UBR4 should no longer be considered a candidate gene for episodic ataxia type 8
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Another common genetic ataxia in South Korea: Spinocerebellar ataxia 36
Spinocerebellar ataxias (SCAs) represent a diverse group of neurodegenerative disorders characterized by progressive cerebellar ataxia. In South Korea, diagnostic laboratories typically focus on common SCA subtypes, leaving the prevalence of rare SCAs uncertain. This study aimed to explore the frequency of rarer forms of SCA, including SCA10, 12, 31, and 36 utilizing molecular techniques including long-read sequencing (LRS). Patients from ataxia cohorts who remained undiagnosed after testing for common genetic ataxias (SCA1, 2, 3, 6, 7, 8 17, and dentatorubral-pallidoluysian atrophy) were analyzed, along with unselected ataxia patients referred for screening of common SCAs. Expanded alleles for SCA10, 12, 31, and 36 were investigated through allele-length PCR, repeat-primed PCR, and LRS. Among 78 patients from 67 families with undiagnosed cerebellar ataxia, SCA36 was identified in 8 families (11.9%), while SCA10, 12, or 31 were not found. In unselected ataxia, SCA36 was present in 1.0% (1/99). Korean SCA36 patients exhibited clinical characteristics similar to global reports, with a higher incidence of hyperreflexia. The haplotype of expanded alleles identified in LRS was consistent among SCA36 patients. The findings indicate that SCA36 accounts for 11.9% of diagnoses after excluding common SCAs and 1.0% in unselected ataxia patients. The study underscores the prevalence of SCA36 in South Korea and emphasizes the potential of LRS as a diagnostic tool for this condition. Integrating LRS into diagnostic protocol could enhance diagnostic efficacy, particularly in populations with a high prevalence of SCA36 like South Korea. Further research is necessary to standardize LRS for routine clinical application.
Neural codes track prior events in a narrative and predict subsequent memory for details
Throughout our lives, we learn schemas that specify what types of events to expect in particular contexts and the temporal order in which these events usually occur. Here, our first goal was to investigate how such context-dependent temporal structures are represented in the brain during processing of temporally extended events. To accomplish this, we ran a 2-day fMRI study (N = 40) in which we exposed participants to many unique animated videos of weddings composed of sequences of rituals; each sequence originated from one of two fictional cultures (North and South), where rituals were shared across cultures, but the transition structure between these rituals differed across cultures. The results, obtained using representational similarity analysis, revealed that context-dependent temporal structure is represented in multiple ways in parallel, including distinct neural representations for the culture, for particular sequences, and for past and current events within the sequence. Our second goal was to test the hypothesis that neural schema representations scaffold memory for specific details. In keeping with this hypothesis, we found that the strength of the neural representation of the North/South schema for a particular wedding predicted subsequent episodic memory for the details of that wedding.
The genomic landscape of gene-level structural variations in Japanese and global soybean Glycine max cultivars
Japanese soybeans are traditionally bred to produce soy foods such as tofu, miso and boiled soybeans. Here, to investigate their distinctive genomic features, including genomic structural variations (SVs), we constructed 11 nanopore-based genome references for Japanese and other soybean lines. Our assembly-based comparative method, designated ‘Asm2sv’, identified gene-level SVs comprehensively, enabling pangenome analysis of 462 worldwide cultivars and varieties. Based on these, we identified selective sweeps between Japanese and US soybeans, one of which was the pod-shattering resistance gene PDH1. Genome-wide association studies further identified several quantitative trait loci that accounted for large-seed phenotypes of Japanese soybean lines, some of which were also close to regions of the selective sweeps, including PDH1. Notably, specific combinations of alleles, including SVs, were found to increase the seed size of some Japanese landraces. In addition to the differences in cultivation environments, distinct food processing usages might result in changes in Japanese soybean genomes.
Type 2 immunity in allergic diseases
Significant advancements have been made in understanding the cellular and molecular mechanisms of type 2 immunity in allergic diseases such as asthma, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis (EoE), food and drug allergies, and atopic dermatitis (AD). Type 2 immunity has evolved to protect against parasitic diseases and toxins, plays a role in the expulsion of parasites and larvae from inner tissues to the lumen and outside the body, maintains microbe-rich skin and mucosal epithelial barriers and counterbalances the type 1 immune response and its destructive effects. During the development of a type 2 immune response, an innate immune response initiates starting from epithelial cells and innate lymphoid cells (ILCs), including dendritic cells and macrophages, and translates to adaptive T and B-cell immunity, particularly IgE antibody production. Eosinophils, mast cells and basophils have effects on effector functions. Cytokines from ILC2s and CD4+ helper type 2 (Th2) cells, CD8 + T cells, and NK-T cells, along with myeloid cells, including IL-4, IL-5, IL-9, and IL-13, initiate and sustain allergic inflammation via T cell cells, eosinophils, and ILC2s; promote IgE class switching; and open the epithelial barrier. Epithelial cell activation, alarmin release and barrier dysfunction are key in the development of not only allergic diseases but also many other systemic diseases. Recent biologics targeting the pathways and effector functions of IL4/IL13, IL-5, and IgE have shown promising results for almost all ages, although some patients with severe allergic diseases do not respond to these therapies, highlighting the unmet need for a more detailed and personalized approach.
Identifying unstable CNG repeat loci in the human genome: a heuristic approach and implications for neurological disorders
Tandem nucleotide repeat (TNR) expansions, particularly the CNG nucleotide configuration, are associated with a variety of neurodegenerative disorders. In this study, we aimed to identify novel unstable CNG repeat loci associated with the neurogenetic disorder spinocerebellar ataxia (SCA). Using a computational approach, 15,069 CNG repeat loci in the coding and noncoding regions of the human genome were identified. Based on the feature selection criteria (repeat length >10 and functional location of repeats), we selected 52 repeats for further analysis and evaluated the repeat length variability in 100 control subjects. A subset of 19 CNG loci observed to be highly variable in control subjects was selected for subsequent analysis in 100 individuals with SCA. The genes with these highly variable repeats also exhibited higher gene expression levels in the brain according to the tissue expression dataset (GTEx). No pathogenic expansion events were identified in patient samples, which is a limitation given the size of the patient group examined; however, these loci contain potential risk alleles for expandability. Recent studies have implicated GLS, RAI1, GIPC1, MED15, EP400, MEF2A, and CNKSR2 in neurological diseases, with GLS, GIPC1, MED15, RAI1, and MEF2A sharing the same repeat loci reported in this study. This finding validates the approach of evaluating repeat loci in different populations and their possible implications for human pathologies.
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