In this study, Gaussian mixture model clustering analysis was carried out to examine characteristics of Global Precipitation Measurement (GPM) Dual‐frequency Precipitation Radar (DPR)‐retrieved ...mass‐weighted mean diameter (Dm), and normalized intercept parameter (Nw) of the drop size distribution (DSD) for heavy rainfalls (>10 mm h−1) for 6 years (2014–2019). Three objective DSD types – continental, oceanic deep, and oceanic shallow convective types – emerged. The means and standard deviations of Dm and Nw obtained for the three types are in good agreement with various ground‐based observations, indicating that global view of DSD characteristics can be obtained from DPR‐derived DSD parameters. Global distributions of occurrence and contribution of each DSD type to total heavy rainfall are produced for the first time, which will help examine the dominant DSD type, its contribution to total heavy rainfall, and composition of different convective types in the rainfall system at a given location.
Plain Language Summary
The surface rainfall is composed of a variety of spectrum of raindrops, which can be best represented by mean drop size and number concentration of droplets. Thus, those magnitude and shape may well describe rainfall‐related features such as convective type and associated atmospheric environments. Thus, information on the rain drop size distribution is important for improving the remote sensing capability or modeling the rainfall phenomena. From the analysis of satellite‐derived rain drop size distribution, it is noted that the heavy rainfall can be largely classified into three types – continental, oceanic deep, and oceanic shallow convective types. Satellite‐derived mean diameter and drop size distribution for heavy rain are found to be very consistent with ground observations from limited local areas, indicating that the global view of drop size distributions can be synthesized from the satellite observations. The newly obtained global features overcome the spatial limitations of existing studies using ground‐based observations. Furthermore, estimated contribution to the heavy rainfall from each classified type shows that a largest portion is from the oceanic deep convective type, and the oceanic shallow convective type contributes as much as the continental type.
Key Points
Global synthesis of drop size distributions for heavy rainfall using satellite‐borne radar measurements
Three heavy rainfall types emerged – continental, oceanic deep, and oceanic shallow convective types
Geographic distributions of occurrence frequencies and rain contributions of three types are presented
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This study investigated the effects of psychological skills training (PST) in shooters psychophysiologically using heart rate variability (HRV) in addition to psychological questionnaires and ...participant interviews. Five junior pistol shooters participated in an 8-week PST program consisting of a group session per week followed by individual counseling. Before and after PST, we collected electrocardiography data during rest, mental imagery of sport-related crisis situations, and successful performance, to analyze differences in HRV indices. Participants also responded to the Psychological Skills Inventory for Archery and Shooting (PSIAS), Intrinsic Motivation Inventory (IMI), Sports Anxiety Scale (SAS), and Trait Sport Confidence Inventory (TSCI). Results showed that the perceived competence (pre: 2.52 ± 0.95, post: 3.36 ± 0.73,
= 0.049) and trait sport confidence (pre: 4.94 ± 1.17, post: 6.60 ± 0.65,
= 0.049) significantly improved after PST. The analysis of HRV indicated that the ratio of low-frequency power to high-frequency power (LF/HF ratio) decreased significantly during imagery of crisis (pre: 3.4 ± 2.3, post: 1.014 ± 0.71,
= 0.038) and success (pre: 1.933 ± 0.917, post: 0.988 ± 0.572,
= 0.046), reflecting a strengthened autonomic nervous system's responsiveness to stress. Our findings illustrate that PST can help athletes better cope with psychologically disturbed situations during competition, by providing psychophysiological evidence through HRV changes.
Mortalin/mthsp70 (HSPA9) is a stress chaperone enriched in many cancers that has been implicated in carcinogenesis by promoting cell proliferation and survival. In the present study, we examined the ...clinical relevance of mortalin upregulation in carcinogenesis. Consistent with high mortalin expression in various human tumors and cell lines, we found that mortalin overexpression increased the migration and invasiveness of breast cancer cells. Expression analyses revealed that proteins involved in focal adhesion, PI3K-Akt and JAK-STAT signaling, all known to play key roles in cell migration and epithelial-to-mesenchymal transition (EMT), were upregulated in mortalin-expressing cancer cells. We further determined that expression levels of the mesenchymal markers vimentin (VIM), fibronectin (FN1), β-catenin (CTNNB1), CK14 (KRT14) and hnRNP-K were also increased upon mortalin overexpression, whereas the epithelial markers E-cadherin (CDH1), CK8 (KRT8), and CK18 (KRT18) were downregulated. Furthermore, shRNA-mediated and pharmacological inhibition of mortalin suppressed the migration and invasive capacity of cancer cells and was associated with a diminished EMT gene signature. Taken together, these findings support a role for mortalin in the induction of EMT, prompting further investigation of its therapeutic value in metastatic disease models.
As hubs for eukaryotic cell signaling, scaffold proteins are attractive targets for engineering and manipulating signaling circuits. We designed synthetic scaffolds with a repeated PDZ domain that ...interacted with engineered kinases of the mitogen-activated protein kinase (MAPK) cascade involved in yeast mating to investigate how modular interactions mediate kinase cascades. The synthetic scaffolds functioned as logic gates of signaling circuits. We replaced the endogenous yeast scaffold Ste5 with designer scaffolds with a variable numbers of a PDZ domain that bound kinases or phosphatases engineered with a PDZ-binding motif. Although association with the membrane was necessary for pathway activity, surprisingly, mating responses occurred when the circuit contained a scaffold with only two PDZ domains, which could only bind two of the three kinases simultaneously. Additionally, the three tiers of the MAPK pathway exhibited decreasing positional plasticity from the top MAPK kinase kinase (MAPKKK) to the bottom (MAPK) tier such that binding of a MAPKKK, but not a MAPK, from the osmoregulatory pathway or protein kinase C pathway to the synthetic scaffold activated a reporter of the mating response. We also showed that the output duration and intensity could be altered by recruiting phosphatases or varying the affinity of the recruited proteins for the scaffold and that a designer MAPK scaffold functioned in mammalian cells. Thus, this synthetic approach with designer scaffolds should enable the rational manipulation or engineering of signaling pathways and provide insight into the functional roles of scaffold proteins.
We developed a novel fluorescent core skeleton, 1,2-dihydropyrrolo3,4-βindolizin-3-one, by complexity-generating one-pot reactions through 1,3-dipolar cyclization followed by oxidative aromatization. ...This fluorescent core skeleton can accommodate various wavelengths of emission maxima by changing the electronic properties of substituents, which was postulated by computational studies. The full-color-tunable emission maxima were achieved with a single core skeleton by changing the substituents using the combinatorial approach. These novel fluorophores have excellent photophysical and photochemical properties: moderate to excellent quantum yields, resistance to the photobleaching, pH-independent fluorescence, large Stokes shifts, druglike lipophilicity for membrane permeability, etc. Further, we successfully demonstrated the bioapplication of fluorophores B1 and B5 in the immunofluorescence for visualizing cellular compartments of HeLa cells.
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IJS, KILJ, NUK, PNG, UL, UM
In this study, we investigated the role of heat shock protein 70 (HSP70) in porcine epidemic diarrhoea virus (PEDV) replication. We found that PEDV infection induced strong HSP70 overexpression in ...the very early stage of infection. We also confirmed that HSP70 overexpression increased the speed of PEDV replication, resulting in the generation of more virions. In contrast, knockout of HSP70 in cells significantly downregulated PEDV protein expression, resulting in a significant reduction in PEDV replication. Most importantly, we confirmed that among the structural proteins of PEDV, membrane (M) proteins have this important role. We found that membrane proteins control cellular HSP70 expression in PEDV-infected cells. We confirmed HSP70/M complex formation by both immunoprecipitation and immunofluorescence assays. Additionally, PEDV M overexpression induced strong HSP70 expression. All our results clearly confirmed that in PEDV-infected cells, the M protein plays a very important role in PEDV replication in collaboration with HSP70.
Deletions in the spike gene of mouse hepatitis virus (MHV) produce several variants with diverse biological characteristics, highlighting the significance of the spike gene in viral pathogenesis. In ...this study, we characterized the JHM-X strain, which has a deletion in the hypervariable region (HVR) of the spike gene, compared with the cl-2 strain, which has a full spike gene. Cytopathic effects (CPEs) induced by the two strains revealed that the size of the CPE produced by cl-2 is much greater than that produced by JHM-X in delayed brain tumor (DBT) cells. Thus, this finding explains the greater fusion activity of cl-2 than JHM-X in cultured cells, and we speculate that the deletion region of the spike protein is involved in the fusion activity differences. In contrast with the fusion activity, a comparison of the virus growth kinetics revealed that the titer of JHM-X was approximately 100 times higher than that of cl-2. We found that the deletion region of the spike protein was involved in fusion activity differences, whereas cl-2 produced significantly higher luciferase activity than JHM-X upon similar expression levels of the spike protein. However, the reason behind the growth difference is still unknown. Overall, we discovered that deletion in the HVR of the spike gene could be involved in the fusion activity differences between the two strains.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In this study, we investigated the correlation between the mechanism involved in porcine epidemic diarrhea virus (PEDV) replication and autophagic flux. In this study, we found that as PEDV ...replicated, production of LC3-II was significantly induced up to 24 h post-infection (hpi). Interestingly, although there was significant production of LC3-II, greater p62 accumulation was simultaneously found. Pretreatment with rapamycin significantly induced PEDV replication, but autolysosome formation was reduced. These results were confirmed by the evaluation of ATG5/ATG12 and LAMP1/LAMP2. Taken together, we conclude that PEDV infection induces autophagosome formation but inhibits autolysosome formation during replication.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The Hsp70 family protein mortalin is an essential chaperone that is frequently enriched in cancer cells and exists in various subcellular sites, including the mitochondrion, plasma membrane, ...endoplasmic reticulum, and cytosol. Although the molecular mechanisms underlying its multiple subcellular localizations are not yet clear, their functional significance has been revealed by several studies. In this study, we examined the nuclear fractions of human cells and found that the malignantly transformed cells have more mortalin than the normal cells. We then generated a mortalin mutant that lacked a mitochondrial targeting signal peptide. It was largely localized in the nucleus, and, hence, is called nuclear mortalin (mot-N). Functional characterization of mot-N revealed that it efficiently protects cancer cells against endogenous and exogenous oxidative stress. Furthermore, compared with the full-length mortalin overexpressing cancer cells, mot-N derivatives showed increased malignant properties, including higher proliferation rate, colony forming efficacy, motility, and tumor forming capacity both in in vitro and in vivo assays. We demonstrate that mot-N promotes carcinogenesis and cancer cell metastasis by inactivation of tumor suppressor protein p53 functions and by interaction and functional activation of telomerase and heterogeneous ribonucleoprotein K (hnRNP-K) proteins.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
One of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused coronavirus disease 2019 (COVID-19) pandemic and threatened worldwide. However, therapy for COVID-19 has ...rarely been proven to possess specific efficacy. As the virus relies on host metabolism for its survival, several studies have reported metabolic intervention by SARS-CoV-2.
We investigated the coronavirus-metabolic hijacking using mouse hepatitis virus (MHV) as a surrogate for SARS-CoV-2. Based on the altered host metabolism by MHV infection, an increase of glycolysis with low mitochondrial metabolism, we tried to investigate possible therapeutic molecules which increase the TCA cycle. Endogenous metabolites and metabolic regulators were introduced to restrain viral replication by metabolic intervention. We observed that cells deprived of cellular energy nutrition with low glycolysis strongly suppress viral replication. Furthermore, viral replication was also significantly suppressed by electron transport chain inhibitors which exhaust cellular energy. Apart from glycolysis and ETC, pyruvate supplement suppressed viral replication by the TCA cycle induction. As the non-glucose metabolite, fatty acids supplement decreased viral replication via the TCA cycle. Additionally, as a highly possible therapeutic metabolite, nicotinamide riboside (NR) supplement, which activates the TCA cycle by supplying NAD+, substantially suppressed viral replication.
This study suggests that metabolite-mediated TCA cycle activation suppresses replication of coronavirus and suggests that NR might play a role as a novel therapeutic metabolite for coronavirus.
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