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Machine learning confirms new records of maniraptoran theropods in Middle Jurassic
Get PDFCurrent research suggests that the initial radiation of maniraptoran theropods occurred in the Middle Jurassic, although their fossil record is known almost exclusively from the Cretaceous. However, fossils of Jurassic maniraptorans are scarce, usually consisting solely of isolated teeth, and their identifications are often disputed. Here, we apply different machine learning models, in conjunction with morphological comparisons, to a suite of isolated theropod teeth from Bathonian microvertebrate sites in the UK to determine whether any of these can be confidently assigned to Maniraptora. We generated three independent models developed on a training dataset with a wide range of theropod taxa and broad geographical and temporal coverage. Classification of the Middle Jurassic teeth in our sample against these models and comparison of the morphology indicates the presence of at least three distinct dromaeosaur morphotypes, plus a therizinosaur and troodontid in these assemblages. These new referrals significantly extend the ranges of Therizinosauroidea and Troodontidae by some 27 myr. These results indicate that not only were maniraptorans present in the Middle Jurassic, as predicted by previous phylogenetic analyses, but they had already radiated into a diverse fauna that pre-dated the break-up of Pangaea. This study also demonstrates the power of machine learning to provide quantitative assessments of isolated teeth in providing a robust, testable framework for taxonomic identifications, and highlights the importance of assessing and including evidence from microvertebrate sites in faunal and evolutionary analyses
Translatome analysis of tuberous sclerosis complex 1 patient-derived neural progenitor cells reveals rapamycin-dependent and independent alterations
Get PDFBackground:
Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder caused by mutations in the TSC1 or TSC2 genes, with patients often exhibiting neurodevelopmental (ND) manifestations termed TSC-associated neuropsychiatric disorders (TAND) including autism spectrum disorder (ASD) and intellectual disability. Hamartin (TSC1) and tuberin (TSC2) proteins form a complex inhibiting mechanistic target of rapamycin complex 1 (mTORC1) signaling. Loss of TSC1 or TSC2 activates mTORC1 that, among several targets, controls protein synthesis by inhibiting translational repressor eIF4E-binding proteins. Using TSC1 patient-derived neural progenitor cells (NPCs), we recently reported early ND phenotypic changes, including increased cell proliferation and altered neurite outgrowth in TSC1-null NPCs, which were unaffected by the mTORC1 inhibitor rapamycin.
Methods:
Here, we used polysome profiling, which quantifies changes in mRNA abundance and translational efficiencies at a transcriptome-wide level, to compare CRISPR-edited TSC1-null with CRISPR-corrected TSC1-WT NPCs generated from one TSC donor (one clone/genotype). To assess the relevance of identified gene expression alterations, we performed polysome profiling in postmortem brains from ASD donors and age-matched controls. We further compared effects on translation of a subset of transcripts and rescue of early ND phenotypes in NPCs following inhibition of mTORC1 using the allosteric inhibitor rapamycin versus a third-generation bi-steric, mTORC1-selective inhibitor RMC-6272.
Results:
Polysome profiling of NPCs revealed numerous TSC1-associated alterations in mRNA translation that were largely recapitulated in human ASD brains. Moreover, although rapamycin treatment partially reversed the TSC1-associated alterations in mRNA translation, most genes related to neural activity/synaptic regulation or ASD were rapamycin-insensitive. In contrast, treatment with RMC-6272 inhibited rapamycin-insensitive translation and reversed TSC1-associated early ND phenotypes including proliferation and neurite outgrowth that were unaffected by rapamycin.
Conclusions:
Our work reveals ample mRNA translation alterations in TSC1 patient-derived NPCs that recapitulate mRNA translation in ASD brain samples. Further, suppression of TSC1-associated but rapamycin-insensitive translation and ND phenotypes by RMC-6272 unveils potential implications for more efficient targeting of mTORC1 as a superior treatment strategy for TAND
The ‘S-Score’ of financial sustainability for professional football clubs
Get PDFThis paper extends the extensive literature on business failure and, in particular, develops the approach of Altman (1968, 2000) to provide quantified recommendations for the financial sustainability of football clubs.
The paper uses multiple discriminant analysis and uniquely identifies financial models that delineate between professional football clubs that experience insolvency events and those that do not. These produce a financial sustainability score (‘S-score’) and are introduced for football clubs in the English Football League (EFL) in four scenarios that have caused insolvency. The models suggest minimum financial tolerances for accounting ratios to provide a reasonable level of resilience for the financial sustainability of clubs in each scenario.
The results are relevant for academics and non-academics with an interest in the business of football, professional football clubs aiming to avoid financial distress and specifically, the Regulator that the UK government has proposed for football in England
Why the West's ‘Anti-war’ camp is so hostile to Ukrainians – and to Jews
Get PDFUgly smears from the Kremlin and the German far right have found a receptive audience among the West’s left-wing, self-described ‘anti-war’ movement. Their attacks on Ukraine's Zelenskyy are reviving age-old antisemitic conspiracy theorie
Identities in flux? National and other changing identities during the Covid-19 pandemic
Get PDFSocial identities, such as identification with the nation, are regarded as core variables in explanations of political attitudes and behaviours. In these accounts, increases in the importance of an identity such as “Englishness” are often seen to be accompanied by decreases in the importance of other, more inclusive, identities such as “British” or “European”. At the same time, increases in exclusive national identities like “Englishness” present challenges to democratic states because they are associated with preferences such as support for Brexit and intolerance of outgroups. Yet we know comparatively little about the relative importance to individuals of different social identities, the extent of changes in the strength of those social identities with contextual shifts, the interrelationships between different social identities, and the influences on different social identities. In this paper, we address each of these questions using a five-wave online panel study administered over two years of the Covid-19 pandemic in England from 2020-22, in which we asked about the importance of eight identities—Europeanness, Britishness, Englishness, the local area, gender, age, race/ethnicity, and social class. We show that national identity is consistently less important to individuals than the social identities of gender and age, though more important than race/ethnicity and social class. We also show that there were general increases in identification with almost all these groups during Covid. We consider why and discuss the implications for our understanding of increases in the strength of national identity as a challenge to democratic states
Publish or perish: coping with peer-review processes through coaching
Get PDFThis study explores how a self-coaching approach assists academics to cope with prolonged peer-review processes. A coaching training workshop, using acceptance and commitment therapy (ACT) and strength-based coaching, was conducted with 22 academics in the U.K. To understand changes in the participants’ attitude to peer-review, their self-reflective diaries and ten semi-structured interviews were analysed. This research reveals that participants tended to identify their intrinsic motivation and commitment to their research career through reflective self-dialogues and interactions with their trusted peers. This research sheds light on coaching practice by indicating constructive self-reflections help individuals to appreciate peer-review as a positive challenge instead of a threat
English for academic purposes
Get PDFEnglish for academic purposes (EAP) ‘is usually defined as teaching English with the aim of assisting learners’ study or research in that language’ but is also a ‘theoretically grounded and research informed enterprise’ (Hyland 2006: 1). This chapter provides an overview of EAP as a dynamic interdisciplinary field of applied linguistics research. The emergence of EAP in the 1960s and its foundations are first outlined, which is followed by a discussion of the major themes explored within EAP research, ranging from the well-established topics, such as approaches to needs analysis and genre analysis, to more recent ones, such as lexical bundles, English for research publication purposes (ERPP), and social justice in EAP. The chapter then moves on to outline the diversity of research methods commonly employed in current EAP research, including corpus-based approaches, genre analysis, interview-based studies, talk-around-text and discourse-based interviews, and ethnographically oriented studies. Pedagogical applications of EAP research are also discussed in areas such as materials development, EAP teacher training, and language assessment, and practical recommendations are made for institutions, EAP programme directors, teacher trainers, and practitioner
Edited special issue of London Review of Education: Belonging and home-making in the internationalised campus
No full textFurther articles to appear in this online only, Open Access edition
Cooperation and the organisation of production and markets: a critical survey
Get PDFThis critical survey examines the role of cooperation in production and exchange, the relationship
between the organisation of production and markets, and, more generally, the nature and functioning of
productive systems. It traces ideas about the relationship between markets, industrial organisation and
power, from Adam Smith and Karl Marx to the early neo-classical economists, before turning to the
evolution of liberal economic thinking that accompanied the emergence and growth of large
organisations with market power. This is then confronted with Alfred Marshall’s methodological and
theoretical contributions to both economics and industrial organisation and development, and his
attempt to reconcile the neo-classical economic dilemma of increasing returns in production and
competition in markets. During the inter-war years, and especially after his death in 1924, Marshall’s
ideas were strongly challenged – and ultimately abandoned – by neo-classical economists. However,
this debate re-emerged nearly a half century later, when the Fordist mass production model faced
growing competition from more cooperative forms of industrial organisation. Based on solid empirical
research into contemporary industrial districts and localised productive systems, there was a rediscovery of the importance of cooperation in production, and an acknowledgement of the significance
of Marshall’s earlier contributions. Inspired by these developments, Frank Wilkinson’s “productive
systems” approach brings together the threads running through Smith’s, Marx’s and Marshall’s analysis
of the dynamics of cooperation in production and exchange, to explore the implications of the mutual
and conflicting interests inherent to production, industrial organisation and economic development
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