Optical bleaching front in bedrock revealed by spatially-resolved infrared photoluminescence.

Optically stimulated luminescence (OSL) dating of sediment, based on the accumulation of trapped charge in natural crystals since their last exposure to daylight, has revolutionised our understanding of the late Quaternary period. Recently, a complementary technique called luminescence rock surface dating (RSD), which uses differential spatial eviction of trapped charges in rocks exposed to daylight, has been developed to derive exposure and burial ages, and hard-rock erosion rates. In its current form, the RSD technique suffers from labour intensive sample preparation, uncertainties in the depth and dose rate estimates, and poor resolution of the luminescence-depth profile. Here, we develop a novel, 2D luminescence imaging technique for RSD of large rock slabs (3 × 5 cm) to overcome these challenges. We utilize the recently discovered infrared photoluminescence (IRPL) signal for direct, non-destructive imaging of the luminescence-depth profile in a sub-aerially exposed granitic rock, with an unprecedented spatial resolution of ~140 µm. We further establish a correlation between luminescence and geochemistry using micro X-ray fluorescence (µXRF) spectroscopy. Our study promises a substantial advancement in luminescence imaging and paves the path towards novel applications using 2D dating, micro-dosimetry in mixed composition samples, and portable instrumentation for in-situ luminescence measurements.

DAMTC regulates cytoskeletal reorganization and cell motility in human lung adenocarcinoma cell line: an integrated proteomics and transcriptomics approach.

DAMTC (7,8-diacetoxy-4-methylcoumarin) is a thioderivative of 4-methyl coumarin, and previously we have shown that DAMTC is a potent inhibitor of cell growth and an inducer of apoptosis in non-small cell lung cancer (A549) cells. It induces apoptosis through mitochondrial pathway by modulating NF-κB, mitogen-activated protein kinase (MAPK) and p53 pathways. Herein, we explored the genome-wide effects of DAMTC in A549 cells using the concerted approach of transcriptomics and proteomics. In addition to apoptotic pathways, which have been validated earlier, the bioinformatic analysis of microarray data identified small GTPase-mediated signal transduction among the significantly altered biological processes. Interestingly, we observed significant downregulation of some members of the Rho family GTPases in the proteomics data too. Downregulation of Rho GTPases (RhoGDIα (Rho GDP dissociation inhibitor-α, also known as ARHGDIA), Ras homolog family member A, Ras-related C3 botulinum toxin substrate 1 and cell division cycle 42) was validated by western blotting. The Rho protein family is implicated in maintaining the actin filament assembly and cell motility, and we also observed that DAMTC treatment causes actin cytoskeletal reorganization, promotes filopodia formation and inhibits cell motility in A549 cells. The effect of DAMTC treatment on cytoskeleton was reversed after the overexpression of RhoGDIα. In addition, DAMTC augmented the apoptotic effect of etoposide, a proapoptotic chemotherapeutic drug. This elucidation of the mechanism behind DAMTC-induced apoptosis and inhibition of cell motility in A549 cells may make it a potential therapeutic for lung cancer.

Chemical constituents of the genus Prunus and their medicinal properties.

Prunus is a genus of trees and shrubs, including the plums, cherries, peaches, apricots and almonds. Nearly five hundred seventy chemical compounds have so far been isolated from several Prunus species. This comprehensive review summarizes the isolation of chemical compounds reported during the period 1908 to June 2010. As per scrutiny of literature, we did not find any review on the chemistry or biology of genus Prunus or on the biological activities of its constituents. Extensive work has been done at the Department of Chemistry, University of Delhi by several groups on the isolation, identification, biological activity evaluation and synthesis of a large number of novel compounds from different Prunus species during the the last six decades (1940-2000), primarly by Seshadri, Nagarajan and Parmar et al. on P. domestica, P. cerasus, P. cerasoides, P. puddum and P. communis. This comprehensive review will benefit a large number of researchers in the fields of chemistry, botany, drug industries and pharmacology.

Coumarins as antioxidants.

Coumarins, a well-known class of naturally occurring compounds, display a remarkable array of biochemical and pharmacological actions, some of which suggest that certain members of this group of compounds may significantly affect the function of various mammalian cellular systems. The development of coumarins as antioxidant agents has attracted much attention in recent years. Coumarins afford an opportunity for the discovery of new antioxidants with truly novel mechanisms of action. This review updates and expands the 2006 review by the same author. The review considers and incorporates the most recently published literature on coumarins as related to their antioxidant properties. A lot of coumarins have been identified from natural sources, especially green plants. These natural compounds have served as valuable leads for further design and synthesis of more active analogues. Beyond doubt, a deep understanding of the mechanisms of existing synthetic and natural coumarins will build the basis for the rational design.

Plant polyphenolics as anti-invasive cancer agents.

Because invasion is, either directly or via metastasis formation, the main cause of death in cancer patients, development of efficient anti-invasive agents is an important research challenge. We have established a screening program for potentially anti-invasive compounds. The assay is based on organotypic confronting cultures between human invasive cancer cells and a fragment of normal tissue in three dimensions. Anti-invasive agents appeared to be heterogeneous with regard to their chemical nature, but plant alkaloids, polyphenolics and some of their synthetic congeners were well represented. Even within this group, active compounds were quite diverse: (+)-catechin, tangeretin, xanthohumol and other prenylated chalcones, 3,7-dimethoxyflavone, a pyrazole derivative, an isoxazolylcoumarin and a prenylated desoxybenzoin. The data gathered in this system are now applied in two projects. Firstly, structure-activity relationships are explored with computer models using an artificial neural network approach, based on quantitative structural descriptors. The aim of this study is the prediction and design of optimally efficient anti-invasive compounds. Secondly, the metabolism of orally ingested plant polyphenolics by colonic bacteria is studied in a simulator of the human intestinal microbial ecosystem (SHIME) and in human intervention trials. This method should provide information on the final bioavailability of the active compounds in the human body, with regard to microbial metabolism, and the feasibility of designing pre- or probiotics that increase the generation of active principles for absorption in the gastro-intestinal tract. The final and global aim of all these studies is to predict, synthesize and apply in vivo molecules with an optimal anti-invasive, and hence an anti-metastatic activity against cancer.

Effect of fly ash inhalation on biochemical and histomorphological changes in rat liver.

The effect of fly ash inhalation (4h daily, 5 days a week) for 28 days on the deposition of metal ions and histopathological changes in the liver and serum clinical enzymes has been studied. The results showed an increase in the concentration of metals such as cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), and lead (Pb) in the tissues of exposed rats. The level of metals varied from metal to metal and from organ to organ. Level of serum enzymes such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, and alkaline phosphatase were increased in fly ash exposed rats using whole body inhalation exposure as compared to sham controls. Histopathological studies of rat liver exposed to fly ash revealed infiltration of mononuclear cells in and around the portal triads, which seems to be laden with fly ash particles. Hepatocytes showed necrotic changes such as pyknotic nuclei, karyorrhexis, and karyolytic. These changes were more towards the centrolobular areas than the midzonal and periportal areas. These findings demonstrate that the toxic metals of inhaled fly ash in rats may get translocated into extrapulmonary organs, become deposited and hence may manifest their toxic effects on different tissues.

Extraction chromatographic studies of metal ions using N,N,N',N'-tetraoctyl diglycolamide as the stationary phase.

N,N,N',N'-tetraoctyl diglycolamide (TODGA) has been used as the stationary phase in the extraction chromatographic separation of actinides and other metal ions from pure nitric acid as well as from simulated high-level waste (SHLW). Chromosorb-W was found to be a better support material amongst the different solid supports evaluated viz. chromosorb-W, chromosorb-102, XAD-4 and XAD-7. Uptake profiles of various metal ions, such as U(VI), Pu(IV), Am(III), Eu(III), Fe(III), Sr(II) and Cs(I) were obtained as a function of acidity by batch studies using TODGA/chromosorb-W. Effect of macro concentration of Nd, Fe and U suggested that the uptake of Am(III) is mainly influenced by the presence of trivalent lanthanide ions. Breakthrough capacity of the resin material for Am(III) in presence of macro amount of Eu(III) was determined in the successive cycles of loading and elution. Loading capacity of the column was found to be 20mg of Eu/g of the resin material. Elution studies of Am(III) suggested that 0.01M EDTA was effective amongst different eluents used.

Selective nanoprobes for 'signalling gases'.

The use of arrays of chemical detectors has been realized in electronic nose applications. Recently attention has been focused on the application of e-Noses in the medical arena. These are electronic devices that typically employ non-selective gas sensitive elements for the monitoring of odours and other gaseous analytes. Currently, the lack of relative specificity to a mixture of gaseous analytes for these sensing elements makes the use of pattern recognition algorithms to process the signal and match the acquired data profile to a known pattern necessary, thus identifying the signature of the odour or gas detected. An alternative approach to chemical detection through the use of small arrays (two or three elements) of selective gas sensors made of nanostructured semiconducting films and membranes is described in this work. Sensor selectivity is defined here as higher sensitivity to a given gas or class of gases in the presence of interfering gaseous species. Transition metal oxides are key sensing elements of resistive type chemical detectors. A given oxide may be found in several polymorph phases, each having a distinct structural configuration. Gas-oxide interactions are strongly dependent on the 'structure sensitivity' of the polymorph used in sensing. This paper reviews the effect of polymorphism on the gas specificity and the importance of nanoscale processing for stabilizing the desirable oxide phases, and it introduces a gas-polymorph selection library for building the next generation of gas sensing systems with inherent selectivity to be used as non-invasive disease diagnosis tools.

Hepatotoxic alterations induced by subchronic exposure of rats to formulated fenvalerate (20% EC) by nose only inhalation.

OBJECTIVE: Fenvalerate (20% EC) is a synthetic pyrethroid, which is commonly used in India by farmers for the protection of many food and vegetable crops against a wide variety of insects. However, its inhalation toxicity data is very limited in the literature due to the fact that the exposure levels associated with these effects were usually not reported. Hence, inhalation exposure was carried out to investigate the hepatotoxic effects. METHOD: Adult male rats were exposed to fen for 4 h/day, 5 days a week for 90 days by using Flow Past Nose Only Inhalation Chamber. Sham treated control rats were exposed to compressed air in the inhalation chamber for the same period. RESULTS: The results indicated hepatomegaly, increased activities of serum clinical enzymes (indicative of liver damage/dysfunction) along with pronounced histopathological damage of liver. CONCLUSION: The hepatotoxic potential of formulated Fen (20% EC) in rats exposed by nose only inhalation is being reported for the first time and warrant adequate safety measures for human beings exposed to this insecticide, particularly by inhalation route.

Effect of fly ash inhalation on biochemical and histomorphological changes in rat lungs.

Effect of respirable fly ash particles inhalation on lungs of rats was investigated by exposing them to respirable aerosols of size classified power plant fly ash at average concentrations of up to 14.4 +/- 1.77 mg/m3 for 4 hr/day for 28 consecutive days. A remarkable increase was found in blood eosinophil counts of fly ash exposed animals. Biochemical indicators of pulmonary damage viz. lactate dehydrogenase (cytoplasmic enzyme used as a measure of cell injury), gamma-glutamyl transferase (Clara cell damage) and alkaline phosphatase (potential measure of Type 11 cell secretions) in broncho alveolar lavage fluid (BALF) of fly ash exposed group showed significant elevation. Clumping of fly ash particles in the lungs was observed as evidenced by fly ash ladened macrophage accumulation in the alveolar region. The results suggest a damage, local inflammation and remodelling of lung as indicated by hypertrophy and hyperplasia. These changes reflect the toxic effects of the fly ash inhalation.

Genetic variability among Group A and B respiratory syncytial virus isolates from a large referral hospital in New Delhi, India.

Respiratory syncytial virus (RSV) is an important childhood pathogen of acute lower respiratory infections in developed and developing countries. The molecular epidemiology of RSV in India is largely unknown. The present study was undertaken to standardize and evaluate reverse transcription-PCR (RT-PCR) for the rapid and simultaneous detection of RSV groups A and B in clinical samples and to study intragroup genetic variability. RT-PCR was evaluated by comparing the results of seminested RT-PCR with centrifugation-enhanced cultures on 200 nasopharyngeal aspirates from children with acute lower respiratory infections. RSV was isolated in 34 nasopharyngeal aspirates by centrifugation-enhanced cultures and identified in 45 samples by RT-PCR. In 15 samples RSV was identified by seminested RT-PCR alone and in four by centrifugation-enhanced cultures alone. Of the 45 samples positive for RSV by nested PCR, 15 belonged to group A, 29 to group B, and one sample suggested a mixed infection. Group B RSV predominated in both years of the 2-year study. Genetic variability within RSV groups was studied by restriction fragment analysis of 35 PCR products. Among both group A and group B RSV, two different composite patterns were observed. Thus, RSV was found to be a major pathogen of acute lower respiratory tract infections in India, as it was detected in 24.5% of children by RT-PCR. RT-PCR provides a sensitive method for detection and typing of RSV group A and B viruses in clinical samples as well as a means to study intragroup variations. However, a higher sensitivity of detection of RSV in clinical samples can be obtained by its combination with additional techniques, such as virus cultivation.

Effect of trichloroethylene (TCE) inhalation on biotransformation enzymes of rat lung and liver.

Trichloroethylene (TCE) is widely used as an industrial solvent and cleaning fluid. In the present study the toxic effects of TCE inhalation on pulmonary and hepatic biotransformation enzymes in rats have been investigated by assay of aniline hydroxylase (AH), aminopyrine-N-demethylase (APD), benzo-a-pyrene hydroxylase (BH) and glutathione-s-transferase (GST) activities and glutathione (GSH) contents in liver as well as lungs of exposed animals. In both organs phase I and phase II drug metabolizing enzymes have been found to be increased along with decrease in GSH contents following TCE inhalation. Pulmonary as well as hepatic MFO's seem to be activated by inhaled TCE probably in an attempt for its rapid detoxification and reduced glutathione is used during its biotransformation.

Steroidogenic alterations in testes and sera of rats exposed to formulated Fenvalerate by inhalation.

Fenvalerate (Fen) is a synthetic pyrethroid, which is commonly used for destroying a variety of insect pests damaging several vegetable, fruit, and cotton crops. This insecticide is also used to mitigate household insects like flies, cockroaches, mosquitoes, and so forth. Human beings are exposed to formulated Fen preparations mostly by inhalation during spraying in fields for crop protection, for control of household insects, and also during handling and packaging at manufacturing plants. Limited online information is available regarding toxic effects of formulated Fen exposure on mammalian reproductive system. The present study has been undertaken to investigate male reproductive toxic effects of a formulated preparation of Fen (20% EC) particularly in relation to steroidogenic alterations in testes and sera of rats exposed by nose-only inhalation for (4 hours/day and five days a week) for three months. The results indicate significant reduction in the weight of testes, epididymal sperm counts, and sperm motility, along with decrease in marker testicular enzymes for testosterone biosynthesis viz. 17-beta-hydroxy steroid dehydrogenase (17-beta-HSD) and glucose-6-phosphate dehydrogenase (G6PDH), leading to net decrease in serum testosterone concentration in group of rats exposed to one-fifth LC50 of Fen (20% EC) by inhalation (4 hours/day, five days a week) subchronically for three months. These results for the first time indicate the role of testosterone in Fen (20% EC)-induced male reproductive toxicity of rats subchronically exposed by inhalation probably due to neuroendocrine-mediated phenomenon and hormone-disrupting property of the insecticide.

Lipase-catalyzed chemo- and enantioselective acetylation of 2-alkyl/aryl-3-hydroxypropiophenones.

The chemo- and enantioselective capabilities of porcine pancreatic lipase (PPL) in tetrahydrofuran, and Candida rugosa lipase (CRL) in diisopropyl ether have been investigated for the acetylation of racemic 2-alkyl/aryl-3-hydroxypropiophenones, which are important precursors in the synthesis of biologically active chromanones and isoflavanones. A highly chemoselective acetylation of primary hydroxy group in preference to phenolic hydroxy group leading to the formation of enantiomerically enriched monoacetates has been observed.

Novel lipase-catalysed enantioselective deacetylation of (+/-)-5-acetoxy-3-(4-fluorophenyl)-2-phenylisoxazolidine.

(+/-)-5-Acetoxy-3-(4-fluorophenyl)-2-phenylisoxazolidine has been synthesised by a highly diastereoselective [3+2] cycloaddition reaction between alpha-(4-fluorophenyl)-N-phenylnitrone and vinyl acetate in good yield. Candida rugosa lipase catalyses the deacetylation of this (+/-)-5-acetoxyisoxazolidine in a highly enantioselective fashion in diisopropyl ether containing n-butanol affording (-)-5-acetoxy-3-(4-fluorophenyl)-2-phenylisoxazolidine in 43% yield and >99% ee.

Influence of influenza viral infection on airway smooth muscle activity.

The contractility of airway smooth muscle (ASM) plays an important role in pathophysiology of several bronchial disorders. Increased contraction of ASM during asthma and respiratory viral infection has been attributed to the release of mediators acting through different receptors. In the present study, influence of influenza type A virus (H1N1) infection has been examined on ASM responsiveness to various bronchoactive agents e.g. adenosine, histamine, 5-hydroxytryptamine (5-HT) and isoproterenol in an organ bath set up for isolated tissue preparation. The contractile effect of adenosine, histamine and 5-HT was enhanced, however, relaxant response of isoproterenol was attenuated with the duration following viral exposure. The most prominent response was observed 48 to 72 hr after infection and tissues from multiple exposure to virus infected animals showed the maximum contractile response. Results demonstrated the deleterious effect of viral infection on ASM function and the findings will be helpful in understanding the mechanism of influenza virus induced bronchoconstriction.

Biocatalytic potential of Fusarium globulosum lipase in selective acetylation/deacetylation reactions and in ester synthesis.

AIMS: The present study was carried out to assess the potential of Fusarium globulosum lipase (FGL) for chemoselective and regioselective biotransformations for the synthesis of industrially important organic compounds. METHODS AND RESULTS: Different acetylation/deacetylation reactions and ester synthesis reactions were carried out in organic media. Fusarium globulosum lipase showed exclusive selectivity for the acetylation of the alcoholic hydroxyl group over the phenolic hydroxyl group of the hydroxymethylated phenols and aryl alkyl ketones. This also led to the enantiomeric resolution of the aryl alkyl ketone. In contrast, the lipase showed reversed selectivity in deacetylation where it preferred the phenolic acetoxy group over the alcoholic acetoxy moiety of the peracetates of hydroxymethylated compounds. The enzyme also exhibited strict regioselection for deacetylation at the para position of the peracetate of an aryl alkyl ketone. In addition, the lipase also synthesized a variety of industrially important fatty acid esters of sugars, sugar alcohols, alcohols and ascorbic acid with high preference for middle-chain fatty acids. CONCLUSION: Fusarium globulosum lipase shows versatile catalytic potential in terms of chemo-, enantio- and regioselectivity and fatty acid specificity in carrying out a variety of industrially important biotransformations. SIGNIFICANCE AND IMPACT OF THE STUDY: The biocatalytic potential of FGL can thus be utilized for the synthesis and modification of different types of polyphenolic compounds and esters. These compounds find widespread uses as surfactants, bioactive analogues, antioxidants and flavour components in the food, detergent, pharmaceutical and cosmetic industries.