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1.  Vitamin D in youth with Type 1 diabetes: prevalence of insufficiency and association with insulin resistance in the SEARCH Nutrition Ancillary Study 
To determine the prevalence of plasma vitamin D insufficiency in individuals with Type 1 diabetes and to determine the cross-sectional and longitudinal associations of plasma vitamin D with insulin resistance.
Participants from the SEARCH for Diabetes in Youth Study [n = 1426; mean age 11.2 years (sd 3.9)] had physician-diagnosed Type 1 diabetes [diabetes duration mean 10.2 months (sd 6.5)] with data available at baseline and follow-up (approximately 12 and 24 months after baseline). Insulin resistance was estimated using a validated equation. Cross-sectional and longitudinal multivariate logistic regression models were used to determine the association of plasma vitamin D with insulin resistance, adjusting for potential confounders.
Forty-nine per cent of individuals had plasma vitamin D < 50 nmol/l and 26% were insulin resistant. In cross-sectional multivariate analyses, participants who had higher plasma vitamin D (65 nmol/l) had lower odds of prevalent insulin resistance than participants with lower plasma vitamin D (25 nmol/l) (odds ratio 0.70, 95% CI 0.57–0.85). This association was attenuated after additional adjustment for BMI z-score, which could be a confounder or a mediator (odds ratio 0.81, 95% CI 0.64–1.03). In longitudinal multivariate analyses, individuals with higher plasma vitamin D at baseline had lower odds of incident insulin resistance, but this was not significant (odds ratio 0.85, 95% CI 0.63–1.14).
Vitamin D insufficiency is common in individuals with Type 1 diabetes and may increase risk for insulin resistance. Additional prospective studies are needed to determine the association between plasma vitamin D and insulin resistance, and to further examine the role of adiposity on this association.
PMCID: PMC3822440  PMID: 23909945
2.  Exploitation of interspecific diversity for monocot crop improvement 
Heredity  2013;110(5):475-483.
In many cultivated crop species there is limited genetic variation available for the development of new higher yielding varieties adapted to climate change and sustainable farming practises. The distant relatives of crop species provide a vast and largely untapped reservoir of genetic variation for a wide range of agronomically important traits that can be exploited by breeders for crop improvement. In this paper, in what we believe to be the largest introgression programme undertaken in the monocots, we describe the transfer of the entire genome of Festuca pratensis into Lolium perenne in overlapping chromosome segments. The L. perenne/F. pratensis introgressions were identified and characterised via 131 simple sequence repeats and 1612 SNPs anchored to the rice genome. Comparative analyses were undertaken to determine the syntenic relationship between L. perenne/F. pratensis and rice, wheat, barley, sorghum and Brachypodium distachyon. Analyses comparing recombination frequency and gene distribution indicated that a large proportion of the genes within the genome are located in the proximal regions of chromosomes which undergo low/very low frequencies of recombination. Thus, it is proposed that past breeding efforts to produce improved varieties have centred on the subset of genes located in the distal regions of chromosomes where recombination is highest. The use of alien introgression for crop improvement is important for meeting the challenges of global food supply and the monocots such as the forage grasses and cereals, together with recent technological advances in molecular biology, can help meet these challenges.
PMCID: PMC3630809  PMID: 23321705
Introgression mapping; comparative mapping; recombination; interspecific diversity; monocots; SNP markers
3.  Buried Penis: Evaluation of Outcomes in Children and Adults, Modification of a Unified Treatment Algorithm, and Review of the Literature 
ISRN Urology  2013;2013:109349.
Introduction. Buried penis is a difficult condition to manage in children and adults and conveys significant physical and psychological morbidity. Surgery is often declined due to morbid obesity, forcing patients to live in disharmony for years until the desired weight reduction is achieved. No single operative technique fits all. We present our experience and surgical approach resulting in an improved algorithm unifying the treatment of adults and children. Methods. We conducted a retrospective analysis of patients treated for buried penis between 2011 and 2012. All patients underwent penile degloving and basal anchoring. Penile shaft coverage was achieved with skin grafts. Suprapubic lipectomies were performed on adult patients. Results. Nine patients were identified: four children and five obese adults. Average postoperative stay was three days for children and five for adults. Three adults were readmitted with superficial wound problems. One child had minor skin breakdown. All patients were pleased with their outcomes. Conclusion. Buried penis is a complex condition, and treatment should be offered by services able to deal with all aspects of reconstruction. Obesity in itself should not delay surgical intervention. Local and regional awareness is essential to manage expectations in these challenging patients aspiring to both aesthetic and functional outcomes.
PMCID: PMC3893803  PMID: 24490087
4.  Development of a Genomic Microsatellite Library in Perennial Ryegrass (Lolium perenne) and its Use in Trait Mapping 
Annals of Botany  2008;101(6):845-853.
Background and Aims
Perennial ryegrass (Lolium perenne) is one of the key forage and amenity grasses throughout the world. In the UK it accounts for 70 % of all agricultural land use with an estimated farm gate value of £6 billion per annum. However, in terms of the genetic resources available, L. perenne has lagged behind other major crops in Poaceae. The aim of this project was therefore the construction of a microsatellite-enriched genomic library for L. perenne to increase the number of genetic markers available for both marker-assisted selection in breeding programmes and gene isolation.
Primers for 229 non-redundant microsatellite markers were designed and used to screen two L. perenne genotypes, one amenity and one forage. Of the 229 microsatellites, 95 were found to show polymorphism between amenity and forage genotypes. A selection of microsatellite primers was selected from these 95 and used to screen two mapping populations derived from intercrossing and backcrossing the two forage and amenity grass genotypes.
Key Results and Conclusions
The utility of the resulting genetic maps for analysis of the genetic control of target traits was demonstrated by the mapping of genes associated with heading date to linkage groups 4 and 7.
PMCID: PMC2710216  PMID: 18281692
Microsatellites; Lolium perenne; perennial ryegrass; trait mapping
5.  Antiviral Activity of β-l-2′,3′-Dideoxy-2′,3′-Didehydro-5-Fluorocytidine in Woodchucks Chronically Infected with Woodchuck Hepatitis Virus 
The l-nucleoside analog β-l-2′,3′-dideoxy-2′,3′-didehydro-5-fluorocytidine (β-l-Fd4C) was first shown to exhibit potent activity against hepatitis B virus (HBV) in tissue culture and then to significantly inhibit viral spread during acute infection in the duck HBV model (F. Le Guerhier et al., Antimicrob. Agents Chemother. 44:111–122, 2000). We have therefore examined its antiviral activity in a mammalian model of chronic HBV infection, the woodchuck chronically infected with woodchuck hepatitis virus (WHV). Side-by-side comparison of β-l-Fd4C and lamivudine administered intraperitoneally during short-term and long-term protocols demonstrated a more profound inhibition of viremia in β-l-Fd4C-treated groups. Moreover, β-l-Fd4C induced a marked inhibition of intrahepatic viral DNA synthesis compared with that induced by lamivudine. Nevertheless, covalently closed circular (CCC) DNA persistence explained the lack of clearance of infected hepatocytes expressing viral antigens and the relapse of WHV replication after drug withdrawal. Liver histology showed a decrease in the inflammatory activity of chronic hepatitis in woodchucks receiving β-l-Fd4C. An electron microscopy study showed the absence of ultrastructural changes of hepatic mitochondria, biliary canaliculi, and bile ducts. However, a loss of weight was observed in all animals, whatever the treatment, as was a transient skin pigmentation in all woodchucks during β-l-Fd4C treatment. There was no evidence that lamivudine or β-l-Fd4C could prevent the development of hepatocellular carcinoma with the protocols used. These results indicate that β-l-Fd4C exhibits a more potent antiviral effect than lamivudine in the WHV model but was not able to eradicate CCC DNA and infected cells from the liver at the dosage and with the protocol used.
PMCID: PMC90426  PMID: 11257017

Results 1-7 (7)