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https://www.readbyqxmd.com/read/29164306/a-structure-activity-relationship-linking-non-planar-pcbs-to-functional-deficits-of-neural-crest-cells-new-roles-for-connexins
#1
Johanna Nyffeler, Petra Chovancova, Xenia Dolde, Anna-Katharina Holzer, Vladimir Purvanov, Ilona Kindinger, Anna Kerins, David Higton, Steve Silvester, Barbara M A van Vugt-Lussenburg, Enrico Glaab, Bart van der Burg, Richard Maclennan, Daniel F Legler, Marcel Leist
Migration of neural crest cells (NCC) is a fundamental developmental process, and test methods to identify interfering toxicants have been developed. By examining cell function endpoints, as in the 'migration-inhibition of NCC (cMINC)' assay, a large number of toxicity mechanisms and protein targets can be covered. However, the key events that lead to the adverse effects of a given chemical or group of related compounds are hard to elucidate. To address this issue, we explored here, whether the establishment of two overlapping structure-activity relationships (SAR)-linking chemical structure on the one hand to a phenotypic test outcome, and on the other hand to a mechanistic endpoint-was useful as strategy to identify relevant toxicity mechanisms...
November 21, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29163229/cx43-isoform-gja1-20k-promotes-microtubule-dependent-mitochondrial-transport
#2
Ying Fu, Shan-Shan Zhang, Shaohua Xiao, Wassim A Basheer, Rachel Baum, Irina Epifantseva, TingTing Hong, Robin M Shaw
Connexin 43 (Cx43, encoded by GJA1) is a cell-cell communication gap junction protein expressed in all organ systems. It was recently found that GJA1 mRNA undergoes alternative translation to generate N-terminal truncated isoforms, of which GJA1-20k is the most abundant. Here we report a surprising finding that, unlike full length GJA1-43k, GJA1-20k has a strong tropism for mitochondria. Exploring function, we found that GJA1-20k appears to be an organelle chaperone and that overexpression of GJA1-20k is sufficient to rescue mitochondrial localization to the cell periphery upon exposure to hydrogen peroxide, which effectively limits the network fragmentation that occurs with oxidative stress...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29161558/electrical-synapses-new-rules-for-assembling-an-old-structure-asymmetrically
#3
James I Nagy, John E Rash
Electrical synapses are emerging as complex structures, consisting of gap junction-forming connexin proteins and also multiple scaffolding and regulatory protein components, which were assumed to be symmetrically organized across these synapses; however, new findings reveal their synaptic asymmetry.
November 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29158514/large-magneto-seebeck-effect-in-magnetic-tunnel-junctions-with-half-metallic-heusler-electrodes
#4
Alexander Boehnke, Ulrike Martens, Christian Sterwerf, Alessia Niesen, Torsten Huebner, Marvin von der Ehe, Markus Meinert, Timo Kuschel, Andy Thomas, Christian Heiliger, Markus Münzenberg, Günter Reiss
Spin caloritronics studies the interplay between charge-, heat- and spin-currents, which are initiated by temperature gradients in magnetic nanostructures. A plethora of new phenomena has been discovered that promises, e.g., to make wasted heat in electronic devices useable or to provide new read-out mechanisms for information. However, only few materials have been studied so far with Seebeck voltages of only some microvolt, which hampers applications. Here, we demonstrate that half-metallic Heusler compounds are hot candidates for enhancing spin-dependent thermoelectric effects...
November 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29156723/effects-of-pharmacological-gap-junction-and-sodium-channel-blockade-on-s1s2-restitution-properties-in-langendorff-perfused-mouse-hearts
#5
Gary Tse, Tong Liu, Guangping Li, Wendy Keung, Jie Ming Yeo, Yin Wah Fiona Chan, Bryan P Yan, Yat Sun Chan, Sunny Hei Wong, Ronald A Li, Jichao Zhao, William K K Wu, Wing Tak Wong
Gap junctions and sodium channels are the major molecular determinants of normal and abnormal electrical conduction through the myocardium, however, their exact contributions to arrhythmogenesis are unclear. We examined conduction and recovery properties of regular (S1) and extrasystolic (S2) action potentials (APs), S1S2 restitution and ventricular arrhythmogenicity using the gap junction and sodium channel inhibitor heptanol (2 mM) in Langendorff-perfused mouse hearts (n=10). Monophasic action potential recordings obtained during S1S2 pacing showed that heptanol increased the proportion of hearts showing inducible ventricular tachycardia (0/10 vs...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155206/inhibition-of-connexin-43-translocation-on-mitochondria-accelerates-cocl2-induced-apoptotic-response-in-a-chemical-model-of-hypoxia
#6
Michela Pecoraro, Aldo Pinto, Ada Popolo
Hypoxia is the basis of many myocardial conditions, and it can initiate cell death programs, among which apoptosis is well-known. Connexin 43 (Cx43), the major component of cardiomyocyte Gap Junctions, is important in cardioprotection. Cx43is involved in ischemia/reperfusion injury and ischemic preconditioning's protection in vitro; however, its role on cardiomyocyte under hypoxia is still unclear. Reports have shown that Cx43 is also located at the inner membrane of mitochondria where it has been implicated in enhanced ischemic preconditioning response...
November 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29153916/a-case-with-cmtx1-disease-showing-transient-ischemic-attack-like-episodes
#7
Zehra Aktan, Nihan Hande Akcakaya, Pinar Tekturk, Engin Deniz, Bahar Koyuncu, Zuhal Yapici
Charcot-Marie-Tooth (CMT) disease is a hereditary neurologic disease which affects the sensorial and motor fibers of the peripheral nerves. CMTX1 is an X-linked dominantly inherited subtype of CMT and is caused by mutations in gap junction beta 1 gene (GJB1). A small proportion of GJB1 mutations are associated with recurrent central nervous system findings. We describe a 15-year-old male patient with CMTX1 who had stroke-like findings along with foot deformities and peripheral neuropathy. Strokes and stroke-like attacks are rarely seen in children and adolescents...
November 9, 2017: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/29149200/heterozygous-deletion-of-both-sclerostin-sost-and-connexin43-gja1-genes-in-mice-is-not-sufficient-to-impair-cortical-bone-modeling
#8
Susan K Grimston, Francesca Fontana, Marcus Watkins, Roberto Civitelli
Connexin43 (Cx43) is the main gap junction protein expressed in bone forming cells, where it modulates peak bone mass acquisition and cortical modeling. Genetic ablation of the Cx43 gene (Gja1) results in cortical expansion with accentuated periosteal bone formation associated with decreased expression of the Wnt inhibitor sclerostin. To determine whether sclerostin (Sost) down-regulation might contribute to periosteal expansion in Gja1 deficient bones, we took a gene interaction approach and crossed mice harboring germline null alleles for Gja1 or Sost to generate single Gja1+/-and Sost+/-and double Gja1+/-;Sost+/-heterozygous mice...
2017: PloS One
https://www.readbyqxmd.com/read/29148914/marginal-gap-formation-in-approximal-bulk-fill-resin-composite-restorations-after-artificial-ageing
#9
A Peutzfeldt, S Mühlebach, A Lussi, S Flury
The aim of this in vitro study was to investigate the marginal gap formation of a packable "regular" resin composite (Filtek Supreme XTE [3M ESPE]) and two flowable "bulk fill" resin composites (Filtek Bulk Fill [3M ESPE] and SDR [DENTSPLY DeTrey]) along the approximal margins of Class II restorations. In each of 39 extracted human molars (n=13 per resin composite), mesial and distal Class II cavities were prepared, placing the gingival margins below the cemento-enamel junction. The cavities were restored with the adhesive system OptiBond FL (Kerr) and one of the three resin composites...
November 17, 2017: Operative Dentistry
https://www.readbyqxmd.com/read/29146153/the-stress-kinase-jnk-regulates-gap-junction-cx43-gene-expression-and-promotes-atrial-fibrillation-in-the-aged-heart
#10
Jiajie Yan, Justin K Thomson, Weiwei Zhao, Xiaomin Wu, Xianlong Gao, Dominic DeMarco, Wei Kong, Min Tong, Jun Sun, Mamdouh Bakhos, Vladimir G Fast, Qingrong Liang, Sumanth D Prabhu, Xun Ai
BACKGROUND: The stress kinase c-jun N-terminal kinase (JNK) is critical in the pathogenesis of cardiac diseases associated with an increased incidence of atrial fibrillation (AF), the most common arrhythmia in the elderly. We recently discovered that JNK activation is linked to the loss of gap junction connexin43 (Cx43) and enhanced atrial arrhythmogenicity. However, direct evidence for JNK-mediated impairment of intercellular coupling (cell-cell communication) in the intact aged atrium is lacking, as is evidence for whether and how JNK suppresses Cx43 in the aged human atrium...
November 13, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29145393/estimating-the-probabilities-of-rare-arrhythmic-events-in-multiscale-computational-models-of-cardiac-cells-and-tissue
#11
Mark A Walker, Viatcheslav Gurev, John J Rice, Joseph L Greenstein, Raimond L Winslow
Ectopic heartbeats can trigger reentrant arrhythmias, leading to ventricular fibrillation and sudden cardiac death. Such events have been attributed to perturbed Ca2+ handling in cardiac myocytes leading to spontaneous Ca2+ release and delayed afterdepolarizations (DADs). However, the ways in which perturbation of specific molecular mechanisms alters the probability of ectopic beats is not understood. We present a multiscale model of cardiac tissue incorporating a biophysically detailed three-dimensional model of the ventricular myocyte...
November 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29144745/high-efficiency-near-infrared-and-semitransparent-non-fullerene-acceptor-organic-photovoltaic-cells
#12
Yongxi Li, Jiu-Dong Lin, Xiaozhou Che, Yue Qu, Feng Liu, Liang-Sheng Liao, Stephen R Forrest
The absence of near-infrared (NIR) solar cells with high open circuit voltage (Voc) and external quantum efficiency (EQE) has impeded progress toward achieving organic photovoltaic (OPV) power conversion efficiency PCE > 15%. Here we report a small energy gap (1.3 eV), chlorinated nonfullerene acceptor-based solar cell with PCE = 11.2 ± 0.4%, short circuit current of 22.5 ± 0.6 mA cm(-2), Voc = 0.70 ± 0.01 V and fill factor of 0.71 ± 0.02, which is the highest performance reported to date for NIR single junction OPVs...
November 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29144224/violence-exposure-and-neural-systems-underlying-working-memory-for-emotional-stimuli-in-youth
#13
Jessica L Jenness, Maya L Rosen, Kelly A Sambrook, Meg J Dennison, Hilary K Lambert, Margaret A Sheridan, Katie A McLaughlin
Violence exposure during childhood is common and associated with poor cognitive and academic functioning. However, little is known about how violence exposure influences cognitive processes that might contribute to these disparities, such as working memory, or their neural underpinnings, particularly for cognitive processes that occur in emotionally salient contexts. We address this gap in a sample of 54 participants aged 8 to 19 years (50% female), half with exposure to interpersonal violence. Participants completed a delayed match to sample task for emotional faces while undergoing functional magnetic resonance imaging scanning...
November 16, 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/29143961/upregulation-of-epidermal-gap-junctional-proteins-in-patients-with-venous-disease
#14
M Kanapathy, R Simpson, L Madden, C Thrasivoulou, A Mosahebi, D L Becker, T Richards
BACKGROUND: Leg ulceration is a feared complication of venous insufficiency. It is not known whether varicose veins predispose skin to poor wound healing. The expression pattern of gap junctional protein connexin, a known marker of poor wound healing, was investigated across various stages of venous disease. METHODS: Patients undergoing intervention for varicose veins were assessed according to the Clinical Etiologic Anatomic Pathophysiologic (CEAP) classification of varicose veins...
November 16, 2017: British Journal of Surgery
https://www.readbyqxmd.com/read/29143947/connexin-30-is-expressed-in-a-subtype-of-mouse-brain-pericytes
#15
Noémie Mazaré, Alice Gilbert, Anne-Cécile Boulay, Nathalie Rouach, Martine Cohen-Salmon
Pericytes are mural cells of blood microvessels which play a crucial role at the neurovascular interface of the central nervous system. They are involved in the regulation of blood-brain barrier integrity, angiogenesis, clearance of toxic metabolites, capillary hemodynamic responses, and neuroinflammation, and they demonstrate stem cell activity. Morphological and molecular studies to characterize brain pericytes recently pointed out some heterogeneity in pericyte population. Nevertheless, a clear definition of pericyte subtypes is still lacking...
November 16, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29143796/angelica-sinensis-polysaccharides-ameliorate-stress-induced-premature-senescence-of-hematopoietic-cell-via-protecting-bone-marrow-stromal-cells-from-oxidative-injuries-caused-by-5-fluorouracil
#16
Hanxianzhi Xiao, Lirong Xiong, Xiaoying Song, Pengwei Jin, Linbo Chen, Xiongbin Chen, Hui Yao, Yaping Wang, Lu Wang
Myelosuppression is the most common complication of chemotherapy. Decline of self-renewal capacity and stress-induced premature senescence (SIPS) of hematopoietic stem cells (HSCs) induced by chemotherapeutic agents may be the cause of long-term myelosuppression after chemotherapy. Whether the mechanism of SIPS of hematopoietic cells relates to chemotherapeutic injury occurred in hematopoietic microenvironment (HM) is still not well elucidated. This study explored the protective effect of Angelica sinensis polysaccharide (ASP), an acetone extract polysaccharide found as the major effective ingredients of a traditional Chinese medicinal herb named Chinese Angelica (Dong Quai), on oxidative damage of homo sapiens bone marrow/stroma cell line (HS-5) caused by 5-fluorouracil (5-FU), and the effect of ASP relieving oxidative stress in HM on SIPS of hematopoietic cells...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29143226/aligned-ovine-diaphragmatic-myoblasts-overexpressing-human-connexin-43-seeded-on-poly-l-lactic-acid-scaffolds-for-potential-use-in-cardiac-regeneration
#17
Carlos Sebastián Giménez, Paola Locatelli, Florencia Montini Ballarin, Alejandro Orlowski, Ricardo A Dewey, Milagros Pena, Gustavo Abel Abraham, Ernesto Alejandro Aiello, María Del Rosario Bauzá, Luis Cuniberti, Fernanda Daniela Olea, Alberto Crottogini
Diaphragmatic myoblasts (DMs) are precursors of type-1 muscle cells displaying high exhaustion threshold on account that they contract and relax 20 times/min over a lifespan, making them potentially useful in cardiac regeneration strategies. Besides, it has been shown that biomaterials for stem cell delivery improve cell retention and viability in the target organ. In the present study, we aimed at developing a novel approach based on the use of poly (L-lactic acid) (PLLA) scaffolds seeded with DMs overexpressing connexin-43 (cx43), a gap junction protein that promotes inter-cell connectivity...
November 15, 2017: Cytotechnology
https://www.readbyqxmd.com/read/29137986/long-range-stress-transmission-guides-endothelial-gap-formation
#18
C Corey Hardin, Joyjit Chattoraj, Greeshma Manomohan, Jader Colombo, Trong Nguyen, Dhananjay Tambe, Jeffrey J Fredberg, Konstantin Birukov, James P Butler, Emanuela Del Gado, Ramaswamy Krishnan
In endothelial gap formation, local tractions exerted by the cell upon its basal adhesions are thought to exceed balancing tensile stresses exerted across the cell-cell junction, thus causing the junction to rupture. To test this idea, we mapped evolving tractions, intercellular stresses, and corresponding growth of paracellular gaps in response to agonist challenge. Contrary to expectation, we found little to no relationship between local tensile stresses and gap formation. Instead, we discovered that intercellular stresses were aligned into striking multi-cellular domains punctuated by defects in stress alignment...
November 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29137203/a-first-principle-theoretical-study-of-mechanical-and-electronic-properties-in-graphene-single-walled-carbon-nanotube-junctions
#19
Ning Yang, Daoguo Yang, Liangbiao Chen, Dongjing Liu, Miao Cai, Xuejun Fan
The new three-dimensional structure that the graphene connected with SWCNTs (G-CNTs, Graphene Single-Walled Carbon Nanotubes) can solve graphene and CNTs' problems. A comprehensive study of the mechanical and electrical performance of the junctions was performed by first-principles theory. There were eight types of junctions that were constituted by armchair and zigzag graphene and (3,3), (4,0), (4,4), and (6,0) CNTs. First, the junction strength was investigated. Generally, the binding energy of armchair G-CNTs was stronger than that of zigzag G-CNTs, and it was the biggest in the armchair G-CNTs (6,0)...
November 13, 2017: Materials
https://www.readbyqxmd.com/read/29134540/acute-connexin43-temporal-and-spatial-expression-in-response-to-ischemic-stroke
#20
Moises Freitas-Andrade, Jennifer She, John Bechberger, Christian C Naus, Wun Chey Sin
Connexin43 (Cx43) gap junctions expressed in astrocytes can significantly impact neuronal survival in stroke. However, little is known regarding Cx43 spatial and temporal expression during the initial stages of brain ischemia. Using immunohistochemistry and Western blot analysis, we examined Cx43 spatial and temporal expression as a function of neuronal injury within the first 24 h after permanent middle cerebral artery occlusion (pMCAO). Western blot analysis showed a significant increase in Cx43 protein expression in the core ischemic area at 2 and 3 h after pMCAO...
November 13, 2017: Journal of Cell Communication and Signaling
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