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Matti F Pronker, Suzanne Lemstra, Joost Snijder, Albert J R Heck, Dominique M E Thies-Weesie, R Jeroen Pasterkamp, Bert J C Janssen
Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. MAG maintains the myelin-axon spacing by interacting with specific neuronal glycolipids (gangliosides), inhibits axon regeneration and controls myelin formation. The mechanisms underlying MAG adhesion and signalling are unresolved. We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5...
December 6, 2016: Nature Communications
Kerry M Goodman, Masahito Yamagata, Xiangshu Jin, Seetha Mannepalli, Phinikoula S Katsamba, Göran Ahlsén, Alina P Sergeeva, Barry Honig, Joshua R Sanes, Lawrence Shapiro
Sidekick (Sdk) 1 and 2 are related immunoglobulin superfamily cell adhesion proteins required for appropriate synaptic connections between specific subtypes of retinal neurons. Sdks mediate cell-cell adhesion with homophilic specificity that underlies their neuronal targeting function. Here we report crystal structures of Sdk1 and Sdk2 ectodomain regions, revealing similar homodimers mediated by the four N-terminal immunoglobulin domains (Ig1-4), arranged in a horseshoe conformation. These Ig1-4 horseshoes interact in a novel back-to-back orientation in both homodimers through Ig1:Ig2, Ig1:Ig1 and Ig3:Ig4 interactions...
September 19, 2016: ELife
Genevieve L Coe, Priscilla S Redd, Amy V Paschall, Chunwan Lu, Lilly Gu, Houjian Cai, Thomas Albers, Iryna O Lebedyeva, Kebin Liu
FasL-mediated cytotoxicity is one of the mechanisms that CTLs use to kill tumor cells. However, human colon carcinoma often deregulates the Fas signaling pathway to evade host cancer immune surveillance. We aimed at testing the hypothesis that novel ceramide analogs effectively modulate Fas function to sensitize colon carcinoma cells to FasL-induced apoptosis. We used rational design and synthesized twenty ceramide analogs as Fas function modulators. Five ceramide analogs, IG4, IG7, IG14, IG17, and IG19, exhibit low toxicity and potent activity in sensitization of human colon carcinoma cells to FasL-induced apoptosis...
August 4, 2016: Scientific Reports
T Flament, S Marchand-Adam, P Gatault, C Dupin, P Diot, L Guilleminault
INTRODUCTION: IgG4 has recently been a subject of great interest in human pathology. No data are available about the characteristics of asthma patients with elevated IgG4 levels. POPULATION AND METHODS: An observational study was conducted from January 2006 to March 2015 in a difficult-to-treat population of asthma patients. Twenty-six difficult-to-treat asthma patients with elevated serum IgG4 levels (IgG4/IgG ratio up to 10%) were compared with a control population of 98 difficult-to-treat asthma patients with normal serum IgG4...
March 2016: Respiratory Medicine
Kenji Otsuka, Mikako Ito, Bisei Ohkawara, Akio Masuda, Yu Kawakami, Ko Sahashi, Hiroshi Nishida, Naoki Mabuchi, Akemi Takano, Andrew G Engel, Kinji Ohno
MuSK antibody-positive myasthenia gravis (MuSK-MG) accounts for 5 to 15% of autoimmune MG. MuSK and LRP4 are coreceptors for agrin in the signaling pathway that causes clustering of acetylcholine receptor (AChR). MuSK also anchors the acetylcholinesterase (AChE)/collagen Q (ColQ) complex to the synaptic basal lamina. We previously reported that anti-MuSK antibodies (MuSK-IgG) block binding of ColQ to MuSK and cause partial endplate AChE deficiency in mice. We here analyzed the physiological significance of binding of ColQ to MuSK and block of this binding by MuSK-IgG...
2015: Scientific Reports
Takaya Oguchi, Masao Ota, Tetsuya Ito, Hideaki Hamano, Norikazu Arakura, Yoshihiko Katsuyama, Akira Meguro, Shigeyuki Kawa
Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis characterized by high serum IgG4 concentration and a variety of complicating extra-pancreatic lesions. In particular, lachrymal/salivary gland lesions tend to manifest in a highly active AIP disease state, and several genes are speculated to be associated with the onset of this complication. We therefore searched for candidate susceptibility genes related to lachrymal/salivary gland lesions in a genome-wide association study (GWAS) with the GeneChip Human Mapping 500k Array Set (Affymetrix, CA) that was followed by fine mapping of additional single nucleotide polymorphisms (SNPs) in strongly significant genes with TaqMan assays...
2015: PloS One
Andreia Noites, Rita Nunes, Ana Isabel Gouveia, Alexandra Mota, Cristina Melo, Ágata Viera, Nuno Adubeiro, José Mesquita Bastos
OBJECTIVE: To analyze the short- and long-term effects of microcurrent used with aerobic exercise on abdominal fat (visceral and subcutaneous). METHODS: Forty-two female students from a university population were randomly assigned into five group: intervention group (IG) 1 (n=9), IG2 (n=9), IG3 (n=7), IG4 (n=8), and placebo group (PG) (n=9). An intervention program of 10 sessions encompassing microcurrent and aerobic exercise (performed with a cycloergometer) was applied in all groups, with slightly differences between them...
April 2015: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
M Braig, N Pällmann, M Preukschas, D Steinemann, W Hofmann, A Gompf, T Streichert, T Braunschweig, M Copland, K L Rudolph, C Bokemeyer, S Koschmieder, A Schuppert, S Balabanov, T H Brümmendorf
Telomere biology is frequently associated with disease evolution in human cancer and dysfunctional telomeres have been demonstrated to contribute to genetic instability. In BCR-ABL(+) chronic myeloid leukemia (CML), accelerated telomere shortening has been shown to correlate with leukemia progression, risk score and response to treatment. Here, we demonstrate that proliferation of murine CML-like bone marrow cells strongly depends on telomere maintenance. CML-like cells of telomerase knockout mice with critically short telomeres (CML-iG4) are growth retarded and proliferation is terminally stalled by a robust senescent cell cycle arrest...
October 2014: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Robert Tweyongyere, Peter Naniima, Patrice A Mawa, Frances M Jones, Emily L Webb, Stephen Cose, David W Dunne, Alison M Elliott
INTRODUCTION: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S...
2013: PLoS Neglected Tropical Diseases
T Watanabe, M Maruyama, T Ito, Y Fujinaga, Y Ozaki, M Maruyama, R Kodama, T Muraki, H Hamano, N Arakura, M Kadoya, S Suzuki, M Komatsu, H Shimojo, K Notohara, M Uchida, S Kawa
OBJECTIVES: Immunoglobulin (Ig)G4-related disease is a recently proposed systemic disorder that includes autoimmune pancreatitis (AIP), Mikulicz's disease, and various other organ lesions. In the present retrospective study, we examined whether thyroid lesions should also be included in IgG4-related disease (Ig4-RD) under the new term IgG4-related thyroiditis. METHOD: We enrolled 114 patients with Ig4-RD, including 92 patients with AIP, 15 patients with Mikulicz's disease, and seven patients with IgG4-related cholangitis, and analysed clinical findings, function, serum values of activity markers, computed tomography (CT) images, and histology of the thyroid gland...
2013: Scandinavian Journal of Rheumatology
Jean Mukherjee, Chase McCann, Kwasi Ofori, Julia Hill, Karen Baldwin, Charles B Shoemaker, Peter Harrison, Saul Tzipori
Botulinum neurotoxin (BoNT) is responsible for causing botulism, a potentially fatal disease characterized by paralysis of skeletal muscle. Existing specific treatments include polyclonal antisera derived from immunized humans or horses. Both preparations have similar drawbacks, including limited supply, risk of adverse effects and batch to batch variation. Here, we describe a panel of six highly protective sheep monoclonal antibodies (SMAbs) derived from sheep immunized with BoNT/A1 toxoid (SMAbs 2G11, 4F7) or BoNT/A1 heavy chain C-terminus (HcC) (SMAbs 1G4, 5E2, 5F7, 16F9) with or without subsequent challenge immunization with BoNT/A1 toxin...
December 2012: Toxins
Rania Ahmed, Safa Al-Shaikh, Mohammed Akhtar
More than a century has passed since the first description of Hashimoto thyroiditis (HT) as a clinicopathologic entity. HT is an autoimmune disease in which a breakdown of immune tolerance is caused by interplay of a variety of immunologic, genetic, and environmental factors. Thyrocyte injury resulting from environmental factors results in expression of new or hidden epitopes that leads to proliferation of autoreactive T and B cells. Infiltration of thyroid by these cells results in HT. In addition to the usual type of HT, several variants such as the fibrous type and Riedal thyroiditis are also recognized...
May 2012: Advances in Anatomic Pathology
M D Lopez, A Maudhuit, M J Pascual-Villalobos, D Poncelet
In recent studies, insecticide activity of a monoterpene, linalool, has been demonstrated, finding, however, limitations in application because of its rapid volatilization. Potential effectiveness of microcapsules and effects of various types of matrices on its stability as controlled-release systems for the slow volatilization of linalool to be applied as insecticide were evaluated. To study controlled-release, linalool was entrapped into microcapsules, inclusion complexes, and beads, obtained by different methods, inverse gelation (IG1, IG2, IG3, IG4, and IG5), oil-emulsion-entrapment (OEE), interfacial coacervation (INCO), and chemical precipitation (Cyc5 and Cyc10)...
February 8, 2012: Journal of Agricultural and Food Chemistry
Xiaowei Dou, Carrie E Menkari, Sivananthaperumal Shanmugasundararaj, Keith W Miller, Michael E Charness
Ethanol may cause fetal alcohol spectrum disorders (FASD) in part by inhibiting cell adhesion mediated by the L1 neural cell adhesion molecule. Azialcohols photolabel Glu-33 and Tyr-418, two residues that are predicted by homology modeling to lie within 2.8 Å of each other at the interface between the Ig1 and Ig4 domains of L1 (Arevalo, E., Shanmugasundararaj, S., Wilkemeyer, M. F., Dou, X., Chen, S., Charness, M. E., and Miller, K. W. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 371-375). Using transient transfection of NIH/3T3 cells with wild type (WT-L1) and mutated L1, we found that cysteine substitution of both residues (E33C/Y418C-L1) significantly increased L1 adhesion above levels observed for WT-L1 or the single cysteine substitutions E33C-L1 or Y418C-L1...
May 6, 2011: Journal of Biological Chemistry
Patrícia Tiemy Hotta, Takami Hirono Hotta, César Bataglion, Solange Aparecida Bataglion, Elaine Angélica de Souza Coronatto, Selma Siéssere, Simone Cecilio Hallak Regalo
The aim of this study was to analyze the effect of low level laser applied to acupuncture points of patients diagnosed with temporomandibular dysfunction (TMD). Ten patients aged between 20 and 50 years were clinically examined with regard to pain and dysfunction of the masticatory system. They received laser applications (GaAlAs diode laser, 780 nm wavelength; 70 mW power output, 35 j/cm(2)) in acupuncture specific points (Ig4, C3, E6, E7) once a week, for ten sessions. The range of jaw movement was registered after each session and visual analogue scale (VAS) was applied...
August 2010: Complementary Therapies in Clinical Practice
Sandra Valéria Rancan, César Bataglion, Solange Aparecida Bataglion, Odinê Maria Rêgo Bechara, Marisa Semprini, Selma Siéssere, João Paulo Machado de Sousa, José Alexandre de Souza Crippa, Jaime Eduardo Cecilio Hallak, Simone Cecilio Hallak Regalo
OBJECTIVES: The purpose of this study was to investigate the levels of electromyographic (EMG) activation and maximal molar bite force before and after a 3-month acupuncture therapy in individuals with temporomandibular disorder (Helkimo Index) from a pool of subjects attending the Special Care Course of the Ribeirão Preto Dental School, São Paulo University, Brazil. DESIGN: All 17 patients, aged between 37 and 50 years (44.2 +/- 4.84 years), with an average weight of 71 +/- 9...
December 2009: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
Ricardo M Gouveia, Cláudio M Gomes, Marcos Sousa, Paula M Alves, Júlia Costa
L1 is a cell adhesion molecule of the immunoglobulin (Ig) superfamily, critical for central nervous system development, and involved in several neuronal biological events. It is a type I membrane glycoprotein. The L1 ectodomain, composed of six Ig-like and five fibronectin (Fn) type-III domains, is involved in homophilic binding. Here, co-immunoprecipitation studies between recombinant truncated forms of human L1 expressed and purified from insect Spodoptera frugiperda Sf9 cells, and endogenous full-length L1 from human NT2N neurons, showed that the L1 ectodomain (L1/ECD) and L1/Ig1-4 interacted homophilically in trans, contrary to mutants L1/Ig1-3 and L1/Ig2-Fn5...
October 17, 2008: Journal of Biological Chemistry
Richard D S Dixon, Daniel K Arneman, Andrew S Rachlin, Naresh R Sundaresan, M Joseph Costello, Sharon L Campbell, Carol A Otey
Palladin is a recently described phosphoprotein that plays an important role in cell adhesion and motility. Previous studies have shown that palladin overexpression results in profound changes in actin organization in cultured cells. Palladin binds to the actin-associated proteins alpha-actinin, vasodilator-stimulated phosphoprotein, profilin, Eps8, and ezrin, suggesting that it may affect actin organization indirectly. To determine its molecular function in generating actin arrays, we purified palladin and asked if it is also capable of binding to F-actin directly...
March 7, 2008: Journal of Biological Chemistry
Enrique Arevalo, Sivananthaperumal Shanmugasundararaj, Michael F Wilkemeyer, Xiaowei Dou, Suzhen Chen, Michael E Charness, Keith W Miller
Prenatal ethanol exposure causes fetal alcohol spectrum disorders (FASD) in part by disrupting the neural cell adhesion molecule L1. L1 gene mutations cause neuropathological abnormalities similar to those of FASD. Ethanol and 1-butanol inhibit L1-mediated cell-cell adhesion (L1 adhesion), whereas 1-octanol antagonizes this action. To test the hypothesis that there are alcohol binding sites on L1, we used 3-azibutanol and 3-azioctanol, the photoactivatable analogs of 1-butanol and 1-octanol, to photolabel the purified Ig1-4 domain of human L1 (hL1 Ig1-4)...
January 8, 2008: Proceedings of the National Academy of Sciences of the United States of America
Halise Inci Gul, Umashankar Das, Bulbul Pandit, Pui-Kai Li
Mono-Mannich bases derived from acetophenones, 1-aryl-3-amino- 1 -propanone hydrochlorides (Igl-Ig4), and their corresponding azine derivatives, N, N'-bis(3-amino-l-aryl-propylidene) hydrazine dihydrochlorides (DI-D4), were designed and synthesized as cellular thiol alkylating agents. The aryl portion was replaced by a phenyl group in Ig1, Ig2, Ig3, D1, D2, and D3, and by a p-hydroxyphenyl group in Ig4 and D4. The amine side chain was replaced by a dimethylamine group in Igl, D1, Ig4 and D4, by a piperidine group in Ig2 and D2, and by a morpholine group in Ig3 and D3...
2006: Arzneimittel-Forschung
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