117 research outputs found

    Cosmological models with interacting components and mass-varying neutrinos

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    A model for a homogeneous and isotropic spatially flat Universe, composed of baryons, radiation, neutrinos, dark matter and dark energy is analyzed. We infer that dark energy (considered to behave as a scalar field) interacts with dark matter (either by the Wetterich model, or by the Anderson and Carroll model) and with neutrinos by a model proposed by Brookfield et al.. The latter is understood to have a mass-varying behavior. We show that for a very-softly varying field, both interacting models for dark matter give the same results. The models reproduce the expected red-shift performances of the present behavior of the Universe.Comment: 8 pages, 5 figures, to be published in Gravitation and Cosmolog

    IFN-γ Production Depends on IL-12 and IL-18 Combined Action and Mediates Host Resistance to Dengue Virus Infection in a Nitric Oxide-Dependent Manner

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    Dengue is a mosquito-borne disease caused by one of four serotypes of Dengue virus (DENV-1–4). Severe dengue infection in humans is characterized by thrombocytopenia, increased vascular permeability, hemorrhage and shock. However, there is little information about host response to DENV infection. Here, mechanisms accounting for IFN-γ production and effector function during dengue disease were investigated in a murine model of DENV-2 infection. IFN-γ expression was greatly increased after infection of mice and its production was preceded by increase in IL-12 and IL-18 levels. In IFN-γ−/− mice, DENV-2-associated lethality, viral loads, thrombocytopenia, hemoconcentration, and liver injury were enhanced, when compared with wild type-infected mice. IL-12p40−/− and IL-18−/− infected-mice showed decreased IFN-γ production, which was accompanied by increased disease severity, higher viral loads and enhanced lethality. Blockade of IL-18 in infected IL-12p40−/− mice resulted in complete inhibition of IFN-γ production, greater DENV-2 replication, and enhanced disease manifestation, resembling the response seen in DENV-2-infected IFN-γ−/− mice. Reduced IFN-γ production was associated with diminished Nitric Oxide-synthase 2 (NOS2) expression and NOS2−/− mice had elevated lethality, more severe disease evolution and increased viral load after DENV-2 infection. Therefore, IL-12/IL-18-induced IFN-γ production and consequent NOS2 induction are of major importance to host resistance against DENV infection

    Isolation and genetic analysis of the chikungunya virus from Aedes aegypti and Aedes albopictus mosquitoes captured in Central America

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    Introduction. The habitat of mosquitoes belonging to the genera Aedes spp., Culex spp., Culiseta spp. is in South and Central America, including Nicaragua. Monitoring of the spread of mosquito vectors and assessment of the infection with arboviruses can provide information on possible occurrence of new diseases or an increase in the reported cases, changes in the infectivity of viruses for humans due to changes in pathogen transmitters. The purpose of this study was isolation and identification of arboviruses belonging to the Flavivirus and Alphavirus genera from A. albopictus, A. aegypti, Culiseta spp., Culex spp. mosquitoes captured in forests of Nicaragua. Materials and methods. A. albopictus, A. aegypti, Culiseta spp., Culex spp. mosquitoes were captured during the dry season in 2021 in forested areas of Nicaragua in four different locations. Mosquitoes were sorted into pools, each containing 5-8 mosquitoes (236 pools in total). Using the reverse transcription polymerase chain reaction, the pools were tested for the presence of chikungunya (CHIKV), dengue, Zika, and yellow fever viruses. Positive pools were inoculated into the C6/36 cell culture to obtain isolates and for their further sequencing. Results. The dengue virus was detected only in Aedes spp. mosquitoes: in 7 pools — A. aegypti, in 1 — A. albopictus. CHIKV was also detected only in Aedes spp. mosquitoes: in 3 pools — A. aegypti, in 1 — A. albopictus. The sequencing of nucleotide sequences of 6К, Е1, Е2, and NS1 genes of CHIKV isolated from A. albopictus mosquitoes showed that compared to the similar gene sequences from CHIKV isolates recovered from A. aegypti mosquitoes, the 6K gene region contained 4 nucleotide and 4 amino acid substitutions, while the E1 region contained 16 nucleotide substitutions, 10 of them led to amino acid substitutions; the E2 region contained 14 nucleotide and 11 amino acid substitutions; the NS1 region contained 33 nucleotide and 19 amino acid substitutions

    Possibilities of improving contrast for the measurements of the 131I volume concentration by scintillation γ-spectrometers

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    The main problem of measuring the 131I volume concentration (364-keV g-line) with gamma spectrometers with low-resolution scintillation detectors (NaI:Tl, CsI:Tl) is due to the overlap with the Compton edge (384 keV) from the attendant radiation of 76As. The problem can be largely eliminated by improving the energy resolution of the spectrometer, increasing the volume of the crystal, or using an anti-Compton spectrometer. Using the Monte Carlo simulation (GEANT4 package), the last two methods of increasing the contrast of instrumental energy spectra were investigated. It was found that an 8-fold increase in the scintillator volume improves the ratio of the 131I peak area to the area of the Compton continuum below it from the 76As radiation only by 1.42 times. Therefore, the main attention was paid to the comparative studies of the constructions of anti-Compton detectors based on CsI:Tl crystals in a detector-analyzer and a detector-protector. Several designs of anti-Compton detectors suitable for harsh application conditions at nuclear power plants were proposed. In the first of them, the protector crystal is in the form of a disk with a diameter equal to the diameter of the crystal analyzer, and in the second - in the form of a “glass” put on the crystal analyzer. The thickness of the protector crystals in both cases was 10 mm. The expected improvement in contrast with respect to the single-crystal design was up to 3 or more times. Modern nuclear electronics and computers make possible the successful application of this method in industrial spectrometric installations. The contrast of the resulting spectra could be increased by an order of magnitude or more in comparison with the simple anticoincidence spectra.Основная проблема измерения объемной концентрации 131I (g-линия 364 кэВ) гамма-спектрометрами со сцинтилляционными детекторами низкого разрешения (NaI:Tl, CsI:Tl) обусловлена перекрытием с комптоновским краем (384 кэВ) от сопутствующего излучения 76As. Проблема может быть в значительной степени устранена улучшением энергетического разрешения спектрометра, увеличением объема кристалла или использованием антикомптоновского спектрометра. С применением моделирования методом Монте-Карло (пакет GEANT4) были исследованы два последних способа увеличения контрастности аппаратурных энергетических спектров. Выяснено, что 8-кратное увеличение объема сцинтиллятора улучшает отношение площади пика 131I к площади комптоновского континуума под ним от излучения 76As лишь в 1.42 раза. Поэтому основное внимание было уделено сравнительным исследованиям конструкций антикомптоновских детекторов на основе кристаллов CsI:Tl в детекторе-анализаторе и детекторе-протекторе. Предложены варианты конструкций антикомптоновских детекторов, пригодных для жестких условий применения на АЭС. В первой из них кристалл-протектор в виде диска с диаметром равным диаметру кристалла-анализатора, а во второй – в виде “стакана”, надеваемого на кристалл-анализатор. Толщина кристаллов-протекторов в обоих случаях равна 10 мм. Ожидаемое улучшение контрастности по отношению к однокристальной конструкции может достигать трех и более раз. Намечены направления дальнейшего совершенствования двухкристальных спектрометров, предназначенных для мониторирования содержания в воздухе радионуклида 131I. Наиболее перспективным представляется известный с 1960-х годов аппаратно-программный метод, использующий вычитание из спектра антисовпадений (антикомптоновский спектр) части спектра совпадений. Современные ядерная электроника и компьютеры делают возможным успешное применение этого метода в промышленных спектрометрических установках. Контрастность результирующих спектров может быть увеличена на порядок и более по сравнению с простыми спектрами антисовпадений

    Молекулярно-генетическое исследование стабильности и подтверждение подлинности штамма Внуково-32, применяемого для производства вакцины антирабической культуральной концентрированной очищенной инактивированной сухой

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    Rabies is an acute viral disease caused by a virus of the Rhabdoviridae family of the Lyssavirus genus, which affects the central nervous system and is characterised by absolute mortality. Vaccination is the only way to prevent the disease in humans. One of the products used for vaccination is a cultural concentrated purified inactivated dry rabies vaccine produced by the Federal State Budgetary Institution of Science “Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences” (hereinafter—Chumakov Center).The aim of the study was to examine the structure of the working virus seed of Vnukovo-32 strain used by the Chumakov Center for rabies vaccine production, to assess its genetic stability during production, to explore the possibility of using molecular genetic methods for identification of the production strain in the finished dosage form, and to study the nucleotide sequence of the CVS strain.Materials and methods: Vnukovo-32 rabies virus production strain, working virus seeds, finished batches of the rabies vaccine, CVS fixed rabies virus strain used in the assessment of specific immunity. The molecular genetic study was performed using RT-PCR followed by restriction and sequencing.Results: the paper presents the results of nucleotide sequence analysis of the G gene fragment obtained from the Vnukovo-32 production strain, batches of the working virus seed, and finished batches of the rabies vaccine produced in 2012, 2018, and 2019, and the CVS fixed rabies virus strain used in the assessment of the vaccine’s specific immunity. The study demonstrated that restriction analysis could be used for Vnukovo-32 strain identification at all production stages, including the finished dosage form.Conclusion: Vnukovo-32 and CVS strains used by the Chumakov Center are rabies viruses. Analysis of the nucleotide sequence of the G gene fragment showed that the Vnukovo-32 strain remains stable throughout different production stages. The obtained nucleotide sequence of gene G of the Vnukovo-32 strain was deposited in GenBank (accession number MN116503). The study demonstrated that restriction analysis could be used for Vnukovo-32 strain identification at all production stages, including the finished dosage form. Бешенство – острая вирусная инфекция, вызываемая вирусом семейства Rhabdoviridae рода Lyssavirus и характеризующаяся симптомами поражения центральной нервной системы и абсолютной летальностью. Единственной возможностью предотвратить возникновение данного заболевания у людей является вакцинопрофилактика. Одним из препаратов, используемых в этих целях, является вакцина антирабическая культуральная концентрированная очищенная инактивированная сухая, выпускаемая ФГБНУ «ФНЦИРИП им. М. П. Чумакова РАН».Цель работы: исследование структуры производственного, рабочего посевного вируса бешенства штамма Внуково-32, используемого ФГБНУ «ФНЦИРИП им. М. П. Чумакова РАН» для производства антирабической вакцины, его генетической стабильности на этапах производства, изучение возможности применения молекулярно-генетических методов для подтверждения подлинности производственного штамма в готовой форме вакцины и изучение нуклеотидной последовательности штамма CVS.Материалы и методы: производственный штамм вируса бешенства Внуково-32, рабочие посевные вирусы, готовые серии вакцины антирабической, штамм CVS фиксированного вируса бешенства, используемый для оценки специфического иммунитета. Молекулярно-генетическое исследование проведено с использованием ОТ-ПЦР с последующей рестрикцией и секвенированием.Результаты: представлены результаты анализа нуклеотидных последовательностей фрагмента гена G, полученного из производственного штамма Внуково-32, серий рабочего посевного вируса и готовых серий вакцины антирабической, изготовленных в 2012, 2018, 2019 г., штамма фиксированного вируса бешенства CVS, используемого для оценки специфической активности вакцины. Показана возможность применения рестрикционного анализа для подтверждения подлинности штамма Внуково-32 на всех этапах производства, включая готовую форму вакцины.Заключение: штаммы Внуково-32 и CVS, используемые в ФГБНУ «ФНЦИРИП им. М. П. Чумакова РАН», являются вирусами бешенства. Анализ нуклеотидной последовательности фрагмента гена G показал, что штамм Внуково-32 стабилен на разных этапах производства. Полученная нуклеотидная последовательность гена G штамма Внуково-32 депонирована в GenBank (номер MN116503). Показана возможность применения рестрикционного анализа для подтверждения подлинности штамма Внуково-32 вируса бешенства на всех этапах производства, включая готовую форму вакцины

    Peptide Bβ15-42 Preserves Endothelial Barrier Function in Shock

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    Loss of vascular barrier function causes leak of fluid and proteins into tissues, extensive leak leads to shock and death. Barriers are largely formed by endothelial cell-cell contacts built up by VE-cadherin and are under the control of RhoGTPases. Here we show that a natural plasmin digest product of fibrin, peptide Bß15-42 (also called FX06), significantly reduces vascular leak and mortality in animal models for Dengue shock syndrome. The ability of Bß15-42 to preserve endothelial barriers is confirmed in rats i.v.-injected with LPS. In endothelial cells, Bß15-42 prevents thrombin-induced stress fiber formation, myosin light chain phosphorylation and RhoA activation. The molecular key for the protective effect of Bß15-42 is the src kinase Fyn, which associates with VE-cadherin-containing junctions. Following exposure to Bß15-42 Fyn dissociates from VE-cadherin and associates with p190RhoGAP, a known antagonists of RhoA activation. The role of Fyn in transducing effects of Bß15-42 is confirmed in Fyn−/− mice, where the peptide is unable to reduce LPS-induced lung edema, whereas in wild type littermates the peptide significantly reduces leak. Our results demonstrate a novel function for Bß15-42. Formerly mainly considered as a degradation product occurring after fibrin inactivation, it has now to be considered as a signaling molecule. It stabilizes endothelial barriers and thus could be an attractive adjuvant in the treatment of shock
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