A5091799404- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Proteoglycans and glycosaminoglycans research
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Biochemical and Molecular Research
- Enzyme Structure and Function
- COVID-19 and healthcare impacts
- Cell Adhesion Molecules Research
- Immune Response and Inflammation
- Cellular transport and secretion
- Influenza Virus Research Studies
- Genomics and Phylogenetic Studies
- Bacteriophages and microbial interactions
- Metabolism and Genetic Disorders
- Lysosomal Storage Disorders Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Microbial infections and disease research
- Cardiac, Anesthesia and Surgical Outcomes
- Blood groups and transfusion
- Milk Quality and Mastitis in Dairy Cows
- Neuroinflammation and Neurodegeneration Mechanisms
- Respiratory Support and Mechanisms
University of California, San Diego
2013-2022
Laboratoire des Sciences de l'Ingénieur, de l'Informatique et de l'Imagerie
2022
Institut de Virologie
2021
NIHR Birmingham Biomedical Research Centre
2021
University of Birmingham
2021
Yorkshire Cancer Research
2021
Urology Foundation
2021
Association for Cancer Surgery
2021
Cell Medica (Switzerland)
2017
National University of Trujillo
2014
Humans are genetically unable to produce the sialic acid N-glycolylneuraminic (Neu5Gc), because of a mutation that occurred after our last common ancestor with great apes. Although Neu5Gc is presumed absent from normal humans, small amounts have been claimed exist in human tumors and fetal meconium. We generated an antibody high specificity avidity for Neu5Gc. Fetal tissues, adult breast carcinomas humans showed reactivity this antibody, primarily within secretory epithelia blood vessels....
Sialic acids are important cell-surface molecules of animals in the deuterostome lineage. Although humans do not express easily detectable amounts N-glycolylneuraminic acid (Neu5Gc, a hydroxylated form common sialic N-acetylneuraminic acid, Neu5Ac), it is major component great ape tissues, except brain. This difference correlates with lack hydroxylase activity that converts CMP-Neu5Ac to CMP-Neu5Gc. Here we report cloning human and chimpanzee cDNAs. this cDNA similar murine homologue,...
P-selectin (CD62, GMP-140, PADGEM), a Ca(2+)-dependent lectin on activated platelets and endothelium, functions as receptor for myeloid cells by interacting with sialylated, fucosylated lactosaminoglycans. binds to limited number of protease-sensitive sites cells, but the protein(s) that carry glycans recognized are unknown. Blotting neutrophil or HL-60 cell membrane extracts [125I]P-selectin affinity chromatography [3H]glucosamine-labeled were used identify ligands. A major ligand was...
N-Glycolylneuraminic acid (Neu5Gc) is a widely expressed sialic in mammalian cells. Although humans are genetically deficient producing Neu5Gc, small amounts present human cells vivo. A dietary origin was suggested by volunteer studies and observing that free Neu5Gc metabolically incorporated into cultured carcinoma unknown mechanisms. We now show uptake also occurs other Inhibitors of certain non-clathrin-mediated endocytic pathways reduce accumulation. Studies with mutant the lysosomal...
Significance We present an unusual mechanism for the well-known association between red meat consumption and carcinoma risk involving nonhuman sialic acid N -glycolylneuraminic (Neu5Gc). first evaluate Neu5Gc content of various foods to show that meats are particularly rich in orally bioavailable then investigate human-like Neu5Gc-deficient mice fed this form Neu5Gc. When such were challenged with anti-Neu5Gc antibodies, they developed evidence systemic inflammation. Long-term exposure...
Humans are genetically deficient in the common mammalian sialic acid N -glycolylneuraminic (Neu5Gc) because of an Alu -mediated inactivating mutation gene encoding enzyme CMP- -acetylneuraminic (CMP-Neu5Ac) hydroxylase (CMAH). This occurred after our last ancestor with bonobos and chimpanzees, before origin present-day humans. Here, we take multiple approaches to estimate timing this relationship human evolutionary history. First, have developed a method extract identify acids from bones...
Lectin-carbohydrate recognition between the selectins and their ligands are among earliest events in leukocyte recirculation, recruitment into inflamed areas, abnormal egress of leukocytes diseases. Previously, we have described a dimeric sialoglycoprotein from myeloid cells with subunits molecular mass = 120 kDa, which is selectively recognized by P-selectin (Moore, K.L., Stults, N.L., Diaz, S., Smith, D.F., Cummings, R.D., Varki, A., McEver, R.P. (1992) J. Cell Biol. 188, 445-456). Here,...
Background Humans are genetically defective in synthesizing the common mammalian sialic acid N-glycolylneuraminic (Neu5Gc), but can metabolically incorporate it from dietary sources (particularly red meat and milk) into glycoproteins glycolipids of human tumors, fetuses some normal tissues. Metabolic incorporation Neu5Gc animal-derived cells medium components also results variable contamination molecules intended for therapies. These Neu5Gc-incorporation phenomena practically significant,...
Influenza viruses cause seasonal flu each year and pandemics or epidemic sporadically, posing a major threat to public health. Recently, new influenza D virus (IDV) was isolated from pigs cattle. Here, we reveal that the IDV utilizes 9-O-acetylated sialic acids as its receptor for entry. Then, determined crystal structures of hemagglutinin-esterase-fusion glycoprotein (HEF) both in free form complex with enzymatic substrate analogs. The HEF shows an extremely similar structural fold...
The sialic acids are major components of the cell surfaces animals deuterostome lineage. Earlier studies suggested that humans may not express N-glycolyl-neuraminic acid (Neu5Gc), a hydroxylated form common N-acetyl-neuraminic (Neu5Ac). We find while Neu5Gc is essentially undetectable on human plasma proteins and erythrocytes, it component in all four extant great apes (chimpanzee, bonobo, gorilla orangutan) as well many other mammals. This marked difference also seen amongst cultured...
We show that the enzymatic acetylation and deacetylation of a cell surface carbohydrate controls B development, signaling, immunological tolerance. Mice with mutation in sialate:O-acetyl esterase, an enzyme specifically removes acetyl moieties from 9-OH position α2–6-linked sialic acid, exhibit enhanced receptor (BCR) activation, defects peripheral spontaneously develop antichromatin autoantibodies glomerular immune complex deposits. The 9-O-acetylation state acid regulates function CD22,...
N-Glycolylneuraminic acid (Neu5Gc) is an oncofetal antigen in humans and developmentally regulated rodents. We have explored the biology of N-acetylneuraminic hydroxylase, enzyme responsible for conversion parent sialic acid, (Neu5Ac) to Neu5Gc. show that major all compartments murine myeloma cell lines Pulse-chase analysis these cells with precursor [6-3H]N-acetylmannosamine demonstrates most newly synthesized Neu5Gc appears initially cytosolic low-molecular weight pool bound CMP. The...
The two major mammalian sialic acids are N-acetylneuraminic acid and N-glycolylneuraminic (Neu5Gc). only known biosynthetic pathway generating Neu5Gc is the conversion of CMP-N-acetylneuraminic into CMP-Neu5Gc, which catalyzed by CMP-Neu5Ac hydroxylase enzyme. Given irreversible nature this reaction, there must be pathways for elimination or degradation Neu5Gc, would allow animal cells to adjust levels their needs. Although humans incapable synthesizing due an inactivated CMAH gene,...
Sialic acids are a family of 9-carbon carboxylated sugars, where different substitutions the backbone define over 30 members. Biological roles these have been missed until recently because their low abundance and lability to conventional isolation/purification methods. This new approach characterizes sialic using electrospray ionization-mass spectrometry (ESI-MS) monitor HPLC separation DMB (1,2-diamino-4,5-methylenedioxy-benzene) derivatives (quinoxalinones). A combination retention times...
We and others previously described the melanoma-associated oncofetal glycosphingolipid antigen 9-O-acetyl-GD3, a disialoganglioside O-acetylated at 9-position of outer sialic acid residue. have now developed methods to examine biosynthesis turnover disialogangliosides in cultured melanoma cells Golgi-enriched vesicles from these cells. O-Acetylation was selectively expressed on di- trisialogangliosides, but not monosialogangliosides, nor glycoprotein-bound acids. Double-labeling with...
Neisseria gonorrhoeae deploys a novel immune evasion strategy wherein the lacto-N-neotetraose (LNnT) structure of lipooligosaccharide (LOS) is capped by bacterial sialyltransferase, using host cytidine-5’-monophosphate (CMP)-activated forms nine-carbon nonulosonate (NulO) sugar N-acetyl-neuraminic acid (Neu5Ac), sialic (Sia) abundant in humans. This allows complement-mediated killing recruiting factor H (FH), an inhibitor alternative complement pathway, and limiting classical pathway...
N-glycolylneuraminic acid (Neu5Gc) is a non-human red-meat-derived sialic immunogenic to humans. Neu5Gc can be metabolically incorporated into glycan chains on human endothelial and epithelial surfaces. This represents the first example of "xeno-autoantigen", against which circulating "xeno-autoantibodies" react. The resulting inflammation ("xenosialitis") has been demonstrated in human-like Neu5Gc-deficient mice contributed carcinoma progression via antibody-mediated inflammation....
O-Acetylation of sialic acids has previously been considered an uncommon modification found on certain salivary mucins and neural gangliosides. We show here that glycosidically bound from total membranes rat liver have surprisingly high levels (approximately 20%) O-acetylation at the 7- or 9-position. This is further enriched in N-linked oligosaccharides but barely detectable ganglioside fractions same tissue. The position acid side chain varies between different subcellular fractions. In...
We have previously shown that radioactivity from [acetyl-3H]AcCoA is concentrated into isolated intact rat liver Golgi vesicles. The incorporated occurred in acid-soluble and acid-insoluble components, the fraction included O-acetylated sialic acids (Varki, A., Diaz, S. (1985) J. Biol. Chem. 260, 6600-6608). Nearly all of protein-associated was found to be alpha 2-6-linked N-linked oligosaccharides on endogenous glycoproteins. Incubation vesicles with CMP-[3H]sialic acid resulted labeling a...