122 research outputs found

    Plasmodium P-Type Cyclin CYC3 Modulates Endomitotic Growth during Oocyst Development in Mosquitoes

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    Cell-cycle progression and cell division in eukaryotes are governed in part by the cyclin family and their regulation of cyclin-dependent kinases (CDKs). Cyclins are very well characterised in model systems such as yeast and human cells, but surprisingly little is known about their number and role in Plasmodium, the unicellular protozoan parasite that causes malaria. Malaria parasite cell division and proliferation differs from that of many eukaryotes. During its life cycle it undergoes two types of mitosis: endomitosis in asexual stages and an extremely rapid mitotic process during male gametogenesis. Both schizogony (producing merozoites) in host liver and red blood cells, and sporogony (producing sporozoites) in the mosquito vector, are endomitotic with repeated nuclear replication, without chromosome condensation, before cell division. The role of specific cyclins during Plasmodium cell proliferation was unknown. We show here that the Plasmodium genome contains only three cyclin genes, representing an unusual repertoire of cyclin classes. Expression and reverse genetic analyses of the single Plant (P)-type cyclin, CYC3, in the rodent malaria parasite, Plasmodium berghei, revealed a cytoplasmic and nuclear location of the GFP-tagged protein throughout the lifecycle. Deletion of cyc3 resulted in defects in size, number and growth of oocysts, with abnormalities in budding and sporozoite formation. Furthermore, global transcript analysis of the cyc3-deleted and wild type parasites at gametocyte and ookinete stages identified differentially expressed genes required for signalling, invasion and oocyst development. Collectively these data suggest that cyc3 modulates oocyst endomitotic development in Plasmodium berghei

    Neuro-Rehabilitation OnLine (N-ROL): description and evaluation of a group-based telerehabilitation programme for acquired brain injury

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    Access to the published version of record is available free of charge at https://jnnp.bmj.com/content/92/12/1354Neuro-Rehabilitation OnLine was supported by a generous donation from the charity SameYou (charity number 1170102) and APL by National Institute of Health Research (RP-2015-06-012)

    Detection of the PAX3-FKHR fusion gene in paediatric rhabdomyosarcoma: a reproducible predictor of outcome?

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    Rhabdomyosarcoma has 2 major histological subtypes, embryonal and alveolar. Alveolar histology is associated with the fusion genes PAX3-FKHR and PAX7-FKHR. Definition of alveolar has been complicated by changes in terminology and subjectivity. It is currently unclear whether adverse clinical behaviour is better predicted by the presence of these fusion genes or by alveolar histology. We have determined the presence of the PAX3/7-FKHR fusion genes in 91 primary rhabdomyosarcoma tumours using a combination of classical cytogenetics, FISH and RT-PCR, with a view to determining the clinical characteristics of tumours with and without the characteristic translocations. There were 37 patients with t(2;13)/PAX3-FKHR, 8 with t(1;13) PAX7-FKHR and 46 with neither translocation. One or other of the characteristic translocations was found in 31/38 (82%) of alveolar cases. Univariate survival analysis revealed the presence of the translocation t(2;13)/PAX3-FKHR to be an adverse prognostic factor. With the difficulties in morphological diagnosis of alveolar rhabdomyosarcoma on increasingly used small needle biopsy specimens, these data suggest that molecular analysis for PAX3-FKHR will be a clinically useful tool in treatment stratification in the future. This hypothesis requires testing in a prospective study. Variant t(1;13)/PAX7-FKHR appears biologically different, occurring in younger patients with more localised disease. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

    The new political economy of higher education: between distributional conflicts and discursive stratification

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    The higher education sector has been undergoing a far-reaching institutional re-orientation during the past two decades. Many adjustments appear to have strengthened the role of competition in the governance of higher education, but the character of the sector?s emerging new political economy has frequently remained unclear. Serving as the introduction for the special issue, this article makes the case for a multidimensional strategy to probe higher education?s competitive transformation. In terms of conceptualizing the major empirical shifts, we argue for analyzing three core phenomena: varieties of academic capitalism, the discursive construction of inequality, and the transformation of hierarchies in competitive settings. With respect to theoretical tools, we emphasize the complementary contributions of institutional, class-oriented, and discourse analytical approaches. As this introduction elaborates and the contributions to the special issue demonstrate, critical dialog among different analytical traditions over the interpretation of change is crucial for improving established understandings. Arguably, it is essential for clarifying the respective roles of capitalist power and hierarchical rule in the construction of the sector?s new order

    The Early Data Release of the Dark Energy Spectroscopic Instrument

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    \ua9 2024. The Author(s). Published by the American Astronomical Society. The Dark Energy Spectroscopic Instrument (DESI) completed its 5 month Survey Validation in 2021 May. Spectra of stellar and extragalactic targets from Survey Validation constitute the first major data sample from the DESI survey. This paper describes the public release of those spectra, the catalogs of derived properties, and the intermediate data products. In total, the public release includes good-quality spectral information from 466,447 objects targeted as part of the Milky Way Survey, 428,758 as part of the Bright Galaxy Survey, 227,318 as part of the Luminous Red Galaxy sample, 437,664 as part of the Emission Line Galaxy sample, and 76,079 as part of the Quasar sample. In addition, the release includes spectral information from 137,148 objects that expand the scope beyond the primary samples as part of a series of secondary programs. Here, we describe the spectral data, data quality, data products, Large-Scale Structure science catalogs, access to the data, and references that provide relevant background to using these spectra

    Beyond equilibrium climate sensitivity

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    ISSN:1752-0908ISSN:1752-089
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