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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. 35, No. 3) include:

A growing heart is like a home under construction, with cardiomyocytes as the diligent builders. Scientists have long contemplated the blueprint guiding these builders in their tasks. A collaborative effort by Dr. Cheng-Fu Kao's team from the Institute of Cellular and Organismic Biology, along with Drs. Yao-Ming Chang, Chien-Chang Chen, and Yu-Ting Yen from the Institute of Biomedical Sciences, has uncovered a key player in this process: a protein named RNF20. Working with a suite of advanced genomic analysis tools, the team traced how RNF20 precisely directs the maturation of cardiomyocytes. RNF20 acts like an architect holding the master blueprint of epigenetic regulation, subtly switching genes on and off without altering the DNA itself. This research not only confirms RNF20's indispensable role as an epigenetic regulator in heart development but also opens new avenues for treating heart diseases. This study, published in Cell Reports, provide new perspectives for the advancement of heart health and treatment.

Institutum Iurisprudentiae has published the 2017 Administrative Regulation and Judicial Remedies: Envisioning Administrative Procedure 2.0. This book is edited by Research Professor Dr. Cheng-Yi Huang.

Distinguished Research Fellow Dr. Patrick C.H. Hsieh’s team at the Institute of Biomedical Sciences, Academia Sinica uncovered a pivotal gut-heart axis in post-myocardial infarction (MI) cardiac repair. Employing human clinical samples, nonhuman primate disease models, and mouse cardiac injury models, they revealed the significance of butyrate-producing bacteria, particularly in synthesizing β-hydroxybutyrate post-injury. This breakthrough offers precision medication targets for MI through gut microbiota adjustments. The study, titled "Gut Butyrate-Producers Confer Post-Infarction Cardiac Protection," published in Nature Communications on November 9, involved collaborators from National Cheng Kung University, China Medical University Hospital, Far Eastern Memorial Hospital, and the University of Wisconsin-Madison (UW-Madison).

Heart failure remains a significant global cause of mortality, characterized by the adult human heart's inability to repair itself or compensate for the loss of cardiac muscle cells. Cell therapy, specifically employing stem cells, has emerged as a promising avenue for restoring lost cardiac muscle cells and reviving heart function. Led by the Distinguished Research Fellow Patrick CH Hsieh at the Institute of Biomedical Sciences, Academia Sinica in Taiwan, a pioneering research team has achieved noteworthy breakthroughs in both murine and non-human primate models. The research successfully restored and regenerated damaged hearts through the co-transplantation of human induced pluripotent stem cell (iPSC)-derived endothelial cells and cardiomyocytes. This groundbreaking study, entitled "Combined Treatment of Human iPSC-derived Cardiomyocytes and Endothelial Cells Regenerate the Infarcted Heart in Mice and Non-human Primates," has been published in the prestigious journal Circulation on October 31, 2023. The collaboration between the research team and esteemed scientists from both Taiwan and the United States, including Dr. Tim Kamp and Dr. Tim Hacker from the University of Wisconsin-Madison, has ushered in a new era of possibilities in the field of cardiac regeneration.

Chloroplasts host photosynthesis and other essential biosynthetic reactions that sustain most life forms on Earth. It is therefore vital to understand the composition and operational mechanism of the motor that powers the import of thousands of proteins into chloroplasts. A recent model depicts this motor as an integral inner-membrane protein complex with a hetero-hexameric ATPase domain protruding into the stroma. Distinguished Research Fellow Dr. Hsou-min Li and her group at the Institute of Molecular Biology, Academia Sinica showed that FtsHi1 has its ATPase domain located outside the stromal compartment and FtsHi2 is a soluble protein. This study provides a critical foundation for structural and functional characterization of the motor complex, and has been published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Most eukaryotic genes contain sequences that interrupt the genes’ continuity yet are not translated into proteins. These sequences are removed at the RNA level in a process termed RNA splicing, which occurs on a large ribonucleoprotein complex known as the spliceosome. The DExD/H-box RNA helicase Prp16 plays a pivotal role in the splicing process. Following the branching reaction, it utilizes its ATP-dependent functions to facilitate exon ligation by displacing step-one factors, Cwc25 and Yju2, from the spliceosome’s catalytic center, thus enabling the positioning of the 3’ splice site to the catalytic center. Additionally, Prp16 is well known for its role in proofreading the 5’ splice site and the branch site of pre-mRNA, a function that requires ATP. A team led by Distinguished Research Fellow Soo-Chen Cheng at the Institute of Molecular Biology, Academia Sinic has unveiled a paradoxical role for Prp16 in splicing of pre-mRNA with mutations at splice sites, resulting in a slower splicing reaction. In such cases, Prp16 exhibits an ATP-independent activity by stabilizing the binding of Cwc25, thereby enhancing the branching reaction and leading to aberrant selection of splice sites. This seemly contradictory function of Prp16 raises questions about its role in proofreading splice sites. Nevertheless, it underscores Prp16’s consistent role in propelling the splicing pathway forward. In normal pre-mRNA, Prp16 destabilizes Cwc25 to facilitate exon ligation, whereas for mutant pre-mRNA, it stabilizes Cwc25 to promotes the branching reaction. These discoveries change the current view of splicing fidelity control, leading to the paper’s recognition as Breakthrough Article by NAR.

Under stressed conditions that increase cell demands on purines, all enzymes in the de novo purine synthesis (DNPS) pathway cluster to form purinosomes. Despite discovered 15 years ago, the mechanism of purinosome assembly remains obscure, which impedes specific dissection of its pathophysiological functions. A team led by Distinguished Research Fellow Ruey-Hwa Chen at the Institute of Biological Chemistry, Academia Sinica has identified the first purinosome assembly mechanism and elucidated the dependence of cancer cells on purinosome formation for their proliferation and survival. Current research on cancer metabolism has mainly focused on the reprogramming of metabolic pathways. The discovery of a key role of purinosome formation in cancer progression has opened a new avenue for studying cancer metabolism. The research uncovers the impacts of metabolic enzyme compartmentalization on human malignancies and highlights a potential of purinosome targeting as an anti-cancer strategy. This study has been published in Molecular Cell on October 16.

In the post-COVID-19 era, developing enduring and broad-spectrum antiviral drugs is paramount to preventing widespread outbreaks from variants of the virus and potential emerging coronaviruses. Driven by the viruses' reliance on hACE2 as the primary cellular receptor, Dr. Mi-Hua Tao and Dr. I-Hsuan Wang's research groups in the Institute of Biomedical Sciences at Academia Sinica discovered a monoclonal antibody ch2H2, which exhibited a high affinity to the viral Spike protein binding site on hACE2. This antibody, without affecting the biological function of hACE2, demonstrated robust inhibitory effects against various COVID-19 viral variants in in vivo neutralization studies. Utilizing adeno-associated virus (AAV) delivery in animal experiments, a single injection resulted in sustained and high levels of ch2H2 antibodies in mice. In prophylactic administration against the Omicron variant BA.5, which led to declined vaccine effectiveness, AAV/ch2H2 significantly reduced viral loads and mitigated pulmonary pathological changes. These findings underscore the potential of AAV-delivered hACE2-blocking antibodies as a promising avenue for broad-spectrum antiviral drug development in the future.

As a group of sessile crustaceans, barnacles establish permanent attachment through initial cement secretion at the larval phase followed by continuous cement secretion in juveniles and adults. However, the origins and evolution of barnacle larval and adult cement proteins remain poorly understood. The research team of Benny K.K. Chan, Research Fellow of Biodiversity Research Center, Academia Sinica performed microdissection of larval cement glands, transcriptome and shotgun proteomics and immunohistochemistry validation, successfully identified 30 larval and 27 adult cement proteins of the epibiotic turtle barnacle Chelonibia testudinaria, of which the majority are stage-and barnacle-specific. While only two proteins, SIPC and CP100K, were expressed in both larvae and adults, detection of protease inhibitors and the cross-linking enzyme lysyl oxidase paralogs in larvae and adult cement. Different CP52k cement protein paralogues could be detected in larval and adult cement, suggesting stage-specific cement proteins may arise from duplication followed by changes in expression timing of the duplicates. Interestingly, the biochemical properties of larval-and adult-specific CP52k paralogues exhibited remarkable differences. We conclude that barnacle larval and adult cement systems evolved independently, and both emerged from co-option of existing genes and de novo formation, duplication and functional divergence of lineage-specific cement protein genes. This study has been published in in the journal Molecular Ecology.

The transcription factor TATA-box binding protein (TBP) modulates gene expression in nuclei. This process requires the involvement of nuclear transport receptors, collectively termed karyopherin- (Kap-) in yeast, and various regulatory factors. Previous studies showed that Kap114p, a Kap- that mediates nuclear import of yeast TBP (yTBP), modulates yTBP-dependent transcription. However, how Kap114p associates with yTBP to exert its multifaceted functions has remained elusive. The team led by Dr. Kuo-Chiang Hsia (Institute of Molecular Biology, Academia Sinica) and Dr. Wei-Yi Chen (Institute of Biochemistry and Molecular Biology, College of Life Sciences, National Yang Ming Chiao Tung University) presents a cryo-EM structure of Kap114p, one of the Kap-βs, in complex with TATA box binding protein and reveals a non-canonical function beyond nuclear transport that modulates TBP-dependent transcription. This study has been published in in the journal Nature Communications.

A research team led by Dr. Yi-Ping Hsueh, Distinguished Research Fellow at the Institute of Molecular Biology, Academia Sinca used high-end optical microscopy and biochemical approaches to demonstrate that KLHL17 and SYNPO, two autism-linked proteins, act in concert to regulate the organization and distribution of the spine apparatus, a specialized endoplasmic reticulum structure at excitatory synapses. KLHL17 and SYNPO promote clustering of the spine apparatus in the excitatory synapse to regulate calcium dynamics and consequently influence neuronal plasticity and activation. Furthermore, via collaboration with Dr. Bi-Chang Chen, Associate Research Fellow at the Research Center of Applied Sciences, they applied an improved expansion microscopy technology to successfully observe the three-dimensional ultrastructure and organization of the spine apparatus, as well as of the KLHL17 and SYNPO proteins, with an ultra-resolution of nearly 30 nanometers. Their research clearly links the function of the spine apparatus to ASD via control of synaptic plasticity. This study has been published in the journal PLOS Biology (August 2023).

A study has unraveled a mystery that persisted for fifty years in plant science – the elusive role of Pathogenesis-Related Protein 1 (PR1) in plant immunity. Led by Dr. Yet-Ran Chen at the Agricultural Biotechnology Research Center, Academia Sinica, this research casts a revealing light on the pivotal mechanism governing the enzymatic transformation of canonical immune biomarker PR1 into a potent CAPE cytokine. This transformation initiates plant systemic acquired resistance (SAR), a critical defense function against pathogenic infection. Remarkably, even plants incapable of synthesizing or perceiving salicylic acid, a central hormone for activating SAR, can activate systemic immunity when exposed to trace amounts of CAPE. This achievement serves as a foundation for enhancing crops' resilience against diseases and introduces novel perspectives for mitigating the adverse effects of global warming on plant immunity. This study has been published in the journal Nature Communications (August 2023).

Unlocking the potential of protein activation has historically posed challenges, necessitating extensive screening and biochemical assays. Dr. Kuen-Phon Wu at the Institute of Biological Chemistry has led a team to demonstrate a paradigm shift. By integrating the advanced deep learning tool, ProteinMPNN, they have engineered ubiquitin into a potent allosteric activator tailored for Rsp5 E3 ligase. The entire process was fully automated from protein designs to sample preparation to functional assays took only three months. This milestone heralds a new era, where AI-driven protein design obviates the need for exhaustive experimental screening and validation. This study has been published in in the journal ACS Synthetic Biology (August 2023).

Using well-preserved fossil fish otoliths from the Solomon Sea in the southwest edge of equatorial Pacific Ocean, Dr. Chien-Hsiang Lin’s research team reconstructed deep-sea fish communities over the past 460,000 years. Combining ancient seawater temperature records with fish diversity and abundance, they discovered a close relationship between tropical deep-sea fish communities and fluctuating seawater temperatures. These insights shed light on the intricate dynamics of fish structures in response to temperature changes. This study has been published in in the journal Science Advances in July 2023

The "IceCube" Neutrino Observatory, consisting of over 350 scientists worldwide, has made a breakthrough in astronomy by generating an image of the Milky Way galaxy using high-energy neutrinos for the first time. This confirms the long-standing speculation about the Milky Way being a source of high-energy neutrinos. Accumulating ten years of data on over 60,000 neutrinos, scientists rely on models and machine learning.

Algorithmic bias is an emerging challenge in law enforcement. Dr. Tzu-Wei Hung, Associate Research Fellow from the Institute of European and American Studies, Academia Sinica and Dr. Chun-Ping Yen, assistant professor from Soochow University, form spearhead efforts to analyze racial discrimination in Chicago’s predictive policing with the contrastive causation model.