Link between MnSOD Ala16Val (rs4880) polymorphism and asthma risk is insignificant from sequential meta-analysis

The mitochondrial manganese superoxide dismutase (MnSOD) enzyme protects lungs against oxidative stress by neutralizing the free radical superoxide produced in the respiratory function. This has relevance to asthma. Therefore, it is of interest to describe the potential effect of MnSOD Ala16Val genetic polymorphism to asthma risk. Known data in this context is inconclusive in nature. The possible link between MnSOD Ala16Val polymorphism and asthma is explored using sequence meta-analysis. Data from the pooled analysis of MnSOD Ala16Val polymorphism using five genetic models i.e., allelic (Val vs. Ala: p=0.846; OR=1.033, 95% CI=0.742 to 1.440) is discussed. Homozygous (Val Val vs. Ala Ala: p=0.517; OR=1.307, 95% CI=0.582 to 2.932) and heterozygous (Val Ala vs. Ala Ala: p=0.307; OR=1.138, 95% CI=0.888 to 1.459) data using the described models are documented. Data from the dominant model (Val Val + Val Ala vs. Ala Ala: p=0.301; OR=1.289, 95% CI=0.797 to 2.085) and the recessive model (Val Val vs. Val Ala + Ala Ala: p=0.761; OR=0.924, 95% CI=0.555 to 1.538) analyses for several ethnic subgroups in this context is reported.     

AlCl3 induced (hetero)arylation of 2,3-dichloroquinoxaline: a one-pot synthesis of mono/disubstituted quinoxalines as potential antitubercular agents

A direct and single-step method has been developed for the synthesis of mono and 2,3-disubstituted quinoxalines by using a AlCl(3) induced (hetero)arylation of 2,3-dichloroquinoxaline. Both symmetrical and unsymmetrical 2,3-disubstituted quinoxalines can be prepared conveniently by using this method under appropriate reaction conditions. The reaction proceeds via C-C bond formation and can be utilized for the preparation of a variety of quinoxaline derivatives from readily available starting materials and reagents. The molecular structure of a representative compound was confirmed by single crystal X-ray diffraction study. Some of the compounds synthesized were tested for chorismate mutase inhibitory properties in vitro and one compound showed promising activity representing one of the few examples of chorismate mutase inhibition by a heteroarene based small molecule.     

Proteome analysis of functionally differentiated bovine (Bos indicus) mammary epithelial cells isolated from milk

Mammary gland is made up of a branching network of ducts that end in alveoli. Terminally differentiated mammary epithelial cells (MECs) constitute the innermost layer of aveoli. They are milk‐secreting cuboidal cells that secrete milk proteins during lactation. Little is known about the expression profile of proteins in the metabolically active MECs during lactation or their functional role in the lactation process. In the present investigation, we have reported the proteome map of MECs in lactating cows using 2DE MALDI‐TOF/TOF MS and 1D‐Gel‐LC‐MS/MS. MECs were isolated from milk using immunomagnetic beads and confirmed by RT‐PCR and Western blotting. The 1D‐Gel‐LC‐MS/MS and 2DE‐MS/MS based approaches led to identification of 431 and 134 proteins, respectively, with a total of 497 unique proteins. Proteins identified in this study were clustered into functional groups using bioinformatics tools. Pathway analysis of the identified proteins revealed 28 pathways (p < 0.05) providing evidence for involvement of various proteins in lactation function. This study further provides experimental evidence for the presence of many proteins that have been predicted in annotated bovine genome. The data generated further provide a set of bovine MEC‐specific proteins that will help the researchers to understand the molecular events taking place during lactation.     

Exploring the effect of vitamin E in cancer chemotherapy—A biochemical and biophysical insight

Many oncologists contend that patient undergoing chemotherapy must avoid antioxidant supplementation as it may interfere with the activity of the drug. In the present investigation, we have explored the influence of vitamin E, a well‐known antioxidant on Camptothecin (CPT), a potent anti‐cancer drug induced cell apoptosis and death of cervical cancer cells. HeLa cells were treated with different concentrations of CPT in presence and absence of 100 μm vitamin E. Treated cells were subjected to cytotoxicity studies, catalase assay, DNA fragmentation assay, clonogenic assay and flow cytometry based apoptosis detection. Also, Raman spectroscopy a label free technique which provides global information, in conjunction with multivariate tools like PCA, PCLDA and FDA, was investigated to explore vitamin E supplementation induced alterations. Our data based on biochemical and biophysical experimental analysis reveals that CPT causes DNA damage along with protein and lipid alteration culminating in cell death. Importantly, Raman spectroscopic analysis could uniquely differentiate the cluster of control and vitamin E control from CPT and CPT + Vit E treated cells. We conclusively prove that presence of vitamin E at 100 μM concentration shows promising antioxidant activity and displays no modulatory role on CPT induced effect, thereby causing no possible hindrance with the efficacy of the drug. Vitamin E may prove beneficial to alleviate chemotherapy associated side effects in patients during clinical settings which may open the doors further for subsequent exploration in in vivo preclinical studies.      

Peptide design 310-helical conformation of a linear pentapeptide containing two dehydrophenylalanines,Boc-Gly-ΔZPhe-Leu-ΔZPhe-Ala-NHCH3

α, β-Dehydroamino acids are expected to provide conformational constraint to the peptide backbone. A pentapeptide containing two dehydrophenylalanines (Δ^ZPhe) separated by one L -amino acid has been synthesized and its solid state conformation determined. The pentapeptide, Boc-Gly-Δ^ZPhe-Leu-Δ^ZPhe-Ala-NHCH₃, crystallizes from aqueous methanol in the orthorhombic space group P2₁2₁2₁. There are four formula units, C₃₅H₄₆N₆O₇, in a unit cell of dimensions a = 10.155(3), b = 15.175(1), and c = 23.447(2) Å, at room temperature. The structure was solved by direct methods program, SIR88, and refined to a final R = 0.038 based on 3049 reflections with I > 2σ(I). All the peptide links are trans and the backbone conformation of the pentapeptide can be described as a 3₁₀-helix, with mean ?, ψ values of ?65.1° and ?22.8° (the value is averaged over the first four residues). There are four intramolecular 4 → 1 type hydrogen bonds characteristic of 3₁₀-type helices. In the crystal, the helices are held together by intermolecular N? H…?O?C head-to-tail and lateral hydrogen bonding between symmetry related molecules. This mode of packing is similar to the packing motifs observed so often in other oligopeptides that adopt a 3₁₀-helical structure. © 1993 John Wiley & Sons, Inc.     

Backbone and side-chain resonance assignments of <Emphasis Type="Italic">Plasmodium falciparum</Emphasis> SUMO

One of the most debilitating diseases Malaria, in its different forms, is caused by protozoan of Plasmodium species. Deadliest among these forms is the “cerebral malaria” which is afflicted upon by Plasmodium falciparum. Plasmodium adopts numerous strategies including various post-translational modifications (PTMs) to infect and survive in the human host. These PTMs have proven their critical requirement in the Plasmodium biology. Recently, sumoylation has been characterized as one of the important PTMs and many of its putative substrates have been identified in Plasmodium. Sumoylation is the covalent attachment of SUMO protein to the substrate protein, which is mediated by an enzyme cascade involving activating (E1), conjugating (E2), and ligating enzymes (E3). Here, we report resonance assignment for ¹H, ¹³C and ¹⁵N of Plasmodium falciparum SUMO (Pf-SUMO) protein determined by various 2D and 3D heteronuclear NMR experiments along with predicted secondary structures.     

Novel oligosaccharide side chains of the collagen-like region of BclA, the major glycoprotein of the Bacillus anthracis exosporium

Spores of Bacillus anthracis, the causative agent of anthrax, are enclosed by a prominent loose fitting layer called the exosporium. The exosporium consists of a basal layer and an external hairlike nap. The filaments of the nap are composed of a highly immunogenic glycoprotein called BclA, which has a long, central collagen-like region with multiple XXG repeats. Most of the triplet repeats are PTG, and nearly all of the triplet repeats contain a threonine residue, providing multiple potential sites for O-glycosylation. In this study, we demonstrated that two O-linked oligosaccharides, a 715-Da tetrasaccharide and a 324-Da disaccharide, are released from spore- and exosporium-associated BclA by hydrazinolysis. Each oligosaccharide is probably attached to BclA through a GalNAc linker, which was lost during oligosaccharide release. We found that multiple copies of the tetrasaccharide are linked to the collagen-like region of BclA, whereas the disaccharide may be attached outside of this region. Using NMR, mass spectrometry, and other analytical techniques, we determined that the structure of the tetrasaccharide is 2-O-methyl-4-(3-hydroxy-3-methylbutamido)-4,6-dideoxy-beta-d-glucopyranosyl-(1-->3)-alpha-l-rhamnopyranosyl-(1-->3)-alpha-l-rhamnopyranosyl-(1-->2)-l-rhamnopyranose. The previously undescribed nonreducing terminal sugar (i.e. 2-O-methyl-4-(3-hydroxy-3-methylbutamido)-4,6-dideoxy-d-glucose) was given the trivial name anthrose. Anthrose was not found in spores of either Bacillus cereus or Bacillus thuringiensis, two species that are the most phylogenetically similar to B. anthracis. Thus, anthrose may be useful for species-specific detection of B. anthracis spores or as a new target for therapeutic intervention.