Redox properties of local anesthetics: A structural determinant of closed channel blockers in BTX-modified Na+ channels

Single channel analyses and macroscopic current measurements have shown that benzocaine is a predominantly closed channel blocker in BTX-modified Na+ channels; cocaine is an open channel blocker; and tetracaine, a dual channel blocker (Wang & Wang, 1994; Wang et al., 1994). The reason for such a selective state-dependent block by local anesthetics in BTX-modified Na+ channels is not clear. We assessed the redox properties of tetracaine, benzocaine, cocaine, and various derivatives by their ability to donate electrons to radical intermediates of eosin dye excited by visible light. Electron-donor properties of the drugs were previously proposed to be involved in Na+ channel blockade (Marinov, 1991). Our results provide evidence that redox properties of tetracaine, benzocaine, and their homologs correlate with their ability to enhance Na+ channel inactivation in BTX-modified Na+ channels. This correlation may be explained in terms of the previously proposed redox model of ion channels.     

Monitoring of IL-10 in the serum of patients with advanced ovarian cancer: Results from a prospective pilot-study

Objectives: The fact that ovarian cancer remains confined to the peritoneal cavity even in advanced stages has allowed us to surmise that local immunosuppressive factors could be involved in the tumor biology of ovarian cancer. In this context, IL-10 can be one of the key factors. By studying the kinetics of IL-10 concentrations prior to and after surgery, this study attempts to reveal once more the ability of tumor micro-environment to produce IL-10. Some studies indicate that IL-10 concentration correlates with the tumor burden and can thus predict the surgical outcome. Data concerning this aim from patients with ovarian cancer do not seem to exist. Methods: In this prospective study, serum blood was collected from 27 patients, one day prior to surgery as well as 24 h, 4 and 8 days after surgery. The concentration of IL-10 was determined using ELISA. Results: While IL-10 levels rise within the first day post-OP, they are found to be reduced significantly when measured at later time points. IL-10 levels also correlate statistically significantly with the tumor grade, with lower IL-10 levels observed in well-differentiated and higher IL-10 levels in undifferentiated or only poorly differentiated tumors. Conclusion: IL-10 expression levels appear to be a good surrogate marker for tumor grading. If validated, this may in future contribute to the understanding of the biology stage cancers.     

First evidence for active carnivorous predation in the European ground squirrel

acta ethologica - The Sciuridae family is generally referred to as herbivorous and occasionally omnivorous. Although sciurids are known to opportunistically feed on carcasses of other vertebrates...     

Tyrosine phosphorylation within the SH3 domain regulates CAS subcellular localization, cell migration, and invasiveness

Crk-associated substrate (CAS) is a major tyrosine-phosphorylated protein in cells transformed by v-crk and v-src oncogenes and plays an important role in invasiveness of Src-transformed cells. A novel phosphorylation site on CAS, Tyr-12 (Y12) within the ligand-binding hydrophobic pocket of the CAS SH3 domain, was identified and found to be enriched in Src-transformed cells and invasive human carcinoma cells. To study the biological significance of CAS Y12 phosphorylation, phosphomimicking Y12E and nonphosphorylatable Y12F mutants of CAS were studied. The phosphomimicking mutation decreased interaction of the CAS SH3 domain with focal adhesion kinase (FAK) and PTP-PEST and reduced tyrosine phosphorylation of FAK. Live-cell imaging showed that green fluorescent protein-tagged CAS Y12E mutant is, in contrast to wild-type or Y12F CAS, excluded from focal adhesions but retains its localization to podosome-type adhesions. Expression of CAS-Y12F in cas-/- mouse embryonic fibroblasts resulted in hyperphosphorylation of the CAS substrate domain, and this was associated with slower turnover of focal adhesions and decreased cell migration. Moreover, expression of CAS Y12F in Src-transformed cells greatly decreased invasiveness when compared to wild-type CAS expression. These findings reveal an important role of CAS Y12 phosphorylation in the regulation of focal adhesion assembly, cell migration, and invasiveness of Src-transformed cells.     

Cloning and sequencing of cDNA encoding glutamine synthetase from the sea anemone Aiptasia pallida

Glutamine synthetase (GS) catalyzes the addition of ammonium to glutamic acid to form glutamine and plays a crucial role in the nitrogen assimilation of the sea anemone Aiptasia pallida and its endosymbiotic algae. We describe the cDNA cloning and sequence analysis of GS mRNA from A. pallida based on polymerase chain reaction (PCR) technology that employed a combination of degenerate and A. pallida-specific primers. The sequenced cDNA approximates 1620 nucleotides and is characterized by an open reading frame of 1107 nucleotides that encodes a protein of 369 amino acid residues. Comparisons of the deduced sea anemone GS protein to a wide range of species demonstrated greatest amino acid sequence identity to sea urchin GS (66%) and least identity to green algae GS (51%). The sequenced cDNA can be used in future research to study GS gene expression in A. pallida.     

Effects of dietary supplementation of nickel and nickel-zinc on femoral bone structure in rabbits

Background  

Nickel (Ni) and zinc (Zn) are trace elements present at low concentrations in agroecosystems. Nickel, however, may have toxic effects on living organisms and is often considered as a contaminant. This study reports the effect of peroral administrated Ni or a combination of Ni and Zn on femoral bone structure in rabbits.     

Amperometric acetylthiocholine sensor based on acetylcholinesterase immobilized on nanostructured polymer membrane containing gold nanoparticles

Poly(acrylonitrile-methylmethacrylate-sodium vinylsulfonate) membranes were chemically modified and loaded with gold nanoparticles. Acetylcholinesterase was immobilized on the prepared membranes in accordance with two distinctive procedures, the first of which involved immobilization of the enzyme by convection, and the other by diffusion. The prepared enzyme carriers were used for the construction of amperometric biosensors for detection of acetylthiocholine.Two sets of experiments were carried out. The first set was designed so that to evaluate the effects of the gold nanoparticle deployment and the immobilization procedures over the biosensor effectiveness. The other set of experiments was conducted in order to determine the influence of the individual components of the enzyme mixture, containing gold nanoparticles, acetylcholinesterase, bovine serum albumin and glutaraldehyde, over the current output of the constructed acetylthiocholine biosensors. The optimum composition of the mixture was determined to be as follows: enzyme, 0.1 U ml^?1; gold nanoparticles, 0.50 ml (per 1 ml enzyme mixture); albumin, 0.5% and glutaraldehyde, 0.7%.On the basis of the experimental results, the most efficient enzyme membrane was selected and used for the preparation of an acetylthiocholine biosensor. Its basic amperometric characteristics were investigated. A calibration plot was obtained for ATCh concentration ranging from 10 to 400 μM. A linear interval was detected along the calibration curve from 10 to 170 μM. The sensitivity of the constructed biosensor was calculated to be 0.066 μA μM^?1 cm^?2. The correlation coefficient for this concentration range was 0.996. The detection limit with regard to ATCh was calculated to be 1.80 μM.The potential application of the biosensor for detection and quantification of organophosphate pesticides was investigated as well. It was tested against sample solutions of Paraoxon. The biosensor detection limit for Paraoxon was determined, 7.39 × 10^?11 g l^?1, as well as the concentration interval (10^?10 to 10^?7 g l^?1) within which the biosensor response was linearly dependant on Paraoxon concentration.Finally the storage stability of the enzyme carrier was traced for a period of 50 days. After storage for 20 days the sensor retained 75% of its initial current response and after 30 days ?25%.     

A design criterion for symmetric model discrimination based on flexible nominal sets

Experimental design applications for discriminating between models have been hampered by the assumption to know beforehand which model is the true one, which is counter to the very aim of the experiment. Previous approaches to alleviate this requirement were either symmetrizations of asymmetric techniques, or Bayesian, minimax, and sequential approaches. Here we present a genuinely symmetric criterion based on a linearized distance between mean-value surfaces and the newly introduced tool of flexible nominal sets. We demonstrate the computational efficiency of the approach using the proposed criterion and provide a Monte-Carlo evaluation of its discrimination performance on the basis of the likelihood ratio. An application for a pair of competing models in enzyme kinetics is given.     

Response to Martin and colleagues: mitochondria do not boost the bioenergetic capacity of eukaryotic cells

A recent paper by (Gerlitz et al., Biol Direct 13:21, 2018) questions the validity of the data underlying prior analyses on the bioenergetics capacities of cells, and continues to promote the idea that the mitochondrion endowed eukaryotic cells with energetic superiority over prokaryotes. The former point has been addressed previously, with no resultant changes in the conclusions, and the latter point remains inconsistent with multiple lines of empirical data.     

Microbiological dehydrogenation of polyfunctional Δ5-3β-acetoxy steroids by Corynebacterium mediolanum strain B-964

Summary A high-yield microbiological transformation of polyfunctional ⁵-3-acetoxy steroids, containing an additional ring E, by Corynebacterium mediolanum strain B-964 was carried out, resulting in the corresponding ⁴-3-ketones. It was shown that the type of transformation and the yield of the reaction depend on the degree of saturation of the ring E and on the position of the oxygen-containing substituents in it.