Способы повышения прочности алюмосиликатной керамики на основе сухарного глинистого сырья

Disrupting the CD40-CD40L co-stimulatory pathway reduces atherosclerosis and induces a stable atherosclerotic plaque phenotype that is low in inflammation and high in fibrosis. Therefore, inhibition of the CD40-CD40L pathway is an attractive therapeutic target to reduce clinical complications of atherosclerosis. The CD40-CD40L dyad is known to interact with other co-stimulatory molecules, to activate antigen-presenting cells (APC) and to contribute to T-cell priming and B-cell isotype switching. Besides their presence on T-cells and APCs, CD40 and CD40L are also present on macrophages, endothelial cells and vascular smooth muscle cells in the plaque, where they can exert pro-atherogenic functions. Moreover, recent progress indicates the involvement of neutrophil CD40, platelet CD40L and dendritic cell CD40 in atherogenesis. Since systemic CD40-CD40L modulation compromises host defense, more targeted interventions are needed to develop superior treatment strategies for atherosclerosis. We believe that by unravelling the cell-cell CD40-CD40L interactions, inhibition of cell-type specific (signalling components of) CD40(L) that do not compromise the patient's immune system, will become possible. In this review, we highlight the cell-type specific multi-functionality of CD40-CD40L signalling in atherosclerosi

The vulnerable patient: refocusing on the plaque?

The term 'vulnerable plaque' is used to refer to the lesions that are prone to rupture and may cause life-threatening events like acute coronary syndrome or stroke. The study of the vulnerable plaque phenotype and its detection has attracted increasing interest over the past decades. During this time, there have been some remarkable transitions in the paradigm on methods to identify patients at risk or patients to treat. Whereas formerly, the key factors used to determine an individual's risk were primarily population-based traditional risk factors such as age, sex, body mass index, hypertension etc., new approaches are based on conditional risk factors that represent an individual's current risk of suffering a cardiovascular event. These population based risk factors fall short in predicting near-future events in a high-risk individual. In the early 2000s, the focus of research into surrogate markers for cardiovascular event prediction shifted from the vulnerable plaque to the identification of the vulnerable patient. This new paradigm stimulated a number of new initiatives that aimed to identify vulnerable patients by testing systemic biomarkers that could identify patients at high risk for cardiovascular events. A second research paradigm is refocusing on the plaque by searching for plaque-derived biomarkers and non-invasive imaging modalities to assess characteristics of a plaque that determine its vulnerability. Although both concepts are attractive, they still need proper validation in large multicenter cohorts, while cost-effectiveness arguments also need to be assesse

Towards high-throughput functional target discovery in angiogenesis research

Angiogenesis is a hallmark of malignancies and other proliferative diseases, and inhibition of this process is considered to be a promising treatment strategy. Classical gene-expression analyses performed during the past decade have generated vast lists of genes associated with disease but have so far yielded only limited novel therapeutic targets for clinical applications. Recently, the focus has shifted from target identification, based on gene-expression analysis, to identification of genes, based on the function of the encoded protein. Disease-target genes can now be identified in a high-throughput fashion based on functional properties that are directly related to the disease phenotype. This new approach significantly shortens the time span for the development of therapeutic applications from the laboratory bench to the hospital bedside

The multi-functionality of CD40L and its receptor CD40 in atherosclerosis

Disrupting the CD40-CD40L co-stimulatory pathway reduces atherosclerosis and induces a stable atherosclerotic plaque phenotype that is low in inflammation and high in fibrosis. Therefore, inhibition of the CD40-CD40L pathway is an attractive therapeutic target to reduce clinical complications of atherosclerosis. The CD40-CD40L dyad is known to interact with other co-stimulatory molecules, to activate antigen-presenting cells (APC) and to contribute to T-cell priming and B-cell isotype switching. Besides their presence on T-cells and APCs, CD40 and CD40L are also present on macrophages, endothelial cells and vascular smooth muscle cells in the plaque, where they can exert pro-atherogenic functions. Moreover, recent progress indicates the involvement of neutrophil CD40, platelet CD40L and dendritic cell CD40 in atherogenesis. Since systemic CD40-CD40L modulation compromises host defense, more targeted interventions are needed to develop superior treatment strategies for atherosclerosis. We believe that by unravelling the cell-cell CD40-CD40L interactions, inhibition of cell-type specific (signalling components of) CD40(L) that do not compromise the patient's immune system, will become possible. In this review, we highlight the cell-type specific multi-functionality of CD40-CD40L signalling in atherosclerosi

Equivalence testing in microarray analysis: similarities in the transcriptome of human atherosclerotic and nonatherosclerotic macrophages

We focus on similarities in the transcriptome of human Kupffer cells and alveolar, splenic, and atherosclerotic plaque-residing macrophages. We hypothesized that these macrophages share a common expression signature. We performed microarray analysis on mRNA from these subsets (4 patients) and developed a novel statistical method to identify genes with significantly similar expression levels. Phenotypic and functional diversity between macrophage subpopulations reflects their plasticity to respond to microenvironmental signals. Apart from detecting differences in expression profiles, the comparison of the transcriptomes of different macrophage populations may also allow the definition of molecular similarities between these subsets. This new method calculates the maximum difference in gene expression level, based on the estimated confidence interval on that gene's expression variance. We listed the genes by equivalence ranking relative to expression level. FDR estimation was used to determine significance. We identified 500 genes with significantly equivalent expression levels in the macrophage subsets at 5.5% FDR using a confidence level of α = 0.05 for equivalence. Among these are the established macrophage marker CD68, IL1 receptor antagonist, and MHC-related CD1C. These 500 genes were submitted to IPA and GO clustering using DAVID. Additionally, hierarchical clustering of these genes in the Novartis human gene expression atlas revealed a subset of 200 genes specifically expressed in macrophages. Equivalently expressed genes, identified by this new method, may not only help to dissect common molecular mechanisms, but also to identify cell- or condition-specific sets of marker genes that can be used for drug targeting and molecular imagin

Tritrichomonas--systematics of an enigmatic genus.

Tritrichomonas spp. are parasitic protozoans that proliferate on mucus membranes of the urogenital, gastro-intestinal or nasal tract. For instance, Tritrichomonas foetus is an important cause of reproductive failure in cattle. Some years ago, T. foetus was also identified as a causative agent of diarrhoea in cats. Previous studies on the morphological, physiological and molecular levels have raised doubts as to the phylogenetic relationship among some Tritrichomonas species, particularly in relation to T. foetus, Tritrichomonas suis, and Tritrichomonas mobilensis. With the advent of molecular genetic tools, it has become clear that these three tritrichomonad species are closely related or may even represent the same species. Indeed, since recently, T. suis and T. foetus are generally considered as one species, with T. mobilensis being a closely related sister taxon. To date, molecular studies have not yet been able to resolve the taxonomic (specific) status of T. foetus from cattle and cats. In the future, novel genomic approaches, particularly those involving next generation sequencing are poised to resolve the taxonomy of Tritrichomonas spp. Here, we review the literature on the current state of knowledge of the taxonomy of T. foetus, T. suis, and T. mobilensis with special reference to the relationship between T. foetus from cattle and cats

cFOS in sponge and artery macrophages from mice.

<p>cFOS is present in the cytoplasm (red) or nucleus (pink, arrows) in isolated macrophages from A) mice fed a high-fat diet (FCMs) or B) a normal diet (NFMs). cFOS was also observed in the cytoplasm (red, orange, yellow) and/or nucleus (pink, arrows) of cells in sections from C) a subcutaneous sponge granuloma or D, E) a brachiocephalic artery from a fat-fed ApoE null mouse. D’) higher magnification of plaque in D. Blue = nuclei (DAPI), green = autofluorescence. Magnification x 400 A-E, x 1000 D’. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128163#pone.0128163.g005" target="_blank">Fig 5C and 5D</a> for negative control staining.</p

LXRα in sponges and arteries from fat-fed ApoE null mice.

<p>LXRα is present in the cytoplasm (red) and/or nucleus (pink, arrows) of A) FCMs in sections from a subcutaneous sponge, or; B) cells in the plaque of a brachiocephalic artery. B’ higher magnification of plaque in B. C) LXRα is occasionally present in the cytoplasm of the adventitial cells that are close to the media; D) sponge section negative control (only the sponge spicule is red); E) negative control in a section from the same plaque as B. Blue = nuclei (DAPI), green = autofluorescence. Magnification x 400 A-E, x 1000 B’.</p

Phosphorylated SMAD proteins in RAW 264.7 cells and sponge or artery macrophages from mice.

<p>RAW cells were exposed to 10 ng/ml TGFβ1 for 45 minutes. A) phospho-SMAD2 and B) phospho-SMAD3 were present in the cytoplasm and nucleus of many cells. pSMAD2 was also found in C) the cytoplasm and nucleus (arrows) from isolated FCMs, but only in the D) cytoplasm of NFMs. E) pSMAD is present in the cytoplasm and nuclei (arrows) of plaques in a brachiocephalic artery a fat-fed ApoE null mouse. E’) higher magnification of plaque in E. F) negative control in a section from the same plaque. G) RAW negative control staining (rabbit IgG). Red/orange = cytoplasmic staining, pink = nuclear staining, blue = nuclei (DAPI), green = autofluorescence. A, B, E’, G magnification x 1000, C, D, E, F magnification x 400.</p