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Applying Digital Spatial Profiling of the Transcriptome to Elucidate Disease Mechanisms of Psychosis in Alzheimer’s disease
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Psychosis occurs in 30-40% of individuals with AD. New insights into disease mechanisms may lead to novel pharmacological targets and treatments. Previous studies have focused on bulk tissue analysis with limited results. Digital spatial profiling (DSP) is a new technique for spatial analysis of RNA or proteins in fixed tissue. It allows quantitative profiling with spatial complexity to be collected from samples in a non-destructive manner. In this pilot study we used DSP to compare whole transcriptome data in amyloid beta and non-amyloid beta regions in participants with and without psychosis (AD+P; AD-P).
Method:
Six post-mortem brain samples from prefrontal cortex were provided by the Kings College London Brains for Dementia Research (BDR) brain bank. Frozen and formalin fixed, paraffin embedded (FFPE) sections were supplied in order to test the platform on each type. Psychosis positive and negative groups were selected based on Neuropsychiatric Inventory (NPI) assessments. Samples were hematoxylin and eosin (H&E) stained as well as stained with fluorescent antibodies for AT8, NeuN, SYTO13 and Aβ. Regions of interest (ROIs) are selected based on morphology markers and tissue morphology (see Figure 1 for Amyloid ROI selection).
Result:
H&E staining revealed the frozen samples to be too badly degraded so the analysis was conducted on FFPE sections. AT8 staining showed widespread tau pathology to the extent that it was not possible to confidently select non-tau ROIs. Analysis of Aβ plaque containing and Aβ plaque free regions, comparing AD+P and AD-P groups, found 314 differentially expressed genes in plaque free regions, and 172 differentially expressed genes in plaque containing regions (Figure 2). Of these 172 genes, 28 were not differentially expressed in plaque free regions, forming a plaque-specific signature of genes differentially expressed in AD+P.
Conclusion:
This pilot study demonstrates the potential of the NanoString GeoMx™ DSP platform as an innovative spatial transcriptomics methodology for investigating AD+P with the potential to uncover differentially expressed genes that may be missed by bulk RNA sequencing studies. FFPE sections appear to be optimal. Analysing earlier stage disease and more sections per subject may help with better differentiation of tau and non-tau ROIs
Judicial review of competition law decisions: an empirical study of the Lithuanian context
Get PDFAcknowledgements:
The author would like to thank the Competition Council of Lithuania for providing the requested information. All comments and observations expressed in this paper are the author’s.Commemorating the 20th anniversary since joining the European Union (EU) (together with an obligation to enforce EU competition law), this study evaluates national judgments reviewing the Lithuanian National Competition Council’s [known as Konkurencijos Taryba (KT)] decisions during the 2004–24 period. Building on comprehensive empirical research on judicial review of the KT’s decisions, which involved employing both quantitative and qualitative methods, this article aims to capture the main trends and patterns of judicial review in the Lithuanian context, with some comparison to other small European countries. The study covers the KT’s decisions in relation to the application of Articles 101 and 102 TFEU (and domestic equivalents), pertaining not only to infringement decisions but also to settlements, commitments, as well as decisions not to launch an investigation or discontinue an investigation. The findings reveal a predominant focus on the national provisions, with only 27 per cent of appealed cases embracing the EU element. As far as the outcomes are concerned, this article notes that the administrative courts mostly confirmed the competition authority’s decisions, with any interventions being calibrated in a manner to avoid any encroachment upon the authority’s discretion, clearly upholding the concept of judicial deference
The Keeper of Paintings at the National Gallery, London: Co-Designing an Immersive Experience in Art with and for Children
No full text...UKRI Arts & Humanities Research Council ref: AH/T011394/1 (StoryFutures China: UK-China Transnational Strategic Partnership for Immersive Storytelling in Museums and Cultural Institutions)
The (non)integration of social identity demands and implicit leadership expectations: A challenge for professional hybrids
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Refugee entrepreneurs: Typologies of emancipation and impact
No full textThe economic and social impacts of refugee entrepreneurs on host countries are becoming increasingly significant. Drawing on interviews with 33 Syrian refugee entrepreneurs from different backgrounds in Turkey, we theorise the conditions, mechanisms and outcomes of individual and collective emancipation that refugee entrepreneurs garner. Our qualitative study offers two theoretical contributions to the literature. First, we develop a typology of emancipation (self-made, political, resource-driven and complete emancipation) among refugee entrepreneurs and identify two emancipation mechanisms (i.e. seeking autonomy and crafting/strengthening) that transform the conditions of refugee entrepreneurs. Second, we demonstrate how emancipation fosters individual empowerment, collective success and positive societal impact. We connect these theoretical expansions to suggest evidence-based policy and practice recommendations on integration and support the emancipatory potential of refugee entrepreneurship.The author(s) received no financial support for the research, authorship and/or publication of this article
Energy allocation explains how protozoan phenotypic traits adapt to temperature and nutrient supply
No full textA preprint version is available online at bioRxiv, https://www.biorxiv.org/content/10.1101/2023.07.25.550219v6.abstract. It has not been certified by peer review....This work was supported by the Royal Society Research Grant RG170282 to Andrea Perna
Right Move? Populist Radical Right Parties and Europe
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This article analyses existing data as cited in the “References” section.While before winning power populist radical right (PRR) parties are often overtly against the European Union (EU) and its policies, once in government their position can change significantly. Their threats to leave the EU are frequently replaced by requests for greater EU involvement, particularly in economic and migration issues. This Special Issue unpacks PRR parties’ discourse and policies in relation to Europe, before and after gaining power. Specifically, this Introduction outlines key theoretical debates on populism, the policy positioning of PRR parties on migration, foreign policy and other issues before and after entering government, and their relationship with the EU. It then addresses the performance of PRR parties in the 2024 European Parliament elections, and provides an overview of the Special Issue
Psychoanalysis In Search of Itself: Jacques Lacan, T. S. Eliot, and the Seductions of Modernism
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World TB Day 2025 Theme “Yes! We Can End TB: Commit, Invest, Deliver” can be made a reality through concerted global efforts to advance diagnosis, treatment and research of tuberculosis infection and disease
Get PDFEditorial comment.World TB Day is observed annually on March 24th to raise awareness of tuberculosis (TB), a preventable and treatable disease [1. World Health Organization (2024) Global Tuberculosis Report 2024. Geneva: WHO. Available at:
https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2024
(accessed December 15, 2024)]. Despite being treatable for over 65 years, there are approximately 10.8 million new TB cases annually, predominantly in low- and middle-income countries. Drug-resistant TB significantly contributes to deaths, impacting an estimated 400,000 individuals each year. TB-HIV coinfection remains a major concern, with an estimated 660,000 individuals affected by the dual infection. TB is an important cause of maternal, child and adolescent morbidity and mortality.DG is partially supported by the Italian Ministry of Health “Ricerca Corrente - Linea 4 - Progetto 2 - INMI L. Spallanzani I.R.C.C.S.” fund and by TBVAC-HORIZON, funded by the European Union's HORIZON program under Grant No.101080309
A Comprehensive Assessment of the Economic Performance of an Innovative Solar Thermal System: A Case Study
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Data used in this study are available from the corresponding author upon request.An economic assessment of an innovative solar thermal system called Application to Solar Thermal Energy to Processes (ASTEP) was conducted. It considered its three main subsystems: a novel rotary Fresnel SunDial, Thermal Energy Storage (TES) and Control System. Current Fresnel collectors are unable to provide thermal energy above 150 °C in high-latitude locations. Therefore, the key contribution of this study is the assessment of the economic performance of the ASTEP system used to provide high-temperature process heat up to 400 °C for industries located at low and high latitudes. The ASTEP system is installed at two end-users: Mandrekas (MAND), a dairy factory located in Greece at a latitude of 37.93 N and ArcelorMittal (AMTP), a manufacturer of steel tubes located in Romania at a latitude of 47.1 N. The life cycle costs (LCC), levelised cost of energy (LCOE), energy cost savings, EU carbon cost savings and benefit–cost ratio (BCR) of the ASTEP system were assessed. The results showed that AMTP’s ASTEP system had higher LCC and LCOE than MAND. This can be attributed to the use of two TES tanks and a double-axis solar tracking system for AMTP’s ASTEP system due to its high latitude location, compared to a single TES tank and single-axis solar tracking system used for MAND at low latitude. The total financial savings of the ASTEP system were EUR 249,248 for MAND and EUR 262,931 for AMTP over a period of 30 years. This study demonstrates that the ASTEP system offers financial benefits through its energy and EU carbon cost savings for industries at different latitudes while enhancing their environmental sustainability.The authors declare that this project is funded by the EU Horizon 2020 research and innovation programme, Application of Solar Energy in Industrial Processes (ASTEP), grant agreement number 884411
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