Yuri Nishino

The chimeric protein p210 BCR-ABL is a major causative factor of chronic myeloid leukemia (CML). Previously, we found that p210 BCR-ABL translocates from the cytosol to the mitochondria upon mitochondrial damage via the interaction of its pleckstrin homology domain (p210-PH) with cardiolipin (CL), a mitochondria-specific phospholipid. However, the precise pathological functions of this event are unknown. Here, using multivalent peptide library screens, we identified a tetravalent peptide, WDD-R4-tet, which binds to the CL-binding region of p210-PH and inhibits the translocation of p210 BCR-ABL to the mitochondria. Notably, WDD-R4-tet induced the apoptosis of CML cells by specifically suppressing the expression of cellular inhibitor of apoptosis 1 and 2 (cIAP1/2), ubiquitin ligases with anti-apoptotic functions, leading to the activation of caspases. Other compounds that inhibited cIAP1/2 also efficiently inhibited the proliferation of CML cells. Thus, WDD-R4-tet might be a novel therapeutic agent for CML, which functions by inhibiting novel cell-survival signaling pathways generated on the mitochondrial outer membrane of CML cells.

Hydrogen polymer electrolyte fuel cells (PEFCs) are key technologies for achieving a low-carbon society, but conventional oxygen reduction reaction (ORR) catalysts sucg as Pt/C suffer from degradadation of carbon supports during operation. To overcome this limitation, we developed a nanostructured catalyst support by coating tin oxide (SnO2) nanoparticles with cobalt-manganese oxide (CMO), enabling nanoscale interface engineering. The CMO layer was formed via electroless deposition of cobalt-manganese oxyhydroxide (CMOH) followed by thermal conversion at 300 °C. Platinum (Pt) and carbon black (Ketjenblack®, KB) were then incorporated to obtain Pt-CMO-SnO2/KB. The resulting catalyst exhibited a 1.97-fold higher mass activity (119.9 A gPt-1 at 0.9 V) than conventional Pt/C and showed significantly enhanced durability, retaining 33% more mass activity after voltage cycliying. Scanning transmission electron microscopy (STEM) combined with energy-dispersive X-ray spectroscopy (EDX) revealed selective Pt deposition on the CMO surface rather than on carbon. X-ray photoelectron spectroscopy (XPS) further confirmed strong metal-support interactions that suppressed Pt agglomeration and detachment. This nanointerface-guided design provides as effective and scalable strategy for improving ORR activity and durability in next-generation PEFC catalysts.

Chloroplast-actin (cp-actin) filaments are crucial for light-induced chloroplast movement, and appear in the front region of moving chloroplasts when visualized using GFP-mouse Talin. They are short and thick, exist between a chloroplast and the plasma membrane, and move actively and rapidly compared to cytoplasmic long actin filaments that run through a cell. The average period during which a cp-actin filament was observed at the same position was less than 0.5 s. The average lengths of the cp-actin filaments calculated from those at the front region of the moving chloroplast and those around the chloroplast periphery after stopping the movement were almost the same, approximately 0.8 µm. Each cp-actin filament is shown as a dotted line consisting of 4-5 dots. The vector sum of cp-actin filaments in a moving chloroplast is parallel to the moving direction of the chloroplast, suggesting that the direction of chloroplast movement is regulated by the vector sum of cp-actin filaments. However, once the chloroplasts stopped moving, the vector sum of the cp-actin filaments around the chloroplast periphery was close to zero, indicating that the direction of movement was undecided. To determine the precise structure of cp-actin filaments under electron microscopy, Arabidopsis leaves and fern Adiantum capillus-veneris gametophytes were frozen using a high-pressure freezer, and observed under electron microscopy. However, no bundled microfilaments were found, suggesting that the cp-actin filaments were unstable even under high-pressure freezing.