PLGA-microsphere mediated clearance of bilirubin in temporarily hyperbilirubinemic rats: an alternate strategy for the treatment of experimental jaundice

In the present study, we have demonstrated the suitability of microspheres in removal of plasma bilirubin from systemic circulation of hyperbilirubinemic rats. Poly (lactide co-glycolide) microspheres (PLGA microspheres) have been shown to bind with bilirubin in both a concentration and time dependent manner. The binding affinity of bilirubin to microspheres was enhanced when rat serum albumin (RSA) was loaded into the microspheres. On evaluating the potential of microspheres in elimination of bilirubin from the systemic circulation, RSA bearing microspheres were found to be competent in both removing bilirubin from the systemic circulation and controlling elevated plasma levels of liver function enzymes in temporarily hyperbilirubinemic rats. On the basis of results of the present study, we suggest that microsphere-based delivery system may help in development of safe, effective and alternate strategy for the treatment of hyperbilirubinemic conditions in model animals.     

A new Bacillus pasteurii urease inhibitor from Euphorbia decipiens

Inhibition of Bacillus pasteurii urease enzyme by 3,7,15-tri-O-acetyl-5-O-nicotinoyl-13,14-dihydroxymyrsinol (1), a diterpene ester with a myrsinol-type skeleton, isolated from Euphorbia decipiens Boiss. and Buhse, was un-competitive consistent with the molecular docking results. The Ki value was 117.40 +/- 0.7 microM.     

In vitro antibacterial, antifungal & cytotoxic activity of some isonicotinoylhydrazide Schiff's bases and their cobalt (II), copper (II), nickel (II) and zinc (II) complexes

Isonicotinoylhydrazide Schiff's bases formed by the reaction of substituted and unsubstituted furyl-2-carboxaldehyde and thiophene-2-carboxaldehyde with isoniazid and, their Co (II), Cu (II), Ni (II) and Zn (II) complexes have been synthesized, characterized and screened for their in vitro antibacterial activity against Mycobacterium tuberculosis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhi, Shigella dysenteriae, Bacillus cereus, Corynebacterium diphtheriae, Staphylococcus aureus and Streptococcus pyogenes bacterial strains and for in vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glabrata. The results of these studies show the metal complexes to be more antibacterial and antifungal against one or more bacterial/fungal strains as compared to the uncomplexed compounds. The brine shrimp bioassay indicated Schiff's bases, L3 and L6 and, their Cu (II) and Ni (II) metal complexes to be cytotoxic against Artemia salina, while all other compounds were inactive (LD50 > 1000).     

Molecular Characterization of Mercury Resistant Bacteria Inhabiting Polluted Water Bodies of Different Geographical Locations in India

Mercury pollution is a major environmental problem that arises as a result of natural processes as well as from anthropogenic sources. In response to toxic mercury compounds, microbes have developed astonishing array of resistance systems to detoxify them. To address this challenge, this study was aimed in screening bacterial isolates for their tolerance against varied concentrations of phenylmercuric acetate. Mercury transformation by bacteria being sensitive to factors such as available carbon source, etc. that affect mer-mediated transformation, screened mercury tolerant bacteria were also studied for their tolerance to different antimicrobials and carbon sources, followed by identification using biochemical as well as 16S rRNA approach. Following identification, gene encoding organomercurial lyase catalyzing protonolytic cleavage of C-Hg bond of organic mercury was amplified using gene specific primers, cloned in pGEMT(?) easy vector and sequenced. Microbe-based approach using organomercurial lyase encoded by merB gene being potentially economic, provides foundation to facilitate genetic manipulation of this environmentally important enzyme to remove high concentrations of obstinate mercury using holistic, multifaceted approach for use in bioremediation through generation of transgenics or as catalyst for use in bioreactors.     

Modulated phases of phospholipid bilayers induced by tocopherols

The influence of α-, γ- and δ-tocopherols on the structure and phase behavior of dipalmitoyl phosphatidylcholine (DPPC) bilayers has been determined from X-ray diffraction studies on oriented multilayers. In all the three cases the main-transition temperature (T(m)) of DPPC was found to decrease with increasing tocopherol concentration up to around 25 mol%. Beyond this the main transition is suppressed in the case of γ-tocopherol, whereas T(m) becomes insensitive to composition in the other two cases. The pre-transition is found to be suppressed over a narrow tocopherol concentration range between 7.5 and 10 mol% in DPPC-γ-tocopherol and DPPC-δ-tocopherol bilayers, and the ripple phase occurs down to the lowest temperature studied. In all the three cases a modulated phase is observed above a tocopherol concentration of about 10 mol%, which is similar to the P(β) phase reported in DPPC-cholesterol bilayers. This phase is found to occur even in excess water conditions at lower tocopherol concentrations, and consists of bilayers with periodic height modulation. These results indicate the ability of tocopherols to induce local curvature in membranes, which could be important for some of their biological functions.     

The role of ERp44 in maturation of serotonin transporter protein

In heterologous and endogenous expression systems, we studied the role of ERp44 and its complex partner endoplasmic reticulum (ER) oxidase 1-α (Ero1-Lα) in mechanisms regulating disulfide bond formation for serotonin transporter (SERT), an oligomeric glycoprotein. ERp44 is an ER lumenal chaperone protein that favors the maturation of disulfide-linked oligomeric proteins. ERp44 plays a critical role in the release of proteins from the ER via binding to Ero1-Lα. Mutation in the thioredoxin-like domain hampers the association of ERp44C29S with SERT, which has three Cys residues (Cys-200, Cys-209, and Cys-109) on the second external loop. We further explored the role of the protein chaperones through shRNA knockdown experiments for ERp44 and Ero1-Lα. Those efforts resulted in increased SERT localization to the plasma membrane but decreased serotonin (5-HT) uptake rates, indicating the importance of the ERp44 retention mechanism in the proper maturation of SERT proteins. These data were strongly supported with the data received from the N-biotinylaminoethyl methanethiosulfonate (MTSEA-biotin) labeling of SERT on ERp44 shRNA cells. MTSEA-biotin only interacts with the free Cys residues from the external phase of the plasma membrane. Interestingly, it appears that Cys-200 and Cys-209 of SERT in ERp44-silenced cells are accessible to labeling by MTSEA-biotin. However, in the control cells, these Cys residues are occupied and produced less labeling with MTSEA-biotin. Furthermore, ERp44 preferentially associated with SERT mutants (C200S, C209S, and C109A) when compared with wild type. These interactions with the chaperone may reflect the inability of Cys-200 and Cys-209 SERT mutants to form a disulfide bond and self-association as evidenced by immunoprecipitation assays. Based on these collective findings, we hypothesize that ERp44 together with Ero1-Lα plays an important role in disulfide formation of SERT, which may be a prerequisite step for the assembly of SERT molecules in oligomeric form.     

Molecular markers in management of ex situ PGR – A case study

Worldwide germplasm collections contain about 7.4 million accessions of plant genetic resources for food and agriculture. One of the 10 largest ex situ genebanks of our globe is located at the Leibniz Institute of Plant Genetics and Crop Plant Research in Gatersleben, Germany. Molecular tools have been used for various gene bank management practices including characterization and utilization of the germplasm. The results on genetic integrity of long-term-stored gene bank accessions of wheat (self-pollinating) and rye (open-pollinating) cereal crops revealed a high degree of identity for wheat. In contrast, the out-pollinating accessions of rye exhibited shifts in allele frequencies. The genetic diversity of wheat and barley germplasm collected at intervals of 40 to 50?years in comparable geographical regions showed qualitative rather than a quantitative change in diversity. The inter- and intraspecific variation of seed longevity was analysed and differences were detected. Genetic studies in barley, wheat and oilseed rape revealed numerous QTL, indicating the complex and quantitative nature of seed longevity. Some of the loci identified were in genomic regions that co-localize with genes determining agronomic traits such as spike architecture or biotic and abiotic stress response. Finally, a genome-wide association mapping analysis of a core collection of wheat for flowering time was performed using diversity array technology (DArT) markers. Maker trait associations were detected in genomic regions where major genes or QTL have been described earlier. In addition, new loci were also detected, providing opportunities to monitor genetic variation for crop improvement.     

Physiological changes induced by chromium stress in plants: an overview

This article presents an overview of the mechanism of chromium (Cr) stress in plants. Toxic effects of Cr on plant growth and development depend primarily on its valence state. Cr(VI) is highly toxic and mobile whereas Cr(III) is less toxic. Cr-induced oxidative stress involves induction of lipid peroxidation in plants that cause severe damage to cell membranes which includes degradation of photosynthetic pigments causing deterioration in growth. The potential of plants with the adequacy to accumulate or to stabilize Cr compounds for bioremediation of Cr contamination has gained engrossment in recent years.