Novel cytogenetic finding: an unusual X;X-translocation in Mehsana buffalo (Bubalus bubalis)

Cytogenetic investigations of a phenotypically normal Mehsana river buffalo calf (Bubalusbubalis) revealed an XXY chromosome complement due to X;X-translocation in all screened metaphase plates. The chromosomal anomaly was identified by GTG-banding while CBG- and RBG-banding revealed two heterochromatin blocks and that one of the two X chromosomes was late replicating, respectively. The normal cytogenetic profiles of sire, dam and relatives of the calf suggest that the anomaly could have arisen spontaneously during oogenesis. This is the first report on a male river buffalo calf having an XXY chromosome complement with translocation between the two X chromosomes.     

Modulation of Mycobacterium tuberculosis proliferation by MtrA, an essential two-component response regulator

Paired two-component regulatory systems consisting of a sensor kinase and a response regulator are the major means by which bacteria sense and respond to different stimuli. The role of essential response regulator, MtrA, in Mycobacterium tuberculosis proliferation is unknown. We showed that elevating the intracellular levels of MtrA prevented M. tuberculosis from multiplying in macrophages, mice lungs and spleens, but did not affect its growth in broth. Intracellular trafficking analysis revealed that a vast majority of MtrA overproducing merodiploids were associated with lysosomal associated membrane protein (LAMP-1) positive vacuoles, indicating that intracellular growth attenuation is, in part, due to an impaired ability to block phagosome-lysosome fusion. A merodiploid strain producing elevated levels of phosphorylation-defective MtrA (MtrA(D53N)) was partially replicative in macrophages, but was attenuated in mice. Quantitative real-time PCR analyses revealed that expression of dnaA, an essential replication gene, was sharply upregulated during intramacrophage growth in the MtrA overproducer in a phosphorylation-dependent manner. Chromatin immunoprecipitation using anti-MtrA antibodies provided direct evidence that MtrA regulator binds to dnaA promoter in vivo indicating that dnaA promoter is a MtrA target. Simultaneous overexpression of mtrA regulator and its cognate mtrB kinase neither inhibited growth nor sharply increased the expression levels of dnaA in macrophages. We propose that proliferation of M. tuberculosis in vivo depends, in part, on the optimal ratio of phosphorylated to non-phosphorylated MtrA response regulator.     

Chiral and achiral macrocyclic copper(II) complexes: Synthesis, characterization, and comparative binding studies with calf-thymus DNA

The new chiral macrocyclic complexes [1,2-bis(1H-benzimidazol-2-yl)-1-(1,8-dihydro-1,3,5,8,10,12-hexaazacyclotetradecane)-2-hydroxyethanolate] copper(II) and -nickel(II) perchlorate, 3 and 4, respectively, were synthesized by the reaction of 1,2-bis(1H-benzimidazol-2-yl)ethane-1,2-diol (L) and (1,8-dihydro-1,3,5,8,10,12-hexaazacyclotetradecane)copper(II) and -nickel(II) diperchlorate complexes, 1 and 2, respectively. All complexes were characterized by various spectroscopic techniques. Molar-conductance measurements showed that all of the complexes are ionic in nature. In complexes 3 and 4, the metal center is encapsulated by the ligand L in a pentacoordinated environment. The optical-rotation values ([alpha](D)) of 3 and 4 at 25 degrees indicate that the complexes are chiral. Absorption- and fluorescence-spectral studies, cyclic voltammetry, and viscosity measurements have been carried out to assess the comparative binding of complexes 1 and 3 with calf thymus (CT)-DNA. Analysis of the results suggests that the new chiral complex 3 binds to CT-DNA through a partial intercalation mode that is different from the binding mode of parent achiral complex 1. The complexes 1 and 3 bind to CT-DNA with binding constants K(b) of 2.7 x 10(4) and 6.6 x 10(4) M(-1), respectively. Circular-dichroism (CD) studies have been further employed to ascertain the binding mode of complex 3, which is consistent with the other spectral studies.     

Thermal stability of dehydrophenylalanine-containing model peptides as probed by infrared spectroscopy: a case study of an alpha-helical and a 3(10)-helical peptide

The temperature-dependent secondary-structural changes in the two known helical model peptides Boc-Val-deltaPhe-Ala-Leu-Gly-OMe (1; alpha-helical) and Boc-Leu-Phe-Ala-deltaPhe-Leu-OMe (2; 3(10)-helical), which both comprise a single dehydrophenylalanine (deltaPhe) residue, were investigated by means of FT-IR spectroscopy (peptide film on KBr). Both the first-order and the better-resolved second-order derivative IR spectra of 1 and 2 were analyzed. The nu(NH) (3240-3340 cm(-1)), the Amide-I (1600-1700 cm(-1)), and the Amide-II (1510-1580 cm(-1)) regions of 1 and 2 showed significant differences in thermal-denaturation experiments (22 degrees --> 144 degrees), with the 3(10)-helical peptide (2) being considerably more stable. This observation was rationalized by different patterns and strengths of intramolecular H-bonds, and was qualitatively related to the different geometries of the peptides. Also, a fair degree of residual secondary-structural elements were found even in the 'denatured' states above 104 degrees (1) or 134 degrees (2).     

Synthesis of new 4-aminoquinolines and quinoline-acridine hybrids as antimalarial agents

Despite emergence of resistance to CQ and other 4-aminoquinoline drugs in most of the endemic regions, research findings provide considerable support that there is still significant potential to discover new affordable, safe, and efficacious 4-aminoquinoline antimalarials. In present study, new side chain modified 4-aminoquinoline derivatives and quinoline-acridine hybrids were synthesized and evaluated in vitro against NF 54 strain of Plasmodium falciparum. Among the evaluated compounds, compound 17 (MIC=0.125 μg/mL) was equipotent to standard drug CQ (MIC=0.125 μg/mL) and compound 21 (MIC=0.031 μg/mL) was four times more potent than CQ. Compound 17 showed the curative response to all the treated swiss mice infected with CQ-resistant N-67 strain of Plasmodium yoelii at the doses 50 mg/kg and 25 mg/kg for four days by intraperitoneal route and was found to be orally active at the dose of 100 mg/kg for four days. The promising antimalarial potency of compound 17 highlights the significance of exploring the privileged 4-aminoquinoline class for new antimalarials.     

Synthesis and biological evaluation of indolyl glyoxylamides as a new class of antileishmanial agents

A series of indolylglyoxylamide derivatives have been synthesized and evaluated in vitro against amastigote form of Leishmania donovani. Compound 8c has been identified as the most active analog of the series with IC₅₀ value of 5.17 μM and SI value of 31.48, and is several folds more potent than the standard drugs sodium stilbogluconate and pentamidine.     

Strawberry Fruit Oxalate Oxidase — Detection, Purification, Characterization and Physiological Role

A soluble oxalate oxidase activity has been detected in homogenate of ripened fruits of strawberry (Fragaria ananassa), as confirmed by the stoichiometric relationship between the disappearance of oxalate and utilization of dissolved O₂, and generation of H₂O₂. The enzyme was purified up to apparent homogeneity and had a Mr of 119 kDa with two identical subunits. K_m for oxalate was found to be 1.67×10^?3 M, and V_max of 0.741 mmoles ml^?1min^?1. It retained 76% of its initial activity, when heated at 60°C for 30 min. The enzyme was found to be glycoprotein in nature. The significant increase in the enzyme activity of ripened fruits compared to that in pre-ripened fruit, and decrease in oxalate level (?0.927 correlation with oxalate oxidase) with advancement of ripening indicated the physiological role of enzyme in fruit ripening.     

Induction of Plant Defense Enzymes and Phenolics by Treatment With Plant Growth–Promoting Rhizobacteria Serratia marcescens NBRI1213

In greenhouse experiments, plant growth–promoting rhizobacteria (PGPR) Serratia marcescens NBRI1213 was evaluated for plant growth promotion and biologic control of foot and root rot of betelvine caused by Phytophthora nicotianae. Bacterization of betelvine (Piper betle L.) cuttings with S. marcescens NBRI1213 induced phenylalanine ammonia-lyase, peroxidase, and polyphenoloxidase activities in leaf and root. Qualitative and quantitative estimation of phenolic compounds was done through high-performance liquid chromatography (HPLC) in leaf and root of betelvine after treatment with S. marcescens NBRI1213 and infection by P. nicotianae. Major phenolics detected were gallic, protocatechuic, chlorogenic, caffeic, ferulic, and ellagic acids by comparison of their retention time with standards through HPLC. In all of the treated plants, synthesis of phenolic compounds was enhanced compared with control. Maximum accumulation of phenolics was increased in S. marcescens NBRI1213–treated plants infected with P. nicotianae. In a greenhouse test, bacterization using S. marcescens NBRI1213 decreased the number of diseased plants compared with nonbacterized controls. There were significant growth increases in shoot length, shoot dry weight, root length, and root dry weight, averaging 81%, 68%, 152%, and 290%, respectively, greater than untreated controls. This is the first report of PGPR–mediated induction of phenolics for biologic control and their probable role in protecting betelvine against P. nicotianae, an important soil-borne phytopathogenic fungus.     

Synthesis and characterization of novel guar gum hydrogels and their use as Cu sorbents

To prepare novel hydrogels for use in water technologies, guar gum was subjected to acid hydrolysis. The depolymerized guar gum obtained there from and the native guar gum were oxidized to their respective polycarboxylic forms using NO_x as oxidant. All these polymers were crosslinked with N,N-methylenebisacrylamide, and were used as Cu²⁺ sorbents. The candidate hydrogel exhibiting the highest uptake was used further to investigate the effect of external stimuli on sorption. The sorption on hydrogels was fast as the highest sorption was observed after 2 h at 40 °C and 20 ppm of Cu²⁺ ions. The hydrogel prepared from the oxidized guar gum afforded the maximum sorption capacity of 125.893 mg g⁻¹. Langmuir and Freundlich isotherms, and pseudo second order kinetics matches the experimental data. The evidence of sorption was obtained by characterizing Cu²⁺-loaded hydrogels by FTIR spectroscopy.     

Model based design of inhibitors for c-jun

Literature shows that various molecular cascades are activated by stress, UV rays and pollutants leading to wrinkle formation of the skin. These cascades start from five types of receptors (EGFR, PDGFR, PAFR, IL1R, TNFRB) and terminate with the production of matrix metalloproteinase's, which degrades collagen leading to wrinkle formation. Signaling pathway leading to wrinkle formation showed that c-jun is involved in these cascades. Therefore, c-jun is the preferential choice for inhibition to reduce the intensity of collagen degradation. Hence, the 3D structure of c-jun was modeled using segment based homology modeling by MODELLER 9v5. Evaluation of the constructed model was done by PROCHECK, WHAT CHECK and through RMSD/RMSF calculations. Ligands for the inhibitory sites were designed using LIGANDSCOUT. The interaction study of ligand and receptor was performed by AUTODOCK. A library of analogues was constructed for three known inhibitory sites. The receptor-analogue study was performed using the software MOLEGRO Virtual Docker. The analogues constructed from the designed novel reference ligands showed good binding with the receptor binding sites. It should be noted that these predicted data should be validated using suitable assays for further consideration.