132 research outputs found

    Law Libraries and Laboratories: The Legacies of Langdell and His Metaphor

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    Law Librarians and others have often referred to Harvard Law School Dean C.C. Langdell’s statements that the law library is the lawyer’s laboratory. Professor Danner examines the context of what Langdell through his other writings, the educational environment at Harvard in the late nineteenth century, and the changing perceptions of university libraries generally. He then considers how the “laboratory metaphor” has been applied by librarians and legal scholars during the twentieth century and into the twenty-first. The article closes with thoughts on Langdell’s legacy for law librarians and the usefulness of the laboratory metaphor

    Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

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    Circulating microparticles: square the circle

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    Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes

    Genetic instability in the tumor microenvironment: a new look at an old neighbor

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    Targeting microRNAs as key modulators of tumor immune response

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    Transcellular communication at the immunological synapse: A vesicular traffic-mediated mutual exchange

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    The cell's ability to communicate with the extracellular environment, with other cells, and with itself is a crucial feature of eukaryotic organisms. In the immune system, T lymphocytes assemble a specialized structure upon contact with antigen-presenting cells bearing a peptide-major histocompatibility complex ligand, known as the immunological synapse (IS). The IS has been extensively characterized as a signaling platform essential for T-cell activation. Moreover, emerging evidence identifies the IS as a device for vesicular traffic-mediated cell-to-cell communication as well as an active release site of soluble molecules. Here, we will review recent advances in the role of vesicular trafficking in IS assembly and focused secretion of microvesicles at the synaptic area in naĂŻve T cells and discuss the role of the IS in transcellular communication

    A preliminary proteomic characterisation of extracellular vesicles released by the ovine parasitic nematode, Teladorsagia circumcincta

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    AbstractTeladorsagia circumcincta is a major cause of ovine parasitic gastroenteritis in temperate climatic regions. The development of high levels of anthelmintic resistance in this nematode species challenges its future control. Recent research indicates that many parasite species release extracellular vesicles into their environment, many of which have been classified as endocytic in origin, termed exosomes. These vesicles are considered to play important roles in the intercellular communication between parasites and their hosts, and thus represent potentially useful targets for novel control strategies. Here, we demonstrate that exosome-like extracellular vesicles can be isolated from excretory-secretory (ES) products released by T. circumcincta fourth stage larvae (Tci-L4ES). Furthermore, we perform a comparative proteomic analysis of vesicle-enriched and vesicle-free Tci-L4ES. Approximately 73% of the proteins identified in the vesicle-enriched fraction were unique to this fraction, whilst the remaining 27% were present in both vesicle-enriched and vesicle-free fraction. These unique proteins included structural proteins, nuclear proteins, metabolic proteins, proteolytic enzymes and activation-associated secreted proteins. Finally, we demonstrate that molecules present within the vesicles-enriched material are targets of the IgA and IgG response in T. circumcincta infected sheep, and could potentially represent useful targets for future vaccine intervention studies

    The elderly hypertensive population: what lies ahead of us?

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    In the next 25 years, the population aged 65 years and over will increase by 88%. Thus, postponing the adverse effects of old age for as long as possible will be a major social and economic issue. Hypertension is common in older people, with a prevalence rate of up to 60%, the majority having isolated systolic hypertension. Both isolated systolic hypertension and increased pulse pressure (PP) are associated with a high cardiovascular (CV) risk, and hypertension remains the biggest treatable risk factor for CV disease in the elderly and in the very old. Randomised, controlled trials have demonstrated the benefit of the treatment of hypertension in this population, such that treating just 43 subjects (95% CI: 31–69) for five years would prevent one cerebro-vascular event and treating 61 (95% CI: 39–141) would prevent one coronary event. It should be stressed that antihypertensive treatment reduces both fatal and nonfatal events and will probably prevent the onset of dementia. In other words, it reduces events that represent a major source of disability and handicap in old age and allows healthy ageing. Ongoing trials, which are addressing the preventive effect of treatment in the very elderly hypertensive, will provide further evidence as to the risk/benefit ratio in this ever increasing age group
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