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https://www.readbyqxmd.com/read/28636876/tissue-alignment-enhances-remodeling-potential-of-tendon-derived-cells-lessons-from-a-novel-microtissue-model-of-tendon-scarring
#1
Jasper Foolen, Stefania L Wunderli, Sandra Loerakker, Jess G Snedeker
Tendinopathy is a widespread and unresolved clinical challenge, in which associated pain and hampered mobility present a major cause for work-related disability. Tendinopathy associates with a change from a healthy tissue with aligned extracellular matrix (ECM) and highly polarized cells that are connected head-to-tail, towards a diseased tissue with a disorganized ECM and randomly distributed cells, scar-like features that are commonly attributed to poor innate regenerative capacity of the tissue. A fundamental clinical dilemma with this scarring process is whether treatment strategies should focus on healing the affected (disorganized) tissue or strengthen the remaining healthy (anisotropic) tissue...
June 18, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28636799/transcriptional-mechanisms-coordinating-tight-junction-assembly-during-epithelial-differentiation
#2
REVIEW
Felix J Boivin, Kai M Schmidt-Ott
Epithelial tissues form a selective barrier via direct cell-cell interactions to separate and establish concentration gradients between the different compartments of the body. Proper function and formation of this barrier rely on the establishment of distinct intercellular junction complexes. These complexes include tight junctions, adherens junctions, desmosomes, and gap junctions. The tight junction is by far the most diverse junctional complex in the epithelial barrier. Its composition varies greatly across different epithelial tissues to confer various barrier properties...
June 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28634726/connexin-channels-at-the-glio-vascular-interface-gatekeepers-of-the-brain
#3
Marijke De Bock, Luc Leybaert, Christian Giaume
Neuronal survival, electrical signaling and synaptic activity require a well-balanced micro-environment in the central nervous system. This is achieved by the blood-brain barrier (BBB), an endothelial barrier situated in the brain capillaries, that controls near-to-all passage in and out of the brain. The endothelial barrier function is highly dependent on signaling interactions with surrounding glial, neuronal and vascular cells, together forming the neuro-glio-vascular unit. Within this functional unit, connexin (Cx) channels are of utmost importance for intercellular communication between the different cellular compartments...
June 20, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28634441/roles-of-pannexin-1-channels-in-inflammatory-response-through-the-tlrs-nf-kappa-b-signaling-pathway-following-experimental-subarachnoid-hemorrhage-in-rats
#4
Ling-Yun Wu, Zhen-Nan Ye, Chen-Hui Zhou, Chun-Xi Wang, Guang-Bin Xie, Xiang-Sheng Zhang, Yong-Yue Gao, Zi-Huan Zhang, Meng-Liang Zhou, Zong Zhuang, Jing-Peng Liu, Chun-Hua Hang, Ji-Xin Shi
Background: Accumulating evidence suggests that neuroinflammation plays a critical role in early brain injury after subarachnoid hemorrhage (SAH). Pannexin-1 channels, as a member of gap junction proteins located on the plasma membrane, releases ATP, ions, second messengers, neurotransmitters, and molecules up to 1 kD into the extracellular space, when activated. Previous studies identified that the opening of Pannexin-1 channels is essential for cellular migration, apoptosis and especially inflammation, but its effects on inflammatory response in SAH model have not been explored yet...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28630124/the-dna-repair-repertoire-of-mycobacterium-smegmatis-fena-includes-the-incision-of-dna-5-flaps-and-the-removal-of-5-adenylylated-products-of-aborted-nick-ligation
#5
Maria Loressa Uson, Shreya Ghosh, Stewart Shuman
We characterize Mycobacterium smegmatis FenA as a manganese-dependent 5' -flap endonuclease homologous to the 5' -exonuclease of DNA polymerase I. FenA incises a nicked 5' flap between the first and second nucleotides of the duplex segment to yield a 1-nucleotide gapped DNA, which is then further resected in dinucleotide steps. Initial FenA cleavage at a Y-flap or nick occurs between the first and second nucleotides of the duplex. However, when the template 3' -single-strand is eliminated to create a 5' -tailed duplex, FenA incision shifts to between the second and third nucleotides...
June 19, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28626554/tuning-the-polarity-of-charge-carriers-using-electron-deficient-thiophenes
#6
Jonathan Z Low, Brian Capozzi, Jing Cui, Sujun Wei, Latha Venkataraman, Luis M Campos
Thiophene-1,1-dioxide (TDO) oligomers have fascinating electronic properties. We previously used thermopower measurements to show that a change in charge carrier from hole to electron occurs with increasing length of TDO oligomers when single-molecule junctions are formed between gold electrodes. In this article, we show for the first time that the dominant conducting orbitals for thiophene/TDO oligomers of fixed length can be tuned by altering the strength of the electron acceptors incorporated into the backbone...
April 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28625689/multiple-and-complex-influences-of-connexins-and-pannexins-on-cell-death
#7
REVIEW
Jérôme Gilleron, Diane Carette, Dominique Segretain, Georges Pointis
Cell death is a fundamental process for organogenesis, immunity and cell renewal. During the last decades a broad range of molecular tools were identified as important players for several different cell death pathways (apoptosis, pyroptosis, necrosis, autosis…). Aside from these direct regulators of cell death programs, several lines of evidence proposed connexins and pannexins as potent effectors of cell death. In the present review we discussed the potential roles played by connexins, pannexins and innexins in the different cell death programs at different scales from gap junction intercellular communication to protein-protein interactions...
June 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28620207/dengue-virus-activates-cgas-through-the-release-of-mitochondrial-dna
#8
Bo Sun, Karin B Sundström, Jun Jie Chew, Pradeep Bist, Esther S Gan, Hwee Cheng Tan, Kenneth C Goh, Tanu Chawla, Choon Kit Tang, Eng Eong Ooi
Cyclic GMP-AMP synthetase (cGAS) is a DNA-specific cytosolic sensor, which detects and initiates host defense responses against microbial DNA. It is thus curious that a recent study identified cGAS as playing important roles in inhibiting positive-sense single-stranded RNA (+ssRNA) viral infection, especially since RNA is not known to activate cGAS. Using a dengue virus serotype 2 (DENV-2) vaccine strain (PDK53), we show that infection creates an endogenous source of cytosolic DNA in infected cells through the release of mitochondrial DNA (mtDNA) to drive the production of cGAMP by cGAS...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619506/near-infra-red-light-attenuates-corneal-endothelial-cell-dysfunction-in-situ-and-in%C3%A2-vitro
#9
Claudia Núñez-Álvarez, Susana Del Olmo-Aguado, Jesús Merayo-Lloves, Neville N Osborne
In the present study mechanical damage to the corneal endothelium was induced by elevation of intraocular pressure (IOP, 140 mmHg, 60 min) to one eye of rats, delivered either in complete darkness or in the presence of red light (16.5 W/m(2), 3000 lx, 625-635 nm). IOP raised in the dark revealed the endothelium to be damaged as staining for the gap junction protein ZO-1 was irregular in appearance with some cells displaced in position or lost to leave gaps or holes. This damage was clearly attenuated when red light was focused through the pupil during the insult of raised IOP...
June 13, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28617969/conditionally-targeted-deletion-of-psen1-leads-to-diastolic-heart-dysfunction
#10
Xiao-Wei Song, Qing-Ning Yuan, Ying Tang, Mi Cao, Ya-Feng Shen, Zhen-Yu Zeng, Chang-Hai Lei, SongHua Li, Xian-Xian Zhao, Yong-Ji Yang
Recently, PSEN1 has been reported to have mutations in dilated cardiomyopathy pedigrees. However, the function and mechanism of PSEN1 in cardiomyopathy remains unresolved. Here, we established 4 types of genetically modified mice to determine the function of PSEN1 in cardiac development and pathology. PSEN1 null mutation resulted in perinatal death, retardation of heart growth, ventricular dilatation, septum defects, and valvular thickening. PSEN1 knockout in adults led to decreased muscle fibers, widened sarcomere Z lines and reduced lengths of sarcomeres in cardiomyocytes...
June 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28617431/nicotine-protects-rat-hypoglossal-motoneurons-from-excitotoxic-death-via-downregulation-of-connexin-36
#11
Silvia Corsini, Maria Tortora, Rossana Rauti, Andrea Nistri
Motoneuron disease including amyotrophic lateral sclerosis may be due, at an early stage, to deficit in the extracellular clearance of the excitatory transmitter glutamate. A model of glutamate-mediated excitotoxic cell death based on pharmacological inhibition of its uptake was used to investigate how activation of neuronal nicotinic receptors by nicotine may protect motoneurons. Hypoglossal motoneurons (HMs) in neonatal rat brainstem slices were exposed to the glutamate uptake blocker DL-threo-β-benzyloxyaspartate (TBOA) that evoked large Ca(2+) transients time locked among nearby HMs, whose number fell by about 30% 4 h later...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28613412/myoendothelial-coupling-through-cx40-contributes-to-edh-induced-vasodilation-in-murine-renal-arteries-evidence-from-experiments-and-modelling
#12
Jens Christian Brasen, Cor de Wit, Charlotte Mehlin Sorensen
Regulation of renal vascular resistance plays a major role in controlling arterial blood pressure. The endothelium participates in this regulation as endothelial derived hyperpolarization plays a significant role in smaller renal arteries and arterioles but the exact mechanisms are still unknown AIM: to investigate the role of vascular gap junctions and potassium channels in the renal endothelial derived hyperpolarization. METHODS: in interlobar arteries from wild-type and connexin40 knock-out mice we assessed the role of calcium activated small (SK) and intermediate (IK) conductance potassium channels...
June 14, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28611680/mono-heteromeric-configurations-of-gap-junction-channels-formed-by-connexin43-and-connexin45-reduce-unitary-conductance-and-determine-both-voltage-gating-and-metabolic-flux-asymmetry
#13
Guoqiang Zhong, Nazem Akoum, Daniel A Appadurai, Volodya Hayrapetyan, Osman Ahmed, Agustin D Martinez, Eric C Beyer, Alonso P Moreno
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...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28607928/extremely-low-frequency-electromagnetic-fields-affect-myogenic-processes-in-c2c12-myoblasts-role-of-gap-junction-mediated-intercellular-communication
#14
Caterina Morabito, Nathalie Steimberg, Francesca Rovetta, Jennifer Boniotti, Simone Guarnieri, Giovanna Mazzoleni, Maria A Mariggiò
Extremely low-frequency electromagnetic fields (ELF-EMFs) can interact with biological systems. Although they are successfully used as therapeutic agents in physiatrics and rehabilitative practice, they might represent environmental pollutants and pose a risk to human health. Due to the lack of evidence of their mechanism of action, the effects of ELF-EMFs on differentiation processes in skeletal muscle were investigated. C2C12 myoblasts were exposed to ELF-EMFs generated by a solenoid. The effects of ELF-EMFs on cell viability and on growth and differentiation rates were studied using colorimetric and vital dye assays, cytomorphology, and molecular analysis of MyoD and myogenin expression, respectively...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28607615/diffuse-interstitial-fibrosis-assessed-by-cardiac-magnetic-resonance-is-associated-with-dispersion-of-ventricular-repolarization-in-patients-with-hypertrophic-cardiomyopathy
#15
David Hurtado-de-Mendoza, Celia P Corona-Villalobos, Iraklis Pozios, Jorge Gonzales, Yalda Soleimanifard, Sanjay Sivalokanathan, Diego Montoya-Cerrillo, Styliani Vakrou, Ihab Kamel, Wilfredo Mormontoy-Laurel, Ketty Dolores-Cerna, Jacsel Suarez, Sergio Perez-Melo, David A Bluemke, Theodore P Abraham, Stefan L Zimmerman, M Roselle Abraham
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by myocyte hypertrophy, disarray, fibrosis, and increased risk for ventricular arrhythmias. Increased QT dispersion has been reported in patients with HCM, but the underlying mechanisms have not been completely elucidated. In this study, we examined the relationship between diffuse interstitial fibrosis, replacement fibrosis, QTc dispersion and ventricular arrhythmias in patients with HCM. We hypothesized that fibrosis would slow impulse propagation and increase dispersion of ventricular repolarization, resulting in increased QTc dispersion on surface electrocardiogram (ECG) and ventricular arrhythmias...
June 2017: Journal of Arrhythmia
https://www.readbyqxmd.com/read/28607585/aberrant-cx43-expression-and-mislocalization-in-metastatic-human-melanomas
#16
Katanya C Alaga, Melissa Crawford, Lina Dagnino, Dale W Laird
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...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28605375/analysis-of-protein-protein-interactions-and-co-localization-between-components-of-gap-tight-and-adherens-junctions-in-murine-mammary-glands
#17
Elham Dianati, Isabelle Plante
Cell-cell interactions play a pivotal role in preserving tissue integrity and the barrier between the different compartments of the mammary gland. These interactions are provided by junctional proteins that form nexuses between adjacent cells. Junctional protein mislocalization and reduced physical associations with their binding partners can result in the loss of function and, consequently, to organ dysfunction. Thus, identifying protein localization and protein-protein interactions (PPIs) in normal and disease-related tissues is essential to finding new evidences and mechanisms leading to the progression of diseases or alterations in developmental status...
May 30, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28604388/targeting-neuronal-gap-junctions-in-mouse-retina-offers-neuroprotection-in-glaucoma
#18
Abram Akopian, Sandeep Kumar, Hariharasubramanian Ramakrishnan, Kaushambi Roy, Suresh Viswanathan, Stewart A Bloomfield
The progressive death of retinal ganglion cells and resulting visual deficits are hallmarks of glaucoma, but the underlying mechanisms remain unclear. In many neurodegenerative diseases, cell death induced by primary insult is followed by a wave of secondary loss. Gap junctions (GJs), intercellular channels composed of subunit connexins, can play a major role in secondary cell death by forming conduits through which toxic molecules from dying cells pass to and injure coupled neighbors. Here we have shown that pharmacological blockade of GJs or genetic ablation of connexin 36 (Cx36) subunits, which are highly expressed by retinal neurons, markedly reduced loss of neurons and optic nerve axons in a mouse model of glaucoma...
June 12, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28603488/hypothesis-of-k-recycling-defect-is-not-a-primary-deafness-mechanism-for-cx26-gjb2-deficiency
#19
REVIEW
Hong-Bo Zhao
K(+)-recycling defect is a long-standing hypothesis for deafness mechanism of Connexin26 (Cx26, GJB2) mutations, which cause the most common hereditary deafness and are responsible for >50% of nonsyndromic hearing loss. The hypothesis states that Cx26 deficiency may disrupt inner ear gap junctions and compromise sinking and recycling of expelled K(+) ions after hair cell excitation, causing accumulation of K(+)-ions in the extracellular space around hair cells producing K(+)-toxicity, which eventually induces hair cell degeneration and hearing loss...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28602541/connexin-43-enhances-bax-activation-via-jnk-activation-in-sunitinib-induced-apoptosis-in-mesothelioma-cells
#20
Miaki Uzu, Hiromi Sato, Ayaka Shimizu, Yukihiro Shibata, Koichi Ueno, Akihiro Hisaka
The constituent protein of gap junctions, connexin (Cx), interacts with various proteins via its C-terminus region, including kinases, cell-adhesion proteins, and a pro-apoptotic protein, Bax. This molecular interaction may affect expression and functioning of the interacting proteins and modulate the cellular physiology. In our previous work, Cx43 was found to interact directly with Bax and in the presence of sunitinib, lead to the Bax-mediated apoptosis in mesothelioma cells. In this study, we investigated the mechanism of how Cx43 promotes Bax-mediated apoptosis using the same cell line...
May 27, 2017: Journal of Pharmacological Sciences
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