2,304 research outputs found

    ‘Dangerous Creatures’: Selected children’s versions of Homer’s Odyssey in English 1699–2014

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    This thesis considers how the Odyssey was adapted for children, as a specific readership, in English literature 1699-2014. It thus traces both the emergence of children’s literature as a publishing category and the transformation of the Odyssey into a tale of adventure – a perception of the Odyssey which is still widely accepted today (and not only among children) but which is not, for example, how Aristotle understood the poem. I explore case studies from three different points in the development of children’s literature, and in the development of the Odyssey as a tale of adventure, and connect them to broader cultural attitudes to children and to classical literature. The first, the successful translation of François Salignac de la Mothe-Fénelon’s Les aventures de Télémaque (The Adventures of Telemachus, 1699) illustrates the clash of the Odyssey with contemporary discourse on literature and education. I then turn to Charles Lamb’s The Adventures of Ulysses (1808) – a text that was at the heart of Romantic cultural upheavals and the commercial development of children’s literature, and which responded directly to Fénelon. Lamb’s work transformed the way the Homeric poem would engage with children by focusing on the fantastic adventures of Odysseus, rather than Telemachus, as Fénelon had done. The nineteenth-century shift in the critical reaction to Lamb’s work, and to the notion of reading adventure for recreational purposes, would eventually see The Adventures of Ulysses become a foundational text for future generations of Odysseys for children, and indeed in the reception of the Odyssey more generally (Lamb’s version was foundational for Joyce, for example). The final part of the thesis explores how Lamb’s influence is still operational in a new generation of texts that use subaltern voices in an apparently antagonistic approach to the poem. The thesis argues that the children’s texts considered, which are often treated as marginal, both as classical receptions and as children’s literature, need to be brought to the core of classical studies

    Mutations in KCNK4 that Affect Gating Cause a Recognizable Neurodevelopmental Syndrome

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    Aberrant activation or inhibition of potassium (K+) currents across the plasma membrane of cells has been causally linked to altered neurotransmission, cardiac arrhythmias, endocrine dysfunction, and (more rarely) perturbed developmental processes. The K+ channel subfamily K member 4 (KCNK4), also known as TRAAK (TWIK-related arachidonic acid-stimulated K+ channel), belongs to the mechano-gated ion channels of the TRAAK/TREK subfamily of two-pore-domain (K2P) K+ channels. While K2P channels are well known to contribute to the resting membrane potential and cellular excitability, their involvement in pathophysiological processes remains largely uncharacterized. We report that de novo missense mutations in KCNK4 cause a recognizable syndrome with a distinctive facial gestalt, for which we propose the acronym FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth). Patch-clamp analyses documented a significant gain of function of the identified KCNK4 channel mutants basally and impaired sensitivity to mechanical stimulation and arachidonic acid. Co-expression experiments indicated a dominant behavior of the disease-causing mutations. Molecular dynamics simulations consistently indicated that mutations favor sealing of the lateral intramembrane fenestration that has been proposed to negatively control K+ flow by allowing lipid access to the central cavity of the channel. Overall, our findings illustrate the pleiotropic effect of dysregulated KCNK4 function and provide support to the hypothesis of a gating mechanism based on the lateral fenestrations of K2P channels

    Quantifying the legacy of the Chinese Neolithic on the maternal genetic heritage of Taiwan and Island Southeast Asia

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    There has been a long-standing debate concerning the extent to which the spread of Neolithic ceramics and Malay-Polynesian languages in Island Southeast Asia (ISEA) were coupled to an agriculturally driven demic dispersal out of Taiwan 4000 years ago (4 ka). We previously addressed this question using founder analysis of mitochondrial DNA (mtDNA) control-region sequences to identify major lineage clusters most likely to have dispersed from Taiwan into ISEA, proposing that the dispersal had a relatively minor impact on the extant genetic structure of ISEA, and that the role of agriculture in the expansion of the Austronesian languages was therefore likely to have been correspondingly minor. Here we test these conclusions by sequencing whole mtDNAs from across Taiwan and ISEA, using their higher chronological precision to resolve the overall proportion that participated in the “out-of-Taiwan” mid-Holocene dispersal as opposed to earlier, postglacial expansions in the Early Holocene. We show that, in total, about 20 % of mtDNA lineages in the modern ISEA pool result from the “out-of-Taiwan” dispersal, with most of the remainder signifying earlier processes, mainly due to sea-level rises after the Last Glacial Maximum. Notably, we show that every one of these founder clusters previously entered Taiwan from China, 6–7 ka, where rice-farming originated, and remained distinct from the indigenous Taiwanese population until after the subsequent dispersal into ISEA

    Mitochondrial DNA signals of late glacial recolonization of Europe from near Eastern refugia

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    Human populations, along with those of many other species, are thought to have contracted into a number of refuge areas at the height of the last Ice Age. European populations are believed to be, to a large extent, the descendants of the inhabitants of these refugia, and some extant mtDNA lineages can be traced to refugia in Franco-Cantabria (haplogroups H1, H3, V, and U5b1), the Italian Peninsula (U5b3), and the East European Plain (U4 and U5a). Parts of the Near East, such as the Levant, were also continuously inhabited throughout the Last Glacial Maximum, but unlike western and eastern Europe, no archaeological or genetic evidence for Late Glacial expansions into Europe from the Near East has hitherto been discovered. Here we report, on the basis of an enlarged whole-genome mitochondrial database, that a substantial, perhaps predominant, signal from mitochondrial haplogroups J and T, previously thought to have spread primarily from the Near East into Europe with the Neolithic population, may in fact reflect dispersals during the Late Glacial period, ?19–12 thousand years (ka) ago.<br/

    A genetic chronology for the Indian Subcontinent points to heavily sex-biased dispersals

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    Background India is a patchwork of tribal and non-tribal populations that speak many different languages from various language families. Indo-European, spoken across northern and central India, and also in Pakistan and Bangladesh, has been frequently connected to the so-called “Indo-Aryan invasions” from Central Asia ~3.5 ka and the establishment of the caste system, but the extent of immigration at this time remains extremely controversial. South India, on the other hand, is dominated by Dravidian languages. India displays a high level of endogamy due to its strict social boundaries, and high genetic drift as a result of long-term isolation which, together with a very complex history, makes the genetic study of Indian populations challenging. Results We have combined a detailed, high-resolution mitogenome analysis with summaries of autosomal data and Y-chromosome lineages to establish a settlement chronology for the Indian Subcontinent. Maternal lineages document the earliest settlement ~55–65 ka (thousand years ago), and major population shifts in the later Pleistocene that explain previous dating discrepancies and neutrality violation. Whilst current genome-wide analyses conflate all dispersals from Southwest and Central Asia, we were able to tease out from the mitogenome data distinct dispersal episodes dating from between the Last Glacial Maximum to the Bronze Age. Moreover, we found an extremely marked sex bias by comparing the different genetic systems. Conclusions Maternal lineages primarily reflect earlier, pre-Holocene processes, and paternal lineages predominantly episodes within the last 10 ka. In particular, genetic influx from Central Asia in the Bronze Age was strongly male-driven, consistent with the patriarchal, patrilocal and patrilineal social structure attributed to the inferred pastoralist early Indo-European society. This was part of a much wider process of Indo-European expansion, with an ultimate source in the Pontic-Caspian region, which carried closely related Y-chromosome lineages, a smaller fraction of autosomal genome-wide variation and an even smaller fraction of mitogenomes across a vast swathe of Eurasia between 5 and 3.5 ka

    Helena’s Many Daughters: More Mitogenome Diversity behind the Most Common West Eurasian mtDNA Control Region Haplotype in an Extended Italian Population Sample

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    The high number of matching haplotypes of the most common mitochondrial (mt)DNA lineages are considered to be the greatest limitation for forensic applications. This study investigates the potential to solve this constraint by massively parallel sequencing a large number of mitogenomes that share the most common West Eurasian mtDNA control region (CR) haplotype motif (263G 315.1C 16519C). We augmented a pilot study on 29 to a total of 216 Italian mitogenomes that represents the largest set of the most common CR haplotype compiled from a single country. The extended population sample confirmed and extended the huge coding region diversity behind the most common CR motif. Complete mitogenome sequencing allowed for the detection of 163 distinct haplotypes, raising the power of discrimination from 0 (CR) to 99.6% (mitogenome). The mtDNAs were clustered into 61 named clades of haplogroup H and did not reveal phylogeographic trends within Italy. Rapid individualization approaches for investigative purposes are limited to the most frequent H clades of the dataset, viz. H1, H3, and H7

    Maternal relationships within an Iron Age burial at the High Pasture Cave, Isle of Skye, Scotland

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    Human remains from the Iron Age in Atlantic Scotland are rare, which makes the assemblage of an adult female and numerous foetal bones at High Pasture Cave, on the Isle of Skye, particularly noteworthy. Archaeological evidence suggests that the female had been deposited as an articulated skeleton when the cave entrance was blocked off, marking the end of use of the site. Particularly intriguing is the deposition of disarticulated remains from a foetus and perinate close to the adult female, which opens the possibility that the female might have been the mother of both of the infants. We used shotgun genome sequencing in order to analyse the mitochondrial genomes of all three individuals and investigate their maternal relationship, and we report here, for the first time, complete ancient mitogenomes from foetal-aged bone fragments. While we could not exclude the possibility that the female was the mother of, or maternally related to, the foetus, we could definitely say that she was not the mother of the perinate buried alongside her. This finding is contrary to the standard archaeological interpretation, that women in such burials most likely died in childbirth and were buried together with their foetuses

    Developing the ArchAIDE Application: A digital workflow for identifying, organising and sharing archaeological pottery using automated image recognition

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    Pottery is of fundamental importance for understanding archaeological contexts, facilitating the understanding of production, trade flows, and social interactions. Pottery characterisation and the classification of ceramics is still a manual process, reliant on analogue catalogues created by specialists, held in archives and libraries. The ArchAIDE project worked to streamline, optimise and economise the mundane aspects of these processes, using the latest automatic image recognition technology, while retaining key decision points necessary to create trusted results. Specifically, ArchAIDE worked to support classification and interpretation work (during both fieldwork and post-excavation analysis) with an innovative app for tablets and smartphones. This article summarises the work of this three-year project, funded by the European Union's Horizon 2020 Research and Innovation Programme under grant agreement N.693548, with a consortium of partners representing both the academic and industry-led ICT (Information and Communications Technology) domains, and the academic and development-led archaeology domains. The collaborative work of the archaeological and technical partners created a pipeline where potsherds are photographed, their characteristics compared against a trained neural network, and the results returned with suggested matches from a comparative collection with typical pottery types and characteristics. Once the correct type is identified, all relevant information for that type is linked to the new sherd and stored within a database that can be shared online. ArchAIDE integrated a variety of novel and best-practice approaches, both in the creation of the app, and the communication of the project to a range of stakeholders

    Biomolecular insights into North African-related ancestry, mobility and diet in eleventh-century Al-Andalus.

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    Funder: Helmholtz Zentrum München – German Research Center for Environmental HealthFunder: Leverhulme TrustHistorical records document medieval immigration from North Africa to Iberia to create Islamic al-Andalus. Here, we present a low-coverage genome of an eleventh century CE man buried in an Islamic necropolis in Segorbe, near Valencia, Spain. Uniparental lineages indicate North African ancestry, but at the autosomal level he displays a mosaic of North African and European-like ancestries, distinct from any present-day population. Altogether, the genome-wide evidence, stable isotope results and the age of the burial indicate that his ancestry was ultimately a result of admixture between recently arrived Amazigh people (Berbers) and the population inhabiting the Peninsula prior to the Islamic conquest. We detect differences between our sample and a previously published group of contemporary individuals from Valencia, exemplifying how detailed, small-scale aDNA studies can illuminate fine-grained regional and temporal differences. His genome demonstrates how ancient DNA studies can capture portraits of past genetic variation that have been erased by later demographic shifts-in this case, most likely the seventeenth century CE expulsion of formerly Islamic communities as tolerance dissipated following the Reconquista by the Catholic kingdoms of the north

    HER2-based recombinant immunogen to target DCs through FcγRs for cancer immunotherapy

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    Dendritic cell (DC)-based immunotherapy is an attractive approach to induce long lasting antitumor effector cells aiming to control cancer progression. DC targeting is a critical step in the design of DC vaccines in order to optimize delivery and processing of the antigen, and several receptors have been characterized for this purpose. In this study, we employed the FcγRs to target DCs both in vitro and in vivo. We designed a recombinant molecule (HER2-Fc) composed of the immunogenic sequence of the human tumor-associated antigen HER2 (aa 364–391) and the Fc domain of a human IgG1. In a mouse model, HER2-Fc cDNA vaccination activated significant T cell-mediated immune responses towards HER2 peptide epitopes as detected by IFN-γ ELIspot and induced longer tumor latency as compared to Ctrl-Fc-vaccinated control mice. Human in vitro studies indicated that the recombinant HER2-Fc immunogen efficiently targeted human DCs through the FcγRs resulting in protein cross-processing and in the activation of autologous HER2-specific CD8+ T cells from breast cancer patients
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