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Ishan S Shah, Scott Lovell, Nurjahan Mehzabeen, Kevin P Battaile, Thomas J Tolbert
Immunoglobulin G (IgG) consists of four subclasses in humans: IgG1, IgG2, IgG3 and IgG4, which are highly conserved but have unique differences that result in subclass-specific effector functions. Though IgG1 is the most extensively studied IgG subclass, study of other subclasses is important to understand overall immune function and for development of new therapeutics. When compared to IgG1, IgG3 exhibits a similar binding profile to Fcγ receptors and stronger activation of complement. All IgG subclasses are glycosylated at N297, which is required for Fcγ receptor and C1q complement binding as well as maintaining optimal Fc conformation...
October 11, 2017: Molecular Immunology
Korcan Demir, Melek Yildiz, Hilla Bahat, Michael Goldman, Nisreen Hassan, Shay Tzur, Ayala Ofir, Daniella Magen
Context: NaPi-IIa, encoded by SLC34A1 is a key phosphate transporter in the mammalian proximal tubule, and plays a cardinal role in renal phosphate handling. NaPi-IIa impairment has been linked to various overlapping clinical syndromes, including hypophosphatemic nephrolithiasis with osteoporosis, renal Fanconi's syndrome with chronic kidney disease, and most recently, with idiopathic infantile hypercalcemia and nephrocalcinosis. Objectives: We studied the molecular basis of idiopathic infantile hypercalcemia with partial proximal tubulopathy in two apparently unrelated patients of Israeli and Turkish descent...
September 29, 2017: Journal of Clinical Endocrinology and Metabolism
Fumi Ota, Yasuhiko Kizuka, Miyako Nakano, Yoshiki Yamaguchi, Shinobu Kitazume, Tomomi Ookawara, Naoyuki Taniguchi
Extracellular superoxide dismutase (EC-SOD, SOD3) protects tissues against oxidative damage by detoxifying superoxide anions, particularly in the lungs and cardiovascular system. EC-SOD undergoes several posttranslational modifications including N-glycosylation and proteolytic cleavage. While the roles of proteolytic cleavage have been well studied, the structure and function of EC-SOD N-glycans are poorly understood. Here we analyzed glycan structures on native EC-SOD purified from human sera, and identified sialylated biantennary structures...
October 4, 2017: Glycobiology
Nino Trattnig, Jean-Baptiste Farcet, Philipp Gritsch, Anna Christler, Ralph Pantophlet, Paul Kosma
The pentasaccharide fragment α-D-Man-(1→5)-[α-D-Kdo-(2→4)-]α-D-Kdo-(2→6)-β-D-GlcNAc-(1→6)-α-D-GlcNAc equipped with a 3-aminopropyl spacer moiety was prepared by a sequential assembly of monosaccharide building blocks. The glucosamine disaccharide - as a backbone surrogate of the bacterial lipid A region - was synthesized using an 1,3-oxazoline donor, which was followed by coupling with an isopropylidene-protected Kdo-fluoride donor to afford a protected tetrasaccharide intermediate. Eventually, an orthogonally protected manno-configured trichloroacetimidate donor was used to achieve the sterically demanding glycosylation of the 5-OH group of Kdo in good yield...
October 13, 2017: Journal of Organic Chemistry
Gui-Zhi Zhang, Shang-Hui Jin, Pan Li, Xiao-Yi Jiang, Yan-Jie Li, Bing-Kai Hou
Ectopic expression of auxin glycosyltransferase UGT84A2 in Arabidopsis can delay flowering through increased indole-3-butyric acid and suppressed transcription of ARF6, ARF8 and flowering-related genes FT, SOC1, AP1 and LFY. Auxins are critical regulators for plant growth and developmental processes. Auxin homeostasis is thus an important issue for plant biology. Here, we identified an indole-3-butyric acid (IBA)-specific glycosyltransferase, UGT84A2, and characterized its role in Arabidopsis flowering development...
October 13, 2017: Plant Cell Reports
Hugh M B Harris, Maxence J B Bourin, Marcus J Claesson, Paul W O'Toole
The genus Lactobacillus is a diverse group with a combined species count of over 200. They are the largest group within the lactic acid bacteria and one of the most important bacterial groups involved in food microbiology and human nutrition because of their fermentative and probiotic properties. Lactobacillus salivarius, a species commonly isolated from the gastrointestinal tract of humans and animals, has been described as having potential probiotic properties and results of previous studies have revealed considerable functional diversity existing on both the chromosomes and plasmids...
August 2017: Microbial Genomics
Chan-Yeong Kwak, Seung-Yeol Park, Chung-Geun Lee, Nozomu Okino, Makoto Ito, Jung Hoe Kim
Sialylation regulates the in vivo half-life of recombinant therapeutic glycoproteins, affecting their therapeutic efficacy. Levels of the precursor molecule cytidine monophospho-N-acetylneuraminic acid (CMP-Neu5Ac) are considered a limiting factor in the sialylation of glycoproteins. Here, we show that by reducing the amount of intracellular CMP-Neu5Ac consumed for glycosphingolipid (GSL) biosynthesis, we can increase the sialylation of recombinant human erythropoietin (rhEPO) produced in CHO cells. Initially, we found that treating CHO cells with a potent inhibitor of GSL biosynthesis increases the sialylation of the rhEPO they produce...
October 12, 2017: Scientific Reports
Joseph T Ortega, Alirica I Suárez, Maria L Serrano, Jani Baptista, Flor H Pujol, Hector R Rangel
BACKGROUND: Plant extracts are sources of valuable compounds with biological activity, especially for the anti-proliferative activity against pathogens or tumor cells. Myricetin is a flavonoid found in several plants that has been described as an inhibitor of Human immunodeficiency virus type 1 (HIV-1) through its action against the HIV reverse transcriptase, but myricetin derivatives have not been fully studied. The aim of this study was to evaluate the anti-HIV-1 activity of glycosylated metabolites obtained from Marcetia taxifolia and derived from myricetin: myricetin rhamnoside and myricetin 3-(6-rhamnosylgalactoside)...
October 12, 2017: AIDS Research and Therapy
Jaire Alves Ferreira Filho, Maria Augusta Crivelente Horta, Lilian Luzia Beloti, Clelton Aparecido Dos Santos, Anete Pereira de Souza
BACKGROUND: Trichoderma harzianum is used in biotechnology applications due to its ability to produce powerful enzymes for the conversion of lignocellulosic substrates into soluble sugars. Active enzymes involved in carbohydrate metabolism are defined as carbohydrate-active enzymes (CAZymes), and the most abundant family in the CAZy database is the glycoside hydrolases. The enzymes of this family play a fundamental role in the decomposition of plant biomass. RESULTS: In this study, the CAZymes of T...
October 12, 2017: BMC Genomics
Fanny Lazo, Dan E Vivas-Ruiz, Gustavo A Sandoval, Edith F Rodríguez, Edgar E G Kozlova, F Costal-Oliveira, Carlos Chávez-Olórtegui, Ruperto Severino, Armando Yarlequé, Eladio F Sanchez
An L-amino acid oxidase from Peruvian Bothrops pictus (Bpic-LAAO) snake venom was purified using a combination of size-exclusion and ion-exchange chromatography. Bpic-LAAO is an homodimeric glycosylated flavoprotein with molecular mass of ∼65 kDa under reducing conditions and ∼132 kDa in its native form as analyzed by SDS-PAGE and gel filtration chromatography, respectively. N-terminal amino acid sequencing showed highly conserved residues in a glutamine-rich motif related to binding substrate. The enzyme exhibited optimal activity towards L-Leu at pH 8...
October 9, 2017: Toxicon: Official Journal of the International Society on Toxinology
Anita D Misra-Hebert, Bo Hu, Phuc H Le, Michael B Rothberg
Background Prediabetes may be improved or reversed with lifestyle interventions. A worksite wellness program offering financial incentives for participation may be effective in improving the health of employees with prediabetes. We studied the effect of employee health plan financial incentives on health outcomes for employees with prediabetes. Methods We conducted a retrospective cohort study using electronic medical record (EMR) data from January 2008- December 2012. Our study participants were employees with prediabetes and propensity-matched non-employees with prediabetes and commercial health insurance, all receiving care within one health system...
October 9, 2017: American Journal of Medicine
Rania Abu El Asrar, Lia Margamuljana, Mikhail Abramov, Omprakash Bande, Stefano Agnello, Miyeon Jang, Piet Herdewijn
A series of nucleotide analogues, with a hypoxanthine base moiety (8-amino-hypoxanthine, 1-methyl-8-amino-hypoxanthine and 8-oxo-hypoxanthine) together with 5-methyl-isocytosine were tested as potential pairing partners of N8-glycosylated nucleotides with an 8-azaguanine and 8-aza-9-deazaguanine base moiety, using DNA polymerases (incorporation studies). The best results were obtained with the 5-methyl-isocytosine nucleotide followed by the 1-metyl-8-amino-hypoxanthine nucleotide. The experiments demonstrate that a) small differences in the structure (8-azaguanine versus 8-aza-9-deazaguanine) might lead to significant differences in recognition efficiency and selectivity b) base pairing via Hoogsteen recognition, at the polymerase level is possible c) 8-aza-9-deazaguanine represents a self-complementary base pair and d) a correlation exists between the in vitro incorporation studies and in vivo recognition by natural bases in Escherichia coli, but this recognition is not absolute (exceptions are observed)...
October 11, 2017: Chembiochem: a European Journal of Chemical Biology
Cathy Su, Alexis H Haskins, Chisato Omata, Yasushi Aizawa, Takamitsu A Kato
High consumption of dietary flavonoids might contribute to a reduction of cancer risks. Quercetin and its glycosides have PARP inhibitory effects and can induce selective cytotoxicity in BRCA2-deficient cells by synthetic lethality. We hypothesized that common flavonoids in diet naringenin, hesperetin and their glycosides have a similar structure to quercetin, which might have comparable PARP inhibitory effects, and can induce selective cytotoxicity in BRCA2-deficient cells. We utilized Chinese hamster V79 wild type, V-C8 BRCA2-deficient and its gene-complemented cells...
October 12, 2017: Pharmaceuticals
Nuria Martínez-Sáez, Jesús M Peregrina, Francisco Corzana
Cancer is currently one of the world's most serious public health problems. Significant efforts are being made to develop new strategies that can eradicate tumours selectively without detrimental effects to healthy cells. One promising approach is focused on the design of vaccines that contain partially glycosylated mucins in their formulation. Although some of these vaccines are in clinical trials, a lack of knowledge about the molecular basis that governs the antigen presentation, and the interactions between antigens and the elicited antibodies has limited their success thus far...
October 12, 2017: Chemical Society Reviews
Abdulmonim A Alqasim, Essam Eldin M Noureldin, Sami H Hammadi, Ghada E Esheba
BACKGROUND: Diabetes mellitus (DM) is a serious chronic disease, with multiple complications including hepatopathy associated with imbalance of the oxidative status. The purpose of this study is to observe possible protective effects of vitamin-D and melatonin on glucose profile, antioxidant-oxidant status, lipid peroxidation, and histopathological protection of the liver in streptozotocin-induced diabetic rats. METHODS: Eighty three male albino rats were divided into nine groups as follows: G1 (n = 10) Normal control rats; G2 (n = 8) were normal rats treated with melatonin only; G3 (n = 10) were normal rats treated with vitamin D only; G4 (n = 9) were diabetic rats, which received no medications; G5 (n = 8) were diabetic rat treated with insulin only; G6 (n = 10) were diabetic rats treated with melatonin only; G7 (n = 9) were diabetic rats treated with melatonin and insulin; G8 (n = 9) were diabetic rats treated with vitamin D only; G9 (n = 10) were diabetic rats treated with vitamin D and insulin...
2017: Journal of Diabetes and Metabolic Disorders
Anjali Joshi, Emily K Cox, Melina J Sedano, Erin B Punke, Raphael Tc Lee, Sebastian Maurer-Stroh, Palvinder Kaur, Oon Tek Ng, Himanshu Garg
HIV subtypes not only predominate in different geographical regions but also differ in key phenotypic characteristics. To determine if genotypic and/or phenotypic differences in the Envelope (Env) glycoprotein can explain subtype related differences, we cloned 37 full length Envs from Subtype B and AE HIV infected individuals from Singapore. Our data demonstrates that CRF01_AE Envs have lower Potential N Glycosylation Sites and higher risk of ×4 development. Phenotypically, CRF01_AE were less infectious than subtype B Envs in cells expressing low levels of CCR5...
October 8, 2017: Virology
Lingda Zhang, Kangli Liu, Bing Han, Zhengping Xu, Xiangwei Gao
Follistatin (FST), a single-chain glycosylated protein, is expressed in various tissues. The essential biological function of FST is binding and neutralizing transforming growth factor β (TGF-β) superfamily, including activin, myostatin, and bone morphogenetic protein (BMP). Emerging evidence indicates that FST also serves as a stress responsive protein, which plays a protective role under a variety of stresses. In most cases, FST performs the protective function through its neutralization of TGF-β superfamily...
October 8, 2017: Gene
Anton V Sinitskiy, Vijay S Pande
N-methyl-D-aspartate (NMDA) receptors, key neuronal receptors playing the central role in learning and memory, are heavily glycosylated in vivo. Astonishingly little is known about the structure, dynamics and physiological relevance of glycans attached to them. We recently demonstrated that certain glycans on the ligand binding domain (LBD) of NMDA receptors (NMDARs) can serve as intramolecular potentiators, changing EC50 of NMDAR co-agonists. In this work, we use molecular dynamics trajectories, in aggregate 86...
October 11, 2017: Journal of Chemical Theory and Computation
Ruidong Chen, Qingbo Zhang, Bin Tan, Liujuan Zheng, Huixian Li, Yiguang Zhu, Changsheng Zhang
A 92 kb silent hybrid polyketide and nonribosomal peptide gene cluster in marine-derived Streptomyces pactum SCSIO 02999 was activated by genetically manipulating the regulatory genes, including the knockout of two negative regulators (totR5 and totR3) and overexpression of a positive regulator totR1, to direct the production of the known totopotensamides (TPMs) A (1) and B (3) and a novel sulfonate-containing analogue TPM C (2). Inactivation of totG led to accumulation of TPM B (3) lacking the glycosyl moiety, which indicated TotG as a dedicated glycosyltransferase in the biosynthesis of 1 and 2...
October 11, 2017: Organic Letters
Kazufumi Yazaki, Gen-Ichiro Arimura, Toshiyuki Ohnishi
Terpenoids are the largest group of plant specialized (secondary) metabolites. These naturally occurring chemical compounds are highly diverse in chemical structure. Although there have been many excellent studies of terpenoids, most have focused on compounds built solely of isoprene units. Plants, however, also contain many "atypical" terpenoids, such as glycosylated volatile terpenes and composite-type terpenoids, the latter of which are synthesized by the coupling of isoprene units on aromatic compounds...
August 29, 2017: Plant & Cell Physiology
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