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Transcriptional rewiring generates phenotypic novelty during evolutionary divergence in all organisms. The detailed molecular mechanisms underlying transcriptional rewiring are not fully understood and the diverse transcriptional regulatory networks are not comprehensively delineated. A research team led by Dr. Jun-Yi Leu at the Institute of Molecular Biology, Academia Sinica characterized the Sef1 regulatory networks in different yeast species, and demonstrated that an incompletely rewired Sef1 network can evolve strong phenotypic divergence by using a conserved target gene NDE1 with a new function. The study provided novel insights to understand the evolutionary trajectories of transcriptional regulatory networks. The research has been published on November 20, 2024 in Nucleic Acids Research. The first and co-corresponding author is Dr. Po-Chen Hsu, the IMB senior scientist. Collaborators include Dr. Tzu-Chiao Lu at the Baylor College of Medicine and Dr. Po-Hsiang Hung at the Stanford University. This study was supported by the Investigator Project Grant (Academia Sinica) and Frontier Science Research Program (National Science and Technology Council).

The latest issue of Taiwan Economic Forecast and Policy has been published. Articles in this issue include:

Theft is undoubtedly one of the most traditional types of crime in human society, yet historical research on this topic has been insufficient.

The newest issue of the Journal of Social Sciences and Philosophy has just been published by the Research Center for Humanities and Social Sciences. Articles in this issue (Vol. 36, No. 3) include:

Levels of progesterone, an endogenous female hormone, increase after ovulation; progesterone is crucial in the luteal phase to maintain successful pregnancy and prevent early miscarriage. Both endogenous and exogenous progesterone are recycled between the liver and gut; thus, the gut microbiota regulate host progesterone levels by inhibiting enterohepatic progesterone circulation. A research team led by Dr. Yin-Ru Chiang at the Biodiversity Research Center, Academia Sinica, and Mei-Jou Chen at the College of Medicine, National Taiwan University, have identified Clostridium innocuum as a major species involved in gut progesterone metabolism in women with infertility. C. innocuum converts progesterone into the neurosteroid epipregnanolone (with negligible progestogenic activity). The study purified and characterized the corresponding enzyme, namely NADPH-dependent 5β-dihydroprogesterone reductase, which is highly oxygen sensitive and whose corresponding genes are prevalent in C. innocuum. Moreover, C. innocuum–administered female C57BL/6 mice (aged 7 weeks) exhibited decreased plasma progesterone levels (~35%). Clostridium-specific antibiotics (metronidazole) restored low plasma progesterone levels in these mice. Furthermore, prolonged C. innocuum administration (12 weeks) arrested ovarian follicular development in female mice. Cytological and histological analyses indicated that C. innocuum may cause luteal phase insufficiency and affect menstrual regularity. The research findings suggest C. innocuum as a causal factor of progesterone resistance in women taking progesterone. The research has been published on November 7, 2024 in Gut Microbes.

Cancer's drug resistance and immune evasion tendencies present significant treatment challenges. A research team led by Dr. Yun Mou and Dr. Che-Ming Hu at the Institute of Biomedical Sciences, Academia Sinica, has developed a probiotic vector capable of delivering multiple immunotherapeutic proteins. This vector penetrates tumors, releasing various anti-cancer fusion proteins to achieve tumor destruction and enhance anti-cancer immunity. The lead investigator, Dr. Cheng-Hao Liu employed genetic engineering to load the probiotic vector with functionalities including cancer cell-targeting ligand, cell perforation proteins, immune checkpoint inhibitors, and immune-stimulatory cytokines. The bacterial vector's safety was also enhanced for high-dose intravenous injection. This design addresses complex issues in multi-target cancer therapies, such as regulatory, logistical, and pharmacokinetic challenges, allowing for large-scale production of combination therapies via a single vector for direct injection and targeted tumor delivery. This research has been published on October 22, 2024 in Cell Reports Medicine.

We are pleased to announce the new publication of issue 25.4 of Language and Linguistics. This issue includes 6 articles, 1 book review and our annual acknowledgements:

Vinca alkaloids, a class of tubulin-binding agent, are widely used in treating cancer, yet the emerging resistance compromises their efficacy. Hepatoma up-regulated protein (HURP), a microtubule-associated protein displaying heighted expression across various cancer types, reduces cancer cells’ sensitivity to vinca-alkaloid drugs upon overexpression. However, the molecular basis behind this drug resistance remains unknown. An international research team led by Dr. Kuo-Chiang Hsia at the Institute of Molecular Biology, Academia Sinica, Dr. Su-Yi Tsai (Department of Life Science, National Taiwan University) and Dr. Yuta Shimamoto (National Institute of Genetics) discover a tubulin-binding domain within HURP, and establish its role in regulating microtubule growth. Cryo-EM analysis reveals interactions between HURP's tubulin-binding domain and the vinca domain on β-tubulin-the site targeted by vinca alkaloid drugs. Importantly, HURP competes directly with the vinorelbine, a vinca alkaloid-based chemotherapeutic agent, countering microtubule growth defects caused by vinorelbine both in vitro and in vivo. The research findings elucidate a mechanism driving drug resistance in HURP-overexpressing cancer cells and emphasize HURP tubulin-binding domain’s role in mitotic spindle assembly. This underscores its potential as a therapeutic target to improve cancer treatment. This research has been published on October 14, 2024 in Nature Communications.

The newest issue of Bulletin of the Institute of History and Philology, Academia Sinica has just been published by the Institute of History and Philology. Articles in this issue (Volume 95 Part 3) include:

Humans are chordates, which together with echinoderms and hemichordates belong to deuterostomes. Their embryogenesis are comparable, but develop into distinct body forms. To understand developmental mechanisms of deuterostomes and their evolutionary history, Research Fellow Yi-Hsien Su and the Marine Research Station Chief Jr-Kai Yu at ICOB collaborated with a Spanish team to globally analyze gene expression dynamics and their regulation during development of a hemichordate from Penghu. The research team deciphered a biphasic regulatory program and proposed that gastrulation is the stage of highest molecular similarity among deuterostomes. This study provides a developmental foundation for the deuterostome common ancestor. How chordates evolved unique body plan from such a foundation would be an important direction for future studies.

The newest issue of Academia Economic Papers has just been published by the Institute of Economics. Articles in this issue (Vol. 52, No. 3) include:

Institutum Iurisprudentiae has published Issue 35 of Academia Sinica Law Journal. It contains the following articles: