Short synthesis and anti-rhinoviral activity of imidazo[1,2-a]pyridines: the effect of acyl groups at 3-position

Various 2-amino-3-acyl-6-[(E)-1-phenyl-2-N-methylcarbamoylvinyl]-imidazo[1,2-a]pyridines, structurally related to Enviroxime were prepared to determine the effect of acyl groups on the antirhinoviral activity. A short and efficient means for the construction of the imidazo nucleus as well as biological evaluation of the final compounds are disclosed.This research was supported by a CDTI program (Plan concertado 96/0036) and the Spanish Farma III programme (Ministerio de Industria y Ministerio de Sanidad). We are also grateful to the Lilly Rhinovirus Action Group for their advice and interest in this work

The atypical 'hippocampal' glutamate receptor coupled to phospholipase D that controls stretch-sensitivity in primary mechanosensory nerve endings is homomeric purely metabotropic GluK2

ACKNOWLEDGEMENTS We would like to thank: Prof. Christophe Mulle, University of Bordeaux, France for the generous donation of the GluK2-Neo mice; Prof. Roberto Pellicciari and Prof. Maura Marinozzi, University of Perugia, Italy for the generous gift of PCCG-13; the Microscopy and Histology core facility at the Institute of Medical Sciences, University of Aberdeen for their support and assistance in some of the imaging in this work. We would also like to thank Prof. Gernot Riedel, University of Aberdeen UK and Prof. David Jane, University of Bristol UK for helpful comments during the work and discussion about drafts of this manuscript.Peer reviewedPublisher PD

Novel genetic loci underlying human intracranial volume identified through genome-wide association

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth

Cytoskeletal Requirements for Hepatitis C Virus (HCV) RNA Synthesis in the HCV Replicon Cell Culture System

Hepatitis C virus (HCV) induces microtubule aggregates in infected hepatocytes. To determine if cytoskeletal elements are important for HCV RNA synthesis, we examined the effect of cytoskeleton inhibitors on HCV replicon transcription in Huh7 cells. The data demonstrate that HCV replication complex-mediated RNA synthesis requires microtubule and actin polymerization