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Natural killer (NK) cells control metastasis, however, the mechanisms are not fully understood. Dr. Nan-Shih Liao”s team at Institute of Molecular Biology established a spontaneous breast cancer metastasis and primary tumor resection mouse model that mimics recurrence in patients after resection. They found that syngeneic NK cell therapy is effective in treating established low-burden metastases depending on CD8+ T cells and induces a tumor-specific protective T cell memory. Furthermore, NK cell transfer augments activation of dendritic cells, Foxp3-CD4+ T cells and stem cell-like CD8+ T cells in metastatic lungs, which requires IFN-γ of the transferred NK cells. A trial of autologous NK cell therapy in six advanced cancer patients was conducted with Dr. Ming-Shen Dai at Tri-Service General Hospital, which showed safety and signs of effectiveness. This work was published on June 19, 2024 in eLife. The three co-first authors are Shih-Wen Huang from TIGP-MCB Ph.D. program, IMB Postdoc Researcher Dr. Yein-Gei Lai, and Hao-Ting Liao from Master program of Department of Life Sciences, National Central University.

A collaborative study led by Dr. Ruey-Bing Yang from Academia Sinica and first author Dr. Yuh-Charn Lin from Taipei Medical University has revealed that the membrane protein SCUBE2 (Signal peptide-CUB-epidermal growth factor-like domain-containing protein 2) plays a critical role in maintaining vascular barrier function during inflammation. Conducted in collaboration with Dr. Ya-Jen Chang from Academia Sinica and Professor Chun-Min Lo from National Yang Ming Chiao Tung University, highlights how SCUBE2 stabilizes endothelial cell adheres junctions to prevent vascular leakage. This research, published on June 13, 2024, in Cardiovascular Research, suggests new therapeutic strategies for inflammation-related diseases.

In some subduction zones, intermediate-depth earthquakes (~70–300 km depth) occur along two separate planes, known as double seismic zones. The subduction system in eastern Taiwan has a similar feature with shallower double seismic zone. Mechanisms forming such intriguing seismicity, however, remain inconclusive. The research, led by Dr. Wen-Pin Hsieh, Research Fellow at the Institute of Earth Sciences, Academia Sinica, has precisely measured the thermal conductivity of antigorite, an important serpentine mineral in subducting slabs, at high pressure-temperature conditions along slab subduction. The study demonstrated that antigorite has a strong thermal conductivity anisotropy. Combined with numerical modeling on slab’s thermal evolution, the team further showed that such strong thermal conductivity anisotropy combined with shear-induced crystal-preferred-orientation creates a thermal blanket effect that suppresses heat flow, significantly affecting slab’s thermal evolution and promoting dehydration embrittlement. Meanwhile, such effect also facilitates thermal runaway, a positive feedback accumulating heat, to trigger intermediate-depth earthquakes. These exciting findings highlight the important role that hydrous minerals play on the thermal state of a slab and the fundamental mechanisms triggering deep earthquakes. This research has been published on June 18, 2024 in Nature Communications. The first author of this research, Yu-Hsiang Chien, is a PhD candidate of TIGP-ESS at Academia Sinica, and coauthors include Yi-Chi Tsao of IES, and Dr. Enrico Marzotto of GeoForschungsZentrum (GFZ), Germany.

The issue contains 1 introduction, 3 articles and 1 speech.

The latest issue of《Bulletin of the Institute of Mathematics Academia Sinica New Series》has been published. Articles in this issue include:

Humans are classified under the phylum Chordata, which together with phyla Echinodermata and Hemichordata belong to Deuterostomia. To trace our own evolutionary history, biologists have strived to understand the characteristics of the deuterostome ancestor. However, due to the lack of chromosomal-level genome assemblies of hemichordates, a key group in deuterostomes, the ancestral genome composition and chromosomal architecture of the deuterostome ancestor remains a mystery.

Hydrothermal vent systems are thought to be the most like the sites on Earth where life began. The shallow-water hydrothermal vent system on Kueishan Island offers marine biologists an exceptional research possibility. Dr. Yung-Che Tseng (Institute of Cellular and Organismic Biology) and Dr. Tzu-Hao Lin (Biodiversity Research Center) took advantage of the Marine Research Station to establish comprehensive research tactics that included marine physicochemical, biological, and soundscape aspects of the hydrothermal vent systems. For the first time, they carefully tracked, over a two-year period and across multiple habitats (including the venting system and surrounding coral reef ecosystems). The research team's findings reveal that shallow earthquakes in close proximity to the vent sites trigger periodic changes in hydrothermal discharge, resulting in significant fluctuations in pH levels, dissolved inorganic carbon, and sulfide concentrations during active venting periods. These variations in physicochemical conditions, in turn, influence the soundscapes of the surrounding marine habitats. Remarkably, the environmental characteristics exhibit notable differences between various geologically active periods, underscoring the complexity of hydrothermal vent impacts. Furthermore, the study suggests that even distant coral ecosystems may be indirectly affected by hydrothermal activity through seasonal changes in soundscapes. These discoveries provide insight into the origins of life and the evolution of early Earth settings facilitated by hydrothermal vent systems, as well as novel perspectives on monitoring and conserving extreme marine ecosystems. The study report was published in Limnology and Oceanography Letters in May 2024, with the co-first author being Ling Chiu (Ph.D. candidate at the Institute of Oceanography, National Taiwan University) and Dr. Min-Chen Wang (Institute of Physiology, Christian-Albrechts-University Kiel). The Academia Sinica's Development Award Project, the Marine Research Station, and the National Science and Technology Council provided funding for the study.

Certain insects, like beetles and butterflies, can undergo massive tissue replacement during their development, a transformation process considered unique to insects. Compared to insects, vertebrates exhibit relatively limited changes in appearance during post-embryonic development. Nonetheless, at the cellular level, whether similar drastic changes occur akin to those observed in insect development remains an unexplored research topic. Dr. Chen-Hui Chen and his team at the Institute of Cellular and Organismic Biology (ICOB) created the palmuscle myofiber tagging and tracking system for in toto monitoring of the growth and fates of ~5000 fast myofibers in developing zebrafish larvae. They found that zebrafish, as a vertebrate model, can similarly undergo complete muscle elimination and replacement during post-embryonic development. Due to limitations in research tools, past studies on vertebrate muscle cells have primarily focused on cell culture models or histological investigations. This study may represent the first instance of simultaneously and continuously observing all muscle cells within an individual at both the organismal and cellular levels. This study finding challenges the current understanding of vertebrate development. This unexpected finding was published in June this year in the EMBO Journal. The first author, Uday Kumar, is affiliated with the Taiwan International Graduate Program, jointly administered by Academia Sinica and National Chung-Hsing University. Other team members include Chun-Yi Fang, Hsiao-Yuh Roan, Shao-Chun Hsu, Chung-Han Wang, and Chen-Hui Chen. This study is supported by funding from the Institute of Cellular and Organismic Biology and grants from Academia Sinica to C.-H.C. (AS-CDA-109-L03 and AS-GCS-112-L01); and grants from National Science and Technology Council, Taiwan, to C.-H.C. (NSTC 110-2628-B-001-016, and NSTC 111-2628-B-001-026).

The transition from natal downs for thermoregulation to juvenile feathers for flight is an environmental adaptation in avian evolution. As the regulatory switches for this transition are mostly unknown, we conducted gene regulatory analysis and functional perturbations in developing feathers. We elucidated four switches. First, extracellular matrix reorganization leads to peripheral pulp formation, mediating epithelial-mesenchymal interactions for branching morphogenesis. Second, α-SMA compartmentalizes dermal papilla stem cells for feather renewal cycling. Third, LEF1 works as a key hub of Wnt signaling to build rachis and convert radial downy to bilateral symmetry. Fourth, scale keratins strengthen feather sheath with SOX14 as the epigenetic regulator. These switches are largely conserved in chicken (precocial) and zebra finch (altricial), two distantly related species, suggesting their conservation in all birds. This study was a collaboration between Dr. Wen-Hsiung Li’s lab (Academia Sinica) and Dr. Cheng-Ming Chuong’s lab (University of South California). Published on May 16 in Nature Communications.

Shifting the focus from land to sea when considering the Cold War in East Asia, Kuan-Jen Chen sheds light on the importance of the ‘oceanic’ lens as a structural imperative in grand strategic thinking.

Expression noise at transcript or protein levels can result in cell-to-cell heterogeneity within an isogenic population. The detailed molecular pathways underlying noise regulation are not fully understood. Dr. Jun-Yi Leu’s group at the Institute of Molecular Biology establishes an experimental evolution strategy to search for mutations that increase expression noise in Saccharomyces cerevisiae and reveals the histone deacetylase Hos2 as a negative noise regulator. They found the Hos2 mutant down-regulated multiple ribosomal protein genes and exhibited partially compromised protein translation, indicating that Hos2 may regulate protein expression noise by modulating the translation machinery. This work was published on May 23, 2024 in Nucleic Acids Research. The lead author of this work, Wei-Han Lin, is a student in the Doctoral Program in Microbial Genomics, which is a collaborating program between Academia Sinica and National Chung Hsing University. Funding was provided by Academia Sinica and the National Science and Technology Council.

Pediatric brain tumors and osteosarcomas often utilize the ALT (Alternative Lengthening of Telomeres) mechanism to length telomeres for cellular immortality. A research team led by Associate Research Fellow Dr. Liuh-yow Chen at the Institute of Molecular Biology, Academia Sinica, discovered that orphan nuclear receptors regulate telomere elongation through APBs (ALT-associated PML bodies) in ALT cancer cells. Additionally, they found that arsenic trioxide (As2O3), a treatment for acute promyelocytic leukemia, can target APBs and inhibit ALT activity in cultured ALT cancer cells and in mouse xenografts, which opens the possibility of repurposing As2O3 for ALT cancer treatments. This research provides deep insights into the biology of ALT-related cancers and a new potential avenue for their treatment. The study was published in Nucleic Acids Research on May 17, 2024. The first author of the paper is Venus Marie Gaela, a PhD student in TIGP-MCB at Academia Sinica. The research was funded by Academia Sinica and the National Science and Technology Council.