Predmet ovog rada je simetrija i asimetrija nacionalizma i globalizma kao kvalitativan društveni odnos determinisan logosnim valentnostima (značaj, značenje i smisao) njihovih strukturnih segmenata. ...Cilj je otkrivanje simetrijskih i asimetrijskih mreža nacionalizma i globalizma koje prate njihove pozitivne i negativne dimenzije. Nacionalizam je, u osnovi, refleksija nacije i kao takav, sadrži sve bitne protivrečnosti nastajanja i razvoja nacije, njene povijesne i metafizičke kategorijalnosti. Nacionalizam kao cjelovit društveni fenomen, genetički strukturiran, može se sociološki identifikovati i objasniti, jedino kao simetrija njegovih pozitivnih i negativnih komponenti. Ne postoji “čista” nacija u idealno-tipskoj formi, koja reflektuje samo pozitivni nacionalizam, ali ni nacija koja reflektuje samo negativni nacionalizam. Redukovanje nacionalizma samo na njegovu negativnu stranu onemogućava otkrivanje njegove pozitivne strane. Refleksija nacionalizma nužno se odvija u državi, u kojoj pravo građanstva znači zadobijanje novog, višeg nivoa slobode, a to je jedina logika nacije. Nacija, država i građanin su tako, neodvojivi subjekti određene demokratske zajednice. Globalizam nije samorefleksija globalnog, već refleksija identitetskih simetrija pojedinih društava-država, koja obuhvata svestranu razmjenu njihovih fundamentalnih ljudskih vrijednosti i interesa. Centralno pitanje je na kojim kvalitativnim sadržajima se održava vladajuća simetrija globalizma i njena veza sa (ne)promjenjivošću suštine načina proizvodnje društvenog života. Odgovor na ovo pitanje nije moguć, bez identifikovanja simetrijskih mreža nacionalizma i globalizma, i njihovog kvalitativnog posredovanja, u kojem posebno značajnu ulogu ima država. Ovdje je sadržan originalan teorijsko-metodološki pristup u sociološkom razumijevanju simetrične refleksivnosti nacionalizma i globalizma u savremenom društvu. Teorijsko-empirijsko i sociološko imaginativno otkrivanje karaktera simetrije i asimetrije nacionalizma i globalizma, jedino može voditi naučno objektivnom i istovremeno društveno angažovanom znanju.
The subject of this paper is the symmetry and asymmetry of nationalism and globalism as a qualitative social relation determined by the logos valences (significance, meaning, and sense) of their structural segments. The aim is to establish symmetrical and asymmetric networks of nationalism and globalism that follow their positive and negative dimensions. Nationalism is, basically, a reflection of the nation that contains all the essential contradictions of the emergence and development of a nation, as well as its historical and metaphysical categorisation. Nationalism as a comprehensive, genetically structured social phenomenon can be socially identified and explained only as a symmetry of its positive and negative components. There is no ‘pure’ nation in an ideal-type form, which reflects only positive nationalism, and neither is there a nation that reflects only negative nationalism. Reducing nationalism only to its negative side prevents the discovery of its positive side. The reflection of nationalism necessarily takes place in a state where the right of citizenship means acquiring a new, higher level of freedom, constituting the only logic of the nation. Thus, the nation, state, and citizen are inseparable subjects of a certain democratic community. Globalism is not a self-reflection of the global but rather a reflection of identity symmetries of individual societies-states, which encompasses a comprehensive exchange of their fundamental human values and interests. The central question is what qualitative contents maintain the dominant symmetry of globalism and its relation to the (in)variability of the essence of social life generation. The answer to this question is not possible without the identification of symmetric networks of nationalism and globalism and their qualitative mediation, in which the state plays a particularly important role. They contain the original theoretical and methodological approach in the sociological understanding of the symmetrical reflexivity of nationalism and globalism in contemporary society. Only the theoretical and empirical as well as sociological and imaginative discovery of the nature of symmetry and asymmetry of nationalism and globalism can lead to scientifically objective and, at the same time, socially engaged knowledge.
In response to mechanical forces and the aging process, bone in the adult skeleton is continuously remodeled by a process in which old and damaged bone is removed by bone-resorbing osteoclasts and ...subsequently is replaced by new bone by bone-forming cells, osteoblasts. During this essential process of bone remodeling, osteoclastic resorption is tightly coupled to osteoblastic bone formation. Bone-resorbing cells, multinuclear giant osteoclasts, derive from the monocyte/macrophage hematopoietic lineage and their differentiation is driven by distinct signaling molecules and transcription factors. Critical factors for this process are Macrophage Colony Stimulating Factor (M-CSF) and Receptor Activator Nuclear Factor-κB Ligand (RANKL). Besides their resorption activity, osteoclasts secrete coupling factors which promote recruitment of osteoblast precursors to the bone surface, regulating thus the whole process of bone remodeling. Bone morphogenetic proteins (BMPs), a family of multi-functional growth factors involved in numerous molecular and signaling pathways, have significant role in osteoblast-osteoclast communication and significantly impact bone remodeling. It is well known that BMPs help to maintain healthy bone by stimulating osteoblast mineralization, differentiation and survival. Recently, increasing evidence indicates that BMPs not only help in the anabolic part of bone remodeling process but also significantly influence bone catabolism. The deletion of the BMP receptor type 1A (BMPRIA) in osteoclasts increased osteoblastic bone formation, suggesting that BMPR1A signaling in osteoclasts regulates coupling to osteoblasts by reducing bone-formation activity during bone remodeling. The dual effect of BMPs on bone mineralization and resorption highlights the essential role of BMP signaling in bone homeostasis and they also appear to be involved in pathological processes in inflammatory disorders affecting bones and joints. Certain BMPs (BMP2 and -7) were approved for clinical use; however, increased bone resorption rather than formation were observed in clinical applications, suggesting the role BMPs have in osteoclast activation and subsequent osteolysis. Here, we summarize the current knowledge of BMP signaling in osteoclasts, its role in osteoclast resorption, bone remodeling, and osteoblast-osteoclast coupling. Furthermore, discussion of clinical application of recombinant BMP therapy is based on recent preclinical and clinical studies.
Several vascular disorders, such as aberrant angiogenesis, atherosclerosis and pulmonary hypertension, have been linked to dysfunctional BMP signaling. Vascular hyperpermeability via distortion of ...endothelial cell adherens junctions is a common feature of these diseases, but the role of BMPs in this process has not been investigated. BMP signaling is initiated by binding of ligand to, and activation of, BMP type I (BMPRI) and type II (BMPRII) receptors. Internalization of VE-cadherin as well as c-Src kinase-dependent phosphorylation have been implicated in the loosening of cell-cell contacts, thereby modulating vascular permeability. Here we demonstrate that BMP6 induces hyperpermeabilization of human endothelial cells by inducing internalization and c-Src-dependent phosphorylation of VE-cadherin. Furthermore, we show BMP-dependent physical interaction of VE-cadherin with the BMP receptor ALK2 (BMPRI) and BMPRII, resulting in stabilization of the BMP receptor complex and, thereby, the support of BMP6-Smad signaling. Our results provide first insights into the molecular mechanism of BMP-induced vascular permeability, a hallmark of various vascular diseases, and provide the basis for further investigations of BMPs as regulators of vascular integrity, both under physiological and pathophysiological conditions.
Despite the high prevalence of ischemic heart diseases worldwide, no antibody-based treatment currently exists. Starting from the evidence that a specific isoform of the Bone Morphogenetic Protein 1 ...(BMP1.3) is particularly elevated in both patients and animal models of myocardial infarction, here we assess whether its inhibition by a specific monoclonal antibody reduces cardiac fibrosis. We find that this treatment reduces collagen deposition and cross-linking, paralleled by enhanced cardiomyocyte survival, both in vivo and in primary cultures of cardiac cells. Mechanistically, we show that the anti-BMP1.3 monoclonal antibody inhibits Transforming Growth Factor β pathway, thus reducing myofibroblast activation and inducing cardioprotection through BMP5. Collectively, these data support the therapeutic use of anti-BMP1.3 antibodies to prevent cardiomyocyte apoptosis, reduce collagen deposition and preserve cardiac function after ischemia.
Bone morphogenetic proteins (BMPs) have a major role in tissue development. BMP3 is synthesized in osteocytes and mature osteoblasts and has an antagonistic effect on other BMPs in bone tissue. The ...main aim of this study was to fully characterize cortical bone and trabecular bone of long bones in both male and female
mice. To investigate the effect of
from birth to maturity, we compared
mice with wild-type littermates at the following stages of postnatal development: 1 day (P0), 2 weeks (P14), 8 weeks and 16 weeks of age.
deletion was confirmed using X-gal staining in P0 animals. Cartilage and bone tissue were examined in P14 animals using Alcian Blue/Alizarin Red staining. Detailed long bone analysis was performed in 8-week-old and 16-week-old animals using micro-CT. The
reporter signal was localized in bone tissue, hair follicles, and lungs. Bone mineralization at 2 weeks of age was increased in long bones of
mice.
deletion was shown to affect the skeleton until adulthood, where increased cortical and trabecular bone parameters were found in young and adult mice of both sexes, while delayed mineralization of the epiphyseal growth plate was found in adult
mice.
Bone morphogenetic proteins (BMPs) possess a unique ability to induce new bone formation. Numerous preclinical studies have been conducted to develop novel, BMP-based osteoinductive devices for the ...management of segmental bone defects and posterolateral spinal fusion (PLF). In these studies, BMPs were combined with a broad range of carriers (natural and synthetic polymers, inorganic materials, and their combinations) and tested in various models in mice, rats, rabbits, dogs, sheep, and non-human primates. In this review, we summarized bone regeneration strategies and animal models used for the initial, intermediate, and advanced evaluation of promising therapeutical solutions for new bone formation and repair. Moreover, in this review, we discuss basic aspects to be considered when planning animal experiments, including anatomical characteristics of the species used, appropriate BMP dosing, duration of the observation period, and sample size.
Abstract Bone has a high potential for endogenous self-repair. However, due to population aging, human diseases with impaired bone regeneration are on the rise. Current strategies to facilitate bone ...healing include various biomolecules, cellular therapies, biomaterials and different combinations of these. Animal models for testing novel regenerative therapies remain the gold standard in pre-clinical phases of drug discovery and development. Despite improvements in animal experimentation, excessive poorly designed animal studies with inappropriate endpoints and inaccurate conclusions are being conducted. In this review, we discuss animal models, procedures, methods and technologies used in bone repair studies with the aim to assist investigators in planning and performing scientifically sound experiments that respect the wellbeing of animals. In the process of designing an animal study for bone repair investigators should consider: skeletal characteristics of the selected animal species; a suitable animal model that mimics the intended clinical indication; an appropriate assessment plan with validated methods, markers, timing, endpoints and scoring systems; relevant dosing and statistically pre-justified sample sizes and evaluation methods; synchronization of the study with regulatory requirements and additional evaluations specific to cell-based approaches. This article is part of a Special Issue entitled “Stem Cells and Bone”.
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