O-glycomic and proteomic signatures of spontaneous and butyrate-stimulated colorectal cancer cell line differentiation

Gut microbiota of the gastrointestinal tract provide health benefits to the human host via bacterial metabolites. Bacterial butyrate has beneficial effects on intestinal homeostasis and is the preferred energy source of intestinal epithelial cells, capable of inducing differentiation. It was previously observed that changes in the expression of specific proteins as well as protein glycosylation occur with differentiation. In this study, specific mucin O-glycans were identified that mark butyrate-induced epithelial differentiation of the intestinal cell line CaCo-2 (Cancer Coli-2), by applying porous graphitized carbon nano-liquid chromatography with electrospray ionization tandem mass spectrometry. Moreover, a quantitative proteomic approach was used to decipher changes in the cell proteome. It was found that the fully differentiated butyrate-stimulated cells are characterized by a higher expression of sialylated O-glycan structures, whereas fucosylation is downregulated with differentiation. By performing an integrative approach, we generated hypotheses about the origin of the observed O-glycome changes. These insights pave the way for future endeavors to study the dynamic O-glycosylation patterns in the gut, either produced via cellular biosynthesis or through the action of bacterial glycosidases as well as the functional role of these patterns in homeostasis and dysbiosis at the gut-microbiota interface

Додатковий том «Словника української мови»

У статті подано історію роботи над Додатковим томом «Словника української мови» в 11-ти томах, описано джерела наповнення реєстру, структуру словникових статей, наведено приклади розробки статей різного типу – як нововведених слів, так і таких, що були в «Словнику української мови» і зазнали доповнення. Завдання лексикографів, які працювали над Додатковим томом, – відобразити динаміку лексичного шару української мови 1980-их рр. ХХ ст. – початку ХХІ ст. з акцентуванням її інноваційних й актуалізованих аспектів

Performance of the 2017 and 2010 Revised McDonald Criteria in Predicting MS Diagnosis After a Clinically Isolated Syndrome: A MAGNIMS Study

BACKGROUND AND OBJECTIVES: To compare the performance of the 2017 revisions to the McDonald criteria with the 2010 McDonald criteria in establishing MS diagnosis and predicting prognosis in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). METHODS: CSF examination, brain and spinal cord MRI obtained ≤5 months from CIS onset, and a follow-up brain MRI acquired within 15 months from CIS onset were evaluated in 785 CIS patients from 9 European centers. Date of second clinical attack and of reaching Expanded Disability Status Score (EDSS) ≥ 3.0, if they occurred, were also collected. Performance of the 2017 and 2010 McDonald criteria for dissemination in space (DIS), time (DIT) (including oligoclonal bands assessment) and DIS + DIT for predicting a second clinical attack (clinically definite [CD] MS) and EDSS ≥ 3.0 at follow-up was evaluated. Time to MS diagnosis for the different criteria was also estimated. RESULTS: At follow-up (median = 69.1 months), 406/785 CIS patients developed CDMS. At 36 months, the 2017 DIS + DIT criteria had higher sensitivity (0.83 vs 0.66), lower specificity (0.39 vs 0.60) and similar area under the curve values (0.61 vs 0.63). Median time to MS diagnosis was shorter with the 2017 vs the 2010 or CDMS criteria (2017 revision = 3.2; 2010 revision = 13.0; CDMS = 58.5 months). The 2 sets of criteria similarly predicted EDSS ≥ 3.0 milestone. Three periventricular lesions improved specificity in patients ≥45 years. DISCUSSION: The 2017 McDonald criteria showed higher sensitivity, lower specificity and similar accuracy in predicting CDMS compared to 2010 McDonald criteria, while shortening time to diagnosis of MS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the 2017 McDonald Criteria more accurately distinguish CDMS in patients early after a CIS when compared to the 2010 McDonald criteria

Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells

Valency requirements for B cell activation upon antigen encounter are poorly understood. OB1 transnuclear B cells express an IgG1 B cell receptor (BCR) specific for ovalbumin (OVA), the epitope of which can be mimicked using short synthetic peptides to allow antigen-specific engagement of the BCR. By altering length and valency of epitope-bearing synthetic peptides, we examined the properties of ligands required for optimal OB1 B cell activation. Monovalent engagement of the BCR with an epitope-bearing 17-mer synthetic peptide readily activated OB1 B cells. Dimers of the minimal peptide epitope oriented in an N to N configuration were more stimulatory than their C to C counterparts. Although shorter length correlated with less activation, a monomeric 8-mer peptide epitope behaved as a weak agonist that blocked responses to cell-bound peptide antigen, a blockade which could not be reversed by CD40 ligation. The 8-mer not only delivered a suboptimal signal, which blocked subsequent responses to OVA, anti-IgG, and anti-kappa, but also competed for binding with OVA. Our results show that fine-tuning of BCR-ligand recognition can lead to B cell nonresponsiveness, activation, or inhibition

Exploring Vitreous Haze as a Potential Biomarker for Accelerated Glymphatic Outflow and Neurodegeneration in Multiple Sclerosis: A Cross-Sectional Study

Background: The glymphatic system removes neurodegenerative debris. The ocular glymphatic outflow is from the eye to the proximal optic nerve. In multiple sclerosis (MS), atrophy of the optic nerve increases the glymphatic outflow space. Here, we tested whether vitreous haze (VH) can provide novel insights into the relationship between neurodegeneration and the ocular glymphatic system in MS. Methods: This cross-sectional study comprised 315 persons with MS and 87 healthy controls (HCs). VH was quantified from optical coherence tomography (OCT) volume scans. Neurodegeneration was determined on three-dimensional T1 (3DT1) MRI, lesion detection on fluid-attenuated inversion (FLAIR), and layer thickness on OCT. Generalized estimating equations, corrected for age, were used to analyze associations between VH and metrics for neurodegeneration, demographics, and clinical scales. Group differences were determined between mild, moderate, and severe disability. Results: On the group level, VH scores were comparable between MS and control (p = 0.629). In MS, VH scores declined with disease duration (β = −0.009, p = 0.004) and age (β = −0.007, p = 0.001). There was no relation between VH scores and higher age in HCs. In MS patients, VH was related to normalized gray (NGMV, β = 0.001, p = 0.011) and white matter volume (NWMV, β = 0.001, p = 0.003), macular ganglion cell–inner plexiform layer thickness (mGCIPL, β = 0.006, p < 0.001), and peripapillary retinal nerve fiber layer thickness (pRNFL, β = 0.004, p = 0.008). VH was significantly lower in severe compared to mild disability (mean difference −28.86%, p = 0.058). Conclusions: There is a correlation between VH on OCT and disease duration, more severe disability and lower brain volumes in MS. Biologically, these relationships suggest accelerated glymphatic clearance with disease-related atrophy

Transcriptional responses of ecologically diverse drosophila species to larval diets differing in relative sugar and protein ratios

We utilized three ecologically diverse Drosophila species to explore the influence of ecological adaptation on transcriptomic responses to isocaloric diets differing in their relative proportions of protein to sugar. Drosophila melanogaster, a cosmopolitan species that breeds in decaying fruit, exemplifies individuals long exposed to a Western diet higher in sugar, while the natural diet of the cactophilic D. mojavensis, is much lower in carbohydrates. Drosophila arizonae, the sister species of D. mojavensis, is largely cactophilic, but also utilizes rotting fruits that are higher in sugars than cacti. We exposed third instar larvae for 24 hours to diets either (1) high in protein relative to sugar, (2) diets with equal amounts of protein and sugar, and (3) diets low in protein but high in sugar. As we predicted, based upon earlier interspecific studies of development and metabolism, the most extreme differences in gene expression under different dietary conditions were found in D. mojavensis followed by D. arizonae. No differential expression among diets was observed for D. melanogaster, a species that survives well under all three conditions, with little impact on its metabolism. We suggest that these three species together provide a model to examine individual and population differences in vulnerability to lifestyle-associated health problems such as metabolic syndrome and diabetes