Development and Characterization of a low intensity vibrational system for microgravity studies.

The advent of extended-duration human spaceflight demands a better comprehension of the physiological impacts of microgravity. One primary concern is the adverse impact on the musculoskeletal system, including muscle atrophy and bone density reduction. Ground-based microgravity simulations have provided insights, with vibrational bioreactors emerging as potential mitigators of these negative effects. Despite the potential they have, the adaptation of vibrational bioreactors for space remains unfulfilled, resulting in a significant gap in microgravity research. This paper introduces the first automated low-intensity vibrational (LIV) bioreactor designed specifically for the International Space Station (ISS) environment. Our research covers the bioreactor's design and characterization, the selection of an optimal linear guide for consistent 1-axis acceleration, a thorough analysis of its thermal and diffusion dynamics, and the pioneering use of BioMed Clear resin for enhanced scaffold design. This advancement sets the stage for more authentic space-based biological studies, vital for ensuring the safety of future space explorations.

c-Jun N-terminal Kinase Mediates Ligand-independent p75NTR Signaling in Mesencephalic Cells Subjected to Oxidative Stress.

The p75 neurotrophin receptor (p75NTR) is a multifunctional protein that regulates cellular responses to pathological conditions in specific regions of the nervous system. Activation of p75NTR in certain neuronal populations induces proteolytic processing of the receptor, thereby generating p75NTR fragments that facilitate downstream signaling. Expression of p75NTR has been reported in neurons of the ventral midbrain, but p75NTR signaling mechanisms in such cells are poorly understood. Here, we used Lund Human Mesencephalic cells, a population of neuronal cells derived from the ventral mesencephalon, to evaluate the effects of oxidative stress on p75NTR signaling. Subjection of the cells to oxidative stress resulted in decreased cell-surface localization of p75NTR and intracellular accumulation of p75NTR fragments. Oxidative stress-induced p75NTR processing was reduced by pharmacological inhibition of metalloproteases or γ-secretase, but was unaltered by blockade of the ligand-binding domain of p75NTR. Furthermore, inhibition of c-Jun N-terminal Kinase (JNK) decreased p75NTR cleavage induced by oxidative damage. Altogether, these results support a mechanism of p75NTR activation in which oxidative stress stimulates JNK signaling, thereby facilitating p75NTR processing via a ligand-independent mechanism involving induction of metalloprotease and γ-secretase activity. These findings reveal a novel role for JNK in ligand-independent p75NTR signaling, and, considering the susceptibility of mesencephalic neurons to oxidative damage associated with Parkinson's disease (PD), merit further investigation into the effects of p75NTR on PD-related neurodegeneration.