Death and Display in the North Atlantic: The Bronze and Iron Age Human Remains from Cnip, Lewis, Outer Hebrides

YesThis paper revisits the series of disarticulated human remains discovered during the 1980s excavations of the Cnip wheelhouse complex in Lewis. Four fragments of human bone, including two worked cranial fragments, were originally dated to the 1st centuries BC/AD based on stratigraphic association. Osteoarchaeological reanalysis and AMS dating now provide a broader cultural context for these remains and indicate that at least one adult cranium was brought to the site more than a thousand years after the death of the individual to whom it had belonged

Allosteric modulation of beta1 integrin function induces lung repair in animal model of emphysema.

Emphysema is a progressive lung disease characterised by loss of lung parenchyma with associated functional changes including decreased tissue elastance. Here we report beta1 integrin is a novel target for tissue repair and regeneration in emphysema. We show a single dose of a monoclonal antibody against beta1 integrin induced both functional and structural reversal of elastase-induced lung injury in vivo, and we found that similar matrix remodelling changes occurred in human lung tissue. We also identified a potential mechanism of action as this allosteric modulation of beta1 integrin inhibited elastase-induced caspase activation, F-actin aggregate formation and changes in cellular ATP levels. This was accompanied by maintenance of beta1?integrin levels and inhibition of caveolin-1 phosphorylation. We propose that allosteric modulation of beta1 integrin-mediated mechanosensing prevents cell death associated with lung injury and progressive emphysema, thus allowing cells to survive and for repair and regeneration to ensue

Absence of p53 in Clara cells favours multinucleation and loss of cell cycle arrest

BACKGROUND: The p53 oncosuppressor protein is a critical mediator of the response to injury in mammalian cells and is mutationally inactivated in the majority of lung malignancies. In this analysis, the effects of p53-deficiency were investigated in short-term primary cultures of murine bronchiolar Clara cells. Clara cells, isolated from gene-targeted p53-deficient mice, were compared to cells derived from wild type littermates. RESULTS: p53 null cultures displayed abnormal morphology; specifically, a high incidence of multinucleation, which increased with time in culture. Multinucleated cells were proficient in S phase DNA synthesis, as determined by BrdU incorporation. However, multinucleation did not reflect altered rates of S phase synthesis, which were similar between wild type and p53-/- cultures. Nucleation defects in p53-/- Clara cells associated with increased centrosome number, as determined by confocal microscopy of pericentrin-stained cultures, and may highlight a novel role of p53 in preserving genomic integrity in lung epithelial cells. Effects of p53-deficiency were also studied following exposure to DNA damage. A p53-dependent reduction in the BrdU index was observed in Clara cells following ionizing radiation. The reduction in BrdU index in wild type cells displayed serum-dependency, and occurred only in the absence of serum. Taken together, these findings demonstrate that in murine primary Clara cell culture, cell cycle arrest is a p53-mediated response to DNA damage, and that extracellular factors, such as serum, influence this response. CONCLUSION: These findings highlight functions of wild type p53 protein in bipolar spindle formation, centrosome regulation, and growth control in bronchiolar Clara cells

Atlas Toolkit: Fast registration of 3D morphological datasets in the absence of landmarks

Image registration is a gateway technology for Developmental Systems Biology, enabling computational analysis of related datasets within a shared coordinate system. Many registration tools rely on landmarks to ensure that datasets are correctly aligned; yet suitable landmarks are not present in many datasets. Atlas Toolkit is a Fiji/ImageJ plugin collection offering elastic group-wise registration of 3D morphological datasets, guided by segmentation of the interesting morphology. We demonstrate the method by combinatorial mapping of cell signalling events in the developing eyes of chick embryos, and use the integrated datasets to predictively enumerate Gene Regulatory Network states

Seeing beyond the site - an innovative approach to examining prehistoric Ireland

Ye

Kombinationstherapie von Entecavir und DNA-Protein-Vakzinen bei chronischen Hepadnavirus-Infektionen im Murmeltier-Modell

Chronische HBV-Infektionen können Folgeschäden nach sich ziehen, z. B. eine Leberzirrhose oder primäre „hepatozelluläre“ Karzinome verursachen. Bisher wurden keine ausreichend wirksamen Monotherapien, z. B. mit Interferonen oder Nukleosidanaloga, gefunden, da Interferone Nebenwirkungen haben und Nukleosidanaloga bei Langzeit-Therapie Resistenzen entwickeln. Daher ist man auf die weitere Erforschung und Evaluierung von Kombinationstherapien angewiesen. Ziel dieser Doktorarbeit war es, eine Kombinationstherapie mit einem Nukleosidanalogon und einer therapeutischen Vakzine auf ihre Wirksamkeit zur Bekämpfung einer chronischen WHV-Infektion hin zu testen. Die grundsätzliche Fragestellung war, in wie weit diese Therapie helfen kann, eine chronische Infektion mit WHV zu beenden bzw. den besten Langzeiteffekt zur Reduktion der Virämie aufweist. Dazu wurden 4 Versuchsgruppen getestet. Gruppe 1 war die unbehandelte Kontrollgruppe, Gruppe 2 erhielt als Monotherapie das Nukleosidanalogon Entecavir (ETV) für 3 Monate täglich, dann für 3 Monate einmal wöchentlich. Die Gruppen 3 und 4 erhielten ebenfalls ETV mit dem gleichen Schema wie die Gruppe 2. Zusätzlich wurden die Tiere der Gruppe 3 ab dem 4. Monat mit einer DNA-Vakzine und die Gruppe 4 mit einer DNA-Protein-Kombinationsvakzine geimpft. In der Gruppe 2 konnte gezeigt werden, dass man durch die Gabe von ETV alleine eine deutliche Reduzierung der Viruslast erreichen kann. Allerdings hält diese Reduzierung nur für die Dauer der Gabe des Medikamentes an. Schon kurze Zeit nach Absetzen des ETV kam es zu einem erneuten Anstieg des Viruslast, der z. T. sogar noch höhere Werte als vor Beginn des Versuches annehmen konnte. Dies deckt sich auch mit früheren Arbeiten, in denen ein Effekt von ETV alleine für Dauer der Gabe gezeigt wurde. In den Gruppen 3 und 4 konnte z. T. eine dramatische Reduzierung der Viruslast, sogar unter die Nachweisgrenze, aufgezeigt werden. Der virämiesenkende Effekt der Kombinationstherapie durch die zusätzliche therapeutische Vakzinierung deutlich verlängert werden. Es gab sogar zwei Tiere, bei denen auch nach 43 Wochen kein messbarer Anstieg der Viruslast festgestellt werden konnte. Es konnte also gezeigt werden, dass der Einsatz von einer Kombinationstherapie aus dem Nukleosidanalogon ETV und einer therapeutischen DNA-Vakzine helfen kann, eine chronische Infektion zu beenden und eine stabile Immunität aufzubauen bzw. über den Zeitraum der Gabe von ETV hinaus eine deutliche Reduktion der Virämie zu erreichen. Dies legt den Schluss nahe, dass der Einsatz dieser Kombinationstherapie auch bei Patienten eine neue Behandlungsmöglichkeit der chronischen HBV-Infektion bietet. In Zukunft muss allerdings noch weiter untersucht werden, um die bestmögliche Kombination beider Behandlungsformen (ETV-Gabe, Vakzinierung) herauszufinden. Insbesondere die Länge der ETV-Gabe, Häufigkeit und Art der therapeutischen Vakzinierung (nur DNA- oder DNA-Protein-Kombinationstherapie), Menge des eingesetzten Antigens in der Vakzine, ist in nachfolgenden Arbeiten noch näher zu untersuchen.Possible consequences of chronic HBV-infections are liver cirrhosis or primary hepatocellular carcinomas. Until now there are no effective mono therapies known. Mono therapies contain the application of interferon’s or nucleoside analogas. The problems of interferons are unwelcome side effects and the developing of resistances during long time therapy of nucleoside analogues. Therefore the developing and evaluation of combination therapies is necessary. Aim of this study has been the test for the effectiveness of combination therapy. The combination therapy consists of the application of nucleoside analogas and therapeutic vaccinations. The main formulation of question has been the investigation either this therapy is able to stop a chronic HBV infection or has a measurable long time effect for reduction of viremia. The study contains of 4 groups of experiments. Group 1 is the control group, group receive only ETV as a mono therapy during 3 months daily and another 3 months weekly. Groups 3 and 4 receive also ETV within the same scheme like group 2. Additionally the animals receive either a DNA-vaccine or DNA-protein-combinationvaccine since the 4th month of therapy. The results of group 2 show a clear reduction of virus titers. But the effect of the reduction last as long as the application of ETV lasts. Shortly after dismission of ETV the virus titers decrease again. Other early papers also show this course. In contrast to these results the groups 3 and 4 show significant reduction of virus titers below detection level. Combination therapy prolongs the effect of decreasing vermeil clearly. There have been already two animals showing now longer virus titers in blood for 43 weeks altogether. This study confirms the positive results of combination therapy, containing therapeutic vaccination and intake of ETV. The combination of these two therapies helps stopping chronic HBV infections and building up firmable immunity already over and above the ETV intake. So there are new possible strategies and approaches for using the combination strategy in human patients within chronic HBV infection. Further investigations are necessary for finding out the possible combination of both axle of the therapy (including ETV-dose, vaccination). Especially the duration of ETV intake, frequency and kind of therapeutic vaccination, quantity of used antigen has to be content of further studies

Archaeological signatures of landscape and settlement change on the Isle of Harris

Between 2004 and 2011, a programme of archaeological investigation by the University of Birmingham on the Isle of Harris, a distinctive island forming part of the Western Isles of Scotland, has allowed the archaeological remains of this enigmatic place to be further characterised and understood. Despite intensive archaeological interest in the archipelago for a number of decades, the Isle of Harris has been overlooked and only now are we beginning to identify the archaeological resource and make comparisons to the wealth of published data from islands such as the Uists, Barra and Lewis. This paper highlights some generic overall patterns of archaeological signatures on the Isle which has been identified through a range of archaeological methods including field walking, intrusive excavation, aerial reconnaissance, geophysical and topographical survey, and documentary research. Several key case studies will be introduced including upland shieling complexes and mulitperiod settlement sites on the west coast machair systems. The purpose of the paper is not to present a gazetteer of the results of the work to date, but to highlight some of the key findings with a view to demonstrating that the Isle of Harris is directly comparable with the archaeologically rich landscapes of the other islands