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https://www.readbyqxmd.com/read/29469653/analytical-similarity-assessment-of-rituximab-biosimilar-ct-p10-to-reference-medicinal-product
#1
Kyoung Hoon Lee, Jihun Lee, Jin Soo Bae, Yeon Jung Kim, Hyun Ah Kang, Sung Hwan Kim, So Jung Lee, Ki Jung Lim, Jung Woo Lee, Soon Kwan Jung, Shin Jae Chang
CT-P10 (TruximaTM) was recently approved as the world's first rituximab biosimilar product in the European Union (EU) and South Korea. To demonstrate biosimilarity of CT-P10 with the reference medicinal product (RMP), extensive 3-way similarity assessment has been conducted between CT-P10, EU-Rituximab and US-Rituximab, focusing on the physicochemical and biological quality attributes. A multitude of state-of-the-art analyses revealed that CT-P10 has identical primary and higher order structures compared to the original product...
February 22, 2018: MAbs
https://www.readbyqxmd.com/read/29469568/venturing-beyond-donor-controlled-glycosylation-new-perspectives-toward-anomeric-selectivity
#2
Wei-Lin Leng, Hui Yao, Jing-Xi He, Xue-Wei Liu
Glycans are complex compounds consisting of sugars linked glycosidically, existing either as pure polysaccharides or as part of glycoconjugates. They are prevalent in nature and possess important functions in regulating biological pathways. However, their diversity coupled with physiochemical similarities makes it challenging to isolate them in large quantities for biochemical studies, hence hampering progress in glycobiology and glycomedicine. Glycochemistry presents an alternative strategy to obtain pure glycan compounds through artificial synthetic methods...
February 22, 2018: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29467823/in-vitro-and-in-vivo-characterization-of-three-cellvibrio-japonicus-glycoside-hydrolase-family-5-members-reveals-potent-xyloglucan-backbone-cleaving-functions
#3
Mohamed A Attia, Cassandra E Nelson, Wendy A Offen, Namrata Jain, Gideon J Davies, Jeffrey G Gardner, Harry Brumer
Background: Xyloglucan (XyG) is a ubiquitous and fundamental polysaccharide of plant cell walls. Due to its structural complexity, XyG requires a combination of backbone-cleaving and sidechain-debranching enzymes for complete deconstruction into its component monosaccharides. The soil saprophyte Cellvibrio japonicus has emerged as a genetically tractable model system to study biomass saccharification, in part due to its innate capacity to utilize a wide range of plant polysaccharides for growth...
2018: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29466327/the-atomic-structure-of-a-eukaryotic-oligosaccharyltransferase-complex
#4
Lin Bai, Tong Wang, Gongpu Zhao, Amanda Kovach, Huilin Li
N-glycosylation is a ubiquitous modification of eukaryotic secretory and membrane-bound proteins; about 90% of glycoproteins are N-glycosylated. The reaction is catalysed by an eight-protein oligosaccharyltransferase complex, OST, embedded in the ER membrane. Our understanding of eukaryotic protein N-glycosylation has been limited owing to the lack of high-resolution structures. Here we report a 3.5-Å resolution cryo-EM structure of the Saccharomyces cerevisiae OST, revealing the structures of Ost1-5, Stt3, Wbp1, and Swp1...
January 22, 2018: Nature
https://www.readbyqxmd.com/read/29463753/signal-peptide-of-hiv-envelope-protein-impacts-glycosylation-and-antigenicity-of-gp120
#5
Jason Yolitz, Catherine Schwing, Julia Chang, Donald Van Ryk, Fatima Nawaz, Danlan Wei, Claudia Cicala, James Arthos, Anthony S Fauci
The HIV-1 envelope protein (Env) of early-replicating viruses encodes several distinct transmission signatures. One such signature involves a reduced number of potential N-linked glycosylation sites (PNGs). This transmission signature underscores the importance of posttranslational modifications in the fitness of early-replicating isolates. An additional signature in Env involves the overrepresentation of basic amino acid residues at a specific position in the Env signal peptide (SP). In this report, we investigated the potential impact of this SP signature on gp120 glycosylation and antigenicity...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29463651/n-glycosylation-of-viral-e-protein-is-the-determinant-for-vector-midgut-invasion-by-flaviviruses
#6
Dan Wen, Suhua Li, Fangfang Dong, Yanan Zhang, Yongfang Lin, Jumei Wang, Zhen Zou, Aihua Zheng
Transmission of flaviviruses by hematophagous insects such as mosquitoes requires acquisition of the virus during blood feeding on the host, with midgut as the primary infection site. Here, we report that N-glycosylation of the E protein, which is conserved among most flaviviruses, is critical for the Zika virus (ZIKV) to invade the vector midgut by inhibiting the reactive oxygen species (ROS) pathway of the mosquito immune system. Our data further show that removal of the ZIKV E glycosylation site prevents mosquito infection by flaviviruses via the oral route, whereas there is no effect on infection by intrathoracic microinjection, which bypasses the midgut...
February 20, 2018: MBio
https://www.readbyqxmd.com/read/29462429/a-glycomics-approach-to-discover-novel-renal-biomarkers-in-birds-by-administration-of-cisplatin-and-diclofenac-to-chickens
#7
C Ishii, Y Ikenaka, O Ichii, S M M Nakayama, S-I Nishimura, T Ohashi, M Tanaka, H Mizukawa, M Ishizuka
Avian species have a unique renal structure and abundant blood flow into the kidneys. Although many birds die due to nephrotoxicity caused by chemicals, there are no early biomarkers for renal lesions. Uric acid level in blood, which is generally used as a renal biomarker, is altered when the kidney function is damaged by over 70%. Therefore, early biomarkers for kidney injury in birds are needed. In humans, glycomics has been at the forefront of biological and medical sciences, and glycans are used as biomarkers of diseases, such as carcinoma...
February 14, 2018: Poultry Science
https://www.readbyqxmd.com/read/29461547/polydiacetylene-liposomes-with-phenylboronic-acid-tags-a-fluorescence-turn-on-sensor-for-sialic-acid-detection-and-cell-surface-glycan-imaging
#8
Dong-En Wang, Jiahang Yan, Jingjing Jiang, Xiang Liu, Chang Tian, Juan Xu, Mao-Sen Yuan, Xiang Han, Jinyi Wang
Sialic acid (SA) located at the terminal end of glycans on cell membranes has been shown to play an important yet distinctive role in various biological and pathological processes. Effective methods for the facile, sensitive and in situ analysis of SA on living cell surfaces are of great significance in terms of clinical diagnostics and therapeutics. Here, a new polydiacetylene (PDA) liposome-based sensor system bearing phenylboronic acid (PBA) and 1,8-naphthalimide derived fluorophore moieties was developed as a fluorescence turn-on sensor for the detection of free SA in aqueous solution and the in situ imaging of SA-terminated glycans on living cell surfaces...
February 20, 2018: Nanoscale
https://www.readbyqxmd.com/read/29460206/deciphering-the-trophic-interaction-between-akkermansia-muciniphila-and-the-butyrogenic-gut-commensal-anaerostipes-caccae-using-a-metatranscriptomic-approach
#9
Loo Wee Chia, Bastian V H Hornung, Steven Aalvink, Peter J Schaap, Willem M de Vos, Jan Knol, Clara Belzer
Host glycans are paramount in regulating the symbiotic relationship between humans and their gut bacteria. The constant flux of host-secreted mucin at the mucosal layer creates a steady niche for bacterial colonization. Mucin degradation by keystone species subsequently shapes the microbial community. This study investigated the transcriptional response during mucin-driven trophic interaction between the specialised mucin-degrader Akkermansia muciniphila and a butyrogenic gut commensal Anaerostipes caccae. A...
February 19, 2018: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/29458681/broad-neutralization-response-in-a-subset-of-hiv-1-subtype-c-infected-viraemic-non-progressors-from-southern-india
#10
Paneerselvam Nandagopal, Jayanta Bhattacharya, Aylur K Srikrishnan, Rajat Goyal, Chinnambedu Ravichandran Swathirajan, Shilpa Patil, Shanmugam Saravanan, Suprit Deshpande, Ramachandran Vignesh, Sunil Suhas Solomon, Nikhil Singla, Joyeeta Mukherjee, Kailapuri G Murugavel
Broadly neutralizing antibodies (bnAbs) have been considered to be potent therapeutic tools and potential vaccine candidates to enable protection against various clades of human immunodeficiency virus (HIV). The generation of bnAbs has been associated with enhanced exposure to antigen, high viral load and low CD4+ T cell counts, among other factors. However, only limited data are available on the generation of bnAbs in viraemic non-progressors that demonstrate moderate to high viraemia. Further, since HIV-1 subtype C viruses account for more than 50 % of global HIV infections, the identification of bnAbs with novel specificities is crucial to enable the development of potent tools to aid in HIV therapy and prevention...
February 5, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29457870/effect-of-the-flow-profile-on-separation-efficiency-in-pressure-assisted-reversed-polarity-capillary-zone-electrophoresis-of-anions-simulation-and-experimental-evaluation
#11
Gabor Jarvas, Marton Szigeti, Andras Guttman
Capillary electrophoresis connected to electrospray ionization mass spectrometry is a promising combination to analyze complex biological samples. The use of sheathless electrospray ionization interfaces, such as a porous nanoelectrospray capillary emitter, requires the application of forward flow (either by pressure or electroosmosis) to maintain the electrospray process. The analysis of solute molecules with strong negative charges (e.g., aminopyrenetrisulfonate labeled glycans) necessitates a reversed-polarity capillary electrophoresis separation mode, in which case the electroosmotic flow is counter current, thus pressure assistance is necessary...
February 19, 2018: Journal of Separation Science
https://www.readbyqxmd.com/read/29457629/antibody-glycoengineering-strategies-in-mammalian-cells
#12
Qiong Wang, Cheng-Yu Chung, Sandra Chough, Michael J Betenbaugh
As a key parameter impacting functional and structural heterogeneity, protein glycosylation is a critical quality attribute for antibody biotherapeutic manufacturing. The glycan patterns on recombinant antibodies, particularly on the conserved fragment crystallizable (Fc) region, can have significant effects on an antibody's functional activities including clearance rate, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and anti-inflammatory activity. In this review, we examined specific glycan attachments (fucosylation, sialylation, galactosylation, oligo-mannose and bisecting glycans) and their importance to antibody properties...
February 19, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29456495/structural-variation-of-chondroitin-sulfate-chains-contributes-to-the-molecular-heterogeneity-of-perineuronal-nets
#13
Shinji Miyata, Satomi Nadanaka, Michihiro Igarashi, Hiroshi Kitagawa
Aggrecan, a chondroitin sulfate (CS) proteoglycan, forms lattice-like extracellular matrix structures called perineuronal nets (PNNs). Neocortical PNNs primarily ensheath parvalbumin-expressing inhibitory neurons (parvalbumin, PV cells) late in brain development. Emerging evidence indicates that PNNs promote the maturation of PV cells by enhancing the incorporation of homeobox protein Otx2 and regulating experience-dependent neural plasticity. Wisteria floribunda agglutinin (WFA), an N-acetylgalactosamine-specific plant lectin, binds to the CS chains of aggrecan and has been widely used to visualize PNNs...
2018: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/29453283/chemical-stresses-fail-to-mimic-the-unfolded-protein-response-resulting-from-luminal-load-with-unfolded-polypeptides
#14
Timothy J Bergmann, Ilaria Fregno, Fiorenza Fumagalli, Andrea Rinaldi, Francesco Bertoni, Paul J Boersema, Paola Picotti, Maurizio Molinari
The stress sensors ATF6, IRE1 and PERK monitor deviations from homeostatic conditions in the endoplasmic reticulum (ER), a protein biogenesis compartment of eukaryotic cells. Their activation elicits unfolded protein responses (UPR) to re-establish proteostasis. UPR have been extensively investigated in cells exposed to chemicals that activate ER stress sensors by perturbing calcium, N-glycans or redox homeostasis. Cell responses to variations in luminal load with unfolded proteins are, in contrast, poorly characterized...
February 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29452367/variant-in-human-pofut1-reduces-enzymatic-activity-and-likely-causes-a-recessive-microcephaly-global-developmental-delay-with-cardiac-and-vascular-features
#15
Hideyuki Takeuchi, Derek Wong, Michael Schneider, Hudson H Freeze, Megumi Takeuchi, Steven J Berardinelli, Atsuko Ito, Hane Lee, Stanley F Nelson, Robert S Haltiwanger
Protein O-fucosyltransferase-1 (POFUT1) adds O-fucose monosaccharides to epidermal growth factor-like (EGF) repeats found on approximately 100 mammalian proteins, including Notch receptors. Haploinsufficiency of POFUT1 has been linked to adult-onset Dowling Degos Disease (DDD) with hyperpigmentation defects. Homozygous deletion of mouse Pofut1 results in embryonic lethality with severe Notch-like phenotypes including defects in somitogenesis, cardiogenesis, vasculogenesis, and neurogenesis, but the extent to which POFUT1 is required for normal human development is not yet understood...
February 14, 2018: Glycobiology
https://www.readbyqxmd.com/read/29451981/high-performance-anion-exchange-and-hydrophilic-interaction-liquid-chromatography-approaches-for-comprehensive-mass-spectrometry-based-characterization-of-the-n-glycome-of-a-recombinant-human-erythropoietin
#16
Zoltan Szabo, James R Thayer, Dietmar Reusch, Yury Agroskin, Rosa Viner, Jeff Rohrer, Sachin P Patil, Michael Krawitzky, Andreas Huhmer, Nebojsa Avdalovic, Shaheer H Khan, Yan Liu, Christopher Pohl
Comprehensive characterization of the N-glycome of a therapeutic is challenging because glycans may harbor numerous modifications (e.g. phosphorylation, sulfation, sialic acids with possible O-acetylation). The current report presents a comparison of two chromatographic platforms for the comprehensive characterization of a recombinant human erythropoietin (rhEPO) N-glycome. The two platforms include a common workflow based on 2-AB-derivatization and hydrophilic interaction chromatography (HILIC) and a native N-linked glycan workflow employing high performance anion exchange (HPAE) chromatography...
February 16, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29449843/insights-into-the-structural-basis-of-antibody-affinity-maturation-from-next-generation-sequencing
#17
REVIEW
Arjun K Mishra, Roy A Mariuzza
Affinity maturation is the process whereby the immune system generates antibodies of higher affinities during a response to antigen. It is unique in being the only evolutionary mechanism known to operate on a molecule in an organism's own body. Deciphering the structural mechanisms through which somatic mutations in antibody genes increase affinity is critical to understanding the evolution of immune repertoires. Next-generation sequencing (NGS) has allowed the reconstruction of antibody clonal lineages in response to viral pathogens, such as HIV-1, which was not possible in earlier studies of affinity maturation...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29446631/mechanistic-investigation-and-multiplexing-of-liposome-assisted-metabolic-glycan-labeling
#18
Yuting Sun, Senlian Hong, Ran Xie, Rongbing Huang, Ruoxing Lei, Bo Cheng, Deen Sun, Yifei Du, Corwin M Nycholat, James C Paulson, Xing Chen
Metabolic labeling of glycans with bioorthogonal reporters has been widely used for glycan imaging and glycoproteomic profiling. One of the intrinsic limitations of metabolic glycan labeling is the lack of cell-type selectivity. The recently developed liposome-assisted bioorthogonal reporter (LABOR) strategy provides a promising means to overcome this limitation, but the mechanism of LABOR has not been investigated in detail. In this work, we performed a mechanistic study on LABOR and explored its multiplexing capability...
February 15, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29446564/glycosylation-on-proteins-of-the-intestine-and-perimicrovillar-membrane-of-triatoma-meccus-pallidipennis-under-different-feeding-conditions
#19
Ana E Gutiérrez-Cabrera, Wesley F Zandberg, Edgar Zenteno, Mario H Rodríguez, Bertha Espinoza, Carl Lowenberger
Trypanosoma cruzi, the causative agent of Chagas disease, interacts with molecules in the midgut of its insect vector to multiply and reach the infective stage. Many studies suggest that the parasite binds to midgut-specific glycans. We identified several glycoproteins expressed in the intestine and perimicrovillar membrane (PMM) of Triatoma (Meccus) pallidipennis under different feeding conditions. In order to assess changes in protein-linked glycans, we performed lectin and immunoblot analyses on glycoprotein extracts from these intestinal tissues using well-characterized lectins, and an antibody, which collectively recognize a wide range of different glycans epitopes...
February 15, 2018: Insect Science
https://www.readbyqxmd.com/read/29445369/turgor-pressure-and-possible-constriction-mechanisms-in-bacterial-division
#20
REVIEW
Masaki Osawa, Harold P Erickson
Bacterial cytokinesis begins with the assembly of FtsZ into a Z ring at the center of the cell. The Z-ring constriction in Gram-negative bacteria may occur in an environment where the periplasm and the cytoplasm are isoosmotic, but in Gram-positive bacteria the constriction may have to overcome a substantial turgor pressure. We address three potential sources of invagination force. (1) FtsZ itself may generate force by curved protofilaments bending the attached membrane. This is sufficient to constrict liposomes in vitro ...
2018: Frontiers in Microbiology
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