225 research outputs found

    More than one dynamic crossover in protein hydration water

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    Studies of liquid water in its supercooled region have led to many insights into the structure and behavior of water. While bulk water freezes at its homogeneous nucleation temperature of approximately 235 K, for protein hydration water, the binding of water molecules to the protein avoids crystallization. Here we study the dynamics of the hydrogen bond (HB) network of a percolating layer of water molecules, comparing measurements of a hydrated globular protein with the results of a coarse-grained model that has been shown to successfully reproduce the properties of hydration water. With dielectric spectroscopy we measure the temperature dependence of the relaxation time of protons charge fluctuations. These fluctuations are associated to the dynamics of the HB network of water molecules adsorbed on the protein surface. With Monte Carlo (MC) simulations and mean--field (MF) calculations we study the dynamics and thermodynamics of the model. In both experimental and model analyses we find two dynamic crossovers: (i) one at about 252 K, and (ii) one at about 181 K. The agreement of the experiments with the model allows us to relate the two crossovers to the presence of two specific heat maxima at ambient pressure. The first is due to fluctuations in the HB formation, and the second, at lower temperature, is due to the cooperative reordering of the HB network

    Cyclic AMP Pathway Suppress Autoimmune Neuroinflammation by Inhibiting Functions of Encephalitogenic CD4 T Cells and Enhancing M2 Macrophage Polarization at the Site of Inflammation

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    Although it has been demonstrated that cAMP pathway affect both adaptive and innate cell functions, the role of this pathway in the regulation of T-cell-mediated central nervous system (CNS) autoimmune inflammation, such as in experimental autoimmune encephalomyelitis (EAE), remains unclear. It is also unclear how cAMP pathway affects the function of CD4 T cells in vivo at the site of inflammation. We found that adenylyl cyclase activator Forskolin besides inhibition of functions autoimmune CD4 T cells also upregulated microRNA (miR)-124 in the CNS during EAE, which is associated with M2 phenotype of microglia/macrophages. Our study further established that in addition to direct influence of cAMP pathway on CD4 T cells, stimulation of this pathway promoted macrophage polarization toward M2 leading to indirect inhibition of function of T cells in the CNS. We demonstrated that Forskolin together with IL-4 or with Forskolin together with IL-4 and IFNγ effectively stimulated M2 phenotype of macrophages indicating high potency of this pathway in reprogramming of macrophage polarization in Th2- and even in Th1/Th2-mixed inflammatory conditions such as EAE. Mechanistically, Forskolin and/or IL-4 activated ERK pathway in macrophages resulting in the upregulation of M2-associated molecules miR-124, arginase (Arg)1, and Mannose receptor C-type 1 (Mrc1), which was reversed by ERK inhibitors. Administration of Forskolin after the onset of EAE substantially upregulated M2 markers Arg1, Mrc1, Fizz1, and Ym1 and inhibited M1 markers nitric oxide synthetase 2 and CD86 in the CNS during EAE resulting in decrease in macrophage/microglia activation, lymphocyte and CD4 T cell infiltration, and the recovery from the disease. Forskolin inhibited proliferation and IFNγ production by CD4 T cells in the CNS but had rather weak direct effect on proliferation of autoimmune T cells in the periphery and in vitro, suggesting prevalence of indirect effect of Forskolin on differentiation and functions of autoimmune CD4 T cells in vivo. Thus, our data indicate that Forskolin has potency to skew balance toward M2 affecting ERK pathway in macrophages and indirectly inhibit pathogenic CD4 T cells in the CNS leading to the suppression of autoimmune inflammation. These data may have also implications for future therapeutic approaches to inhibit autoimmune Th1 cells at the site of tissue inflammation

    ПОВЫШЕНИЕ ЭФФЕКТИВНОСТИ РАСКРЫТИЯ МИНЕРАЛЬНЫХ АССОЦИАЦИЙ РЕДКОЗЕМЕЛЬНЫХ РУД ПО КОМБИНИРОВАННЫМ ТЕХНОЛОГИЯМ

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    In terms of rare-earth ores of the Tatarsky and Tomtorsky deposits (Krasnoyarsky Territory), the possibility of increasing the extent of investigated sample breaking down by means of discharge-impulse intensification of the grinding process is considered. The use of the combined scheme of ore dressing called «grinding for 20 minutes – discharge-impulse processing with specific energy of 9,2 kJ/dm3» allows increasing the extent of lanthanum and yttrium recovery into the acid solution by 3,8 and 2,8 % respectively during sintering of processed samples with soda.На примере редкоземельных руд Татарского и Томторского месторождений (Красноярский кр.) рассмотрена возможность повышения степени раскрытия исследуемых проб за счет разрядно-импульсной интенсификации процесса измельчения. Применение комбинированной схемы рудоподготовки «измельчение 20 мин – разрядно-импульсная обработка с удельной энергией 9,2 кДж/дм3» позволит повысить степень извлечения лантана и иттрия в кислый раствор на 3,8 и 2,8 % соответственно при спекании подготовленных проб с содой

    On the origin of 140 GHz emission from the 4 July 2012 solar flare

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    The sub-THz event observed on the 4 July 2012 with the Bauman Moscow State Technical University Radio Telescope RT-7.5 at 93 and 140~GHz as well as Kislovodsk and Mets\"ahovi radio telescopes, Radio Solar Telescope Network (RSTN), GOES, RHESSI, and SDO orbital stations is analyzed. The spectral flux between 93 and 140 GHz has been observed increasing with frequency. On the basis of the SDO/AIA data the differential emission measure has been calculated. It is shown that the thermal coronal plasma with the temperature above 0.5~MK cannot be responsible for the observed sub-THz flare emission. The non-thermal gyrosynchrotron mechanism can be responsible for the microwave emission near 1010~GHz but the observed millimeter spectral characteristics are likely to be produced by the thermal bremsstrahlung emission from plasma with a temperature of about 0.1~MK.Comment: 18 pages, 6 figure

    Spectroelectrochemistry: ESR of Paramagnetic Intermediates in the Electron Transfer Series [Cr(bpy)<inf>3</inf>]<sup>n</sup> (n = 3+, 2+, 1+, 0, 1-)

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    © 2015 Elsevier Ltd. All rights reserved. A new method of cyclic voltammetry with simultaneous ESR spectra multiple recording (CV-MRESR) has been proposed and implemented. Along with cyclic voltammetry (CV) and electron spin resonance (ESR), the combined method involving cyclic voltammetry and ESR (CV-ESR) has been used for the study of electron transfer in a series of complexes [Cr(bpy)3]n (n = 3+, 2+, 1+, 0, 1-)

    Confinement of Anomalous Liquids in Nanoporous Matrices

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    Using molecular dynamics simulations, we investigate the effects of different nanoconfinements on complex liquids-e.g., colloids or protein solutions-with density anomalies and a liquid-liquid phase transition (LLPT). In all the confinements, we find a strong depletion effect with a large increase in liquid density near the confining surface. If the nano confinement is modeled by an ordered matrix of nanoparticles (NPs), we find that the anomalies are preserved. On the contrary, if the confinement is modeled by a disordered matrix of NPs, we find a drastically different phase diagram: the LLPT shifts to lower pressures and temperatures, and the anomalies become weaker, as the disorder increases. We find that the density heterogeneities induced by the disordered matrix are responsible for the weakening of the LLPT and the disappearance of the anomalies

    A Ni(III) complex stabilized by silica nanoparticles as an efficient nanoheterogeneous catalyst for oxidative C-H fluoroalkylation

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    © The Royal Society of Chemistry 2016.We have developed NiIII-doped silica nanoparticles ([(bpy)xNiIII]@SiO2) as a recyclable, low-leaching, and efficient oxidative functionalization nanocatalyst for aromatic C-H bonds. The catalyst is obtained by doping the complex [(bpy)3NiII] on silica nanoparticles along with its subsequent electrooxidation to [(bpy)xNiIII] without an additional oxidant. The coupling reaction of arenes with perfluoroheptanoic acid occurs with 100% conversion of reactants in a single step at room temperature under nanoheterogeneous conditions. The catalyst content is only 1% with respect to the substrates under electrochemical regeneration conditions. The catalyst can be easily separated from the reaction mixture and reused a minimum of five times. The results emphasize immobilization on the silica support and the electrochemical regeneration of NiIII complexes as a facile route for developing an efficient nanocatalyst for oxidative functionalization

    Post-Training Reward Partially Restores Chronic Stress Induced Effects in Mice

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    Reduced responsiveness to positive stimuli is a core symptom of depression, known as anhedonia. In the present study, we assessed the expression of anhedonia in our chronic stress mouse model using a subset of read-out parameters. In line with this, we investigated in how far chronic stress would affect the facilitating effect of post-training self-administration of sugar, as we previously observed in naïve mice. Male C57BL/6J mice were repeatedly and at unpredictable times exposed to rats (no physical contact) over the course of two weeks. Following novelty exploration, (non-) spatial learning and memory processes with and without post-training sugar acting as reinforcer, emotionality, reward sensitivity and corticosterone levels were determined. We found that (1) the effects of chronic stress persisted beyond the period of the actual rat exposure. (2) Post-training self-administration of sugar as reinforcer improved spatial performance in naïve mice, whereas (3) in stressed mice sugar partially “normalized” the impaired performance to the level of controls without sugar. Chronic stress (4) increased behavioral inhibition in response to novelty; (5) induced dynamic changes in the pattern of circadian corticosterone secretion during the first week after rat stress and (6) increased the intake of sucrose and water. (7) Chronic stress and sugar consumed during spatial training facilitated the memory for the location of the sucrose bottle weeks later. Concluding, our chronic stress paradigm induces the expression of anhedonia in mice, at different levels of behavior. The behavioral inhibition appears to be long lasting in stressed mice. Interestingly, sugar consumed in close context with spatial learning partially rescued the stress-induced emotional and cognitive impairments. This suggests that reward can ameliorate part of the negative consequences of chronic stress on memory

    Understanding How Stress Responses and Stress-Related Behaviors Have Evolved in Zebrafish and Mammals

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    Stress response is essential for the organism to quickly restore physiological homeostasis disturbed by various environmental insults. In addition to well-established physiological cascades, stress also evokes various brain and behavioral responses. Aquatic animal models, including the zebrafish (Danio rerio), have been extensively used to probe pathobiological mechanisms of stress and stress-related brain disorders. Here, we critically discuss the use of zebrafish models for studying mechanisms of stress and modeling its disorders experimentally, with a particular cross-taxon focus on the potential evolution of stress responses from zebrafish to rodents and humans, as well as its translational implications. © 2021 The AuthorsAVK is supported by the Zebrafish Platform Construction Fund from the Southwest University (Chongqing, China). The collaboration was supported by the Russian Science Foundation (RSF) grant 19-15-00053. KAD is supported by the President of Russia Graduate Fellowship, and the Special Rector's Fellowship for SPSU students. ACVVG is supported by the FAPERGS research fellowship 19/2551-0001-669-7. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Dopamine neurons modulate neural encoding and expression of depression-related behaviour

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    Major depression is characterized by diverse debilitating symptoms that include hopelessness and anhedonia1. Dopamine neurons involved in reward and motivation are among many neural populations that have been hypothesized to be relevant, and certain antidepressant treatments, including medications and brain stimulation therapies, can influence the complex dopamine system. Until now it has not been possible to test this hypothesis directly, even in animal models, as existing therapeutic interventions are unable to specifically target dopamine neurons. Here we investigated directly the causal contributions of defined dopamine neurons to multidimensional depression-like phenotypes induced by chronic mild stress, by integrating behavioural, pharmacological, optogenetic and electrophysiological methods in freely moving rodents. We found that bidirectional control (inhibition or excitation) of specified midbrain dopamine neurons immediately and bidirectionally modulates (induces or relieves) multiple independent depression symptoms caused by chronic stress. By probing the circuit implementation of these effects, we observed that optogenetic recruitment of these dopamine neurons potently alters the neural encoding of depression-related behaviours in the downstream nucleus accumbens of freely moving rodents, suggesting that processes affecting depression symptoms may involve alterations in the neural encoding of action in limbic circuitry
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