Adenoviral vector-mediated expression of B-50/GAP-43 induces alterations in the membrane organization of olfactory axon terminals in vivo

NARCIS (Netherlands)

Holtmaat, Anthony J D G; Hermens, W.T.J.M.C.; Sonnemans, M.A.F.; Giger, Roman J; Van Leeuwen, F W; Kaplitt, M G; Oestreicher, A B; Gispen, Willem Hendrik; Verhaagen, J

1997-01-01

B-50/GAP-43 is an intraneuronal membrane-associated growth cone protein with an important role in axonal growth and regeneration. By using adenoviral vector-directed expression of B-50/GAP-43 we studied the morphogenic action of B-50/GAP-43 in mature primary olfactory neurons that have established

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.

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.

Sequence tagging reveals unexpected modifications in toxicoproteomics

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Dasari, Surendra; Chambers, Matthew C.; Codreanu, Simona G.; Liebler, Daniel C.; Collins, Ben C.; Pennington, Stephen R.; Gallagher, William M.; Tabb, David L.

2010-01-01

Toxicoproteomic samples are rich in posttranslational modifications (PTMs) of proteins. Identifying these modifications via standard database searching can incur significant performance penalties. Here we describe the latest developments in TagRecon, an algorithm that leverages inferred sequence tags to identify modified peptides in toxicoproteomic data sets. TagRecon identifies known modifications more effectively than the MyriMatch database search engine. TagRecon outperformed state of the art software in recognizing unanticipated modifications from LTQ, Orbitrap, and QTOF data sets. We developed user-friendly software for detecting persistent mass shifts from samples. We follow a three-step strategy for detecting unanticipated PTMs in samples. First, we identify the proteins present in the sample with a standard database search. Next, identified proteins are interrogated for unexpected PTMs with a sequence tag-based search. Finally, additional evidence is gathered for the detected mass shifts with a refinement search. Application of this technology on toxicoproteomic data sets revealed unintended cross-reactions between proteins and sample processing reagents. Twenty five proteins in rat liver showed signs of oxidative stress when exposed to potentially toxic drugs. These results demonstrate the value of mining toxicoproteomic data sets for modifications. PMID:21214251

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

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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

Domain-Specific Partitioning of Uterine Artery Endothelial Connexin43 and Caveolin-1.

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Ampey, Bryan C; Morschauser, Timothy J; Ramadoss, Jayanth; Magness, Ronald R

2016-10-01

Uterine vascular adaptations facilitate rises in uterine blood flow during pregnancy, which are associated with gap junction connexin (Cx) proteins and endothelial nitric oxide synthase. In uterine artery endothelial cells (UAECs), ATP activates endothelial nitric oxide synthase in a pregnancy (P)-specific manner that is dependent on Cx43 function. Caveolar subcellular domain partitioning plays key roles in ATP-induced endothelial nitric oxide synthase activation and nitric oxide production. Little is known regarding the partitioning of Cx proteins to caveolar domains or their dynamics with ATP treatment. We observed that Cx43-mediated gap junction function with ATP stimulation is associated with Cx43 repartitioning between the noncaveolar and caveolar domains. Compared with UAECs from nonpregnant (NP) ewes, levels of ATP, PGI2, cAMP, NOx, and cGMP were 2-fold higher (PLucifer yellow dye transfer, a response abrogated by Gap27, but not Gap 26, indicating involvement of Cx43, but not Cx37. Confocal microscopy revealed domain partitioning of Cx43 and caveolin-1. In pregnant UAECs, LC/MS/MS analysis revealed only Cx43 in the caveolar domain. In contrast, Cx37 was located only in the noncaveolar pool. Western analysis revealed that ATP increased Cx43 distribution (1.7-fold; P=0.013) to the caveolar domain, but had no effect on Cx37. These data demonstrate rapid ATP-stimulated repartitioning of Cx43 to the caveolae, where endothelial nitric oxide synthase resides and plays an important role in nitric oxide-mediated increasing uterine blood flow during pregnancy. © 2016 American Heart Association, Inc.

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

Evaluation of specific neural marker GAP-43 and TH combined with Masson-trichrome staining for forensic autopsy cases with old myocardial infarction.

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Yu, Tian-Shui; Wang, Xu; Zhang, Hai-Dong; Bai, Ru-Feng; Zhao, Rui; Guan, Da-Wei

2018-01-01

It has been a puzzling forensic task to determine the cause of death as a result of old myocardial infarction (OMI) in the absence of recognizable acute myocardial infarction. Recent studies indicated that the heterogeneous cardiac nerve sprouting and sympathetic hyperinnervation at border zones of the infarcted site played important roles in sudden cardiac death (SCD). So, the present study explored the value of growth associated protein-43 (GAP-43) and tyrosine hydroxylase (TH) as objective and specific neural biomarkers combined with Masson-trichrome staining for forensic autopsy cases. Myocardium of left ventricle of 58 medicolegal autopsy cases, 12 OMI cases, 12 acute/OMI cases, and 34 control cases, were immunostained with anti-GAP-43 and anti-TH antibodies. Immunoreactivity of GAP-43 and TH identified nerve fibers and vascular wall in OMI cases and acute/OMI cases. Specifically, TH-positive nerve fibers were abundant at border zones of the infarcted site. There were a few GAP-43 and TH expressions in the control cases. With Masson-trichrome staining, collagen fibers were blue and cardiac muscle fibers were pink in marked contrast with the surrounding tissue, which improved the location of nerve fibers. Thus, these findings suggest that immunohistochemical detection of GAP-43 and TH combined with Masson-trichrome staining can provide the evidence for the medicolegal expertise of SCD due to OMI, and further demonstrate a close relationship between sympathetic hyperinnervation and SCD.

The prescriptions from Shenghui soup enhanced neurite growth and GAP-43 expression level in PC12 cells.

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Zhang, Qi; Zhang, Zi-Jian; Wang, Xing-Hua; Ma, Jie; Song, Yue-Han; Liang, Mi; Lin, Sen-Xiang; Zhao, Jie; Zhang, Ao-Zhe; Li, Feng; Hua, Qian

2016-09-20

Shenghui soup is a traditional Chinese herbal medicine used in clinic for the treatment of forgetfulness. In order to understanding the prescription principle, the effects of "tonifying qi and strengthening spleen" group (TQSS) including Poria cocos (Schw.) Wolf. and Panax ginseng C.A.Mey and "eliminating phlegm and strengthening intelligence" group (EPSI) composed of Polygala tenuifolia Willd., Acorus calamus L. and Sinapis alba L from the herb complex on neurite growth in PC12 cells, two disassembled prescriptions derived from Shenghui soup and their molecular mechanisms were investigated. Firstly, CCK-8 kit was used to detect the impact of the two prescriptions on PC12 cell viability; and Flow cytometry was performed to measure the cell apoptosis when PC12 cells were treated with these drugs. Secondly, the effect of the two prescriptions on the differentiation of PC12 cells was observed. Finally, the mRNA and protein expression levels of GAP-43 were analyzed by RT-PCR and western blot, respectively. "Tonifying qi and strengthening spleen" prescription decreased cell viability in a dose-dependent manner, but had no significant effect on cell apoptosis. Meanwhile, it could improve neurite growth and elevate the mRNA and protein expression level of GAP-43. "Eliminating phlegm and strengthening intelligence" prescription also exerted the similar effects on cell viability and apoptosis. Furthermore, it could also enhance cell neurite growth, with a higher expression level of GAP-43 mRNA and protein. "Tonifying qi and strengthening spleen" and "eliminating phlegm and strengthening intelligence" prescriptions from Shenghui soup have a positive effect on neurite growth. Their effects are related to the up-regulating expression of GAP-43.

Muscarinic receptor activation stimulates B-50/GAP43 phosphorylation in isolated nerve growth cones

NARCIS (Netherlands)

Gispen, W.H.; Hooff, C.O.M. van; Graan, P.N.E. de; Oestreicher, A.B.

1989-01-01

A characteristic feature of neurite formation is high expression of the phosphoprotein B-50/GAP43. Previous studies with growth cone membranes have indicated that this neuron-specific protein kinase C substrate may be involved in transmembrane signal transduction at the growth cone. We monitored the

Process improvement methodologies uncover unexpected gaps in stroke care.

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Kuner, Anthony D; Schemmel, Andrew J; Pooler, B Dustin; Yu, John-Paul J

2018-01-01

Background The diagnosis and treatment of acute stroke requires timed and coordinated effort across multiple clinical teams. Purpose To analyze the frequency and temporal distribution of emergent stroke evaluations (ESEs) to identify potential contributory workflow factors that may delay the initiation and subsequent evaluation of emergency department stroke patients. Material and Methods A total of 719 sentinel ESEs with concurrent neuroimaging were identified over a 22-month retrospective time period. Frequency data were tabulated and odds ratios calculated. Results Of all ESEs, 5% occur between 01:00 and 07:00. ESEs were most frequent during the late morning and early afternoon hours (10:00-14:00). Unexpectedly, there was a statistically significant decline in the frequency of ESEs that occur at the 14:00 time point. Conclusion Temporal analysis of ESEs in the emergency department allowed us to identify an unexpected decrease in ESEs and through process improvement methodologies (Lean and Six Sigma) and identify potential workflow elements contributing to this observation.

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

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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.

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.

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

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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.

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

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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.

Detailed regulatory mechanism of the interaction between ZO-1 PDZ2 and connexin43 revealed by MD simulations.

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Fei Xiao

Full Text Available The gap junction protein connexin43 (Cx43 binds to the second PDZ domain of Zonula occludens-1 (ZO-1 through its C-terminal tail, mediating the regulation of gap junction plaque size and dynamics. Biochemical study demonstrated that the very C-terminal 12 residues of Cx43 are necessary and sufficient for ZO-1 PDZ2 binding and phosphorylation at residues Ser (-9 and Ser (-10 of the peptide can disrupt the association. However, only a crystal structure of ZO-1 PDZ2 in complex with a shorter 9 aa peptide of connexin43 was solved experimentally. Here, the interactions between ZO-1 PDZ2 and the short, long and phosphorylated Cx43 peptides were studied using molecular dynamics (MD simulations and free energy calculation. The short peptide bound to PDZ2 exhibits large structural variations, while the extension of three upstream residues stabilizes the peptide conformation and enhanced the interaction. Phosphorylation at Ser(-9 significantly weakens the binding and results in conformational flexibility of the peptide. Glu210 of ZO-1 PDZ2 was found to be a key regulatory point in Cx43 binding and phosphorylation induced dissociation.

Specific association of growth-associated protein 43 with calcium release units in skeletal muscles of lower vertebrates

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G.A. Caprara

2014-10-01

Full Text Available Growth-associated protein 43 (GAP43, is a strictly conserved protein among vertebrates implicated in neuronal development and neurite branching. Since GAP43 structure contains a calmodulin-binding domain, this protein is able to bind calmodulin and gather it nearby membrane network, thus regulating cytosolic calcium and consequently calcium-dependent intracellular events. Even if for many years GAP43 has been considered a neuronal-specific protein, evidence from different laboratories described its presence in myoblasts, myotubes and adult skeletal muscle fibers. Data from our laboratory showed that GAP43 is localized between calcium release units (CRUs and mitochondria in mammalian skeletal muscle suggesting that, also in skeletal muscle, this protein can be a key player in calcium/calmodulin homeostasis. However, the previous studies could not clearly distinguish between a mitochondrion- or a triad-related positioning of GAP43. To solve this question, the expression and localization of GAP43 was studied in skeletal muscle of Xenopus and Zebrafish known to have triads located at the level of the Z-lines and mitochondria not closely associated with them. Western blotting and immunostaining experiments revealed the expression of GAP43 also in skeletal muscle of lower vertebrates (like amphibians and fishes, and that the protein is localized closely to the triad junction. Once more, these results and GAP43 structural features, support an involvement of the protein in the dynamic intracellular Ca2+ homeostasis, a common conserved role among the different species.

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

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.

Down-regulation of Connexin43 expression reveals the involvement of caveolin-1 containing lipid rafts in human U251 glioblastoma cell invasion.

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Strale, Pierre-Olivier; Clarhaut, Jonathan; Lamiche, Coralie; Cronier, Laurent; Mesnil, Marc; Defamie, Norah

2012-11-01

Glioblastoma cells are characterized by high proliferation and invasive capacities. Tumor development has been associated with a decrease of gap-junctional intercellular communication, but the concrete involvement of gap junction proteins, connexins, remains elusive since they are also suspected to promote cell invasion. In order to better understand how connexins control the glioma cell phenotype, we studied the consequences of inhibiting the intrinsic expression of the major astrocytic connexin, Connexin43, in human U251 glioblastoma cells by the shRNA strategy. The induced down-regulation of Cx43 expression has various effects on the U251 cells such as increased clonogenicity, angiogenesis and decreased adhesion on specific extracellular matrix proteins. We demonstrate that the invasion capacity measured in vitro and ex vivo correlates with Cx43 expression level. For the first time in a cancer cell context, our work demonstrates that Cx43 cofractionates, colocalizes and coimmunoprecipitates with a lipid raft marker, caveolin-1 and that this interaction is inversely correlated to the level of Cx43. This localization of Cx43 in these lipid raft microdomains regulates both homo- and heterocellular gap junctional communications (respectively between U251 cells, or between U251 cells and astrocytes). Moreover, the adhesive and invasive capacities are not dependent, in our model, on Cav-1 expression level. Our results tend to show that heterocellular gap junctional communication between cancer and stroma cells may affect the behavior of the tumor cells. Altogether, our data demonstrate that Cx43 controls the tumor phenotype of glioblastoma U251 cells and in particular, invasion capacity, through its localization in lipid rafts containing Cav-1. Copyright © 2011 Wiley Periodicals, Inc.

Nos2 inactivation promotes the development of medulloblastoma in Ptch1(+/- mice by deregulation of Gap43-dependent granule cell precursor migration.

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Daniel Haag

Full Text Available Medulloblastoma is the most common malignant brain tumor in children. A subset of medulloblastoma originates from granule cell precursors (GCPs of the developing cerebellum and demonstrates aberrant hedgehog signaling, typically due to inactivating mutations in the receptor PTCH1, a pathomechanism recapitulated in Ptch1(+/- mice. As nitric oxide may regulate GCP proliferation and differentiation, we crossed Ptch1(+/- mice with mice lacking inducible nitric oxide synthase (Nos2 to investigate a possible influence on tumorigenesis. We observed a two-fold higher medulloblastoma rate in Ptch1(+/- Nos2(-/- mice compared to Ptch1(+/- Nos2(+/+ mice. To identify the molecular mechanisms underlying this finding, we performed gene expression profiling of medulloblastomas from both genotypes, as well as normal cerebellar tissue samples of different developmental stages and genotypes. Downregulation of hedgehog target genes was observed in postnatal cerebellum from Ptch1(+/+ Nos2(-/- mice but not from Ptch1(+/- Nos2(-/- mice. The most consistent effect of Nos2 deficiency was downregulation of growth-associated protein 43 (Gap43. Functional studies in neuronal progenitor cells demonstrated nitric oxide dependence of Gap43 expression and impaired migration upon Gap43 knock-down. Both effects were confirmed in situ by immunofluorescence analyses on tissue sections of the developing cerebellum. Finally, the number of proliferating GCPs at the cerebellar periphery was decreased in Ptch1(+/+ Nos2(-/- mice but increased in Ptch1(+/- Nos2(-/ (- mice relative to Ptch1(+/- Nos2(+/+ mice. Taken together, these results indicate that Nos2 deficiency promotes medulloblastoma development in Ptch1(+/- mice through retention of proliferating GCPs in the external granular layer due to reduced Gap43 expression. This study illustrates a new role of nitric oxide signaling in cerebellar development and demonstrates that the localization of pre-neoplastic cells during

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

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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

An unexpected pulmonary bystander

NARCIS (Netherlands)

Wouthuyzen-Bakker, M.; Vorm, van der P. A.; Koning, K. J.; van der Werf, T. S.

A 30-year-old man from Eritrea was admitted with a pulmonary bacterial abscess. Unexpectedly, histopathology of the resected lobe also revealed an infection with Schistosoma mansoni with surrounding granulomatous tissue and fibrosis. Patients from endemic areas are often asymptomatic with blood

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.

Deafferentation-Induced Redistribution of MMP-2, but Not of MMP-9, Depends on the Emergence of GAP-43 Positive Axons in the Adult Rat Cochlear Nucleus

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Michaela Fredrich

2011-01-01

Full Text Available The matrix metalloproteinases MMP-9 and MMP-2, major modulators of the extracellular matrix (ECM, were changed in amount and distribution in the rat anteroventral cochlear nucleus (AVCN following its sensory deafferentation by cochlear ablation. To determine what causal relationships exist between the redistribution of MMP-9 and MMP-2 and deafferentation-induced reinnervation, kainic acid was stereotaxically injected into the ventral nucleus of the trapezoid body (VNTB prior to cochlear ablation, killing cells that deliver the growth associated protein 43 (GAP-43 into AVCN. Deafferentation-induced changes in the pattern of MMP-9 staining remained unaffected by VNTB lesions. By contrast, changes in the distribution of MMP-2 normally evoked by sensory deafferentation were reversed if GAP-43 positive axons were prevented to grow in AVCN. In conclusion, GAP-43-containing axons emerging in AVCN after cochlear ablation seem to be causal for the maintenance of MMP-2-mediated ECM remodeling.

Unexpected pathological findings after laparoscopic cholecystectomy - analysis of 1131 cases.

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Bartosiak, Katarzyna; Liszka, Maciej; Drazba, Tomasz; Paśnik, Krzysztof; Janik, Michal R

2018-03-01

Gallbladder specimens are routinely sent for histopathological examination after cholecystectomy in order to rule out the presence of unexpected pathological findings. To establish the overall incidence of unexpected pathological findings in patients who underwent laparoscopic cholecystectomy for symptomatic gallbladder disease and determine whether the macroscopic appearance of the gallbladder in ultrasound examination could be a valid method for identifying patients with gallbladder malignancy. A retrospective study was conducted between 2013 and 2015. All histological reports (n = 1131) after cholecystectomy were searched for unexpected pathological findings. In cases where unexpected pathological findings were identified the additional analysis of preoperative abdominal ultrasound examination (USG) was done to determine the usefulness of USG in diagnosis of gallbladder malignancy. Of the 1131 patients included in the study, 356 (31.47%) were male and 774 (68.43%) were female. Unexpected pathological findings were present in 21 cases. The overall incidence of unexpected pathological findings was 1.86%. Only in 5 patients were suspicious appearances of gallbladder observed in preoperative ultrasound examination. In 16 patients there was no suspicion of malignancy. The positive predictive value of USG was 0.238. The incidence of unexpected pathological findings after laparoscopic cholecystectomy was 1.86%. Ultrasonography has low positive predictive value for identifying patients with malignant findings in a gallbladder specimen.

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.

Green fluorescent protein changes the conductance of connexin 43 (Cx43) hemichannels reconstituted in planar lipid bilayers.

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Carnarius, Christian; Kreir, Mohamed; Krick, Marcel; Methfessel, Christoph; Moehrle, Volker; Valerius, Oliver; Brüggemann, Andrea; Steinem, Claudia; Fertig, Niels

2012-01-20

In mammalian tissues, connexin 43 (Cx43) is the most prominent member of the connexin family. In a single lipid bilayer, six connexin subunits assemble into a hemichannel (connexon). Direct communication of apposing cells is realized by two adjacent hemichannels, which can form gap junction channels. Here, we established an expression system in Pichia pastoris to recombinantly produce and purify Cx43 as well as Cx43 fused to green fluorescent protein (GFP). Proteins were isolated from crude cell membrane fractions via affinity chromatography. Cx43 and Cx43-GFP hemichannels were reconstituted in giant unilamellar vesicles as proven by fluorescence microscopy, and their electrophysiological behavior was analyzed on the single channel level by planar patch clamping. Cx43 and Cx43-GFP both showed an ohmic behavior and a voltage-dependent open probability. Cx43 hemichannels exhibited one major mean conductance of 224 ± 26 picosiemens (pS). In addition, a subconductance state at 124 ± 5 pS was identified. In contrast, the analysis of Cx43-GFP single channels revealed 10 distinct conductance states in the range of 15 to 250 pS, with a larger open probability at 0 mV as compared with Cx43, which suggests that intermolecular interactions between the GFP molecules alter the electrophysiology of the protein.

Aberrant Cx43 Expression and Mislocalization in Metastatic Human Melanomas.

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Alaga, Katanya C; Crawford, Melissa; Dagnino, Lina; Laird, Dale W

2017-01-01

At present, it is unclear if melanocytes contain Cx43 gap junctions and whether Cx43 expression is regulated in melanoma onset and progression. To this end, we cultured pure populations of mouse melanocytes and found that they had no detectable Cx43 and exhibited an inability for dye transfer indicating they were devoid of functional gap junctions. Given the evidence that melanomas acquire the expression of other connexin isoforms during tumor progression, we assessed if Cx43 was also expressed and assembled into gap junctions at any stage of human melanoma onset and progression to distant metastases. Nearly all primary melanomas within the epidermis lacked Cx43. In contrast, nodal metastases expressed low levels of Cx43 which was markedly higher in distant metastases that had invaded vital organs. Importantly, in all stages of melanoma progression, Cx43 could be detected in intracellular compartments but was rarely assembled into gap junctions indicative of functional gap junction channels. Overall, these studies suggest that melanocytes do not form Cx43 homocellular gap junctions and even though Cx43 levels increase during melanoma progression, this connexin rarely assembles into gap junction structures.

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.

GAP Analysis Program (GAP)

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

Anchored PKA as a gatekeeper for gap junctions.

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Pidoux, Guillaume; Taskén, Kjetil

2015-01-01

Anchored protein kinase A (PKA) bound to A Kinase Anchoring Protein (AKAP) mediates effects of localized increases in cAMP in defined subcellular microdomains and retains the specificity in cAMP-PKA signaling to distinct extracellular stimuli. Gap junctions are pores between adjacent cells constituted by connexin proteins that provide means of communication and transfer of small molecules. While the PKA signaling is known to promote human trophoblast cell fusion, the gap junction communication through connexin 43 (Cx43) is a prerequisite for this process. We recently demonstrated that trophoblast fusion is regulated by ezrin, a known AKAP, which binds to Cx43 and delivers PKA in the vicinity gap junctions. We found that disruption of the ezrin-Cx43 interaction abolished PKA-dependent phosphorylation of Cx43 as well as gap junction communication and subsequently cell fusion. We propose that the PKA-ezrin-Cx43 macromolecular complex regulating gap junction communication constitutes a general mechanism to control opening of Cx43 gap junctions by phosphorylation in response to cAMP signaling in various cell types.

The role of the Cx43 C-terminus in GJ plaque formation and internalization

International Nuclear Information System (INIS)

Wayakanon, Praween; Bhattacharjee, Rajib; Nakahama, Ken-ichi; Morita, Ikuo

2012-01-01

Highlights: ► Cx43-GFP or -DsRed fusion proteins were expressed in HeLa cells. ► Roles of C-terminus were examined using various mutants. ► Gap junction plaque size was dependent on the length of C-terminus. ► C-terminus dependent gap junction plaque internalization was observed. -- Abstract: Connexin 43 (Cx43) is a major gap junction (GJ) protein found in many mammalian cell types. The C-terminal (CT) domain of Cx43 has unique characteristics in terms of amino acid (aa) sequence and its length differs from other connexins. This CT domain can be associated with protein partners to regulate GJ assembly and degradation, which results in the direct control of gap junction intercellular communication (GJIC). However, the essential roles of the CT regions involved in these mechanisms have not been fully elucidated. In this study, we aimed to investigate the specific regions of Cx43CT involved in GJ formation and internalization. Wild type Cx43 (382aa) and 10 CT truncated mutants were stably expressed in HeLa cells as GFP or DsRed tagged proteins. First, we found that the deletion of 235–382aa from Cx43 resulted in failure to make GJ and establish GJIC. Second, the Cx43 with 242–382aa CT deletion could form functional GJs and be internalized as annular gap junctions (AGJs). However, the plaques consisting of Cx43 with CT deletions (Δ242–382aa to Δ271–382aa) were longer than the plaques consisting of Cx43 with CT deletions (Δ302–382aa). Third, co-culture experiments of cells expressing wild type Cx43 (382) with cells expressing Cx43CT mutants revealed that the directions of GJ internalization were dependent on the length of the respective CT. Moreover, a specific region, 325–342aa residues of Cx43, played an important role in the direction of GJ internalization. These results showed the important roles of the Cx43 C-terminus in GJ expression and its turnover.

Green Fluorescent Protein Changes the Conductance of Connexin 43 (Cx43) Hemichannels Reconstituted in Planar Lipid Bilayers*

Science.gov (United States)

Carnarius, Christian; Kreir, Mohamed; Krick, Marcel; Methfessel, Christoph; Moehrle, Volker; Valerius, Oliver; Brüggemann, Andrea; Steinem, Claudia; Fertig, Niels

2012-01-01

In mammalian tissues, connexin 43 (Cx43) is the most prominent member of the connexin family. In a single lipid bilayer, six connexin subunits assemble into a hemichannel (connexon). Direct communication of apposing cells is realized by two adjacent hemichannels, which can form gap junction channels. Here, we established an expression system in Pichia pastoris to recombinantly produce and purify Cx43 as well as Cx43 fused to green fluorescent protein (GFP). Proteins were isolated from crude cell membrane fractions via affinity chromatography. Cx43 and Cx43-GFP hemichannels were reconstituted in giant unilamellar vesicles as proven by fluorescence microscopy, and their electrophysiological behavior was analyzed on the single channel level by planar patch clamping. Cx43 and Cx43-GFP both showed an ohmic behavior and a voltage-dependent open probability. Cx43 hemichannels exhibited one major mean conductance of 224 ± 26 picosiemens (pS). In addition, a subconductance state at 124 ± 5 pS was identified. In contrast, the analysis of Cx43-GFP single channels revealed 10 distinct conductance states in the range of 15 to 250 pS, with a larger open probability at 0 mV as compared with Cx43, which suggests that intermolecular interactions between the GFP molecules alter the electrophysiology of the protein. PMID:22139870

Comparison of GAP-3 and GAP-4 experiments with conduction freezing calculations

International Nuclear Information System (INIS)

Sienicki, J.J.; Spencer, B.W.

1983-01-01

Experiments GAP-3 and GAP-4 were performed at ANL to investigate the ability of molten fuel to penetrate downward through the narrow channels separating adjacent subassemblies during an LMFBR hypothetical core disruptive accident. Molten fuel-metal mixtures (81% UO 2 , 19% Mo) at an initial temperature of 3470 0 K generated by a thermite reaction were injected downward into 1 m long rectangular test sections (gap thickness = 0.43 cm, channel width = 20.3 cm) initially at 1170 0 K simulating the nominal Clinch River Breeder Reactor intersubassembly gap. In the GAP-3 test, a prolonged reaction time of approx. 15 s resulted in segregation of the metallic Mo and oxidic UO 2 constituents within the reaction vessel prior to injection. Consequently, Mo entered the test section first and froze, forming a complete plug at a penetration distance of 0.18 m. In GAP-4, the reaction time was reduced to approx. 3 s and the constituents remained well mixed upon injection with the result that the leading edge penetration distance increased to 0.35 m. Posttest examination of the cut-open test sections has revealed the existence of stable insulating crusts upon the underlying steel walls with melting and ablation of the walls only very localized

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

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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.

Targeting connexin 43 in diabetic wound healing: Future perspectives

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Bajpai S

2009-01-01

Full Text Available The unknown mechanisms of impaired tissue repair in diabetes mellitus are making this disease a serious clinical problem for the physicians worldwide. The lacuna in the knowledge of the etiology of diabetic wounds necessitates more focused research in order to develop new targeting tools with higher efficacy for their effective management. Gap-junction proteins, connexins, have shown some promising results in the process of diabetic wound healing. Till now the role of connexins has been implicated in peripheral neuropathy, deafness, skin disorders, cataract, germ cell development and treatment of cancer. Recent findings have revealed that gap junctions play a key role in normal as well as diabetic wound healing. The purpose of this review is to provide the information related to etiology, epidemiology, clinical presentation of diabetic wounds and to analyze the role of connexin 43 (Cx43 in the diabetic wound healing process. The current control strategies and the future research challenges have also been discussed briefly in this review.

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.

Association of connexin43 with a receptor protein tyrosine phosphatase

NARCIS (Netherlands)

Giepmans, Ben N G; Feiken, Elles; Gebbink, Martijn F B G; Moolenaar, Wouter H

2003-01-01

Connexin-43(Cx43)-based gap junctional communication is transiently inhibited by certain G protein-coupled receptor agonists, including lysophosphatidic acid, endothelin and thrombin. Our previous studies have implicated the c-Src protein tyrosine kinase in mediating closure of Cx43 based gap

Unexpected findings at imaging: Predicting frequency in various types of studies

International Nuclear Information System (INIS)

Lumbreras, Blanca; Gonzalez-Alvarez, Isabel; Lorente, Ma Fernanda; Calbo, Jorge; Aranaz, Jesus; Hernandez-Aguado, Ildefonso

2010-01-01

Objective: The objective was to evaluate the prevalence and associated variables of unsuspected findings from imaging tests in clinical practice. Material and Methods: Cross-sectional study of patients referred for an imaging test in 2006. Two independent radiologists classified the imaging tests according to the presence or absence of an unexpected finding in relation with the causes that prompted the test (kappa = 0.95). A thorough chart review of these patients was carried out as a quality control. Results: Out of 3259 patients in the study, 488 revealed unsuspected findings (15.0%). The prevalence of abnormal findings varied according to age: from 20.4% (150/734) in the over 74-group to 9.0% (76/847) in the under 43-group. The largest prevalence was in the category of infectious diseases (14/49, 28.6%) and in CT (260/901, 28.9%) and ultrasound (138/668, 20.7%). Studies showing moderate clinical information on the referral form were less likely to show unexpected findings than those with null or minor information (OR 0.51; 95% CI 0.36-0.73). Conclusion: Clinicians should expect the frequency of diseases detectable by imaging to increase in the future. Further research with follow-up of these findings is needed to estimate the effect of imaging technologies on final health outcomes.

Unexpected findings at imaging: Predicting frequency in various types of studies

Energy Technology Data Exchange (ETDEWEB)

Lumbreras, Blanca [Public Health Department, Miguel Hernandez University (Spain); CIBER en Epidemiologia y Salud Publica (Spain)], E-mail: blumbreras@umh.es; Gonzalez-Alvarez, Isabel [Radiodiagnostic Department, San Juan Hospital, 03550 Alicante (Spain)], E-mail: gonzalez_isa@gva.es; Lorente, Ma Fernanda [Radiodiagnostic Department, San Juan Hospital, 03550 Alicante (Spain)], E-mail: MARFERLORENTE@telefonica.net; Calbo, Jorge [Radiodiagnostic Department, San Juan Hospital, 03550 Alicante (Spain)], E-mail: jocalma@hotmail.com; Aranaz, Jesus [Preventive Medicine Department, San Juan Hospital, 03550 Alicante (Spain)], E-mail: aranaz_jes@gva.es; Hernandez-Aguado, Ildefonso [Public Health Department, Miguel Hernandez University (Spain); CIBER en Epidemiologia y Salud Publica (Spain)], E-mail: ihernandez@umh.es

2010-04-15

Objective: The objective was to evaluate the prevalence and associated variables of unsuspected findings from imaging tests in clinical practice. Material and Methods: Cross-sectional study of patients referred for an imaging test in 2006. Two independent radiologists classified the imaging tests according to the presence or absence of an unexpected finding in relation with the causes that prompted the test (kappa = 0.95). A thorough chart review of these patients was carried out as a quality control. Results: Out of 3259 patients in the study, 488 revealed unsuspected findings (15.0%). The prevalence of abnormal findings varied according to age: from 20.4% (150/734) in the over 74-group to 9.0% (76/847) in the under 43-group. The largest prevalence was in the category of infectious diseases (14/49, 28.6%) and in CT (260/901, 28.9%) and ultrasound (138/668, 20.7%). Studies showing moderate clinical information on the referral form were less likely to show unexpected findings than those with null or minor information (OR 0.51; 95% CI 0.36-0.73). Conclusion: Clinicians should expect the frequency of diseases detectable by imaging to increase in the future. Further research with follow-up of these findings is needed to estimate the effect of imaging technologies on final health outcomes.

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.

Sphingosine-1-Phosphate reduces ischemia/reperfusion injury by phosphorylating the gap junction protein Connexin43

DEFF Research Database (Denmark)

Morel, Sandrine; Christoffersen, Christina; Axelsen, Lene N

2016-01-01

recruitment seems only indirectly affected. Importantly, short-term S1P treatment at the onset of reperfusion was sufficient to reduce ischemia/reperfusion injury in isolated perfused hearts. Mechanistic in vitro and ex vivo studies revealed that 5 min of S1P treatment induced phosphorylation of the gap...

Connexin 43 Channels are Essential for Normal Bone Structure and Osteocyte Viability

Science.gov (United States)

Xu, Huiyun; Gu, Sumin; Riquelme, Manuel A.; Burra, Sirisha; Callaway, Danielle; Cheng, Hongyun; Guda, Teja; Schmitz, James; Fajardo, Roberto J.; Werner, Sherry L.; Zhao, Hong; Shang, Peng; Johnson, Mark L.; Bonewald, Lynda F.; Jiang, Jean X.

2014-01-01

Connexin (Cx) 43 serves important roles in bone function and development. Targeted deletion of Cx43 in osteoblasts or osteocytes leads to increased osteocyte apoptosis, osteoclast recruitment, and reduced biomechanical properties. Cx43 forms both gap junction channels and hemichannels, which mediate the communication between adjacent cells or between cell and extracellular environments, respectively. Two transgenic mouse models driven by a DMP1 promoter with the overexpression of dominant negative Cx43 mutants were generated to dissect the functional contribution of Cx43 gap junction channels and hemichannels in osteocytes. The R76W mutant blocks gap junction channel, but not hemichannel function, and the Δ130-136 mutant inhibits activity of both types of channels. Δ130-136 mice showed a significant increase in bone mineral density compared to WT and R76W mice. MicroCT analyses revealed a significant increase in total tissue and bone area in midshaft cortical bone of Δ130-136 mice. The bone marrow cavity was expanded, whereas the cortical thickness was increased and associated with increased bone formation along the periosteal area. However, there is no significant alteration in the structure of trabecular bone. Histologic sections of the midshaft showed increased apoptotic osteocytes in Δ130-136, but not in WT and R76W, mice which correlated with altered biomechanical and estimated bone material properties. Osteoclasts were increased along the endocortical surface in both transgenic mice with a greater effect in Δ130-136 mice which likely contributed to the increased marrow cavity. Interestingly, the overall expression of serum bone formation and resorption markers were higher in R76W mice. These findings suggest that osteocytic Cx43 channels play distinctive roles in the bone; hemichannels play a dominant role in regulating osteocyte survival, endocortical bone resorption and periosteal apposition, and gap junction communication is involved in the process of

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

Science.gov (United States)

Zhang, Yuan; Tan, Xiaoming; Xue, Lianfang

2018-01-01

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

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

2013-04-01

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

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.

Ultrastructure and regulation of lateralized connexin43 in the failing heart.

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Hesketh, Geoffrey G; Shah, Manish H; Halperin, Victoria L; Cooke, Carol A; Akar, Fadi G; Yen, Timothy E; Kass, David A; Machamer, Carolyn E; Van Eyk, Jennifer E; Tomaselli, Gordon F

2010-04-02

Gap junctions mediate cell-to-cell electric coupling of cardiomyocytes. The primary gap junction protein in the working myocardium, connexin43 (Cx43), exhibits increased localization at the lateral membranes of cardiomyocytes in a variety of heart diseases, although the precise location and function of this population is unknown. To define the subcellular location of lateralized gap junctions at the light and electron microscopic level, and further characterize the biochemical regulation of gap junction turnover. By electron microscopy, we characterized gap junctions formed between cardiomyocyte lateral membranes in failing canine ventricular myocardium. These gap junctions were varied in structure and appeared to be extensively internalizing. Internalized gap junctions were incorporated into multilamellar membrane structures, with features characteristic of autophagosomes. Intracellular Cx43 extensively colocalized with the autophagosome marker GFP-LC3 when both proteins were exogenously expressed in HeLa cells, and endogenous Cx43 colocalized with GFP-LC3 in neonatal rat ventricular myocytes. Furthermore, a distinct phosphorylated form of Cx43, as well as the autophagosome-targeted form of LC3 (microtubule-associated protein light chain 3) targeted to lipid rafts in cardiac tissue, and both were increased in heart failure. Our data demonstrate a previously unrecognized pathway of gap junction internalization and degradation in the heart and identify a cellular pathway with potential therapeutic implications.

Unexpected MRI findings in clinically suspected Legg-Calve-Perthes disease

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Lobert, Philip F.; Dillman, Jonathan R.; Strouse, Peter J.; Hernandez, Ramiro J. [University of Michigan Health System, Department of Radiology, Section of Pediatric Radiology, C.S. Mott Children' s Hospital/F3503, Ann Arbor, MI (United States)

2011-03-15

In the setting of clinically suspected Legg-Calve-Perthes (LCP) disease and negative/equivocal radiographs, contrast-enhanced MRI can be performed to confirm the diagnosis. To determine the frequency of unexpected causes of hip pain as identified by MRI in children with clinically suspected LCP disease and negative/equivocal radiographs. All pediatric contrast-enhanced MRI examinations of the pelvis and hips performed between January 2000 and February 2009 to evaluate for possible LCP disease in the setting of negative/equivocal radiographs were identified. MRI examinations performed to evaluate for secondary avascular necrosis were excluded. Imaging reports were retrospectively reviewed for unexpected clinically important causes of hip pain. Thirty-six pediatric patients underwent contrast-enhanced MRI examinations for clinically suspected LCP disease in the setting of negative/equivocal radiographs. Twenty-two (61%) imaging studies were normal, while four (11%) imaging studies demonstrated findings consistent with LCP disease. Ten (28%) imaging studies revealed unexpected clinically important causes of hip pain, including nonspecific unilateral joint effusion and synovitis (n = 7, juvenile chronic arthritis was eventually diagnosed in 3 patients), sacral fracture (n = 1), apophyseal injury (n = 1), and femoral head subluxation (n = 1). MRI frequently reveals unexpected clinically important causes of hip pain in children with suspected LCP disease and negative/equivocal radiographs. (orig.)

Control of Vascular Smooth Muscle Cell Growth by Connexin 43

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Chintamani eJoshi

2012-06-01

Full Text Available Connexin 43 (Cx43, the principal gap junction protein in vascular smooth muscle cells (VSMCs, regulates movement of ions and other signaling molecules through gap junction intercellular communication (GJIC and plays important roles in maintaining normal vessel function; however, many of the signaling mechanisms controlling Cx43 in VSMCs are not clearly described. The goal of this study was to investigate mechanisms of Cx43 regulation with respect to VSMC proliferation. Treatment of rat primary VSMCs with the cAMP analog 8Br-cAMP, the soluble guanylate cyclase (sGC stimulator BAY 41-2272 (BAY, or the Cx inducer diallyl disulfide (DADS significantly reduced proliferation after 72 h compared to vehicle controls. Bromodeoxyuridine uptake revealed reduction (p<.001 in DNA synthesis after 6 h and flow cytometry showed reduced (40% S phase cell numbers after 16 h in DADS-treated cells compared to controls. Cx43 expression significantly increased after 270 min treatment with 8Br-cAMP, 8Br-cGMP, BAY or DADS. Inhibition of PKA, PKG or PKC reversed 8Br-cAMP-stimulated increases in Cx43 expression, whereas only PKG or PKC inhibition reversed 8Br-cGMP- and BAY-stimulated increases in total Cx43. Interestingly, stimulation of Cx43 expression by DADS was not dependent on PKA, PKG or PKC. Using fluorescence recovery after photobleaching, only 8Br-cAMP or DADS increased GJIC with 8Br-cAMP mediated by PKC and DADS mediated by PKG. Further, DADS significantly increased phosphorylation at the MAPK-sensitive serine (Ser255 and Ser279, the cell cycle regulatory kinase-sensitive Ser262 and the PKC-sensitive Ser368 after 30 min while 8Br-cAMP significantly increased phosphorylation only at Ser279 compared to controls. This study demonstrates that 8Br-cAMP- and DADS-enhanced GJIC rather than Cx43 expression and/or phosphorylation plays an important role in regulation of VSMC proliferation and provides new insights into the growth-regulatory capacities of Cx43 in VSMCs.

The crystal structures of EAP domains from Staphylococcus aureus reveal an unexpected homology to bacterial superantigens.

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Geisbrecht, Brian V; Hamaoka, Brent Y; Perman, Benjamin; Zemla, Adam; Leahy, Daniel J

2005-04-29

The Eap (extracellular adherence protein) of Staphylococcus aureus functions as a secreted virulence factor by mediating interactions between the bacterial cell surface and several extracellular host proteins. Eap proteins from different Staphylococcal strains consist of four to six tandem repeats of a structurally uncharacterized domain (EAP domain). We have determined the three-dimensional structures of three different EAP domains to 1.8, 2.2, and 1.35 A resolution, respectively. These structures reveal a core fold that is comprised of an alpha-helix lying diagonally across a five-stranded, mixed beta-sheet. Comparison of EAP domains with known structures reveals an unexpected homology with the C-terminal domain of bacterial superantigens. Examination of the structure of the superantigen SEC2 bound to the beta-chain of a T-cell receptor suggests a possible ligand-binding site within the EAP domain (Fields, B. A., Malchiodi, E. L., Li, H., Ysern, X., Stauffacher, C. V., Schlievert, P. M., Karjalainen, K., and Mariuzza, R. (1996) Nature 384, 188-192). These results provide the first structural characterization of EAP domains, relate EAP domains to a large class of bacterial toxins, and will guide the design of future experiments to analyze EAP domain structure/function relationships.

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

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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

Gaps in college biology students' understanding of photosynthesis: Implications for human constructivist learning theory and college classroom practice

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Griffard, Phyllis Baudoin

1999-11-01

The main research question of this study was: What gaps in biochemical understanding are revealed by a range of university introductory biology students as they work through a critically acclaimed multimedia program on photosynthesis, and what are the corresponding implications for elaboration of the Ausubel-Novak-Gowin Learning Theory (ANG, now Human Constructivism)? Twelve students, mixed for ability, gender and ethnicity, were recruited from two sections of "Bio 101." Before and after instruction in photosynthesis, in-depth clinical interviews were conducted during which participants completed a range of cognitive tasks such as sorting, concept mapping, explaining and predicting. Some tasks involved interacting with a computer simulation of photosynthesis. This study primarily employed qualitative case study and verbal analysis methods. Verbal analysis of the clinical interviews revealed numerous gaps that were categorized into typologies. The two major categories were propositional gaps and processing gaps. Propositional gaps were evident in development of participants' concepts, links and constructs. Significant among these were conceptual distance gaps and continuity of matter gaps. Gaps such as convention gaps and relative significance gaps seem to be due to naivete in the discipline. Processing gaps included gaps in graphic decoding skills and relevant cognitive habits such as self-monitoring and consulting prior knowledge. Although the gaps were easier to detect and isolate with the above-average participants, all participants showed evidence of at least some of these gaps. Since some gaps are not unexpected at all but the highest literacy levels, not all the gaps identified are to be considered deficiencies. The gaps identified support the attention given by ANG theorists to the role of prior knowledge and metacognition as well as the value of graphic organizers in knowledge construction. In addition, this study revealed numerous gaps in graphic decoding

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

Resistance to pyridine-based inhibitor KF116 reveals an unexpected role of integrase in HIV-1 Gag-Pol polyprotein proteolytic processing.

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Hoyte, Ashley C; Jamin, Augusta V; Koneru, Pratibha C; Kobe, Matthew J; Larue, Ross C; Fuchs, James R; Engelman, Alan N; Kvaratskhelia, Mamuka

2017-12-01

The pyridine-based multimerization selective HIV-1 integrase (IN) inhibitors (MINIs) are a distinct subclass of allosteric IN inhibitors. MINIs potently inhibit HIV-1 replication during virion maturation by inducing hyper- or aberrant IN multimerization but are largely ineffective during the early steps of viral replication. Here, we investigated the mechanism for the evolution of a triple IN substitution (T124N/V165I/T174I) that emerges in cell culture with a representative MINI, KF116. We show that HIV-1 NL4-3(IN T124N/V165I/T174I) confers marked (>2000-fold) resistance to KF116. Two IN substitutions (T124N/T174I) directly weaken inhibitor binding at the dimer interface of the catalytic core domain but at the same time markedly impair HIV-1 replication capacity. Unexpectedly, T124N/T174I IN substitutions inhibited proteolytic processing of HIV-1 polyproteins Gag and Gag-Pol, resulting in immature virions. Strikingly, the addition of the third IN substitution (V165I) restored polyprotein processing, virus particle maturation, and significant levels of replication capacity. These results reveal an unanticipated role of IN for polyprotein proteolytic processing during virion morphogenesis. The complex evolutionary pathway for the emergence of resistant viruses, which includes the need for the compensatory V165I IN substitution, highlights a relatively high genetic barrier exerted by MINI KF116. Additionally, we have solved the X-ray structure of the drug-resistant catalytic core domain protein, which provides means for rational development of second-generation MINIs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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

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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

Inhibition of Connexin 26/43 and Extracellular-Regulated Kinase Protein Plays a Critical Role in Melatonin Facilitated Gap Junctional Intercellular Communication in Hydrogen Peroxide-Treated HaCaT Keratinocyte Cells

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Hyo-Jung Lee

2012-01-01

Full Text Available Though melatonin was known to regulate gap junctional intercellular communication (GJIC in chick astrocytes and mouse hepatocytes, the underlying mechanism by melatonin was not elucidated in hydrogen peroxide- (H2O2- treated HaCaT keratinocyte cells until now. In the current study, though melatonin at 2 mM and hydrogen peroxide (H2O2 at 300 μM showed weak cytotoxicity in HaCaT keratinocyte cells, melatonin significantly suppressed the formation of reactive oxygen species (ROS in H2O2-treated HaCaT cells compared to untreated controls. Also, the scrape-loading dye-transfer assay revealed that melatonin enhances the intercellular communication by introducing Lucifer Yellow into H2O2-treated cells. Furthermore, melatonin significantly enhanced the expression of connexin 26 (Cx26 and connexin 43 (Cx43 at mRNA and protein levels, but not that of connexin 30 (Cx30 in H2O2-treated HaCaT cells. Of note, melatonin attenuated the phosphorylation of extracellular signal-regulated protein kinases (ERKs more than p38 MAPK or JNK in H2O2-treated HaCaT cells. Conversely, ERK inhibitor PD98059 promoted the intercellular communication in H2O2-treated HaCaT cells. Furthermore, combined treatment of melatonin (200 μM and vitamin C (10 μg/mL significantly reduced ROS production in H2O2-treated HaCaT cells. Overall, these findings support the scientific evidences that melatonin facilitates gap junctional intercellular communication in H2O2-treated HaCaT keratinocyte cells via inhibition of connexin 26/43 and ERK as a potent chemopreventive agent.

Bone morphogenetic protein-2 (BMP-2 and transforming growth factor-β1 (TGF-β1 alter connexin 43 phosphorylation in MC3T3-E1 Cells

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Rudkin George H

2001-07-01

Full Text Available Abstract Background Bone morphogenetic proteins (BMPs and transforming growth factor-βs (TGF-βs are important regulators of bone repair and regeneration. BMP-2 and TGF-β1 have been shown to inhibit gap junctional intercellular communication (GJIC in MC3T3-E1 cells. Connexin 43 (Cx43 has been shown to mediate GJIC in osteoblasts and it is the predominant gap junctional protein expressed in these murine osteoblast-like cells. We examined the expression, phosphorylation, and subcellular localization of Cx43 after treatment with BMP-2 or TGF-β1 to investigate a possible mechanism for the inhibition of GJIC. Results Northern blot analysis revealed no detectable change in the expression of Cx43 mRNA. Western blot analysis demonstrated no significant change in the expression of total Cx43 protein. However, significantly higher ratios of unphosphorylated vs. phosphorylated forms of Cx43 were detected after BMP-2 or TGF-β1 treatment. Immunofluorescence and cell protein fractionation revealed no detectable change in the localization of Cx43 between the cytosol and plasma membrane. Conclusions BMP-2 and TGF-β1 do not alter expression of Cx43 at the mRNA or protein level. BMP-2 and TGF-β1 may inhibit GJIC by decreasing the phosphorylated form of Cx43 in MC3T3-E1 cells.

TGF-beta1 inhibits Cx43 expression and formation of functional syncytia in cultured smooth muscle cells from human detrusor.

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Neuhaus, Jochen; Heinrich, Marco; Schwalenberg, Thilo; Stolzenburg, Jens-Uwe

2009-02-01

Human detrusor smooth muscle cells (hBSMCs) are coupled by connexin 43 (Cx43)-positive gap junctions to form functional syncytia. Gap junctional communication likely is necessary for synchronised detrusor contractions and is supposed to be altered in voiding disturbances. Other authors have shown that the pleiotropic cytokine TGF-beta1 upregulates Cx43 expression in human aortic smooth muscle cells. In this study, we examined the TGF-beta1 effects on Cx43 expression in cultured hBSMCs. hBSMC cultures, established from patients undergoing cystectomy, were treated with recombinant human TGF-beta1. Cx43 expression was then examined by Western blotting, real-time PCR, and immunocytochemistry. Dye-injection experiments were used to study the size of functional syncytia. Dye-coupling experiments revealed stable formation of functional syncytia in passaged cell cultures (P1-P4). Stimulation with TGF-beta1 led to significant reduction of Cx43 immunoreactivity and coupling. Cx43 protein expression was significantly downregulated and Cx43 mRNA was only 30% of the control level. Interestingly, low phosphorylation species of Cx43 were particularly affected. Our experiments demonstrated a significant down regulation of connexin 43 by TGF-beta1 in cultured hBSMCs. These findings support the view that TGF-beta1 is involved in the pathophysiology of urinary bladder dysfunction.

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.

Unexpected Regularity in Swimming Behavior of Clausocalanus furcatus Revealed by a Telecentric 3D Computer Vision System.

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Giuseppe Bianco

Full Text Available Planktonic copepods display a large repertoire of motion behaviors in a three-dimensional environment. Two-dimensional video observations demonstrated that the small copepod Clausocalanus furcatus, one the most widely distributed calanoids at low to medium latitudes, presented a unique swimming behavior that was continuous and fast and followed notably convoluted trajectories. Furthermore, previous observations indicated that the motion of C. furcatus resembled a random process. We characterized the swimming behavior of this species in three-dimensional space using a video system equipped with telecentric lenses, which allow tracking of zooplankton without the distortion errors inherent in common lenses. Our observations revealed unexpected regularities in the behavior of C. furcatus that appear primarily in the horizontal plane and could not have been identified in previous observations based on lateral views. Our results indicate that the swimming behavior of C. furcatus is based on a limited repertoire of basic kinematic modules but exhibits greater plasticity than previously thought.

Regulatory effect of connexin 43 on basal Ca2+ signaling in rat ventricular myocytes.

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Chen Li

Full Text Available BACKGROUND: It has been found that gap junction-associated intracellular Ca(2+ [Ca(2+](i disturbance contributes to the arrhythmogenesis and hyperconstriction in diseased heart. However, whether functional gaps are also involved in the regulation of normal Ca(2+ signaling, in particular the basal [Ca(2+](i activities, is unclear. METHODS AND RESULTS: Global and local Ca(2+ signaling and gap permeability were monitored in cultured neonatal rat ventricular myocytes (NRVMs and freshly isolated mouse ventricular myocytes by Fluo4/AM and Lucifer yellow (LY, respectively. The results showed that inhibition of gap communication by heptanol, Gap 27 and flufenamic acid or interference of connexin 43 (Cx43 with siRNA led to a significant suppression of LY uptake and, importantly, attenuations of global Ca(2+ transients and local Ca(2+ sparks in monolayer NRVMs and Ca(2+ sparks in adult ventricular myocytes. In contrast, overexpression of rat-Cx43 in NRVMs induced enhancements in the above measurements, and so did in HEK293 cells expressing rat Cx43. Additionally, membrane-permeable inositol 1,4,5-trisphosphate (IP(3 butyryloxymethyl ester and phenylephrine, an agonist of adrenergic receptor, could relieve the inhibited Ca(2+ signal and LY uptake by gap uncouplers, whereas blockade of IP(3 receptor with xestospongin C or 2-aminoethoxydiphenylborate mimicked the effects of gap inhibitors. More importantly, all these gap-associated effects on Ca(2+ signaling were also found in single NRVMs that only have hemichannels instead of gap junctions. Further immunostaining/immunoblotting single myocytes with antibody against Cx43 demonstrated apparent increases in membrane labeling of Cx43 and non-junctional Cx43 in overexpressed cells, suggesting functional hemichannels exist and also contribute to the Ca(2+ signaling regulation in cardiomyocytes. CONCLUSIONS: These data demonstrate that Cx43-associated gap coupling plays a role in the regulation of resting Ca(2

Connexin43 orthologues in vertebrates: phylogeny from fish to man

NARCIS (Netherlands)

van der Heyden, Marcel A. G.; van Eijk, Marleen; Wilders, Ronald; de Bakker, Jacques M. T.; Opthof, Tobias

2004-01-01

The gap junction protein connexin43 (Cx43) is widely expressed in all vertebrate species; however, in ventricular myocardium, Cx43 expression is restricted to mammalian species only, where it provides the molecular correlate for both electrical conduction and synchronization of the repolarization

CRISPR/Cas9 and active genetics-based trans-species replacement of the endogenous Drosophila kni-L2 CRM reveals unexpected complexity.

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Xu, Xiang-Ru Shannon; Gantz, Valentino Matteo; Siomava, Natalia; Bier, Ethan

2017-12-23

The knirps ( kni ) locus encodes transcription factors required for induction of the L2 wing vein in Drosophila . Here, we employ diverse CRISPR/Cas9 genome editing tools to generate a series of targeted lesions within the endogenous cis-regulatory module (CRM) required for kni expression in the L2 vein primordium. Phenotypic analysis of these ' in locus ' mutations based on both expression of Kni protein and adult wing phenotypes, reveals novel unexpected features of L2-CRM function including evidence for a chromosome pairing-dependent process that promotes transcription. We also demonstrate that self-propagating active genetic elements (CopyCat elements) can efficiently delete and replace the L2-CRM with orthologous sequences from other divergent fly species. Wing vein phenotypes resulting from these trans-species enhancer replacements parallel features of the respective donor fly species. This highly sensitive phenotypic readout of enhancer function in a native genomic context reveals novel features of CRM function undetected by traditional reporter gene analysis. © 2017, Xu et al.

Chlorpromazine reduces the intercellular communication via gap junctions in mammalian cells

International Nuclear Information System (INIS)

Orellana, Juan A.; Palacios-Prado, Nicolas; Saez, Juan C.

2006-01-01

In the work presented herein, we evaluated the effect of chlorpromazine (CPZ) on gap junctions expressed by two mammalian cell types; Gn-11 cells (cell line derived from mouse LHRH neurons) and rat cortical astrocytes maintained in culture. We also attempted to elucidate possible mechanisms of action of CPZ effects on gap junctions. CPZ, in concentrations comparable with doses used to treat human diseases, was found to reduce the intercellular communication via gap junctions as evaluated with measurements of dye coupling (Lucifer yellow). In both cell types, maximal inhibition of functional gap junctions was reached within about 1 h of treatment with CPZ, an recovery was almost complete at about 5 h after CPZ wash out. In both cell types, CPZ treatment increased the phosphorylation state of connexin43 (Cx43), a gap junction protein subunit. Moreover, CPZ reduced the reactivity of Cx43 (immunofluorescence) at cell interfaces and concomitantly increased its reactivity in intracellular vesicles, suggesting an increased retrieval from and/or reduced insertion into the plasma membrane. CPZ also caused cellular retraction reducing cell-cell contacts in a reversible manner. The reduction in contact area might destabilize existing gap junctions and abrogate formation of new ones. Moreover, the CPZ-induced reduction in gap junctional communication may depend on the connexins (Cxs) forming the junctions. If Cx43 were the only connexin expressed, MAPK-dependent phosphorylation of this connexin would induce closure of gap junction channels

The Effects of IGF-1 on TNF-α-Treated DRG Neurons by Modulating ATF3 and GAP-43 Expression via PI3K/Akt/S6K Signaling Pathway.

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Zhang, Lei; Yue, Yaping; Ouyang, Meishuo; Liu, Huaxiang; Li, Zhenzhong

2017-05-01

Upregulation of the pro-inflammatory cytokine tumor necrosis factor α (TNF-α) is involved in the development and progression of numerous neurological disorders. Recent reports have challenged the concept that TNF-α exhibits only deleterious effects of pro-inflammatory destruction, and have raised the awareness that it may play a beneficial role in neuronal growth and function in particular conditions, which prompts us to further investigate the role of this cytokine. Insulin-like growth factor-1 (IGF-1) is a cytokine possessing powerful neuroprotective effects in promoting neuronal survival, neuronal differentiation, neurite elongation, and neurite regeneration. The association of IGF-1 with TNF-α and the biological effects, produced by interaction of IGF-1 and TNF-α, on neuronal outgrowth status of primary sensory neurons are still to be clarified. In the present study, using an in vitro model of primary cultured rat dorsal root ganglion (DRG) neurons, we demonstrated that TNF-α challenge at different concentrations elicited diverse biological effects. Higher concentration of TNF-α (10 ng/mL) dampened neurite outgrowth, induced activating transcription factor 3 (ATF3) expression, reduced growth-associated protein 43 (GAP-43) expression, and promoted GAP-43 and ATF3 coexpression, which could be reversed by IGF-1 treatment; while lower concentration of TNF-α (1 ng/mL) promoted neurite sprouting, decreased ATF3 expression, increased GAP-43 expression, and inhibited GAP-43 and ATF3 coexpression, which could be potentiated by IGF-1 supplement. Moreover, IGF-1 administration restored the activation of Akt and p70 S6 kinase (S6K) suppressed by higher concentration of TNF-α (10 ng/mL) challenge. In contrast, lower concentration of TNF-α (1 ng/mL) had no significant effect on Akt or S6K activation, and IGF-1 administration activated these two kinases. The effects of IGF-1 were abrogated by phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These data

Inhibition of connexin43 hemichannels impairs spatial short-term memory without affecting spatial working memory

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Laura Walrave

2016-12-01

Full Text Available Astrocytes are active players in higher brain function as they can release gliotransmitters, which are essential for synaptic plasticity. Various mechanisms have been proposed for gliotransmission, including vesicular mechanisms as well as non-vesicular ones, for example by passive diffusion via connexin hemichannels (HCs. We here investigated whether interfering with connexin43 (Cx43 HCs influenced hippocampal spatial memory. We made use of the peptide Gap19 that blocks HCs but not gap junction channels and is specific for Cx43. To this end, we microinfused transactivator of transcription linked Gap19 (TAT-Gap19 into the brain ventricle of male NMRI mice and assessed spatial memory in a Y maze. We found that the in vivo blockade of Cx43 HCs did not affect the locomotor activity or spatial working memory in a spontaneous alternation Y maze task. Cx43 blockade did however significantly impair the spatial short-term memory in a delayed spontaneous alternation Y maze task. These results indicate that Cx43 HCs play a role in spatial short-term memory.

A Global Synthesis Reveals Gaps in Coastal Habitat Restoration Research

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Y. Stacy Zhang

2018-04-01

Full Text Available Coastal ecosystems have drastically declined in coverage and condition across the globe. To combat these losses, marine conservation has recently employed habitat restoration as a strategy to enhance depleted coastal ecosystems. For restoration to be a successful enterprise, however, it is necessary to identify and address potential knowledge gaps and review whether the field has tracked scientific advances regarding best practices. This enables managers, researchers, and practitioners alike to more readily establish restoration priorities and goals. We synthesized the peer-reviewed, published literature on habitat restoration research in salt marshes, oyster reefs, and seagrasses to address three questions related to restoration efforts: (i How frequent is cross-sector authorship in coastal restoration research? (ii What is the geographic distribution of coastal restoration research? and (iii Are abiotic and biotic factors equally emphasized in the literature, and how does this vary with time? Our vote-count survey indicated that one-third of the journal-published studies listed authors from at least two sectors, and 6% listed authors from all three sectors. Across all habitat types, there was a dearth of studies from Africa, Asia, and South America. Finally, despite many experimental studies demonstrating that species interactions can greatly affect the recovery and persistence of coastal foundation species, only one-fourth of the studies we examined discussed their effects on restoration. Combined, our results reveal gaps and discrepancies in restoration research that should be addressed in order to further propel coastal restoration science.

TAT-Gap19 and Carbenoxolone Alleviate Liver Fibrosis in Mice

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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.

Roles of gap junctions, connexins and pannexins in epilepsy

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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

c-Jun N-terminal kinase mediates AML1-ETO protein-induced connexin-43 expression

International Nuclear Information System (INIS)

Gao Fenghou; Wang Qiong; Wu Yingli; Li Xi; Zhao Kewen; Chen Guoqiang

2007-01-01

AML1-ETO fusion protein, a product of leukemia-related chromosomal translocation t(8;21), was reported to upregulate expression of connexin-43 (Cx43), a member of gap junction-constituted connexin family. However, its mechanism(s) remains unclear. By bioinformatic analysis, here we showed that there are two putative AML1-binding consensus sequences followed by two activated protein (AP)1 sites in the 5'-flanking region upstream to Cx43 gene. AML1-ETO could directly bind to these two AML1-binding sites in electrophoretic mobility shift assay, but luciferase reporter assay revealed that the AML1 binding sites were not indispensable for Cx43 induction by AML1-ETO protein. Conversely, AP1 sites exerted an important role in this event. In agreement, AML1-ETO overexpression in leukemic U937 cells activated c-Jun N-terminal kinase (JNK), while its specific inhibitor SP600125 effectively abrogated AML1-ETO-induced Cx43 expression, indicating that JNK signaling pathway contributes to AML1-ETO induced Cx43 expression. These results would shed new insights for understanding mechanisms of AML1-ETO-associated leukemogenesis

Connexin-43 interactions with ZO-1 and alpha- and beta-tubulin

NARCIS (Netherlands)

Giepmans, B N; Verlaan, I; Moolenaar, W H

2001-01-01

Gap junctions are composed of connexins that form transmembrane channels between adjacent cells. The C-terminal tail of connexin-43 (Cx43), the most widely expressed connexin member, has been implicated in the regulation of Cx43 channel gating. Interestingly, channel-independent processes regulated

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....

Effect of enhanced expression of connexin 43 on sunitinib-induced cytotoxicity in mesothelioma cells

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Miaki Uzu

2015-05-01

Full Text Available Connexin (Cx makes up a type of intercellular channel called gap junction (GJ. GJ plays a regulatory role in cellular physiology. The Cx expression level is often decreased in cancer cells compared to that in healthy ones, and the restoration of its expression has been shown to exert antiproliferative effects. This work aims to evaluate the effect of the restoration of connexin 43 (Cx43 (the most ubiquitous Cx subtype expression on sunitinib (SU-induced cytotoxicity in malignant mesothelioma (MM cells. Increased Cx43 expression in an MM cell line (H28 improved the ability of SU to inhibit receptor tyrosine kinase (RTK signaling. Moreover, higher Cx43 expression promoted SU-induced apoptosis. The cell viability test revealed that Cx43 enhanced the cytotoxic effect of SU in a GJ-independent manner. The effect of Cx43 on a proapoptotic factor, Bax, was then investigated. The interaction between Cx43 and Bax was confirmed by immunoprecipitation. Furthermore, higher Cx43 expression increased the production of a cleaved (active form of Bax during SU-induced apoptosis with no alteration in total Bax expression. These findings indicate that Cx43 most likely increases sensitivity to SU in H28 through direct interaction with Bax. In conclusion, we found that Cx43 overcame the chemoresistance of MM cells.

Connexin 43 expression in human and mouse testes with impaired spermatogenesis

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M Kotula-Balak

2009-08-01

Full Text Available Connexin 43 (Cx43 belongs to a family of proteins that form gap junction channels. The aim of this study was to examine the expression of Cx43 in the testis of a patient with Klinefelter’s syndrome and of mice with the mosaic mutation and a partial deletion in the long arm of the Y chromosome. These genetic disorders are characterized by the presence of numerous degenerated seminiferous tubules and impaired spermatogenesis. In mouse testes, the expression and presence of Cx43 were detected by means of immunohistochemistry and Western blot analysis, respectively. In testes of Klinefelter’s patient only immunoexpression of Cx43 was detected. Regardless of the species Cx43 protein was ubiquitously distributed in testes of reproductively normal males, whereas in those with testicular disorders either a weak intensity of staining or no staining within the seminiferous tubules was observed. Moderate to strong or very strong staining was confined to the interstitial tissue. In an immunoblot analysis of testicular homogenates Cx43 appeared as one major band of approximately 43 kDa. Our study adds three more examples of pathological gonads in which the absence or apparent decrease of Cx43 expression within the seminiferous tubules was found. A positive correlation between severe spermatogenic impairment and loss of Cx43 immunoreactivity observed in this study supports previous data that gap junctions play a crucial role in spermatogenesis. Strong Cx43 expression detected mostly in the interstitial tissue of the Klinefelter’s patient may presumably be of importance in sustaining Leydig cell metabolic activity. However, the role of gap junction communication in the control of Leydig cell function seems to be more complex than originally thought.

Ginsenoside Rg1 alleviates corticosterone-induced dysfunction of gap junctions in astrocytes.

Science.gov (United States)

Xia, Cong-Yuan; Chu, Shi-Feng; Zhang, Shuai; Gao, Yan; Ren, Qian; Lou, Yu-Xia; Luo, Piao; Tian, Man-Tong; Wang, Zhi-Qi; Du, Guo-Hua; Tomioka, Yoshihisa; Yamakuni, Tohru; Zhang, Yi; Wang, Zhen-Zhen; Chen, Nai-Hong

2017-08-17

Ginsenoside Rg1 (Rg1), one of the major bioactive ingredients of Panax ginseng C. A. Mey, has neuroprotective effects in animal models of depression, but the mechanism underlying these effects is still largely unknown AIM OF THE STUDY: Gap junction intercellular communication (GJIC) dysfunction is a potentially novel pathogenic mechanism for depression. Thus, we investigated that whether antidepressant-like effects of Rg1 were related to GJIC. Primary rat prefrontal cortical and hippocampal astrocytes cultures were treated with 50μM CORT for 24h to induce gap junction damage. Rg1 (0.1, 1, or 10μM) or fluoxetine (1μM) was added 1h prior to CORT treatment. A scrape loading and dye transfer assay was performed to identify the functional capacity of gap junctions. Western blot was used to detect the expression and phosphorylation of connexin43 (Cx43), the major component of gap junctions. Treatment of primary astrocytes with CORT for 24h inhibited GJIC, decreased total Cx43 expression, and increased the phosphorylation of Cx43 at serine368 in a dose-dependent manner. Pre-treatment with 1μM and 10μM Rg1 significantly improved GJIC in CORT-treated astrocytes from the prefrontal cortex and hippocampus, respectively, and this was accompanied by upregulation of Cx43 expression and downregulation of Cx43 phosphorylation. These findings provide the first evidence indicating that Rg1 can alleviate CORT-induced gap junction dysfunction, which may have clinical significance in the treatment of depression. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Metatranscriptomic analysis of a high-sulfide aquatic spring reveals insights into sulfur cycling and unexpected aerobic metabolism

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Anne M. Spain

2015-09-01

Full Text Available Zodletone spring is a sulfide-rich spring in southwestern Oklahoma characterized by shallow, microoxic, light-exposed spring water overlaying anoxic sediments. Previously, culture-independent 16S rRNA gene based diversity surveys have revealed that Zodletone spring source sediments harbor a highly diverse microbial community, with multiple lineages putatively involved in various sulfur-cycling processes. Here, we conducted a metatranscriptomic survey of microbial populations in Zodletone spring source sediments to characterize the relative prevalence and importance of putative phototrophic, chemolithotrophic, and heterotrophic microorganisms in the sulfur cycle, the identity of lineages actively involved in various sulfur cycling processes, and the interaction between sulfur cycling and other geochemical processes at the spring source. Sediment samples at the spring’s source were taken at three different times within a 24-h period for geochemical analyses and RNA sequencing. In depth mining of datasets for sulfur cycling transcripts revealed major sulfur cycling pathways and taxa involved, including an unexpected potential role of Actinobacteria in sulfide oxidation and thiosulfate transformation. Surprisingly, transcripts coding for the cyanobacterial Photosystem II D1 protein, methane monooxygenase, and terminal cytochrome oxidases were encountered, indicating that genes for oxygen production and aerobic modes of metabolism are actively being transcribed, despite below-detectable levels (<1 µM of oxygen in source sediment. Results highlight transcripts involved in sulfur, methane, and oxygen cycles, propose that oxygenic photosynthesis could support aerobic methane and sulfide oxidation in anoxic sediments exposed to sunlight, and provide a viewpoint of microbial metabolic lifestyles under conditions similar to those seen during late Archaean and Proterozoic eons.

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

Science.gov (United States)

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

2010-08-01

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

Rings and gaps in the disc around Elias 24 revealed by ALMA

Science.gov (United States)

Dipierro, G.; Ricci, L.; Pérez, L.; Lodato, G.; Alexander, R. D.; Laibe, G.; Andrews, S.; Carpenter, J. M.; Chandler, C. J.; Greaves, J. A.; Hall, C.; Henning, T.; Kwon, W.; Linz, H.; Mundy, L.; Sargent, A.; Tazzari, M.; Testi, L.; Wilner, D.

2018-04-01

We present Atacama Large Millimeter/sub-millimeter Array (ALMA) Cycle 2 observations of the 1.3-mm dust continuum emission of the protoplanetary disc surrounding the T Tauri star Elias 24 with an angular resolution of ˜0.2 arcsec (˜28 au). The dust continuum emission map reveals a dark ring at a radial distance of 0.47 arcsec (˜65 au) from the central star, surrounded by a bright ring at 0.58 arcsec (˜81 au). In the outer disc, the radial intensity profile shows two inflection points at 0.71 and 0.87 arcsec (˜99 and 121 au, respectively). We perform global three-dimensional smoothed particle hydrodynamic gas/dust simulations of discs hosting a migrating and accreting planet. Combining the dust density maps of small and large grains with three-dimensional radiative transfer calculations, we produce synthetic ALMA observations of a variety of disc models in order to reproduce the gap- and ring-like features observed in Elias 24. We find that the dust emission across the disc is consistent with the presence of an embedded planet with a mass of ˜0.7 MJ at an orbital radius of ˜ 60 au. Our model suggests that the two inflection points in the radial intensity profile are due to the inward radial motion of large dust grains from the outer disc. The surface brightness map of our disc model provides a reasonable match to the gap- and ring-like structures observed in Elias 24, with an average discrepancy of ˜5 per cent of the observed fluxes around the gap region.

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.

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.

Phosphorylation of connexin43 on S279/282 may contribute to laminopathy-associated conduction defects

Energy Technology Data Exchange (ETDEWEB)

Chen, Steven C., E-mail: bug@uw.edu [Fred Hutchinson Cancer Research Center (FHCRC), Public Health Sciences Division, 1100 Fairview Ave. N., Seattle, WA 98109 (United States); University of Washington Department of Biochemistry, 1959 NE Pacific St., Seattle, WA 98195 (United States); Kennedy, Brian K., E-mail: bkennedy@buckinstitute.org [University of Washington Department of Biochemistry, 1959 NE Pacific St., Seattle, WA 98195 (United States); Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945 (United States); Lampe, Paul D., E-mail: plampe@fhcrc.org [Fred Hutchinson Cancer Research Center (FHCRC), Public Health Sciences Division, 1100 Fairview Ave. N., Seattle, WA 98109 (United States)

2013-04-01

An understanding of the molecular mechanism behind the arrhythmic phenotype associated with laminopathies has yet to emerge. A-type lamins have been shown to interact and sequester activated phospho-ERK1/2(pERK1/2) at the nucleus. The gap junction protein connexin43 (Cx43) can be phosphorylated by pERK1/2 on S279/282 (pS279/282), inhibiting intercellular communication. We hypothesized that without A-type lamins, pS279/282 Cx43 will increase due to inappropriate phosphorylation by pERK1/2, resulting in decreased gap junction function. We observed a 1.6-fold increase in pS279/282 Cx43 levels in Lmna{sup −/−} mouse embryonic fibroblasts (MEFs) compared to Lmna{sup +/+}, and 1.8-fold more pERK1/2 co-precipitated from Lmna{sup −/−} MEFs with Cx43 antibodies. We found a 3-fold increase in the fraction of non-nuclear pERK1/2 and a concomitant 2-fold increase in the fraction of pS279/282 Cx43 in Lmna{sup −/−} MEFs by immunofluorescence. In an assay of gap junctional function, Lmna{sup −/−} MEFs transferred dye to 60% fewer partners compared to Lmna{sup +/+} controls. These results are mirrored in 5–6 week-old Lmna{sup −/−} mice compared to their Lmna{sup +/+} littermates as we detect increased pS279/282 Cx43 in gap junctions by immunofluorescence and 1.7-fold increased levels by immunoblot. We conclude that increased pS279/282 Cx43 in the Lmna{sup −/−} background results in decreased cell communication and may contribute to the arrhythmic pathology in vivo. - Highlights: ► Connexin43 phosphorylation plays a role in laminopathy-associated conduction defects. ► Loss of A-type lamin activity results in release of pERK1/2 from the nucleus. ► Increased cytoplasmic localization of pERK1/2 acts to phosphorylate S279/282 of Cx43. ► Phosphorylation of S279/282 on Cx43 decreases gap junction activity in cell culture. ► Mice lacking A-type lamins have increased phosphorylation on S279/282 of Cx43.

Connexin43 gene and its irradiation-induced expression

International Nuclear Information System (INIS)

Long Xianhui; Zhou Pingkun

2005-01-01

Gap junctions, composed of connexin protein subunits, provide the important channel for the intercellular communication. Connexin43, the most popular component of the connexin protein family, is widely expressed in multiple tissues and cell lines and plays an important role in cell proliferation, differention and tissue homeostasis. Recently it was reported that the expression of connexin43 gene is remarkedly up-regulated by low dose ionizing radiation, the available data suggest connexin43 gene to be a poten-tial sensitive bio-marker in radiation damage. (authors)

Complex role of connexin 43 in astrocytic tumors and possible promotion of glioma‑associated epileptic discharge (Review).

Science.gov (United States)

Dong, Hui; Zhou, Xing-Wang; Wang, Xiang; Yang, Yuan; Luo, Jie-Wen; Liu, Yan-Hui; Mao, Qing

2017-12-01

Connexin (Cx)43 is a multifunction protein which forms gap junction channels and hemi‑channels. It also contains abundant binding domains which possess the ability to interact with certain Cx43‑associated proteins and therefore serve a fundamental role in various physiological and pathological functions. However, the understanding of the association between cancer and Cx43 along with Cx43‑gap junctions (GJ) remains unclear. All available data illustrate that Cx43 and its associated GJ serve important functions in cancers. The expression levels of Cx43 demonstrate a downward trend and an increase in the levels of malignancy, particularly in astrocytomas. The GJ intercellular communication activity in glioma cells can be adjusted via Cx43 phosphorylation and through the combination of Cx43 and its associated protein. Available evidence reveals Cx43 as a tumor‑inhibiting factor that suppresses glioma growth and proliferation. However, its mechanism is also regarded as complicated and ambiguous. Furthermore, it is apparent that Cx43‑GJ and the carboxyl tail may contribute to glioma growth and proliferation too. However, this valuable role could be weakened by its effects on migration and invasiveness. The detailed mechanism remains unclear and full of controversies. Cx43 can enhance the motor ability and invasiveness of astrocytic glioma cells. It is also able to influence glioma cells to detach from the tumor core to the peritumoral neocortex. This peritumoral region has recently been regarded as the basic focus of glioma‑associated seizure. Thus, Cx43 may take part in the onset and development of glioma‑associated epileptic discharge. In addition, change and increase of Cx43 expression in GJs has been observed in seizure perilesional tissue, which is associated with brain tumors. Cx43 or GJ/hemi‑channels exert enduring effects in the promotion of glioma‑associated epileptic release through direct mass effects and change of the tumor microenvironment

Unexpected strong attraction in the presence of continuum bound state

International Nuclear Information System (INIS)

Delfino, A.; Frederico, T.

1992-06-01

The result of few-particle ground-state calculation employing a two-particle non-local potential supporting a continuum bound state in addition to a negative-energy bound state has occasionally revealed unexpected large attraction in producing a very strongly bound ground state. In the presence of the continuum bound state the difference of phase shift between zero and infinite energies has an extra jump of φ as in the presence of an additional bound state. The wave function of the continuum bound state is identical with that of a strongly bound negative-energy state, which leads us to postulate a pseudo bound state in the two-particle system in order to explain the unexpected attraction. The role of the Pauli forbidden states is expected to be similar to these pseudo states. (author)

Unexpected brain finding in pre-autopsy postmortem CT.

Science.gov (United States)

Chatzaraki, Vasiliki; Bolliger, Stephan A; Thali, Michael J; Eggert, Sebastian; Ruder, Thomas D

2017-09-01

A case is presented in which pre-autopsy postmortem computed tomography (PMCT) revealed an unexpected brain abscess with a related frontal sinusitis and an erosion of the posterior wall of the frontal sinus. PMCT findings enabled the forensic pathologists to adapt protective measures during autopsy and protect their health from infection. Pre-autopsy PMCT has been also useful in the early differential diagnosis procedure. The complementary use of postmortem imaging and autopsy can improve the quality of forensic death investigations.

Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling.

Science.gov (United States)

Roell, Wilhelm; Klein, Alexandra M; Breitbach, Martin; Becker, Torsten S; Parikh, Ashish; Lee, Jane; Zimmermann, Katrin; Reining, Shaun; Gabris, Beth; Ottersbach, Annika; Doran, Robert; Engelbrecht, Britta; Schiffer, Miriam; Kimura, Kenichi; Freitag, Patricia; Carls, Esther; Geisen, Caroline; Duerr, Georg D; Sasse, Philipp; Welz, Armin; Pfeifer, Alexander; Salama, Guy; Kotlikoff, Michael; Fleischmann, Bernd K

2018-05-08

Ventricular tachycardia (VT) is the most common and potentially lethal complication following myocardial infarction (MI). Biological correction of the conduction inhomogeneity that underlies re-entry could be a major advance in infarction therapy. As minimal increases in conduction of infarcted tissue markedly influence VT susceptibility, we reasoned that enhanced propagation of the electrical signal between non-excitable cells within a resolving infarct might comprise a simple means to decrease post-infarction arrhythmia risk. We therefore tested lentivirus-mediated delivery of the gap-junction protein Connexin 43 (Cx43) into acute myocardial lesions. Cx43 was expressed in (myo)fibroblasts and CD45 + cells within the scar and provided prominent and long lasting arrhythmia protection in vivo. Optical mapping of Cx43 injected hearts revealed enhanced conduction velocity within the scar, indicating Cx43-mediated electrical coupling between myocytes and (myo)fibroblasts. Thus, Cx43 gene therapy, by direct in vivo transduction of non-cardiomyocytes, comprises a simple and clinically applicable biological therapy that markedly reduces post-infarction VT.

Expression of growth-associated protein 43 in the skin nerve fibers of patients with type 2 diabetes mellitus.

Science.gov (United States)

Bursova, Sarka; Dubovy, Petr; Vlckova-Moravcova, Eva; Nemec, Martin; Klusakova, Ilona; Belobradkova, Jana; Bednarik, Josef

2012-04-15

The growth-associated protein 43 (GAP-43) is known as a marker of regenerating nerve fibers and their continuous remodeling in the adult human skin. The purpose of this pilot study was to investigate a possible role for GAP-43 in the detection of the early stages of small-fiber neuropathy in patients with type 2 diabetes mellitus (DM2) as compared with a well- established and validated parameter - intra-epidermal nerve fiber density (IENFD) of protein gene product 9.5 (PGP 9.5) immunoreactive intra-epidermal C fibers. In a group of 21 patients with DM2 within three years of diagnosis (13 men, 8 women; mean age 53.9±12.8; range 30-74) and a group of 17 healthy volunteers (8 men, 9 women; mean age 55.8±8.5; range 45-70 years), skin punch biopsies were taken from a distal calf and double immunostained with both PGP 9.5 and GAP-43. In healthy controls, 96.8% of 629 PGP 9.5 immunoreactive fibers were immunostained with GAP-43; the proportion of PGP 9.5 intra-epidermal nerve fibers immunoreactive for GAP-43 in control subjects ranged from 86.5 to 100%. In DM2 patients, IENFD was significantly lower compared to controls (median, 1.5 vs. 11.2/mm; pDM2 patients compared to healthy controls (73.6% of 337 PGP 9.5 positive fibers; p<0.001); ranged from 0 to 98.1%. In conclusion, these results show that impaired regeneration of intra-epidermal C fibers in the early stages of type 2 diabetes mellitus, as indicated by GAP-43, might be a marker of incipient diabetic neuropathy. Copyright © 2011 Elsevier B.V. All rights reserved.

Investigating Initial Disclosures and Reactions to Unexpected, Positive HPV Diagnosis.

Science.gov (United States)

Smith, Rachel A; Hernandez, Rachael; Catona, Danielle

2014-07-01

Initial disclosures of health conditions are critical communication moments. Existing research focuses on disclosers; integrating confidants into studies of initial disclosures is needed. Guided by the disclosure decision-making model (DD-MM; Greene, 2009), this study examined what diagnosed persons and confidants may say when faced with unexpected test results and unexpected disclosures, respectively. Participants ( N = 151) recorded an audio-visual message for another person, after imagining that they or the other person had just received unexpected, positive HPV test results. The qualitative analysis revealed four themes: (1) impression management and social distance, (2) invisible symptoms and advice regarding future disclosures, (3) expressing and acknowledging emotional reactions, and (4) misunderstandings and lacking knowledge about HPV. These findings suggested that DD-MM may be a relevant framework for understanding not only when disclosers share, but what disclosers and confidants say in early conversations about new diagnoses. While disclosers' and confidants' messages showed marked similarities, important differences appeared. For example, confidants focused on assuaging disclosers' fear about the consequences, whereas disclosers expressed distress related to their uncertainty about the prognosis of an HPV infection and how to prepare for next steps. The discussion highlighted implications for the DD-MM, HPV disclosures, and future interventions.

Low Band Gap Donor–Acceptor Type Polymers Containing 2,3-Bis(4-(decyloxyphenylpyrido[4,3-b]pyrazine as Acceptor and Different Thiophene Derivatives as Donors

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Yan Zhang

2016-10-01

Full Text Available Four donor–acceptor type conducting polymers, namely poly(2,3-bis(4-decyloxyphenyl-5,8-bis(4-thiophen-2-ylpyrido[4,3-b]pyrazine (P1, poly(2,3-bis(4-decyloxyphenyl-5,8-bis(4-butylthiophen-2-ylpyrido[4,3-b]pyrazine (P2, poly(2,3-bis(4-(decyloxyphenyl-5,8-bis(4-hexyloxythiophen-2-ylpyrido[4,3-b]pyrazine (P3 and poly(2,3-bis(4-(decyloxyphenyl-5,8-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-7-ylpyrido[4,3-b]pyrazine (P4, containing thiophene or its derivative as the donor and pyrido[4,3-b]pyrazine as the acceptor were prepared and characterized by cyclic voltammetry, scanning electron microscopy, and UV-Vis spectroscopy to detect the influence of the donor units’ strength on the electrochromic performances. The results demonstrated that all of the polymers could be reversibly reduced and oxidized by p-type doping and n-type doping, and showed near-infrared activities and different color changes in p-type doping process. Especially, P3 and P4 showed lower optical band gap than P1 and P2 due to the strong electron-donating hexyloxythiophen group of P3 and ethylenedioxythiophene group of P4. Besides, P3 and P4 displayed the saturated green color at the neutral state and the desirable transparency at the oxidized state. All the polymers displayed desirable optical contrasts, satisfactory coloration efficiency, excellent stability and short switching time, which made the polymers fascinating candidates in the electrochromic device applications.

Unexpected high plasma cobalamin

DEFF Research Database (Denmark)

Arendt, Johan F B; Nexo, Ebba

2013-01-01

It is well-established that more than 8% of patients examined for vitamin B12 deficiency unexpectedly have increased plasma levels of the vitamin, but so far there are no guidelines for the clinical interpretation of such findings. In this review, we summarise known associations between high plasma...... cobalamin binding proteins, transcobalamin and haptocorrin. Based on current knowledge, we suggest a strategy for the clinical interpretation of unexpected high plasma cobalamin. Since a number of the associated diseases are critical and life-threatening, the strategy promotes the concept of 'think...

Directed Evolution Reveals Unexpected Epistatic Interactions That Alter Metabolic Regulation and Enable Anaerobic Xylose Use by Saccharomyces cerevisiae.

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Trey K Sato

2016-10-01

Full Text Available The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically. We report that rapid xylose conversion by engineered and evolved S. cerevisiae strains depends upon epistatic interactions among genes encoding a xylose reductase (GRE3, a component of MAP Kinase (MAPK signaling (HOG1, a regulator of Protein Kinase A (PKA signaling (IRA2, and a scaffolding protein for mitochondrial iron-sulfur (Fe-S cluster biogenesis (ISU1. Interestingly, the mutation in IRA2 only impacted anaerobic xylose consumption and required the loss of ISU1 function, indicating a previously unknown connection between PKA signaling, Fe-S cluster biogenesis, and anaerobiosis. Proteomic and metabolomic comparisons revealed that the xylose-metabolizing mutant strains exhibit altered metabolic pathways relative to the parental strain when grown in xylose. Further analyses revealed that interacting mutations in HOG1 and ISU1 unexpectedly elevated mitochondrial respiratory proteins and enabled rapid aerobic respiration of xylose and other non-fermentable carbon substrates. Our findings suggest a surprising connection between Fe-S cluster biogenesis and signaling that facilitates aerobic respiration and anaerobic fermentation of xylose, underscoring how much remains unknown about the eukaryotic signaling systems that regulate carbon metabolism.

Directed Evolution Reveals Unexpected Epistatic Interactions That Alter Metabolic Regulation and Enable Anaerobic Xylose Use by Saccharomyces cerevisiae.

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Sato, Trey K; Tremaine, Mary; Parreiras, Lucas S; Hebert, Alexander S; Myers, Kevin S; Higbee, Alan J; Sardi, Maria; McIlwain, Sean J; Ong, Irene M; Breuer, Rebecca J; Avanasi Narasimhan, Ragothaman; McGee, Mick A; Dickinson, Quinn; La Reau, Alex; Xie, Dan; Tian, Mingyuan; Reed, Jennifer L; Zhang, Yaoping; Coon, Joshua J; Hittinger, Chris Todd; Gasch, Audrey P; Landick, Robert

2016-10-01

The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically. We report that rapid xylose conversion by engineered and evolved S. cerevisiae strains depends upon epistatic interactions among genes encoding a xylose reductase (GRE3), a component of MAP Kinase (MAPK) signaling (HOG1), a regulator of Protein Kinase A (PKA) signaling (IRA2), and a scaffolding protein for mitochondrial iron-sulfur (Fe-S) cluster biogenesis (ISU1). Interestingly, the mutation in IRA2 only impacted anaerobic xylose consumption and required the loss of ISU1 function, indicating a previously unknown connection between PKA signaling, Fe-S cluster biogenesis, and anaerobiosis. Proteomic and metabolomic comparisons revealed that the xylose-metabolizing mutant strains exhibit altered metabolic pathways relative to the parental strain when grown in xylose. Further analyses revealed that interacting mutations in HOG1 and ISU1 unexpectedly elevated mitochondrial respiratory proteins and enabled rapid aerobic respiration of xylose and other non-fermentable carbon substrates. Our findings suggest a surprising connection between Fe-S cluster biogenesis and signaling that facilitates aerobic respiration and anaerobic fermentation of xylose, underscoring how much remains unknown about the eukaryotic signaling systems that regulate carbon metabolism.

Unexpected uncertainty, volatility and decision-making

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Amy Rachel Bland

2012-06-01

Full Text Available The study of uncertainty in decision making is receiving greater attention in the fields of cognitive and computational neuroscience. Several lines of evidence are beginning to elucidate different variants of uncertainty. Particularly, risk, ambiguity and expected and unexpected forms of uncertainty are well articulated in the literature. In this article we review both empirical and theoretical evidence arguing for the potential distinction between three forms of uncertainty; expected uncertainty, unexpected uncertainty and volatility. Particular attention will be devoted to exploring the distinction between unexpected uncertainty and volatility which has been less appreciated in the literature. This includes evidence from computational modelling, neuromodulation, neuroimaging and electrophysiological studies. We further address the possible differentiation of cognitive control mechanisms used to deal with these forms of uncertainty. Particularly we explore a role for conflict monitoring and the temporal integration of information into working memory. Finally, we explore whether the Dual Modes of Control theory provides a theoretical framework for understanding the distinction between unexpected uncertainty and volatility.

Postreplication repair gap filling in an Escherichia coli strain deficient in dnaB gene product

International Nuclear Information System (INIS)

Johnson, R.C.

1975-01-01

Gaps in daughter-strand DNA synthesized after exposure of Escherichia coli E279 to ultraviolet light are filled during reincubation at 30 0 C for 20 min. Escherichia coli E279 is phenotypically DnaB - when incubated at 43 0 C. Cells incubated at 43 0 C were tested for their ability to complete postreplication repair gap filling. It is concluded that the dnaB gene product is essential for postreplication repair gap filling and that the inhibition seen is not initially the result of degradation

Cell motility in models of wounded human skin is improved by Gap27 despite raised glucose, insulin and IGFBP-5

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Wright, Catherine S.; Berends, Rebecca F. [Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow G4 0BA (United Kingdom); Flint, David J. [Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE (United Kingdom); Martin, Patricia E.M., E-mail: Patricia.Martin@gcu.ac.uk [Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow G4 0BA (United Kingdom)

2013-02-15

Reducing Cx43 expression stimulates skin wound healing. This is mimicked in models when Cx43 function is blocked by the connexin mimetic peptide Gap27. IGF-I also stimulates wound healing with IGFBP-5 attenuating its actions. Further, the IGF-I to IGFBP-5 ratio is altered in diabetic skin, where wound closure is impaired. We investigated whether Gap27 remains effective in augmenting scrape-wound closure in human skin wound models simulating diabetes-induced changes, using culture conditions with raised glucose, insulin and IGFBP-5. Gap27 increased scrape-wound closure in normal glucose and insulin (NGI) and to a lesser extent in high glucose and insulin (HGI). IGF-I enhanced scrape-wound closure in keratinocytes whereas IGFBP-5 inhibited this response. Gap27 overcame the inhibitory effects of IGFBP-5 on IGF-I activity. Connexin-mediated communication (CMC) was reduced in HGI, despite raised Cx43, and Gap27 significantly decreased CMC in NGI and HGI. IGF-I and IGFBP-5 did not affect CMC. IGF-I increased keratinocyte proliferation in NGI, and Gap27 increased proliferation in NGI to a greater extent than in HGI. We conclude that IGF-I and Gap27 stimulate scrape-wound closure by independent mechanisms with Gap27 inhibiting Cx43 function. Gap27 can enhance wound closure in diabetic conditions, irrespective of the IGF-I:IGFBP-5 balance. - Highlights: ► Human organotypic and keratinocyte ‘diabetic’ skin models were used to demonstrate the ability of Gap27 to improve scrape-wound closure. ► Gap27 enhanced scrape-wound closure by reducing Cx43-mediated communication, whereas IGFBP-5 retarded cell migration. ► IGF-I and IGFBP-5 did not affect connexin-mediated pathways. ► Gap27 can override altered glucose, insulin, IGF-I, and IGFBP-5 in ‘diabetic’ skin models and thus has therapeutic potential.

Spontaneous formation of stringlike clusters and smectic sheets for colloidal rods confined in thin wedgelike gaps.

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Maeda, Hideatsu; Maeda, Yoshiko

2013-08-20

Monodispersed colloidal rods of β-FeOOH with sizes ranging from 270 to 580 nm in length and 50 to 80 nm in width were synthesized. Narrow wedgelike gaps (0 to 700 nm in height) were formed around the inner bottom edge of the suspension glass cells. Optical microscopic observations revealed the formation of stringlike clusters of the rods and smectic sheets (by spontaneous side-by-side clustering of the strings) in the isotropic phase of the rod suspensions confined in narrow gaps; the electrolyte (HCl) concentrations of the suspensions are 5-40 mM, at which inter-rod interactions are attractive. The strings exhibit different colors that were used to investigate the structures of the strings with the help of interference color theory for thin films. The results are as follows. (1) The rods, lying flat on the gap bottom, are connected side-by-side and stacked upward to form stringlike clusters with different thicknesses depending on the gap height. (2) The stacking numbers (N(sr)) of the rods are estimated to be 1-5. With N(sr) increasing from 2 to 5, the volume fractions (ϕ) of the rods in the strings increased typically from 0.25-0.3 to 0.35-0.42 to reach limiting values (close to the ϕ values of the rods in the bulk smectic phase). (3) Unexpected low-ϕ strings are found in regions with an intermediate height in the gaps. These behaviors of ϕ may be caused by thermal fluctuations of the strings.

Theory of mind for processing unexpected events across contexts.

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Dungan, James A; Stepanovic, Michael; Young, Liane

2016-08-01

Theory of mind, or mental state reasoning, may be particularly useful for making sense of unexpected events. Here, we investigated unexpected behavior across both social and non-social contexts in order to characterize the precise role of theory of mind in processing unexpected events. We used functional magnetic resonance imaging to examine how people respond to unexpected outcomes when initial expectations were based on (i) an object's prior behavior, (ii) an agent's prior behavior and (iii) an agent's mental states. Consistent with prior work, brain regions for theory of mind were preferentially recruited when people first formed expectations about social agents vs non-social objects. Critically, unexpected vs expected outcomes elicited greater activity in dorsomedial prefrontal cortex, which also discriminated in its spatial pattern of activity between unexpected and expected outcomes for social events. In contrast, social vs non-social events elicited greater activity in precuneus across both expected and unexpected outcomes. Finally, given prior information about an agent's behavior, unexpected vs expected outcomes elicited an especially robust response in right temporoparietal junction, and the magnitude of this difference across participants correlated negatively with autistic-like traits. Together, these findings illuminate the distinct contributions of brain regions for theory of mind for processing unexpected events across contexts. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

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

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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.

The Cx43-like connexin protein Cx40.8 is differentially localized during fin ontogeny and fin regeneration.

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Sarah V Gerhart

Full Text Available Connexins (Cx are the subunits of gap junctions, membraneous protein channels that permit the exchange of small molecules between adjacent cells. Cx43 is required for cell proliferation in the zebrafish caudal fin. Previously, we found that a Cx43-like connexin, cx40.8, is co-expressed with cx43 in the population of proliferating cells during fin regeneration. Here we demonstrate that Cx40.8 exhibits novel differential subcellular localization in vivo, depending on the growth status of the fin. During fin ontogeny, Cx40.8 is found at the plasma membrane, but Cx40.8 is retained in the Golgi apparatus during regeneration. We next identified a 30 amino acid domain of Cx40.8 responsible for its dynamic localization. One possible explanation for the differential localization is that Cx40.8 contributes to the regulation of Cx43 in vivo, perhaps modifying channel activity during ontogenetic growth. However, we find that the voltage-gating properties of Cx40.8 are similar to Cx43. Together our findings reveal that Cx40.8 exhibits differential subcellular localization in vivo, dependent on a discrete domain in its carboxy terminus. We suggest that the dynamic localization of Cx40.8 differentially influences Cx43-dependent cell proliferation during ontogeny and regeneration.

Astrocyte sigma-1 receptors modulate connexin 43 expression leading to the induction of below-level mechanical allodynia in spinal cord injured mice.

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Choi, Sheu-Ran; Roh, Dae-Hyun; Yoon, Seo-Yeon; Kwon, Soon-Gu; Choi, Hoon-Seong; Han, Ho-Jae; Beitz, Alvin J; Lee, Jang-Hern

2016-12-01

We have previously shown using a spinal cord injury (SCI) model that gap junctions contribute to the early spread of astrocyte activation in the lumbar spinal cord and that this astrocyte communication plays critical role in the induction of central neuropathic pain. Sigma-1 receptors (Sig-1Rs) have been implicated in spinal astrocyte activation and the development of peripheral neuropathic pain, yet their contribution to central neuropathic pain remains unknown. Thus, we investigated whether SCI upregulates spinal Sig-1Rs, which in turn increase the expression of the astrocytic gap junction protein, connexin 43 (Cx43) leading to the induction of central neuropathic pain. A thoracic spinal cord hemisection significantly increased both astrocyte activation and Cx43 expression in lumbar dorsal horn. Sig-1Rs were also increased in lumbar dorsal horn astrocytes, but not neurons or microglia. Intrathecal injection of an astrocyte metabolic inhibitor (fluorocitrate); a gap junction/hemichannel blocker (carbenoxolone); or a Cx43 mimetic peptide ( 43 Gap26) significantly reduced SCI-induced bilateral below-level mechanical allodynia. Blockade of Sig-1Rs with BD1047 during the induction phase of pain significantly suppressed the SCI-induced development of mechanical allodynia, astrocyte activation, increased expression of Cx43 in both total and membrane levels, and increased association of Cx43 with Sig-1R. However, SCI did not change the expression of oligodendrocyte (Cx32) or neuronal (Cx36) gap junction proteins. These findings demonstrate that SCI activates astrocyte Sig-1Rs leading to increases in the expression of the gap junction protein, Cx43 and astrocyte activation in the lumbar dorsal horn, and ultimately contribute to the induction of bilateral below-level mechanical allodynia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Connexin 43 Communication Channels in Follicular Dendritic Cell Development and in Follicular Lymphomas

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Hajnalka Rajnai

2015-01-01

Full Text Available Follicular dendritic cells (FDC show homo- and heterocellular metabolic coupling through connexin 43 (Cx43 gap junctions and support B cell selection and maturation in germinal centers. In follicular lymphomas B cells escape apoptosis while FDC develop abnormally. Here we tested Cx43 channels in reactive FDC development and follicular lymphomas. In culture, the treatment of FDC-B cell clusters (resembling to “ex vivo” germinal centers with Gap27 peptide, mimicking the 2nd extracellular loop of Cx43 protein, significantly impaired FDC-B cell cluster formation and cell survival. In untreated cultures of intact clusters, cell proliferation showed a moderate reduction. In tissues, Cx43 protein levels run parallel with the density of FDC both in reactive germinal centers and in malformed follicles of follicular lymphomas and showed strong upregulation in newly generated and/or degrading bi-/multinuclear FDC of rudimentary processes. However, the inverse correlation between Cx43 expression and B cell proliferation seen in reactive germinal centers was not detected in follicular lymphomas. Furthermore, Cx43 levels were not associated with either lymphoma grade or bone marrow involvement. Our results suggest that Cx43 channels are critical in FDC and “ex vivo” germinal center development and in the persistence of FDC in follicular lymphomas but do not affect tumor progression.

The C1 domain-targeted isophthalate derivative HMI-1b11 promotes neurite outgrowth and GAP-43 expression through PKCα activation in SH-SY5Y cells.

Science.gov (United States)

Talman, Virpi; Amadio, Marialaura; Osera, Cecilia; Sorvari, Salla; Boije Af Gennäs, Gustav; Yli-Kauhaluoma, Jari; Rossi, Daniela; Govoni, Stefano; Collina, Simona; Ekokoski, Elina; Tuominen, Raimo K; Pascale, Alessia

2013-07-01

Protein kinase C (PKC) is a family of serine/threonine phosphotransferases ubiquitously expressed and involved in multiple cellular functions, such as proliferation, apoptosis and differentiation. The C1 domain of PKC represents an attractive drug target, especially for developing PKC activators. Dialkyl 5-(hydroxymethyl)isophthalates are a novel group of synthetic C1 domain ligands that exhibit antiproliferative effect in HeLa cervical carcinoma cells. Here we selected two isophthalates, HMI-1a3 and HMI-1b11, and characterized their effects in the human neuroblastoma cell line SH-SY5Y. Both of the active isophthalates exhibited significant antiproliferative and differentiation-inducing effects. Since HMI-1b11 did not impair cell survival even at the highest concentration tested (20μM), and supported neurite growth and differentiation of SH-SY5Y cells, we focused on studying its downstream signaling cascades and effects on gene expression. Consistently, genome-wide gene expression microarray and gene set enrichment analysis indicated that HMI-1b11 (10μM) induced changes in genes mainly related to cell differentiation. In particular, further studies revealed that HMI-1b11 exposure induced up-regulation of GAP-43, a marker for neurite sprouting and neuronal differentiation. These effects were induced by a 7-min HMI-1b11 treatment and specifically depended on PKCα activation, since pretreatment with the selective inhibitor Gö6976 abolished the up-regulation of GAP-43 protein observed at 12h. In parallel, we found that a 7-min exposure to HMI-1b11 induced PKCα accumulation to the cytoskeleton, an effect that was again prevented by pretreatment with Gö6976. Despite similar binding affinities to PKC, the isophthalates had different effects on PKC-dependent ERK1/2 signaling: HMI-1a3-induced ERK1/2 phosphorylation was transient, while HMI-1b11 induced a rapid but prolonged ERK1/2 phosphorylation. Overall our data are in accordance with previous studies showing that

Post-genomic analyses of fungal lignocellulosic biomass degradation reveal the unexpected potential of the plant pathogen Ustilago maydis

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Couturier Marie

2012-02-01

Full Text Available Abstract Background Filamentous fungi are potent biomass degraders due to their ability to thrive in ligno(hemicellulose-rich environments. During the last decade, fungal genome sequencing initiatives have yielded abundant information on the genes that are putatively involved in lignocellulose degradation. At present, additional experimental studies are essential to provide insights into the fungal secreted enzymatic pools involved in lignocellulose degradation. Results In this study, we performed a wide analysis of 20 filamentous fungi for which genomic data are available to investigate their biomass-hydrolysis potential. A comparison of fungal genomes and secretomes using enzyme activity profiling revealed discrepancies in carbohydrate active enzymes (CAZymes sets dedicated to plant cell wall. Investigation of the contribution made by each secretome to the saccharification of wheat straw demonstrated that most of them individually supplemented the industrial Trichoderma reesei CL847 enzymatic cocktail. Unexpectedly, the most striking effect was obtained with the phytopathogen Ustilago maydis that improved the release of total sugars by 57% and of glucose by 22%. Proteomic analyses of the best-performing secretomes indicated a specific enzymatic mechanism of U. maydis that is likely to involve oxido-reductases and hemicellulases. Conclusion This study provides insight into the lignocellulose-degradation mechanisms by filamentous fungi and allows for the identification of a number of enzymes that are potentially useful to further improve the industrial lignocellulose bioconversion process.

Autistic Traits Affect P300 Response to Unexpected Events, regardless of Mental State Inferences

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Mitsuhiko Ishikawa

2017-01-01

Full Text Available Limited use of contextual information has been suggested as a way of understanding cognition in people with autism spectrum disorder (ASD. However, it has also been argued that individuals with ASD may have difficulties inferring others’ mental states. Here, we examined how individuals with different levels of autistic traits respond to contextual deviations by measuring event-related potentials that reflect context usage. The Autism Spectrum Quotient (AQ was used to quantify autistic-like traits in 28 university students, and 19 participants were defined as Low or High AQ groups. To additionally examine inferences about mental state, two belief conditions (with or without false belief were included. Participants read short stories in which the final sentence included either an expected or an unexpected word and rated the word’s degree of deviation from expectation. P300 waveform analysis revealed that unexpected words were associated with larger P300 waveforms for the Low AQ group, but smaller P300 responses in the High AQ group. Additionally, AQ social skill subscores were positively correlated with evaluation times in the Unexpected condition, whether a character’s belief was false or not. This suggests that autistic traits can affect responses to unexpected events, possibly because of decreased availability of context information.

Gastrointestinal causes of sudden unexpected death: A review.

Science.gov (United States)

Menezes, Ritesh G; Ahmed, Saba; Pasha, Syed Bilal; Hussain, Syed Ather; Fatima, Huda; Kharoshah, Magdy A; Madadin, Mohammed

2018-01-01

Gastrointestinal conditions are a less common cause of sudden unexpected death when compared to other conditions such as cardiovascular conditions, but they are equally important. Various congenital and acquired gastrointestinal conditions that have resulted in sudden unexpected death are discussed. The possible lethal mechanisms behind each condition, along with any associated risk factors or secondary diseases, have been described. Through this article, we aim to highlight the need for physicians to prevent death in such conditions by ensuring that subclinical cases are diagnosed correctly before it is too late and by providing timely and efficacious treatment to the patient concerned. In addition, this review would certainly benefit the forensic pathologist while dealing with cases of sudden unexpected death due to gastrointestinal causes. This article is a review of the major gastrointestinal causes of sudden unexpected death. In addition, related fatal cases encountered occasionally in forensic autopsy practice are also included. There are several unusual and rare causes of life-threatening gastrointestinal bleeding that may lead to sudden unexpected death to cover all the entities in detail. Nevertheless, this article is a general guide to the topic of gastrointestinal causes of sudden unexpected death.

Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes

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Nathalie Kin

2015-05-01

Full Text Available Human coronavirus OC43 (HCoV-OC43 is one of five currently circulating human coronaviruses responsible for respiratory infections. Like all coronaviruses, it is characterized by its genome’s high plasticity. The objectives of the current study were to detect genetically distinct genotypes and eventually recombinant genotypes in samples collected in Lower Normandy between 2001 and 2013. To this end, we sequenced complete nsp12, S, and N genes of 15 molecular isolates of HCoV-OC43 from clinical samples and compared them to available data from the USA, Belgium, and Hong-Kong. A new cluster E was invariably detected from nsp12, S, and N data while the analysis of nsp12 and N genes revealed the existence of new F and G clusters respectively. The association of these different clusters of genes in our specimens led to the description of thirteen genetically distinct genotypes, among which eight recombinant viruses were discovered. Identification of these recombinant viruses, together with temporal analysis and tMRCA estimation, provides important information for understanding the dynamics of the evolution of these epidemic coronaviruses.

The unexpected in primary care: a multicenter study on the emergence of unvoiced patient agenda.

NARCIS (Netherlands)

Peltenburg, M.; Fischer, J.E.; Bahrs, O.; Dulmen, S. van; Brink-Muinen, A. van den

2004-01-01

PURPOSE: Within the time constraints of a typical physician-patient encounter, the full patient agenda will rarely be voiced. Unexpectedly revealed issues that were neither on the patient's list of items for discussion nor anticipated by the physician constitute an emerging agenda. We aimed to

VNTR analysis reveals unexpected genetic diversity within Mycoplasma agalactiae, the main causative agent of contagious agalactia

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Ayling Roger D

2008-11-01

Full Text Available Abstract Background Mycoplasma agalactiae is the main cause of contagious agalactia, a serious disease of sheep and goats, which has major clinical and economic impacts. Previous studies of M. agalactiae have shown it to be unusually homogeneous and there are currently no available epidemiological techniques which enable a high degree of strain differentiation. Results We have developed variable number tandem repeat (VNTR analysis using the sequenced genome of the M. agalactiae type strain PG2. The PG2 genome was found to be replete with tandem repeat sequences and 4 were chosen for further analysis. VNTR 5 was located within the hypothetical protein MAG6170 a predicted lipoprotein. VNTR 14 was intergenic between the hypothetical protein MAG3350 and the hypothetical protein MAG3340. VNTR 17 was intergenic between the hypothetical protein MAG4060 and the hypothetical protein MAG4070 and VNTR 19 spanned the 5' end of the pseudogene for a lipoprotein MAG4310 and the 3' end of the hypothetical lipoprotein MAG4320. We have investigated the genetic diversity of 88 M. agalactiae isolates of wide geographic origin using VNTR analysis and compared it with pulsed field gel electrophoresis (PFGE and random amplified polymorphic DNA (RAPD analysis. Simpson's index of diversity was calculated to be 0.324 for PFGE and 0.574 for VNTR analysis. VNTR analysis revealed unexpected diversity within M. agalactiae with 9 different VNTR types discovered. Some correlation was found between geographical origin and the VNTR type of the isolates. Conclusion VNTR analysis represents a useful, rapid first-line test for use in molecular epidemiological analysis of M. agalactiae for outbreak tracing and control.

In-Depth Glyco-Peptidomics Approach Reveals Unexpected Diversity of Glycosylated Peptides and Atypical Post-Translational Modifications in Dendroaspis angusticeps Snake Venom.

Science.gov (United States)

Degueldre, Michel; Echterbille, Julien; Smargiasso, Nicolas; Damblon, Christian; Gouin, Charlotte; Mourier, Gilles; Gilles, Nicolas; De Pauw, Edwin; Quinton, Loïc

2017-11-18

Animal venoms represent a valuable source of bioactive peptides that can be derived into useful pharmacological tools, or even innovative drugs. In this way, the venom of Dendroaspis angusticeps (DA), the Eastern Green Mamba, has been intensively studied during recent years. It mainly contains hundreds of large toxins from 6 to 9 kDa, each displaying several disulfide bridges. These toxins are the main target of venom-based studies due to their valuable activities obtained by selectively targeting membrane receptors, such as ion channels or G-protein coupled receptors. This study aims to demonstrate that the knowledge of venom composition is still limited and that animal venoms contain unexpected diversity and surprises. A previous study has shown that Dendroaspis angusticeps venom contains not only a cocktail of classical toxins, but also small glycosylated peptides. Following this work, a deep exploration of DA glycopeptidome by a dual nano liquid chromatography coupled to electrospray ionization mass spectrometry (nanoLC-ESI-MS) and Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) analyses was initiated. This study reveals unsuspected structural diversity of compounds such as 221 glycopeptides, displaying different glycan structures. Sequence alignments underline structural similarities with natriuretic peptides already characterized in Elapidae venoms. Finally, the presence of an S -cysteinylation and hydroxylation of proline on four glycopeptides, never described to date in snake venoms, is also revealed by proteomics and affined by nuclear magnetic resonance (NMR) experiments.

In-Depth Glyco-Peptidomics Approach Reveals Unexpected Diversity of Glycosylated Peptides and Atypical Post-Translational Modifications in Dendroaspis angusticeps Snake Venom

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Michel Degueldre

2017-11-01

Full Text Available Animal venoms represent a valuable source of bioactive peptides that can be derived into useful pharmacological tools, or even innovative drugs. In this way, the venom of Dendroaspis angusticeps (DA, the Eastern Green Mamba, has been intensively studied during recent years. It mainly contains hundreds of large toxins from 6 to 9 kDa, each displaying several disulfide bridges. These toxins are the main target of venom-based studies due to their valuable activities obtained by selectively targeting membrane receptors, such as ion channels or G-protein coupled receptors. This study aims to demonstrate that the knowledge of venom composition is still limited and that animal venoms contain unexpected diversity and surprises. A previous study has shown that Dendroaspis angusticeps venom contains not only a cocktail of classical toxins, but also small glycosylated peptides. Following this work, a deep exploration of DA glycopeptidome by a dual nano liquid chromatography coupled to electrospray ionization mass spectrometry (nanoLC-ESI-MS and Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS analyses was initiated. This study reveals unsuspected structural diversity of compounds such as 221 glycopeptides, displaying different glycan structures. Sequence alignments underline structural similarities with natriuretic peptides already characterized in Elapidae venoms. Finally, the presence of an S-cysteinylation and hydroxylation of proline on four glycopeptides, never described to date in snake venoms, is also revealed by proteomics and affined by nuclear magnetic resonance (NMR experiments.

Mammalian play: training for the unexpected.

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Spinka, M; Newberry, R C; Bekoff, M

2001-06-01

In this review, we present a new conceptual framework for the study of play behavior, a hitherto puzzling array of seemingly purposeless and unrelated behavioral elements that are recognizable as play throughout the mammalian lineage. Our major new functional hypothesis is that play enables animals to develop flexible kinematic and emotional responses to unexpected events in which they experience a sudden loss of control. Specifically, we propose that play functions to increase the versatility of movements used to recover from sudden shocks such as loss of balance and falling over, and to enhance the ability of animals to cope emotionally with unexpected stressful situations. To obtain this "training for the unexpected," we suggest that animals actively seek and create unexpected situations in play through self-handicapping; that is, deliberately relaxing control over their movements or actively putting themselves into disadvantageous positions and situations. Thus, play is comprised of sequences in which the players switch rapidly between well-controlled movements similar to those used in "serious" behavior and self-handicapping movements that result in temporary loss of control. We propose that this playful switching between in-control and out-of-control elements is cognitively demanding, setting phylogenetic and ontogenetic constraints on play, and is underlain by neuroendocrinological responses that produce a complex emotional state known as "having fun." Furthermore, we propose that play is often prompted by relatively novel or unpredictable stimuli, and is thus related to, although distinct from, exploration. We present 24 predictions that arise from our new theoretical framework, examining the extent to which they are supported by the existing empirical evidence and contrasting them with the predictions of four major alternative hypotheses about play. We argue that our "training for the unexpected" hypothesis can account for some previously puzzling

A Point Mutation in p190A RhoGAP Affects Ciliogenesis and Leads to Glomerulocystic Kidney Defects.

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Katherine Stewart

2016-02-01

Full Text Available Rho family GTPases act as molecular switches regulating actin cytoskeleton dynamics. Attenuation of their signaling capacity is provided by GTPase-activating proteins (GAPs, including p190A, that promote the intrinsic GTPase activity of Rho proteins. In the current study we have performed a small-scale ENU mutagenesis screen and identified a novel loss of function allele of the p190A gene Arhgap35, which introduces a Leu1396 to Gln substitution in the GAP domain. This results in decreased GAP activity for the prototypical Rho-family members, RhoA and Rac1, likely due to disrupted ordering of the Rho binding surface. Consequently, Arhgap35-deficient animals exhibit hypoplastic and glomerulocystic kidneys. Investigation into the cystic phenotype shows that p190A is required for appropriate primary cilium formation in renal nephrons. P190A specifically localizes to the base of the cilia to permit axoneme elongation, which requires a functional GAP domain. Pharmacological manipulations further reveal that inhibition of either Rho kinase (ROCK or F-actin polymerization is able to rescue the ciliogenesis defects observed upon loss of p190A activity. We propose a model in which p190A acts as a modulator of Rho GTPases in a localized area around the cilia to permit the dynamic actin rearrangement required for cilia elongation. Together, our results establish an unexpected link between Rho GTPase regulation, ciliogenesis and glomerulocystic kidney disease.

Water in stars: expected and unexpected

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Tsuji, T.; Aoki, W.; Ohnaka, K.

1999-03-01

We have confirmed the presence of water in the early M giant α Cet (M1.5III) and supergiant KK Per (M2Iab) by the highest resolution grating mode of SWS, but this result is quite unexpected from present model atmospheres. In late M giant and supergiant stars, water observed originates partly in the photosphere as expected by the model atmospheres, but ISO SWS has revealed that the 2.7 mic\\ absorption bands appear to be somewhat stronger than predicted while 6.5 mic\\ bands weaker, indicating the contamination by an emission component. In the mid-infrared region extending to 45 mic, pure rotation lines of hho\\ appear as distinct emission on the high resolution SWS spectra of 30g Her (M7III) and S Per (M4-7Ia), along with the dust emission at 10, 13, 20 mic\\ and a new unidentified feature at 30 mic. Thus, together with the dust, water contributes to the thermal balance of the outer atmosphere already in the mid-infrared. The excitation temperature of hho\\ gas is estimated to be 500 - 1000 K. In view of this result for late M (super)giants, unexpected water observed in early M (super)giants should also be of non-photospheric in origin. Thus, ISO has finally established the presence of a new component of the outer atmosphere - a warm molecular envelope - in red giant and supergiant stars from early to late types. Such a rather warm molecular envelope will be a site of various activities such as chemical reactions, dust formation, mass-outflow etc.

The inverse F-BAR domain protein srGAP2 acts through srGAP3 to modulate neuronal differentiation and neurite outgrowth of mouse neuroblastoma cells.

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Yue Ma

Full Text Available The inverse F-BAR (IF-BAR domain proteins srGAP1, srGAP2 and srGAP3 are implicated in neuronal development and may be linked to mental retardation, schizophrenia and seizure. A partially overlapping expression pattern and highly similar protein structures indicate a functional redundancy of srGAPs in neuronal development. Our previous study suggests that srGAP3 negatively regulates neuronal differentiation in a Rac1-dependent manner in mouse Neuro2a cells. Here we show that exogenously expressed srGAP1 and srGAP2 are sufficient to inhibit valporic acid (VPA-induced neurite initiation and growth in the mouse Neuro2a cells. While ectopic- or over-expression of RhoGAP-defective mutants, srGAP1(R542A and srGAP2(R527A exert a visible inhibitory effect on neuronal differentiation. Unexpectedly, knockdown of endogenous srGAP2 fails to facilitate the neuronal differentiation induced by VPA, but promotes neurite outgrowth of differentiated cells. All three IF-BAR domains from srGAP1-3 can induce filopodia formation in Neuro2a, but the isolated IF-BAR domain from srGAP2, not from srGAP1 and srGAP3, can promote VPA-induced neurite initiation and neuronal differentiation. We identify biochemical and functional interactions of the three srGAPs family members. We propose that srGAP3-Rac1 signaling may be required for the effect of srGAP1 and srGAP2 on attenuating neuronal differentiation. Furthermore, inhibition of Slit-Robo interaction can phenocopy a loss-of-function of srGAP3, indicating that srGAP3 may be dedicated to the Slit-Robo pathway. Our results demonstrate the interplay between srGAP1, srGAP2 and srGAP3 regulates neuronal differentiation and neurite outgrowth. These findings may provide us new insights into the possible roles of srGAPs in neuronal development and a potential mechanism for neurodevelopmental diseases.

An unexpected cause of diffuse alveolar hemorrhage in a kidney transplant patient.

Science.gov (United States)

Schlageter, Manuel; Jahn, Kathleen D; Tzankov, Alexandar; Wiese, Mark; Bubendorf, Lukas; Tamm, Michael; Savic, Spasenija

2014-01-01

Diffuse alveolar hemorrhage (DAH) is a life-threatening condition requiring urgent treatment. There are many different treatment-relevant causes of DAH, making the diagnostic approach to these patients complex and necessitating a multidisciplinary team. We report the case of a kidney transplant recipient in whom all diagnostic efforts did not reveal the cause of DAH, and only autopsy was able to establish an unexpected diagnosis. © 2014 S. Karger AG, Basel.

Virtual gap element approach for the treatment of non-matching interface using three-dimensional solid elements

Science.gov (United States)

Song, Yeo-Ul; Youn, Sung-Kie; Park, K. C.

2017-10-01

A method for three-dimensional non-matching interface treatment with a virtual gap element is developed. When partitioned structures contain curved interfaces and have different brick meshes, the discretized models have gaps along the interfaces. As these gaps bring unexpected errors, special treatments are required to handle the gaps. In the present work, a virtual gap element is introduced to link the frame and surface domain nodes in the frame work of the mortar method. Since the surface of the hexahedron element is quadrilateral, the gap element is pyramidal. The pyramidal gap element consists of four domain nodes and one frame node. Zero-strain condition in the gap element is utilized for the interpolation of frame nodes in terms of the domain nodes. This approach is taken to satisfy the momentum and energy conservation. The present method is applicable not only to curved interfaces with gaps, but also to flat interfaces in three dimensions. Several numerical examples are given to describe the effectiveness and accuracy of the proposed method.

Unexpected allergic reactions to food, a prospective study

NARCIS (Netherlands)

Michelsen-Huisman, A.D.; Os-Medendorp, H. van; Versluis, A.; Kruizinga, A.G.; Castenmiller, J.J.M.; Noteborn, H.P.J.M.; Houben, G.F.; Knulst, A.C.

2013-01-01

Unexpected reactions occur in patients with food allergy, but frequency data are scare. This prospective study investigates the frequency, severity and causes of unexpected allergic reactions to food in adults with a doctor's diagnosed food allergy. Participants complete an online questionnaire

Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12

Science.gov (United States)

Landouré, Guida; Zhu, Peng-Peng; Lourenço, Charles M.; Johnson, Janel O.; Toro, Camilo; Bricceno, Katherine V.; Rinaldi, Carlo; Meilleur, Katherine G.; Sangaré, Modibo; Diallo, Oumarou; Pierson, Tyler M.; Ishiura, Hiroyuki; Tsuji, Shoji; Hein, Nichole; Fink, John K.; Stoll, Marion; Nicholson, Garth; Gonzalez, Michael; Speziani, Fiorella; Dürr, Alexandra; Stevanin, Giovanni; Biesecker, Leslie G.; Accardi, John; Landis, Dennis M. D.; Gahl, William A.; Traynor, Bryan J.; Marques, Wilson; Züchner, Stephan; Blackstone, Craig; Fischbeck, Kenneth H.; Burnett, Barrington G.

2013-01-01

We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three-nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly-conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain. PMID:23857908

[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.

Phosphorous dimerization in GaP high-pressure polymorph

Energy Technology Data Exchange (ETDEWEB)

Lavina, Barbara [Univ. of Nevada, Las Vegas, NV (United States). High Pressure Science and Engineering Center (HiPSEC), Dept. of Physics and Astronomy; Kim, Eunja [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Physics and Astronomy; Cynn, Hyunchae [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Weck, Philippe F [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Seaborg, Kelly [Univ. of Nevada, Las Vegas, NV (United States). High Pressure Science and Engineering Center (HiPSEC), Dept. of Physics and Astronomy; Siska, Emily [Univ. of Nevada, Las Vegas, NV (United States). High Pressure Science and Engineering Center (HiPSEC); Meng, Yue [Carnegie Inst. of Washington, Argonne, IL (United States). Geophysical Lab., High Pressure Collaborative Access Team (HPCAT); Evans, Williams [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2016-06-01

We report on the experimental and theoretical characterization of a novel GaP polymorph formed by laser heating of a single crystal of GaP-II in its stable region near 43 GPa. Thereby formed unstrained multigrain sample at 43 GPa and 1300 K, allowed high-resolution crystallographic analysis. We find an oS24 as an energetically optimized crystal structure contrary to oS8 reported by Nelmes et al. (1997). Our DFT calculation confirms a stable existence of oS24 between 18 – 50 GPa. The emergence of the oS24 structure is related to the differentiation of phosphorous atoms between those forming P-P dimers and those forming P-Ga bonds only. Bonding anisotropy explains the symmetry lowering with respect to what is generally expected for semiconductors high-pressure polymorphs. The metallization of GaP does not occur through a uniform change of the nature of its bonds but through the formation of an anisotropic phase containing different bond types.

42 CFR 493.861 - Standard; Unexpected antibody detection.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Unexpected antibody detection. 493.861 Section 493.861 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN..., Or Any Combination of These Tests § 493.861 Standard; Unexpected antibody detection. (a) Failure to...

Training to handle unexpected events

International Nuclear Information System (INIS)

Hamlin, K.W.

1987-01-01

The importance of conducting hands-on training to deal with complex situations is well recognized. Since most utilities now own or have ordered their own control room simulators, access to simulator training facilities has improved greatly. Most utilities now have a control room shift rotation that includes a dedicated training shift. The opportunities for practicing operational control over unexpected and off-normal events are just beginning to be recognized. Areas that are being enhanced include teamwork training, diagnostics training, expanded simulator training programs, improvements in simulator instructor training, emergency procedures training, and training on the use of probabilistic risk assessment studies. All these efforts are aimed at the goal of improving the plant staff's ability to cope with unexpected and off-normal events

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.

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.

Effects of unexpected chords and of performer's expression on brain responses and electrodermal activity.

Science.gov (United States)

Koelsch, Stefan; Kilches, Simone; Steinbeis, Nikolaus; Schelinski, Stefanie

2008-07-09

There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. This study investigates event-related brain potentials (ERPs), skin conductance responses (SCRs) and heart rate (HR) elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression), we also created versions without variations in tempo and loudness (without musical expression) to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing) and an N5 (reflecting processing of meaning information) in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses). The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function) differed between the expressive and the non-expressive condition. These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music.

Effects of unexpected chords and of performer's expression on brain responses and electrodermal activity.

Directory of Open Access Journals (Sweden)

Stefan Koelsch

Full Text Available BACKGROUND: There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: This study investigates event-related brain potentials (ERPs, skin conductance responses (SCRs and heart rate (HR elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression, we also created versions without variations in tempo and loudness (without musical expression to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing and an N5 (reflecting processing of meaning information in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses. The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function differed between the expressive and the non-expressive condition. CONCLUSIONS/SIGNIFICANCE: These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music.

A 43-kDa TDP-43 species is present in aggregates associated with frontotemporal lobar degeneration.

Directory of Open Access Journals (Sweden)

Patrick J Bosque

Full Text Available The transactive response DNA-binding protein (TDP-43 is a major component of the abnormal intracellular inclusions that occur in two common neurodegenerative diseases of humans: (1 a subtype of frontotemporal lobar degeneration and (2 amyotrophic lateral sclerosis. Genetics, experiments in cultured cells and animals, and analogy with other neurodegenerative diseases indicate that the process of TDP-43 aggregation is fundamental to the pathogenesis of these 2 diseases, but the process by which this aggregation occurs is not understood. Biochemical fractionation has revealed truncated, phosphorylated and ubiquitinated forms of TDP-43 in a detergent-insoluble fraction from diseased CNS tissue, while these forms are absent from controls. However, a large amount of the normally predominant 43-kDa form of TDP-43 is present in the detergent-insoluble fraction even from control brains, so it has not been possible to determine if this form of TDP-43 is part of pathological aggregates in frontotemporal lobe degeneration. We used semi-denaturing detergent-agarose gel electrophoresis to isolate high molecular weight aggregates containing TDP-43 that are present in the cerebral cortex of individuals with frontotemporal lobar degeneration but not that of controls. These aggregates include the same covalently modified forms of TDP-43 seen in detergent-insoluble extracts. In addition, aggregates include a 43-kDa TDP-43 species. This aggregated 43-kDa form of TDP-43 is absent or present only at low levels in controls. The presence of 43-kDa TDP-43 in aggregates raises the possibility that covalent modification is not a primary step in the pathogenic aggregation of TDP-43 associated with frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

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

Science.gov (United States)

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.

Unexpected observations of muons from Cygnus X-3

International Nuclear Information System (INIS)

Elbert, J.W.

1986-01-01

One surface experiment (Kiel) and two underground experiments (Soudan and Mt. Blanc) have detected unexpectedly large fluxes of cosmic ray muons from the approximate direction of Cygnus X-3, with signals showing the precise period of the system. The muon signals cannot be produced by any known type of elementary particle unless unexpected processes are involved

Evaluation of Connexin 43 Redistribution and Endocytosis in Astrocytes Subjected to Ischemia/Reperfusion or Oxygen-Glucose Deprivation and Reoxygenation

Directory of Open Access Journals (Sweden)

Hongyan Xie

2017-01-01

Full Text Available Connexin 43 (Cx43 is the major component protein in astrocytic gap junction communication. Recent studies have shown the cellular processes of gap junction internalization and degradation, but many details remain unknown. This study investigated the distribution of Cx43 and its mechanism after ischemic insult. Astrocyte culture system and a model of ischemia/reperfusion (IR or oxygen-glucose deprivation and reoxygenation (OGDR were established. Cx43 distribution was observed by laser scanning confocal microscopy under different cultivation conditions. Western blot and RT-PCR assays were applied to quantify Cx43 and MAPRE1 (microtubule-associated protein RP/EB family member 1 expression at different time points. The total number of Cx43 was unchanged in the normal and IR/OGDR groups, but Cx43 particles in the cytoplasm of the IR/OGDR group were significantly greater than that of the normal group. Particles in the cytoplasm were significantly fewer after endocytosis was blocked by dynasore. There was no difference among the groups at each time point regarding protein or gene expression of MAPRE1. We concluded that internalization of Cx43 into the cytoplasm occurred during ischemia, which was partially mediated through endocytosis, not by the change of Cx43 quantity. Moreover, internalization was not related to microtubule transport.

Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of β-catenin/connexin43 association

International Nuclear Information System (INIS)

Talhouk, Rabih S.; Fares, Mohamed-Bilal; Rahme, Gilbert J.; Hariri, Hanaa H.; Rayess, Tina; Dbouk, Hashem A.; Bazzoun, Dana; Al-Labban, Dania; El-Sabban, Marwan E.

2013-01-01

Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of β-catenin, α-catenin and ZO-2, it decreased nuclear levels of β-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with α-catenin, β-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with α-catenin, β-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering β-catenin away from nucleus. - Highlights: • Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. • Proliferation and growth morphology were affected in a context dependent manner. • Extravasation ability of both MCF

Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of β-catenin/connexin43 association

Energy Technology Data Exchange (ETDEWEB)

Talhouk, Rabih S., E-mail: rtalhouk@aub.edu.lb [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon); Fares, Mohamed-Bilal; Rahme, Gilbert J.; Hariri, Hanaa H.; Rayess, Tina; Dbouk, Hashem A.; Bazzoun, Dana; Al-Labban, Dania [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon); El-Sabban, Marwan E., E-mail: me00@aub.edu.lb [Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon)

2013-12-10

Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of β-catenin, α-catenin and ZO-2, it decreased nuclear levels of β-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with α-catenin, β-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with α-catenin, β-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering β-catenin away from nucleus. - Highlights: • Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. • Proliferation and growth morphology were affected in a context dependent manner. • Extravasation ability of both MCF

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...

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

Science.gov (United States)

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.

Identification of ischemia-regulated phosphorylation sites in connexin43: A possible target for the antiarrhythmic peptide analogue rotigaptide (ZP123)

DEFF Research Database (Denmark)

Axelsen, Lene Nygaard; Stahlhut, Martin; Mohammed, Shabaz

2006-01-01

Previous studies suggest that dephosphorylation of connexin43 (Cx43) is related to uncoupling of gap junction communication, which plays an important role in the genesis of ischemia-induced ventricular tachycardia. We studied changes in Cx43 phosphorylation during global ischemia in the absence...... and presence of the antiarrhythmic peptide analogue rotigaptide (formerly known as ZP123). Phosphorylation analysis was performed on Cx43 purified from isolated perfused rat hearts using matrix-assisted laser desorption/ionization mass spectrometry and liquid chromatography electrospray ionization tandem mass...... of ischemia, the critical time interval where gap junction uncoupling occurs, Ser297 and Ser368 also became fully dephosphorylated. During the same time period, all untreated hearts developed asystole. Treatment with rotigaptide significantly increased the time to ischemia-induced asystole and suppressed...

SUMO modification through rapamycin-mediated heterodimerization reveals a dual role for Ubc9 in targeting RanGAP1 to nuclear pore complexes

International Nuclear Information System (INIS)

Zhu Shanshan; Zhang Hong; Matunis, Michael J.

2006-01-01

SUMOs (small ubiquitin-related modifiers) are eukaryotic proteins that are covalently conjugated to other proteins and thereby regulate a wide range of important cellular processes. The molecular mechanisms by which SUMO modification influences the functions of most target proteins and cellular processes, however, remain poorly defined. A major obstacle to investigating the effects of SUMO modification is the availability of a system for selectively inducing the modification or demodification of an individual protein. To address this problem, we have developed a procedure using the rapamycin heterodimerizer system. This procedure involves co-expression of rapamycin-binding domain fusion proteins of SUMO and candidate SUMO substrates in living cells. Treating cells with rapamycin induces a tight association between SUMO and a single SUMO substrate, thereby allowing specific downstream effects to be analyzed. Using RanGAP1 as a model SUMO substrate, the heterodimerizer system was used to investigate the molecular mechanism by which SUMO modification targets RanGAP1 from the cytoplasm to nuclear pore complexes (NPCs). Our results revealed a dual role for Ubc9 in targeting RanGAP1 to NPCs: In addition to conjugating SUMO-1 to RanGAP1, Ubc9 is also required to form a stable ternary complex with SUMO-1 modified RanGAP1 and Nup358. As illustrated by our studies, the rapamycin heterodimerizer system represents a novel tool for studying the molecular effects of SUMO modification

THE GENDER WAGE GAP IN TURKEY

OpenAIRE

AKTAŞ, Arda; UYSAL, Gokce

2016-01-01

The most prominent form of gender discrimination in the labor market is the gender gap in wages.Using the Wage Structure Survey, a firm-level data set, we study the gender wage gap in Turkey. Weconcentrate on formal employment as this is the jurisdiction of the Labor Code in Turkey. Althoughwomen earn 3% less than men on average, a wider look reveals important differences along the entirewage distribution. There is virtually no gender gap at the lower end of the wage distribution. Moresurpris...

Innervation of taste buds revealed with Brainbow-labeling in mouse.

Science.gov (United States)

Zaidi, Faisal N; Cicchini, Vanessa; Kaufman, Daniel; Ko, Elizabeth; Ko, Abraham; Van Tassel, Heather; Whitehead, Mark C

2016-12-01

Nerve fibers that surround and innervate the taste bud were visualized with inherent fluorescence using Brainbow transgenic mice that were generated by mating the founder line L with nestin-cre mice. Multicolor fluorescence revealed perigemmal fibers as branched within the non-taste epithelium and ending in clusters of multiple rounded swellings surrounding the taste pore. Brainbow-labeling also revealed the morphology and branching pattern of single intragemmal fibers. These taste bud fibers frequently innervated both the peripheral bud, where immature gemmal cells are located, and the central bud, where mature, differentiated cells are located. The fibers typically bore preterminal and terminal swellings, growth cones with filopodia, swellings, and rounded retraction bulbs. These results establish an anatomical substrate for taste nerve fibers to contact and remodel among receptor cells at all stages of their differentiation, an interpretation that was supported by staining with GAP-43, a marker for growing fibers and growth cones. © 2016 Anatomical Society.

Gap Junctions Contribute to the Regulation of Walking-Like Activity in the Adult Mudpuppy (Necturus Maculatus.

Directory of Open Access Journals (Sweden)

Igor Lavrov

Full Text Available Although gap junctions are widely expressed in the developing central nervous system, the role of electrical coupling of neurons and glial cells via gap junctions in the spinal cord in adults is largely unknown. We investigated whether gap junctions are expressed in the mature spinal cord of the mudpuppy and tested the effects of applying gap junction blocker on the walking-like activity induced by NMDA or glutamate in an in vitro mudpuppy preparation. We found that glial and neural cells in the mudpuppy spinal cord expressed different types of connexins that include connexin 32 (Cx32, connexin 36 (Cx36, connexin 37 (Cx37, and connexin 43 (Cx43. Application of a battery of gap junction blockers from three different structural classes (carbenexolone, flufenamic acid, and long chain alcohols substantially and consistently altered the locomotor-like activity in a dose-dependent manner. In contrast, these blockers did not significantly change the amplitude of the dorsal root reflex, indicating that gap junction blockers did not inhibit neuronal excitability nonselectively in the spinal cord. Taken together, these results suggest that gap junctions play a significant modulatory role in the spinal neural networks responsible for the generation of walking-like activity in the adult mudpuppy.

43 CFR 43.655 - Individual.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Individual. 43.655 Section 43.655 Public Lands: Interior Office of the Secretary of the Interior GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 43.655 Individual. Individual means a natural person. ...

Articular chondrocyte network mediated by gap junctions: role in metabolic cartilage homeostasis

Science.gov (United States)

Mayan, Maria D; Gago-Fuentes, Raquel; Carpintero-Fernandez, Paula; Fernandez-Puente, Patricia; Filgueira-Fernandez, Purificacion; Goyanes, Noa; Valiunas, Virginijus; Brink, Peter R; Goldberg, Gary S; Blanco, Francisco J

2017-01-01

Objective This study investigated whether chondrocytes within the cartilage matrix have the capacity to communicate through intercellular connections mediated by voltage-gated gap junction (GJ) channels. Methods Frozen cartilage samples were used for immunofluorescence and immunohistochemistry assays. Samples were embedded in cacodylate buffer before dehydration for scanning electron microscopy. Co-immunoprecipitation experiments and mass spectrometry (MS) were performed to identify proteins that interact with the C-terminal end of Cx43. GJ communication was studied through in situ electroporation, electrophysiology and dye injection experiments. A transwell layered culture system and MS were used to identify and quantify transferred amino acids. Results Microscopic images revealed the presence of multiple cellular projections connecting chondrocytes within the matrix. These projections were between 5 and 150 μm in length. MS data analysis indicated that the C-terminus of Cx43 interacts with several cytoskeletal proteins implicated in Cx trafficking and GJ assembly, including α-tubulin and β-tubulin, actin, and vinculin. Electrophysiology experiments demonstrated that 12-mer oligonucleotides could be transferred between chondrocytes within 12 min after injection. Glucose was homogeneously distributed within 22 and 35 min. No transfer was detected when glucose was electroporated into A549 cells, which have no GJs. Transwell layered culture systems coupled with MS analysis revealed connexins can mediate the transfer of L-lysine and L-arginine between chondrocytes. Conclusions This study reveals that intercellular connections between chondrocytes contain GJs that play a key role in cell-cell communication and a metabolic function by exchange of nutrients including glucose and essential amino acids. A three-dimensional cellular network mediated through GJs might mediate metabolic and physiological homeostasis to maintain cartilage tissue. PMID:24225059

Cognitive Readiness: Preparing for the Unexpected

National Research Council Canada - National Science Library

Fletcher, J. D

2004-01-01

.... Anticipated operational requirements can be decomposed into specific tasks, conditions, and standards, but how should individuals, teams, and units prepare for the unexpected, which, by definition...

43 CFR 43.640 - Employee.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Employee. 43.640 Section 43.640 Public... WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 43.640 Employee. (a) Employee means the employee of a... employees; (2) All indirect charge employees, unless their impact or involvement in the performance of work...

Mezinárodní konference Expected and Unexpected Consequences of the Educational Expansion, Monte Verità, Ascona, Lago Maggiore, Švýcarsko, 8.–13. 7. 2007

Czech Academy of Sciences Publication Activity Database

Simonová, Natalie

2007-01-01

Roč. 43, č. 5 (2007), s. 1080-1081 ISSN 0038-0288. [Expected and Unexpected Consequences of the Educational Expansion. Ascona, 08.07.2007-13.07.2007] R&D Projects: GA ČR(CZ) GA403/06/1241 Institutional research plan: CEZ:AV0Z70280505 Keywords : educational expansion * educational inequality Subject RIV: AO - Sociology, Demography Impact factor: 0.169, year: 2007

Citizen science reveals unexpected continental-scale evolutionary change in a model organism.

Directory of Open Access Journals (Sweden)

Jonathan Silvertown

2011-04-01

Full Text Available Organisms provide some of the most sensitive indicators of climate change and evolutionary responses are becoming apparent in species with short generation times. Large datasets on genetic polymorphism that can provide an historical benchmark against which to test for recent evolutionary responses are very rare, but an exception is found in the brown-lipped banded snail (Cepaea nemoralis. This species is sensitive to its thermal environment and exhibits several polymorphisms of shell colour and banding pattern affecting shell albedo in the majority of populations within its native range in Europe. We tested for evolutionary changes in shell albedo that might have been driven by the warming of the climate in Europe over the last half century by compiling an historical dataset for 6,515 native populations of C. nemoralis and comparing this with new data on nearly 3,000 populations. The new data were sampled mainly in 2009 through the Evolution MegaLab, a citizen science project that engaged thousands of volunteers in 15 countries throughout Europe in the biggest such exercise ever undertaken. A known geographic cline in the frequency of the colour phenotype with the highest albedo (yellow was shown to have persisted and a difference in colour frequency between woodland and more open habitats was confirmed, but there was no general increase in the frequency of yellow shells. This may have been because snails adapted to a warming climate through behavioural thermoregulation. By contrast, we detected an unexpected decrease in the frequency of Unbanded shells and an increase in the Mid-banded morph. Neither of these evolutionary changes appears to be a direct response to climate change, indicating that the influence of other selective agents, possibly related to changing predation pressure and habitat change with effects on micro-climate.

43 CFR 43.665 - State.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false State. 43.665 Section 43.665 Public Lands... (FINANCIAL ASSISTANCE) Definitions § 43.665 State. State means any of the States of the United States, the District of Columbia, the Commonwealth of Puerto Rico, or any territory or possession of the United States. ...

Unexpected Molecular Sieving Properties of Zeolitic Imidazolate Framework-8

KAUST Repository

Zhang, Chen; Lively, Ryan P.; Zhang, Ke; Johnson, Justin R.; Karvan, Oguz; Koros, William J.

2012-01-01

We studied molecular sieving properties of zeolitic imidazolate framework-8 (ZIF-8) by estimating the thermodynamically corrected diffusivities of probe molecules at 35 °C. From helium (2.6 Å) to iso-C 4H 10 (5.0 Å), the corrected diffusivity drops 14 orders of magnitude. Our results further suggest that the effective aperture size of ZIF-8 for molecular sieving is in the range of 4.0 to 4.2 Å, which is significantly larger than the XRD-derived value (3.4 Å) and between the well-known aperture size of zeolite 4A (3.8 Å) and 5A (4.3 Å). Interestingly, because of aperture flexibility, the studied C 4 hydrocarbon molecules that are larger than this effective aperture size still adsorb in the micropores of ZIF-8 with kinetic selectivities for iso-C 4H 8/iso-C 4H 10 of 180 and n-C 4H 10/iso-C 4H 10 of 2.5 × 10 6. These unexpected molecular sieving properties open up new opportunities for ZIF materials for separations that cannot be economically achieved by traditional microporous adsorbents such as synthetic zeolites. © 2012 American Chemical Society.

Unexpected Molecular Sieving Properties of Zeolitic Imidazolate Framework-8

KAUST Repository

Zhang, Chen

2012-08-16

We studied molecular sieving properties of zeolitic imidazolate framework-8 (ZIF-8) by estimating the thermodynamically corrected diffusivities of probe molecules at 35 °C. From helium (2.6 Å) to iso-C 4H 10 (5.0 Å), the corrected diffusivity drops 14 orders of magnitude. Our results further suggest that the effective aperture size of ZIF-8 for molecular sieving is in the range of 4.0 to 4.2 Å, which is significantly larger than the XRD-derived value (3.4 Å) and between the well-known aperture size of zeolite 4A (3.8 Å) and 5A (4.3 Å). Interestingly, because of aperture flexibility, the studied C 4 hydrocarbon molecules that are larger than this effective aperture size still adsorb in the micropores of ZIF-8 with kinetic selectivities for iso-C 4H 8/iso-C 4H 10 of 180 and n-C 4H 10/iso-C 4H 10 of 2.5 × 10 6. These unexpected molecular sieving properties open up new opportunities for ZIF materials for separations that cannot be economically achieved by traditional microporous adsorbents such as synthetic zeolites. © 2012 American Chemical Society.

Rural families' interpretations of experiencing unexpected transition in the wake of a natural disaster.

Science.gov (United States)

Fernandes, Gisele Cristina Manfrini; Boehs, Astrid Eggert; Denham, Sharon A; Nitschke, Rosane Gonçalves; Martini, Jussara Gue

2017-02-13

Natural disasters affect populations in various parts of the world. The impacts of disasters can cause many problems to the health of people and disruption to family life, potentially leading to an unexpected transition. The objective of this paper is to present the unexpected transitional experiences of rural families following a natural disaster. A multiple case study of six families was conducted with children and adolescents in a rural area affected by a 2008 disaster in southern Brazil. For data collection, we used participant observation, narrative interviews, genograms, ecomaps and an instrument called calendar routine. The analysis of the data resulted in different family interpretations about the changes resulting from the storm and compared life before and after the disaster. The loss of homes and loved ones, migration, unemployment, and losses from the farm were the main changes associated with new development tasks. The experiences of family transition after the disaster revealed that losses influenced social lives, daily routines and the preservation of cultural values.

77 FR 21389 - Unexpected Urgent Refugee and Migration Needs

Science.gov (United States)

2012-04-10

... April 3, 2012 Unexpected Urgent Refugee and Migration Needs Memorandum for the Secretary of State By the... 2(c)(1) of the Migration and Refugee Assistance Act of 1962 (the ``Act''), as amended, (22 U.S.C... United States Emergency Refugee and Migration Assistance Fund, for the purpose of meeting unexpected and...

Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala.

Science.gov (United States)

Stehberg, Jimmy; Moraga-Amaro, Rodrigo; Salazar, Christian; Becerra, Alvaro; Echeverría, Cesar; Orellana, Juan A; Bultynck, Geert; Ponsaerts, Raf; Leybaert, Luc; Simon, Felipe; Sáez, Juan C; Retamal, Mauricio A

2012-09-01

Recent in vitro evidence indicates that astrocytes can modulate synaptic plasticity by releasing neuroactive substances (gliotransmitters). However, whether gliotransmitter release from astrocytes is necessary for higher brain function in vivo, particularly for memory, as well as the contribution of connexin (Cx) hemichannels to gliotransmitter release, remain elusive. Here, we microinfused into the rat basolateral amygdala (BLA) TAT-Cx43L2, a peptide that selectively inhibits Cx43-hemichannel opening while maintaining synaptic transmission or interastrocyte gap junctional communication. In vivo blockade of Cx43 hemichannels during memory consolidation induced amnesia for auditory fear conditioning, as assessed 24 h after training, without affecting short-term memory, locomotion, or shock reactivity. The amnesic effect was transitory, specific for memory consolidation, and was confirmed after microinfusion of Gap27, another Cx43-hemichannel blocker. Learning capacity was recovered after coinfusion of TAT-Cx43L2 and a mixture of putative gliotransmitters (glutamate, glutamine, lactate, d-serine, glycine, and ATP). We propose that gliotransmitter release from astrocytes through Cx43 hemichannels is necessary for fear memory consolidation at the BLA. Thus, the present study is the first to demonstrate a physiological role for astroglial Cx43 hemichannels in brain function, making these channels a novel pharmacological target for the treatment of psychiatric disorders, including post-traumatic stress disorder.

Information Interaction as a Mechanism of Semantic Gap Elimination

Directory of Open Access Journals (Sweden)

Victor Y. Tsvetkov

2013-01-01

Full Text Available The article studies semantic gap as an objective phenomenon, shows that semantic gap occurs both in parallel computing and in other areas. Semantic description of the content is revealed as a set of different descriptions. Causes of semantic gap are described. The content of information exchange is explained in the article. Information interaction in the semantic field is interpreted as a mechanism to lessen the gap

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.

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

Msx1 and Msx2 are functional interacting partners of T-box factors in the regulation of Connexin43

NARCIS (Netherlands)

Boogerd, Kees-Jan; Wong, L. Y. Elaine; Christoffels, Vincent M.; Klarenbeek, Meinke; Ruijter, Jan M.; Moorman, Antoon F. M.; Barnett, Phil

2008-01-01

AIMS: T-box factors Tbx2 and Tbx3 play key roles in the development of the cardiac conduction system, atrioventricular canal, and outflow tract of the heart. They regulate the gap-junction-encoding gene Connexin43 (Cx43) and other genes critical for heart development and function. Discovering

[Development of the unexpected reality scale for childcare training].

Science.gov (United States)

Matsuda, Yuko; Shitara, Saeko; Hamada, Shoko

2016-10-01

This study aimed to develop a scale for unexpected reality for childcare training (Study 1) and examine the change and influence it exerts on the efficacy of preschool teachers (Study 2). In Study 1, the sample consisted of 571 university and junior college students enrolled in a childcare course. After exploratory factor analysis, four factors were extracted: “actual feelings for childcare as a field of study,” “difficulties faced during involvement with children,” “negative aspects of the childcare worker,” and “severity of work.” The study’s scale was shown to be internally consistent and valid. In Study 2, the sample consisted of 122 junior college students enrolled in a childcare course. The results showed that the high-scoring groups of each unexpected reality subscales experienced less unexpected reality in the subsequent training session. Moreover, the results of multiple regression showed that preschool teacher efficacy was predicted positively by “actual feelings for childcare as a field of study” and negatively by “difficulties faced during involvement with children.” Thus, we suggest that for effective pre- and post-guidance of childcare training, unexpected realities should be considered.

Nature of chromosome gaps induced by alkylating agents and γ-rays as revealed by caffeine treatment

International Nuclear Information System (INIS)

Dimitrov, B.

1981-01-01

In the cells of primary roots of Crepis capillaris, post-treatment with caffeine increased the frequency of gaps and chromosomal aberrations induced by the alkylating agents ethyleneimine and N-nitroso-N-methylurethane and γ-rays. The increase in the frequency of gaps was considerably lower than that observed in chromosomal aberrations, this being more strongly expressed in the case fo the alkylating agents. The potentiating effect of caffeine on the γ-ray-induced chromosomal gaps was a little higher in S as compared in G 2 . These results lead to the conclusion that the alkylating agents and the γ-rays might induce 2 types of chromosomal gap. (orig.)

Unexpected Binding Mode of a Potent Indeno[1,2-b]indole-Type Inhibitor of Protein Kinase CK2 Revealed by Complex Structures with the Catalytic Subunit CK2α and Its Paralog CK2α′

Directory of Open Access Journals (Sweden)

Jennifer Hochscherf

2017-12-01

Full Text Available Protein kinase CK2, a member of the eukaryotic protein kinase superfamily, is associated with cancer and other human pathologies and thus an attractive drug target. The indeno[1,2-b]indole scaffold is a novel lead structure to develop ATP-competitive CK2 inhibitors. Some indeno[1,2-b]indole-based CK2 inhibitors additionally obstruct ABCG2, an ABC half transporter overexpressed in breast cancer and co-responsible for drug efflux and resistance. Comprehensive derivatization studies revealed substitutions of the indeno[1,2-b]indole framework that boost either the CK2 or the ABCG2 selectivity or even support the dual inhibition potential. The best indeno[1,2-b]indole-based CK2 inhibitor described yet (IC50 = 25 nM is 5-isopropyl-4-(3-methylbut-2-enyl-oxy-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (4p. Herein, we demonstrate the membrane permeability of 4p and describe co-crystal structures of 4p with CK2α and CK2α′, the paralogs of human CK2 catalytic subunit. As expected, 4p occupies the narrow, hydrophobic ATP site of CK2α/CK2α′, but surprisingly with a unique orientation: its hydrophobic substituents point towards the solvent while its two oxo groups are hydrogen-bonded to a hidden water molecule. An equivalent water molecule was found in many CK2α structures, but never as a critical mediator of ligand binding. This unexpected binding mode is independent of the interdomain hinge/helix αD region conformation and of the salt content in the crystallization medium.

Structural imaging biomarkers of sudden unexpected death in epilepsy.

Science.gov (United States)

Wandschneider, Britta; Koepp, Matthias; Scott, Catherine; Micallef, Caroline; Balestrini, Simona; Sisodiya, Sanjay M; Thom, Maria; Harper, Ronald M; Sander, Josemir W; Vos, Sjoerd B; Duncan, John S; Lhatoo, Samden; Diehl, Beate

2015-10-01

Sudden unexpected death in epilepsy is a major cause of premature death in people with epilepsy. We aimed to assess whether structural changes potentially attributable to sudden death pathogenesis were present on magnetic resonance imaging in people who subsequently died of sudden unexpected death in epilepsy. In a retrospective, voxel-based analysis of T1 volume scans, we compared grey matter volumes in 12 cases of sudden unexpected death in epilepsy (two definite, 10 probable; eight males), acquired 2 years [median, interquartile range (IQR) 2.8] before death [median (IQR) age at scanning 33.5 (22) years], with 34 people at high risk [age 30.5 (12); 19 males], 19 at low risk [age 30 (7.5); 12 males] of sudden death, and 15 healthy controls [age 37 (16); seven males]. At-risk subjects were defined based on risk factors of sudden unexpected death in epilepsy identified in a recent combined risk factor analysis. We identified increased grey matter volume in the right anterior hippocampus/amygdala and parahippocampus in sudden death cases and people at high risk, when compared to those at low risk and controls. Compared to controls, posterior thalamic grey matter volume, an area mediating oxygen regulation, was reduced in cases of sudden unexpected death in epilepsy and subjects at high risk. The extent of reduction correlated with disease duration in all subjects with epilepsy. Increased amygdalo-hippocampal grey matter volume with right-sided changes is consistent with histo-pathological findings reported in sudden infant death syndrome. We speculate that the right-sided predominance reflects asymmetric central influences on autonomic outflow, contributing to cardiac arrhythmia. Pulvinar damage may impair hypoxia regulation. The imaging findings in sudden unexpected death in epilepsy and people at high risk may be useful as a biomarker for risk-stratification in future studies. The Author (2015). Published by Oxford University Press on behalf of the Guarantors of

The gender wage GAP ın Turkey

OpenAIRE

AKTAŞ, Arda; UYSAL, Gokce

2017-01-01

The most prominent form of gender discrimination in the labor market is the gender gap in wages. Using the Wage Structure Survey, a firm-level data set, we study the gender wage gap in Turkey. We concentrate on formal employment as this is the jurisdiction of the Labor Code in Turkey. Although women earn 3% less than men on average, a wider look reveals important differences along the entire wage distribution. There is virtually no gender gap at the lower end of the wage distr...

Optical Characterization of Rare Earth-doped Wide Band Gap Semiconductors

National Research Council Canada - National Science Library

Hommerich, Uwe

1999-01-01

...+) PL intensity under below gap excitation. Photoluminescence excitation (PLE) studies revealed that oxygen/carbon introduces a broad below gap PLE band, which provides an efficient pathway for E(3+) excitation...

Correlations of differentially expressed gap junction connexins Cx26, Cx30, Cx32, Cx43 and Cx46 with breast cancer progression and prognosis.

Directory of Open Access Journals (Sweden)

Ivett Teleki

Full Text Available Connexins and their cell membrane channels contribute to the control of cell proliferation and compartmental functions in breast glands and their deregulation is linked to breast carcinogenesis. Our aim was to correlate connexin expression with tumor progression and prognosis in primary breast cancers.Meta-analysis of connexin isotype expression data of 1809 and 1899 breast cancers from the Affymetrix and Illumina array platforms, respectively, was performed. Expressed connexins were also monitored at the protein level in tissue microarrays of 127 patients equally representing all tumor grades, using immunofluorescence and multilayer, multichannel digital microscopy. Prognostic correlations were plotted in Kaplan-Meier curves and tested using the log-rank test and cox-regression analysis in univariate and multivariate models.The expression of GJA1/Cx43, GJA3/Cx46 and GJB2/Cx26 and, for the first time, GJA6/Cx30 and GJB1/Cx32 was revealed both in normal human mammary glands and breast carcinomas. Within their subfamilies these connexins can form homo- and heterocellular epithelial channels. In cancer, the array datasets cross-validated each other's prognostic results. In line with the significant correlations found at mRNA level, elevated Cx43 protein levels were linked with significantly improved breast cancer outcome, offering Cx43 protein detection as an independent prognostic marker stronger than vascular invasion or necrosis. As a contrary, elevated Cx30 mRNA and protein levels were associated with a reduced disease outcome offering Cx30 protein detection as an independent prognostic marker outperforming mitotic index and necrosis. Elevated versus low Cx43 protein levels allowed the stratification of grade 2 tumors into good and poor relapse free survival subgroups, respectively. Also, elevated versus low Cx30 levels stratified grade 3 patients into poor and good overall survival subgroups, respectively.Differential expression of Cx43 and Cx

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...

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.

Rural families' interpretations of experiencing unexpected transition in the wake of a natural disaster

Directory of Open Access Journals (Sweden)

Gisele Cristina Manfrini Fernandes

Full Text Available Abstract: Natural disasters affect populations in various parts of the world. The impacts of disasters can cause many problems to the health of people and disruption to family life, potentially leading to an unexpected transition. The objective of this paper is to present the unexpected transitional experiences of rural families following a natural disaster. A multiple case study of six families was conducted with children and adolescents in a rural area affected by a 2008 disaster in southern Brazil. For data collection, we used participant observation, narrative interviews, genograms, ecomaps and an instrument called calendar routine. The analysis of the data resulted in different family interpretations about the changes resulting from the storm and compared life before and after the disaster. The loss of homes and loved ones, migration, unemployment, and losses from the farm were the main changes associated with new development tasks. The experiences of family transition after the disaster revealed that losses influenced social lives, daily routines and the preservation of cultural values.

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

The Structure of Plasmodium falciparum Blood-Stage 6-Cys Protein Pf41 Reveals an Unexpected Intra-Domain Insertion Required for Pf12 Coordination.

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Michelle L Parker

Full Text Available Plasmodium falciparum is an apicomplexan parasite and the etiological agent of severe human malaria. The complex P. falciparum life cycle is supported by a diverse repertoire of surface proteins including the family of 6-Cys s48/45 antigens. Of these, Pf41 is localized to the surface of the blood-stage merozoite through its interaction with the glycophosphatidylinositol-anchored Pf12. Our recent structural characterization of Pf12 revealed two juxtaposed 6-Cys domains (D1 and D2. Pf41, however, contains an additional segment of 120 residues predicted to form a large spacer separating its two 6-Cys domains. To gain insight into the assembly mechanism and overall architecture of the Pf12-Pf41 complex, we first determined the 2.45 Å resolution crystal structure of Pf41 using zinc single-wavelength anomalous dispersion. Structural analysis revealed an unexpected domain organization where the Pf41 6-Cys domains are, in fact, intimately associated and the additional residues instead map predominately to an inserted domain-like region (ID located between two β-strands in D1. Notably, the ID is largely proteolyzed in the final structure suggesting inherent flexibility. To assess the contribution of the ID to complex formation, we engineered a form of Pf41 where the ID was replaced by a short glycine-serine linker and showed by isothermal titration calorimetry that binding to Pf12 was abrogated. Finally, protease protection assays showed that the proteolytic susceptibility of the ID was significantly reduced in the complex, consistent with the Pf41 ID directly engaging Pf12. Collectively, these data establish the architectural organization of Pf41 and define an essential role for the Pf41 ID in promoting assembly of the Pf12-Pf41 heterodimeric complex.

Unexpected marked seizure improvement in paediatric epilepsy surgery candidates

DEFF Research Database (Denmark)

Hoei-Hansen, Christina E; Mathiasen, René; Uldall, Peter

2017-01-01

PURPOSE: Epilepsy surgery is performed based on the assumption that medical refractory epilepsy will continue. Rarely seizure freedom occurs before surgery is performed, while the patient is being evaluated as an epilepsy surgery candidate. The aim of this study was to describe the number...... of children withdrawn from an epilepsy surgery programme due to unexpected seizure improvement. METHODS: We retrospectively studied 173 children under 18 years with medical refractory epilepsy referred for epilepsy surgery between 1996 and 2010. Medical records were reviewed in 2012 and 2015. RESULTS......: At the first evaluation point in 2012, 13 patients were withdrawn from the epilepsy surgery programme due to unexpected marked improvement. In 2015, 6 of them were still seizure free. They had unexpected seizure freedom due to change in AED treatment (n=3) or after a febrile episode (n=3). The mean number...

From a supply gap to a demand gap? The risk and consequences of over-indebting the underbanked

OpenAIRE

Jessica Schicks

2011-01-01

In the past, the microfinance industry focused mainly on growth and outreach. Addressing financial exclusion implied a huge supply gap. Recent over-indebtedness crises in several countries have shown that this gap can turn into over-supply. The industry urgently requires research to understand the magnitude and consequences of this shift. This chapter reveals the broad spectrum of consequences over-indebtedness can have on borrowers and other stakeholders, mainly MFIs. It emphasizes that over...

Measuring the Tax Gap in the European Economy

Directory of Open Access Journals (Sweden)

Konrad Raczkowski

2015-07-01

Full Text Available The objective of the paper is to reveal the methodology used to examine the tax gap and calculate the tax gap for all EU states over 2011-2014. The paper draws on the review of reference literature addressing the tax gap in the context of tax avoidance and tax evasion. The paper features the GDP size across countries so as to demonstrate the overall level of the shadow economy compared to the aggregate tax burden. Finally, for the first time, the calculations of the tax gap for all EU states over 2011-2014 were displayed.

Unexpected Translations in Urban Policy Mobility

DEFF Research Database (Denmark)

Zapata, Patrik; Zapata Campos, Maria José

2015-01-01

such as prototypes in order to travel. It was made mobile via relational sites or situations providing safe and accessible connections with Chureca residents. Paradoxically, these places also allowed extraordinary connections between actors located in different scales and spaces, facilitating unexpected local...

Unexpected Translations in Urban Policy Mobility

DEFF Research Database (Denmark)

Zapata, Patrik; Zapata Campos, Maria José

such as prototypes in order to travel. It was made mobile via relational sites or situations providing safe and accessible connections with Chureca residents. Paradoxically, these places also allowed extraordinary connections between actors located in different scales and spaces, facilitating unexpected local...

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.

Hydra meiosis reveals unexpected conservation of structural synaptonemal complex proteins across metazoans.

Science.gov (United States)

Fraune, Johanna; Alsheimer, Manfred; Volff, Jean-Nicolas; Busch, Karoline; Fraune, Sebastian; Bosch, Thomas C G; Benavente, Ricardo

2012-10-09

The synaptonemal complex (SC) is a key structure of meiosis, mediating the stable pairing (synapsis) of homologous chromosomes during prophase I. Its remarkable tripartite structure is evolutionarily well conserved and can be found in almost all sexually reproducing organisms. However, comparison of the different SC protein components in the common meiosis model organisms Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealed no sequence homology. This discrepancy challenged the hypothesis that the SC arose only once in evolution. To pursue this matter we focused on the evolution of SYCP1 and SYCP3, the two major structural SC proteins of mammals. Remarkably, our comparative bioinformatic and expression studies revealed that SYCP1 and SYCP3 are also components of the SC in the basal metazoan Hydra. In contrast to previous assumptions, we therefore conclude that SYCP1 and SYCP3 form monophyletic groups of orthologous proteins across metazoans.

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.

The Complex Subtype-Dependent Role of Connexin 43 (GJA1 in Breast Cancer

Directory of Open Access Journals (Sweden)

Mélanie Busby

2018-02-01

Full Text Available Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43 in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression.

The Complex Subtype-Dependent Role of Connexin 43 (GJA1) in Breast Cancer

Science.gov (United States)

Busby, Mélanie; Hallett, Michael T.; Plante, Isabelle

2018-01-01

Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs) that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43) in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression. PMID:29495625

Unexpected Expectations The Curiosities of a Mathematical Crystal Ball

CERN Document Server

Wapner, Leonard M

2012-01-01

Unexpected Expectations: The Curiosities of a Mathematical Crystal Ball explores how paradoxical challenges involving mathematical expectation often necessitate a reexamination of basic premises. The author takes you through mathematical paradoxes associated with seemingly straightforward applications of mathematical expectation and shows how these unexpected contradictions may push you to reconsider the legitimacy of the applications. The book requires only an understanding of basic algebraic operations and includes supplemental mathematical background in chapter appendices. After a history o

43 CFR 43.635 - Drug-free workplace.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Drug-free workplace. 43.635 Section 43.635 Public Lands: Interior Office of the Secretary of the Interior GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 43.635 Drug-free workplace. Drug-free workplace means a site...

Unexpected findings and promoting monocausal claims, a cautionary tale.

Science.gov (United States)

Copeland, Samantha Marie

2017-10-01

Stories of serendipitous discoveries in medicine incorrectly imply that the path from an unexpected observation to major discovery is straightforward or guaranteed. In this paper, I examine a case from the field of research about chronic fatigue syndrome (CFS). In Norway, an unexpected positive result during clinical care has led to the development of a research programme into the potential for the immunosuppressant drug rituximab to relieve the symptoms of CFS. The media and public have taken up researchers' speculations that their research results indicate a causal mechanism for CFS - consequently, patients now have great hope that 'the cause' of CFS has been found, and thus, a cure is sure to follow. I argue that a monocausal claim cannot be correctly asserted, either on the basis of the single case of an unexpected, although positive, result or on the basis of the empirical research that has followed up on that result. Further, assertion and promotion of this claim will have specific harmful effects: it threatens to inappropriately narrow the scope of research on CFS, might misdirect research altogether, and could directly and indirectly harm patients. Therefore, the CFS case presents a cautionary tale, illustrating the risks involved in drawing a theoretical hypothesis from an unexpected observation. Further, I draw attention to the tendency in contemporary clinical research with CFS to promote new research directions on the basis of reductive causal models of that syndrome. Particularly, in the case of CFS research, underdetermination and causal complexity undermine the potential value of a monocausal claim. In sum, when an unexpected finding occurs in clinical practice or medical research, the value of following up on that finding is to be found not in the projected value of a singular causal relationship inferred from the finding but rather in the process of research that follows. © 2016 John Wiley & Sons, Ltd.

On the unexpected oscillation of the total cross section for excitation in He2+ + H collisions

International Nuclear Information System (INIS)

Schultz, D.R.; Reinhold, C.O.; Krstic, P.S.

1996-01-01

Recent calculations and measurements have revealed unexpected oscillations of the total cross section for excitation in low- to intermediate-energy He 2+ + H collisions. A physical explanation of this behavior is given here stemming from analysis of classical trajectory Monte Carlo simulations, molecular orbital close coupling calculations, and solution of the time-dependent Schroedinger equation on a numerical lattice. These results indicate that the observed behavior should be characteristic of a wide range of reactions in ion-atom collisions

Gaps-in-Noise test: gap detection thresholds in 9-year-old normal-hearing children.

Science.gov (United States)

Marculino, Carolina Finetti; Rabelo, Camila Maia; Schochat, Eliane

2011-12-01

To establish the standard criteria for the Gaps-in-Noise (GIN) test in 9-year-old normal-hearing children; to obtain the mean gap detection thresholds; and to verify the influence of the variables gender and ear on the gap detection thresholds. Forty normal-hearing individuals, 20 male and 20 female, with ages ranging from 9 years to 9 years and 11 months, were evaluated. The procedures performed were: anamnesis, audiological evaluation, acoustic immittance measures (tympanometry and acoustic reflex), Dichotic Digits Test, and GIN test. The results obtained were statistically analyzed. The results revealed similar performance of right and left ears in the population studied. There was also no difference regarding the variable gender. In the subjects evaluated, the mean gap detection thresholds were 4.4 ms for the right ear, and 4.2 ms for the left ear. The values obtained for right and left ear, as well as their standard deviations, can be used as standard criteria for 9-year-old children, regardless of ear or gender.

The Generalist versus the Specialist: The New Oxford Dictionary Reveals a Gap.

Science.gov (United States)

Levine, Martin Lyon

1981-01-01

There is a gap, it is suggested, separating the generally cultured person, not just from the scientist, but from specialists in many fields. Dictionary definitions are seen as one means of seeing the extent to which specialists and those in the general culture speak the same language. (MLW)

Hippocampal synapsin I, growth-associated protein-43, and microtubule-associated protein-2 immunoreactivity in learned helplessness rats and antidepressant-treated rats.

Science.gov (United States)

Iwata, M; Shirayama, Y; Ishida, H; Kawahara, R

2006-09-01

Learned helplessness rats are thought to be an animal model of depression. To study the role of synapse plasticity in depression, we examined the effects of learned helplessness and antidepressant treatments on synapsin I (a marker of presynaptic terminals), growth-associated protein-43 (GAP-43; a marker of growth cones), and microtubule-associated protein-2 (MAP-2; a marker of dendrites) in the hippocampus by immunolabeling. (1) Learned helplessness rats showed significant increases in the expression of synapsin I two days after the attainment of learned helplessness, and significant decreases in the protein expression eight days after the achievement of learned helplessness. Subchronic treatment of naïve rats with imipramine or fluvoxamine significantly decreased the expression of synapsin I. (2) Learned helplessness increased the expression of GAP-43 two days and eight days after learned helplessness training. Subchronic treatment of naïve rats with fluvoxamine but not imipramine showed a tendency to decrease the expression of synapsin I. (3) Learned helplessness rats showed increased expression of MAP-2 eight days after the attainment of learned helplessness. Naïve rats subchronically treated with imipramine showed a tendency toward increased expression of MAP-2, but those treated with fluvoxamine did not. These results indicate that the neuroplasticity-related proteins synapsin I, GAP-43, and MAP-2 may play a role in the pathophysiology of depression and the mechanisms of antidepressants.

The CO₂ GAP Project--CO₂ GAP as a prognostic tool in emergency departments.

Science.gov (United States)

Shetty, Amith L; Lai, Kevin H; Byth, Karen

2010-12-01

To determine whether CO₂ GAP [(a-ET) PCO₂] value differs consistently in patients presenting with shortness of breath to the ED requiring ventilatory support. To determine a cut-off value of CO₂ GAP, which is consistently associated with measured outcome and to compare its performance against other derived variables. This prospective observational study was conducted in ED on a convenience sample of 412 from 759 patients who underwent concurrent arterial blood gas and ETCO₂ (end-tidal CO₂) measurement. They were randomized to test sample of 312 patients and validation set of 100 patients. The primary outcome of interest was the need for ventilatory support and secondary outcomes were admission to high dependency unit or death during stay in ED. The randomly selected training set was used to select cut-points for the possible predictors; that is, CO₂ GAP, CO₂ gradient, physiologic dead space and A-a gradient. The sensitivity, specificity and predictive values of these predictors were validated in the test set of 100 patients.   Analysis of the receiver operating characteristic curves revealed the CO₂ GAP performed significantly better than the arterial-alveolar gradient in patients requiring ventilator support (area under the curve 0.950 vs 0.726). A CO₂ GAP ≥10 was associated with assisted ventilation outcomes when applied to the validation test set (100% sensitivity 70% specificity). The CO₂ GAP [(a-ET) PCO₂] differs significantly in patients requiring assisted ventilation when presenting with shortness of breath to EDs and further research addressing the prognostic value of CO₂ GAP in this specific aspect is required. © 2010 The Authors. EMA © 2010 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

START-GAP3/DLC3 is a GAP for RhoA and Cdc42 and is localized in focal adhesions regulating cell morphology

International Nuclear Information System (INIS)

Kawai, Katsuhisa; Kiyota, Minoru; Seike, Junichi; Deki, Yuko; Yagisawa, Hitoshi

2007-01-01

In the human genome there are three genes encoding RhoGAPs that contain the START (steroidogenic acute regulatory protein (StAR)-related lipid transfer)-domain. START-GAP3/DLC3 is a tumor suppressor gene similar to two other human START-GAPs known as DLC1 or DLC2. Although expression of START-GAP3/DLC3 inhibits the proliferation of cancer cells, its molecular function is not well understood. In this study we carried out biochemical characterization of START-GAP3/DLC3, and explored the effects of its expression on cell morphology and intracellular localization. We found that START-GAP3/DLC3 serves as a stimulator of PLCδ1 and as a GAP for both RhoA and Cdc42 in vitro. Moreover, we found that the GAP activity is responsible for morphological changes. The intracellular localization of endogenous START-GAP3/DLC3 was explored by immunocytochemistry and was revealed in focal adhesions. These results indicate that START-GAP3/DLC3 has characteristics similar to other START-GAPs and the START-GAP family seems to share common characteristics

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

An investigation into the causes of unexpected intra-operative transoesophageal echocardiography findings.

Science.gov (United States)

Skinner, H J; Mahmoud, A; Uddin, A; Mathew, T

2012-04-01

There is uncertainty regarding echocardiography before cardiac surgery, especially with regard to timing and disease progression as well as potential errors. We investigated the causes of unexpected intra-operative transoesophageal echocardiography findings by performing a 33-month audit. We found that there were 50/797 (6%) unexpected findings that led to an alteration in surgical strategy in 34 (4%) patients. Of the unexpected findings, 25 (50%) were unrelated to pre-operative pathology. After reviewing pre-operative studies and reports, unexpected findings were found to be due to: reporting errors in 20 patients (44%); limitations in transthoracic compared to transoesophageal echocardiography in 14 patients (30%); disease progression in 10 patients (22%); and inter-observer variability in two patients (4%). We identified six reports out of 797 (0.8%) that contained potentially serious errors. Surgical management changed in 18/20 (90%) patients in whom the unexpected change was due to reporting error, compared to 16/30 (53%) patients whose pre-operative echocardiogram was correctly reported (p = 0.006). Our study suggests that pre-operative echocardiography reporting errors are common and important. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

The gap in the Arctic Cenozoic Record: Expect the Unexpected

Science.gov (United States)

Sangiorgi, F.; Brumsack, H.; Schouten, S.; Brinkhuis, H.; Kaminski, M. A.; Reichart, G.; Stickley, C. E.; Willard, D. A.; Sinninghe Damste', J. S.

2006-12-01

Integrated Ocean Drilling Program Expedition 302, a.k.a. the Arctic Coring Expedition (ACEX), drilled more than 400 meters below the seafloor at the central Lomonosov Ridge, ca 250 km from the modern North Pole in water depths of about 1300 m. The partially recovered sediments provide a unique record of the geological and paleoceanographical evolution of the Arctic Ocean during the Cenozoic. The record indicates a transition from a "greenhouse world", characterized by a relative shallow marine setting, with organic-rich sediment and frequent brackish or even fresh surface waters during the latest Palaeocene and the early Eocene, to an "icehouse world" of hemipelagic sedimentation affected by the occurrence of sea ice from the middle Miocene to present. Much to our surprise, these two states are separated by a major hiatus, not obvious from the seismic record and the lithology of the cores, spanning at least 25 Ma as derived from dinocyst and benthic foraminifer stratigraphies. These testify that deposits of probable late early Miocene age directly overlie early middle Eocene sediments. To unravel the nature of the hiatus, we performed a multiproxy micropaleontological and geochemical study on the surrounding record, i.e. lithological units 1/6, 1/5 and 1/4, where the sediment changes from homogeneous dark into a cm-scaled alternation ("zebra-like") black and grey bands to light grey, blue and reddish-brown. Paleoenvironmental reconstructions based on organic-walled dinoflagellate cysts, pollen and spores, benthic foraminifera, inorganic and organic geochemistry and siliceous remains reveal conspicuous changes, suggesting a transition from brackish-freshwater to shallow-lagoonal and to open marine environments. These environmental turnovers, coupled with the occurrence of such a large hiatus, cannot be due to climatic shifts alone, but suggest that major tectonic rearrangements likely changed the depositional setting. On-going organic geochemical analysis will be

Changes in drug utilization during a gap in insurance coverage: an examination of the medicare Part D coverage gap.

Directory of Open Access Journals (Sweden)

Jennifer M Polinski

2011-08-01

Full Text Available Nations are struggling to expand access to essential medications while curbing rising health and drug spending. While the US government's Medicare Part D drug insurance benefit expanded elderly citizens' access to drugs, it also includes a controversial period called the "coverage gap" during which beneficiaries are fully responsible for drug costs. We examined the impact of entering the coverage gap on drug discontinuation, switching to another drug for the same indication, and drug adherence. While increased discontinuation of and adherence to essential medications is a regrettable response, increased switching to less expensive but therapeutically interchangeable medications is a positive response to minimize costs.We followed 663,850 Medicare beneficiaries enrolled in Part D or retiree drug plans with prescription and health claims in 2006 and/or 2007 to determine who reached the gap spending threshold, n = 217,131 (33%. In multivariate Cox proportional hazards models, we compared drug discontinuation and switching rates in selected drug classes after reaching the threshold between all 1,993 who had no financial assistance during the coverage gap (exposed versus 9,965 multivariate propensity score-matched comparators with financial assistance (unexposed. Multivariate logistic regressions compared drug adherence (≤ 80% versus >80% of days covered. Beneficiaries reached the gap spending threshold on average 222 d ±79. At the drug level, exposed beneficiaries were twice as likely to discontinue (hazard ratio [HR]  = 2.00, 95% confidence interval [CI] 1.64-2.43 but less likely to switch a drug (HR  = 0.60, 0.46-0.78 after reaching the threshold. Gap-exposed beneficiaries were slightly more likely to have reduced adherence (OR  = 1.07, 0.98-1.18.A lack of financial assistance after reaching the gap spending threshold was associated with a doubling in discontinuing essential medications but not switching drugs in 2006 and 2007

Unexpected Coexisting Myocardial Infarction Detected by Delayed Enhancement MRI

Directory of Open Access Journals (Sweden)

Edouard Gerbaud

2009-01-01

Full Text Available We report a case of an unexpected coexisting anterior myocardial infarction detected by delayed enhancement MRI in a 41-year-old man following a presentation with a first episode of chest pain during inferior acute myocardial infarction. This second necrotic area was not initially suspected because there were no ECG changes in the anterior leads and the left descending coronary artery did not present any significant stenoses on emergency coronary angiography. Unrecognised myocardial infarction may carry important prognostic implications. CMR is currently the best imaging technique to detect unexpected infarcts.

Yield gap determinants for wheat production in major irrigated cropping zones of punjab, pakistan

International Nuclear Information System (INIS)

Hussain, A.; Aujla, K.M.; Badar, N.

2014-01-01

Yield gap is useful measurement for crop productivity and the extent to which crop productivity falls below some potential level. The study was carried out to analyze the yield gap and determinants of wheat production in the Punjab province of Pakistan. It is based on cross sectional data from 210 farmers for the crop year 2009-10. Results suggest that farm level wheat yields are less than the potential yield level by 33.0%, 43.0% and 50.6% in the mixed-cropping, cotton-wheat and rice-wheat zones of the province, respectively. Ordinary least square regression analysis of wheat production by assuming Cobb-Douglas specification reveals that the number of irrigations, usage of farm yard manure and fertilizers contribute positively and significantly to wheat crop production. Coefficients of dummy variables for cropping zones indicate that farmers in the mixed cropping zone are obtaining better yield of the wheat crop as compared to their counterparts in other selected cropping zones. These results suggested that farmers can increase wheat productivity by increasing the use of factor inputs; however, poverty may be a constraint on realizing these gains. Thus, wheat production can be increased in the country by helping resource poor farmers through suitable support mechanisms. (author)

The accrual anomaly - focus on changes in specific unexpected accruals results in new evidence

DEFF Research Database (Denmark)

Schøler, Finn

are specifically analyzed, namely the unexpected inventory accrual component and the unexpected accounts receivable accrual component, i.e. changes in accruals not motivated by corresponding changes in company activity-level. Additionally and for comparison, the accounting accruals are split into expected...... and unexpected accruals, estimated by the extended Jones model like in both some US-analyses and some international studies of the accrual anomaly phenomenon. It is found that the persistence of earnings is decreasing in the magnitude of the unexpected accrual components of earnings and that the persistence...... of current earnings performance is particularly decreasing in the magnitude of unexpected changes in inventory. The special accrual parts are related to the perceptions of earnings persistence implicit in the market prices, and it is found that the differences in earnings persistence are not rationally...

Bah humbug: Unexpected Christmas cards and the reciprocity norm.

Science.gov (United States)

Meier, Brian P

2016-01-01

The reciprocity norm refers to the expectation that people will help those who helped them. A well-known study revealed that the norm is strong with Christmas cards, with 20% of people reciprocating a Christmas card received from a stranger. I attempted to conceptually replicate and extend this effect. In Study 1, 755 participants received a Christmas card supposedly from a more- versus less-similar stranger. The reciprocation rate was unexpectedly low (2%), which did not allow for a test of a similarity effect. Two potential reasons for this low rate were examined in Study 2 in which 494 participants reported their likelihood of reciprocating a Christmas card from a stranger as well as their felt suspicions/threat about the card and their frequency of e-mail use. Reciprocation likelihood was negatively correlated with perceived threat/suspicion and e-mail use. It appears that reciprocating a gift from a stranger in offline settings may be less likely than expected.

Hydra meiosis reveals unexpected conservation of structural synaptonemal complex proteins across metazoans

OpenAIRE

Fraune, Johanna; Alsheimer, Manfred; Volff, Jean-Nicolas; Busch, Karoline; Fraune, Sebastian; Bosch, Thomas C. G.; Benavente, Ricardo

2012-01-01

The synaptonemal complex (SC) is a key structure of meiosis, mediating the stable pairing (synapsis) of homologous chromosomes during prophase I. Its remarkable tripartite structure is evolutionarily well conserved and can be found in almost all sexually reproducing organisms. However, comparison of the different SC protein components in the common meiosis model organisms Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealed...

Connexin43 Mediated Delivery of ADAMTS5 Targeting siRNAs from Mesenchymal Stem Cells to Synovial Fibroblasts.

Directory of Open Access Journals (Sweden)

Shuo Liu

Full Text Available Osteoarthritis is a joint-destructive disease that has no effective cure. Human mesenchymal stem cells (hMSCs could offer therapeutic benefit in the treatment of arthritic diseases by suppressing inflammation and permitting tissue regeneration, but first these cells must overcome the catabolic environment of the diseased joint. Likewise, gene therapy also offers therapeutic promise given its ability to directly modulate key catabolic factors that mediate joint deterioration, although it too has limitations. In the current study, we explore an approach that combines hMSCs and gene therapy. Specifically, we test the use of hMSC as a vehicle to deliver ADAMTS5 (an aggrecanase with a key role in osteoarthritis-targeting siRNAs to SW982 synovial fibroblast-like cells via connexin43 containing gap junctions. Accordingly, we transduced hMSCs with ADAMTS5-targeting shRNA or non-targeted shRNA, and co-cultured them with synovial fibroblasts to allow delivery of siRNAs from hMSC to synovial fibroblasts. We found that co-culture of hMSCs-shRNA-ADAMTS5 and synovial fibroblasts reduced ADAMTS5 expression relative to co-culture of hMSCs-shRNA-control and synovial fibroblasts. Furthermore, ADAMTS5 was specifically reduced in the synovial fibroblasts populations as determined by fluorescence-activated cell sorting, suggesting transfer of the siRNA between cells. To test if Cx43-containing gap junctions are involved in the transfer of siRNA, we co-cultured hMSCs-shRNA-ADAMTS5 cells with synovial fibroblasts in which connexin43 was knocked down. Under these conditions, ADAMTS5 levels were not inhibited by co-culture, indicating that connexin43 mediates the delivery of siRNA from hMSCs to synovial fibroblasts. In total, our findings demonstrate that hMSCs can function as donor cells to host and deliver siRNAs to synovial fibroblasts via connexin43 gap junction in vitro. These data may have implications in the combination of hMSCs and gene therapy to treat diseases

Connexin43 Mediated Delivery of ADAMTS5 Targeting siRNAs from Mesenchymal Stem Cells to Synovial Fibroblasts.

Science.gov (United States)

Liu, Shuo; Niger, Corinne; Koh, Eugene Y; Stains, Joseph P

2015-01-01

Osteoarthritis is a joint-destructive disease that has no effective cure. Human mesenchymal stem cells (hMSCs) could offer therapeutic benefit in the treatment of arthritic diseases by suppressing inflammation and permitting tissue regeneration, but first these cells must overcome the catabolic environment of the diseased joint. Likewise, gene therapy also offers therapeutic promise given its ability to directly modulate key catabolic factors that mediate joint deterioration, although it too has limitations. In the current study, we explore an approach that combines hMSCs and gene therapy. Specifically, we test the use of hMSC as a vehicle to deliver ADAMTS5 (an aggrecanase with a key role in osteoarthritis)-targeting siRNAs to SW982 synovial fibroblast-like cells via connexin43 containing gap junctions. Accordingly, we transduced hMSCs with ADAMTS5-targeting shRNA or non-targeted shRNA, and co-cultured them with synovial fibroblasts to allow delivery of siRNAs from hMSC to synovial fibroblasts. We found that co-culture of hMSCs-shRNA-ADAMTS5 and synovial fibroblasts reduced ADAMTS5 expression relative to co-culture of hMSCs-shRNA-control and synovial fibroblasts. Furthermore, ADAMTS5 was specifically reduced in the synovial fibroblasts populations as determined by fluorescence-activated cell sorting, suggesting transfer of the siRNA between cells. To test if Cx43-containing gap junctions are involved in the transfer of siRNA, we co-cultured hMSCs-shRNA-ADAMTS5 cells with synovial fibroblasts in which connexin43 was knocked down. Under these conditions, ADAMTS5 levels were not inhibited by co-culture, indicating that connexin43 mediates the delivery of siRNA from hMSCs to synovial fibroblasts. In total, our findings demonstrate that hMSCs can function as donor cells to host and deliver siRNAs to synovial fibroblasts via connexin43 gap junction in vitro. These data may have implications in the combination of hMSCs and gene therapy to treat diseases like

Complexity in an Unexpected Place: Quantities in Selected Acquisition Reports

Science.gov (United States)

2017-12-01

by the Army Acquisition Executive contains the following language . As a recently delegated Acquisition Category IC program, the AH-64E Apache...Complexity in an Unexpected Place: Quantities in Selected Acquisition Reports Gregory A. Davis, Project Leader Margaret L. Giles David M. Tate I...F E N S E A N A L Y S E S IDA Paper P-8490 Complexity in an Unexpected Place: Quantities in Selected Acquisition Reports Gregory A. Davis

The emissions gap report 2012. A UNEP synthesis report

Energy Technology Data Exchange (ETDEWEB)

NONE

2012-11-15

One of the fundamental questions in the global climate negotiations is: what level of ''ambition'', in terms of collective emission reductions, is needed to protect global climate? To help answer this question UNEP and the scientific community have published a series of reports on the ''emissions gap1'' since 2010. Of particular interest to the ambition question is the gap in 2020 between emission levels consistent with the 2 deg. C climate target and emissions levels projected if country reduction pledges are fulfilled. If there is a gap, then there is doubt that the ambition of countries is great enough to meet the agreed-upon 2 deg. C climate target. In the 2010 Emissions Gap Report, scientists indicated that there would likely be a substantial emissions gap in 2020, although estimates of this gap ranged widely, depending on assumptions about how country pledges would be complied with. In the 2011 Bridging the Emissions Gap Report, scientists noted that enough technical potential existed to close the gap in 2020, but fast action by countries was needed. UNEP has now convened a group of 55 scientists and experts from 43 scientific groups across 22 countries to produce this third emissions gap report which covers the following: 1) An update of global greenhouse gas emission estimates, based on a number of different authoritative scientific sources; 2) An overview of national emission levels, both current (2010) and projected (2020) consistent with current pledges and other commitments; 3) An estimate of the level of global emissions consistent with the two degree target in 2020, 2030 and 2050; 4) An update of the assessment of the emissions gap for 2020; 5) A review of selected examples of the rapid progress being made in different parts of the world to implement policies already leading to substantial emission reductions. These policies could contribute significantly to narrowing the gap if they are scaled up and replicated in other countries. (Author)

Mind the gap: financial London and the regional class pay gap.

Science.gov (United States)

Friedman, Sam; Laurison, Daniel

2017-09-01

The hidden barriers, or 'gender pay gap', preventing women from earning equivalent incomes to men is well documented. Yet recent research has uncovered that, in Britain, there is also a comparable class-origin pay gap in higher professional and managerial occupations. So far this analysis has only been conducted at the national level and it is not known whether there are regional differences within the UK. This paper uses pooled data from the 2014 and 2015 Labour Force Survey (N = 7,534) to stage a more spatially sensitive analysis that examines regional variation in the class pay gap. We find that this 'class ceiling' is not evenly spatially distributed. Instead it is particularly marked in Central London, where those in high-status occupations who are from working-class backgrounds earn, on average, £10,660 less per year than those whose parents were in higher professional and managerial employment. Finally, we inspect the Capital further to reveal that the class pay gap is largest within Central London's banking and finance sector. Challenging policy conceptions of London as the 'engine room' of social mobility, these findings suggest that class disadvantage within high-status occupations is particularly acute in the Capital. The findings also underline the value of investigating regional differences in social mobility, and demonstrate how such analysis can unravel important and previously unrecognized spatial dimensions of class inequality. © London School of Economics and Political Science 2017.

Gaps in affiliation indexing in Scopus and PubMed.

Science.gov (United States)

Schmidt, Cynthia M; Cox, Roxanne; Fial, Alissa V; Hartman, Teresa L; Magee, Martha L

2016-04-01

The authors sought to determine whether unexpected gaps existed in Scopus's author affiliation indexing of publications written by the University of Nebraska Medical Center or Nebraska Medicine (UNMC/NM) authors during 2014. First, we compared Scopus affiliation identifier search results to PubMed affiliation keyword search results. Then, we searched Scopus using affiliation keywords (UNMC, etc.) and compared the results to PubMed affiliation keyword and Scopus affiliation identifier searches. We found that Scopus's records for approximately 7% of UNMC/NM authors' publications lacked appropriate UNMC/NM author affiliation identifiers, and many journals' publishers were supplying incomplete author affiliation information to PubMed. Institutions relying on Scopus to track their impact should determine whether Scopus's affiliation identifiers will, in fact, identify all articles published by their authors and investigators.

Fluoxetin Upregulates Connexin 43 Expression in Astrocyte

Directory of Open Access Journals (Sweden)

Hossein Mostafavi

2014-02-01

Full Text Available Introduction: Recent studies have shown that astrocytes play major roles in normal and disease condition of the central nervous system including multiple sclerosis (MS. Molecular target therapy studies in MS have revealed that connexin-43 (Cx43 and Aquaporin-4 (AQP4 contents of astrocytes undergo expression alteration. Fluoxetine had some effects in MS patients unrelated to its known antidepressant effects. Some of fluoxetine effects were attributed to its capability of cAMP signaling pathway stimulation. This study aimed to investigate possible acute effects of fluoxetine on Cx43 and AQP4 expression in astrocyte.  Methods: Astrocytoma cells were treated for 24 hours with fluoxetine (10 and 20 &mug/ml with or without adenyl cyclase (AC and protein kinase A (PKA inhibition. Cx43 expression at both mRNA and protein levels and AQP4 expression at mRNA level were evaluated.  Results: Acquired results showed that fluoxetine with and without AC and PKA inhibition resulted in Cx43 up-regulation both in mRNA and protein levels, whereas AQP4 expression have not changed.  Discussion: In conclusion, data showed that fluoxetine alone and in the absence of serotonin acutely up-regulated Cx43 expression in astrocytes that can be assumed in molecular target therapy of MS patients. It seems that cAMP involvement in fluoxetine effects need more researches.

Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases.

Science.gov (United States)

Vivante, Asaf; Ityel, Hadas; Pode-Shakked, Ben; Chen, Jing; Shril, Shirlee; van der Ven, Amelie T; Mann, Nina; Schmidt, Johanna Magdalena; Segel, Reeval; Aran, Adi; Zeharia, Avraham; Staretz-Chacham, Orna; Bar-Yosef, Omer; Raas-Rothschild, Annick; Landau, Yuval E; Lifton, Richard P; Anikster, Yair; Hildebrandt, Friedhelm

2017-12-01

Rhabdomyolysis is a clinical emergency that may cause acute kidney injury (AKI). It can be acquired or due to monogenic mutations. Around 60 different rare monogenic forms of rhabdomyolysis have been reported to date. In the clinical setting, identifying the underlying molecular diagnosis is challenging due to nonspecific presentation, the high number of causative genes, and current lack of data on the prevalence of monogenic forms. We employed whole exome sequencing (WES) to reveal the percentage of rhabdomyolysis cases explained by single-gene (monogenic) mutations in one of 58 candidate genes. We investigated a cohort of 21 unrelated families with rhabdomyolysis, in whom no underlying etiology had been previously established. Using WES, we identified causative mutations in candidate genes in nine of the 21 families (43%). We detected disease-causing mutations in eight of 58 candidate genes, grouped into the following categories: (1) disorders of fatty acid metabolism (CPT2), (2) disorders of glycogen metabolism (PFKM and PGAM2), (3) disorders of abnormal skeletal muscle relaxation and contraction (CACNA1S, MYH3, RYR1 and SCN4A), and (4) disorders of purine metabolism (AHCY). Our findings demonstrate a very high detection rate for monogenic etiologies using WES and reveal broad genetic heterogeneity for rhabdomyolysis. These results highlight the importance of molecular genetic diagnostics for establishing an etiologic diagnosis. Because these patients are at risk for recurrent episodes of rhabdomyolysis and subsequent risk for AKI, WES allows adequate prophylaxis and treatment for these patients and their family members and enables a personalized medicine approach.

Sequence and expression analyses of porcine ISG15 and ISG43 genes.

Science.gov (United States)

Huang, Jiangnan; Zhao, Shuhong; Zhu, Mengjin; Wu, Zhenfang; Yu, Mei

2009-08-01

The coding sequences of porcine interferon-stimulated gene 15 (ISG15) and the interferon-stimulated gene (ISG43) were cloned from swine spleen mRNA. The amino acid sequences deduced from porcine ISG15 and ISG43 genes coding sequence shared 24-75% and 29-83% similarity with ISG15s and ISG43s from other vertebrates, respectively. Structural analyses revealed that porcine ISG15 comprises two ubiquitin homologues motifs (UBQ) domain and a conserved C-terminal LRLRGG conjugating motif. Porcine ISG43 contains an ubiquitin-processing proteases-like domain. Phylogenetic analyses showed that porcine ISG15 and ISG43 were mostly related to rat ISG15 and cattle ISG43, respectively. Using quantitative real-time PCR assay, significant increased expression levels of porcine ISG15 and ISG43 genes were detected in porcine kidney endothelial cells (PK15) cells treated with poly I:C. We also observed the enhanced mRNA expression of three members of dsRNA pattern-recognition receptors (PRR), TLR3, DDX58 and IFIH1, which have been reported to act as critical receptors in inducing the mRNA expression of ISG15 and ISG43 genes. However, we did not detect any induced mRNA expression of IFNalpha and IFNbeta, suggesting that transcriptional activations of ISG15 and ISG43 were mediated through IFN-independent signaling pathway in the poly I:C treated PK15 cells. Association analyses in a Landrace pig population revealed that ISG15 c.347T>C (BstUI) polymorphism and the ISG43 c.953T>G (BccI) polymorphism were significantly associated with hematological parameters and immune-related traits.

Identification of transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) as a novel factor for TNF-α expression upon lipopolysaccharide stimulation in human monocytes.

Science.gov (United States)

Murata, H; Hattori, T; Maeda, H; Takashiba, S; Takigawa, M; Kido, J; Nagata, T

2015-08-01

Tumor necrosis factor alpha (TNF-α) is a major cytokine implicated in various inflammatory diseases. The nature of the nuclear factors associated with human TNF-α gene regulation is not well elucidated. We previously identified a novel region located from -550 to -487 in human TNF-α promoter that did not contain the reported binding sites for nuclear factor kappa B (NF-κB) but showed lipopolysaccharide (LPS)-induced transcriptional activity. The purpose of this study is to identify novel factors that bind to the promoter region and regulate TNF-α expression. To identify DNA-binding proteins that bound to the target region of TNF-α promoter, a cDNA library from LPS-stimulated human monocytic cell line THP-1 was screened using a yeast one-hybrid system. Cellular localizations of the DNA-binding protein in the cells were examined by subcellular immunocytochemistry. Nuclear amounts of the protein in LPS-stimulated THP-1 cells were identified by western blot analysis. Expression of mRNA of the protein in the cells was quantified by real-time polymerase chain reaction. Electrophoretic mobility shift assays were performed to confirm the DNA-binding profile. Overexpression of the protein and knockdown of the gene were also performed to investigate the role for TNF-α expression. Several candidates were identified from the cDNA library and transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) was focused on. Western blot analysis revealed that nuclear TDP-43 protein was increased in the LPS-stimulated THP-1 cells. Expression of TDP-43 mRNA was already enhanced before TNF-α induction by LPS. Electrophoretic mobility shift assay analysis showed that nuclear extracts obtained by overexpressing FLAG-tagged TDP-43 bound to the -550 to -487 TNF-α promoter fragments. Overexpression of TDP-43 in THP-1 cells resulted in an increase of TNF-α expression. Knockdown of TDP-43 in THP-1 cells downregulated TNF-α expression. We identified TDP-43 as one of the novel

Gap junctions at the dendritic cell-T cell interface are key elements for antigen-dependent T cell activation.

Science.gov (United States)

Elgueta, Raul; Tobar, Jaime A; Shoji, Kenji F; De Calisto, Jaime; Kalergis, Alexis M; Bono, Maria R; Rosemblatt, Mario; Sáez, Juan C

2009-07-01

The acquired immune response begins with Ag presentation by dendritic cells (DCs) to naive T cells in a heterocellular cell-cell contact-dependent process. Although both DCs and T cells are known to express connexin43, a gap junction protein subunit, the role of connexin43 on the initiation of T cell responses remains to be elucidated. In the present work, we report the formation of gap junctions between DCs and T cells and their role on T cell activation during Ag presentation by DCs. In cocultures of DCs and T cells, Lucifer yellow microinjected into DCs is transferred to adjacent transgenic CD4(+) T cells, only if the specific antigenic peptide was present at least during the first 24 h of cocultures. This dye transfer was sensitive to gap junction blockers, such as oleamide, and small peptides containing the extracellular loop sequences of conexin. Furthermore, in this system, gap junction blockers drastically reduced T cell activation as reflected by lower proliferation, CD69 expression, and IL-2 secretion. This lower T cell activation produced by gap junction blockers was not due to a lower expression of CD80, CD86, CD40, and MHC-II on DCs. Furthermore, gap junction blocker did not affect polyclonal activation of T cell induced with anti-CD3 plus anti-CD28 Abs in the absence of DCs. These results strongly suggest that functional gap junctions assemble at the interface between DCs and T cells during Ag presentation and that they play an essential role in T cell activation.

A new fossil from the mid-Paleocene of New Zealand reveals an unexpected diversity of world's oldest penguins

Science.gov (United States)

Mayr, Gerald; De Pietri, Vanesa L.; Paul Scofield, R.

2017-04-01

We describe leg bones of a giant penguin from the mid-Paleocene Waipara Greensand of New Zealand. The specimens were found at the type locality of Waimanu manneringi and together with this species they constitute the oldest penguin fossils known to date. Tarsometatarsus dimensions indicate a species that reached the size of Anthropornis nordenskjoeldi, one of the largest known penguin species. Stem group penguins therefore attained a giant size very early in their evolution, with this gigantism existing for more than 30 million years. The new fossils are from a species that is phylogenetically more derived than Waimanu, and the unexpected coexistence of Waimanu with more derived stem group Sphenisciformes documents a previously unknown diversity amongst the world's oldest penguins. The characteristic tarsometatarsus shape of penguins evolved early on, and the significant morphological disparity between Waimanu and the new fossil conflicts with recent Paleocene divergence estimates for penguins, suggesting an older, Late Cretaceous, origin.

A new fossil from the mid-Paleocene of New Zealand reveals an unexpected diversity of world's oldest penguins.

Science.gov (United States)

Mayr, Gerald; De Pietri, Vanesa L; Paul Scofield, R

2017-04-01

We describe leg bones of a giant penguin from the mid-Paleocene Waipara Greensand of New Zealand. The specimens were found at the type locality of Waimanu manneringi and together with this species they constitute the oldest penguin fossils known to date. Tarsometatarsus dimensions indicate a species that reached the size of Anthropornis nordenskjoeldi, one of the largest known penguin species. Stem group penguins therefore attained a giant size very early in their evolution, with this gigantism existing for more than 30 million years. The new fossils are from a species that is phylogenetically more derived than Waimanu, and the unexpected coexistence of Waimanu with more derived stem group Sphenisciformes documents a previously unknown diversity amongst the world's oldest penguins. The characteristic tarsometatarsus shape of penguins evolved early on, and the significant morphological disparity between Waimanu and the new fossil conflicts with recent Paleocene divergence estimates for penguins, suggesting an older, Late Cretaceous, origin.

The Importance of Physical Activity in Closing the Achievement Gap

Science.gov (United States)

Burton, Laura J.; VanHeest, Jaci L.

2007-01-01

The most significant concern within the US educational community is the academic achievement gap. Investigation of the achievement gap reveals that minority students across all levels of education are not meeting the same academic measures as their non-Hispanic White peers. In addition, a disproportionate number of minority children are identified…

Chronic hypertension alters the expression of Cx43 in cardiovascular muscle cells

Directory of Open Access Journals (Sweden)

Haefliger J.-A.

2000-01-01

Full Text Available Connexin43 (Cx43, the predominant gap junction protein of muscle cells in vessels and heart, is involved in the control of cell-to-cell communication and is thought to modulate the contractility of the vascular wall and the electrical coupling of cardiac myocytes. We have investigated the effects of arterial hypertension on the expression of Cx43 in aorta and heart in three different models of experimental hypertension. Rats were made hypertensive either by clipping one renal artery (two kidney, one-clip renal (2K,1C model by administration of deoxycorticosterone and salt (DOCA-salt model or by inhibiting nitric oxide synthase with NG-nitro-L-arginine methyl ester (L-NAME model. After 4 weeks, rats of the three models showed a similar increase in intra-arterial mean blood pressure and in the thickness of the walls of both aorta and heart. Analysis of heart mRNA demonstrated no change in Cx43 expression in the three models compared to their respective controls. The same 2K,1C and DOCA-salt hypertensive animals expressed twice more Cx43 in aorta, and the 2K,1C rats showed an increase in arterial distensibility. In contrast, the aortae of L-NAME hypertensive rats were characterized by a 50% decrease in Cx43 and the carotid arteries did not show increased distensibility. Western blot analysis indicated that Cx43 was more phosphorylated in the aortae of 2K,1C rats than in those of L-NAME or control rats, indicating a differential regulation of aortic Cx43 in different models of hypertension. The data suggest that localized mechanical forces induced by hypertension affect Cx43 expression and that the cell-to-cell communication mediated by Cx43 channels may contribute to regulating the elasticity of the vascular wall.

[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.

Nationwide survey of rotavirus-associated encephalopathy and sudden unexpected death in Japan.

Science.gov (United States)

Kawamura, Yoshiki; Ohashi, Masahiro; Ihira, Masaru; Hashimoto, Shuji; Taniguchi, Koki; Yoshikawa, Tetsushi

2014-08-01

Rotavirus can cause severe complications such as encephalopathy/encephalitis and sudden unexpected death. The incidence of rotavirus-associated encephalopathy/encephalitis or sudden unexpected death remains unknown. To clarify the clinical features of rotavirus-associated encephalitis/encephalopathy and sudden unexpected death, we conducted a nationwide survey in Japan. A two-part questionnaire was designed to determine the number of the cases and the clinical features of severe cases of rotavirus infection, including encephalitis/encephalopathy and sudden unexpected death, between 2009 and 2011. Of the 1365 questionnaires sent to hospitals, 963 (70.5%) were returned and eligible for analysis. We determined 58 cases of rotavirus-associated encephalitis/encephalopathy and 7 cases of sudden unexpected death. These patients were diagnosed with rotavirus infection by immunochromatography. Although 36/58 (62.1%) encephalitis/encephalopathy patients had no sequelae, 15/58 (25.9%) patients had neurological sequelae, and 7/58 (12.1%) patients had fatal outcomes. Pleocytosis was observed in 9/40 (22.5%) patients and cerebrospinal fluid protein levels were elevated in only 4/40 (10%) patients. Elevated lactate dehydrogenase (LDH) (>500 IU/L) or acidemia (pHdeath were 44.0 and 4.9 cases in Japan, respectively. Elevated LDH (>500 IU/L) or acidemia (pH<7.15) were related to a poor prognosis of the encephalitis/encephalopathy. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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.

Studies on level of cytokines and expression of connexin43 in tumor and normal cells in culture conditions

International Nuclear Information System (INIS)

Asati, V.; Pandey, B.N.

2016-01-01

Factors secreted from the tumor cells in culture medium have been known to facilitate the growth of fresh cultures and also to affect the cellular radio-sensitivity. Moreover, expression of gap junction proteins like connexin-43 is known as a key player in cell survival and proliferation. The present study is aimed to evaluate the effects of conditioned medium on the growth of respective tumor/normal cells and the expression of connexin-43 in these cells

Electrophysiological gap detection thresholds: effects of age and comparison with a behavioral measure.

Science.gov (United States)

Palmer, Shannon B; Musiek, Frank E

2014-01-01

Temporal processing ability has been linked to speech understanding ability and older adults often complain of difficulty understanding speech in difficult listening situations. Temporal processing can be evaluated using gap detection procedures. There is some research showing that gap detection can be evaluated using an electrophysiological procedure. However, there is currently no research establishing gap detection threshold using the N1-P2 response. The purposes of the current study were to 1) determine gap detection thresholds in younger and older normal-hearing adults using an electrophysiological measure, 2) compare the electrophysiological gap detection threshold and behavioral gap detection threshold within each group, and 3) investigate the effect of age on each gap detection measure. This study utilized an older adult group and younger adult group to compare performance on an electrophysiological and behavioral gap detection procedure. The subjects in this study were 11 younger, normal-hearing adults (mean = 22 yrs) and 11 older, normal-hearing adults (mean = 64.36 yrs). All subjects completed an adaptive behavioral gap detection procedure in order to determine their behavioral gap detection threshold (BGDT). Subjects also completed an electrophysiologic gap detection procedure to determine their electrophysiologic gap detection threshold (EGDT). Older adults demonstrated significantly larger gap detection thresholds than the younger adults. However, EGDT and BGDT were not significantly different in either group. The mean difference between EGDT and BGDT for all subjects was 0.43 msec. Older adults show poorer gap detection ability when compared to younger adults. However, this study shows that gap detection thresholds can be measured using evoked potential recordings and yield results similar to a behavioral measure. American Academy of Audiology.

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

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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

Risk, unexpected uncertainty, and estimation uncertainty: Bayesian learning in unstable settings.

Directory of Open Access Journals (Sweden)

Elise Payzan-LeNestour

Full Text Available Recently, evidence has emerged that humans approach learning using Bayesian updating rather than (model-free reinforcement algorithms in a six-arm restless bandit problem. Here, we investigate what this implies for human appreciation of uncertainty. In our task, a Bayesian learner distinguishes three equally salient levels of uncertainty. First, the Bayesian perceives irreducible uncertainty or risk: even knowing the payoff probabilities of a given arm, the outcome remains uncertain. Second, there is (parameter estimation uncertainty or ambiguity: payoff probabilities are unknown and need to be estimated. Third, the outcome probabilities of the arms change: the sudden jumps are referred to as unexpected uncertainty. We document how the three levels of uncertainty evolved during the course of our experiment and how it affected the learning rate. We then zoom in on estimation uncertainty, which has been suggested to be a driving force in exploration, in spite of evidence of widespread aversion to ambiguity. Our data corroborate the latter. We discuss neural evidence that foreshadowed the ability of humans to distinguish between the three levels of uncertainty. Finally, we investigate the boundaries of human capacity to implement Bayesian learning. We repeat the experiment with different instructions, reflecting varying levels of structural uncertainty. Under this fourth notion of uncertainty, choices were no better explained by Bayesian updating than by (model-free reinforcement learning. Exit questionnaires revealed that participants remained unaware of the presence of unexpected uncertainty and failed to acquire the right model with which to implement Bayesian updating.

Unexpected complications of bonded mandibular lingual retainers.

NARCIS (Netherlands)

Katsaros, C.; Livas, C.; Renkema, A.M.

2007-01-01

INTRODUCTION: The flexible spiral wire (FSW) retainer is the most frequently used type of fixed retainer bonded on all 6 anterior teeth. Our aim in this article was to demonstrate unexpected posttreatment changes in the labiolingual position of the mandibular anterior teeth associated with the use

Ductile gap between the Wenchuan and Lushan earthquakes revealed from the two-dimensional Pg seismic tomography.

Science.gov (United States)

Pei, Shunping; Zhang, Haijiang; Su, Jinrong; Cui, Zhongxiong

2014-09-30

A high-resolution two-dimensional Pg-wave velocity model is obtained for the upper crust around the epicenters of the April 20, 2013 Ms7.0 Lushan earthquake and the May 12, 2008 Ms8.0 Wenchuan earthquake, China. The tomographic inversion uses 47235 Pg arrival times from 6812 aftershocks recorded by 61 stations around the Lushan and Wenchuan earthquakes. Across the front Longmenshan fault near the Lushan earthquake, there exists a strong velocity contrast with higher velocities to the west and lower velocities to the east. Along the Longmenshan fault system, there exist two high velocity patches showing an "X" shape with an obtuse angle along the near northwest-southeast (NW-SE) direction. They correspond to the Precambrian Pengguan and Baoxing complexes on the surface but with a ~20 km shift, respectively. The aftershock gap of the 2008 Wenchuan and the 2013 Lushan earthquakes is associated with lower velocities. Based on the theory of maximum effective moment criterion, this suggests that the aftershock gap is weak and the ductile deformation is more likely to occur in the upper crust within the gap under the near NW-SE compression. Therefore our results suggest that the large earthquake may be hard to happen within the gap.

Association between gap in spousal education and domestic violence in India and Bangladesh.

Science.gov (United States)

Rapp, Daniel; Zoch, Beate; Khan, M Mobarak H; Pollmann, Thorsten; Krämer, Alexander

2012-06-21

Domestic violence (DV) against women is a serious human rights abuse and well recognised global public health concern. The occurrence of DV is negatively associated with the educational level of spouses but studies dealing with educational discrepancies of spouses show contradicting results: Wives with higher education than their husbands were more likely to ever experience DV as compared to equally educated couples. The purpose of this study was to investigate the association between spousal education gap (SEG) and the prevalence and severity of DV in India and Bangladesh. Nationally representative data collected through the 2005/2006 Indian National Family Health Survey (NFHS-3) and 2007 Bangladesh Demographic and Health Survey (BDHS) were used. In total, we analysed data of 69,805 women aged 15-49 years (Bangladesh: 4,195 women, India: 65,610 women). In addition to univariate and bivariable analyses, a multinomial logistic regression model was used to quantify the association between education gap and less severe as well as severe domestic violence. Adjustment was made for age, religion, and family structure. Wives with higher education than their husbands were less likely to experience less severe (OR = 0.83, 95% CI: 0.77-0.89) and severe (OR = 0.79, 95% CI: 0.72-0.87) DV as compared to equally low-educated spouses (reference group). Equally high-educated couples revealed the lowest likelihood of experiencing DV (severe violence: OR 0.43, CI 0.39-0.48; less severe violence: OR 0.59, CI 0.55-0.63). The model's goodness of fit was low (Nagelkerke's R2 = 0.152). Our analysis revealed no increased DV among wives with a higher educational level than their husbands. Moreover, the results point towards a decrease of severe violence with an increase in education levels among spouses. However, the model did not explain a satisfying amount of DV. Therefore, further research should be done to reveal unknown determinants so that suitable interventions to reduce DV can be

Community College Enrollment, College Major, and the Gender Wage Gap.

Science.gov (United States)

Gill, Andrew M.; Leigh, Duane E.

2000-01-01

Independent cross-sections developed using National Longitudinal Survey data reveal a decrease in the gender wage gap from 1989-1994 due to fewer differences in tenure and full-time employment. Disaggregating education by two- and four-year providers and college major accounts for 8.5-11% of the narrower wage gap for the period. (SK)

Direct band gaps in multiferroic h-LuFeO3

International Nuclear Information System (INIS)

Holinsworth, B. S.; Mazumdar, D.; Musfeldt, J. L.; Brooks, C. M.; Mundy, J. A.; Das, H.; Fennie, C. J.; Cherian, J. G.; McGill, S. A.; Schlom, D. G.

2015-01-01

We measured the optical properties of epitaxial thin films of the metastable hexagonal polymorph of LuFeO 3 by absorption spectroscopy, magnetic circular dichroism, and photoconductivity. Comparison with complementary electronic structure calculations reveals a 1.1 eV direct gap involving hybridized Fe 3d z 2 +O 2p z →Fe d excitations at the Γ and A points, with a higher energy direct gap at 2.0 eV. Both charge gaps nicely overlap the solar spectrum

Quantum effect on the energy levels of Eu2+ doped K2Ca2(SO4)3 nanoparticles.

Science.gov (United States)

Salah, Numan; Habib, Sami S; Khan, Zishan H

2010-09-01

Quantum confinement effect on the energy levels of Eu(2+) doped K(2)Ca(2)(SO(4))(3) nanoparticles has been observed. The broad photoluminescence (PL) emission band of Eu(2+) doped K(2)Ca(2)(SO(4))(3) microcrystalline sample observed at ∼436 nm is found to split into two narrow well resolved bands, located at 422 and 445 nm in the nanostructure form of this material. This has been attributed to the reduction in the crystal field strength of the nanomaterials, which results in widening the energy band gap and splitting the broad 4f(6)5d energy level of Eu(2+). Energy band gap values of the micro and nanocrystalline K(2)Ca(2)(SO(4))(3) samples were also determined by measuring the UV-visible absorption spectra. These values are 3.34 and 3.44 eV for the micro and nanocrystalline samples, respectively. These remarkable results suggest that activators having wide emission bands might be subjected to weak crystal strength via nanostructure materials to modify their electronic transitions. This might prove a powerful technique for producing new-advanced materials for use in the fields of solid state lasers and optoelectronic devises.

Designing broad phononic band gaps for in-plane modes

Science.gov (United States)

Li, Yang Fan; Meng, Fei; Li, Shuo; Jia, Baohua; Zhou, Shiwei; Huang, Xiaodong

2018-03-01

Phononic crystals are known as artificial materials that can manipulate the propagation of elastic waves, and one essential feature of phononic crystals is the existence of forbidden frequency range of traveling waves called band gaps. In this paper, we have proposed an easy way to design phononic crystals with large in-plane band gaps. We demonstrated that the gap between two arbitrarily appointed bands of in-plane mode can be formed by employing a certain number of solid or hollow circular rods embedded in a matrix material. Topology optimization has been applied to find the best material distributions within the primitive unit cell with maximal band gap width. Our results reveal that the centroids of optimized rods coincide with the point positions generated by Lloyd's algorithm, which deepens our understandings on the formation mechanism of phononic in-plane band gaps.

Different expressions of connexin 43 and 32 in the fibroblasts of human dental pulp.

Science.gov (United States)

Ibuki, N; Yamaoka, Y; Sawa, Y; Kawasaki, T; Yoshida, S

2002-06-01

The expression and localization of gap junctional proteins connexin (Cx) 26, 32, and 43 was examined in human dental pulp. Dental pulp tissues were obtained from human third molars immediately after extraction. Some pulp tissues were used for cell culture, and the rest for histological observations. Immunostaining for cultured dental pulp fibroblasts (DPFs) showed that Cx32 and 43 were expressed in human DPFs, and proteins corresponding to 27 (Cx32) and 43kDa (Cx43) were identified by Western blot analysis. Immunostaining for tissue sections showed that the expression of Cx32 and 43 was observed in the entire region of the pulp and further strong expression of Cx32 was established beneath the cell-rich zone. Considering the close relationship between Cx types and cell functions, the results indicate that DPFs beneath the cell-rich zone may have specific, Cx32-related functions. The cell rich zone is thought to contain progenitor odontoblasts that can be induced to differentiate into mature odontoblasts in response to wounding. Therefore, it may be hypothesized that DPFs just beneath the cell-rich zone produce proteins and induce odontoblast differentiation from the cells in the cell-rich zone.

A "present" for the future: the unexpected value of rediscovery.

Science.gov (United States)

Zhang, Ting; Kim, Tami; Brooks, Alison Wood; Gino, Francesca; Norton, Michael I

2014-10-01

Although documenting everyday activities may seem trivial, four studies reveal that creating records of the present generates unexpected benefits by allowing future rediscoveries. In Study 1, we used a time-capsule paradigm to show that individuals underestimate the extent to which rediscovering experiences from the past will be curiosity provoking and interesting in the future. In Studies 2 and 3, we found that people are particularly likely to underestimate the pleasure of rediscovering ordinary, mundane experiences, as opposed to extraordinary experiences. Finally, Study 4 demonstrates that underestimating the pleasure of rediscovery leads to time-inconsistent choices: Individuals forgo opportunities to document the present but then prefer rediscovering those moments in the future to engaging in an alternative fun activity. Underestimating the value of rediscovery is linked to people's erroneous faith in their memory of everyday events. By documenting the present, people provide themselves with the opportunity to rediscover mundane moments that may otherwise have been forgotten. © The Author(s) 2014.

Association Between Local Bipolar Voltage and Conduction Gap Along the Left Atrial Linear Ablation Lesion in Patients With Atrial Fibrillation.

Science.gov (United States)

Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Kanda, Takashi; Sunaga, Akihiro; Tsujimura, Takuya; Matsuda, Yasuhiro; Mano, Toshiaki

2017-08-01

A bipolar voltage reflects a thick musculature where formation of a transmural lesion may be hard to achieve. The purpose of this study was to explore the association between local bipolar voltage and conduction gap in patients with persistent atrial fibrillation (AF) who underwent atrial roof or septal linear ablation. This prospective observational study included 42 and 36 consecutive patients with persistent AF who underwent roof or septal linear ablations, respectively. After pulmonary vein isolation, left atrial linear ablations were performed, and conduction gap sites were identified and ablated after first-touch radiofrequency application. Conduction gap(s) after the first-touch roof and septal linear ablation were observed in 13 (32%) and 19 patients (53%), respectively. Roof and septal area voltages were higher in patients with conduction gap(s) than in those without (roof, 1.23 ± 0.77 vs 0.73 ± 0.42 mV, p = 0.010; septal, 0.96 ± 0.43 vs 0.54 ± 0.18 mV, p = 0.001). Trisected regional analyses revealed that the voltage was higher at the region with a conduction gap than at the region without. Complete conduction block across the roof and septal lines was not achieved in 3 (7%) and 6 patients (17%), respectively. Patients in whom a linear conduction block could not be achieved demonstrated higher ablation area voltage than those with a successful conduction block (roof, 1.91 ± 0.74 vs 0.81 ± 0.51 mV, p = 0.001; septal, 1.15 ± 0.56 vs 0.69 ± 0.31 mV, p = 0.006). In conclusion, a high regional bipolar voltage predicts failure to achieve conduction block after left atrial roof or septal linear ablation. In addition, the conduction gap was located at the preserved voltage area. Copyright © 2017 Elsevier Inc. All rights reserved.

The Structure of the Temp Wage Gap in Slack Labor Markets

DEFF Research Database (Denmark)

Jahn, Elke

As a consequence of the rapid growth of temporary agency employment in Germa-ny the debate on the remuneration of temporary agency workers has intensified recently. The study finds that the temp wage gap in Germany is indeed large. Decomposition reveals that the gap is mainly driven by difference...

77 FR 42947 - Unexpected Urgent Refugee and Migration Needs

Science.gov (United States)

2012-07-20

... unexpected and urgent refugee and migration needs, including by contributions to international, governmental, and nongovernmental organizations and payment of administrative expenses of the Bureau of Population...

Featured Image: Simulating Planetary Gaps

Science.gov (United States)

Kohler, Susanna

2017-03-01

The authors model of howthe above disk would look as we observe it in a scattered-light image. The morphology of the gap can be used to estimate the mass of the planet that caused it. [Dong Fung 2017]The above image from a computer simulation reveals the dust structure of a protoplanetary disk (with the star obscured in the center) as a newly formed planet orbits within it. A recent study by Ruobing Dong (Steward Observatory, University of Arizona) and Jeffrey Fung (University of California, Berkeley) examines how we can determine mass of such a planet based on our observations of the gap that the planet opens in the disk as it orbits. The authors models help us to better understand how our observations of gaps might change if the disk is inclined relative to our line of sight, and how we can still constrain the mass of the gap-opening planet and the viscosity of the disk from the scattered-light images we have recently begun to obtain of distant protoplanetary disks. For more information, check out the paper below!CitationRuobing Dong () and Jeffrey Fung () 2017 ApJ 835 146. doi:10.3847/1538-4357/835/2/146

Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.

Directory of Open Access Journals (Sweden)

Katsuhisa Masaki

Full Text Available BACKGROUND: Multiple sclerosis (MS and neuromyelitis optica (NMO occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx pathology and disease aggressiveness in Asian patients with MS and NMO. METHODS/PRINCIPAL FINDINGS: Samples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD, six with MS, and 20 with other neurological diseases (OND. Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59, chronic active (n=58 and chronic inactive (n=23. Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090. Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296. Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients. CONCLUSIONS

Overlapping but distinct TDP-43 and tau pathologic patterns in aged hippocampi.

Science.gov (United States)

Smith, Vanessa D; Bachstetter, Adam D; Ighodaro, Eseosa; Roberts, Kelly; Abner, Erin L; Fardo, David W; Nelson, Peter T

2018-03-01

Intracellular proteinaceous aggregates (inclusion bodies) are almost always detectable at autopsy in brains of elderly individuals. Inclusion bodies composed of TDP-43 and tau proteins often coexist in the same brain, and each of these pathologic biomarkers is associated independently with cognitive impairment. However, uncertainties remain about how the presence and neuroanatomical distribution of inclusion bodies correlate with underlying diseases including Alzheimer's disease (AD). To address this knowledge gap, we analyzed data from the University of Kentucky AD Center autopsy series (n = 247); none of the brains had frontotemporal lobar degeneration. A specific question for this study was whether neurofibrillary tangle (NFT) pathology outside of the Braak NFT staging scheme is characteristic of brains with TDP-43 pathology but lacking AD, that is those with cerebral age-related TDP-43 with sclerosis (CARTS). We also tested whether TDP-43 pathology is associated with comorbid AD pathology, and whether argyrophilic grains are relatively likely to be present in cases with, vs. without, TDP-43 pathology. Consistent with prior studies, hippocampal TDP-43 pathology was associated with advanced AD - Braak NFT stages V/VI. However, argyrophilic grain pathology was not more common in cases with TDP-43 pathology in this data set. In brains with CARTS (TDP-43[+]/AD[-] cases), there were more NFTs in dentate granule neurons than were seen in TDP-43[-]/AD[-] cases. These dentate granule cell NFTs could provide a proxy indicator of CARTS pathology in cases lacking substantial AD pathology. Immunofluorescent experiments in a subsample of cases found that, in both advanced AD and CARTS, approximately 1% of dentate granule neurons were PHF-1 immunopositive, whereas ∼25% of TDP-43 positive cells showed colocalized PHF-1 immunoreactivity. We conclude that NFTs in hippocampal dentate granule neurons are often present in CARTS, and TDP-43 pathology may be secondary to or

[Effect of "Xingnao Kaiqiao Zhenfa" (Acupuncture Technique for Restoring Consciousness) Combined with Rehabilitation Training on Nerve Repair and Expression of Growth-associated Protein-43 of Peri-ischemic Cortex in Ischemic Stroke Rats].

Science.gov (United States)

Xu, Lei; Yan, Xing-Zhou; Li, Zhen-Yu; Cao, Xiao-Fang; Wang, Min

2017-06-25

To observe the effect of "Xingnao Kaiqiao Zhenfa" (acupuncture technique for restoring consciousness) combined with enriched rehabilitation training on motor function and expression of growth-associated protein-43 (GAP-43) of peri-ischemic cortex in ischemic stroke rats, so as to investigate its mechanism underlying improvement of ischemic stroke. SD rats were randomly divided into sham operation, model, rehabilitation and comprehensive rehabilitation groups, which were further divided into 3 time-points:7, 14 and 21 d ( n =6 in each). Cerebral ischemia(CI) model was established by occlusion of the middle cerebral artery with heat-coagulation. The rehabilitation group was treated by enriched rehabilitation training, once a day. The comprehensive rehabilitation group was treated by acupuncture combined with enriched rehabilitation training. Acupuncture was applied to bilateral "Neiguan"(PC 6) and "Shuigou"(GV 26) for 30 min, once a day. The neurological function score, balance-beam walking test and rotating-rod walking test were evaluated at the end of the corresponding treatment time. The expression of GAP-43 in peri-ischemic cortex was detected by immunohistochemistry. In comparison with the sham operation group, the scores of neurological function, beam walking test and rotating-rod walking test were significantly higher in the model group ( P beam walking and rotating-rod walking tests in the rehabilitation group compared with the model group on day 7 ( P >0.05). Compared with the model group at the other time points, the scores of neurological function, balance-beam walking test and rotating-rod walking test were significantly lower in the rehabilitation and comprehensive rehabilitation groups ( P beam walking test and rotating-rod walking test were significantly lower in the comprehensive rehabilitation group ( P <0.05). In comparison with the sham operation group, the number of GAP-43 positive cells of peri-ischemic cortex was significantly higher in the

Expression of connexin 37, 40 and 43 in rat mesenteric arterioles and resistance arteries

DEFF Research Database (Denmark)

Gustafsson, Finn; Mikkelsen, Hanne B; Arensbak, Birgitte

2003-01-01

Connexins are the protein constituents of gap junctions which mediate intercellular communication in most tissues. In arterioles gap junctions appear to be important for conduction of vasomotor responses along the vessel. Studies of the expression pattern of connexin isoforms in the microcirculat......Connexins are the protein constituents of gap junctions which mediate intercellular communication in most tissues. In arterioles gap junctions appear to be important for conduction of vasomotor responses along the vessel. Studies of the expression pattern of connexin isoforms...... in the microcirculation are sparse. We investigated the expression of the three major vascular connexins in mesenteric arterioles (diameter micro m) from male Sprague-Dawley rats, since conducted vasomotor responses have been described in these vessels. The findings were compared with those obtained from upstream...... small resistance arteries. Indirect immunofluorescence techniques were used on whole mounts of mesenteric arterioles and on frozen sections of resistance arteries (diameter approximately 300 micro m). Mesenteric arterioles expressed Cx40 and Cx43 in the endothelial layer, and Cx37 was found in most...

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

Note on Hartman effect in gapped graphene

International Nuclear Information System (INIS)

Jahani, D.

2013-01-01

In this manuscript the effect of an opening gap on the dwell time corresponding to the electronic tunneling in graphene is explored. It is shown that tunneling time of quasiparticles in passing through junctions of gapped graphene as well as pure flakes is not independent of the barrier thickness and therefore Hartman effect is not observed due to tunneling of relativistic electrons with a finite effective mass in graphene. The numerical results also reveal that the traversal time in gapped graphene is equal to the traversal time in absence of the barrier for a broad range of incident energy. It is also found that the origin of the problem of Hartman effect could be explained in terms of an average-constant behavior of the probability density of the electronic wave under the barrier

Inverse gender gap in Germany: social dominance orientation among men and women.

Science.gov (United States)

Küpper, Beate; Zick, Andreas

2011-02-01

Across cultures studies show that men score higher on social dominance orientation than women. This gender gap is considered invariant, but conflicting explanations are discussed: Some authors refer to evolutionary psychology and perceive the gender gap to be driven by sociobiological factors. Other authors argue that social roles or gender-stereotypical self-construals encouraged by intergroup comparisons are responsible for attitudinal gender difference. In Study 1 we analyzed sex differences in social dominance orientation in three German probability surveys (each n > 2300). Unexpectedly, the analyses yielded an inverse gender gap with higher values for social dominance orientation in women than in men. Interactions with age, education, political conservatism, and perceived inequity indicated that the inverse gender gap can be mainly attributed to older, conservative, (and less educated) respondents, and those who feel they get their deserved share. In Study 2 we replicated the well-known gender gap with men scoring higher than women in social dominance orientation among German students. Results are interpreted on the basis of biocultural interaction, which integrates the sociobiological, social role, and self-construal perspectives. Our unusual findings seem to reflect a struggle for status by members of low-status groups who consider group-based hierarchy the most promising option to improve their status. While younger women take advantage of a relational, feminine self-construal that leads to lower social dominance orientation in young women than in young men, older women are supposed to profit from an agentic self-construal that results in stronger social dominance orientation values. Specific characteristics of the culture in Germany seem to promote this strategy. Here, we discuss the female ideal of the national socialist period and the agentic female social role in the post-war era necessitated by the absence of men.

Frequency, severity and causes of unexpected allergic reactions to food: a systematic literature review.

Science.gov (United States)

Versluis, A; Knulst, A C; Kruizinga, A G; Michelsen, A; Houben, G F; Baumert, J L; van Os-Medendorp, H

2015-02-01

Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to food. The frequency, severity and causes of such reactions are unknown. The objective of this review was to describe the frequency, severity and causes of unexpected allergic reactions to food in food allergic patients aged > 12 years, in order to develop improved strategies to deal with their allergy. A systematic review was carried out by two researchers, in six electronic databases (CINAHL, Cochrane, EMBASE, Medline, Psychinfo and Scopus). The search was performed with keywords relating to the frequency, severity and causes of unexpected allergic reactions to food. This resulted in 24 studies which met the inclusion criteria; 18 observational and six qualitative studies. This review shows that knowledge about the frequency of unexpected reactions is limited. Peanut, nuts, egg, fruit/vegetables and milk are the main causal foods. Severe reactions and even fatalities occur. Most reactions take place at home, but a significant number also take place when eating at friends' houses or in restaurants. Labelling issues, but also attitude and risky behaviour of patients can attribute to unexpected reactions. We conclude that prospective studies are needed to get more insight in the frequency, severity, quantity of unintended allergen ingested and causes of unexpected allergic reactions to food, to be able to optimize strategies to support patients in dealing with their food allergy. Although the exact frequency is not known, unexpected reactions to food occur in a significant number of patients and can be severe. For clinical practice, this means that patient education and dietary instructions are necessary. © 2014 John Wiley & Sons Ltd.

The prototype GAPS (pGAPS) experiment

International Nuclear Information System (INIS)

Mognet, S.A.I.; Aramaki, T.; Bando, N.; Boggs, S.E.; Doetinchem, P. von; Fuke, H.; Gahbauer, F.H.; Hailey, C.J.; Koglin, J.E.; Madden, N.; Mori, K.; Okazaki, S.; Ong, R.A.; Perez, K.M.; Tajiri, G.; Yoshida, T.; Zweerink, J.

2014-01-01

The General Antiparticle Spectrometer (GAPS) experiment is a novel approach for the detection of cosmic ray antiparticles. A prototype GAPS (pGAPS) experiment was successfully flown on a high-altitude balloon in June of 2012. The goals of the pGAPS experiment were: to test the operation of lithium drifted silicon (Si(Li)) detectors at balloon altitudes, to validate the thermal model and cooling concept needed for engineering of a full-size GAPS instrument, and to characterize cosmic ray and X-ray backgrounds. The instrument was launched from the Japan Aerospace Exploration Agency's (JAXA) Taiki Aerospace Research Field in Hokkaido, Japan. The flight lasted a total of 6 h, with over 3 h at float altitude (∼33km). Over one million cosmic ray triggers were recorded and all flight goals were met or exceeded

Gap Balancing Sacrifices Joint-Line Maintenance to Improve Gap Symmetry: 5-Year Follow-Up of a Randomized Controlled Trial.

Science.gov (United States)

Babazadeh, Sina; Dowsey, Michelle M; Vasimalla, Michael G; Stoney, James D; Choong, Peter F M

2018-01-01

Gap balancing (GB) has been noted to sacrifice joint-line maintenance to improve gap symmetry. This study aims to determine whether this change affects function or quality of life in the midterm. A prospective blinded randomized controlled trial was completed with 103 patients randomized to measured resection (n = 52) or GB (n = 51). Primary outcome measured was femoral component rotation. Secondary outcomes measured were joint-line change, gap symmetry, and function and quality-of-life outcomes. At 5 years, 83 of 103 patients (85%) were assessed. There was no significant difference between groups in terms of functional or quality of life outcomes. A subgroup analysis revealed that there was no significant association between those with asymmetrical flexion and/or extension or medial and/or lateral gaps during knee replacement and subsequent functional outcomes. No significant difference was detected with those with an elevated joint line and postoperative function. In the midterm, the resultant change in joint-line and maintained gap symmetry noted with GB does not result in significant change to function or quality of life. Copyright © 2017 Elsevier Inc. All rights reserved.

Unexpected secoiridoid glucosides from Manulea corymbosa.

Science.gov (United States)

Gousiadou, Chrysoula; Kokubun, Tetsuo; Gotfredsen, Charlotte H; Jensen, Søren R

2014-03-28

From an extract of Manulea corymbosa were isolated four known secoiridoid glucosides (1-4), 10 new monoterpenoid esters of secologanol, namely, manuleosides A-I (5-11, 13, and 14) and dimethyl rhodanthoside A (12), and four new phenylpropanoid esters of carbocyclic iridoid glucosides, manucorymbosides I-IV (15-18). Also, the caffeoyl phenylethanoid glycoside verbascoside was isolated. The presence of secoiridoids apparently derived from loganic acid in the family Scrophulariaceae is unprecedented and greatly unexpected.

Why don't you like me? Midfrontal theta power in response to unexpected peer rejection feedback.

Science.gov (United States)

van der Molen, M J W; Dekkers, L M S; Westenberg, P M; van der Veen, F M; van der Molen, M W

2017-02-01

Social connectedness theory posits that the brain processes social rejection as a threat to survival. Recent electrophysiological evidence suggests that midfrontal theta (4-8Hz) oscillations in the EEG provide a window on the processing of social rejection. Here we examined midfrontal theta dynamics (power and inter-trial phase synchrony) during the processing of social evaluative feedback. We employed the Social Judgment paradigm in which 56 undergraduate women (mean age=19.67 years) were asked to communicate their expectancies about being liked vs. disliked by unknown peers. Expectancies were followed by feedback indicating social acceptance vs. rejection. Results revealed a significant increase in EEG theta power to unexpected social rejection feedback. This EEG theta response could be source-localized to brain regions typically reported during activation of the saliency network (i.e., dorsal anterior cingulate cortex, insula, inferior frontal gyrus, frontal pole, and the supplementary motor area). Theta phase dynamics mimicked the behavior of the time-domain averaged feedback-related negativity (FRN) by showing stronger phase synchrony for feedback that was unexpected vs. expected. Theta phase, however, differed from the FRN by also displaying stronger phase synchrony in response to rejection vs. acceptance feedback. Together, this study highlights distinct roles for midfrontal theta power and phase synchrony in response to social evaluative feedback. Our findings contribute to the literature by showing that midfrontal theta oscillatory power is sensitive to social rejection but only when peer rejection is unexpected, and this theta response is governed by a widely distributed neural network implicated in saliency detection and conflict monitoring. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiography after unexpected death in infants and children compared to autopsy

International Nuclear Information System (INIS)

Lange, Charlotte de; Stake, Gunnar; Vege, Aashild

2007-01-01

Postmortem radiography may reveal skeletal and soft-tissue abnormalities of importance for the diagnosis of cause of death. To review the radiographs of children under 3 years of age who had died suddenly and unexpectedly. To compare the radiological and autopsy findings evaluating possible differences in children dying of SIDS and of an explainable cause. A total of 110 consecutive skeletal surveys performed between 1998 and 2002 were reviewed. All but one were performed before autopsy and comprised AP views of the appendicular and axial skeleton and thorax/abdomen, lateral views of the axial skeleton and thorax, and two oblique views of the ribs. Radiography and autopsy findings were compared. Causes of death were classified as SIDS/borderline SIDS (n = 52) and non-SIDS (n = 58), with one case of abuse. In 102 infants there were 150 pathological findings, 88 involving the chest, 24 skeletal, and 38 miscellaneous findings. The radiological-pathological agreement was poor concerning pulmonary findings. Skeletal findings were sometimes important for the final diagnosis. Radiography revealed many skeletal and soft-tissue findings. Pulmonary pathology was most frequently found, but showed poor agreement with autopsy findings. Recognizing skeletal findings related to abuse is important, as these may escape recognition at autopsy. (orig.)

The prototype GAPS (pGAPS) experiment

Energy Technology Data Exchange (ETDEWEB)

Mognet, S.A.I., E-mail: mognet@astro.ucla.edu [University of California, Los Angeles, CA 90095 (United States); Aramaki, T. [Columbia University, New York, NY 10027 (United States); Bando, N. [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (ISAS/JAXA), Sagamihara, Kanagawa 252-5210 (Japan); Boggs, S.E.; Doetinchem, P. von [Space Sciences Laboratory, University of California, Berkeley, CA 94720 (United States); Fuke, H. [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (ISAS/JAXA), Sagamihara, Kanagawa 252-5210 (Japan); Gahbauer, F.H.; Hailey, C.J.; Koglin, J.E.; Madden, N. [Columbia University, New York, NY 10027 (United States); Mori, K.; Okazaki, S. [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (ISAS/JAXA), Sagamihara, Kanagawa 252-5210 (Japan); Ong, R.A. [University of California, Los Angeles, CA 90095 (United States); Perez, K.M.; Tajiri, G. [Columbia University, New York, NY 10027 (United States); Yoshida, T. [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (ISAS/JAXA), Sagamihara, Kanagawa 252-5210 (Japan); Zweerink, J. [University of California, Los Angeles, CA 90095 (United States)

2014-01-21

The General Antiparticle Spectrometer (GAPS) experiment is a novel approach for the detection of cosmic ray antiparticles. A prototype GAPS (pGAPS) experiment was successfully flown on a high-altitude balloon in June of 2012. The goals of the pGAPS experiment were: to test the operation of lithium drifted silicon (Si(Li)) detectors at balloon altitudes, to validate the thermal model and cooling concept needed for engineering of a full-size GAPS instrument, and to characterize cosmic ray and X-ray backgrounds. The instrument was launched from the Japan Aerospace Exploration Agency's (JAXA) Taiki Aerospace Research Field in Hokkaido, Japan. The flight lasted a total of 6 h, with over 3 h at float altitude (∼33km). Over one million cosmic ray triggers were recorded and all flight goals were met or exceeded.

Unexpected Secoiridoid Glucosides from Manulea corymbosa

DEFF Research Database (Denmark)

Gousiadou, Chrysoula; Kokubun, Tetsuo; Gotfredsen, Charlotte Held

2014-01-01

From an extract of Manulea corymbosa were isolated four known secoiridoid glucosides (1–4), 10 new monoterpenoid esters of secologanol, namely, manuleosides A–I (5–11, 13, and 14) and dimethyl rhodanthoside A (12), and four new phenylpropanoid esters of carbocyclic iridoid glucosides, manucorymbo......, manucorymbosides I–IV (15–18). Also, the caffeoyl phenylethanoid glycoside verbascoside was isolated. The presence of secoiridoids apparently derived from loganic acid in the family Scrophulariaceae is unprecedented and greatly unexpected....

Circadian variation in unexpected postoperative death

DEFF Research Database (Denmark)

Rosenberg, J; Pedersen, M H; Ramsing, T

1992-01-01

Unexpected deaths still occur following major surgical procedures. The cause is often unknown but may be cardiac or thromboembolic in nature. Postoperative ischaemia, infarction and sudden cardiac death may be triggered by episodic or constant arterial hypoxaemia, which increases during the night...... deaths occurred at night-time. These results suggest a need for further studies of sleep- and respiration-related effects on postoperative nocturnal cardiac function. The efficacy of monitoring during this apparent high-risk period should be evaluated....

Cardiomyopathy-Associated Gene 1-Sensitive PKC-Dependent Connexin 43 Expression and Phosphorylation in Left Ventricular Noncompaction Cardiomyopathy

Directory of Open Access Journals (Sweden)

Yuanyuan Xie

2017-11-01

Full Text Available Background/Aims: Cardiomyopathy-associated gene 1 (CMYA1 plays an important role in embryonic cardiac development, postnatal cardiac remodeling and myocardial injury repair. Abnormal CMYA1 expression may be involved in cardiac dysplasia and primary cardiomyopathy. Our study aims to establish the relationship between CMYA1 and Left ventricular noncompaction cardiomyopathy (LVNC pathogenesis. Methods: We explored the effects of CMYA1 on connexins (Cx, which contribute to gap junction intercellular communication (GJIC, and the underlying signaling pathway in human normal tissues, LVNC myocardial tissues and HL1 cells by means of western blotting, RT-qPCR, immunohistochemistry, immunofluorescence, co-immunoprecipitation and scrape loading-dye transfer. Results: CMYA1 expression was inversely associated with Cx43 and Cx40 expression, as determined by gap junction PCR array analysis. An increased expression and disordered distribution of CMYA1 at the intercalated discs in LVNC myocardial tissue was also observed. CMYA1 and Cx43 are co-expressed and interact in myocardial cells. CMYA1 expression was positively correlated with p-Cx43 (S368 via the Protein kinase C (PKC signaling pathway in myocardial tissue and HL1 cells. The diffusion distance of Lucifer Yellow in the HL1 cells in which CMYA1 was over-expressed or knocked down was significantly less or more than that of the control group, respectively. Conclusion: Abnormal CMYA1 expression affects the expression and phosphorylation of Cx43 through the PKC signaling pathway, which is involved in the regulation of GJIC. CMYA1 participates in the molecular mechanism of LVNC pathogenesis.

New product trial, use of edibles, and unexpected highs among marijuana and hashish users in Colorado.

Science.gov (United States)

Allen, Jane A; Davis, Kevin C; Duke, Jennifer C; Nonnemaker, James M; Bradfield, Brian R; Farrelly, Matthew C

2017-07-01

This study examines the relationships between trial of new marijuana or hashish products and unexpected highs, and use of edible products and unexpected highs. We conducted an online survey of 634 adult, past-year marijuana users in Colorado. We used logistic regression models to examine the relationship between new product trial or edible use and unexpected highs. In the first year that recreational marijuana was legal in Colorado, 71.4% of respondents tried a new marijuana or hashish product, and 53.6% used an edible product. Trial of new products was associated with greater odds of experiencing an unexpected high after controlling for age, gender, education, mental health status, current marijuana or hashish use, and mean amount of marijuana or hashish consumed in the past month (OR=2.13, pmarijuana or hashish products, or use edible marijuana or hashish products, are at greater risk for an unexpected high. It is possible that some negative outcomes associated with marijuana use and unexpected highs may be averted through a better understanding of how to use product packaging to communicate with consumers. Copyright © 2017 Elsevier B.V. All rights reserved.

Proteomic investigation of aphid honeydew reveals an unexpected diversity of proteins.

Directory of Open Access Journals (Sweden)

Ahmed Sabri

Full Text Available Aphids feed on the phloem sap of plants, and are the most common honeydew-producing insects. While aphid honeydew is primarily considered to comprise sugars and amino acids, its protein diversity has yet to be documented. Here, we report on the investigation of the honeydew proteome from the pea aphid Acyrthosiphon pisum. Using a two-Dimensional Differential in-Gel Electrophoresis (2D-Dige approach, more than 140 spots were isolated, demonstrating that aphid honeydew also represents a diverse source of proteins. About 66% of the isolated spots were identified through mass spectrometry analysis, revealing that the protein diversity of aphid honeydew originates from several organisms (i.e. the host aphid and its microbiota, including endosymbiotic bacteria and gut flora. Interestingly, our experiments also allowed to identify some proteins like chaperonin, GroEL and Dnak chaperones, elongation factor Tu (EF-Tu, and flagellin that might act as mediators in the plant-aphid interaction. In addition to providing the first aphid honeydew proteome analysis, we propose to reconsider the importance of this substance, mainly acknowledged to be a waste product, from the aphid ecology perspective.

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.

Estimating yield gaps at the cropping system level.

Science.gov (United States)

Guilpart, Nicolas; Grassini, Patricio; Sadras, Victor O; Timsina, Jagadish; Cassman, Kenneth G

2017-05-01

Yield gap analyses of individual crops have been used to estimate opportunities for increasing crop production at local to global scales, thus providing information crucial to food security. However, increases in crop production can also be achieved by improving cropping system yield through modification of spatial and temporal arrangement of individual crops. In this paper we define the cropping system yield potential as the output from the combination of crops that gives the highest energy yield per unit of land and time, and the cropping system yield gap as the difference between actual energy yield of an existing cropping system and the cropping system yield potential. Then, we provide a framework to identify alternative cropping systems which can be evaluated against the current ones. A proof-of-concept is provided with irrigated rice-maize systems at four locations in Bangladesh that represent a range of climatic conditions in that country. The proposed framework identified (i) realistic alternative cropping systems at each location, and (ii) two locations where expected improvements in crop production from changes in cropping intensity (number of crops per year) were 43% to 64% higher than from improving the management of individual crops within the current cropping systems. The proposed framework provides a tool to help assess food production capacity of new systems ( e.g. with increased cropping intensity) arising from climate change, and assess resource requirements (water and N) and associated environmental footprint per unit of land and production of these new systems. By expanding yield gap analysis from individual crops to the cropping system level and applying it to new systems, this framework could also be helpful to bridge the gap between yield gap analysis and cropping/farming system design.

Intracellular Cleavage of the Cx43 C-Terminal Domain by Matrix-Metalloproteases: A Novel Contributor to Inflammation?

Directory of Open Access Journals (Sweden)

Marijke De Bock

2015-01-01

Full Text Available The coordination of tissue function is mediated by gap junctions (GJs that enable direct cell-cell transfer of metabolic and electric signals. GJs are formed by connexin (Cx proteins of which Cx43 is most widespread in the human body. Beyond its role in direct intercellular communication, Cx43 also forms nonjunctional hemichannels (HCs in the plasma membrane that mediate the release of paracrine signaling molecules in the extracellular environment. Both HC and GJ channel function are regulated by protein-protein interactions and posttranslational modifications that predominantly take place in the C-terminal domain of Cx43. Matrix metalloproteases (MMPs are a major group of zinc-dependent proteases, known to regulate not only extracellular matrix remodeling, but also processing of intracellular proteins. Together with Cx43 channels, both GJs and HCs, MMPs contribute to acute inflammation and a small number of studies reports on an MMP-Cx43 link. Here, we build further on these reports and present a novel hypothesis that describes proteolytic cleavage of the Cx43 C-terminal domain by MMPs and explores possibilities of how such cleavage events may affect Cx43 channel function. Finally, we set out how aberrant channel function resulting from cleavage can contribute to the acute inflammatory response during tissue injury.

TGF-beta induces connexin43 gene expression in normal murine mammary gland epithelial cells via activation of p38 and PI3K/AKT signaling pathways.

Science.gov (United States)

Tacheau, Charlotte; Fontaine, Juliette; Loy, Jennifer; Mauviel, Alain; Verrecchia, Franck

2008-12-01

One of the shared physiological roles between TGF-beta and connexin family members is to inhibit epithelial cell cycle progression and consequently, to provide protection against malignant transformation. Herein, we demonstrated that TGF-beta1 induces the expression of connexin43 (Cx43) in normal murine mammary gland (NMuMG) cell lines at the protein and mRNA levels, and transcriptionally. Using overexpression of a truncated dominant-negative form of Cx43, we determined that the modulation of gap junctional communication by TGF-beta1 plays a key role in the control of NMuMG cells proliferation by TGF-beta1. In addition, using overexpression of truncated dominant-negative forms of either Smad2 or Smad3, and MDA-MB-468 human breast carcinoma cells deficient for Smad4, we determined that the Smad cascade is not implicated in TGF-beta1 effect on Cx43 expression. Using specific pharmacologic inhibitors for JNK, ERK, p38, and PI3K/AKT signaling pathways, we demonstrated the cooperative role of p38 and PI3K/AKT signaling in TGF-beta1-induced Cx43 expression and gap junctional communication. Furthermore, transfection of a c-jun antisense expression vector significantly prevented TGF-beta1-induced Cx43 gene expression demonstrating the involvement of c-Jun/AP-1 pathway together with p38 and PI3K/AKT pathways in mediating TGF-beta1-induced Cx43 gene expression.

Comprehensive study of unexpected microscope condensers formed in sample arrangements commonly used in optical microscopy.

Science.gov (United States)

Desai, Darshan B; Aldawsari, Mabkhoot Mudith S; Alharbi, Bandar Mohammed H; Sen, Sanchari; Grave de Peralta, Luis

2015-09-01

We show that various setups for optical microscopy which are commonly used in biomedical laboratories behave like efficient microscope condensers that are responsible for observed subwavelength resolution. We present a series of experiments and simulations that reveal how inclined illumination from such unexpected condensers occurs when the sample is perpendicularly illuminated by a microscope's built-in white-light source. In addition, we demonstrate an inexpensive add-on optical module that serves as an efficient and lightweight microscope condenser. Using such add-on optical module in combination with a low-numerical-aperture objective lens and Fourier plane imaging microscopy technique, we demonstrate detection of photonic crystals with a period nearly eight times smaller than the Rayleigh resolution limit.

Extremely confined gap surface-plasmon modes excited by electrons

DEFF Research Database (Denmark)

Raza, Søren; Stenger, Nicolas; Pors, Anders Lambertus

2014-01-01

High-spatial and energy resolution electron energy-loss spectroscopy (EELS) can be used for detailed characterization of localized and propagating surface-plasmon excitations in metal nanostructures, giving insight into fundamental physical phenomena and various plasmonic effects. Here, applying...... EELS to ultra-sharp convex grooves in gold, we directly probe extremely confined gap surface-plasmon (GSP) modes excited by swift electrons in nanometre-wide gaps. We reveal the resonance behaviour associated with the excitation of the antisymmetric GSP mode for extremely small gap widths, down to ~5...... mode exploited in plasmonic waveguides with extreme light confinement is a very important factor that should be taken into account in the design of nanoplasmonic circuits and devices....

GapBlaster-A Graphical Gap Filler for Prokaryote Genomes.

Directory of Open Access Journals (Sweden)

Pablo H C G de Sá

Full Text Available The advent of NGS (Next Generation Sequencing technologies has resulted in an exponential increase in the number of complete genomes available in biological databases. This advance has allowed the development of several computational tools enabling analyses of large amounts of data in each of the various steps, from processing and quality filtering to gap filling and manual curation. The tools developed for gap closure are very useful as they result in more complete genomes, which will influence downstream analyses of genomic plasticity and comparative genomics. However, the gap filling step remains a challenge for genome assembly, often requiring manual intervention. Here, we present GapBlaster, a graphical application to evaluate and close gaps. GapBlaster was developed via Java programming language. The software uses contigs obtained in the assembly of the genome to perform an alignment against a draft of the genome/scaffold, using BLAST or Mummer to close gaps. Then, all identified alignments of contigs that extend through the gaps in the draft sequence are presented to the user for further evaluation via the GapBlaster graphical interface. GapBlaster presents significant results compared to other similar software and has the advantage of offering a graphical interface for manual curation of the gaps. GapBlaster program, the user guide and the test datasets are freely available at https://sourceforge.net/projects/gapblaster2015/. It requires Sun JDK 8 and Blast or Mummer.

Differential Connexin Function Enhances Self-Renewal in Glioblastoma

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Masahiro Hitomi

2015-05-01

Full Text Available The coordination of complex tumor processes requires cells to rapidly modify their phenotype and is achieved by direct cell-cell communication through gap junction channels composed of connexins. Previous reports have suggested that gap junctions are tumor suppressive based on connexin 43 (Cx43, but this does not take into account differences in connexin-mediated ion selectivity and intercellular communication rate that drive gap junction diversity. We find that glioblastoma cancer stem cells (CSCs possess functional gap junctions that can be targeted using clinically relevant compounds to reduce self-renewal and tumor growth. Our analysis reveals that CSCs express Cx46, while Cx43 is predominantly expressed in non-CSCs. During differentiation, Cx46 is reduced, while Cx43 is increased, and targeting Cx46 compromises CSC maintenance. The difference between Cx46 and Cx43 is reflected in elevated cell-cell communication and reduced resting membrane potential in CSCs. Our data demonstrate a pro-tumorigenic role for gap junctions that is dependent on connexin expression.

Lifting an unexpectedly heavy object : the effects on low-back loading and balance loss

NARCIS (Netherlands)

van der Burg, J C; van Dieën, J H; Toussaint, H M

OBJECTIVE: This study evaluates the effects of lifting an unexpectedly heavy object on low-back loading and loss of balance. BACKGROUND: It is often suggested that lifting an unexpectedly heavy object may be a major risk factor for low-back pain. This may lead to an increase in muscle activation,

Working memory representations persist in the face of unexpected task alterations.

Science.gov (United States)

Swan, Garrett; Wyble, Brad; Chen, Hui

2017-07-01

It is well known that information can be held in memory while performing other tasks concurrently, such as remembering a color or number during a separate visual search task. However, it is not clear what happens to stored information in the face of unexpected tasks, such as the surprise questions that are often used in experiments related to inattentional and change blindness. Does the unpredicted shift in task context cause memory representations to be cleared in anticipation of new information? To answer this question, we ran two experiments where the task unexpectedly switched partway through the experiment with a surprise question. Half of the participants were asked to report the same attribute (Exp. 1 = Identity, Exp. 2 = Color) of a target stimulus in both presurprise and postsurprise trials, while for the other half, the reported attribute switched from identity to color (Exp. 1) or vice versa (Exp. 2). Importantly, all participants had to read an unexpected set of instructions and respond differently on the surprise trial. Accuracy on the surprise trial was higher for the same-attribute groups than the different-attribute groups. Furthermore, there was no difference in reaction time on the surprise trial between the two groups. These results suggest that information participants expected to report can survive an encounter with an unexpected task. The implication is that failures to report information on a surprise trial in many experiments reflect genuine differences in memory encoding, rather than forgetting or overwriting induced by the surprise question.

The identification of conduction gaps after pulmonary vein isolation using a new electroanatomic mapping system.

Science.gov (United States)

Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Kanda, Takashi; Tsujimura, Takuya; Matsuda, Yasuhiro; Okuno, Shota; Ohashi, Takuya; Tsuji, Aki; Mano, Toshiaki

2017-11-01

The reconnection of left atrial-pulmonary vein (LA-PV) conduction after the initial procedure of pulmonary vein (PV) isolation is not rare, and is one of the main cause of atrial fibrillation (AF) recurrence after PV isolation. We investigated feasibility of a new ultrahigh-resolution mapping system using a 64-pole small basket catheter for the identification of LA-PV conduction gaps. This prospective study included 31 consecutive patients (20 with persistent AF) undergoing a second ablation after a PV isolation procedure with LA-PV reconnected conduction at any of the 4 PVs. An LA-PV map was created using the mapping system, and ablation was performed at the estimated gap location. The propagation map identified 54 gaps from 39 ipsilateral PV pairs, requiring manual electrogram reannotation for 23 gaps (43%). Gaps at the anterior and carinal regions of left and right ipsilateral PVs required manual electrogram reannotation more frequently than the other regions. The voltage map could identify the gap only in 19 instances (35%). Electrophysiological properties of the gaps (multiple gaps in the same ipsilateral PVs, conduction time, velocity, width, and length) did not differ between those needing and not needing manual electrogram reannotation. During the gap ablation, either the activation sequence alteration or elimination of PV potentials was observed using a circular catheter placed in the PV, suggesting that all the identified gaps were correct. This new electroanatomic mapping system visualized all the LA-PV gaps in patients undergoing a second AF ablation. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Mutual incomprehension: U.S.- German value gaps beyond Iraq

OpenAIRE

Larres, Klaus

2003-01-01

Differences over Iraq policy have revealed deep U.S.- German value gaps over multilateralism, nationalism, and the role of force in international relations. Cooperation in four areas of mutual importance can help compensate for them.

Vine vigor, yield and grape quality assessment by airborne remote sensing over three years: Analysis of unexpected relationships in cv. Tempranillo

Energy Technology Data Exchange (ETDEWEB)

Bonilla, I.; Martinez de Toda, F.; Martínez-Casasnovas, J.A.

2015-07-01

The prediction of grape composition is becoming more important due to the need of reducing the current levels of alcohol and pH of the wines, a problem that is exacerbated by climate change. This work presents a 3-year study of the spatial variability of grape composition in a rainfed Tempranillo vineyard located in Rioja (Spain). It is based on the acquisition of multispectral imagery at véraison (start of the ripening process); and zoning based on NDVI, to assess its performance for zonal management. The results reveal a high spatial variability within the plot, with a stable pattern over the years, even with very different climate conditions. NDVI was a good predictor of vegetative growth variables. However, the prediction of grape composition was more complex. Unexpectedly, anthocyanins were found to be higher in the highest vigor zone, which is probably related to the effects of climate change. This unexpected relationship is particularly discussed in the article. (Author)

Closing the Gap: The Maturing of Quality Assurance in Australian University Libraries

Science.gov (United States)

Tang, Karen

2012-01-01

A benchmarking review of the quality assurance practices of the libraries of the Australian Technology Network conducted in 2006 revealed exemplars of best practice, but also sector-wide gaps. A follow-up review in 2010 indicated the best practices that remain relevant. While some gaps persist, there has been improvement across the libraries and…

Methamphetamine compromises gap junctional communication in astrocytes and neurons.

Science.gov (United States)

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

Fatigue life analysis of unexpected failure in a lamellar TiAl alloy

Energy Technology Data Exchange (ETDEWEB)

Chan, K.S.

1999-07-01

Unexpected catastrophic failure occurred in specimens of a lamellar TiAl alloy tested by axial fatigue. The failure initiated at locations away from artificial defects introduced to the specimens as crack starters. Fractographic examination of the fracture surface revealed the presence of featureless, low-energy facets that suggested the catastrophic crack may have initiated in one or more large grains that cleaved on a cleavage plane or an interface. A crack growth analysis of fatigue life of the test specimens suggested that the catastrophic crack propagated at stress intensity levels below the large crack threshold. Furthermore, the catastrophic crack propagated at rates that were higher than the average rates exhibited by small cracks, as well as by the large crack under equivalent stress intensity ranges. Because of this, the conventional life prediction approach based on the large crack growth data grossly overpredicted the fatigue life.

Phononic band gap and mechanical anisotropy in spider silk

Science.gov (United States)

Papadopoulos, Periklis; Gomopoulos, Nikos; Kremer, Friedrich; Fytas, George

2010-03-01

Spider dragline silk is a semi-crystalline biopolymer exhibiting superior properties compared to synthetic polymers with similar chemical structure, such as polyamides. This is ascribed to the hierarchical nanostructure that is created in the spinning duct. During this process the aqueous solution of the two protein constituents of dragline silk is crystallized, while the macromolecules maintain their high orientation, leading to a high value of the Young's modulus (in the order of 10 GPa) along the fiber. We employed spontaneous Brillouin light scattering to measure the longitudinal modulus (M//,,M) along the two symmetry directions of the native fiber with increased (decreased) pre-strain created by stretching (supercontracting after hydration). A strong mechanical anisotropy is found; at about 18% strain M///M˜5. Most important, an unexpected finding is the first observation of a unidirectional hypersonic phononic band gap in biological structures. This relates to the existence of a strain-dependent correlation length of the mechanical modulus in the submicron range along the fiber axis.

Friction and wear behavior of TiC particle reinforced ZA43 matrix composites

Institute of Scientific and Technical Information of China (English)

谢贤清; 张荻; 刘金水; 吴人洁

2001-01-01

TiC/ZA43 composites were fabricated by XDTM and stirring-casting techniques. The tribology properties of the unreinforced ZA43 alloy and the composites were studied by using a block-on-ring apparatus. Experimental results show that the incorporation of TiC particles improves the microstructure of ZA43 matrix alloy. The coefficient of friction μ and the width of worn groove decrease with the increase of TiC volume fraction φ(TiC). The width of worn groove and μ of the composite during wear testing increase with increasing the applied load. Metallographic examinations reveal that unreinforced ZA43 alloy has deep ploughing grooves with obvious adhesion phenomenon, whereas TiC/ZA43 composites have smooth worn surface. Delamination formation is related to the fatigue cracks and the shear cracks on the surface.

Mathematics Placement Test: Typical Results with Unexpected Outcomes

Science.gov (United States)

Ingalls, Victoria

2011-01-01

Based on the results of a prior case-study analysis of mathematics placement at one university, the mathematics department developed and piloted a mathematics placement test. This article describes the implementation process for a mathematics placement test and further analyzes the test results for the pilot group. As an unexpected result, the…

Band gap tunning in BN-doped graphene systems with high carrier mobility

KAUST Repository

Kaloni, T. P.

2014-02-17

Using density functional theory, we present a comparative study of the electronic properties of BN-doped graphene monolayer, bilayer, trilayer, and multilayer systems. In addition, we address a superlattice of pristine and BN-doped graphene. Five doping levels between 12.5% and 75% are considered, for which we obtain band gaps from 0.02 eV to 2.43 eV. We demonstrate a low effective mass of the charge carriers.

Unexpected Convergent Evolution of Nasal Domes between Pleistocene Bovids and Cretaceous Hadrosaur Dinosaurs.

Science.gov (United States)

O'Brien, Haley D; Faith, J Tyler; Jenkins, Kirsten E; Peppe, Daniel J; Plummer, Thomas W; Jacobs, Zenobia L; Li, Bo; Joannes-Boyau, Renaud; Price, Gilbert; Feng, Yue-Xing; Tryon, Christian A

2016-02-22

The fossil record provides tangible, historical evidence for the mode and operation of evolution across deep time. Striking patterns of convergence are some of the strongest examples of these operations, whereby, over time, similar environmental and/or behavioral pressures precipitate similarity in form and function between disparately related taxa. Here we present fossil evidence for an unexpected convergence between gregarious plant-eating mammals and dinosaurs. Recent excavations of Late Pleistocene deposits on Rusinga Island, Kenya, have uncovered a catastrophic assemblage of the wildebeest-like bovid Rusingoryx atopocranion. Previously known from fragmentary material, these new specimens reveal large, hollow, osseous nasal crests: a craniofacial novelty for mammals that is remarkably comparable to the nasal crests of lambeosaurine hadrosaur dinosaurs. Using adult and juvenile material from this assemblage, as well as computed tomographic imaging, we investigate this convergence from morphological, developmental, functional, and paleoenvironmental perspectives. Our detailed analyses reveal broad parallels between R. atopocranion and basal Lambeosaurinae, suggesting that osseous nasal crests may require a highly specific combination of ontogeny, evolution, and environmental pressures in order to develop. Copyright © 2016 Elsevier Ltd. All rights reserved.

Connexin 43-mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells.

Science.gov (United States)

Xu, Xin; Francis, Richard; Wei, Chih Jen; Linask, Kaari L; Lo, Cecilia W

2006-09-01

Connexin 43 knockout (Cx43alpha1KO) mice have conotruncal heart defects that are associated with a reduction in the abundance of cardiac neural crest cells (CNCs) targeted to the heart. In this study, we show CNCs can respond to changing fibronectin matrix density by adjusting their migratory behavior, with directionality increasing and speed decreasing with increasing fibronectin density. However, compared with wild-type CNCs, Cx43alpha1KO CNCs show reduced directionality and speed, while CNCs overexpressing Cx43alpha1 from the CMV43 transgenic mice show increased directionality and speed. Altered integrin signaling was indicated by changes in the distribution of vinculin containing focal contacts, and altered temporal response of Cx43alpha1KO and CMV43 CNCs to beta1 integrin function blocking antibody treatment. High resolution motion analysis showed Cx43alpha1KO CNCs have increased cell protrusive activity accompanied by the loss of polarized cell movement. They exhibited an unusual polygonal arrangement of actin stress fibers that indicated a profound change in cytoskeletal organization. Semaphorin 3A, a chemorepellent known to inhibit integrin activation, was found to inhibit CNC motility, but in the Cx43alpha1KO and CMV43 CNCs, cell processes failed to retract with semaphorin 3A treatment. Immunohistochemical and biochemical analyses suggested close interactions between Cx43alpha1, vinculin and other actin-binding proteins. However, dye coupling analysis showed no correlation between gap junction communication level and fibronectin plating density. Overall, these findings indicate Cx43alpha1 may have a novel function in mediating crosstalk with cell signaling pathways that regulate polarized cell movement essential for the directional migration of CNCs.

A RAB3GAP1 SINE Insertion in Alaskan Huskies with Polyneuropathy, Ocular Abnormalities, and Neuronal Vacuolation (POANV Resembling Human Warburg Micro Syndrome 1 (WARBM1

Directory of Open Access Journals (Sweden)

Michaela Wiedmer

2016-02-01

Full Text Available We observed a hereditary phenotype in Alaskan Huskies that was characterized by polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV. The affected dogs developed a progressive severe ataxia, which led to euthanasia between 8 and 16 months of age. The pedigrees were consistent with a monogenic autosomal recessive inheritance. We localized the causative genetic defect to a 4 Mb interval on chromosome 19 by a combined linkage and homozygosity mapping approach. Whole genome sequencing of one affected dog, an obligate carrier, and an unrelated control revealed a 218-bp SINE insertion into exon 7 of the RAB3GAP1 gene. The SINE insertion was perfectly associated with the disease phenotype in a cohort of 43 Alaskan Huskies, and it was absent from 541 control dogs of diverse other breeds. The SINE insertion induced aberrant splicing and led to a transcript with a greatly altered exon 7. RAB3GAP1 loss-of-function variants in humans cause Warburg Micro Syndrome 1 (WARBM1, which is characterized by additional developmental defects compared to canine POANV, whereas Rab3gap1-deficient mice have a much milder phenotype than either humans or dogs. Thus, the RAB3GAP1 mutant Alaskan Huskies provide an interesting intermediate phenotype that may help to better understand the function of RAB3GAP1 in development. Furthermore, the identification of the presumed causative genetic variant will enable genetic testing to avoid the nonintentional breeding of affected dogs.

Model System for Live Imaging of Neuronal Responses to Injury and Repair

Directory of Open Access Journals (Sweden)

Mathieu Gravel

2011-11-01

Full Text Available Although it has been well established that induction of growth-associated protein-43 (GAP-43 during development coincides with axonal outgrowth and early synapse formation, the existence of neuronal plasticity and neurite outgrowth in the adult central nervous system after injuries is more controversial. To visualize the processes of neuronal injury and repair in living animals, we generated reporter mice for bioluminescence and fluorescence imaging bearing the luc (luciferase and gfp (green fluorescent protein reporter genes under the control of the murine GAP-43 promoter. Reporter functionality was first observed during the development of transgenic embryos. Using in vivo bioluminescence and fluorescence imaging, we visualized induction of the GAP-43 signals from live embryos starting at E10.5, as well as neuronal responses to brain and peripheral nerve injuries (the signals peaked at 14 days postinjury. Moreover, three-dimensional analysis of the GAP-43 bioluminescent signal confirmed that it originated from brain structures affected by ischemic injury. The analysis of fluorescence signal at cellular level revealed colocalization between endogenous protein and the GAP-43-driven gfp transgene. Taken together, our results suggest that the GAP-43-luc/gfp reporter mouse represents a valid model system for real-time analysis of neurite outgrowth and the capacity of the adult nervous system to regenerate after injuries.

Study on models for gap conductance between fuel and sheath for CANDU reactors

International Nuclear Information System (INIS)

Lee, K.M.; Ohn, M.Y.; Lim, H.S.; Choi, J.H.; Hwang, S.T.

1995-01-01

The gap conductance between the fuel and the sheath depends strongly on the gap width and has a significant influence on the amount of initial stored energy. The modified Ross and Stoute gap conductance model in ELESTRES is based on a simplified thermal deformation model for steady-state fuel temperature calculations. A review on a series of experiments reveals that fuel pellets crack, relocate, and are eccentrically positioned within the sheath rather than solid concentric cylinders. In this paper, the two recently-proposed gap conductance models (offset gap model and relocated gap model) are described and are applied to calculate the fuel-sheath gap conductances under experimental conditions and normal operating conditions in CANDU reactors. The good agreement between the experimentally-inferred and calculated gap conductance values demonstrates that the modified Ross and Stoute model was implemented correctly in ELESTRES. The predictions of the modified Ross and Stoute model provide conservative values for gap heat transfer and fuel surface temperature compared to the offset gap and relocated gap models for a limiting power envelope. (author)

High rates of hybridisation reveal fragile reproductive barriers between endangered Australian sea snakes

DEFF Research Database (Denmark)

Sanders, Kate L; Redsted Rasmussen, Arne; Guinea, Michael L.

2014-01-01

designations, but revealed high frequencies of hybrids on all four reefs and individuals of pure A. fuscus ancestry only at Scott and (historically) Ashmore. Most unexpectedly, 95% of snakes sampled at Hibernia were hybrids that resembled A. laevis in phenotype, revealing a collapse of reproductive barriers...... (‘reverse speciation’) at this reef. These results have dire implications for the conservation status of A. fuscus, and highlight the fragility of reproductive barriers in a recent marine radiation....

Gap Dependent Bifurcation Behavior of a Nano-Beam Subjected to a Nonlinear Electrostatic Pressure

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Mohammad Fathalilou

Full Text Available This paper presents a study on the gap dependent bifurcation behavior of an electro statically-actuated nano-beam. The sizedependent behavior of the beam was taken into account by applying the couple stress theory. Two small and large gap distance regimes have been considered in which the intermolecular vdW and Casimir forces are dominant, respectively. It has been shown that changing the gap size can affect the fundamental frequency of the beam. The bifurcation diagrams for small gap distance revealed that by changing the gap size, the number and type of the fixed points can change. However, for large gap regime, where the Casimir force is the dominant intermolecular force, changing the gap size does not affect the quality of the bifurcation behavior.

The processing of unexpected positive response outcomes in the mediofrontal cortex.

Science.gov (United States)

Ferdinand, Nicola K; Mecklinger, Axel; Kray, Jutta; Gehring, William J

2012-08-29

The human mediofrontal cortex, especially the anterior cingulate cortex, is commonly assumed to contribute to higher cognitive functions like performance monitoring. How exactly this is achieved is currently the subject of lively debate but there is evidence that an event's valence and its expectancy play important roles. One prominent theory, the reinforcement learning theory by Holroyd and colleagues (2002, 2008), assigns a special role to feedback valence, while the prediction of response-outcome (PRO) model by Alexander and Brown (2010, 2011) claims that the mediofrontal cortex is sensitive to unexpected events regardless of their valence. However, paradigms examining this issue have included confounds that fail to separate valence and expectancy. In the present study, we tested the two competing theories of performance monitoring by using an experimental task that separates valence and unexpectedness of performance feedback. The feedback-related negativity of the event-related potential, which is commonly assumed to be a reflection of mediofrontal cortex activity, was elicited not only by unexpected negative feedback, but also by unexpected positive feedback. This implies that the mediofrontal cortex is sensitive to the unexpectedness of events in general rather than their valence and by this supports the PRO model.

Unexpected pathological findings in skills training and assessing skills

NARCIS (Netherlands)

Boendermaker, PM; Pols, J; Scherpbier, AJJA

This article draws attention to unexpected pathological findings encountered by students and teachers when examining one another and/or simulated patients in skips training and assessment sessions. Although no literature on the subject was found it appears to be not uncommon far students and

Seed regeneration potential of canopy gaps at early formation stage in temperate secondary forests, Northeast China.

Directory of Open Access Journals (Sweden)

Qiao-Ling Yan

Full Text Available Promoting the seed regeneration potential of secondary forests undergoing gap disturbances is an important approach for achieving forest restoration and sustainable management. Seedling recruitment from seed banks strongly determines the seed regeneration potential, but the process is poorly understood in the gaps of secondary forests. The objectives of the present study were to evaluate the effects of gap size, seed availability, and environmental conditions on the seed regeneration potential in temperate secondary forests. It was found that gap formation could favor the invasion of more varieties of species in seed banks, but it also could speed up the turnover rate of seed banks leading to lower seed densities. Seeds of the dominant species, Fraxinus rhynchophylla, were transient in soil and there was a minor and discontinuous contribution of the seed bank to its seedling emergence. For Quercus mongolica, emerging seedling number was positively correlated with seed density in gaps (R = 0.32, P<0.01, especially in medium and small gaps (<500 m(2. Furthermore, under canopies, there was a positive correlation between seedling number and seed density of Acer mono (R = 0.43, P<0.01. Gap formation could promote seedling emergence of two gap-dependent species (i.e., Q. mongolica and A. mono, but the contribution of seed banks to seedlings was below 10% after gap creation. Soil moisture and temperature were the restrictive factors controlling the seedling emergence from seeds in gaps and under canopies, respectively. Thus, the regeneration potential from seed banks is limited after gap formation.

Seed Regeneration Potential of Canopy Gaps at Early Formation Stage in Temperate Secondary Forests, Northeast China

Science.gov (United States)

Yan, Qiao-Ling; Zhu, Jiao-Jun; Yu, Li-Zhong

2012-01-01

Promoting the seed regeneration potential of secondary forests undergoing gap disturbances is an important approach for achieving forest restoration and sustainable management. Seedling recruitment from seed banks strongly determines the seed regeneration potential, but the process is poorly understood in the gaps of secondary forests. The objectives of the present study were to evaluate the effects of gap size, seed availability, and environmental conditions on the seed regeneration potential in temperate secondary forests. It was found that gap formation could favor the invasion of more varieties of species in seed banks, but it also could speed up the turnover rate of seed banks leading to lower seed densities. Seeds of the dominant species, Fraxinus rhynchophylla, were transient in soil and there was a minor and discontinuous contribution of the seed bank to its seedling emergence. For Quercus mongolica, emerging seedling number was positively correlated with seed density in gaps (R = 0.32, P<0.01), especially in medium and small gaps (<500 m2). Furthermore, under canopies, there was a positive correlation between seedling number and seed density of Acer mono (R = 0.43, P<0.01). Gap formation could promote seedling emergence of two gap-dependent species (i.e., Q. mongolica and A. mono), but the contribution of seed banks to seedlings was below 10% after gap creation. Soil moisture and temperature were the restrictive factors controlling the seedling emergence from seeds in gaps and under canopies, respectively. Thus, the regeneration potential from seed banks is limited after gap formation. PMID:22745771

A dual contribution to the involuntary semantic processing of unexpected spoken words.

Science.gov (United States)

Parmentier, Fabrice B R; Turner, Jacqueline; Perez, Laura

2014-02-01

Sounds are a major cause of distraction. Unexpected to-be-ignored auditory stimuli presented in the context of an otherwise repetitive acoustic background ineluctably break through selective attention and distract people from an unrelated visual task (deviance distraction). This involuntary capture of attention by deviant sounds has been hypothesized to trigger their semantic appraisal and, in some circumstances, interfere with ongoing performance, but it remains unclear how such processing compares with the automatic processing of distractors in classic interference tasks (e.g., Stroop, flanker, Simon tasks). Using a cross-modal oddball task, we assessed the involuntary semantic processing of deviant sounds in the presence and absence of deviance distraction. The results revealed that some involuntary semantic analysis of spoken distractors occurs in the absence of deviance distraction but that this processing is significantly greater in its presence. We conclude that the automatic processing of spoken distractors reflects 2 contributions, one that is contingent upon deviance distraction and one that is independent from it.

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.

An Unexpected Case of Lyme Disease in a Soldier Serving in Northern Iraq

Science.gov (United States)

2010-05-01

MILITARY MEDICINE, 175,5:367,2010 An Unexpected Case of Lyme Disease in a Soldier Serving in Northern Iraq CPT Jeremy B. Fisher, SP USA *; CPT...Christopher E. Curtis, MC USAt 188143 ABSTRACT Lyme disease is a tick-transmitted disease caused by the spirochete Borrelia burgdorferi. Cases have been...Turkey.3-S We report an unexpected case of Lyme disease from Iraq. CASE REPORT A 28-year-old active duty Army male, on a deployment to northern Iraq

The Investigation of Unexpected Arsenic Compounds Observed in Routine Biological Monitoring Urinary Speciation Analysis

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Elizabeth Leese

2017-05-01

Full Text Available This study investigates the identity of two unexpected arsenic species found separately in a number of urine samples sent to the Health and Safety Executive’s Health and Safety Laboratory for arsenic speciation (arsenobetaine, AB; arsenite, As3+; arsenate, As5+; monomethylarsonic acid, MMA5+; and dimethylarsinic acid, DMA5+. Micro liquid chromatography coupled to inductively coupled plasma mass spectrometry (µLC-ICP-MS and electrospray time of flight tandem mass spectrometry (ESI-QqTOF-MS/MS were used to identify the two arsenic peaks by comparison to several characterized arsenicals: arsenocholine, AC; trimethyl arsine oxide, TMAO; dimethylarsenoacetate, DMAA; dimethylarsenoethanol, DMAE; thio-dimethylarsinate, thio-DMA; thio-dimethylarsenoacetate, thio-DMAA and thio-dimethylarsenoethanol, thio-DMAE. The results from both the ICP-MS and ESI-QqTOF-MS/MS investigations indicate that the unexpected arsenic species termed peak 1 was thio-DMA. While the unexpected arsenic species termed peak 2 has yet to be identified, this investigation shows that it was not AC, TMAO, DMAA, DMAE, thio-DMA, thio-DMAA or thio-DMAE. This study demonstrates the incidence of unexpected arsenic species in both routine and non-routine urine samples from both workers and hospital patients.

Modulation of band gap by an applied electric field in BN-based heterostructures

Science.gov (United States)

Luo, M.; Xu, Y. E.; Zhang, Q. X.

2018-05-01

First-principles density functional theory (DFT) calculations are performed on the structural and electronic properties of the SiC/BN van der Waals (vdW) heterostructures under an external electric field (E-field). Our results reveal that the SiC/BN vdW heterostructure has a direct band gap of 2.41 eV in the raw. The results also imply that electrons are likely to transfer from BN to SiC monolayer due to the deeper potential of BN monolayer. It is also observed that, by applying an E-field, ranging from -0.50 to +0.65 V/Å, the band gap decreases from 2.41 eV to zero, which presents a parabola-like relationship around 0.0 V/Å. Through partial density of states (PDOS) plots, it is revealed that, p orbital of Si, C, B, and N atoms are responsible for the significant variations of band gap. These obtained results predict that, the electric field tunable band gap of the SiC/BN vdW heterostructures carries potential applications for nanoelectronics and spintronic device applications.

Prolonged labour associated with lower expression of syndecan 3 and connexin 43 in human uterine tissue

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Malmström Anders

2006-05-01

Full Text Available Abstract Background Prolonged labour is associated with greater morbidity and mortality for mother and child. Connexin 43 is a major myometrial gap junction protein found in human myometrium. Syndecan 3 seems to prevail in the human uterus among heparan sulphate proteoglycans, showing the most significant increase during labour. The aims of the present study were to investigate syndecan 3 and connexin 43 mRNA expressions and protein distributions in human uterine tissue during normal and prolonged labour. Methods Uterine isthmic biopsies were collected from non-pregnant (n = 7, term pregnant women not in labour (n = 14, in normal labour (n = 7 and in prolonged labour (n = 7. mRNA levels of syndecan 3 and connexin 43 were determined by real time RT-PCR. The localization and expression were demonstrated by immunohistochemistry and confocal microscopy. Results In women with prolonged labour, the mRNA expressions of syndecan 3 and Connexin 43 were considerably lower than the expression level at normal labour (p Conclusion The high expression of syndecan 3 and connexin 43 and their co-localization to the smooth muscle bundles during normal labour, together with the significant reduction in prolonged labour, may indicate a role for these proteins in the co-ordination of myometrial contractility.

The perceived organizational impact of the gender gap across a Canadian department of medicine and proposed strategies to combat it: a qualitative study.

Science.gov (United States)

Pattani, Reena; Marquez, Christine; Dinyarian, Camellia; Sharma, Malika; Bain, Julie; Moore, Julia E; Straus, Sharon E

2018-04-10

Despite the gender parity existing in medical schools for over three decades, women remain underrepresented in academic medical centers, particularly in senior ranks and in leadership roles. This has consequences for patient care, education, research, and workplace culture within healthcare organizations. This study was undertaken to explore the perspectives of faculty members at a single department of medicine on the impact of the existing gender gap on organizational effectiveness and workplace culture, and to identify systems-based strategies to mitigate the gap. The study took place at a large university department of medicine in Toronto, Canada, with six affiliated hospitals. In this qualitative study, semi-structured individual interviews were conducted between May and September 2016 with full-time faculty members who held clinical and university-based appointments. Transcripts of the interviews were analyzed using thematic analysis. Three authors independently reviewed the transcripts to determine a preliminary list of codes and establish a coding framework. A modified audit consensus coding approach was applied; a single analyst reviewed all the transcripts and a second analyst audited 20% of the transcripts in each round of coding. Following each round, inter-rater reliability was determined, discrepancies were resolved through discussion, and modifications were made as needed to the coding framework. The analysis revealed faculty members' perceptions of the gender gap, potential contributing factors, organizational impacts, and possible solutions to bridge the gap. Of the 43 full-time faculty members who participated in the survey (29 of whom self-identified as female), most participants were aware of the existing gender gap within academic medicine. Participants described social exclusion, reinforced stereotypes, and unprofessional behaviors as consequences of the gap on organizational effectiveness and culture. They suggested improvements in (1) the

School Administrators' Perceptions of the Achievement Gap between African American Students and White Students

Science.gov (United States)

Royle, Jonathan; Brown, Casey Graham

2014-01-01

This study included an analysis of principal perceptions of the achievement gap between African American and White students. School administrators from campuses with a substantial number of African American students within the subgroup were interviewed to explore their perceptions of the achievement gap. The study revealed factors within the…

Dynamic Maternal Gradients Control Timing and Shift-Rates for Drosophila Gap Gene Expression

Science.gov (United States)

Verd, Berta; Crombach, Anton

2017-01-01

Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory

Kinetics-Driven Superconducting Gap in Underdoped Cuprate Superconductors Within the Strong-Coupling Limit

Directory of Open Access Journals (Sweden)

Yucel Yildirim

2011-09-01

Full Text Available A generic theory of the quasiparticle superconducting gap in underdoped cuprates is derived in the strong-coupling limit, and found to describe the experimental “second gap” in absolute scale. In drastic contrast to the standard pairing gap associated with Bogoliubov quasiparticle excitations, the quasiparticle gap is shown to originate from anomalous kinetic (scattering processes, with a size unrelated to the pairing strength. Consequently, the k dependence of the gap deviates significantly from the pure d_{x^{2}-y^{2}} wave of the order parameter. Our study reveals a new paradigm for the nature of the superconducting gap, and is expected to reconcile numerous apparent contradictions among existing experiments and point toward a more coherent understanding of high-temperature superconductivity.

Gap Resolution

Energy Technology Data Exchange (ETDEWEB)

2017-04-25

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

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain

Science.gov (United States)

Pacheco-Costa, Rafael; Davis, Hannah M.; Sorenson, Chad; Hon, Mary C.; Hassan, Iraj; Reginato, Rejane D.; Allen, Matthew R.; Bellido, Teresita; Plotkin, Lilian I.

2015-01-01

Connexin43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43ΔCT/fl) were studied. Cx43ΔCT/fl mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43fl/fl controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43ΔCT is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43ΔCT mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43ΔCT were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. PMID:26409319

Modeling Plasma Formation in a Micro-gap at Microwave Frequency

Science.gov (United States)

Bowman, Arthur; Remillard, Stephen

2013-03-01

In the presence of a strong electric field, gas molecules become ionized, forming a plasma. The study of this dielectric breakdown at microwave frequency has important applications in improving the operation of radio frequency (RF) devices, where the high electric fields present in small gaps can easily ionize gases like air. A cone and tuner resonant structure was used to induce breakdown of diatomic Nitrogen in adjustable micro-gaps ranging from 13 to 1,156 μm. The electric field for plasma formation exhibited strong pressure dependence in the larger gap sizes, as predicted by previous theoretical and experimental work. Pressure is proportional to the frequency of collision between electrons and molecules, which increases with pressure when the gap is large, but levels off in the micro-gap region. A separate model of the breakdown electric field based on the characteristic diffusion length of the plasma also fit the data poorly for these smaller gap sizes. This may be explained by a hypothesis that dielectric breakdown at and below the 100 μm gap size occurs outside the gap, an argument that is supported by the observation of very high breakdown threshold electric fields in this region. Optical emissions revealed that vibrational and rotational molecular transitions of the first positive electronic system are suppressed in micro-gaps, indicating that transitions into the molecular ground state do not occur in micro-gap plasmas. Acknowledgements: National Science Foundation under NSF-REU Grant No. PHY/DMR-1004811, the Provost's Office of Hope College, and the Hope College Division of Natural and Applied Sciences.

Dealing with unexpected events : efficient and safe solutions to emergent repair on NPP

Energy Technology Data Exchange (ETDEWEB)

Liekens Massazza, I.

2015-07-01

Nuclear Facilities are constantly challenged with unexpected events occurring on Primary Circuit components. A solution must be deployed quickly to minimize impact on the scheduled outage duration while guaranteeing safety, quality and ALARA standards. AREVA NP has demonstrated worldwide recognized capabilities and expertise through efficient management of various unexpected forced events through the time. Turnkey packaged solutions which are proposed are based on proven technics which can be quickly adapted and qualified to the specific problem, resulting in customers’ full satisfaction. (Author)

Gastric Adenomyoma: The Unexpected Mimicker

Directory of Open Access Journals (Sweden)

Marcela Adriana Duran Álvarez

2017-01-01

Full Text Available Gastric adenomyoma is a rare benign tumor composed of epithelial structures and smooth muscle stroma. Here, we report an unusual case of gastric adenomyoma mostly composed of smooth muscle that was incidentally found during a laparoscopic intervention. On radiology, it mimicked an acquired hypertrophic pyloric stenosis in an adult patient, and pathologically it resembled a pure smooth muscle hamartoma. Complete submission of the lesion for histology was necessary to find the epithelial component and make the right diagnosis. As a mimicker of benign and malignant entities, gastric adenomyoma is usually an unexpected finding after surgery. The aim of this report is to analyze this adenomyoma variant in the setting of an unexplained thickening of the gastric wall, with explanations concerning histogenesis and biological potential.

43 CFR 43.230 - How and when must I identify workplaces?

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false How and when must I identify workplaces? 43.230 Section 43.230 Public Lands: Interior Office of the Secretary of the Interior GOVERNMENTWIDE... operation, State employees in each local unemployment office, performers in concert halls or radio studios...

The disengagement of visual attention in the gap paradigm across adolescence.

Science.gov (United States)

Van der Stigchel, S; Hessels, R S; van Elst, J C; Kemner, C

2017-12-01

Attentional disengagement is important for successful interaction with our environment. The efficiency of attentional disengagement is commonly assessed using the gap paradigm. There is, however, a sharp contrast between the number of studies applying the gap paradigm to clinical populations and the knowledge about the underlying developmental trajectory of the gap effect. The aim of the present study was, therefore, to investigate attentional disengagement in a group of children aged 9-15. Besides the typically deployed gap and the overlap conditions, we also added a baseline condition in which the fixation point was removed at the moment that the target appeared. This allowed us to reveal the appropriate experimental conditions to unravel possible developmental differences. Correlational analyses showed that the size of the gap effect became smaller with increasing age, but only for the difference between the gap and the overlap conditions. This shows that there is a gradual increase in the capacity to disengage visual attention with increasing age, but that this effect only becomes apparent when the gap and the overlap conditions are compared. The gradual decrease of the gap effect with increasing age provides additional evidence that the attentional system becomes more efficient with increasing age and that this is a gradual process.

Photoelectron emission yield experiments on evolution of sub-gap states in amorphous In-Ga-Zn-O thin films with post deposition hydrogen treatment

International Nuclear Information System (INIS)

Hayashi, Kazushi; Hino, Aya; Tao, Hiroaki; Ochi, Mototaka; Goto, Hiroshi; Kugimiya, Toshihiro

2015-01-01

Total photoyield emission spectroscopy (TPYS) was applied to study the evolution of sub-gap states in hydrogen-treated amorphous In-Ga-Zn-O (a-IGZO) thin films. The a-IGZO thin films were subjected to hydrogen radicals and subsequently annealed in ultra-high vacuum (UHV) conditions. A clear onset of the electron emission was observed at around 4.3 eV from the hydrogen-treated a-IGZO thin films. After successive UHV annealing at 300 °C, the onset in the TPYS spectra was shifted to 4.15 eV, and the photoelectron emission from the sub-gap states was decreased as the annealing temperature was increased. In conjunction with the results of thermal desorption spectrometer, it was deduced that the hydrogen atoms incorporated in the a-IGZO thin films induced metastable sub-gap states at around 4.3 eV from vacuum level just after the hydrogenation. It was also suggested that the defect configuration was changed due to the higher temperature UHV annealing, and that the hydrogen atoms desorbed with the involvement of Zn atoms. These experiments produced direct evidence to show the formation of sub-gap states as a result of hydrogen incorporation into the a-IGZO thin films

Photoelectron emission yield experiments on evolution of sub-gap states in amorphous In-Ga-Zn-O thin films with post deposition hydrogen treatment

Energy Technology Data Exchange (ETDEWEB)

Hayashi, Kazushi, E-mail: hayashi.kazushi@kobelco.com; Hino, Aya; Tao, Hiroaki; Ochi, Mototaka; Goto, Hiroshi; Kugimiya, Toshihiro [Electronics Research Laboratory, Kobe Steel, Ltd., 1-5-5 Takatsuka-dai, Nishi-ku, Kobe 651-2271 (Japan)

2015-09-14

Total photoyield emission spectroscopy (TPYS) was applied to study the evolution of sub-gap states in hydrogen-treated amorphous In-Ga-Zn-O (a-IGZO) thin films. The a-IGZO thin films were subjected to hydrogen radicals and subsequently annealed in ultra-high vacuum (UHV) conditions. A clear onset of the electron emission was observed at around 4.3 eV from the hydrogen-treated a-IGZO thin films. After successive UHV annealing at 300 °C, the onset in the TPYS spectra was shifted to 4.15 eV, and the photoelectron emission from the sub-gap states was decreased as the annealing temperature was increased. In conjunction with the results of thermal desorption spectrometer, it was deduced that the hydrogen atoms incorporated in the a-IGZO thin films induced metastable sub-gap states at around 4.3 eV from vacuum level just after the hydrogenation. It was also suggested that the defect configuration was changed due to the higher temperature UHV annealing, and that the hydrogen atoms desorbed with the involvement of Zn atoms. These experiments produced direct evidence to show the formation of sub-gap states as a result of hydrogen incorporation into the a-IGZO thin films.

Effects of Muscle Fatigue, Creep, and Musculoskeletal Pain on Neuromuscular Responses to Unexpected Perturbation of the Trunk: A Systematic Review.

Science.gov (United States)

Abboud, Jacques; Lardon, Arnaud; Boivin, Frédéric; Dugas, Claude; Descarreaux, Martin

2016-01-01

Introduction: Trunk neuromuscular responses have been shown to adapt under the influence of muscle fatigue, as well as spinal tissue creep or even with the presence of low back pain (LBP). Despite a large number of studies exploring how these external perturbations affect the spinal stability, characteristics of such adaptations remains unclear. Aim: The purpose of this systematic review was to assess the quality of evidence of studies investigating trunk neuromuscular responses to unexpected trunk perturbation. More specifically, the targeted neuromuscular responses were trunk muscle activity reflex and trunk kinematics under the influence of muscle fatigue, spinal creep, and musculoskeletal pain. Methods: A research of the literature was conducted in Pubmed, Embase, and Sport-Discus databases using terms related to trunk neuromuscular reflex responses, measured by electromyography (baseline activity, reflex latency, and reflex amplitude) and/or trunk kinematic, in context of unexpected external perturbation. Moreover, independent variables must be either trunk muscle fatigue or spinal tissue creep or LBP. All included articles were scored for their electromyography methodology based on the "Surface Electromyography for the Non-Invasive Assessment of Muscles (SENIAM)" and the "International Society of Electrophysiology and Kinesiology (ISEK)" recommendations whereas overall quality of articles was scored using a specific quality checklist modified from the Quality Index. Meta-analysis was performed on reflex latency variable. Results: A final set of 29 articles underwent quality assessments. The mean quality score was 79%. No effect of muscle fatigue on erector spinae reflex latency following an unexpected perturbation, nor any other distinctive effects was found for back muscle fatigue and reflex parameters. As for spinal tissue creep effects, no alteration was found for any of the trunk reflex variables. Finally, the meta-analysis revealed an increased erector

Proteome analysis of a Lactococcus lactis strain overexpressing gapA suggests that the gene product is an auxiliary glyceraldehyde 3-phosphate dehydrogenase

DEFF Research Database (Denmark)

Willemoes, Martin; Kilstrup, Mogens; Roepstorff, P.

2002-01-01

revealed two neighbouring protein spots, GapBI and GapBII, with amino terminal sequences identical to the product of gapA from the L. lactis subspecies cremoris strain LM0230 and that of the two IL1403 sequences. In order to assign the two protein spots to their respective genes we constructed an L. lactis...... was specific for NAD. No NADP dependent activity was detected. Proteome analysis of the gapA overexpressing strain revealed two new protein spots, GapAI and GapAII, not previously detected in proteome analysis of MG1363. Results from mass spectrometry analysis of GapA and GapB and comparison with the deduced......The sequence of the genome from the Lactococcus lactis subspecies lactis strain IL1403 shows the presence of two reading frames, gapA and gapB, putatively encoding glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Previous proteomic analysis of the L. lactis subspecies cremoris strain MG1363 has...

Communication of Unexpected and Significant Findings on Chest Radiographs With an Automated PACS Alert System.

LENUS (Irish Health Repository)

Hayes, Sara A

2014-08-01

An integral part of realizing the enormous potential of imaging in patient care is close communication between radiologists and referring physicians. One key element of this process is the communication of unexpected significant findings. The authors examined the performance of a PACS-based alert system in the appropriate communication of reports containing unexpected significant findings to referring physicians.

Have Gender Gaps in Math Closed? Achievement, Teacher Perceptions, and Learning Behaviors across Two ECLS-K Cohorts

Science.gov (United States)

Cimpian, Joseph R.; Lubienski, Sarah T.; Timmer, Jennifer D.; Makowski, Martha B.; Miller, Emily K.

2016-01-01

Studies using data from the Early Childhood Longitudinal Study-Kindergarten Class of 1998-1999 (ECLS-K:1999) revealed gender gaps in mathematics achievement and teacher perceptions. However, recent evidence suggests that gender gaps have closed on state tests, raising the question of whether such gaps are absent in the ECLS-K:2011 cohort.…

Mitochondrial DNA reveals unexpected diversity of chubs (genus Squalius; Cypriniformes, Actinopterygii in the Adriatic basin

Directory of Open Access Journals (Sweden)

Ivana Buj

2015-12-01

Full Text Available The genus Squalius comprises more than 40 species inhabiting various freshwater habitats. They are distributed in Europe and Asia, with particularly high diversity recorded in the Mediterranean area. The taxonomic status of many populations is still matter of debate. With this investigation we aimed to help in resolving taxonomic uncertainties of the chubs distributed in the Adriatic basin in Croatia and Bosnia and Herzegovina. Phylogenetic reconstruction based on mitochondrial gene for cytochrome b revealed high diversity of chubs in the investigated area. Two evolutionary independent lineages are revealed: the first one comprising species Sq. svallize, Sq. tenellus, Sq. illyricus and Sq. zrmanjae; whereas the second lineage corresponds with Sq. squalus. High intraspecific structuring of Sq. squalus was detected, implying necessity of taxonomic revision of that species. Based on the obtained results, most important aspects of the evolutionary history of the genus Squalius in the Adriatic basin will be discussed and evolutionary significant units identified.

Development of Multidimensional Gap Conductance model using Virtual Link Gap Element

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyo Chan; Yang, Yong Sik; Kim, Dae Ho; Bang, Je Geon; Kim, Sun Ki; Koo, Yang Hyun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-10-15

The gap conductance that determines temperature gradient between pellet and cladding can be quite sensitive to gap thickness. For instance, once the gap size increases up to several micrometers in certain region, difference of pellet surface temperatures increases up to 100 Kelvin. Therefore, iterative thermo-mechanical coupled analysis is required to solve temperature distribution throughout pellet and cladding. Recently, multidimensional fuel performance codes have been being developed in the advanced countries to evaluate thermal behavior of fuel for off normal conditions and DBA(design based accident) conditions using the Finite Element Method (FEM). FRAPCON-FRAPTRAN code system, which is well known as the verified and reliable code, incorporates 1D thermal module and multidimensional mechanical module. In this code, multidimensional gap conductance model is not applied. ALCYONE developed by CEA introduces equivalent heat convection coefficient that represents multidimensional gap conductance as a function of gap thickness. BISON, which is multidimensional fuel performance code developed by INL, owns multidimensional gap conductance model using projected thermal contact. In general, thermal contact algorithm is nonlinear calculation which is expensive approach numerically. The gap conductance model for multi-dimension is difficult issue in terms of convergence and nonlinearity because gap conductance is function of gap thickness which depends on mechanical analysis at each iteration step. In this paper, virtual link gap (VLG) element has been proposed to resolve convergence issue and nonlinear characteristic of multidimensional gap conductance. In terms of calculation accuracy and convergence efficiency, the proposed VLG model was evaluated. LWR fuel performance codes should incorporate thermo-mechanical loop to solve gap conductance problem, iteratively. However, gap conductance in multidimensional model is difficult issue owing to its nonlinearity and

The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting of GPCRs

Directory of Open Access Journals (Sweden)

Chunman Li

2017-10-01

Full Text Available G-protein-coupled receptors (GPCRs constitute the largest superfamily of cell-surface signaling proteins. However, mechanisms underlying their surface targeting and sorting are poorly understood. Here, we screen the Rab family of small GTPases in the surface transport of multiple GPCRs. We find that manipulation of Rab43 function significantly alters the surface presentation and signaling of all GPCRs studied without affecting non-GPCR membrane proteins. Rab43 specifically regulates the transport of nascent GPCRs from the endoplasmic reticulum (ER to the Golgi. More interestingly, Rab43 directly interacts with GPCRs in an activation-dependent fashion. The Rab43-binding domain identified in the receptors effectively converts non-GPCR membrane protein transport into a Rab43-dependent pathway. These data reveal a crucial role for Rab43 in anterograde ER-Golgi transport of nascent GPCRs, as well as the ER sorting of GPCR members by virtue of its ability to interact directly.

Disruption of the Cx43/miR21 pathway leads to osteocyte apoptosis and increased osteoclastogenesis with aging.

Science.gov (United States)

Davis, Hannah M; Pacheco-Costa, Rafael; Atkinson, Emily G; Brun, Lucas R; Gortazar, Arancha R; Harris, Julia; Hiasa, Masahiro; Bolarinwa, Surajudeen A; Yoneda, Toshiyuki; Ivan, Mircea; Bruzzaniti, Angela; Bellido, Teresita; Plotkin, Lilian I

2017-06-01

Skeletal aging results in apoptosis of osteocytes, cells embedded in bone that control the generation/function of bone forming and resorbing cells. Aging also decreases connexin43 (Cx43) expression in bone; and osteocytic Cx43 deletion partially mimics the skeletal phenotype of old mice. Particularly, aging and Cx43 deletion increase osteocyte apoptosis, and osteoclast number and bone resorption on endocortical bone surfaces. We examined herein the molecular signaling events responsible for osteocyte apoptosis and osteoclast recruitment triggered by aging and Cx43 deficiency. Cx43-silenced MLO-Y4 osteocytic (Cx43 def ) cells undergo spontaneous cell death in culture through caspase-3 activation and exhibit increased levels of apoptosis-related genes, and only transfection of Cx43 constructs able to form gap junction channels reverses Cx43 def cell death. Cx43 def cells and bones from old mice exhibit reduced levels of the pro-survival microRNA miR21 and, consistently, increased levels of the miR21 target phosphatase and tensin homolog (PTEN) and reduced phosphorylated Akt, whereas PTEN inhibition reduces Cx43 def cell apoptosis. miR21 reduction is sufficient to induce apoptosis of Cx43-expressing cells and miR21 deletion in miR21 fl/fl bones increases apoptosis-related gene expression, whereas a miR21 mimic prevents Cx43 def cell apoptosis, demonstrating that miR21 lies downstream of Cx43. Cx43 def cells release more osteoclastogenic cytokines [receptor activator of NFκB ligand (RANKL)/high-mobility group box-1 (HMGB1)], and caspase-3 inhibition prevents RANKL/HMGB1 release and the increased osteoclastogenesis induced by conditioned media from Cx43 def cells, which is blocked by antagonizing HMGB1-RAGE interaction. These findings identify a novel Cx43/miR21/HMGB1/RANKL pathway involved in preventing osteocyte apoptosis that also controls osteoclast formation/recruitment and is impaired with aging. © 2017 The Authors. Aging Cell published by the Anatomical Society

Multifaceted Roles of Connexin 43 in Stem Cell Niches.

Science.gov (United States)

Genet, Nafiisha; Bhatt, Neha; Bourdieu, Antonin; Hirschi, Karen K

2018-01-01

Considerable progress has been made in the field of stem cell research; nonetheless, the use of stem cells for regenerative medicine therapies, for either endogenous tissue repair or cellular grafts post injury, remains a challenge. To better understand how to maintain stem cell potential in vivo and promote differentiation ex vivo, it is fundamentally important to elucidate the interactions between stem cells and their surrounding partners within their distinct niches. Among the vast array of proteins depicted as mediators for cell-to-cell interactions, connexin-comprised gap junctions play pivotal roles in the regulation of stem cell fate both in vivo and in vitro. This review summarizes and illustrates the current knowledge regarding the multifaceted roles of Cx43, specifically, in various stem cell niches.

Seasonal cycle of volume transport through Kerama Gap revealed by a 20-year global HYbrid Coordinate Ocean Model reanalysis

Science.gov (United States)

2015-11-10

approaching eddies are both important in deter- mining flow direction through Kerama Gap. The preceding results in- dicate the important role of the... topography and its width is only about 50 km. Thus, esolving the transport requires fine horizontal resolution and a ver- ical coordinate system...complex topography that overs the shallow water near Kerama Gap and Okinawa Island, the kinawa trough, slope, and the deep ocean. The data assimilation

A likely planet-induced gap in the disc around T Cha

Science.gov (United States)

Hendler, Nathanial P.; Pinilla, Paola; Pascucci, Ilaria; Pohl, Adriana; Mulders, Gijs; Henning, Thomas; Dong, Ruobing; Clarke, Cathie; Owen, James; Hollenbach, David

2018-03-01

We present high-resolution (0.11 × 0.06 arcsec2) 3 mm ALMA observations of the highly inclined transition disc around the star T Cha. Our continuum image reveals multiple dust structures: an inner disc, a spatially resolved dust gap, and an outer ring. When fitting sky-brightness models to the real component of the 3 mm visibilities, we infer that the inner emission is compact (≤1 au in radius), the gap width is between 18 and 28 au, and the emission from the outer ring peaks at ˜36 au. We compare our ALMA image with previously published 1.6 μm VLT/SPHERE imagery. This comparison reveals that the location of the outer ring is wavelength dependent. More specifically, the peak emission of the 3 mm ring is at a larger radial distance than that of the 1.6 μm ring, suggesting that millimeter-sized grains in the outer disc are located farther away from the central star than micron-sized grains. We discuss different scenarios to explain our findings, including dead zones, star-driven photoevaporation, and planet-disc interactions. We find that the most likely origin of the dust gap is from an embedded planet, and estimate - for a single planet scenario - that T Cha's gap is carved by a 1.2MJup planet.

Many unexpected abdominal findings on staging computed tomography in patients with colorectal cancer

DEFF Research Database (Denmark)

Holmsted, Kim; Nørring, Keld; Laustrup, Lene Collatz

2011-01-01

; an issue that was previously studied in relation to CT colonography, but not in relation to staging CT with intravenous contrast in CRC patients. The aim of the present study was to evaluate the number and significance of such unexpected findings on staging CTs in CRC patients.......Computed tomography (CT) was proven to be superior to preoperative abdominal ultrasound in the preoperative setting for detection of hepatic metastases from colorectal cancer (CRC). The higher sensitivity of CT has resulted in a number of unexpected abdominal findings of varying importance...

Unexpected nitrile formation in bio-based mesoporous materials (Starbons®).

Science.gov (United States)

Attard, Jennifer; Milescu, Roxana; Budarin, Vitaliy; Matharu, Avtar S; Clark, James H

2018-01-16

The bio-based mesoporous materials made from polysaccharides, Starbons® can be modified by two different routes to give high levels of N-content, unexpectedly including significant quantities of nitrile groups which can improve the materials performance in applications including metal capture.

Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their maturation.

Directory of Open Access Journals (Sweden)

Maria Vittoria Barone

Full Text Available BACKGROUND: Celiac Disease (CD is both a frequent disease (1:100 and an interesting model of a disease induced by food. It consists in an immunogenic reaction to wheat gluten and glutenins that has been found to arise in a specific genetic background; however, this reaction is still only partially understood. Activation of innate immunity by gliadin peptides is an important component of the early events of the disease. In particular the so-called "toxic" A-gliadin peptide P31-43 induces several pleiotropic effects including Epidermal Growth Factor Receptor (EGFR-dependent actin remodelling and proliferation in cultured cell lines and in enterocytes from CD patients. These effects are mediated by delayed EGFR degradation and prolonged EGFR activation in endocytic vesicles. In the present study we investigated the effects of gliadin peptides on the trafficking and maturation of endocytic vesicles. METHODS/PRINCIPAL FINDINGS: Both P31-43 and the control P57-68 peptide labelled with fluorochromes were found to enter CaCo-2 cells and interact with the endocytic compartment in pulse and chase, time-lapse, experiments. P31-43 was localised to vesicles carrying early endocytic markers at time points when P57-68-carrying vesicles mature into late endosomes. In time-lapse experiments the trafficking of P31-43-labelled vesicles was delayed, regardless of the cargo they were carrying. Furthermore in celiac enterocytes, from cultured duodenal biopsies, P31-43 trafficking is delayed in early endocytic vesicles. A sequence similarity search revealed that P31-43 is strikingly similar to Hrs, a key molecule regulating endocytic maturation. A-gliadin peptide P31-43 interfered with Hrs correct localisation to early endosomes as revealed by western blot and immunofluorescence microscopy. CONCLUSIONS: P31-43 and P57-68 enter cells by endocytosis. Only P31-43 localises at the endocytic membranes and delays vesicle trafficking by interfering with Hrs

Endocranial Casts of Pre-Mammalian Therapsids Reveal an Unexpected Neurological Diversity at the Deep Evolutionary Root of Mammals.

Science.gov (United States)

Benoit, Julien; Fernandez, Vincent; Manger, Paul R; Rubidge, Bruce S

2017-01-01

The origin and evolution of the mammalian brain has long been the focus of scientific enquiry. Conversely, little research has focused on the palaeoneurology of the stem group of Mammaliaformes, the Permian and Triassic non-mammaliaform Therapsida (NMT). This is because the majority of the NMT have a non-ossified braincase, making the study of their endocranial cast (sometimes called the "fossil brain") problematic. Thus, descriptions of the morphology and size of NMT endocranial casts have been based largely on approximations rather than reliable determination. Accordingly, here we use micro-CT scans of the skulls of 1 Dinocephalia and 3 Biarmosuchia, which are NMT with a fully ossified braincase and thus a complete endocast. For the first time, our work enables the accurate determination of endocranial shape and size in NMT. This study suggests that NMT brain size falls in the upper range of the reptilian and amphibian variation. Brain size in the dicynodont Kawingasaurus is equivalent to that of early Mammaliaformes, whereas the Dinocephalia show evidence of a secondary reduction of brain size. In addition, unlike other NMT in which the endocast has a tubular shape and its parts are arranged in a linear manner, the biarmosuchian endocast is strongly flexed at the level of the midbrain, creating a near right angle between the fore- and hindbrain. These data highlight an unexpected diversity of endocranial size and morphology in NMT, features that are usually considered conservative in this group. © 2017 S. Karger AG, Basel.

TDP-43 causes differential pathology in neuronal versus glial cells in the mouse brain.

Science.gov (United States)

Yan, Sen; Wang, Chuan-En; Wei, Wenjie; Gaertig, Marta A; Lai, Liangxue; Li, Shihua; Li, Xiao-Jiang

2014-05-15

Mutations in TAR DNA-binding protein 43 (TDP-43) are associated with familial forms of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Although recent studies have revealed that mutant TDP-43 in neuronal and glial cells is toxic, how mutant TDP-43 causes primarily neuronal degeneration in an age-dependent manner remains unclear. Using adeno-associated virus (AAV) that expresses mutant TDP-43 (M337V) ubiquitously, we found that mutant TDP-43 accumulates preferentially in neuronal cells in the postnatal mouse brain. We then ubiquitously or selectively expressed mutant TDP-43 in neuronal and glial cells in the striatum of adult mouse brains via stereotaxic injection of AAV vectors and found that it also preferentially accumulates in neuronal cells. Expression of mutant TDP-43 in neurons in the striatum causes more severe degeneration, earlier death and more robust symptoms in mice than expression of mutant TDP-43 in glial cells; however, aging increases the expression of mutant TDP-43 in glial cells, and expression of mutant TDP-43 in older mice caused earlier onset of phenotypes and more severe neuropathology than that in younger mice. Although expression of mutant TDP-43 in glial cells via stereotaxic injection does not lead to robust neurological phenotypes, systemic inhibition of the proteasome activity via MG132 in postnatal mice could exacerbate glial TDP-43-mediated toxicity and cause mice to die earlier. Consistently, this inhibition increases the expression of mutant TDP-43 in glial cells in mouse brains. Thus, the differential accumulation of mutant TDP-43 in neuronal versus glial cells contributes to the preferential toxicity of mutant TDP-43 in neuronal cells and age-dependent pathology.

Assessing Emphasis Gaps among MBA Alumni: A Model Framework

Science.gov (United States)

Van Auken, Stuart; Chrysler, Earl; Wells, Ludmilla Gricenko

2016-01-01

Purpose: This paper aims to focus on Master of Business Administration (MBA) alumni and their ability to provide institution-specific insights into MBA program delivery. Given desired MBA positioning dimensions, a case exemplar is used to reveal gaps between "should have" program emphases and "actual" emphases. Departures from…

Polytypism and unexpected strong interlayer coupling in two-dimensional layered ReS2

Science.gov (United States)

Qiao, Xiao-Fen; Wu, Jiang-Bin; Zhou, Linwei; Qiao, Jingsi; Shi, Wei; Chen, Tao; Zhang, Xin; Zhang, Jun; Ji, Wei; Tan, Ping-Heng

2016-04-01

Anisotropic two-dimensional (2D) van der Waals (vdW) layered materials, with both scientific interest and application potential, offer one more dimension than isotropic 2D materials to tune their physical properties. Various physical properties of 2D multi-layer materials are modulated by varying their stacking orders owing to significant interlayer vdW coupling. Multilayer rhenium disulfide (ReS2), a representative anisotropic 2D material, was expected to be randomly stacked and lack interlayer coupling. Here, we demonstrate two stable stacking orders, namely isotropic-like (IS) and anisotropic-like (AI) N layer (NL, N > 1) ReS2 are revealed by ultralow- and high-frequency Raman spectroscopy, photoluminescence and first-principles density functional theory calculation. Two interlayer shear modes are observed in AI-NL-ReS2 while only one shear mode appears in IS-NL-ReS2, suggesting anisotropic- and isotropic-like stacking orders in IS- and AI-NL-ReS2, respectively. This explicit difference in the observed frequencies identifies an unexpected strong interlayer coupling in IS- and AI-NL-ReS2. Quantitatively, the force constants of them are found to be around 55-90% of those of multilayer MoS2. The revealed strong interlayer coupling and polytypism in multi-layer ReS2 may stimulate future studies on engineering physical properties of other anisotropic 2D materials by stacking orders.Anisotropic two-dimensional (2D) van der Waals (vdW) layered materials, with both scientific interest and application potential, offer one more dimension than isotropic 2D materials to tune their physical properties. Various physical properties of 2D multi-layer materials are modulated by varying their stacking orders owing to significant interlayer vdW coupling. Multilayer rhenium disulfide (ReS2), a representative anisotropic 2D material, was expected to be randomly stacked and lack interlayer coupling. Here, we demonstrate two stable stacking orders, namely isotropic-like (IS) and

Arctic driftwood reveals unexpectedly rich fungal diversity

Czech Academy of Sciences Publication Activity Database

Blanchette, R.A.; Held, B.W.; Hellmann, L.; Millman, L.; Büntgen, Ulf

2016-01-01

Roč. 23, OCT (2016), s. 58-65 ISSN 1754-5048 R&D Projects: GA MŠk(CZ) EE2.3.20.0248 Institutional support: RVO:67179843 Keywords : Ascomycota * Basidiomycota * Biodegradation * Community ecology * Greenland * Iceland * its * Russia * Soft rot * Taxonomy * Wood decay Subject RIV: EH - Ecology, Behaviour Impact factor: 3.219, year: 2016

KNOWLEDGE GAPS IN ORAL AND MAXILLOFACIAL SURGERY

DEFF Research Database (Denmark)

Österberg, Marie; Holmlund, Anders; Sunzel, Bo

2017-01-01

OBJECTIVES: The aim of this study was to evaluate available knowledge and identify knowledge gaps within the field of oral and maxillofacial surgery, by systematically collecting and evaluating systematic reviews. Twelve specific domains were selected: surgical removal of teeth, antibiotic....... However, in all domains, the search revealed a large number of knowledge gaps. Also of concern was the lack of data regarding health economics and ethics. CONCLUSIONS: In conclusion, there is a need for well-conducted clinical research in the fields of oral and maxillofacial surgery........ RESULTS: In all, 1,778 abstracts were identified, of which 200 met the inclusion criteria. Forty-five systematic reviews were assessed as of high to moderate quality. The results disclosed some existing evidence in a few domains, such as surgical removal of teeth and implant survival after sinus lifts...

Unexpected sneezing after a peribulbar injection in a patient for ...

African Journals Online (AJOL)

... anaesthetic in awake patients. We present a case report of an awake elderly male who experienced unexpected continuous sneezing immediately after the removal of the needle used for the peribulbar block, which was subsequently relieved with pheniramine maleate. Keywords: peribulbar block, pheniramine maleate, ...

Fatal invasive aspergillosis: a rare co-infection with an unexpected image presentation in a patient with dengue shock syndrome.

Science.gov (United States)

Wang, Hui-Ching; Chang, Ko; Lu, Po-Liang; Tsai, Kun-Bow; Chen, Huang-Chi

2017-03-01

Pulmonary infiltration and pleural effusion caused by permeability syndrome are the hallmark of pulmonary manifestation of dengue cases. We report a 95-year-old chronic obstructive pulmonary disease case having dengue shock syndrome. Chest X-ray examination revealed diffuse lung infiltration. However, bilateral pneumotoceles were unexpectedly found in computed tomography (CT) images. Dengue virus type 2 infection was confirmed by virus culture, serology and reverse transcriptase-polymerase chain reaction. Profound shock with bilateral lung infiltration developed rapidly in 2 days with supportive care and empirical ampicillin/ sulbactam. Bronchoscopy revealed a whitish plaque over bilateral upper bronchi. Biopsy via bronchoscopy revealed moulds with vascular invasion. Culture of bronchial alveolar lavage yielded Aspergillus flavus. The patient died despite amphotericin B treatment, which was started since finding the whitish plaque with bronchoscopy examination. Besides to considering capillary leakage syndrome, our case report and literature review alert clinicians that CT and bronchoscopy may help to identify the true pathogen though all cases with concurrent dengue and Aspergillus infections had fatal outcomes. © 2015 John Wiley & Sons Ltd.

Closing the Gender Gap: Improved Performance of U.S.-Born Females on the National Assessment of Adult Literacy

Science.gov (United States)

Cohen, Dale J.; White, Sheida; Cohen, Steffaney B.

2012-01-01

This study analyzed the current state of the gender literacy gap and the change in the gender literacy gap between 1992 and 2003, using the 1992 National Adult Literacy Survey (NALS) and the 2003 National Assessment of Adult Literacy (NAAL). The results revealed that although there were significant gender literacy gaps in 1992, virtually all…

Unexpected inhibition of CO₂ gas hydrate formation in dilute TBAB solutions and the critical role of interfacial water structure

Energy Technology Data Exchange (ETDEWEB)

Nguyen, Ngoc N.; Nguyen, Anh V.; Nguyen, Khoi T.; Rintoul, Llew; Dang, Liem X.

2016-12-01

Gas hydrates formed under moderated conditions open up novel approaches to tackling issues related to energy supply, gas separation, and CO₂ sequestration. Several additives like tetra-n-butylammonium bromide (TBAB) have been empirically developed and used to promote gas hydrate formation. Here we report unexpected experimental results which show that TBAB inhibits CO₂ gas hydrate formation when used at minuscule concentration. We also used spectroscopic techniques and molecular dynamics simulation to gain further insights and explain the experimental results. They have revealed the critical role of water alignment at the gas-water interface induced by surface adsorption of tetra-n-butylammonium cation (TBA⁺) which gives rise to the unexpected inhibition of dilute TBAB solution. The water perturbation by TBA⁺ in the bulk is attributed to the promotion effect of high TBAB concentration on gas hydrate formation. We explain our finding using the concept of activation energy of gas hydrate formation. Our results provide a step toward to mastering the control of gas hydrate formation.

Cardiac Connexin-43 and PKC Signaling in Rats With Altered Thyroid Status Without and With Omega-3 Fatty Acids Intake

Czech Academy of Sciences Publication Activity Database

Szeiffová Bačová, B.; Egan Beňová, T.; Viczenczová, C.; Soukup, Tomáš; Rauchová, Hana; Pavelka, Stanislav; Knezl, V.; Barančík, M.; Tribulová, N.

2016-01-01

Roč. 65, Suppl.1 (2016), S77-S90 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/09/1228; GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : thyroid hormones * cardiac arrhythmias * Connexin-43 * omega-3 polyunsaturated fatty acids Subject RIV: ED - Physiology Impact factor: 1.461, year: 2016

[Research progress of larger flexion gap than extension gap in total knee arthroplasty].

Science.gov (United States)

Zhang, Weisong; Hao, Dingjun

2017-05-01

To summarize the progress of larger flexion gap than extension gap in total knee arthro-plasty (TKA). The domestic and foreign related literature about larger flexion gap than extension gap in TKA, and its impact factors, biomechanical and kinematic features, and clinical results were summarized. During TKA, to adjust the relations of flexion gap and extension gap is one of the key factors of successful operation. The biomechanical, kinematic, and clinical researches show that properly larger flexion gap than extension gap can improve both the postoperative knee range of motion and the satisfaction of patients, but does not affect the stability of the knee joint. However, there are also contrary findings. So adjustment of flexion gap and extension gap during TKA is still in dispute. Larger flexion gap than extension gap in TKA is a new joint space theory, and long-term clinical efficacy, operation skills, and related complications still need further study.

Gap Junctions

Science.gov (United States)

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

2013-01-01

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

Tunable band gaps in bio-inspired periodic composites with nacre-like microstructure

Science.gov (United States)

Chen, Yanyu; Wang, Lifeng

2014-08-01

Periodic composite materials have many promising applications due to their unique ability to control the propagation of waves. Here, we report the existence and frequency tunability of complete elastic wave band gaps in bio-inspired periodic composites with nacre-like, brick-and-mortar microstructure. Numerical results show that complete band gaps in these periodic composites derive from local resonances or Bragg scattering, depending on the lattice angle and the volume fraction of each phase in the composites. The investigation of elastic wave propagation in finite periodic composites validates the simulated complete band gaps and further reveals the mechanisms leading to complete band gaps. Moreover, our results indicate that the topological arrangement of the mineral platelets and changes of material properties can be utilized to tune the evolution of complete band gaps. Our finding provides new opportunities to design mechanically robust periodic composite materials for wave absorption under hostile environments, such as for deep water applications.

Unique C. elegans telomeric overhang structures reveal the evolutionarily conserved properties of telomeric DNA

Czech Academy of Sciences Publication Activity Database

Školáková, Petra; Foldynová-Trantírková, Silvie; Bednářová, Klára; Fiala, R.; Vorlíčková, Michaela; Trantírek, L.

2015-01-01

Roč. 43, č. 9 (2015), s. 4733-4745 ISSN 0305-1048 R&D Projects: GA ČR(CZ) GA13-28310S; GA ČR(CZ) GAP205/12/0466 Institutional support: RVO:68081707 ; RVO:60077344 Keywords : NUCLEASE HYPERSENSITIVE ELEMENT * G-QUADRUPLEX STRUCTURES * I-MOTIF Subject RIV: BO - Biophysics Impact factor: 9.202, year: 2015

TDP-43 inclusion bodies formed in bacteria are structurally amorphous, non-amyloid and inherently toxic to neuroblastoma cells.

Directory of Open Access Journals (Sweden)

Claudia Capitini

Full Text Available Accumulation of ubiquitin-positive, tau- and α-synuclein-negative intracellular inclusions of TDP-43 in the central nervous system represents the major hallmark correlated to amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions. Such inclusions have variably been described as amorphous aggregates or more structured deposits having an amyloid structure. Following the observations that bacterial inclusion bodies generally consist of amyloid aggregates, we have overexpressed full-length TDP-43 and C-terminal TDP-43 in E. coli, purified the resulting full-length and C-terminal TDP-43 containing inclusion bodies (FL and Ct TDP-43 IBs and subjected them to biophysical analyses to assess their structure/morphology. We show that both FL and Ct TDP-43 aggregates contained in the bacterial IBs do not bind amyloid dyes such as thioflavin T and Congo red, possess a disordered secondary structure, as inferred using circular dichroism and infrared spectroscopies, and are susceptible to proteinase K digestion, thus possessing none of the hallmarks for amyloid. Moreover, atomic force microscopy revealed an irregular structure for both types of TDP-43 IBs and confirmed the absence of amyloid-like species after proteinase K treatment. Cell biology experiments showed that FL TDP-43 IBs were able to impair the viability of cultured neuroblastoma cells when added to their extracellular medium and, more markedly, when transfected into their cytosol, where they are at least in part ubiquitinated and phosphorylated. These data reveal an inherently high propensity of TDP-43 to form amorphous aggregates, which possess, however, an inherently high ability to cause cell dysfunction. This indicates that a gain of toxic function caused by TDP-43 deposits is effective in TDP-43 pathologies, in addition to possible loss of function mechanisms originating from the cellular mistrafficking of the protein.

Applying revised gap analysis model in measuring hotel service quality.

Science.gov (United States)

Lee, Yu-Cheng; Wang, Yu-Che; Chien, Chih-Hung; Wu, Chia-Huei; Lu, Shu-Chiung; Tsai, Sang-Bing; Dong, Weiwei

2016-01-01

With the number of tourists coming to Taiwan growing by 10-20 % since 2010, the number has increased due to an increasing number of foreign tourists, particularly after deregulation allowed admitting tourist groups, followed later on by foreign individual tourists, from mainland China. The purpose of this study is to propose a revised gap model to evaluate and improve service quality in Taiwanese hotel industry. Thus, service quality could be clearly measured through gap analysis, which was more effective for offering direction in developing and improving service quality. The HOLSERV instrument was used to identify and analyze service gaps from the perceptions of internal and external customers. The sample for this study included three main categories of respondents: tourists, employees, and managers. The results show that five gaps influenced tourists' evaluations of service quality. In particular, the study revealed that Gap 1 (management perceptions vs. customer expectations) and Gap 9 (service provider perceptions of management perceptions vs. service delivery) were more critical than the others in affecting perceived service quality, making service delivery the main area of improvement. This study contributes toward an evaluation of the service quality of the Taiwanese hotel industry from the perspectives of customers, service providers, and managers, which is considerably valuable for hotel managers. It was the aim of this study to explore all of these together in order to better understand the possible gaps in the hotel industry in Taiwan.

Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.

Directory of Open Access Journals (Sweden)

Zahra Moinfar

Full Text Available Glioma is the most common malignant primary brain tumour with male preponderance and poor prognosis. Glioma cells express variable amounts of connexin 43 (Cx43 and estrogen receptors (ERs. Both, Cx43 and ERs, play important roles in cell proliferation and migration. Therefore, we investigated the effects of 17-ß estradiol (E2 on Cx43 expression in two glioma cell lines with variable native expression of Cx43.F98 and C6 rat glioma cells were cultured for 24 h in the presence of 10 nM or 100 nM E2, and the E2-antagonist, Fulvestrant. An MTT assay was performed to evaluate cell viability. ERα, ERβ and Cx43 protein expressions were analysed by western blotting and Cx43 mRNA expression was analysed by real-time polymerase chain reaction. To quantify cell migration, an exclusive zone migration assay was used. Functional coupling of cells via gap junctions was examined using whole-cell patch-clamp technique.E2 reduced Cx43 expression in C6 cells, but increased Cx43 expression in F98 cultures. These effects were mediated via ERs. Moreover, E2 promoted C6 cell migration, but it did not affect F98 cell migration. The expression level of ERα was found to be high in C6, but low in F98 cells. ERβ was exclusively expressed in C6 cells. In addition, E2 treatment induced a significant decrease of ERβ in C6 cultures, while it decreased ERα expression in F98 glioma cells.These findings show that E2 differentially modulates Cx43 expression in F98 and C6 glioma cells, likely due to the differential expression of ERs in each of these cell lines. Our findings point to the molecular mechanisms that might contribute to the gender-specific differences in the malignancy of glioma and could have implications for therapeutic strategies against glioma.

Mythic gaps

Directory of Open Access Journals (Sweden)

William Hansen

2014-11-01

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

Children and Trauma: Unexpected Resistance and Justice in Film and Drawings

Directory of Open Access Journals (Sweden)

Cheri M. Robinson

2018-02-01

Full Text Available This transnational study examines representations of and by children—whether literal wounds, psychological ones, or wounds transmitted through drawings—that manifest their capacity for unexpected resistance and justice. It considers the Mexican-American director Guillermo del Toro’s use of hauntings and wounds to explore violence during the 1936–1939 Spanish Civil War in the film El espinazo del diablo [The Devil’s Backbone] (2001 and its intersections on strategic and theoretical levels with the traumatic in archival children’s drawings produced during the 1976–1983 Argentine military dictatorship. The drawings illustrate the violence perpetrated against the child artists’ families and were produced in exile for the human rights organization COSOFAM. Utilizing diverse theories from film and trauma studies, among others, this article analyzes key scenes in El espinazo exhibiting commonalities with representations of traumatic violence in the children’s drawings, revealing that, in fiction and in fact, a strategic “showing” of the traumatic wound is designed to remind others of the imperative to intervene in situations of extreme violence, to appeal to/for justice, and to effectively testify from the inside.

43 CFR 43.215 - What must I include in my drug-free awareness program?

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false What must I include in my drug-free awareness program? 43.215 Section 43.215 Public Lands: Interior Office of the Secretary of the Interior GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 43.215 What must I...

"Prince Charming Syndrome?" Gender gap in preferences for defined contribution pensions in Japan.

Science.gov (United States)

Watanabe, Satoshi P

2017-01-01

Using survey data collected by the Japan Institute of Life Insurance in 2002, this study finds that a significant gender gap existed in defined contribution (DC) pension knowledge among workers employed at small- to medium-sized private firms in Japan. Even with similar DC knowledge, however, men and women reveal different preferences for DC pensions, indicating that their perceptional responses may widely differ from actual behaviors. Apart from the knowledge gap, the result shows evidence of the Prince Charming Syndrome among female employees as a significant source of the gender gap in DC participation rates. Among corporate pension-covered employees, the gender difference in the efficacy of DC portability is a more significant gap-generating factor. DC tax advantage is particularly favored by pension-covered female employees over male counterparts, reducing the DC preference gap. No similar evidence is found for employees with no corporate pension coverage.

The Knowledge Gap Versus the Belief Gap and Abstinence-Only Sex Education.

Science.gov (United States)

Hindman, Douglas Blanks; Yan, Changmin

2015-08-01

The knowledge gap hypothesis predicts widening disparities in knowledge of heavily publicized public affairs issues among socioeconomic status groups. The belief gap hypothesis extends the knowledge gap hypothesis to account for knowledge and beliefs about politically contested issues based on empirically verifiable information. This analysis of 3 national surveys shows belief gaps developed between liberals and conservatives regarding abstinence-only sex education; socioeconomic status-based knowledge gaps did not widen. The findings partially support both belief gap and knowledge gap hypotheses. In addition, the unique contributions of exposure to Fox News, CNN, and MSNBC in this process were investigated. Only exposure to Fox News was linked to beliefs about abstinence-only sex education directly and indirectly through the cultivation of conservative ideology.

Evaluation of gap heat transfer model in ELESTRES for CANDU fuel element under normal operating conditions

International Nuclear Information System (INIS)

Lee, Kang Moon; Ohn, Myung Ryong; Im, Hong Sik; Choi, Jong Hoh; Hwang, Soon Taek

1995-01-01

The gap conductance between the fuel and the sheath depends strongly on the gap width and has a significant influence on the amount of initial stored energy. The modified Ross and Stoute gap conductance model in ELESTRES is based on a simplified thermal deformation model for steady-state fuel temperature calculations. A review on a series of experiments reveals that fuel pellets crack, relocate, and are eccentrically positioned within the sheath rather than solid concentric cylinders. In this paper, the two recently-proposed gap conductance models (offset gap model and relocated gap model) are described and are applied to calculate the fuel-sheath gap conductances under experimental conditions and normal operating conditions in CANDU reactors. The good agreement between the experimentally-inferred and calculated gap conductance values demonstrates that the modified Ross and Stoute model was implemented correctly in ELESTRES. The predictions of the modified Ross and Stoute model provide conservative values for gap heat transfer and fuel surface temperature compared to the offset gap and relocated gap models for a limiting power envelope. 13 figs., 3 tabs., 16 refs. (Author)

When an Object Appears Unexpectedly: Object Circumvention in Adults.

Science.gov (United States)

Wilmut, Kate; Du, Wenchong; Barnett, Anna L

2017-01-01

Obstacles often appear unexpectedly in our pathway and these require us to make immediate adjustments. Despite how regularly we encounter such situations only few studies have considered how we adjust to unexpected obstacles in the pathway that require us to walk around them. The authors considered how adults adjust to the possibility of an obstacle appearing and then also how foot placement is adjusted to circumvent an obstacle. Fifteen healthy adults walked down an 11-m walkway, initially they were told this was a clear pathway and nothing in the environment would change (no gate), they then performed a series of trials in which a gate may (gate close) or may not (gate open) partially obstruct their pathway. The authors found that mediolateral trunk velocity and acceleration was significantly increased when there was the possibility of an obstacle but before the obstacle appeared. This demonstrates an adaptive walking strategy that seems to enable healthy young adults to successfully circumvent obstacles. The authors also categorized foot placement adjustments and found that adults favored making shorter and wider steps away from the obstacle. They suggest this combination of adjustments allows participants to maintain stability while successfully circumventing the obstacle.

Regression analysis for bivariate gap time with missing first gap time data.

Science.gov (United States)

Huang, Chia-Hui; Chen, Yi-Hau

2017-01-01

We consider ordered bivariate gap time while data on the first gap time are unobservable. This study is motivated by the HIV infection and AIDS study, where the initial HIV contracting time is unavailable, but the diagnosis times for HIV and AIDS are available. We are interested in studying the risk factors for the gap time between initial HIV contraction and HIV diagnosis, and gap time between HIV and AIDS diagnoses. Besides, the association between the two gap times is also of interest. Accordingly, in the data analysis we are faced with two-fold complexity, namely data on the first gap time is completely missing, and the second gap time is subject to induced informative censoring due to dependence between the two gap times. We propose a modeling framework for regression analysis of bivariate gap time under the complexity of the data. The estimating equations for the covariate effects on, as well as the association between, the two gap times are derived through maximum likelihood and suitable counting processes. Large sample properties of the resulting estimators are developed by martingale theory. Simulations are performed to examine the performance of the proposed analysis procedure. An application of data from the HIV and AIDS study mentioned above is reported for illustration.

Frequentie en oorzaak van onverwachte allergische reacties op voedsel [Frequency and cause of unexpected allergic reactions to food

NARCIS (Netherlands)

Michelsen-Huisman, A.D.; Os-Medendorp, H. van; Versluis, A.; Kruizinga, A.G.; Castenmiller, J.J.M.; Noteborn, H.P.J.M.; Houben, G.F.; Knulst, A.C.

2014-01-01

Unexpected reactions occur in patients with food allergy, but frequency data are scare. This prospective study investigates the frequency, severity and causes of unexpected allergic reactions to food in adults with a doctor's diagnosed food allergy. Participants complete an online questionnaire

Sudden unexpected death in infancy: place and time of death.

Science.gov (United States)

Glasgow, J F T; Thompson, A J; Ingram, P J

2006-01-01

In recent years, many babies who die of Sudden Unexpected Death in Infancy (SUDI) in Northern Ireland are found dead in bed--i.e. co-sleeping--with an adult. In order to assess its frequency autopsy reports between April 1996 and August 2001 were reviewed and linked to temporal factors. The day and month of death, and the place where the baby was found were compared to a reference population of infant deaths between one week of age and the second birthday. Although the rate of SUDI was lower than the UK average, 43 cases of SUDI were identified, and two additional deaths with virtually identical autopsy findings that were attributed to asphyxia caused by suffocation due to overlaying. Thirty-two of the 45 (71%) were less than four months of age. In 30 of the 45 cases (67%) the history stated that the baby was bed sharing with others; 19 died sleeping in an adult bed, and 11 on a sofa or armchair. In 16 of the 30 (53%) there were at least two other people sharing the sleeping surface, and in one case, three. SUDI was twice as frequent at weekends (found dead Saturday-Monday mornings) compared to weekdays (psharing a place of sleep per se may not increase the risk of death, our findings may be linked to factors such as habitual smoking, consumption of alcohol or illicit drugs as reported in case-control studies. In advising parents on safer childcare practices, health professionals must be knowledgeable of current research and when, for example, giving advice on co-sleeping this needs to be person-specific cognisant of the risks within a household. New and better means of targeting such information needs to be researched if those with higher risk life-styles are to be positively influenced.

The Studies of a Vacuum Gap Breakdown after High-Current Arc Interruption with Increasing the Voltage

Science.gov (United States)

Schneider, A. V.; Popov, S. A.; Batrakov, A. V.; Dubrovskaya, E. L.; Lavrinovich, V. A.

2017-12-01

Vacuum-gap breakdown has been studied after high-current arc interruption with a subsequent increase in the transient recovery voltage across a gap. The effects of factors, such as the rate of the rise in the transient voltage, the potential of the shield that surrounds a discharge gap, and the arc burning time, have been determined. It has been revealed that opening the contacts earlier leads to the formation of an anode spot, which is the source of electrode material vapors into the discharge gap after current zero moment. Under the conditions of increasing voltage, this fact results in the breakdown. Too late opening leads to the breakdown of a short gap due to the high electric fields.

Tunable band gap and optical properties of surface functionalized Sc2C monolayer

International Nuclear Information System (INIS)

Wang Shun; Du Yu-Lei; Liao Wen-He

2017-01-01

Using the density functional theory, we have investigated the electronic and optical properties of two-dimensional Sc 2 C monolayer with OH, F, or O chemical groups. The electronic structures reveal that the functionalized Sc 2 C monolayers are semiconductors with a band gap of 0.44–1.55 eV. The band gap dependent optical parameters, like dielectric function, absorption coefficients, reflectivity, loss function, and refraction index were also calculated for photon energy up to 20 eV. At the low-energy region, each optical parameter shifts to red, and the peak increases obviously with the increase of the energy gap. Consequently, Sc 2 C monolayer with a tunable band gap by changing the type of surface chemical groups is a promising 2D material for optoelectronic devices. (paper)

Responding In-the-Moment: Learning to Prepare for the Unexpected

Science.gov (United States)

Mason, John

2015-01-01

Becoming aware of something unexpected can be a form of awakening: sharpening attention, enriching noticing, opening up fresh possibilities of action, and educating awareness so as to enable a sensitive response to similar situations in the future. However it can also trigger tunnel vision (few if any actions available) or freezing (no actions…

Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption.

Science.gov (United States)

Li, Nan; Mruk, Dolores D; Mok, Ka-Wai; Li, Michelle W M; Wong, Chris K C; Lee, Will M; Han, Daishu; Silvestrini, Bruno; Cheng, C Yan

2016-04-01

Earlier studies have shown that rats treated with an acute dose of 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide (adjudin, a male contraceptive under development) causes permanent infertility due to irreversible blood-testis barrier (BTB) disruption even though the population of undifferentiated spermatogonia remains similar to normal rat testes, because spermatogonia fail to differentiate into spermatocytes to enter meiosis. Since other studies have illustrated the significance of connexin 43 (Cx43)-based gap junction in maintaining the homeostasis of BTB in the rat testis and the phenotypes of Sertoli cell-conditional Cx43 knockout mice share many of the similarities of the adjudin-treated rats, we sought to examine if overexpression of Cx43 in these adjudin-treated rats would reseal the disrupted BTB and reinitiate spermatogenesis. A full-length Cx43 cloned into mammalian expression vector pCI-neo was used to transfect testes of adjudin-treated ratsversusempty vector. It was found that overexpression of Cx43 indeed resealed the Sertoli cell tight junction-permeability barrier based on a functionalin vivoassay in tubules displaying signs of meiosis as noted by the presence of round spermatids. Thus, these findings suggest that overexpression of Cx43 reinitiated spermatogenesis at least through the steps of meiosis to generate round spermatids in testes of rats treated with an acute dose of adjudin that led to aspermatogenesis. It was also noted that the round spermatids underwent eventual degeneration with the formation of multinucleated cells following Cx43 overexpression due to the failure of spermiogenesis because no elongating/elongated spermatids were detected in any of the tubules examined. The mechanism by which overexpression of Cx43 reboots meiosis and rescues BTB function was also examined. In summary, overexpression of Cx43 in the testis with aspermatogenesis reboots meiosis and reseals toxicant-induced BTB disruption, even though it fails to

Effects of unexpected lateral mass placement on trunk loading in lifting

NARCIS (Netherlands)

van der Burg, J.C.E.; Kingma, I.; van Dieen, J.H.

2003-01-01

Study Design. A repeated measurements experiment of spinal loading in healthy subjects. Objectives. To test whether unexpected lateral mass placement increases low back loading and trunk movement when subjects are lifting a mass in upright posture. Summary of Background Data. Epidemiologic studies

Potential problems of removing one invasive species at a time: a meta-analysis of the interactions between invasive vertebrates and unexpected effects of removal programs

Directory of Open Access Journals (Sweden)

Sebastián A. Ballari

2016-06-01

Full Text Available Although the co-occurrence of nonnative vertebrates is a ubiquitous global phenomenon, the study of interactions between invaders is poorly represented in the literature. Limited understanding of the interactions between co-occurring vertebrates can be problematic for predicting how the removal of only one invasive—a common management scenario—will affect native communities. We suggest a trophic food web framework for predicting the effects of single-species management on native biodiversity. We used a literature search and meta-analysis to assess current understanding of how the removal of one invasive vertebrate affects native biodiversity relative to when two invasives are present. The majority of studies focused on the removal of carnivores, mainly within aquatic systems, which highlights a critical knowledge gap in our understanding of co-occurring invasive vertebrates. We found that removal of one invasive vertebrate caused a significant negative effect on native species compared to when two invasive vertebrates were present. These unexpected results could arise because of the positioning and hierarchy of the co-occurring invasives in the food web (e.g., carnivore–carnivore or carnivore–herbivore. We consider that there are important knowledge gaps to determinate the effects of multiple co-existing invaders on native ecosystems, and this information could be precious for management.

Potential problems of removing one invasive species at a time: a meta-analysis of the interactions between invasive vertebrates and unexpected effects of removal programs.

Science.gov (United States)

Ballari, Sebastián A; Kuebbing, Sara E; Nuñez, Martin A

2016-01-01

Although the co-occurrence of nonnative vertebrates is a ubiquitous global phenomenon, the study of interactions between invaders is poorly represented in the literature. Limited understanding of the interactions between co-occurring vertebrates can be problematic for predicting how the removal of only one invasive-a common management scenario-will affect native communities. We suggest a trophic food web framework for predicting the effects of single-species management on native biodiversity. We used a literature search and meta-analysis to assess current understanding of how the removal of one invasive vertebrate affects native biodiversity relative to when two invasives are present. The majority of studies focused on the removal of carnivores, mainly within aquatic systems, which highlights a critical knowledge gap in our understanding of co-occurring invasive vertebrates. We found that removal of one invasive vertebrate caused a significant negative effect on native species compared to when two invasive vertebrates were present. These unexpected results could arise because of the positioning and hierarchy of the co-occurring invasives in the food web (e.g., carnivore-carnivore or carnivore-herbivore). We consider that there are important knowledge gaps to determinate the effects of multiple co-existing invaders on native ecosystems, and this information could be precious for management.

Gaps and pseudogaps in perovskite rare earth nickelates

Directory of Open Access Journals (Sweden)

S. James Allen

2015-06-01

Full Text Available We report on tunneling measurements that reveal the evolution of the quasiparticle state density in two rare earth perovskite nickelates, NdNiO3 and LaNiO3, that are close to a bandwidth controlled metal to insulator transition. We measure the opening of a sharp gap of ∼30 meV in NdNiO3 in its insulating ground state. LaNiO3, which remains a correlated metal at all practical temperatures, exhibits a pseudogap of the same order. The results point to both types of gaps arising from a common origin, namely, a quantum critical point associated with the T = 0 K metal-insulator transition. The results support theoretical models of the quantum phase transition in terms of spin and charge instabilities of an itinerant Fermi surface.

Spin-polarized gapped Dirac spectrum of unsupported silicene

Energy Technology Data Exchange (ETDEWEB)

Podsiadły-Paszkowska, A., E-mail: agata.podsiadly@gmail.com; Krawiec, M., E-mail: mariusz.krawiec@umcs.pl

2016-06-15

Highlights: • Effects of spin–orbit interaction and atomic reconstruction of silicene on its electronic properties have been studied. • Spin-polarized gapped Dirac spectrum has been revealed. • Two different AFM phases have been obtained. - Abstract: We study effects of the spin–orbit interaction and the atomic reconstruction of silicene on its electronic spectrum. As an example we consider unsupported silicene pulled off from Pb(111) substrate. Using first principles density functional theory we show that the inversion symmetry broken arrangement of atoms and the spin–orbit interaction generate a spin-polarized electronic spectrum with an energy gap in the Dirac cone. These findings are particularly interesting in view of the quantum anomalous and quantum valley Hall effects and should be observable in weakly interacting silicene-substrate systems.

Quantile regression and the gender wage gap: Is there a glass ceiling in the Turkish labor market?

OpenAIRE

Kaya, Ezgi

2017-01-01

Recent studies from different countries suggest that the gender gap is not constant across the wage distribution and the average wage gap provides limited information on women’s relative position in the labour market. Using micro level data from official statistics, this study explores the gender wage‐gap in Turkey across the wage distribution. The quantile regression and counterfactual decomposition analysis results reveal three striking features of the Turkish labour market. The first is th...

Long-Term Adaptations to Unexpected Surface Perturbations: Postural Control During Stance and Gait in Train Conductors.

Science.gov (United States)

Baumgart, Christian; Hoppe, Matthias Wilhelm; Freiwald, Jürgen

2016-01-01

The authors aimed to evaluate the differences in postural control during stance and gait between train conductors and controls. Twenty-one train conductors and 21 office workers performed 6 unilateral and bilateral balance tests on stable and unstable surfaces as well as a gait analysis. In the balance tests, the mean velocity of the center of pressure and unstable surface was measured. In the bilateral balance tests the selected stance width was measured. During gait the length, width, frequency, and velocity of the steps were calculated from the ground reaction forces. Train conductors showed a significantly greater step width during gait (15.4 ± 4.7 vs. 13.0 ± 3.4 cm; p = .035) and stance width during the bilateral stance on the unstable surface (21.0 ± 5.1 vs. 17.8 ± 3.7 cm; p = .026) than the office workers, while no differences were revealed in balance variables. The revealed differences between train conductors and office workers may represent task-specific feedforward control strategies, which increase the base of support and may be helpful to resist unexpected perturbations in trains.

FOXC1 modulates MYOC secretion through regulation of the exocytic proteins RAB3GAP1, RAB3GAP2 and SNAP25.

Directory of Open Access Journals (Sweden)

Alexandra Rasnitsyn

Full Text Available The neurodegenerative disease glaucoma is one of the leading causes of blindness in the world. Glaucoma is characterized by progressive visual field loss caused by retinal ganglion cell (RGC death. Both surgical glaucoma treatments and medications are available, however, they only halt glaucoma progression and are unable to reverse damage. Furthermore, many patients do not respond well to treatments. It is therefore important to better understand the mechanisms involved in glaucoma pathogenesis. Patients with Axenfeld-Rieger syndrome (ARS offer important insight into glaucoma progression. ARS patients are at 50% risk of developing early onset glaucoma and respond poorly to treatments, even when surgical treatments are combined with medications. Mutations in the transcription factor FOXC1 cause ARS. Alterations in FOXC1 levels cause ocular malformations and disrupt stress response in ocular tissues, thereby contributing to glaucoma progression. In this study, using biochemical and molecular techniques, we show that FOXC1 regulates the expression of RAB3GAP1, RAB3GAP2 and SNAP25, three genes with central roles in both exocytosis and endocytosis, responsible for extracellular trafficking. FOXC1 positively regulates RAB3GAP1 and RAB3GAP2, while either increase or decrease in FOXC1 levels beyond its normal range results in decreased SNAP25. In addition, we found that FOXC1 regulation of RAB3GAP1, RAB3GAP2 and SNAP25 affects secretion of Myocilin (MYOC, a protein associated with juvenile onset glaucoma and steroid-induced glaucoma. The present work reveals that FOXC1 is an important regulator of exocytosis and establishes a new link between FOXC1 and MYOC-associated glaucoma.

Lower incidence of unexpected in-hospital death after interprofessional implementation of a bedside track-and-trigger system

DEFF Research Database (Denmark)

Bunkenborg, Gitte; Samuelson, Karin Samuelsonkarin; Poulsen, Ingrid

2014-01-01

In-hospital patients may suffer unexpected death because of suboptimal monitoring. Early recognition of deviating physiological parameters may enable staff to prevent unexpected in-hospital death. The aim of this study was to evaluate short- and long-term effects of systematic interprofessional u...... of early warning scoring, structured observation charts, and clinical algorithms for bedside action....

Bridging the Gap

DEFF Research Database (Denmark)

Kramer Overgaard, Majken; Broeng, Jes; Jensen, Monika Luniewska

Bridging the Gap (BtG) is a 2-year project funded by The Danish Industry Foundation. The goal of Bridging the Gap has been to create a new innovation model which will increase the rate at which Danish universities can spinout new technology ventures.......Bridging the Gap (BtG) is a 2-year project funded by The Danish Industry Foundation. The goal of Bridging the Gap has been to create a new innovation model which will increase the rate at which Danish universities can spinout new technology ventures....

Costly hide and seek pays: unexpected consequences of deceit in a social dilemma

International Nuclear Information System (INIS)

Szolnoki, Attila; Perc, Matjaž

2014-01-01

Deliberate deceptiveness intended to gain an advantage is commonplace in human and animal societies. In a social dilemma, an individual may only pretend to be a cooperator to elicit cooperation from others, while in reality he is a defector. With this as motivation, we study a simple variant of the evolutionary prisoner's dilemma game entailing deceitful defectors and conditional cooperators that lifts the veil on the impact of such two-faced behavior. Defectors are able to hide their true intentions at a personal cost, while conditional cooperators are probabilistically successful at identifying defectors and act accordingly. By focusing on the evolutionary outcomes in structured populations, we observe a number of unexpected and counterintuitive phenomena. We show that deceitful behavior may fare better if it is costly, and that a higher success rate of identifying defectors does not necessarily favor cooperative behavior. These results are rooted in the spontaneous emergence of cycling dominance and spatial patterns that give rise to fascinating phase transitions, which in turn reveal the hidden complexity behind the evolution of deception. (paper)

Parameters of radiation defects in GaP and GaAssub(1-x)Psub(x) with thermostimulated current measurements

International Nuclear Information System (INIS)

Brajlovskij, E.Yu.; Marchuk, N.D.

1980-01-01

Introduction of point defects in gallium phosphide crystals and GaAssub(1-x)Psub(x) solid solutions under the action of 1 MeV electrons is studied by TSC method on Schottky barriers. The TSC spectra processing using the computer is given. In GaP crystals the dominant electron and hole traps are D-centers (Esub(c)-1.24 eV) and M-centers (Esub(v)+1.43 eV). The received level spectrum explains the compensation of conductivity of n- and p-lGaP under irradiation. It is shown that main defects observed in electron irradiated GaP are most likely phosphorus vacancies (D-center)and gallium vacancies (M-center)

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

Fournier gangrene and unexpected death.

Science.gov (United States)

Bury, Danielle; Byard, Roger W

2012-11-01

Fournier gangrene represents a rare but progressive perineal infection that may result in rapid death. A 70-year-old man with poorly controlled diabetes mellitus and alcohol abuse is reported who was found unexpectedly dead. He had last been contacted the night before his death. At autopsy, the most striking finding was deep necrotic ulceration of the scrotum with exposure of underlying deep muscles and testicles, with blood cultures positive for Escherichia coli. Death was, therefore, attributed to necrotic ulceration/gangrene of the perineum (Fournier gangrene) that was due to E. coli sepsis with underlying contributing factors of diabetes mellitus and alcoholism. In addition there was morbid obesity (body mass index 46.9), cirrhosis of the liver, and marked focal coronary artery atherosclerosis with significant cardiomegaly. Fournier gangrene may be an extremely aggressive condition that can result in rapid death, as was demonstrated by the rapid progression in the reported case. © 2012 American Academy of Forensic Sciences.

Technique for estimating relocated gap width for gap conductance calculations

International Nuclear Information System (INIS)

Klink, P.H.

1978-01-01

Thermally induced fuel fragmentation and relocation has been demonstrated to influence the thermal behavior of a fuel rod in two ways. The effective fuel pellet conductivity is decreased and pellet-to-cladding heat transfer is improved. This paper presents a correlation between as-built and relocated gap width which, used with the Ross and Stoute Gap Conductance Correlation and an appropriate fuel thermal expansion model, closely predicts the measured gap conductances

Next of kin’s experiences of sudden and unexpected death from stroke - a study of narratives

Science.gov (United States)

2013-01-01

Background Death always evokes feelings in those close to the afflicted person. When death comes suddenly the time for preparation is minimal and the next of kin have to cope with the situation despite their own sorrow. The suddenness is found to be stressful for the next of kin and communication both with healthcare professionals and information about what has happened has been found helpful. The aim of this study was to illuminate the experiences of next of kin from the sudden and unexpected death of a relative from acute stroke. Methods Data was collected over a 12-month period in 2009–2010. Twelve next of kin of patients cared for in stroke units who died suddenly and unexpectedly from stroke were interviewed using a narrative method. The narratives were analyzed using narrative thematic analysis. Results Three themes emerged showing facets of next of kin’s experiences of a relative’s sudden and unexpected death from stroke: Divided feelings about the sudden and unexpected death; Perception of time and directed attention when keeping vigil; Contradictions and arbitrary memories when searching for understanding. Conclusions To have to live in the aftermath of severe stroke is absolute horror in people’s imagination and death is seen as the lesser of two evils. The sudden and unexpected death totally pervades the next of kin’s life, directs their attention to the dying person and even causes them to forget themselves and their own needs, and leads to difficulties in information intake. It is a challenge for the healthcare professionals to be able to identify the individual needs of the next of kin in this situation. PMID:23590246

Basic numerical study on gap influence of residual stress and distortion during high-brightness laser butt welding

International Nuclear Information System (INIS)

Serizawa, Hisashi; Mori, Daiki; Murakawa, Hidekazu

2013-01-01

High-brightness laser such as fiber laser or disk laser is expected to minimize the total heat input energy in welding due to its high beam quality, and the welding residual stress and distortion also seem to be reduced as a result. However, the diameter of high-brightness laser beam is less than 0.6 mm and it is difficult to set the beam position to contact face between two parts because in general there would be a gap due to quality of parts. In this study, in order to reveal the effect of gap on the residual stress and the welding distortion during fiber laser welding, the butt welding of two plates were examined through the thermal elastic-plastic analysis with a new gap element. From the result of thermal analyses, it was found that the homogeneous ellipsoid body could be applicable to model the shape of heat source for the fiber laser and the gap width would not influence the penetration shape when the gap width was changed from 0.1 to 0.25 mm. In addition, the elastic-plastic analyses indicated that the transverse shrinkage slightly increased with increasing the gap width, while this shrinkage without gap was much smaller than that with gap. Also, it was revealed that the welding speed largely affects both the welding residual stress and distortion. Moreover, it was found that the residual stress was almost independent of the jig position, while the position of fixtures slightly affected the transverse shrinkage. (author)

Has the gap between pancreas and islet transplantation closed?

Science.gov (United States)

Niclauss, Nadja; Morel, Philippe; Berney, Thierry

2014-09-27

Both pancreas and islet transplantations are therapeutic options for complicated type 1 diabetes. Until recent years, outcomes of islet transplantation have been significantly inferior to those of whole pancreas. Islet transplantation is primarily performed alone in patients with severe hypoglycemia, and recent registry reports have suggested that results of islet transplantation alone in this indication may be about to match those of pancreas transplant alone in insulin independence. Figures of 50% insulin independence at 5 years for either procedure have been cited. In this article, we address the question whether islet transplantation has indeed bridged the gap with whole pancreas. Looking at the evidence to answer this question, we propose that although pancreas may still be more efficient in taking recipients off insulin than islets, there are in fact numerous "gaps" separating both procedures that must be taken into the equation. These "gaps" relate to organ utilization, organ allocation, indication for transplantation, and morbidity. In-depth analysis reveals that islet transplantation, in fact, has an edge on whole pancreas in some of these aspects. Accordingly, attempts should be made to bridge these gaps from both sides to achieve the same level of success with either procedure. More realistically, it is likely that some of these gaps will remain and that both procedures will coexist and complement each other, to ensure that β cell replacement can be successfully implemented in the greatest possible number of patients with type 1 diabetes.

Novel mutations in TARDBP (TDP-43 in patients with familial amyotrophic lateral sclerosis.

Directory of Open Access Journals (Sweden)

Nicola J Rutherford

2008-09-01

Full Text Available The TAR DNA-binding protein 43 (TDP-43 has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U, defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V were identified in the analysis of 92 familial ALS patients (3.3%, while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis.

Association analyses of porcine SERPINE1 reveal sex-specific effects on muscling, growth, fat accretion and meat quality

Czech Academy of Sciences Publication Activity Database

Weisz, Filip; Bartenschlager, H.; Knoll, Aleš; Mileham, A.; Deeb, N.; Geldermann, H.; Čepica, Stanislav

2012-01-01

Roč. 43, č. 5 (2012), s. 614-619 ISSN 0268-9146 R&D Projects: GA ČR GAP502/10/1216 Institutional research plan: CEZ:AV0Z50450515 Keywords : association study * fat deposition * meat quality Subject RIV: GI - Animal Husbandry ; Breeding Impact factor: 2.584, year: 2012

Complex and unexpected dynamics in simple genetic regulatory networks

Science.gov (United States)

Borg, Yanika; Ullner, Ekkehard; Alagha, Afnan; Alsaedi, Ahmed; Nesbeth, Darren; Zaikin, Alexey

2014-03-01

One aim of synthetic biology is to construct increasingly complex genetic networks from interconnected simpler ones to address challenges in medicine and biotechnology. However, as systems increase in size and complexity, emergent properties lead to unexpected and complex dynamics due to nonlinear and nonequilibrium properties from component interactions. We focus on four different studies of biological systems which exhibit complex and unexpected dynamics. Using simple synthetic genetic networks, small and large populations of phase-coupled quorum sensing repressilators, Goodwin oscillators, and bistable switches, we review how coupled and stochastic components can result in clustering, chaos, noise-induced coherence and speed-dependent decision making. A system of repressilators exhibits oscillations, limit cycles, steady states or chaos depending on the nature and strength of the coupling mechanism. In large repressilator networks, rich dynamics can also be exhibited, such as clustering and chaos. In populations of Goodwin oscillators, noise can induce coherent oscillations. In bistable systems, the speed with which incoming external signals reach steady state can bias the network towards particular attractors. These studies showcase the range of dynamical behavior that simple synthetic genetic networks can exhibit. In addition, they demonstrate the ability of mathematical modeling to analyze nonlinearity and inhomogeneity within these systems.

Unexpected flood loss correlations across Europe

Science.gov (United States)

Booth, Naomi; Boyd, Jessica

2017-04-01

Floods don't observe country borders, as highlighted by major events across Europe that resulted in heavy economic and insured losses in 1999, 2002, 2009 and 2013. Flood loss correlations between some countries occur along multi-country river systems or between neighbouring nations affected by the same weather systems. However, correlations are not so obvious and whilst flooding in multiple locations across Europe may appear independent, for a re/insurer providing cover across the continent, these unexpected correlations can lead to high loss accumulations. A consistent, continental-scale method that allows quantification and comparison of losses, and identifies correlations in loss between European countries is therefore essential. A probabilistic model for European river flooding was developed that allows estimation of potential losses to pan-European property portfolios. By combining flood hazard and exposure information in a catastrophe modelling platform, we can consider correlations between river basins across Europe rather than being restricted to country boundaries. A key feature of the model is its statistical event set based on extreme value theory. Using historical river flow data, the event set captures spatial and temporal patterns of flooding across Europe and simulates thousands of events representing a full range of possible scenarios. Some known correlations were identified, such as between neighbouring Belgium and Luxembourg where 28% of events that affect either country produce a loss in both. However, our model identified some unexpected correlations including between Austria and Poland, and Poland and France, which are geographically distant. These correlations in flood loss may be missed by traditional methods and are key for re/insurers with risks in multiple countries. The model also identified that 46% of European river flood events affect more than one country. For more extreme events with a return period higher than 200 years, all events

Sudden unexpected death in children with a previously diagnosed cardiovascular disorder

NARCIS (Netherlands)

Polderman, Florens N.; Cohen, Joeri; Blom, Nico A.; Delhaas, Tammo; Helbing, Wim A.; Lam, Jan; Sobotka-Plojhar, Marta A.; Temmerman, Arno M.; Sreeram, Narayanswani

2004-01-01

BACKGROUND: It is known that children with previously diagnosed heart defects die suddenly. The causes of death are often unknown. OBJECTIVE: The aim of the study was to identify all infants and children within the Netherlands with previously diagnosed heart disease who had a sudden unexpected death

Sudden unexpected death in children with a previously diagnosed cardiovascular disorder

NARCIS (Netherlands)

Polderman, F.N.; Cohen, Joeri; Blom, N.A.; Delhaas, T.; Helbing, W.A.; Lam, J.; Sobotka-Plojhar, M.A.; Temmerman, Arno M.; Sreeram, N.

2004-01-01

Background: It is known that children with previously diagnosed heart defects die suddenly. The causes of death are often unknown. Objective: The aim of the study was to identify all infants and children within the Netherlands with previously diagnosed heart disease who had a sudden unexpected death

Canopy gap edge determination and the importance of gap edges for plant diversity

Directory of Open Access Journals (Sweden)

D. Salvador-Van Eysenrode

2002-01-01

Full Text Available Canopy gaps, i.e. openings in the forest cover caused by the fall of structural elements, are considered to be important for the maintenance of diversity and for the forest cycle. A gap can be considered as a young forest patch in the forest matrix, composed of interior surrounded by an edge, both enclosed by a perimeter. Much of the attention has been focused on the gap interior. However, at gap edges the spectrum of regeneration opportunities for plants may be larger than in the interior. Although definitions of gap are still discussed, any definition can describe it in an acceptable way, if justified, but defining edges is complicated and appropriate descriptors should be used. A method to determine gap interior and edge, using light as a descriptor, is presented with an example of gaps from a beech forest (Fagus sylvatica in Belgium. Also, the relevance and implications of gap edges for plant diversity and calculation of forest turnover is discussed.

Pupil dilation during recognition memory: Isolating unexpected recognition from judgment uncertainty.

Science.gov (United States)

Mill, Ravi D; O'Connor, Akira R; Dobbins, Ian G

2016-09-01

Optimally discriminating familiar from novel stimuli demands a decision-making process informed by prior expectations. Here we demonstrate that pupillary dilation (PD) responses during recognition memory decisions are modulated by expectations, and more specifically, that pupil dilation increases for unexpected compared to expected recognition. Furthermore, multi-level modeling demonstrated that the time course of the dilation during each individual trial contains separable early and late dilation components, with the early amplitude capturing unexpected recognition, and the later trailing slope reflecting general judgment uncertainty or effort. This is the first demonstration that the early dilation response during recognition is dependent upon observer expectations and that separate recognition expectation and judgment uncertainty components are present in the dilation time course of every trial. The findings provide novel insights into adaptive memory-linked orienting mechanisms as well as the general cognitive underpinnings of the pupillary index of autonomic nervous system activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Using Unmanned Aerial Vehicles (UAV to Quantify Spatial Gap Patterns in Forests

Directory of Open Access Journals (Sweden)

Stephan Getzin

2014-07-01

Full Text Available Gap distributions in forests reflect the spatial impact of man-made tree harvesting or naturally-induced patterns of tree death being caused by windthrow, inter-tree competition, disease or senescence. Gap sizes can vary from large (>100 m2 to small (<10 m2, and they may have contrasting spatial patterns, such as being aggregated or regularly distributed. However, very small gaps cannot easily be recorded with conventional aerial or satellite images, which calls for new and cost-effective methodologies of forest monitoring. Here, we used an unmanned aerial vehicle (UAV and very high-resolution images to record the gaps in 10 temperate managed and unmanaged forests in two regions of Germany. All gaps were extracted for 1-ha study plots and subsequently analyzed with spatially-explicit statistics, such as the conventional pair correlation function (PCF, the polygon-based PCF and the mark correlation function. Gap-size frequency was dominated by small gaps of an area <5 m2, which were particularly frequent in unmanaged forests. We found that gap distances showed a variety of patterns. However, the polygon-based PCF was a better descriptor of patterns than the conventional PCF, because it showed randomness or aggregation for cases when the conventional PCF showed small-scale regularity; albeit, the latter was only a mathematical artifact. The mark correlation function revealed that gap areas were in half of the cases negatively correlated and in the other half independent. Negative size correlations may likely be the result of single-tree harvesting or of repeated gap formation, which both lead to nearby small gaps. Here, we emphasize the usefulness of UAV to record forest gaps of a very small size. These small gaps may originate from repeated gap-creating disturbances, and their spatial patterns should be monitored with spatially-explicit statistics at recurring intervals in order to further insights into forest dynamics.

Role of connexin43 and ATP in long-range bystander radiation damage and oncogenesis in vivo.

Science.gov (United States)

Mancuso, M; Pasquali, E; Leonardi, S; Rebessi, S; Tanori, M; Giardullo, P; Borra, F; Pazzaglia, S; Naus, C C; Di Majo, V; Saran, A

2011-11-10

Ionizing radiation is a genotoxic agent and human carcinogen. Recent work has questioned long-held dogmas by showing that cancer-associated genetic alterations occur in cells and tissues not directly exposed to radiation, questioning the robustness of the current system of radiation risk assessment. In vitro, diverse mechanisms involving secreted soluble factors, gap junction intercellular communication (GJIC) and oxidative metabolism are proposed to mediate these indirect effects. In vivo, the mechanisms behind long-range 'bystander' responses remain largely unknown. Here, we investigate the role of GJIC in propagating radiation stress signals in vivo, and in mediating radiation-associated bystander tumorigenesis in mouse central nervous system using a mouse model in which intercellular communication is downregulated by targeted deletion of the connexin43 (Cx43) gene. We show that GJIC is critical for transmission of oncogenic radiation damage to the non-targeted cerebellum, and that a mechanism involving adenosine triphosphate release and upregulation of Cx43, the major GJIC constituent, regulates transduction of oncogenic damage to unirradiated tissues in vivo. Our data provide a novel hypothesis for transduction of distant bystander effects and suggest that the highly branched nervous system, similar to the vascular network, has an important role.

Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43

NARCIS (Netherlands)

Boogerd, C.J.; Wong, L.Y.; van den Boogaard, M.; Bakker, M.A.J.; Tessadori, F.; Bakkers, J.; 't Hoen, P.A.C.; Moorman, A.F.; Christoffels, V.M.; Barnett, P.

2011-01-01

Tbx3, a T-box transcription factor, regulates key steps in development of the heart and other organ systems. Here, we identify Sox4 as an interacting partner of Tbx3. Pull-down and nuclear retention assays verify this interaction and in situ hybridization reveals Tbx3 and Sox4 to co-localize

Sexting: Current Research Gaps and Legislative Issues

OpenAIRE

Ngo, Fawn; Jaishankar, K; Agustina, Jose R.

2017-01-01

'Sexting, the portmanteau of Sex and Texting, has become a hot topic of debate between the legislators, researchers, educators, parents and teens' (Jaishankar, 2009, para 1). In spite of the considerable and growing body of literature on sexting, there are significant gaps in the current research. A review of research to date also reveals a dearth of cross-national and cross-cultural research on the topic of sexting. Notably, legal and ethical issues abound with the current method for punishi...

Proteomic analysis of the crayfish gastrolith chitinous extracellular matrix reveals putative protein complexes and a central role for GAP 65.

Science.gov (United States)

Glazer, Lilah; Roth, Ziv; Weil, Simy; Aflalo, Eliahu D; Khalaila, Isam; Sagi, Amir

2015-10-14

Chitin is a major component of arthropod cuticles, where it forms a three-dimensional network that constitutes the scaffold upon which cuticles form. The chitin fibers that form this network are closely associated with specific structural proteins, while the cuticular matrix contains many additional structural, enzymatic and other proteins. We study the crayfish gastrolith as a simple model for the assembly of calcified cuticular structures, with particular focus on the proteins involved in this process. The present study integrates a gastrolith-forming epithelium transcriptomic library with data from mass spectrometry analysis of proteins extracted from the gastrolith matrix to obtain a near-complete picture of gastrolith protein content. Using native protein separation we identified 24 matrix proteins, of which 14 are novel. Further analysis led to discovery of three putative protein complexes, all containing GAP 65 the most abundant gastrolith structural protein. Using immunological methods we further studied the role of GAP 65 in the gastrolith matrix and forming epithelium, as well as in the newly identified protein complexes. We propose that gastrolith matrix construction is a sequential process in which protein complexes are dynamically assembled and disassembled around GAP 65, thus changing their functional properties to perform each step in the construction process. The scientific interest on which this study is based arises from three main features of gastroliths: (1) Gastroliths possess partial analogy to cuticles both in structural and molecular properties, and may be regarded, with the appropriate reservations (see Introduction), as simple models for cuticle assembly. At the same time, gastroliths are terminally assembled during a well-defined period, which can be controlled in the laboratory, making them significantly easier to study than cuticles. (2) Gastroliths, like the crayfish exoskeleton, contain stable amorphous calcium carbonate (ACC) rather

A comparison of the wide gap and narrow gap resistive plate chamber

International Nuclear Information System (INIS)

Cerron Zeballos, E.; Crotty, I.; Hatzifotiadou, D.; Valverde, J.L.; Neupane, S.; Peskov, V.; Singh, S.; Williams, M.C.S.; Zichichi, A.

1996-01-01

In this paper we study the performance of a wide gap RPC and compare it with that of a narrow gap RPC, both operated in avalanche mode. We have studied the total charge produced in the avalanche. We have measured the dependence of the performance with rate. In addition we have considered the effect of the tolerance of gas gap and calculated the power dissipated in these two types of RPC. We find that the narrow gap RPC has better timing ability; however the wide gap has superior rate capability, lower power dissipation in the gas volume and can be constructed with less stringent mechanical tolerances. (orig.)

A comparison of the wide gap and narrow gap resistive plate chamber

CERN Document Server

Cerron-Zeballos, E; Hatzifotiadou, D; Lamas-Valverde, J; Neupane, S; Peskov, Vladimir; Singh, S; Williams, M C S; Zichichi, Antonino

1996-01-01

In this paper we study the performance of a wide gap RPC and compare it with that of a narrow gap RPC, both operated in avalanche mode. We have studied the total charge produced in the avalanche. We have measured the dependence of the performance with rate. In addition we have considered the effect of the tolerance of gas gap and calculated the power dissipated in these two types of RPC. We find that the narrow gap RPC has better timing ability; however the wide gap has superior rate capability, lower power dissipation in the gas volume and can be constructed with less stringent mechanical tolerances.

Connexin 43-Mediated Astroglial Metabolic Networks Contribute to the Regulation of the Sleep-Wake Cycle.

Science.gov (United States)

Clasadonte, Jerome; Scemes, Eliana; Wang, Zhongya; Boison, Detlev; Haydon, Philip G

2017-09-13

Astrocytes produce and supply metabolic substrates to neurons through gap junction-mediated astroglial networks. However, the role of astroglial metabolic networks in behavior is unclear. Here, we demonstrate that perturbation of astroglial networks impairs the sleep-wake cycle. Using a conditional Cre-Lox system in mice, we show that knockout of the gap junction subunit connexin 43 in astrocytes throughout the brain causes excessive sleepiness and fragmented wakefulness during the nocturnal active phase. This astrocyte-specific genetic manipulation silenced the wake-promoting orexin neurons located in the lateral hypothalamic area (LHA) by impairing glucose and lactate trafficking through astrocytic networks. This global wakefulness instability was mimicked with viral delivery of Cre recombinase to astrocytes in the LHA and rescued by in vivo injections of lactate. Our findings propose a novel regulatory mechanism critical for maintaining normal daily cycle of wakefulness and involving astrocyte-neuron metabolic interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

Multi-flexural band gaps in an Euler–Bernoulli beam with lateral local resonators

Energy Technology Data Exchange (ETDEWEB)

Wang, Ting, E-mail: WT323@mail.nwpu.edu.cn [School of Marine Science and Technology, Northwestern Polytechnical University, Xi' an, Shaanxi, 710072 (China); College of Engineering and Computer Science, The Australian National University, ACT, 2600 (Australia); Sheng, Mei-Ping [School of Marine Science and Technology, Northwestern Polytechnical University, Xi' an, Shaanxi, 710072 (China); Qin, Qing-Hua [College of Engineering and Computer Science, The Australian National University, ACT, 2600 (Australia)

2016-02-05

Flexural vibration suppression in an Euler–Bernoulli beam with attached lateral local resonators (LLR) is studied theoretically and numerically. Hamilton's principle and Bloch's theorem are employed to derive the dispersion relation which reveals that two band gaps are generated. Within both band gaps, the flexural waves are partially transformed into longitudinal waves through a four-link-mechanism and totally blocked. The band gaps can be flexibly tuned by changing the geometry parameter of the four-link-mechanism and the spring constants of the resonators. Frequency response function (FRF) from finite element analysis via commercial software of ANSYS shows large flexural wave attenuation within the band gaps and the effect of damping from the LLR substructures which helps smooth and lower the response peaks at the sacrifice of the band gap effect. The existence of the multi-flexural band gaps can be exploited for the design of flexural vibration control of beams. - Highlights: • A metamaterial beam with lateral local resonance is proposed. • The metamaterial beam can generate multi-band gaps for flexural wave suppression. • The substructure can transform the flexural wave into longitudinal wave and absorb the waves. • Damping from different part has different influence on the band gaps. • The design of the metamaterial beam can be used for multi-flexural vibration control.

Audit of radiology communication systems for critical, urgent, and unexpected significant findings.

Science.gov (United States)

Duncan, K A; Drinkwater, K J; Dugar, N; Howlett, D C

2016-03-01

To determine the compliance of UK radiology departments and trusts/healthcare organisations with National Patient Safety Agency and Royal College of Radiologist's published guidance on the communication of critical, urgent, and unexpected significant radiological findings. A questionnaire was sent to all UK radiology department audit leads asking for details of their current departmental policy regarding the issuing of alerts; use of automated electronic alert systems; methods of notification of clinicians of critical, urgent, and unexpected significant radiological findings; monitoring of results receipt; and examples of the more common types of serious pathologies for which alerts were issued. One hundred and fifty-four of 229 departments (67%) responded. Eighty-eight percent indicated that they had a policy in place for the communication of critical, urgent, and unexpected significant radiological findings. Only 34% had an automated electronic alert system in place and only 17% had a facility for service-wide electronic tracking of radiology reports. In only 11 departments with an electronic acknowledgement system was someone regularly monitoring the read rate. There is wide variation in practice across the UK with regard to the communication and monitoring of reports with many departments/trusts not fully compliant with published UK guidance. Despite the widespread use of electronic systems, only a minority of departments/trusts have and use electronic tracking to ensure reports have been read and acted upon. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

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.

Thallium-201 accumulation in cerebral candidiasis: Unexpected finding on SPECT

International Nuclear Information System (INIS)

Tonami, N.; Matsuda, H.; Ooba, H.; Yokoyama, K.; Hisada, K.; Ikeda, K.; Yamashita, J.

1990-01-01

The authors present an unexpected finding of Tl-201 uptake in the intracerebral lesions due to candidiasis. SPECT demonstrated the extent of the lesions and a high target-to-background ratio. The regions where abnormal Tl-201 accumulation was seen were nearly consistent with CT scans of those enhanced by a contrast agent. After treatment, most of the abnormal Tl-201 accumulation disappeared

Thallium-201 accumulation in cerebral candidiasis: Unexpected finding on SPECT

Energy Technology Data Exchange (ETDEWEB)

Tonami, N.; Matsuda, H.; Ooba, H.; Yokoyama, K.; Hisada, K.; Ikeda, K.; Yamashita, J. (Kanazawa Univ. (Japan))

1990-06-01

The authors present an unexpected finding of Tl-201 uptake in the intracerebral lesions due to candidiasis. SPECT demonstrated the extent of the lesions and a high target-to-background ratio. The regions where abnormal Tl-201 accumulation was seen were nearly consistent with CT scans of those enhanced by a contrast agent. After treatment, most of the abnormal Tl-201 accumulation disappeared.

Demographic characteristics in patients with short-gap and long-gap ...

African Journals Online (AJOL)

Further analysis of this topic is warranted ... Keywords: demographic characteristics, long-gap esophageal atresia, short-gap ... Thus, we conducted the present study to analyze the character- ..... this issue, providing fundamental information.

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

Directory of Open Access Journals (Sweden)

Vladislav Volman

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

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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.

Four unexpected lanthanide coordination polymers involving in situ reaction of solvent N, N-Dimethylformamide

International Nuclear Information System (INIS)

Jin, Jun-Cheng; Tong, Wen-Quan; Fu, Ai-Yun; Xie, Cheng-Gen; Chang, Wen-Gui; Wu, Ju; Xu, Guang-Nian; Zhang, Ya-Nan; Li, Jun; Li, Yong; Yang, Peng-Qi

2015-01-01

Four unexpected 2D lanthanide coordination polymers have been synthesized through in situ reactions of DMF solvent under solvothermal conditions. The isostructural complexes 1–3 contain four types of 2 1 helical chains. While the Nd(III) ions are bridged through μ 2 -HIDC 2− and oxalate to form a 2D sheet along the bc plane without helical character in 4. Therefore, complex 1 exhibits bright red solid-state phosphorescence upon exposure to UV radiation at room temperature. - Graphical abstract: Four unexpected 2D lanthanide coordination polymers have been synthesized through in situ reactions of solvent DMF to formate acid or oxalic acid under solvothermal conditions. The isostructural complexes 1–3 contain four types of different 2 1 helical chains in the 2D layer and 1 exhibits bright red solid-state phosphorescence upon UV radiation. - Highlights: • Four unexpected 2D lanthanide coordination compounds have been synthesized through in situ reactions under solvothermal conditions. • The complexes 1–3 contain four types of 2 1 helical chains in the layer. • Complex 1 exhibits bright red solid-state phosphorescence upon exposure to UV radiation at room temperature

Spin Orbit Coupling Gap and Indirect Gap in Strain-Tuned Topological Insulator-Antimonene

OpenAIRE

Cheung, Chi-Ho; Fuh, Huei-Ru; Hsu, Ming-Chien; Lin, Yeu-Chung; Chang, Ching-Ray

2016-01-01

Recently, searching large-bulk band gap topological insulator (TI) is under intensive study. Through k?P theory and first-principles calculations analysis on antimonene, we find that ?-phase antimonene can be tuned to a 2D TI under an in-plane anisotropic strain and the magnitude of direct bulk band gap (SOC gap) depends on the strength of spin-orbit coupling (SOC) which is strain-dependent. As the band inversion of this TI accompanies with an indirect band gap, the TI bulk band gap is the in...

40 CFR 406.43 - [Reserved

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true [Reserved] 406.43 Section 406.43 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GRAIN MILLS POINT SOURCE CATEGORY Bulgur Wheat Flour Milling Subcategory § 406.43 [Reserved] ...

Openness to the unexpected: Our Pathways to Careers in a Federal Research Laboratory.

Science.gov (United States)

Newman, Kurt R.; Bunnell, David B.; Hondorp, Darryl W.; Taylor, William W.; Lynch, Abigail J.; Léonard, Nancy J.

2014-01-01

Many fisheries professionals may not be in the job they originally envisioned for themselves when they began their undergraduate studies. Rather, their current positions could be the result of unexpected, opportunistic, or perhaps even “lucky” open doors that led them down an unexpected path. In many cases, a mentor helped facilitate the unforeseen trajectory. We offer three unique stories about joining a federal fisheries research laboratory, from the perspective of a scientist, a joint manager-scientist, and a manager. We also use our various experiences to form recommendations that should help the next generation of fisheries professionals succeed in any stop along their journey, including being open to opportunities, setting high expectations, and finding a strong and supportive team environment to work in.

Evolution of the two-gap nature revealed in the upper critical field of Mg1-xAlxB2

International Nuclear Information System (INIS)

Kim, Heon-Jung; Lee, Hyun-Sook; Park, Min-Seok; Lee, H.-G.; Jo, Younghun; Jung, Myung-Hwa; Lee, Sung-Ik; Kang, Byeongwon

2007-01-01

The temperature and the angular dependences of the upper critical field [H c2 (T,θ)] of Mg 1-x Al x B 2 single crystals (x=0.12 and 0.21) were studied. The H c2 (T,θ) was found to be well described by the dirty-limit two-gap theory. A quantitative comparison of the data with this theory indicated that Mg 1-x Al x B 2 single crystals preserved the two-gap nature but became dirtier. We also found that as the Al concentration was increased, anisotropic impurity scattering increased, making the σ bands less anisotropic. In addition, these results are compared with those of 10% C-doped MgB 2 single crystals

Pre-synaptic control of remote fear extinction in the neocortex

Directory of Open Access Journals (Sweden)

Gisella eVetere

2012-06-01

Full Text Available Consolidation of remote memory enhances immediate early genes induction (IEGs, augments the expression of the presynaptic growth associated protein 43 (GAP-43, and increases the density and size of dendritic spines in anterior cingulate (aCC and infra-limbic (ILC cortices. Remote memory extinction, however, does not uniformly alter consolidation-induced structural changes. In the aCC, the density, but not the size, of spines is reset to pseudo-conditioning levels while novel thin spines are formed in the ILC. Whether IEGs and GAP-43 also undergo region-specific changes upon remote memory extinction is undetermined. Here we confirm in the same batch of mice that c-Fos induction and GAP-43 expression are increased in both the aCC and the ILC 36 days after contextual fear conditioning. We then show that, in both regions, remote memory extinction is associated with decrease of c-Fos induction but no change in GAP-43 expression thus revealing similar, although protein-specific, pre-synaptic adaptations in aCC and ILC neurons. These observations, in addition to our previous report of region-specific post-synaptic structural changes, disclose a complex pattern of extinction-driven neocortical alterations suitable to support erasure or reinstatement of fear according to the environment demand.

The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus

DEFF Research Database (Denmark)

Milting, Hendrik; Klauke, Bärbel; Christensen, Alex Hoerby

2014-01-01

atomic force microscopy and revealed that the cell nuclei exhibit an increased stiffness compared with TMEM43 wild-type controls. CONCLUSION: The German family is not affected by a de novo TMEM43 mutation. It is therefore expected that an unknown number of European families may be affected by the TMEM43...... without mutations in desmosomal genes and identified the TMEM43-p.S358L mutation in a German ARVC family. We excluded TMEM43-p.S358L in 22 unrelated patients with dilated cardiomyopathy. The German family shares a common haplotype with those from Newfoundland, USA, and Denmark, suggesting...... that the mutation originated from a common founder. Examination of 40 control chromosomes revealed an estimated age of 1300-1500 years for the mutation, which proves the European origin of the Newfoundland mutation. Skin fibroblasts from a female and two male mutation carriers were analysed in cell culture using...

Mechanics of Fluid-Filled Interstitial Gaps. II. Gap Characteristics in Xenopus Embryonic Ectoderm.

Science.gov (United States)

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

2017-08-22

The ectoderm of the Xenopus embryo is permeated by a network of channels that appear in histological sections as interstitial gaps. We characterized this interstitial space by measuring gap sizes, angles formed between adjacent cells, and curvatures of cell surfaces at gaps. From these parameters, and from surface-tension values measured previously, we estimated the values of critical mechanical variables that determine gap sizes and shapes in the ectoderm, using a general model of interstitial gap mechanics. We concluded that gaps of 1-4 μm side length can be formed by the insertion of extracellular matrix fluid at three-cell junctions such that cell adhesion is locally disrupted and a tension difference between cell-cell contacts and the free cell surface at gaps of 0.003 mJ/m 2 is generated. Furthermore, a cell hydrostatic pressure of 16.8 ± 1.7 Pa and an interstitial pressure of 3.9 ± 3.6 Pa, relative to the central blastocoel cavity of the embryo, was found to be consistent with the observed gap size and shape distribution. Reduction of cell adhesion by the knockdown of C-cadherin increased gap volume while leaving intracellular and interstitial pressures essentially unchanged. In both normal and adhesion-reduced ectoderm, cortical tension of the free cell surfaces at gaps does not return to the high values characteristic of the free surface of the whole tissue. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Platinum-nanoparticle-supported core-shell polymer nanospheres with unexpected water stability and facile further modification

Science.gov (United States)

Yuan, Conghui; Xu, Yiting; Luo, Weiang; Zeng, Birong; Qiu, Wuhui; Liu, Jie; Huang, Huiling; Dai, Lizong

2012-05-01

Core-shell nanospheres (CSNSs) with hydrophobic cores and hydrophilic shells were fabricated via a simple mini-emulsion polymerization for the stabilization of platinum nanoparticles (Pt-NPs). The CSNSs showed extremely high loading capacity of Pt-NPs (the largest loading amount of the Pt-NPs was about 49.2 wt%). Importantly, the Pt-NPs/CSNSs nanocomposites had unexpected stability in aqueous solution. DLS results revealed that the CSNSs loaded with Pt-NPs exhibited almost no aggregation after standing for a long time . However, the Pt-NPs immobilized on the CSNSs were not straitlaced: they could transport and redistribute between CSNSs freely when the environmental temperature was higher than the melting point of the CSNS shell. Owing to their excellent stability in aqueous solution, the surface of the Pt-NPs/CSNSs nanocomposites could be further decorated easily. For example, polyaniline (PANI)-coated Pt-NPs/CSNSs, nickel (Ni)-coated Pt-NPs/CSNSs and PANI/Pt-NPs dual-layer hollow nanospheres were facilely fabricated from the Pt-NPs/CSNS nanocomposites.

Platinum-nanoparticle-supported core–shell polymer nanospheres with unexpected water stability and facile further modification

International Nuclear Information System (INIS)

Yuan Conghui; Xu Yiting; Luo Weiang; Zeng Birong; Qiu Wuhui; Liu Jie; Dai Lizong; Huang Huiling

2012-01-01

Core–shell nanospheres (CSNSs) with hydrophobic cores and hydrophilic shells were fabricated via a simple mini-emulsion polymerization for the stabilization of platinum nanoparticles (Pt-NPs). The CSNSs showed extremely high loading capacity of Pt-NPs (the largest loading amount of the Pt-NPs was about 49.2 wt%). Importantly, the Pt-NPs/CSNSs nanocomposites had unexpected stability in aqueous solution. DLS results revealed that the CSNSs loaded with Pt-NPs exhibited almost no aggregation after standing for a long time . However, the Pt-NPs immobilized on the CSNSs were not straitlaced: they could transport and redistribute between CSNSs freely when the environmental temperature was higher than the melting point of the CSNS shell. Owing to their excellent stability in aqueous solution, the surface of the Pt-NPs/CSNSs nanocomposites could be further decorated easily. For example, polyaniline (PANI)-coated Pt-NPs/CSNSs, nickel (Ni)-coated Pt-NPs/CSNSs and PANI/Pt-NPs dual-layer hollow nanospheres were facilely fabricated from the Pt-NPs/CSNS nanocomposites. (paper)

Density functional theory calculations for the band gap and formation energy of Pr4-xCaxSi12O3+xN18-x; a highly disordered compound with low symmetry and a large cell size.

Science.gov (United States)

Hong, Sung Un; Singh, Satendra Pal; Pyo, Myoungho; Park, Woon Bae; Sohn, Kee-Sun

2017-06-28

A novel oxynitride compound, Pr 4-x Ca x Si 12 O 3+x N 18-x , synthesized using a solid-state route has been characterized as a monoclinic structure in the C2 space group using Rietveld refinement on synchrotron powder X-ray diffraction data. The crystal structure of this compound was disordered due to the random distribution of Ca/Pr and N/O ions at various Wyckoff sites. A pragmatic approach for an ab initio calculation based on density function theory (DFT) for this disordered compound has been implemented to calculate an acceptable value of the band gap and formation energy. In general, for the DFT calculation of a disordered compound, a sufficiently large super cell and infinite variety of ensemble configurations is adopted to simulate the random distribution of ions; however, such an approach is time consuming and cost ineffective. Even a single unit cell model gave rise to 43 008 independent configurations as an input model for the DFT calculations. Since it was nearly impossible to calculate the formation energy and the band gap energy for all 43 008 configurations, an elitist non-dominated sorting genetic algorithm (NSGA-II) was employed to find the plausible configurations. In the NSGA-II, all 43 008 configurations were mathematically treated as genomes and the calculated band gap and the formation energy as the objective (fitness) function. Generalized gradient approximation (GGA) was first employed in the preliminary screening using NSGA-II, and thereafter a hybrid functional calculation (HSE06) was executed only for the most plausible GGA-relaxed configurations with lower formation and higher band gap energies. The final band gap energy (3.62 eV) obtained after averaging over the selected configurations, resembles closely the experimental band gap value (4.11 eV).

Mother-Youth Acculturation Gaps and Health-Risking/Emotional Problems among Latin-American Adolescents.

Science.gov (United States)

Wiesner, Margit; Arbona, Consuelo; Capaldi, Deborah M; Kim, Hyoun K; Kaplan, Charles D

2015-07-20

Second-generation Latin-American adolescents tend to show higher levels of various health-risking behaviors and emotional problems than first-generation Latin-American adolescents. This cross-sectional study of 40 mother-adolescent dyads examined the association of mother-youth acculturation gaps to youth adjustment problems. Intergenerational acculturation gaps were assessed as a bidimensional self-report component and a novel observational measurement component. The Latin-American adolescents were predominantly second-generation of Mexican descent (M age = 13.42 years, SD = 0.55). Most of the mothers were born in Mexico (M age = 39.18 years, SD = 5.17). Data were collected from mothers, adolescents, and coders, using questionnaires, structured interviews, and videotaped mother-youth interaction tasks. Findings revealed generally weak support for the acculturation gap-distress hypothesis. In addition, stronger relative adherence to their heritage culture by the adolescents was significantly (p acculturation processes. Mother-youth acculturation gaps in orientation to the heritage culture were the most salient dimension, changing the focus on the original formulation of the acculturation gap-distress hypothesis.

22 CFR 226.43 - Competition.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Competition. 226.43 Section 226.43 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.43 Competition. All procurement transactions...

7 CFR 966.43 - Accounting.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Accounting. 966.43 Section 966.43 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Expenses and Assessments § 966.43 Accounting. (a) All funds received by the committee...

7 CFR 959.43 - Accounting.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Accounting. 959.43 Section 959.43 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Regulating Handling Expenses and Assessments § 959.43 Accounting. (a) Assessments collected in excess of...

7 CFR 956.43 - Accounting.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Accounting. 956.43 Section 956.43 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... VALLEY OF SOUTHEAST WASHINGTON AND NORTHEAST OREGON Expenses and Assessments § 956.43 Accounting. (a) All...

Unpredictable Root Canal Morphology: Expect the Unexpected

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Sohez J Makani

2015-01-01

Full Text Available Background: A maxillary first molar with more than four canals is an interesting example of anatomic variations, especially when two of these canals are detected, with separate apical foramen in the distal root. The inability to locate the unexpected canals of various anatomical configuration and subsequently treat them , may lead to therapeutic failures. Endodontic retreatment is usually the modality of choice in such cases. This report describes a case of a maxillary first molar with five canals (two mesial canals in mesial root, two distal canals in two distal roots and a palatal canal in palatal root. Additionally it shows a rare anatomic configuration and emphasizes the importance of identifying additional canals.

A propensity score analysis of the impact of surgical intervention on unexpected 30-day readmission following admission for subdural hematoma.

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Franko, Lynze R; Sheehan, Kyle M; Roark, Christopher D; Joseph, Jacob R; Burke, James F; Rajajee, Venkatakrishna; Williamson, Craig A

2017-12-22

OBJECTIVE Subdural hematoma (SDH) is a common disease that is increasingly being managed nonoperatively. The all-cause readmission rate for SDH has not previously been described. This study seeks to describe the incidence of unexpected 30-day readmission in a cohort of patients admitted to an academic neurosurgical center. Additionally, the relationship between operative management, clinical outcome, and unexpected readmission is explored. METHODS This is an observational study of 200 consecutive adult patients with SDH admitted to the neurosurgical ICU of an academic medical center. Demographic information, clinical characteristics, and treatment strategies were compared between readmitted and nonreadmitted patients. Multivariable logistic regression, weighted by the inverse probability of receiving surgery using propensity scores, was used to evaluate the association between operative management and unexpected readmission. RESULTS Of 200 total patients, 18 (9%) died during hospitalization and were not included in the analysis. Overall, 48 patients (26%) were unexpectedly readmitted within 30 days. Sixteen patients (33.3%) underwent SDH evacuation during their readmission. Factors significantly associated with unexpected readmission were nonoperative management (72.9% vs 54.5%, p = 0.03) and female sex (50.0% vs 32.1%, p = 0.03). In logistic regression analysis weighted by the inverse probability of treatment and including likely confounders, surgical management was not associated with likelihood of a good outcome at hospital discharge, but was associated with significantly reduced odds of unexpected readmission (OR 0.19, 95% CI 0.08-0.49). CONCLUSIONS Over 25% of SDH patients admitted to an academic neurosurgical ICU were unexpectedly readmitted within 30 days. Nonoperative management does not affect outcome at hospital discharge but is significantly associated with readmission, even when accounting for the probability of treatment by propensity score weighted

40 CFR 172.43 - Definitions.

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2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Definitions. 172.43 Section 172.43... PERMITS Notification for Certain Genetically Modified Microbial Pesticides § 172.43 Definitions. Terms... material of an isolate and any descendants derived under axenic culture conditions from that isolate. Small...

7 CFR 955.43 - Accounting.

Science.gov (United States)

2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Accounting. 955.43 Section 955.43 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Expenses and Assessments § 955.43 Accounting. (a) All funds received by the committee pursuant to the...