Effectiveness of entomopathogenic nematodes Steinernema feltiae and Heterorhabditis bacteriophora on the Colorado potato beetle Leptinotarsa decemlineata (Say) (Coleoptera: Chrysomelidae) under laboratory and greenhouse conditions

In laboratory and greenhouse studies, the invading ability, virulence, and mortality caused by Stinernema feltiae and Heterorhabditis bacteriophora were compared. After one and two days of exposure to either nematode species, the mortality of Colordo potato beetle (CPB) Leptinotarsa decemlineata larvae at different instars, third and fourth, was recorded and the number of nematodes invading cadavers was more than the number of nematodes inside the larvae at the late last instar (one day before pre-pupa). Two concentrations, 250 and 500 IJs/dish, infective juvenile nematodes/0.5 ml were tested on different CPB larval instar. S. feltiae was more effective, with fourth instar rather than third and late last instar. On the other hand, H. bacteriophora showed a very weak effect with L. decemlineata. Also it was clear that S. feltiae was more effective and faster than H. bacteriophora: more than 70% of larvae were killed within 24 hours compared with H. bacteriophora which killed 40% of larvae within 48–72 hours. A significant difference in invading efficiency was observed with concentration 2500 IJs/pot in the greenhouse test. The number of adult females found in the cadavers of L. decemlineata larvae was always higher than the number of males. Foliage application of S. feltiae and H. bacteriophora resulted in a significant reduction of the number of damaged leaves and a lower index of damage compared with that in the control. We conclude that S. feltiae has significant potential and can help in the management of the Colorado potato beetle.     

Divergence in Olfactory Host Plant Preference in D. mojavensis in Response to Cactus Host Use

Divergence in host adaptive traits has been well studied from an ecological and evolutionary perspective, but identification of the proximate mechanisms underlying such divergence is less well understood. Behavioral preferences for host plants are often mediated by olfaction and shifts in preference may be accompanied by changes in the olfactory system. In this study, we examine the evolution of host plant preferences in cactophilic Drosophila mojavensis that feeds and breeds on different cacti throughout its range. We show divergence in electrophysiological responses and olfactory behavior among populations with host plant shifts. Specifically, significant divergence was observed in the Mojave Desert population that specializes on barrel cactus. Differences were observed in electrophysiological responses of the olfactory organs and in behavioral responses to barrel cactus volatiles. Together our results suggest that the peripheral nervous system has changed in response to different ecological environments and that these changes likely contribute to divergence among D. mojavensis populations.     

Design,synthesis, and molecular modelling of pyridazinone and phthalazinone derivatives as protein kinases inhibitors

The design and synthesis of pyridazinone and phthalazinone derivatives are described. Newly synthesized compounds were tested on a panel of four kinases in order to evaluate their activity and potential selectivity. In addition, the promising compounds were tested on four cancer cell lines to examine cytotoxic effects. The compounds inhibited DYRK1A and GSK3 with different activity. SAR analysis and docking calculations were carried out to aid in the interpretation of the results. Taken together, our findings suggest that pyridazinone and phthalazinone scaffolds are interesting starting points for design of potent GSK3 and DYRK1A inhibitors.     

Breaking the routine: individual Cory's shearwaters shift winter destinations between hemispheres and across ocean basins

There is growing evidence that migratory species are particularly vulnerable to rapid environmental changes arising from human activity. Species are expected to vary in their capacity to respond to these changes: long-distance migrants and those lacking variability in migratory traits are probably at considerable disadvantage. The few studies that have assessed the degree of plasticity in behaviour of marine animals suggest that fidelity to non-breeding destinations is usually high. In the present study, we evaluated individual flexibility in migration strategy of a highly pelagic seabird, the Cory's shearwater Calonectris diomedea. Geolocation data from 72 different migrations, including 14 birds that were tracked for more than one non-breeding season, showed a remarkable capacity to change winter destinations between years. Although some birds exhibited high site fidelity, others shifted from the South to North Atlantic, from the western to eastern South Atlantic, and from the Atlantic to Indian Ocean. Individuals also showed flexibility in stopover behaviour and migratory schedule. Although their K-selected life-history strategy has the disadvantage that the chances of microevolution are slight if circumstances alter rapidly, these results suggest that Cory's shearwaters may be in a better position than many other long-distance migrants to face the consequences of a changing environment.     

Genotyping of eight polymorphic genes encoding drug-metabolizing enzymes and transporters using a customized oligonucleotide array

Polymorphisms in drug-metabolizing genes may lead to the production of dysfunctional proteins and consequently affect therapeutic efficacy and toxicity of drugs. Different frequencies of polymorphic alleles among the races have been postulated to account for the observed ethnic variations in drug responses. In the current study, we aimed to estimate the frequencies of 14 polymorphisms in eight genes (TPMT, NQO1, MTHFR, GSTP1, CYP1A1, CYP2D6, ABCB1, and SLC19A1) in the Singapore multiracial populations by screening 371 cord blood samples from healthy newborns. To improve genotyping efficacy, we designed an oligonucleotide array based on the principle of allele-specific primer extension (AsPEX) that was capable of detecting the 14 polymorphisms simultaneously. Cross-validation using conventional polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) assays demonstrated 99% concordant results. Measurements on the fluorescent intensity displayed clear distinctions among different genotypes. Statistical analyses showed significantly different allele distributions in several genes among the three races, namely Chinese, Malays, and Indians. Comparing the allelic frequencies in Chinese with previous studies in Caucasian populations, NQO1 609C>T and SLC19A1 80G>A were distinctly different, whereas close similarity was observed for MTHFR 677C>T. We have demonstrated an array-based methodology for rapid multiplex detection of genetic polymorphisms. The allelic frequencies reported in this study may have important therapeutic and prognostic implications in the clinical use of relevant drugs.     

Targeting MAPKs,NF-κB,and PI3K/AKT pathways by methyl palmitate ameliorates ethanol-induced gastric mucosal injury in rats

Excessive drinking of alcohol has been frequently associated with gastric injury; however, its underlying molecular mechanisms have been inadequately investigated. Methyl palmitate (MP) has demonstrated marked hepato-, cardio- and pulmonary protective features; however, its effects on ethanol-induced gastric injury have not been studied. The aim of the present study was to evaluate the potential gastroprotective activity of MP against ethanol-evoked gastric mucosal damage in rats and associated molecular mechanisms, for example, mitogen-activated protein kinases (MAPKs), nuclear factor κB (NF-κB), and phosphoinositide 3 kinase/protein kinase B (PI3K/AKT) pathways. The rat stomachs were examined in terms of the inflammatory, oxidative, and apoptotic perturbations. Current data demonstrated that pretreatment with MP attenuated the gross gastric damage, scores of ulcer index, area of mucosal lesions and histopathology outcomes; actions which were similar to the reference antiulcer omeprazole. MP inhibited NF-κB expression, its nuclear translocation, and the expression of its downstream signals, for example, tumor necrosis factor-α and myeloperoxidase besides restoration of interleukin-10 levels. Western blot analysis revealed that MP counteracted the disruption of MAPKs signaling via lowering p-c-Jun N-terminal kinase 1/2 (p-JNK1/2) expression and restoring the phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2) levels without affecting p-p38MAPK levels. Additionally, MP improved the antioxidant milieu via diminishing lipid peroxides and enhancing glutathione, glutathione peroxidase, total antioxidant capacity and mucosal nitric oxide. In the context of apoptosis, MP inhibited the cleavage of caspase-3 and poly(ADP-ribose)polymerase (PARP) and Bax protein expression with upregulating B cell lymphoma-2 expression (Bcl-2), thus, promoting gastric cellular survival. This was confirmed by MP activation of the PI3K/AKT pathway manifested by enhanced expression of PI3K p110α and p-AKT. Together, the present findings report the gastroprotective actions of MP mediated via its anti-inflammatory, antioxidant, and antiapoptotic actions. The underlying molecular mechanisms involve, at least partly, the modulation of MAPKs, NF-κB and PI3K/AKT transduction.     

New spectrofluorimetric analysis of dapagliflozin after derivatization with NBD‐Cl in human plasma using factorial design experiments

A new validated spectrofluorimetric method was proposed for dapagliflozin (DGF) analysis in bulk, plexin its commercially available tablets and in spiked human plasma. The proposed spectrofluorimetric method depended on the formation of a fluorescent complex soluble in organic liquids by a substitution reaction between 4‐chloro‐7‐nitrobenzo‐2‐oxa‐1,3‐diazole (NBD‐Cl) reagent and DGF in aqueous buffered solution at pH 7. The fluorescence intensity was measured at 522 nm after excitation at 453 nm. The high selectivity of the proposed method allowed analysis of DGF in dosage form and human plasma samples with average recovery values of 99.84 ± 1.38% and 98.71 ± 1.80%, respectively, without any interference from matrix components. The calibration range was 50–1000 ng ml^?1. The limit of detection (LOD) and limit of quantitation (LOQ) were 14.24 ng ml^?1 and 43.14 ng ml^?1, respectively. The estimated relative standard deviation values were lower than 2.0%, this showed the excellent precision at both levels. Factorial design was used to get the optimum method conditions for the analysis of the resulting DGF fluorescence complex in different matrices. The proposed method could be used in routine analysis of DGF in quality control laboratories. Also, it could be used to assay DGF in human plasma and be applied for pharmacokinetic investigation of DGF.