Solid-state emissive BODIPY dyes with bulky substituents as spacers

Bright fluorescence of the BODIPY dyes, just like most other fluorophores, is quenched in the solid state due to reabsorption and self-quenching. However, introduction of bulky ferf-butyl substituents on the meso-phenyl groups result in more spaced packing in the solid state, resulting in highly luminescent powders and films. © 2009 American Chemical Society

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

Bioinformatic analyses identifies novel protein-coding pharmacogenomic markers associated with paclitaxel sensitivity in NCI60 cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Paclitaxel is a microtubule-stabilizing drug that has been commonly used in treating cancer. Due to genetic heterogeneity within patient populations, therapeutic response rates often vary. Here we used the NCI60 panel to identify SNPs associated with paclitaxel sensitivity. Using the panel's GI50 response data available from Developmental Therapeutics Program, cell lines were categorized as either sensitive or resistant. PLINK software was used to perform a genome-wide association analysis of the cellular response to paclitaxel with the panel's SNP-genotype data on the Affymetrix 125 k SNP array. FastSNP software helped predict each SNP's potential impact on their gene product. mRNA expression differences between sensitive and resistant cell lines was examined using data from BioGPS. Using Haploview software, we investigated for haplotypes that were more strongly associated with the cellular response to paclitaxel. Ingenuity Pathway Analysis software helped us understand how our identified genes may alter the cellular response to paclitaxel.</p> <p>Results</p> <p>43 SNPs were found significantly associated (FDR < 0.005) with paclitaxel response, with 10 belonging to protein-coding genes (<it>CFTR</it>, <it>ROBO1</it>, <it>PTPRD</it>, <it>BTBD12</it>, <it>DCT</it>, <it>SNTG1</it>, <it>SGCD</it>, <it>LPHN2</it>, <it>GRIK1</it>, <it>ZNF607</it>). SNPs in <it>GRIK1</it>, <it>DCT</it>, <it>SGCD </it>and <it>CFTR </it>were predicted to be intronic enhancers, altering gene expression, while SNPs in <it>ZNF607 </it>and <it>BTBD12 </it>cause conservative missense mutations. mRNA expression analysis supported these findings as <it>GRIK1</it>, <it>DCT</it>, <it>SNTG1</it>, <it>SGCD </it>and <it>CFTR </it>showed significantly (p < 0.05) increased expression among sensitive cell lines. Haplotypes found in <it>GRIK1, SGCD, ROBO1, LPHN2</it>, and <it>PTPRD </it>were more strongly associated with response than their individual SNPs.</p> <p>Conclusions</p> <p>Our study has taken advantage of available genotypic data and its integration with drug response data obtained from the NCI60 panel. We identified 10 SNPs located within protein-coding genes that were not previously shown to be associated with paclitaxel response. As only five genes showed differential mRNA expression, the remainder would not have been detected solely based on expression data. The identified haplotypes highlight the role of utilizing SNP combinations within genomic loci of interest to improve the risk determination associated with drug response. These genetic variants represent promising biomarkers for predicting paclitaxel response and may play a significant role in the cellular response to paclitaxel.</p

Antineuronal antibodies and 8-OHdG an indicator of cerebellar dysfunction in autism spectrum disorder: a case–control study

Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder, that starts in early childhood and presents with deficiencies in social-communicational domains along with restricted and repetitive behaviours/interests. While genetic factors are dominant in its pathogenesis, many factors, including neurological, environmental and immunological have been identified. Furtheremore, although cerebellar dysfunction in the etiology of autism has been shown in different studies, the possible causes of the dysfunction and the role of neuroinflammation among these causes have not been clarified yet. Anti-Yo, anti-Hu, anti-Ri and anti-Amphiphysin antibodies have been found to be associated with cerebellar degeneration. The aim of the present study was to compare anti-Yo, anti-Hu, anti-Ri and anti- Amphiphysin antibodies and 8-OHdG values in blood using the ELISA method between ASD patients and healthy children to demonstrate the role of neuroinflammation as a potential cause of cerebellar dysfunction and DNA damage and evaluate the relationship between Childhood Autism Rating Scale (CARS) scores in children diagnosed with ASD and these parameters. Methods: Thirty-five consecutive children between the ages of 3 and 12 referred to the Child and Adolescent Psychiatry Outpatient Clinic of Harran University Hospital and diagnosed with ASD according to the DSM-5 diagnostic criteria were included in the study. The children did not have any chronic physical disorders and were treatment naive. Thirty-three healthy children between the ages of 3 and 12 without any physical or psychiatric disorders were included as the healthy control group. For psychiatric evaluation, a sociodemographic form and to measure the severity of autism, CARS was used. In the study, anti-Yo, anti-Hu, anti-Ri and anti-Amphiphysin antibodies and 8-OHdG values in blood were investigated using the ELISA method. Results: Thirty-five cases with autism (62.9% males) and thirty-three healthy controls (72.7% males) were included in the present study (p = 0.385). The median age was 6.0 in the ASD group and 7.0 in the control group (p = 0.146). Among ASD patients, anti-Ri antibody positivity was detected, while no anti-Ri antibody positivity was found in the control group (p = 0.002). In the ASD group, the anti-Hu and 8-OHdG values were found to be significantly higher than those of the controls (p < 0.001, p = 0.001); no significant difference was found between the ASD and control groups with regard to the anti-Yo and anti-Amphiphysin values (p = 0.113, p = 0.275). Conclusions: The results of the present study suggest that antibodies against cerebellum may be present among children with ASD and DNA damage may occur due to oxidative stress. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group