An atypical GABARAP binding module drives the pro-autophagic potential of the AML-associated NPM1c variant.

The nucleolar scaffold protein NPM1 is a multifunctional regulator of cellular homeostasis, genome integrity, and stress response. NPM1 mutations, known as NPM1c variants promoting its aberrant cytoplasmic localization, are the most frequent genetic alterations in acute myeloid leukemia (AML). A hallmark of AML cells is their dependency on elevated autophagic flux. Here, we show that NPM1 and NPM1c induce the autophagy-lysosome pathway by activating the master transcription factor TFEB, thereby coordinating the expression of lysosomal proteins and autophagy regulators. Importantly, both NPM1 and NPM1c bind to autophagy modifiers of the GABARAP subfamily through an atypical binding module preserved within its N terminus. The propensity of NPM1c to induce autophagy depends on this module, likely indicating that NPM1c exerts its pro-autophagic activity by direct engagement with GABARAPL1. Our data report a non-canonical binding mode of GABARAP family members that drives the pro-autophagic potential of NPM1c, potentially enabling therapeutic options.

Lane clearance approach for emergency vehicles in highways network.

The steady rise in the number of vehicles in modern urban areas and poor conformance to traffic laws (or rules) lead to avoidable commute delays and traffic jams. Also, there is an increased likelihood of road accidents requiring immediate medical attention. Emergency vehicle (EV) service is adversely affected due to the unavailability of the clear lane that supports EVs to get to their endpoint without being delayed along the national highways. Moreover, the EV's sirens have a limited range, which may fail to reach and notify other vehicular traffic about its mobility promptly. In addition to this range constraint, EVs in motion often lose their communication links while moving from network to network. This paper delineates an approach using the next generation mobile internet protocol, for automated pathway clearance, for EVs. The prototype model of the proposed approach was experimentally designed and implemented. The proposed design concept is validated by performance characterization via numerical analysis.