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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:

This issue has a total of three research articles. The authors and titles of these articles are as follows:

SPHINCS+ is a post-quantum digital signature algorithm designed to address the potential threats posed by quantum computers. It is renowned for its unique ability to resist quantum attacks by using a hash-based signature structure, ensuring long-term security without relying on traditional number-theoretic assumptions. SPHINCS+ prioritizes security over speed or signature size, making it suitable for applications requiring high stability, long-term guarantees, as well as efficiency. The creation of this standard is the result of years of global efforts to combat the threats posed by quantum computers, SPHINCS+ algorithm was developed by an international team and selected as one of the post-quantum cryptography standards in July 2022. Associate Research Fellow Ruben Niederhagen from the Institute of Information Science, Academia Sinica, Taiwan is one of the team members and contributed to the update and revision of the SPHINCS+ program. Another two main members, Dr. Tanja Lange from the Eindhoven University of Technology, Netherlands and Dr. Daniel J. Bernstein from the University of Illinois Chicago, USA, are visiting professors in the Institute of Information Science, Academia Sinica. The standardization signifies a significant milestone in the field of post-quantum cryptography, as SPHINCS+ has become the standard of NIST on Aug. 2024, which is poised to be a widely adopted global standard.

Dark matter consists of about one quarter of the energy density in the present-day Universe and dominates the kinematic of stellar motions inside galaxies. However, physicists have no clue regarding the nature of dark matter, and searching for evidence of interaction between dark matter and the known particles has been one of the Holy Grails in modern physics. Dr. Yen-Hsun Lin, a Postdoctoral Fellow, and Dr. Meng-Ru Wu, Associate Research Fellow at the Institute of Physics, Academia Sinica, have revealed the existence of the diffuse boosted dark matter (DBDM) driven by all past supernova explosions that happened in the Universe. The study predicts that by considering the DBDM with the upcoming neutrino experiment Hyper-Kamiokande, it can probe the previously unexplored parameter space regarding the interaction cross sections of DM with electron and neutrino. This work also highlights a new avenue of utilizing our understanding of astrophysical transients to probe the fundamental particle physics. The research has been published on September 13, 2024 in Physical Review Letters.

The convergence between tectonic plates produces enormous forces, which deform and uplift the continental crust and, eventually, form a mountain range. This is called an orogenic zone. Many orogenic zones, such as those in the European Alps, the Pyrenees, and the Southern Alps of New Zealand, can be understood through the model of orogenic wedge deformation. However, such models have struggled to accurately reproduce the complex tectonic structures in Taiwan. There are two mountain ranges, Backbone Range and Hsuehshan Range, in Taiwan, while the orogenic wedge model can only produce one range. The metamorphic rock in the Taiwan mountains were buried at ~20 km depth. How did it uplift rapidly to the surface during the past 6 Myrs? The research team, led by Dr. Eh Tan, Associate Research Fellow at the Institute of Earth Sciences, Academia Sinica, have introduced a new orogenic model for Taiwan. The model incorporates a strong and vertical backstop at the east, a realistic geothermal gradient, lithology- and slope-dependent erosion, brittle-ductile transitions of geological materials, and the decollement geometry to replicate the complex structures of the Taiwan orogenic belt. This new research method not only can comprehend the orogenic mechanism of Taiwan, but also can help study other orogenic wedges globally. The research has been published on August 28, 2024 in Science Advances. The co-authors of the paper include Professor Yuan-Hsi Lee of the Department of Earth and Environmental Sciences, National Chung Cheng University, Jia-Bin Chang and Ming-Jung Zheng, both master's graduates from National Chung Cheng University, and Chase J. Shyu, a TIGP doctoral student at Academia Sinica.

Some bilateral animals have highly specialized genomes, particularly model organisms like fruit flies, nematodes, zebrafish, and planarians. Evolutionary biologists have observed this specialization since their genomes were sequenced. Conversely, marine invertebrates such as sea urchins, amphioxus, scallops, and ribbon worms exhibit conserved genome structures that have remained unchanged for over 500 million years. Typically, a phylum's genome structure is either conserved or specialized. Studies on Annelida, however, reveal a rare exception.

Per- and Polyfluoroalkyl Substances (PFAS) are a group of contaminants of emerging concern that have been drawing numerous attention in recent years. They are highly persistent in the environment and may pose adverse impacts to marine ecosystems. Moreover, consuming seafood is a primary pathway of human exposure to PFAS. Dr. Cheng-Shiuan Lee, Assistant Research Fellow at the Research Center for Environmental Changes, Academia Sinica, collaborated with teams from Stony Brook University, Beneath the Waves, and Cape Eleuthera Institute, acquiring muscle tissue samples from various shark species for PFAS analysis from two contrasting marine ecosystems: the New York Bight (NYB) and the waters of the Bahamas Archipelago.

Cell adhesion molecules (CAMs) can be utilized as tools to control bacterial community interactions. However, identifying CAMs that target bacterial outer membrane proteins in their native form remains challenging. Dr. See-Yeun Ting's research team from the Institute of Molecular Biology has established a screening platform that effectively identifies CAMs targeting bacterial outer membrane proteins. This platform leverages the bacterial type IV secretion system, a contact-dependent DNA delivery nanomachine whose efficiency is enhanced by specific cell-cell interactions mediated by CAMs and their target antigens on cell surfaces. These stable linkages facilitate the transfer of antibiotic resistance markers, allowing for the selective enrichment of bacteria displaying target CAMs. Using this platform, the research team screened three CAMs that recognize different membrane proteins (TraN, OmpA, OmpC) and successfully applied them to regulate specific bacterial interactions.