Biology subjects

Ito, F.

Publications and source records attributed to Ito, F..

10 recordsLinked to original sources

bioRxiv2026

The "glue-gun ant" Lordomyrma azumai uses an adhesive thread secretion to immobilize opponents

In stinging Hymenoptera, the poison gland and its vesicle have been understood largely as sources of toxic, irritating, or antimicrobial compounds, which the sting injects into a target. However, external uses of poison gland secretions have also been reported: Pseudoneoponera (formerly Pachycondyla) froth a proteinaceous poison gland secretion into foam threads that entangle attacking ants, and Crematogaster smear opponents with a contact toxin generated on a spatulate sting from poison and Dufour gland products4. Here we report that workers of the myrmicine ant Lordomyrma azumai produce, in the poison vesicle, a secretion, likely proteinaceous, that solidifies upon extrusion into an adhesive thread. The sting is retained as the conduit, but the secretion it delivers is applied externally rather than injected, and acts as a structural material: workers wipe the thread onto opponents and tether them to the substrate. To our knowledge, no hymenopteran venom secretion functions as a solid thread; in the closest case, Pseudoneoponera3, the secretion entangles attackers as a foam rather than as a continuous solid filament.

animal behavior and cognition↗

bioRxiv2026

Multi-site Cleavage of Amyloid-β by a Minimal 5-mer Catalytic Peptide: Mimicking Serine Protease Activity via Dynamic Substrate-Induced Anchoring

The development of small synthetic catalytic peptides, or catalytides, offers a promising therapeutic strategy for the targeted degradation of amyloid-beta (Abeta). Among these, the pentapeptide SKGQA mimics the proteolytic activity of serine proteases despite its minimal size. However, the molecular mechanism enabling such a short, highly flexible peptide to execute cleavage across multiple sites remains unclear. In this study, we combined HADDOCK docking and extended molecular dynamics (MD) simulations to investigate the dynamic interaction between SKGQA and the central hydrophobic cluster (CHC, residues 17-21) of Abeta. Our MD simulations reveal a cooperative mechanism underlying this activity. The hydrophobic C-terminal Ala5 residue anchors SKGQA within the Abeta CHC region, stabilizing the bound complex while potentially interfering with Abeta self-assembly through steric hindrance. Simultaneously, while the C-terminus remains anchored, the hydrophilic N-terminal Ser1 residue is positioned in spatial proximity to multiple adjacent backbone carbonyl carbons, including Glu22 and Asp23. Within this anchored conformational ensemble, thermal fluctuations allow Ser1 to stochastically attack these neighboring carbonyl targets. This combination of site-specific hydrophobic anchoring and probabilistic catalytic targeting provides a clear structural rationale for the peptide's multi-site cleavage capability.

neuroscience↗

bioRxiv2025

Time-Series RNA Sequencing Reveals Temperature-Specific and Temperature-Compensated Circadian Genes in Drosophila

Circadian rhythms align the physiology and behavior of living organisms with the 24-hour day. As a defining property of circadian rhythms, temperature compensation preserves the 24-hour rhythmic periodicity despite environmental temperature changes. While the molecular clockwork that drives genome-wide oscillations in gene expression is well characterized, how circadian gene expression contributes to the maintenance of rhythmic outputs under thermal variation and to produce temperature compensation remains uninvestigated. We profiled circadian gene expression in the ectothermic animal Drosophila melanogaster using time-series RNA-seq of head tissues under constant darkness at 18{degrees}C, 25{degrees}C, and 29{degrees}C. Locomotion assays confirmed that behavioral rhythms were temperature compensated under these conditions. Analyses of the time-series RNA-seq samples revealed hundreds of oscillating genes at each temperature, yet the majority were temperature specific. Only 14 genes, including the core clock components period (per) and vrille (vri), oscillated across all three constant darkness conditions at different temperatures. Even among these, the phase, amplitude, and expression levels of these oscillating genes often shifted with temperature. Thus, temperature-compensated oscillating genes are rare and largely confined to core clock genes, while most oscillating genes are temperature-specific. Our results suggested a potential architecture: a robust, temperature-compensated core set of oscillating genes, and a flexible, temperature-responsive output layer. The latter likely establishes temperature-specific oscillating gene expression programs that enable the animal to achieve temperature compensation at behavioral and physiological levels.

molecular biology↗

bioRxiv2024

Structural Basis for Pol theta-Helicase DNA Binding and Microhomology-Mediated End-Joining

DNA double-strand breaks (DSBs) present a critical threat to genomic integrity, often precipitating genomic instability and oncogenesis. Repair of DSBs predominantly occurs through homologous recombination (HR) and non-homologous end joining (NHEJ). In HR-deficient cells, DNA polymerase theta (Pol{theta}) becomes critical for DSB repair via microhomology-mediated end joining (MMEJ), also termed theta-mediated end joining (TMEJ). Thus, Pol{theta} is synthetically lethal with BRCA1/2 and other HR factors, underscoring its potential as a therapeutic target in HR-deficient cancers. However, the molecular mechanisms governing Pol{theta}-mediated MMEJ remain poorly understood. Here we present a series of cryo-electron microscopy structures of the Pol{theta} helicase domain (Pol{theta}-hel) in complex with DNA containing 3'-overhang. The structures reveal the sequential conformations adopted by Pol{theta}-hel during the critical phases of DNA binding, microhomology searching, and microhomology annealing. The stepwise conformational changes within the Pol{theta}-hel subdomains and its functional dimeric state are pivotal for aligning the 3'-overhangs, facilitating the microhomology search and subsequent annealing necessary for DSB repair via MMEJ. Our findings illustrate the essential molecular switches within Pol{theta}-hel that orchestrate the MMEJ process in DSB repair, laying the groundwork for the development of targeted therapies against the Pol{theta}-hel.

molecular biology↗

bioRxiv2024

Molecular mechanism for regulating APOBEC3G DNA editing function by the non-catalytic domain

APOBEC3G (A3G) belongs to the AID/APOBEC cytidine deaminase family and is essential for antiviral immunity. It contains two zinc-coordinated cytidine-deaminase (CD) domains. The N-terminal CD1 domain is non-catalytic but has a strong affinity for nucleic acids, whereas the C-terminal CD2 domain catalyzes C-to-U editing in single-stranded DNA. The interplay between the two domains in DNA binding and editing is not fully understood. Here, our studies on rhesus macaque A3G (rA3G) show that the DNA editing function in linear and hairpin loop DNA is greatly enhanced by AA or GA dinucleotide motifs present downstream (in the 3-direction) but not upstream (in the 5-direction) of the target-C editing sites. The effective distance between AA/GA and the target-C sites depends on the local DNA secondary structure. We present two co-crystal structures of rA3G bound to ssDNA containing AA and GA, revealing the contribution of the non-catalytic CD1 domain in capturing AA/GA DNA and explaining our biochemical observations. Our structural and biochemical findings elucidate the molecular mechanism underlying the cooperative function between the non-catalytic and the catalytic domains of A3G, which is critical for its antiviral role and its contribution to genome mutations in cancer.

biochemistry↗

bioRxiv2023

Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15

SARS-CoV-2 non-structural protein 15 (Nsp15) is critical for productive viral replication and evasion of host immunity. The uridine-specific endoribonuclease activity of Nsp15 mediates the cleavage of the polyuridine [poly(U)] tract of the negative-strand coronavirus genome to minimize the formation of dsRNA that activates the host antiviral interferon signaling. However, the molecular basis for the recognition and cleavage of the poly(U) tract by Nsp15 is incompletely understood. Here, we present cryogenic electron microscopy (cryoEM) structures of SARS-CoV-2 Nsp15 bound to viral replication intermediate dsRNA containing poly(U) tract at 2.7-3.3 [A] resolution. The structures reveal one copy of dsRNA binds to the sidewall of an Nsp15 homohexamer, spanning three subunits in two distinct binding states. The target uracil is dislodged from the base-pairing of the dsRNA by amino acid residues W332 and M330 of Nsp15, and the dislodged base is entrapped at the endonuclease active site center. Up to 20 A/U base pairs are anchored on the Nsp15 hexamer, which explains the basis for a substantially shortened poly(U) sequence in the negative strand coronavirus genome compared to the long poly(A) tail in its positive strand. Our results provide mechanistic insights into the unique immune evasion strategy employed by coronavirus Nsp15.

molecular biology↗

bioRxiv2022

Comparative analysis of temperature preference behavior and effects of temperature on daily behavior in eleven Drosophila species

Temperature is one of the most critical environmental factors that influence various biological processes. Species distributed in different temperature regions are considered to have different optimal temperatures for daily life activities. However, how organisms have acquired various features to cope with particular temperature environments remains to be elucidated. In this study, we have systematically analyzed the temperature preference behavior and effects of temperatures on daily locomotor activity and sleep using 11 Drosophila species. We also investigated the function of antennae in the temperature preference behavior of these species. We found that, (1) an optimal temperature for daily locomotor activity and sleep of each species approximately matches with temperatures it frequently encounters in its habitat, (2) effects of temperature on locomotor activity and sleep are diverse among species, but each species maintains its daily activity and sleep pattern even at different temperatures, and (3) each species has a unique temperature preference behavior, and the contribution of antennae to this behavior is diverse among species. These results suggest that Drosophila species inhabiting different climatic environments have acquired species-specific temperature response systems according to their life strategies. This study provides fundamental information for understanding the mechanisms underlying their temperature adaptation and lifestyle diversification.

evolutionary biology↗

bioRxiv2020

Effective neoantigen vaccination correlates with generation of antigen-specific CX3CR1+CD8+ T cells mediated by CD40 and CD80/86 signaling in cDC1s

The use of tumor mutation-derived neoantigen represents a promising approach for cancer vaccines. Preclinical and early-phase human clinical studies have shown the successful induction of tumor neoepitope-directed responses; however, overall clinical efficacy of neoantigen vaccines has been limited. One major obstacle of this strategy is the prevailing lack of sufficient understanding of the mechanism underlying the generation of neoantigen-specific CD8+ T cells. Here, we report a correlation between antitumor efficacy of neoantigen/toll-like receptor 3 (TLR3)/CD40 vaccination and the generation of antigen-specific CD8+ T cells expressing CX3C chemokine receptor 1 (CX3CR1) in a preclinical model. Mechanistic studies using mixed bone marrow chimeras identified that CD40 and CD80/86, but not CD70 signaling in Batf3-dependent conventional type 1 dendritic cells (cDC1s) is required for antitumor efficacy of neoantigen vaccine and generation of neoantigen-specific CX3CR1+ CD8+ T cells. Although CX3CR1+ CD8+ T cells exhibited robust in vitro effector function, depletion of this subset did not alter the antitumor efficacy of neoantigen/TLR3/CD40 agonists vaccination, suggesting that the expanded CX3CR1+ CD8+ T cell subset represents the post-differentiated in vivo effective CX3CR1-negative CD8+ T cell subset. Taken together, our results reveal a critical role of CD40 and CD80/86 signaling in cDC1s in antitumor efficacy of neoantigen-based therapeutic vaccines, and implicate the potential utility of CX3CR1 as a circulating predictive T-cell biomarker in vaccine therapy.

immunology↗

bioRxiv2020

A circulating T-cell differentiation marker to predict response to immune checkpoint inhibitors

Immune checkpoint inhibitors (ICI) have revolutionized treatment for various cancers; however, durable response is limited to only a subset of patients. Discovery of blood-based biomarkers that reflect dynamic change of the tumor microenvironment, and predict response to ICI will markedly improve current treatment regimens. Here, we investigated a role of CX3C chemokine receptor 1 (CX3CR1), a marker of T-cell differentiation, in predicting response to ICI therapy. Successful treatment of tumor-bearing mice with ICI increased the frequency and T-cell receptor clonality of the peripheral CX3CR1+CD8+ T-cell subset that included an enriched repertoire of tumor-specific and tumor-infiltrating CD8+ T cells. Furthermore, an increase in the frequency of the CX3CR1+ subset in circulating CD8+ T cells early after initiation of anti-PD-1 therapy correlated with response and survival in patients with non-small cell lung cancer (NSCLC). Taken together, these data support T-cell CX3CR1 expression as a blood-based dynamic biomarker to predict response to ICI therapy.

immunology↗

bioRxiv2017

Frequent Non-random Shifts in the Temporal Sequence of Developmental Landmark Events during Fish Evolutionary Diversification

Morphological transformations can be generated by evolutionary changes in the sequence of developmental events. In this study, we examined the evolutionary dynamics of the developmental sequence on a macroevolutionary scale using the teleost. Using the information from previous reports describing the development of 31 species, we extracted the developmental sequences of 19 landmark events involving the formation of phylogenetically conserved body parts; we then inferred ancestral developmental sequences by two different parsimony-based methods--event-pairing (Jeffery, Bininda-Emonds, Coates & Richardson, 2002a) and continuous analysis (Germain & Laurin, 2009). The phylogenetic comparisons of these sequences revealed event-dependent heterogeneity in the frequency of sequence changes. Most of the sequence changes occurred as exchanges of temporally neighboring events. The phylogenetic analyses suggested that the ancestral species had experienced frequent changes in developmental sequences. Although the analyses showed that these heterochronic changes accumulated along phylogenic time, the precise distribution of the changes over the teleost phylogeny remains unclear due to technical limitations. Finally, this first comprehensive analysis of teleost developmental sequences will provide solid ground on which to elucidate the significance of developmental timing in animal morphological diversification.

evolutionary biology↗