Perinatal Protein Restriction Impacts Nuclear O-GalNAc Glycosylation in Cells of Liver and Brain Structures of the Rat.

Background: Post-translational modifications are key factors in the modulation of nuclear protein functions controlling cell physiology and an individual's health.

Objectives: This study examined the influence of protein restriction during the perinatal period on the nuclear O-N-acetylgalactosamine (O-GalNAc) glycosylation of cells from the liver and parts of the brain in the rat.

Methods: Pregnant Wistar rats were divided into 2 groups on day 14 of pregnancy and fed ad libitum 1 of 2 isocaloric diets containing 24% (well-fed) or 8% (protein-restricted diet) casein until the end of the experiment.

Polypeptide N-acetylgalactosamine transferase 3: a post-translational writer on human health.

Polypeptide N-acetylgalactosamine transferase 3 (ppGalNAc-T3) is an enzyme involved in the initiation of O-GalNAc glycan biosynthesis. Acting as a writer of frequent post-translational modification (PTM) on human proteins, ppGalNAc-T3 has key functions in the homeostasis of human cells and tissues. We review the relevant roles of this molecule in the biosynthesis of O-GalNAc glycans, as well as in biological functions related to human physiological and pathological conditions.

How glycobiology can help us treat and beat the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged during the last months of 2019, spreading throughout the world as a highly transmissible infectious illness designated as COVID-19. Vaccines have now appeared, but the challenges in producing sufficient material and distributing them around the world means that effective treatments to limit infection and improve recovery are still urgently needed. This review focuses on the relevance of different glycobiological molecules that could potentially serve as or inspire therapeutic tools during SARS-CoV-2 infection.

Neurological disorders-associated anti-glycosphingolipid IgG-antibodies display differentially restricted IgG subclass distribution.

Antibodies against several self-glycans on glycosphingolipids are frequently detected in different neurological disorders. Their pathogenic role is profusely documented, but the keys for their origin remain elusive. Additionally, antibodies recognizing non-self glycans appear in normal human serum during immune response to bacteria.

Core 1 O-N-acetylgalactosamine (O-GalNAc) glycosylation in the human cell nucleus.

Glycosylation is a very frequent post-translational modification in proteins, and the initiation of O-N-acetylgalactosamine (O-GalNAc) glycosylation has been recently described on relevant nuclear proteins. Here we evaluated the nuclear incorporation of a second sugar residue in the biosynthesis pathway of O-GalNAc glycans to yield the terminal core 1 glycan (C1G, Galβ3GalNAcαSer/Thr). Using confocal microscopy, enzymatic assay, affinity chromatography, and mass spectrometry, we analyzed intact cells, purified nuclei and soluble nucleoplasms to identify the essential factors for C1G biosynthesis in the cell nucleus.

Most of anti-glycolipid IgG-antibodies associated to neurological disorders occur without their IgM counterpart.

Background: Different neurological disorders frequently display antibodies against several self-glycans. Increasing evidence supports their pathogenic role; however, far less is known about their origin. Meanwhile, antibodies recognizing non-self glycans appear in normal human serum during immune response to bacteria.

Purified human anti-Tn and anti-T antibodies specifically recognize carcinoma tissues.

Described in several epithelial cancer cells, Tn- (GalNAcα1-O-Ser/Thr) and T- (Galβ3GalNAcα1-O-Ser/Thr) antigens are examples of tumor-associated antigens. Increased expression of Tn- and T-antigens is associated with tumor invasion and metastasis, and patients with high concentration of anti-Tn and anti-T antibodies have a more benign evolution of pathology. Asialofetuin (ASF) and ovine submaxillary mucin (OSM) are two glycoproteins that expose T- and Tn-antigen, respectively.

Bacillus Calmette-Guérin Alters Melanoma Microenvironment Favoring Antitumor T Cell Responses and Improving M2 Macrophage Function.

Intralesional bacillus Calmette-Guérin (BCG) has long been a relatively inexpensive therapy for inoperable cutaneous metastatic melanoma (CMM), although intralesional BCG skin mechanisms remain understudied. We analyzed intralesional BCG-treated CMM lesions combined with studies to further investigate BCG-altered pathways. Since macrophages play a pivotal role against both cancer and mycobacterial infections, we hypothesized BCG regulates macrophages to promote antitumor immunity.

Cross-platform comparison of independent datasets identifies an immune signature associated with improved survival in metastatic melanoma.

Platform and study differences in prognostic signatures from metastatic melanoma (MM) gene expression reports often hinder consensus arrival. We performed survival/outcome-based pairwise comparisons of three independent MM gene expression profiles using the threshold-free algorithm rank-rank hypergeometric overlap analysis (RRHO). We found statistically significant overlap for genes overexpressed in favorable outcome (FO) groups, but no overlap for poor outcome (PO) groups.

Individual Restriction Of Fine Specificity Variability In Anti-GM1 IgG Antibodies Associated With Guillain-Barré Syndrome.

Elevated titers of serum antibodies against GM1 ganglioside are associated with a variety of autoimmune neuropathies. Much evidence indicates these autoantibodies play a primary role in the disease processes, but the mechanism for their appearance is unclear. We studied the fine specificity of anti-GM1 antibodies of the IgG isotype present in sera from patients with Guillain-Barré syndrome (GBS), using thin-layer chromatogram-immunostaining of GM1, asialo-GM1 (GA1), GD1b and GM1-derivatives with small modifications on the oligosaccharide moiety.

Dysregulated Expression of Glycolipids in Tumor Cells: From Negative Modulator of Anti-tumor Immunity to Promising Targets for Developing Therapeutic Agents.

Glycolipids are complex molecules consisting of a ceramide lipid moiety linked to a glycan chain of variable length and structure. Among these are found the gangliosides, which are sialylated glycolipids ubiquitously distributed on the outer layer of vertebrate plasma membranes. Changes in the expression of certain species of gangliosides have been described to occur during cell proliferation, differentiation, and ontogenesis.

Inducing host protection in pneumococcal sepsis by preactivation of the Ashwell-Morell receptor.

The endocytic Ashwell-Morell receptor (AMR) of hepatocytes detects pathogen remodeling of host glycoproteins by neuraminidase in the bloodstream and mitigates the lethal coagulopathy of sepsis. We have investigated the mechanism of host protection by the AMR during the onset of sepsis and in response to the desialylation of blood glycoproteins by the NanA neuraminidase of Streptococcus pneumoniae. We find that the AMR selects among potential glycoprotein ligands unmasked by microbial neuraminidase activity in pneumococcal sepsis to eliminate from blood circulation host factors that contribute to coagulation and thrombosis.

Anti-GM1 IgG antibodies in Guillain-Barré syndrome: fine specificity is associated with disease severity.

Background: Clinical severity of Guillain-Barré syndrome (GBS) is highly variable, but the immunopathological reason is unknown.

Objective: The study was designed to show which antibody parameters are associated with disease severity in GBS patients with serum anti-GM1 IgG antibodies.

Methods: Thirty-four GBS patients with anti-GM(1) IgG antibodies were grouped into two categories according to disease severity at nadir: mild (grades 1-3 by Hughes functional scale, n=13) and severe (grades 4 and 5, n=21).

Anti-GM1 antibodies as a model of the immune response to self-glycans.

Glycans are a class of molecules with high structural variability, frequently found in the plasma membrane facing the extracellular space. Because of these characteristics, glycans are often considered as recognition molecules involved in cell social functions, and as targets of pathogenic factors. Induction of anti-glycan antibodies is one of the early events in immunological defense against bacteria that colonize the body.

Fine carbohydrate recognition of Euphorbia milii lectin.

Glycans are key structures involved in biological processes such as cell attachment, migration, and invasion. Information coded on cell-surface glycans is frequently deciphered by proteins, as lectins, that recognize specific carbohydrate topology. Here, we describe the fine carbohydrate specificity of Euphorbia milii lectin (EML).

Immune response to Thomsen-Friedenreich disaccharide and glycan engineering.

Cancer-associated mucins show frequent alterations of their oligosaccharide chain profile, with a switch to unmask normally cryptic O-glycan backbone and core regions. Epithelial tumour cells typically show overexpression of the uncovered Gal(beta)1-3GalNAc(alpha)-O-Ser/Thr (Core 1) structure, known as the T antigen or the Thomsen-Friedenreich antigen, the oligosaccharide chain of which is called the Thomsen-Friedenreich disaccharide (TFD). T antigen expression has been associated with immunosuppression, metastasis dissemination, and the proliferation of cancer cells.

Crystallization and preliminary X-ray study of the common edible mushroom (Agaricus bisporus) lectin.

The lectin from the common edible mushroom Agaricus bisporus (ABL) belongs to the group of proteins that have the property of binding the Thomsen-Friedenreich antigen (T-antigen) selectively and with high affinity, but does not show any sequence similarity to the other proteins that share this property. The ABL sequence is instead similar to those of members of the saline-soluble fungal lectins, a protein family with pesticidal properties. The presence of different isoforms has been reported.

Normally occurring human anti-GM1 immunoglobulin M antibodies and the immune response to bacteria.

Anti-GM(1) antibodies of the immunoglobulin M (IgM) isotype are normal components of the antibody repertoire of adult human serum. Using a sensitive high-performance thin-layer chromatography (HPTLC) immunostaining assay, we found that these antibodies were absent in the umbilical vein and children <1 month of age but could be detected after 1 month of age. Although most of the children older than 6 months of age were positive, there were still a few negative children.

The origin of anti-GM1 antibodies in neuropathies: the "binding site drift" hypothesis.

Elevated titers of serum antibodies against GM1-ganglioside are associated with a variety of autoimmune neuropathies. The origin of these autoantibodies is still unknown, although there is evidence that they are produced by CD5+ B-lymphocytes and that antigen mimicry is involved. Anti-GM, IgM-antibodies in the normal human immunological repertoire are low affinity antibodies that cross-react with other glycoconjugates carrying Gal beta1-3GalNAc and probably do not have GM1-mediated biological activity.