Az egykori szocialista blokk államaiban működő titkosszolgálatok működésével, szervezetével kapcsolatos információk felkutatása, elemzése jelen idő tájt is az érdeklődés középpontjában áll. A ...források hiányából, elérhetőségének nehézségeiből adódóan minden szakmai és tudományos közlemény, publikáció megjelenése újabb lehetőség az ismeretszerzésre. Ez a tanulmány rövid betekintést nyújt abba a folyamatba, hogyan és milyen út vezetett – a Csehszlovákia állambiztonsági szervezetét létrehozó kassai kormányprogramtól – Szlovákia egyetlen civil nemzetbiztonsági szolgálatának, a Szlovák Információs Szolgálatnak (SIS) a megalakulásáig. A totalitárius rendszer időszaka mellett bemutatja továbbá az átmenet időszakának fontosabb szervezeti változásait, valamint a Szlovák Információs Szolgálat létrejöttének körülményeit, működésének jellemzőit.
TRH is a tripeptide amide that functions as a neurotransmitter but also serves as a neurohormone that has a critical role in the central regulation of the hypothalamic-pituitary-thyroid axis. ...Hypophysiotropic TRH neurons involved in this neuroendocrine process are located in the hypothalamic paraventricular nucleus and secrete TRH into the pericapillary space of the external zone of the median eminence for conveyance to anterior pituitary thyrotrophs. Under basal conditions, the activity of hypophysiotropic TRH neurons is regulated by the negative feedback effects of thyroid hormone to ensure stable, circulating, thyroid hormone concentrations, a mechanism that involves complex interactions between hypophysiotropic TRH neurons and the vascular system, cerebrospinal fluid, and specialized glial cells called tanycytes. Hypophysiotropic TRH neurons also integrate other humoral and neuronal inputs that can alter the setpoint for negative feedback regulation by thyroid hormone. This mechanism facilitates adaptation of the organism to changing environmental conditions, including the shortage of food and a cold environment. The thyroid axis is also affected by other adverse conditions such as infection, but the central mechanisms mediating suppression of hypophysiotropic TRH may be pathophysiological. In this review, we discuss current knowledge about the mechanisms that contribute to the regulation of hypophysiotropic TRH neurons under physiological and pathophysiological conditions.
The Protestant congregations have been singing in the churches from the beginnings but not as the official part of the service. The singing style changed in the 20th century but only in the case of ...Latin liturgical rites. Singing and the manner of Scripture reading were not similar in the Middle Ages to the Biblical times either. During the centuries, new forms and manners of content expression were adopted by the church. The content and the form were not inseparable. The free-style and set forms of the service, reading and singing for the ministers and the congregation significantly changed. They did not completely break away from the roots, however during the centuries there were several earlier elements that were left aside.In the mid-20th century, Kálmán Csomasz Tóth (1902–1988) wished to stop the process of oblivion by inventorying the Hungarian Protestant airs dating back to the 16th century. And thus, he edited the first Hungarian handbook of this kind. In 2017, another important work by Kálmán Csomasz Tóth was published, namely the air collection known by the profession as RMDT I. It both preserves and creates values, and for this reason, it is our responsibility to preserve it and pass it on by means of today’s modern preservation techniques, namely the Internet.In his study, the author discusses the works that our generation needs to preserve even more so because it sensitively touches upon the current and future use of the Reformed book of chant.
Staphylococcus aureus is a major human and animal pathogen although the animal-associated S. aureus can be a potential risk of human zoonoses. Acquisition of phage-related genomic islands determines ...the S. aureus species diversity. This study characterized and compared the genome architecture, distribution nature, and evolutionary relationship of 65 complete prophages carried by human and animal-associated S. aureus strains spreading across the European regions. The analyzed prophage genomes showed mosaic architecture with extensive variation in genome size. The phylogenetic analyses generated seven clades in which prophages of the animal-associated S. aureus scattered in all the clades. The S. aureus strains with the same SCCmec type, and clonal complex favored the harboring of similar prophage sequences and suggested that the frequency of phage-mediated horizontal gene transfer is higher between them. The presence of various virulence factors in prophages of animal-associated S. aureus suggested that these prophages could have more pathogenic potential than prophages of human-associated S. aureus. This study showed that the S. aureus phages are dispersed among the several S. aureus serotypes and around the European regions. Further, understanding the phage functional genomics is necessary for the phage-host interactions and could be used for tracing the S. aureus strains transmission.
Glucagon-like peptide-1 (GLP-1) inhibits food intake and regulates glucose homeostasis. These actions are at least partly mediated by central GLP-1 receptor (GLP-1R). Little information is available, ...however, about the subcellular localization and the distribution of the GLP-1R protein in the rat brain. To determine the localization of GLP-1R protein in the rat brain, immunocytochemistry was performed at light and electron microscopic levels. The highest density of GLP-1R-immunoreactivity was observed in the circumventricular organs and regions in the vicinity of these areas like in the arcuate nucleus (ARC) and in the nucleus tractus solitarii (NTS). In addition, GLP-1R-immunreactive (IR) neuronal profiles were also observed in a number of telencephalic, diencephalic and brainstem areas and also in the cerebellum. Ultrastructural examination of GLP-1R-immunoreactivity in energy homeostasis related regions showed that GLP-1R immunoreactivity is associated with the membrane of perikarya and dendrites but GLP-1R can also be observed inside and on the surface of axon varicosities and axon terminals. In conclusion, in this study we provide a detailed map of the GLP-1R-IR structures in the CNS. Furthermore, we demonstrate that in addition to the perikaryonal and dendritic distribution, GLP-1R is also present in axonal profiles suggesting a presynaptic action of GLP-1. The very high concentration of GLP-1R-profiles in the circumventricular organs and in the ARC and NTS suggests that peripheral GLP-1 may influence brain functions via these brain areas.
The development of the brain, as well as mood and cognitive functions, are affected by thyroid hormone (TH) signaling. Neurons are the critical cellular target for TH action, with T3 regulating the ...expression of important neuronal gene sets. However, the steps involved in T3 signaling remain poorly known given that neurons express high levels of type 3 deiodinase (D3), which inactivates both T4 and T3. To investigate this mechanism, we used a compartmentalized microfluid device and identified a novel neuronal pathway of T3 transport and action that involves axonal T3 uptake into clathrin-dependent, endosomal/non-degradative lysosomes (NDLs). NDLs-containing T3 are retrogradely transported via microtubules, delivering T3 to the cell nucleus, and doubling the expression of a T3-responsive reporter gene. The NDLs also contain the monocarboxylate transporter 8 (Mct8) and D3, which transport and inactivate T3, respectively. Notwithstanding, T3 gets away from degradation because D3's active center is in the cytosol. Moreover, we used a unique mouse system to show that T3 implanted in specific brain areas can trigger selective signaling in distant locations, as far as the contralateral hemisphere. These findings provide a pathway for L-T3 to reach neurons and resolve the paradox of T3 signaling in the brain amid high D3 activity.
Semaglutide, a glucagon-like peptide 1 (GLP-1) analog, induces weight loss, lowers glucose levels, and reduces cardiovascular risk in patients with diabetes. Mechanistic preclinical studies suggest ...weight loss is mediated through GLP-1 receptors (GLP-1Rs) in the brain. The findings presented here show that semaglutide modulated food preference, reduced food intake, and caused weight loss without decreasing energy expenditure. Semaglutide directly accessed the brainstem, septal nucleus, and hypothalamus but did not cross the blood-brain barrier; it interacted with the brain through the circumventricular organs and several select sites adjacent to the ventricles. Semaglutide induced central c-Fos activation in 10 brain areas, including hindbrain areas directly targeted by semaglutide, and secondary areas without direct GLP-1R interaction, such as the lateral parabrachial nucleus. Automated analysis of semaglutide access, c-Fos activity, GLP-1R distribution, and brain connectivity revealed that activation may involve meal termination controlled by neurons in the lateral parabrachial nucleus. Transcriptomic analysis of microdissected brain areas from semaglutide-treated rats showed upregulation of prolactin-releasing hormone and tyrosine hydroxylase in the area postrema. We suggest semaglutide lowers body weight by direct interaction with diverse GLP-1R populations and by directly and indirectly affecting the activity of neural pathways involved in food intake, reward, and energy expenditure.
Methicillin-resistant
(MRSA) is an opportunistic pathogen and responsible for causing life-threatening infections. The emergence of hypervirulent and multidrug-resistant (MDR)
strains led to ...challenging issues in antibiotic therapy. Consequently, the morbidity and mortality rates caused by
infections have a substantial impact on health concerns. The current worldwide prevalence of MRSA infections highlights the need for long-lasting preventive measures and strategies. Unfortunately, effective measures are limited. In this study, we focus on the identification of vaccine candidates and drug target proteins against the 16 strains of MRSA using reverse vaccinology and subtractive genomics approaches. Using the reverse vaccinology approach, 4 putative antigenic proteins were identified; among these, PrsA and EssA proteins were found to be more promising vaccine candidates. We applied a molecular docking approach of selected 8 drug target proteins with the drug-like molecules, revealing that the ZINC4235426 as potential drug molecule with favorable interactions with the target active site residues of 5 drug target proteins
, biotin protein ligase, HPr kinase/phosphorylase, thymidylate kinase, UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-L-lysine ligase, and pantothenate synthetase. Thus, the identified proteins can be used for further rational drug or vaccine design to identify novel therapeutic agents for the treatment of multidrug-resistant staphylococcal infection.
In the adult brain, both neurons and oligodendrocytes can be generated from neural stem cells located within the Sub-Ventricular Zone (SVZ). Physiological signals regulating neuronal
glial fate are ...largely unknown. Here we report that a thyroid hormone (T
)-free window, with or without a demyelinating insult, provides a favorable environment for SVZ-derived oligodendrocyte progenitor generation. After demyelination, oligodendrocytes derived from these newly-formed progenitors provide functional remyelination, restoring normal conduction. The cellular basis for neuronal
glial determination in progenitors involves asymmetric partitioning of EGFR and TRα1, expression of which favor glio- and neuro-genesis, respectively. Moreover, EGFR
oligodendrocyte progenitors, but not neuroblasts, express high levels of a T
-inactivating deiodinase, Dio3. Thus, TRα absence with high levels of Dio3 provides double-pronged blockage of T
action during glial lineage commitment. These findings not only transform our understanding of how T
orchestrates adult brain lineage decisions, but also provide potential insight into demyelinating disorders.
The thyroid hormone (TH)-controlled recruitment process of brown adipose tissue (BAT) is not fully understood. Here, we show that long-term treatment of T3, the active form of TH, increases the ...recruitment of thermogenic capacity in interscapular BAT of male mice through hyperplasia by promoting the TH receptor α-mediated adipocyte progenitor cell proliferation. Our single-cell analysis reveals the heterogeneous nature and hierarchical trajectory within adipocyte progenitor cells of interscapular BAT. Further analyses suggest that T3 facilitates cell state transition from a more stem-like state towards a more committed adipogenic state and promotes cell cycle progression towards a mitotic state in adipocyte progenitor cells, through mechanisms involving the action of Myc on glycolysis. Our findings elucidate the mechanisms underlying the TH action in adipocyte progenitors residing in BAT and provide a framework for better understanding of the TH effects on hyperplastic growth and adaptive thermogenesis in BAT depot at a single-cell level.
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