1,720,985 research outputs found
Blocking interleukin-1β: a double-edged sword in experimental atherosclerosis
Full text linkNo abstract available
"Blow my mind(in)" - Mindin neutralization for the prevention of atherosclerosis?
Full text linkThe hallmark features of atherosclerosis include accumulation of low-density lipoprotein
(LDL) carrying cholesterol in the vessel wall, formation of lipid laden foam cells and the
creation of a pro-inflammatory microenvironment. To date, no effective treatments are
clinically available for increasing cholesterol efflux from vascular macrophages and inducing
reverse cholesterol transport. In a recent article in Clinical Science, Zhang and colleagues
identify the extracellular matrix protein mindin/spondin 2 as a positive regulator of
atherosclerosis. Genetic knockout of mindin in apolipoprotein-E (apoE)-/- mice attenuated
atherosclerosis, foam cell formation and inflammation within the vessel wall. Conversely,
selective overexpression of mindin in macrophages in apoE-/- mice was sufficient to promote
a greater severity of atherosclerosis. Interestingly, foam cell formation was closely
associated with expression of cholesterol transporters (ABCA1 and ACBG1) that facilitate
cholesterol efflux. Liver X receptor-β (LXR-β) is a key modulator of cholesterol transporter
expression and formed direct interactions with mindin. Furthermore, the protective effects of
mindin deficiency on foam cell formation were blocked by inhibition of LXR-β. This article
highlights a novel role for mindin in modulating foam cell formation and atherosclerosis
development in mice through direct regulation of LXR-β. Thus far, direct targeting of LXR-β
via pharmacological agonists has proven problematic due to the lack of subtype selective
inhibitors and associated adverse effects. Indirect targeting of LXR-β, therefore, via mindin
inhibition offers a new therapeutic strategy for increasing LXR-β induced cholesterol efflux,
reducing foam cell formation and preventing or treating atherosclerosis
Immune mechanisms in atherosclerosis and potential for immunomodulatory therapies
No full textA considerable body of pre-clinical and clinical research data support a pivotal role played by immune-inflammatory responses in atherosclerosis formation and development. Recent clinical trial results confirm the feasibility of targeting immune pathways for the therapeutic control of the pathology. In this chapter, we discuss the key immune-inflammatory mechanisms involved in atherosclerosis development and progression and plaque destabilization. We discuss the anti-inflammatory pleiotropic effects of lipid-lowering drugs and potential therapeutic strategies for the direct control of vascular inflammation. Finally, we discuss vaccination approaches in atherosclerosis and critical questions that should be addressed in future investigations
Molecular imaging of atherosclerosis : spotlight on Raman spectroscopy and surface-enhanced Raman scattering
Full text linkTo accurately predict atherosclerotic plaque progression, a detailed phenotype of the lesion at the molecular level is required. Here, we assess the respective merits and limitations of molecular imaging tools. Clinical imaging includes contrast-enhanced ultrasound (CEUS), an inexpensive and non-toxic technique but with poor sensitivity. Computed tomography (CT) benefits from high spatial resolution but poor sensitivity coupled with an increasing radiation burden that limits multiplexing. Despite high sensitivity, positron emission tomography (PET) and single-photon emission tomography (SPECT) have disadvantages when applied to multiplex molecular imaging due to poor spatial resolution, signal cross talk and increasing radiation dose. In contrast, magnetic resonance imaging (MRI) is non-toxic, displays good spatial resolution but poor sensitivity. Pre-clinical techniques include near-infrared fluorescence (NIRF), which provides good spatial resolution and sensitivity; however, multiplexing with NIRF is limited, due to photobleaching and spectral overlap. Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy are label-free techniques that detect molecules based on the vibrations of chemical bonds. Both techniques offer fast acquisition times with Raman showing superior spatial resolution. Raman signals are inherently weak; however, leading to the development of surface-enhanced Raman spectroscopy (SERS) that offers greatly increased sensitivity due to utilising metallic nanoparticles that can be functionalised with biomolecules targeted against plaque ligands while offering high multiplexing potential. This asset combined with high spatial resolution makes SERS an exciting prospect as a diagnostic tool. The ongoing refinements of SERS technologies such as deep tissue imaging and portable systems making SERS a realistic prospect for translation to the clinic
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
