the O-band. In this work, we look into the design and optimization of silicon phase shifters based on vertical PN junctions for high-modulationefficiency with VπLπ <= 1 V.cm, while meeting the stringent low loss budget of <= 1 dB/mm for data communication in the O-band. This is achieved by varying the offsets of the vertical PN junction with respect to different doping concentrations (2e17/cm3 - 3e18/cm3 ) near the depletion region. Different types of doping schemes are explored and optimized. Our optimized vertical PN junction designs are predicted to give low DC VπLπ of 0.26-0.5 V.cm for low DC reverse bias of >= -2V and low propagation loss of <= 1dB/mm, resulting in α.VπLπ = 1.7 for the best designs, which to the best of our knowledge, is the lowest α.VπLπ at the O-band to date. Electrical and optical modeling are based on our in-house proprietary software that is able to perform both optical and electrical simulations without loss of data fidelity.

Specific membrane lipid composition is important for plasmodesmata function in Arabidopsis.

PubMed

Grison, Magali S; Brocard, Lysiane; Fouillen, Laetitia; Nicolas, William; Wewer, Vera; Dörmann, Peter; Nacir, Houda; Benitez-Alfonso, Yoselin; Claverol, Stéphane; Germain, Véronique; Boutté, Yohann; Mongrand, Sébastien; Bayer, Emmanuelle M

2015-04-01

Plasmodesmata (PD) are nano-sized membrane-lined channels controlling intercellular communication in plants. Although progress has been made in identifying PD proteins, the role played by major membrane constituents, such as the lipids, in defining specialized membrane domains in PD remains unknown. Through a rigorous isolation of "native" PD membrane fractions and comparative mass spectrometry-based analysis, we demonstrate that lipids are laterally segregated along the plasma membrane (PM) at the PD cell-to-cell junction in Arabidopsis thaliana. Remarkably, our results show that PD membranes display enrichment in sterols and sphingolipids with very long chain saturated fatty acids when compared with the bulk of the PM. Intriguingly, this lipid profile is reminiscent of detergent-insoluble membrane microdomains, although our approach is valuably detergent-free. Modulation of the overall sterol composition of young dividing cells reversibly impaired the PD localization of the glycosylphosphatidylinositol-anchored proteins Plasmodesmata Callose Binding 1 and the β-1,3-glucanase PdBG2 and altered callose-mediated PD permeability. Altogether, this study not only provides a comprehensive analysis of the lipid constituents of PD but also identifies a role for sterols in modulating cell-to-cell connectivity, possibly by establishing and maintaining the positional specificity of callose-modifying glycosylphosphatidylinositol proteins at PD. Our work emphasizes the importance of lipids in defining PD membranes. © 2015 American Society of Plant Biologists. All rights reserved.

Specific Membrane Lipid Composition Is Important for Plasmodesmata Function in Arabidopsis

PubMed Central

Grison, Magali S.; Brocard, Lysiane; Fouillen, Laetitia; Nicolas, William; Wewer, Vera; Dörmann, Peter; Nacir, Houda; Benitez-Alfonso, Yoselin; Claverol, Stéphane; Germain, Véronique; Boutté, Yohann; Mongrand, Sébastien; Bayer, Emmanuelle M.

2015-01-01

Plasmodesmata (PD) are nano-sized membrane-lined channels controlling intercellular communication in plants. Although progress has been made in identifying PD proteins, the role played by major membrane constituents, such as the lipids, in defining specialized membrane domains in PD remains unknown. Through a rigorous isolation of “native” PD membrane fractions and comparative mass spectrometry-based analysis, we demonstrate that lipids are laterally segregated along the plasma membrane (PM) at the PD cell-to-cell junction in Arabidopsis thaliana. Remarkably, our results show that PD membranes display enrichment in sterols and sphingolipids with very long chain saturated fatty acids when compared with the bulk of the PM. Intriguingly, this lipid profile is reminiscent of detergent-insoluble membrane microdomains, although our approach is valuably detergent-free. Modulation of the overall sterol composition of young dividing cells reversibly impaired the PD localization of the glycosylphosphatidylinositol-anchored proteins Plasmodesmata Callose Binding 1 and the β-1,3-glucanase PdBG2 and altered callose-mediated PD permeability. Altogether, this study not only provides a comprehensive analysis of the lipid constituents of PD but also identifies a role for sterols in modulating cell-to-cell connectivity, possibly by establishing and maintaining the positional specificity of callose-modifying glycosylphosphatidylinositol proteins at PD. Our work emphasizes the importance of lipids in defining PD membranes. PMID:25818623

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Nteeba, Jackson, E-mail: nteeba@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

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) weremore » 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.« less

A correlative and quantitative imaging approach enabling characterization of primary cell-cell communication: Case of human CD4+ T cell-macrophage immunological synapses.

PubMed

Kasprowicz, Richard; Rand, Emma; O'Toole, Peter J; Signoret, Nathalie

2018-05-22

Cell-to-cell communication engages signaling and spatiotemporal reorganization events driven by highly context-dependent and dynamic intercellular interactions, which are difficult to capture within heterogeneous primary cell cultures. Here, we present a straightforward correlative imaging approach utilizing commonly available instrumentation to sample large numbers of cell-cell interaction events, allowing qualitative and quantitative characterization of rare functioning cell-conjugates based on calcium signals. We applied this approach to examine a previously uncharacterized immunological synapse, investigating autologous human blood CD4 + T cells and monocyte-derived macrophages (MDMs) forming functional conjugates in vitro. Populations of signaling conjugates were visualized, tracked and analyzed by combining live imaging, calcium recording and multivariate statistical analysis. Correlative immunofluorescence was added to quantify endogenous molecular recruitments at the cell-cell junction. By analyzing a large number of rare conjugates, we were able to define calcium signatures associated with different states of CD4 + T cell-MDM interactions. Quantitative image analysis of immunostained conjugates detected the propensity of endogenous T cell surface markers and intracellular organelles to polarize towards cell-cell junctions with high and sustained calcium signaling profiles, hence defining immunological synapses. Overall, we developed a broadly applicable approach enabling detailed single cell- and population-based investigations of rare cell-cell communication events with primary cells.

The role of gap junctions in megakaryocyte-mediated osteoblast proliferation and differentiation.

PubMed

Ciovacco, Wendy A; Goldberg, Carolyn G; Taylor, Amanda F; Lemieux, Justin M; Horowitz, Mark C; Donahue, Henry J; Kacena, Melissa A

2009-01-01

Gap junctions (GJs) are membrane-spanning channels that facilitate intercellular communication by allowing small signaling molecules (e.g. calcium ions, inositol phosphates, and cyclic nucleotides) to pass from cell to cell. Over the past two decades, many studies have described a role for GJ intercellular communication (GJIC) in the proliferation and differentiation of many cells, including bone cells. Recently, we reported that megakaryocytes (MKs) enhance osteoblast (OB) proliferation by a juxtacrine signaling mechanism. Here we determine whether this response is facilitated by GJIC. First we demonstrate that MKs express connexin 43 (Cx43), the predominant GJ protein expressed by bone cells, including OBs. Next, we provide data showing that MKs can communicate with OBs via GJIC, and that the addition of two distinct GJ uncouplers, 18alpha-glycyrrhetinic acid (alphaGA) or oleamide, inhibits this communication. We then demonstrate that inhibiting MK-mediated GJIC further enhances the ability of MKs to stimulate OB proliferation. Finally, we show that while culturing MKs with OBs reduces gene expression of several differentiation markers/matrix proteins (type I collagen, osteocalcin, and alkaline phosphatase), reduces alkaline phosphatase enzymatic activity, and decreases mineralization in OBs, blocking GJIC does not result in MK-induced reductions in OB gene expression, enzymatic levels, or mineralized nodule formation. Overall, these data provide evidence that GJIC between MKs and OBs is functional, and that inhibiting GJIC in MK-OB cultures enhances OB proliferation without apparently altering differentiation when compared to similarly treated OB cultures. Thus, these observations regarding MK-OB GJIC inhibition may provide insight regarding potential novel targets for anabolic bone formation.

The Role of Gap Junctions in Megakaryocyte-Mediated Osteoblast Proliferation and Differentiation

PubMed Central

Ciovacco, Wendy A.; Goldberg, Carolyn G.; Taylor, Amanda F.; Lemieux, Justin M.; Horowitz, Mark C.; Donahue, Henry J.; Kacena, Melissa A.

2009-01-01

Gap junctions (GJs) are membrane-spanning channels that facilitate intercellular communication by allowing small signaling molecules (e.g. calcium ions, inositol phosphates, and cyclic nucleotides) to pass from cell to cell. Over the past two decades, many studies have described a role for GJ intercellular communication (GJIC) in the proliferation and differentiation of many cells, including bone cells. Recently, we reported that megakaryocytes (MKs) enhance osteoblast (OB) proliferation by a juxtacrine signaling mechanism. Here we determine whether that response is facilitated by GJIC. First we demonstrate that MKs express connexin 43 (Cx43), the predominant GJ protein expressed by bone cells, including OBs. Next, we provide data showing that MKs can communicate with OBs via GJIC, and that the addition of two distinct GJ uncouplers, 18α-glycyrrhetinic acid (αGA) or oleamide, inhibits this communication. We then demonstrate that inhibiting MK-mediated GJIC further enhances the ability of MK to stimulate OB proliferation. Finally, we show that while culturing MKs with OBs reduces gene expression of several differentiation markers/matrix proteins (type I collagen, osteocalcin, and alkaline phosphatase), reduces alkaline phosphatase enzymatic activity, and decreases mineralization in OBs, blocking GJIC does not result in MK-induced reductions in OB gene expression, enzymatic levels, or mineralized nodule formation. Overall, these data provide evidence that GJIC between MKs and OBs is functional, and that inhibiting GJIC in MK-OB cultures enhances OB proliferation without apparently altering differentiation when compared to similarly treated OB cultures. Thus, these observations regarding MK-OB GJIC inhibition may provide insight regarding potential novel targets for anabolic bone formation. PMID:18848655

Rescue of perfluorooctanesulfonate (PFOS)-mediated Sertoli cell injury by overexpression of gap junction protein connexin 43

NASA Astrophysics Data System (ADS)

Li, Nan; Mruk, Dolores D.; Chen, Haiqi; Wong, Chris K. C.; Lee, Will M.; Cheng, C. Yan

2016-07-01

Perfluorooctanesulfonate (PFOS) is an environmental toxicant used in developing countries, including China, as a stain repellent for clothing, carpets and draperies, but it has been banned in the U.S. and Canada since the late 2000s. PFOS perturbed the Sertoli cell tight junction (TJ)-permeability barrier, causing disruption of actin microfilaments in cell cytosol, perturbing the localization of cell junction proteins (e.g., occluden-ZO-1, N-cadherin-ß-catenin). These changes destabilized Sertoli cell blood-testis barrier (BTB) integrity. These findings suggest that human exposure to PFOS might induce BTB dysfunction and infertility. Interestingly, PFOS-induced Sertoli cell injury associated with a down-regulation of the gap junction (GJ) protein connexin43 (Cx43). We next investigated if overexpression of Cx43 in Sertoli cells could rescue the PFOS-induced cell injury. Indeed, overexpression of Cx43 in Sertoli cells with an established TJ-barrier blocked the disruption in PFOS-induced GJ-intercellular communication, resulting in the re-organization of actin microfilaments, which rendered them similar to those in control cells. Furthermore, cell adhesion proteins that utilized F-actin for attachment became properly distributed at the cell-cell interface, resealing the disrupted TJ-barrier. In summary, Cx43 is a good target that might be used to manage PFOS-induced reproductive dysfunction.

A Comprehensive Analysis of the Physical Properties of Advanced GaAs/AlGaAs Junctions

NASA Technical Reports Server (NTRS)

Menkara, Hicham M.

1996-01-01

Extensive studies have been performed on MQW junctions and structures because of their potential applications as avalanche photodetectors in optical communications and imaging systems. The role of the avalanche photodiode is to provide for the conversion of an optical signal into charge. Knowledge of junction physics, and the various carrier generation/recombination mechanisms, is crucial for effectively optimizing the conversion process and increasing the structure's quantum efficiency. In addition, the recent interest in the use of APDs in imaging systems has necessitated the development of semiconductor junctions with low dark currents and high gains for low light applications. Because of the high frame rate and high pixel density requirements in new imaging applications, it is necessary to provide some front-end gain in the imager to allow operation under reasonable light conditions. Understanding the electron/hole impact ionization process, as well as diffusion and surface leakage effects, is needed to help maintain low dark currents and high gains for such applications. In addition, the APD must be capable of operating with low power, and low noise. Knowledge of the effects of various doping configurations and electric field profiles, as well as the excess noise resulting from the avalanche process, are needed to help maintain low operating bias and minimize the noise output.

A four-way junction with triple-helical arms: design, characterization, and stability.

PubMed

Makube, N; Klump, H H

2000-05-01

The formation of the four-way junction containing four triple-helical arms has been demonstrated using chemical methods (polyacrylamide gel electrophoresis and chemical footprinting using OsO(4) as a probe) and physical methods (UV absorbance melting and DSC). The junction J(T1T3) was assembled from two 20-mer purine strands and two 44-mer pyrimidine strands. To determine the contribution of the different arms to the stability of the complete structure of J(T1T3), the junction was compared to two simplified substructures, J(T1) and J(T3), respectively. Common to these complexes is the underlying double-helical four-way junction Js. Addition of Na(+) had a profound effect on stabilizing and subsequently folding the junctions into the stacked X-structures. The following results support the structure present: (i) The native polyacrylamide electrophoresis exhibits only a single band(s) corresponding to one species present when all four single strands are mixed in equal amounts. (ii) OsO(4) modifications were investigated at pH 5.0 and in the presence of 10 mM Mg(2+) and 100 mM Na(+). There is no cleavage of thymine residues at the branch point and throughout the structure. (iii) The thermal unfolding of J(T1) and J(T3) illustrates that the triple-helical arms are more stable than the double-helical arms which are contained in these junctions and that J(T1T3) with four triple-helical arms is slightly more stable than J(T1) and J(T3). (iv) The calorimetric transition enthalpies determined for the arms of J(T1T3) are comparable to those associated with the unfolding of its corresponding arms in J(T1) and J(T3). The results also illustrate that the formation of the junctions is not restricted by the pH, [Na(+)], sequence composition of the arms, and/or the loop position. Copyright 2000 Academic Press.

Network Characteristics of Collective Chemosensing

NASA Astrophysics Data System (ADS)

Sun, Bo; Duclos, Guillaume; Stone, Howard A.

2013-04-01

The collective chemosensing of nonexcitable mammalian cells involves a biochemical network that features gap junction communications and heterogeneous single cell activities. To understand the integrated multicellular chemosensing, we study the calcium dynamics of micropatterned fibroblast cell colonies in response to adenosine triphosphate (ATP) stimulation. We find that the cross-correlation function between the responses of individual cells decays with topological distance as a power law for large colonies and much faster for smaller colonies. Furthermore, the strongly correlated cell pairs tend to form clusters and are more likely to exceed the percolation threshold. At a given topological distance, the cross-correlations exhibit characteristics of Poisson distributions, which allows us to estimate the unitary conductance of a single gap junction which is in good agreement with direct experimental measurements.

75 FR 63475 - Radio Broadcasting Services; AM or FM Proposals To Change The Community of License

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-15

... FEDERAL COMMUNICATIONS COMMISSION Radio Broadcasting Services; AM or FM Proposals To Change The... applicants filed AM or FM proposals to change the community of license: 1TV.COM, INC., Station KIKO, Facility..., LLC, Station KVVA-FM, Facility ID 1331, BPH-20100817ABA, From APACHE JUNCTION, AZ, To SUN LAKES, AZ...

Field-induced inversion of resonant tunneling currents through single molecule junctions and the directional photo-electric effect

NASA Astrophysics Data System (ADS)

Kuperman, Maayan; Peskin, Uri

2017-03-01

It has been known for several decades that the electric current through tunneling junctions is affected by irradiation. In particular, photon-assisted currents by asymmetric irradiation of the two leads was demonstrated and studied extensively in tunneling junctions of different compositions and for different radiation wavelengths. In this work, this phenomenon is revisited in the context of single molecule junctions. Restricting the theoretical discussion to adiabatic periodic driving of one lead with respect to the other within a non-interacting electron formulation, the main features of specific molecules are encoded in the discrete electronic energy levels. The detailed level structure of the molecule is shown to yield new effects in the presence of asymmetric driving of the leads. In particular, when the field-free tunneling process is dominated by a single electronic level, the electric current can be suppressed to zero or flow against the direction of an applied static bias. In the presence of a second electronic level, a directional photo-electric effect is predicted, where not only the magnitude but also the direction of the steady state electric current through the tunneling junction can be changed by a monotonous increase of the field intensity. These effects are analyzed and explained by outlying the relevant theory, using analytic expressions in the wide-band limit, as well as numerical simulations beyond this limit.

Visible light electroluminescent diodes of indium-gallium phosphide

NASA Technical Reports Server (NTRS)

Clough, R.; Richman, D.; Tietjen, J.

1970-01-01

Vapor deposition and acceptor impurity diffusion techniques are used to prepare indium-gallium phosphide junctions. Certain problems in preparation are overcome by altering gas flow conditions and by increasing the concentration of phosphine in the gas. A general formula is given for the alloy's composition.

Computational Nanotechnology Molecular Electronics, Materials and Machines

NASA Technical Reports Server (NTRS)

Srivastava, Deepak; Biegel, Bryan A. (Technical Monitor)

2002-01-01

This presentation covers research being performed on computational nanotechnology, carbon nanotubes and fullerenes at the NASA Ames Research Center. Topics cover include: nanomechanics of nanomaterials, nanotubes and composite materials, molecular electronics with nanotube junctions, kinky chemistry, and nanotechnology for solid-state quantum computers using fullerenes.

Communication network in the follicular papilla and connective tissue sheath through gap junctions in human hair follicles.

PubMed

Iguchi, Makiko; Hara, Masahiro; Manome, Hideaki; Kobayasi, Hiromi; Tagami, Hachiro; Aiba, Setsuya

2003-06-01

Epithelial-mesenchymal interactions play a crucial role in the induction of life-long cyclic transformations of hair follicles. Many studies have already demonstrated several candidates for the soluble factors secreted from the mesenchymal components of the hair follicle, i.e. the follicular papilla (FP) and connective tissue sheath (CTS), which may be responsible for hair cycling. In this paper, we focused on cell-cell contact between FP cells (FPCs), between CTS cells (CTSCs), and between FPCs and CTSCs that may allow these mesenchymal components to function as a syncytium during hair cycling. Electron microscopic examination of the FP and the CTS obtained from human scalp revealed a tri-lamellar structure of the plasma membranes, which is a characteristic of gap junctions at the cell-cell contacting area. The immunohistochemical study with anticonnexin 43 Ab using a confocal laser scanning microscope demonstrated numerous spotted positive signals scattered throughout the FP. In the CTS, spotted positive signals were arranged linearly along the basement membrane of the hair follicle. In particular, these positive spots were aggregated in the transitional region between the FP and the CTS. By Western blot analysis of total protein extracts from the cultured FPCs and neonatal human dermal fibroblasts using anticonnexin 43 antibody, a positive band corresponding to connexin 43 was detected at 43 kDa on both the FPC lane and fibroblast lane. These findings suggest that the FP and the CTS form a communicating network through gap junctions, which may play a role in controlling the dynamic structural changes of hair follicles during hair cycling.

Role of connexins in metastatic breast cancer and melanoma brain colonization

PubMed Central

Stoletov, Konstantin; Strnadel, Jan; Zardouzian, Erin; Momiyama, Masashi; Park, Frederick D.; Kelber, Jonathan A.; Pizzo, Donald P.; Hoffman, Robert; VandenBerg, Scott R.; Klemke, Richard L.

2013-01-01

Summary Breast cancer and melanoma cells commonly metastasize to the brain using homing mechanisms that are poorly understood. Cancer patients with brain metastases display poor prognosis and survival due to the lack of effective therapeutics and treatment strategies. Recent work using intravital microscopy and preclinical animal models indicates that metastatic cells colonize the brain, specifically in close contact with the existing brain vasculature. However, it is not known how contact with the vascular niche promotes microtumor formation. Here, we investigate the role of connexins in mediating early events in brain colonization using transparent zebrafish and chicken embryo models of brain metastasis. We provide evidence that breast cancer and melanoma cells utilize connexin gap junction proteins (Cx43, Cx26) to initiate brain metastatic lesion formation in association with the vasculature. RNAi depletion of connexins or pharmacological blocking of connexin-mediated cell–cell communication with carbenoxolone inhibited brain colonization by blocking tumor cell extravasation and blood vessel co-option. Activation of the metastatic gene twist in breast cancer cells increased Cx43 protein expression and gap junction communication, leading to increased extravasation, blood vessel co-option and brain colonization. Conversely, inhibiting twist activity reduced Cx43-mediated gap junction coupling and brain colonization. Database analyses of patient histories revealed increased expression of Cx26 and Cx43 in primary melanoma and breast cancer tumors, respectively, which correlated with increased cancer recurrence and metastasis. Together, our data indicate that Cx43 and Cx26 mediate cancer cell metastasis to the brain and suggest that connexins might be exploited therapeutically to benefit cancer patients with metastatic disease. PMID:23321642

Communication about patient pain in primary care: development of the Physician-Patient Communication about Pain scale (PCAP).

PubMed

Haskard-Zolnierek, Kelly B

2012-01-01

This paper describes the development of the 47-item Physician-Patient Communication about Pain (PCAP) scale for use with audiotaped medical visit interactions. Patient pain was assessed with the Medical Outcomes Study SF-36 Bodily Pain Scale. Four raters assessed 181 audiotaped patient interactions with 68 physicians. Descriptive statistics of PCAP items were computed. Principal components analyses with 20 scale items were used to reduce the scale to composite variables for analyses. Validity was assessed through (1) comparing PCAP composite scores for patients with high versus low pain and (2) correlating PCAP composites with a separate communication rating scale. Principal components analyses yielded four physician and five patient communication composites (mean alpha=.77). Some evidence for concurrent validity was provided (5 of 18 correlations with communication validation rating scale were significant). Paired-sample t tests showed significant differences for 4 patient PCAP composites, showing the PCAP scale discriminates between high and low pain patients' communication. The PCAP scale shows partial evidence of reliability and two forms of validity. More research with this scale (developing more reliable and valid composites) is needed to extend these preliminary findings before this scale is applicable for use in practice. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Protein myozap--a late addition to the molecular ensembles of various kinds of adherens junctions.

PubMed

Rickelt, Steffen; Kuhn, Caecilia; Winter-Simanowski, Stefanie; Zimbelmann, Ralf; Frey, Norbert; Franke, Werner Wilhelm

2011-12-01

The protein myozap, a polypeptide of 54 kDa, has recently been identified as a component of the cytoplasmic plaques of the composite junctions (areae compositae) in the myocardiac intercalated disks and of the adherens junctions (AJs) in vascular endothelia. Now we report that using very sensitive new antibodies and drastic localization methods, we have also identified this protein as a component of the AJ plaques in simple and complex epithelia, in the adluminal cell layer of the transitional epithelium of the urinary tract and in certain cell layers of diverse stratified epithelia, including gingiva, tongue, pharynx and esophagus, cervix, vagina and epidermis. Myozap has not been identified in desmosomal and tight junction plaques. We have also detected protein myozap in AJ structures of carcinomas. The discovery of a novel major protein in AJ plaques now calls for re-examinations of molecular interactions in AJ formation and maintenance and also offers a new marker for diagnostic immunocytochemistry. We also discuss the need for progressive unravelling, extractive treatments and buffer rinses of sections and cultured cells to reveal obscured or masked antigens, before definitive negative conclusions in immunohistochemistry can be made.

Rectification of current responds to incorporation of fullerenes into mixed-monolayers of alkanethiolates in tunneling junctions.

PubMed

Qiu, Li; Zhang, Yanxi; Krijger, Theodorus L; Qiu, Xinkai; Hof, Patrick Van't; Hummelen, Jan C; Chiechi, Ryan C

2017-03-01

This paper describes the rectification of current through molecular junctions comprising self-assembled monolayers of decanethiolate through the incorporation of C 60 fullerene moieties bearing undecanethiol groups in junctions using eutectic Ga-In (EGaIn) and Au conducting probe AFM (CP-AFM) top-contacts. The degree of rectification increases with increasing exposure of the decanethiolate monolayers to the fullerene moieties, going through a maximum after 24 h. We ascribe this observation to the resulting mixed-monolayer achieving an optimal packing density of fullerene cages sitting above the alkane monolayer. Thus, the degree of rectification is controlled by the amount of fullerene present in the mixed-monolayer. The voltage dependence of R varies with the composition of the top-contact and the force applied to the junction and the energy of the lowest unoccupied π-state determined from photoelectron spectroscopy is consistent with the direction of rectification. The maximum value of rectification R = | J (+)/ J (-)| = 940 at ±1 V or 617 at ±0.95 V is in agreement with previous studies on pure monolayers relating the degree of rectification to the volume of the head-group on which the frontier orbitals are localized.

Enhancing phonon flow through one-dimensional interfaces by impedance matching

NASA Astrophysics Data System (ADS)

Polanco, Carlos A.; Ghosh, Avik W.

2014-08-01

We extend concepts from microwave engineering to thermal interfaces and explore the principles of impedance matching in 1D. The extension is based on the generalization of acoustic impedance to nonlinear dispersions using the contact broadening matrix Γ(ω), extracted from the phonon self energy. For a single junction, we find that for coherent and incoherent phonons, the optimal thermal conductance occurs when the matching Γ(ω) equals the Geometric Mean of the contact broadenings. This criterion favors the transmission of both low and high frequency phonons by requiring that (1) the low frequency acoustic impedance of the junction matches that of the two contacts by minimizing the sum of interfacial resistances and (2) the cut-off frequency is near the minimum of the two contacts, thereby reducing the spillage of the states into the tunneling regime. For an ultimately scaled single atom/spring junction, the matching criterion transforms to the arithmetic mean for mass and the harmonic mean for spring constant. The matching can be further improved using a composite graded junction with an exponential varying broadening that functions like a broadband antireflection coating. There is, however, a trade off as the increased length of the interface brings in additional intrinsic sources of scattering.

Structure and chemical composition of the dentin-enamel junction analyzed by Confocal Raman Microscopy

NASA Astrophysics Data System (ADS)

Desoutter, A.; Salehi, H.; Slimani, A.; Marquet, P.; Jacquot, B.; Tassery, H.; Cuisinier, F. J. G.

2014-02-01

The structure and chemical composition of the human dentin-enamel junction (DEJ) was studied using confocal Raman microscopy - a chemical imaging technique. Slices of non-fixed, sound teeth were prepared with an Isomet diamond saw and scanned with Witec Alpha300R system. The combination of different characteristics peaks of phosphate, carbonate and organic matrix (respectively 960, 1072 and 1545 cm-1), generates images representing the chemical composition of the DEJ area. Images are also calculated using peak ratios enabling precise determination of the chemical composition across the DEJ. Then, with two characterized peaks, different pictures are calculated to show the ratio of two components. The images of the spatial distribution of mineral phosphate (960cm-1) to organic matrix (1545 cm-1) ratios, mineral carbonates (1072cm-1) to mineral phosphate ratios; and mineral carbonates to organic matrix ratios were reconstructed. Cross sectional and calculated graphic profile show the variations of the different chemical component ratios through the enamel and the dentin. Phosphate to organic ratio shows an accumulation of organic material under the enamel surface. The cross sectional profile of these pictures shows a high phosphate content compared to enamel in the vicinity of the DEJ. The Confocal Raman imaging technique can be used to further provide full chemical imaging of tooth, particularly of the whole DEJ and to study enamel and dentin decay.

Neto-Mediated Intracellular Interactions Shape Postsynaptic Composition at the Drosophila Neuromuscular Junction

PubMed Central

Ramos, Cathy I.; Igiesuorobo, Oghomwen; Wang, Qi; Serpe, Mihaela

2015-01-01

The molecular mechanisms controlling the subunit composition of glutamate receptors are crucial for the formation of neural circuits and for the long-term plasticity underlying learning and memory. Here we use the Drosophila neuromuscular junction (NMJ) to examine how specific receptor subtypes are recruited and stabilized at synaptic locations. In flies, clustering of ionotropic glutamate receptors (iGluRs) requires Neto (Neuropillin and Tolloid-like), a highly conserved auxiliary subunit that is essential for NMJ assembly and development. Drosophila neto encodes two isoforms, Neto-α and Neto-β, with common extracellular parts and distinct cytoplasmic domains. Mutations that specifically eliminate Neto-β or its intracellular domain were generated. When Neto-β is missing or is truncated, the larval NMJs show profound changes in the subtype composition of iGluRs due to reduced synaptic accumulation of the GluRIIA subunit. Furthermore, neto-β mutant NMJs fail to accumulate p21-activated kinase (PAK), a critical postsynaptic component implicated in the synaptic stabilization of GluRIIA. Muscle expression of either Neto-α or Neto-β rescued the synaptic transmission at neto null NMJs, indicating that Neto conserved domains mediate iGluRs clustering. However, only Neto-β restored PAK synaptic accumulation at neto null NMJs. Thus, Neto engages in intracellular interactions that regulate the iGluR subtype composition by preferentially recruiting and/or stabilizing selective receptor subtypes. PMID:25905467

Increased Cardiac Arrhythmogenesis Associated With Gap Junction Remodeling With Upregulation of RNA-Binding Protein FXR1.

PubMed

Chu, Miensheng; Novak, Stefanie Mares; Cover, Cathleen; Wang, Anne A; Chinyere, Ikeotunye Royal; Juneman, Elizabeth B; Zarnescu, Daniela C; Wong, Pak Kin; Gregorio, Carol C

2018-02-06

Gap junction remodeling is well established as a consistent feature of human heart disease involving spontaneous ventricular arrhythmia. The mechanisms responsible for gap junction remodeling that include alterations in the distribution of, and protein expression within, gap junctions are still debated. Studies reveal that multiple transcriptional and posttranscriptional regulatory pathways are triggered in response to cardiac disease, such as those involving RNA-binding proteins. The expression levels of FXR1 (fragile X mental retardation autosomal homolog 1), an RNA-binding protein, are critical to maintain proper cardiac muscle function; however, the connection between FXR1 and disease is not clear. To identify the mechanisms regulating gap junction remodeling in cardiac disease, we sought to identify the functional properties of FXR1 expression, direct targets of FXR1 in human left ventricle dilated cardiomyopathy (DCM) biopsy samples and mouse models of DCM through BioID proximity assay and RNA immunoprecipitation, how FXR1 regulates its targets through RNA stability and luciferase assays, and functional consequences of altering the levels of this important RNA-binding protein through the analysis of cardiac-specific FXR1 knockout mice and mice injected with 3xMyc-FXR1 adeno-associated virus. FXR1 expression is significantly increased in tissue samples from human and mouse models of DCM via Western blot analysis. FXR1 associates with intercalated discs, and integral gap junction proteins Cx43 (connexin 43), Cx45 (connexin 45), and ZO-1 (zonula occludens-1) were identified as novel mRNA targets of FXR1 by using a BioID proximity assay and RNA immunoprecipitation. Our findings show that FXR1 is a multifunctional protein involved in translational regulation and stabilization of its mRNA targets in heart muscle. In addition, introduction of 3xMyc-FXR1 via adeno-associated virus into mice leads to the redistribution of gap junctions and promotes ventricular tachycardia, showing the functional significance of FXR1 upregulation observed in DCM. In DCM, increased FXR1 expression appears to play an important role in disease progression by regulating gap junction remodeling. Together this study provides a novel function of FXR1, namely, that it directly regulates major gap junction components, contributing to proper cell-cell communication in the heart. © 2017 American Heart Association, Inc.

Intercellular nanotubes: insights from imaging studies and beyond

PubMed Central

Hurtig, Johan; Chiu, Daniel T.; Önfelt, Björn

2017-01-01

Cell-cell communication is critical to the development, maintenance, and function of multicellular organisms. Classical mechanisms for intercellular communication include secretion of molecules into the extracellular space and transport of small molecules through gap junctions. Recent reports suggest that cells also can communicate over long distances via a network of transient intercellular nanotubes. Such nanotubes have been shown to mediate intercellular transfer of organelles as well as membrane components and cytoplasmic molecules. Moreover, intercellular nanotubes have been observed in vivo and have been shown to enhance the transmission of pathogens such as human immunodeficiency virus (HIV)-1 and prions in vitro. These studies indicate that intercellular nanotubes may play a role both in normal physiology and in disease. PMID:20166114

Synaptic communication between neurons and NG2+ cells.

PubMed

Paukert, Martin; Bergles, Dwight E

2006-10-01

Chemical synaptic transmission provides the basis for much of the rapid signaling that occurs within neuronal networks. However, recent studies have provided compelling evidence that synapses are not used exclusively for communication between neurons. Physiological and anatomical studies indicate that a distinct class of glia known as NG2(+) cells also forms direct synaptic junctions with both glutamatergic and GABAergic neurons. Glutamatergic signaling can influence intracellular Ca(2+) levels in NG2(+) cells by activating Ca(2+) permeable AMPA receptors, and these inputs can be potentiated through high frequency stimulation. Although the significance of this highly differentiated form of communication remains to be established, these neuro-glia synapses might enable neurons to influence rapidly the behavior of this ubiquitous class of glial progenitors.

Device useful as a borehole fluid sampler

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freifeld, Barry M.

The present invention provides a device comprising: (a) a proximal end of the device comprises an inner first conduit within the lumen of an outer second conduit, (b) a distal end of the device comprises the outer second conduit in fluid communication with a third conduit and a fourth conduit through a Y-shaped, T-shaped or U-shaped junction, (c) the third conduit terminates in a triggering mechanism, and (d) the fourth conduit is in fluid communication through a one-way valve, wherein fluid can only convey in a direction from the fourth conduit towards the second outer conduit, with an aperture.

Nanoparticle-assisted photo-Fenton reaction for photo-decomposition of humic acid

NASA Astrophysics Data System (ADS)

Banik, Jhuma; Basumallick, Srijita

2017-11-01

We report here the synthesis of CuO-doped ZnO composite nanomaterials (NMs) by chemical route and demonstrated for the first time that these NMs are efficient catalysts for H2O2-assisted photo-decomposition (photo-Fenton type catalyst) of humic acid, a natural pollutant of surface water by solar irradiation. This has been explained by faster electron transfer to OH radical at the p-n hetero-junction of this composite catalyst. Application of this composite catalyst in decomposing humus substances of local pond water by solar energy has been demonstrated.

Inhibitors of connexin and pannexin channels as potential therapeutics

PubMed Central

Willebrords, Joost; Maes, Michaël; Crespo Yanguas, Sara; Vinken, Mathieu

2018-01-01

While gap junctions support the exchange of a number of molecules between neighboring cells, connexin hemichannels provide communication between the cytosol and the extracellular environment of an individual cell. The latter equally holds true for channels composed of pannexin proteins, which display an architecture reminiscent of connexin hemichannels. In physiological conditions, gap junctions are usually open, while connexin hemichannels and, to a lesser extent, pannexin channels are typically closed, yet they can be activated by a number of pathological triggers. Several agents are available to inhibit channels built up by connexin and pannexin proteins, including alcoholic substances, glycyrrhetinic acid, anesthetics and fatty acids. These compounds not always strictly distinguish between gap junctions, connexin hemichannels and pannexin channels, and may have effects on other targets as well. An exception lies with mimetic peptides, which reproduce specific amino acid sequences in connexin or pannexin primary protein structure. In this paper, a state-of-the-art overview is provided on inhibitors of cellular channels consisting of connexins and pannexins with specific focus on their mode-of-action and therapeutic potential. PMID:28720428

K-band high power latching switch. [communication satellite system

NASA Technical Reports Server (NTRS)

Mlinar, M. J.; Piotrowski, W. S.; Raue, J. E.

1980-01-01

A 19 GHz waveguide latching switch with a bandwidth of 1400 MHz and an exceptionally low insertion loss of 0.25 dB was demonstrated. The RF and driver ferrites are separate structures and can be optimized individually. This analysis for each structure is separately detailed. Basically, the RF section features a dual turnstile junction. The circulator consists of a dielectric tube which contains two ferrite rods, and a dielectric spacer separating the ferrite parts along the center of symmetry of the waveguide to form two turnstiles. This subassembly is indexed and locked in the center of symmetry of a uniform junction of three waveguides by the metallic transformers installed in the top and bottom walls of the housing. The switching junction and its actuating circuitry met all RF performance objectives and all shock and vibration requirements with no physical damage or performance degradation. It exceeds thermal requirements by operating over a 100 C temperature range (-44 C to +56 C) and has a high power handling capability allowing up to 100 W of CW input power.

Tags, wireless communication systems, tag communication methods, and wireless communications methods

DOEpatents

Scott,; Jeff W. , Pratt; Richard, M [Richland, WA

2006-09-12

Tags, wireless communication systems, tag communication methods, and wireless communications methods are described. In one aspect, a tag includes a plurality of antennas configured to receive a plurality of first wireless communication signals comprising data from a reader, a plurality of rectifying circuits coupled with. respective individual ones of the antennas and configured to provide rectified signals corresponding to the first wireless communication signals, wherein the rectified signals are combined to produce a composite signal, an adaptive reference circuit configured to vary a reference signal responsive to the composite signal, a comparator coupled with the adaptive reference circuit and the rectifying circuits and configured to compare the composite signal with respect to the reference signal and to output the data responsive to the comparison, and processing circuitry configured to receive the data from the comparator and to process the data.

33 CFR 162.132 - Connecting waters from Lake Huron to Lake Erie; communications rules.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (2) Channel 12 (156.60 mhz) between Lake St. Clair Light and Detroit River Light. (b) Radiotelephone... Cut Light “7” Lake Huron Cut Lighted Buoy “1” Report. Report St. Clair/Black River Junction Light Report. Stag Island Upper Light Report. Report Marine City Salt Dock Light Report. Report Grande Pointe...

Apigenin and tangeretin enhance gap junctional intercellular communication in rat liver epithelial cells.

PubMed

Chaumontet, C; Bex, V; Gaillard-Sanchez, I; Seillan-Heberden, C; Suschetet, M; Martel, P

1994-10-01

Two flavones, apigenin and tangeretin, were studied for their ability to modulate gap junctional intercellular communication (GJIC) in the rat liver epithelial cell line REL. Their cytotoxicity was first determined by cell density and neutral red uptake assays: neither apigenin nor tangeretin are cytotoxic at 10 and 25 microM, the concentrations used in our experiments. We then studied GJIC using the dye transfer assay and we observed that both apigenin and tangeretin enhance it, the maximum stimulation (x 1.7-1.8) being achieved at 25 microM for 24 h. When the dye transfer was enhanced, the amount of connexin 43 increased, which was demonstrated by Western blot and immunofluorescence analysis. For apigenin only, Northern blot analysis showed an accumulation of connexin 43 mRNA. In addition, the incubation of REL cells with the two compounds, for 1 or 24 h, prevented the inhibition of dye transfer by 12-O-tetradecanoylphorbol-13-acetate (1 or 10 ng/ml). The enhancement of GJIC by apigenin could be one of the major mechanisms responsible for apigenin's anti-tumour promoting action in vivo. As for tangeretin, its capacity to enhance GJIC completes its potential protective properties towards the post-initiation process.

Participation of satellite glial cells of the dorsal root ganglia in acute nociception.

PubMed

Lemes, Júlia Borges Paes; de Campos Lima, Tais; Santos, Débora Oliveira; Neves, Amanda Ferreira; de Oliveira, Fernando Silva; Parada, Carlos Almicar; da Cruz Lotufo, Celina Monteiro

2018-05-29

At dorsal root ganglia, neurons and satellite glial cells (SGC) can communicate through ATP release and P2X7 receptor activation. SGCs are also interconnected by gap junctions and have been previously implicated in modulating inflammatory and chronic pain.We now present evidence that SGCs are also involved in processing acute nociception in rat dorsal root ganglia. Using primary dorsal root ganglia cultures we observed that calcium transients induced in neurons by capsaicin administration were followed by satellite glial cells activation. Only satellite glial cells response was reduced by administration of the P2X7 receptor antagonist A740003. In vivo, acute nociception induced by intraplantar injection of capsaicin in rats was inhibited by A740003 or by the gap junction blocker carbenoxolone administered at the dorsal root ganglia (L5 level). Both drugs also reduced the second phase of the formalin test. These results suggest that communication between neurons and satellite glial cells is not only involved in inflammatory or pathological pain, but also in the transmission of the nociceptive signal, possibly in situations involving C-fiber activation. Copyright © 2018 Elsevier B.V. All rights reserved.

Quality of Communication in Robotic Surgery and Surgical Outcomes.

PubMed

Schiff, Lauren; Tsafrir, Ziv; Aoun, Joelle; Taylor, Andrew; Theoharis, Evan; Eisenstein, David

2016-01-01

Robotic surgery has introduced unique challenges to surgical workflow. The association between quality of communication in robotic-assisted laparoscopic surgery and surgical outcomes was evaluated. After each gynecologic robotic surgery, the team members involved in the surgery completed a survey regarding the quality of communication. A composite quality-of-communication score was developed using principal component analysis. A higher composite quality-of-communication score signified poor communication. Objective parameters, such as operative time and estimated blood loss (EBL), were gathered from the patient's medical record and correlated with the composite quality-of-communication scores. Forty robotic cases from March through May 2013 were included. Thirty-two participants including surgeons, circulating nurses, and surgical technicians participated in the study. A higher composite quality-of-communication score was associated with greater EBL (P = .010) and longer operative time (P = .045), after adjustment for body mass index, prior major abdominal surgery, and uterine weight. Specifically, for every 1-SD increase in the perceived lack of communication, there was an additional 51 mL EBL and a 31-min increase in operative time. The most common reasons reported for poor communication in the operating room were noise level (28/36, 78%) and console-to-bedside communication problems (23/36, 64%). Our study demonstrates a significant association between poor intraoperative team communication and worse surgical outcomes in robotic gynecologic surgery. Employing strategies to decrease extraneous room noise, improve console-to-bedside communication and team training may have a positive impact on communication and related surgical outcomes.

Old cogs, new tricks: a scaffolding role for connexin43 and a junctional role for sodium channels?

PubMed

Veeraraghavan, Rengasayee; Poelzing, Steven; Gourdie, Robert G

2014-04-17

Cardiac conduction is the process by which electrical excitation is communicated from cell to cell within the heart, triggering synchronous contraction of the myocardium. The role of conduction defects in precipitating life-threatening arrhythmias in various disease states has spurred scientific interest in the phenomenon. While the understanding of conduction has evolved greatly over the last century, the process has largely been thought to occur via movement of charge between cells via gap junctions. However, it has long been hypothesized that electrical coupling between cardiac myocytes could also occur ephaptically, without direct transfer of ions between cells. This review will focus on recent insights into cardiac myocyte intercalated disk ultrastructure and their implications for conduction research, particularly the ephaptic coupling hypothesis. Published by Elsevier B.V.

SR/ER-mitochondrial local communication: Calcium and ROS

PubMed Central

Csordás, György; Hajnóczky, György

2009-01-01

Mitochondria form junctions with the sarco/endoplasmic reticulum (SR/ER), which support signal transduction and biosynthetic pathways and affect organellar distribution. Recently, these junctions have received attention because of their pivotal role in mediating calcium signal propagation to the mitochondria, which is important for both ATP production and mitochondrial cell death. Many of the SR/ER-mitochondrial calcium transporters and signaling proteins are sensitive to redox regulation and are directly exposed to the reactive oxygen species (ROS) produced in the mitochondria and SR/ER. Although ROS has been emerging as a novel signaling entity, the redox signaling of the SR/ER-mitochondrial interface is yet to be elucidated. We describe here possible mechanisms of the mutual interaction between local Ca2+ and ROS signaling in the control of SR/ER-mitochondrial function. PMID:19527680

FAST TRACK COMMUNICATION: Spontaneous symmetry breaking in a bridge model fed by junctions

NASA Astrophysics Data System (ADS)

Popkov, Vladislav; Evans, Martin R.; Mukamel, David

2008-10-01

We introduce a class of 1D models mimicking a single-lane bridge with two junctions and two particle species driven in opposite directions. The model exhibits spontaneous symmetry breaking (SSB) for a range of injection/extraction rates. In this phase the steady-state currents of the two species are not equal. Moreover, there is a co-existence region in which the symmetry-broken phase co-exists with a symmetric phase. Along a path in which the extraction rate is varied, keeping the injection rate fixed and large, hysteresis takes place. The mean-field phase diagram is calculated and supporting Monte Carlo simulations are presented. One of the transition lines exhibits a kink, a feature which cannot exist in transition lines of equilibrium phase transitions.

Pronounced Photovoltaic Response from Multilayered Transition-Metal Dichalcogenides PN-Junctions.

PubMed

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

2015-11-11

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.

Modulation of Tight Junction Structure and Function by Kinases and Phosphatases Targeting Occludin

PubMed Central

Dörfel, Max Johannes; Huber, Otmar

2012-01-01

Tight junctions (TJs) typically represent the most apical contacts in epithelial and endothelial cell layers where they play an essential role in the separation of extracellular or luminal spaces from underlying tissues in the body. Depending on the protein composition, TJs define the barrier characteristics and in addition maintain cell polarity. Two major families of integral membrane proteins form the typical TJ strand network, the tight junction-associated MARVEL protein (TAMP) family members occludin, tricellulin, and MarvelD3 as well as a specific set of claudins. Occludin was the first identified member of these tetraspanins and is now widely accepted as a regulator of TJ assembly and function. Therefore, occludin itself has to be tightly regulated. Phosphorylation of occludin appears to be of central importance in this context. Here we want to summarize current knowledge on the kinases and phosphatases directly modifying occludin, and their role in the regulation of TJ structure, function, and dynamics. PMID:22315516

High-efficiency p-n junction oxide photoelectrodes for photoelectrochemical water splitting.

PubMed

Liu, Zhifeng; Yan, Lu

2016-11-16

Development of all oxide p-n junctions makes a significant advancement in photoelectrode catalysis functional materials. In this article, we report the preparation of TiO 2 nanorod (NR)/Cu 2 O photoanodes via a simple hydrothermal method followed by an electrochemical deposition process. This facile synthesis route can simultaneously achieve uniform TiO 2 NR/Cu 2 O composite nanostructures and obtain varied amounts of Cu 2 O by controlling the deposition time. The photocurrent density of TiO 2 NR/Cu 2 O heterojunction photoanodes enhanced the photocatalytic activity with a photocurrent density of 5.25 mA cm -2 at 1.23 V versus RHE compared to pristine TiO 2 NR photoanodes under the same conditions. It is demonstrated that the presence of Cu 2 O has played an important role in expanding the spectral response region and reducing the photogenerated charge recombination rate. More importantly, the results provide new insights into the performance of all oxide p-n junctions as photoanodes for PEC water splitting.

Rescue of perfluorooctanesulfonate (PFOS)-mediated Sertoli cell injury by overexpression of gap junction protein connexin 43

PubMed Central

Li, Nan; Mruk, Dolores D.; Chen, Haiqi; Wong, Chris K. C.; Lee, Will M.; Cheng, C. Yan

2016-01-01

Perfluorooctanesulfonate (PFOS) is an environmental toxicant used in developing countries, including China, as a stain repellent for clothing, carpets and draperies, but it has been banned in the U.S. and Canada since the late 2000s. PFOS perturbed the Sertoli cell tight junction (TJ)-permeability barrier, causing disruption of actin microfilaments in cell cytosol, perturbing the localization of cell junction proteins (e.g., occluden-ZO-1, N-cadherin-ß-catenin). These changes destabilized Sertoli cell blood-testis barrier (BTB) integrity. These findings suggest that human exposure to PFOS might induce BTB dysfunction and infertility. Interestingly, PFOS-induced Sertoli cell injury associated with a down-regulation of the gap junction (GJ) protein connexin43 (Cx43). We next investigated if overexpression of Cx43 in Sertoli cells could rescue the PFOS-induced cell injury. Indeed, overexpression of Cx43 in Sertoli cells with an established TJ-barrier blocked the disruption in PFOS-induced GJ-intercellular communication, resulting in the re-organization of actin microfilaments, which rendered them similar to those in control cells. Furthermore, cell adhesion proteins that utilized F-actin for attachment became properly distributed at the cell-cell interface, resealing the disrupted TJ-barrier. In summary, Cx43 is a good target that might be used to manage PFOS-induced reproductive dysfunction. PMID:27436542

Myosin VI facilitates connexin 43 gap junction accretion.

PubMed

Waxse, Bennett J; Sengupta, Prabuddha; Hesketh, Geoffrey G; Lippincott-Schwartz, Jennifer; Buss, Folma

2017-03-01

In this study, we demonstrate myosin VI enrichment at Cx43 (also known as GJA1)-containing gap junctions (GJs) in heart tissue, primary cardiomyocytes and cell culture models. In primary cardiac tissue and in fibroblasts from the myosin VI-null mouse as well as in tissue culture cells transfected with siRNA against myosin VI, we observe reduced GJ plaque size with a concomitant reduction in intercellular communication, as shown by fluorescence recovery after photobleaching (FRAP) and a new method of selective calcein administration. Analysis of the molecular role of myosin VI in Cx43 trafficking indicates that myosin VI is dispensable for the delivery of Cx43 to the cell surface and connexon movement in the plasma membrane. Furthermore, we cannot corroborate clathrin or Dab2 localization at gap junctions and we do not observe a function for the myosin-VI-Dab2 complex in clathrin-dependent endocytosis of annular gap junctions. Instead, we found that myosin VI was localized at the edge of Cx43 plaques by using total internal reflection fluorescence (TIRF) microscopy and use FRAP to identify a plaque accretion defect as the primary manifestation of myosin VI loss in Cx43 homeostasis. A fuller understanding of this derangement may explain the cardiomyopathy or gliosis associated with the loss of myosin VI. © 2017. Published by The Company of Biologists Ltd.

How hormones influence composition and physiological function of the brain-blood barrier.

PubMed

Hampl, R; Bičíková, M; Sosvorová, L

2015-01-01

Hormones exert many actions in the brain. Their access and effects in the brain are regulated by the blood-brain barrier (BBB). Hormones as other substances may enter the brain and vice versa either by paracellular way requiring breaching tight junctions stitching the endothelial cells composing the BBB, or by passage through the cells (transcellular way). Hormones influence both ways through their receptors, both membrane and intracellular, present on/in the BBB. In the review the main examples are outlined how hormones influence the expression and function of proteins forming the tight junctions, as well as how they regulate expression and function of major protein transporters mediating transport of various substances including hormone themselves.

Anomalous reversal of transverse thermoelectric voltage in CoδFe100-δ /YIG junction

NASA Astrophysics Data System (ADS)

Ramos, R.; Wongjom, P.; Iguchi, R.; Yagmur, A.; Qiu, Z.; Pinitsoontorn, S.; Uchida, K.; Saitoh, E.

2018-02-01

We have studied thermoelectric conversion in all-ferromagnetic CoδFe100-δ /YIG bilayer junctions as a function of the chemical composition δ . We performed measurements of the transverse thermoelectric voltage upon application of a magnetic field. The voltage measured in the longitudinal spin Seebeck effect configuration shows a sign reversal at δ = 40%, which cannot be explained by the conventional electronic transport, such as the anomalous Nernst and Hall effects in the CoδFe100-δ layer. Our results suggest a possible role of the sd-type exchange interaction between Co40Fe60 and YIG at the interface as a possible origin for the observed behavior.

Regulation of actin dynamics and protein trafficking during spermatogenesis – insights into a complex process*

PubMed Central

Su, Wenhui; Mruk, Dolores; Cheng, C Yan

2013-01-01

In the mammalian testis, extensive restructuring takes place across the seminiferous epithelium at the Sertoli-Sertoli and Sertoli-germ cell interface during the epithelial cycle of spermatogenesis, which is important to facilitate changes in the cell shape and morphology of developing germ cells. However, precise communications also take place at the cell junctions to coordinate the discrete events pertinent to spermatogenesis, namely spermatogonial renewal via mitosis, cell cycle progression and meiosis, spermiogenesis, and spermiation. It is obvious that these cellular events are intimately related to the underlying actin-based cytoskeleton which is being used by different cell junctions for their attachment. However, little is known on the biology and regulation of this cytoskeleton, in particular its possible involvement in endocytic vesicle-mediated trafficking during spermatogenesis, which in turn affects cell adhesive function and communication at the cell-cell interface. Studies in other epithelia in recent years have shed insightful information on the intimate involvement of actin dynamics and protein trafficking in regulating cell adhesion and communications. The goal of this critical review is to provide an updated assessment of the latest findings in the field on how these complex processes regulate spermatogenesis. We also provide a working model based on the latest findings in the field to provide our thoughts on an apparent complicated subject, which also serves as the framework for investigators in the field. It is obvious that this model will be rapidly updated when more data are available in future years. PMID:23339542

High sensitivity Schottky junction diode based on monolithically grown aligned polypyrrole nanofibers: Broad range detection of m-dihydroxybenzene.

PubMed

Ameen, Sadia; Akhtar, M Shaheer; Seo, Hyung-Kee; Shin, Hyung Shik

2015-07-30

Aligned p-type polypyrrole (PPy) nanofibers (NFs) thin film was grown on n-type silicon (100) substrate by an electrochemical technique to fabricate Schottky junction diode for the efficient detection of m-dihydroxybenzene chemical. The highly dense and well aligned PPy NFs with the average diameter (∼150-200 nm) were grown on n-type Si substrate. The formation of aligned PPy NFs was confirmed by elucidating the structural, compositional and the optical properties. The electrochemical behavior of the fabricated Pt/p-aligned PPy NFs/n-silicon Schottky junction diode was evaluated by cyclovoltametry (CV) and current (I)-voltage (V) measurements with the variation of m-dihydroxybenzene concentration in the phosphate buffer solution (PBS). The fabricated Pt/p-aligned PPy NFs/n-silicon Schottky junction diode exhibited the rectifying behavior of I-V curve with the addition of m-dihydroxybenzene chemical, while a weak rectifying I-V behavior was observed without m-dihydroxybenzene chemical. This non-linear I-V behavior suggested the formation of Schottky barrier at the interface of Pt layer and p-aligned PPy NFs/n-silicon thin film layer. By analyzing the I-V characteristics, the fabricated Pt/p-aligned PPy NFs/n-silicon Schottky junction diode displayed reasonably high sensitivity ∼23.67 μAmM(-1)cm(-2), good detection limit of ∼1.51 mM with correlation coefficient (R) of ∼0.9966 and short response time (10 s). Copyright © 2015 Elsevier B.V. All rights reserved.

Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus.

PubMed

Chen, X; Threlkeld, S W; Cummings, E E; Juan, I; Makeyev, O; Besio, W G; Gaitanis, J; Banks, W A; Sadowska, G B; Stonestreet, B S

2012-12-13

The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (K(i)) and tight junction proteins by Western immunoblot in fetal sheep at 127 days of gestation without ischemia, and 4, 24, or 48 h after ischemia. The largest increase in K(i) (P<0.05) was 4 h after ischemia. Occludin and claudin-5 expressions decreased at 4 h, but returned toward control levels 24 and 48 h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between K(i) and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (K(i)) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4 h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24 and 48 than 4 h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Structures with high number density of carbon nanotubes and 3-dimensional distribution

NASA Technical Reports Server (NTRS)

Chen, Zheng (Inventor); Tzeng, Yonhua (Inventor)

2002-01-01

A composite is described having a three dimensional distribution of carbon nanotubes. The critical aspect of such composites is a nonwoven network of randomly oriented fibers connected at their junctions to afford macropores in the spaces between the fibers. A variety of fibers may be employed, including metallic fibers, and especially nickel fibers. The composite has quite desirable properties for cold field electron emission applications, such as a relatively low turn-on electric field, high electric field enhancement factors, and high current densities. The composites of this invention also show favorable properties for other an electrode applications. Several methods, which also have general application in carbon nanotube production, of preparing these composites are described and employ a liquid feedstock of oxyhydrocarbons as carbon nanotube precursors.

Modulation of connexin expression and gap junction communication in astrocytes by the gram-positive bacterium S. aureus.

PubMed

Esen, Nilufer; Shuffield, Debbie; Syed, Mohsin M D; Kielian, Tammy

2007-01-01

Gap junctions establish direct intercellular conduits between adjacent cells and are formed by the hexameric organization of protein subunits called connexins (Cx). It is unknown whether the proinflammatory milieu that ensues during CNS infection with S. aureus, one of the main etiologic agents of brain abscess in humans, is capable of eliciting regional changes in astrocyte homocellular gap junction communication (GJC) and, by extension, influencing neuron homeostasis at sites distant from the primary focus of infection. Here we investigated the effects of S. aureus and its cell wall product peptidoglycan (PGN) on Cx43, Cx30, and Cx26 expression, the main Cx isoforms found in astrocytes. Both bacterial stimuli led to a time-dependent decrease in Cx43 and Cx30 expression; however, Cx26 levels were elevated following bacterial exposure. Functional examination of dye coupling, as revealed by single-cell microinjections of Lucifer yellow, demonstrated that both S. aureus and PGN inhibited astrocyte GJC. Inhibition of protein synthesis with cyclohexamide (CHX) revealed that S. aureus directly modulates, in part, Cx43 and Cx30 expression, whereas Cx26 levels appear to be regulated by a factor(s) that requires de novo protein production; however, CHX did not alter the inhibitory effects of S. aureus on astrocyte GJC. The p38 MAPK inhibitor SB202190 was capable of partially restoring the S. aureus-mediated decrease in astrocyte GJC to that of unstimulated cells, suggesting the involvement of p38 MAPK-dependent pathway(s). These findings could have important implications for limiting the long-term detrimental effects of abscess formation in the brain which may include seizures and cognitive deficits. Copyright 2006 Wiley-Liss, Inc.

A parallel input composite transimpedance amplifier.

PubMed

Kim, D J; Kim, C

2018-01-01

A new approach to high performance current to voltage preamplifier design is presented. The design using multiple operational amplifiers (op-amps) has a parasitic capacitance compensation network and a composite amplifier topology for fast, precision, and low noise performance. The input stage consisting of a parallel linked JFET op-amps and a high-speed bipolar junction transistor (BJT) gain stage driving the output in the composite amplifier topology, cooperating with the capacitance compensation feedback network, ensures wide bandwidth stability in the presence of input capacitance above 40 nF. The design is ideal for any two-probe measurement, including high impedance transport and scanning tunneling microscopy measurements.

A parallel input composite transimpedance amplifier

NASA Astrophysics Data System (ADS)

Kim, D. J.; Kim, C.

2018-01-01

A new approach to high performance current to voltage preamplifier design is presented. The design using multiple operational amplifiers (op-amps) has a parasitic capacitance compensation network and a composite amplifier topology for fast, precision, and low noise performance. The input stage consisting of a parallel linked JFET op-amps and a high-speed bipolar junction transistor (BJT) gain stage driving the output in the composite amplifier topology, cooperating with the capacitance compensation feedback network, ensures wide bandwidth stability in the presence of input capacitance above 40 nF. The design is ideal for any two-probe measurement, including high impedance transport and scanning tunneling microscopy measurements.

True posterior communicating artery aneurysms: are they more prone to rupture? A biomorphometric analysis.

PubMed

He, Wenzhuan; Hauptman, Jason; Pasupuleti, Latha; Setton, Avi; Farrow, Maria G; Kasper, Lydia; Karimi, Reza; Gandhi, Chirag D; Catrambone, Jeffrey E; Prestigiacomo, Charles J

2010-03-01

Posterior communicating artery (PCoA) aneurysms can occur at the junction with the internal carotid artery, posterior cerebral artery (PCA), or the proximal PCoA itself. Hemodynamic stressors contribute to aneurysm formation and may be associated with parent vessel size and aneurysm location. This study evaluates the correlation of various biomorphometric characteristics in 2 of the aforementioned types of PCoA aneurysms. Patients with PCoA aneurysms were analyzed using CT angiography. Source images and reconstructions were used to determine which aneurysms originated purely from the PCoA and those that originated from the internal carotid artery/PCoA junction. Morphometric analysis was performed on the aneurysm, the precommunicating segment of the PCA (P(1)), the ambient segment of the PCA (P(2)), and both PCoA arteries and were correlated to clinical presentation. Parametric and nonparametric analyses were performed to test for significance. A total of 77 PCoA aneurysms were analyzed, and 10 were found to be true PCoA aneurysms (13.0%). The ipsilateral PCoA/P(1) ratio (1.77 +/- 0.44 vs 0.82 +/- 0.46, p = 0.0001) and ipsilateral P(2)/P(1) ratio (1.73 +/- 0.40 vs 1.22 +/- 0.41, p = 0.0003) were significantly larger in true PCoA aneurysms. Interestingly, aneurysm size was statistically larger in the junctional aneurysms (0.14 +/- 0.1 vs 0.072 +/- 0.04 cm(3), p = 0.03). The prevalence of ruptured aneurysms was similar in both groups (approximately 80%, p value not significant). These data suggest that true PCoA aneurysms have a larger PCoA relative to the ipsilateral P(1) segment. To the authors' knowledge, this represents the first such biomorphometric comparison of these different types of PCoA aneurysms. Although statistically smaller in size, true PCoA aneurysms also have a similar prevalence of presenting as a ruptured aneurysm, suggesting that they might be more prone to rupture than a junctional aneurysms of similar size. Further analysis will be required to determine the biophysical factors affecting rupture rates.

Perpendicular magnetic anisotropy in CoXPd100-X alloys for magnetic tunnel junctions

NASA Astrophysics Data System (ADS)

Clark, B. D.; Natarajarathinam, A.; Tadisina, Z. R.; Chen, P. J.; Shull, R. D.; Gupta, S.

2017-08-01

CoFeB/MgO-based perpendicular magnetic tunnel junctions (p-MTJ's) with high anisotropy and low damping are critical for spin-torque transfer random access memory (STT-RAM). Most schemes of making the pinned CoFeB fully perpendicular require ferrimagnets with high damping constants, a high temperature-grown L10 alloy, or an overly complex multilayered synthetic antiferromagnet (SyAF). We report a compositional study of perpendicular CoxPd alloy-pinned Co20Fe60B20/MgO based MTJ stacks, grown at moderate temperatures in a planetary deposition system. The perpendicular anisotropy of the CoxPd alloy films can be tuned based on the layer thickness and composition. The films were characterized by alternating gradient magnetometry (AGM), energy-dispersive X-rays (EDX), and X-ray diffraction (XRD). Current-in-plane tunneling (CIPT) measurements have also been performed on the compositionally varied CoxPd MTJ stacks. The CoxPd alloy becomes fully perpendicular at approximately x = 30% (atomic fraction) Co. Full-film MTJ stacks of Si/SiO2/MgO (13)/CoXPd100-x (50)/Ta (0.3)/CoFeB (1)/MgO (1.6)/CoFeB (1)/Ta (5)/Ru (10), with the numbers enclosed in parentheses being the layer thicknesses in nm, were sputtered onto thermally oxidized silicon substrates and in-situ lamp annealed at 400 °C for 5 min. CIPT measurements indicate that the highest TMR is observed for the CoPd composition with the highest perpendicular magnetic anisotropy.

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

PubMed

Ambrosi, Cinzia; Walker, Amy E; Depriest, Adam D; Cone, Angela C; Lu, Connie; Badger, John; Skerrett, I Martha; Sosinsky, Gina E

2013-01-01

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 displayed an increased tendency to aggregate. Thus, mutations in TM4 cause a range of phenotypes of dysfunctional gap junction channels that are discussed within the context of the X-ray crystallographic structure.

Conjugated ionomers for photovoltaic applications: electric field driven charge separation in organic photovoltaics. Final Technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lonergan, Mark

Final technical report for Conjugated ionomers for photovoltaic applications, electric field driven charge separation in organic photovoltaics. The central goal of the work we completed was been to understand the photochemical and photovoltaic properties of ionically functionalized conjugated polymers (conjugated ionomers or polyelectrolytes) and energy conversion systems based on them. We primarily studied two classes of conjugated polymer interfaces that we developed based either upon undoped conjugated polymers with an asymmetry in ionic composition (the ionic junction) or doped conjugated polymers with an asymmetry in doping type (the p-n junction). The materials used for these studies have primarily been themore » polyacetylene ionomers. We completed a detailed study of p-n junctions with systematically varying dopant density, photochemical creation of doped junctions, and experimental and theoretical work on charge transport and injection in polyacetylene ionomers. We have also completed related work on the use of conjugated ionomers as interlayers that improve the efficiency or organic photovoltaic systems and studied several important aspects of the chemistry of ionically functionalized semiconductors, including mechanisms of so-called "anion-doping", the formation of charge transfer complexes with oxygen, and the synthesis of new polyfluorene polyelectrolytes. We also worked worked with the Haley group at the University of Oregon on new indenofluorene-based organic acceptors.« less

Electrical Properties of a p-n Heterojunction of Li-Doped NiO and Al-Doped ZnO for Thermoelectrics

NASA Astrophysics Data System (ADS)

Desissa, Temesgen D.; Schrade, Matthias; Norby, Truls

2018-06-01

The electrical properties of a p-n heterojunction of polycrystalline p-type Ni0.98Li0.02O and n-type Zn0.98Al0.02O have been investigated for potential applications in high-temperature oxide-based thermoelectric generators without metallic interconnects. Current-voltage characteristics of the junction were measured in a two-electrode setup in ambient air at 500-1000°C. The resistance and rectification of the junction decreased with increasing temperature. A non-ideal Shockley diode model was used to fit the measured current-voltage data in order to extract characteristic parameters of the junction, such as area-specific series resistance R s and parallel shunt resistance R p, non-ideality factor, and the saturation current density. R s and R p decreased exponentially with temperature, with activation energies of 0.4 ± 0.1 eV and 1.1 ± 0.2 eV, respectively. The interface resistance of the direct p-n junction studied here is as such too high for practical applications in thermoelectrics. However, it is demonstrated that it can be reduced by an order of magnitude by using a composite of the individual materials at the interface, yielding a large effective contact area.

Homophilic and heterophilic polycystin 1 interactions regulate E-cadherin recruitment and junction assembly in MDCK cells

PubMed Central

Streets, Andrew J.; Wagner, Bart E.; Harris, Peter C.; Ward, Christopher J.; Ong, Albert C. M.

2009-01-01

Summary Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited human renal disease and is caused by mutations in two genes, PKD1 (85%) and PKD2 (15%). Cyst epithelial cells are characterised by a complex cellular phenotype including changes in proliferation, apoptosis, basement membrane composition and apicobasal polarity. Since polycystin 1 (PC1), the PKD1 protein, has been located in the basolateral membrane of kidney epithelial cells, we hypothesised that it might have a key role in mediating or stabilising cell-cell interactions. In non-ciliated L929 cells, stable or transient surface expression of the PC1 extracellular domain was sufficient to confer an adhesive phenotype and stimulate junction formation. In MDCK cells, we found that PC1 was recruited to the lateral membranes coincident with E-cadherin within 30 minutes after a `calcium switch'. Recruitment of both proteins was significantly delayed when cells were treated with a PC1 blocking antibody raised to the PKD domains. Finally, PC1 and E-cadherin could be coimmunoprecipitated together from MDCK cells. We conclude that PC1 has a key role in initiating junction formation via initial homophilic interactions and facilitates junction assembly and the establishment of apicobasal polarity by E-cadherin recruitment. PMID:19351715

33 CFR 162.132 - Connecting waters from Lake Huron to Lake Erie; communications rules.

Code of Federal Regulations, 2011 CFR

2011-07-01

... monitor: (1) Channel 11 (156.55 mhz) between Lake Huron Cut Lighted Buoy 11 and Lake St. Clair Light; and (2) Channel 12 (156.60 mhz) between Lake St. Clair Light and Detroit River Light. (b) Radiotelephone... Cut Light “7” Lake Huron Cut Lighted Buoy “1” Report. Report St. Clair/Black River Junction Light...

JPRS Report, East Europe

DTIC Science & Technology

1990-08-02

goods and services were cheaper in the GDR than in the FRG, the price level might well remain nearly constant for households of the gainfully employed ...president, rather than showing interest in whether the factory which employs us or our community is led by capable people. When will this become of...industrial and communication infrastructure encom- passing areas at the junction of three nations: France, Germany, and Switzerland . Meanwhile, Polish

Beige Communication through Gap Junctions and Adaption by Autophagy.

PubMed

Enerbäck, Sven

2016-09-13

How thermogenic stimuli activate and control beige adipocytes is not fully understood. In this issue, Zhu et al. (2016) and Altshuler-Keylin et al. (2016) provide insights into these important issues by demonstrating roles for connexin 43 (Cx43) atg5 and atg12 in signal propagation and phenotypic adaptation in beige adipocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

Flexible Transparent Conductive Films with High Performance and Reliability Using Hybrid Structures of Continuous Metal Nanofiber Networks for Flexible Optoelectronics.

PubMed

Park, Juyoung; Hyun, Byung Gwan; An, Byeong Wan; Im, Hyeon-Gyun; Park, Young-Geun; Jang, Junho; Park, Jang-Ung; Bae, Byeong-Soo

2017-06-21

We report an Ag nanofiber-embedded glass-fabric reinforced hybrimer (AgNF-GFRHybrimer) composite film as a reliable and high-performance flexible transparent conducting film. The continuous AgNF network provides superior optoelectronic properties of the composite film by minimizing transmission loss and junction resistance. In addition, the excellent thermal/chemical stability and mechanical durability of the GFRHybrimer matrix provides enhanced mechanical durability and reliability of the final AgNF-GFRHybrimer composite film. To demonstrate the availability of our AgNF-GFRHybrimer composite as a transparent conducting film, we fabricated a flexible organic light-emitting diode (OLED) device on the AgNF-GFRHybrimer film; the OLED showed stable operation during a flexing.

Preparation of monodisperse PEG hydrogel composite microspheres via microfluidic chip with rounded channels

NASA Astrophysics Data System (ADS)

Yu, Bing; Cong, Hailin; Liu, Xuesong; Ren, Yumin; Wang, Jilei; Zhang, Lixin; Tang, Jianguo; Ma, Yurong; Akasaka, Takeshi

2013-09-01

An effective microfluidic method to fabricate monodisperse polyethylene glycol (PEG) hydrogel composite microspheres with tunable dimensions and properties is reported in this paper. A T-junction microfluidic chip equipped with rounded channels and online photopolymerization system is applied for the microsphere microfabrication. The shape and size of the microspheres are well controlled by the rounded channels and PEG prepolymer/silicon oil flow rate ratios. The obtained PEG/aspirin composite microspheres exhibit a sustained release of aspirin for a wide time range; the obtained PEG/Fe3O4 nanocomposite microspheres exhibit excellent magnetic properties; and the obtained binary PEG/dye composite microspheres show the ability to synchronously load two functional components in the same peanut-shaped or Janus hydrogel particles.

Collective cell migration of thyroid carcinoma cells: a beneficial ability to override unfavourable substrates.

PubMed

Lobastova, Liudmila; Kraus, Dominik; Glassmann, Alexander; Khan, Dilaware; Steinhäuser, Christian; Wolff, Christina; Veit, Nadine; Winter, Jochen; Probstmeier, Rainer

2017-02-01

Tumor cell invasion and metastasis are life threatening events. Invasive tumor cells tend to migrate as collective sheets. In the present in vitro study we aimed to (i) assess whether collective tumor cells gain benefits in their migratory potential compared to single cells and (ii) to identify its putative underlying molecular mechanisms. The migratory potential of single and collective carcinoma cells was assessed using video time lapse microscopy and cell migration assays in the absence and presence of seven potential gap junction inhibitors or the Rac1 inhibitor Z62954982. The perturbation of gap junctions was assessed using a dye diffusion assay. In addition, LDH-based cytotoxicity and RT-PCR-based expression analyses were performed. Whereas single breast, cervix and thyroid carcinoma cells were virtually immobile on unfavourable plastic surfaces, we found that they gained pronounced migratory capacities as collectives under comparable conditions. Thyroid carcinoma cells, that were studied in more detail, were found to express specific subsets of connexins and to form active gap junctions as revealed by dye diffusion analysis. Although all potential gap junction blockers suppressed intercellular dye diffusion in at least one of the cell lines tested, only two of them were found to inhibit collective cell migration and none of them to inhibit single cell migration. In the presence of the Rac1 inhibitor Z62954982 collective migration, but not single cell migration, was found to be reduced up to 20 %. Our data indicate that collective migration enables tumor cells to cross otherwise unfavourable substrate areas. This capacity seems to be independent of intercellular communication via gap junctions, whereas Rac1-dependent intracellular signalling seems to be essential.

Gap-Junctional communication between developing Drosophila muscles is essential for their normal development.

PubMed

Todman, M G; Baines, R A; Stebbings, L A; Davies, J A; Bacon, J P

1999-01-01

Recent experiments have demonstrated that a family of proteins, known as the innexins, are structural components of invertebrate gap junctions. The shaking-B (shak-B) locus of Drosophila encodes two members of this emerging family, Shak-B(lethal) and Shak-B(neural). This study focuses on the role of Shak-B gap junctions in the development of embryonic and larval muscle. During embryogenesis, shak-B transcripts are expressed in a subset of the somatic muscles; expression is strong in ventral oblique muscles (VO4-6) but only weak in ventral longitudinals (VL3 and 4). Carboxyfluorescein injected into VO4 of wild-type early stage 16 embryos spreads, via gap junctions, to label adjacent muscles, including VL3 and 4. In shak-B2 embryos (in which the shak-B(neural) function is disrupted), dye injected into VO4 fails to spread into other muscles. In the first instar larva, when dye coupling between muscles is no longer present, another effect of the shak-B2 mutation is revealed by whole-cell voltage clamp. In a calcium-free saline, only two voltage-activated potassium currents are present in wild-type muscles; a fast IA and a slow IK current. In shak-B2 larvae, these two currents are significantly reduced in magnitude in VO4 and 5, but remain normal in VL3. Expression of shak-B(neural) in a shak-B2 background fully rescues both dye coupling in embryonic muscle and whole-cell currents in first instar VO4 and 5. Our observations show that Shak-B(neural) is one of a set of embryonic gap-junction proteins, and that it is required for the normal temporal development of potassium currents in some larval muscles.

Spin Josephson effect in topological superconductor-ferromagnet junction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ren, C. D.; Wang, J., E-mail: jwang@seu.edu.cn

2014-03-21

The composite topological superconductor (TS), made of one-dimensional spin-orbit coupled nanowire with proximity-induced s-wave superconductivity, is not a pure p-wave superconductor but still has a suppressed s-wave pairing. We propose to probe the spin texture of the p-wave pairing in this composite TS by examining possible spin supercurrents in an unbiased TS/ferromagnet junction. It is found that both the exchange-coupling induced and spin-flip reflection induced spin currents exist in the setup and survive even in the topological phase. We showed that besides the nontrivial p-wave pairing state accounting for Majorana Fermions, there shall be a trivial p-wave pairing state thatmore » contributes to spin supercurrent. The trivial p-wave pairing state is diagnosed from the mixing effect between the suppressed s-wave pairing and the topologically nontrivial p-wave pairing. The d vector of the TS is proved not to be rigorously perpendicular to the spin projection of p-wave pairings. Our findings are also confirmed by the Kitaev's p-wave model with a nonzero s-wave pairing.« less

Unlike myofibers, neuromuscular junctions remain stable during prolonged muscle unloading.

PubMed

Deschenes, Michael R; Will, Kristin M; Booth, Frank W; Gordon, Scott E

2003-06-15

This study assessed the effect of muscle unloading on the neuromuscular system. Sixteen male Fischer 344 rats were randomly assigned to either a hindlimb suspension (unloaded) or control group (N=8/group) for 16 days. Following this intervention period, pre- and postsynaptic features of the neuromuscular junctions (NMJs) of soleus muscles were stained with cytofluorescent techniques, and myofibers were histochemically stained for ATPase activity. The data indicate that 16 days of muscle unloading resulted in significant (P<0.05) atrophy among myofibers (>50%) that was evident among all three major fiber types (I, IIA and IIX), but failed to significantly alter any aspect of NMJ morphology quantified. These results demonstrate an impressive degree of NMJ resilience despite dramatic remodeling of associated myofibers. This may be of benefit during post-unloading rehabilitative measures where effective neuromuscular communication is essential.

Studies of silicon pn junction solar cells

NASA Technical Reports Server (NTRS)

Lindholm, F. A.; Neugroschel, A.

1977-01-01

Modifications of the basic Shockley equations that result from the random and nonrandom spatial variations of the chemical composition of a semiconductor were developed. These modifications underlie the existence of the extensive emitter recombination current that limits the voltage over the open circuit of solar cells. The measurement of parameters, series resistance and the base diffusion length is discussed. Two methods are presented for establishing the energy bandgap narrowing in the heavily-doped emitter region. Corrections that can be important in the application of one of these methods to small test cells are examined. Oxide-charge-induced high-low-junction emitter (OCI-HLE) test cells which exhibit considerably higher voltage over the open circuit than was previously seen in n-on-p solar cells are described.

Photon calorimeter

DOEpatents

Chow, Tze-Show

1988-04-22

A photon calorimeter is provided that comprises a laminar substrate that is uniform in density and homogeneous in atomic composition. A plasma-sprayed coating, that is generally uniform in density and homogeneous in atomic composition within the proximity of planes that are parallel to the surfaces of the substrate, is applied to either one or both sides of the laminar substrate. The plasma-sprayed coatings may be very efficiently spectrally tailored in atomic number. Thermocouple measuring junctions, are positioned within the plasma-sprayed coatings. The calorimeter is rugged, inexpensive, and equilibrates in temperature very rapidly. 4 figs.

Aging characteristics of blue InGaN micro-light emitting diodes at an extremely high current density of 3.5 kA cm-2

NASA Astrophysics Data System (ADS)

Tian, Pengfei; Althumali, Ahmad; Gu, Erdan; Watson, Ian M.; Dawson, Martin D.; Liu, Ran

2016-04-01

The aging characteristics of blue InGaN micro-light emitting diodes (micro-LEDs) with different sizes have been studied at an extremely high current density 3.5 kA cm-2 for emerging micro-LED applications including visible light communication (VLC), micro-LED pumped organic lasers and optogenetics. The light output power of micro-LEDs first increases and then decreases due to the competition of Mg activation in p-GaN layer and defect generation in the active region. The smaller micro-LEDs show less light output power degradation compared with larger micro-LEDs, which is attributed to the lower junction temperature of smaller micro-LEDs. It is found that the high current density without additional junction temperature cannot induce significant micro-LED degradation at room temperature but the combination of the high current density and high junction temperature leads to strong degradation. Furthermore, the cluster LEDs, composed of a micro-LED array, have been developed with both high light output power and less light output degradation for micro-LED applications in solid state lighting and VLC.

Mode of action of claudin peptidomimetics in the transient opening of cellular tight junction barriers.

PubMed

Staat, Christian; Coisne, Caroline; Dabrowski, Sebastian; Stamatovic, Svetlana M; Andjelkovic, Anuska V; Wolburg, Hartwig; Engelhardt, Britta; Blasig, Ingolf E

2015-06-01

In epithelial/endothelial barriers, claudins form tight junctions, seal the paracellular cleft, and limit the uptake of solutes and drugs. The peptidomimetic C1C2 from the C-terminal half of claudin-1's first extracellular loop increases drug delivery through epithelial claudin-1 barriers. However, its molecular and structural mode of action remains unknown. In the present study, >100 μM C1C2 caused paracellular opening of various barriers with different claudin compositions, ranging from epithelial to endothelial cells, preferentially modulating claudin-1 and claudin-5. After 6 h incubation, C1C2 reversibly increased the permeability to molecules of different sizes; this was accompanied by redistribution of claudins and occludin from junctions to cytosol. Internalization of C1C2 in epithelial cells depended on claudin-1 expression and clathrin pathway, whereby most C1C2 was retained in recyclosomes >2 h. In freeze-fracture electron microscopy, C1C2 changed claudin-1 tight junction strands to a more parallel arrangement and claudin-5 strands from E-face to P-face association - drastic and novel effects. In conclusion, C1C2 is largely recycled in the presence of a claudin, which explains the delayed onset of barrier and junction loss, the high peptide concentration required and the long-lasting effect. Epithelial/endothelial barriers are specifically modulated via claudin-1/claudin-5, which can be targeted to improve drug delivery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gap junctions are selectively associated with interlocking ball-and-sockets but not protrusions in the lens.

PubMed

Biswas, Sondip K; Lee, Jai Eun; Brako, Lawrence; Jiang, Jean X; Lo, Woo-Kuen

2010-11-09

Ball-and-sockets and protrusions are specialized interlocking membrane domains between lens fibers of all species studied. Ball-and-sockets and protrusions are similar in their shape, size, and surface morphology, and are traditionally believed to play a key role in maintaining fiber-to-fiber stability. Here, we evaluate the hypothesis that ball-and-sockets and protrusions possess important structural and functional differences during fiber cell differentiation and maturation. Intact lenses of leghorn chickens (E7 days to P62 weeks old) and rhesus monkeys (1.5-20 years old) were studied with SEM, freeze-fracture TEM, freeze-fracture immunogold labeling (FRIL), and filipin cytochemistry for membrane cholesterol detection. SEM showed that ball-and-sockets were distributed along the long and short sides of hexagonal fiber cells, whereas protrusions were located along the cell corners, from superficial to deep cortical regions in both chicken and monkey lenses. Importantly, by freeze-fracture TEM, we discovered the selective association of gap junctions with all ball-and-sockets examined, but not with protrusions, in both species. In the embryonic chicken lens (E18), the abundant distribution of ball-and-socket gap junctions was regularly found in an approximate zone extending at least 300 μm deep from the equatorial surface of the superficial cortical fibers. Many ball-and-socket gap junctions often protruded deeply into neighboring cells. However, in the mature fibers of monkey lenses, several ball-and-sockets exhibited only partial occupancy of gap junctions with disorganized connexons, possibly due to degradation of gap junctions during fiber maturation and aging. FRIL analysis confirmed that both connexin46 (Cx46) and connexin50 (Cx50) antibodies specifically labeled ball-and-socket gap junctions, but not protrusions. Furthermore, filipin cytochemistry revealed that the ball-and-socket gap junctions contained different amounts of cholesterol (i.e., cholesterol-rich versus cholesterol-free) as seen with the filipin-cholesterol-complexes (FCC) in different cortical regions during maturation. In contrast, the protrusions contained consistently high cholesterol amounts (i.e., 402 FCCs/μm2 membrane) which were approximately two times greater than that of the cholesterol-rich gap junctions (i.e., 188 FCCs/μm2 membrane) found in ball-and-sockets. Gap junctions are regularly associated with all ball-and-sockets examined in metabolically active young cortical fibers, but not with protrusions, in both chicken and monkey lenses. Since these unique gap junctions often protrude deeply into neighboring cells to increase membrane surface areas, they may significantly facilitate cell-to-cell communication between young cortical fiber cells. In particular, the large number of ball-and-socket gap junctions found near the equatorial region may effectively facilitate the flow of outward current toward the equatorial surface for internal circulation of ions in the lens. In contrast, a consistent distribution of high concentrations of cholesterol in protrusions would make the protrusion membrane less deformable and would be more suitable for maintaining fiber-to-fiber stability during visual accommodation. Thus, the ball-and-sockets and protrusions are two structurally and functionally distinct membrane domains in the lens.

Gap junctions are selectively associated with interlocking ball-and-sockets but not protrusions in the lens

PubMed Central

Biswas, Sondip K.; Lee, Jai Eun; Brako, Lawrence; Jiang, Jean X.

2010-01-01

Purpose Ball-and-sockets and protrusions are specialized interlocking membrane domains between lens fibers of all species studied. Ball-and-sockets and protrusions are similar in their shape, size, and surface morphology, and are traditionally believed to play a key role in maintaining fiber-to-fiber stability. Here, we evaluate the hypothesis that ball-and-sockets and protrusions possess important structural and functional differences during fiber cell differentiation and maturation. Methods Intact lenses of leghorn chickens (E7 days to P62 weeks old) and rhesus monkeys (1.5–20 years old) were studied with SEM, freeze-fracture TEM, freeze-fracture immunogold labeling (FRIL), and filipin cytochemistry for membrane cholesterol detection. Results SEM showed that ball-and-sockets were distributed along the long and short sides of hexagonal fiber cells, whereas protrusions were located along the cell corners, from superficial to deep cortical regions in both chicken and monkey lenses. Importantly, by freeze-fracture TEM, we discovered the selective association of gap junctions with all ball-and-sockets examined, but not with protrusions, in both species. In the embryonic chicken lens (E18), the abundant distribution of ball-and-socket gap junctions was regularly found in an approximate zone extending at least 300 μm deep from the equatorial surface of the superficial cortical fibers. Many ball-and-socket gap junctions often protruded deeply into neighboring cells. However, in the mature fibers of monkey lenses, several ball-and-sockets exhibited only partial occupancy of gap junctions with disorganized connexons, possibly due to degradation of gap junctions during fiber maturation and aging. FRIL analysis confirmed that both connexin46 (Cx46) and connexin50 (Cx50) antibodies specifically labeled ball-and-socket gap junctions, but not protrusions. Furthermore, filipin cytochemistry revealed that the ball-and-socket gap junctions contained different amounts of cholesterol (i.e., cholesterol-rich versus cholesterol-free) as seen with the filipin-cholesterol-complexes (FCC) in different cortical regions during maturation. In contrast, the protrusions contained consistently high cholesterol amounts (i.e., 402 FCCs/μm2 membrane) which were approximately two times greater than that of the cholesterol-rich gap junctions (i.e., 188 FCCs/μm2 membrane) found in ball-and-sockets. Conclusions Gap junctions are regularly associated with all ball-and-sockets examined in metabolically active young cortical fibers, but not with protrusions, in both chicken and monkey lenses. Since these unique gap junctions often protrude deeply into neighboring cells to increase membrane surface areas, they may significantly facilitate cell-to-cell communication between young cortical fiber cells. In particular, the large number of ball-and-socket gap junctions found near the equatorial region may effectively facilitate the flow of outward current toward the equatorial surface for internal circulation of ions in the lens. In contrast, a consistent distribution of high concentrations of cholesterol in protrusions would make the protrusion membrane less deformable and would be more suitable for maintaining fiber-to-fiber stability during visual accommodation. Thus, the ball-and-sockets and protrusions are two structurally and functionally distinct membrane domains in the lens. PMID:21139982

Connexin 43 expression of foreign body giant cells after implantation of nanoparticulate hydroxyapatite.

PubMed

Herde, Katja; Hartmann, Sonja; Brehm, Ralph; Kilian, Olaf; Heiss, Christian; Hild, Anne; Alt, Volker; Bergmann, Martin; Schnettler, Reinhard; Wenisch, Sabine

2007-11-01

In bone a role of connexin 43 has been implicated with the fusion of mononuclear precursors of the monocyte/macrophage lineage into multinucleated cells. In order to investigate the putative role of connexin 43 in formation of bone osteoclast-like foreign body giant cells which are formed in response to implantation of biomaterials, nanoparticulate hydroxyapatite had been implanted into defects of minipig femura. After 20 days the defect areas were harvested and connexin 43 expression and synthesis were investigated by using immunohistochemistry, Western Blot, and in situ hybridization within macrophages and osteoclast-like foreign body giant cells. Morphological analysis of gap junctions is performed ultrastructurally. As shown on protein and mRNA level numerous connexin 43 positive macrophages and foreign body giant cells (FBGC) were localized within the granulation tissue and along the surfaces of the implanted hydroxyapatite (HA). Besides, the formation of FBGC by fusion of macrophages could be shown ultrastructurally. Connexin 43 labeling observed on the protein and mRNA level could be attributed to gap junctions identified ultrastructurally between macrophages, between FBGC, and between FBGC and macrophages. Annular gap junctions in the cytoplasm of FBGC pointed to degradation of the channels, and the ubiquination that had occurred in the course of degradation was confirmed by Western blot analysis. All in all, the presently observed pattern of connexin 43 labeling refers to an functional role of gap junctional communication in the formation of osteoclast-like foreign body giant cells formed in response to implantation of the nanoparticulate HA.

The distribution and functional properties of Pelizaeus-Merzbacher-like disease-linked Cx47 mutations on Cx47/Cx47 homotypic and Cx47/Cx43 heterotypic gap junctions.

PubMed

Kim, Mi Seong; Gloor, Gregory B; Bai, Donglin

2013-06-01

GJs (gap junctions) allow direct intercellular communication, and consist of Cxs (connexins). In the mammalian central nervous system, oligodendrocytes express Cx47, Cx32 and Cx29, whereas astrocytes express Cx43, Cx30 and Cx26. Homotypic Cx47/Cx47 GJs couple oligodendrocytes, and heterotypic Cx47/Cx43 channels are the primary GJs at oligodendrocyte/astrocyte junctions. Interestingly, autosomal recessive mutations in the gene GJC2 encoding Cx47 have been linked to a central hypomyelinating disease termed PMLD (Pelizaeus-Merzbacher-like disease). The aim of the present study was to determine the cellular distribution and functional properties of PMLD-associated Cx47 mutants (I46M, G149S, G236R, G236S, M286T and T398I). Expressing GFP (green fluorescent protein)-tagged mutant versions of Cx47 in gap-junction-deficient model cells revealed that these mutants were detected at the cell-cell interface similar to that observed for wild-type Cx47. Furthermore, four of the six mutants showed no electrical coupling in both Cx47/Cx47 and Cx47/Cx43 GJ channels. These results suggest that most of the PMLD-linked Cx47 mutants disrupt Cx47/Cx47 and Cx47/Cx43 GJ function in the glial network, which may play a role in leading to PMLD symptoms.

Future Optical Communications Systems

DTIC Science & Technology

2008-06-01

rich handsets are driving growth in the wireless backhaul market. Both the iPhone and Blackberry are growing in popularity. Figure 49 forecasts the...electronic emission and tunneling , and hetero-barrier leakage. In barrier thermo-electronic emission, the conduction band of the quantum well laser is...barrier can reduce the mod- ulation bandwidth of the laser and reduce high-temperature performance due to tunneling out of the p-n junction or due

The functional interrelationship between gap junctions and fenestrae in endothelial cells of the liver organoid.

PubMed

Saito, Masaya; Matsuura, Tomokazu; Nagatsuma, Keisuke; Tanaka, Ken; Maehashi, Haruka; Shimizu, Keiko; Hataba, Yoshiaki; Kato, Fumitaka; Kashimori, Isao; Tajiri, Hisao; Braet, Filip

2007-06-01

Functional intact liver organoid can be reconstructed in a radial-flow bioreactor when human hepatocellular carcinoma (FLC-5), mouse immortalized sinusoidal endothelial M1 (SEC) and A7 (HSC) hepatic stellate cell lines are cocultured. The structural and functional characteristics of the reconstructed organoid closely resemble the in vivo liver situation. Previous liver organoid studies indicated that cell-to-cell communications might be an important factor for the functional and structural integrity of the reconstructed organoid, including the expression of fenestrae. Therefore, we examined the possible relationship between functional intact gap junctional intercellular communication (GJIC) and fenestrae dynamics in M1-SEC cells. The fine morphology of liver organoid was studied in the presence of (1) irsogladine maleate (IM), (2) oleamide and (3) oleamide followed by IM treatment. Fine ultrastructural changes were studied by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and compared with control liver organoid data. TEM revealed that oleamide affected the integrity of cell-to-cell contacts predominantly in FLC-5 hepatocytes. SEM observation showed the presence of fenestrae on M1-SEC cells; however, oleamide inhibited fenestrae expression on the surface of endothelial cells. Interestingly, fenestrae reappeared when IM was added after initial oleamide exposure. GJIC mediates the number of fenestrae in endothelial cells of the liver organoid.

Red paprika (Capsicum annuum L.) and its main carotenoids, capsanthin and β-carotene, prevent hydrogen peroxide-induced inhibition of gap-junction intercellular communication.

PubMed

Kim, Ji-Sun; Lee, Woo-Moon; Rhee, Han Cheol; Kim, Suna

2016-07-25

This study was conducted to investigate the protective effect of red paprika extract (RPE) and its main carotenoids, namely, capsanthin (CST) and β-carotene (BCT), on the H2O2-induced inhibition of gap-junction intercellular communication (GJIC) in WB-F344 rat liver epithelial cells (WB cells). We found that pre-treatment with RPE, CST and BCT protected WB cells from H2O2-induced inhibition of GJIC. RPE, CST and BCT not only recovered connexin 43 (Cx43) mRNA expression but also prevented phosphorylation of Cx43 protein by H2O2 treatment. RPE attenuated the phosphorylation of ERK, p38 and JNK, whereas pre-treatment with CST and BCT only attenuated the phosphorylation of ERK and p38 and did not affect JNK in H2O2-treated WB cells. RPE, CST and BCT significantly suppressed the formation of reactive oxygen species (ROS) in H2O2-treated cells compared to untreated WB cells. These results suggest that dietary intake of red paprika might be helpful for lowering the risk of diseases caused by oxidative stress. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Inhibition of gap-junctional intercellular communication and activation of mitogen-activated protein kinases by cyanobacterial extracts--indications of novel tumor-promoting cyanotoxins?

PubMed

Bláha, Ludĕk; Babica, Pavel; Hilscherová, Klára; Upham, Brad L

2010-01-01

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 0.5-5mgd.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.

Development of metal matrix composite gridlines for space photovoltaics

NASA Astrophysics Data System (ADS)

Abudayyeh, Omar Kamal

Space vehicles today are primarily powered by multi-junction photovoltaic cells due to their high efficiency and high radiation hardness in the space environment. While multi-junction solar cells provide high efficiency, microcracks develop in the crystalline semiconductor due to a variety of reasons, including: growth defects, film stress due to lattice constant mismatch, and external mechanical stresses introduced during shipping, installation, and operation. These microcracks have the tendency to propagate through the different layers of the semiconductor reaching the metal gridlines of the cell, resulting in electrically isolated areas from the busbar region, ultimately lowering the power output of the cell and potentially reducing the lifetime of the space mission. Pre-launch inspection are often expensive and difficult to perform, in which individual cells and entire modules must be replaced. In many cases, such microcracks are difficult to examine even with a thorough inspection. While repairs are possible pre-launch of the space vehicle, and even to some extent in low-to-earth missions, they are virtually impossible for deep space missions, therefore, efforts to mitigate the effects of these microcracks have substantial impact on the cell performance and overall success of the space mission. In this effort, we have investigated the use of multi-walled carbon nanotubes as mechanical reinforcement to the metal gridlines capable of bridging gaps generated in the underlying semiconductor while providing a redundant electrical conduction pathway. The carbon nanotubes are embedded in a silver matrix to create a metal matrix composite, which are later integrated onto commercial triple-junction solar cells.

Black Phosphorus-Zinc Oxide Nanomaterial Heterojunction for p-n Diode and Junction Field-Effect Transistor.

PubMed

Jeon, Pyo Jin; Lee, Young Tack; Lim, June Yeong; Kim, Jin Sung; Hwang, Do Kyung; Im, Seongil

2016-02-10

Black phosphorus (BP) nanosheet is two-dimensional (2D) semiconductor with distinct band gap and attracting recent attention from researches because it has some similarity to gapless 2D semiconductor graphene in the following two aspects: single element (P) for its composition and quite high mobilities depending on its fabrication conditions. Apart from several electronic applications reported with BP nanosheet, here we report for the first time BP nanosheet-ZnO nanowire 2D-1D heterojunction applications for p-n diodes and BP-gated junction field effect transistors (JFETs) with n-ZnO channel on glass. For these nanodevices, we take advantages of the mechanical flexibility of p-type conducting of BP and van der Waals junction interface between BP and ZnO. As a result, our BP-ZnO nanodimension p-n diode displays a high ON/OFF ratio of ∼10(4) in static rectification and shows kilohertz dynamic rectification as well while ZnO nanowire channel JFET operations are nicely demonstrated by BP gate switching in both electrostatics and kilohertz dynamics.

Composite Transparent Electrode of Graphene Nanowalls and Silver Nanowires on Micropyramidal Si for High-Efficiency Schottky Junction Solar Cells.

PubMed

Jiao, Tianpeng; Liu, Jian; Wei, Dapeng; Feng, Yanhui; Song, Xuefen; Shi, Haofei; Jia, Shuming; Sun, Wentao; Du, Chunlei

2015-09-16

The conventional graphene-silicon Schottky junction solar cell inevitably involves the graphene growth and transfer process, which results in complicated technology, loss of quality of the graphene, extra cost, and environmental unfriendliness. Moreover, the conventional transfer method is not well suited to conformationally coat graphene on a three-dimensional (3D) silicon surface. Thus, worse interfacial conditions are inevitable. In this work, we directly grow graphene nanowalls (GNWs) onto the micropyramidal silicon (MP) by the plasma-enhanced chemical vapor deposition method. By controlling growth time, the cell exhibits optimal pristine photovoltaic performance of 3.8%. Furthermore, we improve the conductivity of the GNW electrode by introducing the silver nanowire (AgNW) network, which could achieve lower sheet resistance. An efficiency of 6.6% has been obtained for the AgNWs-GNWs-MP solar cell without any chemical doping. Meanwhile, the cell exhibits excellent stability exposed to air. Our studies show a promising way to develop simple-technology, low-cost, high-efficiency, and stable Schottky junction solar cells.

The desmosome and pemphigus

PubMed Central

2008-01-01

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required. PMID:18386043

Flavonoids (apigenin, tangeretin) counteract tumor promoter-induced inhibition of intercellular communication of rat liver epithelial cells.

PubMed

Chaumontet, C; Droumaguet, C; Bex, V; Heberden, C; Gaillard-Sanchez, I; Martel, P

1997-03-19

We have shown previously that two flavonoids, apigenin and tangeretin, enhance gap junctional intercellular communication (GJIC) in rat liver epithelial cells, named REL cells. Here, we show that these two flavones also antagonize the inhibition of GJIC induced by tumor promoters like 12-O-tetradecanoyl-phorbol-acetate (TPA) and 3,5,di-tertio-butyl-4-hydroxytoluene (BHT). Their preventive effect is rapid. It does not seem to involve any change of the amount of the connexin expressed in REL cells, connexin 43 (Cx 43), and in its phosphorylation state. Other flavonoids tested including naringenin, myricetin, catechin and chrysin did not enhance GJIC nor counteract TPA-induced inhibition of GJIC.

High power microwave components for space communications satellite

NASA Technical Reports Server (NTRS)

Jankowski, H.; Geia, A.

1972-01-01

Analyzed, developed, and tested were high power microwave components for communications satellites systems. Included were waveguide and flange configurations with venting, a harmonic filter, forward and reverse power monitors, electrical fault sensors, and a diplexer for two channel simultaneous transmission. The assembly of 8.36 GHz components was bench tested, and then operated for 60 hours at 3.5 kW CW in a high vacuum. The diplexer was omitted from this test pending a modification of its end irises. An RF leakage test showed only that care is required at flange junctions; all other components were RF tight. Designs were extrapolated for 12 GHz and 2.64 GHz high power satellite systems.

Enamel organic matrix: potential structural role in enamel and relationship to residual basement membrane constituents at the dentin enamel junction

PubMed Central

McGuire, Jacob D.; Walker, Mary P.; Dusevich, Vladimir; Wang, Yong; Gorski, Jeff P.

2015-01-01

Although mature enamel is predominantly composed of mineral, a previously uncharacterized organic matrix layer remains in the post-eruptive tissue that begins at the dentin enamel junction and extends 200–300 µm towards the outer tooth surface. Identification of the composition of this layer has been hampered by its insolubility; however, we have developed a single step method to isolate the organic enamel matrix relatively intact. After dissociative dissolution of the matrix with SDS and urea, initial characterization by Western blotting and gel zymography indicates the presence of type IV and type VII basement membrane collagens and active matrix metalloproteinase-20. When combined with data from transgenic knockout mice and from human mutations, these data suggest that the enamel organic matrix (EOM) and dentin enamel junction may have a structural and functional relationship with basement membranes, e.g. skin. To clarify this relationship, we hypothesize a “foundation” model which proposes that components of the EOM form a support structure that stabilizes the crystalline enamel layer, and bonds it to the underlying dentin along the dentin enamel junction. Since we have also co-localized an active matrix metalloproteinase to this layer, our hypothesis suggests that, under pathologic conditions, MMP-mediated degradation of the EOM could destabilize the enamel–dentin interface. PMID:25158177

A Simple Method for Decreasing the Liquid Junction Potential in a Flow-through-Type Differential pH Sensor Probe Consisting of pH-FETs by Exerting Spatiotemporal Control of the Liquid Junction

PubMed Central

Yamada, Akira; Mohri, Satoshi; Nakamura, Michihiro; Naruse, Keiji

2015-01-01

The liquid junction potential (LJP), the phenomenon that occurs when two electrolyte solutions of different composition come into contact, prevents accurate measurements in potentiometry. The effect of the LJP is usually remarkable in measurements of diluted solutions with low buffering capacities or low ion concentrations. Our group has constructed a simple method to eliminate the LJP by exerting spatiotemporal control of a liquid junction (LJ) formed between two solutions, a sample solution and a baseline solution (BLS), in a flow-through-type differential pH sensor probe. The method was contrived based on microfluidics. The sensor probe is a differential measurement system composed of two ion-sensitive field-effect transistors (ISFETs) and one Ag/AgCl electrode. With our new method, the border region of the sample solution and BLS is vibrated in order to mix solutions and suppress the overshoot after the sample solution is suctioned into the sensor probe. Compared to the conventional method without vibration, our method shortened the settling time from over two min to 15 s and reduced the measurement error by 86% to within 0.060 pH. This new method will be useful for improving the response characteristics and decreasing the measurement error of many apparatuses that use LJs. PMID:25835300

A Broadband Terahertz Waveguide T-Junction Variable Power Splitter.

PubMed

Reichel, Kimberly S; Mendis, Rajind; Mittleman, Daniel M

2016-06-29

In order for the promise of terahertz (THz) wireless communications to become a reality, many new devices need to be developed, such as those for routing THz waves. We demonstrate a power splitting router based on a parallel-plate waveguide (PPWG) T-junction excited by the TE1 waveguide mode. By integrating a small triangular septum into the waveguide plate, we are able to direct the THz light down either one of the two output channels with precise control over the ratio between waveguide outputs. We find good agreement between experiment and simulation in both amplitude and phase. We show that the ratio between waveguide outputs varies exponentially with septum translation offset and that nearly 100% transmission can be achieved. The splitter operates over almost the entire range in which the waveguide is single mode, providing a sensitive and broadband method for THz power splitting.

A Broadband Terahertz Waveguide T-Junction Variable Power Splitter

PubMed Central

Reichel, Kimberly S.; Mendis, Rajind; Mittleman, Daniel M.

2016-01-01

In order for the promise of terahertz (THz) wireless communications to become a reality, many new devices need to be developed, such as those for routing THz waves. We demonstrate a power splitting router based on a parallel-plate waveguide (PPWG) T-junction excited by the TE1 waveguide mode. By integrating a small triangular septum into the waveguide plate, we are able to direct the THz light down either one of the two output channels with precise control over the ratio between waveguide outputs. We find good agreement between experiment and simulation in both amplitude and phase. We show that the ratio between waveguide outputs varies exponentially with septum translation offset and that nearly 100% transmission can be achieved. The splitter operates over almost the entire range in which the waveguide is single mode, providing a sensitive and broadband method for THz power splitting. PMID:27352772

Hemichannels in neurodegenerative diseases: is there a link to pathology?

PubMed Central

Bosch, Megan; Kielian, Tammy

2014-01-01

Although originally considered a structural component of gap junctions, connexin hemichannels (HCs) are now recognized as functional entities capable of influencing metabolic gradients within the CNS, allowing direct communication between the intra- and extracellular milieus. Besides connexins, HCs can also be formed by pannexins, which are not capable of gap junction assembly. Both positive and negative effects have been attributed to HC activity in the context of neurodegenerative diseases. For example, HCs can exert neuroprotective effects by promoting the uptake of neurotoxic molecules, whereas chronic HC opening can disrupt molecular gradients leading to cellular dysfunction and death. The latter scenario has been suggested for multiple neurodegenerative disorders, including Alzheimer’s disease (AD) and more recently, lysosomal storage disorders, which are the focus of this perspective. Currently available evidence suggests a complex role for HCs in neurodegenerative disorders, which sets the stage for future studies to determine whether targeting HC action may improve disease outcomes. PMID:25191227

Response of thyroid follicular cells to gamma irradiation compared to proton irradiation: II. The role of connexin 32

NASA Technical Reports Server (NTRS)

Green, L. M.; Tran, D. T.; Murray, D. K.; Rightnar, S. S.; Todd, S.; Nelson, G. A.

2002-01-01

The objective of this study was to determine whether connexin 32-type gap junctions contribute to the "contact effect" in follicular thyrocytes and whether the response is influenced by radiation quality. Our previous studies demonstrated that early-passage follicular cultures of Fischer rat thyroid cells express functional connexin 32 gap junctions, with later-passage cultures expressing a truncated nonfunctional form of the protein. This model allowed us to assess the role of connexin 32 in radiation responsiveness without relying solely on chemical manipulation of gap junctions. The survival curves generated after gamma irradiation revealed that early-passage follicular cultures had significantly lower values of alpha (0.04 Gy(-1)) than later-passage cultures (0.11 Gy(-1)) (P < 0.0001, n = 12). As an additional way to determine whether connexin 32 was contributing to the difference in survival, cultures were treated with heptanol, resulting in higher alpha values, with early-passage cultures (0.10 Gy(-1)) nearly equivalent to untreated late-passage cultures (0.11 Gy(-1)) (P > 0.1, n = 9). This strongly suggests that the presence of functional connexin 32-type gap junctions was contributing to radiation resistance in gamma-irradiated thyroid follicles. Survival curves from proton-irradiated cultures had alpha values that were not significantly different whether cells expressed functional connexin 32 (0.10 Gy(-1)), did not express connexin 32 (0.09 Gy(-1)), or were down-regulated (early-passage plus heptanol, 0.09 Gy(-1); late-passage plus heptanol, 0.12 Gy(-1)) (P > 0.1, n = 19). Thus, for proton irradiation, the presence of connexin 32-type gap junctional channels did not influence their radiosensitivity. Collectively, the data support the following conclusions. (1) The lower alpha values from the gamma-ray survival curves of the early-passage cultures suggest greater repair efficiency and/or enhanced resistance to radiation-induced damage, coincident with the expression of connexin 32-type gap junctions. (2) The increased sensitivity of FRTL-5 cells to proton irradiation was independent of their ability to communicate through connexin 32 gap junctions. (3) The fact that the beta components of the survival curves from both gamma rays and proton beams were similar (average 0.022 +/- 0.008 Gy(-2), P > 0.1, n = 39) suggests that at higher doses the loss of viability occurs at a relatively constant rate and is independent of radiation quality and the presence of functional gap junctions.

Review Article: Overview of lanthanide pnictide films and nanoparticles epitaxially incorporated into III-V semiconductors

DOE PAGES

Bomberger, Cory C.; Lewis, Matthew R.; Vanderhoef, Laura R.; ...

2017-03-30

The incorporation of lanthanide pnictide nanoparticles and films into III-V matrices allows for semiconductor composites with a wide range of potential optical, electrical, and thermal properties, making them useful for applications in thermoelectrics, tunnel junctions, phototconductive switches, and as contact layers. The similarities in crystal structures and lattice constants allow them to be epitaxially incorporated into III-V semiconductors with low defect densities and high overall film quality. A variety of growth techniques for these composites with be discussed, along with their growth mechanisms and current applications, with a focus on more recent developments. Results obtained from molecular beam epitaxy filmmore » growth will be highlighted, although other growth techniques will be mentioned. Optical and electronic characterization along with the microscopy analysis of these composites is presented to demonstrate influence of nanoinclusion composition and morphology on the resulting properties of the composite material.« less

Review Article: Overview of lanthanide pnictide films and nanoparticles epitaxially incorporated into III-V semiconductors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bomberger, Cory C.; Lewis, Matthew R.; Vanderhoef, Laura R.

The incorporation of lanthanide pnictide nanoparticles and films into III-V matrices allows for semiconductor composites with a wide range of potential optical, electrical, and thermal properties, making them useful for applications in thermoelectrics, tunnel junctions, phototconductive switches, and as contact layers. The similarities in crystal structures and lattice constants allow them to be epitaxially incorporated into III-V semiconductors with low defect densities and high overall film quality. A variety of growth techniques for these composites with be discussed, along with their growth mechanisms and current applications, with a focus on more recent developments. Results obtained from molecular beam epitaxy filmmore » growth will be highlighted, although other growth techniques will be mentioned. Optical and electronic characterization along with the microscopy analysis of these composites is presented to demonstrate influence of nanoinclusion composition and morphology on the resulting properties of the composite material.« less

Gap Junction Intercellular Communication in Bone Marrow Failure

DTIC Science & Technology

2012-10-01

enzyme systems, making individuals with these syndromes highly sensitive to DNA-damaging events. However, researchers suspect that modifier genes or...associated with a single gene defect. A major example of the progress in this area is Fanconi Anemia (FA), where mutations in up to 15 different...proteins have been associated to this disease, being FA-A the most frequent (1, 2). Single mutated genes in the DNA repair or ribosome biogenesis of HSC

Regulation of Glutathione in a Rat Diploid Hepatic Epithelial Cell Line

DTIC Science & Technology

1990-06-01

supporting the contention that they are not pre-neoplastic (60). Metabolic cooperation by gap- junctional intercellular communication has been demonstrated...counted. The resulting population statistics allowed calculation and display of cycle-specific cell characteristics and compartment transit times (see...was repeated in chinese hamster V79 cells to see if the effect is idiosyncratic. It is not - V79 cells respond to CYC in the same fashion as WB344(s) if

A neighbor pixel communication filtering structure for Dynamic Vision Sensors

NASA Astrophysics Data System (ADS)

Xu, Yuan; Liu, Shiqi; Lu, Hehui; Zhang, Zilong

2017-02-01

For Dynamic Vision Sensors (DVS), thermal noise and junction leakage current induced Background Activity (BA) is the major cause of the deterioration of images quality. Inspired by the smoothing filtering principle of horizontal cells in vertebrate retina, A DVS pixel with Neighbor Pixel Communication (NPC) filtering structure is proposed to solve this issue. The NPC structure is designed to judge the validity of pixel's activity through the communication between its 4 adjacent pixels. The pixel's outputs will be suppressed if its activities are determined not real. The proposed pixel's area is 23.76×24.71μm2 and only 3ns output latency is introduced. In order to validate the effectiveness of the structure, a 5×5 pixel array has been implemented in SMIC 0.13μm CIS process. 3 test cases of array's behavioral model show that the NPC-DVS have an ability of filtering the BA.

CRTC2 and Nedd4 ligase involvement in FSH and TGFβ1 upregulation of connexin43 gap junction.

PubMed

Fang, Wei-Ling; Lai, Si-Yi; Lai, Wei-An; Lee, Ming-Ting; Liao, Ching-Fong; Ke, Ferng-Chun; Hwang, Jiuan-Jiuan

2015-12-01

The major mission of the ovarian follicle is the timely production of the mature fertilizable oocyte, and this is achieved by gonadotropin-regulated, gap junction-mediated cell-cell communication between the oocyte and surrounding nurturing granulosa cells. We have demonstrated that FSH and transforming growth factor beta 1 (TGFβ1) stimulate Gja1 gene-encoded connexin43 (Cx43) gap junction formation/function in rat ovarian granulosa cells is important for their induction of steroidogenesis; additionally, cAMP-protein kinase A (PKA)- and calcium-calcineurin-sensitive cAMP response element-binding (CREB) coactivator CRTC2 plays a crucial role during steroidogenesis. This study was to explore the potential molecular mechanism whereby FSH and TGFβ1 regulate Cx43 synthesis and degradation, particularly the involvement of CRTC2 and ubiquitin ligase Nedd4. Primary culture of granulosa cells from ovarian antral follicles of gonadotropin-primed immature rats was used. At 48 h post-treatment, FSH plus TGFβ1 increased Cx43 level and gap junction function in a PKA- and calcineurin-dependent manner, and TGFβ1 acting through its type I receptor modulated FSH action. Chromatin-immunoprecipitation analysis reveals FSH induced an early-phase (45 min) and FSH+TGFβ1 further elicited a late-phase (24 h) increase in CRTC2, CREB and CBP binding to the Gja1 promoter. Additionally, FSH+TGFβ1 increased the half-life of hyper-phosphorylated Cx43 (Cx43-P2). Also, the proteasome inhibitor MG132 prevented the brefeldin A (blocker of protein transport through Golgi)-reduced Cx43-P2 level and membrane Cx43 gap junction plaque. This is associated with FSH+TGFβ1-attenuated Cx43 interaction with Nedd4 and Cx43 ubiquitination. In all, this study uncovers that FSH and TGFβ1 upregulation of Cx43 gap junctions in ovarian granulosa cells critically involves enhancing CRTC2/CREB/CBP-mediated Cx43 expression and attenuating ubiquitin ligase Nedd4-mediated proteosomal degradation of Cx43 protein. © 2015 Society for Endocrinology.

Phase control synthesis of α, β and α/β Bi2O3 hetero-junction with enhanced and synergistic photocatalytic activity on degradation of toxic dye, Rhodamine-B under natural sunlight.

PubMed

Bera, Kamal Kanti; Majumdar, Rituparna; Chakraborty, Malay; Bhattacharya, Swapan Kumar

2018-06-15

Nano particles of a few α/β Bi 2 O 3 hetero-junctions of various compositions synthesized by one- pot hydrothermal method, exhibit exceptional and synergistic photo-catalytic activity for the degradation of Rhodamine-B in aqueous solution under natural sunlight. Pure α and pure β Bi 2 O 3 are also synthesized by control post heating of synthesized hetero-junction. The nano-materials were characterized by diffraction (XRD), microscopic and spectroscopic techniques. The XRD reveals α-β phase hetero-junctions of Bi 2 O 3 are made of α-Bi 2 O 3 and β-Bi 2 O 3 with average dimensions within 13-113 and 5-71 nm respectively and having band gap range of 2.4- 2.9 eV. The spectrophotometrically determined % degradation of the dye and associated rate constant on the best hetero-junction are increased by 4.5(/2.1) and 3.3(/1.2) times than these on pure α (/β). The effects of operational parameters and trapping agents have been analyzed. The maximum removal of the dye was achieved up to 99.6% in 3 h using 0.5 g/L photo-catalyst at pH 3. The reusability test shows that the photo-catalytic activity is retained excellently due to change in chemical nature of the catalyst from α -Bi 2 O 3 to β-Bi 2 O 3, Bi 2 O 2 CO 3 and BiOCl. A suitable mechanism is proposed. Copyright © 2018 Elsevier B.V. All rights reserved.

Csf2 null mutation alters placental gene expression and trophoblast glycogen cell and giant cell abundance in mice.

PubMed

Sferruzzi-Perri, Amanda N; Macpherson, Anne M; Roberts, Claire T; Robertson, Sarah A

2009-07-01

Genetic deficiency in granulocyte-macrophage colony-stimulating factor (CSF2, GM-CSF) results in altered placental structure in mice. To investigate the mechanism of action of CSF2 in placental morphogenesis, the placental gene expression and cell composition were examined in Csf2 null mutant and wild-type mice. Microarray and quantitative RT-PCR analyses on Embryonic Day (E) 13 placentae revealed that the Csf2 null mutation caused altered expression of 17 genes not previously known to be associated with placental development, including Mid1, Cd24a, Tnfrsf11b, and Wdfy1. Genes controlling trophoblast differentiation (Ascl2, Tcfeb, Itgav, and Socs3) were also differentially expressed. The CSF2 ligand and the CSF2 receptor alpha subunit were predominantly synthesized in the placental junctional zone. Altered placental structure in Csf2 null mice at E15 was characterized by an expanded junctional zone and by increased Cx31(+) glycogen cells and cyclin-dependent kinase inhibitor 1C (CDKN1C(+), P57(Kip2+)) giant cells, accompanied by elevated junctional zone transcription of genes controlling spongiotrophoblast and giant cell differentiation and secretory function (Ascl2, Hand1, Prl3d1, and Prl2c2). Granzyme genes implicated in tissue remodeling and potentially in trophoblast invasion (Gzmc, Gzme, and Gzmf) were downregulated in the junctional zone of Csf2 null mutant placentae. These data demonstrate aberrant placental gene expression in Csf2 null mutant mice that is associated with altered differentiation and/or functional maturation of junctional zone trophoblast lineages, glycogen cells, and giant cells. We conclude that CSF2 is a regulator of trophoblast differentiation and placental development, which potentially influences the functional capacity of the placenta to support optimal fetal growth in pregnancy.

Photon Calorimeter

DOEpatents

Chow, Tze-Show

1989-01-01

A photon calorimeter (20, 40) is provided that comprises a laminar substrate (10, 22, 42) that is uniform in density and homogeneous in atomic composition. A plasma-sprayed coating (28, 48, 52), that is generally uniform in density and homogeneous in atomic composition within the proximity of planes that are parallel to the surfaces of the substrate, is applied to either one or both sides of the laminar substrate. The plasma-sprayed coatings may be very efficiently spectrally tailored in atomic number. Thermocouple measuring junctions (30, 50, 54) are positioned within the plasma-sprayed coatings. The calorimeter is rugged, inexpensive, and equilibrates in temperature very rapidly.

Confocal Raman mapping of collagen cross-link and crystallinity of human dentin-enamel junction

NASA Astrophysics Data System (ADS)

Slimani, Amel; Nouioua, Fares; Desoutter, Alban; Levallois, Bernard; Cuisinier, Frédéric J. G.; Tassery, Hervé; Terrer, Elodie; Salehi, Hamideh

2017-08-01

The separation zone between enamel and dentin [dentin-enamel junction (DEJ)] with different properties in biomechanical composition has an important role in preventing crack propagation from enamel to dentin. The understanding of the chemical structure (inorganic and organic components), physical properties, and chemical composition of the human DEJ could benefit biomimetic materials in dentistry. Spatial distribution of calcium phosphate crystallinity and the collagen crosslinks near DEJ were studied using confocal Raman microscopy and calculated by different methods. To obtain collagen crosslinking, the ratio of two peaks 1660 cm-1 over 1690 cm-1 (amide I bands) is calculated. For crystallinity, the inverse full-width at half maximum of phosphate peak at 960 cm-1, and the ratio of two Raman peaks of phosphate at 960/950 cm-1 is provided. In conclusion, the study of chemical and physical properties of DEJ provides many benefits in the biomaterial field to improve the synthesis of dental materials in respect to the natural properties of human teeth. Confocal Raman microscopy as a powerful tool provides the molecular structure to identify the changes along DEJ and can be expanded for other mineralized tissues.

Electric polarization switching in an atomically thin binary rock salt structure

NASA Astrophysics Data System (ADS)

Martinez-Castro, Jose; Piantek, Marten; Schubert, Sonja; Persson, Mats; Serrate, David; Hirjibehedin, Cyrus F.

2018-01-01

Inducing and controlling electric dipoles is hindered in the ultrathin limit by the finite screening length of surface charges at metal-insulator junctions1-3, although this effect can be circumvented by specially designed interfaces4. Heterostructures of insulating materials hold great promise, as confirmed by perovskite oxide superlattices with compositional substitution to artificially break the structural inversion symmetry5-8. Bringing this concept to the ultrathin limit would substantially broaden the range of materials and functionalities that could be exploited in novel nanoscale device designs. Here, we report that non-zero electric polarization can be induced and reversed in a hysteretic manner in bilayers made of ultrathin insulators whose electric polarization cannot be switched individually. In particular, we explore the interface between ionic rock salt alkali halides such as NaCl or KBr and polar insulating Cu2N terminating bulk copper. The strong compositional asymmetry between the polar Cu2N and the vacuum gap breaks inversion symmetry in the alkali halide layer, inducing out-of-plane dipoles that are stabilized in one orientation (self-poling). The dipole orientation can be reversed by a critical electric field, producing sharp switching of the tunnel current passing through the junction.

Technical Communication: Perspectives for the Eighties, Part 1. Proceedings of the Technical Communications Sessions at the 32Nd Annual Meeting of the Conference on College Composition and Communication

NASA Technical Reports Server (NTRS)

Mathes, J. C. (Compiler); Pinelli, T. E. (Compiler)

1981-01-01

Proceeding of the technical communication sessions at the 32nd annual meeting of the Conference on College Composition and Communication held in Dallas, Texas, March 26-28, 1981 are summarized. The proceeding suggest that technical communication has become an important subfield and is becoming an intrinsic part of many undergraduate curricula. Technical communication as a separate discipline, however, is relatively new. For that reason, proceedings that can make current research available as quickly as possible are suggested for preparation. The following topics were addressed: (1) a history and definition of technical writing, (2) the case method is technical communication (3) teaching technical writing (4) oral communication and rhetorical theory, and (5) new approaches in and practical applications of technical writing.

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 5: intercellular junctions and contacts between germs cells and Sertoli cells and their regulatory interactions, testicular cholesterol, and genes/proteins associated with more than one germ cell generation.

PubMed

Hermo, Louis; Pelletier, R-Marc; Cyr, Daniel G; Smith, Charles E

2010-04-01

In the testis, cell adhesion and junctional molecules permit specific interactions and intracellular communication between germ and Sertoli cells and apposed Sertoli cells. Among the many adhesion family of proteins, NCAM, nectin and nectin-like, catenins, and cadherens will be discussed, along with gap junctions between germ and Sertoli cells and the many members of the connexin family. The blood-testis barrier separates the haploid spermatids from blood borne elements. In the barrier, the intercellular junctions consist of many proteins such as occludin, tricellulin, and claudins. Changes in the expression of cell adhesion molecules are also an essential part of the mechanism that allows germ cells to move from the basal compartment of the seminiferous tubule to the adluminal compartment thus crossing the blood-testis barrier and well-defined proteins have been shown to assist in this process. Several structural components show interactions between germ cells to Sertoli cells such as the ectoplasmic specialization which are more closely related to Sertoli cells and tubulobulbar complexes that are processes of elongating spermatids embedded into Sertoli cells. Germ cells also modify several Sertoli functions and this also appears to be the case for residual bodies. Cholesterol plays a significant role during spermatogenesis and is essential for germ cell development. Lastly, we list genes/proteins that are expressed not only in any one specific generation of germ cells but across more than one generation. Copyright 2009 Wiley-Liss, Inc.

Intercellular Diffusion of a Fluorescent Sucrose Analog via the Septal Junctions in a Filamentous Cyanobacterium

PubMed Central

Nürnberg, Dennis J.; Mariscal, Vicente; Bornikoel, Jan; Nieves-Morión, Mercedes; Krauß, Norbert; Herrero, Antonia

2015-01-01

ABSTRACT Many filamentous cyanobacteria produce specialized nitrogen-fixing cells called heterocysts, which are located at semiregular intervals along the filament with about 10 to 20 photosynthetic vegetative cells in between. Nitrogen fixation in these complex multicellular bacteria depends on metabolite exchange between the two cell types, with the heterocysts supplying combined-nitrogen compounds but dependent on the vegetative cells for photosynthetically produced carbon compounds. Here, we used a fluorescent tracer to probe intercellular metabolite exchange in the filamentous heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120. We show that esculin, a fluorescent sucrose analog, is incorporated by a sucrose import system into the cytoplasm of Anabaena cells. The cytoplasmic esculin is rapidly and reversibly exchanged across vegetative-vegetative and vegetative-heterocyst cell junctions. Our measurements reveal the kinetics of esculin exchange and also show that intercellular metabolic communication is lost in a significant fraction of older heterocysts. SepJ, FraC, and FraD are proteins located at the intercellular septa and are suggested to form structures analogous to gap junctions. We show that a ΔsepJ ΔfraC ΔfraD triple mutant shows an altered septum structure with thinner septa but a denser peptidoglycan layer. Intercellular diffusion of esculin and fluorescein derivatives is impaired in this mutant, which also shows a greatly reduced frequency of nanopores in the intercellular septal cross walls. These findings suggest that FraC, FraD, and SepJ are important for the formation of junctional structures that constitute the major pathway for feeding heterocysts with sucrose. PMID:25784700

Gap Junctional Coupling is Essential for Epithelial Repair in the Avian Cochlea

PubMed Central

Nickel, Regina; Forge, Andrew

2014-01-01

The loss of auditory hair cells triggers repair responses within the population of nonsensory supporting cells. When hair cells are irreversibly lost from the mammalian cochlea, supporting cells expand to fill the resulting lesions in the sensory epithelium, an initial repair process that is dependent on gap junctional intercellular communication (GJIC). In the chicken cochlea (the basilar papilla or BP), dying hair cells are extruded from the epithelium and supporting cells expand to fill the lesions and then replace hair cells via mitotic and/or conversion mechanisms. Here, we investigated the involvement of GJIC in the initial epithelial repair process in the aminoglycoside-damaged BP. Gentamicin-induced hair cell loss was associated with a decrease of chicken connexin43 (cCx43) immunofluorescence, yet cCx30-labeled gap junction plaques remained. Fluorescence recovery after photobleaching experiments confirmed that the GJIC remained robust in gentamicin-damaged explants, but regionally asymmetric coupling was no longer evident. Dye injections in slice preparations from undamaged BP explants identified cell types with characteristic morphologies along the neural-abneural axis, but these were electrophysiologically indistinct. In gentamicin-damaged BP, supporting cells expanded to fill space formerly occupied by hair cells and displayed more variable electrophysiological phenotypes. When GJIC was inhibited during the aminoglycoside damage paradigm, the epithelial repair response halted. Dying hair cells were retained within the sensory epithelium and supporting cells remained unexpanded. These observations suggest that repair of the auditory epithelium shares common mechanisms across vertebrate species and emphasize the importance of functional gap junctions in maintaining a homeostatic environment permissive for subsequent hair cell regeneration. PMID:25429127

Tumor-induced loss of mural Connexin 43 gap junction activity promotes endothelial proliferation.

PubMed

Choudhary, Mayur; Naczki, Christine; Chen, Wenhong; Barlow, Keith D; Case, L Douglas; Metheny-Barlow, Linda J

2015-05-23

Proper functional association between mural cells and endothelial cells (EC) causes EC of blood vessels to become quiescent. Mural cells on tumor vessels exhibit decreased attachment to EC, which allows vessels to be unstable and proliferative. The mechanisms by which tumors prevent proper association between mural cells and EC are not well understood. Since gap junctions (GJ) play an important role in cell-cell contact and communication, we investigated whether loss of GJ plays a role in tumor-induced mural cell dissociation. Mural cell regulation of endothelial proliferation was assessed by direct co-culture assays of fluorescently labeled cells quantified by flow cytometry or plate reader. Gap junction function was assessed by parachute assay. Connexin 43 (Cx43) protein in mural cells exposed to conditioned media from cancer cells was assessed by Western and confocal microscopy; mRNA levels were assessed by quantitative real-time PCR. Expression vectors or siRNA were utilized to overexpress or knock down Cx43. Tumor growth and angiogenesis was assessed in mouse hosts deficient for Cx43. Using parachute dye transfer assay, we demonstrate that media conditioned by MDA-MB-231 breast cancer cells diminishes GJ communication between mural cells (vascular smooth muscle cells, vSMC) and EC. Both protein and mRNA of the GJ component Connexin 43 (Cx43) are downregulated in mural cells by tumor-conditioned media; media from non-tumorigenic MCF10A cells had no effect. Loss of GJ communication by Cx43 siRNA knockdown, treatment with blocking peptide, or exposure to tumor-conditioned media diminishes the ability of mural cells to inhibit EC proliferation in co-culture assays, while overexpression of Cx43 in vSMC restores GJ and endothelial inhibition. Breast tumor cells implanted into mice heterozygous for Cx43 show no changes in tumor growth, but exhibit significantly increased tumor vascularization determined by CD31 staining, along with decreased mural cell support detected by NG2 staining. Our data indicate that i) functional Cx43 is required for mural cell-induced endothelial quiescence, and ii) downregulation of Cx43 GJ by tumors frees endothelium to respond to angiogenic cues. These data define a novel and important role for maintained Cx43 function in regulation of vessel quiescence, and suggest its loss may contribute to pathological tumor angiogenesis.

Associations of Pd, U and Ag in the SiC layer of neutron-irradiated TRISO fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lillo, Thomas; Rooyen, Isabella Van

2015-05-01

Knowledge of the associations and composition of fission products in the neutron irradiated SiC layer of high-temperature gas reactor TRISO fuel is important to the understanding of various aspects of fuel performance that presently are not well understood. Recently, advanced characterization techniques have been used to examine fuel particles from the Idaho National Laboratory’s AGR-1 experiment. Nano-sized Ag and Pd precipitates were previously identified in grain boundaries and triple points in the SiC layer of irradiated TRISO nuclear fuel. Continuation of this initial research is reported in this paper and consists of the characterization of a relatively large number ofmore » nano-sized precipitates in three areas of the SiC layer of a single irradiated TRISO nuclear fuel particle using standardless EDS analysis on focused ion beam-prepared transmission electron microscopy samples. Composition and distribution analyses of these precipitates, which were located on grain boundaries, triple junctions and intragranular precipitates, revealed low levels, generally <10 atomic %, of palladium, silver and/or uranium with palladium being the most common element found. Palladium by itself, or associated with either silver or uranium, was found throughout the SiC layer. A small number of precipitates on grain boundaries and triple junctions were found to contain only silver or silver in association with palladium while uranium was always associated with palladium but never found by itself or in association with silver. Intergranular precipitates containing uranium were found to have migrated ~23 μm along a radial direction through the 35 μm thick SiC coating during the AGR-1 experiment while silver-containing intergranular precipitates were found at depths up to ~24 μm in the SiC layer. Also, Pd-rich, nano-precipitates (~10 nm in diameter), without evidence for the presence of either Ag or U, were revealed in intragranular regions throughout the SiC layer. Because not all grain boundaries and triple junctions contained precipitates with fission products and/or uranium, along with the differences in migration behavior between Pd, Ag and U, it was concluded that crystallographic grain boundary and triple junction parameters likely influence migration behavior.« less

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

NASA Technical Reports Server (NTRS)

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

2016-01-01

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 immunohistological observation. Increased CX43 expression is also observed with the three-dimensional co-cultures with MC3T3-E1 MCS stimulation but the increased gap-junction protein presence was limited to the osteoblast-osteocyte interface region. Previously reported PCR evaluation of osteogenic markers further corroborate that the co-cultured populations communicative networks play a role in translating mechanical signals to molecular messaging. These findings suggests an osteocyte-osteoblast gap-junction signaling feedback mechanism may regulate mechanotransduction of apoptosis initiation and transcription of cytokine signaling proteins responsible for stem cell niche recruitment much more directly than previously believed.

Characterization of Nonjunctional Hemichannels in Caterpillar Cells

PubMed Central

Luo, Kaijun; Turnbull, Matthew W.

2011-01-01

Recent studies have demonstrated that hemichannels, which form gap junctions when paired from apposing cells, may serve additional roles when unpaired including cell adhesion and paracrine communication. Hemichannels in mammals are formed by connexins or pannexins, while in insects they are formed by pannexin homologues termed innexins. The formation of functional gap junctions by insect innexins has been established, although their ability to form functional nonjunctional hemichannels has not been reported. Here the characteristics of nonjunctional hemichannels were examined in three lepidopteran cell types, two cell lines (High Five and Sf9) and explanted hemocytes from Heliothis virescens (Fabricius) (Lepidoptera: Noctuidae). Selective fluorescent dye uptake by hemichannels was observed in a significant minority of cells, using fluorescence microscopy and flow cytometry. Carbenoxelone, an inhibitor of mammalian junctions, disrupted dye uptake, while flufenamic acid and mefloquine did not. The presence of Ca2+ and Mg2+ in the media increased hemichannel activity. Additionally, lipopolysaccharide, a stimulator of immune activity in lepidopterans, decreased dye uptake. These results demonstrate for the first time the activity of nonjunctional hemichannels in insect cells, as well as pharmacological tools to manipulate them. These results will facilitate the further examination of the role of innexins and nonjunctional hemichannels in insect cell biology, including paracrine signaling, and comparative studies of mammalian pannexins and insect innexins. PMID:21521140

Anticonvulsant effects of mefloquine on generalized tonic-clonic seizures induced by two acute models in rats.

PubMed

Franco-Pérez, Javier; Ballesteros-Zebadúa, Paola; Manjarrez-Marmolejo, Joaquín

2015-03-01

Mefloquine can cross the blood-brain barrier and block the gap junction intercellular communication in the brain. Enhanced electrical coupling mediated by gap junctions is an underlying mechanism involved in the generation and maintenance of seizures. For this reason, the aim of this study was to analyze the effects of the systemic administration of mefloquine on tonic-clonic seizures induced by two acute models such as pentylenetetrazole and maximal electroshock. All the control rats presented generalized tonic-clonic seizures after the administration of pentylenetetrazole. However, the incidence of seizures induced by pentylenetetrazole significantly decreased in the groups administered systematically with 40 and 80 mg/kg of mefloquine. In the control group, none of the rats survived after the generalized tonic-clonic seizures induced by pentylenetetrazole, but survival was improved by mefloquine. Besides, mefloquine significantly modified the total spectral power as well as the duration, amplitude and frequency of the epileptiform activity induced by pentylenetetrazole. For the maximal electroshock model, mefloquine did not change the occurrence of tonic hindlimb extension. However, this gap junction blocker significantly decreased the duration of the tonic hindlimb extension induced by the acute electroshock. These data suggest that mefloquine at low doses might be eliciting some anticonvulsant effects when is systemically administered to rats.

Complexity of gap junctions between horizontal cells of the carp retina.

PubMed

Greb, H; Hermann, S; Dirks, P; Ommen, G; Kretschmer, V; Schultz, K; Zoidl, G; Weiler, R; Janssen-Bienhold, U

2017-01-06

In the vertebrate retina, horizontal cells (HCs) reveal homologous coupling by gap junctions (gj), which are thought to consist of different connexins (Cx). However, recent studies in mouse, rabbit and zebrafish retina indicate that individual HCs express more than one connexin. To provide further insights into the composition of gj connecting HCs and to determine whether HCs express multiple connexins, we examined the molecular identity and distribution of gj between HCs of the carp retina. We have cloned four carp connexins designated Cx49.5, Cx55.5, Cx52.6 and Cx53.8 with a close relationship to connexins previously reported in HCs of mouse, rabbit and zebrafish, respectively. Using in situ hybridization, Cx49.5 expression was detected in different subpopulations of retinal neurons including HCs, whereas the Cx52.6 transcript was localized exclusively in HCs. Using specific antibodies, Cx55.5 and Cx53.8 were detected on dendrites of all four HC subtypes and axon terminals. Immunoelectron microscopy confirmed the presence of Cx55.5 and Cx53.8 in gap junctions between these processes and Cx55.5 was additionally observed in HC dendrites invaginating cone pedicles, suggesting its participation in the modulation of photoreceptor output in the carp retina. Furthermore, using single-cell RT-PCR, all four connexins were detected in different subtypes of HCs, suggesting overlapping expression patterns. Thus, the composition of gj mediating homologous coupling between subtypes of carp HCs appears to be more complex than expected. Moreover, BLAST searches of the preliminary carp genome, using novel sequences as query, suggest that most of the analyzed connexin genes are duplicated in carp. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Junctional bradycardia is a potential risk factor of stroke.

PubMed

Kim, Gwang Sil; Uhm, Jae-Sun; Kim, Tae-Hoon; Lee, Hancheol; Park, Junbeom; Park, Jin-Kyu; Joung, Boyoung; Pak, Hui-Nam; Lee, Moon-Hyoung

2016-07-25

This study aimed to determine the risk of thromboembolic events in patients with junctional bradycardia(JB). We retrospectively reviewed electrocardiograms(ECGs) for 380,682 patients. Those with JB on an ECG at least twice over a ≥3-month interval were included for analysis. We additionally included 138 CHADS2 score-matched patients(age, 68.4 ± 15.7 years; male, 52.2%) in sinus rhythm as a control group. Between the JB patients(with or without retrograde P wave) and controls, we compared incidences of ischemic stroke and a composite of ischemic stroke, renal infarction, ischemic colitis, acute limb ischemia, and pulmonary embolism. Among 380,682 patients (age, 47.6 ± 19.9 years; male, 49.3%), 69 patients (age, 68.5 ± 16.5 years; male, 50.7%) exhibited JB on an ECG at least twice over a ≥3-month interval; the overall prevalence of JB was 0.02%. The mean follow-up period was 27.2 ± 26.2 months. Forty-five patients (65.2%) in the JB group had no retrograde P wave. Ischemic stroke incidence was significantly higher in JB patients without a retrograde P wave than in controls (6/45 patients [13.3%] and 3/138 patients [2.2%], respectively; P = 0.007). The incidence of composite thromboembolic events was also significantly higher in JB patients without a retrograde P wave than in controls (8/45 patients [17.8%] and 4/138 patients [2.9%], respectively; P = 0.011). In a Cox proportional hazards model, JB patients without a P wave showed a greater incidence of stroke (hazard ratio, 8.89 [2.20-33.01], P = 0.007) than controls and JB patients with a P wave. Junctional bradycardia is potentially associated with ischemic stroke, particularly in the absence of an identifiable retrograde P wave.

Bisphenol A alters oocyte maturation by prematurely closing gap junctions in the cumulus cell-oocyte complex.

PubMed

Acuña-Hernández, Deyanira Guadalupe; Arreola-Mendoza, Laura; Santacruz-Márquez, Ramsés; García-Zepeda, Sihomara Patricia; Parra-Forero, Lyda Yuliana; Olivares-Reyes, Jesús Alberto; Hernández-Ochoa, Isabel

2018-04-01

In ovarian follicles, cumulus cells communicate with the oocyte through gap junction intercellular communication (GJIC), to nurture the oocyte and control its meiosis arrest and division. Bisphenol A (BPA) is a monomer found in polycarbonate-made containers that can induce functional alterations, including impaired oocyte meiotic division and reduced molecule transfer in GJIC. However, how BPA alters oocyte meiotic division is unclear. We investigated whether BPA effects on oocyte meiotic division were correlated with reduced transfer in GJIC. Cumulus cell-oocyte complexes (COCs) isolated from mouse preovulatory follicles were cultured with 0, 0.22, 2.2, 22, 220, and 2200 nM BPA for 2 h. An additional 16-h incubation with epidermal growth factor (EGF) was performed to promote the occurrence of meiotic resumption and progression to metaphase II. Without EGF stimulus, BPA treatment increased the percentage of oocytes undergoing meiotic resumption, decreased GJIC in the COCs, and did not modify GJIC gene (Cx43 and Cx37) and protein (CX43) expression. Following EGF stimulus, BPA increased the percentage of oocytes that remained at the anaphase and telophase stages, and decreased the percentage of oocytes reaching the metaphase II stage. Concomitantly, BPA reduced the expansion of cumulus cells. Carbenoxolone (a GJIC inhibitor) and 6-diazo-5-oxo-l-norleucine (a cumulus cell-expansion inhibitor) exerted effects on meiotic division similar to those exerted by BPA. These data suggest that BPA accelerates meiotic progression, leading to impaired prophase I-to-metaphase II transition, and that this adverse effect is correlated with reduced bidirectional communication in the COC. Copyright © 2018 Elsevier Inc. All rights reserved.

Local Oxidative Stress Expansion through Endothelial Cells – A Key Role for Gap Junction Intercellular Communication

PubMed Central

Feine, Ilan; Pinkas, Iddo; Salomon, Yoram; Scherz, Avigdor

2012-01-01

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 O2•− 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. PMID:22911831

Osteogenic Transcription Regulated by Exaggerated Stretch Loading via Convergent Wnt Signaling

NASA Technical Reports Server (NTRS)

Juran, Cassandra M.; Blaber, Elizabeth A.; Almeida, Eduardo A. C.

2017-01-01

Cell and animal studies conducted onboard the International Space Station and formerly the Shuttle flights have provided data illuminating the deleterious biological response of bone to mechanical unloading. Down regulation of proliferative mechanisms within stem cell populations of the osteogenic niche is a suggested mechanism for loss of bone mass. However the intercellular communicative cues from osteoblasts and osteocytes in managing stem cell proliferation and osteogenic differentiation are largely unknown. In this investigation, MLO-Y4 osteocyte-like and MC3T3-E1 osteoblast-like cells, are co-culture under dynamic tensile conditions and evaluated for phenotypic expression of biochemical signaling proteins influential in driving stem cell differentiation. MLO-Y4 and MC3T3-E1 were co-cultured on polyethersulfone membrane with a 0.45m porosity to permit soluble factor transfer and direct cell-cell gap junction signaling. Cyclic tensile stimulation was applied for 48 h at a frequency of 0.1Hz and strain of 0.1. Total Live cell counts indicate mechanical activation of MC3T3-E1s inhibits proliferation while MLO-Y4s increase in number. However, the percent of live MLO-Y4s within the population is low (46.3 total count, *p0.05, n4) suggesting a potential apoptotic signaling cascade. Immunofluorescence demonstrated that stimulation of co-cultures elicits increased gap junction communication. Previously reported PCR evaluation of osteogenic markers further corroborate that the co-cultured populations communicative networks play a role in translating mechanical signals to molecular messaging. These findings suggest that an osteocyte-osteoblast signaling feedback mechanism may regulate mechanotransduction of an apoptotic cascade within osteocytes and transcription of cytokine signaling proteins responsible for stem cell niche recruitment much more directly than previously believed.

Perfluorooctanesulfonate (PFOS) Perturbs Male Rat Sertoli Cell Blood-Testis Barrier Function by Affecting F-Actin Organization via p-FAK-Tyr407: An in Vitro Study

PubMed Central

Wan, Hin-Ting; Mruk, Dolores D.; Wong, Chris K. C.

2014-01-01

Environmental toxicants such as perfluorooctanesulfonate (PFOS) have been implicated in male reproductive dysfunction, including reduced sperm count and semen quality, in humans. However, the underlying mechanism(s) remains unknown. Herein PFOS at 10–20 μM (∼5–10 μg/mL) was found to be more potent than bisphenol A (100 μM) in perturbing the blood-testis barrier (BTB) function by disrupting the Sertoli cell tight junction-permeability barrier without detectable cytotoxicity. We also delineated the underlying molecular mechanism by which PFOS perturbed Sertoli cell BTB function using an in vitro model that mimics the BTB in vivo. First, PFOS perturbed F-actin organization in Sertoli cells, causing truncation of actin filaments at the BTB. Thus, the actin-based cytoskeleton was no longer capable of supporting the distribution and/or localization of actin-regulatory and adhesion proteins at the cell-cell interface necessary to maintain BTB integrity. Second, PFOS was found to perturb inter-Sertoli cell gap junction (GJ) communication based on a dye-transfer assay by down-regulating the expression of connexin-43, a GJ integral membrane protein. Third, phosphorylated focal adhesion kinase (FAK)-Tyr407 was found to protect the BTB from the destructive effects of PFOS as shown in a study via an overexpression of an FAK Y407E phosphomimetic mutant. Also, transfection of Sertoli cells with an FAK-specific microRNA, miR-135b, to knock down the expression of phosphorylated FAK-Tyr407 was found to worsen PFOS-mediated Sertoli cell tight junction disruption. In summary, PFOS-induced BTB disruption is mediated by down-regulating phosphorylated FAK-Tyr407 and connexin-43, which in turn perturbed F-actin organization and GJ-based intercellular communication, leading to mislocalization of actin-regulatory and adhesion proteins at the BTB. PMID:24169556

Sulforaphane counteracts aggressiveness of pancreatic cancer driven by dysregulated Cx43-mediated gap junctional intercellular communication

PubMed Central

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

2014-01-01

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

Role of Two Cell Wall Amidases in Septal Junction and Nanopore Formation in the Multicellular Cyanobacterium Anabaena sp. PCC 7120

PubMed Central

Bornikoel, Jan; Carrión, Alejandro; Fan, Qing; Flores, Enrique; Forchhammer, Karl; Mariscal, Vicente; Mullineaux, Conrad W.; Perez, Rebeca; Silber, Nadine; Wolk, C. Peter; Maldener, Iris

2017-01-01

Filamentous cyanobacteria have developed a strategy to perform incompatible processes in one filament by differentiating specialized cell types, N2-fixing heterocysts and CO2-fixing, photosynthetic, vegetative cells. These bacteria can be considered true multicellular organisms with cells exchanging metabolites and signaling molecules via septal junctions, involving the SepJ and FraCD proteins. Previously, it was shown that the cell wall lytic N-acetylmuramyl-L-alanine amidase, AmiC2, is essential for cell–cell communication in Nostoc punctiforme. This enzyme perforates the septal peptidoglycan creating an array of nanopores, which may be the framework for septal junction complexes. In Anabaena sp. PCC 7120, two homologs of AmiC2, encoded by amiC1 and amiC2, were identified and investigated in two different studies. Here, we compare the function of both AmiC proteins by characterizing different Anabaena amiC mutants, which was not possible in N. punctiforme, because there the amiC1 gene could not be inactivated. This study shows the different impact of each protein on nanopore array formation, the process of cell–cell communication, septal protein localization, and heterocyst differentiation. Inactivation of either amidase resulted in significant reduction in nanopore count and in the rate of fluorescent tracer exchange between neighboring cells measured by FRAP analysis. In an amiC1 amiC2 double mutant, filament morphology was affected and heterocyst differentiation was abolished. Furthermore, the inactivation of amiC1 influenced SepJ localization and prevented the filament-fragmentation phenotype that is characteristic of sepJ or fraC fraD mutants. Our findings suggest that both amidases are to some extent redundant in their function, and describe a functional relationship of AmiC1 and septal proteins SepJ and FraCD. PMID:28929086

Role of Two Cell Wall Amidases in Septal Junction and Nanopore Formation in the Multicellular Cyanobacterium Anabaena sp. PCC 7120.

PubMed

Bornikoel, Jan; Carrión, Alejandro; Fan, Qing; Flores, Enrique; Forchhammer, Karl; Mariscal, Vicente; Mullineaux, Conrad W; Perez, Rebeca; Silber, Nadine; Wolk, C Peter; Maldener, Iris

2017-01-01

Filamentous cyanobacteria have developed a strategy to perform incompatible processes in one filament by differentiating specialized cell types, N 2 -fixing heterocysts and CO 2 -fixing, photosynthetic, vegetative cells. These bacteria can be considered true multicellular organisms with cells exchanging metabolites and signaling molecules via septal junctions, involving the SepJ and FraCD proteins. Previously, it was shown that the cell wall lytic N -acetylmuramyl-L-alanine amidase, AmiC2, is essential for cell-cell communication in Nostoc punctiforme . This enzyme perforates the septal peptidoglycan creating an array of nanopores, which may be the framework for septal junction complexes. In Anabaena sp. PCC 7120, two homologs of AmiC2, encoded by amiC1 and amiC2 , were identified and investigated in two different studies. Here, we compare the function of both AmiC proteins by characterizing different Anabaena amiC mutants, which was not possible in N. punctiforme , because there the amiC1 gene could not be inactivated. This study shows the different impact of each protein on nanopore array formation, the process of cell-cell communication, septal protein localization, and heterocyst differentiation. Inactivation of either amidase resulted in significant reduction in nanopore count and in the rate of fluorescent tracer exchange between neighboring cells measured by FRAP analysis. In an amiC1 amiC2 double mutant, filament morphology was affected and heterocyst differentiation was abolished. Furthermore, the inactivation of amiC1 influenced SepJ localization and prevented the filament-fragmentation phenotype that is characteristic of sepJ or fraC fraD mutants. Our findings suggest that both amidases are to some extent redundant in their function, and describe a functional relationship of AmiC1 and septal proteins SepJ and FraCD.

Gap junction intercellular communication mediated by connexin43 in astrocytes is essential for their resistance to oxidative stress.

PubMed

Le, Hoa T; Sin, Wun Chey; Lozinsky, Shannon; Bechberger, John; Vega, José Luis; Guo, Xu Qiu; Sáez, Juan C; Naus, Christian C

2014-01-17

Oxidative stress induced by reactive oxygen species (ROS) is associated with various neurological disorders including aging, neurodegenerative diseases, as well as traumatic and ischemic insults. Astrocytes have an important role in the anti-oxidative defense in the brain. The gap junction protein connexin43 (Cx43) forms intercellular channels as well as hemichannels in astrocytes. In the present study, we investigated the contribution of Cx43 to astrocytic death induced by the ROS hydrogen peroxide (H2O2) and the mechanism by which Cx43 exerts its effects. Lack of Cx43 expression or blockage of Cx43 channels resulted in increased ROS-induced astrocytic death, supporting a cell protective effect of functional Cx43 channels. H2O2 transiently increased hemichannel activity, but reduced gap junction intercellular communication (GJIC). GJIC in wild-type astrocytes recovered after 7 h, but was absent in Cx43 knock-out astrocytes. Blockage of Cx43 hemichannels incompletely inhibited H2O2-induced hemichannel activity, indicating the presence of other hemichannel proteins. Panx1, which is predicted to be a major hemichannel contributor in astrocytes, did not appear to have any cell protective effect from H2O2 insults. Our data suggest that GJIC is important for Cx43-mediated ROS resistance. In contrast to hypoxia/reoxygenation, H2O2 treatment decreased the ratio of the hypophosphorylated isoform to total Cx43 level. Cx43 has been reported to promote astrocytic death induced by hypoxia/reoxygenation. We therefore speculate the increase in Cx43 dephosphorylation may account for the facilitation of astrocytic death. Our findings suggest that the role of Cx43 in response to cellular stress is dependent on the activation of signaling pathways leading to alteration of Cx43 phosphorylation states.

Sulforaphane counteracts aggressiveness of pancreatic cancer driven by dysregulated Cx43-mediated gap junctional intercellular communication.

PubMed

Forster, Tobias; Rausch, Vanessa; 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

2014-03-30

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.

Promotion of lens epithelial-fiber differentiation by the C-terminus of connexin 45.6 a role independent of gap junction communication.

PubMed

Banks, Eric A; Yu, X Sean; Shi, Qian; Jiang, Jean X

2007-10-15

We previously reported that, among the three connexins expressed in chick lens, overexpression of connexin (Cx) 45.6, not Cx43 or Cx56, stimulates lens cell differentiation; however, the underlying mechanism responsible for this effect is unclear. Here, we took advantage of naturally occurring loss-of-gap-junction function mutations of Cx50 (ortholog of chick Cx45.6) and generated the corresponding site mutants in Cx45.6: Cx45.6(D47A) and Cx45.6(P88S). In contrast to wild-type Cx45.6, the mutants failed to form functional gap junctions, and Cx45.6(P88S) and, to a lesser degree, Cx45.6(D47A) functioned in a dominant-negative manner. Interestingly, overexpression of both mutants incapable of forming gap junctions significantly increased epithelial-fiber differentiation to a level comparable to that of wild-type Cx45.6. To map the functional domain of Cx45.6, we generated a C-terminus chimera as well as deletion mutants. Overexpression of Cx56(*)45.6C, the mutant in which the C-terminus of Cx56 was replaced with that of Cx45.6, had a stimulatory effect on lens cell differentiation similar to that of Cx45.6. However, cells overexpressing Cx45.6(*)56C, the mutant in which C-terminus of Cx45.6 was replaced with that of Cx56, and Cx45.6(-C), in which the C-terminus was deleted, failed to promote differentiation. Taken together, we conclude that the expression of Cx45.6, but not Cx45.6-dependent gap junction channels, is involved in lens epithelial-fiber cell differentiation, and the C-terminal domain of Cx45.6 plays a predominant role in mediating this process.

Transfected connexin45 alters gap junction permeability in cells expressing endogenous connexin43

PubMed Central

1995-01-01

Many cells express multiple connexins, the gap junction proteins that interconnect the cytosol of adjacent cells. Connexin43 (Cx43) channels allow intercellular transfer of Lucifer Yellow (LY, MW = 443 D), while connexin45 (Cx45) channels do not. We transfected full-length or truncated chicken Cx45 into a rat osteosarcoma cell line ROS-17/2.8, which expresses endogenous Cx43. Both forms of Cx45 were expressed at high levels and colocalized with Cx43 at plasma membrane junctions. Cells transfected with full-length Cx45 (ROS/Cx45) and cells transfected with Cx45 missing the 37 carboxyl-terminal amino acids (ROS/Cx45tr) showed 30-60% of the gap junctional conductance exhibited by ROS cells. Intercellular transfer of three negatively charged fluorescent reporter molecules was examined. In ROS cells, microinjected LY was transferred to an average of 11.2 cells/injected cell, while dye transfer between ROS/Cx45 cells was reduced to 3.9 transfer between ROS/Cx45 cells was reduced to 3.9 cells. In contrast, ROS/Cx45tr cells transferred LY to > 20 cells. Transfer of calcein (MW = 623 D) was also reduced by approximately 50% in ROS/Cx45 cells, but passage of hydroxycoumarin carboxylic acid (HCCA; MW = 206 D) was only reduced by 35% as compared to ROS cells. Thus, introduction of Cx45 altered intercellular coupling between cells expressing Cx43, most likely the result of direct interaction between Cx43 and Cx45. Transfection of Cx45tr and Cx45 had different effects in ROS cells, consistent with a role of the carboxyl-terminal domain of Cx45 in determining gap junction permeability or interactions between connexins. These data suggest that coexpression of multiple connexins may enable cells to achieve forms of intercellular communication that cannot be attained by expression of a single connexin. PMID:7642714

Gap-junction blocker carbenoxolone differentially enhances NMDA-induced cell death in hippocampal neurons and astrocytes in co-culture.

PubMed

Zündorf, Gregor; Kahlert, Stefan; Reiser, Georg

2007-07-01

The beneficial or detrimental role of gap junction communication in the pathophysiology of brain injury is still controversial. We used co-cultures of hippocampal astrocytes and neurons, where we identified homocellular astrocyte-astrocyte and heterocellular astrocyte-neuron coupling by fluorescence recovery after photobleaching, which was decreased by the gap junction blocker carbenoxolone (CBX). In these cultures, we determined the cell type-specific effects of CBX on the excitotoxic damage caused by N-methyl-D-aspartate (NMDA). We determined in both astrocytes and neurons the influence of CBX, alone or together with NMDA challenge, on cytotoxicity using propidium iodide labeling. CBX alone was not cytotoxic, but CBX treatment differentially accelerated the NMDA-induced cell death in both astrocytes and neurons. In addition, we measured mitochondrial potential using rhodamine 123, membrane potential using the oxonol dye bis(1,3-diethylthiobarbituric acid)trimethine oxonol, cytosolic Ca(2+) level using fura-2, and formation of reactive oxygen species (ROS) using dihydroethidium. CBX alone induced neither an intracellular Ca(2+) rise nor a membrane depolarization. However, CBX elicited a mitochondrial depolarization in both astrocytes and neurons and increased the ROS formation in neurons. In contrast, NMDA caused a membrane depolarization in neurons, coinciding with intracellular Ca(2+) rise, but neither mitochondrial depolarization nor ROS production seem to be involved in NMDA-mediated cytotoxicity. Pre-treatment with CBX accelerated the NMDA-induced membrane depolarization and prevented the repolarization of neurons after the NMDA challenge. We hypothesize that these effects are possibly mediated via blockage of gap junctions, and might be involved in the mechanism of CBX-induced acceleration of excitotoxic cell death, whereas the CBX-induced mitochondrial depolarization and ROS formation are not responsible for the increase in cytotoxicity. We conclude that both in astrocytes and neurons gap junctions provide protection against NMDA-induced cytotoxicity.

3D Architecture of the Trypanosoma brucei Flagella Connector, a Mobile Transmembrane Junction.

PubMed

Höög, Johanna L; Lacomble, Sylvain; Bouchet-Marquis, Cedric; Briggs, Laura; Park, Kristin; Hoenger, Andreas; Gull, Keith

2016-01-01

Cellular junctions are crucial for the formation of multicellular organisms, where they anchor cells to each other and/or supportive tissue and enable cell-to-cell communication. Some unicellular organisms, such as the parasitic protist Trypanosoma brucei, also have complex cellular junctions. The flagella connector (FC) is a three-layered transmembrane junction that moves with the growing tip of a new flagellum and attaches it to the side of the old flagellum. The FC moves via an unknown molecular mechanism, independent of new flagellum growth. Here we describe the detailed 3D architecture of the FC suggesting explanations for how it functions and its mechanism of motility. We have used a combination of electron tomography and cryo-electron tomography to reveal the 3D architecture of the FC. Cryo-electron tomography revealed layers of repetitive filamentous electron densities between the two flagella in the interstitial zone. Though the FC does not change in length and width during the growth of the new flagellum, the interstitial zone thickness decreases as the FC matures. This investigation also shows interactions between the FC layers and the axonemes of the new and old flagellum, sufficiently strong to displace the axoneme in the old flagellum. We describe a novel filament, the flagella connector fibre, found between the FC and the axoneme in the old flagellum. The FC is similar to other cellular junctions in that filamentous proteins bridge the extracellular space and are anchored to underlying cytoskeletal structures; however, it is built between different portions of the same cell and is unique because of its intrinsic motility. The detailed description of its structure will be an important tool to use in attributing structure / function relationships as its molecular components are discovered in the future. The FC is involved in the inheritance of cell shape, which is important for the life cycle of this human parasite.

Cooling system for a nuclear reactor

DOEpatents

Amtmann, Hans H.

1982-01-01

A cooling system for a gas-cooled nuclear reactor is disclosed which includes at least one primary cooling loop adapted to pass coolant gas from the reactor core and an associated steam generator through a duct system having a main circulator therein, and at least one auxiliary cooling loop having communication with the reactor core and adapted to selectively pass coolant gas through an auxiliary heat exchanger and circulator. The main and auxiliary circulators are installed in a common vertical cavity in the reactor vessel, and a common return duct communicates with the reactor core and intersects the common cavity at a junction at which is located a flow diverter valve operative to effect coolant flow through either the primary or auxiliary cooling loops.

Detection of Serum Lysophosphatidic Acids Using Affinity Binding and Surface Enhanced Laser Deorption/Ionization (SELDI) Time of Flight Mass Spectrometry

DTIC Science & Technology

2006-04-01

Schmidt, S. A., Clark, K. J. & Murray, A. W. Lysophosphatidic acid inhibits gap-junctional communication and stimulates phosphorylation of connexin - 43 in...hours later adherent and floating cells were collected and analyzed for cell cycle and apoptosis (hypodiploid peak) using flow cytometry of propidium...pathophysiology of ovarian cancer, provides a major opportunity to identify markers that could contribute to early diagnosis. We have demonstrated that the

Gap junction communications influence upon fibroblast synthesis of Type I collagen and fibronectin.

PubMed

Ehrlich, H Paul; Sun, Bonnie; Saggers, Gregory C; Kromath, Fatuma

2006-07-01

In rats polyvinyl alcohol sponge subcutaneous implants treated with gap junctional intercellular communications (GJIC) uncouplers showed reduced deposition of connective tissue. Do uncouplers inhibit the synthesis and deposition of a new connective tissue by fibroblasts? Confluent human dermal fibroblasts in serum-free medium received either endosulfan or oleamide, GJIC uncouplers. Collected media were subjected to Dot Blot analysis for native Type I collagen and fibronectin. Uncoupler-treated fibroblasts released less Type I collagen, while there was no change in fibronectin release. Collagen synthesis was restored to normal, when the uncouplers were removed, showing that these uncouplers were reversible and not toxic to cells. Northern blot analysis revealed procollagen alpha1 (I) mRNA was minimally affected by endosulfan. Oleamide-treated 17-day chick embryo calvaria explants were incubated with Type I collagen antibody, frozen, cryosectioned, and then subjected to rhodamine (Rh) tagged anti-mouse-IgG antibody, to detect newly deposited Type I collagen. Fluorescent antibody-collagen complexes were localized on the periphery of cells in control calvaria, but absent around cells in oleamide-treated calvaria. GJIC optimize collagen synthesis but not fibronectin synthesis. The lack of connective tissue deposited in granulation tissues treated with uncouplers appears related to the inhibition of collagen synthesis. These findings suggest that altering GJIC might control collagen deposition in scarring. 2006 Wiley-Liss, Inc.

Connexin 32 and its derived homotypic gap junctional intercellular communication inhibit the migration and invasion of transfected HeLa cells via enhancement of intercellular adhesion.

PubMed

Yang, Jie; Liu, Bing; Wang, Qin; Yuan, Dongdong; Hong, Xiaoting; Yang, Yan; Tao, Liang

2011-01-01

The effects of connexin (Cx) and its derived homotypic gap junctional intercellular communication (GJIC) between tumor cells on the invasion of metastatic cancers and the underlying mechanisms remain unclear. In this study, we investigated the influence of Cx32 and the homotypic GJIC mediated by this Cx on the migration, invasion and intercellular adhesion of transfected HeLa cells. The expression of Cx32 significantly increased cell adhesion and inhibited migration and invasion. The inhibition of GJIC by oleamide, a widely used GJIC inhibitor, reduced the enhanced adhesion and partly reversed the decreased migration and invasion that had been induced by Cx32 expression. Blockage of the p38 and extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase (ERK1/2 MAPKs) pathways using their specific inhibitors attenuated the effects of Cx32, but not those of GJIC, on cell adhesion, migration and invasion. These results indicate that the homotypic GJIC mediated by Cx32, as well as the Cx itself, inhibit cell migration and invasion, most likely through the elevation of intercellular adhesion. The suppressive effect of Cx32 on the migration and invasion of cancer cells, but not that of its derived homotypic GJIC, partly depends on the activation of the p38 and the ERK1/2 MAPKs pathways.

Expression of connexin 43 mRNA and protein in developing follicles of prepubertal porcine ovaries

USGS Publications Warehouse

Melton, C.M.; Zaunbrecher, G.M.; Yoshizaki, G.; Patio, R.; Whisnant, S.; Rendon, A.; Lee, V.H.

2001-01-01

A major form of cell-cell communication is mediated by gap junctions, aggregations of intercellular channels composed of connexins (Cxs), which are responsible for exchange of low molecular weight (< 1200 Da) cytosolic materials. These channels are a growing family of related proteins. This study was designed to determine the ontogeny of connexin 43 (Cx43) during early stages of follicular development in prepubertal porcine ovaries. A partial-length (412 base) cDNA clone was obtained from mature porcine ovaries and determined to have 98% identity with published porcine Cx43. Northern blot analysis demonstrated a 4.3-kb mRNA in total RNA isolated from prepubertal and adult porcine ovaries. In-situ hybridization revealed that Cx43 mRNA was detectable in granulosa cells of primary follicles but undetectable in dormant primordial follicles. The intensity of the signal increased with follicular growth and was greatest in the large antral follicles. Immunohistochemical evaluation indicated that Cx43 protein expression correlated with the presence of Cx43 mRNA. These results indicate that substantial amounts of Cx43 are first expressed in granulosa cells following activation of follicular development and that this expression increases throughout follicular growth and maturation. These findings suggest an association between the enhancement of intercellular gap-junctional communication and onset of follicular growth. ?? 2001 Elsevier Science Inc. All rights reserved.

Propagation Distance of the α-Particle-Induced Bystander Effect: The Role of Nuclear Traversal and Gap Junction Communication

PubMed Central

Gaillard, Sylvain; Pusset, David; de Toledo, Sonia M.; Fromm, Michel; Azzam, Edouard I.

2009-01-01

When cell populations are exposed to low-dose α-particle radiation, a significant fraction of the cells will not be traversed by a radiation track. However, stressful effects occur in both irradiated and bystander cells in the population. Characterizing these effects, and investigating their underlying mechanism(s), is critical to understanding human health risks associated with exposure to α particles. To this end, confluent normal human fibroblast cultures were grown on polyethylene terephthalate foil grafted to an ultrathin solid-state nuclear track detector and exposed under non-perturbing conditions to low-fluence α particles from a broadbeam irradiator. Irradiated and affected bystander cells were localized with micrometer precision. The stress-responsive protein p21Waf1 (also known as CDKN1A) was induced in bystander cells within a 100-µm radius from an irradiated cell. The mean propagation distance ranged from 20 to 40 µm around the intranuclear α-particle impact point, which corresponds to a set of ∼30 cells. Nuclear traversal, induced DNA damage, and gap junction communication were critical contributors to propagation of this stressful effect The strategy described here may be ideal to investigate the size of radiation-affected target and the relative contribution of different cellular organelles to bystander effects induced by energetic particles, which is relevant to radioprotection and cancer radiotherapy. PMID:19580486

TLR2 mediates gap junctional intercellular communication through connexin-43 in intestinal epithelial barrier injury.

PubMed

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

2009-08-14

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.

TLR2 Mediates Gap Junctional Intercellular Communication through Connexin-43 in Intestinal Epithelial Barrier Injury*

PubMed Central

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

2009-01-01

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 MDR1α-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. PMID:19528242

Zoledronate promotes bone formation by blocking osteocyte-osteoblast communication during bone defect healing.

PubMed

Cui, Pingping; Liu, Hongrui; Sun, Jing; Amizuka, Norio; Sun, Qinfeng; Li, Minqi

2018-01-01

Nitrogen-containing bisphosphonates (N-BPs) are potent antiresorptive drugs and their actions on osteoclasts have been studied extensively. Recent studies have suggested that N-BPs also target bone-forming cells. However, the precise mechanism of N-BPs in osteoblasts is paradoxical, and the specific role of osteocytes is worthy of in-depth study. Here, we investigated the cellular mechanisms of N-BPs regulating bone defect healing by zoledronate (ZA). Bone histomorphometry confirmed an increase in new bone formation by systemic ZA administration. ZA induced more alkaline phosphatase-positive osteoblasts and tartrate-resistant acid phosphatase-positive osteoclasts residing on the bone surface. Inexplicably, ZA increased SOST expression in osteocytes embedded in the bone matrix, which was not compatible with the intense osteoblast activity on the bone surface. ZA induced heterogeneous osteocytes and disturbed the distribution of the osteocytic-canalicular system (OLCS). Furthermore, according to the degree of OLCS regularity, dentin matrix protein 1 reactivity had accumulated around osteocytes in the ZA group, but it was distributed evenly in the OLCS of the control group. The control group showed a dense array of the gap junction protein connexin 43. However, connexin 43 was extremely sparse after ZA administration. In summary, ZA treatment reduces gap junction connections and blocks cellular communication between osteocytes and osteoblasts. Retaining SOST expression in osteocytes leads to activation of the Wnt signaling pathway and subsequent bone formation.

Soyasaponins prevent H₂O₂-induced inhibition of gap junctional intercellular communication by scavenging reactive oxygen species in rat liver cells.

PubMed

Chen, Jiading; Sun, Suxia; Zha, Dingsheng; Wu, Jiguo; Mao, Limei; Deng, Hong; Chu, Xinwei; Luo, Haiji; Zha, Longying

2014-01-01

It appears to be more practical and effective to prevent carcinogenesis by targeting the tumor promotion stage. Gap junctional intercellular communication (GJIC) is strongly involved in carcinogenesis, especially the tumor promotion stage. Considerable interest has been focused on the chemoprevention activities of soyasaponin (SS), which are major phytochemicals found in soybeans and soy products. However, less is known about the preventive effects of SS (especially SS with different chemical structures) against tumor promoter-induced inhibition of GJIC. We investigated the protective effects of SS-A1, SS-A2, and SS-I against hydrogen peroxide (H2O2)-induced GJIC inhibition and reactive oxygen species (ROS) production in Buffalo rat liver (BRL) cells. The present results clearly show for the first time that SS-A1, SS-A2, and SS-I prevent the H2O2-induced GJIC inhibition by scavenging ROS in BRL cells in a dose-dependent manner at the concentration range of from 25 to 100 μg/mL. Soyasaponins attenuated the H2O2-induced ROS through potentiating the activities of superoxide dismutase and glutathione peroxidase. This may be an important mechanism by which SS protects against tumor promotion. In addition, various chemical structures of SS appear to exhibit different protective abilities against GJIC inhibition. This may partly attribute to their differences in ROS-scavenging activities.

A high-performance, flexible and robust metal nanotrough-embedded transparent conducting film for wearable touch screen panels

NASA Astrophysics Data System (ADS)

Im, Hyeon-Gyun; An, Byeong Wan; Jin, Jungho; Jang, Junho; Park, Young-Geun; Park, Jang-Ung; Bae, Byeong-Soo

2016-02-01

We report a high-performance, flexible and robust metal nanotrough-embedded transparent conducting hybrid film (metal nanotrough-GFRHybrimer). Using an electro-spun polymer nanofiber web as a template and vacuum-deposited gold as a conductor, a junction resistance-free continuous metal nanotrough network is formed. Subsequently, the metal nanotrough is embedded on the surface of a glass-fabric reinforced composite substrate (GFRHybrimer). The monolithic composite structure of our transparent conducting film allows simultaneously high thermal stability (24 h at 250 °C in air), a smooth surface topography (Rrms < 1 nm) and excellent opto-electrical properties. A flexible touch screen panel (TSP) is fabricated using the transparent conducting films. The flexible TSP device stably operates on the back of a human hand and on a wristband.We report a high-performance, flexible and robust metal nanotrough-embedded transparent conducting hybrid film (metal nanotrough-GFRHybrimer). Using an electro-spun polymer nanofiber web as a template and vacuum-deposited gold as a conductor, a junction resistance-free continuous metal nanotrough network is formed. Subsequently, the metal nanotrough is embedded on the surface of a glass-fabric reinforced composite substrate (GFRHybrimer). The monolithic composite structure of our transparent conducting film allows simultaneously high thermal stability (24 h at 250 °C in air), a smooth surface topography (Rrms < 1 nm) and excellent opto-electrical properties. A flexible touch screen panel (TSP) is fabricated using the transparent conducting films. The flexible TSP device stably operates on the back of a human hand and on a wristband. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07657a

Structures with three dimensional nanofences comprising single crystal segments

DOEpatents

Goyal, Amit; Wee, Sung-Hun

2013-08-27

An article includes a substrate having a surface and a nanofence supported by the surface. The nanofence includes a multiplicity of primary nanorods and branch nanorods, each of the primary nanorods being attached to said substrate, and each of the branch nanorods being attached to a primary nanorods and/or another branch nanorod. The primary and branch nanorods are arranged in a three-dimensional, interconnected, interpenetrating, grid-like network defining interstices within the nanofence. The article further includes an enveloping layer supported by the nanofence, disposed in the interstices, and forming a coating on the primary and branch nanorods. The enveloping layer has a different composition from that of the nanofence and includes a radial p-n single junction solar cell photovoltaic material and/or a radial p-n multiple junction solar cell photovoltaic material.

Utilization of Low Temperatures in Electrical Machines,

DTIC Science & Technology

1983-09-08

quality 8 | | -. . * - . * . . .. . . . - * , . . , . . . . . * of the obtained junctions. For welding of steels, we used the TIG * method which is the...most frequently used technique for joining alloy steels. We studied the effects of the chemical composition of the * weld , linear energy of welding and...disappearance of resistance in certain metals and alloys at very low temperatures, in the vicinity of abso- lute zero. This fact enables currents to

Energy Finite Element Analysis Developments for Vibration Analysis of Composite Aircraft Structures

NASA Technical Reports Server (NTRS)

Vlahopoulos, Nickolas; Schiller, Noah H.

2011-01-01

The Energy Finite Element Analysis (EFEA) has been utilized successfully for modeling complex structural-acoustic systems with isotropic structural material properties. In this paper, a formulation for modeling structures made out of composite materials is presented. An approach based on spectral finite element analysis is utilized first for developing the equivalent material properties for the composite material. These equivalent properties are employed in the EFEA governing differential equations for representing the composite materials and deriving the element level matrices. The power transmission characteristics at connections between members made out of non-isotropic composite material are considered for deriving suitable power transmission coefficients at junctions of interconnected members. These coefficients are utilized for computing the joint matrix that is needed to assemble the global system of EFEA equations. The global system of EFEA equations is solved numerically and the vibration levels within the entire system can be computed. The new EFEA formulation for modeling composite laminate structures is validated through comparison to test data collected from a representative composite aircraft fuselage that is made out of a composite outer shell and composite frames and stiffeners. NASA Langley constructed the composite cylinder and conducted the test measurements utilized in this work.

Alternation in the gap-junctional intercellular communication capacity during the maturation of osteocytes in the embryonic chick calvaria.

PubMed

Wang, Ziyi; Odagaki, Naoya; Tanaka, Tomoyo; Hashimoto, Mana; Nakamura, Masahiro; Hayano, Satoru; Ishihara, Yoshihito; Kawanabe, Noriaki; Kamioka, Hiroshi

2016-10-01

The intercellular network of cell-cell communication among osteocytes is mediated by gap junctions. Gap junctional intercellular communication (GJIC) is thought to play an important role in the integration and synchronization of bone remodeling. To further understand the mechanism of bone development it is important to quantify the difference in the GJIC capacity of young and developmentally mature osteocytes. We first established an embryonic chick calvaria growth model to show the growth of the calvaria in embryos at 13 to 21days of age. We then applied a fluorescence recovery after photobleaching (FRAP) technique to compare the difference in the GJIC capacity of young osteocytes with that of developmentally mature osteocytes. Finally, we quantified the dye (Calcein) diffusion from the FRAP data using a mathematic model of simple diffusion which was also used to identify simple diffusion GJIC pattern cells (fitted model) and accelerated diffusion GJIC pattern cells (non-fitted model). The relationship between the longest medial-lateral length of the calvaria (frontal bone) and the embryonic age fit a logarithmic growth model: length=5.144×ln(day)-11.340. The morphometric data during osteocyte differentiation showed that the cellular body becomes more spindle-shaped and that the cell body volume decreased by approximately 22% with an increase in the length of the processes between the cells. However, there were no significant differences in the cellular body surface area or in the distance between the mass centres of the cells. The dye-displacement rate in young osteocytes was significantly higher than that in developmentally mature osteocytes: dye displacement only occurred in 26.88% of the developmentally mature osteocytes, while it occurred in 64.38% of the young osteocytes. Additionally, in all recovered osteocytes, 36% of the developmentally mature osteocytes comprised non-fitted model cells while 53.19% of the young osteocytes were the non-fitted model, which indicates the active transduction of dye molecules. However, there were no statistically significant differences between the young and developmentally mature osteocytes with regard to the diffusion coefficient, permeability coefficient, or permeance of the osteocyte processes, which were 3.93±3.77 (×10(-8)cm(2)/s), 5.12±4.56 (×10(-5)cm(2)/s) and 2.99±2.47 (×10(-13)cm(2)/s) (mean±SD), respectively. These experiments comprehensively quantified the GJIC capacity in the embryonic chick calvaria and indicated that the cell-cell communication capacity of the osteocytes in the embryonic chick calvaria was related to their development. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

PubMed Central

Billaud, Marie; Lohman, Alexander W.; Johnstone, Scott R.; Biwer, Lauren A.; Mutchler, Stephanie; Isakson, Brant E.

2014-01-01

It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the blood vessel wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the blood vessel wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to vessel wall function. PMID:24671377

Acetylation mediates Cx43 reduction caused by electrical stimulation

PubMed Central

Meraviglia, Viviana; Azzimato, Valerio; Colussi, Claudia; Florio, Maria Cristina; Binda, Anna; Panariti, Alice; Qanud, Khaled; Suffredini, Silvia; Gennaccaro, Laura; Miragoli, Michele; Barbuti, Andrea; Lampe, Paul D.; Gaetano, Carlo; Pramstaller, Peter P.; Capogrossi, Maurizio C.; Recchia, Fabio A.; Pompilio, Giulio; Rivolta, Ilaria; Rossini, Alessandra

2015-01-01

Communication between cardiomyocytes depends upon Gap Junctions (GJ). Previous studies have demonstrated that electrical stimulation induces GJ remodeling and modifies histone acetylases (HAT) and deacetylases (HDAC) activities, although these two results have not been linked. The aim of this work was to establish whether electrical stimulation modulates GJ-mediated cardiac cell-cell communication by acetylation-dependent mechanisms. Field stimulation of HL-1 cardiomyocytes at 0.5 Hz for 24 hours significantly reduced Connexin43 (Cx43) expression and cell-cell communication. HDAC activity was down-regulated whereas HAT activity was not modified resulting in increased acetylation of Cx43. Consistent with a post-translational mechanism, we did not observe a reduction in Cx43 mRNA in electrically stimulated cells, while the proteasomal inhibitor MG132 maintained Cx43 expression. Further, the treatment of paced cells with the HAT inhibitor Anacardic Acid maintained both the levels of Cx43 and cell-cell communication. Finally, we observed increased acetylation of Cx43 in the left ventricles of dogs subjected to chronic tachypacing as a model of abnormal ventricular activation. In conclusion, our findings suggest that altered electrical activity can regulate cardiomyocyte communication by influencing the acetylation status of Cx43. PMID:26264759

Regulation of cellular communication by signaling microdomains in the blood vessel wall.

PubMed

Billaud, Marie; Lohman, Alexander W; Johnstone, Scott R; Biwer, Lauren A; Mutchler, Stephanie; Isakson, Brant E

2014-01-01

It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the blood vessel wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the blood vessel wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to vessel wall function.

Polymer-Coated Graphene Aerogel Beads and Supercapacitor Application.

PubMed

Ouyang, An; Cao, Anyuan; Hu, Song; Li, Yanhui; Xu, Ruiqiao; Wei, Jinquan; Zhu, Hongwei; Wu, Dehai

2016-05-04

Graphene aerogels are highly porous materials with many energy and environmental applications; tailoring the structure and composition of pore walls within the aerogel is the key to those applications. Here, by freeze casting the graphene oxide sheets, we directly fabricated freestanding porous graphene beads containing radially oriented through channels from the sphere center to its surface. Furthermore, we introduced pseudopolymer to make reinforced, functional composite beads with a unique pore morphology. We showed that polymer layers can be coated smoothly on both sides of the pore walls, as well as on the junctions between adjacent pores, resulting in uniform polymer-graphene-polymer sandwiched structures (skeletons) throughout the bead. These composite beads significantly improved the electrochemical properties, with specific capacitances up to 669 F/g and good cyclic stability. Our results indicate that controlled fabrication of homogeneous hierarchical structures is a potential route toward high performance composite electrodes for various energy applications.

Exploring High-Performance n-Type Thermoelectric Composites Using Amino-Substituted Rylene Dimides and Carbon Nanotubes.

PubMed

Wu, Guangbao; Zhang, Zhi-Guo; Li, Yongfang; Gao, Caiyan; Wang, Xin; Chen, Guangming

2017-06-27

Taking advantage of the high electrical conductivity of a single-walled carbon nanotube (SWCNT) and the large Seebeck coefficient of rylene diimide, a convenient strategy is proposed to achieve high-performance n-type thermoelectric (TE) composites containing a SWCNT and amino-substituted perylene diimide (PDINE) or naphthalene diimide (NDINE). The obtained n-type composites display greatly enhanced TE performance with maximum power factors of 112 ± 8 (PDINE/SWCNT) and 135 ± 14 (NDINE/SWCNT) μW m -1 K -2 . A short doping time of 0.5 h can ensure high TE performance. The corresponding TE module consisting of five p-n junctions reaches a large output power of 3.3 μW under a 50 °C temperature gradient. In addition, the n-type composites exhibit high air stability and excellent thermal stability. This design strategy benefits the future fabricating of high-performance n-type TE materials and devices.

The Novel Roles of Connexin Channels and Tunneling Nanotubes in Cancer Pathogenesis

PubMed Central

Valdebenito, Silvana; Lou, Emil; Baldoni, John

2018-01-01

Neoplastic growth and cellular differentiation are critical hallmarks of tumor development. It is well established that cell-to-cell communication between tumor cells and “normal” surrounding cells regulates tumor differentiation and proliferation, aggressiveness, and resistance to treatment. Nevertheless, the mechanisms that result in tumor growth and spread as well as the adaptation of healthy surrounding cells to the tumor environment are poorly understood. A major component of these communication systems is composed of connexin (Cx)-containing channels including gap junctions (GJs), tunneling nanotubes (TNTs), and hemichannels (HCs). There are hundreds of reports about the role of Cx-containing channels in the pathogenesis of cancer, and most of them demonstrate a downregulation of these proteins. Nonetheless, new data demonstrate that a localized communication via Cx-containing GJs, HCs, and TNTs plays a key role in tumor growth, differentiation, and resistance to therapies. Moreover, the type and downstream effects of signals communicated between the different populations of tumor cells are still unknown. However, new approaches such as artificial intelligence (AI) and machine learning (ML) could provide new insights into these signals communicated between connected cells. We propose that the identification and characterization of these new communication systems and their associated signaling could provide new targets to prevent or reduce the devastating consequences of cancer. PMID:29695070

Moving Responses: Communication and Difference in Performative Pedagogies

ERIC Educational Resources Information Center

Gould, Elizabeth

2012-01-01

During the 1990s an African American university band director brought together Rosa Parks and Mark Camphouse for a performance of Camphouse's composition, A Movement for Rosa. Teaching the composition, the conductor and Camphouse communicated with language describing musical and lived realities that student musicians attempted to express and…

An NLRA Transducer for Dual Use Bone Conduction Audio and Haptic Communication. Summary Report

DTIC Science & Technology

2016-12-30

VIBRANT COMPOSITES INC. 1 A16-019 Phase 1 Summary Report Vibrant Composites Inc. December 30, 2016 I. ABSTRACT A combined transducer capable of bone ...transducer core capable of both precise haptic communication and high fidelity bone conduction audio. The transducer design leverages Micro-Multilayer...head-mounted system. In this Phase I SBIR, Vibrant Composites has delivered functional dual-mode bone conduction and vibrotactile transducer prototypes

Leader emergence through interpersonal neural synchronization

PubMed Central

Jiang, Jing; Chen, Chuansheng; Dai, Bohan; Shi, Guang; Ding, Guosheng; Liu, Li; Lu, Chunming

2015-01-01

The neural mechanism of leader emergence is not well understood. This study investigated (i) whether interpersonal neural synchronization (INS) plays an important role in leader emergence, and (ii) whether INS and leader emergence are associated with the frequency or the quality of communications. Eleven three-member groups were asked to perform a leaderless group discussion (LGD) task, and their brain activities were recorded via functional near infrared spectroscopy (fNIRS)-based hyperscanning. Video recordings of the discussions were coded for leadership and communication. Results showed that the INS for the leader–follower (LF) pairs was higher than that for the follower–follower (FF) pairs in the left temporo-parietal junction (TPJ), an area important for social mentalizing. Although communication frequency was higher for the LF pairs than for the FF pairs, the frequency of leader-initiated and follower-initiated communication did not differ significantly. Moreover, INS for the LF pairs was significantly higher during leader-initiated communication than during follower-initiated communications. In addition, INS for the LF pairs during leader-initiated communication was significantly correlated with the leaders’ communication skills and competence, but not their communication frequency. Finally, leadership could be successfully predicted based on INS as well as communication frequency early during the LGD (before half a minute into the task). In sum, this study found that leader emergence was characterized by high-level neural synchronization between the leader and followers and that the quality, rather than the frequency, of communications was associated with synchronization. These results suggest that leaders emerge because they are able to say the right things at the right time. PMID:25831535

Leader emergence through interpersonal neural synchronization.

PubMed

Jiang, Jing; Chen, Chuansheng; Dai, Bohan; Shi, Guang; Ding, Guosheng; Liu, Li; Lu, Chunming

2015-04-07

The neural mechanism of leader emergence is not well understood. This study investigated (i) whether interpersonal neural synchronization (INS) plays an important role in leader emergence, and (ii) whether INS and leader emergence are associated with the frequency or the quality of communications. Eleven three-member groups were asked to perform a leaderless group discussion (LGD) task, and their brain activities were recorded via functional near infrared spectroscopy (fNIRS)-based hyperscanning. Video recordings of the discussions were coded for leadership and communication. Results showed that the INS for the leader-follower (LF) pairs was higher than that for the follower-follower (FF) pairs in the left temporo-parietal junction (TPJ), an area important for social mentalizing. Although communication frequency was higher for the LF pairs than for the FF pairs, the frequency of leader-initiated and follower-initiated communication did not differ significantly. Moreover, INS for the LF pairs was significantly higher during leader-initiated communication than during follower-initiated communications. In addition, INS for the LF pairs during leader-initiated communication was significantly correlated with the leaders' communication skills and competence, but not their communication frequency. Finally, leadership could be successfully predicted based on INS as well as communication frequency early during the LGD (before half a minute into the task). In sum, this study found that leader emergence was characterized by high-level neural synchronization between the leader and followers and that the quality, rather than the frequency, of communications was associated with synchronization. These results suggest that leaders emerge because they are able to say the right things at the right time.

Prospects for small cryocoolers. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radebaugh, R.

1982-01-01

Small cryocoolers are commonly used in the areas of infrared detection, satellite communication, and cryopumps. Some emerging application areas deal with SQUID and Josephson junction devices, which require temperatures of about 8 K or below. The need for high reliability in these small cryocoolers has dictated the use of regenerative-cycle machines, but such machines are presently limited to temperatures above about 8 K. This paper discusses some of the research being done to improve reliability, decrease noise, and reduce the low-temperature limit of small cryocoolers.

Connexin-dependent gap junction enhancement is involved in the synergistic effect of sorafenib and all-trans retinoic acid on HCC growth inhibition.

PubMed

Yang, Yan; Qin, Shu-Kui; Wu, Qiong; Wang, Zi-Shu; Zheng, Rong-Sheng; Tong, Xu-Hui; Liu, Hao; Tao, Liang; He, Xian-Di

2014-02-01

Increasing gap junction activity in tumor cells provides a target by which to enhance antineoplastic therapies. Previously, several naturally occurring agents, including all-trans retinoic acid (ATRA) have been demonstrated to increase gap junctional intercellular communication (GJIC) in a number of types of cancer cells. In the present study, we investigated in vitro whether ATRA modulates the response of human hepatocellular carcinoma (HCC) cells to sorafenib, the only proven oral drug for advanced HCC, and the underlying mechanisms. HepG2 and SMMC-7721 cells were treated with sorafenib and/or ATRA, and cell proliferation and apoptosis were analyzed; the role of GJIC was also explored. We found that ATRA, at non-toxic concentrations, enhanced sorafenib-induced growth inhibition in both HCC cell lines, and this effect was abolished by two GJIC inhibitors, 18-α-GA and oleamide. Whereas lower concentrations of sorafenib (5 µM) or ATRA (0.1 or 10 µM) alone modestly induced GJIC activity, the combination of sorafenib plus ATRA resulted in a strong enhancement of GJIC. However, the action paradigm differed in the HepG2 and SMMC-7721 cells, with the dominant effect of GJIC dependent on the cell-specific connexin increase in protein amounts and relocalization. RT-PCR assay further revealed a transcriptional modification of the key structural connexin in the two cell lines. Thus, a connexin-dependent gap junction enhancement may play a central role in ATRA plus sorafenib synergy in inhibiting HCC cell growth. Since both agents are available for human use, the combination treatment represents a future profitable strategy for the treatment of advanced HCC.

Connexin 43 Is Necessary for Salivary Gland Branching Morphogenesis and FGF10-induced ERK1/2 Phosphorylation*

PubMed Central

Yamada, Aya; Futagi, Masaharu; Fukumoto, Emiko; Saito, Kan; Yoshizaki, Keigo; Ishikawa, Masaki; Arakaki, Makiko; Hino, Ryoko; Sugawara, Yu; Ishikawa, Momoko; Naruse, Masahiro; Miyazaki, Kanako; Nakamura, Takashi; Fukumoto, Satoshi

2016-01-01

Cell-cell interaction via the gap junction regulates cell growth and differentiation, leading to formation of organs of appropriate size and quality. To determine the role of connexin43 in salivary gland development, we analyzed its expression in developing submandibular glands (SMGs). Connexin43 (Cx43) was found to be expressed in salivary gland epithelium. In ex vivo organ cultures of SMGs, addition of the gap junctional inhibitors 18α-glycyrrhetinic acid (18α-GA) and oleamide inhibited SMG branching morphogenesis, suggesting that gap junctional communication contributes to salivary gland development. In Cx43−/− salivary glands, submandibular and sublingual gland size was reduced as compared with those from heterozygotes. The expression of Pdgfa, Pdgfb, Fgf7, and Fgf10, which induced branching of SMGs in Cx43−/− samples, were not changed as compared with those from heterozygotes. Furthermore, the blocking peptide for the hemichannel and gap junction channel showed inhibition of terminal bud branching. FGF10 induced branching morphogenesis, while it did not rescue the Cx43−/− phenotype, thus Cx43 may regulate FGF10 signaling during salivary gland development. FGF10 is expressed in salivary gland mesenchyme and regulates epithelial proliferation, and was shown to induce ERK1/2 phosphorylation in salivary epithelial cells, while ERK1/2 phosphorylation in HSY cells was dramatically inhibited by 18α-GA, a Cx43 peptide or siRNA. On the other hand, PDGF-AA and PDGF-BB separately induced ERK1/2 phosphorylation in primary cultured salivary mesenchymal cells regardless of the presence of 18α-GA. Together, our results suggest that Cx43 regulates FGF10-induced ERK1/2 phosphorylation in salivary epithelium but not in mesenchyme during the process of SMG branching morphogenesis. PMID:26565022

Gap junction protein expression and cellularity: comparison of immature and adult equine digital tendons

PubMed Central

Stanley, Rachael L; Fleck, Roland A; Becker, David L; Goodship, Allen E; Ralphs, Jim R; Patterson-Kane, Janet C

2007-01-01

Injury to the energy-storing superficial digital flexor tendon is common in equine athletes and is age-related. Tenocytes in the superficial digital flexor tendon of adult horses appear to have limited ability to respond adaptively to exercise or prevent the accumulation of strain-induced microdamage. It has been suggested that conditioning exercise should be introduced during the growth period, when tenocytes may be more responsive to increased quantities or intensities of mechanical strain. Tenocytes are linked into networks by gap junctions that allow coordination of synthetic activity and facilitate strain-induced collagen synthesis. We hypothesised that there are reductions in cellular expression of the gap junction proteins connexin (Cx) 43 and 32 during maturation and ageing of the superficial digital flexor tendon that do not occur in the non-injury-prone common digital extensor tendon. Cryosections from the superficial digital flexor tendon and common digital extensor tendon of 5 fetuses, 5 foals (1–6 months), 5 young adults (2–7 years) and 5 old horses (18–33 years) were immunofluorescently labelled and quantitative confocal laser microscopy was performed. Expression of Cx43 and Cx32 protein per tenocyte was significantly higher in the fetal group compared with all other age groups in both tendons. The density of tenocytes was found to be highest in immature tissue. Higher levels of cellularity and connexin protein expression in immature tendons are likely to relate to requirements for tissue remodelling and growth. However, if further studies demonstrate that this correlates with greater gap junctional communication efficiency and synthetic responsiveness to mechanical strain in immature compared with adult tendons, it could support the concept of early introduction of controlled exercise as a means of increasing resistance to later injury. PMID:17848160

Robust integration schemes for junction-based modulators in a 200mm CMOS compatible silicon photonic platform (Conference Presentation)

NASA Astrophysics Data System (ADS)

Szelag, Bertrand; Abraham, Alexis; Brision, Stéphane; Gindre, Paul; Blampey, Benjamin; Myko, André; Olivier, Segolene; Kopp, Christophe

2017-05-01

Silicon photonic is becoming a reality for next generation communication system addressing the increasing needs of HPC (High Performance Computing) systems and datacenters. CMOS compatible photonic platforms are developed in many foundries integrating passive and active devices. The use of existing and qualified microelectronics process guarantees cost efficient and mature photonic technologies. Meanwhile, photonic devices have their own fabrication constraints, not similar to those of cmos devices, which can affect their performances. In this paper, we are addressing the integration of PN junction Mach Zehnder modulator in a 200mm CMOS compatible photonic platform. Implantation based device characteristics are impacted by many process variations among which screening layer thickness, dopant diffusion, implantation mask overlay. CMOS devices are generally quite robust with respect to these processes thanks to dedicated design rules. For photonic devices, the situation is different since, most of the time, doped areas must be carefully located within waveguides and CMOS solutions like self-alignment to the gate cannot be applied. In this work, we present different robust integration solutions for junction-based modulators. A simulation setup has been built in order to optimize of the process conditions. It consist in a Mathlab interface coupling process and device electro-optic simulators in order to run many iterations. Illustrations of modulator characteristic variations with process parameters are done using this simulation setup. Parameters under study are, for instance, X and Y direction lithography shifts, screening oxide and slab thicknesses. A robust process and design approach leading to a pn junction Mach Zehnder modulator insensitive to lithography misalignment is then proposed. Simulation results are compared with experimental datas. Indeed, various modulators have been fabricated with different process conditions and integration schemes. Extensive electro-optic characterization of these components will be presented.

Localization of connexin 43 gap junctions and hemichannels in tanycytes of adult mice.

PubMed

Szilvásy-Szabó, Anett; Varga, Edina; Beliczai, Zsuzsa; Lechan, Ronald M; Fekete, Csaba

2017-10-15

Tanycytes are specialized glial cells lining the lateral walls and the floor of the third ventricle behind the optic chiasm. In addition to functioning as barrier cells, they also have an important role in the regulation of neuroendocrine axes and energy homeostasis. To determine whether tanycytes communicate with each other via Connexin 43 (Cx43) gap junctions, individual tanycytes were loaded with Lucifer yellow (LY) through a patch pipette. In all cases, LY filled a larger group of tanycytes as well as blood vessels adjacent to tanycyte processes. The Cx43-blocker, carbenoxolone, inhibited spreading of LY. The greatest density of Cx43-immunoreactive spots was observed in the cell membrane of α-tanycyte cell bodies. Cx43-immunoreactivity was also present in the membrane of β-tanycyte cell bodies, but in lower density. Processes of both types of tanycytes also contained Cx43-immunoreactivity. At the ultrastructural level, Cx43-immunoreactivity was present in the cell membrane of all types of tanycytes including their ventricular surface, but gap junctions were more frequent among α-tanycytes. Cx43-immunoreactivity was also observed in the cell membrane between contacting tanycyte endfeet processes, and between tanycyte endfeet process and axon varicosities in the external zone of the median eminence and capillaries in the arcuate nucleus and median eminence. These results suggest that gap junctions are present not only among tanycytes, but also between tanycytes and the axons of hypophysiotropic neurons. Cx43 hemichannels may also facilitate the transport between tanycytes and extracellular fluids, including the cerebrospinal fluid, extracellular space of the median eminence and bloodstream. Copyright © 2017 Elsevier B.V. All rights reserved.

Confocal Raman mapping of collagen cross-link and crystallinity of human dentin-enamel junction.

PubMed

Slimani, Amel; Nouioua, Fares; Desoutter, Alban; Levallois, Bernard; Cuisinier, Frédéric J G; Tassery, Hervé; Terrer, Elodie; Salehi, Hamideh

2017-08-01

The separation zone between enamel and dentin [dentin-enamel junction (DEJ)] with different properties in biomechanical composition has an important role in preventing crack propagation from enamel to dentin. The understanding of the chemical structure (inorganic and organic components), physical properties, and chemical composition of the human DEJ could benefit biomimetic materials in dentistry. Spatial distribution of calcium phosphate crystallinity and the collagen crosslinks near DEJ were studied using confocal Raman microscopy and calculated by different methods. To obtain collagen crosslinking, the ratio of two peaks 1660  cm-1 over 1690  cm-1 (amide I bands) is calculated. For crystallinity, the inverse full-width at half maximum of phosphate peak at 960  cm-1, and the ratio of two Raman peaks of phosphate at 960/950  cm-1 is provided. In conclusion, the study of chemical and physical properties of DEJ provides many benefits in the biomaterial field to improve the synthesis of dental materials in respect to the natural properties of human teeth. Confocal Raman microscopy as a powerful tool provides the molecular structure to identify the changes along DEJ and can be expanded for other mineralized tissues. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Stand Up and Write: Completing the Freshman Communications Course.

ERIC Educational Resources Information Center

Goldstein, Richard M.; Nelson, Charles W.

Members of the English and speech faculty at Michigan Technological University combined and coordinated their ideas to find a way to introduce the basics of oral communication into the composition course. The course itself is structured according to the quarter system, in which basic composition is taught in the first term, research methods and…

At the Atrioventricular Crossroads: Dual Pathway Electrophysiology in the Atrioventricular Node and its Underlying Heterogeneities

PubMed Central

George, Sharon A; Faye, N Rokhaya; Murillo-Berlioz, Alejandro; Lee, K Benjamin; Trachiotis, Gregory D; Efimov, Igor R

2017-01-01

The atrioventricular node (AVN) is a complex structure that performs a variety of functions in the heart. The AVN is primarily an electrical gatekeeper between the atria and ventricles and introduces a delay between atrial and ventricular excitation, allowing for efficient ventricular filling. The AVN is composed of several compartments that safely transmit electrical excitation from the atria to the ventricles via the fast or slow pathways. There are many electrophysiological differences between these pathways, including conduction time and electrical refractoriness, that increase the predisposition of the atrioventricular junction to arrhythmias such as atrioventricular nodal re-entrant tachycardia. These varied electrophysiological characteristics of the fast and slow pathways stem from their unique structural and molecular composition (tissue and cellular geometry, ion channels and gap junctions). This review summarises the structural and molecular heterogeneities of the human AVN and how they result in electrophysiological variations and arrhythmias. PMID:29326832

Terahertz emission from the intrinsic Josephson junctions of high-symmetry thermally-managed Bi2Sr2CaCu2O8+δ microstrip antennas

NASA Astrophysics Data System (ADS)

Klemm, Richard A.; Davis, Andrew E.; Wang, Qing X.; Yamamoto, Takashi; Cerkoney, Daniel P.; Reid, Candy; Koopman, Maximiliaan L.; Minami, Hidetoshi; Kashiwagi, Takanari; Rain, Joseph R.; Doty, Constance M.; Sedlack, Michael A.; Morales, Manuel A.; Watanabe, Chiharu; Tsujimoto, Manabu; Delfanazari, Kaveh; Kadowaki, Kazuo

2017-12-01

We show for high-symmetry disk, square, or equilateral triangular thin microstrip antennas of any composition respectively obeying C ∞v , C 4v , and C 3v point group symmetries, that the transverse magnetic electromagnetic cavity mode wave functions are restricted in form to those that are one-dimensional representations of those point groups. Plots of the common nodal points of the ten lowest-energy non-radiating two-dimensional representations of each of these three symmetries are presented. For comparison with symmetry-broken disk intrinsic Josephson junction microstrip antennas constructed from the highly anisotropic layered superconductor Bi2Sr2CaCu2O8+δ (BSCCO), we present plots of the ten lowest frequency orthonormal wave functions and of their emission power angular distributions. These results are compared with previous results for square and equilateral triangular thin microstrip antennas.

Adjustable 3-D structure with enhanced interfaces and junctions towards microwave response using FeCo/C core-shell nanocomposites.

PubMed

Li, Daoran; Liang, Xiaohui; Liu, Wei; Ma, Jianna; Zhang, Yanan; Ji, Guangbin; Meng, Wei

2017-12-01

In this work, the 3-D honeycomb-like FeCo/C nanocomposites were synthesized through the carbon thermal reduction under an inert atmosphere. The enhanced microwave absorption properties of the composites were mainly attributed to the unique three dimensional structure of the FeCo/C nanocomposites, abundant interfaces and junctions, and the appropriate impedance matching. The Cole-Cole semicircles proved the sufficient dielectric relaxation process. The sample calcinated at 600°C for 4h showed the best microwave absorption properties. A maximum reflection loss of -54.6dB was achieved at 10.8GHz with a thickness of 2.3mm and the frequency bandwidth was as large as 5.3GHz. The results showed that the as-prepared FeCo/C nanocomposite could be a potential candidate for microwave absorption. Copyright © 2017 Elsevier Inc. All rights reserved.

Compositions and methods for direct capture of organic materials from process streams

DOEpatents

Lin, YuPo J.; Brotzman, Richard W.; Snyder, Seth W.

2016-08-09

A particulate magnetic nanostructured solid sorbent (MNSS) material is described herein. The particles of the MNSS comprise a plurality of tethered nanoparticles. The nanoparticles are tethered together by substantially linear hydrocarbon chains, a poly(alkylene oxide) chains, or a combination thereof connecting the nanoparticles in a three-dimensional elastic network with the nanoparticles as junctions of the network having junction functionality of about 2.1 to about 6. The surfaces of at least some of the nanoparticles comprise a polymerized siloxane bearing at least one sorption-aiding substituent selected from a hydrophilic group and a lipophilic group. The plurality of nanoparticles is made up of superparamagnetic nanoparticles or a combination of superparamagnetic and non-magnetic nanoparticles. The individual superparamagnetic nanoparticles comprise a passivating metal oxide coating around a core comprising at least one nanocrystalline metal or alloy having ferromagnetic or ferrimagnetic properties.

Gating connexin 43 channels reconstituted in lipid vesicles by mitogen-activated protein kinase phosphorylation.

PubMed

Kim, D Y; Kam, Y; Koo, S K; Joe, C O

1999-02-26

The regulation of gap junctional permeability by phosphorylation was examined in a model system in which connexin 43 (Cx43) gap junction hemichannels were reconstituted in lipid vesicles. Cx43 was immunoaffinity-purified from rat brain, and Cx43 channels were reconstituted into unilamellar phospholipid liposomes. The activities of the reconstituted channels were measured by monitoring liposome permeability. Liposomes containing the Cx43 protein were fractionated on the basis of permeability to sucrose using sedimentation in an iso-osmolar density gradient. The gradient allowed separation of the sucrose-permeable and -impermeable liposomes. Liposomes that were permeable to sucrose were also permeable to the communicating dye molecule lucifer yellow. Permeability, and therefore activity of the reconstituted Cx43 channels, were directly dependent on the state of Cx43 phosphorylation. The permeability of liposomes containing Cx43 channels was increased by treatment of liposomes with calf intestinal phosphatase. Moreover, liposomes formed with Cx43 that had been dephosphorylated by calf intestinal phosphatase treatment showed increased permeability to sucrose. The role of phosphorylation in the gating mechanism of Cx43 channels was supported further by the observation that phosphorylation of Cx43 by mitogen-activated protein kinase reversibly reduced the permeability of liposomes containing dephosphorylated Cx43. Our results show a direct correlation between gap junctional permeability and the phosphorylation state of Cx43.

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

PubMed Central

Rovetta, Francesca; Boniotti, Jennifer; Mazzoleni, Giovanna

2017-01-01

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. PMID:28607928

Cell line specific modulation of connexin43 expression after exposure to ionizing radiation.

PubMed

Banaz-Yaşar, Ferya; Tischka, Rabea; Iliakis, George; Winterhager, Elke; Gellhaus, Alexandra

2005-01-01

Gap junctional intercellular communication plays a significant role in mediating radiation-induced bystander effects. However, the level of Cx43 itself is influenced by ionizing radiation, which could modify the bystander effect. Here we have investigated several cell lines for the modulation of Cx43 expression 24 h after irradiation with 5 Gy X-rays. The mouse endothelial cell line bEnd3 revealed a significantly elevated level of Cx43 already 15 min after exposure to X-rays, whereas human hybrid endothelial cells (EA.hy926) exhibited a transient downregulation of Cx43 mRNA. No obvious changes in the communication properties of the different cell lines could be observed after irradiation. The communication-deficient malignant human trophoblast cell line Jeg3 stably transfected with Cx43 did not reveal any induction of endogenous nor alteration in the exogenous Cx43 transcript level upon exposure to 5 Gy. Taken together, our data show a cell line specific modulation of Cx43 expression after exposure to X-rays.