Characterization of Coupled Ground State and Excited State Equilibria by Fluorescence Spectral Deconvolution

Fluorescence probes with multiparametric response based on the relative variation in the intensities of several emission bands are of great general utility. An accurate interpretation of the system requires the determination of the number, positions and intensities of the spectral components. We have developed a new algorithm for spectral deconvolution that is applicable to fluorescence probes exhibiting a two-state ground-state equilibrium and a two-state excited-state reaction. Three distinct fluorescence emission bands are resolved, with a distribution of intensities that is excitation-wavelength-dependent. The deconvolution of the spectrum into individual components is based on their representation as asymmetric Siano-Metzler log-normal functions. The application of the algorithm to the solvation response of a 3-hydroxychromone (3HC) derivative that exhibits an H-bonding-dependent excited-state intramolecular proton transfer (ESIPT) reaction allowed the separation of the spectral signatures characteristic of polarity and hydrogen bonding. This example demonstrates the ability of the method to characterize two potentially uncorrelated parameters characterizing dye environment and interactions

Synthesis and self-assembly of new unsymmetrical bolaamphiphiles: spontaneous monolayer formation on mica surface.

International audienc

Cytogenetic results of amniocentesis materials: Incidence of abnormal karyotypes in the Turkish collaborative study

Cytogenetic results of amniocentesis materials: incidence of abnormal karyotypes in the Turkish collaborative study: The experience on prenatal chromosome diagnosis of four Turkish centers participating in a collaborative study on 6041 genetic amniocentesis performed during a 4-8 years period were reviewed. 5887 (97.5%) patients had strong clinical indications for prenatal chromosome studies and 154 (2.5%) were referred because of maternal anxiety and a bad history of previous gestations. The main indication groups were: advanced maternal age (3197 cases), positive serum screening (2011 cases), ultrasound-identified anomaly (492 cases), previous fetus/child with chromosomal aberrations (103 cases), a history of a previous abnormal and / or mentally handicapped child (70 cases) and a parental chromosome rearrangement (14 cases). The average maternal age was 33.9 years and average gestational age was 18 weeks. A total of 179 affected fetuses were detected in this collaborative study (3%) of which 133 were unbalanced (74.3%). Among the 124 (69%) numerical aberrations, 102 (82.3%) were autosomal aneuploidies, 20 (16.1%) were gonosomal aneuploidies and 2 (1.6%) were poliploidies. Among the 55 (31%) structural aberrations, balanced translocation was the most common (63.6%) and I 1 cases of inversion, four cases of unbalanced translocation, two cases of marker chromosome and three cases of other abnormalities were found. The overall culture success rate was 99.7%. Pregnancy termination that is permitted by legal authorities was accepted by 94.7% (126/133) with parents at unbalanced cytogenetic result announcement

Design and Synthesis of Chalcone and Chromone Derivatives as Novel Anticancer Agents

This thesis comprises the design and synthesis of chalcone and chromone derivatives and their use in various biological applications, particularly as anticancer agents (targeting proteins associated with cancer pathogenesis) and as potential fluorophores for live-cell imaging. Conveniently, all structures presented were synthesized from commercially available 2 ́-hydroxyacetophenones. Different synthetic strategies were used to obtain an easily accessible chromone scaffold with appropriate handles that allows regioselective introduction of various substituents. Structural diversity was accomplished by using palladium-mediated reactions for the incorporation of suitable substituents for the generation of chromone derivatives that possess different biological activities. Challenging synthesis provided a series of fluorescent 2,6,8-trisubstituted 3- hydroxychromone derivatives with high quantum yields and molar extinction coefficients. Two of these derivatives were studied as fluorophores in live-cell imaging and showed rapid absorption, non-cytotoxic profiles and excellent fluorescent properties in a cellular environment. Synthetic chromone precursors, i.e. chalcones, and related dienones were evaluated as antiproliferative agents that interfere with the tubulin-microtubule equilibrium, crucial for cellular mitosis. It was shown that several of the synthesized compounds destabilize tubulin assembly. However, one of the compounds was instead found to stabilize tubulin to the same extent as the known anticancer drug docetaxel, thus representing the first chalcone with microtubule stabilizing activity. Molecular docking was used in order to theoretically investigate the interactions of the chalcones with ␣-tubulin mainly focusing on binding modes, potential interactions and specific binding sites. Structural-based design and extensive synthesis provided chromone-based derivatives that target two different MAP kinases (p38␣ and MEK1), involved in essential cellular signal transduction pathways. The study resulted in a series of highly selective ATP-competitive chromone-based p38␣ inhibitors with IC50 values in the nanomolar range. Among those, two derivatives also showed inhibition of p38 signaling in human breast cancer cells. Furthermore, molecular docking was used to study potential structural modifications on the chromone structure in order to obtain highly potent derivatives that selectively target the allosteric pocket on MEK1. Initial studies provided a first generation of non-ATP- competitive chromone derivatives that prevents the activation of MEK1 with micromolar activities

Zebrafish as a tool in Alzheimer's disease research

Alzheimer's disease is the most prevalent form of neurodegenerative disease. Despite many years of intensive research our understanding of the molecular events leading to this pathology is far from complete. No effective treatments have been defined and questions surround the validity and utility of existing animal models. The zebrafish (and, in particular, its embryos) is a malleable and accessible model possessing a vertebrate neural structure and genome. Zebrafish genes orthologous to those mutated in human familial Alzheimer's disease have been defined. Work in zebrafish has permitted discovery of unique characteristics of these genes that would have been difficult to observe with other models. In this brief review we give an overview of Alzheimer's disease and transgenic animal models before examining the current contribution of zebrafish to this research area. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases.Morgan Newman, Giuseppe Verdile, Ralph N. Martins and Michael Lardellihttp://www.elsevier.com/wps/find/journaldescription.cws_home/506068/description#descriptio

Intradiscal Electrothermal Therapy, Percutaneous Discectomy, and Nucleoplasty: What is the Current Evidence?

Over the past decade, there has been a surge of minimally invasive techniques aimed at treating both discogenic low back pain (LBP) and radicular pain. This article assesses the current evidence for three such treatments: intradiscal electrothermal therapy (IDET), percutaneous discectomy, and nucleoplasty. An electronic search of the literature carried out using the Cochrane Library database (2007) and Medline (1966-2007) identified 77 references relating to IDET, 363 to percutaneous discectomy, and 36 to nucleoplasty. Two randomized controlled trials (RCTs) assessed the effectiveness of IDET; one demonstrated a positive effect on pain severity only, whereas the other demonstrated no substantial benefit. Other RCTs show that percutaneous intradiscal radiofrequency thermocoagulation is ineffective for the treatment of discogenic LBP. Trials of automated percutaneous discectomy suggest that clinical outcomes after treatment are at best fair and often worse when compared with microdiscectomy. There are no published RCTs assessing Coblation (ArthroCare Spine, Stockholm, Sweden) technology.Brian J. C. Freeman and Roshana Mehdia

Biocompatible Flavone-Based Fluorogenic Probes for Quick Wash-Free Mitochondria! Imaging in Living Cells

Mitochondria, vital organelles existing in almost all eukaryotic cells, play a crucial role in energy metabolism and apoptosis of aerobic organisms. In this work, we report two new flavone-based fluorescent probes, MC-Mito1 and MC-Mito2, for monitoring mitochondria in living cells. These two probes exhibit remarkably low toxicity, good cell permeability, and high specificity; these probes complement the existing library of mitochondrial imaging agents. The new dyes give nearly no background fluorescence, and their application does not require tedious postwashing after cell staining. The appreciable tolerance of MC-Mito2 encourages a broader range of biological applications for understanding the cell degeneration and apoptosis mechanism