Iowa Mutant Apolipoprotein A-I (ApoA-IIowa) Fibrils Target Lysosomes

The single amino acid mutation G26R in human apolipoprotein A-I (apoA-IIowa) is the first mutation that was associated with familial AApoA1 amyloidosis. The N-terminal fragments (amino acid residues 1–83) of apoA-I containing this mutation deposit as amyloid fibrils in patients’ tissues and organs, but the mechanisms of cellular degradation and cytotoxicity have not yet been clarified. In this study, we demonstrated degradation of apoA-IIowa fibrils via the autophagy-lysosomal pathway in human embryonic kidney 293 cells. ApoA-IIowa fibrils induced an increase in lysosomal pH and the cytosolic release of the toxic lysosomal protease cathepsin B. The mitochondrial dysfunction caused by apoA-IIowa fibrils depended on cathepsin B and was ameliorated by increasing the degradation of apoA-IIowa fibrils. Thus, although apoA-IIowa fibril transport to lysosomes and fibril degradation in lysosomes may have occurred, the presence of an excess number of apoA-IIowa fibrils, more than the lysosomes could degrade, may be detrimental to cells. Our results thus provide evidence that the target of apoA-IIowa fibrils is lysosomes, and we thereby gained a novel insight into the mechanism of AApoA1 amyloidosis

Low energy radioactivity BG model in Super-Kamiokande detector from SK-IV data

n/

Follow-up of GWTC-2 gravitational wave events with neutrinos from the Super-Kamiokande detector

n/

Combined Pre-Supernova Alert System with Kamland and Super-Kamiokande

International audiencePreceding a core-collapse supernova, various processes produce an increasing amount of neutrinos of all flavors characterized by mounting energies from the interior of massive stars. Among them, the electron antineutrinos are potentially detectable by terrestrial neutrino experiments such as KamLAND and Super-Kamiokande via inverse beta decay interactions. Once these pre-supernova neutrinos are observed, an early warning of the upcoming core-collapse supernova can be provided. In light of this, KamLAND and Super-Kamiokande have been monitoring pre-supernova neutrinos since 2015 and 2021, respectively. Recently, we performed a joint study between KamLAND and Super-Kamiokande on pre-supernova neutrino detection. A pre-supernova alert system combining the KamLAND detector and the Super-Kamiokande detector is developed and put into operation, which can provide a supernova alert to the astrophysics community. Fully leveraging the complementary properties of these two detectors, the combined alert is expected to resolve a pre-supernova neutrino signal from a 15 M$_{\odot}$ star within 510 pc of the Earth, at a significance level corresponding to a false alarm rate of no more than 1 per century. For a Betelgeuse-like model with optimistic parameters, it can provide early warnings up to 12 hours in advance