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

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

2015-04-17

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

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

DEFF Research Database (Denmark)

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

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 Cx...

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

International Nuclear Information System (INIS)

Ganesan, Shanthi; Nteeba, Jackson; Keating, Aileen F.

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-01-01

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

Inhibition of connexin43 gap junction channels by the endocrine disruptor ioxynil

International Nuclear Information System (INIS)

Leithe, Edward; Kjenseth, Ane; Bruun, Jarle; Sirnes, Solveig; Rivedal, Edgar

2010-01-01

Gap junctions are intercellular plasma membrane domains containing channels that mediate transport of ions, metabolites and small signaling molecules between adjacent cells. Gap junctions play important roles in a variety of cellular processes, including regulation of cell growth and differentiation, maintenance of tissue homeostasis and embryogenesis. The constituents of gap junction channels are a family of trans-membrane proteins called connexins, of which the best-studied is connexin43. Connexin43 functions as a tumor suppressor protein in various tissue types and is frequently dysregulated in human cancers. The pesticide ioxynil has previously been shown to act as an endocrine disrupting chemical and has multiple effects on the thyroid axis. Furthermore, both ioxynil and its derivative ioxynil octanoate have been reported to induce tumors in animal bioassays. However, the molecular mechanisms underlying the possible tumorigenic effects of these compounds are unknown. In the present study we show that ioxynil and ioxynil octanoate are strong inhibitors of connexin43 gap junction channels. Both compounds induced rapid loss of connexin43 gap junctions at the plasma membrane and increased connexin43 degradation. Ioxynil octanoate, but not ioxynil, was found to be a strong activator of ERK1/2. The compounds also had different effects on the phosphorylation status of connexin43. Taken together, the data show that ioxynil and ioxynil octanoate are potent inhibitors of intercellular communication via gap junctions.

Gemcitabine intercellular diffusion mediated by gap junctions: new implications for cancer therapy

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Caruso Manuel

2010-06-01

Full Text Available Abstract Background Solid tumors are often poorly vascularized, with cells that can be 100 μm away from blood vessels. These distant cells get less oxygen and nutrients and are exposed to lower doses of chemotherapeutic agents. As gap junctions allow the passage of small molecules between cells, we tested the possibility that the chemotherapeutic agent gemcitabine can diffuse through gap junctions in solid tumors. Results We first showed with a dye transfer assay that the glioblastoma and the osteosarcoma cells used in this study have functional gap junctions. These cells were genetically engineered to express the herpes simplex virus thymidine kinase (TK, and induced a "bystander effect" as demonstrated by the killing of TK-negative cells in presence of the nucleoside analogue ganciclovir (GCV. The ability of gemcitabine to induce a similar bystander effect was then tested by mixing cells treated with 3 μM gemcitabine for 24 hours with untreated cells at different ratios. In all cell lines tested, bystander cells were killed with ratios containing as low as 5% treated cells, and this toxic effect was reduced in presence of α-glycyrrhetinic acid (AGA, a specific gap junction inhibitor. We also showed that a 2- or a 24-hour gemcitabine treatment was more efficient to inhibit the growth of spheroids with functional gap junctions as compared to the same treatment made in presence of AGA. Finally, after a 24-hour gemcitabine treatment, the cell viability in spheroids was reduced by 92% as opposed to 51% in presence of AGA. Conclusion These results indicate that gemcitabine-mediated toxicity can diffuse through gap junctions, and they suggest that gemcitabine treatment could be more efficient for treating solid tumors that display gap junctions. The presence of these cellular channels could be used to predict the responsiveness to this nucleoside analogue therapy.

7-Ketocholesterol modulates intercellular communication through gap-junction in bovine lens epithelial cells

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Pereira Paulo

2004-06-01

Full Text Available Abstract Background Connexin43 (Cx43 is an integral membrane protein that forms intercellular channels called gap junctions. Intercellular communication in the eye lens relies on an extensive network of gap junctions essential for the maintenance of lens transparency. The association of Cx43 with cholesterol enriched lipid raft domains was recently demonstrated. The objective of this study is to assess if products of cholesterol oxidation (oxysterols affect gap junction intercellular communication (GJIC. Results Primary cultures of lens epithelial cells (LEC were incubated with 7-ketocholesterol (7-Keto, 25-hydroxycholesterol (25-OH or cholesterol and the subcellular distribution of Cx43 was evaluated by immunofluorescence confocal microscopy. The levels of Cx43 present in gap junction plaques were assessed by its insolubility in Triton X-100 and quantified by western blotting. The stability of Cx43 at the plasma membrane following incubation with oxysterols was evaluated by biotinylation of cell surface proteins. Gap junction intercellular communication was evaluated by transfer of the dye Lucifer yellow. The results obtained showed that 7-keto induces an accumulation of Cx43 at the plasma membrane and an increase in intercellular communication through gap junction. However, incubation with cholesterol or 25-OH did not lead to significant alterations on subcellular distribution of Cx43 nor in intercellular communication. Data further suggests that increased intercellular communication results from increased stability of Cx43 at the plasma membrane, presumably forming functional gap-junctions, as suggested by decreased solubility of Cx43 in 1% Triton X-100. The increased stability of Cx43 at the plasma membrane seems to be specific and not related to disruption of endocytic pathway, as demonstrated by dextran uptake. Conclusions Results demonstrate, for the first time, that 7-keto induces an increase in gap junction intercellular communication

Terbinafine inhibits gap junctional intercellular communication

International Nuclear Information System (INIS)

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

2016-01-01

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. - 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 2+ concentration. • Inhibition of squalene epoxidase is not involved in this new effect of terbinafine.

Gap junctions and connexin-interacting proteins

NARCIS (Netherlands)

Giepmans, Ben N G

2004-01-01

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

Progressive age-dependence and frequency difference in the effect of gap junctions on active cochlear amplification and hearing.

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Zong, Liang; Chen, Jin; Zhu, Yan; Zhao, Hong-Bo

2017-07-22

Mutations of Connexin 26 (Cx26, GJB2), which is a predominant gap junction isoform in the cochlea, can induce high incidence of nonsyndromic hearing loss. We previously found that targeted-deletion of Cx26 in supporting Deiters cells and outer pillar cells in the cochlea can influence outer hair cell (OHC) electromotility and reduce active cochlear amplification leading to hearing loss, even though there are no gap junction connexin expressions in the auditory sensory hair cells. Here, we further report that hearing loss and the reduction of active amplification in the Cx26 targeted-deletion mice are progressive and different at high and low frequency regions, first occurring in the high frequency region and then progressively extending to the middle and low frequency regions with mouse age increased. The speed of hearing loss extending was fast in the basal high frequency region and slow in the apical low frequency region, showing a logarithmic function with mouse age. Before postnatal day 25, there were no significant hearing loss and the reduction of active cochlear amplification in the low frequency region. Hearing loss and the reduction of active cochlear amplification also had frequency difference, severe and large in the high frequency regions. These new data indicate that the effect of gap junction on active cochlear amplification is progressive, but, consistent with our previous report, exists in both high and low frequency regions in adulthood. These new data also suggest that cochlear gap junctions may have an important role in age-related hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.

Terbinafine inhibits gap junctional intercellular communication

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Lee, Ju Yeun, E-mail: whitewndus@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Yoon, Sei Mee, E-mail: sei_mee@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Department of Integrated OMICS for Biomedical Sciences, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Choi, Eun Ju, E-mail: yureas@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Lee, Jinu, E-mail: jinulee@yonsei.ac.kr [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of)

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{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 inhibits 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.

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

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Jie Wu

2016-06-01

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

Connexin 43 Expression on Peripheral Blood Eosinophils: Role of Gap Junctions in Transendothelial Migration

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Harissios Vliagoftis

2014-01-01

Full Text Available 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 (Cx43 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.

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

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Richard David Veenstra

2013-05-01

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

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

Science.gov (United States)

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.

Joint diseases: from connexins to gap junctions.

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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.

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

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Meeri Eeva-Liisa Mäkinen

2018-03-01

Full Text Available 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.

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

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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

Nonlinear gap junctions enable long-distance propagation of pulsating calcium waves in astrocyte networks.

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Mati Goldberg

Full Text Available 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 Ca(2+ waves. An identified mode of propagation is based on cytoplasm-to-cytoplasm transport of inositol trisphosphate (IP(3 through gap junctions that locally trigger Ca(2+ pulses via IP(3-dependent Ca(2+-induced Ca(2+ release. It is, however, currently unknown whether this intracellular route is able to support the propagation of long-distance regenerative Ca(2+ 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 Ca(2+ 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 Ca(2+ 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 Ca(2+ waves across astrocytes and the precise conditions under which glial cells may participate in information processing in the brain.

Methamphetamine compromises gap junctional communication in astrocytes and neurons.

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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

HYS-32, a novel analogue of combretastatin A-4, enhances connexin43 expression and gap junction intercellular communication in rat astrocytes.

Science.gov (United States)

Lin, Pei-Chun; Shen, Chien-Chang; Liao, Chih-Kai; Jow, Guey-Mei; Chiu, Chi-Ting; Chung, Tun-Hui; Wu, Jiahn-Chun

2013-05-01

HYS-32 [4-(3,4-dimethoxyphenyl)-3-(naphthalen-2-yl)-2(5H)-furanone] is a new analogue of the anti-tumor compound combretastatin A-4 containing a cis-stilbene moiety. In this study, we investigated its effects on Cx43 gap junction intercellular communication (GJIC) and the signaling pathway involved in rat primary astrocytes. Western blot analyses showed that HYS-32 dose- and time-dependently upregulated Cx43 expression. A confocal microscopic study and scrape-loading/dye transfer analyses demonstrated that HYS-32 (5μM) induced microtubule coiling, accumulation of Cx43 in gap junction plaques, and increased GJIC in astrocytes. The HYS-32-induced microtubule coiling and Cx43 accumulation in gap junction plaques was reversed when HYS-32 was removed. Treatment of astrocytes with cycloheximide resulted in time-dependent degradation of by co-treatment with HYS-32 by increasing the half-life of Cx43. Co-treatment with HYS-32 also prevented the LPS-induced downregulation of Cx43 and inhibition of GJIC in astrocytes. HYS-32 induced activation of PKC, ERK, and JNK, and co-treatment with the PKC inhibitor Go6976 or the ERK inhibitor PD98059, but not the JNK inhibitor SP600125, prevented the HYS-32-induced increase in Cx43 expression and GJIC. Go6976 suppressed the HYS-32-induced PKC phosphorylation and increase in phospho-ERK levels, while PD98059 did not prevent the HYS-32-induced increase in phospho-PKC levels, suggesting that PKC is an upstream effector of ERK. In conclusion, our results show that HYS-32 increases the half-life of Cx43 and enhances Cx43 expression and GJIC in astrocytes via a PKC-ERK signaling cascade. These novel biological effects of HYS-32 on astrocyte gap junctions support its potential for therapeutic use as a protective agent for the central nervous system. Copyright © 2013 Elsevier Ltd. All rights reserved.

impairs gap junction function causing congenital cataract

Indian Academy of Sciences (India)

Navya

2017-03-24

Mar 24, 2017 ... experiment showed a lower dye diffusion distance of Cx46 V44M cells, ... Studies of connexins show that channel gating and permeability .... have found that connexin assembled into gap junction plaques is not soluble in 1% ..... high glucose reduces gap junction activity in microvascular endothelial cells.

impairs gap junction function causing congenital cataract

Indian Academy of Sciences (India)

LIJUAN CHEN

2017-12-20

Dec 20, 2017 ... showed a lower dye diffusion distance of Cx46 V44M cells, which indicates that the gap junction intercellular ... permeability could be affected by alterations of charged residues of .... bled into gap junction plaques is not soluble in 1% Triton ..... regulation of connexin 43 expression by high glucose reduces.

Heterocellular interaction enhances recruitment of α and β-catenins and ZO-2 into functional gap-junction complexes and induces gap junction-dependant differentiation of mammary epithelial cells

International Nuclear Information System (INIS)

Talhouk, Rabih S.; Mroue, Rana; Mokalled, Mayssa; Abi-Mosleh, Lina; Nehme, Ralda; Ismail, Ayman; Khalil, Antoine; Zaatari, Mira; El-Sabban, Marwan E.

2008-01-01

Gap junctions (GJ) are required for mammary epithelial differentiation. Using epithelial (SCp2) and myoepithelial-like (SCg6) mouse-derived mammary cells, the role of heterocellular interaction in assembly of GJ complexes and functional differentiation (β-casein expression) was evaluated. Heterocellular interaction is critical for β-casein expression, independent of exogenous basement membrane or cell anchoring substrata. Functional differentiation of SCp2, co-cultured with SCg6, is more sensitive to GJ inhibition relative to homocellular SCp2 cultures differentiated by exogenous basement membrane. Connexin (Cx)32 and Cx43 levels were not regulated across culture conditions; however, GJ functionality was enhanced under differentiation-permissive conditions. Immunoprecipitation studies demonstrated association of junctional complex components (α-catenin, β-catenin and ZO-2) with Cx32 and Cx43, in differentiation conditions, and additionally with Cx30 in heterocellular cultures. Although β-catenin did not shuttle between cadherin and GJ complexes, increased association between connexins and β-catenin in heterocellular cultures was observed. This was concomitant with reduced nuclear β-catenin, suggesting that differentiation in heterocellular cultures involves sequestration of β-catenin in GJ complexes

The psychostimulant modafinil enhances gap junctional communication in cortical astrocytes.

Science.gov (United States)

Liu, Xinhe; Petit, Jean-Marie; Ezan, Pascal; Gyger, Joël; Magistretti, Pierre; Giaume, Christian

2013-12-01

Sleep-wake cycle is characterized by changes in neuronal network activity. However, for the last decade there is increasing evidence that neuroglial interaction may play a role in the modulation of sleep homeostasis and that astrocytes have a critical impact in this process. Interestingly, astrocytes are organized into communicating networks based on their high expression of connexins, which are the molecular constituents of gap junction channels. Thus, neuroglial interactions should also be considered as the result of the interplay between neuronal and astroglial networks. Here, we investigate the effect of modafinil, a wakefulness-promoting agent, on astrocyte gap junctional communication. We report that in the cortex modafinil injection increases the expression of mRNA and protein of connexin 30 but not those of connexin 43, the other major astroglial connexin. These increases are correlated with an enhancement of intercellular dye coupling in cortical astrocytes, which is abolished when neuronal activity is silenced by tetrodotoxin. Moreover, gamma-hydroxybutyric acid, which at a millimolar concentration induces sleep, has an opposite effect on astroglial gap junctions in an activity-independent manner. These results support the proposition that astroglia may play an important role in complex physiological brain functions, such as sleep regulation, and that neuroglial networking interaction is modified during sleep-wake cycle. This article is part of the Special Issue Section entitled 'Current Pharmacology of Gap Junction Channels and Hemichannels'. Copyright © 2013. Published by Elsevier Ltd.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

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

OpenAIRE

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

2014-01-01

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

Hyperglycaemia and diabetes impair gap junctional communication among astrocytes.

Science.gov (United States)

Gandhi, Gautam K; Ball, Kelly K; Cruz, Nancy F; Dienel, Gerald A

2010-03-15

Sensory and cognitive impairments have been documented in diabetic humans and animals, but the pathophysiology of diabetes in the central nervous system is poorly understood. Because a high glucose level disrupts gap junctional communication in various cell types and astrocytes are extensively coupled by gap junctions to form large syncytia, the influence of experimental diabetes on gap junction channel-mediated dye transfer was assessed in astrocytes in tissue culture and in brain slices from diabetic rats. Astrocytes grown in 15-25 mmol/l glucose had a slow-onset, poorly reversible decrement in gap junctional communication compared with those grown in 5.5 mmol/l glucose. Astrocytes in brain slices from adult STZ (streptozotocin)-treated rats at 20-24 weeks after the onset of diabetes also exhibited reduced dye transfer. In cultured astrocytes grown in high glucose, increased oxidative stress preceded the decrement in dye transfer by several days, and gap junctional impairment was prevented, but not rescued, after its manifestation by compounds that can block or reduce oxidative stress. In sharp contrast with these findings, chaperone molecules known to facilitate protein folding could prevent and rescue gap junctional impairment, even in the presence of elevated glucose level and oxidative stress. Immunostaining of Cx (connexin) 43 and 30, but not Cx26, was altered by growth in high glucose. Disruption of astrocytic trafficking of metabolites and signalling molecules may alter interactions among astrocytes, neurons and endothelial cells and contribute to changes in brain function in diabetes. Involvement of the microvasculature may contribute to diabetic complications in the brain, the cardiovascular system and other organs.

The B[a]P-increased intercellular communication via translocation of connexin-43 into gap junctions reduces apoptosis

International Nuclear Information System (INIS)

Tekpli, X.; Rivedal, E.; Gorria, M.; Landvik, N.E.; Rissel, M.; Dimanche-Boitrel, M.-T.; Baffet, G.; Holme, J.A.; Lagadic-Gossmann, D.

2010-01-01

Gap junctions are channels in plasma membrane composed of proteins called connexins. These channels are organized in special domains between cells, and provide for direct gap junctional intercellular communication (GJIC), allowing diffusion of signalling molecules < 1 kD. GJIC regulates cell homeostasis and notably the balance between proliferation, cell cycle arrest, cell survival and apoptosis. Here, we have investigated benzo[a]pyrene (B[a]P) effects on GJIC and on the subcellular localization of the major protein of gap junction: connexin-43 (Cx43). Our results showed that B[a]P increased GJIC between mouse hepatoma Hepa1c1c7 cells via translocation of Cx43 from Golgi apparatus and lipid rafts into gap junction plaques. Interestingly, inhibition of GJIC by chlordane or small interference RNA directed against Cx43 enhanced B[a]P-induced apoptosis in Hepa1c1c7 cells. The increased apoptosis caused by inhibition of GJIC appeared to be mediated by ERK/MAPK pathway. It is suggested that B[a]P could induce transfer of cell survival signal or dilute cell death signal via regulation of ERK/MAPK through GJIC.

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

DEFF Research Database (Denmark)

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

2003-01-01

INTRODUCTION: The aim of this study was to determine if the stable antiarrhythmic peptide (AAP) analogue ZP123 increases gap junctional intercellular conductance and prevents reentrant ventricular tachycardia (VT) during coronary artery occlusion. METHODS AND RESULTS: Voltage clamp experiments...... demonstrated that 10 nM ZP123 improved gap junctional intercellular conductance by 69% +/- 20% in pairs of guinea pig ventricular myocytes. VT was induced by programmed stimulation in alpha-chloralose anaesthetized open chest dogs 1 to 4 hours after coronary artery occlusion. Three-dimensional activation...... AAP analogue ZP123 increased gap junctional intercellular conductance and specifically prevented the induction of reentrant VT during ischemia in a broad dose range without proarrhythmic or hemodynamic side effects. ZP123 is a promising candidate for use in preventing ischemia-induced VT....

Roles of gap junctions, connexins and pannexins in epilepsy

Directory of Open Access Journals (Sweden)

Shanthini eMylvaganam

2014-05-01

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

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

Directory of Open Access Journals (Sweden)

Li eXin

2013-12-01

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

‘Gap Junctions and Cancer: Communicating for 50 Years’

Science.gov (United States)

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

2017-01-01

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

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

African Journals Online (AJOL)

Yomi

2012-04-03

Apr 3, 2012 ... Three dimensional (3 D) structure is very useful for understanding biological functions. Gap junction beta 2 (GJB2), human gene encoding for gap junction beta 2 protein is involved in ... Research in deafness became real.

Gap junctions-guards of excitability

DEFF Research Database (Denmark)

Stroemlund, Line Waring; Jensen, Christa Funch; Qvortrup, Klaus

2015-01-01

Cardiomyocytes are connected by mechanical and electrical junctions located at the intercalated discs (IDs). Although these structures have long been known, it is becoming increasingly clear that their components interact. This review describes the involvement of the ID in electrical disturbances...... of the heart and focuses on the role of the gap junctional protein connexin 43 (Cx43). Current evidence shows that Cx43 plays a crucial role in organizing microtubules at the intercalated disc and thereby regulating the trafficking of the cardiac sodium channel NaV1.5 to the membrane....

Non-genotoxic carcinogens: early effects on gap junctions, cell proliferation and apoptosis in the rat

International Nuclear Information System (INIS)

Mally, Angela; Chipman, James Kevin

2002-01-01

Non-genotoxic carcinogens are thought to induce tumour formation by disturbing the balance between cell growth and cell death. Gap junctions (GJ) contribute to the maintenance of tissue homeostasis by allowing the intercellular exchange of growth regulatory signals and potential inhibition of GJ intercellular communication through loss of connexin (Cx) plaques has been shown to be involved in the cancer process. We have investigated the time- and dose-dependent effects of the non-genotoxic hepatocarcinogens Wy-14,643, 2,3,7,8-tetrachlorodibenzo-p-dioxin, methapyrilene and hexachlorobenzene and the male rat kidney carcinogens chloroform, p-dichlorobenzene and d-limonene on gap junction plaque expression in relation to proliferation and apoptosis. With the exception of limonene, all non-genotoxic carcinogens significantly reduced the expression of GJ plaques containing Cx32 in their respective target tissue. No dose-dependent, significant effects were seen in non-target organs. Although alteration of Cx32 expression did not appear to correlate with induction of cell proliferation, out data suggest that the interaction of both processes--interference of GJ coupled with a proliferative stimulus (at the carcinogenic dose)--may be important in non-genotoxic carcinogenesis and provide a potential alert for non-genotoxic carcinogens in short-term toxicity tests

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

Science.gov (United States)

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.

Ischemic preconditioning protects against gap junctional uncoupling in cardiac myofibroblasts.

Science.gov (United States)

Sundset, Rune; Cooper, Marie; Mikalsen, Svein-Ole; Ytrehus, Kirsti

2004-01-01

Ischemic preconditioning increases the heart's tolerance to a subsequent longer ischemic period. The purpose of this study was to investigate the role of gap junction communication in simulated preconditioning in cultured neonatal rat cardiac myofibroblasts. Gap junctional intercellular communication was assessed by Lucifer yellow dye transfer. Preconditioning preserved intercellular coupling after prolonged ischemia. An initial reduction in coupling in response to the preconditioning stimulus was also observed. This may protect neighboring cells from damaging substances produced during subsequent regional ischemia in vivo, and may preserve gap junctional communication required for enhanced functional recovery during subsequent reperfusion.

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

Science.gov (United States)

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

2012-01-12

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.

Intracellular trafficking pathways of Cx43 gap junction channels.

Science.gov (United States)

Epifantseva, Irina; Shaw, Robin M

2018-01-01

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

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

Directory of Open Access Journals (Sweden)

Mika Tanaka

2008-04-01

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

Long-range gap junctional signaling controls oncogene-mediated tumorigenesis in Xenopus laevis embryos

Directory of Open Access Journals (Sweden)

Brook T Chernet

2015-01-01

Full Text Available In addition to the immediate microenvironment, long-range signaling may be an important component of cancer. Molecular-genetic analyses have implicated gap junctions – key mediators of cell-cell communication – in carcinogenesis. We recently showed that the resting voltage potential of distant cell groups is a key determinant of metastatic transformation and tumor induction. Here, we show in the Xenopus laevis model that gap junctional communication (GJC is a modulator of the long-range bioelectric signaling that regulates tumor formation. Genetic disruption of GJC taking place within tumors, within remote host tissues, or between the host and tumors – significantly lowers the incidence of tumors induced by KRAS mutations. The most pronounced suppression of tumor incidence was observed upon GJC disruption taking place farther away from oncogene-expressing cells, revealing a role for GJC in distant cells in the control of tumor growth. In contrast, enhanced GJC communication through the overexpression of wild-type connexin Cx26 increased tumor incidence. Our data confirm a role for GJC in tumorigenesis, and reveal that this effect is non-local. Based on these results and on published data on movement of ions through GJs, we present a quantitative model linking the GJC coupling and bioelectrical state of cells to the ability of oncogenes to initiate tumorigenesis. When integrated with data on endogenous bioelectric signaling during left-right patterning, the model predicts differential tumor incidence outcomes depending on the spatial configurations of gap junction paths relative to tumor location and major anatomical body axes. Testing these predictions, we found that the strongest influence of GJ modulation on tumor suppression by hyperpolarization occurred along the embryonic left-right axis. Together, these data reveal new, long-range aspects of cancer control by the host’s physiological parameters.

[Inhibition of gap junctional intercellular communication protects astrocytes from hypoxia/reoxygenation injury].

Science.gov (United States)

Tong, Xu-Hui; Gu, Yu-Chen; Jiao, Hao; Yu, Li; Dong, Shu-Ying

2015-01-01

To investigate the effects of inhibiting gap junctional intercellular communication on hypoxia/reoxygenation injury in astrocytes. Primary cultured cerebral cortical astrocytes of neonate rats were divided into normal control group, hypoxia reoxygenation injury group and 18-α-glycyrrhetinic acid and oleamide (gap junctional intercellular channel inhibitors) group. The gap junction intercellular communication was determined by Parachute assay. The viability of astrocyes was detected by MTT assay. The apoptosis of astrocytes were detected with annexin V/PI and Hoechst 33258 staining. Compared with the normal control group, the gap junctional function of astrocytes was increased significantly in ischemia/reperfusion group (Pastrocytes decreased significantly (Pastrocytes in18-α-glycyrrhetinic acid and oleamide group decreased significantly (Pastrocytes increased significantly (Pastrocytes.

Terbinafine inhibits gap junctional intercellular communication.

Science.gov (United States)

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.

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

Czech Academy of Sciences Publication Activity Database

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

2016-01-01

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

Gap junctional coupling in the vertebrate retina: variations on one theme?

Science.gov (United States)

Völgyi, Béla; Kovács-Oller, Tamás; Atlasz, Tamás; Wilhelm, Márta; Gábriel, Róbert

2013-05-01

Gap junctions connect cells in the bodies of all multicellular organisms, forming either homologous or heterologous (i.e. established between identical or different cell types, respectively) cell-to-cell contacts by utilizing identical (homotypic) or different (heterotypic) connexin protein subunits. Gap junctions in the nervous system serve electrical signaling between neurons, thus they are also called electrical synapses. Such electrical synapses are particularly abundant in the vertebrate retina where they are specialized to form links between neurons as well as glial cells. In this article, we summarize recent findings on retinal cell-to-cell coupling in different vertebrates and identify general features in the light of the evergrowing body of data. In particular, we describe and discuss tracer coupling patterns, connexin proteins, junctional conductances and modulatory processes. This multispecies comparison serves to point out that most features are remarkably conserved across the vertebrate classes, including (i) the cell types connected via electrical synapses; (ii) the connexin makeup and the conductance of each cell-to-cell contact; (iii) the probable function of each gap junction in retinal circuitry; (iv) the fact that gap junctions underlie both electrical and/or tracer coupling between glial cells. These pan-vertebrate features thus demonstrate that retinal gap junctions have changed little during the over 500 million years of vertebrate evolution. Therefore, the fundamental architecture of electrically coupled retinal circuits seems as old as the retina itself, indicating that gap junctions deeply incorporated in retinal wiring from the very beginning of the eye formation of vertebrates. In addition to hard wiring provided by fast synaptic transmitter-releasing neurons and soft wiring contributed by peptidergic, aminergic and purinergic systems, electrical coupling may serve as the 'skeleton' of lateral processing, enabling important functions such

Gap junctions and inhibitory synapses modulate inspiratory motoneuron synchronization.

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Bou-Flores, C; Berger, A J

2001-04-01

Interneuronal electrical coupling via gap junctions and chemical synaptic inhibitory transmission are known to have roles in the generation and synchronization of activity in neuronal networks. Uncertainty exists regarding the roles of these two modes of interneuronal communication in the central respiratory rhythm-generating system. To assess their roles, we performed studies on both the neonatal mouse medullary slice and en bloc brain stem-spinal cord preparations where rhythmic inspiratory motor activity can readily be recorded from both hypoglossal and phrenic nerve roots. The rhythmic inspiratory activity observed had two temporal characteristics: the basic respiratory frequency occurring on a long time scale and the synchronous neuronal discharge within the inspiratory burst occurring on a short time scale. In both preparations, we observed that bath application of gap-junction blockers, including 18 alpha-glycyrrhetinic acid, 18 beta-glycyrrhetinic acid, and carbenoxolone, all caused a reduction in respiratory frequency. In contrast, peak integrated phrenic and hypoglossal inspiratory activity was not significantly changed by gap-junction blockade. On a short-time-scale, gap-junction blockade increased the degree of synchronization within an inspiratory burst observed in both nerves. In contrast, opposite results were observed with blockade of GABA(A) and glycine receptors. We found that respiratory frequency increased with receptor blockade, and simultaneous blockade of both receptors consistently resulted in a reduction in short-time-scale synchronized activity observed in phrenic and hypoglossal inspiratory bursts. These results support the concept that the central respiratory system has two components: a rhythm generator responsible for the production of respiratory cycle timing and an inspiratory pattern generator that is involved in short-time-scale synchronization. In the neonatal rodent, properties of both components can be regulated by interneuronal

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

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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.

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

Science.gov (United States)

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.

Effect of sound on gap-junction-based intercellular signaling: Calcium waves under acoustic irradiation.

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

2015-01-01

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

Gap junctions mediate large-scale Turing structures in a mean-field cortex driven by subcortical noise

Science.gov (United States)

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

2007-07-01

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

Gap junction diseases of the skin.

NARCIS (Netherlands)

Steensel, M.A.M. van

2004-01-01

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

Gap junction protein connexin-43 interacts directly with microtubules

NARCIS (Netherlands)

Giepmans, B N; Verlaan, I; Hengeveld, T; Janssen, H; Calafat, J; Falk, M M; Moolenaar, W H

2001-01-01

Gap junctions are specialized cell-cell junctions that mediate intercellular communication. They are composed of connexin proteins, which form transmembrane channels for small molecules [1, 2]. The C-terminal tail of connexin-43 (Cx43), the most widely expressed connexin member, has been implicated

Tumor-induced loss of mural Connexin 43 gap junction activity promotes endothelial proliferation

International Nuclear Information System (INIS)

Choudhary, Mayur; Naczki, Christine; Chen, Wenhong; Barlow, Keith D.; Case, L. Douglas; Metheny-Barlow, Linda J.

2015-01-01

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

Size dependence of spin-torque induced magnetic switching in CoFeB-based perpendicular magnetization tunnel junctions (invited)

Science.gov (United States)

Sun, J. Z.; Trouilloud, P. L.; Gajek, M. J.; Nowak, J.; Robertazzi, R. P.; Hu, G.; Abraham, D. W.; Gaidis, M. C.; Brown, S. L.; O'Sullivan, E. J.; Gallagher, W. J.; Worledge, D. C.

2012-04-01

CoFeB-based magnetic tunnel junctions with perpendicular magnetic anisotropy are used as a model system for studies of size dependence in spin-torque-induced magnetic switching. For integrated solid-state memory applications, it is important to understand the magnetic and electrical characteristics of these magnetic tunnel junctions as they scale with tunnel junction size. Size-dependent magnetic anisotropy energy, switching voltage, apparent damping, and anisotropy field are systematically compared for devices with different materials and fabrication treatments. Results reveal the presence of sub-volume thermal fluctuation and reversal, with a characteristic length-scale of the order of approximately 40 nm, depending on the strength of the perpendicular magnetic anisotropy and exchange stiffness. To have the best spin-torque switching efficiency and best stability against thermal activation, it is desirable to optimize the perpendicular anisotropy strength with the junction size for intended use. It also is important to ensure strong exchange-stiffness across the magnetic thin film. These combine to give an exchange length that is comparable or larger than the lateral device size for efficient spin-torque switching.

Abundance of gap junctions at glutamatergic mixed synapses in adult Mosquitofish spinal cord neurons

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Jose L Serrano-Velez

2014-06-01

Full Text Available Dye-coupling, whole-mount immunohistochemistry for gap junction channel protein connexin 35 (Cx35, and freeze-fracture replica immunogold labeling (FRIL reveal an abundance of electrical synapses/gap junctions at glutamatergic mixed synapses in the 14th spinal segment that innervates the adult male gonopodium of Western Mosquitofish, Gambusia affinis (Mosquitofish.To study gap junctions’ role in fast motor behavior, we used a minimally-invasive neural-tract-tracing technique to introduce gap junction-permeant or -impermeant dyes into deep muscles controlling the gonopodium of the adult male Mosquitofish, a teleost fish that rapidly transfers (complete in 50 of the 62 gap junctions at mixed synapses are in the 14th spinal segment.Our results support and extend studies showing gap junctions at mixed synapses in spinal cord segments involved in control of genital reflexes in rodents, and they suggest a link between mixed synapses and fast motor behavior. The findings provide a basis for studies of specific roles of spinal neurons in the generation/regulation of sex-specific behavior and for studies of gap junctions’ role in regulating fast motor behavior. Finally, the CoPA IN provides a novel candidate neuron for future studies of gap junctions and neural control of fast motor behaviors.

First-principles spin-transfer torque in CuMnAs |GaP |CuMnAs junctions

Science.gov (United States)

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

2017-02-01

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

Two-dimensional macroscopic quantum tunneling in multi-gap superconductor Josephson junctions

International Nuclear Information System (INIS)

Asai, Hidehiro; Kawabata, Shiro; Ota, Yukihiro; Machida, Masahiko

2014-01-01

Low-temperature characters of superconducting devices yield definite probes for different superconducting phenomena. We study the macroscopic quantum tunneling (MQT) in a Josephson junction, composed of a single-gap superconductor and a two-gap superconductor. Since this junction has two kinds to the superconducting phase differences, calculating the MQT escape rate requires the analysis of quantum tunneling in a multi-dimensional configuration space. Our approach is the semi-classical approximation along a 1D curve in a 2D potential- energy landscape, connecting two adjacent potential (local) minimums through a saddle point. We find that this system has two plausible tunneling paths; an in-phase path and an out-of-phase path. The former is characterized by the Josephson-plasma frequency, whereas the latter is by the frequency of the characteristic collective mode in a two-band superconductor, Josephson- Leggett mode. Depending on external bias current and inter-band Josephson-coupling energy, one of them mainly contributes to the MQT. Our numerical calculations show that the difference between the in-phase path and the out-of-phase path is manifest, with respect to the bias- current-dependence of the MQT escape rate. This result suggests that our MQT setting be an indicator of the Josephson-Leggett mode

Changes in homologous and heterologous gap junction contacts during maturation-inducing hormone-dependent meiotic resumption in ovarian follicles of Atlantic croaker

Science.gov (United States)

Bolamba, D.; Patino, R.; Yoshizaki, G.; Thomas, P.

2003-01-01

Homologous (granulosa cell-granulosa cell) gap junction (GJ) contacts increase in ovarian follicles of Atlantic croaker (Micropogonias undulatus) during the early (first) stage of maturation, but their profile during the second stage [i.e., during maturation-inducing hormone (MIH)-mediated meiotic resumption] is unknown. The profile of homologous GJ contacts during the second stage of maturation in croaker follicles was examined in this study and compared to that of heterologous (granulosa cell-oocyte) GJ, for which changes have been previously documented. Follicles were incubated with human chorionic gonadotropin to induce maturational competence (first stage), and then with MIH to induce meiotic resumption. The follicles were collected for examination immediately before and after different durations of MIH exposure until the oocyte had reached the stage of germinal vesicle breakdown (GVBD; index of meiotic resumption). Ultrathin sections were observed by transmission electron microscopy, and homologous and heterologous GJ contacts were quantified along a 100-??m segment of granulosa cell-zona radiata complex per follicle (three follicles/time/fish, n=3 fish). Relatively high numbers of both types of GJ were observed before and after the first few hours of MIH exposure (up to the stage of oil droplet coalescence). GJ numbers declined during partial yolk globule coalescence (at or near GVBD) and were just under 50% of starting values after the completion of GVBD (P<0.05). These results confirm earlier observations that GVBD temporally correlates with declining heterologous GJ contacts, and for the first time in teleosts show that there is a parallel decline in homologous GJ. The significance of the changes in homologous and heterologous GJ is uncertain and deserves further study. ?? 2003 Elsevier Science (USA). All rights reserved.

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

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Cinzia Ambrosi

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

Gap junction modulation by extracellular signaling molecules: the thymus model

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Alves L.A.

2000-01-01

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

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

KAUST Repository

Takaku, Yasuharu

2014-01-07

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

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

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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.

Effects of maturation-inducing hormone on heterologous gap junctional coupling in ovarian follicles of Atlantic croaker

Science.gov (United States)

Yoshizaki, G.; Patino, R.; Thomas, P.; Bolamba, D.; Chang, Xiaotian

2001-01-01

A previous ultrastructural study of heterologous (granulosa cell-oocyte) gap junction (GJ) contacts in ovarian follicles of Atlantic croaker suggested that these contacts disappear late during the process of resumption of oocyte meiosis. This observation suggested that, unlike scenarios proposed for a number of other species, uncoupling of GJ is not necessary for the onset of meiotic resumption in croaker follicles. However, the functionality of heterologous GJ contacts and the temporal association between maturation-inducing hormone (MIH)-induced changes in heterologous coupling and resumption of oocyte meiosis have not been examined in Atlantic croaker. These questions were addressed with a cell-cell coupling assay that is based on the transfer of a GJ marker, Lucifer Yellow, from oocytes to granulosa cells. Follicle-enclosed oocytes injected with Lucifer Yellow allowed transfer of the dye into the follicle cell layer, thus confirming that there is functional heterologous coupling between the oocyte and the granulosa cells. Dye transfer was observed in vitellogenic, full-grown/maturation-incompetent, and full-grown /maturation-competent follicles. Treatment of maturation-competent follicles with MIH caused a time-dependent decline in the number of follicles transferring dye. However, although GJ uncoupling in some of the follicles was observed before germinal vesicle breakdown (GVBD, index of meiotic resumption), about 50% of the follicles maintained the ability to transfer dye even after GVBD had occurred. Further, a known GJ inhibitor (phorbol 12-myristate 13-acetate) blocked heterologous GJ within a time frame similar to that seen with MIH but without inducing any of the morphological changes (including GVBD) associated with follicular maturation. In conclusion, uncoupling of heterologous GJ seems insufficient and unnecessary for the onset of meiotic resumption in ovarian follicles of Atlantic croaker. ?? 2001 Elsevier Science.

Symposia for a Meeting on Ion Channels and Gap Junctions

CERN Document Server

Sáez, Juan

1997-01-01

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

Sustained inhibition of rat myometrial gap junctions and contractions by lindane

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Grindatti Carmen M

2003-10-01

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

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

Science.gov (United States)

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.

Gap junction protein connexin43 exacerbates lung vascular permeability.

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James J O'Donnell

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

Histone deacetylase inhibition reduces cardiac Connexin43 expression and gap junction communication

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Qin eXu

2013-04-01

Full Text Available Histone deactylase (HDAC inhibitors are being investigated as novel therapies for cancer, inflammation, neurodegeneration, and heart failure. The effects of HDAC inhibitors on the functional expression of cardiac gap junctions (GJ are essentially unknown. The purpose of this study was to determine the effects of trichostatin A (TSA and vorinostat (VOR on functional GJ expression in ventricular cardiomyocytes. The effects of HDAC inhibition on connexin43 (Cx43 expression and functional GJ assembly were examined in primary cultured neonatal mouse ventricular myocytes. TSA and VOR reduced Cx43 mRNA, protein expression, and immunolocalized Cx43 GJ plaque area within ventricular myocyte monolayer cultures in a dose-dependent manner. Chromatin-immunoprecipitation experiments revealed altered protein interactions with the Cx43 promoter. VOR also altered the phosphorylation state of several key regulatory Cx43 phospho-serine sites. Patch clamp analysis revealed reduced electrical coupling between isolated ventricular myocyte pairs, altered transjunctional voltage-dependent inactivation kinetics, and steady state junctional conductance inactivation and recovery relationships. Single GJ channel conductance was reduced to 54 pS only by maximum inhibitory doses of TSA (>= 100 nM. These two hydroxamate pan-HDAC inhibitors exert multiple levels of regulation on ventricular GJ communication by altering Cx43 expression, GJ area, post-translational modifications (e.g. phosphorylation, acetylation, gating, and channel conductance. Although a 50% downregulation of Cx43 GJ communication alone may not be sufficient to slow ventricular conduction or induce arrhythmias, the development of class-selective HDAC inhibitors may help avoid the potential negative cardiovascular effects of pan-HDACI.

Gap junction networks can generate both ripple-like and fast ripple-like oscillations

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Simon, Anna; Traub, Roger D.; Vladimirov, Nikita; Jenkins, Alistair; Nicholson, Claire; Whittaker, Roger G.; Schofield, Ian; Clowry, Gavin J.; Cunningham, Mark O.; Whittington, Miles A.

2014-01-01

Fast ripples (FRs) are network oscillations, defined variously as having frequencies of > 150 to > 250 Hz, with a controversial mechanism. FRs appear to indicate a propensity of cortical tissue to originate seizures. Here, we demonstrate field oscillations, at up to 400 Hz, in spontaneously epileptic human cortical tissue in vitro, and present a network model that could explain FRs themselves, and their relation to ‘ordinary’ (slower) ripples. We performed network simulations with model pyramidal neurons, having axons electrically coupled. Ripples ( 250 Hz, were sustained or interrupted, and had little jitter in the firing of individual axons. The form of model FR was similar to spontaneously occurring FRs in excised human epileptic tissue. In vitro, FRs were suppressed by a gap junction blocker. Our data suggest that a given network can produce ripples, FRs, or both, via gap junctions, and that FRs are favored by clusters of axonal gap junctions. If axonal gap junctions indeed occur in epileptic tissue, and are mediated by connexin 26 (recently shown to mediate coupling between immature neocortical pyramidal cells), then this prediction is testable. PMID:24118191

Gap junction intercellular communication mediated by connexin43 in astrocytes is essential for their resistance to oxidative stress.

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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.

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

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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.

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

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J.C. Sáez

2000-04-01

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

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

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

2014-06-01

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

Chaotic synchronization with gap junction of multi-neurons in external electrical stimulation

International Nuclear Information System (INIS)

Deng Bin; Wang Jiang; Fei Xiangyang

2005-01-01

The synchronization of n(n 3) neurons coupled with gap junction in external electrical stimulation is investigated. In this paper, the coupled model is established on the basis of nonlinear cable model, and then the relation between coupling strength of the gap junction and the synchronization is discussed in detail. The sufficient condition of complete synchronization is attained from rigorous mathematical derivation. The synchronizations of periodic neurons and chaotic neurons are studied respectively

Astrocytic gap junctional networks suppress cellular damage in an in vitro model of ischemia

International Nuclear Information System (INIS)

Shinotsuka, Takanori; Yasui, Masato; Nuriya, Mutsuo

2014-01-01

Highlights: • Astrocytes exhibit characteristic changes in [Ca 2+ ] i under OGD. • Astrocytic [Ca 2+ ] i increase is synchronized with a neuronal anoxic depolarization. • Gap junctional couplings protect neurons as well as astrocytes during OGD. - Abstract: Astrocytes play pivotal roles in both the physiology and the pathophysiology of the brain. They communicate with each other via extracellular messengers as well as through gap junctions, which may exacerbate or protect against pathological processes in the brain. However, their roles during the acute phase of ischemia and the underlying cellular mechanisms remain largely unknown. To address this issue, we imaged changes in the intracellular calcium concentration ([Ca 2+ ] i ) in astrocytes in mouse cortical slices under oxygen/glucose deprivation (OGD) condition using two-photon microscopy. Under OGD, astrocytes showed [Ca 2+ ] i oscillations followed by larger and sustained [Ca 2+ ] i increases. While the pharmacological blockades of astrocytic receptors for glutamate and ATP had no effect, the inhibitions of gap junctional intercellular coupling between astrocytes significantly advanced the onset of the sustained [Ca 2+ ] i increase after OGD exposure. Interestingly, the simultaneous recording of the neuronal membrane potential revealed that the onset of the sustained [Ca 2+ ] i increase in astrocytes was synchronized with the appearance of neuronal anoxic depolarization. Furthermore, the blockade of gap junctional coupling resulted in a concurrent faster appearance of neuronal depolarizations, which remain synchronized with the sustained [Ca 2+ ] i increase in astrocytes. These results indicate that astrocytes delay the appearance of the pathological responses of astrocytes and neurons through their gap junction-mediated intercellular network under OGD. Thus, astrocytic gap junctional networks provide protection against tissue damage during the acute phase of ischemia

Heavy-ion-induced bystander killing of human lung cancer cells. Role of gap junctional intercellular communication

International Nuclear Information System (INIS)

Harada, Kosaku; Nonaka, Tetsuo; Hamada, Nobuyuki; Sakurai, Hideyuki; Hasegawa, Masatoshi; Kobayashi, Yasuhiko; Nakano, Takashi; Funayama, Tomoo; Kakizaki, Takehiko

2009-01-01

The aim of the present study was to clarify the mechanisms of cell death induced by heavy-ion irradiation focusing on the bystander effect in human lung cancer A549 cells. In microbeam irradiation, each of 1, 5, and 25 cells under confluent cell conditions was irradiated with 1, 5, or 10 particles of carbon ions (220 MeV), and then the surviving fraction of the population was measured by a clonogenic assay in order to investigate the bystander effect of heavy-ions. In this experiment, the limited number of cells (0.0001-0.002%, 5-25 cells) under confluent cell conditions irradiated with 5 or 10 carbon ions resulted in an exaggerated 8-14% increase in cell death by clonogenic assay. However, these overshooting responses were not observed under exponentially growing cell conditions. Furthermore, these responses were inhibited in cells treated with an inhibitor of gap junctional intercellular communication (GJIC), whereas they were markedly enhanced by the addition of a stimulator of GJIC. The present results suggest that bystander cell killing by heavy-ions was induced mainly by direct cell-to-cell communication, such as GJIC, which might play important roles in bystander responses. (author)

Magnetic reconstruction induced magnetoelectric coupling and spin-dependent tunneling in Ni/KNbO_3/Ni multiferroic tunnel junctions

International Nuclear Information System (INIS)

Zhang, Hu; Dai, Jian-Qing; Song, Yu-Min

2016-01-01

We investigate the magnetoelectric coupling and spin-polarized tunneling in Ni/KNbO_3/Ni multiferroic tunnel junctions with asymmetric interfaces based on density functional theory. The junctions have two stable polarization states. We predict a peculiar magnetoelectric effect in such junctions originating from the magnetic reconstruction of Ni near the KO-terminated interface. This reconstruction is induced by the reversal of the ferroelectric polarization of KNbO_3. Furthermore, the change in the magnetic ordering filters the spin-dependent current. This effect leads to a change in conductance by about two orders of magnitude. As a result we obtain a giant tunneling electroresistance effect. In addition, there exist sizable tunneling magnetoresistance effects for two polarization states. - Highlights: • We study the ME coupling and electron tunneling in Ni/KNbO_3/Ni junctions. • There is magnetic reconstruction of Ni atoms near the KO-terminated interface. • A peculiar magnetoelectric coupling effect is obtained. • Predicted giant tunneling electroresistance effects.

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

Science.gov (United States)

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.

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

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Aiqing Zhang

2015-06-01

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

Gap junction coupling confers isopotentiality on astrocyte syncytium

Science.gov (United States)

Ma, Baofeng; Buckalew, Richard; Du, Yixing; Kiyoshi, Conrad M.; Alford, Catherine C.; Wang, Wei; McTigue, Dana D.; Enyeart, John J.; Terman, David; Zhou, Min

2015-01-01

Astrocytes are extensively coupled through gap junctions into a syncytium. However, the basic role of this major brain network remains largely unknown. Using electrophysiological and computational modeling methods, we demonstrate that the membrane potential (VM) of an individual astrocyte in a hippocampal syncytium, but not in a single, freshly isolated cell preparation, can be well-maintained at quasi-physiological levels when recorded with reduced or K+ free pipette solutions that alter the K+ equilibrium potential to non-physiological voltages. We show that an astrocyte’s associated syncytium provides powerful electrical coupling, together with ionic coupling at a lesser extent, that equalizes the astrocyte’s VM to levels comparable to its neighbors. Functionally, this minimizes VM depolarization attributable to elevated levels of local extracellular K+ and thereby maintains a sustained driving force for highly efficient K+ uptake. Thus, gap junction coupling functions to achieve isopotentiality in astrocytic networks, whereby a constant extracellular environment can be powerfully maintained for crucial functions of neural circuits. PMID:26435164

Astrocytic gap junctional networks suppress cellular damage in an in vitro model of ischemia

Energy Technology Data Exchange (ETDEWEB)

Shinotsuka, Takanori; Yasui, Masato; Nuriya, Mutsuo, E-mail: mnuriya@z2.keio.jp

2014-02-07

Highlights: • Astrocytes exhibit characteristic changes in [Ca{sup 2+}]{sub i} under OGD. • Astrocytic [Ca{sup 2+}]{sub i} increase is synchronized with a neuronal anoxic depolarization. • Gap junctional couplings protect neurons as well as astrocytes during OGD. - Abstract: Astrocytes play pivotal roles in both the physiology and the pathophysiology of the brain. They communicate with each other via extracellular messengers as well as through gap junctions, which may exacerbate or protect against pathological processes in the brain. However, their roles during the acute phase of ischemia and the underlying cellular mechanisms remain largely unknown. To address this issue, we imaged changes in the intracellular calcium concentration ([Ca{sup 2+}]{sub i}) in astrocytes in mouse cortical slices under oxygen/glucose deprivation (OGD) condition using two-photon microscopy. Under OGD, astrocytes showed [Ca{sup 2+}]{sub i} oscillations followed by larger and sustained [Ca{sup 2+}]{sub i} increases. While the pharmacological blockades of astrocytic receptors for glutamate and ATP had no effect, the inhibitions of gap junctional intercellular coupling between astrocytes significantly advanced the onset of the sustained [Ca{sup 2+}]{sub i} increase after OGD exposure. Interestingly, the simultaneous recording of the neuronal membrane potential revealed that the onset of the sustained [Ca{sup 2+}]{sub i} increase in astrocytes was synchronized with the appearance of neuronal anoxic depolarization. Furthermore, the blockade of gap junctional coupling resulted in a concurrent faster appearance of neuronal depolarizations, which remain synchronized with the sustained [Ca{sup 2+}]{sub i} increase in astrocytes. These results indicate that astrocytes delay the appearance of the pathological responses of astrocytes and neurons through their gap junction-mediated intercellular network under OGD. Thus, astrocytic gap junctional networks provide protection against tissue damage

Neuroinflammation leads to region-dependent alterations in astrocyte gap junction communication and hemichannel activity.

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Karpuk, Nikolay; Burkovetskaya, Maria; Fritz, Teresa; Angle, Amanda; Kielian, Tammy

2011-01-12

Inflammation attenuates gap junction (GJ) communication in cultured astrocytes. Here we used a well-characterized model of experimental brain abscess as a tool to query effects of the CNS inflammatory milieu on astrocyte GJ communication and electrophysiological properties. Whole-cell patch-clamp recordings were performed on green fluorescent protein (GFP)-positive astrocytes in acute brain slices from glial fibrillary acidic protein-GFP mice at 3 or 7 d after Staphylococcus aureus infection in the striatum. Astrocyte GJ communication was significantly attenuated in regions immediately surrounding the abscess margins and progressively increased to levels typical of uninfected brain with increasing distance from the abscess proper. Conversely, astrocytes bordering the abscess demonstrated hemichannel activity as evident by enhanced ethidium bromide (EtBr) uptake that could be blocked by several pharmacological inhibitors, including the connexin 43 (Cx43) mimetic peptide Gap26, carbenoxolone, the pannexin1 (Panx1) mimetic peptide (10)Panx1, and probenecid. However, hemichannel opening was transient with astrocytic EtBr uptake observed near the abscess at day 3 but not day 7 after infection. The region-dependent pattern of hemichannel activity at day 3 directly correlated with increases in Cx43, Cx30, Panx1, and glutamate transporter expression (glial L-glutamate transporter and L-glutamate/L-aspartate transporter) along the abscess margins. Changes in astrocyte resting membrane potential and input conductance correlated with the observed changes in GJ communication and hemichannel activity. Collectively, these findings indicate that astrocyte coupling and electrical properties are most dramatically affected near the primary inflammatory site and reveal an opposing relationship between the open states of GJ channels versus hemichannels during acute infection. This relationship may extend to other CNS diseases typified with an inflammatory component.

Gap Junctional Intercellular Communication and Breast Cancer Metastasis to Bone

National Research Council Canada - National Science Library

Donahue, Henry

2001-01-01

.... We found that: 1) expressing the metastasis suppressing gene BRMS1 in diverse cancer cell lines, including breast and melanoma, restores homotypic gap junctional intercellular communication (GJIC); 2...

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-09-15

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

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

International Nuclear Information System (INIS)

Asai, Hidehiro; Ota, Yukihiro; Kawabata, Shiro; Nori, Franco

2014-01-01

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

Fabrication-process-induced variations of Nb/Al/AlOx/Nb Josephson junctions in superconductor integrated circuits

International Nuclear Information System (INIS)

Tolpygo, Sergey K; Amparo, Denis

2010-01-01

Currently, superconductor digital integrated circuits fabricated at HYPRES, Inc. can operate at clock frequencies approaching 40 GHz. The circuits present multilayered structures containing tens of thousands of Nb/Al/AlO x /Nb Josephson junctions (JJs) of various sizes interconnected by four Nb wiring layers, resistors, and other circuit elements. In order to be fully operational, the integrated circuits should be fabricated such that the critical currents of the JJs are within the tight design margins and the proper relationships between the critical currents of JJs of different sizes are preserved. We present experimental data and discuss mechanisms of process-induced variations of the critical current and energy gap of Nb/Al/AlO x /Nb JJs in integrated circuits. We demonstrate that the Josephson critical current may depend on the type and area of circuit elements connected to the junction, on the circuit pattern, and on the step in the fabrication process at which the connection is made. In particular, we discuss the influence of (a) the junction base electrode connection to the ground plane, (b) the junction counter electrode connection to the ground plane, and (c) the counter electrode connection to the Ti/Au or Ti/Pd/Au contact pads by Nb wiring. We show that the process-induced changes of the properties of Nb/Al/AlO x /Nb junctions are caused by migration of impurity atoms (hydrogen) between the different layers comprising the integrated circuits.

Fractional Josephson vortices in two-gap superconductor long Josephson junctions

Science.gov (United States)

Kim, Ju

2014-03-01

We investigated the phase dynamics of long Josephson junctions (LJJ) with two-gap superconductors in the broken time reversal symmetry state. In this LJJ, spatial phase textures (i-solitons) can be excited due to the presence of two condensates and the interband Joesphson effect between them. The presence of a spatial phase texture in each superconductor layer leads to a spatial variation of the critical current density between the superconductor layers. We find that this spatial dependence of the crtitical current density can self-generate magnetic flux in the insulator layer, resulting in Josephson vortices with fractional flux quanta. Similar to the situation in a YBa2 Cu3O7 - x superconductor film grain boundary, the fractionalization of a Josephson vortex arises as a response to either periodic or random excitation of i-solitions. This suggests that magnetic flux measurements may be used to probe i-soliton excitations in multi-gap superconductor LJJs.

Pallidal gap junctions-triggers of synchrony in Parkinson's disease?

NARCIS (Netherlands)

Schwab, B.C.; Heida, T.; Zhao, Y.; Gils, S.A. van; Wezel, R.J.A. van

2014-01-01

Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a

Pallidal gap junctions - Triggers of synchrony in Parkinson's disease?

NARCIS (Netherlands)

Schwab, B.C.; Heida, Tjitske; Zhao, Yan; van Gils, Stephanus A.; van Wezel, Richard Jack Anton

2014-01-01

Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a

Superluminescence from an optically pumped molecular tunneling junction by injection of plasmon induced hot electrons

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Kai Braun

2015-05-01

Full Text Available Here, we demonstrate a bias-driven superluminescent point light-source based on an optically pumped molecular junction (gold substrate/self-assembled molecular monolayer/gold tip of a scanning tunneling microscope, operating at ambient conditions and providing almost three orders of magnitude higher electron-to-photon conversion efficiency than electroluminescence induced by inelastic tunneling without optical pumping. A positive, steadily increasing bias voltage induces a step-like rise of the Stokes shifted optical signal emitted from the junction. This emission is strongly attenuated by reversing the applied bias voltage. At high bias voltage, the emission intensity depends non-linearly on the optical pump power. The enhanced emission can be modelled by rate equations taking into account hole injection from the tip (anode into the highest occupied orbital of the closest substrate-bound molecule (lower level and radiative recombination with an electron from above the Fermi level (upper level, hence feeding photons back by stimulated emission resonant with the gap mode. The system reflects many essential features of a superluminescent light emitting diode.

Gap junctions and memory: an investigation using a single trial discrimination avoidance task for the neonate chick.

Science.gov (United States)

Verwey, L J; Edwards, T M

2010-02-01

Gap junctions are important to how the brain functions but are relatively under-investigated with respect to their contribution towards behaviour. In the present study a single trial discrimination avoidance task was used to investigate the effect of the gap junction inhibitor 18-alpha-glycyrrhetinic acid (alphaGA) on retention. Past studies within our research group have implied a potential role for gap junctions during the short-term memory (STM) stage which decays by 15 min post-training. A retention function study comparing 10 microM alphaGA and vehicle given immediately post-training demonstrated a significant main effect for drug with retention loss at all times of test (10-180 min post-training). Given that the most common gap junction in the brain is that forming the astrocytic network it is reasonable to conclude that alphaGA was acting upon these. To confirm this finding and interpretation two additional investigations were undertaken using endothelin-1 (ET-1) and ET-1+tolbutamide. Importantly, a retention function study using 10nM ET-1 replicated the retention loss observed for alphaGA. In order to confirm that ET-1 was acting on astrocytic gap junctions the amnestic action of ET-1 was effectively challenged with increasing concentrations of tolbutamide. The present findings suggest that astrocytic gap junctions are important for memory processing. Copyright 2009 Elsevier Inc. All rights reserved.

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

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Hideyuki eTakeuchi

2014-09-01

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

Gap junctions are selectively associated with interlocking ball-and-sockets but not protrusions in the lens.

Science.gov (United States)

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

Phase-dependent noise in Josephson junctions

Science.gov (United States)

Sheldon, Forrest; Peotta, Sebastiano; Di Ventra, Massimiliano

2018-03-01

In addition to the usual superconducting current, Josephson junctions (JJs) support a phase-dependent conductance related to the retardation effect of tunneling quasi-particles. This introduces a dissipative current with a memory-resistive (memristive) character that should also affect the current noise. By means of the microscopic theory of tunnel junctions we compute the complete current autocorrelation function of a Josephson tunnel junction and show that this memristive component gives rise to both a previously noted phase-dependent thermal noise, and an undescribed non-stationary, phase-dependent dynamic noise. As experiments are approaching ranges in which these effects may be observed, we examine the form and magnitude of these processes. Their phase dependence can be realized experimentally as a hysteresis effect and may be used to probe defects present in JJ based qubits and in other superconducting electronics applications.

Quantitative analysis of dual whole-cell voltage-clamp determination of gap junctional conductance

NARCIS (Netherlands)

van Rijen, H. V.; Wilders, R.; van Ginneken, A. C.; Jongsma, H. J.

1998-01-01

The dual whole-cell voltage-clamp technique is used widely for determination of kinetics and conductance of gap junctions. The use of this technique may, however, occasion to considerable errors. We have analysed the errors in steady state junctional conductance measurements under different

Limitations of the dual voltage clamp method in assaying conductance and kinetics of gap junction channels

NARCIS (Netherlands)

Wilders, R.; Jongsma, H. J.

1992-01-01

The electrical properties of gap junctions in cell pairs are usually studied by means of the dual voltage clamp method. The voltage across the junctional channels, however, cannot be controlled adequately due to an artificial resistance and a natural resistance, both connected in series with the gap

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

Science.gov (United States)

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.

Ouabain Increases Gap Junctional Communication in Epithelial Cells

Directory of Open Access Journals (Sweden)

Arturo Ponce

2014-11-01

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

Oligomeric structure and functional characterization of Caenorhabditis elegans Innexin-6 gap junction protein.

Science.gov (United States)

Oshima, Atsunori; Matsuzawa, Tomohiro; Nishikawa, Kouki; Fujiyoshi, Yoshinori

2013-04-12

Innexin is the molecular component of invertebrate gap junctions. Here we successfully expressed and purified Caenorhabditis elegans innexin-6 (INX-6) gap junction channels and characterized the molecular dimensions and channel permeability using electron microscopy (EM) and microinjection of fluorescent dye tracers, respectively. Negative staining and thin-section EM of isolated INX-6 gap junction membranes revealed a loosely packed hexagonal lattice and a greater cross-sectional width than that of connexin26 and connexin43 (Cx43)-GFP. In gel filtration analysis, the elution profile of purified INX-6 channels in dodecyl maltoside solution exhibited a peak at ∼400 kDa that was shifted to ∼800 kDa in octyl glucose neopentyl glycol. We also obtained the class averages of purified INX-6 channels from these peak fractions by single particle analysis. The class average from the ∼800-kDa fraction showed features of the junction form with a longitudinal height of 220 Å, a channel diameter of 110 Å in the absence of detergent micelles, and an extracellular gap space of 60 Å, whereas the class averages from the ∼400-kDa fraction showed diameters of up to 140 Å in the presence of detergent micelles. These findings indicate that the purified INX-6 channels are predominantly hemichannels in dodecyl maltoside and docked junction channels in octyl glucose neopentyl glycol. Dye transfer experiments revealed that the INX-6-GFP-His channels are permeable to 3- and 10-kDa tracers, whereas no significant amounts of these tracers passed through the Cx43-GFP channels. Based on these findings, INX-6 channels have a larger overall structure and greater permeability than connexin channels.

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

Directory of Open Access Journals (Sweden)

Jianyong Xiao

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

Inhibition of hepatocyte gap junctional intercellular communication by tumor promoters

International Nuclear Information System (INIS)

Ruch, R.J.

1988-01-01

The mechanisms by which tumor promoters enhance neoplasia are poorly understood. One effect common to most tumor promoters is their ability to inhibit the cell-to-cell exchange of small molecules and ions through gap junctions, i.e., gap junctional intercellular communication (IC). IC maybe necessary for normal growth control and the loss of IC may predispose cells to enhanced growth. In the present studies, the effects of liver tumor promoters and other agents on IC between rodent hepatocytes in primary culture has been studied. IC was detected between hepatocytes: (1) autoradiographically following the passage and incorporation of [5- 3 H]uridine nucleotides from pre-labeled donor hepatocytes to non-labeled, adjacent recipient hepatocytes and (2) by fluorescence microscopy after microinjection of fluorescent Lucifer Yellow CH dye into hepatocytes and visualizing dye spread into adjacent hepatocytes

Limitations of the dual voltage clamp method in assaying conductance and kinetics of gap junction channels

OpenAIRE

Wilders, R.; Jongsma, H.J.

1992-01-01

The electrical properties of gap junctions in cell pairs are usually studied by means of the dual voltage clamp method. The voltage across the junctional channels, however, cannot be controlled adequately due to an artificial resistance and a natural resistance, both connected in series with the gap junction. The access resistances to the cell interior of the recording pipettes make up the artificial resistance. The natural resistance consists of the cytoplasmic access resistances to the tigh...

GAP junctional communication in brain secondary organizers.

Science.gov (United States)

Bosone, Camilla; Andreu, Abraham; Echevarria, Diego

2016-06-01

Gap junctions (GJs) are integral membrane proteins that enable the direct cytoplasmic exchange of ions and low molecular weight metabolites between adjacent cells. They are formed by the apposition of two connexons belonging to adjacent cells. Each connexon is formed by six proteins, named connexins (Cxs). Current evidence suggests that gap junctions play an important part in ensuring normal embryo development. Mutations in connexin genes have been linked to a variety of human diseases, although the precise role and the cell biological mechanisms of their action remain almost unknown. Among the big family of Cxs, several are expressed in nervous tissue but just a few are expressed in the anterior neural tube of vertebrates. Many efforts have been made to elucidate the molecular bases of Cxs cell biology and how they influence the morphogenetic signal activity produced by brain signaling centers. These centers, orchestrated by transcription factors and morphogenes determine the axial patterning of the mammalian brain during its specification and regionalization. The present review revisits the findings of GJ composed by Cx43 and Cx36 in neural tube patterning and discuss Cx43 putative enrollment in the control of Fgf8 signal activity coming from the well known secondary organizer, the isthmic organizer. © 2016 The Authors. Development, Growth & Differentiation published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Developmental Biologists.

Valley dependent transport in graphene L junction

Science.gov (United States)

Chan, K. S.

2018-05-01

We studied the valley dependent transport in graphene L junctions connecting an armchair lead and a zigzag lead. The junction can be used in valleytronic devices and circuits. Electrons injected from the armchair lead into the junction is not valley polarized, but they can become valley polarized in the zigzag lead. There are Fermi energies, where the current in the zigzag lead is highly valley polarized and the junction is an efficient generator of valley polarized current. The features of the valley polarized current depend sensitively on the widths of the two leads, as well as the number of dimers in the armchair lead, because this number has a sensitive effect on the band structure of the armchair lead. When an external potential is applied to the junction, the energy range with high valley polarization is enlarged enhancing its function as a generator of highly valley polarized current. The scaling behavior found in other graphene devices is also found in L junctions, which means that the results presented here can be extended to junctions with larger dimensions after appropriate scaling of the energy.

Entrainment, retention, and transport of freely swimming fish in junction gaps between commercial barges operating on the Illinois Waterway

Science.gov (United States)

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

2016-01-01

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

Oligomeric Structure and Functional Characterization of Caenorhabditis elegans Innexin-6 Gap Junction Protein*

Science.gov (United States)

Oshima, Atsunori; Matsuzawa, Tomohiro; Nishikawa, Kouki; Fujiyoshi, Yoshinori

2013-01-01

Innexin is the molecular component of invertebrate gap junctions. Here we successfully expressed and purified Caenorhabditis elegans innexin-6 (INX-6) gap junction channels and characterized the molecular dimensions and channel permeability using electron microscopy (EM) and microinjection of fluorescent dye tracers, respectively. Negative staining and thin-section EM of isolated INX-6 gap junction membranes revealed a loosely packed hexagonal lattice and a greater cross-sectional width than that of connexin26 and connexin43 (Cx43)-GFP. In gel filtration analysis, the elution profile of purified INX-6 channels in dodecyl maltoside solution exhibited a peak at ∼400 kDa that was shifted to ∼800 kDa in octyl glucose neopentyl glycol. We also obtained the class averages of purified INX-6 channels from these peak fractions by single particle analysis. The class average from the ∼800-kDa fraction showed features of the junction form with a longitudinal height of 220 Å, a channel diameter of 110 Å in the absence of detergent micelles, and an extracellular gap space of 60 Å, whereas the class averages from the ∼400-kDa fraction showed diameters of up to 140 Å in the presence of detergent micelles. These findings indicate that the purified INX-6 channels are predominantly hemichannels in dodecyl maltoside and docked junction channels in octyl glucose neopentyl glycol. Dye transfer experiments revealed that the INX-6-GFP-His channels are permeable to 3- and 10-kDa tracers, whereas no significant amounts of these tracers passed through the Cx43-GFP channels. Based on these findings, INX-6 channels have a larger overall structure and greater permeability than connexin channels. PMID:23460640

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

Science.gov (United States)

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.

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

DEFF Research Database (Denmark)

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

2006-01-01

Treatment with non-selective drugs (eg, long-chain alcohols, halothane) that reduce gap junction intercellular communication (GJIC) is associated with reduced infarct size after myocardial infarction (MI). Therefore, it has been suggested that gap junction intercellular communication stimulating ...

Chemical Synaptic and Gap Junctional Interactions Between Principal Neurons: Partners in Epileptogenesis

Science.gov (United States)

Traub, Roger D.; Cunningham, Mark O.; Whittington, Miles A.

2010-01-01

Field potential signals, corresponding to electrographic seizures in cortical structures, often contain two components, which sometimes appear to be separable and other times to be superimposed. The first component consists of low-amplitude very fast oscillations (VFO, > 70–80 Hz); the second component consists of larger amplitude transients, lasting tens to hundreds of ms, and variously called population spikes, EEG spikes, or bursts – terms chosen in part because of the cellular correlates of the field events. To first approximation, the two components arise because of distinctive types of cellular interactions: gap junctions for VFO (a model of which is reviewed in the following), and recurrent synaptic excitation and/or inhibition for the transients. With in vitro studies of epileptic human neocortical tissue, it is possible to elicit VFO alone, or VFO superimposed on a large transient, but not a large transient without the VFO. If such observations prove to be general, they would imply that gap junction-mediated interactions are the primary factor in epileptogenesis. It appears to be the case then, that in the setting of seizure initiation (but not necessarily under physiological conditions), the gain of gap junction-mediated circuits can actually be larger than the gain in excitatory synaptic circuits. PMID:21168305

Gold nanoparticle-mediated (GNOME) laser perforation: a new method for a high-throughput analysis of gap junction intercellular coupling.

Science.gov (United States)

Begandt, Daniela; Bader, Almke; Antonopoulos, Georgios C; Schomaker, Markus; Kalies, Stefan; Meyer, Heiko; Ripken, Tammo; Ngezahayo, Anaclet

2015-10-01

The present report evaluates the advantages of using the gold nanoparticle-mediated laser perforation (GNOME LP) technique as a computer-controlled cell optoperforation to introduce Lucifer yellow (LY) into cells in order to analyze the gap junction coupling in cell monolayers. To permeabilize GM-7373 endothelial cells grown in a 24 multiwell plate with GNOME LP, a laser beam of 88 μm in diameter was applied in the presence of gold nanoparticles and LY. After 10 min to allow dye uptake and diffusion through gap junctions, we observed a LY-positive cell band of 179 ± 8 μm width. The presence of the gap junction channel blocker carbenoxolone during the optoperforation reduced the LY-positive band to 95 ± 6 μm. Additionally, a forskolin-related enhancement of gap junction coupling, recently found using the scrape loading technique, was also observed using GNOME LP. Further, an automatic cell imaging and a subsequent semi-automatic quantification of the images using a java-based ImageJ-plugin were performed in a high-throughput sequence. Moreover, the GNOME LP was used on cells such as RBE4 rat brain endothelial cells, which cannot be mechanically scraped as well as on three-dimensionally cultivated cells, opening the possibility to implement the GNOME LP technique for analysis of gap junction coupling in tissues. We conclude that the GNOME LP technique allows a high-throughput automated analysis of gap junction coupling in cells. Moreover this non-invasive technique could be used on monolayers that do not support mechanical scraping as well as on cells in tissue allowing an in vivo/ex vivo analysis of gap junction coupling.

Intracerebroventricular Injection of Lipopolysaccharide Increases Gene Expression of Connexin32 Gap Junction in Rat Hippocampus

Directory of Open Access Journals (Sweden)

Mohammad Abbasian

2013-11-01

Full Text Available Introduction: Gap junctions are intercellular membrane channels that provide direct cytoplasmic continuity between adjacent cells. This communication can be affected by changes in expression of gap junctional subunits called Connexins (Cx. Changes in the expression and function of connexins are associated with number of brain neurodegenerative diseases. Neuroinflammation is a hallmark of various central nervous system (CNS diseases, like multiple sclerosis, Alzheimer's disease and epilepsy. Neuroinflammation causes change in Connexins expression. Hippocampus, one of the main brain regions with a wide network of Gap junctions between different neural cell types, has particular vulnerability to damage and consequent inflammation. Cx32 – among Connexins– is expressed in hippocampal Olygodandrocytes and some neural subpopulations. Although multiple lines of evidence indicate that there is an association between neuroinflammation and the expression of connexin, the direct effect of neuroinflammation on the expression of connexins has not been well studied. In the present study, the effect of neuroinflammation induced by the Lipopolysaccharide (LPS on Cx32 gene and protein expressions in rat hippocampus is evaluated. Methods: LPS (2.5μg/rat was infused into the rat cerebral ventricles for 14 days. Cx32 mRNA and protein levels were measured by Real Time PCR and Western Blot after 1st, 7th and 14th injection of LPS in the hippocampus. Results: Significant increase in Cx32 mRNA expression was observed after 7th injection of LPS (P<0.001. However, no significant change was observed in Cx32 protein level. Conclusion: LPS seems to modify Cx32 GJ communication in the hippocampus at transcription level but not at translation or post-translation level. In order to have a full view concerning modification of Cx32 GJ communication, effect of LPS on Cx32 channel gating should also be determined.

Oxaliplatin-induced neurotoxicity is mediated through gap junction channels and hemichannels and can be prevented by octanol.

Science.gov (United States)

Kagiava, Alexia; Theophilidis, George; Sargiannidou, Irene; Kyriacou, Kyriacos; Kleopa, Kleopas A

2015-10-01

Oxaliplatin-induced neurotoxicity (OIN) is a common complication of chemotherapy without effective treatment. In order to clarify the mechanisms of both acute and chronic OIN, we used an ex-vivo mouse sciatic nerve model. Exposure to 25 μM oxaliplatin caused a marked prolongation in the duration of the nerve evoked compound action potential (CAP) by nearly 1200% within 300 min while amplitude remained constant for over 20 h. This oxaliplatin effect was almost completely reversed by the gap junction (GJ) inhibitor octanol in a concentration-dependent manner. Further GJ blockers showed similar effects although with a narrower therapeutic window. To clarify the target molecule we studied sciatic nerves from connexin32 (Cx32) and Cx29 knockout (KO) mice. The oxaliplatin effect and neuroprotection by octanol partially persisted in Cx29 better than in Cx32 KO nerves, suggesting that oxaliplatin affects both, but Cx32 GJ channels more than Cx29 hemichannels. Oxaliplatin also accelerated neurobiotin uptake in HeLa cells expressing the human ortholog of Cx29, Cx31.3, as well as dye transfer between cells expressing the human Cx32, and this effect was blocked by octanol. Oxaliplatin caused no morphological changes initially (up to 3 h of exposure), but prolonged nerve exposure caused juxtaparonodal axonal edema, which was prevented by octanol. Our study indicates that oxaliplatin causes forced opening of Cx32 channels and Cx29 hemichannels in peripheral myelinated fibers leading to disruption of axonal K(+) homeostasis. The GJ blocker octanol prevents OIN at very low concentrations and should be further studied as a neuroprotectant. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interaction between fractional Josephson vortices in multi-gap superconductor tunnel junctions

Science.gov (United States)

Kim, Ju H.

In a long Josephson junction (LJJ) with two-band superconductors, fractionalization of Josephson vortices (fluxons) can occur in the broken time reversal symmetry state when spatial phase textures (i-solitons) are excited. Excitation of i-solitons in each superconductor layer of the junction, arising due to the presence of two condensates and the interband Josephson effect, leads to spatial variation of the critical current density between the superconductor layers. Similar to the situation in a YBa2 Cu3O7 - x superconductor film grain boundary, this spatial dependence of the crtitical current density can self-generate magnetic flux in the insulator layer, resulting in fractional fluxons with large and small fraction of flux quantum. Similar to fluxons in one-band superconductor LJJ, these fractional fluxons are found to interact with each other. The interaction between large and small fractional fluxons determines the size of a fluxon which includes two (one large and one small) fractional fluxons. We discuss the nature of interaction between fractional fluxons and suggest that i-soliton excitations in multi-gap superconductor LJJs may be probed by using magnetic flux measurements.

Feature of the energy gap in YBa2 Cu3 O7 from break junction measurements

International Nuclear Information System (INIS)

Ekino, T.; Minami, T.; Fujii, H.

1995-01-01

Superconducting energy gap in YBa 2 Cu 3 O 7 have been investigated using break junctions. The tunneling conductance, dI/dV, at T=4.2 K shows no leakage around zero bias, while the gap edge peaks are broadened compared to the simple BCS density of states. These features suggest the spatial distribution of the energy gap or the anisotropic s-wave pairing. The observed largest gap value, determined by the peak-to-peak (p-p) separation in dI/dV, is 140 meV, which corresponds to the 4 δ p-p of an SIS junction. The observed tunneling density of states is fairly well expressed by the probability distribution of the energy gap using the BCS density of states

PI3K/Akt signaling is involved in the disruption of gap junctional communication caused by v-Src and TNF-α.

Science.gov (United States)

Ito, Satoko; Hyodo, Toshinori; Hasegawa, Hitoki; Yuan, Hong; Hamaguchi, Michinari; Senga, Takeshi

2010-09-17

Gap junctional communication, which is mediated by the connexin protein family, is essential for the maintenance of normal tissue function and homeostasis. Loss of intercellular communication results in a failure to coordinately regulate cellular functions, and it can facilitate tumorigenesis. Expression of oncogenes and stimulation with cytokines has been shown to suppress intercellular communication; however, the exact mechanism by which intercellular communication is disrupted by these factors remains uncertain. In this report, we show that Akt is essential for the disruption of gap junctional communication in v-Src-transformed cells. In addition, inhibition of Akt restores gap junctional communication after it is suppressed by TNF-α signaling. Furthermore, we demonstrate that the expression of a constitutively active form of Akt1, but not of Akt2 or Akt3, is sufficient to suppress gap junctional communication. Our results clearly define Akt1 as one of the critical regulators of gap junctional communication. Copyright © 2010 Elsevier Inc. All rights reserved.

Gap-Junctional communication between developing Drosophila muscles is essential for their normal development.

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

Hussein Mansour

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

Xenobiotic Modulation of Human Mammary Epithelial Cell Gap Junctional Intercellular Communication and Growth

National Research Council Canada - National Science Library

Ruch, Randall

1999-01-01

.... These agents also inhibit gap junctional intercellular communication (GJIC). This inhibition may contribute to the enhancement of breast epithelial growth and breast cancer formation by xenobiotics...

Vortex-Breakdown-Induced Particle Capture in Branching Junctions.

Science.gov (United States)

Ault, Jesse T; Fani, Andrea; Chen, Kevin K; Shin, Sangwoo; Gallaire, François; Stone, Howard A

2016-08-19

We show experimentally that a flow-induced, Reynolds number-dependent particle-capture mechanism in branching junctions can be enhanced or eliminated by varying the junction angle. In addition, numerical simulations are used to show that the features responsible for this capture have the signatures of classical vortex breakdown, including an approach flow aligned with the vortex axis and a pocket of subcriticality. We show how these recirculation regions originate and evolve and suggest a physical mechanism for their formation. Furthermore, comparing experiments and numerical simulations, the presence of vortex breakdown is found to be an excellent predictor of particle capture. These results inform the design of systems in which suspended particle accumulation can be eliminated or maximized.

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

Science.gov (United States)

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.

Enhanced Andreev reflection in gapped graphene

Science.gov (United States)

Majidi, Leyla; Zareyan, Malek

2012-08-01

We theoretically demonstrate unusual features of superconducting proximity effect in gapped graphene that presents a pseudospin symmetry-broken ferromagnet with a net pseudomagnetization. We find that the presence of a band gap makes the Andreev conductance of graphene superconductor/pseudoferromagnet (S/PF) junction to behave similar to that of a graphene ferromagnet-superconductor junction. The energy gap ΔN can enhance the pseudospin inverted Andreev conductance of S/PF junction to reach a limiting maximum value for ΔN≫μ, which depending on the bias voltage can be larger than the value for the corresponding junction with no energy gap. We further demonstrate a damped-oscillatory behavior for the local density of states of the PF region of S/PF junction and a long-range crossed Andreev reflection process in PF/S/PF structure with antiparallel alignment of pseudomagnetizations of PFs, which confirm that, in this respect, the gapped normal graphene behaves like a ferromagnetic graphene.

Homeostatic Plasticity Mediated by Rod-Cone Gap Junction Coupling in Retinal Degenerative Dystrophic RCS Rats

Science.gov (United States)

Hou, Baoke; Fu, Yan; Weng, Chuanhuang; Liu, Weiping; Zhao, Congjian; Yin, Zheng Qin

2017-01-01

Rod-cone gap junctions open at night to allow rod signals to pass to cones and activate the cone-bipolar pathway. This enhances the ability to detect large, dim objects at night. This electrical synaptic switch is governed by the circadian clock and represents a novel form of homeostatic plasticity that regulates retinal excitability according to network activity. We used tracer labeling and ERG recording in the retinae of control and retinal degenerative dystrophic RCS rats. We found that in the control animals, rod-cone gap junction coupling was regulated by the circadian clock via the modulation of the phosphorylation of the melatonin synthetic enzyme arylalkylamine N-acetyltransferase (AANAT). However, in dystrophic RCS rats, AANAT was constitutively phosphorylated, causing rod-cone gap junctions to remain open. A further b/a-wave ratio analysis revealed that dystrophic RCS rats had stronger synaptic strength between photoreceptors and bipolar cells, possibly because rod-cone gap junctions remained open. This was despite the fact that a decrease was observed in the amplitude of both a- and b-waves as a result of the progressive loss of rods during early degenerative stages. These results suggest that electric synaptic strength is increased during the day to allow cone signals to pass to the remaining rods and to be propagated to rod bipolar cells, thereby partially compensating for the weak visual input caused by the loss of rods. PMID:28473754

Lens intracellular hydrostatic pressure is generated by the circulation of sodium and modulated by gap junction coupling

Science.gov (United States)

Gao, Junyuan; Sun, Xiurong; Moore, Leon C.; White, Thomas W.; Brink, Peter R.

2011-01-01

We recently modeled fluid flow through gap junction channels coupling the pigmented and nonpigmented layers of the ciliary body. The model suggested the channels could transport the secretion of aqueous humor, but flow would be driven by hydrostatic pressure rather than osmosis. The pressure required to drive fluid through a single layer of gap junctions might be just a few mmHg and difficult to measure. In the lens, however, there is a circulation of Na+ that may be coupled to intracellular fluid flow. Based on this hypothesis, the fluid would cross hundreds of layers of gap junctions, and this might require a large hydrostatic gradient. Therefore, we measured hydrostatic pressure as a function of distance from the center of the lens using an intracellular microelectrode-based pressure-sensing system. In wild-type mouse lenses, intracellular pressure varied from ∼330 mmHg at the center to zero at the surface. We have several knockout/knock-in mouse models with differing levels of expression of gap junction channels coupling lens fiber cells. Intracellular hydrostatic pressure in lenses from these mouse models varied inversely with the number of channels. When the lens’ circulation of Na+ was either blocked or reduced, intracellular hydrostatic pressure in central fiber cells was either eliminated or reduced proportionally. These data are consistent with our hypotheses: fluid circulates through the lens; the intracellular leg of fluid circulation is through gap junction channels and is driven by hydrostatic pressure; and the fluid flow is generated by membrane transport of sodium. PMID:21624945

Methylmercury inhibits gap junctional intercellular communication in primary cultures of rat proximal tubular cells

Energy Technology Data Exchange (ETDEWEB)

Yoshida, Minoru; Sumi, Yawara [Department of Chemistry, St. Marianna University School of Medicine, Kawasagi (Japan); Kujiraoka, Toru [Department of Physiology, St. Marianna University School of Medicine, Kawasagi (Japan); Hara, Masayuki [Department of Anatomy, St. Marianna University School of Medicine, Kawasagi (Japan); Nakazawa, Hirokazu [Department of Chemistry, Faculty of Sciences, Meisei University (Japan)

1998-03-01

Methylmercury (MeHg) causes renal injury in addition to central and peripheral neuropathy. To clarify the mechanism of nephrotoxicity by MeHg, we investigated the effect of this compound on intercellular communication through gap junction channels in primary cultures of rat renal proximal tubular cells. Twenty minutes after exposure to 30 {mu}M MeHg, gap junctional intercellular communication (GJIC), which was assessed by dye coupling, was markedly inhibited before appearance of cytotoxicity. When the medium containing MeHg was exchanged with MeHg-free medium, dye coupling recovered abruptly. However, the dye-coupling was abolished again 30 min after replacement with control medium, and the cells were damaged. Intracellular calcium concentration, [Ca{sup 2+}]{sub i}, which modulates the function of gap junctions, significantly increased following exposure of the cells to 30 {mu}M MeHg and returned to control level following replacement with MeHg-free medium. These results suggest that the inhibiting effect of MeHg on GJIC is related to the change in [Ca{sup 2+}]{sub i}, and may be involved in the pathogenesis of renal dysfunction. (orig.) With 5 figs., 23 refs.

Role of gap junctions and protein kinase A during the development of oocyte maturational competence in Ayu (Plecoglossus altivelis)

Science.gov (United States)

Yamamoto, Y.; Yoshizaki, G.; Takeuchi, T.; Soyano, K.; Patino, R.

2008-01-01

Meiotic resumption in teleost oocytes is induced by a maturation-inducing hormone (MIH). The sensitivity of oocytes to MIH, also known as oocyte maturational competence (OMC), is induced by LH via mechanisms that are not fully understood. A previous study of Ayu (Plecoglossus altivelis) showed the presence of functional heterologous gap junctions (GJs) between oocytes and their surrounding granulosa cells. The objectives of this study were to determine the role of ovarian GJs and of protein kinase A (PKA) during the acquisition of OMC. We examined the effects of the specific GJ inhibitor carbenoxolone (CBX) and 18??-glycyrrhetinic acid (??-GA) on the LH-(hCG)-dependent acquisition of OMC and on MIH-(17,20??-dihydroxy-4-pregnen-3-one)-dependent meiotic resumption; measured the cAMP content of ovarian follicles during the hCG-dependent acquisition of OMC; and determined the effects of PK activators and inhibitors on hCG-dependent OMC. Production of follicular cAMP increased during the hCG-dependent acquisition of OMC. Both GJ inhibitors and the PKA inhibitor H8-dihydrochloride, but not the PKC inhibitor GF109203X, suppressed the hCG-dependent acquisition of OMC in a dose-dependent manner. The PKA activator forskolin induced OMC with a similar potency to hCG. Unlike previous observations with teleosts where disruption of heterologous GJ either blocks or stimulates meiotic resumption, treatment with GJ inhibitors did not affect MIH-dependent meiotic resumption in maturationally competent follicles of Ayu. These observations suggest that ovarian GJs are essential for LH-dependent acquisition of OMC but not for MIH-dependent meiotic resumption, and that the stimulation of OMC by LH is mediated by cAMP-dependent PKA. They are also consistent with the view that a precise balance between GJ-mediated signals (positive or negative) and oocyte maturational readiness is required for hormonally regulated meiotic resumption. ?? 2007 Elsevier Inc. All rights reserved.

A versatile optical junction using photonic band-gap guidance and self collimation

Energy Technology Data Exchange (ETDEWEB)

Gupta, Man Mohan; Medhekar, Sarang, E-mail: smedhekarbit@gmail.com [Centre for Applied Physics, Central University of Jharkhand, Ranchi 835205 (India)

2014-09-29

We show that it is possible to design two photonic crystal (PC) structures such that an optical beam of desired wavelength gets guided within the line defect of the first structure (photonic band gap guidance) and the same beam gets guided in the second structure by self-collimation. Using two dimensional simulation of a design made of the combination of these two structures, we propose an optical junction that allows for crossing of two optical signals of same wavelength and same polarization with very low crosstalk. Moreover, the junction can be operated at number of frequencies in a wide range. Crossing of multiple beams with very low cross talk is also possible. The proposed junction should be important in future integrated photonic circuits.

Temperature-Dependent Asymmetry of Anisotropic Magnetoresistance in Silicon p-n Junctions.

Science.gov (United States)

Yang, D Z; Wang, T; Sui, W B; Si, M S; Guo, D W; Shi, Z; Wang, F C; Xue, D S

2015-09-01

We report a large but asymmetric magnetoresistance in silicon p-n junctions, which contrasts with the fact of magnetoresistance being symmetric in magnetic metals and semiconductors. With temperature decreasing from 293 K to 100 K, the magnetoresistance sharply increases from 50% to 150% under a magnetic field of 2 T. At the same time, an asymmetric magnetoresistance, which manifests itself as a magnetoresistance voltage offset with respect to the sign of magnetic field, occurs and linearly increases with magnetoresistance. More interestingly, in contrast with other materials, the lineshape of anisotropic magnetoresistance in silicon p-n junctions significantly depends on temperature. As temperature decreases from 293 K to 100 K, the width of peak shrinks from 90° to 70°. We ascribe these novel magnetoresistance to the asymmetric geometry of the space charge region in p-n junction induced by the magnetic field. In the vicinity of the space charge region the current paths are deflected, contributing the Hall field to the asymmetric magnetoresistance. Therefore, the observed temperature-dependent asymmetry of magnetoresistance is proved to be a direct consequence of the spatial configuration evolution of space charge region with temperature.

Costimulation of N-methyl-d-aspartate and muscarinic neuronal receptors modulates gap junctional communication in striatal astrocytes

OpenAIRE

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

2002-01-01

Cocultures of neurons and astrocytes from the rat striatum were used to determine whether the stimulation of neuronal receptors could affect the level of intercellular communication mediated by gap junctions in astrocytes. The costimulation of N-methyl-D-asparte (NMDA) and muscarinic receptors led to a prominent reduction of astrocyte gap junctional communication (GJC) in coculture. This treatment was not effective in astrocyte cultures, these cells being devoid of NMDA receptors. Both types ...

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

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Jinmi Koo

2015-09-01

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

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

NARCIS (Netherlands)

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

2007-01-01

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

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

DEFF Research Database (Denmark)

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

2014-01-01

arises, a virtual arteriole was developed that introduces variation in the activities of ion-transport proteins between cells. By varying the level of heterogeneity and subpopulations of gap junctions (GJs), the resulting simulations shows that GJs suppress electrical variation but can only reduce...

Opposite effects of the gap junction blocker octanol on focal cerebral ischemia occluded for different durations.

Science.gov (United States)

Ding, Wenting; Zhou, Lequan; Liu, Wei; Guan, Li; Li, Xiaoying; Liu, Haimei; Yan, Fuman; Xu, Jinwen; Zeng, Weiyong; Qiu, Min

2014-06-01

Protectants and executioners have been demonstrated to be used by gap junctions in focal cerebral ischemia. Certain researchers hypothesized that the opposite role of gap junctions may be associated with the injury extent, which has been demonstrated to be highly correlated with occlusion duration. In order to examine this hypothesis directly, the effects of octanol, a frequently used drug, were examined to investigate the role of gap junctions, in rats following middle cerebral artery occlusion (MCAO) for 30 min/2 h and 24 h reperfusion, respectively. Octanol significantly reduced the infarct volume following 2 h of occlusion concomitant with lower neurological deficits, whereas it enlarged the infarct volume following 30 min of occlusion. Consistently, octanol attenuated the number of transferase dUTP nick-end labeling (TUNEL) positive neurons in the hippocampal CA1 region following 2 h of occlusion, while opposite effects were observed for 30 min of occlusion. Further immunohistochemical studies demonstrated that the expression of B-cell leukemia-2 (Bcl-2, anti-apoptotic protein) was upregulated and that Bcl-2-associated X (Bax, proapoptotic protein) was downregulated following 2 h of occlusion in the octanol group compared with the ischemic group. Conversely, octanol downregulated the expression of the Bcl-2 protein concomitant with increased Bax protein following 30 min of occlusion. These results indicated that the gap junction blocker octanol can protect against ischemic injury following long-term occlusion, however, can aggravate ischemic injury following short-term occlusion.

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

Directory of Open Access Journals (Sweden)

Jan eHahne

2015-09-01

Full Text Available 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...

MgB2 energy gap determination by scanning tunnelling spectroscopy

International Nuclear Information System (INIS)

Heitmann, T W; Bu, S D; Kim, D M; Choi, J H; Giencke, J; Eom, C B; Regan, K A; Rogado, N; Hayward, M A; He, T; Slusky, J S; Khalifah, P; Haas, M; Cava, R J; Larbalestier, D C; Rzchowski, M S

2004-01-01

We report scanning tunnelling spectroscopy (STS) measurements of the gap properties of both ceramic MgB 2 and c-axis oriented epitaxial MgB 2 thin films. Both show a temperature dependent zero bias conductance peak and evidence for two superconducting gaps. We report tunnelling spectroscopy of superconductor-insulator-superconductor (S-I-S) junctions formed in two ways in addition to normal metal-insulator-superconductor (N-I-S) junctions. We find a gap δ = 2.2-2.8 meV, with spectral features and temperature dependence that are consistent between S-I-S junction types. In addition, we observe evidence of a second, larger gap, δ 7.2 meV, consistent with a proposed two-band model

Connexin 26-mediated gap junctional intercellular communication suppresses paracellular permeability of human intestinal epithelial cell monolayers

International Nuclear Information System (INIS)

Morita, Hidekazu; Katsuno, Tatsuro; Hoshimoto, Aihiro; Hirano, Noriaki; Saito, Yasushi; Suzuki, Yasuo

2004-01-01

In some cell types, gap junctional intercellular communication (GJIC) is associated with tight junctions. The present study was performed to determine the roles of GJIC in regulation of the barrier function of tight junctions. Caco-2 human colonic cells were used as a monolayer model, and barrier function was monitored by measuring mannitol permeability and transepithelial electrical resistance (TER). The monolayers were chemically disrupted by treatment with oleic acid and taurocholic acid. Western blotting analyses were performed to evaluate the protein levels of connexins, which are components of gap junctional intercellular channels. Cx26 expression was detected in preconfluent Caco-2 cells, and its level increased gradually after the monolayer reached confluency. These results prompted us to examine whether overexpression of Cx26 affects barrier function. Monolayers of Caco-2 cells stably expressing Cx26 showed significantly lower mannitol permeability and higher TER than mock transfectants when the monolayers were chemically disrupted. The levels of claudin-4, an important component of tight junctions, were significantly increased in the stable Cx26 transfectant. These results suggest that Cx26-mediated GJIC may play a crucial role in enhancing the barrier function of Caco-2 cell monolayers

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

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Guoqiang Zhong

2017-05-01

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

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

Science.gov (United States)

Zhong, Guoqiang; Akoum, Nazem; Appadurai, Daniel A.; Hayrapetyan, Volodya; Ahmed, Osman; Martinez, Agustin D.; Beyer, Eric C.; Moreno, Alonso P.

2017-01-01

In cardiac tissues, the expression of multiple connexins (Cx40, Cx43, Cx45, and Cx30.2) is a requirement for proper development and function. Gap junctions formed by these connexins have distinct permeability and gating mechanisms. Since a single cell can express more than one connexin isoform, the formation of hetero-multimeric gap junction channels provides a tissue with an enormous repertoire of combinations to modulate intercellular communication. To study further the perm-selectivity and gating properties of channels containing Cx43 and Cx45, we studied two monoheteromeric combinations in which a HeLa cell co-transfected with Cx43 and Cx45 was paired with a cell expressing only one of these connexins. Macroscopic measurements of total conductance between cell pairs indicated a drastic reduction in total conductance for mono-heteromeric channels. In terms of Vj dependent gating, Cx43 homomeric connexons facing heteromeric connexons only responded weakly to voltage negativity. Cx45 homomeric connexons exhibited no change in Vj gating when facing heteromeric connexons. The distributions of unitary conductances (γj) for both mono-heteromeric channels were smaller than predicted, and both showed low permeability to the fluorescent dyes Lucifer yellow and Rhodamine123. For both mono-heteromeric channels, we observed flux asymmetry regardless of dye charge: flux was higher in the direction of the heteromeric connexon for MhetCx45 and in the direction of the homomeric Cx43 connexon for MhetCx43. Thus, our data suggest that co-expression of Cx45 and Cx43 induces the formation of heteromeric connexons with greatly reduced permeability and unitary conductance. Furthermore, it increases the asymmetry for voltage gating for opposing connexons, and it favors asymmetric flux of molecules across the junction that depends primarily on the size (not the charge) of the crossing molecules. PMID:28611680

Targeting neuronal gap junctions in mouse retina offers neuroprotection in glaucoma

Science.gov (United States)

Kumar, Sandeep; Ramakrishnan, Hariharasubramanian; Roy, Kaushambi; Viswanathan, Suresh; Bloomfield, Stewart A.

2017-01-01

The progressive death of retinal ganglion cells and resulting visual deficits are hallmarks of glaucoma, but the underlying mechanisms remain unclear. In many neurodegenerative diseases, cell death induced by primary insult is followed by a wave of secondary loss. Gap junctions (GJs), intercellular channels composed of subunit connexins, can play a major role in secondary cell death by forming conduits through which toxic molecules from dying cells pass to and injure coupled neighbors. Here we have shown that pharmacological blockade of GJs or genetic ablation of connexin 36 (Cx36) subunits, which are highly expressed by retinal neurons, markedly reduced loss of neurons and optic nerve axons in a mouse model of glaucoma. Further, functional parameters that are negatively affected in glaucoma, including the electroretinogram, visual evoked potential, visual spatial acuity, and contrast sensitivity, were maintained at control levels when Cx36 was ablated. Neuronal GJs may thus represent potential therapeutic targets to prevent the progressive neurodegeneration and visual impairment associated with glaucoma. PMID:28604388

On the universality of the ''smile''-gap in the density of states of a chaotic Josephson junction

Energy Technology Data Exchange (ETDEWEB)

Reutlinger, Johannes; Belzig, Wolfgang [University of Konstanz, Department of Physics (Germany); Nazarov, Yuli [Kavli Institute of Nanoscience Delft, Delft University of Technology, Delft (Netherlands); Glazman, Leonid [Department of Physics, Yale University, New Haven, CT (United States)

2015-07-01

The superconducting proximity effect strongly modifies the local density of states in chaotic Josephson junctions. Recently we found that besides the well-known minigap a secondary gap appears just below the superconducting gap edge Δ in the limit of a large Thouless energy E{sub Th} >or similar Δ. To check the universality of this novel gap phenomenon we study the effect of nonideal contacts and show that the ''smile''-gap crucially depends on the transmission eigenvalue distribution. In a next step we use the random matrix method to investigate the ''smile''-gap. This allows us to approach the statistics of Andreev levels, going beyond the quasiclassical Greens function method. It turns out that the hard gap edge softens similar to what is already known from the minigap.

A PC microsimulation of a gap acceptance model for turning left at a T-junction

NARCIS (Netherlands)

Schaap, Nina; Dijck, T.; van Arem, Bart; Morsink, Peter L.J.

2009-01-01

Vehicles are controlled by sub-behavioral models in a microsimulation model, this includes the gap acceptance model where the decision about how to cross a junction is made. The critical gap in these models must serve as a threshold value to accept or reject the space between two successive vehicles

Ochratoxim A alters cell adhesion and gap junction intercellular communication in MDCK cells

International Nuclear Information System (INIS)

Mally, Angela; Decker, Martina; Bekteshi, Michaela; Dekant, Wolfgang

2006-01-01

Ochratoxin A (OTA) is one of the most potent renal carcinogens studied to date, but the mechanism of tumor formation by ochratoxin A remains largely unknown. Cell adhesion and cell-cell communication participate in the regulation of signaling pathways involved in cell proliferation and growth control and it is therefore not surprising that modulation of cell-cell signaling has been implicated in cancer development. Several nephrotoxicants and renal carcinogens have been shown to alter cell-cell signaling by interference with gap junction intercell communication (GJIC) and/or cell adhesion, and the aim of this study was to determine if disruption of cell-cell interactions occurs in kidney epithelial cells in response to OTA treatment. MDCK cells were treated with OTA (0-50 μM) for up to 24 h and gap junction function was analyzed using the scrape-load/dye transfer assay. In addition, expression and intracellular localization of Cx43, E-cadherin and β-catenin were determined by immunoblot and immunofluorescence analysis. A clear decrease in the distance of dye transfer was evident following treatment with OTA at concentrations/incubation times which did not affect cell viability. Consistent with the functional inhibition of GJIC, treatment with OTA resulted in a dose-dependent decrease in Cx43 expression. In contrast to Cx43, OTA did not alter total amount of the adherens junction proteins E-cadherin and β-catenin. Moreover, Western blot analysis of Triton X-100 soluble and insoluble protein fractions did not indicate translocation of cell adhesion molecules from the membrane to the cytoplasm. However, a ∼78 kDa fragment of β-catenin was detected in the detergent soluble fraction, indicating proteolytic cleavage of β-catenin. Immunofluorescence analysis also revealed changes in the pattern of both β-catenin and E-cadherin labeling, suggesting that OTA may alter cell-adhesion. Taken together, these data support the hypothesis that disruption of cell

In vitro study of stem cell communication via gap junctions for fibrocartilage regeneration at entheses.

Science.gov (United States)

Nayak, Bibhukalyan Prasad; Goh, James Cho Hong; Toh, Siew Lok; Satpathy, Gyan Ranjan

2010-03-01

Entheses are fibrocartilaginous organs that bridge ligament with bone at their interface and add significant insertional strength. To replace a severely damaged ligament, a tissue-engineered graft preinstalled with interfacial fibrocartilage, which is being regenerated from stem cells, appears to be more promising than ligament-alone graft. Such a concept can be realized by a biomimetic approach of establishing a dynamic communication of stem cells with bone cells and/or ligament fibroblasts in vitro. The current study has two objectives. The first objective is to demonstrate functional coculture of bone marrow-derived stem cells (BMSCs) with mature bone cells/ligament fibroblasts as evidenced by gap-junctional communication in vitro. The second objective is to investigate the role of BMSCs in the regeneration of fibrocartilage within the coculture. Rabbit bone/ligament fibroblasts were dual-stained with DiI-Red and calcein (gap-junction permeable dye), and cocultured with unlabeled BMSCs at fixed ratio (1:10). The functional gap junction was demonstrated by the transfer of calcein from donor to recipient cells that was confirmed and quantified by flow cytometry. Type 2 collagen (cartilage extracellular matrix-specific protein) expressed by the mixed cell lines in the cocultures were estimated by real-time reverse transcription PCR and compared with that of the ligament-bone coculture (control). Significant transfer of calcein into BMSCs was observed and flow cytometry analyses showed a gradual increase in the percentage of BMSCs acquiring calcein with time. Cocultures that included BMSCs expressed significantly more type 2 collagen compared with the control. The current study, for the first time, reported the expression of gap-junctional communication of BMSCs with two adherent cell lines of musculoskeletal system in vitro and also confirmed that incorporation of stem cells augments fibrocartilage regeneration. The results open up a path to envisage a composite

Astrocytic Gap Junctional Communication is Reduced in Amyloid-β-Treated Cultured Astrocytes, but not in Alzheimer's Disease Transgenic Mice

Directory of Open Access Journals (Sweden)

Nancy F Cruz

2010-07-01

Full Text Available Alzheimer's disease is characterized by accumulation of amyloid deposits in brain, progressive cognitive deficits and reduced glucose utilization. Many consequences of the disease are attributed to neuronal dysfunction, but roles of astrocytes in its pathogenesis are not well understood. Astrocytes are extensively coupled via gap junctions, and abnormal trafficking of metabolites and signalling molecules within astrocytic syncytia could alter functional interactions among cells comprising the neurovascular unit. To evaluate the influence of amyloid-β on astrocyte gap junctional communication, cultured astrocytes were treated with monomerized amyloid-β1-40 (1 μmol/l for intervals ranging from 2 h to 5 days, and the areas labelled by test compounds were determined by impaling a single astrocyte with a micropipette and diffusion of material into coupled cells. Amyloid-β-treated astrocytes had rapid, sustained 50-70% reductions in the area labelled by Lucifer Yellow, anionic Alexa Fluor® dyes and energy-related compounds, 6-NBDG (a fluorescent glucose analogue, NADH and NADPH. Amyloid-β treatment also caused a transient increase in oxidative stress. In striking contrast with these results, spreading of Lucifer Yellow within astrocytic networks in brain slices from three regions of 8.5-14-month-old control and transgenic Alzheimer's model mice was variable, labelling 10-2000 cells; there were no statistically significant differences in the number of dye-labelled cells among the groups or with age. Thus amyloid-induced dysfunction of gap junctional communication in cultured astrocytes does not reflect the maintenance of dye transfer through astrocytic syncytial networks in transgenic mice; the pathophysiology of Alzheimer's disease is not appropriately represented by the cell culture system.

Astrocytic gap junctional communication is reduced in amyloid-β-treated cultured astrocytes, but not in Alzheimer's disease transgenic mice.

Science.gov (United States)

Cruz, Nancy F; Ball, Kelly K; Dienel, Gerald A

2010-08-17

Alzheimer's disease is characterized by accumulation of amyloid deposits in brain, progressive cognitive deficits and reduced glucose utilization. Many consequences of the disease are attributed to neuronal dysfunction, but roles of astrocytes in its pathogenesis are not well understood. Astrocytes are extensively coupled via gap junctions, and abnormal trafficking of metabolites and signalling molecules within astrocytic syncytia could alter functional interactions among cells comprising the neurovascular unit. To evaluate the influence of amyloid-beta on astrocyte gap junctional communication, cultured astrocytes were treated with monomerized amyloid-β(1-40) (1 μmol/l) for intervals ranging from 2 h to 5 days, and the areas labelled by test compounds were determined by impaling a single astrocyte with a micropipette and diffusion of material into coupled cells. Amyloid-β-treated astrocytes had rapid, sustained 50-70% reductions in the area labelled by Lucifer Yellow, anionic Alexa Fluor® dyes and energy-related compounds, 6-NBDG (a fluorescent glucose analogue), NADH and NADPH. Amyloid-β treatment also caused a transient increase in oxidative stress. In striking contrast with these results, spreading of Lucifer Yellow within astrocytic networks in brain slices from three regions of 8.5-14-month-old control and transgenic Alzheimer's model mice was variable, labelling 10-2000 cells; there were no statistically significant differences in the number of dye-labelled cells among the groups or with age. Thus amyloid-induced dysfunction of gap junctional communication in cultured astrocytes does not reflect the maintenance of dye transfer through astrocytic syncytial networks in transgenic mice; the pathophysiology of Alzheimer's disease is not appropriately represented by the cell culture system.

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

DEFF Research Database (Denmark)

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

2005-01-01

Gap junctions play an important role in bone development and function, but the lack of pharmacological tools has hampered the gap junction research. The antiarrhythmic peptides stimulate gap junction communication between cardiomyocytes, but effects in noncardiac tissue are unknown. The purpose...... of this study was to examine whether antiarrhythmic peptides, which are small peptides increasing gap junctional conductivity, show specific binding to osteoblasts and investigate the effect of the stable analog rotigaptide (ZP123) on gap junctional intercellular communication in vitro and on bone mass...... and strength in vivo. Cell coupling and calcium signaling were assessed in vitro on human, primary, osteoblastic cells. In vivo effects of rotigaptide on bone strength and density were determined 4 wk after ovariectomy in rats treated with either vehicle, sc injection twice daily (300 nmol per kilogram body...

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

Science.gov (United States)

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

Temperature dependence of interlayer coupling in perpendicular magnetic tunnel junctions with GdOX barriers

Science.gov (United States)

Newhouse-Illige, T.; Xu, Y. H.; Liu, Y. H.; Huang, S.; Kato, H.; Bi, C.; Xu, M.; LeRoy, B. J.; Wang, W. G.

2018-02-01

Perpendicular magnetic tunnel junctions with GdOX tunneling barriers have shown a unique voltage controllable interlayer magnetic coupling effect. Here, we investigate the quality of the GdOX barrier and the coupling mechanism in these junctions by examining the temperature dependence of the tunneling magnetoresistance and the interlayer coupling from room temperature down to 11 K. The barrier is shown to be of good quality with the spin independent conductance only contributing a small portion, 14%, to the total room temperature conductance, similar to AlOX and MgO barriers. The interlayer coupling, however, shows an anomalously strong temperature dependence including sign changes below 80 K. This non-trivial temperature dependence is not described by previous models of interlayer coupling and may be due to the large induced magnetic moment of the Gd ions in the barrier.

Resonance Transport of Graphene Nanoribbon T-Shaped Junctions

International Nuclear Information System (INIS)

Xiao-Lan, Kong; Yong-Jian, Xiong

2010-01-01

We investigate the transport properties of T-shaped junctions composed of armchair graphene nanoribbons of different widths. Three types of junction geometries are considered. The junction conductance strongly depends on the atomic features of the junction geometry. When the shoulders of the junction have zigzag type edges, sharp conductance resonances usually appear in the low energy region around the Dirac point, and a conductance gap emerges. When the shoulders of the junction have armchair type edges, the conductance resonance behavior is weakened significantly, and the metal-metal-metal junction structures show semimetallic behaviors. The contact resistance also changes notably due to the various interface geometries of the junction

Doping enhanced barrier lowering in graphene-silicon junctions

Science.gov (United States)

Zhang, Xintong; Zhang, Lining; Chan, Mansun

2016-06-01

Rectifying properties of graphene-semiconductor junctions depend on the Schottky barrier height. We report an enhanced barrier lowering in graphene-Si junction and its essential doping dependence in this paper. The electric field due to ionized charge in n-type Si induces the same type doping in graphene and contributes another Schottky barrier lowering factor on top of the image-force-induced lowering (IFIL). We confirm this graphene-doping-induced lowering (GDIL) based on well reproductions of the measured reverse current of our fabricated graphene-Si junctions by the thermionic emission theory. Excellent matching between the theoretical predictions and the junction data of the doping-concentration dependent barrier lowering serves as another evidence of the GDIL. While both GDIL and IFIL are enhanced with the Si doping, GDIL exceeds IFIL with a threshold doping depending on the as-prepared graphene itself.

Relative Roles of Gap Junction Channels and Cytoplasm in Cell-to-Cell Diffusion of Fluorescent Tracers

Science.gov (United States)

Safranyos, Richard G. A.; Caveney, Stanley; Miller, James G.; Petersen, Nils O.

1987-04-01

Intercellular (tissue) diffusion of molecules requires cytoplasmic diffusion and diffusion through gap junctional (or cell-to-cell) channels. The rates of tissue and cytoplasmic diffusion of fluorescent tracers, expressed as an effective diffusion coefficient, De, and a cytoplasmic diffusion coefficient, Dcyt, have been measured among the developing epidermal cells of a larval beetle, Tenebrio molitor L., to determine the contribution of the junctional channels to intercellular diffusion. Tracer diffusion was measured by injecting fluorescent tracers into cells and quantitating the rate of subsequent spread into adjacent cells. Cytoplasmic diffusion was determined by fluorescence photobleaching. These experiments show that gap junctional channels constitute approximately 70-80% of the total cell-to-cell resistance to the diffusion of organic tracers at high concentrations in this tissue. At low concentrations, however, the binding of tracer to cytoplasm slows down the cytoplasmic diffusion, which may limit intercellular diffusion.

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

NARCIS (Netherlands)

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

1988-01-01

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

The effects of the Histone Deacetylase (HDAC Inhibitor 4-Phenylbutyrate on gap junction conductance and permeability

Directory of Open Access Journals (Sweden)

Joshua eKaufman

2013-09-01

Full Text Available Longitudinal resistance is a key factor in determining cardiac action potential propagation. Action potential conduction velocity has been shown to be proportional to the square root of longitudinal resistance. A major determinant of longitudinal resistance in myocardium is the gap junction channel, comprised of connexin proteins. Within the ventricular myocardium connexin 43 (Cx43 is the dominantly expressed connexin. Reduced numbers of gap junction channels will result in an increase in longitudinal resistance creating the possibility of slowed conduction velocity while increased numbers of channels would potentially result in an increase in conduction velocity. We sought to determine if inhibition of histone deacetylase (HDAC by 4-phenylbutyrate (4-PB, a known inhibitor of HDAC resulted in an increase in junctional conductance and permeability, which is not the result of changes in single channel unitary conductance. These experiments were performed using HEK-293 cells and HeLa cells stably transfected with Cx43. Following treatment with increasing concentrations of 4-PB up-regulation of Cx43 was observed via Western blot analysis. Junctional (gj conductance and unitary single channel conductance were measured via whole-cell patch clamp. In addition intercellular transfer of Lucifer Yellow (LY was determined by fluorescence microscopy. The data in this study indicates that 4-PB is able to enhance functional Cx43 gap junction coupling as indicated by LY dye transfer and multichannel and single channel data along with Western blot analysis. As a corollary, pharmacological agents such as 4-PB have the potential, by increasing intercellular coupling, to reduce the effect of ischemia. It remains to be seen whether drugs like 4-PB will be effective in preventing cardiac maladies.

Strain-dependent augmentation of tight-junction barrier function in human primary epidermal keratinocytes by Lactobacillus and Bifidobacterium lysates.

Science.gov (United States)

Sultana, Reshma; McBain, Andrew J; O'Neill, Catherine A

2013-08-01

In this study, we investigated whether probiotic lysates can modify the tight-junction function of human primary keratinocytes. The keratinocytes were grown on cell culture inserts and treated with lysates from Bifidobacterium longum, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus fermentum, or Lactobacillus rhamnosus GG. With the exception of L. fermentum (which decreased cell viability), all strains markedly enhanced tight-junction barrier function within 24 h, as assessed by measurements of transepithelial electrical resistance (TEER). However, B. longum and L. rhamnosus GG were the most efficacious, producing dose-dependent increases in resistance that were maintained for 4 days. These increases in TEER correlated with elevated expression of tight-junction protein components. Neutralization of Toll-like receptor 2 abolished both the increase in TEER and expression of tight-junction proteins induced by B. longum, but not L. rhamnosus GG. These data suggest that some bacterial strains increase tight-junction function via modulation of protein components but the different pathways involved may vary depending on the bacterial strain.

Star junctions and watermelons of pure or random quantum Ising chains: finite-size properties of the energy gap at criticality

Science.gov (United States)

Monthus, Cécile

2015-06-01

We consider M  ⩾  2 pure or random quantum Ising chains of N spins when they are coupled via a single star junction at their origins or when they are coupled via two star junctions at the their two ends leading to the watermelon geometry. The energy gap is studied via a sequential self-dual real-space renormalization procedure that can be explicitly solved in terms of Kesten variables containing the initial couplings and and the initial transverse fields. In the pure case at criticality, the gap is found to decay as a power-law {ΔM}\\propto {{N}-z(M)} with the dynamical exponent z(M)=\\frac{M}{2} for the single star junction (the case M   =   2 corresponds to z   =   1 for a single chain with free boundary conditions) and z(M)   =   M  -  1 for the watermelon (the case M   =   2 corresponds to z   =   1 for a single chain with periodic boundary conditions). In the random case at criticality, the gap follows the Infinite Disorder Fixed Point scaling \\ln {ΔM}=-{{N}\\psi}g with the same activated exponent \\psi =\\frac{1}{2} as the single chain corresponding to M   =   2, and where g is an O(1) random positive variable, whose distribution depends upon the number M of chains and upon the geometry (star or watermelon).

Theory of spin-dependent tunnelling in magnetic junctions

International Nuclear Information System (INIS)

Mathon, J.

2002-01-01

Rigorous theory of the tunnelling magnetoresistance (TMR) based on the real-space Kubo formula and fully realistic tight-binding bands fitted to an ab initio band structure is described. It is first applied to calculate the TMR of two Co electrodes separated by a vacuum gap. The calculated TMR ratio reaches ∼65% in the tunnelling regime but can be as high as 280% in the metallic regime when the vacuum gap is of the order of the Co interatomic distance (abrupt domain wall). It is also shown that the spin polarization P of the tunnelling current is negative in the metallic regime but becomes positive P∼35% in the tunnelling regime. Calculation of the TMR of an epitaxial Fe/MgO/Fe(001) junction is also described. The calculated optimistic TMR ratio is in excess of 1000% for an MgO barrier of ∼20 atomic planes and the spin polarization of the tunnelling current is positive for all MgO thicknesses. It is also found that spin-dependent tunnelling in an Fe/MgO/Fe(001) junction is not entirely determined by states at the Γ point (k parallel = 0) even for MgO thicknesses as large as ∼20 atomic planes. Finally, it is demonstrated that the TMR ratio calculated from the Kubo formula remains non-zero when one of the Co electrodes is covered with a copper layer. It is shown that non-zero TMR is due to quantum well states in the Cu layer which do not participate in transport. Since these only occur in the down-spin channel, their loss from transport creates a spin asymmetry of electrons tunnelling from a Cu interlayer, i.e. non-zero TMR. Numerical modelling is used to show that diffuse scattering from a random distribution of impurities in the barrier may cause quantum well states to evolve into propagating states, in which case the spin asymmetry of the non-magnetic layer is lost and with it the TMR. (author)

Effects of gap junction blockers on human neocortical synchronization.

Science.gov (United States)

Gigout, S; Louvel, J; Kawasaki, H; D'Antuono, M; Armand, V; Kurcewicz, I; Olivier, A; Laschet, J; Turak, B; Devaux, B; Pumain, R; Avoli, M

2006-06-01

Field potentials and intracellular recordings were obtained from human neocortical slices to study the role of gap junctions (GJ) in neuronal network synchronization. First, we examined the effects of GJ blockers (i.e., carbenoxolone, octanol, quinine, and quinidine) on the spontaneous synchronous events (duration = 0.2-1.1 s; intervals of occurrence = 3-27 s) generated by neocortical slices obtained from temporal lobe epileptic patients during application of 4-aminopyridine (4AP, 50 muM) and glutamatergic receptor antagonists. The synchronicity of these potentials (recorded at distances up to 5 mm) was decreased by GJ blockers within 20 min of application, while prolonged GJ blockers treatment at higher doses made them disappear with different time courses. Second, we found that slices from patients with focal cortical dysplasia (FCD) could generate in normal medium spontaneous synchronous discharges (duration = 0.4-8 s; intervals of occurrence = 0.5-90 s) that were (i) abolished by NMDA receptor antagonists and (ii) slowed down by carbenoxolone. Finally, octanol or carbenoxolone blocked 4AP-induced ictal-like discharges (duration = up to 35 s) in FCD slices. These data indicate that GJ play a role in synchronizing human neocortical networks and may implement epileptiform activity in FCD.

Understanding the length dependence of molecular junction thermopower

DEFF Research Database (Denmark)

Karlström, Sven Olov Harald; Strange, Mikkel; Solomon, Gemma

2014-01-01

Thermopower of molecular junctions is sensitive to details in the junction and may increase, decrease, or saturate with increasing chain length, depending on the system. Using McConnell's theory for exponentially suppressed transport together with a simple and easily interpretable tight binding...... model, we show how these different behaviors depend on the molecular backbone and its binding to the contacts. We distinguish between resonances from binding groups or undercoordinated electrode atoms, and those from the periodic backbone. It is demonstrated that while the former gives a length......-independent contribution to the thermopower, possibly changing its sign, the latter determines its length dependence. This means that the question of which orbitals from the periodic chain that dominate the transport should not be inferred from the sign of the thermopower but from its length dependence. We find...

Genomic instability induced in distant progeny of bystander cells depends on the connexins expressed in the irradiated cells.

Science.gov (United States)

de Toledo, Sonia M; Buonanno, Manuela; Harris, Andrew L; Azzam, Edouard I

2017-10-01

To examine the time window during which intercellular signaling though gap junctions mediates non-targeted (bystander) effects induced by moderate doses of ionizing radiation; and to investigate the impact of gap junction communication on genomic instability in distant progeny of bystander cells. A layered cell culture system was developed to investigate the propagation of harmful effects from irradiated normal or tumor cells that express specific connexins to contiguous bystander normal human fibroblasts. Irradiated cells were exposed to moderate mean absorbed doses from 3.7 MeV α particle, 1000 MeV/u iron ions, 600 MeV/u silicon ions, or 137 Cs γ rays. Following 5 h of co-culture, pure populations of bystander cells, unexposed to secondary radiation, were isolated and DNA damage and oxidative stress was assessed in them and in their distant progeny (20-25 population doublings). Increased frequency of micronucleus formation and enhanced oxidative changes were observed in bystander cells co-cultured with confluent cells exposed to either sparsely ionizing ( 137 Cs γ rays) or densely ionizing (α particles, energetic iron or silicon ions) radiations. The irradiated cells propagated signals leading to biological changes in bystander cells within 1 h of irradiation, and the effect required cellular coupling by gap junctions. Notably, the distant progeny of isolated bystander cells also exhibited increased levels of spontaneous micronuclei. This effect was dependent on the type of junctional channels that coupled the irradiated donor cells with the bystander cells. Previous work showed that gap junctions composed of connexin26 (Cx26) or connexin43 (Cx43) mediate toxic bystander effects within 5 h of co-culture, whereas gap junctions composed of connexin32 (Cx32) mediate protective effects. In contrast, the long-term progeny of bystander cells expressing Cx26 or Cx43 did not display elevated DNA damage, whereas those coupled by Cx32 had enhanced DNA

High performance as-grown and annealed high band gap tunnel junctions: Te behavior at the interface

Energy Technology Data Exchange (ETDEWEB)

Bedair, S. M., E-mail: bedair@ncsu.edu; Harmon, Jeffrey L.; Carlin, C. Zachary; Hashem Sayed, Islam E.; Colter, P. C. [Department of Electrical and Computer Engineering, North Carolina State University, Raleigh, North Carolina 27695 (United States)

2016-05-16

The performance of n{sup +}-InGaP(Te)/p{sup +}-AlGaAs(C) high band gap tunnel junctions (TJ) is critical for achieving high efficiency in multijunction photovoltaics. Several limitations for as grown and annealed TJ can be attributed to the Te doping of InGaP and its behavior at the junction interface. Te atoms in InGaP tend to get attached at step edges, resulting in a Te memory effect. In this work, we use the peak tunneling current (J{sub pk}) in this TJ as a diagnostic tool to study the behavior of the Te dopant at the TJ interface. Additionally, we used our understanding of Te behavior at the interface, guided by device modeling, to modify the Te source shut-off procedure and the growth rate. These modifications lead to a record performance for both the as-grown (2000 A/cm{sup 2}) and annealed (1000 A/cm{sup 2}) high band gap tunnel junction.

Localization of connexin 43 gap junctions and hemichannels in tanycytes of adult mice.

Science.gov (United States)

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.

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

DEFF Research Database (Denmark)

Willecke, Klaus; Nielsen, Morten Schak

2008-01-01

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

Spin-filtering effect and proximity effect in normal metal/ferromagnetic insulator/normal metal/superconductor junctions

International Nuclear Information System (INIS)

Li Hong; Yang Wei; Yang Xinjian; Qin Minghui; Xu Yihong

2007-01-01

Taking into account the thickness of the ferromagnetic insulator (FI), the spin-filtering effect and proximity effect in normal metal/ferromagnetic insulator/normal metal/superconductor (NM/FI/NM/SC) junctions are studied based on an extended Blonder-Tinkham-Klapwijk (BTK) theory. It is shown that a spin-dependent energy shift during the tunneling process induces splitting of the sub-energy gap conductance peaks and the spin polarization in the ferromagnetic insulator causes an imbalance of the peak heights. Different from the ferromagnet the spin-filtering effect of the FI cannot cause the reversion of the normalized conductance in NM/FI/NM/SC junctions

Ketamine alleviates bradykinin-induced disruption of the mouse cerebrovascular endothelial cell-constructed tight junction barrier via a calcium-mediated redistribution of occludin polymerization

International Nuclear Information System (INIS)

Chen, Jui-Tai; Lin, Yi-Ling; Chen, Ta-Liang; Tai, Yu-Ting; Chen, Cheng-Yu; Chen, Ruei-Ming

2016-01-01

Highlights: • Ketamine could suppress bradykinin-induced intracellular calcium mobilization. • Ketamine induced B1R protein and mRNA expressions but did not change B2R protein levels. • Ketamine attenuated bradykinin-induced redistribution of occludin tight junctions. • Ketamine prevented bradykinin-induced breakage of the MCEC-constructed tight junction barrier. - Abstract: Following brain injury, a sequence of mechanisms leads to disruption of the blood-brain barrier (BBB) and subsequent cerebral edema, which is thought to begin with activation of bradykinin. Our previous studies showed that ketamine, a widely used intravenous anesthetic agent, can suppress bradykinin-induced cell dysfunction. This study further aimed to evaluate the protective effects of ketamine against bradykinin-induced disruption of the mouse cerebrovascular endothelial cell (MCEC)-constructed tight junction barrier and the possible mechanisms. Exposure of MCECs to bradykinin increased intracellular calcium (Ca 2+ ) concentrations in a time-dependent manner. However, pretreatment of MCECs with ketamine time- and concentration-dependently lowered the bradykinin-induced calcium influx. As to the mechanisms, although exposure of MCECs to ketamine induced bradykinin R1 receptor protein and mRNA expression, this anesthetic did not change levels of the bradykinin R2 receptor, a major receptor that responds to bradykinin stimulation. Bradykinin increased amounts of soluble occludin in MCECs, but pretreatment with ketamine alleviated this disturbance in occludin polymerization. Consequently, exposure to bradykinin decreased the transendothelial electronic resistance in the MCEC-constructed tight junction barrier. However, pretreatment with ketamine attenuated the bradykinin-induced disruption of the tight junction barrier. Taken together, this study shows that ketamine at a therapeutic concentration can protect against bradykinin-induced breakage of the BBB via suppressing calcium-dependent

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

Directory of Open Access Journals (Sweden)

Zongqi Zhang

2016-07-01

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

[Effects of gap junction blocking on the oxygen partial pressure in acupoints of the bladder meridian].

Science.gov (United States)

Wang, Qi; Yu, Wei-Chang; Jiang, Hong-Zhi; Chen, Sheng-Li; Zhang, Ming-Min; Kong, E-Sheng; Huang, Guang-Ying

2010-12-01

To explore the relation between gap junction and meridian phenomenon. The oxygen partial pressure in acupoints [see text for formula] and in their corresponding non-acupoints of the Bladder Meridian was observed with the needle-type tissue oxygen tension sensor in the gap junction blocking goats by 1-Heptanol injection and the Connexin 43 (Cx43) gene knockout mice. (1) The oxygen partial pressure in acupoints of Bladder Meridian on goats was higher than that in non-acupoints after 1-Heptanol injection with significant differences between them (both P oxygen partial pressure in acupoints of Bladder Meridian on goats increased significantly after injecting 1-Heptanol as compare with that either injecting normal saline or injecting nothing with significant differences between them (all P oxygen partial pressure in acupoints of the Bladder Meridian was significantly higher than that in the non-acupoint controls in Cx43 wild type (WT) mice (all P oxygen partial pressure between acupoints and non-acupoint controls showed no significant differences (all P > 0.05). (4) In acupoints, the oxygen partial pressure in Cx43 WT mice was significantly higher than that in Cx43 HT mice (all P 0.05). Gap junction maybe the essential factor in signal transduction of acupuncture.

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

Science.gov (United States)

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.

Magnetization induced by odd-frequency spin-triplet Cooper pairs in a Josephson junction with metallic trilayers

Science.gov (United States)

Hikino, S.; Yunoki, S.

2015-07-01

We theoretically study the magnetization inside a normal metal induced in an s -wave superconductor/ferromagnetic metal/normal metal/ferromagnetic metal/s -wave superconductor (S /F 1 /N /F 2 /S ) Josephson junction. Using the quasiclassical Green's function method, we show that the magnetization becomes finite inside the N . The origin of this magnetization is due to odd-frequency spin-triplet Cooper pairs formed by electrons of equal and opposite spins, which are induced by the proximity effect in the S /F 1 /N /F 2 /S junction. We find that the magnetization M (d ,θ ) in the N can be decomposed into two parts, M (d ,θ ) =MI(d ) +MII(d ,θ ) , where θ is the superconducting phase difference between the two S s and d is the thickness of N . The θ -independent magnetization MI(d ) exists generally in S /F junctions, while MII(d ,θ ) carries all θ dependence and represents the fingerprint of the phase coherence between the two S s in Josephson junctions. The θ dependence thus allows us to control the magnetization in the N by tuning θ for a fixed d . We show that the θ -independent magnetization MI(d ) weakly decreases with increasing d , while the θ -dependent magnetization MII(d ,θ ) rapidly decays with d . Moreover, we find that the time-averaged magnetization exhibits a discontinuous peak at each resonance dc voltage Vn=n ℏ ωS/2 e (n : integer) when dc voltage V as well as ac voltage vac(t ) with frequency ωS are both applied to the S /F 1 /N /F 2 /S junction. This is because MII(d ,θ ) oscillates generally in time t (ac magnetization) with d θ /d t =2 e [V +vac(t ) ]/ℏ and thus =0 , but can be converted into the time-independent dc magnetization for the dc voltage at Vn. We also discuss that the magnetization induced in the N can be measurably large in realistic systems. Therefore, the measurement of the induced magnetization serves as an alternative way to detect the phase coherence between the two S s in Josephson junctions. Our results

Measurements of quasiparticle tunneling dynamics in a band-gap-engineered transmon qubit.

Science.gov (United States)

Sun, L; DiCarlo, L; Reed, M D; Catelani, G; Bishop, Lev S; Schuster, D I; Johnson, B R; Yang, Ge A; Frunzio, L; Glazman, L; Devoret, M H; Schoelkopf, R J

2012-06-08

We have engineered the band gap profile of transmon qubits by combining oxygen-doped Al for tunnel junction electrodes and clean Al as quasiparticle traps to investigate energy relaxation due to quasiparticle tunneling. The relaxation time T1 of the qubits is shown to be insensitive to this band gap engineering. Operating at relatively low-E(J)/E(C) makes the transmon transition frequency distinctly dependent on the charge parity, allowing us to detect the quasiparticles tunneling across the qubit junction. Quasiparticle kinetics have been studied by monitoring the frequency switching due to even-odd parity change in real time. It shows the switching time is faster than 10  μs, indicating quasiparticle-induced relaxation has to be reduced to achieve T1 much longer than 100  μs.

Perfect GMR effect in gapped graphene-based ferromagnetic normal ferromagnetic junctions

Institute of Scientific and Technical Information of China (English)

Hossein Karbaschi; Gholam Reza Rashedi

2015-01-01

We investigate the quantum transport property in gapped graphene-based ferromagnetic/normal/ferromagnetic (FG/NG/FG) junctions by using the Dirac–Bogoliubov–de Gennes equation. The graphene is fabricated on SiC and BN substrates separately, so carriers in FG/NG/FG structures are considered as massive relativistic particles. Transmission prob-ability, charge, and spin conductances are studied as a function of exchange energy of ferromagnets (h), size of graphene gap, and thickness of normal graphene region (L) respectively. Using the experimental values of Fermi energy in the normal graphene part (EFN∼400 meV) and energy gap in graphene (260 meV for SiC and 50 meV for BN substrate), it is shown that this structure can be used for both spin-up and spin-down polarized current. The latter case has different behavior of gapped FG/NG/FG from that of gapless FG/NG/FG structures. Also perfect charge giant magnetoresistance is observed in a range of EFN−mv2F

Gap junctions composed of connexins 41.8 and 39.4 are essential for colour pattern formation in zebrafish

Science.gov (United States)

Irion, Uwe; Frohnhöfer, Hans Georg; Krauss, Jana; Çolak Champollion, Tuǧba; Maischein, Hans-Martin; Geiger-Rudolph, Silke; Weiler, Christian; Nüsslein-Volhard, Christiane

2014-01-01

Interactions between all three pigment cell types are required to form the stripe pattern of adult zebrafish (Danio rerio), but their molecular nature is poorly understood. Mutations in leopard (leo), encoding Connexin 41.8 (Cx41.8), a gap junction subunit, cause a phenotypic series of spotted patterns. A new dominant allele, leotK3, leads to a complete loss of the pattern, suggesting a dominant negative impact on another component of gap junctions. In a genetic screen, we identified this component as Cx39.4 (luchs). Loss-of-function alleles demonstrate that luchs is required for stripe formation in zebrafish; however, the fins are almost not affected. Double mutants and chimeras, which show that leo and luchs are only required in xanthophores and melanophores, but not in iridophores, suggest that both connexins form heteromeric gap junctions. The phenotypes indicate that these promote homotypic interactions between melanophores and xanthophores, respectively, and those cells instruct the patterning of the iridophores. DOI: http://dx.doi.org/10.7554/eLife.05125.001 PMID:25535837

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

Directory of Open Access Journals (Sweden)

Neves-dos-Santos Sandra

2010-01-01

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

Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.

Science.gov (United States)

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

2016-11-01

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

Linker-dependent Junction Formation Probability in Single-Molecule Junctions

Energy Technology Data Exchange (ETDEWEB)

Yoo, Pil Sun; Kim, Taekyeong [HankukUniversity of Foreign Studies, Yongin (Korea, Republic of)

2015-01-15

We compare the junction formation probabilities of single-molecule junctions with different linker molecules by using a scanning tunneling microscope-based break-junction technique. We found that the junction formation probability varies as SH > SMe > NH2 for the benzene backbone molecule with different types of anchoring groups, through quantitative statistical analysis. These results are attributed to different bonding forces according to the linker groups formed with Au atoms in the electrodes, which is consistent with previous works. Our work allows a better understanding of the contact chemistry in the metal.molecule junction for future molecular electronic devices.

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

Czech Academy of Sciences Publication Activity Database

Sovadinová, I.; Babica, Pavel; Böke, H.; Kumar, E.; Wilke, A.; Park, J.-S.; Trosko, J. E.; Upham, B. L.

2015-01-01

Roč. 10, 5 no.e0124454 (2015), s. 1-16 E-ISSN 1932-6203 R&D Projects: GA MŠk LH12034 Institutional support: RVO:67985939 Keywords : gap junctional intercellular communication * resveratrol * phosphatidylcholine-specific phospholipase C Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.057, year: 2015

Neutron induced permanent damage in Josephson junctions

International Nuclear Information System (INIS)

Mueller, G.P.; Rosen, M.

1982-01-01

14 MeV neutron induced permanent changes in the critical current density of Josephson junctions due to displacement damage in the junction barrier are estimated using a worst case model and the binary collision simulation code MARLOWE. No likelihood of single event hard upsets is found in this model. It is estimated that a fluence of 10 18 -10 19 neutrons/cm 2 are required to change the critical current density by 5%

A three-dimensional model of a gap junction

International Nuclear Information System (INIS)

Xylouris, K.; Wittum, G.

2009-01-01

Gap junctions are effective electric couplings between neurons and form a very important way of communication between them. Since they can be considered as the points on the neuron's membrane on which for example dendrites of different cells become one piece, in three dimensions they can be modelled by observing this property in the created geometry. Thus they can be easily made part in an already existing 3-dimensional model for signal propagation on the neuron's membrane, if the geometries are chosen in such a way respect the blending of the membranes. A small network of two cells was created, which blend in their dendrites and a simulation of the three-dimensional model was carried out which reveals the fast transmission of the signal from one cell to the other.

Na,K-ATPase regulates intercellular communication in the vascular wall via cSrc kinase dependent connexin43 phosphorylation

DEFF Research Database (Denmark)

Hangaard, Lise; Bouzinova, Elena; Stæhr, Christian Albeck

2017-01-01

Communication between vascular smooth muscle cells (VSMCs) is dependent on gap junctions and is regulated by the Na-K-ATPase. The Na-K-ATPase is therefore important for synchronized VSMC oscillatory activity, i.e., vasomotion. The signaling between the Na-K-ATPase and gap junctions is unknown. We...... coupling in rat mesenteric small arteries in vitro. Phosphorylation of cSrc kinase and connexin43 (Cx43) were semiquantified by Western blotting. Micromole concentration of ouabain reduced the amplitude of norepinephrine-induced vasomotion and desynchronized Ca2+ transients in VSMC in the arterial wall...

Quantification of gap junctional intercellular communication based on digital image analysis

DEFF Research Database (Denmark)

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

2009-01-01

Intercellular communication via gap junction channels can be quantified by several methods based on diffusion of fluorescent dyes or metabolites. Given the variation in intercellular coupling of cells, even under untreated control conditions, it is of essence to quantify the coupling between...... and in cells receiving dye by intercellular diffusion. The analysis performed is semiautomatic, and comparison with traditional cell counting shows that this method reliably determines the effect of uncoupling by several interventions. This new method of analysis yields a rapid and objective quantification...

Reliability of twin-dependent triple junction distributions measured from a section plane

International Nuclear Information System (INIS)

Hardy, Graden B.; Field, David P.

2016-01-01

Numerous studies indicate polycrystalline triple junctions are independent microstructural features with distinct properties from their constituent grain boundaries. Despite the influence of triple junctions on material properties, it is impractical to characterize triple junctions on a large scale using current three-dimensional methods. This work demonstrates the ability to characterize twin-dependent triple junction distributions from a section plane by adopting a grain boundary plane stereology. The technique is validated through simulated distributions and simulated electron back-scatter diffraction (EBSD) data. Measures of validation and convergence are adopted to demonstrate the quantitative reliability of the technique as well as the convergence behavior of twin-dependent triple junction distributions. This technique expands the characterization power of EBSD and prepares the way for characterizing general triple junction distributions from a section plane. - Graphical abstract: The distribution of planes forming a triple junction with a given twin boundary is shown partially in the stereographic projections below from a given projection. The plot on the left shows the ideal/measured distribution and the plot on the right shows the distribution obtained from the stereological method presented here.

Temperature-sensitive junction transformations for mid-wavelength HgCdTe photovoltaic infrared detector arrays by laser beam induced current microscope

Energy Technology Data Exchange (ETDEWEB)

Qiu, Weicheng [College of Photoelectric Science and Engineering, National University of Defense Technology, Changsha, Hunan 410073 (China); National Laboratory for Infrared Physics, Shanghai Institute of Technical Physics, Chinese Academy of Sciences, Shanghai 200083 (China); Hu, Weida, E-mail: wdhu@mail.sitp.ac.cn; Lin, Tie; Yin, Fei; Zhang, Bo; Chen, Xiaoshuang; Lu, Wei [National Laboratory for Infrared Physics, Shanghai Institute of Technical Physics, Chinese Academy of Sciences, Shanghai 200083 (China); Cheng, Xiang' ai, E-mail: xiang-ai-cheng@126.com; Wang, Rui [College of Photoelectric Science and Engineering, National University of Defense Technology, Changsha, Hunan 410073 (China)

2014-11-10

In this paper, we report on the disappearance of the photosensitive area extension effect and the unusual temperature dependence of junction transformation for mid-wavelength, n-on-p HgCdTe photovoltaic infrared detector arrays. The n-type region is formed by B{sup +} ion implantation on Hg-vacancy-doped p-type HgCdTe. Junction transformations under different temperatures are visually captured by a laser beam induced current microscope. A physical model of temperature dependence on junction transformation is proposed and demonstrated by using numerical simulations. It is shown that Hg-interstitial diffusion and temperature activated defects jointly lead to the p-n junction transformation dependence on temperature, and the weaker mixed conduction compared with long-wavelength HgCdTe photodiode contributes to the disappearance of the photosensitive area extension effect in mid-wavelength HgCdTe infrared detector arrays.

Gap junction connexins in female reproductive organs: implications for women's reproductive health.

Science.gov (United States)

Winterhager, Elke; Kidder, Gerald M

2015-01-01

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

Temperature dependence of microwave oscillations in magnetic tunnel junctions with a perpendicularly magnetized free layer

International Nuclear Information System (INIS)

Guo, Peng; Feng, Jiafeng; Wei, Hongxiang; Han, Xiufeng; Fang, Bin; Zhang, Baoshun; Zeng, Zhongming

2015-01-01

We experimentally study the temperature dependence of the spin-transfer-torque-induced microwave oscillations in MgO-based magnetic tunnel junction nanopillars with a perpendicularly magnetized free layer. We demonstrate that the oscillation frequency increases rapidly with decreasing temperature, which is mainly ascribed to the temperature dependence of both the saturation magnetization and the perpendicular magnetic anisotropy. We also find that a strong temperature dependence of the output power while a nonmonotonic temperature dependence of spectral linewidth are maintained for a constant dc bias in measured temperature range. Possible mechanisms leading to the different dependences of oscillation frequency, output power, and linewidth are discussed

Traction force dynamics predict gap formation in activated endothelium

International Nuclear Information System (INIS)

Valent, Erik T.; Nieuw Amerongen, Geerten P. van; Hinsbergh, Victor W.M. van; Hordijk, Peter L.

2016-01-01

In many pathological conditions the endothelium becomes activated and dysfunctional, resulting in hyperpermeability and plasma leakage. No specific therapies are available yet to control endothelial barrier function, which is regulated by inter-endothelial junctions and the generation of acto-myosin-based contractile forces in the context of cell-cell and cell-matrix interactions. However, the spatiotemporal distribution and stimulus-induced reorganization of these integral forces remain largely unknown. Traction force microscopy of human endothelial monolayers was used to visualize contractile forces in resting cells and during thrombin-induced hyperpermeability. Simultaneously, information about endothelial monolayer integrity, adherens junctions and cytoskeletal proteins (F-actin) were captured. This revealed a heterogeneous distribution of traction forces, with nuclear areas showing lower and cell-cell junctions higher traction forces than the whole-monolayer average. Moreover, junctional forces were asymmetrically distributed among neighboring cells. Force vector orientation analysis showed a good correlation with the alignment of F-actin and revealed contractile forces in newly formed filopodia and lamellipodia-like protrusions within the monolayer. Finally, unstable areas, showing high force fluctuations within the monolayer were prone to form inter-endothelial gaps upon stimulation with thrombin. To conclude, contractile traction forces are heterogeneously distributed within endothelial monolayers and force instability, rather than force magnitude, predicts the stimulus-induced formation of intercellular gaps. - Highlights: • Endothelial monolayers exert dynamic- and heterogeneous traction forces. • High traction forces correlate with junctional areas and the F-actin cytoskeleton. • Newly formed inter-endothelial gaps are characterized by opposing traction forces. • Force stability is a key feature controlling endothelial permeability.

Traction force dynamics predict gap formation in activated endothelium

Energy Technology Data Exchange (ETDEWEB)

Valent, Erik T.; Nieuw Amerongen, Geerten P. van; Hinsbergh, Victor W.M. van; Hordijk, Peter L., E-mail: p.hordijk@vumc.nl

2016-09-10

In many pathological conditions the endothelium becomes activated and dysfunctional, resulting in hyperpermeability and plasma leakage. No specific therapies are available yet to control endothelial barrier function, which is regulated by inter-endothelial junctions and the generation of acto-myosin-based contractile forces in the context of cell-cell and cell-matrix interactions. However, the spatiotemporal distribution and stimulus-induced reorganization of these integral forces remain largely unknown. Traction force microscopy of human endothelial monolayers was used to visualize contractile forces in resting cells and during thrombin-induced hyperpermeability. Simultaneously, information about endothelial monolayer integrity, adherens junctions and cytoskeletal proteins (F-actin) were captured. This revealed a heterogeneous distribution of traction forces, with nuclear areas showing lower and cell-cell junctions higher traction forces than the whole-monolayer average. Moreover, junctional forces were asymmetrically distributed among neighboring cells. Force vector orientation analysis showed a good correlation with the alignment of F-actin and revealed contractile forces in newly formed filopodia and lamellipodia-like protrusions within the monolayer. Finally, unstable areas, showing high force fluctuations within the monolayer were prone to form inter-endothelial gaps upon stimulation with thrombin. To conclude, contractile traction forces are heterogeneously distributed within endothelial monolayers and force instability, rather than force magnitude, predicts the stimulus-induced formation of intercellular gaps. - Highlights: • Endothelial monolayers exert dynamic- and heterogeneous traction forces. • High traction forces correlate with junctional areas and the F-actin cytoskeleton. • Newly formed inter-endothelial gaps are characterized by opposing traction forces. • Force stability is a key feature controlling endothelial permeability.

Tensile-strain effect of inducing the indirect-to-direct band-gap transition and reducing the band-gap energy of Ge

Energy Technology Data Exchange (ETDEWEB)

Inaoka, Takeshi, E-mail: inaoka@phys.u-ryukyu.ac.jp; Furukawa, Takuro; Toma, Ryo; Yanagisawa, Susumu [Department of Physics and Earth Sciences, Faculty of Science, University of the Ryukyus, 1 Senbaru, Nishihara, Okinawa 903-0213 (Japan)

2015-09-14

By means of a hybrid density-functional method, we investigate the tensile-strain effect of inducing the indirect-to-direct band-gap transition and reducing the band-gap energy of Ge. We consider [001], [111], and [110] uniaxial tensility and (001), (111), and (110) biaxial tensility. Under the condition of no normal stress, we determine both normal compression and internal strain, namely, relative displacement of two atoms in the primitive unit cell, by minimizing the total energy. We identify those strain types which can induce the band-gap transition, and evaluate the critical strain coefficient where the gap transition occurs. Either normal compression or internal strain operates unfavorably to induce the gap transition, which raises the critical strain coefficient or even blocks the transition. We also examine how each type of tensile strain decreases the band-gap energy, depending on its orientation. Our analysis clearly shows that synergistic operation of strain orientation and band anisotropy has a great influence on the gap transition and the gap energy.

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

Science.gov (United States)

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.

Molecular Diffusion through Cyanobacterial Septal Junctions.

Science.gov (United States)

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

Stat3 is a positive regulator of gap junctional intercellular communication in cultured, human lung carcinoma cells

Directory of Open Access Journals (Sweden)

Geletu Mulu

2012-12-01

Full Text Available Abstract Background Neoplastic transformation of cultured cells by a number of oncogenes such as src suppresses gap junctional, intercellular communication (GJIC; however, the role of Src and its effector Signal transducer and activator of transcription-3 (Stat3 upon GJIC in non small cell lung cancer (NSCLC has not been defined. Immunohistochemical analysis revealed high Src activity in NSCLC biopsy samples compared to normal tissues. Here we explored the potential effect of Src and Stat3 upon GJIC, by assessing the levels of tyr418-phosphorylated Src and tyr705-phosphorylated Stat3, respectively, in a panel of NSCLC cell lines. Methods Gap junctional communication was examined by electroporating the fluorescent dye Lucifer yellow into cells grown on a transparent electrode, followed by observation of the migration of the dye to the adjacent, non-electroporated cells under fluorescence illumination. Results An inverse relationship between Src activity levels and GJIC was noted; in five lines with high Src activity GJIC was absent, while two lines with extensive GJIC (QU-DB and SK-LuCi6 had low Src levels, similar to a non-transformed, immortalised lung epithelial cell line. Interestingly, examination of the mechanism indicated that Stat3 inhibition in any of the NSCLC lines expressing high endogenous Src activity levels, or in cells where Src was exogenously transduced, did not restore GJIC. On the contrary, Stat3 downregulation in immortalised lung epithelial cells or in the NSCLC lines displaying extensive GJIC actually suppressed junctional permeability. Conclusions Our findings demonstrate that although Stat3 is generally growth promoting and in an activated form it can act as an oncogene, it is actually required for gap junctional communication both in nontransformed lung epithelial cells and in certain lung cancer lines that retain extensive GJIC.

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

Energy Technology Data Exchange (ETDEWEB)

Polusani, Srikanth R.; Kar, Rekha; Riquelme, Manuel A.; Masters, Bettie Sue [The University of Texas Health Science Center at San Antonio, Department of Biochemistry, San Antonio, TX 78229 (United States); Panda, Satya P., E-mail: panda@uthscsa.edu [The University of Texas Health Science Center at San Antonio, Department of Biochemistry, San Antonio, TX 78229 (United States)

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 the 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.

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

International Nuclear Information System (INIS)

Polusani, Srikanth R.; Kar, Rekha; Riquelme, Manuel A.; Masters, Bettie Sue; Panda, Satya P.

2011-01-01

Highlights: → Humans with severe forms of cytochrome P450 oxidoreductase (CYPOR) mutations show bone defects as observed in Antley-Bixler Syndrome. → 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. → Knockdown of CYPOR decreased Gap Junctional Intercellular Communication and hemichannel activity. → Knockdown of CYPOR decreased Cx43 in mouse primary calvarial osteoblasts. → 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 the reducing equivalents to various redox partners, such as cytochromes P450 (CYPs), heme oxygenase (HO), cytochrome b 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.

Temperature dependence of shot noise in double barrier magnetic tunnel junctions

Science.gov (United States)

Niu, Jiasen; Liu, Liang; Feng, J. F.; Han, X. F.; Coey, J. M. D.; Zhang, X.-G.; Wei, Jian

2018-03-01

Shot noise reveals spin dependent transport properties in a magnetic tunnel junction. We report measurement of shot noise in CoFeB/MgO/CoFeB/MgO/CoFeB double barrier magnetic tunnel junctions, which shows a strong temperature dependence. The Fano factor used to characterize shot noise increases with decreasing temperature. A sequential tunneling model can be used to account for these results, in which a larger Fano factor results from larger spin relaxation length at lower temperatures.

Josephson junction analog and quasiparticle-pair current

DEFF Research Database (Denmark)

Bak, Christen Kjeldahl; Pedersen, Niels Falsig

1973-01-01

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

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

DEFF Research Database (Denmark)

Axelsen, Lene Nygaard; Callø, Kirstine; von Holstein-Rathlou, Niels-Henrik

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...... 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...

Humidity dependence of molecular tunnel junctions with an AlOx/COOH- interface

Science.gov (United States)

Zhang, Xiaohang; McGill, Stephen; Xiong, Peng

2006-03-01

We have studied the electron transport in planar tunneling junctions with aluminum oxide and an organic self-assembled monolayer (SAM) as the tunnel barrier. The structure of the junctions is Al/AlOx/SAM/(Au, Pb) with a junction area of ˜ 0.4mm^2. The organic molecules investigated include mercaptohexadecanoic acid (MHA), hexadecanoic acid (HDA), and octadecyltrichlorosilane (OTS); all of which form ordered SAMs on top of aluminum oxide. The use of a superconducting electrode (Al) enables us to determine unambiguously that these are high-quality tunnel junctions. For junctions incorporating MHA, the transport behavior is found to be strongly humidity dependent. The resistance of these junctions drops more than 50% when placed in dry nitrogen and recovers when returned into the ambient. The same drop also occurs when the sample is placed into a vacuum, and backfilling the vacuum with either dry N2 or O2 has negligible effect on the resistance. For comparison, junctions with HDA show the same humidity dependence, while OTS samples do not. Since both MHA and HDA have carboxylic groups and OTS does not, the results suggest that water molecules at the AlOx/COOH- interface play the central role in the observed behavior. Inelastic tunneling spectroscopy (IETS) has also been performed to understand the role of water. This work was supported by a FSU Research Foundation PEG grant.

Modulation of Connexin-36 Gap Junction Channels by Intracellular pH and Magnesium Ions.

Science.gov (United States)

Rimkute, Lina; Kraujalis, Tadas; Snipas, Mindaugas; Palacios-Prado, Nicolas; Jotautis, Vaidas; Skeberdis, Vytenis A; Bukauskas, Feliksas F

2018-01-01

Connexin-36 (Cx36) protein forms gap junction (GJ) channels in pancreatic beta cells and is also the main Cx isoform forming electrical synapses in the adult mammalian brain. Cx36 GJs can be regulated by intracellular pH (pH i ) and cytosolic magnesium ion concentration ([Mg 2+ ] i ), which can vary significantly under various physiological and pathological conditions. However, the combined effect and relationship of these two factors over Cx36-dependent coupling have not been previously studied in detail. Our experimental results in HeLa cells expressing Cx36 show that changes in both pH i and [Mg 2+ ] i affect junctional conductance (g j ) in an interdependent manner; in other words, intracellular acidification cause increase or decay in g j depending on whether [Mg 2+ ] i is high or low, respectively, and intracellular alkalization cause reduction in g j independently of [Mg 2+ ] i . Our experimental and modelling data support the hypothesis that Cx36 GJ channels contain two separate gating mechanisms, and both are differentially sensitive to changes in pH i and [Mg 2+ ] i . Using recombinant Cx36 we found that two glutamate residues in the N-terminus could be partly responsible for the observed interrelated effect of pH i and [Mg 2+ ] i . Mutation of glutamate at position 8 attenuated the stimulatory effect of intracellular acidification at high [Mg 2+ ] i , while mutation at position 12 and double mutation at both positions reversed stimulatory effect to inhibition. Moreover, Cx36 * E8Q lost the initial increase of g j at low [Mg 2+ ] i and double mutation lost the sensitivity to high [Mg 2+ ] i . These results suggest that E8 and E12 are involved in regulation of Cx36 GJ channels by Mg 2+ and H + ions.

Energy gap in MgB2 superconductor: Andreev reflection studies

International Nuclear Information System (INIS)

Aswal, D.K.

2003-01-01

To investigate the nature of energy gap in MgB 2 superconductor, we have performed Andreev-reflection studies on MgB 2 / Ag planar junctions. The differential resistance (dV/dI) versus voltage (V) characteristics were recorded as a function of temperature, magnetic field and junction-type. The dV/dI vs V characteristic recorded at low temperature and zero-field for a clean MgB 2 / Ag planar junction exhibited several interesting features, such as, zero bias anomaly, a distinct double-minima, sharp resonance peaks near the energy gap etc. The data, however, could not be explained using Blonder-Tinkham-Klapwijk theory of isotropic superconductor, which indicated that energy gap in MgB 2 is not consistent with the weak-coupling BCS theory. This is further supported by unusual temperature and magnetic field dependence of the tunneling characteristics. The results indicate several possibilities for the energy gap in MgB 2 , such as, an anisotropic energy gap, two-energy or an unconventional gap scenario. (author)

A15 Nb-Sn tunnel junction fabrication and properties

International Nuclear Information System (INIS)

Rudman, D.A.; Hellman, F.; Hammond, R.H.; Beasley, M.R.

1984-01-01

We have investigated the deposition conditions necessary to produce optimized films of A15 Nb-Sn (19--26 at. % Sn) by electron-beam codeposition. Reliable high-quality superconducting tunnel junctions can be made on this material by using an oxidized-amorphous silicon overlayer as the tunneling barrier and lead as the counter-electrode. These junctions have been used both as a tool for materials diagnosis and as a probe of the superconducting properties (critical temperature and gap) of the films. Careful control of the substrate temperature during the growth of the films has proved critical to obtain homogeneous samples. When the substrate temperature is properly stabilized, stoichiometric Nb 3 Sn is found to be relatively insensitive to the deposition temperature and conditions. In contrast, the properties of the off-stoichiometry (Sn-poor) material depend strongly on the deposition temperature. For this Sn-poor material the ratio 2Δ/kT/sub c/ at a given composition increases with increasing deposition temperature. This change appears to be due to an increase in the gap at the surface of the material (as measured by tunneling) relative to the critical temperature of the bulk. All the tunnel junctions exhibit some persistent nonidealities in their current-voltage characteristics that are qualitatively insensitive to composition or deposition conditions. In particular, the junctions show excess conduction below the sum of the energy gaps (with onset at the counter-electrode gap) and a broadened current rise at the sum gap. The detailed origins of these problems are not yet understood

Electron optics with ballistic graphene junctions

Science.gov (United States)

Chen, Shaowen

Electrons transmitted across a ballistic semiconductor junction undergo refraction, analogous to light rays across an optical boundary. A pn junction theoretically provides the equivalent of a negative index medium, enabling novel electron optics such as negative refraction and perfect (Veselago) lensing. In graphene, the linear dispersion and zero-gap bandstructure admit highly transparent pn junctions by simple electrostatic gating, which cannot be achieved in conventional semiconductors. Robust demonstration of these effects, however, has not been forthcoming. Here we employ transverse magnetic focusing to probe propagation across an electrostatically defined graphene junction. We find perfect agreement with the predicted Snell's law for electrons, including observation of both positive and negative refraction. Resonant transmission across the pn junction provides a direct measurement of the angle dependent transmission coefficient, and we demonstrate good agreement with theory. Comparing experimental data with simulation reveals the crucial role played by the effective junction width, providing guidance for future device design. Efforts toward sharper pn junction and possibility of zero field Veselago lensing will also be discussed. This work is supported by the Semiconductor Research Corporations NRI Center for Institute for Nanoelectronics Discovery and Exploration (INDEX).

p-n Junction Dynamics Induced in a Graphene Channel by Ferroelectric-Domain Motion in the Substrate

International Nuclear Information System (INIS)

Kurchak, Anatolii I.; Eliseev, Eugene A.; Kalinin, Sergei V.; Strikha, Maksym V.; Morozovska, Anna N.

2017-01-01

The p - n junction dynamics induced in a graphene channel by stripe-domain nucleation, motion, and reversal in a ferroelectric substrate is explored using a self-consistent approach based on Landau-Ginzburg-Devonshire phenomenology combined with classical electrostatics. Relatively low gate voltages are required to induce the hysteresis of ferroelectric polarization and graphene charge in response to the periodic gate voltage. Pronounced nonlinear hysteresis of graphene conductance with a wide memory window corresponds to high amplitudes of gate voltage. Also, we reveal the extrinsic size effect in the dependence of the graphene-channel conductivity on its length. We predict that the top-gate–dielectric-layer–graphene-channel–ferroelectric-substrate nanostructure considered here can be a promising candidate for the fabrication of the next generation of modulators and rectifiers based on the graphene p - n junctions.

Transparent Semiconductor-Superconductor Interface and Induced Gap in an Epitaxial Heterostructure Josephson Junction

NARCIS (Netherlands)

Kjaergaard, M.; Suominen, H. J.; Nowak, M.P.; Akhmerov, A.R.; Shabani, J.; Palmstrøm, C. J.; Nichele, F.; Marcus, C.M.

2017-01-01

Measurement of multiple Andreev Reflection (MAR) in a Josephson junction made from an InAs quantum well heterostructure with epitaxial aluminum is used to quantify a highly transparent effective semiconductor-superconductor interface with near-unity transmission. The observed temperature

Mechanics of Fluid-Filled Interstitial Gaps. I. Modeling Gaps in a Compact Tissue.

Science.gov (United States)

Parent, Serge E; Barua, Debanjan; Winklbauer, Rudolf

2017-08-22

Fluid-filled interstitial gaps are a common feature of compact tissues held together by cell-cell adhesion. Although such gaps can in principle be the result of weak, incomplete cell attachment, adhesion is usually too strong for this to occur. Using a mechanical model of tissue cohesion, we show that, instead, a combination of local prevention of cell adhesion at three-cell junctions by fluidlike extracellular material and a reduction of cortical tension at the gap surface are sufficient to generate stable gaps. The size and shape of these interstitial gaps depends on the mechanical tensions between cells and at gap surfaces, and on the difference between intracellular and interstitial pressures that is related to the volume of the interstitial fluid. As a consequence of the dependence on tension/tension ratios, the presence of gaps does not depend on the absolute strength of cell adhesion, and similar gaps are predicted to occur in tissues of widely differing cohesion. Tissue mechanical parameters can also vary within and between cells of a given tissue, generating asymmetrical gaps. Within limits, these can be approximated by symmetrical gaps. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Measured Temperature Dependence of the cos-phi Conductance in Josephson Tunnel Junctions

DEFF Research Database (Denmark)

Sørensen, O. H.; Mygind, Jesper; Pedersen, Niels Falsig

1977-01-01

The temperature dependence of the cosϕ conductance in Sn-O-Sn Josephson tunnel junctions has been measured just below the critical temperature, Tc. From the resonant microwave response at the junction plasma frequency as the temperature is decreased from Tc it is deduced that the amplitude of the...

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

Directory of Open Access Journals (Sweden)

Leif eHertz

2014-09-01

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

Behavior of tight-junction, adherens-junction and cell polarity proteins during HNF-4α-induced epithelial polarization

International Nuclear Information System (INIS)

Satohisa, Seiro; Chiba, Hideki; Osanai, Makoto; Ohno, Shigeo; Kojima, Takashi; Saito, Tsuyoshi; Sawada, Norimasa

2005-01-01

We previously reported that expression of tight-junction molecules occludin, claudin-6 and claudin-7, as well as establishment of epithelial polarity, was triggered in mouse F9 cells expressing hepatocyte nuclear factor (HNF)-4α [H. Chiba, T. Gotoh, T. Kojima, S. Satohisa, K. Kikuchi, M. Osanai, N. Sawada. Hepatocyte nuclear factor (HNF)-4α triggers formation of functional tight junctions and establishment of polarized epithelial morphology in F9 embryonal carcinoma cells, Exp. Cell Res. 286 (2003) 288-297]. Using these cells, we examined in the present study behavior of tight-junction, adherens-junction and cell polarity proteins and elucidated the molecular mechanism behind HNF-4α-initiated junction formation and epithelial polarization. We herein show that not only ZO-1 and ZO-2, but also ZO-3, junctional adhesion molecule (JAM)-B, JAM-C and cell polarity proteins PAR-3, PAR-6 and atypical protein kinase C (aPKC) accumulate at primordial adherens junctions in undifferentiated F9 cells. In contrast, CRB3, Pals1 and PATJ appeared to exhibit distinct subcellular localization in immature cells. Induced expression of HNF-4α led to translocation of these tight-junction and cell polarity proteins to beltlike tight junctions, where occludin, claudin-6 and claudin-7 were assembled, in differentiated cells. Interestingly, PAR-6, aPKC, CRB3 and Pals1, but not PAR-3 or PATJ, were also concentrated on the apical membranes in differentiated cells. These findings indicate that HNF-4α provokes not only expression of tight-junction adhesion molecules, but also modulation of subcellular distribution of junction and cell polarity proteins, resulting in junction formation and epithelial polarization

Optically induced bistable states in metal/tunnel-oxide/semiconductor /MTOS/ junctions

Science.gov (United States)

Lai, S. K.; Dressendorfer, P. V.; Ma, T. P.; Barker, R. C.

1981-01-01

A new switching phenomenon in metal-oxide semiconductor tunnel junction has been discovered. With a sufficiently large negative bias applied to the electrode, incident visible light of intensity greater than about 1 microW/sq cm causes the reverse-biased junction to switch from a low-current to a high-current state. It is believed that hot-electron-induced impact ionization provides the positive feedback necessary for switching, and causes the junction to remain in its high-current state after the optical excitation is removed. The junction may be switched back to the low-current state electrically. The basic junction characteristics have been measured, and a simple model for the switching phenomenon has been developed.

Connexin domains relevant to the chemical gating of gap junction channels

Directory of Open Access Journals (Sweden)

C. Peracchia

1997-05-01

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

Dynamic trafficking and delivery of connexons to the plasma membrane and accretion to gap junctions in living cells

NARCIS (Netherlands)

Lauf, Undine; Giepmans, Ben N G; Lopez, Patricia; Braconnot, Sebastien; Chen, Shu-Chih; Falk, Matthias M

2002-01-01

Certain membrane channels including acetylcholine receptors, gap junction (GJ) channels, and aquaporins arrange into large clusters in the plasma membrane (PM). However, how these channels are recruited to the clusters is unknown. To address this question, we have investigated delivery of GJ channel

History-dependent friction and slow slip from time-dependent microscopic junction laws studied in a statistical framework.

Science.gov (United States)

Thøgersen, Kjetil; Trømborg, Jørgen Kjoshagen; Sveinsson, Henrik Andersen; Malthe-Sørenssen, Anders; Scheibert, Julien

2014-05-01

To study how macroscopic friction phenomena originate from microscopic junction laws, we introduce a general statistical framework describing the collective behavior of a large number of individual microjunctions forming a macroscopic frictional interface. Each microjunction can switch in time between two states: a pinned state characterized by a displacement-dependent force and a slipping state characterized by a time-dependent force. Instead of tracking each microjunction individually, the state of the interface is described by two coupled distributions for (i) the stretching of pinned junctions and (ii) the time spent in the slipping state. This framework allows for a whole family of microjunction behavior laws, and we show how it represents an overarching structure for many existing models found in the friction literature. We then use this framework to pinpoint the effects of the time scale that controls the duration of the slipping state. First, we show that the model reproduces a series of friction phenomena already observed experimentally. The macroscopic steady-state friction force is velocity dependent, either monotonic (strengthening or weakening) or nonmonotonic (weakening-strengthening), depending on the microscopic behavior of individual junctions. In addition, slow slip, which has been reported in a wide variety of systems, spontaneously occurs in the model if the friction contribution from junctions in the slipping state is time weakening. Next, we show that the model predicts a nontrivial history dependence of the macroscopic static friction force. In particular, the static friction coefficient at the onset of sliding is shown to increase with increasing deceleration during the final phases of the preceding sliding event. We suggest that this form of history dependence of static friction should be investigated in experiments, and we provide the acceleration range in which this effect is expected to be experimentally observable.

Coherence-enhanced phase-dependent dissipation in long SNS Josephson junctions: Revealing Andreev bound state dynamics

Science.gov (United States)

Dassonneville, B.; Murani, A.; Ferrier, M.; Guéron, S.; Bouchiat, H.

2018-05-01

One of the best known causes of dissipation in ac-driven quantum systems stems from photon absorption causing transitions between levels. Dissipation can also be caused by the retarded response to the time-dependent excitation, and in general gives insight into the system's relaxation times and mechanisms. Here we address the dissipation in a mesoscopic normal wire with superconducting contacts, that sustains a dissipationless supercurrent at zero frequency and that may therefore naively be expected to remain dissipationless at a frequency lower than the superconducting gap. We probe the high-frequency linear response of such a normal metal/superconductor (NS) ring to a time-dependent flux by coupling it to a highly sensitive multimode microwave resonator. Far from being the simple, dissipationless derivative of the supercurrent-versus-phase relation, the ring's ac susceptibility also displays a dissipative component whose phase dependence is a signature of the dynamical processes occurring within the Andreev spectrum. We show how dissipation is driven by the competition between two mechanisms. The first is the relaxation of the Andreev level distribution function, while the second corresponds to microwave-induced transitions within the spectrum. Depending on the relative strength of those contributions, dissipation can be maximal at π , a phase at which the proximity-induced minigap closes, or can be maximal near π /2 , a phase at which the dc supercurrent is maximal. We also find that the dissipative response paradoxically increases at low temperature and can even exceed the normal-state conductance. The results are successfully confronted with theoretical predictions of the Kubo linear response and time-dependent Usadel equations, derived from the Bogoliubov-de Gennes Hamiltonian describing the SNS junction. These experiments thus demonstrate the power of the ac susceptibility measurement of individual hybrid mesoscopic systems in probing in a controlled way

Flexible 2D layered material junctions

Science.gov (United States)

Balabai, R.; Solomenko, A.

2018-03-01

Within the framework of the methods of the electron density functional and the ab initio pseudopotential, we have obtained the valence electron density spatial distribution, the densities of electron states, the widths of band gaps, the charges on combined regions, and the Coulomb potentials for graphene-based flexible 2D layered junctions, using author program complex. It is determined that the bending of the 2D layered junctions on the angle α leads to changes in the electronic properties of these junctions. In the graphene/graphane junction, there is clear charge redistribution with different signs in the regions of junctions. The presence in the heterojunctions of charge regions with different signs leads to the formation of potential barriers. The greatest potential jump is in the graphene/fluorographene junction. The greatest value of the band gap width is in the graphene/graphane junction.

Light-Induced Switching of Tunable Single-Molecule Junctions

KAUST Repository

Sendler, Torsten; Luka-Guth, Katharina; Wieser, Matthias; Lokamani; Wolf, Jannic Sebastian; Helm, Manfred; Gemming, Sibylle; Kerbusch, Jochen; Scheer, Elke; Huhn, Thomas; Erbe, Artur

2015-01-01

A major goal of molecular electronics is the development and implementation of devices such as single-molecular switches. Here, measurements are presented that show the controlled in situ switching of diarylethene molecules from their nonconductive to conductive state in contact to gold nanoelectrodes via controlled light irradiation. Both the conductance and the quantum yield for switching of these molecules are within a range making the molecules suitable for actual devices. The conductance of the molecular junctions in the opened and closed states is characterized and the molecular level E 0, which dominates the current transport in the closed state, and its level broadening Γ are identified. The obtained results show a clear light-induced ring forming isomerization of the single-molecule junctions. Electron withdrawing side-groups lead to a reduction of conductance, but do not influence the efficiency of the switching mechanism. Quantum chemical calculations of the light-induced switching processes correlate these observations with the fundamentally different low-lying electronic states of the opened and closed forms and their comparably small modification by electron-withdrawing substituents. This full characterization of a molecular switch operated in a molecular junction is an important step toward the development of real molecular electronics devices.

Light-Induced Switching of Tunable Single-Molecule Junctions

KAUST Repository

Sendler, Torsten

2015-04-16

A major goal of molecular electronics is the development and implementation of devices such as single-molecular switches. Here, measurements are presented that show the controlled in situ switching of diarylethene molecules from their nonconductive to conductive state in contact to gold nanoelectrodes via controlled light irradiation. Both the conductance and the quantum yield for switching of these molecules are within a range making the molecules suitable for actual devices. The conductance of the molecular junctions in the opened and closed states is characterized and the molecular level E 0, which dominates the current transport in the closed state, and its level broadening Γ are identified. The obtained results show a clear light-induced ring forming isomerization of the single-molecule junctions. Electron withdrawing side-groups lead to a reduction of conductance, but do not influence the efficiency of the switching mechanism. Quantum chemical calculations of the light-induced switching processes correlate these observations with the fundamentally different low-lying electronic states of the opened and closed forms and their comparably small modification by electron-withdrawing substituents. This full characterization of a molecular switch operated in a molecular junction is an important step toward the development of real molecular electronics devices.

Photon-assisted Andreev transport and sub-gap structures

DEFF Research Database (Denmark)

Wildt, M; Kutchinsky, Jonatan; Taboryski, Rafael Jozef

2000-01-01

We report new measurements of microwave-induced perturbations of the sub-harmonic energy gap structures in the current-voltage characteristics of superconductor-semiconductor-superconductor junctions. Around the sub-gap bias voltages associated with the enhanced quasi-particle transfer mediated...... by multiple Andreev reflection processes we observe microwave induced satellites, shifted in voltage by multiples of hf/en, where hf is the photon energy and n is the number of quasi-particle traversals as determined by the Andreev processes. The observed behavior is the analogue of the so-called photon...

Rescue of Notch signaling in cells incapable of GDP-L-fucose synthesis by gap junction transfer of GDP-L-fucose in Drosophila.

Science.gov (United States)

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

2012-09-18

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

On the role of the gap junction protein Cx43 (GJA1 in human cardiac malformations with Fallot-pathology. a study on paediatric cardiac specimen.

Directory of Open Access Journals (Sweden)

Aida Salameh

Full Text Available INTRODUCTION: Gap junction channels are involved in growth and differentiation. Therefore, we wanted to elucidate if the main cardiac gap junction protein connexin43 (GJA1 is altered in patients with Tetralogy of Fallot or double-outlet right ventricle of Fallot-type (62 patients referred to as Fallot compared to other cardiac anomalies (21 patients referred to as non-Fallot. Patients were divided into three age groups: 0-2years, 2-12years and >12years. Myocardial tissue samples were collected during corrective surgery and analysis of cell morphology, GJA1- and N-cadherin (CDH2-distribution, as well as GJA1 protein- and mRNA-expression was carried out. Moreover, GJA1-gene analysis of 16 patients and 20 healthy subjects was performed. RESULTS: Myocardial cell length and width were significantly increased in the oldest age group compared to the younger ones. GJA1 distribution changed significantly during maturation with the ratio of polar/lateral GJA1 increasing from 2.93±0.68 to 8.52±1.41. While in 0-2years old patients ∼6% of the lateral GJA1 was co-localised with CDH2 this decreased with age. Furthermore, the changes in cell morphology and GJA1-distribution were not due to the heart defect itself but were significantly dependent on age. Total GJA1 protein expression decreased during growing-up, whereas GJA1-mRNA remained unchanged. Sequencing of the GJA1-gene revealed only few heterozygous single nucleotide polymorphisms within the Fallot and the healthy control group. CONCLUSION: During maturation significant changes in gap junction remodelling occur which might be necessary for the growing and developing heart. In our study point mutations within the Cx43-gene could not be identified as a cause of the development of TOF.

The gap junction protein connexin43 interacts with the second PDZ domain of the zona occludens-1 protein

NARCIS (Netherlands)

Giepmans, B N; Moolenaar, W H

1998-01-01

Gap junctions mediate cell-cell communication in almost all tissues and are composed of channel-forming integral membrane proteins, termed connexins [1-3]. Connexin43 (Cx43) is the most widely expressed and the most well-studied member of this family. Cx43-based cell-cell communication is regulated

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

Directory of Open Access Journals (Sweden)

Md. Abdur Rakib

2013-01-01

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

Charge distribution dependency on gap thickness of CMS endcap RPC

CERN Document Server

Park, Sung Keun

2016-01-01

We present a systematic study of charge distribution dependency of CMS Resistive Plate Chamber (RPC) on gap thickness.Prototypes of double-gap with five different gap thickness from 1.8mm to 1.0mm in 0.2mm steps have been built with 2mm thick phenolic high-pressure-laminated (HPL) plates. The charges of cosmic-muon signals induced on the detector strips are measured as a function of time using two four-channel 400-MHz fresh ADCs. In addition, the arrival time of the muons and the strip cluster sizes are measured by digitizing the signal using a 32-channel voltage-mode front-end-electronics and a 400-MHz 64-channel multi-hit TDC. The gain and the input impedance of the front-end-electronics were 200mV/mV and 20 Ohm, respectively.

Intracellular Ca2+ release mediates cationic but not anionic poly(amidoamine) (PAMAM) dendrimer-induced tight junction modulation.

Science.gov (United States)

Avaritt, Brittany R; Swaan, Peter W

2014-09-01

Poly(amidoamine) (PAMAM) dendrimers show great promise for utilization as oral drug delivery vehicles. These polymers are capable of traversing epithelial barriers, and have been shown to translocate by both transcellular and paracellular routes. While many proof-of-concept studies have shown that PAMAM dendrimers improve intestinal transport, little information exists on the mechanisms of paracellular transport, specifically dendrimer-induced tight junction modulation. Using anionic G3.5 and cationic G4 PAMAM dendrimers with known absorption enhancers, we investigated tight junction modulation in Caco-2 monolayers by visualization and mannitol permeability and compared dendrimer-mediated tight junction modulation to that of established permeation enhancers. [(14)C]-Mannitol permeability in the presence and absence of phospholipase C-dependent signaling pathway inhibitors was also examined and indicated that this pathway may mediate dendrimer-induced changes in permeability. Differences between G3.5 and G4 in tight junction protein staining and permeability with inhibitors were evident, suggesting divergent mechanisms were responsible for tight junction modulation. These dissimilarities are further intimated by the intracellular calcium release caused by G4 but not G3.5. Based on our results, it is apparent that the underlying mechanisms of dendrimer permeability are complex, and the complexities are likely a result of the density and sign of the surface charges of PAMAM dendrimers. The results of this study will have implications on the future use of PAMAM dendrimers for oral drug delivery.

TAT-Gap19 and Carbenoxolone Alleviate Liver Fibrosis in Mice

Directory of Open Access Journals (Sweden)

Sara Crespo Yanguas

2018-03-01

Full Text Available Although a plethora of signaling pathways are known to drive the activation of hepatic stellate cells in liver fibrosis, the involvement of connexin-based communication in this process remains elusive. Connexin43 expression is enhanced in activated hepatic stellate cells and constitutes the molecular building stone of hemichannels and gap junctions. While gap junctions support intercellular communication, and hence the maintenance of liver homeostasis, hemichannels provide a circuit for extracellular communication and are typically opened by pathological stimuli, such as oxidative stress and inflammation. The present study was set up to investigate the effects of inhibition of connexin43-based hemichannels and gap junctions on liver fibrosis in mice. Liver fibrosis was induced by administration of thioacetamide to Balb/c mice for eight weeks. Thereafter, mice were treated for two weeks with TAT-Gap19, a specific connexin43 hemichannel inhibitor, or carbenoxolone, a general hemichannel and gap junction inhibitor. Subsequently, histopathological analysis was performed and markers of hepatic damage and functionality, oxidative stress, hepatic stellate cell activation and inflammation were evaluated. Connexin43 hemichannel specificity of TAT-Gap19 was confirmed in vitro by fluorescence recovery after photobleaching analysis and the measurement of extracellular release of adenosine-5′-triphosphate. Upon administration to animals, both TAT-Gap19 and carbenoxolone lowered the degree of liver fibrosis accompanied by superoxide dismutase overactivation and reduced production of inflammatory proteins, respectively. These results support a role of connexin-based signaling in the resolution of liver fibrosis, and simultaneously demonstrate the therapeutic potential of TAT-Gap19 and carbenoxolone in the treatment of this type of chronic liver disease.

Gap features of layered iron-selenium-tellurium compound below and above the superconducting transition temperature by break-junction spectroscopy combined with STS

Science.gov (United States)

Ekino, T.; Sugimoto, A.; Gabovich, A. M.

2018-05-01

We studied correlations between the superconducting gap features of Te-substituted FeSe observed by scanning tunnelling spectroscopy (STS) and break-junction tunnelling spectroscopy (BJTS). At bias voltages outside the superconducting gap-energy range, the broad gap structure exists, which becomes the normal-state gap above the critical temperature, T c. Such behaviour is consistent with the model of the partially gapped density-wave superconductor involving both superconducting gaps and pseudogaps, which has been applied by us earlier to high-Tc cuprates. The similarity suggests that the parent electronic spectrum features should have much in common for these classes of materials.

Visualizing the effect of dynamin inhibition on annular gap vesicle formation and fission.

Science.gov (United States)

Nickel, Beth; Boller, Marie; Schneider, Kimberly; Shakespeare, Teresa; Gay, Vernon; Murray, Sandra A

2013-06-15

Although gap junction plaque assembly has been extensively studied, mechanisms involved in plaque disassembly are not well understood. Disassembly involves an internalization process in which annular gap junction vesicles are formed. These vesicles undergo fission, but the molecular machinery needed for these fissions has not been described. The mechanoenzyme dynamin has been previously demonstrated to play a role in gap junction plaque internalization. To investigate the role of dynamin in annular gap junction vesicle fission, immunocytochemical, time-lapse and transmission electron microscopy were used to analyze SW-13 adrenocortical cells in culture. Dynamin was demonstrated to colocalize with gap junction plaques and vesicles. Dynamin inhibition, by siRNA knockdown or treatment with the dynamin GTPase inhibitor dynasore, increased the number and size of gap junction 'buds' suspended from the gap junction plaques. Buds, in control populations, were frequently released to form annular gap junction vesicles. In dynamin-inhibited populations, the buds were larger and infrequently released and thus fewer annular gap junction vesicles were formed. In addition, the number of annular gap junction vesicle fissions per hour was reduced in the dynamin-inhibited populations. We believe this to be the first report addressing the details of annular gap junction vesicle fissions and demonstrating a role of dynamin in this process. This information is crucial for elucidating the relationship between gap junctions, membrane regulation and cell behavior.

Gap junctions and hydrogen peroxide are involved in endothelium-derived hyperpolarising responses to bradykinin in omental arteries and veins isolated from pregnant women.

Science.gov (United States)

Hammond, Stephanie; Mathewson, Alastair M; Baker, Philip N; Mayhew, Terry M; Dunn, William R

2011-10-01

Altered endothelial function may underlie human cardiovascular diseases, including hypertension, diabetes and pre-eclampsia. While much is known about endothelial function in small arteries, very little is known about endothelial responses in small veins isolated from humans. Therefore, we assessed endothelium-dependent responses in omental arteries and veins isolated from healthy pregnant women, focussing on endothelium-dependent hyperpolarising (EDH) mechanisms. Human omental arteries and veins were obtained from women undergoing elective caesarean sections and examined using pressure myography. In pressurised vessels, the effects of proposed inhibitors of EDH production/function were examined on responses to bradykinin. The expression of connexins Cx37, 40 and 43 was assessed using immunohistochemistry. Bradykinin caused vasodilatation in human pressurised omental arteries and veins. In both vessels, responses to bradykinin were partially blocked in the presence of the gap junction uncoupler, carbenoxolone, and reduced further with the addition of catalase, which acts to degrade H(2)O(2). The effect of catalase alone was more pronounced in venous preparations. All three connexins were expressed in both arteries and veins, with a similar distribution pattern, where Cx37 and Cx40 were located mainly in the endothelium and Cx43 located mostly in the media. These data show that, in human omental vessels, an EDH mechanism is produced in response to bradykinin that involves gap junction communication and the production of H(2)O(2). These mechanisms may be involved in the haemodynamic alterations that take place during pregnancy, and any aberration in their function could contribute to raised blood pressure in hypertensive disorders of pregnancy, such as pre-eclampsia. Copyright © 2011 Elsevier B.V. All rights reserved.

Vector spin modeling for magnetic tunnel junctions with voltage dependent effects

International Nuclear Information System (INIS)

Manipatruni, Sasikanth; Nikonov, Dmitri E.; Young, Ian A.

2014-01-01

Integration and co-design of CMOS and spin transfer devices requires accurate vector spin conduction modeling of magnetic tunnel junction (MTJ) devices. A physically realistic model of the MTJ should comprehend the spin torque dynamics of nanomagnet interacting with an injected vector spin current and the voltage dependent spin torque. Vector spin modeling allows for calculation of 3 component spin currents and potentials along with the charge currents/potentials in non-collinear magnetic systems. Here, we show 4-component vector spin conduction modeling of magnetic tunnel junction devices coupled with spin transfer torque in the nanomagnet. Nanomagnet dynamics, voltage dependent spin transport, and thermal noise are comprehended in a self-consistent fashion. We show comparison of the model with experimental magnetoresistance (MR) of MTJs and voltage degradation of MR with voltage. Proposed model enables MTJ circuit design that comprehends voltage dependent spin torque effects, switching error rates, spin degradation, and back hopping effects

Interplay between tip-induced band bending and voltage-dependent surface corrugation on GaAs(110) surfaces

NARCIS (Netherlands)

Raad, de G.J.; Bruls, D.M.; Koenraad, P.M.; Wolter, J.H.

2002-01-01

Atomically resolved, voltage-dependent scanning tunneling microscopy (STM) images of GaAs(110) are compared to the results of a one-dimensional model used to calculate the amount of tip-induced band bending for a tunneling junction between a metal and a semiconductor. The voltage-dependent changes

Thin film hybrid Josephson junctions with Co doped Ba-122

Energy Technology Data Exchange (ETDEWEB)

Schmidt, Stefan; Doering, Sebastian; Schmidl, Frank; Tympel, Volker; Grosse, Veit; Seidel, Paul [Friedrich-Schiller-Universitaet Jena, Institut fuer Festkoerperphysik, Helmholtzweg 5, 07743 Jena (Germany); Haindl, Silvia; Iida, Kazumasa; Kurth, Fritz; Holzapfel, Bernhard [IFW Dresden, Institut fuer Metallische Werkstoffe, Helmholtzstrasse 20, 01069 Dresden (Germany); Moench, Ingolf [IFW Dresden, Institut fuer Integrative Nanowissenschaften, Helmholtzstrasse 20, 01069 Dresden (Germany)

2011-07-01

Josephson junctions are a strong tool to investigate fundamental superconducting properties, such as gap behaviour, dependencies from external fields and the order parameter symmetry. Finding secure values enables the possibility of theoretical descriptions to understand the physical processes within the new iron-based superconductors. Based on Co-doped BaFe{sub 2}As{sub 2} (Ba-122) layers produced via pulsed laser deposition (PLD) on (La,Sr)(Al,Ta)O{sub 3} substrates, we manufactured superconductor-normal conductor-superconductor (S-N-S) junctions structures by using photolithography, ion beam etching as well as insulating SiO{sub 2} layers. We present working Ba-122/Au/PbIn thin film Josephson junctions with different contact areas and barrier thicknesses, their temperature dependence and response to microwave irradiation. The calculated I{sub c}R{sub N} product is in the range of a couple of microvolts.

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

Directory of Open Access Journals (Sweden)

Sun Qian-Quan

2009-10-01

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

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

Directory of Open Access Journals (Sweden)

James E. Trosko

2016-06-01

Full Text Available 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.

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.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Scattering theory of superconductive tunneling in quantum junctions

International Nuclear Information System (INIS)

Shumeiko, V.S.; Bratus', E.N.

1997-01-01

A consistent theory of superconductive tunneling in single-mode junctions within a scattering formulation of Bogolyubov-de Gennes quantum mechanics is presented. The dc Josephson effect and dc quasiparticle transport in the voltage-biased junctions are considered. Elastic quasiparticle scattering by the junction determines the equilibrium Josephson current. The origin of Andreev bound states in tunnel junctions and their role in equilibrium Josephson transport are discussed. In contrast, quasiparticle tunneling in voltage-biased junctions is determined by inelastic scattering. A general expression for inelastic scattering amplitudes is derived and the quasiparticle current is calculated at all voltages with emphasis on a discussion of the properties of sub gap tunnel current and the nature of subharmonic gap structure

Chirality effect in disordered graphene ribbon junctions

International Nuclear Information System (INIS)

Long Wen

2012-01-01

We investigate the influence of edge chirality on the electronic transport in clean or disordered graphene ribbon junctions. By using the tight-binding model and the Landauer-Büttiker formalism, the junction conductance is obtained. In the clean sample, the zero-magnetic-field junction conductance is strongly chirality-dependent in both unipolar and bipolar ribbons, whereas the high-magnetic-field conductance is either chirality-independent in the unipolar or chirality-dependent in the bipolar ribbon. Furthermore, we study the disordered sample in the presence of magnetic field and find that the junction conductance is always chirality-insensitive for both unipolar and bipolar ribbons with adequate disorders. In addition, the disorder-induced conductance plateaus can exist in all chiral bipolar ribbons provided the disorder strength is moderate. These results suggest that we can neglect the effect of edge chirality in fabricating electronic devices based on the magnetotransport in a disordered graphene ribbon. (paper)

Tunnelling determined superconducting energy gap of bulk single crystal aluminum

International Nuclear Information System (INIS)

Civiak, R.L.

1974-01-01

A procedure has been developed for fabricating Giaver tunnel junctions on bulk aluminum. Al-I-Ag junctions were prepared, where I is the naturally formed oxide on the polished, chemically treated aluminum surface. The aluminum energy gap was determined from tunneling conductance curves obtained from samples oriented in three different crystal directions, and as a function of magnetic field in each of these orientations. In contrast to the results of microwave absorption measurements on superconducting aluminum, no magnetic field dependence could be measured for either the average gap or the spread in gap values of the tunneling electrons. This is consistent with commonly accepted tunneling selection rules, and Garfunkel's interpretation of the microwave behavior which depended upon adjusting the energy spectrum of only the electrons traveling parallel to the surface in the presence of a magnetic field. The energy gaps measured for samples oriented in the 100, 110 and 111 directions are 3.52, 3.50 and 3.39 kT/sub c/, respectively. The trend in the anisotropy is the same as in the calculation of Leavens and Carbotte, however, the magnitude of the anisotropy is smaller than in their calculation and that which previous measurements have indicated

HDAC inhibition amplifies gap junction communication in neural progenitors: Potential for cell-mediated enzyme prodrug therapy

International Nuclear Information System (INIS)

Khan, Zahidul; Akhtar, Monira; Asklund, Thomas; Juliusson, Bengt; Almqvist, Per M.; Ekstroem, Tomas J.

2007-01-01

Enzyme prodrug therapy using neural progenitor cells (NPCs) as delivery vehicles has been applied in animal models of gliomas and relies on gap junction communication (GJC) between delivery and target cells. This study investigated the effects of histone deacetylase (HDAC) inhibitors on GJC for the purpose of facilitating transfer of therapeutic molecules from recombinant NPCs. We studied a novel immortalized midbrain cell line, NGC-407 of embryonic human origin having neural precursor characteristics, as a potential delivery vehicle. The expression of gap junction protein connexin 43 (C x 43) was analyzed by western blot and immunocytochemistry. While C x 43 levels were decreased in untreated differentiating NGC-407 cells, the HDAC inhibitor 4-phenylbutyrate (4-PB) increased C x 43 expression along with increased membranous deposition in both proliferating and differentiating cells. Simultaneously, Ser 279/282-phosphorylated form of C x 43 was declined in both culture conditions by 4-PB. The 4-PB effect in NGC-407 cells was verified by using HNSC.100 human neural progenitors and Trichostatin A. Improved functional GJC is of imperative importance for therapeutic strategies involving intercellular transport of low molecular-weight compounds. We show here an enhancement by 4-PB, of the functional GJC among NGC-407 cells, as well as between NGC-407 and human glioma cells, as indicated by increased fluorescent dye transfer

Different mechanisms of modulation of gap junction communication by non-genotoxic carcinogens in rat liver in vivo

International Nuclear Information System (INIS)

Cowles, C.; Mally, A.; Chipman, J.K.

2007-01-01

This is a comparative study of the mechanisms by which three different rodent non-genotoxic carcinogens modulate connexin-mediated gap junction intercellular communication in male rat liver in vivo. In the case of the peroxisome proliferating agent Wy-14,643, a non-hepatotoxic dose of 50 mg/kg led to a marked loss of inter-hepatocyte dye transfer associated with a loss of both Cx32 and Cx26 protein expression. In contrast, p,p'-dichlorodiphenyltrichloroethane (DDT) at a non-hepatotoxic dose (25 mg/kg) was not found to alter Cx32 or Cx26 expression or to produce a measurable Cx32 serine phosphorylation but did give a small, significant reduction of cell communication. Carbon tetrachloride (CCl 4 ) did not affect cell communication (despite a small significant reduction of Cx32 content) at a non-hepatotoxic dose. Both loss of communication and Cx32 expression was observed only at a dose that caused hepatocyte toxicity as evidenced by increased serum alanine aminotransferase activity. Overall, the findings emphasise that loss of gap junctional communication in vivo can contribute to carcinogenesis by non-genotoxic carcinogens through different primary mechanism. In contrast to Wy-14,643 and DDT, the results with CCl 4 are consistent with a requirement for hepatotoxicity in its carcinogenic action

Keratitis-Ichthyosis-Deafness syndrome-associated Cx26 mutants produce nonfunctional gap junctions but hyperactive hemichannels when co-expressed with wild type Cx43

Science.gov (United States)

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

2015-01-01

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

dc properties of series-parallel arrays of Josephson junctions in an external magnetic field

International Nuclear Information System (INIS)

Lewandowski, S.J.

1991-01-01

A detailed dc theory of superconducting multijunction interferometers has previously been developed by several authors for the case of parallel junction arrays. The theory is now extended to cover the case of a loop containing several junctions connected in series. The problem is closely associated with high-T c superconductors and their clusters of intrinsic Josephson junctions. These materials exhibit spontaneous interferometric effects, and there is no reason to assume that the intrinsic junctions form only parallel arrays. A simple formalism of phase states is developed in order to express the superconducting phase differences across the junctions forming a series array as functions of the phase difference across the weakest junction of the system, and to relate the differences in critical currents of the junctions to gaps in the allowed ranges of their phase functions. This formalism is used to investigate the energy states of the array, which in the case of different junctions are split and separated by energy barriers of height depending on the phase gaps. Modifications of the washboard model of a single junction are shown. Next a superconducting inductive loop containing a series array of two junctions is considered, and this model is used to demonstrate the transitions between phase states and the associated instabilities. Finally, the critical current of a parallel connection of two series arrays is analyzed and shown to be a multivalued function of the externally applied magnetic flux. The instabilities caused by the presence of intrinsic serial junctions in granular high-T c materials are pointed out as a potential source of additional noise

Generation and detection of high-energy phonons by superconducting junctions

International Nuclear Information System (INIS)

Singer, I.L.

1976-01-01

Superconducting tunnel junctions are used to investigate the dynamics of energy exchange that takes place in superconductors driven out of equilibrium. In a Sn junction biased at a voltage V much greater than 2Δ(Sn)/e, the tunneling current sustains a continual energy exchange amongst the quasiparticles, phonons, and Cooper pairs. Repeatedly, high-energy quasiparticles decay, emitting phonons; and phonons with energy greater than 2Δ(Sn) break pairs, producing quasiparticles. The phonon-induced component of the current is recovered by synchronously detecting the full tunneling current with respect to a small modulation current in the generator. Sharp onsets observed at intervals of the gap energies require that the escaping phonons are produced by the direct decay of the injected quasiparticles and are not merely the high-energy tail of the thermalized phonons. Both primary and secondary phonons can be abserved distinctly. Theoretical transconductance curves have been computed. The experimental and theoretical curves are in good qualitative agreement. A more detailed comparison suggests that the escape rate of high-energy phonons depends on the energy of the phonons. The dependence of the observed transconductance signal on the temperature and the total junction thickness suggests that the presence of quasiparticles plays a major role in the escape of high-energy phonons. The dependence on temperature can be fitted to exp(b/kT), 0.74 less than b less than 1.05 MeV. It is speculated that the excitation energy is first transported across the superconductor and then carried out of the film by the phonons. It is concluded that high-energy phonons are a sensitive probe of the very reabsorption effects that make their escape so unlikely, and analysis of the detected phonons rich details of the behavior of superconductors removed from equilibrium

Pannexin-1 channels show distinct morphology and no gap junction characteristics in mammalian cells.

Science.gov (United States)

Beckmann, Anja; Grissmer, Alexander; Krause, Elmar; Tschernig, Thomas; Meier, Carola

2016-03-01

Pannexins (Panx) are proteins with a similar membrane topology to connexins, the integral membrane protein of gap junctions. Panx1 channels are generally of major importance in a large number of system and cellular processes and their function has been thoroughly characterized. In contrast, little is known about channel structure and subcellular distribution. We therefore determine the subcellular localization of Panx1 channels in cultured cells and aim at the identification of channel morphology in vitro. Using freeze-fracture replica immunolabeling on EYFP-Panx1-overexpressing HEK 293 cells, large particles were identified in plasma membranes, which were immunogold-labeled using either GFP or Panx1 antibodies. There was no labeling or particles in the nuclear membranes of these cells, pointing to plasma membrane localization of Panx1-EYFP channels. The assembly of particles was irregular, this being in contrast to the regular pattern of gap junctions. The fact that no counterparts were identified on apposing cells, which would have been indicative of intercellular signaling, supported the idea of Panx1 channels within one membrane. Control cells (transfected with EYFP only, non-transfected) were devoid of both particles and immunogold labeling. Altogether, this study provides the first demonstration of Panx1 channel morphology and assembly in intact cells. The identification of Panx1 channels as large particles within the plasma membrane provides the knowledge required to enable recognition of Panx1 channels in tissues in future studies. Thus, these results open up new avenues for the detailed analysis of the subcellular localization of Panx1 and of its nearest neighbors such as purinergic receptors in vivo.

Astrocytes protect glioma cells from chemotherapy and upregulate survival genes via gap junctional communication.

Science.gov (United States)

Lin, Qingtang; Liu, Zhao; Ling, Feng; Xu, Geng

2016-02-01

Gliomas are the most common type of primary brain tumor. Using current standard treatment regimens, the prognosis of patients with gliomas remains poor, which is predominantly due to the resistance of glioma cells to chemotherapy. The organ microenvironment has been implicated in the pathogenesis and survival of tumor cells. Thus, the aim of the present study was to test the hypothesis that astrocytes (the housekeeping cells of the brain microenvironment) may protect glioma cells from chemotherapy and to investigate the underlying mechanism. Immunofluorescent and scanning electron microscopy demonstrated that glioma cells were surrounded and infiltrated by activated astrocytes. In vitro co-culture of glioma cells with astrocytes significantly reduced the cytotoxic effects on glioma cells caused by various chemotherapeutic agents, as demonstrated by fluorescein isothiocyanate-propidium iodide flow cytometry. Transwell experiments indicated that this protective effect was dependent on physical contact and the gap junctional communication (GJC) between astrocytes and glioma cells. Microarray expression profiling further revealed that astrocytes upregulated the expression levels of various critical survival genes in the glioma cells via GJC. The results of the present study indicated that the organ microenvironment may affect the biological behavior of tumor cells and suggest a novel mechanism of resistance in glioma cells, which may be of therapeutic relevance clinically.

Local dynamics of gap-junction-coupled interneuron networks

International Nuclear Information System (INIS)

Lau, Troy; Zochowski, Michal; Gage, Gregory J; Berke, Joshua D

2010-01-01

Interneurons coupled by both electrical gap-junctions (GJs) and chemical GABAergic synapses are major components of forebrain networks. However, their contributions to the generation of specific activity patterns, and their overall contributions to network function, remain poorly understood. Here we demonstrate, using computational methods, that the topological properties of interneuron networks can elicit a wide range of activity dynamics, and either prevent or permit local pattern formation. We systematically varied the topology of GJ and inhibitory chemical synapses within simulated networks, by changing connection types from local to random, and changing the total number of connections. As previously observed we found that randomly coupled GJs lead to globally synchronous activity. In contrast, we found that local GJ connectivity may govern the formation of highly spatially heterogeneous activity states. These states are inherently temporally unstable when the input is uniformly random, but can rapidly stabilize when the network detects correlations or asymmetries in the inputs. We show a correspondence between this feature of network activity and experimental observations of transient stabilization of striatal fast-spiking interneurons (FSIs), in electrophysiological recordings from rats performing a simple decision-making task. We suggest that local GJ coupling enables an active search-and-select function of striatal FSIs, which contributes to the overall role of cortical-basal ganglia circuits in decision-making

Magnetometry with Low-Resistance Proximity Josephson Junction

Science.gov (United States)

Jabdaraghi, R. N.; Peltonen, J. T.; Golubev, D. S.; Pekola, J. P.

2018-06-01

We characterize a niobium-based superconducting quantum interference proximity transistor (Nb-SQUIPT) and its key constituent formed by a Nb-Cu-Nb SNS weak link. The Nb-SQUIPT and SNS devices are fabricated simultaneously in two separate lithography and deposition steps, relying on Ar ion cleaning of the Nb contact surfaces. The quality of the Nb-Cu interface is characterized by measuring the temperature-dependent equilibrium critical supercurrent of the SNS junction. In the Nb-SQUIPT device, we observe a maximum flux-to-current transfer function value of about 55 nA/Φ_0 in the sub-gap regime of bias voltages. This results in suppression of power dissipation down to a few fW. Low-bias operation of the device with a relatively low probe junction resistance decreases the dissipation by up to two orders of magnitude compared to a conventional device based on an Al-Cu-Al SNS junction and an Al tunnel probe (Al-SQUIPT).

Valley detection using a graphene gradual pn junction with spin–orbit coupling: An analytical conductance calculation

Energy Technology Data Exchange (ETDEWEB)

Yang, Mou, E-mail: yang.mou@hotmail.com [Guangdong Provincial Key Laboratory of Quantum Engineering and Quantum Materials, School of Physics and Telecommunication Engineering, South China Normal University, Guangzhou 510006 (China); Wang, Rui-Qiang [Guangdong Provincial Key Laboratory of Quantum Engineering and Quantum Materials, School of Physics and Telecommunication Engineering, South China Normal University, Guangzhou 510006 (China); Bai, Yan-Kui [College of Physical Science and Information Engineering and Hebei Advance Thin Films Laboratory, Hebei Normal University, Shijiazhuang, Hebei 050024 (China)

2015-09-04

Graphene pn junction is the brick to build up variety of graphene nano-structures. The analytical formula of the conductance of graphene gradual pn junctions in the whole bipolar region has been absent up to now. In this paper, we analytically calculated that pn conductance with the spin–orbit coupling and stagger potential taken into account. Our analytical expression indicates that the energy gap causes the conductance to drop a constant value with respect to that without gap in a certain parameter region, and manifests that the curve of the conductance versus the stagger potential consists of two Gaussian peaks – one valley contributes one peak. The latter feature allows one to detect the valley polarization without using double-interface resonant devices. - Highlights: • Analytical conductance formula of the gradual graphene pn junction with spin–orbit coupling in the whole bipolar region. • Exploring the valley-dependent transport of gradual graphene pn junctions analytically. • Conductance peak without resonance.

Effect of d-wave pairing symmetry in transport properties of silicene-based superconductor junction

Science.gov (United States)

Vosoughi-nia, S.; Rashedi, G.; hajati, Y.

2018-06-01

We theoretically study the tunneling conductance of a normal/d-wave superconductor silicene junction using Blonder-Tinkham-Klapwijk (BTK) formalism. We discuss how the conductance spectra are affected by changing the chemical potential (μN) in the normal silicene region. It is obtained that the amplitude of the spin/valley-dependent Andreev reflection (AR) and charge conductance (G) of the junction can be strongly modulated by the orientation angle of superconductive gap (β) and perpendicular electric field (Ez). We demonstrate that the charge conductance exhibits an oscillatory behavior as a function of β by a period of π/2. Remarkably, variation of μN strongly modifies the amplitude of the oscillations and periodically there are transport gaps in the G - β oscillations for a range of μN. These findings suggest that one may experimentally tune the transport properties of the junction through changing β, Ez and μN.

Observation of supercurrent in graphene-based Josephson junction

Energy Technology Data Exchange (ETDEWEB)

Wang, Libin; Li, Sen; Kang, Ning [Key Laboratory for the Physics and Chemistry of Nanodevices and Department of Electronics, Peking University, Beijing 100871 (China); Xu, Chuan; Ren, Wencai [Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China)

2015-07-01

Josephson junctions with a normal metal region sandwiched between two superconductors (S) are known as superconductor- normal-superconductor (SNS) structures. It has attracted significant attention especially when changing the normal metal with graphene, which allow for high tunability with the gate voltage and to study the proximity effect of the massless Dirac fermions. Here we report our work on graphene-based Josephson junction with a new two dimensional superconductor crystal, which grown directly on graphene, as superconducting electrodes. At low temperature, we observer proximity effect induced supercurrent flowing through the junction. The temperature and the magnetic field dependences of the critical current characteristics of the junction are also studied. The critical current exhibits a Fraunhofer-type diffraction pattern against magnetic field. Our experiments provided a new route of fabrication of graphene-based Josephson junction.

Temperature dependence of the cosphi conductance in Josephson tunnel junctions determined from plasma resonance experiments

DEFF Research Database (Denmark)

Pedersen, Niels Falsig; Sørensen, O. H.; Mygind, Jesper

1978-01-01

The microwave response at 9 GHz of Sn-O-Sn tunnel-junction current biased at zero dc voltage has been measured just below the critical temperature Tc of the Sn films. The temperature dependence of the cosφ conductance is determined from the resonant response at the junction plasma frequency fp...

Terahertz radiation-induced sub-cycle field electron emission across a split-gap dipole antenna

International Nuclear Information System (INIS)

Zhang, Jingdi; Averitt, Richard D.; Zhao, Xiaoguang; Fan, Kebin; Wang, Xiaoning; Zhang, Xin; Zhang, Gu-Feng; Geng, Kun

2015-01-01

We use intense terahertz pulses to excite the resonant mode (0.6 THz) of a micro-fabricated dipole antenna with a vacuum gap. The dipole antenna structure enhances the peak amplitude of the in-gap THz electric field by a factor of ∼170. Above an in-gap E-field threshold amplitude of ∼10 MV/cm −1 , THz-induced field electron emission is observed as indicated by the field-induced electric current across the dipole antenna gap. Field emission occurs within a fraction of the driving THz period. Our analysis of the current (I) and incident electric field (E) is in agreement with a Millikan-Lauritsen analysis where log (I) exhibits a linear dependence on 1/E. Numerical estimates indicate that the electrons are accelerated to a value of approximately one tenth of the speed of light

Time scales of bias voltage effects in FE/MgO-based magnetic tunnel junctions with voltage-dependent perpendicular anisotropy

International Nuclear Information System (INIS)

Lytvynenko, Ia.M.; Hauet, T.; Montaigne, F.; Bibyk, V.V.; Andrieu, S.

2015-01-01

Interplay between voltage-induced magnetic anisotropy transition and voltage-induced atomic diffusion is studied in epitaxial V/Fe (0.7 nm)/ MgO/ Fe(5 nm)/Co/Au magnetic tunnel junction where thin Fe soft electrode has in-plane or out-of-plane anisotropy depending on the sign of the bias voltage. We investigate the origin of the slow resistance variation occurring when switching bias voltage in opposite polarity. We demonstrate that the time to reach resistance stability after voltage switching is reduced when increasing the voltage amplitude or the temperature. A single energy barrier of about 0.2 eV height is deduced from temperature dependence. Finally, we demonstrate that the resistance change is not correlated to a change in soft electrode anisotropy. This conclusion contrasts with observations recently reported on analogous systems. - Highlights: • Voltage-induced time dependence of resistance is studied in epitaxial Fe/MgO/Fe. • Resistance change is not related to the bottom Fe/MgO interface. • The effect is thermally activated with an energy barrier of the order of 0.2 eV height

Strong Depletion in Hybrid Perovskite p-n Junctions Induced by Local Electronic Doping.

Science.gov (United States)

Ou, Qingdong; Zhang, Yupeng; Wang, Ziyu; Yuwono, Jodie A; Wang, Rongbin; Dai, Zhigao; Li, Wei; Zheng, Changxi; Xu, Zai-Quan; Qi, Xiang; Duhm, Steffen; Medhekar, Nikhil V; Zhang, Han; Bao, Qiaoliang

2018-04-01

A semiconductor p-n junction typically has a doping-induced carrier depletion region, where the doping level positively correlates with the built-in potential and negatively correlates with the depletion layer width. In conventional bulk and atomically thin junctions, this correlation challenges the synergy of the internal field and its spatial extent in carrier generation/transport. Organic-inorganic hybrid perovskites, a class of crystalline ionic semiconductors, are promising alternatives because of their direct badgap, long diffusion length, and large dielectric constant. Here, strong depletion in a lateral p-n junction induced by local electronic doping at the surface of individual CH 3 NH 3 PbI 3 perovskite nanosheets is reported. Unlike conventional surface doping with a weak van der Waals adsorption, covalent bonding and hydrogen bonding between a MoO 3 dopant and the perovskite are theoretically predicted and experimentally verified. The strong hybridization-induced electronic coupling leads to an enhanced built-in electric field. The large electric permittivity arising from the ionic polarizability further contributes to the formation of an unusually broad depletion region up to 10 µm in the junction. Under visible optical excitation without electrical bias, the lateral diode demonstrates unprecedented photovoltaic conversion with an external quantum efficiency of 3.93% and a photodetection responsivity of 1.42 A W -1 . © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Geometric dependence of Nb-Bi2Te3-Nb topological Josephson junction transport parameters

International Nuclear Information System (INIS)

Molenaar, C G; Leusink, D P; Brinkman, A; Wang, X L

2014-01-01

Superconductor-topological insulator–superconductor Josephson junctions have been fabricated in order to study the width dependence of the critical current, normal state resistance and flux periodicity of the critical current modulation in an external field. Previous literature reports suggest anomalous scaling in topological junctions due to the presence of Majorana bound states. However, for most realized devices, one would expect that trivial 2π-periodic Andreev levels dominate transport. We also observe anomalous scaling behaviour of junction parameters, but the scaling can be well explained by mere geometric effects, such as the parallel bulk conductivity shunt and flux focusing. (paper)

Capacitance measurement of Josephson tunnel junctions with microwave-induced dc quasiparticle tunneling currents

International Nuclear Information System (INIS)

Hamasaki, K.; Yoshida, K.; Irie, F.; Enpuku, K.

1982-01-01

The microwave response of the dc quasiparticle tunneling current in Josephson tunnel junctions, where the Josephson current is suppressed by an external magnetic field, has been studied quantitatively in order to clarify its characteristics as a probe for the measurement of the junction capacitance. Extensive experiments for both small and long junctions are carried out for distinguishing between microwave behaviors of lumped and distributed constant junctions. It is shown that the observed voltage dependence of the dc quasiparticle tunneling current modified by an applied rf field is in good agreement with a theoretical result which takes into account the influence of the microwave circuit connected to the junction. The comparison between theory and experiment gives the magnitude of the internal rf field in the junction. Together with the applied rf field, this internal rf field leads to the junction rf impedance which is dominated by the junction capacitance in our experimental condition. In the case of lumped junctions, this experimental rf impedance is in reasonable agreement with the theoretical one with the junction capacitance estimated from the Fiske step of the distributed junction fabricated on the same substrate; the obtained ratio of the experimental impedance to the theoretical one is approximately 0.6--1.7. In the case of distributed junctions, however, experimental values of their characteristic impedances are approximately 0.2--0.3 of theoretical values calculated by assuming the one-dimensional junction model and taking account of the standing-wave effect in the junction

Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles.

Science.gov (United States)

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

2015-04-28

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

Gap Junctions Are Involved in the Rescue of CFTR-Dependent Chloride Efflux by Amniotic Mesenchymal Stem Cells in Coculture with Cystic Fibrosis CFBE41o- Cells

Directory of Open Access Journals (Sweden)

Annalucia Carbone

2018-01-01

Full Text Available We previously found that human amniotic mesenchymal stem cells (hAMSCs in coculture with CF immortalised airway epithelial cells (CFBE41o- line, CFBE on Transwell® filters acquired an epithelial phenotype and led to the expression of a mature and functional CFTR protein. In order to explore the role of gap junction- (GJ- mediated intercellular communication (GJIC in this rescue, cocultures (hAMSC : CFBE, 1 : 5 ratio were studied for the formation of GJIC, before and after silencing connexin 43 (Cx43, a major component of GJs. Functional GJs in cocultures were inhibited when the expression of the Cx43 protein was downregulated. Transfection of cocultures with siRNA against Cx43 resulted in the absence of specific CFTR signal on the apical membrane and reduction in the mature form of CFTR (band C, and in parallel, the CFTR-dependent chloride channel activity was significantly decreased. Cx43 downregulation determined also a decrease in transepithelial resistance and an increase in paracellular permeability as compared with control cocultures, implying that GJIC may regulate CFTR expression and function that in turn modulate airway epithelium tightness. These results indicate that GJIC is involved in the correction of CFTR chloride channel activity upon the acquisition of an epithelial phenotype by hAMSCs in coculture with CF cells.

Gap Junctions Are Involved in the Rescue of CFTR-Dependent Chloride Efflux by Amniotic Mesenchymal Stem Cells in Coculture with Cystic Fibrosis CFBE41o- Cells.

Science.gov (United States)

Carbone, Annalucia; Zefferino, Roberto; Beccia, Elisa; Casavola, Valeria; Castellani, Stefano; Di Gioia, Sante; Giannone, Valentina; Seia, Manuela; Angiolillo, Antonella; Colombo, Carla; Favia, Maria; Conese, Massimo

2018-01-01

We previously found that human amniotic mesenchymal stem cells (hAMSCs) in coculture with CF immortalised airway epithelial cells (CFBE41o- line, CFBE) on Transwell® filters acquired an epithelial phenotype and led to the expression of a mature and functional CFTR protein. In order to explore the role of gap junction- (GJ-) mediated intercellular communication (GJIC) in this rescue, cocultures (hAMSC : CFBE, 1 : 5 ratio) were studied for the formation of GJIC, before and after silencing connexin 43 (Cx43), a major component of GJs. Functional GJs in cocultures were inhibited when the expression of the Cx43 protein was downregulated. Transfection of cocultures with siRNA against Cx43 resulted in the absence of specific CFTR signal on the apical membrane and reduction in the mature form of CFTR (band C), and in parallel, the CFTR-dependent chloride channel activity was significantly decreased. Cx43 downregulation determined also a decrease in transepithelial resistance and an increase in paracellular permeability as compared with control cocultures, implying that GJIC may regulate CFTR expression and function that in turn modulate airway epithelium tightness. These results indicate that GJIC is involved in the correction of CFTR chloride channel activity upon the acquisition of an epithelial phenotype by hAMSCs in coculture with CF cells.

Jump in current at the gap voltage in a superconducting junction

International Nuclear Information System (INIS)

Coombes, J.M.; Carbotte, J.P.

1986-01-01

For many materials not previously considered, we have calculated the jump, at the gap voltage, in the quasiparticle current of a tunnel junction. An empirical relationship between the jump and the effective electron-phonon coupling λ-μ/sup */ previously established is confirmed. Further, a new and equally as accurate correlation is found with the strong coupling index T/sub c//ω/sub ln/, where T/sub c/ is the critical temperature and ω/sub ln/ a specific characteristic phonon energy. A simple formula for the jump which includes a strong-coupling correction is derived and found to fit the observed correlation well. Finally, we study the effect on the jump of unusual values of Coulomb pseudopotential μ/sup */. Also a δ-function electron-phonon spectral density α 2 F(ω) is used to help in the understanding of the range of values that is possible for the jump when α 2 F(ω) is not restricted to realistic shapes

Firing patterns and synchronization in nonsynaptic epileptiform activity: the effect of gap junctions modulated by potassium accumulation

International Nuclear Information System (INIS)

Santos, D O C; Dickman, R; Rodrigues, A M; De Almeida, A C G

2009-01-01

Several lines of evidence point to the modification of firing patterns and of synchronization due to gap junctions (GJs) as having a role in the establishment of epileptiform activity (EA). However, previous studies consider GJs as ohmic resistors, ignoring the effects of intense variations in ionic concentration known to occur during seizures. In addition to GJs, extracellular potassium is regarded as a further important factor involved in seizure initiation and sustainment. To analyze how these two mechanisms act together to shape firing and synchronization, we use a detailed computational model for in vitro high-K + and low-Ca 2+ nonsynaptic EA. The model permits us to explore the modulation of electrotonic interactions under ionic concentration changes caused by electrodiffusion in the extracellular space, altered by tortuosity. In addition, we investigate the special case of null GJ current. Increased electrotonic interaction alters bursts and action potential frequencies, favoring synchronization. The particularities of pattern changes depend on the tortuosity and array size. Extracellular potassium accumulation alone modifies firing and synchronization when the GJ coupling is null

High-performance germanium n+/p junction by nickel-induced dopant activation of implanted phosphorus at low temperature

International Nuclear Information System (INIS)

Huang Wei; Lu Chao; Yu Jue; Wei Jiang-Bin; Chen Chao-Wen; Wang Jian-Yuan; Xu Jian-Fang; Li Cheng; Chen Song-Yan; Lai Hong-Kai; Wang Chen; Liu Chun-Li

2016-01-01

High-performance Ge n + /p junctions were fabricated at a low formation temperature from 325 °C to 400 °C with a metal(nickel)-induced dopant activation technique. The obtained NiGe electroded Ge n + /p junction has a rectification ratio of 5.6× 10 4 and a forward current of 387 A/cm 2 at −1 V bias. The Ni-based metal-induced dopant activation technique is expected to meet the requirement of the shallow junction of Ge MOSFET. (paper)

Tunneling rates in electron transport through double-barrier molecular junctions in a scanning tunneling microscope.

Science.gov (United States)

Nazin, G V; Wu, S W; Ho, W

2005-06-21

The scanning tunneling microscope enables atomic-scale measurements of electron transport through individual molecules. Copper phthalocyanine and magnesium porphine molecules adsorbed on a thin oxide film grown on the NiAl(110) surface were probed. The single-molecule junctions contained two tunneling barriers, vacuum gap, and oxide film. Differential conductance spectroscopy shows that electron transport occurs via vibronic states of the molecules. The intensity of spectral peaks corresponding to the individual vibronic states depends on the relative electron tunneling rates through the two barriers of the junction, as found by varying the vacuum gap tunneling rate by changing the height of the scanning tunneling microscope tip above the molecule. A simple, sequential tunneling model explains the observed trends.

Spin-dependent transport in ferromagnet/semiconductor/ferromagnet junctions: a fully relativistic approach

International Nuclear Information System (INIS)

Popescu, Voicu; Ebert, Hubert; Papanikolaou, Nikolaos; Zeller, Rudolf; Dederichs, Peter H

2004-01-01

We present a fully relativistic generalization of the Landauer-Buettiker formalism that has been implemented within the framework of the spin-polarized relativistic screened Korringa-Kohn-Rostoker Green function method. This approach, going beyond the two-current model, supplies a more general description of the electronic transport. It is shown that the relativistic conductance can be split in terms of individual spin-diagonal and spin-off-diagonal (spin-flip) components, which allows a detailed analysis of the influence of spin-orbit-coupling-induced spin-flip processes on the spin-dependent transport. We apply our method to calculate the ballistic conductance in Fe/GaAs/Fe magnetic tunnel junctions. We find that, by removing the spin selection rules, the spin-orbit coupling strongly influences the conductance, not only qualitatively but also quantitatively, especially in the anti-parallel alignment of the magnetization in the two Fe leads

Downregulation of blood-brain barrier phenotype by proinflammatory cytokines involves NADPH oxidase-dependent ROS generation: consequences for interendothelial adherens and tight junctions.

Directory of Open Access Journals (Sweden)

Keith D Rochfort

Full Text Available Blood-brain barrier (BBB dysfunction is an integral feature of neurological disorders and involves the action of multiple proinflammatory cytokines on the microvascular endothelial cells lining cerebral capillaries. There is still however, considerable ambiguity throughout the scientific literature regarding the mechanistic role(s of cytokines in this context, thereby warranting a comprehensive in vitro investigation into how different cytokines may cause dysregulation of adherens and tight junctions leading to BBB permeabilization.The present study employs human brain microvascular endothelial cells (HBMvECs to compare/contrast the effects of TNF-α and IL-6 on BBB characteristics ranging from the expression of interendothelial junction proteins (VE-cadherin, occludin and claudin-5 to endothelial monolayer permeability. The contribution of cytokine-induced NADPH oxidase activation to altered barrier phenotype was also investigated.In response to treatment with either TNF-α or IL-6 (0-100 ng/ml, 0-24 hrs, our studies consistently demonstrated significant dose- and time-dependent decreases in the expression of all interendothelial junction proteins examined, in parallel with dose- and time-dependent increases in ROS generation and HBMvEC permeability. Increased expression and co-association of gp91 and p47, pivotal NADPH oxidase subunits, was also observed in response to either cytokine. Finally, cytokine-dependent effects on junctional protein expression, ROS generation and endothelial permeability could all be attenuated to a comparable extent using a range of antioxidant strategies, which included ROS depleting agents (superoxide dismutase, catalase, N-acetylcysteine, apocynin and targeted NADPH oxidase blockade (gp91 and p47 siRNA, NSC23766.A timely and wide-ranging investigation comparing the permeabilizing actions of TNF-α and IL-6 in HBMvECs is presented, in which we demonstrate how either cytokine can similarly downregulate the

Asymmetric angular dependence of spin-transfer torques in CoFe/Mg-B-O/CoFe magnetic tunnel junctions

Energy Technology Data Exchange (ETDEWEB)

Tang, Ling, E-mail: lingtang@zjut.edu.cn; Xu, Zhi-Jun, E-mail: xzj@zjut.edu.cn; Zuo, Xian-Jun; Yang, Ze-Jin, E-mail: zejinyang@zjut.edu.cn [Department of Applied Physics, College of Science, Zhejiang University of Technology, Hangzhou 310023 (China); Gao, Qing-He [College of Science, Northeastern University, Shenyang 110004, China, Information Engineering College, Liaoning University of Traditional Chinese Medicine, Shenyang 110847 (China); Linghu, Rong-Feng, E-mail: linghu@gznu.edu.cn [School of Physics and Electronics Sciences, Guizhou Education University, Guiyang 550018 (China); Guo, Yun-Dong, E-mail: g308yd@126.com [College of Engineering and Technology, Neijiang Normal University, Neijiang 641112 (China)

2016-04-28

Using a first-principles noncollinear wave-function-matching method, we studied the spin-transfer torques (STTs) in CoFe/Mg-B-O/CoFe(001) magnetic tunnel junctions (MTJs), where three different types of B-doped MgO in the spacer are considered, including B atoms replacing Mg atoms (Mg{sub 3}BO{sub 4}), B atoms replacing O atoms (Mg{sub 4}BO{sub 3}), and B atoms occupying interstitial positions (Mg{sub 4}BO{sub 4}) in MgO. A strong asymmetric angular dependence of STT can be obtained both in ballistic CoFe/Mg{sub 3}BO{sub 4} and CoFe/Mg{sub 4}BO{sub 4} based MTJs, whereas a nearly symmetric STT curve is observed in the junctions based on CoFe/Mg{sub 4}BO{sub 3}. Furthermore, the asymmetry of the angular dependence of STT can be suppressed significantly by the disorder of B distribution. Such skewness of STTs in the CoFe/Mg-B-O/CoFe MTJs could be attributed to the interfacial resonance states induced by the B diffusion into MgO spacer.

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

KAUST Repository

Ren, Jian; Wang, Xuhui; Wang, Guangchao; Wu, Junhua

2013-01-01

Connexin 43 (Cx43) plays an essential role in osteocyte mechanotransduction. Although estrogen involves in the adaptive responses of bone cells to mechanical loadings, its effects on osteocytic Cx43-based gap junction intercellular communication

Oncostatin M induces upregulation of claudin-2 in rodent hepatocytes coinciding with changes in morphology and function of tight junctions

International Nuclear Information System (INIS)

Imamura, Masafumi; Kojima, Takashi; Lan, Mengdong; Son, Seiichi; Murata, Masaki; Osanai, Makoto; Chiba, Hideki; Hirata, Koichi; Sawada, Norimasa

2007-01-01

In rodent livers, integral tight junction (TJ) proteins claudin-1, -2, -3, -5 and -14 are detected and play crucial roles in the barrier to keep bile in bile canaculi away from the blood circulation. Claudin-2 shows a lobular gradient increasing from periportal to pericentral hepatocytes, whereas claudin-1 and -3 are expressed in the whole liver lobule. Although claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells, the physiological functions and regulation of claudin-2 in hepatocytes remain unclear. Oncostatin M (OSM) is a multifunctional cytokine implicated in the differentiation of hepatocytes that induces formation of E-cadherin-based adherens junctions in fetal hepatocytes. In this study, we examined whether OSM could induce expression and function of claudin-2 in rodent hepatocytes, immortalized mouse and primary cultured proliferative rat hepatocytes. In the immortalized mouse and primary cultured proliferative rat hepatocytes, treatment with OSM markedly increased mRNA and protein of claudin-2 together with formation of developed networks of TJ strands. The increase of claudin-2 enhanced the paracellular barrier function which depended on molecular size. The increase of claudin-2 expression induced by OSM in rodent hepatocytes was regulated through distinct signaling pathways including PKC. These results suggest that expression of claudin-2 in rodent hepatocytes may play a specific role as controlling the size of paracellular permeability in the barrier to keep bile in bile canaculi

Gate-voltage control of equal-spin Andreev reflection in half-metal/semiconductor/superconductor junctions

Energy Technology Data Exchange (ETDEWEB)

Wu, Xiuqiang, E-mail: xianqiangzhe@126.com [National Laboratory of Solid State Microstructures and Department of Physics, Nanjing University, Nanjing 210093 (China); Meng, Hao, E-mail: menghao1982@shu.edu.cn [School of Physics and Telecommunication Engineering, Shanxi University of Technology, Hanzhong 723001 (China)

2016-04-22

With the Blonder–Tinkham–Klapwijk (BTK) approach, we investigate conductance spectrum in Ferromagnet/Semiconductor/Superconductor (FM/Sm/SC) double tunnel junctions where strong Rashba spin–orbit interaction (RSOI) is taken into account in semiconductors. For the half-metal limit, we find that the in-gap conductance becomes finite except at zero voltage when inserting a ferromagnetic insulator (FI) at the Sm/SC interface, which means that the appearance of a long-range triplet states in the half-metal. This is because of the emergence of the unconventional equal-spin Andreev reflection (ESAR). When the FI locates at the FM/Sm interface, however, we find the vanishing in-gap conductance due to the absence of the ESAR. Moreover, the non-zero in-gap conductance shows a nonmonotonic dependence on RSOI which can be controlled by applying an external gate voltage. Our results can be used to generate and manipulate the long-range spin triplet correlation in the nascent field of superconducting spintronics. - Highlights: • We study the equal-spin Andreev reflection in half-metal/semiconductor/superconductor (HM/Sm/SC) junctions. • The equal-spin Andreev reflection appearance when inserting a ferromagnetic insulator at the Sm/SC interface. • The finite in-gap conductance is attributed to the emergence of the equal-spin Andreev reflection. • The finite in-gap conductance shows a nonmonotonic dependence on Rashba spin–orbit interaction. • The finite in-gap conductance can be controlled by applying an external gate voltage.

Realistic-contact-induced enhancement of rectifying in carbon-nanotube/graphene-nanoribbon junctions

International Nuclear Information System (INIS)

Zhang, Xiang-Hua; Li, Xiao-Fei; Wang, Ling-Ling; Xu, Liang; Luo, Kai-Wu

2014-01-01

Carbon-nanotube/graphene-nanoribbon junctions were recently fabricated by the controllable etching of single-walled carbon-nanotubes [Wei et al., Nat. Commun. 4, 1374 (2013)] and their electronic transport properties were studied here. First principles results reveal that the transmission function of the junctions show a heavy dependence on the shape of contacts, but rectifying is an inherent property which is insensitive to the details of contacts. Interestingly, the rectifying ratio is largely enhanced in the junction with a realistic contact and the enhancement is insensitive to the details of contact structures. The stability of rectifying suggests a significant feasibility to manufacture realistic all-carbon rectifiers in nanoelectronics

Dynamics of fractional vortices in long Josephson junctions

International Nuclear Information System (INIS)

Gaber, Tobias

2007-01-01

In this thesis static and dynamic properties of fractional vortices in long Josephson junctions are investigated. Fractional vortices are circulating supercurrents similar to the well-known Josephson fluxons. Yet, they show the distinguishing property of carrying only a fraction of the magnetic flux quantum. Fractional vortices are interesting non-linear objects. They spontaneously appear and are pinned at the phase discontinuity points of so called 0-κ junctions but can be bend or flipped by external forces like bias currents or magnetic fields. 0-κ junctions and fractional vortices are generalizations of the well-known 0-π junctions and semifluxons, where not only phase jumps of pi but arbitrary values denoted by kappa are considered. By using so-called artificial 0-κ junctions that are based on standard Nb-AlO x -Nb technology the classical dynamics of fractional vortices has been investigated experimentally for the very first time. Here, half-integer zero field steps could be observed. These voltage steps on the junction's current-voltage characteristics correspond to the periodic flipping/hopping of fractional vortices. In addition, the oscillatory eigenmodes of fractional vortices were investigated. In contrast to fluxons fractional vortices have an oscillatory eigenmode with a frequency within the plasma gap. Using resonance spectroscopy the dependence of the eigenmode frequency on the flux carried by the vortex and an applied bias current was determined. (orig.)

Theory of tunneling in metal--superconductor devices: Supercurrents in the superconductor gap at zero temperature

International Nuclear Information System (INIS)

Garcia, N.; Flores, F.; Guinea, F.

1988-01-01

Tunneling experiments in metal-oxide superconductor have shown the existence of ''leakage'' currents for applied voltages V smaller than one-half of the superconductor gap Δ. These currents are independent of temperature T. Recently experiments with scanning tunneling microscopy (STM) and squeezable tunnel junctions have shown that the observation of the superconductor gap depends strongly on the resistance in the junction. In fact only for resistances larger than ∼10 6 Ω the gap is clearly observable. These experiments have been explained in terms of the perturbative Hamiltonian formalism of Bardeen. However, it may happen that this theory while applicable for very large resistances may not be so for small tunnel resistances. We present here a nonperturbative theory in all orders of the transmitivity chemical bondTochemical bond 2 and show the existence of supercurrents for values of V 2 . We believe that experiments in STM and other junctions should be interpreted in the frame of this theory

Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

Energy Technology Data Exchange (ETDEWEB)

Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: 2010lijianguo@sina.cn [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)

2012-11-16

Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

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

Energy Technology Data Exchange (ETDEWEB)

Feng, Liefeng, E-mail: fengliefeng@tju.edu.cn, E-mail: lihongru@nankai.edu.cn; Yang, Xiufang; Wang, Cunda; Yao, Dongsheng [Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, Faculty of Science, Tianjin University, Tianjin 300072 (China); Li, Yang [Business and Vocational College of Hainan, Haikou 570203 (China); Li, Ding; Hu, Xiaodong [Research Center for Wide Band Gap Semiconductors, State Key Laboratory for Artificial Microstructure and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871 (China); Li, Hongru, E-mail: fengliefeng@tju.edu.cn, E-mail: lihongru@nankai.edu.cn [State Key Laboratory for Medicinal Chemistry and Biology, College of Pharmacy, Nankai University, Tianjin 300071 (China)

2015-04-15

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

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

International Nuclear Information System (INIS)

Feng, Liefeng; Yang, Xiufang; Wang, Cunda; Yao, Dongsheng; Li, Yang; Li, Ding; Hu, Xiaodong; Li, Hongru

2015-01-01

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

Neuromodulation of activity-dependent synaptic enhancement at crayfish neuromuscular junction.

Science.gov (United States)

Qian, S M; Delaney, K R

1997-10-17

Action potential-evoked transmitter release is enhanced for many seconds after moderate-frequency stimulation (e.g. 15 Hz for 30 s) at the excitor motorneuron synapse of the crayfish dactyl opener muscle. Beginning about 1.5 s after a train, activity-dependent synaptic enhancement (ADSE) is dominated by a process termed augmentation (G.D. Bittner, D.A. Baxter, Synaptic plasticity at crayfish neuromuscular junctions: facilitation and augmentation, Synapse 7 (1991) 235-243'[4]; K.L. Magleby, Short-term changes in synaptic efficacy, in: G.M. Edelman, L.E. Gall, C.W. Maxwell (Eds.), Synaptic Function, John Wiley and Sons, New York, 1987, pp. 21-56; K.L. Magleby; J.E. Zengel, Augmentation: a process that acts to increase transmitter release at the frog neuromuscular junction, J. Physiol. (Lond.) 257 (1976) 449-470) which decays approximately exponentially with a time constant of about 10 s at 16 degrees C, reflecting the removal of Ca2+ which accumulates during the train in presynaptic terminals (K.R. Delaney, D.W. Tank, R.S. Zucker, Serotonin-mediated enhancement of transmission at crayfish neuromuscular junction is independent of changes in calcium, J. Neurosci. 11 (1991) 2631-2643). Serotonin (5-HT, 1 microM) increases evoked and spontaneous transmitter release several-fold (D. Dixon, H.L. Atwood, Crayfish motor nerve terminal's response to serotonin examined by intracellular microelectrode, J. Neurobiol. 16 (1985) 409-424; J. Dudel, Modulation of quantal synaptic release by serotonin and forskolin in crayfish motor nerve terminals, in: Modulation of Synaptic Transmission and Plasticity in Nervous Systems, G. Hertting, H.-C. Spatz (Eds.), Springer-Verlag, Berlin, 1988; S. Glusman, E.A. Kravitz. The action of serotonin on excitatory nerve terminals in lobster nerve-muscle preparations, J. Physiol. (Lond.) 325 (1982) 223-241). We found that ADSE persists about 2-3 times longer after moderate-frequency presynaptic stimulation in the presence of 5-HT. This slowing of the

rf power dependence of subharmonic voltage spectra of two-dimensional Josephson-junction arrays

International Nuclear Information System (INIS)

Hebboul, S.E.; Garland, J.C.

1993-01-01

We have measured the rf-bias-current dependence of the ν/2 subharmonic spectral response of planar 300x300 Nb-Au-Nb proximity-coupled Josephson-junction arrays. The ν/2 subharmonic voltage spectrum was examined at two rf-bias frequencies, ν/ν c ∼1.4, 2.0 (ν c ∼120 MHz), and in applied magnetic fields corresponding to f=0,1/2 flux quantum per plaquette. The measurements were compared to analytical predictions for an rf-biased asymmetric superconducting quantum interference device with non-negligble loop inductance and large rf-bias-current amplitudes, based on the resistively shunted Josephson-junction model. Reasonable agreement was found between experiment and theory, suggesting that a possible origin for the observed subharmonic behavior in arrays involves an interplay between array plaquette inductances and junction critical-current variations

Inhibition of gap junctional intercellular communication by noncoplanar polychlorinated biphenyls: Inhibitory potencies and screening for potential mode(s) of action

Czech Academy of Sciences Publication Activity Database

Machala, M.; Bláha, L.; Vondráček, Jan; Trosko, J. E.; Scott, J.; Upham, B. L.

2003-01-01

Roč. 76, č. 1 (2003), s. 102-111 ISSN 1096-6080 R&D Projects: GA MZe QC0194; GA ČR GA525/00/D101 Grant - others:National Institute of Health(US) P42 ES04911-07 Institutional research plan: CEZ:AV0Z5004920 Keywords : WB-F344 cell line * gap junction * PCB congeners Subject RIV: BO - Biophysics Impact factor: 3.067, year: 2003

Photon energy dependence of photo-induced inverse spin-Hall effect in Pt/GaAs and Pt/Ge

Energy Technology Data Exchange (ETDEWEB)

Isella, Giovanni, E-mail: giovanni.isella@polimi.it; Bottegoni, Federico; Ferrari, Alberto; Finazzi, Marco; Ciccacci, Franco [LNESS-Dipartimento di Fisica, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)

2015-06-08

We report the photon energy dependence of photo-induced inverse spin Hall effect (ISHE) in Pt/GaAs and Pt/Ge Schottky junctions. The experimental results are compared with a spin drift-diffusion model, which highlights the role played by the different spin lifetime in the two semiconductors, in determining the energy dependence of the ISHE signal detected in the Pt layer. The good qualitative agreement between experiments and modelling indicates that photo-induced ISHE can be used as a tool to characterize spin lifetime in semiconductors.

Influence of drugs on gap junctions in glioma cell lines and primary astrocytes in vitro

Directory of Open Access Journals (Sweden)

Zahra eMoinfar

2014-05-01

Full Text Available Gap junctions (GJs are hemichannels on cell membrane. Once they are intercellulary connected to the neighboring cells, they build a functional syncytium which allows rapid transfer of ions and molecules between cells. This characteristic makes GJs a potential modulator in proliferation, migration and development of the cells. So far, several types of GJs are recognized on different brain cells as well as in glioma. Astrocytes, as one of the major cells that maintain neuronal homeostasis, express different types of GJs that let them communicate with neurons, oligodendrocytes and endothelial cells of the blood brain barrier; however, the main GJ in astrocytes is connexin 43. There are different cerebral diseases in which astrocyte GJs might play a role. Several drugs have been reported to modulate gap junctional communication in the brain which can consequently have beneficial or detrimental effects on the course of treatment in certain diseases. However, the exact cellular mechanism behind those pharmaceutical efficacies on GJs is not well-understood. Accordingly, how specific drugs would affect GJs and what some consequent specific brain diseases would be are the interests of the authors of this chapter. We would focus on pharmaceutical effects on GJs on astrocytes in specific diseases where GJs could possibly play a role including: 1 migraine and a novel therapy for migraine with aura, 2 neuroautoimmune diseases and immunomodulatory drugs in the treatment of demyelinating diseases of the central nervous system such as multiple sclerosis, 3 glioma and antineoplastic and anti-inflammatory agents that are used in treating brain tumors and 4 epilepsy and anticonvulsants that are widely used for seizures therapy. All of the above-mentioned therapeutic categories can possibly affect GJs expression of astrocytes and the role is discussed in the upcoming chapter.

Field modulation of the critical current in magnetic Josephson junctions

International Nuclear Information System (INIS)

Blamire, M G; Smiet, C B; Banerjee, N; Robinson, J W A

2013-01-01

The dependence of the critical current of a simple Josephson junction on the applied magnetic field is well known and, for a rectangular junction, gives rise to the classic ‘Fraunhofer’ modulation with periodic zeros at the fields that introduce a flux quantum into the junction region. Much recent work has been performed on Josephson junctions that contain magnetic layers. The magnetization of such layers introduces additional flux into the junction and, for large junction areas or strong magnetic materials, can significantly distort the modulation of the critical current and strongly suppress the maximum critical current. The growing interest in junctions that induce odd-frequency triplet pairing in a ferromagnet, and the need to make quantitative comparisons with theory, mean that a full understanding of the role of magnetic barriers in controlling the critical current is necessary. This paper analyses the effect of magnetism and various magnetic configurations on Josephson critical currents; the overall treatment applies to junctions of general shape, but the specific cases of square and rectangular junctions are considered. (paper)

Magnetic field dependence of the critical superconducting current induced by the proximity effect in silicon

International Nuclear Information System (INIS)

Nishino, T.; Kawabe, U.; Yamada, E.

1986-01-01

The magnetic field dependence of the critical superconducting current induced by the proximity effect in heavily-boron-doped Si is studied experimentally. It is found that the critical current flowing through the p-type-Si-coupled junction decreases with increasing applied magnetic field. The critical current can be expressed as the product of three factors: the current induced by de Gennes's proximity effect, the exponential decrease due to pair breaking by the magnetic field, and the usual diffraction-pattern-like dependence on the magnetic field due to the Josephson effect. The second factor depends on the carrier concentration in the semiconductor. The local critical current shows a rapid decrease at the edge of the electrodes

Strain- and electric field-induced band gap modulation in nitride nanomembranes

International Nuclear Information System (INIS)

Amorim, Rodrigo G; Zhong Xiaoliang; Mukhopadhyay, Saikat; Pandey, Ravindra; Rocha, Alexandre R; Karna, Shashi P

2013-01-01

The hexagonal nanomembranes of the group III-nitrides are a subject of interest due to their novel technological applications. In this paper, we investigate the strain- and electric field-induced modulation of their band gaps in the framework of density functional theory. For AlN, the field-dependent modulation of the bandgap is found to be significant whereas the strain-induced semiconductor-metal transition is predicted for GaN. A relatively flat conduction band in AlN and GaN nanomembranes leads to an enhancement of their electronic mobility compared to that of their bulk counterparts. (paper)

Spatial dependence of plasma oscillations in Josephson tunnel junctions

DEFF Research Database (Denmark)

Holst, Thorsten; Hansen, Jørn Bindslev

1991-01-01

of an applied magnetic field. Numerical simulations of the governing partial-differential sine-Gordon equation were performed and compared to the experimental results and a perturbation analysis. The theoretical results support the experiments and allow us to interpret the observed crossover as due...... field threading the tunneling barrier. We compare measurements where the plasma frequency was tuned either by applying a magnetic field or by raising the temperature. A crossover from short- to long-junction behavior of the functional dependence of the plasma oscillations was observed in the case...

Complexity in neuronal noise depends on network interconnectivity.

Science.gov (United States)

Serletis, Demitre; Zalay, Osbert C; Valiante, Taufik A; Bardakjian, Berj L; Carlen, Peter L

2011-06-01

"Noise," or noise-like activity (NLA), defines background electrical membrane potential fluctuations at the cellular level of the nervous system, comprising an important aspect of brain dynamics. Using whole-cell voltage recordings from fast-spiking stratum oriens interneurons and stratum pyramidale neurons located in the CA3 region of the intact mouse hippocampus, we applied complexity measures from dynamical systems theory (i.e., 1/f(γ) noise and correlation dimension) and found evidence for complexity in neuronal NLA, ranging from high- to low-complexity dynamics. Importantly, these high- and low-complexity signal features were largely dependent on gap junction and chemical synaptic transmission. Progressive neuronal isolation from the surrounding local network via gap junction blockade (abolishing gap junction-dependent spikelets) and then chemical synaptic blockade (abolishing excitatory and inhibitory post-synaptic potentials), or the reverse order of these treatments, resulted in emergence of high-complexity NLA dynamics. Restoring local network interconnectivity via blockade washout resulted in resolution to low-complexity behavior. These results suggest that the observed increase in background NLA complexity is the result of reduced network interconnectivity, thereby highlighting the potential importance of the NLA signal to the study of network state transitions arising in normal and abnormal brain dynamics (such as in epilepsy, for example).

High doses of salicylate causes prepulse facilitation of onset-gap induced acoustic startle response.

Science.gov (United States)

Sun, Wei; Doolittle, Lauren; Flowers, Elizabeth; Zhang, Chao; Wang, Qiuju

2014-01-01

Prepulse inhibition of acoustic startle reflex (PPI), a well-established method for evaluating sensorimotor gating function, has been used to detect tinnitus in animal models. Reduced gap induced PPI (gap-PPI) was considered as a sign of tinnitus. The silent gap used in the test contains both onset and offset signals. Tinnitus may affect these cues differently. In this experiment, we studied the effects of a high dose of salicylate (250 mg/kg, i.p.), an inducer of reversible tinnitus and sensorineural hearing loss, on gap-PPI induced by three different gaps: an onset-gap with 0.1 ms onset and 25 ms offset time, an offset-gap with 25 ms onset and 0.1 ms offset time, and an onset-offset-gap with 0.1 ms onset and offset time. We found that the onset-gaps induced smaller inhibitions than the offset-gaps before salicylate treatment. The offset-gap induced PPI was significantly reduced 1-3h after salicylate treatment. However, the onset-gap caused a facilitation of startle response. These results suggest that salicylate induced reduction of gap-PPI was not only caused by the decrease of offset-gap induced PPI, but also by the facilitation induced by the onset-gap. Since the onset-gap induced PPI is caused by neural offset response, our results suggest that salicylate may cause a facilitation of neural response to an offset acoustical signal. Treatment of vigabatrin (60 mg/kg/day, 14 days), which elevates the GABA level in the brain, blocked the offset-gap induced PPI and onset-gap induced facilitation caused by salicylate. These results suggest that enhancing GABAergic activities can alleviate salicylate induced tinnitus. Published by Elsevier B.V.

Dependences of the Tunnel Magnetoresistance and Spin Transfer Torque on the Sizes and Concentration of Nanoparticles in Magnetic Tunnel Junctions

Science.gov (United States)

Esmaeili, A. M.; Useinov, A. N.; Useinov, N. Kh.

2018-01-01

Dependences of the tunnel magnetoresistance and in-plane component of the spin transfer torque on the applied voltage in a magnetic tunnel junction have been calculated in the approximation of ballistic transport of conduction electrons through an insulating layer with embedded magnetic or nonmagnetic nanoparticles. A single-barrier magnetic tunnel junction with a nanoparticle embedded in an insulator forms a double-barrier magnetic tunnel junction. It has been shown that the in-plane component of the spin transfer torque in the double-barrier magnetic tunnel junction can be higher than that in the single-barrier one at the same thickness of the insulating layer. The calculations show that nanoparticles embedded in the tunnel junction increase the probability of tunneling of electrons, create resonance conditions, and ensure the quantization of the conductance in contrast to the tunnel junction without nanoparticles. The calculated dependences of the tunnel magnetoresistance correspond to experimental data demonstrating peak anomalies and suppression of the maximum magnetoresistances at low voltages.

Methylglyoxal Induces Changes in the Glyoxalase System and Impairs Glutamate Uptake Activity in Primary Astrocytes.

Science.gov (United States)

Hansen, Fernanda; Galland, Fabiana; Lirio, Franciane; de Souza, Daniela Fraga; Da Ré, Carollina; Pacheco, Rafaela Ferreira; Vizuete, Adriana Fernanda; Quincozes-Santos, André; Leite, Marina Concli; Gonçalves, Carlos-Alberto

2017-01-01

The impairment of astrocyte functions is associated with diabetes mellitus and other neurodegenerative diseases. Astrocytes have been proposed to be essential cells for neuroprotection against elevated levels of methylglyoxal (MG), a highly reactive aldehyde derived from the glycolytic pathway. MG exposure impairs primary astrocyte viability, as evaluated by different assays, and these cells respond to MG elevation by increasing glyoxalase 1 activity and glutathione levels, which improve cell viability and survival. However, C6 glioma cells have shown strong signs of resistance against MG, without significant changes in the glyoxalase system. Results for aminoguanidine coincubation support the idea that MG toxicity is mediated by glycation. We found a significant decrease in glutamate uptake by astrocytes, without changes in the expression of the major transporters. Carbenoxolone, a nonspecific inhibitor of gap junctions, prevented the cytotoxicity induced by MG in astrocyte cultures. Thus, our data reinforce the idea that astrocyte viability depends on gap junctions and that the impairment induced by MG involves glutamate excitotoxicity. The astrocyte susceptibility to MG emphasizes the importance of this compound in neurodegenerative diseases, where the neuronal damage induced by MG may be aggravated by the commitment of the cells charged with MG clearance.

Ca2+-dependent localization of integrin-linked kinase to cell junctions in differentiating keratinocytes.

Science.gov (United States)

Vespa, Alisa; Darmon, Alison J; Turner, Christopher E; D'Souza, Sudhir J A; Dagnino, Lina

2003-03-28

Integrin complexes are necessary for proper proliferation and differentiation of epidermal keratinocytes. Differentiation of these cells is accompanied by down-regulation of integrins and focal adhesions as well as formation of intercellular adherens junctions through E-cadherin homodimerization. A central component of integrin adhesion complexes is integrin-linked kinase (ILK), which can induce loss of E-cadherin expression and epithelial-mesenchymal transformation when ectopically expressed in intestinal and mammary epithelia. In cultured primary mouse keratinocytes, we find that ILK protein levels are independent of integrin expression and signaling, since they remain constant during Ca(2+)-induced differentiation. In contrast, keratinocyte differentiation is accompanied by marked reduction in kinase activity in ILK immunoprecipitates and altered ILK subcellular distribution. Specifically, ILK distributes in close apposition to actin fibers along intercellular junctions in differentiated but not in undifferentiated keratinocytes. ILK localization to cell-cell borders occurs independently of integrin signaling and requires Ca(2+) as well as an intact actin cytoskeleton. Further, and in contrast to what is observed in other epithelial cells, ILK overexpression in differentiated keratinocytes does not promote E-cadherin down-regulation and epithelial-mesenchymal transition. Thus, novel tissue-specific mechanisms control the formation of ILK complexes associated with cell-cell junctions in differentiating murine epidermal keratinocytes.

Spin-dependent quasiparticle tunneling in junction superconductor-isolator-ferromagnetic

International Nuclear Information System (INIS)

Shlapak, Yu.V.; Shaternik, V.E.; Rudenko, E.M.

2001-01-01

The influence of Andreev reflection of quasiparticles in transparent tunnel junctions of superconductor-isolator-ferromagnetic on electric-current transport is studied within the framework of the Blonder-Tinkham-Klapwijk (BTK) model. It's obtained that current and signal-to-noise ratio can be increased for the memory cell by using in it the double-barrier tunnel junction ferromagnetic-isolator-superconductor-isolator-ferromagnetic instead off the usual tunnel junction ferromagnetic-isolator-ferromagnetic. The evolution of non-linear (tunnel-type) current-voltage characteristics with increasing of the junction transparency is described. (orig.)

Charge and spin current oscillations in a tunnel junction induced by magnetic field pulses

Energy Technology Data Exchange (ETDEWEB)

Dartora, C.A., E-mail: cadartora@eletrica.ufpr.br [Electrical Engineering Department, Federal University of Parana (UFPR), C.P. 19011 Curitiba, 81.531-970 PR (Brazil); Nobrega, K.Z., E-mail: bzuza1@yahoo.com.br [Federal Institute of Education, Science and Technolgy of Maranhão (IFMA), Av. Marechal Castelo Branco, 789, São Luís, 65.076-091 MA (Brazil); Cabrera, G.G., E-mail: cabrera@ifi.unicamp.br [Instituto de Física ‘Gleb Wataghin’, Universidade Estadual de Campinas (UNICAMP), C.P. 6165, Campinas 13.083-970 SP (Brazil)

2016-08-15

Usually, charge and spin transport properties in tunnel junctions are studied in the DC bias regime and/or in the adiabatic regime of time-varying magnetic fields. In this letter, the temporal dynamics of charge and spin currents in a tunnel junction induced by pulsed magnetic fields is considered. At low bias voltages, energy and momentum of the conduction electrons are nearly conserved in the tunneling process, leading to the description of the junction as a spin-1/2 fermionic system coupled to time-varying magnetic fields. Under the influence of pulsed magnetic fields, charge and spin current can flow across the tunnel junction, displaying oscillatory behavior, even in the absence of DC bias voltage. A type of spin capacitance function, in close analogy to electric capacitance, is predicted.

Electronic transport through EuO spin-filter tunnel junctions

KAUST Repository

Jutong, Nuttachai

2012-11-12

Epitaxial spin-filter tunnel junctions based on the ferromagnetic semiconductor europium monoxide (EuO) are investigated by means of density functional theory. In particular, we focus on the spin transport properties of Cu(100)/EuO(100)/Cu(100) junctions. The dependence of the transmission coefficient and the current-voltage curves on the interface spacing and EuO thickness is explained in terms of the EuO density of states and the complex band structure. Furthermore, we also discuss the relation between the spin transport properties and the Cu-EuO interface geometry. The level alignment of the junction is sensitively affected by the interface spacing, since this determines the charge transfer between EuO and the Cu electrodes. Our calculations indicate that EuO epitaxially grown on Cu can act as a perfect spin filter, with a spin polarization of the current close to 100%, and with both the Eu-5d conduction-band and the Eu-4f valence-band states contributing to the coherent transport. For epitaxial EuO on Cu, a symmetry filtering is observed, with the Δ1 states dominating the transmission. This leads to a transport gap larger than the fundamental EuO band gap. Importantly, the high spin polarization of the current is preserved up to large bias voltages.

Resistance switch employing a simple metal nanogap junction

International Nuclear Information System (INIS)

Naitoh, Yasuhisa; Horikawa, Masayo; Abe, Hidekazu; Shimizu, Tetsuo

2006-01-01

In recent years, several researchers have reported the occurrence of reversible resistance switching effects in simple metal nanogap junctions. A large negative resistance is observed in the I-V characteristics of such a junction when high-bias voltages are applied. This phenomenon is characteristic behaviour on the nanometre scale; it only occurs for gap widths slightly under 13 nm. Furthermore, such a junction exhibits a non-volatile resistance hysteresis when the bias voltage is reduced very rapidly from a high level to around 0 V, and when the bias voltage is reduced slowly. This non-volatile resistance change occurs as a result of changes in the gap width between the metal electrodes, brought about by the applied bias voltage

Impurity-induced tuning of quantum-well States in spin-dependent resonant tunneling.

Science.gov (United States)

Kalitsov, Alan; Coho, A; Kioussis, Nicholas; Vedyayev, Anatoly; Chshiev, M; Granovsky, A

2004-07-23

We report exact model calculations of the spin-dependent tunneling in double magnetic tunnel junctions in the presence of impurities in the well. We show that the impurity can tune selectively the spin channels giving rise to a wide variety of interesting and novel transport phenomena. The tunneling magnetoresistance, the spin polarization, and the local current can be dramatically enhanced or suppressed by impurities. The underlying mechanism is the impurity-induced shift of the quantum well states (QWSs), which depends on the impurity potential, impurity position, and the symmetry of the QWS. Copyright 2004 The American Physical Society

Extending prematuration with cAMP modulators enhances the cumulus contribution to oocyte antioxidant defence and oocyte quality via gap junctions.

Science.gov (United States)

Li, H J; Sutton-McDowall, M L; Wang, X; Sugimura, S; Thompson, J G; Gilchrist, R B

2016-04-01

cumulus cells and oocytes for the duration (6 h) of pre-IVM examined, and persisted for a further 8 h in the IVM phase. Cyclic AMP-modulated pre-IVM increased intra-oocyte GSH levels at the completion of both pre-IVM and IVM, in a pre-IVM duration-dependent manner (P gap junctions, or whether a GSH synthesis signal and/or amino acid substrates are supplied to the oocyte via gap junctions. Embryo transfer experiments are required to determine if the cAMP-mediated improvement in blastocyst rates leads to improved live birth rates. IVM offers significant benefits to infertile and cancer patients and has the potential to significantly alter ART practice, if IVM efficiency in embryo production could be improved closer to that of conventional IVF (using ovarian hyperstimulation). Pre-IVM with cAMP modulators is a simple and reliable means to improve IVM outcomes. This work was supported by grants and fellowships from the National Health and Medical Research Council of Australia (1007551, 627007, 1008137, 1023210) and by scholarships from the Chinese Scholarship Council (CSC) awarded to H.J.L. and the Japanese Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad awarded to S.S. The Fluoview FV10i confocal microscope was purchased as part of the Sensing Technologies for Advanced Reproductive Research (STARR) facility, funded by the South Australian Premier's Science and Research Fund. We acknowledge partial support from the Australian Research Council Centre of Excellence for Nanoscale BioPhotonics (CE140100003). We declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Anomalous spin-dependent tunneling statistics in Fe/MgO/Fe junctions induced by disorder at the interface

Science.gov (United States)

Yan, Jiawei; Wang, Shizhuo; Xia, Ke; Ke, Youqi

2018-01-01

We present first-principles analysis of interfacial disorder effects on spin-dependent tunneling statistics in thin Fe/MgO/Fe magnetic tunnel junctions. We find that interfacial disorder scattering can significantly modulate the tunneling statistics in the minority spin of the parallel configuration (PC) while all other spin channels remain dominated by the Poissonian process. For the minority-spin channel of PC, interfacial disorder scattering favors the formation of resonant tunneling channels by lifting the limitation of symmetry conservation at low concentration, presenting an important sub-Poissonian process in PC, but is destructive to the open channels at high concentration. We find that the important modulation of tunneling statistics is independent of the type of interfacial disorder. A bimodal distribution function of transmission with disorder dependence is introduced and fits very well our first-principles results. The increase of MgO thickness can quickly change the tunneling from a sub-Poissonian to Poissonian dominated process in the minority spin of PC with disorder. Our results provide a sensitive detection method of an ultralow concentration of interfacial defects.

Junction depth dependence of breakdown in silicon detector diodes

International Nuclear Information System (INIS)

Beck, G.A.; Carter, A.A.; Carter, J.R.; Greenwood, N.M.; Lucas, A.D.; Munday, D.J.; Pritchard, T.W.; Robinson, D.; Wilburn, C.D.; Wyllie, K.

1996-01-01

The high voltage capability of detector diodes fabricated in the planar process is limited by the high field generated at the edge of the junction.We have fabricated diodes with increased junction depth with respect to our standard process and find a significantly higher breakdown voltage,in reasonable agreement with previous studies of junction breakdown. (orig.)

Barreloid Borders and Neuronal Activity Shape Panglial Gap Junction-Coupled Networks in the Mouse Thalamus.

Science.gov (United States)

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

2018-01-01

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

Membrane junctions in Xenopus eggs: their distribution suggests a role in calcium regulation.

Science.gov (United States)

Gardiner, D M; Grey, R D

1983-04-01

We have observed the presence of membrane junctions formed between the plasma membrane and cortical endoplasmic reticulum of mature, unactivated eggs of xenopus laevis. The parallel, paired membranes of the junction are separated by a 10-mn gap within which electron-dense material is present. This material occurs in patches with an average center-to-center distance of approximately 30 nm. These junctions are rare in immature (but fully grown) oocytes (approximately 2 percent of the plasma membrane is associated with junctions) and increase dramatically during progesterone-induced maturation. Junctions in the mature, unactivated egg are two to three times more abundant in the animal hemisphere (25-30 percent of the plasma membrane associated with junction) as compared with the vegetal hemisphere (10-15 percent). Junction density decreases rapidly to values characteristic of immature oocytes in response to egg activation. The plasma membrane-ER junctions of xenopus eggs are strikingly similar in structure to membrane junctions in muscle cells thought to be essential in the triggering of intracellular calcium release from the sarcoplasmic reticulum. In addition, the junctions' distinctive, animal-vegetal polarity of distribution, their dramatic appearance during maturation, and their disapperance during activation are correlated with previously documented patterns of calcium-mediated events in anuran eggs. We discuss several lines of evidence supporting the hypothesis that these junctions in xenopus eggs are sites that transduce extracellular events into intracellular calcium release during fertilization and activation of development.

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-04-01

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

Exploring the Tilt-Angle Dependence of electron tunneling across Molecular junction of Self-Assembled Alkanethiols

DEFF Research Database (Denmark)

Frederiksen, Thomas; Munuera, C.; Ocal, C.

2009-01-01

Electronic transport mechanisms in molecular junctions are investigated by a combination of first-principles calculations and current−voltage measurements of several well-characterized structures. We study self-assembled layers of alkanethiols grown on Au(111) and form tunnel junctions...... for the longer molecular chains. Our calculations confirm the observed trends and explain them as a result of two mechanisms, namely, a previously proposed intermolecular tunneling enhancement as well as a hitherto overlooked tilt-dependent molecular gate effect....

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

Science.gov (United States)

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...

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

Directory of Open Access Journals (Sweden)

Chun-Ping Jen

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

Resonance modes in one-dimensional parallel arrays of Josephson junctions

International Nuclear Information System (INIS)

Van der Zant, H.S.J.; Delin, K.A.; Bock, R.D.; Berman, D.; Phillips, J.R.; Orlando, T.P.

1994-01-01

We investigate both experimentally and numerically the dynamics of discrete one-dimensional parallel arrays of underdamped Josephson junctions. In a magnetic field, measurements show steps in the current-voltage characteristics which are the discrete analogs of Fiske steps in a long Josephson junction. From the position of the steps, one can construct a plot of the dispersion relation ω(k). We observe a sine--dependence in the dispersion relation due to the discrete nature of our arrays. We also observe an additional, smaller gap at a k-value determined by the periodicity of the vortex lattice. Our measurements are supported by numerical simulations of the full dynamics. The Fiske steps provide an experimental method to measure the self-inductance of 1D parallel arrays. (orig.)

Vinculin but not alpha-actinin is a target of PKC phosphorylation during junctional assembly induced by calcium

DEFF Research Database (Denmark)

Perez-Moreno, M; Avila, A; Islas, S

1998-01-01

and alpha-actinin, two actin binding proteins of the adherent junctions. We found that during the junctional sealing induced by Ca2+, both proteins move towards the cell periphery and, while there is a significant increase in the phosphorylation of vinculin, alpha-actinin remains unchanged. The increased...

Current–voltage characteristics of manganite–titanite perovskite junctions

Directory of Open Access Journals (Sweden)

Benedikt Ifland

2015-07-01

Full Text Available After a general introduction into the Shockley theory of current voltage (J–V characteristics of inorganic and organic semiconductor junctions of different bandwidth, we apply the Shockley theory-based, one diode model to a new type of perovskite junctions with polaronic charge carriers. In particular, we studied manganite–titanate p–n heterojunctions made of n-doped SrTi1−yNbyO3, y = 0.002 and p-doped Pr1−xCaxMnO3, x = 0.34 having a strongly correlated electron system. The diffusion length of the polaron carriers was analyzed by electron beam-induced current (EBIC in a thin cross plane lamella of the junction. In the J–V characteristics, the polaronic nature of the charge carriers is exhibited mainly by the temperature dependence of the microscopic parameters, such as the hopping mobility of the series resistance and a colossal electro-resistance (CER effect in the parallel resistance. We conclude that a modification of the Shockley equation incorporating voltage-dependent microscopic polaron parameters is required. Specifically, the voltage dependence of the reverse saturation current density is analyzed and interpreted as a voltage-dependent electron–polaron hole–polaron pair generation and separation at the interface.

Electric field-induced ferromagnetic resonance in a CoFeB/MgO magnetic tunnel junction under dc bias voltages

Science.gov (United States)

Kanai, Shun; Gajek, Martin; Worledge, D. C.; Matsukura, Fumihiro; Ohno, Hideo

2014-12-01

We measure homodyne-detected ferromagnetic resonance (FMR) induced by the electric-field effect in a CoFeB/MgO/CoFeB magnetic tunnel junction (MTJ) with perpendicular magnetic easy axis under dc bias voltages up to 0.1 V. From the bias dependence of the resonant frequency, we find that the first order perpendicular magnetic anisotropy is modulated by the applied electric field, whereas the second order component is virtually independent of the electric field. The lineshapes of the FMR spectra are bias dependent, which are explained by the combination of electric-field effect and reflection of the bias voltage from the MTJ.

NbN tunnel junctions

International Nuclear Information System (INIS)

Villegier, J.C.; Vieux-Rochaz, L.; Goniche, M.; Renard, P.; Vabre, M.

1984-09-01

All-niobium nitride Josephon junctions have been prepared successfully using a new processing called SNOP: Selective Niobium (nitride) Overlap Process. Such a process involves the ''trilayer'' deposition on the whole wafer before selective patterning of the electrodes by optically controlled dry reactive ion etching. Only two photomask levels are need to define an ''overlap'' or a ''cross-type'' junction with a good accuracy. The properties of the niobium nitride films deposited by DC-magnetron sputtering and the surface oxide growth are analysed. The most critical point to obtain high quality and high gap value junctions resides in the early stage of the NbN counterelectrode growth. Some possibilities to overcome such a handicap exist even if the fabrication needs substrate temperatures below 250 0 C

Vortex trapping in Pb-alloy Josephson junctions induced by strong sputtering of the base electrode

International Nuclear Information System (INIS)

Wada, M.; Nakano, J.; Yanagawa, F.

1985-01-01

It is observed that strong rf sputtering of the Pb-alloy base electrodes causes the junctions to trap magnetic vortices and thus induces Josephson current (I/sub J/) suppression. Trapping begins to occur when the rf sputtering that removes the native thermal oxide on the base electrode is carried out prior to rf plasma oxidation. Observed large I/sub J/ suppression is presumably induced by the concentration of vortices into the sputtered area upon cooling the sample below the transition temperature. This suggests a new method of the circumvention of the vortex trapping by strongly rf sputtering the areas of the electrode other than the junction areas

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

Science.gov (United States)

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.

Limitations in cooling electrons using normal-metal-superconductor tunnel junctions.

Science.gov (United States)

Pekola, J P; Heikkilä, T T; Savin, A M; Flyktman, J T; Giazotto, F; Hekking, F W J

2004-02-06

We demonstrate both theoretically and experimentally two limiting factors in cooling electrons using biased tunnel junctions to extract heat from a normal metal into a superconductor. First, when the injection rate of electrons exceeds the internal relaxation rate in the metal to be cooled, the electrons do not obey the Fermi-Dirac distribution, and the concept of temperature cannot be applied as such. Second, at low bath temperatures, states within the gap induce anomalous heating and yield a theoretical limit of the achievable minimum temperature.

Dynamical photo-induced electronic properties of molecular junctions

Science.gov (United States)

Beltako, K.; Michelini, F.; Cavassilas, N.; Raymond, L.

2018-03-01

Nanoscale molecular-electronic devices and machines are emerging as promising functional elements, naturally flexible and efficient, for next-generation technologies. A deeper understanding of carrier dynamics in molecular junctions is expected to benefit many fields of nanoelectronics and power devices. We determine time-resolved charge current flowing at the donor-acceptor interface in molecular junctions connected to metallic electrodes by means of quantum transport simulations. The current is induced by the interaction of the donor with a Gaussian-shape femtosecond laser pulse. Effects of the molecular internal coupling, metal-molecule tunneling, and light-donor coupling on photocurrent are discussed. We then define the time-resolved local density of states which is proposed as an efficient tool to describe the absorbing molecule in contact with metallic electrodes. Non-equilibrium reorganization of hybridized molecular orbitals through the light-donor interaction gives rise to two phenomena: the dynamical Rabi shift and the appearance of Floquet-like states. Such insights into the dynamical photoelectronic structure of molecules are of strong interest for ultrafast spectroscopy and open avenues toward the possibility of analyzing and controlling the internal properties of quantum nanodevices with pump-push photocurrent spectroscopy.

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

Science.gov (United States)

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

2016-12-01

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

Closing the gap between glia and neuroblast proliferation.

Science.gov (United States)

Limmer, Stefanie; Klämbt, Christian

2014-08-11

Reporting in this issue of Developmental Cell, Spéder and Brand (2014) show that gap junctions are required in blood-brain barrier glial cells to reactivate proliferation of quiescent neuroblasts. Gap junctions allow synchronous Ca(2+) waves and control insulin-like protein Dipl6 expression and secretion to trigger neuroblast division. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of the spatially inhomogeneous gap distribution on the quasiparticle current in c-axis junctions involving d-wave superconductors with charge density waves.

Science.gov (United States)

Ekino, T; Gabovich, A M; Suan Li, Mai; Szymczak, H; Voitenko, A I

2016-11-09

The quasiparticle tunnel current J(V) between the superconducting ab-planes along the c-axis and the corresponding conductance [Formula: see text] were calculated for symmetric junctions composed of disordered d-wave layered superconductors partially gapped by charge density waves (CDWs). Here, V is the voltage. Both the checkerboard and unidirectional CDWs were considered. It was shown that the spatial spread of the CDW-pairing strength substantially smears the peculiarities of G(V) appropriate to uniform superconductors. The resulting curves G(V) become very similar to those observed for a number of cuprates in intrinsic junctions, e.g. mesas. In particular, the influence of CDWs may explain the peak-dip-hump structures frequently found for high-T c oxides.

Temperature dependence of differential conductance in Co-based Heusler alloy Co2TiSn and superconductor Pb junctions

Science.gov (United States)

Ooka, Ryutaro; Shigeta, Iduru; Umetsu, Rie Y.; Nomura, Akiko; Yubuta, Kunio; Yamauchi, Touru; Kanomata, Takeshi; Hiroi, Masahiko

2018-05-01

We investigated temperature dependence of differential conductance G (V) in planar junctions consisting of Co-based Heusler alloy Co2TiSn and superconductor Pb. Ferromagnetic Co2TiSn was predicted to be half-metal by first-principles band calculations. The spin polarization P of Co2TiSn was deduced to be 60.0% at 1.4 K by the Andreev reflection spectroscopy. The G (V) spectral shape was smeared gradually with increasing temperature and its structure was disappeared above the superconducting transition temperature Tc. Theoretical model analysis revealed that the superconducting energy gap Δ was 1.06 meV at 1.4 K and the Tc was 6.8 K , indicating that both values were suppressed from bulk values. However, the temperature dependent Δ (T) behavior was in good agreement with that of the Bardeen-Cooper-Schrieffer (BCS) theory. The experimental results exhibit that the superconductivity of Pb attached to half-metallic Co2TiSn was kept the conventional BCS mechanism characterized strong-coupling superconductors while its superconductivity was slightly suppressed by the superconducting proximity effect at the Co2TiSn/Pb interface.

Proximity effect and Andreev reflection in single-C{sub 60} junctions

Energy Technology Data Exchange (ETDEWEB)

Brand, Jonathan; Neel, Nicolas; Kroeger, Joerg [Institut fuer Physik, Technische Universitaet Ilmenau, D-98693 Ilmenau (Germany)

2016-07-01

Single C{sub 60} molecules deposited on an ultrathin oxide film on Nb(110) were investigated using a low-temperature scanning tunnelling microscope. Spectroscopy of the differential conductance (dI/dV) in the tunnelling range indicates proximity-induced superconductivity in junctions comprising the oxide layer as well as single C{sub 60} molecules. Andreev reflection is enhanced upon controlled fabrication of tip-surface contacts. With decreasing electrode separation the Bardeen-Cooper-Schrieffer energy gap gradually evolves into a zero-bias peak in dI/dV spectra reflecting the spectroscopic signature of Andreev reflection. The current-voltage characteristics of the tunnelling and contact junctions are well described by the Blonder-Tinkham-Klapwijk theory. Our spectroscopic data evidence the influence of the electrodes' atomic-scale structure on electron transport across normal metal-superconductor interfaces.

The oligodendroglial precursor cell line Oli-neu represents a cell culture system to examine functional expression of the mouse gap junction gene connexin29 (Cx29

Directory of Open Access Journals (Sweden)

Goran Christoph Söhl

2013-06-01

Full Text Available The potential gap junction forming mouse connexin29 (Cx29 protein is concomitantly expressed with connexin32 (Cx32 in peripheral myelin forming Schwann cells and together with both Cx32 and connexin47 (Cx47 in oligodendrocytes of the CNS. To study the genomic structure and functional expression of Cx29, either primary cells or cell culture systems might be selected, from which the latter are easier to cultivate. Both structure and expression of Cx29 is still not fully understood. In the mouse sciatic nerve, brain and the oligodendroglial precursor cell line Oli-neu the Cx29 gene is processed in two transcript isoforms both harbouring a unique reading frame. In contrast to Cx32 and Cx47, only Cx29 protein is abundantly expressed in undifferentiated as well as differentiated Oli-neu cells but the absence of Etbr dye transfer after microinjection concealed the function of Cx29 mediated gap junction communication between those cells. Although HeLa cells stably transfected with Cx29 or Cx29-eGFP neither demonstrated any permeability for Lucifer yellow nor for neurobiotin, blocking of Etbr uptake from the media by gap junction blockers does suppose a role of Cx29 in hemi-channel function. Thus, we conclude that, due to its high abundance of Cx29 expression and its reproducible culture conditions, the oligodendroglial precursor cell line Oli-neu might constitute an appropriate cell culture system to study molecular mechanisms or putative extracellular stimuli to functionally open Cx29 channels or hemi-channels.

Four-junction superconducting circuit

Science.gov (United States)

Qiu, Yueyin; Xiong, Wei; He, Xiao-Ling; Li, Tie-Fu; You, J. Q.

2016-01-01

We develop a theory for the quantum circuit consisting of a superconducting loop interrupted by four Josephson junctions and pierced by a magnetic flux (either static or time-dependent). In addition to the similarity with the typical three-junction flux qubit in the double-well regime, we demonstrate the difference of the four-junction circuit from its three-junction analogue, including its advantages over the latter. Moreover, the four-junction circuit in the single-well regime is also investigated. Our theory provides a tool to explore the physical properties of this four-junction superconducting circuit. PMID:27356619

Gap enhancement in phonon-irradiated superconducting tin films

International Nuclear Information System (INIS)

Miller, N.D.; Rutledge, J.E.

1982-01-01

We have measured the current-voltage (I-V) characteristics of tin-tin tunnel junctions driven out of equilibrium by a flux of near-thermal phonons from a heater. The reduced ambient temperature was T/T/sub c/ = 0.41. The nonequilibrium I-V curves are compared to equilibrium thermal I-V curves at an elevated temperature chosen to match the total number of quasiparticles. The nonequilibrium curves show a smaller current near zero bias and a larger gap than the thermal curves. This is the first experimental evidence of phonon-induced gap enhancement far below T/sub c/. The results are discussed in terms of the coupled kinetic equations of Chang and Scalapino

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-12-15

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

GAP junctional intercellular communication confers an enhanced bystander effect as well as a protective effect in HSV-TK/gancyclovir mediated cytotoxicity

International Nuclear Information System (INIS)

Wygoda, Marc R.; Rehemtulla, Alnawaz; Davis, Mary A.; Lawrence, Theodore S.

1996-01-01

Purpose/Objective: The 'Bystander Effect' is the phenomenon by which cells which are not transduced with the Herpes Simplex Virus - Thymidine Kinase (HSV-TK) gene are killed by the guanosine analog Gancyclovir (GCV) when they are nearby HSV-TK positive cells. Since currently available gene transfer technologies have a low efficiency (typically less than 10% of cells are transduced), a better understanding of the mechanism underlying the bystander effect is crucial for the success of the HSV-TK/GCV enzyme prodrug gene therapy approach. Gap junctions, which are specialized cell membrane channels allowing the passage of molecules < 1000 daltons in size directly from cell to cell, have been proposed as a possible mediator of the bystander effect. In particular, gap junctions could permit the transfer of toxic metabolites from the HSV-TK positive cells to the bystander cells. Our aim was to assess the role of gap junctional intercellular communication (GJIC) in the bystander effect. Materials and Methods: Co-culture of an HSV-TK transduced rat liver epithelial cell line (WB-TK), with either its communication competent parental cell line (WB), or an isogenic cell line differing by its communication incompetence (aB1). The ratios of effector cells (WB-TK) to bystander cells (WB or aB1), were (100(0)), (50(50)), (5(95)), or(0(100)) . These various mixed populations were exposed for 24 hours to 10μM GCV and thereafter placed at clonal density into selective media, allowing for growth of either the bystander (TK negative) cells or the effector (TK-positive) cells. Results: 1) When the effector/bystander ratio was (50(50)) the surviving fraction of the bystander cells was 3.5% and 37% for the WB and aB1, respectively. When the effector/bystander ratio was (5(95)), the surviving fraction was 51% and 65% for the WB and aB1, respectively. Either cell line (WB or aB1) cultured alone was unaffected by GCV. These results demonstrate that the bystander effect is much higher when

Dirac gap-induced graphene quantum dot in an electrostatic potential

Science.gov (United States)

Giavaras, G.; Nori, Franco

2011-04-01

A spatially modulated Dirac gap in a graphene sheet leads to charge confinement, thus enabling a graphene quantum dot to be formed without the application of external electric and magnetic fields [G. Giavaras and F. Nori, Appl. Phys. Lett. 97, 243106 (2010)]. This can be achieved provided the Dirac gap has a local minimum in which the states become localized. In this work, the physics of such a gap-induced dot is investigated in the continuum limit by solving the Dirac equation. It is shown that gap-induced confined states couple to the states introduced by an electrostatic quantum well potential. Hence the region in which the resulting hybridized states are localized can be tuned with the potential strength, an effect which involves Klein tunneling. The proposed quantum dot may be used to probe quasirelativistic effects in graphene, while the induced confined states may be useful for graphene-based nanostructures.

Magnetization-induced dynamics of a Josephson junction coupled to a nanomagnet

Science.gov (United States)

Ghosh, Roopayan; Maiti, Moitri; Shukrinov, Yury M.; Sengupta, K.

2017-11-01

We study the superconducting current of a Josephson junction (JJ) coupled to an external nanomagnet driven by a time-dependent magnetic field both without and in the presence of an external ac drive. We provide an analytic, albeit perturbative, solution for the Landau-Lifshitz (LL) equations governing the coupled JJ-nanomagnet system in the presence of a magnetic field with arbitrary time dependence oriented along the easy axis of the nanomagnet's magnetization and in the limit of weak dimensionless coupling ɛ0 between the JJ and the nanomagnet. We show the existence of Shapiro-type steps in the I -V characteristics of the JJ subjected to a voltage bias for a constant or periodically varying magnetic field and explore the effect of rotation of the magnetic field and the presence of an external ac drive on these steps. We support our analytic results with exact numerical solution of the LL equations. We also extend our results to dissipative nanomagnets by providing a perturbative solution to the Landau-Lifshitz-Gilbert (LLG) equations for weak dissipation. We study the fate of magnetization-induced Shapiro steps in the presence of dissipation both from our analytical results and via numerical solution of the coupled LLG equations. We discuss experiments which can test our theory.

Photo-Induced Electron Spin Polarization in a Narrow Band Gap Semiconductor Nanostructure

International Nuclear Information System (INIS)

Peter, A. John; Lee, Chang Woo

2012-01-01

Photo-induced spin dependent electron transmission through a narrow gap InSb/InGa x Sb 1−x semiconductor symmetric well is theoretically studied using transfer matrix formulism. The transparency of electron transmission is calculated as a function of electron energy for different concentrations of gallium. Enhanced spin-polarized photon assisted resonant tunnelling in the heterostructure due to Dresselhaus and Rashba spin-orbit coupling induced splitting of the resonant level and compressed spin-polarization are observed. Our results show that Dresselhaus spin-orbit coupling is dominant for the photon effect and the computed polarization efficiency increases with the photon effect and the gallium concentration

Nonlinearity in superconductivity and Josephson junctions

International Nuclear Information System (INIS)

Lazarides, N.

1995-01-01

Within the framework of the Bardeen, Cooper and Schrieffers (BCS) theory, the influence of anisotropy on superconducting states are investigated. Crystal anisotropy exists in un-conventional low temperature superconductors as e.g. U 1-x Th x Be 13 and in high temperature superconductors. Starting from a phenomenological pairing interaction of the electrons or holes, the BCS approach is used to derive a set of coupled nonlinear algebraic equations for the momentum dependent gap parameter. The emphasis is put on bifurcation phenomena between s-, d-wave and mixed s- and d-wave symmetry and the influence on measurable quantities as the electron specific heat, spin susceptibility and Josephson tunnelling. Pitch-fork and perturbed pitch-fork bifurcations have been found separating s- and d-wave superconducting states from mixed s- and d-wave states. The additional superconducting states give rise to jumps in the electron specific heat below the transition temperature. These jumps are rounded in the case of perturbed pitch-fork bifurcations. An experiment to measure the sign of the interlayer interaction using dc SQUIDS is suggested. The Ambegaokar-Baratoff formalism has been used for calculating the quasiparticle current and the two phase coherent tunnelling currents in a Josephson junction made of anisotropic superconductors. It is shown that anisotropy can lead to a reduction in the product of the normal resistance and the critical current. For low voltages across the junction the usual resistively shunted Josephson model can be used. Finally, bunching in long circular Josephson junctions and suppression of chaos in point junctions have been investigated. (au) 113 refs

Lysophosphatidic Acid Disrupts Junctional Integrity and Epithelial Cohesion in Ovarian Cancer Cells

Directory of Open Access Journals (Sweden)

Yueying Liu

2012-01-01

Full Text Available Ovarian cancer metastasizes via exfoliation of free-floating cells and multicellular aggregates from the primary tumor to the peritoneal cavity. A key event in EOC metastasis is disruption of cell-cell contacts via modulation of intercellular junctional components including cadherins. Ascites is rich in lysophosphatidic acid (LPA, a bioactive lipid that may promote early events in ovarian cancer dissemination. The objective of this paper was to assess the effect of LPA on E-cadherin junctional integrity. We report a loss of junctional E-cadherin in OVCAR3, OVCA429, and OVCA433 cells exposed to LPA. LPA-induced loss of E-cadherin was concentration and time dependent. LPA increased MMP-9 expression and promoted MMP-9-catalyzed E-cadherin ectodomain shedding. Blocking LPA receptor signaling inhibited MMP-9 expression and restored junctional E-cadherin staining. LPA-treated cells demonstrated a significant decrease in epithelial cohesion. Together these data support a model wherein LPA induces MMP-9 expression and MMP-9-catalyzed E-cadherin ectodomain shedding, resulting in loss of E-cadherin junctional integrity and epithelial cohesion, facilitating metastatic dissemination of ovarian cancer cells.

Voltage-dependent conductance states of a single-molecule junction

DEFF Research Database (Denmark)

Wang, Y F; Néel, N; Kröger, J

2012-01-01

Ag–Sn-phthalocyanine–Ag junctions are shown to exhibit three conductance states. While the junctions are conductive at low bias, their impedance drastically increases above a critical bias. Two-level fluctuations occur at intermediate bias. These characteristics may be used to protect a nanoscale...

Equivalent Josephson junctions

International Nuclear Information System (INIS)

Boyadzhiev, T.L.; ); Semerdzhieva, E.G.; Shukrinov, Yu.M.; Fiziko-Tekhnicheskij Inst., Dushanbe

2008-01-01

The magnetic field dependences of critical current are numerically constructed for a long Josephson junction with a shunt- or resistor-type microscopic inhomogeneities and compared to the critical curve of a junction with exponentially varying width. The numerical results show that it is possible to replace the distributed inhomogeneity of a long Josephson junction by an inhomogeneity localized at one of its ends, which has certain technological advantages. It is also shown that the critical curves of junctions with exponentially varying width and inhomogeneities localized at the ends are unaffected by the mixed fluxon-antifluxon distributions of the magnetic flux [ru

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

International Nuclear Information System (INIS)

Asami, Koji

2007-01-01

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 P j , the low-frequency (LF) relaxation curve became broader, especially at P j of 0.2-0.5, and its intensity was proportional to P j 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

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

Science.gov (United States)

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.

Charge Distribution Dependency on Gap Thickness of CMS Endcap RPC

CERN Document Server

Park, Sung K.; Lee, Kyongsei

2016-01-01

We report a systematic study of charge distribution dependency of CMS Resistive Plate Chamber (RPC) on gap thickness. Prototypes of double-gap RPCs with six different gap thickness ranging from from 1.0 to 2.0 mm in 0.2-mm steps have been built with 2-mm-thick phenolic high-pressure-laminated plates. The efficiencies of the six gaps are measured as a function of the effective high voltages. We report that the strength of the electric fields of the gap is decreased as the gap thickness is increased. The distributions of charges in six gaps are measured. The space charge effect is seen in the charge distribution at the higher voltages. The logistic function is used to fit the charge distribution data. Smaller charges can be produced within smaller gas gap. But the digitization threshold should be also lowered to utilize these smaller charges.

NbN/AlN/NbN tunnel junctions with high current density up to 54 kA/cm2

International Nuclear Information System (INIS)

Wang, Z.; Kawakami, A.; Uzawa, Y.

1997-01-01

We report on progress in the development of high current density NbN/AlN/NbN tunnel junctions for applications as submillimeter wave superconductor-insulator-superconductor mixers. A very high current density up to 54 kA/cm 2 , roughly an order of magnitude larger than any reported results for all-NbN tunnel junctions, was achieved in the junctions with about 1 nm thick AlN barriers. The magnetic field and temperature dependence of critical supercurrents were measured to investigate the Josephson tunneling behavior of critical supercurrents in the high-J c junctions. The junctions showed high-quality junction characteristics with a large gap voltage of 5 mV and sharp quasiparticle current rise (ΔV g =0.1 mV). The R sg /R N ratio was about 5 with a V m value of 14 mV measured at 4.2 K. copyright 1997 American Institute of Physics

Electronic transmission through p-n and n-p-n junctions of graphene

Energy Technology Data Exchange (ETDEWEB)

Setare, M R [Department of Science of Bijar, University of Kurdistan, Bijar (Iran, Islamic Republic of); Jahani, D, E-mail: rezakord@ipm.co, E-mail: Dariush110@gmail.co [Department of Physics, Razi University, Kermanshah (Iran, Islamic Republic of)

2010-06-23

In this paper, we first evaluate the electronic transmission of Dirac fermions into a p-n junction of gapped graphene and show that the final result depends on the sign of the refractive index, n. We also, by considering the appropriate wavefunctions in the region of the electrostatic potential, show that both transmission and the reflection probability turn out to be positive and less than unity instead of the negative transmission and higher than unity reflection coefficient commonly referred to as the Klein paradox. We then obtain the transmission probability corresponding to a special p-n junction for which there exists a region in which the low energy excitations of graphene acquire a finite mass and, interestingly, find that in this case the transmission is independent of the index of refraction, in contrast with the corresponding result for gapped graphene. We then discuss the validity of the solutions reported in some of the papers cited in this work which, considering the Buettiker formula, turn out to lead to the wrong results for conductivity.

Field angle dependence of voltage-induced ferromagnetic resonance under DC bias voltage

International Nuclear Information System (INIS)

Shiota, Yoichi; Miwa, Shinji; Tamaru, Shingo; Nozaki, Takayuki; Kubota, Hitoshi; Fukushima, Akio; Suzuki, Yoshishige; Yuasa, Shinji

2016-01-01

We studied the rectification function of microwaves in CoFeB/MgO-based magnetic tunnel junctions using voltage-induced ferromagnetic resonance (FMR). Our findings reveal that the shape of the structure of the spectrum depends on the rotation angle of the external magnetic field, providing clear evidence that FMR dynamics are excited by voltage-induced magnetic anisotropy changes. Further, enhancement of the rectified voltage was demonstrated under a DC bias voltage. In our experiments, the highest microwave detection sensitivity obtained was 350 mV/mW, at an RF frequency of 1.0 GHz and field angle of θ_H=80°, ϕ_H=0°. The experimental results correlated with those obtained via simulation, and the calculated results revealed the magnetization dynamics at the resonance state. - Highlights: • Examined voltage-induced ferromagnetic resonance (FMR) under various field angles. • FMR dynamics are excited by voltage-induced magnetic anisotropy changes. • Microwave detection sensitivity depends on input RF and elevation angle. • Microwave detection sensitivity=350 mV/mW at RF=1.0 GHz, θ_H=80°, ϕ_H=0°.

Grain size dependent optical band gap of CdI2 films

Indian Academy of Sciences (India)

Unknown

absorption data near band edge can be fitted to an indirect band gap of 3 eV. The dependence of band gap ... while to carry out the optical studies on CdI2 films in order to .... replotted as (αhν)1/2 vs hν to determine indirect gap as shown in the ...

The role of remote closure in the perception of occlusion at junctions and illusory contours.

Science.gov (United States)

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

2010-01-01

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

Self-limited plasmonic welding of silver nanowire junctions

KAUST Repository

Garnett, Erik C.

2012-02-05

Nanoscience provides many strategies to construct high-performance materials and devices, including solar cells, thermoelectrics, sensors, transistors, and transparent electrodes. Bottom-up fabrication facilitates large-scale chemical synthesis without the need for patterning and etching processes that waste material and create surface defects. However, assembly and contacting procedures still require further development. Here, we demonstrate a light-induced plasmonic nanowelding technique to assemble metallic nanowires into large interconnected networks. The small gaps that form naturally at nanowire junctions enable effective light concentration and heating at the point where the wires need to be joined together. The extreme sensitivity of the heating efficiency on the junction geometry causes the welding process to self-limit when a physical connection between the wires is made. The localized nature of the heating prevents damage to low-thermal-budget substrates such as plastics and polymer solar cells. This work opens new avenues to control light, heat and mass transport at the nanoscale. © 2012 Macmillan Publishers Limited. All rights reserved.

Vortex induced vibrations in gapped restrainted pipes

International Nuclear Information System (INIS)

Veloso, P. de A.A.; Loula, A.F.D.

1984-01-01

The vortex induced vibration problem of gapped restrained piping is solved numerically. The model proposed by Skop-Griffin is used to describe the pipe-fluid interaction. The variational formulation is obtained modeling the gapped restraints as non-linear elastic springs. The regularized problem is solved using a finite element discretization for the spatial domain. In the time domain a finite difference discretization is used for the lift coefficient equatin and a Newmark discretization for the equation of motion. (Author) [pt

Two-dimensional simulations of the superconducting proximity in superconductor-semiconductor junctions

Science.gov (United States)

Chua, Victor; Vissers, Michael; Law, Stephanie A.; Vishveshwara, Smitha; Eckstein, James N.

2015-03-01

We simulate the consequences of the superconducting proximity effect on the DC current response of a semiconductor-superconductor proximity device within the quasiclassical formalism in the diffusively disordered limit. The device is modeled on in-situ fabricated NS junctions of superconducting Nb films on metallic doped InAs films, with electrical terminals placed in an N-S-N T-junction configuration. Due to the non-collinear configuration of this three terminal device, a theoretical model based on coupled two dimensional spectral and distributional Usadel equations was constructed and numerically solved using Finite-Elements methods. In the regime of high junction conductance, our numerical results demonstrate strong temperature and spatial dependencies of the proximity induced modifications to spectral and transport properties. Such characteristics deviate strongly from usual tunnel junction behavior and aspects of this have been observed in prior experiments[arXiv:1402.6055].

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

DEFF Research Database (Denmark)

Qin, Yu; Han, Limin; Yang, Di

2018-01-01

Silver nanoparticles (AgNPs) are widely used in health and consumer products that routinely contact skin. However, the biological effects and possible mechanisms of AgNPs on skin remain unclear. Gap junctional intercellular communication (GJIC) plays a critical role in multicellular organisms to ...

Robust spin transfer torque in antiferromagnetic tunnel junctions

KAUST Repository

Saidaoui, Hamed Ben Mohamed

2017-04-18

We theoretically study the current-induced spin torque in antiferromagnetic tunnel junctions, composed of two semi-infinite antiferromagnetic layers separated by a tunnel barrier, in both clean and disordered regimes. We find that the torque enabling electrical manipulation of the Néel antiferromagnetic order parameter is out of plane, ∼n×p, while the torque competing with the antiferromagnetic exchange is in plane, ∼n×(p×n). Here, p and n are the Néel order parameter direction of the reference and free layers, respectively. Their bias dependence shows behavior similar to that in ferromagnetic tunnel junctions, the in-plane torque being mostly linear in bias, while the out-of-plane torque is quadratic. Most importantly, we find that the spin transfer torque in antiferromagnetic tunnel junctions is much more robust against disorder than that in antiferromagnetic metallic spin valves due to the tunneling nature of spin transport.

Cellular entry of G3.5 poly (amido amine) dendrimers by clathrin- and dynamin-dependent endocytosis promotes tight junctional opening in intestinal epithelia.

Science.gov (United States)

Goldberg, Deborah S; Ghandehari, Hamidreza; Swaan, Peter W

2010-08-01

This study investigates the mechanisms of G3.5 poly (amido amine) dendrimer cellular uptake, intracellular trafficking, transepithelial transport and tight junction modulation in Caco-2 cells in the context of oral drug delivery. Chemical inhibitors blocking clathrin-, caveolin- and dynamin-dependent endocytosis pathways were used to investigate the mechanisms of dendrimer cellular uptake and transport across Caco-2 cells using flow cytometry and confocal microscopy. Dendrimer cellular uptake was found to be dynamin-dependent and was reduced by both clathrin and caveolin endocytosis inhibitors, while transepithelial transport was only dependent on dynamin- and clathrin-mediated endocytosis. Dendrimers were quickly trafficked to the lysosomes after 15 min of incubation and showed increased endosomal accumulation at later time points, suggesting saturation of this pathway. Dendrimers were unable to open tight junctions in cell monolayers treated with dynasore, a selective inhibitor of dynamin, confirming that dendrimer internalization promotes tight junction modulation. G3.5 PAMAM dendrimers take advantage of several receptor-mediated endocytosis pathways for cellular entry in Caco-2 cells. Dendrimer internalization by dynamin-dependent mechanisms promotes tight junction opening, suggesting that dendrimers act on intracellular cytoskeletal proteins to modulate tight junctions, thus catalyzing their own transport via the paracellular route.

Self-induced steps in a small Josephson junction strongly coupled to a multimode resonator

DEFF Research Database (Denmark)

Larsen, A.; Jensen, H. Dalsgaard; Mygind, Jesper

1991-01-01

An equally spaced series of very large and nearly constant-voltage self-induced singularities has been observed in the dc I-V characteristics of a small Josephson tunnel junction strongly coupled to a resonant section of a superconducting transmission line. The system allows extremely high values...... of the coupling parameter. The current steps are due to subharmonic parametric excitation of the fundamental mode of the resonator loaded by the junction admittance. Using an applied magnetic field to vary the coupling parameter, we traced out half-integer steps as well as the mode steps known from more weakly...

Radiation induced deep level defects in bipolar junction transistors under various bias conditions

International Nuclear Information System (INIS)

Liu, Chaoming; Yang, Jianqun; Li, Xingji; Ma, Guoliang; Xiao, Liyi; Bollmann, Joachim

2015-01-01

Bipolar junction transistor (BJT) is sensitive to ionization and displacement radiation effects in space. In this paper, 35 MeV Si ions were used as irradiation source to research the radiation damage on NPN and PNP bipolar transistors. The changing of electrical parameters of transistors was in situ measured with increasing irradiation fluence of 35 MeV Si ions. Using deep level transient spectroscopy (DLTS), defects in the bipolar junction transistors under various bias conditions are measured after irradiation. Based on the in situ electrical measurement and DLTS spectra, it is clearly that the bias conditions can affect the concentration of deep level defects, and the radiation damage induced by heavy ions.

Spin-dependent tunnelling in magnetic tunnel junctions

International Nuclear Information System (INIS)

Tsymbal, Evgeny Y; Mryasov, Oleg N; LeClair, Patrick R

2003-01-01

The phenomenon of electron tunnelling has been known since the advent of quantum mechanics, but continues to enrich our understanding of many fields of physics, as well as creating sub-fields on its own. Spin-dependent tunnelling (SDT) in magnetic tunnel junctions (MTJs) has recently aroused enormous interest and has developed in a vigorous field of research. The large tunnelling magnetoresistance (TMR) observed in MTJs garnered much attention due to possible applications in non-volatile random-access memories and next-generation magnetic field sensors. This led to a number of fundamental questions regarding the phenomenon of SDT. In this review article we present an overview of this field of research. We discuss various factors that control the spin polarization and magnetoresistance in MTJs. Starting from early experiments on SDT and their interpretation, we consider thereafter recent experiments and models which highlight the role of the electronic structure of the ferromagnets, the insulating layer, and the ferromagnet/insulator interfaces. We also discuss the role of disorder in the barrier and in the ferromagnetic electrodes and their influence on TMR. (topical review)

Electronic properties of single-molecule junction: Effect of the molecular distortion

International Nuclear Information System (INIS)

Gao, W.; Zhao, M.; Jiang, Q.

2009-01-01

For a model system consisting of a benzenedithio (BDT) molecule sandwiched between two Au plates, the electronic properties as a function of different BDT geometry are investigated using density functional theory. The distorted BDT structures are got through stretching the electrode distance. The corresponding electronic properties, including the spatial distribution of the frontier orbits, the gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital levels and density of states at the Fermi energy are determined. It reveals that the molecular distortion essentially determines electronic structures. The result should be beneficial to understand the stress-dependent or structure-dependent transport mechanism of electrons of the BDT junction.

NbN-AlN-NbN Josephson junctions on different substrates

Energy Technology Data Exchange (ETDEWEB)

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

2016-07-01

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

Small--radiation-amplitude dynamical voltage model of an irradiated, externally unbiased Josephson tunnel junction

International Nuclear Information System (INIS)

McAdory, R.T. Jr.

1988-01-01

A theory is presented for the nonequilibrium voltage states of an irradiated Josephson junction shunted by an external resistor but with no external current or voltage biasing. This device, referred to as a free-running Josephson junction, is modeled in a small--radiation-amplitude, deterministic regime extending the previous work of Shenoy and Agarwal. The time-averaged induced voltage is treated as a dynamical variable, the external radiation is modeled as a current source, and the induced junction-radiation vector potential, with and without a mode structure, is treated to first order in the driving currents. A dynamical equation for the time-averaged induced voltage yields a (nonequilibrium) steady-state relation between the time-averaged induced voltage and the incident radiation amplitude valid for a wide range of voltages, including zero. Regions of bistability occur in the voltage--versus--incident-amplitude curves, some of which are dependent on the external resistor. The zero-voltage state breaks down, as the external radiation amplitude is increased, at a critical value of the incident-radiation amplitude inversely proportional to the external resistance

Cation substitution induced blue-shift of optical band gap

Indian Academy of Sciences (India)

Cation substitution induced blue-shift of optical band gap in nanocrystalline Zn ( 1 − x ) Ca x O thin films deposited by sol–gel dip coating technique ... thin films giving 13.03% enhancement in theenergy gap value due to the electronic perturbation caused by cation substitution as well as deterioration in crystallinity.

Chromosomal instability can be induced by the formation of breakage-prone chromosome rearrangement junctions

International Nuclear Information System (INIS)

Allen, R.N.; Ritter, L.; Moore, S.R.; Grosovsky, A.J.

2003-01-01

Full text: Studies in our lab have led to the hypothesis that chromosomal rearrangements can generate novel breakage-prone sites, resulting in chromosomal instability acting predominantly in cis. For example, specific breakage of large blocks of centromeric region heterochromatin on chromosome 16q by treatment with 2,6-diaminopurine (DAP) is associated with repeated rearrangement of chromosome 16q during outgrowth of DAP-treated clones, thereby establishing a link between the initial site of damage and the occurrence of persistent chromosomal instability. Similarly, karyotypic analysis of gamma ray induced instability demonstrated that chromosomal rearrangements in sub-clones were significantly clustered near the site of previously identified chromosomal rearrangement junctions in unstable parental clones. This study investigates the hypothesis that integration of transfected sequences into host chromosomes could create breakage-prone junction regions and persistent genomic instability without exposure to DNA-damage agents. These junctions may mimic the unstable chromosomal rearrangements induced by DAP or radiation, and thus provide a test of the broader hypothesis that instability can to some extent be attributed to the formation of novel chromosomal breakage hot spots. These experiments were performed using human-hamster hybrid AL cells containing a single human chromosome 11, which was used to monitor instability in a chromosomal painting assay. AL cells were transfected with a 2.5 Kb fragment containing multiple copies of the 180 bp human alpha heterochromatic repeat, which resulted in chromosomal instability in 41% of the transfected clones. Parallel exposure to gamma-radiation resulted in a similar level of chromosomal instability, although control transfections with plasmid alone did not lead to karyotypic instability. Chromosomal instability induced by integration of alpha heterochromatic repeats was also frequently associated with delayed reproductive

Inductively Coupled Plasma-Induced Etch Damage of GaN p-n Junctions

International Nuclear Information System (INIS)

SHUL, RANDY J.; ZHANG, LEI; BACA, ALBERT G.; WILLISON, CHRISTI LEE; HAN, JUNG; PEARTON, S.J.; REN, F.

1999-01-01

Plasma-induced etch damage can degrade the electrical and optical performance of III-V nitride electronic and photonic devices. We have investigated the etch-induced damage of an Inductively Coupled Plasma (ICP) etch system on the electrical performance of mesa-isolated GaN pn-junction diodes. GaN p-i-n mesa diodes were formed by Cl 2 /BCl 3 /Ar ICP etching under different plasma conditions. The reverse leakage current in the mesa diodes showed a strong relationship to chamber pressure, ion energy, and plasma flux. Plasma induced damage was minimized at moderate flux conditions (≤ 500 W), pressures ≥2 mTorr, and at ion energies below approximately -275 V

Molecular Diffusion through Cyanobacterial Septal Junctions

Directory of Open Access Journals (Sweden)

Mercedes Nieves-Morión

2017-01-01

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

Stereoelectronic Effect-Induced Conductance Switching in Aromatic Chain Single-Molecule Junctions.

Science.gov (United States)

Xin, Na; Wang, Jinying; Jia, Chuancheng; Liu, Zitong; Zhang, Xisha; Yu, Chenmin; Li, Mingliang; Wang, Shuopei; Gong, Yao; Sun, Hantao; Zhang, Guanxin; Liu, Zhirong; Zhang, Guangyu; Liao, Jianhui; Zhang, Deqing; Guo, Xuefeng

2017-02-08

Biphenyl, as the elementary unit of organic functional materials, has been widely used in electronic and optoelectronic devices. However, over decades little has been fundamentally understood regarding how the intramolecular conformation of biphenyl dynamically affects its transport properties at the single-molecule level. Here, we establish the stereoelectronic effect of biphenyl on its electrical conductance based on the platform of graphene-molecule single-molecule junctions, where a specifically designed hexaphenyl aromatic chain molecule is covalently sandwiched between nanogapped graphene point contacts to create stable single-molecule junctions. Both theoretical and temperature-dependent experimental results consistently demonstrate that phenyl twisting in the aromatic chain molecule produces different microstates with different degrees of conjugation, thus leading to stochastic switching between high- and low-conductance states. These investigations offer new molecular design insights into building functional single-molecule electrical devices.

Niobium nitride Josephson tunnel junctions with magnesium oxide barriers

International Nuclear Information System (INIS)

Shoji, A.; Aoyagi, M.; Kosaka, S.; Shinoki, F.; Hayakawa, H.

1985-01-01

Niobium nitride-niobium nitride Josephson tunnel junctions have been fabricated using amorphous magnesium oxide (a-MgO) films as barriers. These junctions have excellent tunneling characteristics. For example, a large gap voltage (V/sub g/ = 5.1 mV), a large product of the maximum critical current and the normal tunneling resistance (I/sub c/R/sub n/ = 3.25 mV), and a small subgap leakage current (V/sub m/ = 45 mV, measured at 3 mV) have been obtained for a NbN/a-MgO/NbN junction. The critical current of this junction remains finite up to 14.5 K

Estrogenic compounds inhibit gap junctional intercellular communication in mouse Leydig TM3 cells

International Nuclear Information System (INIS)

Iwase, Yumiko; Fukata, Hideki; Mori, Chisato

2006-01-01

Some estrogenic compounds are reported to cause testicular disorders in humans and/or experimental animals by direct action on Leydig cells. In carcinogenesis and normal development, gap junctional intercellular communication (GJIC) plays an essential role in maintaining homeostasis. In this study, we examine the effects of diethylstilbestrol (DES, a synthetic estrogen), 17β-estradiol (E 2 , a natural estrogen), and genistein (GEN, a phytoestrogen) on GJIC between mouse Leydig TM3 cells using Lucifer yellow microinjection. The three compounds tested produced GJIC inhibition in the TM3 cells after 24 h. Gradually, 10 μM DES began to inhibit GJIC for 24 h and this effect was observed until 72 h. On the other hand, both 20 μM E 2 and 25 μM GEN rapidly inhibited GJIC in 6 h and 2 h, respectively. The effects continued until 24 h, but weakened by 72 h. Furthermore, a combined effect at μM level between DES and E 2 on GJIC inhibition was observed, but not between GEN and E 2 . DES and E 2 showed GJIC inhibition at low dose levels (nearly physiological estrogen levels) after 72 h, but GEN did not. DES-induced GJIC inhibition at 10 pM and 10 μM was completely counteracted by ICI 182,780 (ICl), an estrogen receptor antagonist. On the other hand, the inhibitory effects on GJIC with E 2 (10 pM and 20 μM) and GEN (25 μM) were partially blocked by ICI or calphostin C, a protein kinase C (PKC) inhibitor, and were completely blocked by the combination of ICI and calphostin C. These results demonstrate that DES inhibits GJIC between Leydig cells via the estrogen receptor (ER), and that E 2 and GEN inhibit GJIC via ER and PKC. These estrogenic compounds may have different individual nongenotoxic mechanism including PKC pathway on testicular carcinogenesis or development

Thermal stability study of the insulator layer in NiFe/CoFe/Al2O3/Co spin-dependent tunnel junction

International Nuclear Information System (INIS)

Liao, C.C.; Ho, C.H.; Huang, R.-T.; Chen, F.-R.; Kai, J.J.; Chen, L.-C.; Lin, M.-T.; Yao, Y.D.

2002-01-01

Spin-dependent tunnel junction, NiFe/CoFe/Al 2 O 3 /Co//Si, was fabricated to investigate the thermal stability induced diffusion behaviors. The interfacial diffusion causes the degradation of the ratio of the TMR, the enhancement of the switching field of the two magnetic electrodes, the thickness decrease of the insulator layer, and the increase of the interfacial roughness. The outward diffusion of oxygen from the insulator layer is faster than that of aluminum for samples annealed below 400 deg. C. The degradation of the ratio of TMR is attributed to the disturbance of the spin polarization in the magnetic layers, and the increase of the pinholes and spin-flip effect in the insulator layer. The relative roughness between the two interfaces of the insulator induces the surface magnetic dipoles, and hence, increases the switching field of the ferromagnetic electrodes

Evaluations of two-phase natural circulation flow induced in the reactor vessel annular gap under ERVC conditions

Energy Technology Data Exchange (ETDEWEB)

Ha, Kwang Soon, E-mail: tomo@kaeri.re.kr [Korea Atomic Energy Research Institute, 1045 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Cheung, Fan-Bill [The Pennsylvania State University, University Park, PA 16802 (United States); Park, Rae Joon; Kim, Sang Baik [Korea Atomic Energy Research Institute, 1045 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of)

2012-12-15

Highlights: Black-Right-Pointing-Pointer Two-phase natural circulation flow induced in insulation gap was investigated. Black-Right-Pointing-Pointer Half-scaled non-heating experiments were performed to evaluate flow behavior. Black-Right-Pointing-Pointer The loop-integrated momentum equation was formulated and solved asymptotically. Black-Right-Pointing-Pointer First-order approximate solution was obtained and agreed with experimental data. - Abstract: The process of two-phase natural circulation flow induced in the annular gap between the reactor vessel and the insulation under external reactor vessel cooling conditions was investigated experimentally and analytically in this study. HERMES-HALF experiments were performed to observe and quantify the induced two-phase natural circulation flow in the annular gap. A half-scaled non-heating experimental facility was designed by utilizing the results of a scaling analysis to simulate the APR1400 reactor and its insulation system. The behavior of the boiling-induced two-phase natural circulation flow in the annular gap was observed, and the liquid mass flow rates driven by the natural circulation loop and the void fraction distribution were measured. Direct flow visualization revealed that choking would occur under certain flow conditions in the minimum gap region near the shear keys. Specifically, large recirculation flows were observed in the minimum gap region for large air injection rates and small outlet areas. Under such conditions, the injected air could not pass through the minimum gap region, resulting in the occurrence of choking near the minimum gap with a periodical air back flow being generated. Therefore, a design modification of the minimum gap region needs to be done to facilitate steam venting and to prevent choking from occurring. To complement the HERMES-HALF experimental effort, an analytical study of the dependence of the induced natural circulation mass flow rate on the inlet area and the

Evidence for differential changes of junctional complex proteins in murine neurocysticercosis dependent upon CNS vasculature.

Science.gov (United States)

Alvarez, Jorge I; Teale, Judy M

2007-09-12

The delicate balance required to maintain homeostasis of the central nervous system (CNS) is controlled by the blood-brain barrier (BBB). Upon injury, the BBB is disrupted compromising the CNS. BBB disruption has been represented as a uniform event. However, our group has shown in a murine model of neurocysticercosis (NCC) that BBB disruption varies depending upon the anatomical site/vascular bed analyzed. In this study further understanding of the mechanisms of BBB disruption was explored in blood vessels located in leptomeninges (pial vessels) and brain parenchyma (parenchymal vessels) by examining the expression of junctional complex proteins in murine brain infected with Mesocestoides corti. Both pial and parenchymal vessels from mock infected animals showed significant colocalization of junctional proteins and displayed an organized architecture. Upon infection, the patterned organization was disrupted and in some cases, particular tight junction and adherens junction proteins were undetectable or appeared to be undergoing proteolysis. The extent and timing of these changes differed between both types of vessels (pial vessel disruption within days versus weeks for parenchymal vessels). To approach potential mechanisms, the expression and activity of matrix metalloproteinase-9 (MMP-9) were evaluated by in situ zymography. The results indicated an increase in MMP-9 activity at sites of BBB disruption exhibiting leukocyte infiltration. Moreover, the timing of MMP activity in pial and parenchymal vessels correlated with the timing of permeability disruption. Thus, breakdown of the BBB is a mutable process despite the similar structure of the junctional complex between pial and parenchymal vessels and involvement of MMP activity.

Fabrication of Josephson Junction without shadow evaporation

Science.gov (United States)

Wu, Xian; Ku, Hsiangsheng; Long, Junling; Pappas, David

We developed a new method of fabricating Josephson Junction (Al/AlOX/Al) without shadow evaporation. Statistics from room temperature junction resistance and measurement of qubits are presented. Unlike the traditional ``Dolan Bridge'' technique, this method requires two individual lithographies and straight evaporations of Al. Argon RF plasma is used to remove native AlOX after the first evaporation, followed by oxidation and second Al evaporation. Junction resistance measured at room temperature shows linear dependence on Pox (oxidation pressure), √{tox} (oxidation time), and inverse proportional to junction area. We have seen 100% yield of qubits made with this method. This method is promising because it eliminates angle dependence during Junction fabrication, facilitates large scale qubits fabrication.

Fabrication of sandwich-type MgB{sub 2}/Boron/MgB{sub 2} Josephson junctions with rapid annealing method

Energy Technology Data Exchange (ETDEWEB)

Zhang, Song; Wang, Xu; Ma, Junli; Cui, Ruirui; Deng, Chaoyong, E-mail: cydeng@gzu.edu.cn

2015-11-15

Sandwich-type MgB{sub 2}/Boron/MgB{sub 2} Josephson junctions were fabricated using magnetron sputtering system. The rapid-anneal process was adopted to replace traditional way of annealing, trying to solve the problem of interdiffusion and oxidation with multilayer films. The boron film was used as barrier layer to avoid the introduction of impurities and improve reproducibility of the junctions. The bottom MgB{sub 2} thin films deposited on c-plane sapphire substrate exhibits a critical temperature T{sub C} of 37.5 K and critical current density J{sub C} at 5 K of 8.7 × 10{sup 6} A cm{sup −2}. From the XRD pattern, the bottom MgB{sub 2} thin film shows c-axis orientation, whereas the top MgB{sub 2} became polycrystalline as Boron barrier layer grown thicker. Therefore, all junction samples show lower T{sub C} than single MgB{sub 2} thin film. The junctions exhibit excellent quasiparticle characteristics with ideal dependence on temperature and Boron barrier thickness. Subharmonic gap structure was appeared in conductance characteristics, which was attributed to the multiple Andreev reflections (MAR). The result demonstrates great promise of this new fabrication technology for MgB{sub 2} Josephson junction fabrication. - Highlights: • Sandwich-type MgB{sub 2}/Boron/MgB{sub 2} Josephson junctions were fabricated. • The junctions were annealed after deposition with the rapid-anneal process. • The highest critical current is 25.3 mA at 5 K and remains non-zero near 25 K. • Subharmonic gap features can be observed in the dI/dV – V curves.

Large spin accumulation due to spin-charge coupling across a break-junction

Science.gov (United States)

Chen, Shuhan; Zou, Han; Chui, Siu-Tat; Ji, Yi

2013-03-01

We investigate large spin signals in break-junction nonlocal spin valves (NLSV). The break-junction is a nanometer-sized vacuum tunneling gap between the spin detector and the nonmagnetic channel, formed by electro-static discharge. The spin signals can be either inverted or non-inverted and the magnitudes are much larger than those of standard NLSV. Spin signals with high percentage values (10% - 0%) have been observed. When the frequency of the a.c. modulation is varied, the absolute magnitudes of signals remain the same although the percentage values change. These observations affirm the nonlocal nature of the measurements and rule out local magnetoresistive effects. Owing to the spin-charge coupling across the break-junction, the spin accumulation in a ferromagnet splits into two terms. One term decays on the charge screening length (0.1 nm) and the other decays on the spin diffusion length (10 nm nm). The magnitude of the former is proportional to the resistance of the junction. Therefore a highly resistive break-junction leads to a large spin accumulation and thereby a large spin signal. The signs of the spin signal are determined by the relationship between spin-dependent conductivities, diffusion constants, and density of states of the ferromagnet. This work was supported by US DOE grant No. DE-FG02-07ER46374.

p\text{-}n Junction Dynamics Induced in a Graphene Channel by Ferroelectric-Domain Motion in the Substrate

Energy Technology Data Exchange (ETDEWEB)

Kurchak, Anatolii I. [National Academy of Sciences of Ukraine (NASU), Kiev (Ukraine); Eliseev, Eugene A. [National Academy of Sciences of Ukraine (NASU), Kiev (Ukraine); Kalinin, Sergei V. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Strikha, Maksym V. [National Academy of Sciences of Ukraine (NASU), Kiev (Ukraine); Taras Shevchenko Kyiv National Univ., Kyiv (Ukraine); Morozovska, Anna N. [National Academy of Sciences of Ukraine (NASU), Kiev (Ukraine)

2017-08-30

The p - n junction dynamics induced in a graphene channel by stripe-domain nucleation, motion, and reversal in a ferroelectric substrate is explored using a self-consistent approach based on Landau-Ginzburg-Devonshire phenomenology combined with classical electrostatics. Relatively low gate voltages are required to induce the hysteresis of ferroelectric polarization and graphene charge in response to the periodic gate voltage. Pronounced nonlinear hysteresis of graphene conductance with a wide memory window corresponds to high amplitudes of gate voltage. Also, we reveal the extrinsic size effect in the dependence of the graphene-channel conductivity on its length. We predict that the top-gate–dielectric-layer–graphene-channel–ferroelectric-substrate nanostructure considered here can be a promising candidate for the fabrication of the next generation of modulators and rectifiers based on the graphene p - n junctions.

Current-induced magnetization switching in atom-thick tungsten engineered perpendicular magnetic tunnel junctions with large tunnel magnetoresistance.

Science.gov (United States)

Wang, Mengxing; Cai, Wenlong; Cao, Kaihua; Zhou, Jiaqi; Wrona, Jerzy; Peng, Shouzhong; Yang, Huaiwen; Wei, Jiaqi; Kang, Wang; Zhang, Youguang; Langer, Jürgen; Ocker, Berthold; Fert, Albert; Zhao, Weisheng

2018-02-14

Perpendicular magnetic tunnel junctions based on MgO/CoFeB structures are of particular interest for magnetic random-access memories because of their excellent thermal stability, scaling potential, and power dissipation. However, the major challenge of current-induced switching in the nanopillars with both a large tunnel magnetoresistance ratio and a low junction resistance is still to be met. Here, we report spin transfer torque switching in nano-scale perpendicular magnetic tunnel junctions with a magnetoresistance ratio up to 249% and a resistance area product as low as 7.0 Ω µm 2 , which consists of atom-thick W layers and double MgO/CoFeB interfaces. The efficient resonant tunnelling transmission induced by the atom-thick W layers could contribute to the larger magnetoresistance ratio than conventional structures with Ta layers, in addition to the robustness of W layers against high-temperature diffusion during annealing. The critical switching current density could be lower than 3.0 MA cm -2 for devices with a 45-nm radius.

Current-induced forces: a new mechanism to induce negative differential resistance and current-switching effect in molecular junctions

Science.gov (United States)

Gu, Lei; Fu, Hua-Hua

2015-12-01

Current-induced forces can excite molecules, polymers and other low-dimensional materials, which in turn leads to an effective gate voltage through Holstein interaction. Here, by taking a short asymmetric DNA junction as an example, and using the Langevin approach, we find that when suppression of charge transport by the effective gate voltage surpasses the current increase from an elevated voltage bias, the current-voltage (I-V) curves display strong negative differential resistance (NDR) and perfect current-switching characteristics. The asymmetric DNA chain differs in mechanical stability under inverse voltages and the I-V curve is asymmetric about inverse biases, which can be used to understand recent transport experiments on DNA chains, and meanwhile provides a new strategy to realize NDR in molecular junctions and other low-dimensional quantum systems.

Current-induced forces: a new mechanism to induce negative differential resistance and current-switching effect in molecular junctions

International Nuclear Information System (INIS)

Gu, Lei; Fu, Hua-Hua

2015-01-01

Current-induced forces can excite molecules, polymers and other low-dimensional materials, which in turn leads to an effective gate voltage through Holstein interaction. Here, by taking a short asymmetric DNA junction as an example, and using the Langevin approach, we find that when suppression of charge transport by the effective gate voltage surpasses the current increase from an elevated voltage bias, the current-voltage (I–V) curves display strong negative differential resistance (NDR) and perfect current-switching characteristics. The asymmetric DNA chain differs in mechanical stability under inverse voltages and the I–V curve is asymmetric about inverse biases, which can be used to understand recent transport experiments on DNA chains, and meanwhile provides a new strategy to realize NDR in molecular junctions and other low-dimensional quantum systems. (paper)

Superconducting β-ZrNClx probed by scanning-tunnelling and break-junction spectroscopy

International Nuclear Information System (INIS)

Ekino, Toshikazu; Sugimoto, Akira; Gabovich, Alexander M.; Zheng, Zhanfeng; Yamanaka, Shoji

2013-01-01

Highlights: •STM/STS combined with break-junction tunnelling spectroscopy (BJTS) on β-ZrNCl. •STM image on the ab plane shows triangular atomic lattice spots with a period of 0.36 nm. •The gap peaks are widely distributed (Δ p–p = 9–28 meV)over the area of 100 nm 2 . •Average gap ratio 2Δ/k B T c ∼ 10 is confirmed by both STS and BJTS. -- Abstract: Superconducting layered compound β-ZrNCl x (x = 0.7) with the critical temperature T c = 13–14 K was investigated by means of scanning tunnelling microscopy/spectroscopy. The single-crystal domain facet of ∼100 μm 2 in the c-axis-oriented polycrystal was used as a probing surface. The STM image at 4.9 K shows triangular atomic lattice spots with the period of ∼0.36 nm, which agrees with the X-ray diffraction measurements. The STS measurements of the local conductance, dI/dV, exhibit broadened gap structures with a substantial distribution of the gap-edge values. Most frequently observed peak-to-peak value of ∼20 mV is remarkably similar to the superconducting gap edge of the isostructural β-HfNCl x with T c = 24 K. Temperature, T, dependence of the dI/dV shows that the gap structure disappears above T c ∼ 13 K. Fitting of the dI/dV curve by the broadened BCS density of states leads to the superconducting gap of 2Δ(4.9 K) = 11–13 meV. This is in accordance with our former break-junction data confirming the intrinsic character of the previously obtained extremely large gap to T c ratio 2Δ(0)/k B T c ≈ 10 (k B is the Boltzmann constant), thereby pointing to the unusual superconducting properties of this compound

Dynamics of fractional vortices in long Josephson junctions; Dynamik fraktionaler Flusswirbel in langen Josephsonkontakten

Energy Technology Data Exchange (ETDEWEB)

Gaber, Tobias

2007-07-01

In this thesis static and dynamic properties of fractional vortices in long Josephson junctions are investigated. Fractional vortices are circulating supercurrents similar to the well-known Josephson fluxons. Yet, they show the distinguishing property of carrying only a fraction of the magnetic flux quantum. Fractional vortices are interesting non-linear objects. They spontaneously appear and are pinned at the phase discontinuity points of so called 0-{kappa} junctions but can be bend or flipped by external forces like bias currents or magnetic fields. 0-{kappa} junctions and fractional vortices are generalizations of the well-known 0-{pi} junctions and semifluxons, where not only phase jumps of pi but arbitrary values denoted by kappa are considered. By using so-called artificial 0-{kappa} junctions that are based on standard Nb-AlO{sub x}-Nb technology the classical dynamics of fractional vortices has been investigated experimentally for the very first time. Here, half-integer zero field steps could be observed. These voltage steps on the junction's current-voltage characteristics correspond to the periodic flipping/hopping of fractional vortices. In addition, the oscillatory eigenmodes of fractional vortices were investigated. In contrast to fluxons fractional vortices have an oscillatory eigenmode with a frequency within the plasma gap. Using resonance spectroscopy the dependence of the eigenmode frequency on the flux carried by the vortex and an applied bias current was determined. (orig.)

Electron Elevator: Excitations across the Band Gap via a Dynamical Gap State.

Science.gov (United States)

Lim, A; Foulkes, W M C; Horsfield, A P; Mason, D R; Schleife, A; Draeger, E W; Correa, A A

2016-01-29

We use time-dependent density functional theory to study self-irradiated Si. We calculate the electronic stopping power of Si in Si by evaluating the energy transferred to the electrons per unit path length by an ion of kinetic energy from 1 eV to 100 keV moving through the host. Electronic stopping is found to be significant below the threshold velocity normally identified with transitions across the band gap. A structured crossover at low velocity exists in place of a hard threshold. An analysis of the time dependence of the transition rates using coupled linear rate equations enables one of the excitation mechanisms to be clearly identified: a defect state induced in the gap by the moving ion acts like an elevator and carries electrons across the band gap.

Many-junction photovoltaic device performance under non-uniform high-concentration illumination

Science.gov (United States)

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

2017-09-01

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

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

Science.gov (United States)

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

Effect of cAMP derivates on assembly and maintenance of tight junctions in human umbilical vein endothelial cells

Directory of Open Access Journals (Sweden)

Beese Michaela

2010-09-01

Full Text Available Abstract Background Endothelial tight and adherens junctions control a variety of physiological processes like adhesion, paracellular transport of solutes or trafficking of activated leukocytes. Formation and maintenance of endothelial junctions largely depend on the microenvironment of the specific vascular bed and on interactions of the endothelium with adjacent cell types. Consequently, primary cultures of endothelial cells often lose their specific junctional pattern and fail to establish tight monolayer in vitro. This is also true for endothelial cells isolated from the vein of human umbilical cords (HUVEC which are widely used as model for endothelial cell-related studies. Results We here compared the effect of cyclic 3'-5'-adenosine monophosphate (cAMP and its derivates on formation and stabilization of tight junctions and on alterations in paracellular permeability in HUVEC. We demonstrated by light and confocal laser microscopy that for shorter time periods the sodium salt of 8-bromoadenosine-cAMP (8-Br-cAMP/Na and for longer incubation periods 8-(4-chlorophenylthio-cAMP (pCPT-cAMP exerted the greatest effects of all compounds tested here on formation of continuous tight junction strands in HUVEC. We further demonstrated that although all compounds induced protein kinase A-dependent expression of the tight junction proteins claudin-5 and occludin only pCPT-cAMP slightly enhanced paracellular barrier functions. Moreover, we showed that pCPT-cAMP and 8-Br-cAMP/Na induced expression and membrane translocation of tricellulin. Conclusions pCPT-cAMP and, to a lesser extend, 8-Br-cAMP/Na improved formation of continuous tight junction strands and decreased paracellular permeability in primary HUVEC. We concluded that under these conditions HUVEC represent a feasible in vitro model to study formation and disassembly of endothelial tight junctions and to characterize tight junction-associated proteins

Wh-filler-gap dependency formation guides reflexive antecedent search

Directory of Open Access Journals (Sweden)

Michael eFrazier

2015-10-01

Full Text Available Prior studies on online sentence processing have shown that the parser can resolve non-local dependencies rapidly and accurately. This study investigates the interaction between the processing of two such non-local dependencies: wh-filler-gap dependencies (WhFGD and reflexive-antecedent dependencies. We show that reflexive-antecedent dependency resolution is sensitive to the presence of a WhFGD, and argue that the filler-gap dependency established by WhFGD resolution is selected online as the antecedent of a reflexive dependency. We investigate the processing of constructions like (1, where two NPs might be possible antecedents for the reflexive, namely which cowgirl and Mary. Even though Mary is linearly closer to the reflexive, the only grammatically licit antecedent for the reflexive is the more distant wh-NP, which cowgirl. 1. Which cowgirl did Mary expect to have injured herself due to negligence?Four eye-tracking text-reading experiments were conducted on examples like (1, differing in whether the embedded clause was non-finite (1 and 3 or finite (2 and 4, and in whether the tail of the wh-dependency intervened between the reflexive and its closest overt antecedent (1 and 2 or the wh-dependency was associated with a position earlier in the sentence (3 and 4.The results of Experiments 1 and 2 indicate the parser accesses the result of WhFGD formation during reflexive antecedent search. The resolution of a wh-dependency alters the representation that reflexive antecedent search operates over, allowing the grammatical but linearly distant antecedent to be accessed rapidly. In the absence of a long-distance WhFGD (Exp. 3 and 4, wh-NPs were not found to impact reading times of the reflexive, indicating that the parser's ability to select distant wh-NPs as reflexive antecedents crucially involves syntactic structure.

Bipolar cell gap junctions serve major signaling pathways in the human retina.

Science.gov (United States)

Kántor, Orsolya; Varga, Alexandra; Nitschke, Roland; Naumann, Angela; Énzsöly, Anna; Lukáts, Ákos; Szabó, Arnold; Németh, János; Völgyi, Béla

2017-08-01

Connexin36 (Cx36) constituent gap junctions (GJ) throughout the brain connect neurons into functional syncytia. In the retina they underlie the transmission, averaging and correlation of signals prior conveying visual information to the brain. This is the first study that describes retinal bipolar cell (BC) GJs in the human inner retina, whose function is enigmatic even in the examined animal models. Furthermore, a number of unique features (e.g. fovea, trichromacy, midget system) necessitate a reexamination of the animal model results in the human retina. Well-preserved postmortem human samples of this study are allowed to identify Cx36 expressing BCs neurochemically. Results reveal that both rod and cone pathway interneurons display strong Cx36 expression. Rod BC inputs to AII amacrine cells (AC) appear in juxtaposition to AII GJs, thus suggesting a strategic AII cell targeting by rod BCs. Cone BCs serving midget, parasol or koniocellular signaling pathways display a wealth of Cx36 expression to form homologously coupled arrays. In addition, they also establish heterologous GJ contacts to serve an exchange of information between parallel signaling streams. Interestingly, a prominent Cx36 expression was exhibited by midget system BCs that appear to maintain intimate contacts with bistratified BCs serving other pathways. These findings suggest that BC GJs in parallel signaling streams serve both an intra- and inter-pathway exchange of signals in the human retina.

Size dependence of magnetization reversal of ring shaped magnetic tunnel junction

International Nuclear Information System (INIS)

Chen, C.C.; Kuo, C.Y.; Chang, Y.C.; Chang, C.C.; Horng, Lance; Wu, Teho; Chern, G.; Huang, C.Y.; Tsunoda, M.; Takahashi, M.; Wu, J.C.

2007-01-01

The size dependence of magnetization reversal of magnetic tunnel junction (MTJ) rings has been investigated. The MTJ rings, with outer diameter of 4, 2 and 1 μm and inner diameter of 1.5, 1 and 0.5 μm were fabricated by a top-down technique. The magnetoresistance curves manifest all of the magnetic domain configurations during magnetization reversal in different sized rings. Various transition processes were observed, such as four transition, three transition and two transition in the largest, middle and smallest MTJ ring, respectively. Furthermore, the biasing fields observed from major loops decrease with decreasing size, which may result from edge roughness produced in the ion-milling process

Theoretical and experimental investigations on synchronization in many-junction arrays of HTSC Josephson junctions. Final report

International Nuclear Information System (INIS)

Seidel, P.; Heinz, E.; Pfuch, A.; Machalett, F.; Krech, W.; Basler, M.

1996-06-01

Different many-junction arrays of Josephson junctions were studied theoretically to analyse the mechanisms of synchronization, the influence of internal and external parameters and the maximal allowed spread of parameters for the single junctions. Concepts to realize arrays using standard high-T c superconductor technology were created, e.g. the new arrangement of multijunction superconducting loops (MSL). First experimental results show the relevance of this concept. Intrinsic one-dimensional arrays in thin film technology were prepared as mesas out of Bi or Tl 2212 films. to characterize HTSC Josephson junctions methods based on the analysis of microwave-induced steps were developed. (orig.) [de

Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes

Directory of Open Access Journals (Sweden)

Götz Pilarczyk

2016-01-01

Full Text Available The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds.

The role of engineered materials in superconducting tunnel junction X-ray detectors - Suppression of quasiparticle recombination losses via a phononic band gap

Science.gov (United States)

Rippert, Edward D.; Ketterson, John B.; Chen, Jun; Song, Shenian; Lomatch, Susanne; Maglic, Stevan R.; Thomas, Christopher; Cheida, M. A.; Ulmer, Melville P.

1992-01-01

An engineered structure is proposed that can alleviate quasi-particle recombination losses via the existence of a phononic band gap that overlaps the 2-Delta energy of phonons produced during recombination of quasi-particles. Attention is given to a 1D Kronig-Penny model for phonons normally incident to the layers of a multilayered superconducting tunnel junction as an idealized example. A device with a high density of Bragg resonances is identified as desirable; both Nb/Si and NbN/SiN superlattices have been produced, with the latter having generally superior performance.

S-I-N tunneling spectroscopy of MgB2 superconductor: evidence of two superconducting energy gaps

International Nuclear Information System (INIS)

Sen, Shashwati; Aswal, D.K.; Singh, Ajay; Gadkari, S.C.; Shah, K.; Gupta, S.K.; Sahni, V.C.

2002-01-01

The tunneling spectra of polycrystalline MgB 2 , have been recorded, at different temperatures between 29 K and T c , using planar superconductor- insulating-normal (S-I-N) tunneling spectroscopy. The planar S-I-N tunnel junctions have been fabricated by thermally evaporating Ag electrodes on MgB 2 surface. The naive layer, which forms at the surface of MgB 2 , due to atmospheric degradation, was employed as an insulating layer between Ag electrodes and MgB 2 . We have found presence of two clear superconducting energy gaps in MgB 2 . The magnitudes of these gaps at 29.5 K are 1.8 and 5.9 MeV, respectively. In the vicinity of T c , while larger energy gap obeyed BCS temperature dependence, the smaller energy gap deviated from BCS dependence. All the spectra exhibited zero-bias conductance, which decreased linearly with temperature and vanished at T c . (author)

Co-culture of neural crest stem cells (NCSC and insulin producing beta-TC6 cells results in cadherin junctions and protection against cytokine-induced beta-cell death.

Directory of Open Access Journals (Sweden)

Anongnad Ngamjariyawat

Full Text Available PURPOSE: Transplantation of pancreatic islets to Type 1 diabetes patients is hampered by inflammatory reactions at the transplantation site leading to dysfunction and death of insulin producing beta-cells. Recently we have shown that co-transplantation of neural crest stem cells (NCSCs together with the islet cells improves transplantation outcome. The aim of the present investigation was to describe in vitro interactions between NCSCs and insulin producing beta-TC6 cells that may mediate protection against cytokine-induced beta-cell death. PROCEDURES: Beta-TC6 and NCSC cells were cultured either alone or together, and either with or without cell culture inserts. The cultures were then exposed to the pro-inflammatory cytokines IL-1β and IFN-γ for 48 hours followed by analysis of cell death rates (flow cytometry, nitrite production (Griess reagent, protein localization (immunofluorescence and protein phosphorylation (flow cytometry. RESULTS: We observed that beta-TC6 cells co-cultured with NCSCs were protected against cytokine-induced cell death, but not when separated by cell culture inserts. This occurred in parallel with (i augmented production of nitrite from beta-TC6 cells, indicating that increased cell survival allows a sustained production of nitric oxide; (ii NCSC-derived laminin production; (iii decreased phospho-FAK staining in beta-TC6 cell focal adhesions, and (iv decreased beta-TC6 cell phosphorylation of ERK(T202/Y204, FAK(Y397 and FAK(Y576. Furthermore, co-culture also resulted in cadherin and beta-catenin accumulations at the NCSC/beta-TC6 cell junctions. Finally, the gap junction inhibitor carbenoxolone did not affect cytokine-induced beta-cell death during co-culture with NCSCs. CONCLUSION: In summary, direct contacts, but not soluble factors, promote improved beta-TC6 viability when co-cultured with NCSCs. We hypothesize that cadherin junctions between NCSC and beta-TC6 cells promote powerful signals that maintain beta

Shunted-Josephson-junction model. I. The autonomous case

DEFF Research Database (Denmark)

Belykh, V. N.; Pedersen, Niels Falsig; Sørensen, O. H.

1977-01-01

The shunted-Josephson-junction model: the parallel combination of a capacitance, a phase-dependent conductance, and an ideal junction element biased by a constant current, is discussed for arbitrary values of the junction parameters. The main objective is to provide a qualitative understanding...... current-voltage curves are presented. The case with a time-dependent monochromatic bias current is treated in a similar fashion in the companion paper....

Gap-related trapped magnetic flux dependence between single and combined bulk superconductors

International Nuclear Information System (INIS)

Deng, Z.; Miki, M.; Felder, B.; Tsuzuki, K.; Shinohara, N.; Uetake, T.; Izumi, M.

2011-01-01

Highlights: → Rectangular YBCO bulks to realize a compact combination. → The gap effect was added to consider in the trapped flux density mapping. → The trapped-flux dependence between single and combined bulks is gap related. → It is possible to estimate the total magnetic flux of bulk combinations. - Abstract: Aiming at examining the trapped-flux dependence between single and combined bulk superconductors for field-pole applications, three rectangular Y 1.65 Ba 2 Cu 3 O 7-x (YBCO) bulks with a possibly compact combination were employed to investigate the trapped-flux characteristics of single and combined bulks with a field-cooling magnetization (FCM) method. A gap-related dependence was found between them. At lower gaps of 1 mm and 5 mm, the peak trapped fields and total magnetic flux of combined bulks are both smaller than the additive values of each single bulk, which can be ascribed to the demagnetization influences of the field around the bulk generated by the adjacent ones. While, at larger gaps like 10 mm, the situation becomes reversed. The combined bulks can attain bigger peak trapped fields as well as total magnetic flux, which indicates that the magnetic field by the bulk combination can reach higher gaps, thanks to the bigger magnetic energy compared with the single bulk. The presented results show that, on one hand, it is possible to estimate the total trapped magnetic flux of combined bulks by an approximate additive method of each single bulk while considering a demagnetization factor; on the other hand, it also means that the performance of combined bulks will be superior to the addition of each single bulk at larger gaps, thus preferable for large-scaled magnet applications.

Gap-related trapped magnetic flux dependence between single and combined bulk superconductors

Energy Technology Data Exchange (ETDEWEB)

Deng, Z., E-mail: zgdeng@gmail.co [Laboratory of Applied Physics, Department of Marine Electronics and Mechanical Engineering, Tokyo University of Marine Science and Technology, Tokyo 135-8533 (Japan); Miki, M.; Felder, B.; Tsuzuki, K.; Shinohara, N.; Uetake, T.; Izumi, M. [Laboratory of Applied Physics, Department of Marine Electronics and Mechanical Engineering, Tokyo University of Marine Science and Technology, Tokyo 135-8533 (Japan)

2011-05-15

Highlights: {yields} Rectangular YBCO bulks to realize a compact combination. {yields} The gap effect was added to consider in the trapped flux density mapping. {yields} The trapped-flux dependence between single and combined bulks is gap related. {yields} It is possible to estimate the total magnetic flux of bulk combinations. - Abstract: Aiming at examining the trapped-flux dependence between single and combined bulk superconductors for field-pole applications, three rectangular Y{sub 1.65}Ba{sub 2}Cu{sub 3}O{sub 7-x} (YBCO) bulks with a possibly compact combination were employed to investigate the trapped-flux characteristics of single and combined bulks with a field-cooling magnetization (FCM) method. A gap-related dependence was found between them. At lower gaps of 1 mm and 5 mm, the peak trapped fields and total magnetic flux of combined bulks are both smaller than the additive values of each single bulk, which can be ascribed to the demagnetization influences of the field around the bulk generated by the adjacent ones. While, at larger gaps like 10 mm, the situation becomes reversed. The combined bulks can attain bigger peak trapped fields as well as total magnetic flux, which indicates that the magnetic field by the bulk combination can reach higher gaps, thanks to the bigger magnetic energy compared with the single bulk. The presented results show that, on one hand, it is possible to estimate the total trapped magnetic flux of combined bulks by an approximate additive method of each single bulk while considering a demagnetization factor; on the other hand, it also means that the performance of combined bulks will be superior to the addition of each single bulk at larger gaps, thus preferable for large-scaled magnet applications.

Functional Molecular Junctions Derived from Double Self-Assembled Monolayers.

Science.gov (United States)

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