Analysis of the proximal promoter of the human colon-specific B4GALNT2 (Sda synthase) gene: B4GALNT2 is transcriptionally regulated by ETS1

13siopenBackground: The Sda antigen and corresponding biosynthetic enzyme B4GALNT2 are primarily expressed in normal colonic mucosa and are down-regulated to a variable degree in colon cancer tissues. Although their expression profile is well studied, little is known about the underlying regulatory mechanisms. Methods: To clarify the molecular basis of Sda expression in the human gastrointestinal tract, we investigated the transcriptional regulation of the human B4GALNT2 gene. The proximal promoter region was delineated using luciferase assays and essential trans-acting factors were identified through transient overexpression and silencing of several transcription factors. Results: A short cis-regulatory region restricted to the −72 to +12 area upstream of the B4GALNT2 short-type transcript variant contained the essential promoter activity that drives the expression of the human B4GALNT2 regardless of the cell type. We further showed that B4GALNT2 transcriptional activation mostly requires ETS1 and to a lesser extent SP1. Conclusions: Results presented herein are expected to provide clues to better understand B4GALNT2 regulatory mechanisms.openWavelet-Vermuse C.; Groux-Degroote S.; Vicogne D.; Cogez V.; Venturi G.; Trinchera M.; Brysbaert G.; Krzewinski-Recchi M.-A.; Bachir E.H.; Schulz C.; Vincent A.; Van Seuningen I.; Harduin-Lepers A.Wavelet-Vermuse, C.; Groux-Degroote, S.; Vicogne, D.; Cogez, V.; Venturi, G.; Trinchera, M.; Brysbaert, G.; Krzewinski-Recchi, M. -A.; Bachir, E. H.; Schulz, C.; Vincent, A.; Van Seuningen, I.; Harduin-Lepers, A

B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen

Analysis of non-Gal antibody induced after pig-to-baboon cardiac xenotransplantation identified the glycan produced by porcine beta-1,4-N-acetyl-galactosaminyltransferase 2 (B4GALNT2) as an immunogenic xenotransplantation antigen. The porcine B4GALNT2 enzyme is homologous to the human enzyme, which synthesizes the human SDa blood group antigen. Most humans produce low levels of anti-SDa IgM which polyagglutinates red blood cells from rare individuals with high levels of SDa expression. The SDa glycan is also present on GM2 gangliosides. Clinical GM2 vaccination studies for melanoma patients suggest that a human antibody response to SDa can be induced. Expression of porcine B4GALNT2 in human HEK293 cells results in increased binding of anti-SDa antibody and increased binding of Dolichos biflorus agglutinin (DBA), a lectin commonly used to detect SDa. In pigs, B4GALNT2 is expressed by vascular endothelial cells and endothelial cells from a wide variety of pig backgrounds stain with DBA, suggesting that porcine vascular expression of B4GALNT2 is not polymorphic. Mutations in B4GALNT2 have been engineered in mice and pigs. In both species, the B4GALNT2-KO animals are apparently normal and no longer show evidence of SDa antigen expression. Pig tissues with a mutation in B4GALNT2, added to a background of alpha-1,3-galactosyltransferase deficient (GGTA1-KO) and cytidine monophosphate-N-acetylneuraminic acid hydroxylase deficient (CMAH-KO), show reduced antibody binding, confirming the presence of B4GALNT2-dependent antibodies in both humans and non-human primates. Preclinical xenotransplantation using B4GALNT2-deficient donors has recently been reported. Elimination of this source of immunogenic pig antigen should minimize acute injury by preformed anti-pig antibody and eliminate an induced clinical immune response to this newly appreciated xenotransplantation antigen

Aurora, 1941

https://commons.emich.edu/aurora/1047/thumbnail.jp

The role of the blood group-related glycosyltransferases FUT2 and B4GALNT2 in susceptibility to infectious disease

The glycosylation profile of the gastrointestinal tract is an important factor mediating host-microbe interactions. Variation in these glycan structures is often mediated by blood group-related glycosyltransferases, and can lead to wide-ranging differences in susceptibility to both infectious- as well as chronic disease. In this review, we focus on the interplay between host glycosylation, the intestinal microbiota and susceptibility to gastrointestinal pathogens based on studies of two exemplary blood group-related glycosyltransferases that are conserved between mice and humans, namely FUT2 and B4GALNT2. We highlight that differences in susceptibility can arise due to both changes in direct interactions, such as bacterial adhesion, as well as indirect effects mediated by the intestinal microbiota. Although a large body of experimental work exists for direct interactions between host and pathogen, determining the more complex and variable mechanisms underlying three-way interactions involving the intestinal microbiota will be the subject of much-needed future research

Aurora, 1942

https://commons.emich.edu/aurora/1048/thumbnail.jp

The expanding roles of the Sda/Cad carbohydrate antigen and its cognate glycosyltransferase B4GALNT2

Background The histo-blood group antigens are carbohydrate structures present in tissues and body fluids, which contribute to the definition of the individual immunophenotype. One of these, the Sda antigen, is expressed on the surface of erythrocytes and in secretions of the vast majority of the Caucasians and other ethnic groups. Scope of review We describe the multiple and unsuspected aspects of the biology of the Sda antigen and its biosynthetic enzyme \u3b21,4-N-acetylgalactosaminyltransferase 2 (B4GALNT2) in various physiological and pathological settings. Major conclusions The immunodominant sugar of the Sda antigen is a \u3b21,4-linked N-acetylgalactosamine (GalNAc). Its cognate glycosyltransferase B4GALNT2 displays a restricted pattern of tissue expression, is regulated by unknown mechanisms - including promoter methylation, and encodes at least two different proteins, one of which with an unconventionally long cytoplasmic portion. In different settings, the Sda antigen plays multiple and unsuspected roles. 1) In colon cancer, its dramatic down-regulation plays a potential role in the overexpression of sialyl Lewis antigens, increasing metastasis formation. 2) It is involved in the lytic function of murine cytotoxic T lymphocytes. 3) It prevents the development of muscular dystrophy in various dystrophic murine models, when overexpressed in muscular fibers. 4) It regulates the circulating half-life of the von Willebrand factor (vWf), determining the onset of a bleeding disorder in a murine model. General significance The expression of the Sda antigen has a wide impact on the physiology and the pathology of different biological systems

Alloantibodies to High-Incidence Antigen: Review of Cases and Transfusion Experiences in Korea

Antibodies to high-incidence red blood cell antigens should be considered if panagglutination reactions are noted in all panel cells, and negative reactions to autologous red blood cells are detected on antibody screening and identification tests. In Korea, most of those antibodies are identified through international reference laboratories. To prevent a hemolytic transfusion reaction, antigen-negative red cells should be provided for those patients who have antibodies to red cell antigens. However, this is nearly impossible when the antibody has specificity to high-incidence red cell antigen. In those cases, transfusion of autologous blood, cryopreserved rare blood and the least incompatible blood components can be considered. In the case of surgery, acute normovolemic hemodilution or intraoperative blood salvage can also be considered. For the patients who have antibodies to high-incidence red cell antigens, it should be discussed to set up a national reference laboratory to quickly identify antibody specificities, and to consider establishing rare blood donor registry and frozen rare blood storage/supply system. This article reviews characteristics of antibodies to high-incidence antigens found in Koreans and also the transfusion experiences of those patients based on literature.ope

Pictorial history of the 447th Bombardment Group (H)

Published as an unofficial history of the Group\u27s activities from activation to completion of 258 Combat Missions in the European Theatre of Operations, through the courtesy of the Officers\u27 Club, whose Board of Governors made available funds to apply against publication costs on copies for distribution to members of the 447th Group who were on its rosters as of the dates of departure from the E. T. 0. for the Z. of I. This pictorial, and unofficial, history of the 447th Bombardment Group is not as complete as its editors would have liked it to be, due to the fact that the work of preparing and assembling it had to be done by the very limited staff on hand at Drew Field, Florida, whose primary task was the job of deactivating the Group. So it was prepared amid considerable confusion by the short handed staff and using as much of the material as could be found among the Group and Squadron records. The editors have used every possible photo whether of personnel, combat crews, ground crews, social activities, etc. that could be found. Without doubt, many other photos exist, but these were not on hand at the time the history was prepared. -The Editors [Captains Surridge and Dooley]https://digicom.bpl.lib.me.us/ww_reg_his/1108/thumbnail.jp

The London Mechanics' Institution: Social and Cultural Foundations 1823-1830

This study of the founding in 1823 of the London Mechanics’ Institution examines its constituency, catchment, and mandate to teach working men science and technology. To explain the Institution’s distinctive character, it is necessary to move beyond the flourishing patent/invention journalism, which provides one explanatory context, to the cheap literature disputes, debating society connotations, and Francis Place’s network. These radical associations show why George Birkbeck was quickly designated the ‘founder’, even though he was unknown to J. C. Robertson and Thomas Hodgskin when they proposed such an institute in the Mechanics’ Magazine. Birkbeck’s social standing would allay Establishment fears. An older historiography stressing middle-class social control is tested by analysing contemporary journals, newspapers and manuscripts. The first two volumes of manuscript Members’ Registers (1824-29), recording 8,343 names with occupations and addresses, have been transcribed and appended. These allow a comparison of members’ occupations with London trades generally and highlight diverse occupations within families. They also reveal family relationships between clerks and mechanics – important because clerks have been cited as a sign of middle-class invasion. Indeed the lack of any gross change in class composition suggests that there was no working-class exodus in these pre-Reform years. By statute two-thirds of the committee had to be working class. The encouragement of invention and student autonomy through mutual instruction classes, introduced by the Pestalozzian Charles Lane, points to a more humanitarian ethos, as do the lectures which (contra the learned societies) often presented science as negotiable rather than given. Iconic radical members are highlighted: Henry Hetherington (on the committee regularly from 1825-1830), William Lovett, James Watson, G. G. Ward, and P. O. Skene. Finally, the thesis analyses the committee’s relationships with controversial outsiders who rented the theatre, including Robert Owen, Eliza Macauley, William Cobbett, the Radical Reform Association, and the London Co-operative Society