Thimet oligopeptidase (EC 3.4.24.15) key functions suggested by knockout mice phenotype characterization

Thimet oligopeptidase (THOP1) is thought to be involved in neuropeptide metabolism, antigen presentation, neurodegeneration, and cancer. Herein, the generation of THOP1 C57BL/6 knockout mice (THOP1(-/-)) is described showing that they are viable, have estrus cycle, fertility, and a number of puppies per litter similar to C57BL/6 wild type mice (WT). In specific brain regions, THOP1(-/-) exhibit altered mRNA expression of proteasome beta5, serotonin 5HT2a receptor and dopamine D2 receptor, but not of neurolysin (NLN). Peptidomic analysis identifies differences in intracellular peptide ratios between THOP1(-/-) and WT mice, which may affect normal cellular functioning. In an experimental model of multiple sclerosis THOP1(-/-) mice present worse clinical behavior scores compared to WT mice, corroborating its possible involvement in neurodegenerative diseases. THOP1(-/-) mice also exhibit better survival and improved behavior in a sepsis model, but also a greater peripheral pain sensitivity measured in the hot plate test after bradykinin administration in the paw. THOP1(-/-) mice show depressive-like behavior, as well as attention and memory retention deficits. Altogether, these results reveal a role of THOP1 on specific behaviors, immune-stimulated neurodegeneration, and infection-induced inflammation

Analysis of the dynamics of a spacecraft in the vicinity of an asteroid binary system with equal masses

In this work, we performed a dynamical analysis of a spacecraft around a nearly equal-mass binary near-Earth asteroid with application to the asteroid 2017 YE5, which is also a possible dormant Jupiter-family comet. Thus, we investigated the motion of a particle around this binary system using the circular restricted three-body problem. We calculated the locations of the Lagrangian points of the system and their Jacobi constant. Through numerical simulations, using the Poincaré Surface of Sections, it was possible to find several prograde and retrograde periodic orbits around each binary system's primary, some exhibiting significantly-sized higher-order behavior. We also calculated the stability of these orbits. After finding the periodic orbits, we investigated the influence of solar radiation pressure on these orbits. For this analysis, we considered that the area-to-mass ratio equals 0.01 and 0.1. We also performed a spacecraft lifetime analysis considering the physical and orbital characteristics of the 2017YE5 system and investigated the behavior of a spacecraft in the vicinity of this system. We analyzed direct and retrograde orbits for different values of Jacobi's constant. This study investigated orbits that survive for at least six months, not colliding or escaping the system during that time. We also analyze the initial conditions that cause the spacecraft to collide with M1 or M2, or escape from the system. In this work, we take into account the gravitational forces of the binary asteroid system and the solar radiation pressure (SRP). Finally, we calculated optimal bi-impulsive orbital maneuvers between the collinear Lagrangian points. We found a family of possible orbital transfers considering times of flight between 0.1 and 1 day.publishe