Molecular docking of potential inhibitors with the mTOR protein

The mTOR (mammalian or mechanistic Target of Rapamycin) is linked with oral cancer. Therefore, it is of interest to study the molecular docking-based binding of paclitaxel (a FDA approved drug for oral cancer) and its analogues with mTOR. Hence, we report the binding features of 10-Deacetyltaxol, 7-Epi-10-deacetyltaxol, 7-Epi-Taxol and 6alpha-Hydroxypaclitaxel with mTOR for further consideration.     

Spectral Analysis of Naturally Occurring Methylxanthines (Theophylline,Theobromine and Caffeine) Binding with DNA

Nucleic acids exist in a dynamic equilibrium with a number of molecules that constantly interact with them and regulate the cellular activities. The inherent nature of the structure and conformational integrity of these macromolecules can lead to altered biological activity through proper targeting of nucleic acids binding ligands or drug molecules. We studied the interaction of naturally occurring methylxanthines such as theophylline, theobromine and caffeine with DNA, using UV absorption and Fourier transform infrared (FTIR) spectroscopic methods, and especially monitored their binding affinity in the presence of Mg²⁺ and during helix-coil transitions of DNA by temperature (T_m) or pH melting profiles. The study indicates that all these molecules effectively bind to DNA in a dose dependent manner. The overall binding constants of DNA-theophylline = 3.5×10³ M⁻¹, DNA-theobromine = 1.1×10³ M⁻¹, and DNA-Caffeine = 3.8×10³ M⁻¹. On the other hand T_m/pH melting profiles showed 24–35% of enhanced binding activity of methylxanthines during helix-coil transitions of DNA rather than to its native double helical structure. The FTIR analysis divulged that theophylline, theobromine and caffeine interact with all the base pairs of DNA (A-T; G-C) and phosphate group through hydrogen bond (H-bond) interaction. In the presence of Mg²⁺, methylxanthines altered the structure of DNA from B to A-family. However, the B-family structure of DNA remained unaltered in DNA-methylxanthines complexes or in the absence of Mg²⁺. The spectral analyses indicated the order of binding affinity as “caffeine≥theophylline>theobromine” to the native double helical DNA, and “theophylline≥theobromine>caffeine to the denatured form of DNA and in the presence of divalent metal ions.     

Group I introns and gnra tetraloops: remnants of ‘The RNA world’?

GNRA tetraloops, found in high frequency in natural RNAs, make loop-receptor interactions, stabilizing the tertiary structure of Group I introns, a class of small RNAs. Analyzing 230 Group I introns, to study the distribution and sequence pattern of the GNRA tetraloops, we suggest that these features reflect the ancestral nature of these catalytic molecules, in a prebiotic RNA world. The adenosine rich GNRA tetraloops would have interacted with each other through long range RNA-RNA interactions to form higher order structures forming potential sites that render the propensity for the short RNAs to bind to metal ions from the prebiotic pool, aiding them to act as metalloenzymes.     

Development of a Specific Detection Technique for Cowpea Golden Mosaic Virus

Whitefly transmitted begomoviruses are on increase in tropical and subtropical countries. It is especially true of yellow mosaic viruses infecting legumes. Management of viral diseases requires specific detection techniques to demonstrate their presence in several other alternative and weed hosts. With this in view, nucleic acid hybridization test to detect Cowpea golden mosaic virus (CPGMV) in many crops and weed species was developed. This study showed that while probe to CPGMV DNA A detected all the begomoviruses, DNA B probe was highly specific and detected only CPGMV showing its specific nature.     

Expression analysis on mycoparasitism related genes during antagonism of <Emphasis Type="Italic">Trichoderma</Emphasis> with <Emphasis Type="Italic">Colletotrichum falcatum</Emphasis> causing red rot in sugarcane

Present study was aimed to select a suitable Trichoderma isolate as candidate antagonist based on its efficacy in producing cell wall degrading enzymes (CWDEs), its mycoparasitism activity and expression of related genes against the red rot pathogen caused by Colletotrichum falcatum in sugarcane. For which, six different isolates of Trichoderma selected from our earlier studies (T. harzianum, T. asperullum) were evaluated based on their capability in releasing cell wall degrading enzymes individually and during antagonism with C. falcatum in dual plate. Amongst T. harzianum (T20) exhibited the greatest mycoparasitic potential against the C. falcatum, by producing higher concentration of  CWDEs viz., chitinase and β-1, 3-glucanase, slightly lower amounts of cellulase and protease with significant reduction in polygalacturonase produced by pathogen. Further microscopic observation on interaction of C. falcatum with the selected isolate of T. harzianum (T20) exhibited the mycoparasitic activity of antagonist over pathogen in dual culture and inhibition of C. falcatum pathogenesis in detached sugarcane leaves. In addition, expression pattern of eight genes coding various enzymes involved in mycoparasitism by T. harzianum over C. falcatum were analyzed using qRT-PCR in vitro and on sugarcane leaves. In in vitro interactions, five genes of  cell wall degrading enzymes viz., chitinase (chit33), endochitinase (endo42), β-1, 3-glucanase (glu), exochitinase 1 (exc1), exochitinase 2 (exc2), were upregulated during and after contact as compared to before contact, while three genes related with proteases such as alkaline proteinase (prb1), trypsin-like protease (Pra1), subtilin-like serine protease (ssp), genes were upregulated during the contact with C. falcatum and slightly down regulated after contact. In detached leaves, seven genes were potentially upregulated except subtilin-like serine protease, which was down regulated during interaction of C. falcatum and T. harzianum as compared to T. harzianum inoculation alone. All these biochemical and molecular results confirm the efficacy of T. harzianum (T20) against C. falcatum and justify the right selection of candidate antagonist for our further studies on identification of antifungal genes/proteins against C. falcatum in sugarcane.     

Masking Terror: How Women Contain Violence in Southern Sri Lanka; Scarred Minds: The Psychological Impact of War on Sri Lankan Tamils; The Ocean of Stories: Children's Imagination, Creativity, and Reconciliation in Eastern Sri Lanka

Masking Terror: How Women Contain Violence in Southern Sri Lanka. Alex Argenti-Pillen. Philadelphia: University of Pennsylvania Press, 2003. xv. 235 pp.
Scarred Minds: The Psychological Impact of War on Sri Lankan Tamils. Daya Somasunderam New Delhi: Sage, 1998. 353 pp.
The Ocean of Stories: Children's Imagination, Creativity, and Reconciliation in Eastern Sri Lanka. Patricia Lawrence. Colombo, Sri Lanka: International Centre for Ethnic Studies, 2003.94 pp.