The naked truth: Sphynx and Devon Rex cat breed mutations in KRT71

Hair is a unique structure, characteristic of mammals, controlling body homeostasis, as well as cell and tissue integration. Previous studies in dog, mouse, and rat have identified polymorphisms in Keratin 71 (KRT71) as responsible for the curly/wavy phenotypes. The coding sequence and the 3′ UTR of KRT71 were directly sequenced in randomly bred and pedigreed domestic cats with different pelage mutations, including hairless varieties. A SNP altering a splice site was identified in the Sphynx breed and suggested to be the hairless (hr) allele, and a complex sequence alteration, also causing a splice variation, was identified in the Devon Rex breed and suggested to be the curly (re) allele. The polymorphisms were genotyped in approximately 200 cats. All the Devon Rex were homozygous for the complex alterations and most of the Sphynx were either homozygous for the hr allele or compound heterozygotes with the Devon-associated re allele, suggesting that the phenotypes are a result of the identified SNPs. Two Sphynx carrying the proposed hr mutation did not carry the Devon-associated alteration. No other causative mutations for eight different rexoid and hairless cat phenotypes were identified. The allelic series KRT71+ > KRT71hr > KRT71re is suggested

PAX4 Enhances Beta-Cell Differentiation of Human Embryonic Stem Cells

Background Human embryonic stem cells (HESC) readily differentiate into an apparently haphazard array of cell types, corresponding to all three germ layers, when their culture conditions are altered, for example by growth in suspension as aggregates known as embryoid bodies (EBs). However, this diversity of differentiation means that the efficiency of producing any one particular cell type is inevitably low. Although pancreatic differentiation has been reported from HESC, practicable applications for the use of β-cells derived from HESC to treat diabetes will only be possible once techniques are developed to promote efficient differentiation along the pancreatic lineages. Methods and Findings Here, we have tested whether the transcription factor, Pax4 can be used to drive the differentiation of HESC to a β-cell fate in vitro. We constitutively over-expressed Pax4 in HESCs by stable transfection, and used Q-PCR analysis, immunocytochemistry, ELISA, Ca2+ microfluorimetry and cell imaging to assess the role of Pax4 in the differentiation and intracellular Ca2+ homeostasis of β-cells developing in embryoid bodies produced from such HESC. Cells expressing key β-cell markers were isolated by fluorescence-activated cell sorting after staining for high zinc content using the vital dye, Newport Green. Conclusion Constitutive expression of Pax4 in HESC substantially enhances their propensity to form putative β-cells. Our findings provide a novel foundation to study the mechanism of pancreatic β-cells differentiation during early human development and to help evaluate strategies for the generation of purified β-cells for future clinical applications

Persistence of weekly alendronate: a real-world study in Croatia

Long-term treatment of osteoporosis is required for optimal efficacy, but adherence to therapy is suboptimal with daily and weekly oral bisphosphonates. The aim of this study was to assess real-world persistence (long-term adherence) with weekly alendronate. Persistence data were collected according to World Health Organization criteria for the prior month and year for 102 consecutive patients with osteoporosis at three outpatient clinics in Croatia. Persistence was assessed using medication possession ratios (MPR). Adequate persistence was defined as sufficient medication supply to ensure antifracture efficacy (MPR >or=80%). Self-reported persistence data were compared with resupply prescription data from primary care physicians (PCPs). The effect of patient age, co-therapy, co-morbidity, and time since osteoporosis was diagnosed were evaluated. A diagnosis of osteoporosis was established 3.21+/-1.83 years prior for the 96 women and six men enrolled (mean age 66.92+/-8.05 years). During the previous year, 86.3% patients reported not missing any tablets. Age correlated with the number of missed tablets, with older patients missing more tablets (p=0.038). Patients with co-therapy (p=0.042) missed more tablets. PCPs reported that 65.7% of the patients were issued prescriptions for 52 tablets. A total of 68.7% had MPR >80%. Patients with rheumatoid arthritis did not impact MPR (p=0.936). Previous fractures or number of fractures were not associated with persistence (p>0.05). In Croatia, persistence was superior with weekly-administered alendronate than has been reported elsewhere, perhaps due to socio-cultural factors. Larger, longitudinal studies are needed to confirm these results