Sequestosome1 (p62/SQSTM 1) is a multidomain protein that interacts with the autophagy machinery as a key adaptor of target cargo. It interacts with phagophores through the LC3-interacting (LIR) domain and with the ubiquitinated protein aggregates through the ubiquitin-associated domain (UBA) domain. It sequesters the target cargo into inclusion bodies by its PB1 domain. This protein is further the central hub that interacts with several key signaling proteins. Emerging evidence implicates p62 in the induction of multiple cellular oncogenic transformations. Indeed, p62 upregulation and/or reduced degradation have been implicated in tumor formation, cancer promotion as well as in resistance to therapy. It has been established that the process of autophagy regulates the levels of p62. Autophagy-dependent apoptotic activity of p62 is recently being reported. It is evident that p62 plays a critical role in both autophagy and apoptosis. Therefore in this review we discuss the role of p62 in autophagy, apoptosis and cancer through its different domains and outline the importance of modulating cellular levels of p62 in cancer therapeutics.
Astrocytes directly participate in learning and memory. However, the structural association between astrocytes and memory-encoding engram neurons after learning remains to be elucidated. We developed astrocyte-enhanced green fluorescent protein reconstitution across synaptic partners (eGRASP) to examine tripartite synapses between astrocytes and engram neurons. Using astrocyte-eGRASP, we found that astrocytes had increased connections to engram neurons after learning. Dendritic spines with astrocytic contacts showed enhanced morphology. Live-cell imaging of astrocyte-eGRASP revealed that astrocytic connections are stabilized by neuronal activity. These results indicate that astrocytes distinguish contact between engram neurons and generate engram-specific contact patterns during learning.
Despite their significance in numerous applications, many critical minerals and metals are still considered minor. Since most of them are not found alone in mineral deposits, their co- or by-production depends on the production of base metals and other major commodities. In many cases, the concentration of the minor metals is low enough not to be considered part of the production. Hence, their supply is not always secured, their availability decreases, and their criticality increases. Many researchers have addressed this issue, but no one has set actual impact factors other than economic ones that should determine the production of these minor commodities. This study identified several parameters, the number and diversity of which gave birth to developing a computational tool using a multi-criteria-decision analysis model based on the Analytical Hierarchical Process (AHP) and Python. This unprecedented methodology was applied to evaluate the production status of different commodities in a polymetallic deposit located in Chovdar, Azerbaijan. The evaluation outcomes indicated in quantifiable terms the production potentials for several commodities in the deposit and justified the great perspectives of this tool to evaluate all kinds of polymetallic deposits concerning the co- and by-production of several minor critical raw materials.
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