Structure–activity Relationships of Amyloid Beta-aggregation Inhibitors Based on Curcumin: Influence of Linker Length and Flexibility

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66293/1/j.1747-0285.2007.00557.x.pd

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch

Rapid sex identification of chicken by fluorescence in situ hybridization using a W chromosome-specific DNA probe

It has been known that the sex of chicken cells can be most accurately identified by fluorescence in situ hybridization (FISH). However, the presently available FISH has not been widely used for sex identification, because the procedures for cell preparation and FISH itself are complicated and time-consuming. The present study was undertaken to test a rapid FISH procedure for sexing chicken. A FISH probe was simultaneously synthesized and labeled with digoxigenin by polymerase chain reaction (PCR) targeting a 416 bp segment of the 717 bp XhoI family fragment which is repeated over 10 thousand times exclusively in the W chromosome. Sexing by FISH was performed on cytological preparations of early embryos, adult lymphocytes and feather pulps of newly hatched chicks. The DNA probe hybridized to all types of uncultured interphase as well as metaphase female but not male cells that had been examined. Moreover, consistent with the known site of the XhoI family, the hybridization signal was localized to the pericentromeric region of the W chromosome. We, therefore, conclude that the present PCR-based FISH can be used as a rapid and reliable sex identification procedure for chicken

Enabling an Online Community for Sharing Oral Medicine Cases Using Semantic Web Technologies

This paper describes how Semantic Web technologies have been used in an online community for knowledge sharing between clinicians in oral medicine in Sweden. The main purpose of this community is to serve as repository of interesting and difficult cases, and as a support for monthly teleconferences. All information regarding users, meetings, news, and cases is stored in RDF. The community was built using the Struts framework and Jena was used for interacting with RDF