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https://www.readbyqxmd.com/read/29352264/cell-autonomous-role-of-iaspp-deficiency-in-causing-cardiocutaneous-disorders
#1
Zinaida Dedeić, Gopinath Sutendra, Ying Hu, Kathryn Chung, Elizabeth A Slee, Michael J White, Felix Y Zhou, Robert D Goldin, David J P Ferguson, Debra McAndrew, Jurgen E Schneider, Xin Lu
Desmosome components are frequently mutated in cardiac and cutaneous disorders in animals and humans and enhanced inflammation is a common feature of these diseases. Previous studies showed that inhibitor of Apoptosis Stimulating p53 Protein (iASPP) regulates desmosome integrity at cell-cell junctions and transcription in the nucleus, and its deficiency causes cardiocutaneous disorder in mice, cattle, and humans. As iASPP is a ubiquitously expressed shuttling protein with multiple functions, a key question is whether the observed cardiocutaneous phenotypes are caused by loss of a cell autonomous role of iASPP in cardiomyocytes and keratinocytes specifically or by a loss of iASPP in other cell types such as immune cells...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352236/control-of-neural-crest-induction-by-marveld3-mediated-attenuation-of-jnk-signalling
#2
Barbara Vacca, Elena Sanchez-Heras, Emily Steed, Sophie L Busson, Maria S Balda, Shin-Ichi Ohnuma, Noriaki Sasai, Roberto Mayor, Karl Matter
Tight junctions are required for the formation of tissue barriers and function as suppressors of signalling mechanisms that control gene expression and cell behaviour; however, little is known about the physiological and developmental importance of such signalling functions. Here, we demonstrate that depletion of MarvelD3, a transmembrane protein of tight junctions, disrupts neural crest formation and, consequently, development of neural crest-derived tissues during Xenopus embryogenesis. Using embryos and explant cultures combined with a small molecule inhibitor or mutant mRNAs, we show that MarvelD3 is required to attenuate JNK signalling during neural crest induction and that inhibition of JNK pathway activation is sufficient to rescue the phenotype induced by MarvelD3 depletion...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352171/a-urine-dependent-human-urothelial-organoid-offers-a-potential-alternative-to-rodent-models-of-infection
#3
Harry Horsley, Dhanuson Dharmasena, James Malone-Lee, Jennifer L Rohn
Murine models describe a defined host/pathogen interaction for urinary tract infection, but human cell studies are scant. Although recent human urothelial organoid models are promising, none demonstrate long-term tolerance to urine, the natural substrate of the tissue and of the uropathogens that live there. We developed a novel human organoid from progenitor cells which demonstrates key structural hallmarks and biomarkers of the urothelium. After three weeks of transwell culture with 100% urine at the apical interface, the organoid stratified into multiple layers...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351453/superoxide-inhibition-restores-endothelium-dependent-dilatation-in-aging-arteries-by-enhancing-impaired-adherens-junctions
#4
Fumin Chang, Sheila Flavahan, Nicholas A Flavahan
Endothelium-dependent, nitric oxide (NO)-mediated dilatation is impaired in aging arteries. The dysfunction reflects increased production of reactive oxygen species (ROS), is reversed by inhibiting superoxide with superoxide dismutase (SOD) mimics, and is assumed to reflect superoxide-mediated inactivation of NO. However, the dysfunction also reflects Src-dependent degradation and loss of VE-cadherin from adherens junctions, resulting in a selective impairment in the ability of the junctions to amplify endothelial dilatation...
January 12, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351411/disruption-of-the-lens-circulation-causes-calcium-accumulation-and-precipitates-in-connexin-mutant-mice
#5
Junyuan Gao, Peter J Minogue, Eric C Beyer, Richard T Mathias, Viviana M Berthoud
The lens is an avascular organ whose function and survival depend on an internal circulation system. Cx46fs380 mice model a human autosomal dominant cataract caused by a mutant lens connexin. In these mice, fiber cell connexin levels and gap junction coupling are severely decreased. The present studies were conducted to examine components of the lens circulation system that might be altered and contribute to the pathogenesis of cataracts. Lenses from wild type mice and Cx46fs380 heterozygotes and homozygotes were studied at 2 months of age...
January 3, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351282/a-four-component-model-of-the-action-potential-in-mouse-detrusor-smooth-muscle-cell
#6
Mithun Padmakumar, Keith L Brain, John S Young, Rohit Manchanda
BACKGROUND AND HYPOTHESIS: Detrusor smooth muscle cells (DSMCs) of the urinary bladder are electrically connected to one another via gap junctions and form a three dimensional syncytium. DSMCs exhibit spontaneous electrical activity, including passive depolarizations and action potentials. The shapes of spontaneous action potentials (sAPs) observed from a single DSM cell can vary widely. The biophysical origins of this variability, and the precise components which contribute to the complex shapes observed are not known...
2018: PloS One
https://www.readbyqxmd.com/read/29351227/differential-association-of-cx37-and-cx40-genetic-variants-in-atrial-fibrillation-with-and-without-underlying-structural-heart-disease
#7
Sebastian Carballo, Anna Pfenniger, David Carballo, Nicolas Garin, Richard W James, François Mach, Dipen Shah, Brenda R Kwak
Atrial fibrillation (AF) appears in the presence or absence of structural heart disease. The majority of foci causing AF are located near the ostia of pulmonary veins (PVs), where cardiomyocytes and vascular smooth muscle cells interdigitate. Connexins (Cx) form gap junction channels and participate in action potential propagation. Genetic variants in genes encoding Cx40 and Cx37 affect their expression or function and may contribute to PV arrhythmogenicity. DNA was obtained from 196 patients with drug-resistant, symptomatic AF with and without structural heart disease, who were referred for percutaneous catheter ablation...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29350877/effects-of-human-rhinovirus-on-epithelial-barrier-integrity-and-function-in-children-with-asthma
#8
Kevin Looi, Alysia G Buckley, Paul J Rigby, Luke W Garratt, Thomas Iosifidis, Graeme R Zosky, Alexander N Larcombe, Francis J Lannigan, Kak-Ming Ling, Kelly M Martinovich, Elizabeth Kicic-Starcevich, Nicole C Shaw, Erika N Sutanto, Darryl A Knight, Anthony Kicic, Stephen M Stick
BACKGROUND: Bronchial epithelial tight junctions (TJ) have been extensively assessed in healthy airway epithelium. However, no studies have yet assessed the effect of human rhinovirus (HRV) infection on the expression and resultant barrier function in epithelial tight junctions (TJ) in childhood asthma. OBJECTIVES: To investigate the impact of HRV infection on airway epithelial TJ expression and barrier function in airway epithelial cells (AEC) of children with and without asthma...
January 19, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29349851/clinical-and-molecular-implications-of-structural-changes-to-desmosomes-and-corneodesmosomes
#9
REVIEW
Akemi Ishida-Yamamoto, Satomi Igawa, Mari Kishibe, Masaru Honma
Desmosomes provide the main intercellular adhesive properties between epidermal keratinocytes. Their distribution becomes uneven in severe dermatitis, multiple allergies and metabolic wasting syndrome due to desmoglein 1 deficiency and the loss of intercellular adhesion or acantholysis. When keratinocytes differentiate from granular cells into cornified cells, desmosomes are transformed into corneodesmosomes and can provide stronger intercellular adhesion. Degradation of corneodesmosomes is a tightly regulated process involving a number of proteases and their inhibitors...
January 19, 2018: Journal of Dermatology
https://www.readbyqxmd.com/read/29348685/overexpression-of-adhesion-molecules-and-barrier-molecules-is-associated-with-differential-infiltration-of-immune-cells-in-non-small-cell-lung-cancer
#10
Young Kwang Chae, Wooyoung M Choi, William H Bae, Jonathan Anker, Andrew A Davis, Sarita Agte, Wade T Iams, Marcelo Cruz, Maria Matsangou, Francis J Giles
Immunotherapy is emerging as a promising option for lung cancer treatment. Various endothelial adhesion molecules, such as integrin and selectin, as well as various cellular barrier molecules such as desmosome and tight junctions, regulate T-cell infiltration in the tumor microenvironment. However, little is known regarding how these molecules affect immune cells in patients with lung cancer. We demonstrated for the first time that overexpression of endothelial adhesion molecules and cellular barrier molecule genes was linked to differential infiltration of particular immune cells in non-small cell lung cancer...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348563/disruption-of-cxcr3-function-impedes-the-development-of-sj%C3%A3-gren-s-syndrome-like-xerostomia-in-non-obese-diabetic-mice
#11
Jing Zhou, Qing Yu
The chemokine receptor CXCR3 plays an important role in T cell recruitment in various immune responses and autoimmune diseases. Expression of CXCR3 ligands, including CXCL9, CXCL10, and CXCL11, is elevated in the salivary glands of patients with Sjögren's syndrome (SS). To elucidate whether interaction between CXCR3 and its ligands is required for the development of SS, we administrated an anti-CXCR3 blocking antibody (CXCR3-173) to the non-obese diabetic (NOD) mice, a well-defined model of SS, during the stage prior to disease onset...
January 18, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29348327/genome-instability-as-a-consequence-of-defects-in-the-resolution-of-recombination-intermediates
#12
Stephen C West, Ying Wai Chan
The efficient processing of homologous recombination (HR) intermediates, which often contain four-way structures known as Holliday junctions (HJs), is required for proper chromosome segregation at mitosis. Eukaryotic cells possess three distinct pathways of resolution: (i) HJ dissolution mediated by BLM-topoisomerase IIIα-RMI1-RMI2 (BTR) complex, and HJ resolution catalyzed by either (ii) SLX1-SLX4-MUS81-EME1-XPF-ERCC1 (SMX complex) or (iii) GEN1. The BTR pathway acts at all times throughout the cell cycle, whereas the actions of SMX and GEN1 are restrained in S phase and become elevated late in the cell cycle to ensure the resolution of persistent recombination intermediates before mitotic division...
January 18, 2018: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29348177/dasatinib-increases-endothelial-permeability-leading-to-pleural-effusion
#13
Carole Phan, Etienne-Marie Jutant, Ly Tu, Raphaël Thuillet, Andrei Seferian, David Montani, Alice Huertas, Jan van Bezu, Fabian Breijer, Anton Vonk Noordegraaf, Marc Humbert, Jurjan Aman, Christophe Guignabert
Pleural effusion is a frequent side-effect of dasatinib, a second-generation tyrosine kinase inhibitor used in the treatment of chronic myelogenous leukaemia. However, the underlying mechanisms remain unknown. We hypothesised that dasatinib alters endothelial integrity, resulting in increased pulmonary vascular endothelial permeability and pleural effusion.To test this, we established the first animal model of dasatinib-related pleural effusion, by treating rats with a daily regimen of high doses of dasatinib (10 mg·kg-1·day-1 for 8 weeks)...
January 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29346932/gap-junction-coupling-and-atp-sensitive-potassium-channels-in-human-%C3%AE-cell-clusters-effects-on-emergent-dynamics
#14
A Loppini, M G Pedersen, M Braun, S Filippi
The importance of gap-junction coupling between β cells in pancreatic islets is well established in mouse. Such ultrastructural connections synchronize cellular activity, confine biological heterogeneity, and enhance insulin pulsatility. Dysfunction of coupling has been associated with diabetes and altered β-cell function. However, the role of gap junctions between human β cells is still largely unexplored. By using patch-clamp recordings of β cells from human donors, we previously estimated electrical properties of these channels by mathematical modeling of pairs of human β cells...
September 2017: Physical Review. E
https://www.readbyqxmd.com/read/29346364/mutations-in-caenorhabditis-elegans-neuroligin-like-glit-1-the-apoptosis-pathway-and-the-calcium-chaperone-crt-1-increase-dopaminergic-neurodegeneration-after-6-ohda-treatment
#15
Sarah-Lena Offenburger, Elisabeth Jongsma, Anton Gartner
The loss of dopaminergic neurons is a hallmark of Parkinson's disease, the aetiology of which is associated with increased levels of oxidative stress. We used C. elegans to screen for genes that protect dopaminergic neurons against oxidative stress and isolated glit-1 (gliotactin (Drosophila neuroligin-like) homologue). Loss of the C. elegans neuroligin-like glit-1 causes increased dopaminergic neurodegeneration after treatment with 6-hydroxydopamine (6-OHDA), an oxidative-stress inducing drug that is specifically taken up into dopaminergic neurons...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29346110/a-three-dimensional-arrayed-microfluidic-blood-brain-barrier-model-with-integrated-electrical-sensor-array
#16
Sehoon Jeong, Sunja Kim, John Buonocore, Jaewon Park, C Jane Welsh, Jianrong Li, Arum Han
OBJECTIVE: The blood-brain barrier (BBB) poses a unique challenge to the development of therapeutics against neurological disorders due to its impermeabi-lity to most of the chemical compounds. Most in vitro BBB models have limitations in mimicking in vivo conditions and functions. Here, we show a co-culture microfluidic BBB-on-a-chip that provides interactions between neurovascular endothelial cells and neuronal cells across a porous polycarbonate membrane, which better mimics the in vivo conditions, as well as allows in vivo level shear stress to be applied...
February 2018: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/29345911/role-of-glycanation-and-convertase-maturation-of-the-soluble-glypican-3-in-inhibiting-proliferation-of-hepatocellular-carcinoma-cells
#17
Ahmad Saad, Benjamin Liet, Gilles Joucla, Xavier Santarelli, Justine Charpentier, Stéphane Claverol, Christophe F Grosset, Véronique Trézéguet
Glypican 3 (GPC3) is a complex heparan sulfate proteoglycan associated with the outer surface of the plasma membrane by a glycosyl-phosphatidylinositol anchor (GPI). It is also N-glycosylated and processed by a furine-like convertase. GPC3 has numerous biological functions. While undetectable in normal liver tissue, it is abnormally and highly overexpressed in hepatocellular carcinoma (HCC). Interestingly, proliferation of HCC cells such as HepG2 and HuH7 is inhibited when they express a soluble form of GPC3 after lentiviral transduction...
January 18, 2018: Biochemistry
https://www.readbyqxmd.com/read/29345370/inhibition-of-soluble-epoxide-hydrolase-attenuates-eosinophil-recruitment-and-food-allergen-induced-gastrointestinal-inflammation
#18
Idil Bastan, Xiao Na Ge, Mythili Dileepan, Yana G Greenberg, Alonso G Guedes, Sung Hee Hwang, Bruce D Hammock, Robert J Washabau, Savita P Rao, P Sriramarao
Prevalence of food allergies in the United States is on the rise. Eosinophils are recruited to the intestinal mucosa in substantial numbers in food allergen-driven gastrointestinal (GI) inflammation. Soluble epoxide hydrolase (sEH) is known to play a pro-inflammatory role during inflammation by metabolizing anti-inflammatory epoxyeicosatrienoic acids (EETs) to pro-inflammatory diols. We investigated the role of sEH in a murine model of food allergy and evaluated the potential therapeutic effect of a highly selective sEH inhibitor (trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]-cyclohexyloxy}-benzoic acid [t-TUCB])...
January 17, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344503/genetics-of-magnesium-disorders
#19
REVIEW
Heng Li, Shiren Sun, Jianghua Chen, Goushuang Xu, Hanmin Wang, Qi Qian
Background: Magnesium (Mg2+), the second most abundant cation in the cell, is woven into a multitude of cellular functions. Dysmagnesemia is associated with multiple diseases and, when severe, can be life-threatening. Summary: This review discusses Mg2+ homeostasis and function with specific focus on renal Mg2+ handling. Intrarenal channels and transporters related to Mg2+ absorption are discussed. Unraveling the rare genetic diseases with manifestations of dysmagnesemia has greatly increased our understanding of the complex and intricate regulatory network in the kidney, specifically, functions of tight junction proteins including claudin-14, -16, -19, and -10; apical ion channels including: TRPM6, Kv1...
December 2017: Kidney Diseases
https://www.readbyqxmd.com/read/29344497/a-case-of-adenocarcinoma-of-the-retinal-pigment-epithelium-an-immunohistochemical-and-electron-microscopic-study
#20
Hidetsugu Mori, Kanji Takahashi
Purpose: Retinal pigment epithelium (RPE) adenocarcinoma is a very rare malignant intraocular tumor. Herein we describe the histopathological features of RPE adenocarcinoma. Case: A 36-year-old male was referred to our clinic because of floaters in his left eye. The initial diagnosis was malignant melanoma of the choroid. We resected the tumor and studied it histopathologically. The tumor tissue was investigated by light microscopy including immunohistochemistry using antibodies against S-100, HMB-45, EMA, and AE-1...
December 2017: Ocular Oncology and Pathology
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