Development of an allele-specific real-time PCR assay for discrimination and quantification of p63 R279H mutation in EEC syndrome

The ectrodactyly-ectodermal dysplasiaclefting syndrome is a rare autosomal dominant disorder caused by heterozygous mutations in the p63 gene, a transcription factor belonging to the p53 family. The majority of cases of ectrodactyly-ectodermal dysplasia syndrome are caused by de novo mutations and are therefore sporadic in approximately 60% of patients. The substitution of arginine to histidine (R279H), due to a c.836G>A mutation in exon 7 of the p63 gene, represents 55% of the identified mutations and is considered a mutational hot spot. A quantitative and sensitive real-time PCR was performed to quantify both wild-type and R279H alleles in DNA extracted from peripheral blood and RNA from cultured epithelial cells. Standard curves were constructed for both wild-type and mutant probes. The sensitivity of the assay was determined by generating serial dilutions of the DNA isolated from heterozygous patients (50% of alleles mutated) with wild-type DNA, thus obtaining decreasing percentages of p63 R279H mutant allele (50%, 37.5%, 25%, 12.5%, 10%, 7.5%, 5%, 2.5%, and 0.0%). The assay detected up to 1% of the mutant p63. The high sensitivity of the assay is of particular relevance to prenatal diagnosis and counseling and to detect therapeutic effects of drug treatment or gene therapy aimed at reducing the amount of mutated p63. © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Olfactory discrimination in the western lowland gorilla, Gorilla gorilla gorilla

The olfactory abilities of great apes have been subject to little empirical investigation, save for a few observational reports. This study, using an habituation/dishabituation task, provides experimental evidence for a core olfactory ability, namely, olfactory discrimination, in the gorilla. In Experiment 1, six zoo-housed western lowland gorillas were individually presented with the same odour on four trials, and with a novel odour on the fifth trial. Odours (almond and vanilla) were presented on plastic balls, and behavioural responses of sniffing and chewing/licking the balls were recorded. A second experiment presented the same odour on four trials and no odour on the fifth to examine whether any dishabituation was due to the presence of a new odour or the absence of the familiar odour. Gorillas habituated their behaviour with repeated presentation of the same odour, but dishabituated, i. e. increased sniffing and chewing/licking, when presented with the novel odour. No dishabituation was noted when using water as the stimulus across all trials or when used as the novel odour. Overall, results show that gorillas are able to discriminate between odours. © 2012 Japan Monkey Centre and Springer.

Managing Cultural Diversity in Healthcare Partnerships: The Case of LIFT

Purpose: The National Health Service (NHS) Local Improvement Finance Trust (LIFT) programme was launched in 2001 as an innovative public-private partnership to address the historical under-investment in local primary care facilities in England. The organisations from the public and private sector that comprise a local LIFT partnership each have their own distinctive norms of behaviour and acceptable working practices - ultimately different organisational cultures. The purpose of this article is to assess the role of organisational culture in facilitating (or impeding) LIFT partnerships and to contribute to an understanding of how cultural diversity in public-private partnerships is managed at the local level. Design/methodology/approach: The approach taken was qualitative case studies, with data gathering comprising interviews and a review of background documentation in three LIFT companies purposefully sampled to represent a range of background factors. Elite interviews were also conducted with senior policy makers responsible for implementing LIFT policy at the national level. Findings: Interpreting the data against a conceptual framework designed to assess approaches to managing strategic alliances, the authors identified a number of key differences in the values, working practices and cultures in public and private organisations that influenced the quality of joint working. On the whole, however, partners in the three LIFT companies appeared to be working well together, with neither side dominating the development of strategy. Differences in culture were being managed and accommodated as partnerships matured. Research limitations/implications: As LIFT develops and becomes the primary source of investment for managing, developing and channelling funding into regenerating the primary care infrastructure, further longitudinal work might examine how ongoing partnerships are working, and how changes in the cultures of public and private partners impact upon wider relationships within local health economies and shape the delivery of patient care. Originality/value: To the authors' knowledge this is the first study of the role of culture in mediating LIFT partnerships and the findings add to the evidence on public-private partnerships in the NHS