Down-Regulation of Myogenin Can Reverse Terminal Muscle Cell Differentiation

Certain higher vertebrates developed the ability to reverse muscle cell differentiation (dedifferentiation) as an additional mechanism to regenerate muscle. Mammals, on the other hand, show limited ability to reverse muscle cell differentiation. Myogenic Regulatory Factors (MRFs), MyoD, myogenin, Myf5 and Myf6 are basic-helix-loop-helix (bHLH) transcription factors essential towards the regulation of myogenesis

A single-cell analysis of myogenic dedifferentiation induced by small molecules

An important direction in chemical biology is the derivation of compounds that affect cellular differentiation or its reversal. The fragmentation of multinucleate myofibers into viable mononucleates (called cellularization) occurs during limb regeneration in urodele amphibians, and the isolation of myoseverin, a trisubstituted purine that could apparently activate this pathway of myogenic dedifferentlation in mammalian cells, generated considerable interest. We have explored the mechanism and outcome of cellularization at a single-cell level, and we report findings that significantly extend the previous work with myoseverin. Using a panel of compounds, including a triazine compound with structural similarity and comparable activity to myoseverin, we have identified microtubule disruption as critical for activation of the response. Time-lapse microscopy has enabled us to analyze the fate of identified mononucleate progeny, and directly assess the extent of dedifferentiation.1141sciescopu

A study of the quality of life of the severely mentally ill

conducted a total of 85 times with 55 clients with serious mental illness. Results revealed widespread adverse objective circumstances (unemployment, poverty and social isolation) despite which most clients rated their satisfaction levels about average (about equally satisfied and dissatisfied). As expected, subjective quality of life indicators were generally better predictors of global well-being (GWB) (itself based on subjective ratings) than were objective indicators. Correlations between objective and subjective indicators were very low and insignificant. Moderate relationships were found between GWB and levels of personal functioning, and changes in levels of personal functioning, as rated by mental health workers. Retests showed that subjective quality of life was relatively stable over intervals of several months. The findings suggest that leisure and social relations would be suitable areas for interventions that might improve clients ’ quality of life

Cu° promoted cyclization of unsaturated alpha-halogeno amides to give beta- and gamma-lactams.

Efficient 5-exo-trig atom-transfer radical cyclisation of 13 unsaturated α-halogeno amides mediated by Cu0 (copper wire) with tripyridylmethanimine ligand (TPMA; 1 mol-%) in a mixed solvent of EtOAc/EtOH (3:1) is reported (89–98 %), with recycling of the copper wire. A substantial improvement in conversion and selectivity was obtained when Na2CO3 (5 mol-%)was added to the reaction mixture. The Cu0 acts as a supplementary activator and reducing agent in a SARA-ATRC process. The protocol was extended to the cyclisation onto alkynes and the formation of -lactams, although these reactions gave lower yields (35–76 %)

Cu0-promoted cyclisation of unsaturated α-halogeno amides to give β- and γ-Lactams

Efficient 5-exo-trig atom-transfer radical cyclisation of 13 unsaturated α-halogeno amides mediated by Cu0 (copper wire) with tripyridylmethanimine ligand (TPMA; 1 mol-%) in a mixed solvent of EtOAc/EtOH (3:1) is reported (89–98 %), with recycling of the copper wire. A substantial improvement in conversion and selectivity was obtained when Na2CO3 (5 mol-%) was added to the reaction mixture. The Cu0 acts as a supplementary activator and reducing agent in a SARA-ATRC process. The protocol was extended to the cyclisation onto alkynes and the formation of β-lactams, although these reactions gave lower yields (35–76 %)