Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice

Background Recent in vivo and in vitro studies in non-neuronal and neuronal tissues have shown that different pathways of macrophage activation result in cells with different properties. Interleukin (IL)-6 triggers the classically activated inflammatory macrophages (M1 phenotype), whereas the alternatively activated macrophages (M2 phenotype) are anti-inflammatory. The objective of this study was to clarify the effects of a temporal blockade of IL-6/IL-6 receptor (IL-6R) engagement, using an anti-mouse IL-6R monoclonal antibody (MR16-1), on macrophage activation and the inflammatory response in the acute phase after spinal cord injury (SCI) in mice. Methods MR16-1 antibodies versus isotype control antibodies or saline alone were administered immediately after thoracic SCI in mice. SC tissue repair was compared between the two groups by Luxol fast blue (LFB) staining for myelination and immunoreactivity for the neuronal markers growth-associated protein (GAP)-43 and neurofilament heavy 200 kDa (NF-H) and for locomotor function. The expression of T helper (Th)1 cytokines (interferon (IFN)-? and tumor necrosis factor-a) and Th2 cytokines (IL-4, IL-13) was determined by immunoblot analysis. The presence of M1 (inducible nitric oxide synthase (iNOS)-positive, CD16/32-positive) and M2 (arginase 1-positive, CD206-positive) macrophages was determined by immunohistology. Using flow cytometry, we also quantified IFN-? and IL-4 levels in neutrophils, microglia, and macrophages, and Mac-2 (macrophage antigen-2) and Mac-3 in M2 macrophages and microglia. Results LFB-positive spared myelin was increased in the MR16-1-treated group compared with the controls, and this increase correlated with enhanced positivity for GAP-43 or NF-H, and improved locomotor Basso Mouse Scale scores. Immunoblot analysis of the MR16-1-treated samples identified downregulation of Th1 and upregulation of Th2 cytokines. Whereas iNOS-positive, CD16/32-positive M1 macrophages were the predominant phenotype in the injured SC of non-treated control mice, MR16-1 treatment promoted arginase 1-positive, CD206-positive M2 macrophages, with preferential localization of these cells at the injury site. MR16-1 treatment suppressed the number of IFN-?-positive neutrophils, and increased the number of microglia present and their positivity for IL-4. Among the arginase 1-positive M2 macrophages, MR16-1 treatment increased positivity for Mac-2 and Mac-3, suggestive of increased phagocytic behavior. Conclusion The results suggest that temporal blockade of IL-6 signaling after SCI abrogates damaging inflammatory activity and promotes functional recovery by promoting the formation of alternatively activated M2 macrophages.

Classic beta-amyloid deposits cluster around large diameter blood vessels rather than capillaries in sporadic Alzheimer's disease

Various hypotheses could explain the relationship between beta-amyloid (Abeta) deposition and the vasculature in Alzheimer's disease (AD). Amyloid deposition may reduce capillary density, affect endothelial cells of blood vessels, result in diffusion from blood vessels, or interfere with the perivascular clearance mechanism. Hence, the spatial pattern of the classic ('cored') type of Abeta deposit was studied in the upper laminae (I,II/III) of the superior frontal gyrus in nine cases of sporadic AD (SAD). Sections were immunostained with antibodies against Abeta and with collagen IV to study the relationships between the spatial distribution of the classic deposits and the blood vessel profiles. Both the classic deposits and blood vessel profiles were distributed in clusters. In all cases, there was a positive spatial correlation between the clusters of the classic deposits and the larger diameter (>10 microm) blood vessel profiles and especially the vertically penetrating arterioles. In only 1 case, was there a significant spatial correlation between the clusters of the classic deposits and the smaller diameter (<10 microm) capillaries. There were no negative correlations between the density of Abeta deposits and the smaller diameter capillaries. In 9/11 cases, the clusters of the classic deposits were significantly larger than those of the clusters of the larger blood vessel profiles. In addition, the density of the classic deposits declined as a negative exponential function with distance from a vertically penetrating arteriole. These results suggest that the classic Abeta deposits cluster around the larger blood vessels in the upper laminae of the frontal cortex. This aggregation could result from diffusion of proteins from blood vessels or from overloading the system of perivascular clearance from the brain.

Spatial distribution of diffuse, primitive, and classic amyloid-beta deposits and blood vessels in the upper laminae of the frontal cortex in Alzheimer disease

The spatial distribution of the diffuse, primitive, and classic amyloid-beta deposits was studied in the upper laminae of the superior frontal gyrus in cases of sporadic Alzheimer disease (AD). Amyloid-beta-stained tissue was counterstained with collagen IV to determine whether the spatial distribution of the amyloid-beta deposits along the cortex was related to blood vessels. In all patients, amyloid-beta deposits and blood vessels were aggregated into distinct clusters and in many patients, the clusters were distributed with a regular periodicity along the cortex. The clusters of diffuse and primitive deposits did not coincide with the clusters of blood vessels in most patients. However, the clusters of classic amyloid-beta deposits coincided with those of the large diameter (>10 microm) blood vessels in all patients and with clusters of small-diameter (< 10 microm) blood vessels in four patients. The data suggest that, of the amyloid-beta subtypes, the clusters of classic amyloid-beta deposits appear to be the most closely related to blood vessels and especially to the larger-diameter, vertically penetrating arterioles in the upper cortical laminae.

Dispersion of classic beta-amyloid deposits around blood vessels in Alzheimer’s disease

The spatial pattern of the classic (‘cored’) type of beta-amyloid (Abeta) deposit was studied in the upper laminae of the superior temporal gyrus in 9 cases of sporadic Alzheimer’s disease (SAD). Abeta stained tissue was counterstained with collagen IV to study the relationships between the spatial distribution of the classic deposits and the blood vessel profiles. Both the classic deposits and blood vessel profiles were distributed in clusters. In all cases, there was a spatial correlation between the clusters of the classic deposits and the larger diameter (>10 micron) blood vessel profiles and especially the vertically penetrating arterioles. In only 1 case, was there a significant spatial correlation between the clusters of the classic deposits and the smaller diameter (<10 micron) capillaries. In 9/11 cases, the clusters of the classic deposits were significantly larger than those of the clusters of the larger blood vessels. In addition, the density of the classic deposits declined as a negative exponential function with distance from the vertically penetrating arterioles. These results suggest that the classic Abeta deposits cluster around the larger blood vessels in the frontal cortex and that diffusion of proteins from these blood vessels could be involved in the pathogenesis of the classic deposits in SAD.

Metaphors of identity in dating ads and newspaper articles

This article investigates metaphors of identity in dating ads and in two types of newspaper writing, 'hard' and 'soft' news articles. It focuses on issues of textualization and processing, and particularly on the role of cotext in decoding metaphors. Taking a pragmatic approach founded in the cooperative principle, it argues that the maxims of quality and relation play related but separable roles in the interpretation of identity metaphors; and that this process is guided and constrained by cotextual selections in the environment of the metaphorical term. The particular kinds of cotextual guidance provided by the writer are seen to vary according to genre-driven issues. These include the purpose and stylistic conventions of the genre in which the metaphor occurs and the circumstances under which the text is composed and read. Differing functional motivations are suggested for the use of identity metaphors in each of the genres considered. © Walter de Gruyter 2007.

An introduction to Point-Counterpoint articles

Editorial

An unsupervised Bayesian modelling approach to storyline detection from news articles

Storyline detection from news articles aims at summarizing events described under a certain news topic and revealing how those events evolve over time. It is a difficult task because it requires first the detection of events from news articles published in different time periods and then the construction of storylines by linking events into coherent news stories. Moreover, each storyline has different hierarchical structures which are dependent across epochs. Existing approaches often ignore the dependency of hierarchical structures in storyline generation. In this paper, we propose an unsupervised Bayesian model, called dynamic storyline detection model, to extract structured representations and evolution patterns of storylines. The proposed model is evaluated on a large scale news corpus. Experimental results show that our proposed model outperforms several baseline approaches.

Grounded theory, a kvalitatív kutatás klasszikus mérföldköve (Grounded theory, the classic milestone of qualitative research)

A grounded theory olyan kutatási módszer, ahol az elmélet az empirikus adatokból fejlődik ki és abban gyökerezik (Glaser - Strauss, 1967). Annak ellenére, hogy a módszer nemzetközileg rendkívül népszerű, a grounded theory nem igazán vert gyökeret a hazai menedzsment- és marketingkutatás talajában. A cikk célja a grounded theory kulcsfontosságú mozzanatainak bemutatása és a módszer népszerűsítése. / === / Grounded theory is a research method in which theory emerges from the data and is grounded in it (Glaser - Strauss, 1967). Despite the international popularity of the method, the grounded theory unfortunately hasn't taken roots in the Hungarian management and marketing research fields. The purpose of this article is to highlight some features and key points of the method and to popularize it among researchers.

A számviteli érdekhordozói elméletek evolúciója és a szabályozás – klasszikus tézisek és új irányok a pénzügyi beszámolásban (Evolution of the financial accounting stakeholder theories and the regulation – classic theses and new ways in the financial report)

A modernkori számvitel egyik alapvető kérdése, hogy a pénzügyi beszámolás címzettjét – az érdekhordozókat – miként lehet azonosítani. Ez a törekvés már a klasszikus, azóta meghaladottá vált elméletekben is központi szerepet töltött be és modern, posztmodern elméletekben kulcsfontosságúvá vált. A tapasztalatok alapján az azonosított érdekhordozók köre módosult, bővült. Ennek a fejlődésnek a vizsgálata során a számvitel számos olyan ismérvét sikerült azonosítani, amely segítségével a vonatkozó szabályok tökéletesíthetők. Emellett az evolúció vizsgálata segítségével közvetlenül is megfigyelhetővé vált az, hogy a számvitelt extern módon szabályozó hatalom szükségessége milyen feltételek teljesítése mellett igazolható. A vizsgálat során azonosíthatóvá váltak olyan helyzetek, amikor a számviteli szabályozó és „kívülről irányított” pénzügyi beszámolás szuboptimális helyzethez vezet. A cikk az érdekhordozói elméletek fejlődését a klasszikus felfogásoktól indulva mutatja be. Feltárja, hogy a modern – jelenleg elfogadott – koalíciós vállalatfelfogás miben hozott újat, elsősorban miként hívta életre az extern szabályozót. _____ One of the key problems of the modern financial accounting is how to define the stakeholders. This problem was already a key issue in the already outdated classical stakeholder theories. Research and experience noted that the group of stakeholders has widened and has been modified. Through this evolution researchers identified many characteristics of financial reporting through which the regulation could have been improved. This advance pointed out which are the situations when the existence of an extern accounting regulator may be justified, since under given circumstances this existence led to suboptimal scenario. This paper deals with the stakeholder theories, starting with the classical ones. The article points out how did the currently accepted theory changed the assertions of the previous one and how was the external regulator created as an inevitable consequence. The paper also highlights the main issues raised by the post-modern theories; those, which try to fit the current questions into the current stakeholder models. The article also produces a Hungarian evidence for the previously mentioned suboptimal scenario, where the not tax-driven regulation proves to be suboptimal.