101 research outputs found

    Stochastic phenomena in pattern formation for distributed nonlinear systems

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    We study a stochastic spatially extended population model with diffusion, where we find the coexistence of multiple non-homogeneous spatial structures in the areas of Turing instability. Transient processes of pattern generation are studied in detail. We also investigate the influence of random perturbations on the pattern formation. Scenarios of noise-induced pattern generation and stochastic transformations are studied using numerical simulations and modality analysis. © 2020 The Author(s) Published by the Royal Society. All rights reserved.Russian Science Foundation, RSF: 16-11-10098Data accessibility. This article has no additional data. Authors’ contributions. All authors contributed equally. Competing interests. We declare we have no competing interests. Funding. The work was supported by the Russian Science Foundation (grant no. 16-11-10098)

    Sequential Metabolism of 7-Dehydrocholesterol to Steroidal 5,7-Dienes in Adrenal Glands and Its Biological Implication in the Skin

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    Since P450scc transforms 7-dehydrocholesterol (7DHC) to 7-dehydropregnenolone (7DHP) in vitro, we investigated sequential 7DHC metabolism by adrenal glands ex vivo. There was a rapid, time- and dose-dependent metabolism of 7DHC by adrenals from rats, pigs, rabbits and dogs with production of more polar 5,7-dienes as detected by RP-HPLC. Based on retention time (RT), UV spectra and mass spectrometry, we identified the major products common to all tested species as 7DHP, 22-hydroxy-7DHC and 20,22-dihydroxy-7DHC. The involvement of P450scc in adrenal metabolic transformation was confirmed by the inhibition of this process by DL-aminoglutethimide. The metabolism of 7DHC with subsequent production of 7DHP was stimulated by forscolin indicating involvement of cAMP dependent pathways. Additional minor products of 7DHC metabolism that were more polar than 7DHP were identified as 17-hydroxy-7DHP (in pig adrenals but not those of rats) and as pregna-4,7-diene-3,20-dione (7-dehydroprogesterone). Both products represented the major identifiable products of 7DHP metabolism in adrenal glands. Studies with purified enzymes show that StAR protein likely transports 7DHC to the inner mitochondrial membrane, that 7DHC can compete effectively with cholesterol for the substrate binding site on P450scc and that the catalytic efficiency of 3βHSD for 7DHP (Vm/Km) is 40% of that for pregnenolone. Skin mitochondria are capable of transforming 7DHC to 7DHP and the 7DHP is metabolized further by skin extracts. Finally, 7DHP, its photoderivative 20-oxopregnacalciferol, and pregnenolone exhibited biological activity in skin cells including inhibition of proliferation of epidermal keratinocytes and melanocytes, and melanoma cells. These findings define a novel steroidogenic pathway: 7DHC→22(OH)7DHC→20,22(OH)27DHC→7DHP, with potential further metabolism of 7DHP mediated by 3βHSD or CYP17, depending on mammalian species. The 5–7 dienal intermediates of the pathway can be a source of biologically active vitamin D3 derivatives after delivery to or production in the skin, an organ intermittently exposed to solar radiation

    Estrogen Alters the Splicing of Type 1 Corticotropin-Releasing Hormone Receptor in Breast Cancer Cells

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    Hormonal stress response is associated with the pathogenesis of disease, including cancer. The role of the stress hormone CRH (corticotropin-releasing hormone) in breast cancer is complex, and its abundance and biological activity may be modulated by estrogen. In the estrogen receptor–positive (ER+) malignant mammary epithelial cell line MCF7, CRH activated numerous kinases and downstream effectors, at least some of which were mediated by the CRH receptor type 1 (CRH-R1). CRH also increased the transcription of many genes that encode effectors, transcriptional targets, or regulators associated with estrogen signaling. Estrogen increased the abundance of the mRNA encoding CRH-R2 and an alternative splice variant encoding CRH-R1 in which exon 12 was deleted [CRH-R1(Δ12)]. Estrogen inhibited the expression SRSF6, which encodes serine/arginine-rich splicing factor 55 (SRp55). An increase in CRH-R1(Δ12), in response to either estrogen or SRp55 knockdown, dampened the cellular response to CRH and prevented its inhibitory effects on cell invasion. SRp55 knockdown also induced additional splicing events within exons 9 to 12 of CRH-R1, whereas overexpression of SRp55 prevented estrogen-induced generation of CRH-R1(Δ12). ER+ breast tumors had increased CRH-R2 and CRH-R1(Δ12) mRNA abundance, which was associated with decreased abundance of the mRNA encoding SRp55, compared with the amounts in ER– tumors, suggesting that estrogen contributes to the pathophysiology of ER+ breast cancer by altering CRH receptor diversity and disrupting CRH-mediated signaling

    Обзор наиболее важных достижений в технологии магнитоэнцефалографии

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    Original manuscript received February 04, 2021. Revised manuscript accepted June 26, 2021. First published online October 25, 2021.The overview of the latest advances in magnetoencephalography (MEG) technology, including the development of optically pumped magnetometers (OPM), is presented. The main advantage of OPM over conventional superconducting quantum interference devices (SQUID) is the absence of cryogenic cooling, which reduces the cost of equipment by 2–3 times. Moreover, the OPM can be positioned a few millimeters from the scalp, which roughly doubles the signal-to-noise ratio. In addition, they are not as susceptible to muscle artifacts as electroencephalography (EEG) signals. Moreover, placing the OPM in a nulling magnetic field reduces the effects of head movement artifacts in the surrounding field. All these advantages open up great potential for the development of a new generation of OPMbased brain-computer interfaces (BCIs) that are cheaper, more flexible and more responsive than SQUID-based BCIs, which can perform both motor and non-motor tasks. Despite the tremendous progress made over the past few years, OPM–MEG is still an evolving technology that requires further improvement. Due to the large size of the sensors, the number of channels is relatively small (less than 50), so they cannot cover the entire head. Although many BCI applications require only a few sensors, their correct placement in selected areas of the scalp is very important. The miniaturization and versatility of lightweight helmets could be an important step towards the further development of OPM for BCI and other applications.Представлен обзор новейших достижений в технологии магнитоэнцефалографии (MEG), включая разработку магнитометров с оптической накачкой (OPM). Основным преимуществом OPM перед обычными сверхпроводящими квантовыми интерференционными устройствами (SQUID) является отсутствие криогенного охлаждения, что снижает стоимость оборудования в 2–3 раза. OPM можно расположить на расстоянии нескольких миллиметров от кожи головы, что примерно вдвое увеличивает соотношение сигнал/шум. Кроме того, они не так восприимчивы к мышечным артефактам, как сигналы электроэнцефалографии (ЭЭГ). Размещение OPM в обнуляющем магнитном поле снижает влияние артефактов движения головы в окружающем поле. Все эти преимущества открывают большой потенциал для разработки нового поколения интерфейсов мозг — компьютер (BCI) на основе OPM, они дешевле, гибче и чувствительнее, чем BCI на основе SQUID, которые могут выполнять как моторные, так и немоторные задачи. Несмотря на огромный прогресс, достигнутый за последние несколько лет, OPM–MEG все еще является развивающейся технологией, требующей дальнейшего совершенствования. Из-за большого размера датчиков количество каналов относительно невелико (менее 50), поэтому они не могут покрыть всю голову. Для многих приложений BCI требуется всего несколько датчиков, но при этом очень важно правильно разместить их в выбранных областях черепа. Миниатюризация и универсальность легких шлемов может стать важным шагом на пути дальнейшего развития OPM для BCI и других приложений

    Strange periodic attractor: Extremely high stochastic sensitivity of a parametrically modulated system

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    Periodical parametric modulation in a chaotic system induces a periodic orbit with a negative global Lyapunov exponent. However, the local Lyapunov exponent takes positive values during certain time intervals in the cycle. The stochastic sensitivity analysis of this strange periodic attractor reveals its extremely high sensitivity to noise. For relatively slow modulation, the stochastic sensitivity function (SSF) reaches the values of 1050 in the time intervals where the local Lyapunov exponent is positive, whereas in the region of the negative exponent it is 1. Such extraordinary stochastic sensitivity can be used for creating sensors to detect very small disturbances or noise, based on parametrically modulated chaotic systems with strange periodic attractors
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