Survival strategies of the malarial parasite Plasmodium falciparum

Plasmodium falciparum, the protozoan parasite causing falciparum malaria, is undoubtedly highly versatile when it comes to survival and defence strategies. Strategies adopted by the asexual blood stages of Plasmodium range from unique pathways of nutrient uptake to immune evasion strategies and multiple drug resistance. Studying the survival strategies of Plasmodium could help us envisage strategies of tackling one of the worst scourges of mankind

Plasmepsin inhibitors: design, synthesis, inhibitory studies and crystal structure analysis

Plasmepsin group of enzymes are key enzymes in the life cycle of malarial parasites. As inhibition of plasmepsins leads to the parasite's death, these enzymes can be utilized as potential drug targets. Although many drugs are available, it has been observed that Plasmodium falciparum, the species that causes most of the malarial infections and subsequent death, has developed resistance against most of the drugs. Based on the cleavage sites of hemglobin, the substrate for plasmepsins, we have designed two compounds (p-nitrobenzoyl-leucine-β -alanine and p-nitrobenzoyl-leucine-isonipecotic acid), synthesized them, solved their crystal structures and studied their inhibitory effect using experimental and theoretical (docking) methods. In this paper, we discuss the synthesis, crystal structures and inhibitory nature of these two compounds which have a potential to inhibit plasmepsins

Structural plasticity of peanut lectin: an X-ray analysis involving variation in pH, ligand binding and crystal structure

Until recently, it has only been possible to grow crystals of peanut lectin when complexed with sugar ligands. It is now shown that it is possible to grow peanut lectin crystals at acidic pH in the presence of oligopeptides corresponding to a loop in the lectin molecule. Crystals have also been prepared in the presence of these peptides as well as lactose. Low-pH crystal forms of the lectin-lactose complex similar to those obtained at neutral pH have also been grown. Thus, crystals of peanut lectin grown under different environmental conditions, at two pH values with and without sugar bound to the lectin, are now available. They have been used to explore the plasticity and hydration of the molecule. A detailed comparison between different structures shows that the lectin molecule is sturdy and that the effect of changes in pH, ligand binding and environment on it is small. The region involving the curved front β-sheet and the loops around the second hydrophobic core is comparatively rigid. The back β-sheet involved in quaternary association, which exhibits considerable variability, is substantially flexible, as is the sugar-binding region. The numbers of invariant water molecules in the hydration shell are small and they are mainly involved in metal coordination or in stabilizing unusual structural features. Small consistent movements occur in the combining site upon sugar binding, although the site is essentially preformed

Investigations on Hepatoprotective Activity of Leaf Extracts of Aegle marmelos (L.) Corr. (Rutaceae)

The present study was carried out to screen and evaluate the hepatoprotective activity of leaf extracts of Aegle marmelos (L.) Corr. Hepatoprotective activities of ethanolic and aqueous extracts of A. marmelos were examined against carbon tetrachloride induced liver damage in mice using silymarin as control. Enzyme activities of Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT) and Alkaline Phosphatase (ALP) were analyzed. Results indicate that ethanolic and aqueous leaf extracts of A. marmelos had moderate activity over carbon tetrachloride treatment as compared to control. Results of the present investigation confirm the traditional uses of this plant as a potential hepatoprotective agent

GMRT Observations of the 2006 outburst of the Nova RS Ophiuchi: First detection of emission at radio frequencies < 1.4 GHz

The first low radio frequency (<1.4 GHz) detection of the outburst of the recurrent nova RS Ophiuchi is presented in this letter. Radio emission was detected at 0.61 GHz on day 20 with a flux density of ~48 mJy and at 0.325 GHz on day 38 with a flux density of ~ 44 mJy. This is in contrast with the 1985 outburst when it was not detected at 0.327 GHz even on day 66. The emission at low radio frequencies is clearly non-thermal and is well-explained by a synchrotron spectrum of index alpha ~ -0.8 (S propto nu^alpha) suffering foreground absorption due to the pre-existing, ionized, warm, clumpy red giant wind. The absence of low frequency radio emission in 1985 and the earlier turn-on of the radio flux in the current outburst are interpreted as being due to higher foreground absorption in 1985 compared to that in 2006, suggesting that the overlying wind densities in 2006 are only ~30% of those in 1985.Comment: 14 pages, 1 figure. Accepted for publication in ApJ

Studies on Hepatoprotective Properties of Leaf Extracts of Azadirachta indica A. Juss (Meliaceae)

The present study was carried out to evaluate the hepatoprotective role of leaf extracts of Azadirachta indica A. Juss. Hepatoprotective activities of ethanolic and aqueous extracts of A. indica were examined against carbon tetrachloride induced liver damage in mice using silymarin as control. Enzyme activities of Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT) and Alkaline Phosphatase (ALP) were analyzed. Phytochemical leaf extracts of A. indica exhibited significant hepatoprotective activity. Ethanolic and aqueous leaf extracts of A. indica exhibited moderate activity over carbon tetrachloride treated animals. Results confirm the traditional - ethnomedicinal use of A. indica as a potential source of hepatoprotective agent

Giant metrewave radio telescope observations of the 2006 outburst of the Nova RS Ophiuchi: first detection of emission at radio frequencies &#60;1.4 GHz

The first low radio frequency (&#60;1.4 GHz) detection of the outburst of the recurrent nova RS Ophiuchi is presented in this Letter. Radio emission was detected at 0.61 GHz on day 20 with a flux density of ~48 mJy and at 0.325 GHz on day 38 with a flux density of ~44 mJy. This is in contrast with the 1985 outburst, when it was not detected at 0.327 GHz even on day 66. The emission at low radio frequencies is clearly nonthermal and is well explained by a synchrotron spectrum of index α ~ -0.8 (S &#8733; &#957;&#945;) suffering foreground absorption due to the preexisting, ionized, warm, clumpy red giant wind. The absence of low-frequency radio emission in 1985 and the earlier turn-on of the radio flux in the current outburst are interpreted as being due to higher foreground absorption in 1985 compared to that in 2006, suggesting that the overlying wind densities in 2006 are only ~30% of those in 1985

Identification of AFLP markers linked to Fusarium wilt disease in pigeonpea [Cajanus cajan (L.) Millsp.]

An experiment was conducted to identify markers linked to Fusarium wilt disease resistance, Parents namely TTB 7 and ICP 8863 were screened using 151 SSRs markers and 16 AFLP primer combinations. Parental screening revealed five SSR primers and 12 AFLP primer combinations polymorphic between parents. Bulk segregant analysis identified five AFLP primer combinations generating seven markers polymorphic between resistant and susceptible bulks while, none of the SSR markers were polymorphic. This indicates that, these markers are putatively linked to wilt disease. Screening of F2 segregating population of cross TTB 7 x ICP 8863 with these putatively linked markers revealed four markers (E-AAT/M-CTG850, ETCG/M-CTT650, E-TCG/M-CTA730 and E-TCG/M-CTT230) which segregated in 3:1 mendelian pattern. Simple linear regression performed on these four markers had identified two markers namely E-TCG/M-CTT650 and E-TCG/M-CTA730 linked to disease

SDSS-IV MaNGA-resolved Star Formation and Molecular Gas Properties of Green Valley Galaxies: A First Look with ALMA and MaNGA

We study the role of cold gas in quenching star formation in the green valley by analyzing ALMA 12 CO (1-0) observations of three galaxies with resolved optical spectroscopy from the MaNGA survey. We present resolution-matched maps of the star formation rate and molecular gas mass. These data are used to calculate the star formation efficiency (SFE) and gas fraction (f gas ) for these galaxies separately in the central "bulge" regions and outer disks. We find that, for the two galaxies whose global specific star formation rate (sSFR) deviates most from the star formation main sequence, the gas fraction in the bulges is significantly lower than that in their disks, supporting an "inside-out" model of galaxy quenching. For the two galaxies where SFE can be reliably determined in the central regions, the bulges and disks share similar SFEs. This suggests that a decline in f gas is the main driver of lowered sSFR in bulges compared to disks in green valley galaxies. Within the disks, there exist common correlations between the sSFR and SFE and between sSFR and f gas on kiloparsec scales - the local SFE or f gas in the disks declines with local sSFR. Our results support a picture in which the sSFR in bulges is primarily controlled by f gas , whereas both SFE and f gas play a role in lowering the sSFR in disks. A larger sample is required to confirm if the trend established in this work is representative of the green valley as a whole.The work is supported by the Ministry of Science & Technology of Taiwan under the grant MOST 103-2112-M-001-031-MY3 and 106-2112-M-001-034. R.M. and F.B. acknowledge support by the UK Science and Technology Facilities Council (STFC). R.M. acknowledges ERC Advanced Grant 695671 "QUENCH.

Star Formation Histories of the LEGUS Dwarf Galaxies (I): recent History of NGC1705, NGC4449 and Holmberg II

We use HST observations from the Legacy Extragalactic UV Survey to reconstruct the recent star formation histories (SFHs) of three actively star-forming dwarf galaxies, NGC4449, Holmberg II and NGC1705, from their UV color-magnitude diagrams (CMDs). We apply a CMD fitting technique using two independent sets of stellar isochrones, PARSEC-COLIBRI and MIST, to assess the uncertainties related to stellar evolution modelling. Irrespective of the adopted stellar models, all the three dwarfs are found to have had almost constant star formation rates (SFRs) in the last 100-200 Myr, with modest enhancements (a factor of $\sim$2) above the 100 Myr-averaged-SFR. Significant differences among the three dwarfs are found in the overall SFR, the timing of the most recent peak and the SFR$/$area. The Initial Mass Function (IMF) of NGC1705 and Holmberg II is consistent with a Salpeter slope down to $\approx$ 5 M$_{\odot}$, whereas it is slightly flatter, s$=-2.0$, in NGC4449. The SFHs derived with the two different sets of stellar models are consistent with each other, except for some quantitative details, attributable to their input assumptions. They also share the drawback that all synthetic diagrams predict a clear separation in color between upper main sequence and helium burning stars, which is not apparent in the data. Since differential reddening, significant in NGC4449, or unresolved binaries don't appear to be sufficient to fill the gap, we suggest this calls for a revision of both sets of stellar evolutionary tracks.Comment: 22 pages, 17 figures, accepted for publication on Ap