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Miyashita, A.

Publications and source records attributed to Miyashita, A..

3 recordsLinked to original sources

Enhancer variants associated with Alzheimer’s disease affect gene expression via chromatin looping

BackgroundGenome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) that may be genetic factors underlying Alzheimers disease (AD). However, how these AD-associated SNPs (AD SNPs) contribute to the pathogenesis of this disease is poorly understood because most of them are located in non-coding regions, such as introns and intergenic regions. Previous studies reported that some disease-associated SNPs affect regulatory elements including enhancers. We hypothesized that non-coding AD SNPs are located in enhancers and affect gene expression levels via chromatin loops.\n\nResultsWe examined enhancer locations that were predicted in 127 human tissues or cell types, including ten brain tissues, and identified chromatin-chromatin interactions by Hi-C experiments. We report the following findings: (1) nearly 30% of non-coding AD SNPs are located in enhancers; (2) expression quantitative trait locus (eQTL) genes affected by non-coding AD SNPs within enhancers are associated with amyloid beta clearance, synaptic transmission, and immune responses; (3) 95% of the AD SNPs located in enhancers co-localize with their eQTL genes in topologically associating domains suggesting that regulation may occur through chromatin higher-order structures; (4) rs1476679 spatially contacts the promoters of eQTL genes via CTCF-CTCF interactions; (5) the effect of other AD SNPs such as rs7364180 is likely to be, at least in part, indirect through regulation of transcription factors that in turn regulate AD associated genes.\n\nConclusionOur results suggest that non-coding AD SNPs may affect the function of enhancers thereby influencing the expression levels of surrounding or distant genes via chromatin loops. This result may explain how some non-coding AD SNPs contribute to AD pathogenesis.

genomics

Calling song maturity in two-spotted cricket, Gryllus bimaculatus: its patterns and a possible physical explanation

Males of Gryllus bimaculatus (two-spotted cricket) emit acoustic signals by stridulating two forewings. One of their songs, calling song, plays a role in attracting females to mate, yet the significance of each song trait in attracting conspecific females remains unclear. Among such traits, the relevance of frequency component (i.e. song pitch) has been underestimated, as orthopterans had long been believed incapable of song pitch recognition. However, recent literatures suggested that ears of orthopteran species are capable of frequency recognition as mammalians do. My previous report demonstrated that their calling song recorded from mature adults has constant and pure peak frequency component around 5.7 kHz, further supporting a biological significance of the frequency component. In this study, I tracked its change over time in sexual maturity phase (i.e. from early adult phase). 300 calling songs were recorded over time from a pool of 122 adult crickets, as it required large number of animals because the crickets rarely sing at very early adult stage. A maturation process of calling song was observed, where the peak frequency distributed lower and more variable frequency in early adult phase (e.g. mean peak value was 4.9 kHz on day 3), then it gradually increased and converged to 5.8 kHz with two weeks. The coefficient of variance also decreased over the process, showing minimum around day 20. Also, I found that the young crickets (supposed to emit immature song), emit perfectly tuned calling song with 5.8 kHz peak in helium-substituted (80% Helium and 20% Oxygen) environment. These findings suggest that the robustly regulated frequency of the calling song is acquired during the early-to-mid adult stage, and it may be associated with sexual maturity of males. Also, the helium-substitution experiment suggests that physical resistance from surrounding gas molecules negatively impacts stability of calling songs of young males, implying that a muscle development and/or forewing hardening may help song maturation. This study highlights a biological significance of the frequency component, such that females may adaptively select sexually mature males based on the song trait.

zoology

A fast immune priming that confers a complete infection resistance on silkworm (Bombyx mori)

I have previously reported an immune priming in silkworm triggered by peptidoglycans, which is long-lasting but slow-acting. Here I report a faster immune priming, which can be triggered by an injection of gelatin or collagen, that confers a complete infection resistance to Gram-negative bacteria on silkworms. Gelatin-injected silkworms showed 100% viability in a lethal dose of a Gram-negative bacterial infection within two hours after the gelatin injection. Injection of collagen showed a similar effect. Whereas, an injection of non-gelatin protein (bovine serum albumin) solution did not induce such reaction. These results suggest that the silkworm possesses a fast and gelatin-inducible pathway that confers infection resistance to Gram-negative bacteria, which may act as a front-line defense. This finding highlights the potency of gelatin as a tool for investigating the primed immune responses in insect species.

immunology