193 research outputs found

    Inhibition of the epidermal growth factor receptor by erlotinib prevents immortalization of human cervical cells by Human Papillomavirus type 16

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    AbstractThe Human Papillomavirus type-16 (HPV-16) E6 and E7 oncogenes are selectively retained and expressed in cervical carcinomas, and expression of E6 and E7 is sufficient to immortalize human cervical epithelial cells. Expression of the epidermal growth factor receptor (EGFR) is often increased in cervical dysplasia and carcinoma, and HPV oncoproteins stimulate cell growth via the EGFR pathway. We found that erlotinib, a specific inhibitor of EGFR tyrosine kinase activity, prevented immortalization of cultured human cervical epithelial cells by the complete HPV-16 genome or the E6/E7 oncogenes. Erlotinib stimulated apoptosis in cells that expressed HPV-16 E6/E7 proteins and induced senescence in a subpopulation of cells that did not undergo apoptosis. Since immortalization by HPV E6/E7 is an important early event in cervical carcinogenesis, the EGFR is a potential target for chemoprevention or therapy in women who have a high risk for cervical cancer

    The languages of peace during the French religious wars

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    The desirability of peace was a common topos in sixteenth-century political rhetoric, and the duty of the king to uphold the peace for the benefit of his subjects was also a long-established tradition. However, the peculiar circumstances of the French religious wars, and the preferred royal policy of pacification, galvanized impassioned debate among both those who supported and those who opposed confessional coexistence. This article looks at the diverse ways in which peace was viewed during the religious wars through an exploration of language and context. It draws not only on the pronouncements of the crown and its officials, and of poets and jurists, but also on those of local communities and confessional groups. Opinion was not just divided along religious lines; political imperatives, philosophical positions and local conditions all came into play in the arguments deployed. The variegated languages of peace provide a social and cultural dimension for the contested nature of sixteenth-century French politics. However, they could not restore harmony to a war-torn and divided kingdom

    The last forests on Antarctica: Reconstructing flora and temperature from the Neogene Sirius Group, Transantarctic Mountains

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    Fossil-bearing deposits in the Transantarctic Mountains, Antarctica indicate that, despite the cold nature of the continent’s climate, a tundra ecosystem grew during periods of ice sheet retreat in the mid to late Neogene (17–2.5 Ma), 480 km from the South Pole. To date, palaeotemperature reconstruction has been based only on biological ranges, thereby calling for a geochemical approach to understanding continental climate and environment. There is contradictory evidence in the fossil record as to whether this flora was mixed angiosperm-conifer vegetation, or whether by this point conifers had disappeared from the continent. In order to address these questions, we have analysed, for the first time in sediments of this age, plant and bacterial biomarkers in terrestrial sediments from the Transantarctic Mountains to reconstruct past temperature and vegetation during a period of East Antarctic Ice Sheet retreat. From tetraether lipids (MBT’/CBT palaeothermometer), we conclude that the mean continental summer temperature was ca. 5 °C, in agreement with previous reconstructions. This was warm enough to have allowed woody vegetation to survive and reproduce even during the austral winter. Biomarkers from vascular plants indicate a low diversity and spatially variable flora consisting of higher plants, moss and algal mats growing in microenvironments in a glacial outwash system. Abietane-type compounds were abundant in some samples, indicating that conifers, most likely Podocarpaceae, grew on the Antarctic continent well into the Neogene. This is supported by the palynological record, but not the macrofossil record for the continent, and has implications for the evolution of vegetation on Antarctica

    Bighorn Basin Coring Project (BBCP): a continental perspective on early Paleogene hyperthermals

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    During the summer of 2011, the Bighorn Basin Coring Project (BBCP) recovered over 900m of overlapping core from 3 different sites in late Paleocene to early Eocene fluvial deposits of northwestern Wyoming. BBCP cores are being used to develop high-resolution proxy records of the Paleocene–Eocene Thermal Maximum (PETM) and Eocene Thermal Maximum 2 (ETM2) hyperthermal events. These events are short-term, large magnitude global warming events associated with extreme perturbations to the earth’s carbon cycle. Although the PETM and ETM2 occurred ~55–52 million years ago, they are analogous in many ways to modern anthropogenic changes to the carbon cycle. By applying various sedimentological, geochemical, and palynological methods to the cores, we hope to better understand what caused these events, study the biogeochemical and ecological feedbacks that operated during them, and reveal precisely how they impacted continental environments. Core recovery was > 98% in all holes and most drilling was carried out without fluid additives, showing that continuous coring of continental smectitic deposits like these can be achieved with minimal risk of contamination to molecular biomarkers. Cores were processed in the Bremen Core Repository where the science team convened for 17 days to carry out data collection and sampling protocols similar to IODP projects. Initial results show that the weathered horizon extends to as much as ~30m below the surface and variations in magnetic susceptibility within the cores record an interplay between grain size and pedogenesis. Previous investigations of outcrops near the BBCP drill sites allow detailed evaluation of the effects of weathering on common proxy methods. Studies of lithofacies, organic geochemistry, stable isotope geochemistry, calibrated XRF core scanning, paleomagnetics, and palynology are underway and will represent the highest resolution and most integrated proxy records of the PETM from a continental setting yet known. An extensive outreach program is in place to capitalize on the educational value associated with the Bighorn Basin’s unusually complete record of Phanerozoic earth history

    Hamburg's Spaces of Danger: Race, Violence and Memory in a Contemporary Global City

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    Germany today is experiencing the strongest upsurge of right-wing populism since the second world war, most notably with the rise of Pegida and Alternative für Deutschland. Yet wealthy global cities like Hamburg continue to present themselves as the gatekeepers of liberal progress and cosmopolitan openness. This article argues that Hamburg’s urban boosterism relies on, while simultaneously obscuring, the same structures of racial violence that embolden reactionary movements. Drawing on the work of Walter Benjamin and Allan Pred, we present an archaeology of Hamburg’s landscape, uncovering some of its ‘spaces of danger’––sites layered with histories of violence, many of which lie buried and forgotten. We find that these spaces, when they become visible, threaten to undermine Hamburg’s cosmopolitan narrative. They must, as a result, be continually erased or downplayed in order to secure the city as an attractive site for capital investment. To illustrate this argument, we give three historical examples: Hamburg’s role in the Hanseatic League during the medieval and early modern period; the city under the Nazi regime; and the recent treatment of Black African refugees. The article’s main contribution is to better situate issues of historical landscape, collective memory and racialized violence within the political economy of today’s global city

    Carbon stable isotopes as a palaeoclimate proxy in vascular plant dominated peatlands

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    Carbon stable isotope (δ¹³C) records from vascular plant dominated peatlands have been used as a palaeoclimate proxy, but a better empirical understanding of fractionation processes in these ecosystems is required. Here, we test the potential of δ¹³C analysis of ombrotrophic restiad peatlands in New Zealand, dominated by the wire rush (Empodisma spp.), to provide a methodology for developing palaeoclimatic records. We took surface plant samples alongside measurements of water table depth and (micro)climate over spatial (six sites spanning > 10 latitude) and temporal (monthly measurements over 1 year) gradients and analysed the relationships between cellulose δ¹³C values and environmental parameters. We found strong, significant negative correlations between δ¹³C and temperature, photosynthetically active radiation and growing degree days above 0 C. No significant relationships were observed between δ¹³C and precipitation, relative humidity, soil moisture or water table depth, suggesting no growing season water limitation and a decoupling of the expected link between δ¹³C in vascular plants and hydrological variables. δ¹³C of Empodisma spp. roots may therefore provide a valuable temperature proxy in a climatically sensitive region, but further physiological and sub-fossil calibration studies are required to fully understand the observed signal

    Lake isotope records of the 8200-year cooling event in western Ireland: Comparison with model simulations

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    The early Holocene cooling, which occurred around 8200 calendar years before present, was a prominent abrupt event around the north Atlantic region. Here, we investigate the timing, duration, magnitude and regional coherence of the event as expressed in carbonate oxygen-isotope records from three lakes on northwest Europe's Atlantic margin in western Ireland, namely Loch Avolla, Loch Gealáin and Lough Corrib. An abrupt negative oxygen-isotope excursion lasted about 200 years. Comparison of records from three sites suggests that the excursion was primarily the result of a reduction of the oxygen-isotope values of precipitation, which was likely caused by lowered air temperatures, possibly coupled with a change in atmospheric circulation. Comparison of records from two of the lakes (Loch Avolla and Loch Gealáin), which have differing bathymetries, further suggests a reduction in evaporative loss of lake water during the cooling episode. Comparison of climate model experiments with lake-sediment isotope data indicates that effective moisture may have increased along this part of the northeast Atlantic seaboard during the 8200-year climatic event, as lower evaporation compensated for reduced precipitation

    Fire and brief human occupations in Iberia during MIS 4: Evidence from Abric del Pastor (Alcoy, Spain)

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    There is a relatively low amount of Middle Paleolithic sites in Europe dating to MIS 4. Of the few that exist, several of them lack evidence for anthropogenic fire, raising the question of how this period of global cooling may have affected the Neanderthal population. The Iberian Peninsula is a key area to explore this issue, as it has been considered as a glacial refugium during critical periods of the Neanderthal timeline and might therefore yield archaeological contexts in which we can explore possible changes in the behaviour and settlement patterns of Neanderthal groups during MIS 4. Here we report recent data from Abric del Pastor, a small rock shelter in Alcoy (Alicante, Spain) with a stratified deposit containing Middle Palaeolithic remains. We present absolute dates that frame the sequence within MIS 4 and multi-proxy geoarchaeological evidence of in situ anthropogenic fire, including microscopic evidence of in situ combustion residues and thermally altered sediment. We also present archaeostratigraphic evidence of recurrent, functionally diverse, brief human occupation of the rock shelter. Our results suggest that Neanderthals occupied the Central Mediterranean coast of the Iberian Peninsula during MIS 4, that these Neanderthals were not undergoing climatic stress and they were habitual fire users.This research was funded by a Leakey Foundation General Grant, Spanish Ministry of Science, Innovation and Universities Projects HAR2008-06117/HIST and HAR2015-68321-P, Junta de Castilla y León-FEDER Project BU235P18, the LabEx Sciences Archéologiques de Bordeaux (LaScArBx ANR-10-LABX-52) and ERC Consolidator Grant ERC-CoG-2014. Archaeological excavations at Abric del Pastor are supported by the Archaeological Museum of Alcoy and the Government of Valencia Cultural Heritage Department
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