Synthetic 3-arylideneflavanones as inhibitors of the initial stages of biofilm formation by Staphylococcus aureus and Enterococcus faecalis

The antimicrobial activity of twenty two synthetic flavonoids is reported. Among them three 3-arylideneflavanones, 2b, 2c, and 2i, were shown to be highly active against Staphylococcus aureus, S. epidermidis, and Enterococcus faecalis reference strains, with MIC (minimal inhibitory concentration) values ranging from 4.68 microg/ml (14.3 microM) to 37.5 microg/ml (119.7 microM). The synergy of oxacillin and vancomycin with 2c, evaluated as fractional inhibitory concentration index (FICI) was shown (against planktonic culture of S. aureus A3 and E. faecium 138/09 clinical strains). The presence of 2c in the culture medium diminished the initial adhesion of bacteria to an abiotic surface. Such an effect resulted in a decrease in biofilm formation during prolonged culture. Unfortunately, 2e failed to eradicate the S. aureus mature biofilm which was already preformed, however, decreased the number of live biofilm cells. The biofilm of E. faecalis was more susceptible to the action of 3-arylideneflavanone 2c than the S. aureus biofilm. The finding that 3-arylideneflavanones are lipophilic, cause bacterial aggregation, and influence the integrity of membranes making them permeable to SYTO 9/propidium iodide dyes may implicate the cytoplasmic membrane as a target site for these compounds activity.     

Detection of the quantitative trait loci for α-amylase activity on a high-density genetic map of rye and comparison of their localization to loci controlling preharvest sprouting and earliness

The objectives of the research were to determine the position of quantitative trait loci (QTL) for α-amylase activity on the genetic map of a rye recombinant inbred line population-S120?×?S76-and to compare them to known QTL for preharvest sprouting and heading earliness. Fourteen QTL for α-amylase activity on all seven chromosomes were identified. The detected QTL were responsible for 6.09-23.32% of α-amylase activity variation. The lowest LOD value (2.22) was achieved by locus QAa4R-M3 and the highest (7.79) by locus QAa7R-M1. Some QTL intervals for features of interest overlapped partially or completely. There were six overlapping QTL for α-amylase activity and preharvest sprouting (on 1R, 3R, 4R, 6R, 7R) and the same number for preharvest sprouting and heading earliness (on 1R, 2R, 6R, 7R). Furthermore, there was one interval partially common to all three traits, mapped on the long arm of chromosome 1R. Testing of lines originating from hybrid breeding programs, such as S120 and S76, may provide important information about the most significant genes and markers for selection in commercial breeding. Among the statistically significant markers selected in the Kruskal-Wallis test (P?相似文献   

Age, parasites, and condition affect humoral immune response in tropical pythons

Mounting an immune response has been suggested to be physiologicallycostly because of metabolic requirements of immune cells specificallyand upregulation of the immune system in general. We investigatedsuch costs in free-living water pythons (Liasis fuscus), immunizedwith a harmless antigen, keyhole limpet hemocyanin. In the presentstudy, we analyze the independent effects of age, blood parasiteload, and body condition on the ability to mount a humoral immuneresponse (level of antibody production to novel antigens). Pythonhumoral immune response decreased with increasing body length/age,decreased with increasing blood parasite load, and decreasedwith declining body condition. The results suggest an energetictrade-off between immunocompetence and other energetically costlyprocesses.     

Amyloid-Precursor-Protein-Lowering Small Molecules for Disease Modifying Therapy of Alzheimer's Disease

Alzheimer''s disease (AD) is the most common form of dementia in the elderly with progressive cognitive decline and memory loss. According to the amyloid-hypothesis, AD is caused by generation and subsequent cerebral deposition of β-amyloid (Aβ). Aβ is generated through sequential cleavage of the transmembrane Amyloid-Precursor-Protein (APP) by two endoproteinases termed beta- and gamma-secretase. Increased APP-expression caused by APP gene dosage effects is a risk factor for the development of AD. Here we carried out a large scale screen for novel compounds aimed at decreasing APP-expression. For this we developed a screening system employing a cell culture model of AD. A total of 10,000 substances selected for their ability of drug-likeness and chemical diversity were tested for their potential to decrease APP-expression resulting in reduced Aβ-levels. Positive compounds were further evaluated for their effect at lower concentrations, absence of cytotoxicity and specificity. The six most promising compounds were characterized and structure function relationships were established. The novel compounds presented here provide valuable information for the development of causal therapies for AD.