Allosteric interactions among pyrethroid,brevetoxin, and scorpion toxin receptors on insect sodium channels raise an alternative approach for insect control

Intensive pyrethroid use in insect control has led to resistance buildup among various pests. One alternative to battle this problem envisions the combined use of synergistically acting insecticidal compounds. Pyrethroids, scorpion - and β-toxins, and brevetoxins bind to distinct receptor sites on voltage-gated sodium channels (NaChs) and modify their function. The binding affinity of scorpion -toxins to locust, but not rat-brain NaChs, is allosterically increased by pyrethroids and by brevetoxin-1. Brevetoxin-1 also increases the binding of an excitatory β-toxin to insect NaChs. These results reveal differences between insect and mammalian NaChs and may be exploited in new strategies of insect control.     

The identification of the acid-base catalyst of alpha-arabinofuranosidase from Geobacillus stearothermophilus T-6, a family 51 glycoside hydrolase

The alpha-L-arabinofuranosidase from Geobacillus stearothermophilus T-6 (AbfA T-6) belongs to the retaining family 51 glycoside hydrolases. The conserved Glu175 was proposed to be the acid-base catalytic residue. AbfA T-6 exhibits residual activity towards aryl beta-D-xylopyranosides. This phenomenon was used to examine the catalytic properties of the putative acid-base mutant E175A. Data from kinetic experiments, pH profiles, azide rescue, and the identification of the xylopyranosyl azide product provide firm support to the assignment of Glu175 as the acid-base catalyst of AbfA T-6.     

Infection of APC by human cytomegalovirus controlled through recognition of endogenous nuclear immediate early protein 1 by specific CD4(+) T lymphocytes

Infections by human CMV are controlled by cellular immune responses. Professional APC such as monocytes and macrophages can be infected in vivo and are considered as a reservoir of virus. However, CMV-specific CD4(+) responses against infected APC have not been reported. To develop a model of CD4-infected APC interaction, we have transfected the U373MG astrocytoma cell line with the class II transactivator (CIITA). Confocal microscopy experiments showed that U373MG-CIITA cells expressed markers characteristic of APC. Functional assays demonstrated that infected U373MG-CIITA APC processed and presented both exogenous and endogenously neosynthesized nuclear immediate early (IE) protein 1 through the MHC class II pathway. More importantly, endogenous presentation of IE1 by infected APC lead to efficient control of CMV infection as revealed by decreased viral titer. Thus, these results describe the endogenous presentation of a nuclear viral protein by the MHC class II pathway and suggest that IE1-specific CD4(+) T cells may play an important role in CMV infection by directly acting against infected APC.     

Diazoxide and Pinacidil Uncouple Pyruvate–Malate-Induced Mitochondrial Respiration

We investigated the effects of K_ATP channel openers diazoxide and pinacidil on the respiration rate and membrane potential () of rat heart mitochondria, oxidizing pyruvate and malate. Diazoxide and pinacidil (58.8–1348.3 M) increased the V ₂ (-ADP) respiration rate accordingly by 13–208% and 30–273% and decreased the by 2–17% and 6–55%. These effects were also similar in the respiration medium without K⁺. Moreover, carboxyatractyloside completely abolished diazoxide- and pinacidil-induced uncoupling, indicating a role for the mitochondrial adenine nucleotide translocase in this process.     

Tumor necrosis factors in a murine model of allergic peritonitis: effects on eosinophil accumulation and inflammatory mediators' release

In allergic disorders, the role of tumor necrosis factors (TNF) is not well established. We investigated the role of TNF in allergic peritonitis induced by ovalbumin (OVA) challenge in double TNF (TNF-alpha(-/-)/lymphotoxin-alpha(-/-)) knock out (TNF-KO) mice. In the peritoneal lavage of TNF-KO mice, mast cell number and histamine level (radioenzymatic assay) were similar to that in wild type (WT) mice. TNF-alpha (ELISA) and histamine were increased 1 h after challenge in WT mice. However, three days later eosinophil number and eosinophil peroxidase (EPO) levels (colorimetric-enzymatic assay) were found to be lower in TNF-KO mice. A second challenge three days after the first, increased EPO, histamine and IL-6 (ELISA) but did not alter eosinophil and mast cell numbers in both types of mice. On the other hand histamine and IL-6 were higher, while EPO was lower in TNF-KO mice. In conclusion, our findings show that TNF is involved in eosinophil accumulation and inflammatory mediators' release in a murine model of allergy.     

Biotransformation of constituents of essential oils by germinating wheat seed

Wheat seeds, when exposed to essential oils, are able to metabolise certain monoterpenes. The actual amounts of the compounds and their derivatives in the endosperm and embryo of wheat seeds, after exposure to the monoterpenes were determined. Neral and geranial, which are the constituents of citral, are reduced and oxidised to the corresponding alcohols and acids. Similarly citronellal, pulegone and carvacrol are converted partly to the corresponding reduction and oxidation products. The aromatic compound vanillin is partly reduced to vanillyl alcohol or oxidised to vanillic acid. In all cases it seems that part of the compounds applied are degraded, as indicated by the inability to account for all the compounds, which were supplied to the germinated seeds. In most cases the derivatives of the essential oil applied were less toxic than the parent compound. The possible role of non-specific enzymes by which the compounds are oxidised or reduced is discussed.     

StructureActivity Relationships of Antimicrobial Gallic Acid Derivatives from Pomegranate and Acacia Fruit Extracts against Potato Bacterial Wilt Pathogen

Bacterial wilts of potato, tomato, pepper, and or eggplant caused by Ralstonia solanacearum are among the most serious plant diseases worldwide. In this study, the issue of developing bactericidal agents from natural sources against R. solanacearum derived from plant extracts was addressed. Extracts prepared from 25 plant species with antiseptic relevance in Egyptian folk medicine were screened for their antimicrobial properties against the potato pathogen R. solancearum by using the disc‐zone inhibition assay and microtitre plate dilution method. Plants exhibiting notable antimicrobial activities against the tested pathogen include extracts from Acacia arabica and Punica granatum. Bioactivity‐guided fractionation of A. arabica and P. granatum resulted in the isolation of bioactive compounds 3,5‐dihydroxy‐4‐methoxybenzoic acid and gallic acid, in addition to epicatechin. All isolates displayed significant antimicrobial activities against R. solanacearum (MIC values 0.5–9 mg/ml), with 3,5‐dihydroxy‐4‐methoxybenzoic acid being the most effective one with a MIC value of 0.47 mg/ml. We further performed a structure–activity relationship (SAR) study for the inhibition of R. solanacearum growth by ten natural, structurally related benzoic acids.