Quantitative structure-activity relationship analysis of a series of 2,3-diaryl benzopyran analogues as novel selective cyclooxygenase-2 inhibitors

A series of recently synthesized 2,3-diaryl benzopyrans reported as novel selective cycloxygenase-2 inhibitors was subjected to quantitative structure-activity relationship (QSAR) analysis. Our attempt in correlating the derived physicochemical properties with the COX-2 inhibitory activity resulted in some statistically significant QSAR models with good predictive ability. The QSAR results and the probable pharmacophore features investigated through our study explored some interesting findings for the design of potent new class of selective COX-2 inhibitors.     

Block‐cyclic redistribution over heterogeneous networks

Clusters of workstations and networked parallel computing systems are emerging as promising computational platforms for HPC applications. The processors in such systems are typically interconnected by a collection of heterogeneous networks such as Ethernet, ATM, and FDDI, among others. In this paper, we develop techniques to perform block-cyclic redistribution over P processors interconnected by such a collection of heterogeneous networks. We represent the communication scheduling problem using a timing diagram formalism. Here, each interprocessor communication event is represented by a rectangle whose height denotes the time to perform this event over the heterogeneous network. The communication scheduling problem is then one of appropriately positioning the rectangles so as to minimize the completion time of all the communication events. For the important case where the block size changes by a factor of K, we develop a heuristic algorithm whose completion time is at most twice the optimal. The running time of the heuristic is O(PK ²). Our heuristic algorithm is adaptive to variations in network performance, and derives schedules at run-time, based on current information about the available network bandwidth. Our experimental results show that our schedules always have communication times that are very close to optimal. This revised version was published online in July 2006 with corrections to the Cover Date.     

Interstitial cell network volume is reduced in the terminal bowel of ageing mice

Ageing is associated with impaired neuromuscular function of the terminal gastrointestinal (GI) tract, which can result in chronic constipation, faecal impaction and incontinence. Interstitial cells of cajal (ICC) play an important role in regulation of intestinal smooth muscle contraction. However, changes in ICC volume with age in the terminal GI tract (the anal canal including the anal sphincter region and rectum) have not been studied. Here, the distribution, morphology and network volume of ICC in the terminal GI tract of 3‐ to 4‐month‐old and 26‐ to 28‐month‐old C57BL/6 mice were investigated. ICC were identified by immunofluorescence labelling of wholemount preparations with an antibody against c‐Kit. ICC network volume was measured by software‐based 3D volume rendering of confocal Z stacks. A significant reduction in ICC network volume per unit volume of muscle was measured in aged animals. No age‐associated change in ICC morphology was detected. The thickness of the circular muscle layer of the anal sphincter region and rectum increased with age, while that in the distal colon decreased. These results suggest that ageing is associated with a reduction in the network volume of ICC in the terminal GI tract, which may influence the normal function of these regions.     

Prospecting endophytes from different Fe or Zn accumulating wheat genotypes for their influence as inoculants on plant growth,yield, and micronutrient content

The plant microbiome is known to play a significant role in improving plant productivity and quality of produce, and the endophytic component was explored toward developing inoculants for enhancing micronutrient concentration in grains. A set of 213 endophytes (201 bacteria and 12 fungi) were isolated, from a set of 13 wheat genotypes, identified through preliminary screening as low and high iron and zinc accumulating genotypes. A pot experiment, with two low accumulator genotypes and eight selected endophytes, was undertaken, followed by field evaluation with both high and low Zn or Fe accumulator genotypes. Screening of these endophytes identified 11 bacteria and 2 fungi as being efficient for zinc solubilization, while 10 bacteria and 2 fungi were promising siderophore producers. Zinc and iron uptake were enhanced by one to several folds over the recommended dose of NPK (RDF) in the pot experiment. Two sets of promising endophytes, identified as Bacillus subtilis (DS-178) and Arthrobacter sp. (DS-179) for zinc accumulation, and Arthrobacter sulfonivorans (DS-68) and Enterococcus hirae (DS-163) for iron acquisition in grains, were selected. Significant increase of 14–20% in plant growth and yield was recorded in field experiment, with 75% increase, over RDF, in terms of Fe or Zn accumulation in wheat grains. Phytic acid, an anti-nutritional factor, was significantly lower in grains from endophyte inoculated treatments in the wheat genotypes evaluated. This illustrated the promise of these endophytes in improving both the translocation of micronutrients and enhancing the quality of wheat grains.     

Discovery and validation of genomic regions associated with resistance to maize lethal necrosis in four biparental populations

In sub-Saharan Africa, maize is the key determinant of food security for smallholder farmers. The sudden outbreak of maize lethal necrosis (MLN) disease is seriously threatening the maize production in the region. Understanding the genetic basis of MLN resistance is crucial. In this study, we used four biparental populations applied linkage mapping and joint linkage mapping approaches to identify and validate the MLN resistance-associated genomic regions. All populations were genotyped with low to high density markers and phenotyped in multiple environments against MLN under artificial inoculation. Phenotypic variation for MLN resistance was significant and heritability was moderate to high in all four populations for both early and late stages of disease infection. Linkage mapping revealed three major quantitative trait loci (QTL) on chromosomes 3, 6, and 9 that were consistently detected in at least two of the four populations. Phenotypic variance explained by a single QTL in each population ranged from 3.9% in population 1 to 43.8% in population 2. Joint linkage association mapping across three populations with three biometric models together revealed 16 and 10 main effect QTL for MLN-early and MLN-late, respectively. The QTL identified on chromosomes 3, 5, 6, and 9 were consistent with the QTL identified by linkage mapping. Ridge regression best linear unbiased prediction with five-fold cross-validation revealed high accuracy for prediction across populations for both MLN-early and MLN-late. Overall, the study discovered and validated the presence of major effect QTL on chromosomes 3, 6, and 9 which can be potential candidates for marker-assisted breeding to improve the MLN resistance.     

Molecular Characterization of a Fungicidal Endoglucanase from the Cyanobacterium Calothrix elenkinii

A gene responsible for fungicidal activity was identified in the cyanobacterial strain Calothrix elenkinii RPC1, which had shown promise as a biocontrol agent. Functional screening of the genomic library revealed fungicidal (against Pythium aphanidermatum) and endoglucanase activities in two clones. Sequencing revealed an open reading frame of 1,044 bp, encoding 348 amino acid residues with a predicted molecular weight of 38 kDa. Analysis of the deduced amino acid sequence of the putative gene (cael1) showed 99% similarity with the β-1,4-endoglucanase from Anabaena laxa RPAN8 and 97% with the glucanase belonging to the peptidase M20 family of Anabaena variabilis and Nostoc sp. PCC7120, respectively. The putative promoters, ribosomal binding sites and a signal peptide of 22 amino acid residues were identified, revealing the secretory nature of the protein. The phylogenetic tree indicated a close relationship of the gene with Bacillus sp. This study is the first to report on the characterization of an endoglucanase in Calothrix sp.     

MicroRNA-133a-1 regulates inflammasome activation through uncoupling protein-2

Inflammasomes are multimeric protein complexes involved in the processing of IL-1β through Caspase-1 cleavage. NLRP3 is the most widely studied inflammasome, which has been shown to respond to a large number of both endogenous and exogenous stimuli. Although studies have begun to define basic pathways for the activation of inflammasome and have been instrumental in identifying therapeutics for inflammasome related disorders; understanding the inflammasome activation at the molecular level is still incomplete. Recent functional studies indicate that microRNAs (miRs) regulate molecular pathways and can lead to diseased states when hampered or overexpressed. Mechanisms involving the miRNA regulatory network in the activation of inflammasome and IL-1β processing is yet unknown. This report investigates the involvement of miR-133a-1 in the activation of inflammasome (NLRP3) and IL-1β production. miR-133a-1 is known to target the mitochondrial uncoupling protein 2 (UCP2). The role of UCP2 in inflammasome activation has remained elusive. To understand the role of miR-133a-1 in regulating inflammasome activation, we either overexpressed or suppressed miR-133a-1 in differentiated THP1 cells that express the NLRP3 inflammasome. Levels of Caspase-1 and IL-1β were analyzed by Western blot analysis. For the first time, we showed that overexpression of miR-133a-1 increases Caspase-1 p10 and IL-1β p17 cleavage, concurrently suppressing mitochondrial uncoupling protein 2 (UCP2). Surprisingly, our results demonstrated that miR-133A-1 controls inflammasome activation without affecting the basal expression of the individual inflammasome components NLRP3 and ASC or its immediate downstream targets proIL-1β and pro-Caspase-1. To confirm the involvement of UCP2 in the regulation of inflammasome activation, Caspase-1 p10 and IL-1β p17 cleavage in UCP2 of overexpressed and silenced THP1 cells were studied. Suppression of UCP2 by siRNA enhanced the inflammasome activity stimulated by H₂O₂ and, conversely, overexpression of UCP2 decreased the inflammasome activation. Collectively, these studies suggest that miR-133a-1 suppresses inflammasome activation via the suppression of UCP2.     

Out of America: tracing the genetic footprints of the global diffusion of maize

Maize was first domesticated in a restricted valley in south-central Mexico. It was diffused throughout the Americas over thousands of years, and following the discovery of the New World by Columbus, was introduced into Europe. Trade and colonization introduced it further into all parts of the world to which it could adapt. Repeated introductions, local selection and adaptation, a highly diverse gene pool and outcrossing nature, and global trade in maize led to difficulty understanding exactly where the diversity of many of the local maize landraces originated. This is particularly true in Africa and Asia, where historical accounts are scarce or contradictory. Knowledge of post-domestication movements of maize around the world would assist in germplasm conservation and plant breeding efforts. To this end, we used SSR markers to genotype multiple individuals from hundreds of representative landraces from around the world. Applying a multidisciplinary approach combining genetic, linguistic, and historical data, we reconstructed possible patterns of maize diffusion throughout the world from American “contribution” centers, which we propose reflect the origins of maize worldwide. These results shed new light on introductions of maize into Africa and Asia. By providing a first globally comprehensive genetic characterization of landraces using markers appropriate to this evolutionary time frame, we explore the post-domestication evolutionary history of maize and highlight original diversity sources that may be tapped for plant improvement in different regions of the world.     

Quantifying the relationship between disease severity and the amount of Aphanomyces euteiches detected in roots of alfalfa and pea with a real-time PCR assay

A real-time PCR assay was used to quantify the relationship in alfalfa and pea between disease severity and the amount of Aphanomyces euteiches detected in roots. The study included isolates of race 1 and race 2 of the alfalfa pathovar of A. euteiches and an isolate obtained from diseased pea. Spearman rank correlations between pathogen DNA content and disease severity index (DSI) ratings were positive ( ? 0.57) and significant (P  0.0007) for individual alfalfa plants, bulked alfalfa plant samples, and individual pea plants. In all experiments, significantly more pathogen was detected in susceptible populations than in resistant populations. The results clearly demonstrate that resistance to A. euteiches in both alfalfa and pea is characterized by a reduction in pathogen colonization relative to levels observed for susceptible reactions. The assay was very specific for A. euteiches, producing very linear assays with DNA extracted from pathogen isolates obtained from alfalfa, pea, and bean. Possible applications of the assay in conjunction with other real-time PCR assays specific to other legume pathogens are discussed in relation to simultaneous disease screening for multiple plant pathogens and the study of microbial population dynamics in mixed plant infections.     

Enhancing the production of an antifungal compound from Anabaena laxa through modulation of environmental conditions and its characterization

An investigation was undertaken to optimize the physiological conditions and characterize the bioactive compound responsible for fungicidal activity in Anabaena laxa. Fungicidal activity against Pythium debaryanum in the A. laxa cultures increased, when grown under continuous light (CL) at the stationary phase (28 d), with further enhancement on doubling phosphorus levels and high pH (9.0) in the growth medium. Preparatory thin layer chromatography analyses revealed the peptide nature of the fungicidal metabolite, with highest activity in a spot with R_f 0.13. The bioactive fraction (in terms of fungicidal activity) was isolated and identified using HPLC with a retention time of 14.7. Fourier transform infrared (FT-IR) spectrum of the purified bioactive fraction indicated the cyclic peptide nature of the antifungal compound. The structural elucidation using ¹H, and ¹³C NMR analyses revealed the same number and type of carbons as present in previously reported majusculamide C from Lyngbya majuscula. GC–MS indicated a similar major mass ion fragment spectra, with peaks as previously obtained from majusculamide C. This represents a first report on biosynthesis of a fungicidal compound in A. laxa, with structural similarities to majusculamide C.