RIKEN Advanced Science Institute

Abstract We report the detection of methanol (CH 3 OH) toward interstellar comet 3I/ATLAS using the Atacama Compact Array of the Atacama Large Millimeter/submillimeter Array (ALMA) on UT 2025 August 28, September 18 and 22, and October 1 and of hydrogen cyanide (HCN) on September 12 and 15. These observations spanned pre-perihelion heliocentric distances ( r H ) of 2.6–1.7 au. The molecules showed outgassing patterns distinct from one another, with HCN production being depleted in the sunward hemisphere of the coma, whereas CH 3 OH was enhanced in that direction. Statistical analysis of molecular scale lengths in 3I/ATLAS indicated that CH 3 OH included production from coma sources at L p &gt; 258 km at 99% confidence. However, low signal-to-noise ratio (S/N) on long baselines, which sample emission on small spatial scales closest to the nucleus, prevented definitively ruling out CH 3 OH as purely a parent species. In contrast, HCN production was indistinguishable from direct nucleus sublimation. The CH 3 OH production rate increased sharply from August through October, including an uptick near the inner edge of the H 2 O sublimation zone at r H = 2 au. Compared to comets measured to date at radio wavelengths, the derived CH 3 OH/HCN ratios in 3I/ATLAS of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mn>12</mml:mn> <mml:msubsup> <mml:mrow> <mml:mn>4</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>−</mml:mo> <mml:mn>34</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>+</mml:mo> <mml:mn>30</mml:mn> </mml:mrow> </mml:msubsup> </mml:math> and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:mn>7</mml:mn> <mml:msubsup> <mml:mrow> <mml:mn>9</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>−</mml:mo> <mml:mn>14</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>+</mml:mo> <mml:mn>11</mml:mn> </mml:mrow> </mml:msubsup> </mml:math> on September 12 and 15, respectively, are among the most enriched values measured in any comet, surpassed only by anomalous solar system comet C/2016 R2 (Pan-STARRS).

Abstract Cytosolic peptide:N-glycanase (Ngly1 in mammals) and endo-β-N-acetylglucosaminidase (ENGase) are deglycosylating enzymes. Detection methods for the Ngly1 and ENGase activities in the cytosol are necessary for understanding the deglycosylation of the N-glycoproteins during endoplasmic reticulum-associated degradation. We previously reported the development of a detection method for Ngly1 using an engineered split intein that self-catalyzes protein trans-splicing (PTS) and NanoLuc luciferase. Here, we report a detection method for the ENGase activity using a PTS-based approach. By employing bioluminescence resonance energy transfer (BRET), we successfully detected the endogenous levels of Ngly1 and ENGase. The PTS-based BRET assay can be used to characterize the enzyme functions in the cell cytosol.

Mechanical oscillations play fundamental roles in cellular processes such as motility, signalling, and structural regulation; however, the mechanisms by which artificial cytoskeletal networks can be engineered to reproduce such autonomous oscillatory behaviours remain poorly understood. In this study, we demonstrate that a chemically polyethylene glycol-crosslinked filamentous actin hydrogel exhibits autonomous, long-lasting, and synchronised mechanical oscillations during self-organised polymerisation. These oscillations arise from chemo-mechanical responses coupled with the treadmilling polymerisation-depolymerisation equilibrium of filamentous actin. We propose that the rigid and highly hierarchical structure of the chemically crosslinked network plays an important role in the emergence of such autonomous mechanical oscillations. Our results reveal how hierarchical crosslinking and chemo-mechanical coupling drive sustained oscillations in active polymer networks, providing new insight into the fundamental mechanisms underlying autonomous dynamics in soft materials.

Abstract Receptor tyrosine kinases (RTKs) are a major family of cell surface receptor proteins responsible for various cellular functions in animal cells, including fate decisions, metabolism, polarization and migration. Lateral mobility, dimerization, clustering, and oligomerization are crucial behaviors in the activation process of RTKs on the cell surface. However, relationships between these molecular behaviors and molecular function remain to be elucidated, except for a few RTK members. Here, using an automated live-cell single-molecule imaging and analysis system, we studied the behavior of 52 of the 58 human RTK species on living cells over time during stimulation with ligands. We extracted 72 single-molecule parameters for each RTK species to examine their relationship to function, structure, and evolution. We noticed that RTKs’ ability to inhibit or support cell growth, as observed in a large-scale loss-of-function experiment in the public domain, significantly relates to their behavior. Growth-inhibitory signaling was coupled with the immediate formation of immobile clusters, followed by the enlargement of immobile and slow-mobile domains. In contrast, growth-supportive signaling coupled with higher lateral diffusivity and delayed clustering of immobile molecules. The relationship between structure and function suggests that functional differences are related to partitioning into membrane rafts and changes in mobility associated with phosphatidylinositol turnover. In multiple linear regression models, molecular behavior explained half or more of the molecular function related to cell growth. This level of explainability is comparable to that of evolutionary grouping.

Zwitterionic heterocycles hold significant therapeutic potential; however, their application is often hindered by poor membrane permeability and limited target-cell selectivity. Here, we report an innovative strategy for the in situ synthesis of these compounds within cancer cells, using a rationally designed precursor that is nontoxic, non-ionic, and membrane permeable. The synthesis is initiated by endogenous acrolein, an oncometabolite elevated in cancer cells, which triggers a cascade involving 1,3-dipolar cycloaddition, diazo formation, carbamate cleavage, imine formation, intramolecular 6π-azaelectrocyclization, oxidative aromatization, and ester hydrolysis. We validated this methodology in human lung adenocarcinoma (A549) cells, where the in situ-synthesized zwitterionic heterocycle exhibited anticancer activity. Conversely, its pre-synthesized congener showed minimal cytotoxicity, underscoring the poor membrane permeability of the zwitterionic form. Precursor optimization resulted in a lead compound that, upon administration to A549 cells, converted into a cytotoxic zwitterionic heterocycle with a half-maximal inhibitory concentration (IC50) of 6.2 µM. The lead precursor showed exceptional selectivity, with no cytotoxicity in normal human diploid (TIG3) cells. This selectivity arises because healthy cells contain low acrolein levels, insufficient to trigger the activation cascade. Our approach effectively addresses the key therapeutic challenges associated with zwitterionic heterocycles.

The Irbene single-baseline radio interferometer (ISBI), operated by the Ventspils International Radio Astronomy Centre (VIRAC), offers a rare and versatile configuration in modern radio astronomy. Combining the 32-m and 16-m fully steerable parabolic radio telescopes separated by an 800-m baseline, this system possesses a unique capability for high-sensitivity, time-domain interferometric observations. Unlike large interferometric arrays optimized for sub-arcsecond resolution imaging, the Irbene system is tailored for studies that require high temporal resolution and a strong signal-to-noise ratio. This paper reviews key scientific applications of the Irbene interferometer, including simultaneous methanol maser and radio continuum variability studies, high-cadence monitoring of quasi-periodic pulsations (QPPs) in stellar flares, ionospheric diagnostics using GNSS signals, orbit determination of navigation satellites and forward scatter radar techniques for space object detection. These diverse applications demonstrate the scientific potential of compact interferometric systems in an era dominated by large-scale observatories.

Polydopamine-coated magnetoliposomes (PDA-MLs) are adhesivebiocompositenanomaterials commonly employed in intracellular applications suchas controlled drug delivery, theranostics, and biosensing. However,the influence of their adhesive properties on lectin–glycaninteractions remains unexplored. In this study, we developed PDA-MLsas magnetic sensing labels for the rapid detection of lectin–glycanbinding using alternating current (AC) magnetization measurementsin liquid media. The adhesive PDA-ML surface enables facile biomoleculeadsorption, facilitating their integration into biosensors. The effectsof dopamine-polymerization time on the morphological and functionalproperties of PDA-MLs were systematically investigated. Extended polymerizationresulted in a thicker PDA layer that enhanced lectin immobilizationon the ML surface. Multivalent N-glycan-clustered albumin facilitatedcross-linking among lectin-immobilized PDA-MLs, leading to remarkablechanges in the AC magnetization, compared with interactions with monovalentGal-N-glycan and Sia-N-glycan. Specific lectin–glycan pairsproduced distinct changes in AC magnetization spectra, whereas mismatchedcombinations showed minimal changes. These findings reveal that structure–propertyrelationships are critical to the design of PDA-ML-based biorecognitionsystems, highlighting their potential in biosensing and bioanalyticalapplications.