Synovial tissue macrophages: friend or foe?

Healthy synovial tissue includes a lining layer of synovial fibroblasts and macrophages. The influx of leucocytes during active rheumatoid arthritis (RA) includes monocytes that differentiate locally into proinflammatory macrophages, and these produce pathogenic tumour necrosis factor. During sustained remission, the synovial tissue macrophage numbers recede to normal. The constitutive presence of tissue macrophages in the lining layer of the synovial membrane in healthy donors and in patients with RA during remission suggests that this macrophage population may have a role in maintaining and reinstating synovial tissue homeostasis respectively. Recent appreciation of the different origins and functions of tissue-resident compared with monocyte-derived macrophages has improved the understanding of their relative involvement in organ homeostasis in mouse models of disease. In this review, informed by mouse models and human data, we describe the presence of different functional subpopulations of human synovial tissue macrophages and discuss their distinct contribution to joint homeostasis and chronic inflammation in RA

Freedom of self-discreditation. On Witkacy’s letters to his wife

„If these letters are to be found by someone after my death, I will be brought into disrepute (…)” – wrote Witkacy to Jadwiga and he reminded his wife of destroying all the letters she receives from him. The question what and why could put the artist in disgrace seems fundamental and not so simple as one could assume. In order to find answer to this question I analyze letters in reference to Witkacy’s theory of Pure Form. According to Marshall Berman, the elements of antimodernity in modernism, i.e. an art which strived for originality and innovation, were of utmost importance because due to them the artist keeps his identity. Witkacy, an artist from the provinces, who wished to become an artist fitting modern West European art, and who tailored his theory of Pure Form to that, did not express his anti-modernist resistance directly. His resistance is visible in creating low, carnal, trivial and autobiographic forms – brought into disrepute from the point of view of modernist art and Witkacy’s own theory. Thus in his letters to his wife, Witkacy found a peculiar area of freedom – freedom of self-discreditation. Although he constantly blamed Jadwiga for lack of interest in philosophy, he was glad to communicate with her via the low art and low carnality

MicroRNA-155—at the critical interface of innate and adaptive immunity in arthritis

MicroRNAs (miRNAs) are small non-coding RNAs that fine-tune the cell response to a changing environment by modulating the cell transcriptome. MiR-155 is a multifunctional miRNA enriched in cells of the immune system and is indispensable for the immune response. However, when deregulated, miR-155 contributes to the development of chronic inflammation, autoimmunity, cancer and fibrosis. Herein, we review the evidence for the pathogenic role of miR-155 in driving aberrant activation of the immune system in Rheumatoid Arthritis, and its potential as a disease biomarker and therapeutic target

Towards cell replacement therapy in Parkinson’s disease. Proteoglycans and Nogo-A as modulators of axonal growth in midbrain dopaminergic neurons

Parkinson’s disease (PD) is currently the second most common neurodegenerative disorder (after Alzheimer’s disease). PD is diagnosed on its motor symptoms, which include akinesia, bradykinesia, rigidity, postural imbalance and resting tremor. It is well established that the motor symptoms develop due to lack of dopamine in the striatum. This is caused by progressive degeneration of dopaminergic neurons (DNs) in the midbrain (substantia nigra pars compacta), which innervate the striatum. Although initially efficacious, the therapeutic effect of various anti-parkinsonian pharmacological treatments is limited to five to ten years. Hence, the new therapeutic strategies for PD are highly warranted. The concept of cell replacement therapy in PD is based on the idea that the diminished dopamine levels in the striatum would be restored by the functional DNs, obtained from donated, electively aborted fetuses, and subsequently injected into the patients’ striatum. In several clinical trials, about 400 patients received such therapy worldwide. Although the therapeutic effects varied, some individuals experienced major motor improvement even for up to 16 years. Other PD patients did not respond so favorably and even developed adverse effects, i.e. graft-induced dyskinesia. The clinical trials are currently on hold. In the first project, we have analyzed the survival and integration of the graft in a patient who underwent the transplantation in Lund, in 1987, as one of the first transplanted cases in the world. Clinically, the patient did not show the symptomatic relief in response to the transplantation. Examining the postmortem brain, we observed a very small surviving graft. In addition, we also detected signs of PD-like pathology in the transplanted DNs. Nonetheless, the graft survived in this brain for 22 years and such a long graft-life has never before been reported. It is certain that embryonic tissue will not be routinely used as a cell source for transplantation therapy in PD. Yet, stem cells bear a great potential for future PD therapy. Recent publications show that DNs of the midbrain subtype could be differentiated from stem cells in a time-efficient manner. Moreover, those DNs could form well surviving tumor-free grafts which reverted the PD-like motor symptoms in animal models. Nonetheless, the differentiation of embryonic stem cells to DNs is still not fully understood and therefore difficult to control. Proteoglycans may be engaged in differentiation of DNs, as they govern the formation of the nervous system in developing vertebrate embryo. My second project aimed at defining the genes encoding proteoglycans and the enzymatic machinery fine-tuning their structure during the DN differentiation. From around 2000 proteoglycan-related genes, we identified two (neurocan and HS3ST5) that potentially could enhance the differentiation efficiency of DNs from stem cells. Our results can serve as a starting point for the further functional studies. After transplantation, the grafted DNs have to survive, and also integrate with the host brain, i.e. grow neurites, form synapses and release dopamine in a regulated fashion. In the third project, we studied how Nogo-A protein affects the survival and neurite growth in DNs. Nogo-A is a strong growth-inhibitory protein in the brain and spinal cord. Interestingly, in recent years, the growth- and survival-supportive role of Nogo-A in various types of neurons has been shown. We have demonstrated here for the first time the Nogo-A roles in the substantia nigra pars compacta DNs. A careful analysis of all data coming from initial clinical trials, studies on animal parkinsonian models, and the emergence of recent safe and effective dopaminergic differentiation protocols, collectively imply that the cell replacement approach in PD holds a great therapeutic potential. Understanding of the mechanisms governing the DNs differentiation, survival and neurite growth will help develop safe and efficient cell replacement therapies in PD. The work presented in this thesis will hopefully contribute to such advancement

Multi‐polarity as resistance to liberal norms::Russia’s position on Responsibility to Protect

In Western analysis, Russia's insistence on the supremacy of international law serves as little more than a strategy to sustain parity with the West. The Kremlin's justification of its use of responsibility to protect is seen as an abuse of humanitarian language and a smokescreen in the pursuit of geopolitical interests. Formulated from within the liberal paradigm, such interpretations underestimate the normative saturation of strategic action. This article examines Russia's discourse of multipolarity not as being purely strategic - as is widely held - but rather as a form of resistance to the perceived liberal hegemony of the West. The effects of such resistance resemble the outcomes of strategic manoeuvring but they should not be reduced to such. Bolstered by a sense of betrayal by the West, Russia's evolving discourse of multipolarity provides an alternative vision of the world order that contests the imposition of liberal values and bestows upon the authorities an actual responsibility to contain the West's dominance. Both Russia's interpretation of responsibility to protect and its position in the debate arise from this agenda

Sustainable planning of cross-border cooperation: a strategy for alliances in border cities

In recent years, cooperation among nations has become a critical issue towards sustainable development of neighbor cities in border areas. In this regard, sustainable common planning approaches and policies are an increasing reality, particularly in European territories. Considering the significant amount of cross-border cooperation (CBC) projects and strategies within Europe, it is crucial to promote research approaches that are able to identify the most positive approaches towards the establishment of alliances in border territories, serving as pivotal methodologies for achieving success. Contextually, the present study considered direct and indirect research methods and tools, literature reviews, data collection, computer-assisted telephone interviewing (CATI) and computer-assisted web interview (CAWI), all applied over two European border cities: Cieszyn (Poland) and Cesky Tesin (Czech Republic). These methods enabled the assembly of perspectives of local authorities, public and private institutions, non-governmental organizations, and entrepreneurs from the cities under study. Through the analysis of the collected data, five conditions have been identified for the success of strategic alliances in CBC projects: (i) well defining the alliance goals; (ii) ensuring participation in the alliance of various groups of stakeholders; (iii) involvement of both partners with extensive experience in CBC; (iv) ensuring the coherence of the key objective; and (v) guaranteeing the alliance benefits both sides. These conditions might effectively contribute to achieve more successful outputs in CBC projects, highlighting the relevance of previously developed strategies on the definition of future approaches.info:eu-repo/semantics/publishedVersio

Obawy rodziców dzieci sześcio-i siedmioletnich rozpoczynających edukację szkolną. Komunikat z badań

School start is an important moment not only for the child, but also for their parents. They need to make sure that their child’s basic needs are met in the institution where they would be placed and that all activities would be carried out in consideration of the child’s abilities. The article presents the results of research which aimed to identify the concerns of parents of six and seven-year-old children starting school and to determine the relationship between the occurrence of these concerns and parents’ acceptance or rejection of the assumptions of the reform lowering the compulsory school age (expressed by their decision to send a child to school at the age of six or seven). The experience of the Polish educational system and the reforms it has introduced has shown that if parents do not accept the changes and see them as positive for their children, they are able to block them effectively.Rozpoczynanie nauki w szkole jest ważnym momentem nie tylko dla dziecka, lecz także dla jego rodziców. Muszą mieć oni pewność, że w miejscu, do którego trafi ich dziecko, zostaną zaspokajane jego podstawowe potrzeby, a wszystkie realizowane działania będą na miarę jego możliwości. W artykule zaprezentowano wyniki badań, których celem było poznanie obaw towarzyszących rodzicom dzieci sześcio-i siedmioletnich rozpoczynających edukację szkolną oraz określenie zależności między występowaniem tych obaw a akceptacją bądź odrzuceniem przez rodziców założeń reformy obniżającej wiek realizacji obowiązku szkolnego (wyrażonymi decyzją o posłaniu dziecka do szkoły w wieku sześciu lub siedmiu lat). Doświadczenia rodzimego systemu oświaty i reform wprowadzanych w jego zakresie pokazały, że jeżeli rodzice nie akceptują zmian i nie widzą w nich pozytywnych efektów dla swoich dzieci, są w stanie je skutecznie zablokować