Synthesis and characterisation of novel fluorescent imides by a rhodium(III)-catalysed C-H activation/annulation cascade

Regioselective rhodium(III)-catalysed C-H activation/annulation of O-pivaloyl benzoylhydroxamates with ortho-alkynylbenzoate esters facilitates the rapid preparation of a novel class of fluorophores based on the isoindolo[2,1-b]isoquinoline-5,7-dione core. The photophysical, electrochemical and coordination properties of these novel structures are investigated

Experimental support of the scaling rule for demographic stochasticity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73613/1/j.1461-0248.2006.00903.x.pd

Impact of the calcium form of β-hydroxy-β-methylbutyrate upon human skeletal muscle protein metabolism

Background & aims: β-hydroxy-β-methylbutyrate (HMB) is purported as a key nutritional supplement for the preservation of muscle mass in health, disease and as an ergogenic aid in exercise. Of the two available forms of HMB (calcium (Ca-HMB) salt or free acid (FA-HMB)) – differences in plasma bioavailability have been reported. We previously reported that ∼3 g oral FA-HMB increased muscle protein synthesis (MPS) and reduced muscle protein breakdown (MPB). The objective of the present study was to quantify muscle protein metabolism responses to oral Ca-HMB. Methods: Eight healthy young males received a primed constant infusion of 1,2 13C2 leucine and 2H5 phenylalanine to assess MPS (by tracer incorporation in myofibrils) and MPB (via arterio-venous (A-V) dilution) at baseline and following provision of ∼3 g of Ca-HMB; muscle anabolic (MPS) and catabolic (MPB) signalling was assessed via immunoblotting. Results: Ca-HMB led a significant and rapid (<60 min) peak in plasma HMB concentrations (483.6 ± 14.2 μM, p < 0.0001). This rise in plasma HMB was accompanied by increases in MPS (PA: 0.046 ± 0.004%/h, CaHMB: 0.072 ± 0.004%/h, p < 0001) and suppressions in MPB (PA: 7.6 ± 1.2 μmol Phe per leg min−1, Ca-HMB: 5.2 ± 0.8 μmol Phe per leg min−1, p < 0.01). Increases in the phosphorylation of mTORc1 substrates i.e. p70S6K1 and RPS6 were also observed, with no changes detected in the MPB targets measured. Conclusions: These findings support the pro-anabolic properties of HMB via mTORc1, and show that despite proposed differences in bioavailability, Ca-HMB provides a comparable stimulation to MPS and suppression of MPB, to FA-HMB, further supporting its use as a pharmaconutrient in the modulation of muscle mass

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Genome-wide association study in frontal fibrosing alopecia identifies four susceptibility loci including HLA-B*07:02

Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02

Towards a virtual research environment for language and literature researchers

Language and literature researchers use variety of data resources in order to conduct their day-to-day research. Such resources include dictionaries, thesauri, corpora, images, audio and video collections. These resources are typically distributed, and comprise non-interoperable repositories of data that are often license protected. In this context, researchers conduct their research through direct access to individual resources. This form of research is non-scalable, time consuming and often frustrating to the researchers. The JISC funded project Enhancing Repositories for Language and Literature Researchers (ENROLLER, http://www.gla.ac.uk/enroller/) aims to address by provision of an interactive, research infrastructure providing seamless access to major language and literature repositories. This paper describes this infrastructure and the services that have been developed to overcome the issues in access and use of digital resources in humanities. In particular, we describe how high performance computing facilities including the UK e-Science National Grid Service (NGS, http://www.ngs.ac.uk) have been exploited to support advanced, bulk search capabilities, implemented using Google’s MapReduce algorithm. We also describe our experiences in the use of the resource brokering Workload Management System (WMS) and the Virtual Organization Membership Service (VOMS) solutions in this space. Finally we outline the experiences from the arts and humanities community on the usage of this infrastructure

Towards a virtual research environment for language and literature researchers

Language and literature researchers often use a variety of data resources in order to conduct their day-to-day research. Such resources include dictionaries, thesauri, corpora, images, audio and video collections. These resources are typically distributed, and comprise non-interoperable repositories of data that are often licence protected. In this context, researchers typically conduct their research through direct access to individual web-based resources. This form of research is non-scalable, time consuming and often frustrating to the researchers. The JISC funded project Enhancing Repositories for Language and Literature Researchers (ENROLLER, http://www.gla.ac.uk/enroller/) aims to address this by provision of an interactive, research infrastructure providing seamless access to a range of major language and literature repositories. This paper describes this infrastructure and the services that have been developed to overcome the issues in access and use of digital resources in humanities. In particular, we describe how high performance computing facilities including the UK e-Science National Grid Service (NGS, http://www.ngs.ac.uk) have been exploited to support advanced, bulk search capabilities, implemented using Google’s MapReduce algorithm. We also describe our experiences in the use of the resource brokering Workload Management System (WMS) and the Virtual Organization Membership Service (VOMS) solutions in this space. Finally we outline the experiences from the arts and humanities community on the usage of this infrastructure