2,551 research outputs found

    Human metapneumovirus:Evolution and interaction with the innate immune system

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    Involvement of Astrocytes in the Formation, Maintenance, and Function of the Blood-Brain Barrier

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    : The blood-brain barrier (BBB) is a fundamental structure that protects the composition of the brain by determining which ions, metabolites, and nutrients are allowed to enter the brain from the blood or to leave it towards the circulation. The BBB is structurally composed of a layer of brain capillary endothelial cells (BCECs) bound to each other through tight junctions (TJs). However, its development as well as maintenance and properties are controlled by the other brain cells that contact the BCECs: pericytes, glial cells, and even neurons themselves. Astrocytes seem, in particular, to have a very important role in determining and controlling most properties of the BBB. Here, we will focus on these latter cells, since the comprehension of their roles in brain physiology has been continuously expanding, even including the ability to participate in neurotransmission and in complex functions such as learning and memory. Accordingly, pathological conditions that alter astrocytic functions can alter the BBB's integrity, thus compromising many brain activities. In this review, we will also refer to different kinds of in vitro BBB models used to study the BBB's properties, evidencing its modifications under pathological conditions

    Fake News: Finding Truth in Strategic Communication

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    Fake news is an old phenomenon that has become a new obsession and a menace to society due to technological advancement and the proliferation of social media, which has changed traditional journalism norms. As the spread of false information has increased these past few years, it has become increasingly difficult for information consumers to distinguish between facts and fakes. A comprehensive systematic literature review to extract themes revealed the major factors responsible for spreading fake news. This qualitative interpretative meta-synthesis (QIMS) aims to better understand and offer solutions to combat fake news. This Ph.D. dissertation will serve as a guide for ethical communication practice and a reference for future research studies

    The Role of the HUSH complex and LINE-1 elements in the Regulation of Type 1 Interferon

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    Although Transposable Elements (TEs) have been a reliable source of genetic variation throughout evolution (Rishishwar et al., 2018), host genomes have simultaneously coevolved with TEs to employ a variety of strategies to regulate their aberrant activity. In fact, mounting evidence indicates the deleterious consequences of dysregulated TE expression in a number of human diseases including autoimmune and inflammatory disorders (M. K. Crow, 2010), monogenic diseases (Cordaux & Batzer, 2009; Nakamura et al., 2015) and various cancers (Helman et al., 2014; Lee et al., 2012). The goal of this project is to explore how the human genome continues to adapt to the ongoing evolutionary arms race between TEs and the innate immune defence system and to uncover novel epigenetic pathways that help suppress their aberrant activity and characterise how these pathways regulate innate immune genes. The Human Silencing Hub (HUSH) is an epigenetic silencing complex that is necessary for the repression of LINE-1 elements (Fukuda et al., 2018; N. Liu et al., 2018; Robbez-Masson et al., 2018). Here, we reveal the depletion of the HUSH complex component, MPP8, in human cell lines and primary fibroblasts leads to the induction of interferon-stimulated genes (ISGs) through JAK/STAT signalling and demonstrate that this effect is mainly attributable to MDA5 and RIG-I-mediated sensing of double-stranded RNAs (dsRNAs). This response coincides with the upregulation of primate-conserved LINE-1 elements, as well as increased expression of a subset of full-length hominid-specific LINE-1s that produce sense and antisense transcribed RNA products, which may form dsRNAs. Furthermore, we show that LINE-1 shRNAs could abrogate the HUSH-dependent response, while overexpression of an engineered full-length LINE-1 construct activates interferon signalling in somatic cells. Finally, we provide some insights into the physiological regulation of HUSH and HUSH-regulated LINE-1s during the normal immune response in primary human fibroblasts. Taken together, our results suggest that endogenous LINE-1s drive physiological and autoinflammatory responses through dsRNA sensing and gene-regulatory roles that are ultimately under HUSH control. Our work thus serves to highlight HUSH/MPP8 as a potential drug target for future cancer immunotherapies, where MPP8 inactivation may be harnessed to drive type 1 IFNs and anti-tumour immunity

    Placental origins of health & disease:Therapeutic opportunities

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    Strategy Tripod Perspective on the Determinants of Airline Efficiency in A Global Context: An Application of DEA and Tobit Analysis

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    The airline industry is vital to contemporary civilization since it is a key player in the globalization process: linking regions, fostering global commerce, promoting tourism and aiding economic and social progress. However, there has been little study on the link between the operational environment and airline efficiency. Investigating the amalgamation of institutions, organisations and strategic decisions is critical to understanding how airlines operate efficiently. This research aims to employ the strategy tripod perspective to investigate the efficiency of a global airline sample using a non-parametric linear programming method (data envelopment analysis [DEA]). Using a Tobit regression, the bootstrapped DEA efficiency change scores are further regressed to determine the drivers of efficiency. The strategy tripod is employed to assess the impact of institutions, industry and resources on airline efficiency. Institutions are measured by global indices of destination attractiveness; industry, including competition, jet fuel and business model; and finally, resources, such as the number of full-time employees, alliances, ownership and connectivity. The first part of the study uses panel data from 35 major airlines, collected from their annual reports for the period 2011 to 2018, and country attractiveness indices from global indicators. The second part of the research involves a qualitative data collection approach and semi-structured interviews with experts in the field to evaluate the impact of COVID-19 on the first part’s significant findings. The main findings reveal that airlines operate at a highly competitive level regardless of their competition intensity or origin. Furthermore, the unpredictability of the environment complicates airline operations. The efficiency drivers of an airline are partially determined by its type of business model, its degree of cooperation and how fuel cost is managed. Trade openness has a negative influence on airline efficiency. COVID-19 has toppled the airline industry, forcing airlines to reconsider their business model and continuously increase cooperation. Human resources, sustainability and alternative fuel sources are critical to airline survival. Finally, this study provides some evidence for the practicality of the strategy tripod and hints at the need for a broader approach in the study of international strategies

    Placental origins of health & disease:Therapeutic opportunities

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    Exploring Host Factors of the Human Metabolism as Promising Targets for Dengue Treatment

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    The absence of specific therapy and the challenges posed by currently available palliative drugs, such as paracetamol, underscore the urgent need for targeting medications against dengue. Extensive research in the field of antiviral therapies has primarily focused on investigating viral proteins as potential targets. However, despite these efforts, finding an effective therapy for dengue fever remains a daunting task. Importantly, like all viruses, Dengue virus relies on human host proteins to enable infection. Recognizing this fact has prompted the consideration of host factors as viable targets for intervention strategies to combat the infection. This chapter aims to provide an overview of host-virus interactions during Dengue virus infection, emphasizing the importance of metabolic pathways, as well as molecular and cellular processes such as lipid metabolism, autophagy, apoptosis, and the immune system, which are critical for virus propagation. The main goal here is to expand the list of human factors that could serve as potential drug targets. Additionally, molecules that interact with these factors are explored for their therapeutic potential. This comprehensive exploration of host-virus interactions lays the groundwork for more effective dengue treatments. The molecules highlighted here hold promise as antiviral agents, and their inclusion in repurposing research could expedite the development of therapies for dengue fever

    Investigating the Innate Immune Systems of Bats and Their Roles as Zoonotic Viral Reservoirs

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    The zoonotic spillover of viral pathogens from wild animal reservoirs into human populations remains the leading cause of emerging and re-emerging infectious diseases globally. Bats represent important viral reservoirs, notorious for the diversity and richness of the viruses they host, several of which are highly pathogenic when transmitted to humans. Remarkably, bats appear to host an abundance of these viruses without exhibiting any clinical signs of disease. A dominant hypothesis for this ability suggests that bats can control viral replication early in the innate immune response, which acts as the first line of defence against infection. However, bat immunology remains fundamentally understudied, largely due to their high species diversity and the lack of accessible reagents required for bat research. Therefore, in this work we explored and characterised key components of bat innate immunity to gain a better understanding of bats as viral reservoirs and contribute to the currently limited literature. Here, we demonstrated the in vitro transcriptomic response of the bat model species, Pteropus alecto (P.alecto) upon stimulation with the bat henipavirus Cedar virus and also with a type III bat interferon (paIFNλ). These investigations highlighted key transcripts, some of which were immune-related, in the response of bats to the separate stimuli and presents a foundation for further research into significant genes concerned in bat viral infection. Building from genome-wide transcriptomics, three distinctive bat innate immune genes representative of different stages of interferon signalling were selected for comparative genomics and functional characterisation. Our work demonstrated the conservation of genes between bats and humans, including IRF7, IFIT5 and IFI35. Specific findings for IRF7 included its successful translocation to the cell nucleus upon stimulation. IFIT5 and IFI35 were specifically selected for exploration due to previous research demonstrating the respective antiviral and conflicting anti- or pro-viral roles of these genes in humans. Significantly, our research demonstrated the direct antiviral action of P.alecto IFIT5 against negative-sense RNA viruses. Collectively, our findings offer valuable contributions to the field of bat antiviral immunity and provide the framework for future investigative studies into the role and function of the bat innate immune system and bat viral tolerance mechanisms
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