Lindsayankersen8694

Pyrrolidinophenones (PPs) are synthetic cathinones containing a pyrrolidine ring that are used recreationally worldwide. Dansylcadaverine Recently, many studies on the metabolism and cytotoxicity of PPs have been published. Here, we focus on new designer drug containing an indan skeleton, 1-(2,3-dihydro-1H-inden-5-yl)-2-(pyrrolidine-1-yl)butan-1-one (5-PPDI), because there have been no reports to date regarding the metabolism of indan-type cathinones. The identification of 5-PPDI phase I metabolites in human urine enables us to determine whether a person has taken 5-PPDI. This metabolite detection approach plays a very important role in the field of forensic science. We synthesized analytical standards of 5-PPDI and four proposed metabolites. A urine sample was prepared by salting-out assisted liquid-liquid extraction with acetonitrile. Analyses of all standards and the urine sample were performed by liquid chromatography high resolution tandem mass spectrometry. As a result, we were able to detect 5-PPDI and its metabolites in the urine specimen. Two diastereomers of synthesized 1-OH metabolites were successfully separated, and only one diastereomer was observed in the urine specimen. To the best of our knowledge, this is the first report on the stereoselective reduction of PPs in humans. Further, we performed quantitative analyses of 5-PPDI and its metabolites in the urine. We identified three characteristic features of 5-PPDI phase I metabolism (1) hydroxylation at the indan skeleton, (2) stereoselective reduction of the carbonyl group, and (3) hydroxylation of the indan skeleton possibly proceeding more preferentially than any other metabolization. In addition, several structural isomers and diastereomers of 2'-OH metabolites were detected. Based on these data, we propose phase I metabolic pathways of 5-PPDI, which will be essential in understanding the metabolism of other PPs with an indan skeleton. Photodynamic therapy (PDT) is considered a very promising therapeutic modality for antimicrobial therapy. Although several studies have demonstrated that Gram-positive bacteria are very sensitive to PDT, Gram-negative bacteria are more resistant to photodynamic action. This difference is due to a different cell wall structure. Gram-negative bacteria have an outer cell membrane containing lipopolysaccharides (LPS) that hinder the binding of photosensitizer molecules, protecting the bacterial cells from chemical attacks. Combination of the lipopolysaccharides-binding activity of Concanavalin A (ConA) with the photodynamic properties of Rose Bengal (RB) holds the potential of an innovative protein platform for targeted photodynamic therapy against Gram-negative bacteria. A ConA-RB bioconjugate was synthesized and characterized. Approximately 2.4 RB molecules were conjugated per ConA monomer. The conjugation of RB to ConA determines a decrease of the singlet oxygen generation and an increase of superoxide and peroxide production. The photokilling efficacy of the ConA-RB bioconjugate was demonstrated in a planktonic culture of E. coli. Irradiation with white light from a LED lamp produced a dose-dependent photokilling of bacteria. ConA-RB conjugates exhibited a consistent improvement over RB (up to 117-fold). The improved uptake of the photosensitizer explains the enhanced PDT effect accompanying increased membrane damages induced by the ConA-RB conjugate. The approach can be readily generalized (i) using different photo/sonosensitizers, (ii) to target other pathogens characterized by cell membranes containing lipopolysaccharides (LPS). V.Telomeres are part of the system that guards genome integrity in eukaryotes, protecting linear chromosomes from fusions and degradations. The protective functions of telomeres are put at risk in physiological situations where telomeres shorten and trigger replicative senescence. Current models suggest that when telomeres shorten, combined actions of the DNA damage signalling network, DNA repair pathways, and the mechanics of mitosis result in translocations, gene losses, and aneuploidy. In yeasts, many of these processes (signalling, repair, mitosis) can be molecularly dissected because telomerase can be experimentally removed to enable detection of early and rare events. Here we review recent findings on telomere-driven mutational processes in yeast models and discuss how telomere dynamics may contribute to genome evolution. Telomeres are composed of DNA repeat sequences at the ends of chromosomes that recruit a multitude of proteins to form a complex loop structure at each extremity. The integrity of this structure is critical and correct conformation of the loop is essential for the protection of chromosome ends from DDR signaling. The properties of telomere composition and synthesis result in telomere shortening at each cell division, programming cellular lifespan by driving aged cells towards death. Indeed, many external factors, such as cellular stress, trigger cell-cycle dysfunction and, in some cases, enable the survival of cells with dysfunctionally short telomeres. Destabilized loops at chromosome ends can then lead to dramatic consequences, via a butterfly effect such as multiple chromosomal fusions and rearrangements causing large chromosomal deletions, XXL-LOH (loss of heterozygoty due to very large chromosome deletions, up to whole chromosome arm), the expression of recessive mutations, and potential cell transformation. BACKGROUND Rising from a chair is an important functional measure after stroke. Originally developed as a measure of lower-limb strength, the five times sit-to-stand test has shown associations with other measures of impairment, such as balance ability. We aimed to compare strength and balance in their relationship with the five times sit-to-stand test following stroke. METHODS Sixty-one participants following stroke were recruited from two hospitals in this cross-sectional observational study. Participants underwent assessment of the five times sit-to-stand (measured with a stopwatch), bilateral lower-limb muscle strength of seven individual muscle groups (hand-held dynamometry), and standing balance (computerised posturography). Partial correlations (controlling for body mass and height) were used to examine bivariate associations. Regression models with partial F-tests (including pertinent covariates) compared the contribution of strength (both limbs) and balance to five times sit-to-stand time. RESULTS The strength of the majority of lower-limb muscle groups (6/7) on the paretic side had a significant (P less then 0.