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https://www.readbyqxmd.com/read/28628327/impact-of-the-niemann-pick-c1-gene-mutation-on-the-total-cellular-glycomics-of-cho-cells
#1
Jun-Ichi Furukawa, Minami Soga, Kazue Okada, Ikuko Yokota, Jinhua Piao, Tetsumi Irie, Takumi Era, Yasuro Shinohara
Niemann-Pick disease type C (NPC) is an autosomal recessive lipid storage disorder, and the majority of cases are caused by mutations in the NPC1 gene. In this study, we clarified how a single gene mutation in the NPC1 gene impacts the cellular glycome by analyzing the total glycomic expression profile of Chinese hamster ovary cell mutants defective in the Npc1 gene (Npc1 KO CHO cells). A number of glycomic alterations were identified, including increased expression of lactosylceramide, GM1, GM2, GD1, various neolacto-series glycosphingolipids, and sialyl-T (O-glycan), which was found to be the major sialylated protein-bound glycan, as well as various N-glycans, which were commonly both fucosylated and sialylated...
June 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28600215/a-new-type-of-pharmacological-chaperone-for-gm1-gangliosidosis-related-human-lysosomal-%C3%AE-galactosidase-n-substituted-5-amino-1-hydroxymethyl-cyclopentanetriols
#2
Michael Schalli, Patrick Weber, Christina Tysoe, Bettina M Pabst, Martin Thonhofer, Eduard Paschke, Arnold E Stütz, Marion Tschernutter, Werner Windischhofer, Stephen G Withers
N-Functionalized amino(hydroxymethyl)cyclopentanetriols are potent inhibitors of β-d-galactosidases and, for the first time, could be shown to act as pharmacological chaperones for GM1-gangliosidosis-associated lysosomal acid β-galactosidase thus representing a new structural type of pharmacological chaperones for this lysosomal storage disease.
May 30, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28593141/glycosyl-chains-and-25-hydroxycholesterol-contribute-to-the-intracellular-transport-of-amyloid-beta-a%C3%AE-42-in-jurkat-t-cells
#3
Neha Sharma, KeangOK Baek, Huong T T Phan, Naofumi Shimokawa, Masahiro Takagi
Amyloid beta (Aβ) is a peptide responsible for the development of Alzheimer's disease (AD). Misfolding and accumulation of endogenous Aβ can lead to neural cell apoptosis through endoplasmic reticulum (ER) stress. Added exogenous Aβ can also result in ER stress, leading to neurotoxicity and apoptosis, which is identical to that caused by the endogenous peptide. We have speculated that the endocytic transport of Aβ causes ER stress and have previously shown that the oxysterol, in particular, 7-ketocholesterol (7-keto) induces more surface interaction between Aβ-42 and Jurkat cells than cholesterol...
June 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28579983/effect-of-dietary-minerals-on-virulence-attributes-of-vibrio-cholerae
#4
Varunkumar Bhattaram, Abhinav Upadhyay, Hsin-Bai Yin, Shankumar Mooyottu, Kumar Venkitanarayanan
Vibrio cholerae is a water-borne pathogen responsible for causing a toxin-mediated profuse diarrhea in humans, leading to severe dehydration and death in unattended patients. With increasing reports of antibiotic resistance in V. cholerae, there is a need for alternate interventional strategies for controlling cholera. A potential new strategy for treating infectious diseases involves targeting bacterial virulence rather than growth, where a pathogen's specific mechanisms critical for causing infection in hosts are inhibited...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28577204/the-treatment-of-juvenile-adult-gm1-gangliosidosis-with-miglustat-may-reverse-disease-progression
#5
Federica Deodato, Elena Procopio, Angelica Rampazzo, Roberta Taurisano, Maria Alice Donati, Carlo Dionisi-Vici, Anna Caciotti, Amelia Morrone, Maurizio Scarpa
Juvenile and adult GM1-gangliosidosis are invariably characterized by progressive neurological deterioration. To date only symptomatic therapies are available. We report for the first time the positive results of Miglustat (OGT 918, N-butyl-deoxynojirimycin) treatment on three Italian GM1-gangliosidosis patients. The first two patients had a juvenile form (enzyme activity ≤5%, GLB1 genotype p.R201H/c.1068 + 1G > T; p.R201H/p.I51N), while the third patient had an adult form (enzyme activity about 7%, p...
June 3, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28558200/multiplexed-lipid-bilayers-on-silica-microspheres-for-analytical-screening-applications
#6
Nadiezda Fernandez Oropeza, Nesia A Zurek, Mirella Galvan-De La Cruz, Aurora Fabry-Wood, Jennifer M Fetzer, Steven W Graves, Andrew P Shreve
Most druggable targets are membrane components, including membrane proteins and soluble proteins that interact with ligands or receptors embedded in membranes. Current target-based screening and intermolecular interaction assays generally do not include the lipid membrane environment in presenting these targets, possibly altering their native structure and leading to misleading or incorrect results. To address this issue, an ideal assay involving membrane components would (1) mimic the natural membrane environment, (2) be amenable to high-throughput implementation, and (3) be easily multiplexed...
June 9, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28539625/towards-new-cholera-prophylactics-and-treatment-crystal-structures-of-bacterial-enterotoxins-in-complex-with-gm1-mimics
#7
Julie Elisabeth Heggelund, Alasdair Mackenzie, Tobias Martinsen, Joel Benjamin Heim, Pavel Cheshev, Anna Bernardi, Ute Krengel
Cholera is a life-threatening disease in many countries, and new drugs are clearly needed. C-glycosidic antagonists may serve such a purpose. Here we report atomic-resolution crystal structures of three such compounds in complexes with the cholera toxin. The structures give unprecedented atomic details of the molecular interactions and show how the inhibitors efficiently block the GM1 binding site. These molecules are well suited for development into low-cost prophylactic drugs, due to their relatively easy synthesis and their resistance to glycolytic enzymes...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536532/phase-partitioning-of-gm1-and-its-bodipy-labeled-analog-determine-their-different-binding-to-cholera-toxin
#8
Sami Rissanen, Michal Grzybek, Adam Orłowski, Tomasz Róg, Oana Cramariuc, Ilya Levental, Christian Eggeling, Erdinc Sezgin, Ilpo Vattulainen
Driven by interactions between lipids and proteins, biological membranes display lateral heterogeneity that manifests itself in a mosaic of liquid-ordered (Lo) or raft, and liquid-disordered (Ld) or non-raft domains with a wide range of different properties and compositions. In giant plasma membrane vesicles and giant unilamellar vesicles, specific binding of Cholera Toxin (CTxB) to GM1 glycolipids is a commonly used strategy to label raft domains or Lo membrane environments. However, these studies often use acyl-chain labeled bodipy-GM1 (bdGM1), whose headgroup accessibility and membrane order or phase partitioning may differ from those of GM1, rendering the interpretation of CTxB binding data quite problematic...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28522391/polysaccharides-from-ginseng-leaves-inhibit-tumor-metastasis-via-macrophage-and-nk-cell-activation
#9
Myoung-Sook Shin, Su-Hyun Hwang, Taek-Joon Yoon, Kwang-Soon Shin
In this study, we purified the polysaccharide fraction (GS-P) from the leaves of Panax ginseng C.A. Meyer and analyzed its monosaccharide composition and antitumor and antimetastatic activity in vitro and in vivo. GS-P is a 10.2kDa pectic polysaccharide consisting of 15 different monosaccharides. GS-P treatment significantly inhibited metastasis in mice, in a dose-dependent manner. GS-P was not cytotoxic to colon 26-M3.1 cells and increased mouse splenocyte proliferation. Secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-12 was enhanced in the peritoneal exudate macrophages (PEMs) of GS-P-treated mice...
May 15, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28499815/new-insight-into-the-interaction-of-traf2-c-terminal-domain-with-lipid-raft-microdomains
#10
Arianna Ceccarelli, Almerinda Di Venere, Eleonora Nicolai, Anastasia De Luca, Nicola Rosato, Enrico Gratton, Giampiero Mei, Anna Maria Caccuri
In this study we provide the first evidence of the interaction of a truncated-TRAF2 with lipid raft microdomains. We have analyzed this interaction by measuring the diffusion coefficient of the protein in large and giant unilamellar vesicles (LUVs and GUVs, respectively) obtained both from synthetic lipid mixtures and from natural extracts. Steady-state fluorescence measurements performed with synthetic vesicles indicate that this truncated form of TRAF2 displays a tighter binding to raft-like LUVs with respect to the control (POPC-containing LUVs), and that this process depends on the protein oligomeric state...
May 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28499578/building-a-biomimetic-membrane-for-neutron-reflectivity-investigation-complexity-asymmetry-and-contrast
#11
Valeria Rondelli, Paola Brocca, Nicola Tranquilli, Giovanna Fragneto, Elena Del Favero, Laura Cantù
The preparation and investigation of model membranes is deserving growing interest both for the physics of complex systems, and for biology. The need of simplified models should preserve mimicking the qualifying characteristics of biological membranes, and keep non-invasive and detailed description. As a main feature, biological membranes are non-homogeneous in the disposition of components, both in the lateral and in the transverse direction. We prepared asymmetric supported membranes containing GM1 ganglioside in biomimetic proportion according to different protocols...
April 29, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28497346/enhanced-autophagy-contributes-to-protective-effects-of-gm1-ganglioside-against-a%C3%AE-1-42-induced-neurotoxicity-and-cognitive-deficits
#12
Ruwei Dai, Shijie Zhang, Wenjun Duan, Renrong Wei, Huifang Chen, Weibin Cai, Lei Yang, Qi Wang
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. The aggregation of Aβ peptides, Aβ1-42 in particular, is thought to be a fundamental pathogenic mechanism leading to the neuronal damage in AD. Recently, monosialoganglioside GM1 is reported to possess pivotal neuroprotection in neurodegenerative diseases. Previous studies have focused on the conformational dynamics and the biochemical interaction of the amyloid-peptide with the GM1 ganglioside, as well as the protective effect of GM1 on cognition...
May 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28483053/gm1-mmp-is-involved-in-growth-and-development-of-leaf-and-seed-and-enhances-tolerance-to-high-temperature-and-humidity-stress-in-transgenic-arabidopsis
#13
Sushuang Liu, Yanmin Liu, Yanhong Jia, Jiaping Wei, Shuang Wang, Xiaolin Liu, Yali Zhou, Yajing Zhu, Weihong Gu, Hao Ma
Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent endopeptidases. Gm1-MMP was found to play an important role in soybean tissue remodeling during leaf expansion. In this study, Gm1-MMP was isolated and characterized. Its encoding protein had a relatively low phylogenetic relationship with the MMPs in other plant species. Subcellular localization indicated that Gm1-MMP was a plasma membrane protein. Gm1-MMP showed higher expression levels in mature leaves, old leaves, pods, and mature seeds, as well as was involved in the development of soybean seed...
June 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28477283/linking-mitochondrial-dysfunction-to-neurodegeneration-in-lysosomal-storage-diseases
#14
REVIEW
Afshin Saffari, Stefan Kölker, Georg F Hoffmann, Darius Ebrahimi-Fakhari
Lysosomal storage diseases (LSD) are inborn errors of metabolism resulting in multisystem disease. Central nervous system involvement, often with progressive neurodegeneration, accounts for a large portion of the morbidity and mortality seen in many LSD. Available treatments fail to prevent or correct neurologic symptoms and decline. Emerging evidence points to an important role for mitochondrial dysfunction in the pathogenesis and progression of LSD-associated neurodegeneration. Mitochondrial dysfunction in LSD is characterized by alterations in mitochondrial mass, morphology and function...
May 5, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28476546/infantile-gangliosidoses-mapping-a-timeline-of-clinical-changes
#15
Jeanine R Jarnes Utz, Sarah Kim, Kelly King, Richard Ziegler, Lynn Schema, Evelyn S Redtree, Chester B Whitley
BACKGROUND: Infantile gangliosidoses include GM1 gangliosidosis and GM2 gangliosidosis (Tay-Sachs disease, Sandhoff disease). To date, natural history studies in infantile GM2 (iGM2) have been retrospective and conducted through surveys. Compared to iGM2, there is even less natural history information available on infantile GM1 disease (iGM1). There are no approved treatments for infantile gangliosidoses. Substrate reduction therapy using miglustat has been tried, but is limited by gastrointestinal side effects...
April 29, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28463983/imaging-mass-spectrometry-identifies-prognostic-ganglioside-species-in-rodent-intracranial-transplants-of-glioma-and-medulloblastoma
#16
Leonardo Ermini, Elena Morganti, Alexander Post, Behzad Yeganeh, Isabella Caniggia, Michael Leadley, Claudia C Faria, James T Rutka, Martin Post
Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (MALDI-MSI) allows us to investigate the distribution of lipid molecules within tissues. We used MALDI-MSI to identify prognostic gangliosides in tissue sections of rat intracranial allografts of rat glioma and mouse intracranial xenografts of human medulloblastoma. In the healthy adult rodent brain, GM1 and GD1 were the main types of glycolipids. Both gangliosides were absent in both intracranial transplants. The ganglioside GM3 was not present in the healthy adult brain but was highly expressed in rat glioma allografts...
2017: PloS One
https://www.readbyqxmd.com/read/28456990/prenatal-diagnosis-of-lysosomal-storage-disorders-using-chorionic-villi
#17
Jyotsna Verma, Sunita Bijarnia-Mahay, Ishwar C Verma
Prenatal enzymatic diagnosis for an array of lysosomal storage disorders (LSDs) can be performed accurately, provided that a confirmed diagnosis by biochemical/molecular study in the index case is available and a strict defined protocol, specific to each individual disorder is followed. The present chapter describes the protocols for reliable and accurate prenatal enzymatic diagnoses by fluorometric and spectrophotometric methods of lysosomal storage disorders: Gaucher, Fabry, Pompe, Niemann Pick A/B, Tay Sach, Sandhoff, GM1, Mucoplysaccharidoses, Wolman, Krabbe, Metachromatic leukodystrophy, and Batten diseases using uncultured chorionic villi samples...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28442549/neuraminidases-3-and-4-regulate-neuronal-function-by-catabolizing-brain-gangliosides
#18
Xuefang Pan, Camila De Britto Pará De Aragão, Juan P Velasco-Martin, David A Priestman, Harry Y Wu, Kohta Takahashi, Kazunori Yamaguchi, Luisella Sturiale, Domenico Garozzo, Frances M Platt, Nathalie Lamarche-Vane, Carlos R Morales, Taeko Miyagi, Alexey V Pshezhetsky
Gangliosides (sialylated glycolipids) play an essential role in the CNS by regulating recognition and signaling in neurons. Metabolic blocks in processing and catabolism of gangliosides result in the development of severe neurologic disorders, including gangliosidoses manifesting with neurodegeneration and neuroinflammation. We demonstrate that 2 mammalian enzymes, neuraminidases 3 and 4, play important roles in catabolic processing of brain gangliosides by cleaving terminal sialic acid residues in their glycan chains...
April 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28425215/lipid-raft-dynamics-linked-to-sperm-competency-for-fertilization-in-mice
#19
Hitomi Watanabe, Rie Takeda, Keiji Hirota, Gen Kondoh
It is well known that mammalian sperm acquires fertilization ability after several maturation processes, particularly within the female reproductive tract. In a previous study, we found that both glycosylphosphatidylinositol (GPI)-anchored protein (GPI-AP) release and lipid raft movement occur during the sperm maturation process. In several genetic studies, release of GPI-AP is a crucial step for sperm fertilization ability in the mouse. Here, we show that lipid raft movement is also fundamental for sperm to be competent for fertilization by comparing the sperm maturation process of two mouse inbred strains, C57BL/6 and BALB/c...
May 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28418610/localization-patterns-of-the-ganglioside-gm1-in-human-sperm-are-indicative-of-male-fertility-and-independent-of-traditional-semen-measures
#20
Cristina Cardona, Queenie V Neri, Alana J Simpson, Melissa A Moody, G Charles Ostermeier, Eric K Seaman, Theodore Paniza, Zev Rosenwaks, Gianpiero D Palermo, Alexander J Travis
Semen analysis lacks a functional component and best identifies extreme cases of infertility. The ganglioside GM1 is known to have functional roles during capacitation and acrosome exocytosis. Here, we assessed whether GM1 localization patterns (Cap-Score™) correspond with male fertility in different settings: Study 1 involved couples pursuing assisted reproduction in a tertiary care fertility clinic, while Study 2 involved men with known fertility versus those questioning their fertility at a local urology center...
May 2017: Molecular Reproduction and Development
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