Association of CAT polymorphisms with catalase activity and exposure to environmental oxidative stimuli

We tested the hypotheses that catalase activity is modified by CAT single nucleotide polymorphisms (SNPs) (-262;-844), and by their interactions with oxidant exposures (coal dusts, smoking), lymphotoxin alpha (LTA, NcoI) and tumor necrosis factor (TNF, -308) in 196 miners. Erythrocyte catalase, superoxide dismutase, and glutathione peroxidase activities were measured. The CAT -262 SNP was related to lower catalase activity (104, 87 and 72 k/g hemoglobin for CC, CT and TT, respectively, p < 0.0001). Regardless of CAT SNPs, the LTA NcoI but not the TNF-308 SNP was associated with catalase activity (p = 0.04 and p = 0.8). CAT -262 T carriers were less frequent in highly exposed miners (OR = 0.39 [0.20–0.78], p = 0.007). In CAT -262 T carriers only, catalase activity decreased with high dust exposure (p = 0.01). Haplotype analyses (combined CAT SNPs) confirm these results. Results show that CAT -262 and LTA NcoI SNPs, and interaction with coal dust exposure, influenced catalase activity.     

Glycosidic juvenogens: derivatives bearing alpha,beta-unsaturated ester functionalities

A series of the protected alkyl glycosides 5a/5b-12a/12b was synthesized from the parent isomeric alcohols (insect juvenile hormone bioanalogs; juvenoids), 4-[4'-(2'-hydroxycyclohexyl)methylphenoxy]-3-methyl-but-2-enoic acid ethyl ester (1a/1b-4a/4b; racemic structures) and (1a-4a; enantiopure structures). Cadmium carbonate was used as a promoter of this Koenigs-Knorr reaction, and the products were obtained in 82-92% yields. Deprotection of the carbohydrate functionality of 5a/5b-12a/12b was carefully performed using ethanolysis in the presence of zinc acetate, due to the presence of another ester functionality in the aglycone part of the molecule of protected alkyl glycosides. Resulting alkyl glycosides 13a/13b-20a/20b (diastereoisomeric mixtures) and 13a-20a (enantiopure compounds), biochemically activated hormonogenic compounds (juvenogens), were obtained in 82-93% yields. Finally, chiral HPLC separation of the diastereoisomeric mixtures of alkyl glycosides was applied to get sufficient quantities of the respective enantiomers 13b-20b of the alkyl glycosides for their structure elucidation and (13)C chemical shift assignment by (1)H and (13)C NMR spectroscopy. Partial introductory entomological screening tests of the target alkyl glycosides 13a/13b-20a/20b were performed on the red firebug (Pyrrhocoris apterus). The results of this biological testing clearly demonstrated the time-extended effect of several juvenogens on P. apterus due to their biochemical activation, i.e., hydrolysis of the juvenogen molecule, which results in liberation of the biologically active juvenoid in the insect organism.     

Inhibitory transmission, activity-dependent ionic changes and neuronal network oscillations

Oscillatory network activity arises from interactions between synaptic and intrinsic membrane properties of neurons. In this review, we summarize general mechanisms of synchronous neuronal oscillations. In addition, we focus on recent experimental and computational studies which suggest that activity-dependent changes of ionic environment can affect both the synaptic and intrinsic neuronal properties and influence the network behavior. GABA(A) receptor (GABA(A)R)-mediated signaling, that is based on Cl(-) and HCO(3)(-) permeability, is thought to be important for the oscillogenesis and synchronization in cortical networks. A remarkable feature of GABAergic synapses is that prolonged GABA(A)R activation may lead to switching from a hyperpolarizing to a depolarizing response. This is partly due to a positive shift of the GABA(A) R reversal potential (E(GABA)) that is generated by GABA-induced Cl(-) accumulation in neurons. Recent studies suggest that activity-dependent E(GABA) changes may have important implications for the mechanisms of gamma oscillations and seizure-like discharges. Thus, a better understanding of the impact of intracellular Cl(-) dynamics on network behavior may provide insights into the mechanisms of physiological and pathological brain rhythms. Combination of experiments and simulations is a promising approach for elucidating which properties of the time-varying ionic environment can shape the dynamics of a given circuit.