Differential expression of Snail1 transcription factor and Snail1-related genes in alveolar and embryonal rhabdomyosarcoma subtypes

Rhabdomyosarcoma (RMS) represents the most common sarcoma of soft tissue among children. Two main RMS subtypes are alveolar (ARMS) and embryonal (ERMS). The major goal of this study was to find differentially expressed genes between RMS subtypes that could explain higher metastatic potential in ARMS and would be useful for the differential diagnosis. Using RQ-PCR analysis we compared expression of Snail1 and Snail-related genes among 7 ARMS and 8 ERMS patients' samples obtained from the primary tumors and among 2 alveolar and 2 embryonal cell lines. Our results show that Snail1 is highly expressed both in ARMS patients' samples and the alveolar cell lines. We also found that the expression of E-Cadherin was downregulated and the expression of Matrix Metalloproteinases 2 and 9 (MMP-2 and MMP-9) was upregulated in ARMS. We assume that, as in many tumors, also in RMS Snail1 acts as a regulator for pathways known for their role in cells' metastasis and that Snail1 activity results in increased MMPs and decreased E-Cadherin expression. Our findings may explain higher ARMS aggressiveness. Moreover, we suggest that further studies should be performed to verify if Snail1 can be considered as a potential target for ARMS therapy.     

Profiles of phenotype resistance to antibiotic other than β-lactams in Klebsiella pneumoniae ESBLs-producers, carrying blaSHV genes

Extended spectrum β-lactamases production is one of the most common mechanism of resistance to extended spectrum β-lactam antibiotics is increasing worldwide. Twenty five strains of Klebsiella pneumoniae isolated from clinical specimens were tested. Based on the phenotypic confirmatory test all these strains were defined as ESBL producers named ESBL(+). The plasmid DNA from each strains was used to investigate the presence of blaSHV genes responsible for extended spectrum β-lactamases production. Moreover, susceptibility of these strains to antibiotic other than β-lactams in was tested.     

Simultaneously accounting for population structure, genotype by environment interaction, and spatial variation in marker-trait associations in sugarcane

Few association mapping studies have simultaneously accounted for population structure, genotype by environment interaction (GEI), and spatial variation. In this sugarcane association mapping study we tested models accounting for these factors and identified the impact that each model component had on the list of markers declared as being significantly associated with traits. About 480 genotypes were evaluated for cane yield and sugar content at three sites and scored with DArT markers. A mixed model was applied in analysis of the data to simultaneously account for the impacts of population structure, GEI, and spatial variation within a trial. Two forms of the DArT marker data were used in the analysis: the standard discrete data (0, 1) and a continuous DArT score, which is related to the marker dosage. A large number of markers were significantly associated with cane yield and sugar content. However, failure to account for population structure, GEI, and (or) spatial variation produced both type I and type II errors, which on the one hand substantially inflated the number of significant markers identified (especially true for failing to account for GEI) and on the other hand resulted in failure to detect markers that could be associated with cane yield or sugar content (especially when failing to account for population structure). We concluded that association mapping based on trials from one site or analysis that failed to account for GEI would produce many trial-specific associated markers that would have low value in breeding programs.     

VGLUT2-dependent sensory neurons in the TRPV1 population regulate pain and itch

The natural response to itch sensation is to scratch, which relieves the itch through an unknown mechanism. Interaction between pain and itch has been frequently demonstrated, and the selectivity hypothesis of itch, based on data from electrophysiological and behavioral experiments, postulates the existence of primary pain afferents capable of repressing itch. Here, we demonstrate that deletion of vesicular glutamate transporter (VGLUT) 2 in a subpopulation of neurons partly overlapping with the vanilloid receptor (TRPV1) primary afferents resulted in a dramatic increase in itch behavior accompanied by a reduced responsiveness to thermal pain. The increased itch behavior was reduced by administration of antihistaminergic drugs and by genetic deletion of the gastrin-releasing peptide receptor, demonstrating a dependence on VGLUT2 to maintain normal levels of both histaminergic and nonhistaminergic itch. This study establishes that VGLUT2 is a major player in TRPV1 thermal nociception and also serves to regulate a normal itch response.     

Methods of the site-selective solid phase synthesis of peptide-derived Amadori products

Two procedures of glycated peptides’ synthesis have been developed. The first method involves reductive alkylation of the ε-amino groups of lysine with 2,3:4,5-di-O-isopropylidene-β-d-arabino-hexos-2-ulo-2,6-pyranose in the presence of sodium cyanoborohydride on solid support. The second one uses a new fully protected lysine derivative, which is a building block designed for direct introduction of the glycated lysine moiety into a peptide, according to the standard solid phase synthesis protocol. The applicability of the proposed methods for the synthesis of peptide-derived Amadori products is discussed. The structure of the synthesized glycated peptides was confirmed by high-resolution mass spectrometry and enzymatic hydrolysis. Circular dichroism studies, performed in water solution, revealed that the formation of the Amadori rearrangement product in the lysine side chain does not influence significantly the conformational preferences of the peptides studied. However, when the solvent was changed to trifluoroethanol, the glycated peptides preferred β-turn conformation.     

The actinobacterial signature protein ParJ (SCO1662) regulates ParA polymerization and affects chromosome segregation and cell division during Streptomyces sporulation

Bacterial chromosome segregation usually involves cytoskeletal ParA proteins, ATPases which can form dynamic filaments. In aerial hyphae of the mycelial bacterium Streptomyces coelicolor, ParA filaments extend over tens of microns and are responsible for segregation of dozens of chromosomes. We have identified a novel interaction partner of S. coelicolor ParA, ParJ. ParJ negatively regulates ParA polymerization in vitro and is important for efficient chromosome segregation in sporulating aerial hyphae. ParJ-EGFP formed foci along aerial hyphae even in the absence of ParA. ParJ, which is encoded by sco1662, turned out to be one of the five actinobacterial signature proteins, and another of the five is a ParJ paralogue. We hypothesize that polar growth, which is characteristic not only of streptomycetes, but even of simple Actinobacteria, may be interlinked with ParA polymer assembly and its specific regulation by ParJ.     

Antibiosis against the green peach aphid requires the Arabidopsis thaliana MYZUS PERSICAE-INDUCED LIPASE1 gene

The green peach aphid (GPA) (Myzus persicae Sülzer) is an important sap-sucking pest of a large variety of plants, including Arabidopsis thaliana. Arabidopsis utilizes a combination of defenses that deter insects from settling on the plant, limit insect feeding and curtail insect reproduction. We demonstrate that the previously uncharacterized Arabidopsis MPL1 (MYZUS PERSICAE-INDUCED LIPASE1) gene has an important role in defense against the GPA. MPL1 expression was rapidly induced to high level in GPA-infested plants. Furthermore, the GPA population was larger on the mpl1 mutant than the wild-type (WT) plant. In contrast, constitutive over-expression of MPL1 from the Cauliflower mosaic virus 35S gene promoter curtailed the size of the GPA population. Insect settling and feeding behavior were unaffected on the mpl1 mutant. However, compared with the phloem-sap enriched petiole exudate from the WT plant, mpl1 petiole exudate was deficient in an activity that restricts insect reproduction on a synthetic diet. Furthermore, MPL1 was required for the heightened accumulation of an antibiotic activity in petiole exudate of the Arabidopsis ssi2 mutant, which exhibits enhanced resistance to GPA. These results indicate that MPL1 has an essential function in antibiosis against GPA. The MPL1 protein exhibits homology to lipases and recombinant MPL1 has lipase activity, thus suggesting that a MPL1-dependent lipid, or a product thereof, has an important role in antibiosis against GPA.     

Does molecular docking reveal alternative chemopreventive mechanism of activation of oxidoreductase by sulforaphane isothiocyanates?

Isothiocyanates (ITC) are well-known chemopreventive agents extracted from vegetables. This activity results from the activation of human oxidoreductase. In this letter, the uncompetitive activatory mechanism of ITC was investigated using docking and molecular dynamics simulations. This indicates that NAD(P)H:quinone oxidoreductase can efficiently improve enzyme-substrate recognition within the catalytic site if the ITC activator supports the interaction in the uncompetitive binding site.