1,951 research outputs found

    Innate immune system activation in zebrafish and cellular models of Diamond Blackfan Anemia.

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    Deficiency of ribosomal proteins (RPs) leads to Diamond Blackfan Anemia (DBA) associated with anemia, congenital defects, and cancer. While p53 activation is responsible for many features of DBA, the role of immune system is less defined. The Innate immune system can be activated by endogenous nucleic acids from non-processed pre-rRNAs, DNA damage, and apoptosis that occurs in DBA. Recognition by toll like receptors (TLRs) and Mda5-like sensors induces interferons (IFNs) and inflammation. Dying cells can also activate complement system. Therefore we analyzed the status of these pathways in RP-deficient zebrafish and found upregulation of interferon, inflammatory cytokines and mediators, and complement. We also found upregulation of receptors signaling to IFNs including Mda5, Tlr3, and Tlr9. TGFb family member activin was also upregulated in RP-deficient zebrafish and in RPS19-deficient human cells, which include a lymphoid cell line from a DBA patient, and fetal liver cells and K562 cells transduced with RPS19 shRNA. Treatment of RP-deficient zebrafish with a TLR3 inhibitor decreased IFNs activation, acute phase response, and apoptosis and improved their hematopoiesis and morphology. Inhibitors of complement and activin also had beneficial effects. Our studies suggest that innate immune system contributes to the phenotype of RPS19-deficient zebrafish and human cells

    Morphological changes in the kidneys of rats with experimental hemorrhagic stroke (intracerebral hemorrhage)

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    The article presents the results of the study of morphological changes in the kidneys in Wistar rats during the stroke. Hemorrhagic stroke modeling was performed by injecting 0.1-0.2 ml of autoblood through an opening in the temporal bone into the region of the inner capsule of the right hemisphere. To form a hematoma, a stereotaxic destruction was performed. The experimental group consisted of 6 animals, the control group was represented by intact rats (n=3) and rats after trepanation of the temporal bone but without the introduction of autoblood (n=3). The animals were removed from the experiment on days 3 and21. Inthe course of the study, the structural changes in the right and left kidneys were compared to determine the difference in the location of the disorders. According to the results of the histological examination of the medulla, the tendency to reduction of cytological disorders of the epithelium of the tubules of the left kidney was revealed, while in the right kidney the structural disturbances of the tubules of the nephrons and the collecting ducts of the papilla of the kidney were recorded. Based on these data, it is possible to assume renal involvement in rats on day 3 after a stroke and a frequency recovery on day 21. The described histological studies give  a new data on the development of structural changes in renal medulla in rats with hemorrhagic stroke, which can be associated with a violation of electrolyte exchanges at the level of the distal nephron segment

    Fundamentals and applications of Raman-based techniques for the design and development of active biomedical materials

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    Raman spectroscopy is an analytical method based on light–matter interactions that can interrogate the vibrational modes of matter and provide representative molecular fingerprints. Mediated by its label-free, non-invasive nature, and high molecular specificity, Raman-based techniques have become ubiquitous tools for in situ characterization of materials. This review comprehensively describes the theoretical and practical background of Raman spectroscopy and its advanced variants. The numerous facets of material characterization that Raman scattering can reveal, including biomolecular identification, solid-to-solid phase transitions, and spatial mapping of biomolecular species in bioactive materials, are highlighted. The review illustrates the potential of these techniques in the context of active biomedical material design and development by highlighting representative studies from the literature. These studies cover the use of Raman spectroscopy for the characterization of both natural and synthetic biomaterials, including engineered tissue constructs, biopolymer systems, ceramics, and nanoparticle formulations, among others. To increase the accessibility and adoption of these techniques, the present review also provides the reader with practical recommendations on the integration of Raman techniques into the experimental laboratory toolbox. Finally, perspectives on how recent developments in plasmon- and coherently-enhanced Raman spectroscopy can propel Raman from underutilized to critical for biomaterial development are provided

    Genesis of the institute of procedural guidance: Historical and legal aspect

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    The result of the reform of the criminal process in 2012 was the introduction of a new institute of procedural guidance for pre-trial investigations. This institute has become the object of many scientific discussions, and therefore there is a need to analyse its historical and legal genesis to clearly understand the place and role of the prosecutor in modern criminal proceedings. The purpose of the study is to examine the institute of procedural guidance in criminal proceedings and identify promising areas for improving its legal regulation. The study used dialectical, system-structural, synthesis, formal-logical, and historical methods. It is proved that the institute of procedural guidance originated quite a long time ago. From the very beginning, monarchs used civil servants to represent exclusively their interests in certain processes that were important to them. It is established that the genesis of the institute of the prosecutor’s office began to be used quite widely, up to the development of a separate structure of the relevant state bodies and assigning them the function of supervision over certain spheres of life, that is, the functions of the prosecutor’s office expanded sufficiently and representation of the interests of the state in criminal proceedings became part of the overall function of supervision. With the change in the socio-political orientation of Ukraine’s development after independence, the place and role of the prosecutor’s office in the system of state bodies have evolved under the influence of advanced European trends. The reverse process of changing the functions of the prosecutor’s office in criminal proceedings has begun, namely, the function of total prosecutor’s supervision has begun to narrow and be reduced to procedural guidance of the criminal process and representation exclusively in certain cases. As a result of the study, it was stated that the legislation regulating the legal status of the prosecutor’s office has contradictions, namely, the Law of Ukraine “On Prosecutor’s Office” imposes broader powers on the prosecutor than the Constitution of Ukraine, which undoubtedly requires legislative correction by making appropriate changes. The findings of the study can be used in rule-making and law enforcement activitie

    Strong alkalinization of Chara cell surface in the area of cell wall incision as an early event in mechanoperception

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    AbstractMechanical wounding of cell walls occurring in plants under the impact of pathogens or herbivores can be mimicked by cell wall incision with a glass micropipette. Measurements of pH at the surface of Chara corallina internodes following microperforation of cell wall revealed a rapid (10–30s) localized alkalinization of the apoplast after a lag period of 10–20s. The pH increase induced by incision could be as large as 3 pH units and relaxed slowly, with a halftime up to 20min. The axial pH profile around the incision zone was bell-shaped and localized to a small area, extending over a distance of about 100μm. The pH response was suppressed by lowering cell turgor upon the replacement of artificial pond water (APW) with APW containing 50mM sorbitol. Stretching of the plasma membrane during its impression into the cell wall defect is likely to activate the Ca2+ channels, as evidenced from sensitivity of the incision-induced alkalinization to the external calcium concentration and to the addition of Ca2+-channel blockers, such as La3+, Gd3+, and Zn2+. The maximal pH values attained at the incision site (~10.0) were close to pH in light-dependent alkaline zones of Chara cells. The involvement of cytoskeleton in the origin of alkaline patch was documented by observations that the incision-induced pH transients were suppressed by the inhibitors of microtubules (oryzalin and taxol) and, to a lesser extent, by the actin inhibitor (cytochalasin B). The results indicate that the localized increase in apoplastic pH is an early event in mechanoperception and depends on light, cytoskeleton, and intracellular calcium

    Motivational basis of teaching latin at a medical university

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    The relevance of the research is due to the fact that teaching Latin is an integral part of a competent specialist’s training. The main goal of studying this subject at a university is to lay the foundations of the terminological competence of a future medical professional who is able to competently and consciously use medical terminology of Greek-Latin origin in both Russian and Latin spelling. An analysis of the results of the survey conducted at the Faculty of Dentistry has revealed the need to use techniques that can significantly increase the motivation of students to learn the Latin language. Weakened motivation or its absence affects negatively any human activity, including educational one. The interconnection of external and internal motives contributes to an understanding of the meaning of learning, awareness of the need to learn the Latin language, which in turn contributes to the formation of positive motivation. In the framework of this research, an attempt has been made to identify the most effective innovative methods of teaching the Latin language. Empirical, diagnostic methods and methods of mathematical statistics have been used. As a result of the study, it has been shown that the use of a variety of innovative methods helps to increase motivation to learn the Latin language and is an effective way to solve this problem
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