The Role of Fractalkine and CX3CR1-expressing lymphocytes during myocardial ischaemia/reperfusion injury

PhD ThesisIntroduction: Ischaemia/reperfusion (I/R) injury contributes up to 50% of the final infarct size following myocardial infarction (MI). Lymphocytes expressing the fractalkine receptor (CX3CR1) are associated with poor long-term survival. This project aims to investigate the role of fractalkine in lymphocyte-mediated myocardial I/R injury and evaluate whether this damage can be reduced by inhibiting fractalkine/receptor (CX3CL1/CX3CR1) interaction. Methods: Flow cytometry, microscopy, qPCR, mass cytometry and MRI are used to study lymphocyte infiltration following MI in a surgical mouse model of I/R injury. Results: CX3CR1 knockout leads to over 30% reduction in leukocyte infiltration at the MI site 2h after reperfusion, both in heterozygous (p≤0.01) and knockout (p≤0.001) mice. This returns to WT levels by 24h I/R. Despite the 20% increase in leukocyte infiltration at 24h, CX3CR1 knockout mice show a 2-fold decrease in T cell infiltrate, compared to WT (p≤0.01) and heterozygous animals (p≤0.001). Knockout mice show 30% reduction in the number of CX3CR1-expressing T cells and 50% in total CX3CR1+ cells (p≤0.01) that infiltrate the injured myocardium. MRI shows a trend towards more detrimental cardiac function in CX3CR1 heterozygous and knockout mice. Moreover, RAG2 knockout mice show non-significant 35% increase (p=0.067) in leukocyte infiltrate. Finally, significant T cell maturation and increase in CX3CR1 expression is detected in mouse models of ageing and infection. Conclusions: These findings suggest that knockout of CX3CR1 leads to delayed recruitment of leukocytes following cardiac I/R. This results in an altered immune cell infiltrate including reduced number of T cells. In addition, the role for CX3CR1-expressing T cells in myocardial I/R is supported by results showing that the number of CX3CR1+ CD3+ cells is significantly reduced from heterozygous to knockout animals following injury. However, more clinically representative mouse models may be required in order to elucidate the role of CX3CR1+ T cells in myocardial I/R

Modelling the Functionality of the Multimedia Digital Library for Fashion Objects

This paper describes a project of a multimedia digital library for fashion objects. The presented work aims to provide an environment for the National Art Academy students works, showing in front a professional and nonprofessional public the significant values of the fashion domain

Towards Content-Sensitive Access to the Artefacts of the Bulgarian Iconography

his paper presents an ontological model of the knowledge about Bulgarian iconographical artefacts. It also describes content-sensitive services for access, browse, search and group iconographical objects, based on the presented ontology that will be implemented in the multimedia digital library “Virtual encyclopedia of Bulgarian iconography”

Virtual Encyclopaedia of the Bulgarian Iconography

East-Christian icon art is recognised as one of the most significant areas of the art of painting. Regrettably, it is still being neglected in the digital documentation and the registry of the art of painting. The accessibility to that large part of mankind's cultural and historical ancestry would be enhanced greatly if icons of all possible kinds and origins were digitised, classified, and „exhibited“ in the Internet. That would allow the preservation and even the future digital restoration of a large number of rare specimens of the East-Christian art of painting. This article aims to introduce how modern techniques from the area of digital libraries can be used for implementing the demonstrative multimedia library “Virtual encyclopaedia of the Bulgarian iconography ” 4, containing a large number of Bulgarian iconic art masterpieces and iconography of various authors, periods and schools

Ontological Presentation of East-Christian Iconographical Art Domain

In the recent years the East-Christian iconographical art works have been digitized providing a large volume of data. The need for effective classification, indexing and retrieval of iconography repositories was the motivation of the design and development of a systemized ontological structure for description of iconographical art objects. This paper presents the ontology of the East-Christian iconographical art, developed to provide content annotation in the Virtual encyclopedia of Bulgarian iconography multimedia digital library. The ontology’s main classes, relations, facts, rules, and problems appearing during the design and development are described. The paper also presents an application of the ontology for learning analysis on an iconography domain implemented during the SINUS project “Semantic Technologies for Web Services and Technology Enhanced Learning”.* This work is partly funded by the Bulgarian NSF under the project D-002-189 SINUS “Semantic Technologies for Web Services and Technology Enhanced Learning”

Services for Content Creation and Presentation in an Iconographical Digital Library

Content creation and presentation are key activities in a multimedia digital library (MDL). The proper design and intelligent implementation of these services provide a stable base for overall MDL functionality. This paper presents the framework and the implementation of these services in the latest version of the “Virtual Encyclopaedia of Bulgarian Iconography” multimedia digital library. For the semantic description of the iconographical objects a tree-based annotation template is implemented. It provides options for autocompletion, reuse of values, bilingual entering of data, automated media watermarking, resizing and conversing. The paper describes in detail the algorithm for automated appearance of dependent values for different characteristics of an iconographical object. An algorithm for avoiding duplicate image objects is also included. The service for automated appearance of new objects in a collection after their entering is included as an important part of the content presentation. The paper also presents the overall service-based architecture of the library, covering its main service panels, repositories and their relationships. The presented vision is based on a long-term observation of the users’ preferences, cognitive goals, and needs, aiming to find an optimal functionality solution for the end users.* This work is partly funded by Bulgarian NSF under the project D-002-189 SINUS "Semantic Technologies for Web Services and Technology Enhanced Learning"

Există oare o ,,personalitate migrenoasă”? studiu clinico-psihologic şi perspectivele de cercetare

Scopul acestei cercetări a fost încercarea de a confirma sau infi rma prezenţa ”personalităţii migrenoase” la pacienţii cu migrenă episodică şi cronică, comparându-i cu un grup de pacienţi cu tulburări afective, dar fără fenomene algice. Analiza factorială a scos în evidenţă prezenţa a 2 factori, care par a fi şi 2 mecanisme care „guvernează” comportamentul pacienţilor, dar şi starea lor psihofi ziologică. Autorii subliniază difi cultăţile metodologice de rezolvare a enigmei „personalităţii migrenoase”, în special faptul că tulburarea afectivă este o comorbiditate cvasi-inevitabilă asociată migrenei „eclipsând” şi „umbrind” însăşi accesul la personalitatea pacientului ca atare. Autorii punctează exigenţele viitoarelor cercetări, ce vor lua în calcul şi „insight”- urile ultimelor publicaţii în cercetarea tulburărilor cefalalgice şi ale comorbidităţilor asociate, dar şi abordările moderne ce ţin de noile viziuni ale conceptului tulburărilor de personalitate (conform DSM -5)

CMV-independent increase in CD27−CD28+ CD8+ EMRA T cells is inversely related to mortality in octogenarians

Funder: The author is supported by the British Heart FoundationFunder: British Heart Foundation PG/15/85/31744 and PG/18/25/33587, Newcastle Healthcare Charity, Medical Research Council (G0500997 to TK, CJ and TvZ, G0601333 to TvZ) and the NIHR Biomedical Research Centre in Ageing and Chronic Disease.Funder: BK holds a British Heart Foundation personal chair.Abstract: Cytomegalovirus (CMV) seropositivity in adults has been linked to increased cardiovascular disease burden. Phenotypically, CMV infection leads to an inflated CD8 T-lymphocyte compartment. We employed a 8-colour flow cytometric protocol to analyse circulating T cells in 597 octogenarians from the same birth cohort together with NT-proBNP measurements and followed all participants over 7 years. We found that, independent of CMV serostatus, a high number of CD27−CD28+ CD8 EMRA T-lymphocytes (TEMRA) protected from all-cause death after adjusting for known risk factors, such as heart failure, frailty or cancer (Hazard ratio 0.66 for highest vs lowest tertile; confidence interval 0.51–0.86). In addition, CD27−CD28+ CD8 EMRA T-lymphocytes protected from both, non-cardiovascular (hazard ratio 0.59) and cardiovascular death (hazard ratio 0.65). In aged mice treated with the senolytic navitoclax, in which we have previously shown a rejuvenated cardiac phenotype, CD8 effector memory cells are decreased, further indicating that alterations in T cell subpopulations are associated with cardiovascular ageing. Future studies are required to show whether targeting immunosenescence will lead to enhanced life- or healthspan

CMV-independent increase in CD27-CD28+ CD8+ EMRA T cells is inversely related to mortality in octogenarians.

Cytomegalovirus (CMV) seropositivity in adults has been linked to increased cardiovascular disease burden. Phenotypically, CMV infection leads to an inflated CD8 T-lymphocyte compartment. We employed a 8-colour flow cytometric protocol to analyse circulating T cells in 597 octogenarians from the same birth cohort together with NT-proBNP measurements and followed all participants over 7 years. We found that, independent of CMV serostatus, a high number of CD27-CD28+ CD8 EMRA T-lymphocytes (TEMRA) protected from all-cause death after adjusting for known risk factors, such as heart failure, frailty or cancer (Hazard ratio 0.66 for highest vs lowest tertile; confidence interval 0.51-0.86). In addition, CD27-CD28+ CD8 EMRA T-lymphocytes protected from both, non-cardiovascular (hazard ratio 0.59) and cardiovascular death (hazard ratio 0.65). In aged mice treated with the senolytic navitoclax, in which we have previously shown a rejuvenated cardiac phenotype, CD8 effector memory cells are decreased, further indicating that alterations in T cell subpopulations are associated with cardiovascular ageing. Future studies are required to show whether targeting immunosenescence will lead to enhanced life- or healthspan