Dynamically induced Coulomb failure in the overriding wedge significantly affects energy radiation of shallow subduction earthquakes. For a wedge on the verge of failure, extensive fluid-assisted ...coseismic failure due to updip rupture causes significant seafloor uplift above a shallow dipping basal fault. The large inelastic uplift, greatly enhanced by the presence of free surface, significantly dilates the fault behind the rupture front during the rupture propagation, which reduces the effective normal stress and sliding friction on the fault, and increases the dynamic stress drop and slip velocity. As a result, slip-velocity time histories in the shallow section of the fault tend to have a ‘snail-like’ shape, leading to depletion of high frequencies in the slip velocity field and the resultant source time function. We also show that the failure in the wedge acts as a large energy sink (while contributing to seismic moment), giving rise to distributed heat generation (i.e., small heat flow anomaly across the fault), low moment-scaled radiated energy, slow rupture velocity, and small directivity, which provides a unifying interpretation for nearly all anomalous observations documented for shallow subduction earthquakes.
•Extensive wedge failure and free surface promote ‘snail-like’ earthquake ruptures.•The ‘snail-like’ rupture leads to depletion in high-frequency radiation.•Extensive failure is an energy sink, leading to low moment-scaled energy.
We examined the association between living alone and mental health and the moderating effects of face-to-face and non–face-to-face social contacts, among community-dwelling older adults.
...Cross-sectional study.
This cross-sectional study recruited Japanese adults older than 60 years, who attended health check-ups held in a suburban town hall in July and August of 2018 and 2019. As mental health outcomes, depression was assessed using the Geriatric Depression Scale 15-items, loneliness was assessed using the University of California, Los Angeles Loneliness Scale 3-items, and happiness was self-rated on a 10-point scale. Face-to-face social contacts were evaluated by participants' frequency of meetings with relatives or friends, whereas non–face-to-face contacts were measured by the frequency of interactions via letter, telephone or e-mail. Multivariable linear regression analysis was conducted to examine the association between living alone with each mental health outcome and the effect modifications of having face-to-face and non–face-to-face social contacts.
Data from 300 older adults were analysed. The participants' mean age was 73.0 years, 51.3% were female, and 16.0% lived alone. Living alone was significantly associated with poorer mental health. Regarding loneliness and low happiness, having face-to-face and non–face-to-face contacts more than once a week alleviated the adverse association of living alone (loneliness: face-to-face contacts, P = 0.020; non–face-to-face contacts, P = 0.028; happiness: face-to-face contacts, P = 0.020; non–face-to-face contacts, P = 0.001).
Our findings suggest that non–face-to-face, as well as face-to-face social contacts have a moderating effect on the adverse association of living alone with loneliness and happiness.
Gene mutations were found in acute myeloid leukemia (AML) and their importance has been noted. To clarify the importance and stability of mutations, we examined gene mutations in paired samples at ...diagnosis and relapse of 34 adult AML patients. Five acquired gene mutations were detected at relapse. Of the 45 gene mutations at diagnosis, 11 of them were lost at relapse. The acquired mutations at relapse were all class I mutations as Fms-like tyrosine kinase 3 (FLT3) and rat sarcoma viral oncogene homolog (RAS) mutations. The disappeared mutations at relapse were 3 of 11 internal tandem duplications of FLT3 (FLT3-ITD) (27.3%), 3 of 3 FLT3 tyrosine kinase domain (FLT3-TKD) (100%), 3 of 13 Nucleophosmin 1 (23.1%) and 2 of 5 CCAAT/enhancer-binding protein-α (40%) mutations. However, epigenetics-modifying gene (DNMT3a, TET2 and IDH1/2) mutations had no change between diagnosis and relapse samples, and may become minimal residual disease marker. The frequency of FLT3-ITD at relapse in patients with DNMT3a mutation at diagnosis is significantly higher than those in patients without them (P=0.001). Moreover, the high frequency of FLT3-ITD at relapse is also seen in AML cases that initially present with any epigenetics-modifying gene mutations (P<0.001). Our results indicate that epigenetics-modifying gene mutations may cause genetic instability and induce FLT3-ITD, leading to resistance to therapy and relapse.
We conducted a comprehensive analysis of 28 recurrently mutated genes in acute myeloid leukemia (AML) in 271 patients with de novo AML. Co-mutations were frequently detected in the intermediate ...cytogenetic risk group, at an average of 2.76 co-mutations per patient. When assessing the prognostic impact of these co-mutations in the intermediate cytogenetic risk group, overall survival (OS) was found to be significantly shorter (P=0.0006) and cumulative incidence of relapse (CIR) significantly higher (P=0.0052) in patients with complex molecular genetic abnormalities (CMGAs) involving three or more mutations. This trend was marked even among patients aged ⩽65 years who were also FLT3-ITD (FMS-like tyrosine kinase 3 internal tandem duplications)-negative (OS: P=0.0010; CIR: P=0.1800). Moreover, the multivariate analysis revealed that CMGA positivity was an independent prognostic factor associated with OS (P=0.0007). In stratification based on FLT3-ITD and CEBPA status and 'simplified analysis of co-mutations' using seven genes that featured frequently in CMGAs, CMGA positivity retained its prognostic value in transplantation-aged patients of the intermediate cytogenetic risk group (OS: P=0.0002. CIR: P<0.0001). In conclusion, CMGAs in AML were found to be strong independent adverse prognostic factors and simplified co-mutation analysis to have clinical usefulness and applicability.
Abstract
STUDY QUESTION
Is there a relation between specific Na+/K+ ATPase isoform expression and localization in human blastocysts and the developmental behavior of the embryo?
SUMMARY ANSWER
Na+/K+ ...ATPase α1, β1 and β3 are the main isoforms expressed in human blastocysts and no association was found between the expression level of their respective mRNAs and the rate of blastocyst expansion.
WHAT IS KNOWN ALREADY
In mouse embryos, Na+/K+ ATPase α1 and β1 are expressed in the basolateral membrane of trophectoderm (TE) cells and are believed to be involved in blastocoel formation (cavitation).
STUDY DESIGN, SIZE, DURATION
A total of 20 surplus embryos from 11 patients who underwent IVF and embryo transfer at a university hospital between 2009 and 2018 were analyzed.
PARTICIPANTS/MATERIALS, SETTING, METHODS
After freezing and thawing Day 5 human blastocysts, their developmental behavior was observed for 24 h using time-lapse imaging, and the expression of Na+/K+ ATPase isoforms was examined using quantitative RT-PCR (RT-qPCR). The expressed isoforms were then localized in blastocysts using fluorescent immunostaining.
MAIN RESULTS AND THE ROLE OF CHANCE
RT-qPCR results demonstrated the expression of Na+/K+ ATPase α1, β1 and β3 isoforms in human blastocysts. Isoforms α1 and β3 were localized to the basolateral membrane of TE cells, and β1 was localized between TE cells. A high level of β3 mRNA expression correlated with easier hatching (P = 0.0261).
LARGE SCALE DATA
N/A.
LIMITATIONS, REASONS FOR CAUTION
The expression of mRNA and the localization of proteins of interest were verified, but we have not been able to perform functional analysis.
WIDER IMPLICATIONS OF THE FINDINGS
Of the various Na+/K+ ATPase isoforms, expression levels of the α1, β1 and β3 mRNAs were clearly higher than other isoforms in human blastocysts. Since α1 and β3 were localized to the basolateral membrane via fluorescent immunostaining, we believe that these subunits contribute to the dilation of the blastocoel. The β1 isoform is localized between TE cells and may be involved in tight junction formation, as previously reported in mouse embryos.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by the JSPS KAKENHI (https://www.jsps.go.jp/english/index.html), grant number 17K11215. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no conflicts of interest.
BACKGROUND & AIMS: An antiulcer drug, geranylgeranylacetone (GGA), rapidly induces resistance of gastric mucosal cells to irritants in vivo and in vitro. The aim of this study was to elucidate the ...mechanism of this action. METHODS: Heat shock proteins (HSPs) were detected by immunoblotting with antibody against HSP90, HSP70, heat shock cognate protein 70, or HSP60. HSP70 messenger RNA level was measured by Northern hybridization with an HSP70 complementary DNA probe. Activation of the heat shock factor was detected by gel mobility shift assay with the heat shock element oligonucleotide. RESULTS: GGA induced resistance of cultured guinea pig gastric mucosal cells against ethanol- induced exfoliation and damage within 30 minutes, proportionally to the induction of the HSPs. This protection was blocked by cycloheximide but not by indomethacin. GGA caused rapid activation of heat shock factor 1 and expression of HSP70 messenger RNA in the cells. Intragastric administration of GGA to rats induced HSPs in gastric mucosa. The administration of GGA additionally enhanced the heat shock response and reduced ulcer formation in rats subjected to restraint and water- immersion stress. CONCLUSIONS: GGA may induce transcriptional activation of HSP genes, and this novel action may increase gastric mucosal defense at conditions of stress. (Gastroenterology 1996 Aug;111(2):345-57)
In order to clarify the association between hyperglycemia during the early period after allogeneic stem cell transplantation (allo-SCT) and adverse outcomes, we retrospectively analyzed 563 ...consecutive patients who underwent allo-SCT at our institute between 2008 and 2015. Patients were categorized into three groups according to mean fasting blood glucose levels on days 0-7 (normoglycemia group<110 mg/dL, n=347; mild hyperglycemia group 110-149 mg/dL, n=192 and moderate/severe hyperglycemia group≥150 mg/dL, n=24). The median follow-up was 2.7 years. Patients in the moderate/severe hyperglycemia group had significantly worse characteristics. The cumulative incidences of 2-year non-relapse mortality (NRM) and the probabilities of 2-year overall survival (OS) in the normoglycemia, mild hyperglycemia and moderate/severe hyperglycemia groups were 7.5%, 19% and 29%, respectively (P<0.01), and 69%, 53% and 33%, respectively (P<0.01). In multivariate analyses, hyperglycemia was an independent predictor of high NRM (vs normoglycemia; mild hyperglycemia, hazard ratio (HR) 2.56, 95% confidence interval (CI) 1.56-4.18; moderate/severe hyperglycemia, HR 4.46, 95% CI 1.92-10.3) and poor OS (vs normoglycemia; mild hyperglycemia, HR 1.54, 95% CI 1.14-2.07; moderate/severe hyperglycemia, HR 1.61, 95% CI 0.89-2.91). In conclusion, hyperglycemia on days 0-7 after allo-SCT was associated with inferior outcomes.
Electromagnetically driven microactuators are of interest because they have the potential to generate large deflections. Thus, we have been studying magnetically driven microactuators. This time, a ...magnetically driven linear microactuator has been newly developed by using microfabrication techniques. The microactuator is composed of a mobile microplatform (mover) with some permanent magnets (PMs) and a stator with a large number of planar coils. In this paper, two types of microplatforms are fabricated and compared with each other. Furthermore, static and dynamic characteristics of the magnetically driven linear microactuator are discussed.
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