Hexamerization-enhanced CD20 antibody mediates complement-dependent cytotoxicity in serum genetically deficient in C9

We examined complement-dependent cytotoxicity (CDC) by hexamer formation-enhanced CD20 mAb Hx-7D8 of patient-derived chronic lymphocytic leukemia (CLL) cells that are relatively resistant to CDC. CDC was analyzed in normal human serum (NHS) and serum from an individual genetically deficient for C9. Hx-7D8 was able to kill up to 80% of CLL cells in complete absence of C9. We conclude that the narrow C5b-8 pores formed without C9 are sufficient for CDC due to efficient antibody-mediated hexamer formation. In the absence of C9, we observed transient intracellular increases of Ca2 + during CDC (as assessed with FLUO-4) that were extended in time. This suggests that small C5b-8 pores allow Ca2 + to enter the cell, while dissipation of the fluorescent signal accompanying cell disintegration is delayed. The Ca2 + signal is retained concomitantly with TOPRO-3 (viability dye) staining, thereby confirming that Ca2 + influx represents the most proximate mediator of cell death by CDC

Hepatitis E in England and Wales

In 2005, 329 cases of hepatitis E virus infection were confirmed in England and Wales; 33 were confirmed indigenous infections, and a further 67 were estimated to be indigenous infections. Hepatitis E should be considered in the investigation of patients with hepatitis even if they have no history of travel

Smooth muscle cells affect differential nanoparticle accumulation in disturbed blood flow-induced murine atherosclerosis

Atherosclerosis is a lipid-driven chronic inflammatory disease that leads to the formation of plaques in the inner lining of arteries. Plaques form over a range of phenotypes, the most severe of which is vulnerable to rupture and causes most of the clinically significant events. In this study, we evaluated the efficacy of nanoparticles (NPs) to differentiate between two plaque phenotypes based on accumulation kinetics in a mouse model of atherosclerosis. This model uses a perivascular cuff to induce two regions of disturbed wall shear stress (WSS) on the inner lining of the instrumented artery, low (upstream) and multidirectional (downstream), which, in turn, cause the development of an unstable and stable plaque phenotype, respectively. To evaluate the influence of each WSS condition, in addition to the final plaque phenotype, in determining NP uptake, mice were injected with NPs at intermediate and fully developed stages of plaque growth. The kinetics of artery wall uptake were assessed in vivo using dynamic contrast-enhanced magnetic resonance imaging. At the intermediate stage, there was no difference in NP uptake between the two WSS conditions, although both were different from the control arteries. At the fully-developed stage, however, NP uptake was reduced in plaques induced by low WSS, but not multidirectional WSS. Histological evaluation of plaques induced by low WSS revealed a significant inverse correlation between the presence of smooth muscle cells and NP accumulation, particularly at the plaque-lumen interface, which did not exist with other constituents (lipid and collagen) and was not present in plaques induced by multidirectional WSS. These findings demonstrate that NP accumulation can be used to differentiate between unstable and stable murine atherosclerosis, but accumulation kinetics are not directly influenced by the WSS condition. This tool could be used as a diagnostic to evaluate the efficacy of experimental therapeutics for atherosclerosis

Громадянське суспільство як категорія етнополітології

У статті «громадянське суспільство» розглядається як категорія етнополітології, акцентується увага на визначальному впливі громадянського суспільства на формування сучасної нації.В статье «гражданское общество» рассматривается как категория этнополитологии, акцентируется внимание на определяющем влиянии гражданского общества на формирование современной нации.In the article «civil society» is considered as a category ethnopolitology, emphasized the decisive influence of civil society on the formation of modern nation

The principle of situated practice in literacy learning: students’ perspectives

O artigo resulta de uma investigação realizada no âmbito de uma iniciativa governamental destinada a melhorar os níveis de literacia nas séries iniciais do ensino fundamental em Portugal. A investigadora estudou as representações dos alunos sobre essa experiência por meio da realização de entrevistas em grupo. Este artigo analisa os dados referentes às representações dos alunos sobre uma das dimensões pedagógicas centrais da aprendizagem da literacia, nomeadamente a constituída pela prática situada. A análise qualitativa revela representações muito positivas sobre a prática que situou a aprendizagem, tendo os alunos expressado opiniões e sentimentos extremamente favoráveis sobre a prática de aprendizagem de literacia que experimentaram. A análise dos dados desvelou ainda que o contexto que situou a aprendizagem foi ativo, lúdico, colaborativo e mediado pelas TIC. Esses resultados fundamentam, do ponto de vista único dos próprios aprendentes, uma redefinição do entendimento atual do princípio da prática situada da literacia nas séries iniciais do ensino fundamental, no sentido do reconhecimento da centralidade da ludicidade nessa aprendizagem.This article derives from research developed in the context of the implementation of a governmental initiative aimed to enhance literacy learning in primary education in Portugal. The researcher studied students’ representations about their learning experience through group interviews. This article focuses on data concerning students’ representations about one of the central pedagogical dimensions of literacy learning, namely situated practice. Qualitative analysis revealed students’ very positive representations about the practice which situated their learning, as they expressed extremely favourable opinions and feelings. Data analysis further unveiled that the context of learning was active, playful, collaborative, and mediated by ICT. Such results provide foundations for a theoretical redefinition of current conceptions of situated practice by evidencing the centrality of playfulness as learning practice in the education of the first grades of primary education. This is an original contribution made from the perspectives of learners themselves(undefined)info:eu-repo/semantics/publishedVersio

Reciprocal regulation of GAS5 lncRNA levels and mTOR inhibitor action in prostate cancer cells.

This is the peer reviewed version of the following article: Yacqub-Usman, K., Pickard, M. R., & Williams, G. T. (2015). Reciprocal regulation of GAS5 lncRNA levels and mTOR inhibitor action in prostate cancer cells. Prostate, 75(7), 693-705. DOI: 10.1002/pros.22952, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/pros.22952/abstract;jsessionid=B9892067CCD9082275B1EFFFC59926F6.f02t02. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingBACKGROUND: New therapies are required for castrate-resistant prostate cancer (CRPC), and growth-arrest specific 5 (GAS5) lncRNA, which riborepresses androgen receptor action, may offer novel opportunities in this regard. This lncRNA promotes the apoptosis of prostate cancer cells and its levels decline as prostate cancer cells acquire castrate-resistance, so that enhancing GAS5 expression may improve the effectiveness of chemotherapies. Since GAS5 is a member of the 5' terminal oligopyrimidine gene family, we have examined mTOR inhibition as a strategy to increase GAS5 expression. Furthermore, we have determined if GAS5 itself mediates the action of mTOR inhibitors, as demonstrated for other chemotherapeutic agents in prostate cancer cells. METHODS: The effects of mTOR inhibitors on GAS5 lncRNA levels and cell growth were determined in a range of prostate cancer cell lines. Transfection of cells with GAS5 siRNAs and plasmid constructs was performed to determine the involvement of GAS5 lncRNA in mTOR inhibitor action. RESULTS: First generation mTORC1, combined mTORC1/mTORC2 and dual PI3K/mTOR inhibitors all increased cellular GAS5 levels and inhibited culture growth in androgen-dependent (LNCaP) and androgen-sensitive (22Rv1) cell lines, but not in androgen-independent (PC-3 and DU 145) cell lines. The latter exhibited low endogenous GAS5 expression, and GAS5 silencing in LNCaP and 22Rv1 cells decreased the sensitivity to mTOR inhibitors, whereas transfection of GAS5 lncRNA sensitized PC-3 and DU 145 cells to these agents. CONCLUSION: mTOR inhibition enhances GAS5 transcript levels in certain prostate cancer cell lines. This selectivity is likely to be related to endogenous GAS5 expression levels, since GAS5 lncRNA is itself required for mTOR inhibitor action in prostate cancer cells.Prostate Cancer Collaborative, United Kingdom (PCUK

Accentuating institutional brands: A multimodal analysis of the homepages of selected South African universities

In seeking to disentangle themselves from the constraints of apartheid, South African universities have immersed themselves in an identity modification process in which they not only seek to redress the past, but also to reposition their identities as equal opportunity and non-racial institutions. In this paper, we investigate how the University of the Western Cape, the University of Cape Town and Stellenbosch University have used visual and verbal semiotics to re-design their identities on their homepages to appeal to diverse national and international clients. Using Multimodal Discourse Analysis (MDA), we show how the multi-semiotic choices work together on the homepages to give the universities differentiated, competitive, powerful and attractive brands. We conclude that the homepages blended cultural semiotic artefacts, historical, global and transformational discourses, and architectural landscapes to construct different brand identities that, in turn, rebrand the universities from edifices of apartheid education to equal opportunity institutions

Characterization of the in situ magnetic architecture of oceanic crust (Hess Deep) using near-source vector magnetic data

Marine magnetic anomalies are a powerful tool for detecting geomagnetic polarity reversals, lithological boundaries, topographic contrasts, and alteration fronts in the oceanic lithosphere. Our aim here is to detect lithological contacts in fast-spreading lower crust and shallow mantle by characterizing magnetic anomalies and investigating their origins. We conducted a high-resolution, near-bottom, vector magnetic survey of crust exposed in the Hess Deep “tectonic window” using the remotely operated vehicle (ROV) Isis during RRS James Cook cruise JC21 in 2008. Hess Deep is located at the western tip of the propagating rift of the Cocos-Nazca plate boundary near the East Pacific Rise (EPR) (2°15′N, 101°30′W). ROV Isis collected high-resolution bathymetry and near-bottom magnetic data as well as seafloor samples to determine the in situ lithostratigraphy and internal structure of a section of EPR lower crust and mantle exposed on the steep (~20°dipping) south facing slope just north of the Hess Deep nadir. Ten magnetic profiles were collected up the slope using a three-axis fluxgate magnetometer mounted on ROV Isis. We develop and extend the vertical magnetic profile (VMP) approach of Tivey (1996) by incorporating, for the first time, a three-dimensional vector analysis, leading to what we here termed as “vector vertical magnetic profiling” approach. We calculate the source magnetization distribution, the deviation from two dimensionality, and the strike of magnetic boundaries using both the total field Fourier-transform inversion approach and a modified differential vector magnetic analysis. Overall, coherent, long-wavelength total field anomalies are present with a strong magnetization contrast between the upper and lower parts of the slope. The total field anomalies indicate a coherently magnetized source at depth. The upper part of the slope is weakly magnetized and magnetic structure follows the underlying slope morphology, including a “bench” and lobe-shaped steps, imaged by microbathymetry. The lower part of the slope is strongly magnetized, with a gradual reduction in amplitude from east to west across the slope. Surface morphology and recent drilling results indicate that the slope has been affected by mass wasting, but the observation of internally coherent magnetization distributions within the upper and lower slopes suggest that the disturbance is surficial. We attribute the spatial differences in magnetization distribution to the combination of changes in in situ lithology and depth to the source. These survey lines document the first magnetic profiles that capture the gabbro-ultramafic and possibly dike-gabbro boundaries in fast-spreading lower crust