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Kevin Lynch, Oliver Treacy, Jared Q Gerlach, Heidi Annuk, Paul Lohan, Joana Cabral, Lokesh Joshi, Aideen E Ryan, Thomas Ritter
Dendritic cellular therapies and dendritic cell vaccines show promise for the treatment of autoimmune diseases, the prolongation of graft survival in transplantation, and in educating the immune system to fight cancers. Cell surface glycosylation plays a crucial role in the cell-cell interaction, uptake of antigens, migration, and homing of DCs. Glycosylation is known to change with environment and the functional state of DCs. Tolerogenic DCs (tDCs) are commonly generated using corticosteroids including dexamethasone, however, to date, little is known on how corticosteroid treatment alters glycosylation and what functional consequences this may have...
2017: Frontiers in Immunology
Sicai Zhang, Ronnie P-A Berntsson, William H Tepp, Liang Tao, Eric A Johnson, Pål Stenmark, Min Dong
Botulinum neurotoxins (BoNTs), the most potent toxins known, are potential bioterrorism agents. It is well established that all seven serotypes of BoNTs (BoNT/A-G) require complex gangliosides as co-receptors. Here, we report that BoNT/DC, a presumed mosaic toxin between BoNT/D and BoNT/C1, binds and enters efficiently into neurons lacking complex gangliosides and shows no reduction in toxicity in mice deficient in complex gangliosides. The co-crystal structure of BoNT/DC with sialyl-Thomsen-Friedenreich antigen (Sialyl-T) suggests that BoNT/DC recognizes only the sialic acid, but not other moieties in gangliosides...
November 21, 2017: Nature Communications
Xiumei Wei, Dinglong Yang, Huiying Li, Hailin Jiang, Xiangquan Liu, Qin Zhang, Jialong Yang
Sialic acid-binding lectins (SABLs) are ubiquitous ancient molecules with binding properties to N-acetyl or N-glycolyl carbohydrates, and play crucial roles in both adaptive and innate immune responses. In present study, recombinant protein and antibodies of two SABLs from mollusk Solen grandis (SgSABL-1 and SgSABL-2) were prepared to investigate their functions in innate immunity. The recombinant protein of SgSABL-1 (rSgSABL-1) could bind LPS, PGN and β-glucan in vitro, while rSgSABL-2 could only bind PGN rather than LPS and β-glucan...
November 14, 2017: Fish & Shellfish Immunology
Amin Alborzian Deh Sheikh, Chizuru Akatsu, Akihiro Imamura, Hajjaj H M Abdu-Allah, Hiromu Takematsu, Hiromune Ando, Hideharu Ishida, Takeshi Tsubata
Lectins expressed on the cell surface are often bound and regulated by the membrane molecules containing the glycan ligands on the same cell (cis-ligands). However, molecular nature and function of cis-ligands are generally poorly understood partly because of weak interaction between lectins and glycan ligands. Cis-ligands are most extensively studied in CD22 (also known as Siglec-2), an inhibitory B lymphocyte receptor specifically recognizing α2,6 sialic acids. CD22, CD45 and IgM are suggested to be ligands of CD22...
November 13, 2017: Biochemical and Biophysical Research Communications
Rui Zhang, Junpei Zhou, Zhifeng Song, Zunxi Huang
β-N-Acetylglucosaminidases (GlcNAcases) hydrolyse N-acetylglucosamine-containing oligosaccharides and proteins. These enzymes produce N-acetylglucosamine (GlcNAc) and have a wide range of promising applications in the food, energy, and pharmaceutical industries, such as synergistic degradation of chitin with endo-chitinases and using GlcNAc to produce sialic acid, bioethanol, single-cell proteins, and pharmaceutical therapeutics. GlcNAcases also play an important role in the dynamic balance of cellular O-linked GlcNAc levels, catabolism of ganglioside storage in Tay-Sachs disease, and bacterial cell wall recycling and flagellar assembly...
November 16, 2017: Applied Microbiology and Biotechnology
Sylvie Marion, Anthony Béhin, Shahram Attarian
No abstract text is available yet for this article.
November 2017: Médecine Sciences: M/S
Seyedmehdi Hossaini Nasr, Hovig Kouyoumdjian, Christiane Mallett, Sherif Ramadan, David C Zhu, Erik M Shapiro, Xuefei Huang
The accumulation and formation of β-amyloid (Aβ) plaques in the brain are distinctive pathological hallmarks of Alzheimer's disease (AD). Designing nanoparticle (NP) contrast agents capable of binding with Aβ highly selectively can potentially facilitate early detection of AD. However, a significant obstacle is the blood brain barrier (BBB), which can preclude the entrance of NPs into the brain for Aβ binding. In this work, bovine serum albumin (BSA) coated NPs are decorated with sialic acid (NP-BSAx -Sia) to overcome the challenges in Aβ imaging in vivo...
November 14, 2017: Small
Kesatebrhan Haile Asressu, Cheng-Chung Wang
In N-acetylneuraminic acid, apart from O9 and O8, a possible glycosylation site is the O4 position. For example, gangliosides HLG-2 and HPG-7 are considered to be potential lead compounds for carbohydrate-based drug development to treat neural disorders. However, the construction of their α(1 → 4) fucosyl sialic acid and α(2 → 4) linkages between sialic acids is difficult because of the regioselectivity problem. Herein, N-acetyl-2,7-anhydroneuraminic acid was synthesized in three steps from Neu5Ac methyl ester through per-O-trimethylsilylation, heating-assisted intramolecular anomeric protection (iMAP) and desilylation...
October 19, 2017: Carbohydrate Research
Marina Martínez-Carmona, Daniel Lozano, Montserrat Colilla, María Vallet-Regí
A novel multifunctional nanodevice based in doxorubicin (DOX)-loaded mesoporous silica nanoparticles (MSNs) as nanoplatforms for the assembly of different building blocks has been developed for bone cancer treatment. These building blocks consists of: i) a polyacrylic acid (PAA) capping layer grafted to MSNs via an acid-cleavable acetal linker, to minimize premature cargo release and provide the nanosystem of pH-responsive drug delivery ability; and ii) a targeting ligand, the plant lectin concanavalin A (ConA), able to selectively recognize, bind and internalize owing to certain cell-surface glycans, such as sialic acids (SA), overexpressed in given tumor cells...
November 7, 2017: Acta Biomaterialia
Xiaolei Yang, Shuang Liang, Lin Wang, Panpan Han, Xitao Jiang, Jianli Wang, Yanqiu Hao, Lijie Wu
BACKGROUND: Autism spectrum disorders (ASD) may result from a combination of genetic and environmental factors, and impact neurological functions and behaviors. Sialic acid (SA) is an indispensable nutrient for early brain development, and its polymer polySia (PSA) can modify neural cell adhesion molecules (NCAM), thereby indirectly mediating neuronal outgrowth, synaptic connectivity and memory formation. To investigate the association between SA and ASD, we conducted a case-control study...
November 1, 2017: Brain Research
Nikéa Pittman, Adam Misseldine, Lorena Geilen, Sujata Halder, J Kennon Smith, Justin Kurian, Paul Chipman, Mandy Janssen, Robert Mckenna, Timothy S Baker, Anthony D'Abramo, Susan Cotmore, Peter Tattersall, Mavis Agbandje-McKenna
LuIII, a protoparvovirus pathogenic to rodents, replicates in human mitotic cells, making it applicable for use to kill cancer cells. This virus group includes H-1 parvovirus (H-1PV) and minute virus of mice (MVM). However, LuIII displays enhanced oncolysis compared to H-1PV and MVM, a phenotype mapped to the major capsid viral protein 2 (VP2). This suggests that within LuIII VP2 are determinants for improved tumor lysis. To investigate this, the structure of the LuIII virus-like-particle was determined using single particle cryo-electron microscopy and image reconstruction to 3...
October 30, 2017: Viruses
Gerlind Sulzenbacher, Véronique Roig-Zamboni, Régine Lebrun, Yann Guérardel, Dorothée Murat, Pascal Mansuelle, Nao Yamakawa, Xin-Xin Quian, Renaud Vincentelli, Yves Bourne, Long-Fei Wu, François Alberto
The flagella of various Gram-negative bacteria are decorated with diverse glycan structures, amongst them nonulosonic acids related to the sialic acid family. Although nonulosonic sugar biosynthesis pathways have been dissected in various pathogens, the enzymes transferring the sugars onto flagellin are still poorly characterized. The deletion of genes coding for Motility associated factors (Mafs) found in many pathogenic strains systematically gives rise to non-flagellated bacteria lacking specific nonulosonic sugars on the flagellins, therefore relating Maf function to flagellin glycosylation and bacterial motility...
October 27, 2017: Environmental Microbiology
Manoj Chugh, Vladimir Piskarev, Oxana Galanina, Nailya Khasbiullina, Pallavi Kadam, Nadezhda Shilova, Galina Pazynina, Kira Dobrochaeva, Paresh Bhanushali, Nikolay Kozlov, Nikolay Tupitsin, Nicolai Bovin
A repertoire of monoclonal antibodies was generated by immunization of mice with cancer-associated glycoprotein CA19.9, and two of them were selected as optimal capture and detecting counterparts for sandwich test system for detection of CA19.9. Fine epitope specificity of the antibodies was determined using printed glycan array, enzyme-linked immunosorbent assay, and inhibitory enzyme-linked immunosorbent assay. Unexpectedly, both immunoglobulins did not bind key epitope of CA19.9 glycoprotein, tetrasaccharide SiaLe(A), as well as its defucosylated form sialyl Le(C) (known as CA-50 epitope)...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Jae-Sung Ryu, Kinarm Ko, Kisung Ko, Ji-Su Kim, Sun-Uk Kim, Kyu-Tae Chang, Young-Kug Choo
Glycosphingolipids are important components of the outer layer of the plasma membrane in the majority of eukaryotic cells. Specifically, gangliosides are sialic acid‑containing glycosphingolipids that participate in cell‑cell recognition, adhesion, proliferation, differentiation and signal transduction, and are integral components of cell surface microdomains and lipid rafts. Stem cells are defined functionally as cells that have the capacity to self‑renewal and differentiate to generate various cell types...
August 2017: Molecular Medicine Reports
Taylor Pini, Tamara Leahy, Simon Paul de Graaf
Spermatozoa deposited vaginally must navigate the physical, chemical and immune barriers of the cervix to reach the site of fertilisation. Characteristics that favour successful cervical transit remain largely unknown beyond the obvious factors of motility and viability. Epididymal and cryopreserved ram spermatozoa demonstrate poor cervical transit, for unknown reasons. We hypothesised that seminal plasma exposure and cryopreservation alter the surface sugars of these sperm populations and, consequently, their interaction with immune cells, both potential factors for successful cervical transit...
October 25, 2017: Reproduction, Fertility, and Development
Diana Czuchry, Walter A Szarek, Inka Brockhausen
The intestinal pathogen Escherichia coli serotype O104:H4 (ECO104) can cause bloody diarrhea and haemolytic uremic syndrome. The ECO104 O antigen has the unique repeating unit structure [4Galα1-4Neu5,7,9Ac3α2-3Galβ1-3GalNAcβ1-], which includes the mammalian sialyl-T antigen as an internal structure. Previously, we identified WbwC from ECO104 as the β3Gal-transferase that synthesizes the T antigen, and showed that α3-sialyl-transferase WbwA transfers sialic acid to the T antigen. Here we identify the wbwB gene product as a unique α1,4-Gal-transferase WbwB that transfers Gal from UDP-Gal to the terminal sialic acid residue of Neu5Acα2-3Galβ1-3GalNAcα-diphosphate-lipid acceptor...
October 24, 2017: Glycoconjugate Journal
Weizhun Yang, Bo Yang, Sherif Ramadan, Xuefei Huang
Most glycosylation reactions are performed by mixing the glycosyl donor and acceptor together followed by the addition of a promoter. While many oligosaccharides have been synthesized successfully using this premixed strategy, extensive protective group manipulation and aglycon adjustment often need to be performed on oligosaccharide intermediates, which lower the overall synthetic efficiency. Preactivation-based glycosylation refers to strategies where the glycosyl donor is activated by a promoter in the absence of an acceptor...
2017: Beilstein Journal of Organic Chemistry
Maitrayee Chatterjee, Anju Choorakottayil Pushkaran, Anil Kumar Vasudevan, Krishna Kumar N Menon, Raja Biswas, Chethampadi Gopi Mohan
Lactobacillus species possesses surface exposed Mucin Binding Protein (MucBP) which plays a role in adhesion to gastrointestinal mucin. MucBP contains one or more mucin binding domain (MBD), the functionality of which has yet not been characterized thoroughly. Here, we have characterized a 93-amino acid MBD (MBD93) of MucBP (LAF_0673) from Lactobacillus fermentum. Multiple sequence alignment of L. fermentum MBD93 exhibited ∼60% sequence homology with MBDs from other Lactobacillus species. Further, we cloned, expressed and purified MBD93 from Escherichia coli as N-terminal histidine-tagged protein (6X His-MBD93)...
October 20, 2017: International Journal of Biological Macromolecules
Roman Hájek, Robert Jirásko, Miroslav Lísa, Eva Cífková, Michal Holčapek
The hydrophilic interaction liquid chromatography (HILIC) coupled to a negative-ion electrospray ionization tandem mass spectrometry (ESI-MS/MS) method has been developed for the identification of a wide range of gangliosides in biological samples. Gangliosides consist of a backbone of sphingoid base and a polar oligosaccharide chain containing at least one sialic acid. Gangliosides are extracted by chloroform-methanol-water mixture, where an upper aqueous layer containing gangliosides and other polar lipid subclasses is further purified by C18 solid-phase extraction...
November 3, 2017: Analytical Chemistry
Zachary Klamer, Ben Staal, Anthony R Prudden, Lin Liu, David F Smith, Geert-Jan Boons, Brian Haab
Knowledge of lectin and glycosidase specificities is fundamental to the study of glycobiology. The primary specificities of such molecules can be uncovered using well-established tools, but the complex details of their specificities are difficult to determine and describe. Here we present a language and algorithm for the analysis and description of glycan motifs with high complexity. The language uses human-readable notation and wildcards, modifiers, and logical operators to define motifs of nearly any complexity...
November 3, 2017: Analytical Chemistry
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