01733nas a2200205   4500008004100000022001400041245006900055210006800124260007200192300001400264490000700278520102700285100001801312700001701330700002301347700001501370700002401385700001801409856010001427       2015                        eng d  a0305-104800aSelective inhibition of miR-21 by phage display screened peptide0 aSelective inhibition of miR21 by phage display screened peptide  aGREAT CLARENDON ST, OXFORD OX2 6DP, ENGLANDbOXFORD UNIV PRESScAPR  a4342-43520 v433 a<p>miRNAs are nodal regulators of gene expression and deregulation of miRNAs is causally associated with different diseases, including cancer. Modulation of miRNA expression is thus of therapeutic importance. Small molecules are currently being explored for their potential to downregulate miRNAs. Peptides have shown to have better potency and selectivity toward their targets but their potential in targeting and modulating miRNAs remain unexplored. Herein, using phage display we found a very selective peptide against pre-miR-21. Interestingly, the peptide has the potential to downregulate miR-21, by binding to pre-miR-21 and hindering Dicer processing. It is selective towards miR-21 inside the cell. By antagonising miR-21 function, the peptide is able to increase the expression of its target proteins and thereby increase apoptosis and suppress cell proliferation, invasion and migration. This peptide can further be explored for its anti-cancer activity in vivo and may be even extended to clinical studies.</p>1 aBose, Debojit1 aNahar, Smita1 aRai, Manish, Kumar1 aRay, Arjun1 aChakraborty, Kausik1 aMaiti, Souvik  uhttps://library.ncl.res.in/content/selective-inhibition-mir-21-phage-display-screened-peptide-001926nas a2200253   4500008004100000022001400041245011500055210006900170260000800239300000900247490000700256520106700263100001801330700001901348700002301367700002201390700002301412700001901435700001801454700001901472700002801491700002401519856012901543       2020                        eng d  a2041-172300aDistinct metabolic states of a cell guide alternate fates of mutational buffering through altered proteostasis0 aDistinct metabolic states of a cell guide alternate fates of mut  cJUN  a29260 v113 a<p>Metabolic changes alter the cellular milieu; can this also change intracellular protein folding? Since proteostasis can modulate mutational buffering, if change in metabolism has the ability to change protein folding, arguably, it should also alter mutational buffering. Here we find that altered cellular metabolic states in E. coli buffer distinct mutations on model proteins. Buffered-mutants have folding problems in vivo and are differently chaperoned in different metabolic states. Notably, this assistance is dependent upon the metabolites and not on the increase in canonical chaperone machineries. Being able to reconstitute the folding assistance afforded by metabolites in vitro, we propose that changes in metabolite concentrations have the potential to alter protein folding capacity. Collectively, we unravel that the metabolite pools are bona fide members of proteostasis and aid in mutational buffering. Given the plasticity in cellular metabolism, we posit that metabolic alterations may play an important role in cellular proteostasis.</p>
1 aVerma, Kanika1 aSaxena, Kanika1 aDonaka, Rajashekar1 aChaphalkar, Aseem1 aRai, Manish, Kumar1 aShukla, Anurag1 aZaidi, Zainab1 aDandage, Rohan1 aShanmugam, Dhanasekaran1 aChakraborty, Kausik  uhttps://library.ncl.res.in/content/distinct-metabolic-states-cell-guide-alternate-fates-mutational-buffering-through-altered