A role for the extracellular calcium-sensing receptor in cell-cell communication in pancreatic islets of Langerhans

Background: The extracellular calcium-sensing receptor (CaR) is expressed in many tissues that are not associated with Ca2+ homeostasis, including the endocrine cells in pancreatic islets of Langerhans. We have demonstrated previously that pharmacological activation of the CaR stimulates insulin secretion from islet -cells and insulin-secreting MIN6 cells. Methods: In the present study we have investigated the effects of CaR activation on MIN6 cell proliferation and have used shRNA-mediated CaR knockdown to determine whether the CaR is involved in the regulation of insulin secretion via cell-cell communication. Results: CaR activation caused the phosphorylation and activation of the p42/44 MAPK signalling cascade, and this activation was prevented by the shRNA-induced down-regulation of CaR mRNA expression. CaR activation also resulted in increased proliferation of MIN6 cells, consistent with the known role of the p42/44 MAPK system in the regulation of -cell proliferation. Down-regulation of CaR expression had no detectable effects on glucose-induced insulin secretion from MIN6 cells maintained as monolayers, but blocked the increases in insulin secretion that were observed when the cells were configured as three-dimensional islet-like structures (pseudoislets), consistent with a role for the CaR in cell-cell communication in pseudoislets. Conclusion: It is well established that islet function is dependent on communication between islet cells and the results of this study suggest that the CaR is required for -cell to -cell interactions within islet-like structures

Beyond departure: the Greek in Egypt, 1962-1976

This dissertation examines the continued, yet hitherto overlooked, engagement of the Greek community in Egypt from the period after the en masse departure of most of its members (1962), until the implementation of the infitāh policies in 1976 by Anwar Sadat. Beyond Departure: The Greeks in Egypt, 1962-1976 explores the Greeks’ multiple personal, local and institutional histories that make up the Greek presence in history after 1962. It reveales the diversity of Greek experiences based on geographical, socioeconomic and individual context. It analyzes the motivations and strategies they employed to respond to the economic and social changes in Egyptian society, such as the end of the Capitulations, WWI and WWII, the formation of the post-colonial state, and the 1961 Nationalization laws, among others, and the relations these events formed between Egyptian nationals and non nationals and the Egyptian state. It also explores how Greeks negotiated their presence, identity and feelings of belonging, in mind and practice, as a diaspora with a transnational agency.Middle Eastern Studie

Self-adjusted active contours using multi-directional texture cues

Parameterization is an open issue in active contour research, associated with the cumbersome and time-consuming process of empirical adjustment. This work introduces a novel framework for self-adjustment of region-based active contours, based on multi-directional texture cues. The latter are mined by applying filtering transforms characterized by multi-resolution, anisotropy, localization and directionality. This process yields to entropy-based image “heatmaps”, used to weight the regularization and data fidelity terms, which guide contour evolution. Experimental evaluation is performed on a large benchmark dataset as well as on textured images. Τhe segmentation results demonstrate that the proposed framework is capable of accelerating contour convergence, maintaining a segmentation quality which is comparable to the one obtained by empirically adjusted active contours

The origins of haplotype 58 (H58) Salmonella enterica serovar Typhi

Antimicrobial resistance (AMR) poses a serious threat to the clinical management of typhoid fever. AMR in Salmonella Typhi (S. Typhi) is commonly associated with the H58 lineage, a lineage that arose comparatively recently before becoming globally disseminated. To better understand when and how H58 emerged and became dominant, we performed detailed phylogenetic analyses on contemporary genome sequences from S. Typhi isolated in the period spanning the emergence. Our dataset, which contains the earliest described H58 S. Typhi organism, indicates that ancestral H58 organisms were already multi-drug resistant (MDR). These organisms emerged spontaneously in India in 1987 and became radially distributed throughout South Asia and then globally in the ensuing years. These early organisms were associated with a single long branch, possessing mutations associated with increased bile tolerance, suggesting that the first H58 organism was generated during chronic carriage. The subsequent use of fluoroquinolones led to several independent mutations in gyrA. The ability of H58 to acquire and maintain AMR genes continues to pose a threat, as extensively drug-resistant (XDR; MDR plus resistance to ciprofloxacin and third generation cephalosporins) variants, have emerged recently in this lineage. Understanding where and how H58 S. Typhi originated and became successful is key to understand how AMR drives successful lineages of bacterial pathogens. Additionally, these data can inform optimal targeting of typhoid conjugate vaccines (TCVs) for reducing the potential for emergence and the impact of new drug-resistant variants. Emphasis should also be placed upon the prospective identification and treatment of chronic carriers to prevent the emergence of new drug resistant variants with the ability to spread efficiently

Benevolent characteristics promote cooperative behaviour among humans

Cooperation is fundamental to the evolution of human society. We regularly observe cooperative behaviour in everyday life and in controlled experiments with anonymous people, even though standard economic models predict that they should deviate from the collective interest and act so as to maximise their own individual payoff. However, there is typically heterogeneity across subjects: some may cooperate, while others may not. Since individual factors promoting cooperation could be used by institutions to indirectly prime cooperation, this heterogeneity raises the important question of who these cooperators are. We have conducted a series of experiments to study whether benevolence, defined as a unilateral act of paying a cost to increase the welfare of someone else beyond one's own, is related to cooperation in a subsequent one-shot anonymous Prisoner's dilemma. Contrary to the predictions of the widely used inequity aversion models, we find that benevolence does exist and a large majority of people behave this way. We also find benevolence to be correlated with cooperative behaviour. Finally, we show a causal link between benevolence and cooperation: priming people to think positively about benevolent behaviour makes them significantly more cooperative than priming them to think malevolently. Thus benevolent people exist and cooperate more