Biology subjects

Takano, M.

Publications and source records attributed to Takano, M..

4 recordsLinked to original sources

bioRxiv2026

CDK12/13 inhibitor, CTX-439, suppresses tumor growth and potentiates BCL-2 family blockade

CDK12 and CDK13 (CDK12/13) regulate transcription by phosphorylating Serine 2 (S2) of the C-terminal domain of RNA polymerase II and have been proposed as therapeutic targets in cancer. Here we report the development of CTX-439, a novel, orally bioavailable, ATP-competitive small-molecule CDK12/13 inhibitor. CTX-439 specifically inhibits S2 phosphorylation and downregulates many genes including those involved in DNA damage repair, thereby exerting a profound anti-cancer effect in vitro and in vivo including breast cancer PDX models. A CRISPR activation screen identified BCL-2 and BCL-xL, anti-apoptotic BCL-2 family members, as genes that when upregulated confer resistance to CTX-439. Simultaneous inhibition of BCL-2/BCL-xL and CDK12/13 rapidly induced apoptosis and significantly suppressed xenograft tumor growth. Mechanistically, CTX-439 downregulates MCL1 protein levels through transcriptional readthrough, shifting cell survival dependency to BCL-2 and BCL-xL. Our study provides novel insights into the anti-tumor effect of CDK12/13 inhibition and proposes a new combination therapy strategy with anti-apoptotic BCL-2 family inhibitors, which may improve therapeutic outcomes in cancer treatment.

cancer biology↗

bioRxiv2025

Validation of EEG data assimilation-based prefrontal excitation-inhibition balance estimation using TMS-EEG

The excitation and inhibition (E/I) balance of neural circuits is a crucial index reflecting neurophysiological homeostasis. Although several cutting-edge methods have been established to assess E/I balance in an intact brain, they have inherent limitations, such as difficulties in tracking changes in E/I balance over time. To tackle this issue, we have proposed neural-mass-model-based tracking of the brain states using a data assimilation (DA) scheme in our previous work. However, although we verified that sleep-dependent changes in E/I balance can be estimated from electroencephalography data, the neurophysiological validity of the method was not evaluated. Therefore, in the current study, we directly compared estimated E/I states based on the DA methods with the concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) based methods. The results showed that the E/I changes estimated by the DA-based method correlated significantly with E/I in the dorsolateral prefrontal cortex, as indexed by TMS-evoked EEG. These findings indicate that our proposed method can estimate neurophysiologically valid changes in E/I balance.

neuroscience↗

bioRxiv2025

Repeated environmental change mitigates inter-individual inequal food gain in a group foraging experiment of crow

Animal group foraging produces inequality of food gain among individuals due to their differences, particularly dominance rank. External environmental factors, such as the spatial distribution of food, may mitigate the influence of social features on individual food acquisition. However, the role of environmental fluctuation in social foraging inequality remains largely unexplored Here, we investigated how repeated environmental changes affect inequality in food acquisition among captive large-billed crows (Corvus macrorhynchos). By repeatedly altering the relationship between feeding sites and food quantity, we examined changes in the inequality of food gains using Gini coefficient. In the short-term, food allocation became unequal immediately after each change but subsequently recovered. Over successive fluctuations, inequality in food acquisition declined in the long-term, while group foraging efficiency increased. We observed a significant influence of sex on food acquisition, while the expected effect of dominance rank was not detected. Our findings provide the first experimental evidence that changing environments can mitigate inequalities in food gains within foraging groups, highlighting the importance of incorporating naturalistic environmental changes into experimental designs for future group-foraging studies.

animal behavior and cognition↗

bioRxiv2022

Molecular mechanisms of Plasmodium development in male and female Anopheles mosquitoes

Vector competence influences the ability of Anopheles mosquitoes to transmit Plasmodium parasites. The aim of this study was to determine the competence of male and female Anopheles mosquitoes to support the development of Plasmodium parasites. Male and female A. stephensi (STE2 strain) were infected with in vitro-cultured P. berghei (ANKA strain) ookinetes. We found that the number of oocysts produced was higher in males than in females. RNA-seq analysis of male and female mosquitoes injected with P. berghei ookinetes showed that predominantly genes of unknown function changed in expression levels in response to ookinete infection; however, further studies are required to elucidate their functions. Moreover, male mosquitoes were injected with in vitro-cultured P. falciparum (3D7 strain) gametocytes or zygotes. The development of P. falciparum in males was detected using nested polymerase chain reaction. We found the DNA content was higher on day 15 than on day 0, indicating that P. falciparum developed in the mosquito hemocoel. This study revealed promising new mechanisms underlying the interactions between Plasmodium and mosquitoes. Author SummaryAnopheles mosquitoes transmit Plasmodium parasites that cause malaria disease. Vector competence is the ability of vectors to support pathogen development. The aim of this study was to determine the competence of male and female mosquitoes for Plasmodium parasites. Oocysts were formed in both male and female mosquitoes injected with ookinetes from in vitro-cultured Plasmodium berghei, which causes malaria in mice. The number of oocysts was higher in males, indicating that the competence in males was higher than that in females. RNA-seq analysis showed that the expression of genes of unknown function was highly variable in males and females. The genes defining the competence factors need further study, but the results indicate novel genes may be discovered. Furthermore, the development of Plasmodium falciparum, which causes the most severe malaria in humans, in male mosquitoes injected with in vitro-cultured gametocytes or zygotes was detected. As male mosquitoes do not suck blood, this method may allow us to experiment with Plasmodium more safely.

microbiology↗