Small serum protein-1 changes the susceptibility of an apoptosis-inducing metalloproteinase HV1 to a metalloproteinase inhibitor in habu snake (Trimeresurus flavoviridis)

Viperidae snakes containing various venomous proteins also have several anti-toxic proteins in their sera. However, the physiological function of serum protein has been elucidated incompletely. Small serum protein (SSP)-1 is a major component of the SSPs isolated from the serum of a Japanese viper, the habu snake (Trimeresurus flavoviridis). It exists in the blood as a binary complex with habu serum factor (HSF), a snake venom metalloproteinase inhibitor. Affinity chromatography of the venom on an SSP-1-immobilized column identified HV1, an apoptosis-inducing metalloproteinase, as the target protein of SSP-1. Biacore measurements revealed that SSP-1 was bound to HV1 with a dissociation constant of 8.2 Â 10 À8 M. However, SSP-1 did not inhibit the peptidase activity of HV1. Although HSF alone showed no inhibitory activity or binding affinity to HV1, the SSP-1HSF binary complex bound to HV1 formed a ternary complex that non-competitively inhibited the peptidase activity of HV1 with a inhibition constant of 5.1 AE 1.3 Â 10 À9 M. The SSP-1HSF complex also effectively suppressed the apoptosis of vascular endothelial cells and caspase 3 activation induced by HV1. Thus, SSP-1 is a unique protein that non-covalently attaches to HV1 and changes its susceptibility to HSF. Keywords: apoptosis/proteinase inhibitor/small serum protein/snake serum/snake venom metalloproteinase. Abbreviations: ADAM, a disintegrin and metalloproteinase; ADAMTS, ADAM with thrombospondin type-1 motif; CRISP-3, cysteine-rich secretory protein-3; Dnp, dinitrophenyl; HSF, habu serum factor; HVR, hypervariable region; K i , inhibition constant; Mca, (7-methoxycoumarin-4-yl)-acetyl; MDC, metalloproteinase/disintegrin/ cysteine-rich; MMP, matrix metalloproteinase; PSP94, prostatic secretory protein of 94 amino acids; SSP, small serum protein; SVMP, snake venom metalloproteinase; VEC, vascular endothelial cell

Geo-social media as a proxy for hydrometeorological data for streamflow estimation and to improve flood monitoring

Floods are one of the most devastating types of worldwide disasters in terms of human, economic, and social losses. If authoritative data is scarce, or unavailable for some periods, other sources of information are required to improve streamflow estimation and early flood warnings. Georeferenced social media messages are increasingly being regarded as an alternative source of information for coping with flood risks. However, existing studies have mostly concentrated on the links between geo-social media activity and flooded areas. Thus, there is still a gap in research with regard to the use of social media as a proxy for rainfall-runoff estimations and flood forecasting. To address this, we propose using a transformation function that creates a proxy variable for rainfall by analysing geo-social media messages and rainfall measurements from authoritative sources, which are later incorporated within a hydrological model for streamflow estimation. We found that the combined use of official rainfall values with the social media proxy variable as input for the Probability Distributed Model (PDM), improved streamflow simulations for flood monitoring. The combination of authoritative sources and transformed geo-social media data during flood events achieved a 71% degree of accuracy and a 29% underestimation rate in a comparison made with real streamflow measurements. This is a significant improvement on the respective values of 39% and 58%, achieved when only authoritative data were used for the modelling. This result is clear evidence of the potential use of derived geo-social media data as a proxy for environmental variables for improving flood early-warning systems

Yeast screening system reveals the inhibitory mechanism of cancer cell proliferation by benzyl isothiocyanate through down-regulation of Mis12

Benzyl isothiocyanate (BITC) is a naturally-occurring isothiocyanate derived from cruciferous vegetables. BITC has been reported to inhibit the proliferation of various cancer cells, which is believed to be important for the inhibition of tumorigenesis. However, the detailed mechanisms of action remain unclear. In this study, we employed a budding yeast Saccharomyces cerevisiae as a model organism for screening. Twelve genes including MTW1 were identified as the overexpression suppressors for the antiproliferative effect of BITC using the genome-wide multi-copy plasmid collection for S. cerevisiae. Overexpression of the kinetochore protein Mtw1 counteracts the antiproliferative effect of BITC in yeast. The inhibitory effect of BITC on the proliferation of human colon cancer HCT-116 cells was consistently suppressed by the overexpression of Mis12, a human orthologue of Mtw1, and enhanced by the knockdown of Mis12. We also found that BITC increased the phosphorylated and ubiquitinated Mis12 level with consequent reduction of Mis12, suggesting that BITC degrades Mis12 through an ubiquitin-proteasome system. Furthermore, cell cycle analysis showed that the change in the Mis12 level affected the cell cycle distribution and the sensitivity to the BITC-induced apoptosis. These results provide evidence that BITC suppresses cell proliferation through the post-transcriptional regulation of the kinetochore protein Mis12

Yeast screening system reveals the inhibitory mechanism of cancer cell proliferation by benzyl isothiocyanate through down-regulation of Mis12

Benzyl isothiocyanate (BITC) is a naturally-occurring isothiocyanate derived from cruciferous vegetables. BITC has been reported to inhibit the proliferation of various cancer cells, which is believed to be important for the inhibition of tumorigenesis. However, the detailed mechanisms of action remain unclear. In this study, we employed a budding yeast Saccharomyces cerevisiae as a model organism for screening. Twelve genes including MTW1 were identified as the overexpression suppressors for the antiproliferative effect of BITC using the genome-wide multi-copy plasmid collection for S. cerevisiae. Overexpression of the kinetochore protein Mtw1 counteracts the antiproliferative effect of BITC in yeast. The inhibitory effect of BITC on the proliferation of human colon cancer HCT-116 cells was consistently suppressed by the overexpression of Mis12, a human orthologue of Mtw1, and enhanced by the knockdown of Mis12. We also found that BITC increased the phosphorylated and ubiquitinated Mis12 level with consequent reduction of Mis12, suggesting that BITC degrades Mis12 through an ubiquitin-proteasome system. Furthermore, cell cycle analysis showed that the change in the Mis12 level affected the cell cycle distribution and the sensitivity to the BITC-induced apoptosis. These results provide evidence that BITC suppresses cell proliferation through the post-transcriptional regulation of the kinetochore protein Mis12

High-mobility group box 1-mediated heat shock protein beta 1 expression attenuates mitochondrial dysfunction and apoptosis

AbstractAimsApoptosis of cardiomyocytes is thought to account for doxorubicin cardiotoxicity as it contributes to loss of myocardial tissue and contractile dysfunction. Given that high-mobility group box 1 (HMGB1) is a nuclear DNA-binding protein capable of inhibiting apoptosis, we aimed to clarify the role of HMGB1 in heat shock protein beta 1 (HSPB1) expression during doxorubicin-induced cardiomyopathy.Methods and resultsMitochondrial damage, cardiomyocyte apoptosis, and cardiac dysfunction after doxorubicin administration were significantly attenuated in mice with cardiac-specific overexpression of HMGB1 (HMGB1-Tg) compared with wild type (WT) -mice. HSPB1 levels after doxorubicin administration were significantly higher in HMGB1-Tg mice than in WT mice. Transfection with HMGB1 increased the expression of HSPB1 at both the protein and mRNA levels, and HMGB1 inhibited mitochondrial dysfunction and apoptosis after exposure of cardiomyocytes to doxorubicin. HSPB1 silencing abrogated the inhibitory effect of HMGB1 on cardiomyocyte apoptosis. Doxorubicin increased the binding of HMGB1 to heat shock factor 2 and enhanced heat shock element promoter activity. Moreover, HMGB1 overexpression greatly enhanced heat shock element promoter activity. Silencing of heat shock factor 2 attenuated HMGB1-dependent HSPB1 expression and abrogated the ability of HMGB1 to suppress cleaved caspase-3 accumulation after doxorubicin stimulation.ConclusionsWe report the first in vivo and in vitro evidence that cardiac HMGB1 increases HSPB1 expression and attenuates cardiomyocyte apoptosis associated with doxorubicin-induced cardiomyopathy. Cardiac HMGB1 increases HSPB1 expression in cardiomyocytes in a heat shock factor 2-dependent manner

Field-Induced Magnetic Ordering in the Quantum Spin System KCuCl3_3

KCuCl$_3$ is a three-dimensional coupled spin-dimer system and has a singlet ground state with an excitation gap ${\Delta}/k_{\rm B}=31$ K. High-field magnetization measurements for KCuCl$_3$ have been performed in static magnetic fields of up to 30 T and in pulsed magnetic fields of up to 60 T. The entire magnetization curve including the saturation region was obtained at $T=1.3$ K. From the analysis of the magnetization curve, it was found that the exchange parameters determined from the dispersion relations of the magnetic excitations should be reduced, which suggests the importance of the renormalization effect in the magnetic excitations. The field-induced magnetic ordering accompanied by the cusplike minimum of the magnetization was observed as in the isomorphous compound TlCuCl$_3$. The phase boundary was almost independent of the field direction, and is represented by the power law. These results are consistent with the magnon Bose-Einstein condensation picture for field-induced magnetic ordering.Comment: 9 pages, 7 figures, 9 eps files, revtex styl

Competency of Education for Interntional Understanding: By analyzing Dircke Geography: For Bilingual Classes in Germany

This paper aims to clarify the characteristics of learning units on Education for International Understanding (EIU) and their structure, appropriate geographical teaching materials on EIU, streategies for competence acquisition, and perspectives of ESD within learning units on EIU by analyzing two learning units “Globalisation” and “Global Disparities” in the geography textbook for bilingual lesson ”Diercke Geography: For Bilingual Classes”. The results of the analysis showed that 1)“Globalisation” focuses on the theories of globalisation and “Global Disparities” aims to learn not only theories but also regionl images; 2) Competency is repeatedly acquired through different learning activities ; 3) “Global Disparities” is designed from the viewpoint of “think globally, act locally”

Age- and sex-specific associations between sarcopenia severity and poor cognitive function among community-dwelling older adults in Japan: The IRIDE Cohort Study

IntroductionThis study examined whether the association between sarcopenia severity and cognitive function differed according to sex and age in community-dwelling older adults in Japan.MethodsThis is a cross-sectional study of older adults (age ≥ 65 years) consisting of five regional cohorts integrated as the Integrated Research Initiative for Living Well with Dementia (IRIDE) Cohort Study. Sarcopenia severity was determined based on the Asian Working Group for Sarcopenia 2019, which assessed grip strength, walking speed, and skeletal muscle mass index. Poor cognitive function was defined as a Mini-Mental State Examination score of ≤ 23. Odds ratios (ORs) and 95% confidence intervals (CIs) for poor cognitive function were calculated by sex and age group (65–74 and ≥75 years) using binomial logistic regression models, which were adjusted for age, educational attainment, history of non-communicable diseases, smoking and drinking habits, living alone, frequency of going outdoors, exercise habits, and depressive symptom.ResultsOf the 8,180 participants, 6,426 (1,157 men aged 65–74 and 1,063 men aged 75 or older; 2,281 women aged 65–74 and 1,925 women aged 75 or older) were analyzed. The prevalence ratio of sarcopenia and severe sarcopenia were 309 (13.9%) and 92 (4.1%) among men and 559 (13.3%) and 166 (3.7%) among women, respectively. A total of 127 (5.8%) men and 161 (3.9%) women had a poor cognitive function. Setting non-sarcopenia as a reference, the adjusted ORs (95% CI) of poor cognitive function were 2.20 (1.54, 3.15) for sarcopenia and 3.56 (2.20, 5.71) for severe sarcopenia. A similar trend was observed in analyses stratified by sex and age, with linear associations (P for trend <0.05) in both categories. Furthermore, there was a significant interaction (P < 0.05) between sex and sarcopenia severity, indicating a stronger linear association of sarcopenia severity with poor cognitive function in women compared with men.Discussion and conclusionSarcopenia severity was linearly associated with poor cognitive function in adults aged ≥ 65 years, with a stronger association in women compared with men

A High-Speed Congenic Strategy Using First-Wave Male Germ Cells

BACKGROUND: In laboratory mice and rats, congenic breeding is essential for analyzing the genes of interest on specific genetic backgrounds and for analyzing quantitative trait loci. However, in theory it takes about 3-4 years to achieve a strain carrying about 99% of the recipient genome at the tenth backcrossing (N10). Even with marker-assisted selection, the so-called 'speed congenic strategy', it takes more than a year at N4 or N5. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a new high-speed congenic system using round spermatids retrieved from immature males (22-25 days of age). We applied the technique to three genetically modified strains of mice: transgenic (TG), knockin (KI) and N-ethyl-N-nitrosourea (ENU)-induced mutants. The donor mice had mixed genetic backgrounds of C57BL/6 (B6):DBA/2 or B6:129 strains. At each generation, males used for backcrossing were selected based on polymorphic marker analysis and their round spermatids were injected into B6 strain oocytes. Backcrossing was repeated until N4 or N5. For the TG and ENU-mutant strains, the N5 generation was achieved on days 188 and 190 and the proportion of B6-homozygous loci was 100% (74 markers) and 97.7% (172/176 markers), respectively. For the KI strain, N4 was achieved on day 151, all the 86 markers being B6-homozygous as early as on day 106 at N3. The carrier males at the final generation were all fertile and propagated the modified genes. Thus, three congenic strains were established through rapid generation turnover between 41 and 44 days. CONCLUSIONS/SIGNIFICANCE: This new high-speed breeding strategy enables us to produce congenic strains within about half a year. It should provide the fastest protocol for precise definition of the phenotypic effects of genes of interest on desired genetic backgrounds

CsFTL3, a chrysanthemum FLOWERING LOCUS T-like gene, is a key regulator of photoperiodic flowering in chrysanthemums

Chrysanthemum is a typical short-day (SD) plant that responds to shortening daylength during the transition from the vegetative to the reproductive phase. FLOWERING LOCUS T (FT)/Heading date 3a (Hd3a) plays a pivotal role in the induction of phase transition and is proposed to encode a florigen. Three FT-like genes were isolated from Chrysanthemum seticuspe (Maxim.) Hand.-Mazz. f. boreale (Makino) H. Ohashi & Yonek, a wild diploid chrysanthemum: CsFTL1, CsFTL2, and CsFTL3. The organ-specific expression patterns of the three genes were similar: they were all expressed mainly in the leaves. However, their response to daylength differed in that under SD (floral-inductive) conditions, the expression of CsFTL1 and CsFTL2 was down-regulated, whereas that of CsFTL3 was up-regulated. CsFTL3 had the potential to induce early flowering since its overexpression in chrysanthemum could induce flowering under non-inductive conditions. CsFTL3-dependent graft-transmissible signals partially substituted for SD stimuli in chrysanthemum. The CsFTL3 expression levels in the two C. seticuspe accessions that differed in their critical daylengths for flowering closely coincided with the flowering response. The CsFTL3 expression levels in the leaves were higher under floral-inductive photoperiods than under non-inductive conditions in both the accessions, with the induction of floral integrator and/or floral meristem identity genes occurring in the shoot apexes. Taken together, these results indicate that the gene product of CsFTL3 is a key regulator of photoperiodic flowering in chrysanthemums