Shock waves play an important role in turbulent astrophysical media by compressing the gas and dissipating the turbulent energy into the thermal energy. Here, we study shocks in magnetohydrodynamic ...turbulence using high-resolution simulations. Turbulent Mach numbers of and initial magnetic fields of plasma beta β0 = 0.1-10 are considered, targeting turbulences in interstellar and intracluster media. Specifically, we present the statistics of fast and slow shocks, such as the distribution of shock Mach numbers (Ms) and the energy dissipation at shocks, based on refined methodologies for their quantifications. While most shocks form with low Ms, strong shocks follow exponentially decreasing distributions of Ms. More shocks appear for larger and larger β0. Fast shock populations dominate over slow shocks if β0 > 1, but substantial populations of slow shocks develop in the cases of β 1, i.e., strong background fields. The shock dissipation of turbulent energy occurs preferentially at fast shocks with Ms of a few to several, and the dissipation at strong shocks shows exponentially decreasing functions of Ms. The energy dissipation at shocks, normalized to the energy injection, ϵshock/ϵinj, is estimated to be in the range of ∼0.1-0.5, except for the case of and β0 = 0.1, where the shock dissipation is negligible. The fraction decreases with it is close to ∼0.4-0.6 for , while it is ∼0.1-0.25 for . The rest of the turbulent energy is expected to dissipate through the turbulent cascade. Our work will add insights into the interpretations of physical processes in turbulent interstellar and intracluster media.
Oxidative stresses caused by reactive oxygen species (ROS) can induce rapid depolarization of inner mitochondrial membrane potential and subsequent impairment of oxidative phosphorylation. Damaged ...mitochondria produce more ROS, especially the superoxide anion (O(2)(-)) and hydrogen peroxide (H(2)O(2)), which potentiate mitochondria-driven ROS propagation, so-called ROS-induced ROS release (RIRR), via activation of an inter-mitochondria signaling network. Therefore, loss of function in only a fraction of mitochondria might eventually affect cell viability through this positive feedback loop. Since ROS are very short-lived molecules in the biological milieu, mitochondrial network dynamics, such as density, number, and spatial distribution, can affect mitochondria-driven ROS propagation. To address this issue, we developed a mathematical model using an agent-based modeling approach, and tested the effect of mitochondrial network dynamics on RIRR for mitochondria under various conditions. Simulation results show that the intracellular ROS signaling pattern, such as ROS propagation speed and oxidative stress vulnerability, are critically affected by mitochondrial network dynamics. Mitochondrial network dynamics of mitochondrial distribution, density, activity, and size can mediate inter-mitochondrial signaling under certain conditions and determine the identity of the ROS signaling pattern. We further elucidated the potential mechanism of these actions, i.e., conversion of major messenger molecules involved in ROS signaling. If the average distance between neighboring mitochondria is large or mitochondrial distribution becomes randomized, messenger molecule of the ROS signaling network can be switched from O(2)(-) to H(2)O(2). In this case, mitochondria-driven ROS propagation is efficiently blocked by introduction of excess cytosolic glutathione peroxidase 1, while introduction of cytosolic superoxide dismutase has no effect. Together, these results suggest that mitochondrial network dynamics is a major determinant for cellular responses to RIRR through changing the key messenger molecules.
In this study, deep eutectic solvents (DESs) were synthesized using different ratios of choline chloride (CC) and dicarboxylic acids, and their eutectic temperatures were determined. The DES ...synthesized using CC and glutaric acid (GA), which showed a higher extraction efficiency than conventional solvents, was used for the extraction of flavonoid components from
leaves (PUL), and the extraction efficiency was evaluated using the response surface methodology. The flavonoid components rutin, hyperoside, and isoquercitrin were identified through high-performance liquid chromatography (HPLC), equipped with a Waters 2996 PDA detector, and HPLC mass spectrometry (LC-MS/MS) analyses. The optimum extraction was achieved at a temperature of 30 °C using DES in a concentration of 30.85 wt.% at a stirring speed of 1113 rpm and an extraction time of 1 h. The corresponding flavonoid content was 217.56 μg/mL. The results were verified by performing three reproducibility experiments, and a high significance, with a confidence range of 95%, was achieved. In addition, the PUL extracts exhibited appreciable antioxidant activity. The results showed that the extraction process using the DES based on CC and GA in a 1:1 molar ratio could effectively improve the yield of flavonoids from PUL.
Strand selection is a critical step in microRNA (miRNA) biogenesis. Although the dominant strand may change depending on cellular contexts, the molecular mechanism and physiological significance of ...such alternative strand selection (or “arm switching”) remain elusive. Here we find miR-324 to be one of the strongly regulated miRNAs by arm switching and identify the terminal uridylyl transferases TUT4 and TUT7 to be the key regulators. Uridylation of pre-miR-324 by TUT4/7 re-positions DICER on the pre-miRNA and shifts the cleavage site. This alternative processing produces a duplex with a different terminus from which the 3′ strand (3p) is selected instead of the 5′ strand (5p). In glioblastoma, the TUT4/7 and 3p levels are upregulated, whereas the 5p level is reduced. Manipulation of the strand ratio is sufficient to impair glioblastoma cell proliferation. This study uncovers a role of uridylation as a molecular switch in alternative strand selection and implicates its therapeutic potential.
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•Arm switching of miR-324 is regulated by terminal uridylyl transferases•TUT4 and TUT7 uridylate pre-miR-324, resulting in alternative processing by DICER•The altered cleavage leads to selection of the 3p strand instead of the 5p strand•Perturbation of the miR-324 arm usage disrupts glioblastoma cell proliferation
Alternative strand selection (or “arm switching”) of miRNAs takes place depending on cellular context, but its molecular mechanism is unknown. Kim et al. identify miR-324 as one of the prominently regulated miRNAs by arm switching and reveal the mechanism involving uridylation.
Epigallocatechin gallate (EGCG) is a catechin and an abundant polyphenol in green tea. Although several papers have evaluated EGCG as a cosmetic constituent, the skin hydration effect of EGCG is ...poorly understood. We aimed to investigate the mechanism by which EGCG promotes skin hydration by measuring
(
) and
(
) gene expression and antioxidant and anti-pigmentation properties using cell proliferation assay, Western blotting analysis, luciferase assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and reverse transcription polymerase chain reaction (RT-PCR) analysis. RT-PCR showed that EGCG increased the expression of natural moisturizing factor-related genes
(
),
,
, and
. Under UVB irradiation conditions, the expression level of
was decreased in HaCaT cells. Furthermore, we confirmed the antioxidant activity of EGCG and also showed a preventive effect against radical-evoked apoptosis by downregulation of caspase-8 and -3 in HaCaT cells. EGCG reduced melanin secretion and production in melanoma cells. Together, these results suggest that EGCG might be used as a cosmetic ingredient with positive effects on skin hydration, moisture retention, and wrinkle formation, in addition to radical scavenging activity and reduction of melanin generation.
Three flavone derivatives, 3,4′,5,7‐tetrahydroxyflavone (3,4′,5,7‐THF) and their glycosides 3,4′,5,7‐tetrahydroxyflavone‐3‐rhamnoglucoside, and 3,4′,5,7‐tetrahydroxyflavone‐3‐glucoside, were ...identified by partial enzymatic conversion of Camellia sinensis seed extract (CSSE). 2,2‐Diphenyl‐1‐picrylhydrazyl radical scavenging activity of these compounds and lipid peroxidation inhibition effects of 3.4′,5,7‐THF were tested to evaluate their antioxidant properties. To investigate the effects of 3,4′,5,7‐THF on squalene monohydroperoxide (SQLOOH)‐induced wrinkle formation, the dorsal skin of SKH1 hairless mice was used. Four weeks of treatment with 3,4′,5,7‐THF reduced wrinkle formation, in contrast to that observed in the group treated with SQLOOH only. A green and simple method has been suggested for the extraction of 3,4′,5,7‐THF from CSSE hydrolysate with nine deep eutectic solvents. A mixture of choline chloride and xylose yielded the best extraction result. These findings suggest that 3,4′,5,7‐THF is a natural compound with potential application in preventing SQLOOH associated skin aging.
Squalene is the most abundant oxidative component of skin surface lipids and is activated by UV exposure. Products of squalene oxidation lead to adverse skin conditions. Therefore, preventing squalene oxidation‐induced skin damage can promote general skin health in the human population. This study was to examine whether 3,4′,5,7‐THF possesses the potential to ameliorate the skin damage caused by SQLOOH in a hairless mouse model and to investigate the enzymatic hydrolysis of flavonoid glycosides in Camellia sinensis seed extract (CSSE) for preparing 3,4′,5,7‐THF by treatment with commercial enzymes. In addition, to isolate 3,4′,5,7‐THF from the CSSE hydrolysate in an environmentally friendly manner, an effective DES candidate was presented by testing the carbohydrate‐based DES by comparing its efficiency with that of the conventional solvent.
Loss of contractility and acquisition of an epithelial phenotype of vascular smooth muscle cells (VSMCs) are key events in proliferative vascular pathologies such as atherosclerosis and ...post-angioplastic restenosis. There is no proper cell culture system allowing differentiation of VSMCs so that it is difficult to delineate the molecular mechanism responsible for proliferative vasculopathy. We investigated whether a micropatterned substrate could restore the contractile phenotype of VSMCs in vitro. To induce and maintain the differentiated VSMC phenotype in vitro, we introduced a micropatterned groove substrate to modulate the morphology and function of VSMCs. Later than 7(th) passage of VSMCs showed typical synthetic phenotype characterized by epithelial morphology, increased proliferation rates and corresponding gene expression profiles; while short-term culture of these cells on a micropatterned groove induced a change to an intermediate phenotype characterized by low proliferation rates, increased migration, a spindle-like morphology associated with cytoskeletal rearrangement and expression of muscle-specific genes. Microarray analysis showed preferential expression of contractile and smooth muscle cell-specific genes in cells cultured on the micropatterned groove. Culture on a patterned groove may provide a valuable model for the study the role of VSMCs in normal vascular physiology and a variety of proliferative vascular diseases.
Immunopathogenesis of ANCA-Associated Vasculitis Kronbichler, Andreas; Lee, Keum Hwa; Denicolò, Sara ...
International journal of molecular sciences,
10/2020, Letnik:
21, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder which affects small- and, to a lesser degree, medium-sized vessels. ANCA-associated vasculitis encompasses ...three disease phenotypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). This classification is largely based on clinical presentations and has several limitations. Recent research provided evidence that genetic background, risk of relapse, prognosis, and co-morbidities are more closely related to the ANCA serotype, proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, compared to the disease phenotypes GPA or MPA. This finding has been extended to the investigation of biomarkers predicting disease activity, which again more closely relate to the ANCA serotype. Discoveries related to the immunopathogenesis translated into clinical practice as targeted therapies are on the rise. This review will summarize the current understanding of the immunopathogenesis of ANCA-associated vasculitis and the interplay between ANCA serotype and proposed disease biomarkers and illustrate how the extending knowledge of the immunopathogenesis will likely translate into development of a personalized medicine approach in the management of ANCA-associated vasculitis.
Vascular endothelial growth factor (VEGF) signaling is a key pathway for angiogenesis and requires highly coordinated regulation. Although the Notch pathway-mediated suppression of excessive VEGF ...activity via negative feedback is well known, the positive feedback control for augmenting VEGF signaling remains poorly understood. Transcription factor Sox17 is indispensable for angiogenesis, but its association with VEGF signaling is largely unknown. The contribution of other Sox members to angiogenesis also remains to be determined.
To reveal the genetic interaction of Sox7, another Sox member, with Sox17 in developmental angiogenesis and their functional relationship with VEGF signaling.
Sox7 is expressed specifically in endothelial cells and its global and endothelial-specific deletion resulted in embryonic lethality with severely impaired angiogenesis in mice, substantially overlapping with Sox17 in both expression and function. Interestingly, compound heterozygosity for Sox7 and Sox17 phenocopied vascular defects of Sox7 or Sox17 homozygous knockout, indicating that the genetic cooperation of Sox7 and Sox17 is sensitive to their combined gene dosage. VEGF signaling upregulated both Sox7 and Sox17 expression in angiogenesis via mTOR pathway. Furthermore, Sox7 and Sox17 promoted VEGFR2 (VEGF receptor 2) expression in angiogenic vessels, suggesting a positive feedback loop between VEGF signaling and SoxF.
Our findings demonstrate that SoxF transcription factors are indispensable players in developmental angiogenesis by acting as positive feedback regulators of VEGF signaling.
As is the case with other emerging technologies, commercializing blockchain technology via business models can provide radical opportunities for innovation. Existing studies on blockchain-service ...businesses lack research on how to develop business model ideas systematically; this study proposes a methodical process for generating these new ideas. Blockchain technology features were organized from the perspective of idea generation and leveraged to solve customer requirements. Through workshops, six business ideas were generated and evaluated by 26 experts. The proposed process proved it could generate innovative and qualitative ideas and could, thus, help business planners who are looking to generate new blockchain-service business model ideas.
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