Lytic and mechanical stability of clots composed of fibrin and blood vessel wall components.

Background Proteases expressed in atherosclerotic plaque lesions generate collagen fragments, release glycosaminoglycans (chondroitin sulfate [CS] and dermatan sulfate [DS]) and expose extracellular matrix (ECM) proteins (e.g. decorin) at sites of fibrin formation. Objective Here we address the effect of these vessel wall components on the lysis of fibrin by the tissue plasminogen activator (tPA)/plasminogen system and on the mechanical stability of clots. Methods and results MMP-8-digested collagen fragments, isolated CS, DS, glycosylated decorin and its core protein were used to prepare mixed matrices with fibrin (additives present at a 50-fold lower mass concentration than fibrinogen). Scanning electron microscopy (SEM) showed that the presence of ECM components resulted in a coarse fibrin structure, most pronounced for glycosylated decorin causing an increase in the median fiber diameter from 85 to 187 nm. Rheological measurements indicated that these structural alterations were coupled to decreased shear resistance (1.8-fold lower shear stress needed for gel/fluid transition of the clots containing glycosylated decorin) and rigidity (reduction of the storage modulus from 54.3 to 33.2 Pa). The lytic susceptibility of the modified fibrin structures was increased. The time to 50% lysis by plasmin was reduced approximately 2-fold for all investigated ECM components (apart from the core protein of decorin which produced a moderate reduction of the lysis time by 25%), whereas fibrin-dependent plasminogen activation by tPA was inhibited by up to 30%. Conclusion ECM components compromise the chemical and mechanical stability of fibrin as a result of changes in its ultrastructure

Differential Roles of the Two Raphe Nuclei in Amiable Social Behavior and Aggression – An Optogenetic Study

Serotonergic mechanisms hosted by raphe nuclei have important roles in affiliative and agonistic behaviors but the separate roles of the two nuclei are poorly understood. Here we studied the roles of the dorsal (DR) and median raphe region (MRR) in aggression by optogenetically stimulating the two nuclei. Mice received three 3 min-long stimulations, which were separated by non-stimulation periods of 3 min. The stimulation of the MRR decreased aggression in a phasic-like manner. Effects were rapidly expressed during stimulations, and vanished similarly fast when stimulations were halted. No carryover effects were observed in the subsequent three trials performed at 2-day intervals. No effects on social behaviors were observed. By contrast, DR stimulation rapidly and tonically promoted social behaviors: effects were present during both the stimulation and non-stimulation periods of intermittent stimulations. Aggressive behaviors were marginally diminished by acute DR stimulations, but repeated stimulations administered over 8 days considerably decreased aggression even in the absence of concurrent stimulations, indicating the emergence of carryover effects. No such effects were observed in the case of social behaviors. We also investigated stimulation-induced neurotransmitter release in the prefrontal cortex, a major site of aggression control. MRR stimulation rapidly but transiently increased serotonin release, and induced a lasting increase in glutamate levels. DR stimulation had no effect on glutamate, but elicited a lasting increase of serotonin release. Prefrontal serotonin levels remained elevated for at least 2 h subsequent to DR stimulations. The stimulation of both nuclei increased GABA release rapidly and transiently. Thus, differential behavioral effects of the two raphe nuclei were associated with differences in their neurotransmission profiles. These findings reveal a surprisingly strong behavioral task division between the two raphe nuclei, which was associated with a nucleus-specific neurotransmitter release in the prefrontal cortex

A Sequence of Phase Transformations and Phases in NiCoFeCrGa High Entropy Alloy

The present investigation is directed to phase transitions in the equimolar NiCoFeCrGa high entropy alloy, which is a mixture of face-centered cubic (FCC) and body-centered cubic (BCC) crystalline phases. The microstructure of the samples was investigated by using scanning electron microscopy (SEM), time-of-flight secondary ion mass spectroscopy (TOF-SIMS), transmission electron microscopy-based energy-dispersive spectroscopy (EDS) and electron energy loss spectroscopy (EELS), as well as X-ray diffraction (XRD) measurements. Based on the phases observed in different temperature ranges, a sequence of the phase transitions can be established, showing that in a realistic process, when freely cooling the sample with the furnace from high to room temperature, a microstructure having spinodal-like decomposition can also be expected. The elemental mapping and magnetic behaviors of this decomposed structure are also studied

A tértapasztalat esztétikai, történeti és társadalmi koncepciói a 20. században = Aesthetical, Historical and Social Concepts of Space Experience in the 20th Century

A projekt keretében kiadott fordításkötetek és a hozzájuk kapcsolódó, részben nemzetközi résztvevőkkel szervezett workshopok elsődleges szakmai hozama a térfogalom és a tértapasztalat modern történetének beható interdiszciplináris és módszertani vizsgálata volt, amely három súlypont, az esztétikai tér, a történeti tér valamint a társadalmi és kulturális tér koncepciói köré rendeződött. Ezek elemzése során megmutatkozott, hogy az „esztétikai modernség” vizsgálatát a filozófia, esztétika, társadalomtörténet és kultúratudomány területén egyaránt meghatározza, illetve új szempontokkal gazdagítja a „spatial turn” nyomán végbement általános módszertani váltás. A fordítások révén a kutatás hozzáférhetővé tett olyan központi jelentőségű, idegen nyelvű elméleti írásokat, amelyek elősegítik, hogy a hazai humántudományok közös fogalmi eszköztárral, valamint módszertanilag felkészülten tárgyalják és alkalmazzák a térfogalom és tértapasztalat 20. századi változásai nyomán kialakult térkoncepciókat mind a tudományelméletben, mind pedig az egyes humán diszciplínák terén. | The key result of the translated works and the related workshops partially organized with participants from abroad was that the research conducted in the framework of the project could deliver an in-depth interdisciplinary and methodological analysis of the modern history of the notion and experience of space. The research was arranged in three main topics: different conceptions of aesthetic space, historical space, and social and cultural space were investigated. Their analysis could confirm, that the methodological shift, which was caused by the “spatial turn”, not only affects the way of how “aesthetic modernity” is being examined in the realms of philosophy, aesthetics, social history and cultural studies, but it also enriches these inquiries by adding new aspects to them. By means of the publication and translation activities, the project made important theoretical texts available for the Hungarian academic community working in the field of the humanities. They enable the scientific discourse to use common concepts and thorough methodological principles when studying and applying spatial conceptions, which developed in course of the modifications of the notion and experience of space in the 20th century, both in theory of science and in different disciplines of the humanities

Hypercholesterolemia downregulates autophagy in the rat heart

Background: We have previously shown that efficiency of ischemic conditioning is diminished in hypercholesterolemia and that autophagy is necessary for cardioprotection. However, it is unknown whether isolated hypercholesterolemia disturbs autophagy or the mammalian target of rapamycin (mTOR) pathways. Therefore, we investigated whether isolated hypercholesterolemia modulates cardiac autophagy-related pathways or programmed cell death mechanisms such as apoptosis and necroptosis in rat heart. Methods: Male Wistar rats were fed either normal chow (NORM; n=9) or with 2% cholesterol and 0.25% cholic acid-enriched diet (CHOL; n=9) for 12 weeks. CHOL rats exhibited a 41% increase in plasma total cholesterol level over that of NORM rats (4.09mmol/L vs. 2.89mmol/L) at the end of diet period. Animals were sacrificed, hearts were excised and briefly washed out. Left ventricles were snap-frozen for determination of markers of autophagy, mTOR pathway, apoptosis, and necroptosis by Western blot. Results: Isolated hypercholesterolemia was associated with a significant reduction in expression of cardiac autophagy markers such as LC3-II, Beclin-1, Rubicon and RAB7 as compared to controls. Phosphorylation of ribosomal S6, a surrogate marker for mTOR activity, was increased in CHOL samples. Cleaved caspase-3, a marker of apoptosis, increased in CHOL hearts, while no difference in the expression of necroptotic marker RIP1, RIP3 and MLKL was detected between treatments. Conclusions: This is the first comprehensive analysis of autophagy and programmed cell death pathways of apoptosis and necroptosis in hearts of hypercholesterolemic rats. Our data show that isolated hypercholesterolemia suppresses basal cardiac autophagy and that the decrease in autophagy may be a result of an activated mTOR pathway. Reduced autophagy was accompanied by increased apoptosis, while cardiac necroptosis was not modulated by isolated hypercholesterolemia. Decreased basal autophagy and elevated apoptosis may be responsible for the loss of cardioprotection reported in hypercholesterolemic animals

An appraisal: How notifiable infectious diseases are reported by Hungarian family physicians

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Thallium Labeled Citrate-Coated Prussian Blue Nanoparticles as Potential Imaging Agent

Background. The aim of this study was to develop and characterize a nanoparticle-based image-contrast platform which is biocompatible, chemically stable, and accessible for radiolabeling with 201Tl. We explored whether this nanoparticle enhanced the T1 signal which might make it an MRI contrast agent as well. Methods. The physical properties of citrate-coated Prussian blue nanoparticles (PBNPs) (iron(II);iron(III);octadecacyanide) doped with 201Tl isotope were characterized with atomic force microscopy, dynamic light scattering, and zeta potential measurement. PBNP biodistribution was determined by using SPECT and MRI following intravenous administration into C57BL6 mice. Activity concentrations (MBq/cm3) were calculated from the SPECT scans for each dedicated volume of interest (VOI) of liver, kidneys, salivary glands, heart, lungs, and brain. Results. PBNP accumulation peaked at 2 hours after injection predominantly in the kidneys and the liver followed by a gradual decrease in activity in later time points. Conclusion. We synthetized, characterized, and radiolabeled a Prussian blue-based nanoparticle platform for contrast material applications. Its in vivo radiochemical stability and biodistribution open up the way for further diagnostic applications