Activity

observed in Kcnb1R/R mice, as well as seizures induced by exposure to novel environments and/or handling. Both Kcnb1R/+ and Kcnb1R/R mutants were more susceptible to proconvulsant-induced seizures. In addition, both Kcnb1R/+ and Kcnb1R/R mice exhibited abnormal interictal EEG activity, including isolated spike and slow waves. Overall, the Kcnb1G379R mice recapitulate many features observed in individuals with DEE due to pathogenic variants in KCNB1. This new mouse model of KCNB1-associated DEE will be valuable for improving the understanding of the underlying pathophysiology and will provide a valuable tool for the development of therapies to treat this pharmacoresistant DEE.In order to increase our understanding of the insecticidal potential of the entomopathogenic bacterium Brevibacillus laterosporus strain UNISS 18 against insect pests, investigations were conducted on a selection of dipteran species including fruit flies, house flies, blow flies, and mosquitoes, characterized by adaptations to very diverse habitats. According to lethal concentration (LC50) values, the common house mosquito Culex pipiens (LC50 = 0.10 × 106 spores/mL) and the yellow fever mosquito Aedes aegypti (LC50 = 0.18 × 106 spores/mL) were significantly more susceptible than the flies. The blow flies were the second taxon in term of susceptibility to B. laterosporus spores, with a higher mortality in Calliphora vomitoria (LC50 = 78.84 × 106 spores/mL) than Lucilia caesar (LC50 = 148.30 × 106 spores/mL). The effectiveness of B. laterosporus spores was reduced by half in the house fly Musca domestica (LC50 = 82.41 × 106 spores/mL). The lowest susceptibility was observed in the fruit flies, among which the spotted wing drosophila (SWD), Drosophila suzukii, was the most susceptible (LC50 = 217.51 × 106 spores/mL) in comparison with the medfly Ceratitis capitata and the olive fly Bactrocera oleae (LC50 = 2567.32 and 2567.36 × 106 spores/mL, respectively). The present study demonstrated that significantly different degrees of susceptibility are associated with diverse dipteran species including plant and animal parasites, and we suggest that B. laterosporus established different relationships with dipteran species in different ecosystems.Chronic intermittent hypoxia (CIH) is a model for obstructive sleep apnea. selleck The paraventricular nucleus (PVN) of the hypothalamus has been suggested to contribute to CIH-induced exaggerated cardiorespiratory reflexes, sympathoexcitation and hypertension. This may occur, in part, via activation of the dense catecholaminergic projections to the PVN that originate in the brainstem. However, the contribution of norepinephrine (NE) and activation of its alpha-adrenergic receptors (α-ARs) in the PVN after CIH exposure is unknown. We hypothesized CIH would increase the contribution of catecholaminergic input. To test this notion, we determined the expression of α-AR subtypes, catecholamine terminal density, and synaptic properties of PVN parvocellular neurons in response to α-AR activation in male Sprague-Dawley normoxic (Norm) and CIH exposed rats. CIH decreased mRNA for α1d and α2b AR. Dopamine-β-hydroxylase (DβH) terminals in the PVN were similar between groups. NE and the α1-AR agonist phenylephrine (PE) increased sEPSC frequency after Norm but not CIH. Block of α1-ARs with prazosin alone did not alter sEPSCs after either Norm or CIH but did prevent agonist augmentation of sEPSC frequency following normoxia. These responses to NE were mimicked by PE during action potential block suggesting presynaptic terminal alterations in CIH. Altogether, these results demonstrate that α1-AR activation participates in neuronal responses in Norm, but are attenuated after CIH. These results may provide insight into the cardiovascular, respiratory and autonomic nervous systems alterations in obstructive sleep apnea.Yersinia pestis, the causative agent of plague mainly infects rodents, while humans are the accidental host. The conventional diagnostic methods available for Y. pestis exhibit cross-reactivity with other enteropathogenic bacteria which makes its detection difficult. Rapid and reliable point-of-care detection of Y. pestis is essential for timely initiation of medical treatment. In the present study, a pair of loop mediated isothermal amplification (LAMP) assays has been developed for rapid detection of Y. pestis. Two sets of LAMP primers, each containing 6 primers were specifically designed targeting caf1 and 3a genes located on pFra plasmid and chromosome of Y. pestis, respectively. Isothermal amplification was accomplished at 65 °C for 40 min for caf1 target, and at 63 °C for 50 min for 3a choromosomal target. The analytical sensitivity of the assay for the caf1 and 3a targets was found to be 500 fg and 100 fg genomic DNA of Y. pestis, respectively. The caf1 and 3a LAMP assays detected as few as 100 copies of caf1 and 10 copies of 3a gene targets harboured in the respective recombinant plasmids. The amplified products were detected visually under visible and UV light using SYBR Green 1 dye. The assay pair was found to be highly specific as it did not cross-react with closely related and other bacterial species.

Quinazolines 1 to 6, with an aromatic or aryl-vinyl substituent in position 2 are selected with the aim to compare their structures and biological activity. The selection includes a natural alkaloid, schizocommunin, and the synthetic 2-(2′-quinolyl)-3H-quinazolin-4-one, known to interact with guanine-quadruplex dependent enzymes, respectively telomerase and topoisomerase.

Breast cancer cells of the MDA cell line have been used to study the bioactivity of the tested compounds by the method of Comet Assay and FACS analyses. We model observed effects assuming stacking interactions of studied heterocycles with a naked skeleton of G-quadruplex, consisting of guanine quartet layers and potassium ions. Interaction energies are computed using a dispersion corrected density functional theory method, and an electron-correlated molecular orbital theory method.

Selected compounds do not remarkably delay nor change the dynamics of cellular progression through the cell cycle phases, while changing significantly cell morphology.