Development and characterization of lysine based tripeptide analogues as inhibitors of Sir2 activity

Sirtuins are NAD(+) dependent deacetylases that modulate various essential cellular functions. Development of peptide based inhibitors of Sir2s would prove useful both as pharmaceutical agents and as effectors by which downstream cellular alterations can be monitored. Click chemistry that utilizes Huisgen's 1,3-dipolar cycloaddition permits attachment of novel modifications onto the side chain of lysine. Herein, we report the synthesis of peptide analogues prepared using click reactions on N epsilon-propargyloxycarbonyl protected lysine residues and their characterization as inhibitors of Plasmodium falciparum Sir2 activity. The peptide based inhibitors exhibited parabolic competitive inhibition with respect to acetylated-peptide substrate and parabolic non-competitive inhibition with NAD(+) supporting the formation of EI2 and E.NAD(+).I-2 complexes. Cross-competition inhibition analysis with the non-competitive inhibitor nicotinamide (NAM) ruled out the possibility of the NAM-binding site being the second inhibitor binding site, suggesting the presence of a unique alternate pocket commodating the inhibitor. One of these compounds was also found to be a potent inhibitor of the intraerythrocytic growth of P. falciparum with 50% inhibitory concentration in the micromolar range.

A physical mechanism for North Atlantic SST influence on the Indian summer monsoon

A link between the Atlantic Multidecadal Oscillation (AMO) and multidecadal variability of the Indian summer monsoon rainfall is unraveled and a long sought physical mechanism linking Atlantic climate and monsoon has been identified. The AMO produces persistent weakening (strengthening) of the meridional gradient of tropospheric temperature (TT) by setting up negative (positive) TT anomaly over Eurasia during northern late summer/autumn resulting in early (late) withdrawal of the south west monsoon and persistent decrease (increase) of seasonal monsoon rainfall. On inter-annual time scales, strong North Atlantic Oscillation (NAO) or North Annular mode (NAM) influences the monsoon by producing similar TT anomaly over Eurasia. The AMO achieves the interdecadal modulation of the monsoon by modulating the frequency of occurrence of strong NAO/NAM events. This mechanism also provides a basis for explaining the observed teleconnection between North Atlantic temperature and the Asian monsoon in paleoclimatic proxies. Citation: Goswami, B. N., M. S. Madhusoodanan, C. P. Neema, and D. Sengupta (2006), A physical mechanism for North Atlantic SST influence on the Indian summer monsoon

Origin of 1/f noise in graphene produced for large-scale applications in electronics

The authors report a detailed investigation of the flicker noise (1/f noise) in graphene films obtained from chemical vapour deposition (CVD) and chemical reduction of graphene oxide. The authors find that in the case of polycrystalline graphene films grown by CVD, the grain boundaries and other structural defects are the dominant source of noise by acting as charged trap centres resulting in huge increase in noise as compared with that of exfoliated graphene. A study of the kinetics of defects in hydrazine-reduced graphene oxide (RGO) films as a function of the extent of reduction showed that for longer hydrazine treatment time strong localised crystal defects are introduced in RGO, whereas the RGO with shorter hydrazine treatment showed the presence of large number of mobile defects leading to higher noise amplitude.