Extracellular vesicles (EVs) contain a variety of biomolecules and provide information about the cells that produce them. EVs from cancer cells found in urine can be used as biomarkers to detect ...cancer, enabling early diagnosis and treatment. The potential of alpha-2-macroglobulin (A2M) and clusterin (CLU) as novel diagnostic urinary EV (uEV) biomarkers for bladder cancer (BC) was demonstrated previously. To validate the diagnostic value of these proteins in uEVs in a large BC cohort, urine handling conditions before uEV isolation should be optimized during sample transportation from medical centers. In this study, we analyzed the uEV protein quantity, EV particle number, and uEV-A2M/CLU after urine storage at 20°C and 4°C for 0–6 days, each. A2M and CLU levels in uEVs were relatively stable when stored at 4°C for a maximum of three days and at 20°C for up to 24 h, with minimal impact on analysis results. Interestingly, pre-processing to remove debris and cells by centrifugation and filtration of urine did not show any beneficial effects on the preservation of protein biomarkers of uEVs during storage. Here, the importance of optimizing shipping conditions to minimize the impact of pre-analytical handling on the uEVs protein biomarkers was emphasized. These findings provide insights for the development of clinical protocols that use uEVs for diagnostic purposes.
Defining architectural shapes and then clarifying their geometric differences has always been a demanding task.. There appears to be relatively few research papers on the description of the definite ...geometric properties in architectural shapes. This research proposes methods for quantitatively describing an architectural shape as the degree to which they represent the three primary shapes of circles, triangles and squares. History has ensured that the shapes are regarded as primary ones, but any shape can also be viewed as one of them. A series of automated models that gradually deform the basic shapes into other forms have been developed to identify and verify the best methods for describing the architectural forms. The three architectural shape descriptors, referred to as "circularity", "triangularity" and "squareness", produce the second index of "shape deformity", measuring the degree of how a shape is deformed from the primary shapes. This measurement makes it possible to investigate the degree to which a particular type of primary shape is dominant among those three primary shape descriptions. These shape description techniques were tested on 60 shapes consisting of the facades and floor plans of 30 well-known buildings.
To increase their efficiency and improve their chemical stability, hybrid organic–inorganic perovskites (HOIPs) have been studied intensely over the past few years. There are some unresolved issues ...with the properties of HOIPs, such as the relation between the configuration of methylammonium (MA) ions and their electronic and structural properties. For example, it was theoretically proposed that the change in the bandgap from direct to indirect and/or structural distortion can be caused by a change in the orientation of the MA ions with respect to the PbX3 cage in CH3NH3PbX3 (X = I, Br, or Cl). By using polarized Raman scattering spectroscopy, we experimentally show that the MA ions in CH3NH3PbCl3 single crystals are parallelly oriented toward a special crystallographic direction in the low-temperature orthorhombic phase at least on our measurement scale of approximately square micrometers. Experimental measurement results verified by density functional theory calculations indicate the presence of a macroscopic domain consists of a parallel directional alignment of the MA ions, a strong signature of ferroelectricity in HOIPs.
High-mobility group box 1 (HMGB1) is a protein that binds to DNA and participates in various cellular processes, including DNA repair, transcription, and inflammation. It is also associated with ...cancer progression and therapeutic resistance. Despite its known role in promoting tumor growth and immune evasion in the tumor microenvironment, the contribution of HMGB1 to the development of Kaposi's sarcoma (KS) is not well understood. We investigated the effect of HMGB1 on KS pathogenesis using immortalized human endothelial cells infected with Kaposi's sarcoma-associated human herpes virus (KSHV). Our results showed that a higher amount of HMGB1 was detected in the supernatant of KSHV-infected cells compared to that of mock-infected cells, indicating that KSHV infection induced the secretion of HMGB1 in human endothelial cells. By generating HMGB1 knockout clones from immortalized human endothelial cells using CRISPR/Cas9, we elucidated the role of HMGB1 in KSHV-infected endothelial cells. Our findings indicate that the absence of HMGB1 did not induce lytic replication in KSHV-infected cells, but the cell viability of KSHV-infected cells was decreased in both 2D and 3D cultures. Through the antibody array for cytokines and growth factors, CXCL5, PDGF-AA, G-CSF, Emmprin, IL-17A, and VEGF were found to be suppressed in HMGB1 KO KSHV-infected cells compared to the KSHV-infected wild-type control. Mechanistically, phosphorylation of p38 would be associated with transcriptional regulation of CXCL5, PDGF-A and VEGF. These observations suggest that HMGB1 may play a critical role in KS pathogenesis by regulating cytokine and growth factor secretion and emphasize its potential as a therapeutic target for KS by modulating the tumor microenvironment.
The object of visual experiences in three-dimensional built environments can be considered as a collection of surfaces that are recognized by the human senses. This study suggests a way to interpret ...mutual visual relationships of surfaces based on the visual amount of light that reflects between surfaces. For this purpose, Three-dimensional Visibility Analysis (TVA) has been created as a platform for understanding the architectural implications of visual experiences in three-dimensional built environments by classifying the visual experiences into seven indices and quantifying them. We first examined the architectural meaning of each visual index through simple models to comprehend how visual relations operate between objects′ surfaces and explored the visual properties of the three-dimensional built environments and their architectural significance in them. Two types of case studies using these visibility indices were undertaken to investigate their objective meanings and to provide potential applications that might be adoptable for practical applications of the built environment, as well as to find associations with how these factors are affected by the social behavior that occurs in it.
Tetrodotoxin (TTX) poisoning through the consumption of contaminated fish leads to lethal symptoms, including severe hypotension. This TTX-induced hypotension is likely due to the downfall of ...peripheral arterial resistance through direct or indirect effects on adrenergic signaling. TTX is a high-affinity blocker of voltage-gated Na
(Na
) channels. In arteries, Na
channels are expressed in sympathetic nerve endings, both in the intima and media. In this present work, we aimed to decipher the role of Na
channels in vascular tone using TTX. We first characterized the expression of Na
channels in the aorta, a model of conduction arteries, and in mesenteric arteries (MA), a model of resistance arteries, in C57Bl/6J mice, by Western blot, immunochemistry, and absolute RT-qPCR. Our data showed that these channels are expressed in both endothelium and media of aorta and MA, in which
and
were the most abundant transcripts, suggesting that murine vascular Na
channels consist of Na
1.2 channel subtype with Na
β1 auxiliary subunit. Using myography, we showed that TTX (1 µM) induced complete vasorelaxation in MA in the presence of veratridine and cocktails of antagonists (prazosin and atropine with or without suramin) that suppressed the effects of neurotransmitter release. In addition, TTX (1 µM) strongly potentiated the flow-mediated dilation response of isolated MA. Altogether, our data showed that TTX blocks Na
channels in resistance arteries and consecutively decreases vascular tone. This could explain the drop in total peripheral resistance observed during mammal tetrodotoxications.
Neonicotinoid insecticides are nicotine-derived molecules which exert acute neurotoxic effects over the insect central nervous system by activating nicotinic acetylcholine receptors (nAChRs). ...However, these receptors are also present in the mammalian central and peripheral nervous system, where the effects of neonicotinoids are faintly known. In mammals, cholinergic synapses are crucial for the control of vascular tone, blood pressure and skeletal muscle contraction. We therefore hypothesized that neonicotinoids could affect cholinergic networks in mammals and sought to highlight functional consequences of acute intoxication in rats with sub-lethal concentrations of the highly used acetamiprid (ACE) and clothianidin (CLO). In this view, we characterized their electrophysiological effects on rat α3β4 nAChRs, knowing that it is predominantly expressed in ganglia of the vegetative nervous system and the adrenal medulla, which initiates catecholamine secretion. Both molecules exhibited a weak agonist effect on α3β4 receptors. Accordingly, their influence on epinephrine secretion from rat adrenal glands was also weak at 100 μM, but it was stronger at 500 μM. Challenging ACE or CLO together with nicotine (NIC) ended up with paradoxical effects on secretion. In addition, we measured the rat arterial blood pressure (ABP) in vivo by arterial catheterization. As expected, NIC induced a significant increase in ABP. ACE and CLO did not affect the ABP in the same conditions. However, simultaneous exposure of rats to both NIC and ACE/CLO promoted an increase of ABP and induced a biphasic response. Modeling the interaction of ACE or CLO on α3β4 nAChR is consistent with a binding site located in the agonist pocket of the receptor. We present a transversal experimental approach of mammal intoxication with neonicotinoids at different scales, including in vitro, ex vivo, in vivo and in silico. It paves the way of the acute and chronic toxicity for this class of insecticides on mammalian organisms.
Thanks to the crosstalk between Na+ and Ca2+ channels, Na+ and Ca2+ homeostasis interplay in so-called excitable cells enables the generation of action potential in response to electrical ...stimulation. Here, we investigated the impact of persistent activation of voltage-gated Na+ (NaV) channels by neurotoxins, such as veratridine (VTD), on intracellular Ca2+ concentration (Ca2+i) in a model of excitable cells, the rat pituitary GH3b6 cells, in order to identify the molecular actors involved in Na+-Ca2+ homeostasis crosstalk. By combining RT-qPCR, immunoblotting, immunocytochemistry, and patch-clamp techniques, we showed that GH3b6 cells predominantly express the NaV1.3 channel subtype, which likely endorses their voltage-activated Na+ currents. Notably, these Na+ currents were blocked by ICA-121431 and activated by the β-scorpion toxin Tf2, two selective NaV1.3 channel ligands. Using Fura-2, we showed that VTD induced a Ca2+i increase. This effect was suppressed by the selective NaV channel blocker tetrodotoxin, as well by the selective L-type CaV channel (LTCC) blocker nifedipine. We also evidenced that crobenetine, a NaV channel blocker, abolished VTD-induced Ca2+i elevation, while it had no effects on LTCC. Altogether, our findings highlight a crosstalk between NaV and LTCC in GH3b6 cells, providing a new insight into the mode of action of neurotoxins.
Wrong: Acknowledgement This work was supported by the Korea Research Foundation Grant funded by the Korean Government (2015R1D1A1A01059898). Correct: Acknowledgement This study was supported by ...research fund from Chosun University, 2014.
Ellobium chinense is an airbreathing, pulmonate gastropod species that inhabits saltmarshes in estuaries of the northwestern Pacific. Due to a rapid population decline and their unique ecological ...niche in estuarine ecosystems, this species has attracted special attention regarding their conservation and the genomic basis of adaptation to frequently changing environments. Here we report a draft genome assembly of E. chinense with a total size of 949.470 Mb and a scaffold N50 of 1.465 Mb. Comparative genomic analysis revealed that the GO terms enriched among four gastropod species are related to signal transduction involved in maintaining electrochemical gradients across the cell membrane. Population genomic analysis using the MSMC model for 14 re-sequenced individuals revealed a drastic decline in Korean and Japanese populations during the last glacial period, while the southern Chinese population retained a much larger effective population size (N
). These contrasting demographic changes might be attributed to multiple environmental factors during the glacial-interglacial cycles. This study provides valuable genomic resources for understanding adaptation and historical demographic responses to climate change.
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