Recruitment of Pontin/Reptin by E2f1 amplifies E2f transcriptional response during cancer progression

Changes in gene expression during tumorigenesis are often considered the consequence of de novo mutations occurring in the tumour. An alternative possibility is that the transcriptional response of oncogenic transcription factors evolves during tumorigenesis. Here we show that aberrant E2f activity, following inactivation of the Rb gene family in a mouse model of liver cancer, initially activates a robust gene expression programme associated with the cell cycle. Slowly accumulating E2f1 progressively recruits a Pontin/Reptin complex to open the chromatin conformation at E2f target genes and amplifies the E2f transcriptional response. This mechanism enhances the E2f-mediated transactivation of cell cycle genes and initiates the activation of low binding affinity E2f target genes that regulate non-cell-cycle functions, such as the Warburg effect. These data indicate that both the physiological and the oncogenic activities of E2f result in distinct transcriptional responses, which could be exploited to target E2f oncogenic activity for therapy

Recruitment of Pontin/Reptin by E2f1 amplifies E2f transcriptional response during cancer progression

Changes in gene expression during tumorigenesis are often considered the consequence of de novo mutations occurring in the tumour. An alternative possibility is that the transcriptional response of oncogenic transcription factors evolves during tumorigenesis. Here we show that aberrant E2f activity, following inactivation of the Rb gene family in a mouse model of liver cancer, initially activates a robust gene expression programme associated with the cell cycle. Slowly accumulating E2f1 progressively recruits a Pontin/Reptin complex to open the chromatin conformation at E2f target genes and amplifies the E2f transcriptional response. This mechanism enhances the E2f-mediated transactivation of cell cycle genes and initiates the activation of low binding affinity E2f target genes that regulate non-cell-cycle functions, such as the Warburg effect. These data indicate that both the physiological and the oncogenic activities of E2f result in distinct transcriptional responses, which could be exploited to target E2f oncogenic activity for therapy

Frequent Follow-Up of Delisted Liver Transplant Candidates Is Necessary: An Observational Study about Characteristics and Outcomes of Delisted Liver Transplant Candidates

This observational study focuses on the characteristics and survival of patients taken off of the liver transplant waiting list. Assessment of post-delisting survival and a frequent follow-up of patients after delisting are important keys to improve the survival rate of patients with liver failure after being delisted. Within this study, delisted liver transplant candidates were divided into the following groups: (1) "too good" (54%) or (2) "too sick" (22%) for transplantation, (3) adherence issues (12%) or (4) therapy goal changed (11%). The 5-year survival after delisting within these groups was 84%, 9%, 50%, and 68%, respectively. Less than 3% of the delisted patients had to be relisted again. The clinical expert decision of the multidisciplinary transplant team was sufficiently accurate to differentiate between patients requiring liver transplantation and those who were delisted after a stable recovery of liver function. The assessment of post-delisting survival may serve as a complementary metric to assess differences in center practices and to estimate cumulative post-delisting mortality risk

Negotiating Value: Comparing Human and Animal Fracture Care in Industrial Societies

At the beginning of the twentieth-century, human and veterinary surgeons faced the challenge of a medical marketplace transformed by technology. The socio-economic value ascribed to their patients – people and domestic animals – was changing, reflecting the increasing mechanisation of industry and the decreasing dependence of society upon non-human animals for labour. In human medicine, concern for the economic consequences of fractures “pathologised” any significant level of post-therapeutic disability, a productivist perspective contrary to the traditional corpus of medical values. In contrast, veterinarians adapted to the mechanisation of horse-power by shifting their primary professional interest to companion animals; a type of veterinary patient generally valued for the unique emotional attachment of the owner, and not the productive capacity of the animal. The economic rationalisation of human fracture care and the “sentimental” transformation of veterinary orthopaedic expertise indicates how these specialists utilised increasingly convergent rhetorical arguments to justify the application of innovative fracture care technologies to their humans and animal patients. Keywords: Fracture care, Industrialisation, Veterinary History, Human/animal relation

B2B e-marketplaces in the airline industry:process drivers and performance indicators

Competitive pressures are increasing within and between different strategically oriented groups of airlines. This paper focuses on the level of efficiency improvements gained by using e-Marketplaces in the procurement process. Findings from a survey among 88 international airlines reveal that the use of Business-to-Business (B2B) e-Marketplaces does play different roles across the various airline groupings. Airlines that are involved in strategic alliances show higher joint procurement activities than airlines that are not involved in strategic alliances. However, alliances are probably viewed as loose arrangements and thus airlines may be reluctant to share information on procurement prices and processes with another airline that could also be acting as a competitor. The financial involvement in or initiation of e-Marketplaces by airlines is very low. Low cost airlines show high use of e-Marketplaces, but demonstrate little financial involvement in contrast. Overall, the categories of spares and repairs, office supplies, tools and ground support equipment (GSE) show the greatest potential for reducing costs and increasing procurement process efficiencies. The intense competitive pressures facing carriers will make their search for tools to realise even incremental savings and efficiency gains ever more urgent. There is evidence that e-Marketplaces are one tool to improve such performance indicators

The spectrum of Apert syndrome: phenotype, particularities in orthodontic treatment, and characteristics of orthognathic surgery

In the PubMed accessible literature, information on the characteristics of interdisciplinary orthodontic and surgical treatment of patients with Apert syndrome is rare. The aim of the present article is threefold: (1) to show the spectrum of the phenotype, in order (2) to elucidate the scope of hindrances to orthodontic treatment, and (3) to demonstrate the problems of surgery and interdisciplinary approach. Children and adolescents who were born in 1985 or later, who were diagnosed with Apert syndrome, and who sought consultation or treatment at the Departments of Orthodontics or Craniomaxillofacial Surgery at the Dental School of the University Hospital of Münster (n = 22; 9 male, 13 female) were screened. Exemplarily, three of these patients (2 male, 1 female), seeking interdisciplinary (both orthodontic and surgical treatment) are presented. Orthodontic treatment before surgery was performed by one experienced orthodontist (AH), and orthognathic surgery was performed by one experienced surgeon (UJ), who diagnosed the syndrome according to the criteria listed in OMIM™. In the sagittal plane, the patients suffered from a mild to a very severe Angle Class III malocclusion, which was sometimes compensated by the inclination of the lower incisors; in the vertical dimension from an open bite; and transversally from a single tooth in crossbite to a circular crossbite. All patients showed dentitio tarda, some impaction, partial eruption, idopathic root resorption, transposition or other aberrations in the position of the tooth germs, and severe crowding, with sometimes parallel molar tooth buds in each quarter of the upper jaw. Because of the severity of malocclusion, orthodontic treatment needed to be performed with fixed appliances, and mainly with superelastic wires. The therapy was hampered with respect to positioning of bands and brackets because of incomplete tooth eruption, dense gingiva, and mucopolysaccharide ridges. Some teeth did not move, or moved insufficiently (especially with respect to rotations and torque) irrespective of surgical procedures or orthodontic mechanics and materials applied, and without prognostic factors indicating these problems. Establishing occlusal contact of all teeth was difficult. Tooth movement was generally retarded, increasing the duration of orthodontic treatment. Planning of extractions was different from that of patients without this syndrome. In one patient, the sole surgical procedure after orthodontic treatment with fixed appliances in the maxilla and mandible was a genioplasty. Most patients needed two- jaw surgery (bilateral sagittal split osteotomy [BSSO] with mandibular setback and distraction in the maxilla). During the period of distraction, the orthodontist guided the maxilla into final position by means of bite planes and intermaxillary elastics. To our knowledge, this is the first article in the PubMed accessible literature describing the problems with respect to interdisciplinary orthodontic and surgical procedures. Although the treatment results are not perfect, patients undergoing these procedures benefit esthetically to a high degree. Patients need to be informed with respect to the different kinds of extractions that need to be performed, the increased treatment time, and the results, which may be reached using realistic expectations

Analyzing Childlessness

Childlessness has been on the rise in many European societies. In Germany, the UK, Austria, the Netherlands, and Switzerland, childlessness has increased starting with the 1950s cohorts. In these countries, about 20 % of the women born around 1965 will remain childless. In southern Europe and the former state-socialist countries of Central and Eastern Europe, the rise in levels of childlessness is a more recent phenomenon. Yet among younger cohorts in these countries, childlessness has reached levels of 15 % or higher. In this introductory chapter, we summarize the long-term trends in childlessness and discuss the differences between European countries in the prevalence of childlessness. We also outline the structure and the logic of this volume

A Combined Perceptual, Physico-Chemical, and Imaging Approach to ‘Odour-Distances’ Suggests a Categorizing Function of the Drosophila Antennal Lobe

How do physico-chemical stimulus features, perception, and physiology relate? Given the multi-layered and parallel architecture of brains, the question specifically is where physiological activity patterns correspond to stimulus features and/or perception. Perceived distances between six odour pairs are defined behaviourally from four independent odour recognition tasks. We find that, in register with the physico-chemical distances of these odours, perceived distances for 3-octanol and n-amylacetate are consistently smallest in all four tasks, while the other five odour pairs are about equally distinct. Optical imaging in the antennal lobe, using a calcium sensor transgenically expressed in only first-order sensory or only second-order olfactory projection neurons, reveals that 3-octanol and n-amylacetate are distinctly represented in sensory neurons, but appear merged in projection neurons. These results may suggest that within-antennal lobe processing funnels sensory signals into behaviourally meaningful categories, in register with the physico-chemical relatedness of the odours

Facilitating tree-ring dating of historic conifer timbers using Blue Intensity

The Scottish pine network expansion has been an ongoing task since 2006 and funding must be acknowledged to the following projects: EU project ‘Millennium’ (017008-2), Leverhulme Trust project ‘RELiC: Reconstructing 8000 years of Environmental and Landscape change in the Cairngorms (F/00268/BG)’, the Native Oak and Pine project or ‘NOAP’ (Historic Scotland) and the NERC project ‘SCOT2K:Reconstructing 2000 years of Scottish climate from tree rings (NE/K003097/1)’. Further PhD funding for Milos Rydval is acknowledged from The Carnegie Trust.Dendroarchaeology almost exclusively uses ring-width (RW) data for dating historical structures and artefacts. Such data can be used to date tree-ring sequences when regional climate dominates RW variability. However, the signal in RW data can be obscured due to site specific ecological influences (natural and anthropogenic) that impact crossdating success. In this paper, using data from Scotland, we introduce a novel tree-ring parameter (Blue Intensity – BI) and explore its utility for facilitating dendro historical dating of conifer samples. BI is similar to latewood density as they both reflect the combined hemicellulose, cellulose and lignin content in the latewood cell walls of conifer species and the amount of these compounds is strongly controlled, at least for trees growing in temperature limited locations, by late summer temperatures. BI not only expresses a strong climate signal, but is also less impacted by site specific ecological influences. It can be concurrently produced with RW data from images of finely sanded conifer samples but at a significantly reduced cost compared to traditional latewood density. Our study shows that the probability of successfully crossdating historical samples is greatly increased using BI compared to RW. Furthermore, due to the large spatial extent of the summer temperature signal expressed by such data, a sparse multi-species conifer network of long BI chronologies across Europe could be used to date and loosely provenance imported material.PostprintPeer reviewe