PKCε phosphorylation regulates the mitochondrial translocation of ATF2 in ischemia-induced neurodegeneration

Background

Global cerebral ischemia triggers neurodegeneration in the hippocampal CA1 region, but the mechanism of neuronal death remains elusive. The epsilon isoform of protein kinase C (PKCε) has recently been identified as a master switch that controls the nucleocytoplasmic trafficking of ATF2 and the survival of melanoma cells. It is of interest to assess the role of PKCε–ATF2 signaling in neurodegeneration.

Results

Phosphorylation of ATF2 at Thr-52 was reduced in the hippocampus of PKCε null mice, suggesting that ATF2 is a phosphorylation substrate of PKCε. PKCε protein concentrations were significantly reduced 4, 24, 48 and 72 h after transient global cerebral ischemia, resulting in translocation of nuclear ATF2 to the mitochondria. Degenerating neurons staining positively with Fluoro-Jade C exhibited cytoplasmic ATF2.

Conclusions

Our results support the hypothesis that PKCε regulates phosphorylation and nuclear sequestration of ATF2 in hippocampal neurons during ischemia-induced neurodegeneration.

     

Experimental investigation of the performance of an indirect-mode natural convection solar dryer for drying fenugreek leaves

The main objectives of the present work are firstly to study and compare the thin layer drying characteristics of fenugreek leaves by open sun and solar drying methods, and secondly to select a mathematical model for describing the drying process under open sun and solar drying of fenugreek leaves using thin layer drying models available in the literature. Eight thin layer drying models, which are empirical or semi-empirical, are tested to validate the experimental data. A non-linear regression analysis using a statistical computer programme is used to evaluate the constants of the models. The performance of the models was investigated by comparing the coefficient of correlation (R ²), sum of squares error (SSE), mean squared error (MSE) and root mean square error (RMSE) between observed and predicted moisture ratios. According to results, Wang and Singh model gives the highest value of R ² and the lowest values of SSE, MSE and RMSE. Therefore, Wang and Singh model is the best for explaining drying behaviour of fenugreek leaves in both the trays inside the solar dryer and in the tray under open sun.     

Off-line integration of CE and MALDI-MS using a closed-open-closed microchannel system

In this work, a new technique for off-line hyphenation between CE and MALDI-MS is presented. Two closed fused-silica capillaries were connected via a silicon chip comprising an open microcanal. The EOF in the system was evaluated using mesityloxide or leucine-enkephalin as a sample and with a running buffer that rendered the analyte neutrally charged. Comparison was made between the EOF in a closed system (first capillary solely included in the electrical circuit) and in a closed-open system (first capillary and microcanal included in the electrical circuit). It was concluded that the experimental values of the EOF agreed with the theory. The influence of the capillary outer diameter on the peak dispersion was investigated using a closed-open-closed system (first capillary, microcanal and second capillary included in the electrical circuit). It was clearly seen that a capillary with 375 microm od induced considerably higher peak dispersion than a 150 microm od capillary, due to a larger liquid dead volume in the connection between the first capillary outlet and the microcanal. Mass spectrometric analysis has also been performed following CE separation runs in a closed-open-closed system with cytochrome c and lysozyme as model proteins. It was demonstrated that a signal distribution profile of the separated analytes could be recorded over a 30 mm long microcanal.     

Reaction on Water: A Greener Approach for the Thia Michael Addition on N-Aryl Maleimides

A greener, economical, and efficient methodology for the Michael addition of thiols to N-aryl maleimides has been developed.     

Iron chemistry of an asymmetrically substituted,triazole-functionalised calixarene ligand

The synthesis and characterisation of an asymmetrically substituted calix-triazole ligand are reported. The ligand reacts with the Fe(II) precursor Fe₂Mes₄ to yield an iron(II) calixarene complex that is oxidised by dioxygen to provide a dinuclear Fe(III) compound featuring an oxido bridge.     

Facile Syntheses of Novel Salts of a Triazole Antifungal Agent with Enhanced Solubility

Acid addition salts of a triazole antifungal agent itraconazole were prepared with an aim to enhance the aqueous solubility and dissolution characteristics of the drug. Nitric, sulfuric, and p‐toluenesulfonic acid addition salts ( 1a , 1b , 1c ) were prepared using facile synthetic procedures. The solubility of the salts in water was found to be 24, 22, and 58 mg/mL, respectively, for 1a , 1b , and 1c , which is significantly higher than that of itraconazole (1 ng/mL). In addition to this, solubility of the salts in simulated gastric fluid (SGF) and other pharmaceutically used solvents such as ethanol and propylene glycol was also improved to a great extent. Also, it was observed that from 1a , 1b , and 1c , approximately 33, 26, and 45% drug was released in SGF in 3 h, whereas less than 10% drug was released from the free base form.     

Rapid communication: Permeability of hydrogen in two-dimensional graphene and hexagonal boron nitride sheets

This paper concerns an application to optimal energy by incorporating thermal equilibrium on MHD-generalised non-Newtonian fluid model with melting heat effect. Highly nonlinear system of partial differential equations is simplified to a nonlinear system using boundary layer approach and similarity transformations. Numerical solutions of velocity and temperature profile are obtained by using shooting method. The contribution of entropy generation is appraised on thermal and fluid velocities. Physical features of relevant parameters have been discussed by plotting graphs and tables. Some noteworthy findings are: Prandtl number, power law index and Weissenberg number contribute in lowering mass boundary layer thickness and entropy effect and enlarging thermal boundary layer thickness. However, an increasing mass boundary layer effect is only due to melting heat parameter. Moreover, thermal boundary layers have same trend for all parameters, i.e., temperature enhances with increase in values of significant parameters. Similarly, Hartman and Weissenberg numbers enhance Bejan number.     

Therapeutic Potential of Tuna Backbone Peptide and Its Analogs: An In Vitro and In Silico Study

Tuna backbone peptide (TBP) has been reported to exert potent inhibitory activity against lipid peroxidation in vitro. Since this bears relevant physiological implications, this study was undertaken to assess the impact of peptide modifications on its bioactivity and other therapeutic potential using in vitro and in silico approach. Some TBP analogs, despite lower purity than the parent peptide, exerted promising antioxidant activities in vitro demonstrated by ABTS radical scavenging assay and cellular antioxidant activity assay. In silico digestion of the peptides resulted in the generation of antioxidant, angiotensin-converting enzyme (ACE), and dipeptidyl peptidase-IV (DPPIV) inhibitory dipeptides. Using bioinformatics platforms, we found five stable TBP analogs that hold therapeutic potential with their predicted multifunctionality, stability, non-toxicity, and low bitterness intensity. This work shows how screening and prospecting for bioactive peptides can be improved with the use of in vitro and in silico approaches.     

Detection of intermediates through high-resolution mass spectrometry for constructing biosynthetic pathways for major chemical constituents in a medicinally important herb,Swertia chirayita

Swertia chirayita is an endangered medicinal herb widely used as an antidiabetic. It contains two major classes of metabolites, secoiridoids and xanthones, i.e. swertiamarin, mangiferin, amarogentin and amaroswerin. The biosynthetic pathways for these chemical constituents are not completely deciphered due to gaps and redundancy of routes proposed such as for mangiferin. The missing intermediates in pathways were detected through LC-ESI-QToF-HRMS/MS, including the detection of new secoiridoids, amaronitidin and gentiopicroside. The study also reports that the biosynthesis of amaronitidin occurs through the coupling of gentiopicroside and biphenyl acid derivatives such as amarogentin and amaroswerin. This study reports for the first time complete biosynthetic pathways for gentiopicroside, mangiferin, amarogentin, amaroswerin and amaronitidin in S. chirayita with the detection of intermediate metabolites iriflophenone, maclurin, deoxyloganic acid, loganic acid and 1,3,6,7-tetrahydroxy-9H-xanthen-9-one.