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Smog is a harmfulmixture of fog, smoke, dust and air pollutantssuch as nitrogen oxides, volatile organic compounds etc. Ground ozone can cause distressing health effect. Smog is a complex atmospheric pollutant mixture consisting of ozone, a pollutant with adverse effects on human health, vegetation, and materials; other eye-irritant and phytotoxic pollutants (such as aldehydes and peroxyacetyl nitrates); nitrogen dioxide (cause of the “whiskey-brown” color in the Los-Angeles atmosphere); and fine particles that cause adverse health effects, reduce visibility, and cause the “brown cloud” phenomenon. Photochemical smog is produced by vehicular emission mainly. Here we are discussing chemistry of formation of PAN (Peroxyacetyl nitrate), its impact environment & human health.

Cytoplasmic pattern recognition receptors (PRRs) for double-stranded RNA (RIG-I/MDA5) are key mediators of anti-viral responses. PRR agonists, such as dsRNA oncolytic Reovirus type 3 Dearing (Rt3D), potently activate RNA sensors. We used an unbiased cytotoxicity screen to reveal synergistic drug-virotherapy combinations and found potent effects of Rt3D combined with the CDK4/6 inhibitor, palbociclib. The combination augmented oncolytic virus-induced endoplasmic reticulum (ER) stress/unfolded protein response (UPR) and the expression and activation/signaling of RNA sensors. Combined Rt3D-palbociclib treatment potently increased interferon production and signaling, and knockdown studies implicated key UPR proteins and the RNA sensor, RIG-I, as essential to the phenotype observed. Further experiments, using canonical RIG-I agonists and an ER stress inducer, thapsigargin, confirmed cross-talk between RNA sensing and ER stress pathways that augmented cancer cell death and interferon production. Combined Rt3D-palbociclib also increased innate immune activation within tumour cells and IFN-induced HLA expression. Analysis of the immunopeptidome revealed changes to HLA-captured peptides with Rt3D-palbociclib, including altered expression of peptides from cancer/testis antigens (CTA) and endogenous retroviral elements (ERVs). Our findings highlight cross-talk between UPR signaling and RNA-mediated PRR activation as a means of enhancing anti-cancer efficacy with potential pro-immunogenic consequences. This has implications for future clinical development of PRR agonists and oncolytic viruses, and broadens the therapeutic remit of CDK4/6 inhibitors to include roles as both ER stress and dsRNA PRR sensitizers.

Background:Shiga toxins comprise a family of related proteins produced by bacteria Shigella dysenteriae and some strains of Escherichia coli that cause severe clinical manifestations. Severe Shiga toxin intoxication results in Haemolytic-Uremic Syndrome (HUS), up to 50% of HUS patients manifest some degree of renal failure and ~10% of such cases develop permanent renal failure or death. Objective: In present research work production of biologically active rStx from non-toxic rStxA and rStxB subunits were established that can be used in many biomedical applications.Methods:Purification of Shiga toxin from bacteria is a multistep time consuming process resulting in low yield. To overcome this problem, the rStxA and rStxB protein were separately cloned and expressed in E. coli host and purified through affinity chromatography. GST pull-down assay was performed for interaction study between rStxA and pentameric rStxB. The affinity between A and B subunits of reconstituted recombinant Shiga toxin (AB5) was determined by SPR. The biological activity of the toxin was confirmed in Vero cells and mouse lethality assay.Results:The yield of GST-StxA and His6X-StxB obtained after affinity chromatography was estimated to 2 and 5 mg/l, respectively. Samples analyzed in pull down assay revealed two bands of ~58 kDa (rStxA) and ~7.7 kDa (rStxB) on SDS-PAGE. Affinity was confirmed through SPR with KD of 0.85 pM. This rStx produced from 1:5 molar ratio found to be cytotoxic in Vero cell line and resulted lethality in mouse.Conclusions:Large scale production of rStx using the method can facilitate screening and evaluation of small molecule inhibitors for therapeutics development.

BackgroundUnderstanding the pathways that drive adrenocortical carcinoma (ACC) is essential to the development of more effective therapies. This study investigates the role of the transcription factor HOXB9 and other HOX factors in ACC and its treatment.MethodsWe used transgenic mouse models to determine the role ofHoxb9in adrenal tumour development. Patient transcriptomic data was analysed for the expression of HOX genes and their association with disease. Drug response studies on various adrenocortical models were done to establish novel therapeutic options.ResultsOur human ACC dataset analyses showed high expression ofHOXB9, and other HOX factors, are associated with poorer prognosis. Transgenic overexpression ofHoxb9in the adrenal cortex of mice with activatedCtnnb1led to larger adrenal tumours. This phenotype was preferentially observed in male mice and was characterised by more proliferating cells and an increase in the expression of cell cycle genes, includingCcne1. Adrenal tumour cells were found to be dependent on HOX function for survival and were sensitive to a specific peptide inhibitor.ConclusionsThese studies showHoxb9can promote adrenal tumour progression in a sex-dependent manner and have identified HOX factors as potential drug targets, leading to novel therapeutic approaches in ACC.

Aneuploidy, defined as the loss and gain of whole and part chromosomes, is a near-ubiquitous feature of cancer genomes, is prognostic, and likely an important determinant of cancer cell biology. In colorectal cancer (CRC), aneuploidy is found in virtually all tumours, including precursor adenomas. However, the temporal evolutionary dynamics that select for aneuploidy remain broadly uncharacterised. Here we perform genomic analysis of 755 samples from a total of 167 patients with colorectal-derived neoplastic lesions that cross-sectionally represent the distinct stages of tumour evolution, and longitudinally track individual tumours through metastasis and treatment. Precancer lesions (adenomas) exhibited low levels of aneuploidy but high intra-tumour heterogeneity, whereas cancers had high aneuploidy but low heterogeneity, indicating that progression is through a genetic bottleneck that suppresses diversity. Individual CRC glands from the same tumour have similar karyotypes, despite prior evidence of ongoing instability at the cell level. Pseudo-stable aneuploid genomes were observed in metastatic lesions sampled from liver and other organs, after chemo- or targeted therapies, and late recurrences detected many years after the diagnosis of a primary tumour. Modelling indicates that these data are consistent with the action of stabilising selection that ‘traps’ cancer cell genomes on a fitness peak defined by the specific pattern of aneuploidy. These data show that the initial progression of CRC requires the traversal of a rugged fitness landscape and subsequent genomic evolution, including metastatic dissemination and therapeutic resistance, is constrained by stabilising selection.

Botulinum neurotoxins (BoNTs) are the most toxic biological substances known. Their potential use as biological warfare agent results in their classification as category A biowarfare agent by Centers for Disease Control and Prevention (CDC), USA. Presently, there are no approved detection system and pharmacological treatments for BoNT intoxication. Although a toxoid vaccine is available for immuno-prophylaxis, vaccines cannot reverse the effect of pre-translocated toxin. Direct handling of the live BoNTs for developing detection and therapeutics may pose fatal danger. This concern was addressed by purifying the recombinant catalytically active light chain of BoNT/F. BoNT/F-LC gene was amplified from the genomic DNA using specifically designed primers and expressed in Escherichia coli. Expression and purification profile were optimized under different conditions for biologically active light chain production. Specific polyclonal antibodies generated against type F illustrates in vivo neutralization in mice and rabbit. These antibodies play key role in conceiving the development of high throughput SPR based detection system which is a highly precise label free technique for protein interaction analysis. The presented work is first of its kind, signifying the production of highly stable and active rBoNT/F-LC and its immunochemical characterization. The study aids in paving the path towards developing a persistent detection system as well as in presenting comprehended scheme for in vitro small molecule therapeutics analysis.

1. Background: The application of massively parallel sequencing has led to the identification of aberrant druggable pathways and somatic mutations within therapeutically relevant genes in gastro-oesophageal cancer. Given the widespread use of formalin-fixed paraffin-embedded (FFPE) samples in the study of this disease, it would be beneficial, especially for the purposes of biomarker evaluation, to assess the concordance between comprehensive exome-wide sequencing data from archival FFPE samples originating from a prospective clinical study and those derived from fresh-frozen material. 2. Methods: We analysed whole-exome sequencing data to define the mutational concordance of 16 matched fresh-frozen and FFPE gastro-oesophageal tumours (N = 32) from a prospective clinical study. We assessed DNA integrity prior to sequencing and then identified coding mutations in genes that have previously been implicated in other cancers. In addition, we calculated the mutant-allele heterogeneity (MATH) for these samples. 3. Results: Although there was increased degradation of DNA in FFPE samples compared with frozen samples, sequencing data from only two FFPE samples failed to reach an adequate mapping quality threshold. Using a filtering threshold of mutant read counts of at least ten and a minimum of 5% variant allele frequency (VAF) we found that there was a high median mutational concordance of 97% (range 80.1–98.68%) between fresh-frozen and FFPE gastro-oesophageal tumour-derived exomes. However, the majority of FFPE tumours had higher mutant-allele heterogeneity (MATH) scores when compared with corresponding frozen tumours (p < 0.001), suggesting that FFPE-based exome sequencing is likely to over-represent tumour heterogeneity in FFPE samples compared to fresh-frozen samples. Furthermore, we identified coding mutations in 120 cancer-related genes, including those associated with chromatin remodelling and Wnt/β-catenin and Receptor Tyrosine Kinase signalling. 4. Conclusions: These data suggest that comprehensive genomic data can be generated from exome sequencing of selected DNA samples extracted from archival FFPE gastro-oesophageal tumour tissues within the context of prospective clinical trials.

Tetra coordinated copper(II) complex of formula [Cu(L1)(imid)] is synthesized using imidazole and a tridentate O,N,O hydrazone ligand L1 prepared by condensation of 1,1,1-trifluoropentanedione and 4-chlorobenzhydrazide. The ligand and complex are characterized by UV–Visible, FTIR, NMR, mass and single crystal XRD techniques. DNA binding mode is assessed by UV absorption, fluorescence spectral and circular dichroism studies. Based on the results, it is observed that complex has preferred intercalative mode of binding with DNA. The binding constant, Kb, was found to be 4.02 ± 0.09 × 104 M− 1. Thermodynamic parameters such as ΔH, ΔS and ΔG obtained from acridine orange fluorescence displacement assay revealed that the hydrophobic and hydrogen bonding interactions are playing a major role in the binding pattern. In addition, cytotoxicity of the complex towards MCF-7 breast cancer cell line has also been assessed.

Botulinum neurotoxins (BoNTs) are the most toxic category A biological warfare agents. There is no therapeutics available for BoNT intoxication yet, necessitating the development of a medical countermeasure against these neurotoxins. The discovery of small molecule-based drugs has revolutionized in the last two decades resulting in the identification of several small molecule inhibitors of BoNTs. However, none progressed to clinical trials. 8-Hydroxyquinolines scaffold-based molecules are important ‘privileged structures’ that can be exploited as inhibitors of a diverse range of targets. In this review, our study of recent reports suggests the development of 8-hydroxyquinoline derived molecules as a potential drug may be on the horizon.

Actinomycetes strain was isolated from leaf litter soil sample and was identified as Streptomyces sp. by conventional and molecular approaches. The biologically active compound responsible for antimicrobial and anticancer activity of the strain JAR6 was elucidated by solid state fermentation followed by subsequent chromatographic and spectroscopic analysis. Extraction, purification and structural confirmation of red pigment metabolite viz undecylprodigiosin were established on the basis of spectroscopic studies and comparing the data from the literature. The biologically active compound was tested against Gram-positive and Gram-negative clinical isolates and its minimum inhibitory concentration was recorded. The antimicrobial activity of undecylprodigiosin is more prominent against Salmonella sp., Proteus mirabilis, Shigella sp. and Enterococcus sp. whereas, it was less effective against Staphylococcus aureus, Klebsiella pneumonia and Escherichia coli. The anticancer activity of undecylprodigiosin was tested against HeLa cell lines and it exhibited commendable cytotoxicity effect with IC50 value of 145 µg/ml. The present investigation reveals that undecylprodigiosin produced by Streptomyces strain JAR6 is a potent bioactive metabolite with effective pharmaceutical properties.

Actinomycetes strain was isolated from leaf litter soil sample and was identified as Streptomyces sp. by conventional and molecular approaches. The biologically active compound responsible for antimicrobial and anticancer activity of the strain JAR6 was elucidated by solid state fermentation followed by subsequent chromatographic and spectroscopic analysis. Extraction, purification and structural confirmation of red pigment metabolite viz undecylprodigiosin were established on the basis of spectroscopic studies and comparing the data from the literature. The biologically active compound was tested against Gram-positive and Gram-negative clinical isolates and its minimum inhibitory concentration was recorded. The antimicrobial activity of undecylprodigiosin is more prominent against Salmonella sp., Proteus mirabilis, Shigella sp. and Enterococcus sp. whereas, it was less effective against Staphylococcus aureus, Klebsiella pneumonia and Escherichia coli. The anticancer activity of undecylprodigiosin was tested against HeLa cell lines and it exhibited commendable cytotoxicity effect with IC50 value of 145 µg/ml. The present investigation reveals that undecylprodigiosin produced by Streptomyces strain JAR6 is a potent bioactive metabolite with effective pharmaceutical properties.

CAN is found to be an efficient catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives via one-pot coupling reaction of phthalhydrazide, aromatic aldehydes, and malononitrile or ethyl cyanoacetate in PEG as solvent. The major attributes of this synthetic protocol are the use of nontoxic, inexpensive, and readily available catalyst, mild conditions, easy work up, improved yields, and the PEG 400 as solvent that is environmentally benign as well as recyclable.

Objectives Botulinum neurotoxins are highly potent biological warfare agents. The unavailability of countermeasures against these neurotoxins has been a matter of extensive research. However, no clinical therapeutics has come to existence till date. The 8-hydroxyquinoline (8-HQ) scaffold is established privileged compound and its potential as drug candidate against BoNTs is recently being explored. Methods In present work, three course studies were performed involving in silico, in vitro and in vivo cascade to screen 8-HQ small molecule inhibitors against BoNT/F intoxication. ~800 molecules obtained from open repositories were screened in silico and commercially obtained twenty-four 8-HQ derived small molecule inhibitors were evaluated against rBoNT/F light chain through fluorescence thermal shift (FTS) assay. Selected compounds were further evaluated through endopeptidase assay. Further binding affinity analysis was done through surface plasmon resonance (SPR) based Proteon™ XPR 36 system. Finally, the in vivo efficacy of these compounds was evaluated in mice model. Results Three compounds NSC1011, NSC1014 and NSC84094 were found to be highly inhibitory after screening of 8-HQ compounds through FTS assay and endopeptidase assay. SPR based protein-small molecule interaction studies showed highest affinity binding of NSC1014 (KD: 5.58E-06) with BoNT/F-LC. NSC1011, NSC1014, and NSC84094 displayed IC50 of 30.47 ± 6.24, 14.91 ± 2.49 and 17.39 ± 2.74 μM, respectively, in endopeptidase assay. NSC1011 and NSC1014 displayed marked extension of survival time in mice model. Conclusion NSC1011 and NSC1014 have emerged as promising drug candidate against BoNT/F intoxication displaying higher potential than previously reported compounds.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

A series of 2-amino-3,5-dicarbonitrile-6-thio-pyridine derivatives have been synthesized by a simple method via a one-pot, three-component condensation reaction of aromatic aldehydes and malononitrile with substituted thiophenols using potassium carbonate as a green base in polyethylene glycol (PEG-400) as a reusable solvent. This protocol proved to be efficient and environmentally benign in terms of high yields, short reaction times, mild conditions, and reusability of the reaction medium. .

Nafion-H® served as an effective and environmental friendly heterogeneous catalyst for the convenient synthesis of a series of [1,2,4]triazolo[5,1-b]quinazolinones and [1,2,4]triazolo[1,5-a]pyrimidines by condensation of 3-amino-1,2,4-triazole as an amine source, different aldehydes and 1,3-dicarbonyl compounds in polyethylene glycol as solvent. The catalyst exhibited excellent recyclability without any significant loss of catalytic activity. This protocol offers several merits like simple work-up, mild conditions, higher yields and recyclability of the catalyst as well as solvent. Moreover, there was no need of product purification via column chromatography as the crude products obtained were very much pure.

Cytochrome P450s are important both in the metabolism of xenobiotics and the production of compounds such as cyanogenic glucosides, which insects use in their defence. In the present study, we use transcriptomic and genomic information to isolate and name P450-encoding genes from the butterfly Heliconius melpomene. We classify each of the putative genes into its appropriate superfamily and compare the distribution of P450s across sequenced insects. We also identify homologues of two P450s known to be involved in cyanogenesis in the six-spot Burnet moth, Zygaena filipendulae. Classification of Heliconius P450s should be an important step in the dissection of their role in the exploitation of their host plant, the passion vine Passiflora.

The biological approach to synthesize metal nanoparticles is an important aspect of current nanotechnology research. Silver nanoparticles have been well-known for their inhibitory and antimicrobial effects. The ever-increasing antibiotic resistance in pathogenic and opportunistic microorganisms is a major threat to the health care industry. In the present investigation, silver nanoparticles have been successfully biosynthesized by Streptomyces sp JAR1. Biosynthesized silver nanoparticles were characterized by means of several analytical techniques including a UV-Visible spectrophotometer, Fourier transform infrared spectroscopy, X-ray diffraction pattern analysis, and atomic force microscopy. An evaluation of the antimicrobial activity of silver nanoparticles (AgNPs) was carried out against clinically important pathogenic microorganisms. The metal nanoparticles were also evaluated for their combined effects with antibiotics against the clinical pathogens. The anti-bacterial activities of the antibiotics increased in the presence of the biologically synthesized AgNPs against the clinically important pathogens. The highest enhancing effect was observed for erythromycin against the test pathogens.

A facile and efficient one-pot, four-component synthesis of polyhydroquinoline derivatives via the Hantzsch reaction using Nafion-H® as heterogeneous catalyst in PEG 400–water solvent system is described herein. The present methodology offers several advantages such as excellent yields, simple procedure, shorter reaction times, and milder conditions with remarkable recyclability.

A new green protocol has been developed for the synthesis of 2 H -indazolo[2,1- b ]phthalazine-triones via one-pot, three-component condensation reaction of aromatic aldehydes with 1,3-dicarbonyl compounds and phthalhydrazide using reusable dodecylphosphonic acid (DPA) as heterogeneous solid acid catalyst under solvent-free conditions. This protocol provides a novel and improved method for obtaining 2 H -indazolo[2,1- b ]phthalazine-triones in terms of good yields with little catalyst loading.

A simple, efficient, single step and environmentally benign synthesis of 2-aminothiazoles is described in this paper. This green protocol was catalyzed by recyclable solid supported Nafion-H using polyethylene glycol–water solvent system with improved efficiency and reduced waste production.

Despite showing clinical activity in BRAF-mutant melanoma, the MEK inhibitor (MEKi) trametinib failed to show clinical benefit in KRAS-mutant colorectal cancer. To identify mechanisms of resistance to MEK inhibition we identified gene expression differences between MEKi-sensitive and MEKi-resistant colorectal cancer cell lines. Strikingly, inflammation-related gene sets were the most significantly enriched in cell lines exhibiting intrinsic or acquired resistance to MEK inhibition. The bromodomain inhibitor JQ1 suppressed inflammatory gene expression and in combination with MEK inhibitors displayed synergistic anti-proliferative activity, inhibited colony formation and induced apoptosis in colorectal cancer cell lines. NFkB activation was greater in cell lines resistant to MEK inhibition and JQ1 treatment suppressed TNF-induced translocation of NFkB to the nucleus. Resistance to MEK inhibition could be induced by inflammatory cytokines or by conditioned medium from macrophage cultures and was associated with greater NFkB activation. In 2-dimensional cell culture and in 3-dimensional spheroid models of colorectal cancer, resistance to trametinib was readily established; however, co-treatment of cells with JQ1 and trametinib suppressed the emergence of resistant populations. Notably, high inflammatory gene expression was confirmed in patient-derived organoid (PDO) models of colorectal cancer, which displayed resistance to trametinib. JQ1 treatment of PDOs suppressed inflammatory gene expression and showed synergistic anti-proliferative activity in combination with trametinib. Combination treatment of in vivo models of KRAS-mutant colorectal cancer significantly suppressed tumor growth. Our findings provide a potential explanation for the limited response to MEK inhibitors in KRAS-mutant colorectal cancer, where a highly inflammatory environment may prime cells to be resistant to MEK inhibition. Moreover, the high expression of inflammatory genes was associated with significantly reduced survival of colorectal cancer patients. Excitingly, this opens novel therapeutic opportunities to overcome intrinsic and acquired resistance to MEK inhibition in colorectal cancer. Citation Format: Steve Wagner, George Vlachogiannis, Alexis de Haven Brandon, Melanie Valenti, Gary Box, Liam Jenkins, Caterina Mancusi, Annette Self, Ritika Chauhan, Alistair Rust, Nik Matthews, Kate Eason, Anguraj Sadanandam, Clare Isacke, Vladimir Kirkin, Nicola Valeri, Steven R. Whittaker. Suppression of inflammatory gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-094.

CAN is found to be an efficient catalyst for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives via one-pot coupling reaction of phthalhydrazide, aromatic aldehydes, and malononitrile or ethyl cyanoacetate in PEG as solvent. The major attributes of this synthetic protocol are the use of nontoxic, inexpensive, and readily available catalyst, mild conditions, easy work up, improved yields, and the PEG 400 as solvent that is environmentally benign as well as recyclable.

Polyethylene glycol (PEG) was found to be an inexpensive nontoxic and effective medium for the synthesis of imidazo[2,1-b]-1,3,4-thiadiazoles in the presence of potassium carbonate as a green base in high yields. In addition, the solvent system can be recovered and reused, making this protocol economically and potentially viable.

Objective: Prodigiosin is a red tripyrrole pigment which is synthesized as a secondary metabolite by biotypes A1, A2, and A6 of Serretia marcescens. This study was aimed to optimize production parameters for prodigiosin pigment produced by S. marcescens strain JAR8 and to determine its antimicrobial, cytotoxicity, and dyeing properties.Methods: The effect of various media components, process parameters (temperature, pH, incubation period), and other supplements was investigated, and the maximum production of prodigiosin was found to be at temperature 28°C, pH 7.0, incubation period of 5 day with peptone in the media. Antibacterial, cytotoxicity, and dyeing properties of prodigiosin were studied in depth.Results: The antimicrobial study of prodigiosin revealed that it is a potent inhibitor of Gram-positive bacteria as well as Gram-negative bacteria. The prodigiosin exhibited commendable dose-dependent cytotoxicity effect against human bone cancer cells with the IC50 of 108 μg/ml. Prodigiosin produced by strain JAR8 resisted the action of acid, alkali and detergent when applied to textile cloth.Conclusion: The deep red pigment prodigiosin produced by strain JAR8 is economically effective and can be categorized as microbial natural product for further pharmaceutical applications.

This three-component one-pot condensation in water affords the title compounds in high yields under mild conditions.

A facile and efficient one-pot, four-component synthesis of polyhydroquinoline derivatives via the Hantzsch reaction using Nafion-H® as heterogeneous catalyst in PEG 400–water solvent system is described herein. The present methodology offers several advantages such as excellent yields, simple procedure, shorter reaction times, and milder conditions with remarkable recyclability.

The fungal strain AJA1 was isolated from leaf litter sample and identified as Penicillium decumbens through 18S rRNA gene sequencing. The antimicrobial potential of Penicillium decumbens strain AJA1 was investigated against medically important pathogenic microorganisms. The mycelium obtained in the presence of four different nitrogen sources sodium nitrate, potassium nitrate, casein, and soybean meal was extracted with methanol and the extracts obtained were determined for antimicrobial and antioxidant properties. The Gram positive bacteria (Staphylococcus aureus, Bacillius subtilis) were effectively inhibited by obtained methanol extract, while Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella sp., Shigella sp., Proteus mirabilis, Kelbsiella sp., Enterococcus sp., and Alcaligens sp.) were resistant to the extracts. The antioxidant activity was evaluated by hydroxyl free radicals and 2, 2-diphenyl-1-(2, 4, 6-trinitrophenyl) hydrazyl (DPPH). The determination of antimicrobial activity against test organisms indicated that the concentration of active components was directly influenced on the antimicrobial activity of the extracts obtained.

A novel protocol is developed for the synthesis of title compounds (IV) by means of one-pot three-component condensation.

The evolutionary importance of hybridization and introgression has long been debated. Hybrids are usually rare and unfit, but even infrequent hybridization can aid adaptation by transferring beneficial traits between species. Here we use genomic tools to investigate introgression in Heliconius, a rapidly radiating genus of neotropical butterflies widely used in studies of ecology, behaviour, mimicry and speciation. We sequenced the genome of Heliconius melpomene and compared it with other taxa to investigate chromosomal evolution in Lepidoptera and gene flow among multiple Heliconius species and races. Among 12, 669 predicted genes, biologically important expansions of families of chemosensory and Hox genes are particularly noteworthy. Chromosomal organization has remained broadly conserved since the Cretaceous period, when butterflies split from the Bombyx (silkmoth) lineage. Using genomic resequencing, we show hybrid exchange of genes between three co-mimics, Heliconius melpomene, Heliconius timareta and Heliconius elevatus, especially at two genomic regions that control mimicry pattern. We infer that closely related Heliconius species exchange protective colour-pattern genes promiscuously, implying that hybridization has an important role in adaptive radiation. © 2012 Macmillan Publishers Limited.

Background The whitefly Trialeurodes vaporariorum is an economically important crop pest in temperate regions that has developed resistance to most classes of insecticides. However, the molecular mechanisms underlying resistance have not been characterised and, to date, progress has been hampered by a lack of nucleotide sequence data for this species. Here, we use pyrosequencing on the Roche 454-FLX platform to produce a substantial and annotated EST dataset. This 'unigene set' will form a critical reference point for quantitation of over-expressed messages via digital transcriptomics. Results Pyrosequencing produced around a million sequencing reads that assembled into 54,748 contigs, with an average length of 965 bp, representing a dramatic expansion of existing cDNA sequences available for T. vaporariorum (only 43 entries in GenBank at the time of this publication). BLAST searching of non-redundant databases returned 20,333 significant matches and those gene families potentially encoding gene products involved in insecticide resistance were manually curated and annotated. These include, enzymes potentially involved in the detoxification of xenobiotics and those encoding the targets of the major chemical classes of insecticides. A total of 57 P450s, 17 GSTs and 27 CCEs were identified along with 30 contigs encoding the target proteins of six different insecticide classes. Conclusion Here, we have developed new transcriptomic resources for T. vaporariorum. These include a substantial and annotated EST dataset that will serve the community studying this important crop pest and will elucidate further the molecular mechanisms underlying insecticide resistance.

The present investigation was aimed to explore in vitro and in silico antimicrobial potential of secondary metabolites produced by terrestrial actinomycetes, S. xanthochromogenes JAR5 isolated from deep forest of Kodaikanal, Tamil Nadu, India and was confirmed by 16S rRNA gene sequencing analysis. The bioactive metabolites produced by the strain JAR5 were obtained from the optimized culture medium through solvent extraction method. The crude extract obtained was purified using silica gel column chromatography and partially purified active elute was characterized using UV, FTIR and GC-MS spectroscopic analysis. The partially purified bioactive metabolites produced by strain JAR5 showed 23.333±0.471 diameter zone of inhibition and minimum inhibitory concentration of 80 μg/ml against Enterococcus sp. In silico molecular docking studies revealed binding into crystal structure of topoisomerase II using Autodock vina 4.2 program. The molecular docking of biological active compounds is in good agreement with in vitro antimicrobial screening where the bioactive metabolites showed effective inhibitory effect against Enterococcus sp.

Adenanthera pavonina is an important traditional plant with various medicinal properties which cures major human ailments. The present study was carried out to explore the antimicrobial as well as anticancer effect of seed and leaves extract of red wood plant. The seed and leaves methanolic extract exhibited efficacious antimicrobial and anticancer activity against various pathogens whereas acetone seed extract did not show any biological activity. The methanol extract has anticancer effect being effective against bone cancer cell line when compared with acetone extract. A. pavonia is known to produce anti-inflammatory drugs whereas this traditional plant is used for anticancer drugs as well which will be greater benefit to mankind.

BACKGROUND: Understanding how alternative phenotypes arise from the same genome is a major challenge in modern biology. Eusociality in insects requires the evolution of two alternative phenotypes - workers, who sacrifice personal reproduction, and queens, who realize that reproduction. Extensive work on honeybees and ants has revealed the molecular basis of derived queen and worker phenotypes in highly eusocial lineages, but we lack equivalent deep-level analyses of wasps and of primitively eusocial species, the latter of which can reveal how phenotypic decoupling first occurs in the early stages of eusocial evolution. RESULTS: We sequenced 20 Gbp of transcriptomes derived from brains of different behavioral castes of the primitively eusocial tropical paper wasp Polistes canadensis. Surprisingly, 75% of the 2,442 genes differentially expressed between phenotypes were novel, having no significant homology with described sequences. Moreover, 90% of these novel genes were significantly upregulated in workers relative to queens. Differential expression of novel genes in the early stages of sociality may be important in facilitating the evolution of worker behavioral complexity in eusocial evolution. We also found surprisingly low correlation in the identity and direction of expression of differentially expressed genes across similar phenotypes in different social lineages, supporting the idea that social evolution in different lineages requires substantial de novo rewiring of molecular pathways. CONCLUSIONS: These genomic resources for aculeate wasps and first transcriptome-wide insights into the origin of castes bring us closer to a more general understanding of eusocial evolution and how phenotypic diversity arises from the same genome. This work was supported by RCUK, CONSOLIDER (CSD2007-0005), the Spanish Ministry of Science/n(BIO2006-03380, BFU2009-09168), GTEX (NIH Project 1RO1MH090941-01), a UK Research Council (RCUK) fellowship, and PGF by a FCT postdoctoral grant (SFRH/BPD/42003/2007) from the Portuguese Ministry of Science and Technology. The fieldwork was/nconducted under ANAM Permit No. SE/A-33-09

Sulfamic acid (SA) is successfully utilized as a green, cost-effective and reusable catalyst for the synthesis of triazole[1,2-a]indazole-trione derivatives involving the one-pot, three-component condensation of urazole, aldehydes and cyclic β-diketones in high yields in water as a sole solvent. The salient features of this new methodology are cheaper process, easy availability of the catalyst, mild conditions, versatility, and the catalyst could be recycled easily without affecting the catalytic activity.