Recent near-Earth supernovae probed by global deposition of interstellar radioactive (60)Fe.

The rate of supernovae in our local Galactic neighbourhood within a distance of about 100 parsecs from Earth is estimated to be one every 2-4 million years, based on the total rate in the Milky Way (2.0 ± 0.7 per century). Recent massive-star and supernova activity in Earth's vicinity may be traced by radionuclides with half-lives of up to 100 million years, if trapped in interstellar dust grains that penetrate the Solar System. One such radionuclide is (60)Fe (with a half-life of 2.6 million years), which is ejected in supernova explosions and winds from massive stars. Here we report that the (60)Fe signal observed previously in deep-sea crusts is global, extended in time and of interstellar origin from multiple events. We analysed deep-sea archives from all major oceans for (60)Fe deposition via the accretion of interstellar dust particles. Our results reveal (60)Fe interstellar influxes onto Earth at 1.5-3.2 million years ago and at 6.5-8.7 million years ago. The signal measured implies that a few per cent of fresh (60)Fe was captured in dust and deposited on Earth. Our findings indicate multiple supernova and massive-star events during the last ten million years at distances of up to 100 parsecs.

Serum immunoglobulin G antibody titer to Fusobacterium nucleatum is associated with unfavorable outcome after stroke.

Stroke can be a cause of death, while in non-fatal cases it is a common cause of various disabilities resulting from associated brain damage. However, whether a specific periodontal pathogen is associated with increased risk of unfavorable outcome after stroke remains unknown. We examined risk factors for unfavorable outcome following stroke occurrence, including serum antibody titers to periodontal pathogens. The enrolled cohort included 534 patients who had experienced an acute stroke, who were divided into favorable (n = 337) and unfavorable (n = 197) outcome groups according to modified ranking scale (mRS) score determined at 3 months after onset (favorable = score 0 or 1; unfavorable = score 2-6). The associations of risk factors with unfavorable outcome, including serum titers of IgG antibodies to 16 periodontal pathogens, were examined. Logistic regression analysis showed that the initial National Institutes of Health stroke scale score [odds ratio (OR) = 1·24, 95% confidence interval (CI) = 1·18-1·31, P < 0·001] and C-reactive protein (OR = 1·29, 95% CI = 1·10-1·51, P = 0·002) were independently associated with unfavorable outcome after stroke. Following adjustment with those, detection of the antibody for Fusobacterium nucleatum ATCC 10953 in serum remained an independent predictor of unfavorable outcome (OR = 3·12, 95% CI = 1·55-6·29, P = 0·002). Determination of the antibody titer to F. nucleatum ATCC 10953 in serum may be useful as a predictor of unfavorable outcome after stroke.

Nightlife clusters of coronavirus disease in Tokyo between March and April 2020.

We analysed associations between exposure to nightlife businesses and severe acute respiratory syndrome coronavirus 2 PCR test results at a tertiary hospital in Tokyo between March and April 2020. A nightlife group was defined as those who had worked at or visited the businesses. We included 1517 individuals; 196 (12.9%) were categorised as the nightlife group. After propensity score matching, the proportion of positive PCR tests in the nightlife group was significantly higher than that in the non-nightlife group (nightlife, 63.8%; non-nightlife, 23.0%; P < 0.001). An inclusive approach to mitigate risks related to the businesses needs to be identified.

Periodontal disease and gene-expression levels of metalloendopeptidases in human buccal mucosal epithelium.

BACKGROUND AND OBJECTIVE: Endopeptidases, such as neutral endopeptidase (NEP), endothelin-converting enzyme-1 (ECE-1) and a disintegrin and metalloprotease 17 (ADAM17), are believed to have various important roles in oral mucosal and epidermal tissue for the regulation of defensive biological responses in the oral cavity, and their expression and activity are influenced by various factors, including oral diseases. However, knowledge concerning these endopeptidases in the oral cavity has been minimal until now. This study focused on three metalloendopeptidases - NEP, ECE-1 and ADAM17 - in the oral buccal mucosal epithelium of patients with periodontal diseases and investigated the relationship between their gene-expression levels and periodontal disease. MATERIAL AND METHODS: The levels of expression of NEP, ECE-1 and ADAM17 mRNAs in tissue samples collected from the oral buccal mucosal epithelium of 61 patients were investigated by relative quantification using real-time RT-PCR analysis. information on oral and systemic health was obtained from the clinical record of each patient. RESULTS: Among the three groups, classified based on the diagnosis of periodontal diseases (healthy/gingivitis, early periodontitis and moderate/advanced periodontitis), the relative expression level of NEP mRNA was significantly increased in the early periodontitis group and in the moderate/advanced periodontitis group compared with that in the healthy/gingivitis group. Moreover, the relative expression levels of ECE1 and ADAM17 mRNAs were significantly increased in the moderate/advanced periodontitis group compared with those in the healthy/gingivitis group. The correlation coefficients between the mean relative expression levels of NEP and ECE1 mRNAs, NEP and ADAM17 mRNAs, and ECE1 and ADAM17 mRNAs were r = 0.758, r = 0.707 and r = 0.934, respectively (p < 0.001). Furthermore, among the oral-related factors, there was a significant correlation between the number of sites with probing pocket depths of more than 4 mm and of more than 6 mm and the relative expression levels of NEP, ECE1 and ADAM17 mRNAs. In stepwise logistic regression models, high relative expression levels of ECE1 and ADAM17 mRNAs were significantly associated with moderate/advanced periodontitis. CONCLUSION: The present study suggests that the severity of periodontal disease may be associated with the expression of metalloendopeptidase genes, including NEP, ECE1 and ADAM17, in the buccal mucosal epithelium.

Effects of nitrogen on caesium allocation in rice plants (Oryza sativa).

After the nuclear accident in Fukushima Prefecture, Japan, in 2011, 137 Caesium (Cs) contaminated nearby agricultural regions. Studies in these rice fields found that low K and high N fertilizer application enhanced Cs uptake in rice shoots. However, the influence of root and soil physics on these findings, as well as precise nutrient levels, remain to be clarified. We sought to analyse these relationships utilizing hydroponically grown rice plants. The rice plants were subjected to various concentrations of K and N nutrient solutions. We measured Cs allocation within the plants and performed transcript analyses using root tissues. Under low-K conditions, low-N plants accumulated less Cs in shoots and more in roots when compared to control-N conditions, even though overall Cs uptake remained unchanged. Expression analyses of root mRNAs showed that low-N plants accumulated reduced levels of OsAKT1 mRNA, encoding a K transporter. We also found a negative relationship between shoot Cs and K status in control-N but not in low-N conditions. Our results suggest that the application of N shifts Cs from roots into the shoots and that OsAKT1 in root vascular tissues influences Cs allocation. In practice, fine tuning N/K application and targeted breeding of K transporters might mitigate Cs contamination in rice plants.

60Fe and 244Pu deposited on Earth constrain the r-process yields of recent nearby supernovae.

Half of the chemical elements heavier than iron are produced by the rapid neutron capture process (r-process). The sites and yields of this process are disputed, with candidates including some types of supernovae (SNe) and mergers of neutron stars. We search for two isotopic signatures in a sample of Pacific Ocean crust-iron-60 (60Fe) (half-life, 2.6 million years), which is predominantly produced in massive stars and ejected in supernova explosions, and plutonium-244 (244Pu) (half-life, 80.6 million years), which is produced solely in r-process events. We detect two distinct influxes of 60Fe to Earth in the last 10 million years and accompanying lower quantities of 244Pu. The 244Pu/60Fe influx ratios are similar for both events. The 244Pu influx is lower than expected if SNe dominate r-process nucleosynthesis, which implies some contribution from other sources.

Phosphorylation of adducin by Rho-kinase plays a crucial role in cell motility.

Adducin is a membrane skeletal protein that binds to actin filaments (F-actin) and thereby promotes the association of spectrin with F-actin to form a spectrin-actin meshwork beneath plasma membranes such as ruffling membranes. Rho-associated kinase (Rho- kinase), which is activated by the small guanosine triphosphatase Rho, phosphorylates alpha-adducin and thereby enhances the F-actin-binding activity of alpha-adducin in vitro. Here we identified the sites of phosphorylation of alpha-adducin by Rho-kinase as Thr445 and Thr480. We prepared antibody that specifically recognized alpha-adducin phosphorylated at Thr445, and found by use of this antibody that Rho-kinase phosphorylated alpha-adducin at Thr445 in COS7 cells in a Rho-dependent manner. Phosphorylated alpha-adducin accumulated in the membrane ruffling area of Madin-Darby canine kidney (MDCK) epithelial cells and the leading edge of scattering cells during the action of tetradecanoylphorbol-13-acetate (TPA) or hepatocyte growth factor (HGF). The microinjection of Botulinum C3 ADP-ribosyl-transferase, dominant negative Rho-kinase, or alpha-adducinT445A,T480A (substitution of Thr445 and Thr480 by Ala) inhibited the TPA-induced membrane ruffling in MDCK cells and wound-induced migration in NRK49F cells. alpha-AdducinT445D,T480D (substitution of Thr445 and Thr480 by Asp), but not alpha-adducinT445A,T480A, counteracted the inhibitory effect of the dominant negative Rho-kinase on the TPA-induced membrane ruffling in MDCK cells. Taken together, these results indicate that Rho-kinase phosphorylates alpha-adducin downstream of Rho in vivo, and that the phosphorylation of adducin by Rho-kinase plays a crucial role in the regulation of membrane ruffling and cell motility.

beta-Glucuronidase catalyzed hydrolysis of benzo(a)pyrene-3-glucuronide and binding to DNA.

beta-Glucuronidase catalyzes the hydrolysis of benzo[a]pyrene-3-glucuronide to 3-hydroxybenzo[a]pyrene. During the enzymatic hydrolysis, a benzo[a]pyrene derivative is formed which binds to DNA to a far greater extent than either the 3-hydroxybenzo[a]pyrene or its glucuronide. These results suggest that conjugates of benzo(a)pyrene may be converted by beta-glucuronidase at intracellular and organ sites distal to the initial sites of oxygenation and conjugation of benzo(a)pyrene to activated intermediates that are possibly carcinogenic.

Mitotic regulation of protein phosphatases by the fission yeast sds22 protein.

BACKGROUND: Cell cycle progression requires the activity of protein kinases and phosphatases at critical points in the cell cycle in all eukaryotes. We have previously reported that the dis2(+) and sds2(+) genes of fission yeast encode redundant catalytic subunits of a type 1-like protein phosphatase. The sds22(+) gene was shown to be essential for cell viability and to interact genetically with dis2(+) and sds21(+). RESULTS: Here we show by immunoprecipitation that the sds22 protein physically interacts with the dis2 and sds21 proteins, and that sds22-associated phosphatase activity has altered substrate specificity, The loss of sds22 function by a temperature sensitive mutation leads to cell cycle arrest at mid-mitosis, at which point cdc2-dependent histone Hl kinase activity is high while sds22-dependent H1 phosphatase activity is low. To examine the unusual properties of sds22 protein structure, we analyzed a collection of sds22 deletion and point mutants by a variety of functional criteria. CONCLUSION: We propose that sds22 is a regulatory subunit of the dis2/sds21 phosphatase catalytic subunits and that sds22-bound phosphatase carries a key phosphatase activity essential for the progression from metaphase to anaphase. Mutational analysis indicates that dis2/sds21 interacts with the central repetitive domain of sds22, while the C-terminal and central regions of sds22 may be involved in subcellular targeting and the N-terminus is important for stability.

The fission yeast dis3+ gene encodes a 110-kDa essential protein implicated in mitotic control.

The fission yeast mutant dis3-54 is defective in mitosis and fails in chromosome disjunction. Its phenotype is similar to that of dis2-11, a mutant with a mutation in the type 1 protein phosphatase gene. We cloned the dis3+ gene by transformation. Nucleotide sequencing predicts a coding region of 970 amino acids interrupted by a 164-bp intron at the 65th codon. The predicted dis3+ protein shares a weak but significant similarity with the budding yeast SSD1 or SRK1 gene product, the gene for which is a suppressor for the absence of a protein phosphatase SIT4 gene or the BCY1 regulatory subunit of cyclic AMP-dependent protein kinase. Anti-dis3 antibodies recognized the 110-kDa dis3+ gene product, which is part of a 250- to 350-kDa oligomer and is enriched in the nucleus. The cellular localization of the dis3+ protein is reminiscent of that of the dis2+ protein, but these two proteins do not form a complex. A type 1 protein phosphatase activity in the dis3-54 mutant extracts is apparently not affected. The dis3+ gene is essential for growth; gene disruptant cells do not germinate and fail in cell division. Increased dis3+ gene dosage reverses the Ts+ phenotype of a cdc25 wee1 strain, as does increased type 1 protein phosphatase gene dosage. Double mutant dis3 dis2 is lethal even at the permissive temperature, suggesting that the dis2+ and dis3+ genes may be functionally overlapped. The role of the dis3+ gene product in mitosis is unknown, but this gene product may be directly or indirectly involved in the regulation of mitosis.

Isolation and characterization of the fission yeast protein phosphatase gene ppe1+ involved in cell shape control and mitosis.

We isolated a fission yeast putative protein serine/threonine phosphatase gene designated ppe1+ by hybridization. The predicted amino acid sequence is similar to those of the fission yeast ppa2 (53% identity) and dis2 (39%) phosphatases, and highly similar to those of the budding yeast SIT4 (72%), Drosophila PPV (68%) and rabbit PPX (61%) phosphatases. Antibodies against ppe1 protein identified a 37-kd polypeptide in fission yeast. A gene disruption (designated delta ppe1) caused cold-sensitive lethality and short, pear-shaped cells. These phenotypes were fully suppressed by a plasmid carrying ppe1+. Three classes of multicopy suppressor genes for delta ppe1 were identified as follows: 1) ppa1+ and ppa2+ encoding type 2A-like phosphatases, 2) mitotically essential dis3+ similar to the budding yeast SSD1/SRK1, a suppressor for sit4, and 3) pck1+ coding for a protein kinase C-like kinase. Consistently, the budding yeast SIT4 gene was also a multicopy suppressor for delta ppe1. Phosphatase ppe1 may play a role in cell morphogenesis and mitosis by either regulating or being regulated by these multicopy suppressor gene products. Consistent with this hypothesis, double mutants ppe1-ppa2 and ppe1-pck1 are lethal at the permissive temperature.

Formation of methylnitrosocyanamide from methylguanidine and sodium nitrite in simulated gastric juice and in stomachs of rats: quantitative estimation by a mutagenicity assay.

The formation of methylnitrosocyanamide (MNC), a carcionogenic N-nitroso compound, from methylguanidine (MG) and NaNO2 in simulated gastric juice (SGJ) and in the stomachs of rats was quantitatively investigated. With a reverse mutation assay in which a tester strain of Salmonella typhimurium was used, MNC formation was shown to increase linearly for about 40--60 minutes after the incubation of MG with NaNO2 in SGJ. However, it decreased rapidly thereafter. The initial rate of MNC formation was directly proportional to the initial molar ratio of MG to NaNO2, but the yields of MNC depended only on the amount of MG added and were fairly constant (0.3--0.5% of the initial MG). MNC did not form at a pH above 2.5 or in the presence of 2% casein in SGJ at pH 1.2. It decomposed rapidly in SGJ at pH 1.2 with a half-life of approximately 2 minutes, whereas it was stable in phosphate buffer at pH 7.0. Following concurrent administration of MG and NaNO2 via stomach tube, MNC formation was detected in the pylorus-ligated stomachs of rats preconditioned with a casein-free dextrin diet but not in those of rats preconditioned with a casein-containing or synthetic diet. The yields of MNC observed 40--60 minutes after administration of reactants ranged from 0.02 to 0.05% of the initial MG. The possible environment significance of MNC formation in vivo was considered.

Formation of a transplacental mutagen, 1,3-Di(4-sulfamoylphenyl)triazene, from sodium nitrite and sulfanilamide in human gastric juice and in the stomachs of hamsters.

1,3-Di(4-sulfamoylphenyl)triazene was abundantly produced by incubation of sulfanilamide (SA) and NaNO2 in human gastric juice. This reaction also occurred in acetate buffer (pH approximately 4) at 37 degrees C as well as in hydrochloric acid (pH < 1) under ice cooling, with the product forming in almost the same amount. This phenomenon indicated the broad range of conditions under which the reaction occurs. The intragastric formation of this triazene was also demonstrated in Syrian golden hamsters by the concurrent administration of SA and NaNO2. Mutants resistant to 8-azaguanine were induced in a dose-dependent manner in the culture of embryo cells that were derived from pregnant hamsters 24 hours after ip injection of this triazene.

Glycosylation at the Fab portion of myeloma immunoglobulin G and increased fucosylated biantennary sugar chains: structural analysis by high-performance liquid chromatography and antibody-lectin enzyme immunoassay using Lens culinaris agglutinin.

An antibody-lectin enzyme immunoassay technique which had been developed for the analysis of sugar chains of alpha-fetoprotein (N. Kinoshita et al., Clin. Chim. Acta, 179: 143-152, 1989) was used for analysis of sugar chains of myeloma immunoglobulin G (IgG). The IgG sugar chains of four of nine patients with myeloma were found to be highly reactive to Lens culinaris agglutinin as compared with those of six normal controls and 177 patients without myeloma. This reflected a high L. culinaris agglutinin/concanavalin A ratio. The IgGs of these patients were found to have highly sialylated, fucosylated, and bisected biantennary sugar chains at Fab portions as judged by the lectin-blotting technique as well as by high-performance liquid chromatography analysis. These results indicate that some of the myeloma IgG proteins undergo unusual glycosylation processes.

Right atrial flow topography in healthy subjects studied with real-time two-dimensional Doppler flow imaging technique.

The pattern of normal blood flow in the right atrial cavity was studied using the newly developed real-time two-dimensional Doppler flow imaging technique as a standard reference for the Doppler diagnosis of heart diseases with intracardiac shunts at the atrial level. The study was performed primarily with use of the apical four chamber and the parasternal right ventricular inflow tract views in 21 healthy subjects. The following patterns were observed: blood from the inferior vena cava flowed up along the posterior wall of the right atrium and joined with blood from the superior vena cava in the posterocranial part of the right atrial cavity; the flow then coursed along the roof of the right atrium toward the tricuspid valve in the atrial relaxation phase. This flow was always noted along the interatrial septum in the four chamber view. During and after mid-systole of the right ventricle, additional blood flow away from the tricuspid valve appeared, moving from the valve to the central part of the right atrial cavity, that is, at the lower right of the preceding inflow; this flow was interpreted as arising from eddy currents caused by the preceding inflow. In early diastole of the right ventricle, the flow signal area along the interatrial septum and the roof of the right atrium extended into the right ventricular cavity through the tricuspid valve. In the atrial contraction phase only the blood near the tricuspid valve in the right atrial cavity appeared to flow into the right ventricular cavity. Inflow from the coronary sinus was almost undetectable.(ABSTRACT TRUNCATED AT 250 WORDS)

Semiquantitative grading of severity of mitral regurgitation by real-time two-dimensional Doppler flow imaging technique.

An attempt was made to determine whether mitral regurgitation could be detected and its severity evaluated semiquantitatively by newly developed real-time two-dimensional Doppler flow imaging in 109 patients who underwent left ventriculography. In the Doppler flow imaging technique, Doppler signals due to blood flow in the cardiac chambers are processed using a high speed autocorrelation technique, so that the direction, velocity and turbulence of the intracardiac blood flow are displayed in the color-coded mode on the monochrome B-mode echocardiogram in real time. Mitral regurgitant flow was imaged as a jet spurting out from the mitral valve orifice into the left atrial cavity. It was noted that the regurgitant jet in the left atrial cavity had a variety of orientations and dynamic features when studied by the present technique. The sensitivity of the technique in the detection of mitral regurgitation was 86% as compared with that of left ventriculography. Mitral regurgitation in the false negative cases was mostly mild. On the basis of the farthest distance reached by the regurgitant flow signal from the mitral valve orifice, the severity of regurgitation was graded on a four point scale and these results were compared with those of angiography. A significant correlation (r = 0.87) was found between Doppler imaging and angiography in the evaluation of the severity of mitral regurgitation. A similar result was obtained for the evaluation based on the area covered by the regurgitant signals in the left atrial cavity. Thus, noninvasive semiquantitative evaluation by real-time two-dimensional Doppler flow imaging appears to be a promising clinical technique.

Doppler echocardiographic features of ventricular septal rupture in myocardial infarction.

Doppler echocardiography was used to evaluate the features of interventricular septal rupture in six patients with acute myocardial infarction and to substantiate the hemodynamic data and morphologic findings at surgery or autopsy. Although echocardiographic visualization of the septal rupture was obtained in only two of the six patients, unusual Doppler flow signals were detected in the apical portion of the right ventricle in all six patients. Five patients had unusual flow signals during both systole and diastole; one had such signals only during systole. The location of these unusual flow signals coincided with the site of septal rupture confirmed at surgery or autopsy. The pattern of the flow signals in one cardiac cycle was very similar to that of the pressure difference between the left and right ventricular cavities. These findings indicate that the unusual flow signals represent the left to right shunt flows resulting from septal rupture. In conclusion, Doppler echocardiography may be a very useful tool for diagnosing interventricular septal rupture easily and noninvasively in patients with acute myocardial infarction.