Delayed particles in EAS at Akeno

Using two 2.25 square meter fast scintillation detectors, delayed particles in cosmic ray showers (CRS) have been observed at Akeno Observatory. These are set under 1 m concrete and 2.5 cm lead plates respectively. About 2500 CRS are analyzed. The lateral distribution of delayed particles for the CRS size 10 to the 7th power is flatter than that for to the 7th power. The lateral density of delayed particles is almost constant for the size range 2.2 X 10 to the 5th power approx. 10 to the 7th power and increases rapidly above 10 to the 7th power. These facts may suggest change of nuclear interaction at 10 to the 7th power and substantially the existence of heavy particles with long life

p62 targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding

p62 is recruited to the ER at an early-stage autophagosome formation independently of most Atg proteins

Variable-grasping-mode underactuated soft gripper with environmental contact-based operation

A novel robotic gripper with soft surfaces and underactuated joints was proposed. The soft surface was fabricated from a deformable rubber bag filled with incompressible fluid and a microgripper inside the fluid. A ratchet was installed at the underactuated joint so that the joint\u27s rotation caused by contact with an environment, such as a supporting surface, can be preserved, and the actions of scooping and enveloping an object are realized. With one actuator, the gripper realized three modes, i.e., parallel gripper, pinching, and enveloping. The range of graspable objects was wide and included soft, rigid, deformable, fragile, small (boundary length less than 30 mm), large (more than 80 mm long), thin (less than 0.5 mm), and heavy (more than 3 kg) objects.INSPEC Accession Number: 1671251

The Intriguing Life of Autophagosomes

Autophagosomes are double-membrane vesicles characteristic of macroautophagy, a degradative pathway for cytoplasmic material and organelles terminating in the lysosomal or vacuole compartment for mammals and yeast, respectively. This highly dynamic, multi-step process requires significant membrane reorganization events at different stages of the macroautophagic process. Such events include exchange and flow of lipids and proteins between membranes and vesicles (e.g., during initiation and growth of the phagophore), vesicular positioning and trafficking within the cell (e.g., autophagosome location and movement) and fusion of autophagosomes with the boundary membranes of the degradative compartment. Here, we review current knowledge on the contribution of different organelles to the formation of autophagosomes, their trafficking and fate within the cell. We will consider some of the unresolved questions related to the molecular mechanisms that regulate the “life and death” of the autophagosome

Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism

The Keap1-Nrf2 system is central for mammalian cytoprotection against various stresses and a drug target for disease prevention and treatment. One model for the molecular mechanisms leading to Nrf2 activation is the Hinge-Latch model, where the DLGex-binding motif of Nrf2 dissociates from Keap1 as a latch, while the ETGE motif remains attached to Keap1 as a hinge. To overcome the technical difficulties in examining the binding status of the two motifs during protein-protein interaction (PPI) simultaneously, we utilized NMR spectroscopy titration experiments. Our results revealed that latch dissociation is triggered by low-molecular-weight Keap1-Nrf2 PPI inhibitors and occurs during p62-mediated Nrf2 activation, but not by electrophilic Nrf2 inducers. This study demonstrates that Keap1 utilizes a unique Hinge-Latch mechanism for Nrf2 activation upon challenge by non-electrophilic PPI-inhibiting stimuli, and provides critical insight for the pharmacological development of next-generation Nrf2 activators targeting the Keap1-Nrf2 PPI

Starvation Induced Cell Death in Autophagy-Defective Yeast Mutants Is Caused by Mitochondria Dysfunction

Autophagy is a highly-conserved cellular degradation and recycling system that is essential for cell survival during nutrient starvation. The loss of viability had been used as an initial screen to identify autophagy-defective (atg) mutants of the yeast Saccharomyces cerevisiae, but the mechanism of cell death in these mutants has remained unclear. When cells grown in a rich medium were transferred to a synthetic nitrogen starvation media, secreted metabolites lowered the extracellular pH below 3.0 and autophagy-defective mutants mostly died. We found that buffering of the starvation medium dramatically restored the viability of atg mutants. In response to starvation, wild-type (WT) cells were able to upregulate components of the respiratory pathway and ROS (reactive oxygen species) scavenging enzymes, but atg mutants lacked this synthetic capacity. Consequently, autophagy-defective mutants accumulated the high level of ROS, leading to deficient respiratory function, resulting in the loss of mitochondria DNA (mtDNA). We also showed that mtDNA deficient cells are subject to cell death under low pH starvation conditions. Taken together, under starvation conditions non-selective autophagy, rather than mitophagy, plays an essential role in preventing ROS accumulation, and thus in maintaining mitochondria function. The failure of response to starvation is the major cause of cell death in atg mutants