Aberrant metabolic forms of the prion protein (PrP), membrane-associated CtmPrP and cytosolic (cyPrP) interact with the cytosolic ubiquitin E3 ligase, Mahogunin Ring Finger-1 (MGRN1) and affect lysosomes. MGRN1 also interacts with and ubiquitinates TSG101, an ESCRT-I protein, involved in endocytosis. We report that MGRN1 modulates macroautophagy. In cultured cells, functional depletion of MGRN1 or overexpression of CtmPrP and cyPrP blocks autophagosome–lysosome fusion, alleviates the autophagic flux and its degradative competence. Concurrently, the degradation of cargo from the endo-lysosomal pathway is also affected. This is significant because catalytic inactivation of MGRN1 alleviates fusion of lysosomes with either autophagosomes (via amphisomes) or late endosomes (either direct or mediated through amphisomes), without drastically perturbing maturation of late endosomes, generation of amphisomes or lysosomal proteolytic activity. The compromised lysosomal fusion events are rescued by overexpression of TSG101 and/or its monoubiquitination in the presence of MGRN1. Thus, for the first time we elucidate that MGRN1 simultaneously modulates both autophagy and heterophagy via ubiquitin-mediated post-translational modification of TSG101.

A pandemic is a disease that spreads across a large area like multiple continents or worldwide. More than 211 nations are already affected by Covid-19. The World Health Organization (WHO) on 11 March 2020 declared Covid-19 a pandemic. There are more than 1,282,931 cases of the coronavirus illness over 211 countries and territories around the world. Currently coronavirus has no proper treatment in Medical Science, increasing the number of affected people day by day with the number of cases worldwide of novel coronavirus surpassing 1,282,931, with some 72,616 deaths approximately. That is why the main objective of the present investigation is to identify the significant risk factor. Also, in this study we are continuously monitoring the spread of coronavirus. In this study we use a new TOPSIS MCDM approach and GMDH apply to select the significant risk factor and continuous monitoring of death due to Covid-19. Result indicates that "contamination due to contact with the infected person" is the main responsible factor behind the pandemic COVID-19. Also, in this investigation we get an optimal model by which we can monitor the death from Coronavirus within the affected person continuously.

MGRN1-mediated ubiquitination of α-tubulin regulates microtubule stability and mitotic spindle positioning in mitotic cells. This study elucidates the effect of MGRN1-mediated ubiquitination of α-tubulin in interphase cells. Here, we show that MGRN1-mediated ubiquitination regulates dynamics of EB1-labeled plus ends of microtubules. Intracellular transport of mitochondria and endosomes are affected in cultured cells where functional MGRN1 is depleted. Defects in microtubule-dependent organellar transport are evident in cells where noncanonical K6-mediated ubiquitination of α-tubulin by MGRN1 is compromised. Loss of MGRN1 has been previously correlated with late-onset spongiform neurodegeneration. Mislocalised cytosolically exposed PrP ( PrP) interacts with MGRN1 leading to its loss of function. Expression of PrP generating mutants of PrP[PrP(A117V) and PrP(KHII)] lead to decrease in MGRN1-mediated ubiquitination of α-tubulin and intracellular transport defects. Brain lysates from PrP(A117V) transgenic mice also indicate loss of tubulin polymerization as compared to non-transgenic controls. Depletion of MGRN1 activity may hamper physiologically important processes like mitochondrial movement in neuronal processes and intracellular transport of ligands through the endosomal pathway thereby contributing to the pathogenesis of neurodegeneration in certain types of prion diseases.

In this investigation, we have put forward a novel multi-criteria decision-making (MCDM) technique, intuitionistic fuzzy best-worst method (intuitionistic fuzzy BWM). Moreover, we have designed a novel hybrid MCDM technique called intuitionistic fuzzy best-worst analytic hierarchy process (intuitionistic fuzzy BWAHP) which is the amalgamation of intuitionistic fuzzy BWM and analytic hierarchy process (AHP). In this study, BWM finds its use to evaluate the weightage (or priority value) of criteria, and using AHP, the local weights of alternatives are decided. The proposed technique is utilized to recognize the most significant alternative (or indicator), for the efficiency of a water treatment plant. Observing the result, it can be said that the 'water quality' is the most responsible alternative. The consistency ratio value which is found by our proposed method is less, compared to the existing BWM and fuzzy BWM techniques. Finally, using a comparative study and sensitivity analysis, we verify the findings produced by our proposed method.

No abstract