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Biology subjects

Matsushita, A.

Publications and source records attributed to Matsushita, A..

4 recordsLinked to original sources

Time-series foundation modeling enables accurate lake ecosystem forecasting

Accurate ecological forecasting is increasingly essential for understanding and managing ecosystem responses to climate variability and anthropogenic pressures; however, prediction remains difficult in lakes because key biological variables, such as phytoplankton biomass, exhibit nonlinear dynamics, observational noise, data sparsity, and non-stationarity. This study aimed to test whether large pre-trained time-series foundation models can improve forecasts of lake phytoplankton dynamics, focusing on chlorophyll-a (Chl.a) and water-quality variables in two ecologically contrasting Japanese lakes, the deep-stratified Lake Biwa and the shallow nutrient-rich Lake Kasumigaura. Using extensive monthly monitoring records spanning up to 30 years, we benchmarked two time-series foundation models - Transformer-based Chronos-T5 and probabilistic Lag-Llama - against 15 statistical (AR, ARIMA, SARIMA, Prophet), machine learning (Random Forest, XGBoost, KNN, SVR), and deep learning (LSTM, CNN, TCN, and SSA-hybrid) approaches. Chronos-T5 achieved superior reproduction accuracy and stability across diverse environmental variables and outperformed all other tested models. This performance stemmed from its ability to capture long-term dependencies and complex temporal patterns through large-scale pre-training. We further identified an optimal training window of approximately 14 years, balancing data sufficiency with regime stability, beyond which model accuracy diminished owing to ecological regime shifts. Our findings highlight the transformative potential of time-series foundation models for ecological forecasting, providing a scalable, data-driven framework that can underpin robust early warning systems and adaptive management strategies for aquatic ecosystems worldwide.

ecology↗

Expanding and Decoding the Chemistry of Phospholipid Headgroup in Eukaryotes

Cellular membranes have diverse phospholipids, chemical differences in whose headgroups impact many biological processes. Phosphatidylcholine is an essential phospholipid for human health, but not universally required for life. The evolutionary mechanisms underlying phospholipid preferences remain poorly understood, due to the difficulty of investigating metabolite structure-activity relationships in a cellular context. Here, we developed a generalizable metabolic-rewiring method to manipulate phospholipid headgroups together and their biological effects. This approach utilizes synthetic media to hijack evolutionarily conserved phosphatidylcholine biosynthesis, leveraging xenobiotics as principal precursors for scalable headgroup transformations. By identifying over 100 artificial headgroups, we expanded the chemical diversity of xenobiotic phospholipids. Unexpectedly, we discovered that subtle headgroup alterations produced distinct mammalian cellular activities. We demonstrated that chemical headgroup modifications differentially elicited structure-dependent effects on phospholipid-protein interactions, calcium dynamics, transcriptomic profiles, and stem cell differentiation. Notably, cross-species comparison revealed that human and yeast cells have different headgroup preferences critical for cell life and death. As proof-of-concept, interactome analysis identified headgroup-sensitive human microproteins vital for mitochondrial respiration, but non-conserved in yeast. These results exemplify the evolutionary diversity of key phospholipid-protein interactions, illustrating why humans depend on phosphatidylcholine. Overall, our findings establish a programmable platform for elucidating and engineering phospholipid-driven cellular functions.

cell biology↗

A combination of two-enzyme system and enzyme engineering improved the activity of a new PET hydrolase identified from soil bacterial genome

We here report a novel PET hydrolase originating from a soil microbial genome sequence. This enzyme, bbPET0069, exhibits characteristics resembling a cutinase-like Type I PET-degrading enzyme but lacks disulfide bonds. Notably, bbPET0069 displayed remarkable synergy with Candida antarctica lipase B (CALB), demonstrating rapid and efficient PET degradation. To improve the PET degradation activity of bbPET0069, we employed a three-dimensional (3D) structural modeling to identify mutation sites around its substrate binding domain combined with a protein language model for effective mutation prediction. Through three initial rounds of directed evolution, we achieved a significant enhancement in PET degradation with CALB, resulting in a 12.6-fold increase compared to wild-type bbPET0069 without CALB. We confirmed its PET degradation activity in PET nanoparticles and films, and our proposed approach enabled efficient PET degradation to terephthalic acid monomers up to 95.5%. Our approach, which integrates a two-enzyme system with protein engineering, demonstrates the potential for enhancing the activity of emerging PET-degradation enzymes, which may possess unique attributes. Graphical AbstractA novel PET hydrolase, bbPET0069, was identified from a soil microbial genome. bbPET0069 and CALB showed remarkable synergy in PET degradation. Using surface feature analysis, PET degradation activity of bbPET0069 was significantly improved. This combination of a two-enzyme system and surface feature analysis holds promise for enhancing emerging PET-degradation enzymes. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=130 SRC="FIGDIR/small/578500v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@4c1c08org.highwire.dtl.DTLVardef@c47c74org.highwire.dtl.DTLVardef@1c6cd19org.highwire.dtl.DTLVardef@c32e73_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Uncovering novel endolysins against methicillin-resistant Staphylococcus aureus using microbial single-cell genome sequencing

Endolysins, peptidoglycan hydrolases derived from bacteriophages (phages), are being developed as a promising alternative to conventional antibiotics. To obtain highly active endolysins, a diverse library of endolysins is vital. We here propose microbial single-cell genome sequencing as an efficient tool to discover dozens of previously unknown endolysins, owing to its culture-independent sequencing method. As a proof-of-concept, we analyzed and recovered endolysin genes within prophage regions of Staphylococcus single-amplified genomes (SAGs) in human skin microbiome samples. We constructed a library of chimeric endolysins by shuffling domains of the natural endolysins and performed high-throughput screening against Staphylococcus aureus. One of the lead endolysins, bbst1027, exhibited desirable antimicrobial properties such as rapid bactericidal activity, no detectable resistance development, and in vivo efficacy. We foresee that this endolysin discovery pipeline is in principle applicable to any bacterial target, and boost the development of novel antimicrobial agents.

microbiology↗