Abnormally high content of free glucosamine residues identified in a preparation of commercially available porcine intestinal heparan sulfate

Heparan sulfate (HS) polysaccharides are ubiquitous in animal tissues as components of proteoglycans, and they participate in many important biological processes. HS carbohydrate chains are complex and can contain rare structural components such as N-unsubstituted glucosamine (GlcN). Commercially available HS preparations have been invaluable in many types of research activities. In the course of preparing microarrays to include probes derived from HS oligosaccharides, we found an unusually high content of GlcN residue in a recently purchased batch of porcine intestinal mucosal HS. Composition and sequence analysis by mass spectrometry of the oligosaccharides obtained after heparin lyase III digestion of the polysaccharide indicated two and three GlcN in the tetrasaccharide and hexasaccharide fractions, respectively. (1)H NMR of the intact polysaccharide showed that this unusual batch differed strikingly from other HS preparations obtained from bovine kidney and porcine intestine. The very high content of GlcN (30%) and low content of GlcNAc (4.2%) determined by disaccharide composition analysis indicated that N-deacetylation and/or N-desulfation may have taken place. HS is widely used by the scientific community to investigate HS structures and activities. Great care has to be taken in drawing conclusions from investigations of structural features of HS and specificities of HS interaction with proteins when commercial HS is used without further analysis. Pending the availability of a validated commercial HS reference preparation, our data may be useful to members of the scientific community who have used the present preparation in their studies

Globalization and the outbreak of COVID-19 : an empirical analysis

The purpose of this study is to examine the relationship between the extension of globalization and coronavirus disease 2019 (COVID-19) case fatality rate (CFR) calculated on 28 July 2020 in more than 150 countries. Our regression analyses show that countries with higher levels of socio-economic globalization are exposed to higher levels of CFR. The positive association between the level of globalization of countries and their COVID-19 fatality rate remains robust, controlling for cross-country differences in economic development and demographics, health care costs, health care capacity, quality of governance and continental dummies

Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates

Protein O-mannosylation is a post-translational modification essential for correct development of mammals. In humans, deficient O-mannosylation results in severe congenital muscular dystrophies often associated with impaired brain and eye development. Although various O-mannosylated proteins have been identified in the recent years, the distribution of O-mannosyl glycans in the mammalian brain and target proteins are still not well defined. In the present study, rabbit monoclonal antibodies directed against the O-mannosylated peptide YAT(α1-Man)AV were generated. Detailed characterization of clone RKU-1-3-5 revealed that this monoclonal antibody recognizes O-linked mannose also in different peptide and protein contexts. Using this tool, we observed that mono-O-mannosyl glycans occur ubiquitously throughout the murine brain but are especially enriched at inhibitory GABAergic neurons and at the perineural nets. Using a mass spectrometry-based approach, we further identified glycoproteins from the murine brain that bear single O-mannose residues. Among the candidates identified are members of the cadherin and plexin superfamilies and the perineural net protein neurocan. In addition, we identified neurexin 3, a cell adhesion protein involved in synaptic plasticity, and inter-alpha-trypsin inhibitor 5, a protease inhibitor important in stabilizing the extracellular matrix, as new O-mannosylated glycoproteins

High temperature optical absorption investigation into the electronic transitions in sol–gel derived C12A7 thin films

Optical absorption into 6 mm thick sol–gel derived films, annealed at 1300 °C of 12CaO·7Al2O3 calcium aluminate binary compound on MgO〈100〉 single crystal substrates was studied at temperatures ranging from room temperature to 300 °C. Experimental data were analysed in both Tauc and Urbach regions. The optical band gap decreased from 4.088 eV at 25 °C to 4.051 eV at 300 °C, while Urbach energy increased from 0.191 eV at 25 °C to 0.257 eV at 300 °C. The relationship between the optical band gap and the Urbach energy at different temperatures showed an almost linear relationship from which the theoretical values of 4.156 and 0.065 eV were evaluated for the band gap energy and Urbach energy of a 12CaO·7Al2O3 crystal with zero structural disorder at 0 K

Defining the glycosaminoglycan interactions of complement factor H-related protein 5

Complement activation is an important mediator of kidney injury in glomerulonephritis. Complement factor H (FH) and FH-related protein 5 (FHR-5) influence complement activation in C3 glomerulopathy and IgA nephropathy by differentially regulating glomerular complement. FH is a negative regulator of complement C3 activation. Conversely, FHR-5 in vitro promotes C3 activation either directly or by competing with FH for binding to complement C3b. The FH-C3b interaction is enhanced by surface glycosaminoglycans (GAGs) and the FH-GAG interaction is well-characterized. In contrast, the contributions of carbohydrates to the interaction of FHR-5 and C3b are unknown. Using plate-based and microarray technologies we demonstrate that FHR-5 interacts with sulfated GAGs and that this interaction is influenced by the pattern and degree of GAG sulfation. The FHR-5-GAG interaction that we identified has functional relevance as we could show that the ability of FHR-5 to prevent binding of FH to surface C3b is enhanced by surface kidney heparan sulfate. Our findings are important in understanding the molecular basis of the binding of FHR-5 to glomerular complement and the role of FHR-5 in complement-mediated glomerular disease

A new software tool for carbohydrate microarray data storage, processing, presentation, and reporting

Publisher Copyright: © 2022 The Author(s) 2022. Published by Oxford University Press. This project is supported by Wellcome Trust Biomedical Resource grants (WT099197/Z/12/Z, 108430/Z/15/Z and 218304/Z/19/Z); March of Dimes European Prematurity Research Centre grant 22-FY18-82 and NIH Commons Fund 1U01GM125267-01Glycan microarrays are essential tools in glycobiology and are being widely used for assignment of glycan ligands in diverse glycan recognition systems. We have developed a new software, called Carbohydrate microArray Analysis and Reporting Tool (CarbArrayART), to address the need for a distributable application for glycan microarray data management. The main features of CarbArrayART include: (i) Storage of quantified array data from different array layouts with scan data and array-specific metadata, such as lists of arrayed glycans, array geometry, information on glycan-binding samples, and experimental protocols. (ii) Presentation of microarray data as charts, tables, and heatmaps derived from the average fluorescence intensity values that are calculated based on the imaging scan data and array geometry, as well as filtering and sorting functions according to monosaccharide content and glycan sequences. (iii) Data export for reporting in Word, PDF, and Excel formats, together with metadata that are compliant with the guidelines of MIRAGE (Minimum Information Required for A Glycomics Experiment). CarbArrayART is designed for routine use in recording, storage, and management of any slide-based glycan microarray experiment. In conjunction with the MIRAGE guidelines, CarbArrayART addresses issues that are critical for glycobiology, namely, clarity of data for evaluation of reproducibility and validity.publishersversionpublishe

Staphylococcal Periscope proteins Aap, SasG, and Pls project noncanonical legume-like lectin adhesin domains from the bacterial surface

Staphylococcus aureus and Staphylococcus epidermidis are frequently associated with medical device infections that involve establishment of a bacterial biofilm on the device surface. Staphylococcal surface proteins Aap, SasG, and Pls are members of the Periscope Protein class and have been implicated in biofilm formation and host colonization; they comprise a repetitive region ("B region") and an N-terminal host colonization domain within the "A region," predicted to be a lectin domain. Repetitive E-G5 domains (as found in Aap, SasG, and Pls) form elongated "stalks" that would vary in length with repeat number, resulting in projection of the N-terminal A domain variable distances from the bacterial cell surface. Here, we present the structures of the lectin domains within A regions of SasG, Aap, and Pls and a structure of the Aap lectin domain attached to contiguous E-G5 repeats, suggesting the lectin domains will sit at the tip of the variable length rod. We demonstrate that these isolated domains (Aap, SasG) are sufficient to bind to human host desquamated nasal epithelial cells. Previously, proteolytic cleavage or a deletion within the A domain had been reported to induce biofilm formation; the structures suggest a potential link between these observations. Intriguingly, while the Aap, SasG, and Pls lectin domains bind a metal ion, they lack the nonproline cis peptide bond thought to be key for carbohydrate binding by the lectin fold. This suggestion of noncanonical ligand binding should be a key consideration when investigating the host cell interactions of these bacterial surface proteins

Treatment-related complications in childhood acute lymphoblastic leukemia: Results of medical research council UKALL X

Background: Acute lymphoblastic leukemia (ALL) is a heterogeneous group of lymphoid neoplasms resulting from the proliferation of malignant lymphoid cells. The aim of this study was to evaluate treatment-related complications in children with ALL receiving the Medical Research Council (MRC) UKALL X protocol. Methods: In this retrospective cross-sectional study, children with ALL receiving the MRC UKALL X protocol from 2008 to 2015 in Bahrami University Hospital, Iran, were enrolled. The clinical and morphological features were analysed and treatment-related complications were assessed. Results: Out of 67 children with ALL receiving the MRC UKALL X protocol, 44 (65.6 ) were boys and 23 (34.4) were girls. Seven patients (10.7) relapsed in the three years of diagnosis, and 50 children (74.6) had an overall survival of three years. Average age in three-year-survival group and mortality group was 6.92 (SD: 3.96) and 6.35 (SD: 7.47), respectively (P= 0.38). Conclusion: Overall survival and relapse rates in this study confirm that this protocol is an appropriate treatment strategy. © 2020, Shiraz University of Medical Sciences. All rights reserved

Reliability and validity of the Persian version of Foot and Ankle Ability Measure (FAAM) to measure functional limitations in patients with foot and ankle disorders

Objective: To translate the Foot and Ankle Ability Measure (FAAM) into Persian and to evaluate the psychometric properties of the Persian version of FAAM. Methods: 93 patients with a range of foot and ankle disorders, completed the Persian version of the FAAM and Short-Form 36 Health Survey (SF-36) in the test session. With an interval of 2-6 days, 60 patients filled out the FAAM in the retest session. The FAAM is composed of two subscales including activities of daily living (ADL) and SPORTS. Internal consistency was assessed using Cronbach's alpha, test-retest reliability using intraclass correlation coefficient (ICC) and standard error of measurement (s.e.m.), item internal consistency and discriminant validity using Spearman's correlation coefficient and construct validity using Spearman's correlation coefficient and Independent t-test. Results: Cronbach's alpha coefficient of 0.97 and 0.94 was obtained for ADL and SPORTS subscales, respectively. The ICC and s.e.m. were 0.98 and 3.13 for ADL and 0.98 and 3.53 for SPORTS subscale. Items were stronger measures of their hypothesized subscale than of other subscale. The ADL and SPORTS subscales had stronger correlation with SF-36 physical function (r=0.60, 0.53) and physical health summary measure (r=0.61, 0.48) than with SF-36 mental health (r=0.21, 0.10) and mental health summary measure (r=0.36, 0.27). A high correlation was found between FAAM scores and global scale of functional status for SPORTS (r=0.73) but not for ADL (r=0.42). FAAM scores were greater in individuals who rated their function as normal or nearly normal compared with those who rated as abnormal or severely abnormal for SPORTS (P=0.04) but not for ADL (P=0.15). Conclusion: The Persian version of FAAM is a reliable and valid measure to quantify physical functioning in patients with foot and ankle disorders. © 2010 Osteoarthritis Research Society International