Reinvestigation of the internal glycan rearrangement of Lewis a and blood group type H1 epitopes.

Protonated ions of fucose-containing oligosaccharides are prone to undergo internal glycan rearrangement which results in chimeric fragments that obfuscate mass-spectrometric analysis. Lack of accessible tools that would facilitate systematic analysis of glycans in the gas phase limits our understanding of this phenomenon. In this work, we use density functional theory modeling to interpret cryogenic IR spectra of Lewis a and blood group type H1 trisaccharides and to establish whether these trisaccharides undergo the rearrangement during gas-phase analysis. Structurally unconstrained search reveals that none of the parent ions constitute a thermodynamic global minimum. In contrast, predicted collision cross sections and anharmonic IR spectra provide a good match to available experimental data which allowed us to conclude that fucose migration does not occur in these antigens. By comparing the predicted structures with those obtained for Lewis x and blood group type H2 epitopes, we demonstrate that the availability of the mobile proton and a large difference in the relative stability of the parent ions and rearrangement products constitute the prerequisites for the rearrangement reaction.

Prognostic Significance of Biologic Factors in Patients with a Modest Radiologic Response to Neoadjuvant Treatment for Resectable and Borderline Resectable Pancreatic Cancers: Impact of the Combination Index of Sialyl-Lewis Antigen-Related Tumor Markers.

BACKGROUND: Appropriate re-evaluation after neoadjuvant treatment (NAT) is important for optimal treatment selection. Nonetheless, determining the operative eligibility of patients with a modest radiologic response remains controversial. This study aimed to assess the prognostic significance of biologic factors for patients showing a modest radiologic response to NAT and investigate the tumor markers (TMs), CA19-9 alone, DUPAN-II alone, and their combination, to create an index that combines these sialyl-Lewis antigen-related TMs associated with treatment outcomes. METHODS: This study enrolled patients deemed to have a "stable disease" by RECIST classification with slight progression (tumor size increase rate, ≤20%) as their radiologic response after NAT. A sialyl-Lewis-related index (sLe index), calculated by adding one fourth of the serum DUPAN-II value to the CA19-9 value, was created. The prognostic significances of CA19-9, DUPAN-II, and the sLe index were assessed in relation to postoperative outcomes. RESULTS: An sLe index lower than the cutoff value (45.25) was significantly associated with favorable disease-free survival. Moreover, the post-NAT sLe index had a higher area under the curve value for recurrence within 24 months than the post-NAT levels of CA19-9 or DUPAN-II alone. Multivariable analysis showed that a post-NAT sLe index higher than 45.25 was the single independent predictive factor for recurrence within 24 months. CONCLUSIONS: Additional evaluation of biologic factors can potentially enhance patient selection, particularly for patients showing a limited radiologic response to NAT. The authors' index is a simple indicator for the biologic evaluation of multiple combined sialyl-Lewis antigen-related TMs and may offer a better predictive significance.

Pathophysiology of Atrial Fibrillation and Approach to Therapy in Subjects Less than 60 Years Old.

Atrial fibrillation (AF) is an arrhythmia that affects the left atrium, cardiac function, and the patients' survival rate. Due to empowered diagnostics, it has become increasingly recognized among young individuals as well, in whom it is influenced by a complex interplay of autoimmune, inflammatory, and electrophysiological mechanisms. Deepening our understanding of these mechanisms could contribute to improving AF management and treatment. Inflammation is a complexly regulated process, with interactions among various immune cell types, signaling molecules, and complement components. Addressing circulating antibodies and designing specific autoantibodies are promising therapeutic options. In cardiomyopathies or channelopathies, the first manifestation could be paroxysmal AF; persistent forms tend not to respond to antiarrhythmic drugs in these conditions. Further research, both in vitro and in vivo, on the use of genomic biotechnology could lead to new therapeutic approaches. Additional triggers that can be encountered in AF patients below 60 years of age are systemic hypertension, overweight, diabetes, and alcohol abuse. The aims of this review are to briefly report evidence from basic science and results of clinical studies that might explain the juvenile burden of the most encountered sustained supraventricular tachyarrhythmias in the general population.

Lipopolysaccharide O-antigen profiles of Helicobacter pylori strains from Southwest China.

BACKGROUND: Helicobacter pylori lipopolysaccharide (LPS) structures vary among strains of different geographic origin. The aim of this study was to characterize the LPS O-antigen profiles of H. pylori strains isolated from Southwest China, and to further analyze the association of Lewis antigen expression with clinical outcomes and antibiotic resistance. RESULTS: A total of 71 H. pylori isolates from Southwest China were included for LPS profiling by silver staining and Western blotting after SDS-PAGE electrophoresis. We demonstrated that all the clinical isolates had the conserved lipid A and core-oligosaccharide, whereas the O-antigen domains varied significantly among the isolates. Compared with the common presence of the glucan/heptan moiety in LPS O-antigen structure of European strains, the clinical isolates in this study appeared to lack the glucan/heptan moiety. The expression frequency of Lex, Ley, Lea, and Leb was 66.2% (47/71), 84.5% (60/71), 56.3% (40/71), and 31.0% (22/71), respectively. In total, the expression of type II Lex and/or Ley was observed in 69 (97.2%) isolates, while type I Lea and/or Leb were expressed in 49 (69.0%) isolates. No association of Lewis antigen expression with clinical outcomes or with antibiotic resistance was observed. CONCLUSIONS: H. pylori strains from Southwest China tend to produce heptan-deficient LPS and are more likely to express type I Lewis antigens as compared with Western strains. This may suggest that H. pylori evolves to change its LPS structure for adaptation to different hosts.

How thresholding in segmentation affects the regression performance of the linear model.

Evaluating any model underlying the control of speech requires segmenting the continuous flow of speech effectors into sequences of movements. A virtually universal practice in this segmentation is to use a velocity-based threshold which identifies a movement onset or offset as the time at which the velocity of the relevant effector breaches some threshold percentage of the maximal velocity. Depending on the threshold choice, more or less of the movement's trajectory is left in for model regression. This paper makes explicit how the choice of this threshold modulates the regression performance of a dynamical model hypothesized to govern speech movements.

Stability of the personal relationship networks in a longitudinal study of middle school students.

The personal network of relationships is structured in circles of friendships, that go from the most intense relationships to the least intense ones. While this is a well established result, little is known about the stability of those circles and their evolution in time. To shed light on this issue, we study the temporal evolution of friendships among teenagers during two consecutive academic years by means of a survey administered on five occasions. We show that the first two circles, best friends and friends, can be clearly observed in the survey but also that being in one or the other leads to more or less stable relationships. We find that being in the same class is one of the key drivers of friendship evolution. We also observe an almost constant degree of reciprocity in the relationships, around 60%, a percentage influenced both by being in the same class and by gender homophily. Not only do our results confirm the mounting evidence supporting the circle structure of human social networks, but they also show that these structures persist in time despite the turnover of individual relationships-a fact that may prove particularly useful for understanding the social environment in middle schools.

Identification of system-level features in HIV migration within a host.

OBJECTIVE: Identify system-level features in HIV migration within a host across body tissues. Evaluate heterogeneity in the presence and magnitude of these features across hosts. METHOD: Using HIV DNA deep sequencing data generated across multiple tissues from 8 people with HIV, we represent the complex dependencies of HIV migration among tissues as a network and model these networks using the family of exponential random graph models (ERGMs). ERGMs allow for the statistical assessment of whether network features occur more (or less) frequently in viral migration than might be expected by chance. The analysis investigates five potential features of the viral migration network: (1) bi-directional flow between tissues; (2) preferential migration among tissues in the same biological system; (3) heterogeneity in the level of viral migration related to HIV reservoir size; (4) hierarchical structure of migration; and (5) cyclical migration among several tissues. We calculate the Cohran's Q statistic to assess heterogeneity in the magnitude of the presence of these features across hosts. The analysis adjusts for missing data on body tissues. RESULTS: We observe strong evidence for bi-directional flow between tissues; migration among tissues in the same biological system; and hierarchical structure of the viral migration network. This analysis shows no evidence for differential level of viral migration with respect to the HIV reservoir size of a tissue. There is evidence that cyclical migration among three tissues occurs less frequent than expected given the amount of viral migration. The analysis also provides evidence for heterogeneity in the magnitude that these features are present across hosts. Adjusting for missing tissue data identifies system-level features within a host as well as heterogeneity in the presence of these features across hosts that are not detected when the analysis only considers the observed data. DISCUSSION: Identification of common features in viral migration may increase the efficiency of HIV cure efforts as it enables targeting specific processes.

ABO, Lewis blood group systems and secretory status with H.pylori infection in yemeni dyspeptic patients: a cross- sectional study.

BACKGROUND: The ABO and Lewis blood group antigens are potential factors in susceptibility to H. pylori infection. This research aimed to examine the prevalence of Helicobater pylori (H.pylori) infection and its association with ABO, Lewis blood group systems, and secretory status in Yemeni symptomatic patients. METHODS: In a cross-sectional study, 103 patients referred for endoscopy due to dyspepsia were included. H pylori infection was assessed using stool antigen and serum antibody rapid tests. ABO and Lewis blood group systems were examined using hemagglutination assay. Saliva samples were investigated for identification of the secretory phenotype using hemagglutination inhibition test. RESULTS: The prevalence of H. pylori infection was (80.6%), with a higher rate of infection in females than males. The ABO blood groups were found to be significantly different between males and females (p = 0.047). The O blood group was prevalent among H. pylori patients, especially secretors. There was a significant association between ABO blood groups and H. pylori infection (p = 0.001). The Le (a + b+) phenotype was the most common, followed by Le (a + b-), Le (a-b+), and Le (a-b-). Lewis blood group systems and secretory status of symptomatic patients were not associated with H. pylori infection. The results showed that serum Ab test for H. pylori achieved poor sensitivity (68%), specificity of 55%; positive predictive value (PPV) 86%, negative predictive value (NPV) 29% and accuracy 65.1%. CONCLUSION: The prevalence of H. pylori infection was high in Yemeni patients. This infection was linked to the O and Le (a + b+) secretor phenotype. The H. pylori stool Ag test is the most reliable noninvasive diagnostic method for detecting H. pylori infection.

Ag(e)ing and Degradation of Supercapacitors: Causes, Mechanisms, Models and Countermeasures.

The most prominent and highly visible advantage attributed to supercapacitors of any type and application, beyond their most notable feature of high current capability, is their high stability in terms of lifetime, number of possible charge/discharge cycles or other stability-related properties. Unfortunately, actual devices show more or less pronounced deterioration of performance parameters during time and use. Causes for this in the material and component levels, as well as on the device level, have only been addressed and discussed infrequently in published reports. The present review attempts a complete coverage on these levels; it adds in modelling approaches and provides suggestions for slowing down ag(e)ing and degradation.

Structural basis for Lewis antigen synthesis by the α1,3-fucosyltransferase FUT9.

Mammalian cell surface and secreted glycoproteins exhibit remarkable glycan structural diversity that contributes to numerous physiological and pathogenic interactions. Terminal glycan structures include Lewis antigens synthesized by a collection of α1,3/4-fucosyltransferases (CAZy GT10 family). At present, the only available crystallographic structure of a GT10 member is that of the Helicobacter pylori α1,3-fucosyltransferase, but mammalian GT10 fucosyltransferases are distinct in sequence and substrate specificity compared with the bacterial enzyme. Here, we determined crystal structures of human FUT9, an α1,3-fucosyltransferase that generates Lewisx and Lewisy antigens, in complex with GDP, acceptor glycans, and as a FUT9-donor analog-acceptor Michaelis complex. The structures reveal substrate specificity determinants and allow prediction of a catalytic model supported by kinetic analyses of numerous active site mutants. Comparisons with other GT10 fucosyltransferases and GT-B fold glycosyltransferases provide evidence for modular evolution of donor- and acceptor-binding sites and specificity for Lewis antigen synthesis among mammalian GT10 fucosyltransferases.

Histo-blood group antigen profile of Australian Aboriginal children and seropositivity following oral rotavirus vaccination.

BACKGROUND: Histo-blood group antigens (HBGAs) may influence immune responses to rotavirus vaccination. METHODS: HBGA phenotyping was determined by detection of antigens A, B, H and Lewis a and b in saliva using enzyme-linked immunosorbent assay. Secretor status was confirmed by lectin antigen assay if A, B and H antigens were negative or borderline (OD ± 0.1 of threshold of detection). PCR-RFLP analysis was used to identify the FUT2 'G428A' mutation in a subset. Rotavirus seropositivity was defined as serum anti-rotavirus IgA ≥ 20 AU/mL. RESULTS: Of 156 children, 119 (76 %) were secretors, 129 (83 %) were Lewis antigen positive, and 105 (67 %) were rotavirus IgA seropositive. Eighty-seven of 119 (73 %) secretors were rotavirus seropositive, versus 4/9 (44 %) weak secretors and 13/27 (48 %) non-secretors. CONCLUSIONS: Most Australian Aboriginal children were secretor and Lewis antigen positive. Non-secretor children were less likely to be seropositive to rotavirus antibodies following vaccination, but this phenotype was less common. HBGA status is unlikely to fully explain underperformance of rotavirus vaccines among Australian Aboriginal children.

Situation analysis and blood transfusion strategy of Lewis antibodies in Hunan Province

Background: Detection rate, serological characteristics, and clinical data of patients with Lewis blood group antibodies in Hunan Province were analyzed through retrospective analysis. This was undertaken in order to optimize the detection methods and blood transfusion strategies of these patients. Methods: Blood typing, antibody screening, and cross-matching were performed by microcolumn gel, and Lewis antigen was detected by immediate spin test, antibody identification of positive and negative ABO samples, positive antibody screening, and cross-blood mismatch samples. Antibodies were identified by immediate spin test and microcolumn gel antiglobulin method, and the clinical data of the patients with Lewis antibody characteristics were analyzed. Results: A total of 74 samples (15.91%) with Lewis antibodies were detected from 465 positive samples; cases were distributed in different cities of Hunan Province, with Changsha city being the most frequent (28%) one, with mostly non-O (66), anti-Lea (31; 41.89%), anti-Lea+anti-Leb (23; 31.08%), anti-Leb (5; 6.76%), anti-LebH and anti-Lea+anti-LebH (1+4; 6.76%), and antibody types immunoglobulin M (IgM) (51; 68.92%), immunoglobulin G (8; 10.81%), and IgG+IgM (4; 5.41%) cases. Patients included more females (67.57%) than males. The detection rate of gynecological diseases and patients with solid tumors was highest (44.59%). In all cases, the Lewis blood group was Le (a-b-); none of the 15 transfusion patients had hemolytic transfusion reaction. Conclusion: A variety of experimental methods must be adopted simultaneously to determine specificity and prevent the leakage of Lewis antibodies. The infusion of red blood cells matching with antiglobulin media at 37°C was recommended to ensure safe transfusion for recipients with Lewis antibodies (AU)

Glycan Stability and Flexibility: Thermodynamic and Kinetic Characterization of Nonconventional Hydrogen Bonding in Lewis Antigens.

We provide evidence for CH-based nonconventional hydrogen bonds (H-bonds) for 10 Lewis antigens and two of their rhamnose analogues. We also characterize the thermodynamics and kinetics of the H-bonds in these molecules and present a plausible explanation for the presence of nonconventional H-bonds in Lewis antigens. Using an alternative method to simultaneously fit a series of temperature-dependent fast exchange nuclear magnetic resonance (NMR) spectra, we determined that the H-bonded conformation is favored by ∼1 kcal/mol over the non-H-bonded conformation. Additionally, a comparison of temperature-dependent 13C linewidths in various Lewis antigens and the two rhamnose analogues reveals H-bonds between the carbonyl oxygen of the N-acetyl group of N-acetylglucosamine and the OH2 group of galactose/fucose. The data presented herein provide insight into the contribution of nonconventional H-bonding to molecular structure and could therefore be used for the rational design of therapeutics.

X-ray inhibits FUT4-mediated proliferation in A549 cells by downregulating SP1 expression.

Objective: To identify the mechanism of down-regulation of Lewis Y antigen caused by X-ray irradiation. METHODS: The present original research study was conducted at Zhejiang University City College, Hangzhou, Republic of China, from 2020 to 2022. Western blotting, Co-immunoprecipitation (CO-IP), electrophoretic mobility shift assay and Cell Counting Kit-8 (CCK8) were performed to confirm the effect of X-ray irradiation on A549 cell proliferation and its mechanism. Data was analysed using Statistical Package for Social Sciences (SPSS) 11.5. RESULTS: The expressions of fucosyltransferase IV and Lewis Y were decreased after X-ray irradiation, thus inhibiting the proliferation of A549 lung cancer cells. Deoxyribonucleic acid damage caused by the irradiation caused higher level of poly- adenosinediphosphate-ribosylated Specific Protein 1(SP1), and translocation of SP1 from the nucleus, decreasing the expression of fucosyltransferase IV and Lewis Y. Conclusion: There was a significant role of glycosylation in radiation therapy for lung cancer.

A novel genotyping method for rapid identification of the Le gene to select patients for diagnosis with CA19-9.

BACKGROUND: The antigenic determinant of CA19-9 is synthesized by the α1,3/4fucosyltransferase encoded by the Le gene in the Lewis blood group system. Accordingly, a diagnosis with CA19-9 is not appropriate forLe-negative patients who possess the Le gene-mutated le alleles homozygously. METHODS: A Le gene-specific PCR was undertaken to determine c59T>G by using a set of tag-sense and biotin-labeled anti-sense primers and a peptide nucleic acid-le-clamp which bound to G59 in the le alleles. Following mixing with streptavidin-coatedbluelatex beads, the PCR products were developed on a strip on which the complementary tag oligonucleotide to theLe gene-specific amplicon was immobilized. RESULTS: When the PCR products were developed on the strip, a clear line was rapidly observed in Le-positive but not in Le-negative individuals. In contrast, a significant number of cancer patients with Lewis-negative phenotype were found to possess CA19-9, while they were specifically genotyped asLe/-. No contradictory results were observed in cancer patients (n = 315) with respect to their Lewis genotypes and CA19-9 levels. CONCLUSIONS: c59T>G occurred commonly in the le alleles could be specifically and rapidly identified by the present method. This method appeared to be relevant forselecting cancer patientsto bediagnosed with CA19-9.

The story of the Sda antigen and of its cognate enzyme B4GALNT2: What is new?

The structure Siaα2,3(GalNAcß1,4)Gal- is the epitope of the Sda antigen, which is expressed on the erythrocytes and secretions of the vast majority of Caucasians, carried by N- and O-linked chains of glycoproteins, as well as by glycolipids. Sda is very similar, but not identical, to ganglioside GM2 [Siaα2,3(GalNAcß1,4)Galß1,4Glc-Cer]. The Sda synthase ß1,4 N-acetylgalactosaminyl transferase 2 (B4GALNT2) exists in a short and a long form, diverging in the aminoterminal domain. The latter has a very long cytoplasmic tail and displays a Golgi- as well as a post-Golgi localization. The biosynthesis of Sda is mutually exclusive with that of the cancer-associated sialyl Lewis antigens, whose structure is Siaα2,3Galß1,3/4(Fucα1,4/3)GlcNAc-. B4GALNT2 is down-regulated in colon cancer but patients with higher expression survive longer. In experimental systems, B4GALNT2 inhibits colon cancer progression,not only through inhibition of sialyl Lewis antigen biosynthesis. By contrast, in breast cancer B4GALNT2 is associated with malignancy. In colon cancer, the B4GALNT2 gene is regulated by multiple mechanisms, which include miRNA and transcription factor expression, as well as CpG methylation. In addition, Sda/B4GALNT2 regulates the susceptibility to infectious agents, the protection from muscle dystrophy, the activity of immune system in pregnancy and the immune rejection in xenotransplantation.

Serological characteristics of Lewis antibodies and their clinical significance - A case series

Abstract Introduction Lewis antibodies have been thought to play a small role in clinical transfusion practice, but recent reports suggest that they have gained more importance in the context of transfusion and transplantation. Data regarding the prevalence of Lewis antibodies and their clinical significance in the Indian context is very limited. Hence, this study was aimed at analyzing the serological characteristics and clinical significance of Lewis antibodies encountered in our patient and donor populations. Methods The retrospective data analyzed the records of red cell antibody screening results and the additional serological evaluation performed on the donor and patient samples included in the study. Results A total of 26 study subjects were noted to have Lewis antibodies (including 6 healthy donors and 20 patients). Of them, 13 individuals had anti-Leb, 10 had anti-Lea and the remaining three had an anti-Lea/Leb mixture. IgG Lewis antibodies were detected in 7 individuals. All cases of IgM Lewis antibodies detected were reacting at 37°C. Two patients were suspected of having hemolytic transfusion reactions due to Lewis antibodies. Antigen-negative cross-match compatible units were provided for transfusion in the recipients. Conclusion Lewis antibodies of the IgM class reacting at 37°C should be regarded as clinically important. The present study findings urge that the lab personnel look for the thermal amplitude of Lewis antibodies, irrespective of the fact that the antibody class and antigen-negative crossmatch compatible units should be provided to avoid hemolytic transfusion reactions.

The Association between Symptomatic Rotavirus Infection and Histo-Blood Group Antigens in Young Children with Diarrhea in Pretoria, South Africa.

OBJECTIVES: Recently, histo-blood group antigens (HBGAs) have been identified as receptors or attachment factors of several viral pathogens. Among rotaviruses, HBGAs interact with the outer viral protein, VP4, which has been identified as a potential susceptibility factor, although the findings are inconsistent throughout populations due to HBGA polymorphisms. We investigated the association between HBGA phenotypes and rotavirus infection in children with acute gastroenteritis in northern Pretoria, South Africa. METHODS: Paired diarrheal stool and saliva samples were collected from children aged ≤ 59 months (n = 342) with acute moderate to severe diarrhea, attending two health care facilities. Rotaviruses in the stool samples were detected by commercial EIA and the rotavirus strains were characterized by RT-PCR targeting the outer capsid VP7 (G-type) and VP4 (P-type) antigens for genotyping. Saliva-based ELISAs were performed to determine A, B, H, and Lewis antigens for blood group typing. RESULTS: Blood type O was the most common blood group (62.5%) in this population, followed by groups A (26.0%), B (9.3%), and AB (2.2%). The H1-based secretors were common (82.7%) compared to the non-secretors (17.3%), and the Lewis antigen positive phenotypes (Le(a+b+)) were predominant (54.5%). Blood type A children were more likely to be infected by rotavirus (38.8%) than any other blood types. P[4] rotaviruses (21/49; 42.9%) infected only secretor individuals, whereas P[6] rotaviruses (3/49; 6.1%) only infected Le(a-b-), although the numbers were very low. On the contrary, P[8] rotaviruses infected children with a wide range of blood group phenotypes, including Le(a-b-) and non-secretors. CONCLUSIONS: Our findings demonstrated that Lewis antigens, or the lack thereof, may serve as susceptibility factors to rotaviral infection by specific VP4 genotypes as observed elsewhere. Potentially, the P[8] strains remain the predominant human VP4 genotype due to their ability to bind to a variety of HBGA phenotypes.

Features of the distribution of the antigens of Kell, Duffy, Kidd, MNS, Lewis, Lutheran blood group systems in blood donors in the Kirov region.

The frequency of occurrence of antigens of the Kell (Kpa, Kpb), Kidd, Duffy, MNS and Lutheran systems in donors of the Kirov region corresponds to the distribution of antigens characteristic of white Europeans. Antigens K (Kell system) and Lea (Lewis system) are detected in the population of the region much less frequently, antigen Leb (Lewis system) - more often than in the population of Europe. The presence of a registry of donors typed according to a wide range of red blood antigens is a prerequisite for the immunohematological safety of blood transfusions.