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The capability to sense and respond to the environment is essential for survival and fitness in all organisms. Recent studies have shown organisms from different kingdoms, such as fungi, plants, and mammals can recognize and respond to conserved nematode pheromones, named ascarosides. However, the mechanisms underlying cross kingdom perception of nematode pheromones remain unclear. A research team led by Dr. Yen-Ping Hsueh at the Institute of Molecular Biology, Academia Sinica, revealed that two families of GPCRs are responsible for ascarosides detection, leading to the activation of the cAMP-PKA pathway for trap development in nematode-trapping fungus Arthrobotrys oligospora. The expansion of GPCRs in A. oligospora may have been advantageous for recognizing diverse nematode-derived signals to ensure robust prey recognition during co-evolution. Moreover, the identification of ascarosides receptors in a fungal species sheds light on the molecular mechanisms of ascaroside-mediated cross-kingdom communication. This research has been published on April 22, 2024 in Nature Microbiology. The lead author of this research, Chih-Yen Kuo, is a TIGP-MCB student at Academia Sinica, and collaborators of this research includes Dr. Frank Schroeder at Cornell University and Dr. Yu-Chu Chang at Taipei Medical University. Funding was provided by Academia Sinica and the National Science and Technology Council.

This is a popular history of horse racing in China’s leading treaty port, namely Shanghai. This monograph describes how horse racing was introduced, transformed and eventually disappeared due to its implication of British imperialism and colonialism.

We are pleased to announce the new publication of issue 25.2 of Language and Linguistics. This issue includes 4 articles and our annual acknowledgements:

【Foreword】 【Invited Article】 Jiunn-rong Yeh, “Constitutional Dialogism for Basic Rights: Beyond Constitutional Interpretation”

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

Please see the table of contents below:

The newest issue of Academia Economic Papers has just been published by the Institute of Economics. Articles in this issue (Vol. 52, No. 1) include:

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

The use of protein stabilizers or pharmacological chaperones to protect specific enzymes and impart a therapeutic benefit is an emerging strategy in drug discovery. However, designing molecules that can bind optimally to their targets at physiological pH remains a major challenge. The research, led by Dr. Wei-Chieh Cheng at Genomics Research Center, Academia Sinica, found that a dibasic polyhydroxylated pyrrolidine ACK170 (US 10995067 B2) exhibited superior pH-selective inhibitory activity and chaperoning activity for human α-galactosidase A (α-Gal A) through the Natural Product-Inspired Combinatorial Chemistry (NPICC) strategy. To further investigate the role of different C-1 moieties on the pH-selectivity and protecting effects of these compounds, researchers designed and synthesized a library of monobasic and dibasic iminosugars, screened them for α-Gal A stabilizing activity using thermal shift and heat-induced denaturation assays, and characterized the mechanistic basis for this stabilization using X-ray crystallography and binding assays. It was noted that the dibasic iminosugar ACK170 protect α-Gal A from denaturation and inactivation at lower concentrations than monobasic or other N-substituted derivatives; a finding attributed to the nitrogen on the C-1 methylene of ACK170 which forms the bifurcated salt bridges with two carboxyl residues, E203 and D231, and is responsible for their pH-selective binding to α-Gal A. Moreover, ACK170 demonstrated promising results to improve enzyme replacement therapy and exhibited significant chaperoning effects in Fabry cells. These findings suggest that amino-iminosugar ACK170 is a useful model to demonstrate how an additional exocyclic amino group can improve their pH-selectivity and protecting effects. This research has been published on February 23, 2024 in JACS Au, providing new insights into the design of pH-selective small molecules for the treatment of lysosomal storage diseases.

Earth’s long-term, stable magnetic field is critical for being a habitable planet. Mars had a global magnetic field at ~4.3 billion years ago, which, however, only lasted for ~0.7 billion years. To decipher the origin of such short-lived dynamo, an international research team led by Dr. Wen-Pin Hsieh at the Institute of Earth Sciences, Academia Sinica, has precisely measured the thermal conductivity of iron-sulfur alloys at Martian core’s high pressure-temperature conditions. Research team demonstrated that Martian core is much more thermally conductive than previously inferred. Combined with numerical modeling on Martian core’s thermal evolution, they further found that such high thermal conduction with efficient cooling diminishes thermal convection, significantly contributing to the cessation of Martian dynamo. As the seismic data from Insight mission showed important advances in the internal structure of Mars, the research findings further provide crucial insights to the thermal and magnetic evolution, energy budget, and dynamics of Mars. The international team includes Drs. Wen-Pin Hsieh and Frédéric Deschamps of IES, etc. The results have been published in Science Advances on March 20, 2024.

UFMylation is an emerging ubiquitin-like post-translational modification that regulates various biological processes. Dysregulation of the UFMylation pathway leads to human diseases including cancers. However, the physiological role of UFMylation in T cells remains unclear. A research team led by Dr. Yu-Ru Lee at the Institute of Biomedical Sciences, Academia Sinica, reported that mice with conditional knockout (cKO) Ufl1, a UFMylation E3 ligase, in T cells exhibit effective tumor control. Single-cell RNA sequencing analysis shows that tumor-infiltrating cytotoxic CD8+ T cells are increased in Ufl1 cKO mice. Moreover, UFL1 promotes PD-1 UFMylation to antagonize PD-1 ubiquitination and degradation. Furthermore, AMPK phosphorylates UFL1 at Thr536, disrupting PD-1 UFMylation to trigger its degradation. Of note, UFL1 ablation in T cells reduces PD-1 UFMylation, subsequently destabilizing PD-1 and enhancing CD8+ T cell activation. Thus, Ufl1 cKO mice bearing tumors have a better response to anti-CTLA-4 immunotherapy. Collectively, This research findings uncover a crucial role of UFMylation in T cells and highlight UFL1 as a potential target for cancer treatment. This research has been published on February 19, 2024 in Molecular Cell.

The goal of this edited volume is to introduce the roles that popular customs and culture have played in Wenzhou’s social and cultural history.