Electrochemical behaviour of Ti/Al2O3/Ni nanocomposite material in artificial physiological solution: Prospects for biomedical application

Inorganic-based nanoelements such as nanoparticles (nanodots), nanopillars and nanowires, which have at least one dimension of 100 nm or less, have been extensively developed for biomedical applications. Furthermore, their properties can be varied by controlling such parameters as element shape, size, surface functionalization, and mutual interactions. In this study, Ni-alumina nanocomposite material was synthesized by the dc-Ni electrodeposition into a porous anodic alumina template (PAAT). The structural, morphological, and corrosion properties were studied using x-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), and electrochemical techniques (linear sweep voltammetry). Template technology was used to obtain Ni nanopillars (NiNPs) in the PAAT nanocomposite. Low corrosion current densities (order of 0.5 μA/cm2) were indicators of this nanocomposite adequate corrosion resistance in artificial physiological solution (0.9% NaCl). A porous anodic alumina template is barely exposed to corrosion and performs protective functions in the composite. The results may be useful for the development of new nanocomposite materials technologies for a variety of biomedical applications including catalysis and nanoelectrodes for sensing and fuel cells. They are also applicable for various therapeutic purposes including targeting, diagnosis, magnetic hyperthermia, and drug delivery. Therefore, it is an ambitious task to research the corrosion resistance of these magnetic nanostructures in simulated body fluid. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.Government Council on Grants, Russian FederationBelarusian Republican Foundation for Fundamental Research, BRFFR: Ф18Д-00720163522Funding: The work was performed with support of State Scientific and Technical Program “Nanotech” (ГБЦ No 20163522), Belarusian Republican Foundation for Fundamental Research (Grant No. Ф18Д-007), Act 211 of Government of Russian Federation (contract No. 02.A03.21.0011). Additionally, the work was partially supported by the Grant of World Federation of Scientists (Geneva, Switzerland)

Vaccinia virus immunomodulator A46 : a lipid and protein-binding scaffold for sequestering host TIR-domain proteins

TS received Austrian Science Fund (FWF) grants P24038, W1221 and W1258. GAB is a member of Max F. Perutz Laboratories and the Vienna International PostDoctoral Program (VIPS). TKS is a holder of Wellcome Trust grant 097831. IU has Spanish Ministry of Economy and Competitiveness grant BIO2013-49604-EXP.Vaccinia virus interferes with early events of the activation pathway of the transcriptional factor NF-kB by binding to numerous host TIR-domain containing adaptor proteins. We have previously determined the X-ray structure of the A46 C-terminal domain; however, the structure and function of the A46 N-terminal domain and its relationship to the C-terminal domain have remained unclear. Here, we biophysically characterize residues 1-83 of the N-terminal domain of A46 and present the X-ray structure at 1.55 Å. Crystallographic phases were obtained by a recently developed ab initio method entitled ARCIMBOLDO_BORGES that employs tertiary structure libraries extracted from the Protein Data Bank; data analysis revealed an all β-sheet structure. This is the first such structure solved by this method which should be applicable to any protein composed entirely of β-sheets. The A46(1-83) structure itself is a β-sandwich containing a co-purified molecule of myristic acid inside a hydrophobic pocket and represents a previously unknown lipid-binding fold. Mass spectrometry analysis confirmed the presence of long-chain fatty acids in both N-terminal and full-length A46; mutation of the hydrophobic pocket reduced the lipid content. Using a combination of high resolution X-ray structures of the N-and C-terminal domains and SAXS analysis of full-length protein A46(1-240), we present here a structural model of A46 in a tetrameric assembly. Integrating affinity measurements and structural data, we propose how A46 simultaneously interferes with several TIR-domain containing proteins to inhibit NF-κB activation and postulate that A46 employs a bipartite binding arrangement to sequester the host immune adaptors TRAM and MyD88.Publisher PDFPeer reviewe

The effect of heat treatment on the microstructure and mechanical properties of 2d nanostructured au/nife system

Nanostructured NiFe film was obtained on silicon with a thin gold sublayer via pulsed electrodeposition and annealed at a temperature from 100 to 400◦C in order to study the effect of heat treatment on the surface microstructure and mechanical properties. High-resolution atomic force microscopy made it possible to trace stepwise evolving microstructure under the influence of heat treatment. It was found that NiFe film grains undergo coalescence twice—at ~100 and ~300°C—in the process of a gradual increase in grain size. The mechanical properties of the Au/NiFe nanostructured system have been investigated by nanoindentation at two various indentation depths, 10 and 50 nm. The results showed the opposite effect of heat treatment on the mechanical properties in the near-surface layer and in the material volume. Surface homogenization in combination with oxidation activation leads to abnormal strengthening and hardening-up of the near-surface layer. At the same time, a nonlinear decrease in hardness and Young’s modulus with increasing temperature of heat treatment characterizes the internal volume of nanostructured NiFe. An explanation of this phenomenon was found in the complex effect of changing the ratio of grain volume/grain boundaries and increasing the concentration of thermally activated diffuse gold atoms from the sublayer to the NiFe film. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.Funding: The work was supported by Act 211 Government of the Russian Federation, contract № 02.A03.21.0011

Electrochemical behaviour of Ti/Al2O3/Ni nanocomposite material in artificial physiological solution: Prospects for biomedical application

Inorganic-based nanoelements such as nanoparticles (nanodots), nanopillars and nanowires, which have at least one dimension of 100 nm or less, have been extensively developed for biomedical applications. Furthermore, their properties can be varied by controlling such parameters as element shape, size, surface functionalization, and mutual interactions. In this study, Ni-alumina nanocomposite material was synthesized by the dc-Ni electrodeposition into a porous anodic alumina template (PAAT). The structural, morphological, and corrosion properties were studied using x-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), and electrochemical techniques (linear sweep voltammetry). Template technology was used to obtain Ni nanopillars (NiNPs) in the PAAT nanocomposite. Low corrosion current densities (order of 0.5 μA/cm2) were indicators of this nanocomposite adequate corrosion resistance in artificial physiological solution (0.9% NaCl). A porous anodic alumina template is barely exposed to corrosion and performs protective functions in the composite. The results may be useful for the development of new nanocomposite materials technologies for a variety of biomedical applications including catalysis and nanoelectrodes for sensing and fuel cells. They are also applicable for various therapeutic purposes including targeting, diagnosis, magnetic hyperthermia, and drug delivery. Therefore, it is an ambitious task to research the corrosion resistance of these magnetic nanostructures in simulated body fluid. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.Government Council on Grants, Russian FederationBelarusian Republican Foundation for Fundamental Research, BRFFR: Ф18Д-00720163522Funding: The work was performed with support of State Scientific and Technical Program “Nanotech” (ГБЦ No 20163522), Belarusian Republican Foundation for Fundamental Research (Grant No. Ф18Д-007), Act 211 of Government of Russian Federation (contract No. 02.A03.21.0011). Additionally, the work was partially supported by the Grant of World Federation of Scientists (Geneva, Switzerland)

Efficiency of Magnetostatic Protection Using Nanostructured Permalloy Shielding Coatings Depending on Their Microstructure

The effect of microstructure on the efficiency of shielding or shunting of the magnetic fluxby permalloy shields was investigated in the present work. For this purpose, the FeNi shieldingcoatings with different grain structures were obtained using stationary and pulsed electrodeposition.The coatings’ composition, crystal structure, surface microstructure, magnetic domain structure, andshielding efficiency were studied. It has been shown that coatings with 0.2–0.6μm grains have adisordered domain structure. Consequently, a higher value of the shielding efficiency was achieved,but the working range was too limited. The reason for this is probably the hindered movement of thedomain boundaries. Samples with nanosized grains have an ordered two-domain magnetic structurewith a permissible partial transition to a superparamagnetic state in regions with a grain size of lessthan 100 nm. The ordered magnetic structure, the small size of the domain, and the coexistenceof ferromagnetic and superparamagnetic regions, although they reduce the maximum value ofthe shielding efficiency, significantly expand the working range in the nanostructured permalloyshielding coatings. As a result, a dependence between the grain and domain structure and theefficiency of magnetostatic shielding was found

Влияние габаритных параметров цилиндрического экрана на эффективность экранирования

Study of dimensional parametersʼ influence on shielding properties of cylindrical shields will allow to optimise the fusion process, as well as to reduce production costs by reducing the material used. The purpose of this work was to compare results of theoretical calculation of shielding effectiveness of an infinite cylindrical shield with the data obtained in real conditions.A cylindrical Ni-Fe shield was synthesised by electrochemical deposition with length of 32 cm, diameter of 4.5 cm and shielding thickness of ≈ 100 µm. The cylinder length was then reduced from 32 cm to 6 cm in 4 cm increments and for each cylinder length shielding effectiveness was measured using three-coordinate Helmholtz field-forming system.The measurement results show that the calculation of shielding effectiveness of infinite cylindrical shield is valid for cylinder lengths l ≥ 18–20 cm. Shielding effectiveness is markedly reduced at values of l ˂ 15 cm.Analysis of data obtained allowed to conclude that it is necessary to determine the correction factor when calculating a cylindrical screen shielding efficiencyИзучение влияния габаритных параметров на экранирующие свойства цилиндрических экранов позволит оптимизировать процесс синтеза, а также снизить затраты на производство, за счёт уменьшения используемого материала. Целью данной работы было сравнение результатов теоретического расчёта эффективности экранирования бесконечного цилиндрического экрана и данных, полученных в реальных условиях.Методом электрохимического осаждения был синтезирован цилиндрический экран Ni-Fe, длина которого составила 32 см, диаметр 4,5 см, толщина экранирующего покрытия составила≈ 100 мкм. Затем длина цилиндра уменьшалась от 30 до 6 см с шагом в 4 см, для каждой длины цилиндра была измерена эффективность экранирования с помощью полеобразующей системы трёхкоординатных катушек Гельмгольца.Результаты измерений показали, что расчёт эффективности экранирования бесконечного цилиндрического экрана справедлив при длине цилиндра l ≥ 18–20 см. При значениях l ˂ 15 см эффективность экранирования заметно снижается.Анализ полученных данных позволил сделать вывод о необходимости определения поправочного коэффициента при расчётах эффективности экранирования цилиндрического экрана

O-GlcNAc regulates the mitochondrial integrated stress response by regulating ATF4

BackgroundAccumulation of mitochondrial dysfunctional is a hallmark of age-related neurodegeneration including Alzheimer’s disease (AD). Impairment of mitochondrial quality control mechanisms leading to the accumulation of damaged mitochondria and increasing neuronal stress. Therefore, investigating the basic mechanisms of how mitochondrial homeostasis is regulated is essential. Herein, we investigate the role of O-GlcNAcylation, a single sugar post-translational modification, in controlling mitochondrial stress-induced transcription factor Activating Transcription Factor 4 (ATF4). Mitochondrial dysfunction triggers the integrated stress response (ISRmt), in which the phosphorylation of eukaryotic translation initiation factor 2α results in the translation of ATF4.MethodsWe used patient-derived induced pluripotent stem cells, a transgenic mouse model of AD, SH-SY5Y neuroblastoma and HeLa cell-lines to examine the effect of sustained O-GlcNAcase inhibition by Thiamet-G (TMG) on ISRmt using biochemical analyses.ResultsWe show that TMG elevates ATF4 protein levels upon mitochondrial stress in SH-SY5Y neuroblastoma and HeLa cell-lines. An indirect downstream target of ATF4 mitochondrial chaperone glucose-regulated protein 75 (GRP75) is significantly elevated. Interestingly, knock-down of O-GlcNAc transferase (OGT), the enzyme that adds O-GlcNAc, in SH-SY5Y increases ATF4 protein and mRNA expression. Additionally, ATF4 target gene Activating Transcription Factor 5 (ATF5) is significantly elevated at both the protein and mRNA level. Brains isolated from TMG treated mice show elevated levels of ATF4 and GRP75. Importantly, ATF4 occupancy increases at the ATF5 promoter site in brains isolated from TMG treated mice suggesting that O-GlcNAc is regulating ATF4 targeted gene expression. Interestingly, ATF4 and GRP75 are not induced in TMG treated familial Alzheimer’s Disease mice model. The same results are seen in a human in vitro model of AD.ConclusionTogether, these results indicate that in healthy conditions, O-GlcNAc regulates the ISRmt through regulating ATF4, while manipulating O-GlcNAc in AD has no effect on ISRmt

Особенности кристаллической структуры и магнитных характеристик твердых растворов систем Ni1–xMxMnSb (M = Fe, Co)

The results of studying the effect on the crystal structure and magnetic properties of compounds based on NiMnSb when Ni cations are replaced by Fe and Co cations are presented. The solid solution Ni1–xMxMnSb (M = Fe, Co) systems were synthesized by the method of solid-phase reactions. With the help of X-ray diffraction analysis, the presence of a concentration structural transition was established. Using the ponderomotive method, it was found that the temperatures of the “magnetic order – magnetic disorder” phase transformation decrease as nickel is replaced by iron and cobalt. The field dependences of the specific magnetization demonstrate the typical behavior of a magnetically soft ferromagnet. The results of an experiment on the study of the crystal and magnetic structure of solid solutions of the Ni0.90M0.10MnSb (M = Fe, Co) systems using thermal neutron diffraction in the temperature range of ~(3–300) K are presented. It is found that the studied compositions exhibit ferromagnetic ordering along the c axis. On the spectra of Ni0.90Co0.10MnSb solid solutions in the region of 2Θ  = 28.6° the appearance of a reflection indicating the formation of antiferromagnetic ordering is observed. Within the framework of the density functional theory, an ab initio calculation of the magnetic moments for Ni1-xMxMnSb (M = Fe, Co; x = 0; 0.125; 0.250) was carried out. The results of theoretical calculations predict the existence of magnetic moments for Fe and Co ions, and they are antiferromagnetically coupled to the spins of Mn and Ni ions.Представлены результаты исследования влияния на кристаллическую структуру и магнитные свойства соединений на основе NiMnSb при замещении катионов Ni на катионы Fe и Co. Твердые растворы систем Ni1–xMxMnSb (M = Fe, Co) синтезированы методом твердофазных реакций. С помощью рентгеноструктурного анализа установлено наличие концентрационного структурного перехода. Пондеромоторным методом обнаружено, что температуры фазового превращения «магнитный порядок – магнитный беспорядок» снижаются по мере замещения никеля железом и кобальтом. Полевые зависимости удельной намагниченности демонстрируют типичное поведение магнитомягкого ферромагнетика. Приведены результаты эксперимента по изучению кристаллической и магнитной структуры твердых растворов систем Ni0,90M0,10MnSb (M = Fe, Co) с помощью дифракции тепловых нейтронов в интервале температур (3–300) K. Обнаружено, что исследуемые составы обладают ферромагнитным упорядочением вдоль оси с. На спектрах твердых растворов Ni0,90Co0,10MnSb в области 2Θ = 28,6° наблюдается появление рефлекса, указывающего на формирование антиферромагнитного упорядочения. В рамках теории функционала плотности проведен ab initio расчет магнитных моментов для Ni1–xMxMnSb (M = Fe, Co; x = 0; 0,125; 0,250). Результаты теоретических расчетов предсказывают существование магнитных моментов у ионов Fe и Co, и они антиферромагнитно связаны со спинами ионов Mn и Ni

Композиционные материалы системы эпоксидная смола–W для радиационной защиты от гамма-излучения

Сomposite materials based on the epoxy resin–W system with varying W content (0–80 %) were obtained using the method of chemical curing. Microstructural investigations of the samples showed that with increasing W content there is a more uniform distribution of grains in the epoxy resin matrix could be observed. Agglomeration of W grains is noted for samples with filler content up to 40 %. Statistical analysis of the grain size of the initial W powder revealed that the probable diameter of W grains is 475 nm. The values of effective and relative densities of the experimental samples were obtained using the Archimedes method. The effective density varied from 1.16 to 4.36 g/cm3 with W powder content rising. The relative density values received ranged from 91 to 94 %, indica ting that there were no significant defects in the samples. X-ray diffraction analysis showed the presence of vcc-W and WO2 phases, indicating the oxidation of W in the thin surface layer of the powder. Calculation in Phy-X/PSD software allowed to evaluate the gamma radiation shielding efficiency for the epoxy resin–W system composite materials in 0.8–2.5 MeV energy range. It was observed that samples with filler content of 60 and 80 % were the most suitable for radiation shielding. It was found that the addition of W powder to the epoxy matrix contributed to the reduction of half attenuation layer values by 3.5 times from 9.448 to 2.672 cm for samples with 0 and 80 % W content, respectively, for 1.25 MeV radiation energy. The obtained results demonstrate the high efficiency of the proposed composite materials for shielding gamma radiation, which makes them a perspective candidate for manufacturing radiation shields.С использованием метода химического отверждения получены композиционные материалы на основе системы эпоксидная смола–W с варьированием содержания W от 0 до 80 %. Проведенное исследование микроструктуры образцов показало, что при увеличении содержания W наблюдается более равномерное распределение зерен в матрице эпоксидной смолы. Для образцов с содержанием наполнителя до 40 % отмечена агломерация зерен W. Статистический анализ размеров зерен исходного порошка W выявил, что вероятный их диаметр составляет 475 нм. Получены значения эффективной и относительной плотностей экспериментальных образцов с помощью метода Архимеда. Эффективная плотность изменялась в пределах от 1,16 до 4,36 г/см3 с увеличением содержания порошка W. Значения относительной плотности варьировались от 91 до 94 %, что свидетельствовало об отсутствии существенных дефектов при проведении испытания. Рентгеноструктурный анализ показал наличие фаз ОЦК-W и WO2, что указывает на окисление W в тонком поверхностном слое материала. Моделирование в программном обеспечении Phy-X/PSD позволило оценить эффективность экранирования от гамма-излучения композиционных материалов при энергии излучения в диапазоне 0,8–2,5 МэВ. Образцы с содержанием наполнителя 60 и 80 % оказались наиболее подходящими для создания экранов радиационной защиты. Обнаружено, что добавление порошка W в эпоксидную матрицу способствовало уменьшению значений слоя половинного ослабления в 3,5 раза с 9,448 до 2,672 см для образцов с содержанием W 0 и 80 % соответственно при энергии излучения гамма-квантов 1,25 МэВ. Полученные результаты демонстрируют высокую эффективность предложенных композиционных материалов в экранировании гамма-излучения, что делает их достойным вариантом для создания экранов радиационной защиты

Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach

We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases