Processes In Culture Research Articles

PHILOSOPHICAL AND PEDAGOGICAL ASPECT OF THE CREATIVE HERITAGE OF G. S. SKOVORODA IN THE FORMATION OF A NEW EDUCATIONAL PARADIGM OF UKRAINE

The article is timed to the 300th anniversary of the birth of the outstanding philosopher, teacher, and writer Hryhoriy Savych Skovoroda, and is aimed at understanding the relevance of his ideas, the spiritual and moral education of Ukrainian youth in conditions of military aggression. We made an attempt to consider and understand the events of the confrontation between Ukraine and Russia and the impact on these processes of culture and education through the prism of value ideas of G. S. Skovoroda. The author considers democracy, culture, and education to be the key values in this struggle. We tried to focus on the preconditions that contributed to the formation of both democratic values and authoritarian worldview in both countries, which now are calshing in Ukraine. We substantiated the thesis of gradual value changes in the minds of a certain part of the Ukrainian population, especially in the eastern and southern regions, towards democratic values, which significantly influenced not only the further vector of this movement but also the intensification of the aggressor's resistance. We also pay attention to the mental side of this process, which was formed under the high pressure of historical, social, and economic events of the struggle for independence. The result was the creation of a new image of the country – the country-warrior, the country-defender, the country-flag bearer. Through the analysis of the manifestation of plagiarism in the field of songwriting, we have shown that this immoral phenomenon was part of Russia's public policy. From this we can conclude that it is necessary to review the works of Russian culture, from a value point of view, to educate the younger generation. In addition, we propose to increase the promotion of Ukrainian culture in connection with the growing demand for it in the world. We focus on building a new educational policy focused on the highest world standards. We also emphasize that the priorities for future recovery should be: education – science – the latest technologies – a harmonious society. The key in this list is education, which should provide not only the basis for the development of other components but also promote the formation of higher spiritual values.

Vector field techniques for the detection of neuronal dynamics in the presence of mercury

Abstract. The role of mercury in the development of various neuropathologies is well known. The biogeochemical cycles of mercury indicate the possibility of its introduction into various organisms (including humans) through the corresponding trophic chains. However, as it turns out from the literature analysis, until recent years, there have been almost no works on the dynamic microscopic study (either in situ or in vivo) of the processes of connectome involution in aquatic organisms (including fishes, marine mammals, etc.) under the action of mercury. In this regard, we attempted to study the dynamics of morphogenesis and breakdown of the emerging connectome under the mercury exposure. A dynamic study of frames with the dynamics of the axonal path search was carried out in a series with an address-time code, on which it is possible to track the vector fields of displacements and reaction-diffusion processes in the cell culture immediately after the introduction of a drop of mercury or a mercury-containing liquid using capillary pipettes. This paper describes the observed effects and the possible mechanisms underlying them.

Cultural Diffusion in the Architecture of the Ancient World (on the Example of the Cult of Isis in the 3rd Century BC – 2nd Century AD)

The practice of borrowing and mixing architectural forms and meanings from different cultural environments dates back to the architecture of the ancient world and is still relevant today. Therefore, discovering its origins, mechanisms and causes of development is an important subject in the theory and history of architecture. The purpose of the study is to introduce the concept of cultural diffusion, as a methodological technique for mixing architectural forms from different artistic environments, which contributes to the development of qualitatively new solutions that form new architectural styles and synthesise new meanings. It is also vital to substantiate the phenomena of cultural diffusion as the first and necessary stage of subsequent processes of development of architectural meaning and shape – the stage of conscious and reasonable choice of an architectural prototype for a new design. The main material for the study is objects related to the cult of Isis – one of the most common religious cults in the architecture of the ancient world, which belonged to the Greco-Roman civilisation. In terms of methodology, the study is based on the analysis and systematisation of papers on architectural objects associated with the cult of Isis, and the results of visual observations (description and comparative analysis). Using the example of architectural objects associated with the cult of Isis, the study demonstrates that in the architecture of the ancient world, various methodological approaches were developed in architectural form-making: both autonomous processes in different cultures and mixed, which involved the capabilities and means of various cultural environments, opening unlimited prospects for the development of architectural form and meaning. Scientific originality is the interpretation of the process of cultural diffusion as an important methodological prerequisite for a new architectural form and meaning development. This determines the practical importance of the study, since the phenomenon of cultural diffusion, as a methodological technique for the architect's work, is still relevant today

Танцевальная культура тамбовского провинциального дворянства конца XIX – начала XX века

The purpose of the study is to consider the dance culture of the provincial nobility of the Tambov province of the late 19th – early 20th centuries. From the standpoint of a culturological approach, the evolution of ballroom culture in Russia as a socio-cultural phenomenon based on the relationship of family, public education and upbringing of young people of the Russian provincial nobility is analyzed. The curricula and programs of educational institutions of the Tambov prov-ince are analyzed: the Noble School Building, the Government Men’s Gymnasium, the Pitiri-movskaya Gymnasium, as well as private educational institutions: the Ptashnik Gymnasium, the Music School, the Catherine Teachers’ Institute, the Alexandria Institute of Noble Maidens, the Diocesan Women’s School and others. The importance of the main characteristics of the dance evening and its functional significance for Russian society is determined. The role of educational institutions of the Tambov province in the choreographic training and education of the provincial nobility is established. Public, merchant, and private balls are characterized. The changes of bal-lroom dance determined by socio-cultural processes in Russian culture and education are consi-dered. The conclusion is made about the need to revive the dance ballroom culture and fill it with regional peculiarities, its own character and content, traditions, rituals, beliefs. The role of dance culture in the preservation of aesthetic values in modern society is determined.

Интеграционные процессы в современной проектно-художественной культуре

The paper is to comprehend the experience of design and artistic shaping in environmental design as an integral phenomenon. Artistic and synthetic foundations of design practices, where figurative-content and spatial-plastic connections are given a central place, determine the vector of design research in a holistic relationship with spatial and plastic arts. The authors consider the integration processes in project culture using the example of environmental design. The paper outlines modern approaches to art and design organization of space, where axiologically-oriented design thinking of a designer and understanding of the continuity of artistic traditions in shaping the spatial environment are of critical value. In this context, a new quality is given to the natural conformity and the place of conformity of design solutions, taking into account architectural asset of the area and architectural environmental scenario. The study demonstrates that design and artistic integration processes represent a new and complex design synthesis, determining integrity of the environment and aesthetic shaping. The design and artistic synthesis allows expressing the concepts, values, creative intentions and perceptual actions of the designer and establishing connections with historical and cultural reality which enables us to consider the definition of “project-artistic synthesis” as a holistically structured system in the existence of project culture.

Photocontrolling Microtubule Dynamics with Photoswitchable Chemical Reagents.

Microtubule dynamics can be inhibited with sub-second temporal resolution and cellular-scale spatial resolution, by using precise illuminations to optically pattern where and when photoswitchable microtubule-inhibiting chemical reagents exert their latent bioactivity. The recently available reagents (SBTub, PST, STEpo, AzTax, PHTub) now enable researchers to use light to reversibly modulate microtubule-dependent processes in eukaryotes, in 2D and 3D cell culture as well as in vivo, across a variety of model organisms: with applications in fields from cargo transport to cell migration, cell division, and embryonic development.Here we give an introduction to using these photoswitchable microtubule inhibitors in cells. We describe the theory of small molecule photoswitching, andthe unique performance features, usage requirements, and limitations that photoswitchable chemical reagents have; then we summarize the major classes of photoswitchable microtubule inhibitors that are currently available, withthe properties that suit them to different applications, and troubleshooting measures for avoiding common mistakes. We outline workflows to establish cellular assays where they are used to optically control microtubule dynamics in a temporally reversible fashion with spatial specificity down to a single selected cell within a field of view. The methods in this chapter also equip the reader to tackle advanced uses of photoswitchable chemical reagents, in 3D culture and in vivo.

Format of Musical Theatre Director's Training in Socio-Cultural Realities of Independent Ukraine

The relevance of the study lies in the need to find a solution to the problem of training music directors in Ukraine under the influence of a paradigm shift in theatrical art, which requires the harmonization of Ukrainian and European educational systems. The scientific novelty of the article is in determining the ways of professional education modernization in accordance to the rector O. Tymoshenko’s strategic vision of the ‘musical directing’ specialization development at the Tchaikovsky National Academy of Music of Ukraine. The purpose of the study is to determine the strategic directions of training a musical theatre director in the socio-cultural realities of independent Ukraine, to predict the prospects for their further transformations in the context of European integration of art and educational directing schools. Applied research methods were: culturological - to analyze the impact of socio-cultural challenges of today on changing the paradigm of theatrical art; system analysis - to determine the strategic directions of training a music director in the context of O. Tymoshenko's conceptual vision; structural and functional - to determine the model of education of a music director in the context of integrative links between specializations in the implementation of joint projects. Evolutionary changes in music directing education which are connected to European integration processes in culture and art were considered. It was found that the paradigm of theatrical art is influenced by the socio-cultural challenges of today, which have both positive and negative consequences and require modernization of professional training of music directors. It was found out that: positive results consist in exchange of achievements in the field of musical theater, growth of art skills, joint international projects, innovative searches in the context of competition-festival activity, negative - in decrease of national repertoire in comparison with foreign, partial loss of national art identity and change of value orientations from permissive-cognitive to entertaining-hedonistic, creation of art performances on show-market of consumer products. Prospects for further research related to the analysis of world directing and educational systems, creative and pedagogical work of iconic figures of musical theatre and their extrapolation to Ukrainian realities were predicted.

About the nature of the supra-personal reality of spiritual culture

The article shows that the suprapersonal reality of spiritual culture is an autonomous complex, purposeful reflection, a self-contained cultural process, which in the process of its development over two and a half thousand years has acquired the most developed structure and form. Hegel and Hartmann sufficiently revealed its peculiar nature, complex structure, and cultural-historical significance. Their conceptual constructions can serve as a methodological basis for general cultural studies.The thematic culturological approach allows us to analize the genesis of world culture and individual cultures of different peoples. Thematic analysis of the written sources (up to the 6th century B.C.) convincingly shows the naturalistic-power character of the mental spaces of all cultures. This means that in one culture by the sixth century B.C. we can not find any representations of reason and goodness as purely spiritual, independent realities. The thematic approach allows us to investigate the revolutionary transformation of the Axial Age, when a revolutionary transition from the naturalistic-force to the mentally charitable and mental space of culture is carried out. The purpose and objectives of the article. The aim of the article is to show the features of suprapersonal reality and the productive significance of thematic culturological analysis. Research methodology. The research was based on the methodology of thematic culturological analysis, which allows to study cultural processes in individual cultures and cultural regions.Leading methodological settings were the principles of objectivity, systemicity, integrity, unity of historical and logical, interconnection, convergence from the abstract to the concrete. Conclusions. Thus, the suprapersonal reality is a complex, autonomous, purposeful, reflection, a self-contained cultural process, which as it developed over two and a half thousand years acquired the most developed structure and content. The thematic approach allows to successfully study the genesis of both world culture and individual cultures of peoples

ON ONE TENDENCY IN THE DEVELOPMENT OF THE LENINGRAD LANDSCAPE IN THE SECOND HALF OF THE 1950S — 1960S

In the scientific literature, the concept of the Leningrad landscape school is usually concretised in the chronology of the 1930s-1940s. The article examines a stylistically integral trend in landscape painting of the second half of the 1950s – 1960s, associated with A. Semyonov, S. Osipov, K. Gushchin and several other masters. The genesis of this trend is outlined: the Thaw period processes in culture and society. The formation of a new visual image of time, fixed by the so-called modern style, is shown. The problem of re-actualization of this concept in connection with a number of recent exhibitions is considered. The formative and worldview factors, due to which the creative searches of these painters converge into a single trend that determines the nature of the Leningrad landscape of the specified period, are analysed. It can be traced how this trend, which absorbed many impulses of the modern style, became its major component. An attempt to identify an essential tendency in the Leningrad landscape of the next stage, the second half of the 1950s - 1960s, is the purpose of the article. Are there grounds for focusing on this period in the development of the Leningrad landscape? Are there any connections between the trend in landscape painting, which we will consider, with the general style vector of Soviet art of the period we are interested in? Namely, with the socalled modern style? The very formulation of the question was initiated by several exhibitions dedicated to the so-called Thaw period in the State Tretyakov Gallery, the Pushkin Museum, the Moscow Museum in 2017–2018. But above all, by the exhibition “In Search of Modern Style. Leningrad Experience. The Second Half of the 1950s - Mid1960s”, which was held in the Russian Museum in 2018. (3). The concept of the organisers of the exhibition in the Russian museum was somewhat different from that of their Moscow colleagues. The creators of the expositions mentioned above sought to show a cross-section of social problems and moods, the history of mentalities. The curators of the exhibition in the Russian Museum were more focused on identifying stylistic vectors, shaping, and visual practices. Based on practical and theoretical research outlined in the article, the author returns the concept of modern style to scientific circulation.

The Reading of the Piece: An Upcycler’s Embodied Experience of Working with Material Culture of the Deceased

An upcycling practice involves working with remnants of material culture. It is about engaging with and responding to signs of wear. Interacting with traces of use—a smell, finger prints, imprints of a body that are left behind—this study documents and questions the experiences of working with clothing from a specific 1920s–30s historic archive belonging to a deceased female, and the way it informs and shapes the redesign of those garments. It is about understanding narratives behind the experiences of use. How does this affect the designer and their process? This study aims to enrich available knowledge of upcycling and upcyclers and their relationship to objects and attachment. In this article I will be reflecting on the first stage of my practice’s methodology, the reading of the piece; the initial engagement and interaction with the historic archive, which includes photographic documentation and exerpts from a reflective diary that records my material interactions whilst critically analysing and contextualising this process within fashion theory. My aim is to enrich the field of sustainable fashion by shedding light on a complex process that deals with death, memory, value, attachment, and history. By reflecting on my personal experiences with material, I will add to the discussion of designing with strategies that encourage sustainable design relationships; highlight and expand on existing theoretical discourse on textiles and mnemonic energy; and provide a deeper understanding of the practice of upcycling and the intimate materiality of wear. Upcycling fashion practices contribute a materiality perspective to anthropological processes of reading and understanding material culture.

Fate of sulfamethoxazole and potential formation of haloacetic acids during chlorine disinfection process in aquaculture water

There exist two common processes in fishery culture, i.e. antibiotic addition to reduce disease in fishery, and chlorination disinfection to inhibit infectious pathogenic microorganisms. However, antibiotic residues might play important reverse side roles for both aquaculture water pollution and potential formation of chlorination side products. Herein, the transformation behaviour, intermediates analyses and conversion pathway of antibiotic sulfamethoxazole (SMX), and potential generation of halogenated acetic acids (HAAs) in the process of chlorination in fishery water were examined, and the results revealed that the decomposing of SMX satisfied a pseudo first-order kinetic equation. Both the addition of available chlorine and high temperature had affirmative influences on the decontamination of SMX and production of HAAs, and the near-neutral pHs promoted the removal of SMX and generation of HAAs. Br− was favorable for the removal of SMX and yields of brominated acetic acids (Br-AAs). Based on the identified intermediate products, the transformation path of SMX in chlorination process was propounded, to wit, the C–S and S–N bonds in the SMX molecules were firstly cracked, and the primeval intermediate groups are then transformed to form chloroanilines, chlorophenols, etc., and subsequently, chlorophenols were chlorinated and ring-opened to generate toxic HAAs. This study might be meaningful to evaluate the effective removal of sulfonamide antibiotic residues and the potential generation of halogenated DBPs (H-DBPs) when chlorinated in aquaculture water.

Approaches and involved principles to control pH/pCO2 stability in algal cultures

Experimental cultures of both microalgae and macroalgae are commonly carried out by phycologists or environmental biologists to look into morphological, physiological, and molecular responses to aquatic environmental changes. However, the species of inorganic carbon in algae cultures is often altered by algal photosynthetic CO2 removal and/or bicarbonate utilization. The pH changes associated with altered carbonate chemistry in cultures impact physiological processes in microalgae and macroalgae even at their exponential growth phases, since extra energy is required to sustain intracellular acid–base homeostasis. Usually, pH increases during light period due to inorganic carbon uptake and utilization for photosynthesis and decreases during dark period because of respiratory CO2 release. Therefore, to obtain relevant data aimed for physiological and/or molecular responses of algae to changed levels of environmental factors, stability of pH/pCO2 in the cultures should be considered and controlled to rule out impacts of carbonate chemistry and pH changes. In this work, principles involved in changing pH processes in algal cultures are mechanistically analyzed and several approaches to control pH and pCO2 are introduced. In order to sustain stability of pH/pCO2, the principles underline the following key points: (1) maintaining the rate of photosynthetic C removal less than or equal to the rate of CO2 dissolution into the cultures which are aerated; or (2) sustaining dilute cultures with very low cell density without aeration, so that photosynthetic C removal is small enough not to cause significant pH/pCO2 changes; or (3) stabilizing the changes in micro-environments surrounding the cells or thallus. To maintain pH drift < 1% in growing typical unicellular microalgae, the recommended cell concentration ranges from 50 × 103 to 200 × 103 mL−1 with aeration (air replacement rate of ca 500–1000 mL L−1 min−1) in semi-continuous cultures of < 1 L, and it ranges from 100 to 5000 cells mL−1 for diatoms and from 100 to 100 × 103 cells mL−1 for coccolithophores in dilute cultures without aeration, respectively. For macroalgae, maintaining the thalli in flowing through- system or in semi-continuous cultures (continuously control algal biomass density) is recommended.

Product development process of a digital irrigameter: a water sizing proposal for sprinkler irrigation process in different cultures

This paper aimed to propose the development of a digital irrigimeter, in order to assist in water sizing, to be used in the sprinkler irrigation process, in different cultures. From the realization of a market research, it was verified the existence of a gap represented by individuals who have difficulty in dimensioning the water, to be used in irrigation. Thus, it was used the Hargreaves-Samani methodology, for the realization of calculations of the optimum amount of water to be precipitated, per square meter of planted area, weighted by crop coefficients and local soil. So, customer requirements, such as flexibility and response speed were translated into technical characteristics of the final product. Thus, the cost of the final product is directly associated with the level of technology adopted in each component of the product.

Structural processes in local societies and cultures: A dialogue between historiography and anthropology in Pearl River Delta studies

As a major area of dialogue between socio-economic history research and anthropology, land settlement, lineage development, worship of gods, the evolution of household registration system, and ethnic group issues all showed the dynamic process of the regional socio-cultural structure. The study of history was not only an account of people's agency in the social construction of territories, but also an examination of how historical narratives themselves were structured in the social construction of territories, and how this structure drove and constrained people's actions.

Word and Digit

The author analyzes the negative processes in modern Russian culture including the degradation of the Russian language use in literature, society and mass media; general substitution of Russian terms for borrowed foreign analogues; low artistic level of local television serials; openly pro-Western character of entertainment TV shows. Still these processes have a deeper layer: actual denial of the art educational and instructive role in Russia, including literature, theatre and cinema; the loss of the tradition that envisaged artistic research of social and moral state of the society. Against this background the author studies the dual-community factor of modern Russian literature: “pochvenicheskiy” and “intertextual”. The first interprets literature as part of the national life, when the last defines it as strictly personal issue. The isolation of two communities from each other, the state self-barring from the support of the most important from the point of view of self-identity issues, senses and directions in modern Russian literature, in particular, and in culture and art, in general, lead Russian literature (philology) in the direction of Russophobia commercial exploitation. An important part here is played by the degradation of the institutes of the literary community inner expertise, and in particular – the lowering of the level and quality of literary critic.

UKRAINIAN ELECTRONIC MUSIC IN GLOBALISATION AND NATIONAL REVIVAL

The article considers the impact of globalisation and national revival processes on the development of electronic music in Ukraine. It is shown that in the early stages of development (the late 1990s – early 2000s) Ukrainian electronic music is dominated by the focus on Western European music culture, and early festivals of dance electronic music (“The Republic of Kazantip”, “Ultrasonic”) also borrow Russian traditions, which indicates the predominance of globalization and peripheral tendencies in this area. At the same time, the first creative searches related to the combination of electronic sounds with the sounds of Ukrainian folklore are intensified. In particular, the article considers the works of the 2000s-2010s by O. Nesterov and A. Zahaikevych, representing folk electronics in the academic sphere, and works by Katya Chilly, Stelsi, Kind of Zero representing folk electronics in non-academic music. The aesthetic basis of such combinations was the musical neo-folklore of the last third of the XX century and the achievements of folk rock in the late 1990s. Intensification of these searches in the late 2010s, in particular the popularity of such artists as Ruslana, Onuka, Go_A allow us to talk about intensifying the national revival processes in the musical culture of Ukraine and involving Ukrainian music in the world culture preserving its national identity.

The N-Formyl Peptide Receptor 2 (FPR2) Agonist MR-39 Exhibits Anti-Inflammatory Activity in LPS-Stimulated Organotypic Hippocampal Cultures.

Accumulating evidence indicates a pivotal role for chronic inflammatory processes in the pathogenesis of neurodegenerative and psychiatric disorders. G protein-coupled formyl peptide receptor 2 (FPR2) mediates pro-inflammatory or anti-/pro-resolving effects upon stimulation with biased agonists. We aimed to evaluate the effects of a new FPR2 ureidopropanamide agonist, compound MR-39, on neuroinflammatory processes in organotypic hippocampal cultures (OHCs) derived from control (WT) and knockout FPR2−/− mice (KO) exposed to bacterial endotoxin (lipopolysaccharide; LPS). Higher LPS-induced cytokine expression and basal release were observed in KO FPR2 cultures than in WT cultures, suggesting that a lack of FPR2 enhances the OHCs response to inflammatory stimuli. Pretreatment with MR-39 abolished some of the LPS-induced changes in the expression of genes related to the M1/M2 phenotypes (including Il-1β, Il-6, Arg1, Il-4, Cd74, Fizz and Cx3cr1) and TNF-α, IL-1β and IL-4 release in tissue derived from WT but not KO mice. Receptor specificity was confirmed by adding the FPR2 antagonist WRW4, which abolished the abovementioned effects of MR-39. Further biochemical data showed an increase in the phospho-p65/total p65 ratio after LPS stimulation in hippocampal tissues from both WT and KO mice, and MR-39 only reversed this effect on WT OHCs. LPS also increased TRAF6 levels, which are critical for the TLR4-mediated NF-κB pro-inflammatory responses. MR-39 attenuated the LPS-evoked increase in the levels of the NLRP3 and caspase-1 proteins in WT but not KO hippocampal cultures. Since NLRP3 may be involved in the pyroptosis, a lytic type of programmed cell death in which the main role is played by Gasdermin D (GSDMD), we examined the effects of LPS and/or MR-39 on the GSDMD protein level. LPS only increased GSDMD production in the WT tissues, and this effect was ameliorated by MR-39. Collectively, this study indicates that the new FPR2 agonist efficiently abrogates LPS-induced neuroinflammation in an ex vivo model, as evidenced by a decrease in pro-inflammatory cytokine expression and release as well as the downregulation of NLRP3 inflammasome-related pathways.

Biological autoluminescence for assessing oxidative processes in yeast cell cultures

Nowadays, modern medicine is looking for new, more gentle, and more efficient diagnostic methods. A pathological state of an organism is often closely connected with increased amount of reactive oxygen species. They can react with biomolecules and subsequent reactions can lead to very low endogenous light emission (biological autoluminescence—BAL). This phenomenon can be potentially used as a non-invasive and low-operational-cost tool for monitoring oxidative stress during diseases. To contribute to the understanding of the parameters affecting BAL, we analyzed the BAL from yeast Saccharomyces cerevisiae as a representative eukaryotic organism. The relationship between the BAL intensity and the amount of reactive oxygen species that originates as a result of the Fenton reaction as well as correlation between spontaneous BAL and selected physical and chemical parameters (pH, oxygen partial pressure, and cell concentration) during cell growth were established. Our results contribute to real-time non-invasive methodologies for monitoring oxidative processes in biomedicine and biotechnology.

Nanohydroxyapatite as a Biomaterial for Peripheral Nerve Regeneration after Mechanical Damage-In Vitro Study.

Hydroxyapatite has been used in medicine for many years as a biomaterial or a cover for other biomaterials in orthopedics and dentistry. This study characterized the physicochemical properties (structure, particle size and morphology, surface properties) of Li+- and Li+/Eu3+-doped nanohydroxyapatite obtained using the wet chemistry method. The potential regenerative properties against neurite damage in cultures of neuron-like cells (SH-SY5Y and PC12 after differentiation) were also studied. The effect of nanohydroxyapatite (nHAp) on the induction of repair processes in cell cultures was assessed in tests of metabolic activity, the level of free oxygen radicals and nitric oxide, and the average length of neurites. The study showed that nanohydroxyapatite influences the increase in mitochondrial activity, which is correlated with the increase in the length of neurites. It has been shown that the doping of nanohydroxyapatite with Eu3+ ions enhances the antioxidant properties of the tested nanohydroxyapatite. These basic studies indicate its potential application in the treatment of neurite damage. These studies should be continued in primary neuronal cultures and then with in vivo models.

Aminopeptidase A contributes to biochemical, anatomical and cognitive defects in Alzheimer\u2019s disease (AD) mouse model and is increased at early stage in sporadic AD brain

One of the main components of senile plaques in Alzheimer’s disease (AD)-affected brain is the Aβ peptide species harboring a pyroglutamate at position three pE3-Aβ. Several studies indicated that pE3-Aβ is toxic, prone to aggregation and serves as a seed of Aβ aggregation. The cyclisation of the glutamate residue is produced by glutaminyl cyclase, the pharmacological and genetic reductions of which significantly alleviate AD-related anatomical lesions and cognitive defects in mice models. The cyclisation of the glutamate in position 3 requires prior removal of the Aβ N-terminal aspartyl residue to allow subsequent biotransformation. The enzyme responsible for this rate-limiting catalytic step and its relevance as a putative trigger of AD pathology remained yet to be established. Here, we identify aminopeptidase A as the main exopeptidase involved in the N-terminal truncation of Aβ and document its key contribution to AD-related anatomical and behavioral defects. First, we show by mass spectrometry that human recombinant aminopeptidase A (APA) truncates synthetic Aβ1-40 to yield Aβ2-40. We demonstrate that the pharmacological blockade of APA with its selective inhibitor RB150 restores the density of mature spines and significantly reduced filopodia-like processes in hippocampal organotypic slices cultures virally transduced with the Swedish mutated Aβ-precursor protein (βAPP). Pharmacological reduction of APA activity and lowering of its expression by shRNA affect pE3-42Aβ- and Aβ1-42-positive plaques and expressions in 3xTg-AD mice brains. Further, we show that both APA inhibitors and shRNA partly alleviate learning and memory deficits observed in 3xTg-AD mice. Importantly, we demonstrate that, concomitantly to the occurrence of pE3-42Aβ-positive plaques, APA activity is augmented at early Braak stages in sporadic AD brains. Overall, our data indicate that APA is a key enzyme involved in Aβ N-terminal truncation and suggest the potential benefit of targeting this proteolytic activity to interfere with AD pathology.