The landscape of a Swedish boat-grave cemetery

This is the published PDF version of an article published in Landscapes© 2010. The definitive version is available at http://www.maneyonline.com/toc/lan/11/1The paper integrates topographical and experiential approaches to the mortuary landscape of a Viking period inhumation-grave excavated in 2005 within the cemetery at Skamby, Kuddy parish, Östergötland province, Sweden. We argue that the landscape context was integral to the performance of the funerary ceremonies and the subsequent monumental presence of the dead in the landscape. We offer a way to move beyond monocausal explanations for burial location based on single-scale analyses. Instead, we suggest that boat-inhumation at Skamby was a commemorative strategy that operated on multiple scales and drew its significance from multiple landscape attributes.British Academ

Immunohistochemical assessment of intrinsic and extrinsic markers of hypoxia in reproductive tissue: differential expression of HIF1α and HIF2α in rat oviduct and endometrium

Hypoxia is thought to be critical in regulating physiological processes within the female reproductive system, including ovulation, composition of the fluid in the oviductal/uterine lumens and ovarian follicle development. This study examined the localisation of exogenous (pimonidazole) and endogenous [hypoxia inducible factor 1α and 2α (HIF1α, -2α), glucose transporter type 1 (GLUT1) and carbonic anhydrase 9 (CAIX)] hypoxia-related antigens within the oviduct and uterus of the rat reproductive tract. The extent to which each endogenous antigen co-compartmentalised with pimonidazole was also assessed. Female Wistar Furth rats (n = 10) were injected intraperitoneally with pimonidazole (60 mg/kg) 1 h prior to death. Reproductive tissues were removed immediately following death and fixed in 4% paraformaldehyde before being embedded in paraffin. Serial sections were cut (6–7 μm thick) and antigens of interest identified using standard immunohistochemical procedures. The mucosal epithelia of the ampulla, isthmus and uterus were immunopositive for pimonidazole in most sections. Co-compartmentalisation of pimonidazole with HIF1α was only expressed in the mucosa of the uterus whilst co-compartmentalisation with HIF2α was observed in the mucosa of the ampulla, isthmus and uterus. Both GLUT1 and CAIX were co-compartmentalised with pimonidazole in mucosa of the isthmus and uterus. This study confirms that mucosal regions of the rat oviduct and uterus frequently experience severe hypoxia and there are compartment specific variations in expression of endogenous hypoxia-related antigens, including the HIF isoforms. The latter observation may relate to target gene specificity of HIF isoforms or perhaps HIF2α’s responsiveness to non-hypoxic stimuli such as hypoglycaemia independently of HIF1α

Imaging oxygenation of human tumours

Tumour hypoxia represents a significant challenge to the curability of human tumours leading to treatment resistance and enhanced tumour progression. Tumour hypoxia can be detected by non-invasive and invasive techniques but the inter-relationships between these remains largely undefined. (18)F-MISO and Cu-ATSM-PET, and BOLD-MRI are the lead contenders for human application based on their non-invasive nature, ease of use and robustness, measurement of hypoxia status, validity, ability to demonstrate heterogeneity and general availability, these techniques are the primary focus of this review. We discuss where developments are required for hypoxia imaging to become clinically useful and explore potential new uses for hypoxia imaging techniques including biological conformal radiotherapy

Recombinant human erythropoietin α modulates the effects of radiotherapy on colorectal cancer microvessels

Recent data suggest that recombinant human erythropoietin (rhEPO) modulates tumour growth and therapy response. The purpose of the present study was to examine the modulation of radiotherapy (RT) effects on tumour microvessels by rhEPO in a rat colorectal cancer model. Before and after 5 × 5 Gy of RT, dynamic contrast-enhanced -magnetic resonance imaging was performed and endothelial permeability surface product (PS), plasma flow (F), and blood volume (V) were modelled. Imaging was combined with pO2 measurements, analysis of microvessel density, microvessel diameter, microvessel fractal dimension, and expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 α (HIF-1α), Bax, and Bcl-2. We found that RT significantly reduced PS and V in control rats, but not in rhEPO-treated rats, whereas F was unaffected by RT. Oxygenation was significantly better in rhEPO-treated animals, and RT induced a heterogeneous reoxygenation in both groups. Microvessel diameter was significantly larger in rhEPO animals, whereas VEGF expression was significantly lower in the rhEPO group. No differences were observed in HIF-1α, Bax, or Bcl-2 expression. We conclude that rhEPO results in spatially heterogeneous modulation of RT effects on tumour microvessels. Direct effects of rhEPO on neoplastic endothelium are likely to explain these findings in addition to indirect effects induced by increased oxygenation

In vivo Hypoxia and a Fungal Alcohol Dehydrogenase Influence the Pathogenesis of Invasive Pulmonary Aspergillosis

Currently, our knowledge of how pathogenic fungi grow in mammalian host environments is limited. Using a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA) and 1H-NMR metabolomics, we detected ethanol in the lungs of mice infected with Aspergillus fumigatus. This result suggests that A. fumigatus is exposed to oxygen depleted microenvironments during infection. To test this hypothesis, we utilized a chemical hypoxia detection agent, pimonidazole hydrochloride, in three immunologically distinct murine models of IPA (chemotherapeutic, X-CGD, and corticosteroid). In all three IPA murine models, hypoxia was observed during the course of infection. We next tested the hypothesis that production of ethanol in vivo by the fungus is involved in hypoxia adaptation and fungal pathogenesis. Ethanol deficient A. fumigatus strains showed no growth defects in hypoxia and were able to cause wild type levels of mortality in all 3 murine models. However, lung immunohistopathology and flow cytometry analyses revealed an increase in the inflammatory response in mice infected with an alcohol dehydrogenase null mutant strain that corresponded with a reduction in fungal burden. Consequently, in this study we present the first in vivo observations that hypoxic microenvironments occur during a pulmonary invasive fungal infection and observe that a fungal alcohol dehydrogenase influences fungal pathogenesis in the lung. Thus, environmental conditions encountered by invading pathogenic fungi may result in substantial fungal metabolism changes that influence subsequent host immune responses

Classifying the evolutionary and ecological features of neoplasms

The consensus conference was supported by Wellcome Genome Campus Advanced Courses and Scientific Conferences. C.C.M. is supported in part by US NIH grants P01 CA91955, R01 CA149566, R01 CA170595, R01 CA185138 and R01 CA140657 as well as CDMRP Breast Cancer Research Program Award BC132057. M.J. is supported by NIH grant K99CA201606. K.S.A. is supported by NCI 5R21 CA196460. K. Polyak is supported by R35 CA197623, U01 CA195469, U54 CA193461, and the Breast Cancer Research Foundation. K.J.P. is supported by NIH grants CA143803, CA163124, CA093900 and CA143055. D.P. is supported by the European Research Council (ERC-617457- PHYLOCANCER), the Spanish Ministry of Economy and Competitiveness (BFU2015-63774-P) and the Education, Culture and University Development Department of the Galician Government. K.S.A. is supported in part by the Breast Cancer Research Foundation and NCI R21CA196460. C.S. is supported by the Royal Society, Cancer Research UK (FC001169), the UK Medical Research Council (FC001169), and the Wellcome Trust (FC001169), NovoNordisk Foundation (ID 16584), the Breast Cancer Research Foundation (BCRF), the European Research Council (THESEUS) and Marie Curie Network PloidyNet. T.A.G. is a Cancer Research UK fellow and a Wellcome Trust funded Investigator. E.S.H. is supported by R01 CA185138-01 and W81XWH-14-1-0473. M.Gerlinger is supported by Cancer Research UK and The Royal Marsden/ICR National Institute of Health Research Biomedical Research Centre. M.Ge., M.Gr., Y.Y., and A.So. were also supported in part by the Wellcome Trust [105104/Z/14/Z]. J.D.S. holds the Edward B. Clark, MD Chair in Pediatric Research, and is supported by the Primary Children's Hospital (PCH) Pediatric Cancer Research Program, funded by the Intermountain Healthcare Foundation and the PCH Foundation. A.S. is supported by the Chris Rokos Fellowship in Evolution and Cancer. Y.Y. is a Cancer Research UK fellow and supported by The Royal Marsden/ICR National Institute of Health Research Biomedical Research Centre. E.S.H. was supported in part by PCORI grants 1505–30497 and 1503–29572, NIH grants R01 CA185138, T32 CA093245, and U10 CA180857, CDMRP Breast Cancer Research Program Award BC132057, a CRUK Grand Challenge grant, and the Breast Cancer Research Foundation. A.R.A.A. was funded in part by NIH grant U01CA151924. A.R.A.A., R.G. and J.S.B. were funded in part by NIH grant U54CA193489

Exhaled particles and small airways

Abstract Background Originally, studies on exhaled droplets explored properties of airborne transmission of infectious diseases. More recently, the interest focuses on properties of exhaled droplets as biomarkers, enabled by the development of technical equipment and methods for chemical analysis. Because exhaled droplets contain nonvolatile substances, particles is the physical designation. This review aims to outline the development in the area of exhaled particles, particularly regarding biomarkers and the connection with small airways, i e airways with an internal diameter < 2 mm. Main body Generation mechanisms, sites of origin, number concentrations of exhaled particles and the content of nonvolatile substances are studied. Exhaled particles range in diameter from 0.01 and 1000 μm depending on generation mechanism and site of origin. Airway reopening is one scientifically substantiated particle generation mechanism. During deep expirations, small airways close and the reopening process produces minute particles. When exhaled, these particles have a diameter of < 4 μm. A size discriminating sampling of particles < 4 μm and determination of the size distribution, allows exhaled particle mass to be estimated. The median mass is represented by particles in the size range of 0.7 to 1.0 μm. Half an hour of repeated deep expirations result in samples in the order of nanogram to microgram. The source of these samples is the respiratory tract ling fluid of small airways and consists of lipids and proteins, similarly to surfactant. Early clinical studies of e g chronic obstructive pulmonary disease and asthma, reported altered particle formation and particle composition. Conclusion The physical properties and content of exhaled particles generated by the airway reopening mechanism offers an exciting noninvasive way to obtain samples from the respiratory tract lining fluid of small airways. The biomarker potential is only at the beginning to be explored