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Abstract: Mannose-binding lectin (MBL) is a major, soluble, pattern-recognition molecule and an important component of the innate host defense. The role of MBL in inflammatory bowel diseases (IBDs) is controversial. We determined the prevalence of MBL deficiency in a Hungarian IBD patients'' cohort, and whether it is associated with the antimicrobial antibody formation or particular clinical manifestations. Nine hundred ninety IBD patients and 225 healthy subjects were investigated. Sera were assayed for MBL and a panel of antimicrobial antibodies (anti-OMP, anti-Saccharomyces cerevisiae antibodies, and antiglycans) by ELISA. TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism. Median MBL level was not significantly different between IBDs (Crohn''s disease [CD]: 929; ulcerative colitis [UC]: 810 ng/ml) and the control group (1027 ng/ml), as well as the prevalence of absolute MBL deficiency (<100 ng/ml) (CD: 15.0%, UC: 18.4%, controls: 15.6%). The presence of a low MBL level (<500 ng/ml) was not associated with any of the examined serologic markers, or their combinations. In addition, there was no association with the clinical presentation, disease course, or response to treatment. TLR4 variant genotype was more common in CD patients without MBL deficiency (11% vs. 1.7%, OR: 7.29, 95% CI: 1.08–53.9, p = 0.02). We failed to confirm any association between MBL deficiency and serologic marker positivity. MBL deficiency was not predictive for clinical phenotype or disease activity in IBDs. [Copyright &y& Elsevier]

Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neurons with extensive L1 branching, but whether L1 interneurons are similarly diverse is underexplored. Using Patch-seq recordings from human neurosurgical tissue, we identified four transcriptomic subclasses with mouse L1 homologs, along with distinct subtypes and types unmatched in mouse L1. Subclass and subtype comparisons showed stronger transcriptomic differences in human L1 and were correlated with strong morphoelectric variability along dimensions distinct from mouse L1 variability. Accompanied by greater layer thickness and other cytoarchitecture changes, these findings suggest that L1 has diverged in evolution, reflecting the demands of regulating the expanded human neocortical circuit.

Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid-producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology plus single-cell RNA sequencing) sampling in human brain slices was used to reliably target and analyze GABAergic neuron subclasses and individual transcriptomic types. This characterization elucidated transitions between PVALB and SST subclasses, revealed morphological heterogeneity within an abundant transcriptomic type, identified multiple spatially distinct types of the primate-specialized double bouquet cells (DBCs), and shed light on cellular differences between homologous mouse and human neocortical GABAergic neuron types. These results highlight the importance of multimodal phenotypic characterization for refinement of emerging transcriptomic cell type taxonomies and for understanding conserved and specialized cellular properties of human brain cell types.

The pathogenesis of multiple sclerosis (MS), a devastating neuroinflammatory disorder of the central nervous system, has been presumed to involve the possible importance of the receptor for advanced glycation end products (RAGE). The aim of this study was to investigate the relevance of the genetic polymorphisms of RAGE in MS patients. A total of 168 patients with MS were enrolled; 136 healthy blood donors served as controls. The -374 T/ A, -479 T/C, and the G82S polymorphisms of RAGE were determined by restriction fragment length polymorphism (RFLP). There was a significant difference in RAGE -374 T/A genotype distribution between the controls and the MS patients. The AA homozygote variants were detected in 8% of the patients with MS, as compared with 19% of healthy controls (OR=2.75; 95% CI=1.319-5.733, p = 0.007). No differences were observed between the MS patients and the controls, concerning the frequencies of the -479 T/C and G82S genotypes of the RAGE. Our results revealed an association between the -374 T/A polymorphism of the RAGE promoter and MS. The genetic variant -374 AA (which has previously been shown to exert significant effects on transcriptional activity) can be considered a preventive factor as regards the occurrence of MS. Our findings support the view that RAGE plays a role in the development of MS.

Objective: Helicobacter pylori-induced gastric inflammation is dependent on the persistence of the microorganism in the gastric epithelium. Modulation of the host epithelial antimicrobial responses may be a critical determinant in H. pylori-induced gastritis. Human beta-defensins (hBDs) are important components of the host defence at mucosal surfaces. The aim of the present study was to investigate the relevance of three single nucleotide polymorphisms (SNPs) of the human beta defensin-1 (hBD-1) gene in H. pylori-induced gastritis and to assess the mRNA expression of hBD-1 in H. pylori-infected AGS cells., Material and Methods: Three SNPs of the beta defensin DEFB1 gene, DEFB1 G-20A (rs11362), DEFB1 C-44G (rs1800972) and DEFB1 G-52A (rs1799946), were genotyped either by Custom TaqMan SNP genotyping assays or by restriction fragment length polymorphism (RFLP) in 150 patients with chronic active gastritis; 100 serologically H. pylori-positive subjects without gastric or duodenal symptoms served as controls. hBD-1 mRNA expression in AGS cells was measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR)., Results: Significant differences in frequencies of the GA and AA genotypes of G-52A SNPs were observed between patients with chronic active gastritis and healthy controls. The maximum level of hBD-1 mRNA expression in AGS cells was observed at 24 h after infection with H. pylori, this not being dependent on the presence of the cag pathogenicity island (PAI)., Conclusions: The results of these genetic and in vitro experiments suggest that not only the inducible, but also the constitutive form of hBD may be important in the pathogenesis of H. pylori-induced gastritis.

Objective: It has been suggested that deficient defensin expression is associated with the chronic inflammation of Crohn's disease. The regional localization of Crohn's disease, ileal or colonic disease can be linked to different defensin profiles. As constitutive beta-defensin 1 has a colonic expression, we considered it of interest to investigate single nucleotide polymorphisms (SNPs) of the beta-defensin 1 gene (DEFB1) in Crohn's disease., Material and Methods: Three SNPs of the DEFB1 gene, DEFB1 G-20A (rs11362), DEFB1 C-44G (rs1800972) and DEFB1 G-52A (rs1799946), were genotyped either by Custom TaqMan SNP genotyping assays or by restriction fragment length polymorphisms (RFLP) in 190 patients with Crohn's disease and 95 Hungarian controls., Results: It was found that the G-20A and C-44G SNPs had a strong association with the colonic and ileocolonic localizations of the disease, respectively, but no association was detected for the ileal localization. A significantly higher frequency of the GA genotype of G-20A was observed among patients with colonic localization (60%) as compared with healthy controls (39%), with an odds ratio (OR) of 2.39. The GG genotype of C-44G SNP, which is regarded as a protective genotype, was much less frequent (4%) among patients than among controls (12%), OR 3.367., Conclusions: These results indicate that genetic variations in the DEFB1 gene encoding constitutive human beta-defensin 1 may be associated with the risk for Crohn's disease and may determine disease phenotype, e.g. colonic localization.