Biology subjects

Asano, T.

Publications and source records attributed to Asano, T..

8 recordsLinked to original sources

bioRxiv2026

Sex peptide-SPR-serotonin signaling regulates mating-induced Sex peptide replenishment in Drosophila, suggesting an ancestral role in males

Seminal fluid not only assists successful fertilization but also induces changes in female post-mating behavior and physiology. Consequently, males with depleted or inadequate seminal fluid produce fewer offspring. Males of iteroparous species therefore increase seminal fluid production to replenish exhausted supplies. However, it remains unclear how mating-induced replenishment of seminal fluid components is regulated at the molecular and cellular levels. Here, we show that replenishment of Sex peptide (SP) in male Drosophila melanogaster requires both SP and its receptor SPR. Mechanistically, mating-induced SP replenishment in the male accessory gland (MAG) is regulated by MAG-projecting serotonergic neurons, and this regulation depends on SPR, which is likely activated by SP as it passes through the reproductive tract during mating. This inter-tissue signaling pathway is not limited to SP but also coordinates the post-mating upregulation of an additional seminal fluid protein gene. While SP-SPR signaling is a well-known regulator of female post-mating responses, we demonstrate that it also modulates male physiology. Furthermore, comparative analyses across 12 drosophilid species are consistent with the hypothesis that SP-SPR signaling acquired a role in males before its role in canonical female post-mating responses evolved. We therefore propose that the role of SP-SPR signaling as a mating signal in males is ancestral to its more familiar but evolutionarily derived role in females.

physiology↗

bioRxiv2026

Long-read sequencing based genomic data of a dipluran species, Occasjapyx japonicus

We present the genome dataset of a dipluran species, Occasjapyx japonicus, representing the first dipluran genome assembled using HiFi long-read sequencing technology. The assembled genome is approximately 439.3 Mbp in size, comparable to those of other dipluran species available in public databases. The N50 value of 15.5 Mbp exceeds that reported for other dipluran species. The assembled gene set contains 19,635 genes, a number not significantly different from those estimated in previous analyses of two other dipluran species. Functional gene annotation was conducted using predicted amino acid sequences derived from the gene set. BUSCO analysis indicated that the assembled genome contains the majority of conserved core genes. These findings suggest that the O. japonicus genome and associated data are of sufficient quality to serve as a reference genome. The dataset will be valuable for studies in comparative or evolutionary biology, particularly in understanding hexapod evolution and the emergence of insects.

genomics↗

bioRxiv2026

Co-targeting an AMPK--MAPK axis reprograms CAFs and suppresses PDAC

Pancreatic ductal adenocarcinoma (PDAC) is a fatal cancer characterized by limited therapeutic options and a highly treatment-resistant tumor microenvironment. Beyond tumor-intrinsic genetic alterations, growing evidence indicates that host-microbiome interactions influence cancer progression through microbial metabolites. However, how microbiome-derived metabolites influence oncogenic signaling in PDAC remains unclear. Here, integrated profiling revealed a consistent reduction of the microbial metabolite acetic acid in fecal samples from treatment-naive patients with PDAC and in a genetically defined Drosophila model recapitulating key PDAC driver alterations. Acetic acid activates AMP-activated protein kinase, and pharmacological activation of this pathway together with inhibition of mitogen-activated protein kinase signaling suppressed tumor growth in fly and mouse models. Combined pathway targeting restored AMPK activity and suppressed cancer-associated fibroblast activation. These findings identify a microbiome-associated metabolic vulnerability in PDAC and suggest that coordinated targeting of metabolic and oncogenic signaling may restrain tumor progression and improve therapeutic strategies.

cancer biology↗

bioRxiv2025

Resilin, the gene for the molecular spring: its roles in the flight and jumpingof Drosophila

Resilin is a member of the chitin-binding protein family that was originally found as a major component of an elastic matrix present in insects. The knockdown of the gene for this protein in Drosophila melanogaster causes the characteristic downturned wing posture, and the knockdown flies cannot move their wings. The jump distance of the knockdown flies is around 50% shorter than that of the controls. Null mutant flies show the same phenotypes, which can be rescued by introducing a 4.7 kb genomic fragment harboring the whole coding region of Resilin. In vitro experiments have shown that the elasticity of the matrix made of Resilin is due to the dityrosine-mediated polymerization of Resilin molecules. Dual oxidase (Duox) is the most likely candidate for the in vivo polymerization of Resilin molecules. Duox knockdown induces phenotypes similar to those observed in wing posture and jump performance of the Resilin knockdown and knockout flies, which can be rescued by the overexpression of Duox gene from a beetle. These findings suggest that Duox is an essential factor for the proper function of Resilin as the major component of the resilin matrix.

genetics↗

bioRxiv2022

Integrating pharmacogenomics and cheminformatics with diverse disease phenotypes for cell type-guided drug discovery

Large-scale pharmacogenomic resources, such as the Connectivity Map (CMap), have greatly assisted computational drug discovery. However, despite their widespread use, CMap-based methods have thus far been agnostic to the biological activity of drugs, as well as to the genomic effects of drugs in multiple disease contexts. Here, we present a network-based statistical approach, Pathopticon, that uses CMap to build cell type-specific gene-drug perturbation networks and integrates these networks with cheminformatic data and diverse disease phenotypes for a nested prioritization of cell lines and drugs. Pathopticon demonstrates a better prediction performance than solely cheminformatic measures and state-of-the-art methods that rely exclusively on pharmacogenomic data. Top predictions made by Pathopticon have high chemical structural diversity, suggesting their potential for building compound libraries. In a proof-of-concept application on vein graft disease, we validate the predicted drugs in vitro and demonstrate that Pathopticon helps pinpoint the shared intermediate phenotypes targeted by each prediction. Overall, our analytical framework integrating pharmacogenomics and cheminformatics provides a feasible blueprint for a cell typespecific drug discovery and repositioning platform with broad implications for the efficiency and success of drug development.

systems biology↗

bioRxiv2021

Tandem mass spectrum similarity-based network analysis using 13C-labeled and non-labeled metabolome data to identify the biosynthesis pathway of the blood pressure-lowering asparagus metabolite asparaptine A

Asparaptine, a conjugate of arginine and asparagusic acid, was found in asparagus (Asparagus officinalis) as a naturally occurring inhibitor of angiotensin-converting enzyme (ACE) in vitro. The biosynthetic pathway to asparaptine is largely unknown; however, it is suggested that asparagusic acid may be biosynthesized from valine. To determine which metabolites are involved in the asparaptine biosynthetic pathway, we performed tandem mass spectrometry similarity-based metabolome network analysis using 13C labeled and non-labeled valine-fed asparagus calluses. We determined that valine is used as a starting material, S(2-carboxy-n-propyl)-cysteine as an intermediate, and two new metabolites as asparaptine analogs, lysine- and histidine-type conjugates, are involved in the pathway. Asparaptine was therefore renamed asparaptine A (arginine type), and the two analogs were named asparaptines B (lysine type) and C (histidine type). Oral feeding of asparaptine A to a hypertensive mouse species showed that this metabolite lowers both blood pressure and heart rate within two hours and both of which were back to normal two days later. These results suggest that asparaptine A may not only have effects as an ACE inhibitor, but also has {beta}-antagonistic effects, which are well-known to be preventive for cardiovascular diseases.

plant biology↗

bioRxiv2020

Postharvest properties of ultra-late maturing peach cultivars and their attributions to Melting Flesh (M) locus: Re-evaluation of M locus in association with flesh texture

The postharvest properties of two ultra-late maturing peach cultivars, Tobihaku (TH) and Daijumitsuto (DJ), were investigated. Fruit were harvested at commercial maturity and held at 25{degrees}C. TH exhibited the characteristics of normal melting flesh (MF) peach, including rapid fruit softening associated with an increase in endogenous ethylene production In contrast, DJ did not soften at all during three-week experimental period even though substantial ethylene production was observed. Fruit of TH and DJ were treated with 5000 ppm of propylene, an ethylene analog, continuously for seven days. TH softened rapidly whereas DJ maintained high flesh firmness in spite of an increase in endogenous ethylene production, suggesting that DJ but not TH lacked the ability to be softened in response to endogenous and exogenous ethylene/propylene. DNA-seq analysis showed that tandem endo-polygalacturonase (endoPG) genes located at melting flesh (M) locus, Pp-endoPGM (PGM) and Pp-endoPGF (PGF), were deleted in DJ. The endoPG genes at M locus are known to control flesh texture of peach fruit, and it was suggested that the non-softening property of DJ is due to the lack of endoPG genes. On the other hand, TH possessed an unidentified M haplotype that is involved in determination of MF phenotype. Structural identification of the unknown M haplotype, designated as M0, through comparison with previously reported M haplotypes revealed distinct differences between PGM on M0 haplotype (PGM-M0) and PGM on other haplotypes (PGM-M1). Peach M haplotypes were classified into four main haplotypes: M0 with PGM-M0; M1 with both PGM-M1 and PGF; M2 with PGM-M1; and M3 lacking both PGM and PGF. Re-evaluation of M locus in association with MF/non-melting flesh (NMF) phenotypes in more than 400 accessions by using whole genome shotgun sequencing data on database and/or by PCR genotyping demonstrated that M0 haplotype was the common haplotype in MF accessions, and M0 and M1 haplotypes were dominant over M2 and M3 haplotypes and co-dominantly determined the MF trait. It was also assumed on the basis of structural comparison of M haplotypes among Prunus species that the ancestral haplotype of M0 diverged from those of the other haplotypes before the speciation of Prunus persica.

plant biology↗

bioRxiv2019

ppGpp functions as an alarmone in metazoa

Guanosine 3,5-bis(pyrophosphate) (ppGpp) functions as a second messenger in bacteria to adjust their physiology in response to environmental changes. In recent years, the ppGpp-specific hydrolase, metazoan SpoT homolog-1 (Mesh1), was shown to have important roles for growth under nutrient deficiency in Drosophila melanogaster. Curiously, however, ppGpp has never been detected in animal cells, and therefore the physiological relevance of this molecule, if any, in metazoans has not been established. Here, we report the detection of ppGpp in Drosophila and human cells and demonstrate that ppGpp accumulation induces metabolic changes, cell death, and eventually lethality in Drosophila. Our results provide the first evidence of the existence and function of the ppGpp-dependent stringent response in animals.

molecular biology↗