Biology subjects

Tashiro, K.

Publications and source records attributed to Tashiro, K..

10 recordsLinked to original sources

bioRxiv2026

Independent evolution of flavour and parthenocarpy in fig, one of the earliest domesticated fruit trees

Domestication often modifies multiple traits in concert, but whether fruit quality and reproductive mode share a genetic basis in perennial crops has not been tested at multi-omics resolution. In fig (Ficus carica), one of the earliest domesticated fruit trees and a crop with archaeobotanical evidence of cultivation over 11,000 years ago, domestication yielded both distinctive flavour and parthenocarpy, fruit development without pollination. We integrated whole-genome resequencing, transcriptomics, volatile and metabolite profiling, and taste sensor data across a diverse accession panel, using Bayesian GWAS/TWAS and multi-omics factor analysis. Flavour emerges as an integrated sensory system led by aroma, which modulates taste through cross-modal interactions, with sugar-acid balance as a secondary axis; these quality traits map to numerous independent loci. Parthenocarpy instead traces to a single perfectly concordant chromosome 04 haplotype (Eden) centred on FcMYB101-like, carrying a selective-sweep signature and a derived allele fixed in cultivated figs but rare across the genus. Flavour and reproductive mode thus evolved along separate genomic trajectories, allowing each to be improved independently.

plant biology↗

bioRxiv2025

Deciphering cytokine-driven ADP-ribosylation signaling networks via Af1521-based mass spectrometry analysis of labile Glu/Asp-linkages

ADP-ribosylation (ADPr) is a regulatory post-translational modification targeting nine amino acid residues. Glutamate- and aspartate-linked ADPr (Glu/Asp-ADPr) is chemically unstable during sample preparation for conventional mass spectrometry (MS)-based proteomics workflows, limiting its detection. Here, we systematically assessed the stability of ADPr linkages using synthetic peptides and confirmed that ester-linked Glu/Asp-ADPr is lost under alkaline conditions, elevated temperatures, or through hydrolysis by wildtype Af1521. We established an acidic enrichment workflow encompassing an Af1521 mutant, robustly preserving Glu/Asp-ADPr enabling their site-specific and systems-wide MS analysis. Applying this strategy to cytokine-stimulated A549 and HeLa cells, we identified >600 Glu/Asp-ADPr and >200 Cys-ADPr sites. Our analysis uncovered that Glu/Asp-ADPr marks distinct cytoplasmic protein networks enriched in immune functions, contrasting with Ser-ADPr typically observed on nuclear and chromatin-associated proteins. Quantitative profiling revealed reproducible ADPr patterns specific to cell type and treatment. Notably, PARP10 promoted Glu/Asp modification of ubiquitin, highlighting crosstalk between ADPr and ubiquitin signaling. Across interferon treatments, we identified a conserved network of antiviral PARPs and associated cofactors extensively modified on Glu/Asp residues, emphasizing residue-specific ADPr as a regulator of innate immune signaling. Together, our work establishes an MS-based proteomics workflow for identification of Glu/Asp-ADPr, provides a resource of site-specific modification events, and reveals residue-specific ADPr dynamics in immune signaling.

cell biology↗

bioRxiv2025

A newly developed model of atherosclerosis caused by the stress of metabolic syndrome in apolipoprotein E knockout mouse

BackgroundAtherosclerotic disease is influenced by multiple factors including hypertension, dyslipidemia, and diabetes and it is rarely due to a single pathology in clinical conditions. In this study, we created a mouse model of metabolic syndrome and aimed to elucidate the mechanism of atherosclerosis in metabolic syndrome. MethodsTwelve-week-old male apolipoprotein E knockout mice were fed a high-fat diet to produce dyslipidemia, administered angiotensin II continuously to develop hypertension, and infused with streptozotocin intraperitoneally at 18 weeks to produce diabetes mellitus for metabolic syndrome (METS) mice. Control (CTL), high-fat diet alone, angiotensin II alone, and streptozotocin alone mice were also produced and the results in the various groups were compared. ResultsThe METS group showed increased body weight, blood pressure, and serum total cholesterol. The METS group exhibited a significantly higher rate of atherosclerosis formation than the CTL group (METS; 25.7{+/-}11.6 %, CTL: 3.3{+/-}1.5 %, p<0.001). The expressions of nicotinamide adenine dinucleotide phosphate oxidase 2, nuclear factor-kappa B1, and matrix metalloproteinase-2 in the METS group were significantly higher than those in the CTL group by reverse transcription-polymerase chain reaction analysis. ConclusionsThe METS model mouse showed severe atherosclerosis caused by oxidative stress, inflammation, and atherosclerotic plaque formation. This model is expected to be useful as a model that more closely resembles the pathophysiology of clinical atherosclerosis. PerspectiveO_ST_ABSWhat Is New?C_ST_ABSThis study introduces a novel metabolic syndrome mouse model that closely resembles human atherosclerosis by integrating hypertension, dyslipidemia, and diabetes into an apolipoprotein E knockout mouse. What Are the Clinical Implications?The metabolic syndrome mouse model demonstrates severe atherosclerosis driven by oxidative stress and inflammation, making it a valuable tool for testing therapeutic strategies targeting metabolic syndrome-related cardiovascular diseases.

animal behavior and cognition↗

bioRxiv2025

Synergistic RAS-MAPK and AKT Activation in MYC-Driven Tumors via Adjacent PVT1 Rearrangements

MYC-driven (MYC+) cancers are aggressive and often fatal. MYC dysregulation is a key event in these cancers, but overexpression of MYC alone is not always enough to cause cancer. Plasmocytoma Variant Translocation 1 (PVT1), a long non-coding RNA (lncRNA) adjacent to MYC on chromosome 8 is a rearrangement hotspot in many MYC+ cancers. In addition to being co-amplified with MYC, the genomic rearrangement at PVT1 involves translocation, which has had obscure functional consequences. We report that translocation at the PVT1 locus cause asymmetric enrichment of 5-PVT1 and loss of 3-PVT1. Despite being classified as a non-coding RNA, the retained 5 region of PVT1 generates a circular RNA (CircPVT1) that codes for the novel peptide we call Firefox (FFX). FFX augments AKT signaling and synergistically activates MYC and mTORC1 in these cells. Further, the 3 end of PVT1, which is lost during the translocation, codes for a tumor-suppressing micropeptide we named as Honeybadger (HNB). We demonstrate that HNB interacts with KRAS and disrupts the activation of KRAS effectors. Loss of HNB leads to activation of RAS/MAPK signaling pathway, and enhances MYC stability by promoting phosphorylation of MYC at Ser62. These findings identify PVT1 as a critical node that synchronizes MYC, AKT, and RAS-MAPK activities in cancer. Our study thus identifies a key mechanism by which rearrangements at the PVT1 locus activate additional oncogenic pathways that synergize with MYC to exacerbate the aggressiveness of MYC+ cancers. This newfound understanding explains the poor prognosis associated with MYC+ cancers and offers potential therapeutic targets that could be leveraged in treatment strategies for these cancers.

cancer biology↗

bioRxiv2025

Evolutionary and structural basis of SLAM utilization in morbilliviruses - Its implications for host range and cross-species transmission

Morbilliviruses, including measles virus (MV), canine distemper virus (CDV), and cetacean morbillivirus, pose a significant threat to humans and animals. While the host range of morbilliviruses is generally well-defined, severe cross-species transmission events also have been reported. Their entry into immune cells, the primary targets of morbilliviruses, relies on the signaling lymphocytic activation molecule (SLAM), a receptor whose species-specific variations influence viral host range. However, the extent to which SLAM diversity is a barrier to cross-species transmission remains poorly understood. In this study, we systematically investigated SLAM-mediated host specificity. We found that most morbilliviruses efficiently utilize SLAM from multiple host species, except for human SLAM. Among the morbilliviruses tested, only MV efficiently utilized human SLAM. Bats are natural reservoirs for many zoonotic viruses. Recent discoveries of novel morbilliviruses in bats provide new insights into morbillivirus evolution. Bats may have played a significant role in morbillivirus evolution because bat (Myotis) SLAM also functioned as an efficient receptor for multiple morbilliviruses. Unlike other morbilliviruses, MV utilized Myotis bat SLAM inefficiently. We conducted an MV adaptation experiment with Myotis bat SLAM to better understand SLAM recognition by morbilliviruses. MV readily adapted to utilize Myotis bat SLAM by acquiring a single N187Y mutation in its hemagglutinin protein, and computational structural modeling and fragment molecular orbital calculations with molecular dynamics simulations revealed key interaction changes that facilitated MVs adaptation to Myotis bat SLAM. These findings highlight the adaptability of morbilliviruses in utilizing diverse animal SLAMs. Notably, hypothetical ancestral SLAMs reconstructed in this study acted as universal receptors for all morbilliviruses. These results reinforced that morbillivirus receptor usage is primarily supported by evolutionarily conserved structural features of SLAM, highlighting a molecular basis that enables morbilliviruses to rapidly adapt to diverse animal SLAMs. Author SummaryOur study explores how viruses in the genus morbillivirus, such as measles virus, canine distemper virus, and rinderpest virus, which are notorious for deadly outbreaks in humans and animals, can jump between species. The host range of morbilliviruses is significantly influenced by a receptor molecule on cell surfaces known as the signaling lymphocytic activating molecule (SLAM). By examining SLAMs from various animals, including humans, dolphins, dogs, seals, and bats, we observed how these viruses can infect or adapt to infect different hosts. We found that in some cases slight differences in SLAM may act as initial barriers to cross-species transmission. However, these viruses rapidly overcome such barriers, showing a remarkable ability to adapt. Our research highlights the importance of monitoring these viruses to predict and prevent potential cross-species infections, which is crucial for protecting public health and animal welfare over time.

microbiology↗

bioRxiv2022

A protein semisynthesis-based strategy to probe the impact of site-specific serine ADP-ribosylation on linker histone function

Recently developed chemical and enzyme-based technologies to install serine ADP-ribosylation onto synthetic peptides have enabled new approaches to study PARP biology. Here, we establish a generalizable strategy to prepare ADP-ribosylated peptides that are compatible with N-terminal, C-terminal and sequential protein ligation reactions. Two unique protein-assembly routes are employed to generate full-length linker histone constructs that are homogenously ADP-ribosylated at known DNA damage-dependent modification sites. We found that serine mono-ADP-ribosylation is sufficient to alleviate linker histone-dependent chromatin compaction, and that this effect is amplified by ADP-ribose chain elongation. Our work will greatly expand the scope of ADP-ribose-modified proteins that can be constructed via semisynthesis, which is rapidly emerging as a robust approach to elucidate the direct effects that site-specific serine mono- and poly-ADP-ribosylation have on protein function.

biochemistry↗

bioRxiv2021

Tracing the genetics of neurological disease to the mutation-directed addition of single hydrogen bonds

Mutations causative of neurological and neurodegenerative disease can occur in coding regions that specify protein domains of low sequence complexity. These autosomal dominant mutations can be idiosyncratic in their recurrent appearance at the same amino acid. Here we report studies of recurrent mutations in proline residues located within low complexity (LC) domains associated with the neurofilament light chain protein, the microtubule-associated tau protein, and the heterogeneous nuclear RNPA2 protein. All such mutations manifest their effects by directing formation of variant proteins endowed with the addition of a single, main chain hydrogen bond specified by the variant amino acid replacing proline. Here we show that methylation of the peptide backbone nitrogen atom associated with these variant amino acids eliminates the aberrant hydrogen bond and restores normal protein function.

biochemistry↗

bioRxiv2021

Serine ADP-ribosylation marks nucleosomes for ALC1-dependent chromatin remodeling

Serine ADP-ribosylation (ADPr) is a DNA damage-induced post-translational modification catalyzed by the PARP1/2:HPF1 complex. As the list of PARP1/2:HPF1 substrates continues to expand, there is a need for technologies to prepare mono- and poly-ADP-ribosylated proteins for biochemical interrogation. Here we investigate the unique peptide ADPr activities catalyzed by PARP1 in the absence and presence of HPF1. We then exploit these activities to develop a method that facilitates installation of ADP-ribose polymers onto full-length proteins with precise control over chain length and modification site. A series of semi-synthetic ADP-ribosylated histone proteins are prepared which demonstrate that ADPr at H2BS6 or H3S10 converts nucleosomes into robust substrates for the chromatin remodeler ALC1. Importantly, we found ALC1 selectively remodels activated substrates within heterogeneous nucleosome populations and that nucleosome serine ADPr is sufficient to stimulate ALC1 activity in nuclear extracts. Our study identifies a biochemical function for nucleosome serine ADPr and describes a method that is broadly applicable to explore the impact that site-specific serine mono- and poly-ADPr have on protein function.

biochemistry↗

bioRxiv2020

Fingerprinting of hatchery haplotypes by whole-mitogenome sequencing improves genetic studies of masu salmon Oncorhynchus masou masou

Stocking hatchery fish can lead to disturbance and extinction of the local indigenous population. Stocking similar lineages to the indigenous population makes it difficult to conduct genetic studies to determine conservation units. We considered that, due to the length of the mitogenome, whole-mitogenome analysis might overcome this problem by enabling identification of hatchery haplotypes. Here, to provide basic information for conservation of indigenous masu salmon Oncorhynchus masou masou, a commonly stocked fish in the Kase River system, Japan, we used whole-mitogenome analysis of fish to identify hatchery haplotypes in the river and in several hatcheries that might be used for stocking. Whole-mitogenome sequencing clearly identified hatchery haplotypes like fingerprints, identifying the tributaries contaminated with hatchery haplotypes. The results suggest that informal stocking of O. m. masou has been performed widely across the Kase River system. Non-hatchery haplotypes mainly belonged to clade I, which was not found in northern Hokkaido Island. Sites without hatchery haplotypes were estimated three, suggesting that these sites are suitable for conservation of the indigenous fish. This study demonstrated that the resolution of the conventional analysis using partial mitogenome is insufficient to distinguish hatchery haplotype from similar lineages. The whole-mitogenome sequences provided accurate information that was not available in the partial sequences, enabling various inferences: e.g., estimation of the origin of stocked fish and circulation of the reared strains. We conclude that whole-mitogenome analysis is useful for the genetic study of this species. The whole-mitogenome data produced will contribute to the conservation, resource management, and further study of O. m. masou.Competing Interest StatementThe authors have declared no competing interest.View Full Text

genetics↗

bioRxiv2018

A comprehensive reference transcriptome resource for the Iberian ribbed newt Pleurodeles waltl, an emerging model for developmental and regeneration biology

Urodele amphibian newts have unique biological properties, notably including prominent regeneration ability. Iberian ribbed newt, Pleurodeles waltl, is a promising model newt along with the successful development of the easy breeding system and efficient transgenic and genome editing methods. However, genetic information of P. waltl was limited. In the present study, we conducted an intensive transcriptome analysis of P. waltl using RNA-sequencing to build gene models and annotate them. We generated 1.2 billion Illumina reads from a wide variety of samples across 11 different tissues and 9 time points during embryogenesis. They were assembled into 202,788 non-redundant contigs that appear to cover nearly complete (~98%) P. waltl protein-coding genes. Using the gene set as a reference, our gene network analysis identified regeneration-, developmental-stage-, and tissue-specific co-expressed gene modules. Ortholog analyses with other vertebrates revealed the gene repertoire evolution of amphibians which includes urodele-specific loss of bmp4 and duplications of wnt11b. Our transcriptome resource will enhance future research employing this emerging model animal for regeneration research as well as other areas such as developmental biology, stem cell biology, cancer research, ethology and toxico-genomics. These data are available via our portal website, iNewt (http://www.nibb.ac.jp/imori/main/).

genomics↗