Ion‐Transfer Electrochemistry of Rat Amylin at the Water–Organogel Microinterface Array and Its Selective Detection in a Protein Mixture

The behavior of proteins and polypeptides at electrified aqueous–organic interfaces is of benefit in label‐free detection strategies. In this work, rat amylin (or islet amyloid polypeptide) was studied at the interface formed between aqueous liquid and gelled organic phases. Amylin is a polypeptide that is co‐secreted with insulin from islet beta‐cells and is implicated in fibril formation. In this study, rat amylin was used, which does not undergo aggregation. The polypeptide underwent an interfacial transfer process, from water to the gelled organic phase, under applied potential stimulation. Cyclic voltammetry revealed steady‐state forward and peak‐shaped reverse voltammograms, which were consistent with diffusion‐controlled water‐to‐organic transfer and thin‐film stripping or desorptive back‐transfer. The diffusion‐controlled forward current was greater when amylin was present in an acidic aqueous phase than when it was present in an aqueous phase at physiological pH; this reflects the greater charge on the polypeptide under acidic conditions. The amylin transfer current was concentration dependent over the range 2–10 μM , at both acidic and physiological pH. At physiological pH, amylin was selectively detected in the presence of a protein mixture, which illustrated the bioanalytical possibilities for this electrochemical behavior.     

STUDIES OF ADHESION OF METAL PARTICLES TO SILICA PARTICLES BASED ON ZETA POTENTIAL MEASUREMENTS

The zeta-potentials of silica, copper, platinum and gold particles have been measured as a function of pH. The isoelectric points were found to be at pH 3.0, 5.8, 3.0 and 3.5, respectively. In the pH range 3.0 to 5.8 copper and silica particles are oppositely charged and accordingly the coating of silica with copper particles could be demonstrated. In the case of gold and platinum the sign of the charge is such that direct adhesion to silica particles cannot be expected and this was also demonstrated in the case of platinum.     

<Emphasis Type="Italic">N</Emphasis>-arachidonoyl glycine,an abundant endogenous lipid,potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor

Background  

Microglia provide continuous immune surveillance of the CNS and upon activation rapidly change phenotype to express receptors that respond to chemoattractants during CNS damage or infection. These activated microglia undergo directed migration towards affected tissue. Importantly, the molecular species of chemoattractant encountered determines if microglia respond with pro- or anti-inflammatory behaviour, yet the signaling molecules that trigger migration remain poorly understood. The endogenous cannabinoid system regulates microglial migration via CB₂ receptors and an as yet unidentified GPCR termed the 'abnormal cannabidiol' (Abn-CBD) receptor. Abn-CBD is a synthetic isomer of the phytocannabinoid cannabidiol (CBD) and is inactive at CB₁ or CB₂ receptors, but functions as a selective agonist at this G_i/o-coupled GPCR. N-arachidonoyl glycine (NAGly) is an endogenous metabolite of the endocannabinoid anandamide and acts as an efficacious agonist at GPR18. Here, we investigate the relationship between NAGly, Abn-CBD, the unidentified 'Abn-CBD' receptor, GPR18, and BV-2 microglial migration.     

Two-dimensional electrophoresis of liver proteins: characterization of a drug-induced hepatomegaly in rats

Two-dimensional electrophoresis (2-DE) of liver proteins was applied to further characterize an unusual drug-induced increase in hepatocellular rough endoplasmic reticulum (RER) in Sprague-Dawley rats given a substituted pyrimidine derivative. Absolute liver weights of drug-treated rats (9.9 +/- 0.4 g) increased above vehicle-treated controls (7.2 +/- 0.2 g) by 37%. Light microscopy revealed diffuse granular basophilia of the hepatocellular cytoplasm, uncharacteristic of hepatocytes and suggested cells rich in ribosomes, which was confirmed by electron microscopy. Immunostaining for cell proliferation, viz., 5-bromo-2'-deoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA), indicated marked hepatocellular proliferative activity. 2-DE of solubilized liver using an ISO-DALT gel system indicated significant (p<0.001) quantitative changes in at least 17 liver proteins (12 increased, 5 decreased) compared to controls. The protein with the largest increase was homologous to acute-phase reactant, contrapsin-like protein inhibitor-6. Other markedly upregulated proteins were methionine adenosyltransferase, a catalyst in methionine/ATP metabolism and mitochondrial HMG-CoA synthase, involved in cholesterol synthesis. The complementary strategies of 2-DE coupled either with database spot mapping or protein isolation and amino acid sequencing successfully identified a subset of proteins from xenobiotic-damaged rodent livers, the expression of which differed from controls. However, the current bioinformatics platform for rodent hepatic proteins and limited knowledge of specific protein functionality restricted application of this proteomics profile to further define a mechanistic basis for this unusual hepatotoxicity.     

Set the controls for the heart of the Sun

In this paper we describe experiments conducted with high-power lasers that are attempting to replicate, for a very short time and in miniature, conditions found in the Sun. Experiments to date have reached conditions in the outer part of the Sun. To reach the Sun's centre requires compression of material to very much greater than solid density and heating to over ten million degrees. To achieve this, a new class of experiments and a new generation of high-power lasers are required.