Short tandem repeat expansions in cortical layer-specific genes implicate in phenotypic severity and adaptability of autism spectrum disorder.

AIM: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. METHODS: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci. RESULTS: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers. CONCLUSION: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population.

Integrative Multi-Omics Approaches in Cancer Research: From Biological Networks to Clinical Subtypes.

Multi-omics approaches are novel frameworks that integrate multiple omics datasets generated from the same patients to better understand the molecular and clinical features of cancers. A wide range of emerging omics and multi-view clustering algorithms now provide unprecedented opportunities to further classify cancers into subtypes, improve the survival prediction and therapeutic outcome of these subtypes, and understand key pathophysiological processes through different molecular layers. In this review, we overview the concept and rationale of multi-omics approaches in cancer research. We also introduce recent advances in the development of multi-omics algorithms and integration methods for multiple-layered datasets from cancer patients. Finally, we summarize the latest findings from large-scale multi-omics studies of various cancers and their implications for patient subtyping and drug development.

Brewing Rutin-Enriched Lager Beer with Buckwheat Malt as Adjuncts.

Brewing with buckwheat as an ingredient has been proven to be successful in several previous studies. However, few studies have focused on the effects of buckwheat on the rutin content and antioxidant activity of beer. In order to develop a lager beer with high rutin content and desirable sensory characteristics, tartary buckwheat malt was used as a brewing adjunct. The results showed that the rutin-degrading enzyme was the key factor affecting the rutin content in the wort and beer. Compared to beer made using the common mashing method, the rutin content in the buckwheat beers produced using an improved mashing method was approximately 60 times higher. The total flavonoid contents in buckwheat beers also depended strongly on the mashing methods, ranging from 530.75 to 1,704.68 mg QE/l. The rutin-rich beers also showed better oxidative stability during forced-aging. Meanwhile, the buckwheat beers were found to be acceptable in terms of the main quality attributes, flavor, and taste.

Anti-cariogenic Characteristics of Rubusoside.

Streptococcus mutans plays an important role in the development of dental caries in humans by synthesizing adhesive insoluble glucans from sucrose by mutansucrase activity. To explore the anti-cariogenic characteristics of rubusoside (Ru), a natural sweetener component in Rubus suavissimus S. Lee (Rosaceae), we investigated the inhibitory effect of Ru against the activity of mutansucrase and the growth of Streptococcus mutans. Ru (50 mM) showed 97% inhibitory activity against 0.1 U/mL mutansucrase of S. mutans with 500 mM sucrose. It showed competitive inhibition with a K i value of 1.1 ± 0.2 mM and IC50 of 2.3 mM. Its inhibition activity was due to hydrophobic and hydrogen bonding interactions based on molecular docking analysis. Ru inhibited the growth of S. mutans as a bacteriostatic agent, with MIC and MBC values of 6 mM and 8 mM, respectively. In addition, Ru showed synergistic anti-bacterial activity when it was combined with curcumin. Therefore, Ru is a natural anti-cariogenic agent with anti-mutansucrase activity and antimicrobial activity against S. mutans. ELECTRONIC SUPPLEMENTARY MATERIAL ESM: The online version of this article (doi: 10.1007/s12257-018-0408-0) contains supplementary material, which is available to authorized users.

Composition and biochemical properties of l-carnitine fortified Makgeolli brewed by using fermented buckwheat.

Makgeolli is a traditional Korean alcoholic rice beverage. It is brewed of ingredients containing starch, Nuruk, and water. In order to improve the quality and functionality of Makgeolli, the Rhizopus oligosporus fermented buckwheat containing 18.7 mg/kg of l-carnitine were utilized to brew l-carnitine fortified Makgeolli with rice. Makgeolli was prepared in two-stage fermentation method and total rutin and quercetin in each fermented buckwheat Makgeolli were increased 1.8-fold greater than buckwheat Makgeolli. DPPH antioxidant activity was enhanced in fermented buckwheat Makgeolli than buckwheat Makgeolli (21.9%-65.7%). The amounts of l-carnitine in rice Makgeolli, buckwheat Makgeolli, and fermented buckwheat Makgeolli were 0.9, 0.8-1.0, and 1.0-1.9 mg/L, respectively. The fermented buckwheat Makgeolli not only promoted health benefit by increasing l-carnitine and flavonols, but also made effective alcohol production (2.8%-8.4%) compared to common buckwheat Makgeolli, indicating the potential industrial application with health benefits.