Biology subjects

Khan, M. R.

Publications and source records attributed to Khan, M. R..

4 recordsLinked to original sources

bioRxiv2022

Enhanced mTORC1 signaling and Protein Synthesis in Parkinson Disease Pathogenesis

Pathologic -syn destabilizes the TSC 1 and 2 complex leading to mTORC1 activation, enhanced protein translation and neurodegeneration in PD. AbstractPathological -synuclein (-syn) plays an important role in the pathogenesis of -synucleinopathies such as Parkinsons disease (PD). Disruption of protein homeostasis is thought be central to PD pathogenesis, however the molecular mechanism of this deregulation is poorly understood. Here we report that pathologic -syn binds to tuberous sclerosis protein (TSC) 2 and destabilizes the TSC1-TSC2 complex leading to activation of the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and enhanced mRNA translation. Dopamine neuron loss, behavioral deficits and aberrant biochemical signaling in the -syn preformed fibril (PFF) and Drosophila -syn transgenic models of pathologic -syn induced degeneration were attenuated by genetic and pharmacologic inhibition of mTOR and protein translation. Our findings establish a potential molecular mechanism by which pathologic -syn activates mTORC1 leading to enhanced protein translation and concomitant neurodegeneration in PD.

neuroscience↗

bioRxiv2022

Miltefosine attenuates inflammation, reduces atherosclerosis, and alters gut microbiota in hyperlipidemic mice.

Excess cholesterol induces foam cell formation, NLRP3 inflammasome activation, and IL-1{beta} release in atherosclerotic plaques. We have shown previously that Miltefosine increased cholesterol release and dampened NLRP3 inflammasome assembly in macrophages. Here, we show that Miltefosine reduced LPS-induced choline uptake by macrophages and attenuated NLRP3 inflammasome assembly in mice. Miltefosine-fed mice showed reduced plasma IL-1{beta} in a polymicrobial cecal slurry injection model of systemic inflammation. Miltefosine-fed mice showed increased reverse cholesterol transport from macrophages to plasma, liver, and feces. Hyperlipidemic apoE-/- mice fed with Miltefosine showed significantly reduced weight gain and markedly reduced atherosclerotic lesions vs. control mice. 16S rDNA sequencing and analysis showed alterations in the gut microbiota profile of Miltefosine-fed hyperlipidemic apoE-/- vs. control mice, with the most notable changes in Romboutsia and Bacteroidetes species. Taken together, these data indicate that Miltefosine causes pleiotropic effects on lipid metabolism, inflammasome activity, atherosclerosis, and the gut microbiota.

cell biology↗

bioRxiv2021

Impact of pre-anthesis drought stress on physiology, yield-related traits and drought responsive genes in green super rice

Optimum soil water availability is vital for maximum yield production in rice which is challenged by increasing spells of drought. The reproductive stage drought is among the main limiting factors leading to the drastic reduction in grain yield. Objective of this study was to investigate the molecular and morpho-physiological responses of pre-anthesis stage drought stress in green super rice. The study assessed the performance of 26 rice lines under irrigated and drought conditions. Irrigated treatment was allowed to grow normally while drought stress was imposed for 30 days at pre-anthesis stage. Three important physiological traits including pollen fertility percentage (PFP), cell membrane stability (CMS) and normalized difference vegetative index (NDVI) were recorded at anthesis stage during the last week of drought stress. Agronomic traits of economic importance including grain yield were recorded at maturity stage. The analysis of variance demonstrated significant variation among the genotypes for most of the studied traits. Correlation and principal component analyses demonstrated highly significant associations of particular agronomic traits with grain yield, and genetic diversity among genotypes, respectively. Our study demonstrated a higher drought tolerance potential of GSR lines compared to local cultivars, mainly by higher pollen viability, plant biomass, CMS, and harvest index under drought. In addition, the molecular basis of drought tolerance in GSR lines was related to upregulation of certain drought responsive genes including OsSADRI, OsDSM1, and OsDT11. Our study identified novel drought tolerance related genes (OsDRG-1, OsDRG-2, OsDRG-3 and OsDRG-4) that could be further characterized using reverse genetics to be utilized in molecular breeding for drought tolerance.

plant biology↗

bioRxiv2021

Fractions of traditionally brewed rice beverage ameliorate anxiety and improve spatial memory in mice

Rice beverages are traditionally prepared and consumed popularly by the different ethnic groups of North East India. To investigate its effects on behavior, mice were treated with different fractions of rice beverage that included the beverage as a whole, insoluble and soluble fractions. Intragastric treatments of these fractions were given to the mice (n=6 per group) for 30 days and behavioral studies were performed on elevated plus and Y maze to evaluate anxiety and spatial memory, respectively. Next generation sequencing of metagenomic DNA of the beverage indicated presence of 157 OTUs and 26 bacterial genera were dominant with an abundance of 0.1%. The insoluble fraction treated animals showed lowest anxiety like symptoms. Spatial memory improved in all the treatments compared to the control, of which the rice beverage treatment showed the highest levels (p<0.05). Gas chromatography and mass spectroscopy-based metabolite profiling of the beverage revealed 10 alcohols, 29 sachharides, 43 acids and 13 amino acids. Findings of this study suggest a positive effect of rice beverage components on anxiety and spatial memory of mice.

neuroscience↗