Collisional bending of the western Paleo-Kuril Arc deduced from paleomagnetic analysis and U–Pb age determination

The Paleo‐Kuril Arc in the eastern Hokkaido region of Japan, the westernmost part of the Kuril Arc in the northwestern Pacific region, shows a tectonic bent structure. This has been interpreted, using paleomagnetic data, to be the result of block rotations in the Paleo‐Kuril Arc. To understand the timing and origin of this tectonic bent structure in the Paleo‐Kuril arc‐trench system, paleomagnetic surveys and U–Pb radiometric dating were conducted in the Paleogene Urahoro Group, which is distributed in the Shiranuka‐hill region, eastern Hokkaido. The U–Pb radiometric dating indicated that the Urahoro Group was deposited at approximately 39 Ma. Paleomagnetic analysis of the Urahoro Group suggested that the Shiranuka‐hill region experienced a 28° clockwise rotation with respect to East Asia. The degree of clockwise rotation implied from the Urahoro Group is smaller than that of the underlying Lower Eocene Nemuro Group (62°) but larger than that of the overlying Onbetsu Group (−9°). It is thus suggested that the Shiranuka‐hill region experienced a clockwise rotation of approximately 34° between the deposition of the Nemuro and Urahoro Groups (50–39 Ma), and a 38° clockwise rotation between the deposition of the Urahoro and Onbetsu Groups (39–34 Ma). The origin of the curved tectonic belt of the Paleo‐Kuril Arc was previously explained by the opening of the Kuril Basin after 34 Ma. The age constraint for the rotational motion of the Shiranuka‐hill region in this study contradicts this hypothesis. Consequently, it is suggested that the process of arc–arc collision induced the bent structure of the western Paleo‐Kuril Arc

Bayesian phase difference estimation algorithm for direct calculation of fine structure splitting: accelerated simulation of relativistic and quantum many-body effects

Despite rapid progress in the development of quantum algorithms in quantum computing as well as numerical simulation methods in classical computing for atomic and molecular applications, no systematic and comprehensive electronic structure study of atomic systems that covers almost all of the elements in the periodic table using a single quantum algorithm has been reported. In this work, we address this gap by implementing the recently-proposed quantum algorithm, the Bayesian Phase Difference Estimation (BPDE) approach, to compute accurately fine-structure splittings, which are relativistic in origin and it also depends on quantum many-body (electron correlation) effects, of appropriately chosen states of atomic systems, including highly-charged superheavy ions. Our numerical simulations reveal that the BPDE algorithm, in the Dirac--Coulomb--Breit framework, can predict the fine-structure splitting of Boron-like ions to within 605.3 cm$^{-1}$ of root mean square deviations from the experimental ones, in the (1s, 2s, 2p, 3s, 3p) active space. We performed our simulations of relativistic and electron correlation effects on Graphics Processing Unit (GPU) by utilizing NVIDIA's cuQuantum, and observe a $\times 42.7$ speedup as compared to the CPU-only simulations in an 18-qubit active space.Comment: 7+4 pages, 2 figure

Significant association between high serum CCL5 levels and better disease‐free survival of patients with early breast cancer

Analysis of anticancer immunity aids in assessing the prognosis of patients with breast cancer. From 250 operated breast cancers, we focused on serum levels of C-C motif chemokine ligand 5 (CCL5), which is involved in cancer immune reactions. Serum levels of CCL5 were measured using a cytometric bead-based immunoassay kit and CCL5 expression in cancer cells was determined using immunohistochemical staining. In addition, mRNA in cancer and stromal cells was analyzed by microdissection and comparison with the public dataset. Disease-free survival (DFS) of patients with high CCL5 levels (cut-off, 13.87 ng/mL; n = 192) was significantly better than those with low CCL5 levels (n = 58; hazard ratio, 0.20; 95% confidence interval, 0.10- 0.39; P < .0001). An improved overall survival was observed in patients with high CCL5 levels compared to those with low CCL5 levels (P = .024). On the contrary, high immunohistochemical expression of CCL5 in cancer cells was significantly associated with decreased DFS. As serum CCL5 levels did not correlate with CCL5 expression in cancer cells and the relative expression of mRNA CCL5 was elevated in stromal cells in relation to cancer cells, serum CCL5 might be derived not from cancer cells, but from stromal cells. Expression of CCL5 in serum, but not in cancer cells, might contribute to improved patient prognosis mediating through not only immune reaction, but through other mechanisms. Determination of circulating CCL5 levels could be useful for predicting patient prognosis

Perceptions and attitudes of users and non-users of mental health services concerning mental illness and services in Japan

ObjectivesThere is a global movement to develop and implement community-based integrated mental health systems. The present study attempted to clarify the perceptions and attitudes of users and non-users of mental health services concerning mental illness and services in Japan.MethodsA new questionnaire was developed for this internet survey. Data from 500 outpatients with depression and 500 healthy subjects were sampled according to the demographics of the Japanese population.ResultsOver 90% of healthy subjects and over 70% of patients were unaware of the common age of onset or lifetime prevalence of mental illness. Over 90% of the healthy subjects and about 70% of the patients could not describe any services where they would feel comfortable discussing mental health problems. In both groups, “adolescents and young adults” were ranked first as a target population for mental health and illness policies. The top requirement for the integrated care systems was the promotion and awareness of correct knowledge of mental illness in both the healthy subjects and patients.ConclusionSocietal requirements could include disseminating correct knowledge, awareness-raising actions for society, and implementing services where people, especially young people, can easily consult and receive support in the community

Overexpression of C16orf74 is involved in aggressive pancreatic cancers

Clinical outcome of pancreatic ductal adenocarcinoma (PDAC) has not been improved in the last three decades due to the lack of effective molecular-targeted drugs. To identify a novel therapeutic target for PDAC, we have performed genome-wide anamysis and found that Homo sapiens chromosome 16 open reading frame 74 (C16orf74) was up-regulated in the vast majority of PDAC. Overexpression of C16orf74 protein detected by immunohistochemical analysis was an independent prognostic factor for patients with PDAC. The knockdown of endogenous C16orf74 expression in the PDAC cell lines KLM-1 and PK-59 by vector-based small hairpin-RNA (shRNA) drastically attenuated the growth of those cells, whereas ectopic C16orf74 overexpression in HEK293T and NIH3T3 cells promoted cell growth and invasion, respectively. More importantly, the endogenous threonine 44 (T44)-phosphorylated form of C16orf74 interacted with the protein phosphatase 3 catalytic subunit alpha (PPP3CA) via the PDIIIT sequence in the PPP3CA-binding motif within the middle portion of C16orf74 in PDAC cells. The overexpression of mutants of C16orf74 lacking the PDIIIT sequence or T44 phosphorylation resulted in the suppression of invasive activity compared with wild-type C16orf74, indicating that their interaction should be indispensable for PDAC cell invasion. These results suggest that C16orf74 plays an important role for PDAC invasion and proliferation, and is a promising target for a specific treatment for patients with PDAC

Cloning and expression of vacuolar proton-pumping ATPase subunits in the follicular epithelium of the bullfrog endolymphatic sac

金沢大学環日本海域環境研究センター生物多様性研究部門In an investigation aimed at clarifying the mechanism of crystal dissolution of the calcium carbonate lattice in otoconia (the mineral particles embedded in the otolithic membrane) of the endolymphatic sac (ELS) of the bullfrog, cDNAs encoding the A- and E-subunits of bullfrog vacuolar proton-pumping ATPase (V-ATPase) were cloned and sequenced. The cDNA of the A-subunit consisted of an 11-bp 5′-untranslated region (UTR), a 1,854-bp open reading frame (ORF) encoding a protein comprising 617 amino acids with a calculated molecular mass of 68,168 Da, and a 248-bp 3′-UTR followed by a poly(A) tail. The cDNA of the E-subunit consisted of a 72-bp 5′-UTR, a 681-bp ORF encoding a protein of 226 amino acids with a calculated molecular mass of 26,020 Da, and a 799-bp 3′-UTR followed by a poly(A) tail. Western blot and immunofluorescence analyses using specific anti-peptide antisera against the V-ATPase A- and E-subunits revealed that these subunits were present in the ELS, urinary bladder, skin, testes, and kidneys. In the ELS, positive cells were scattered in the follicular epithelium which, as revealed by electron microscopy, corresponds to the location of mitochondria-rich cells. These findings suggest that V-ATPase, including the A- and E-subunits, exists in mitochondria-rich cells of the ELS, which might be involved in dissolution of the calcium carbonate crystals in the lumen of the ELS. © 2007 Zoological Society of Japan

Metformin directly binds the alarmin HMGB1 and inhibits its proinflammatory activity

Metformin is the first-line drug in the treatment of type 2 diabetes. In addition to its hypoglycemic effect, metformin has an anti-inflammatory function, but the precise mechanism promoting this activity remains unclear. High mobility group box 1 (HMGB1) is an alarmin that is released from necrotic cells and induces inflammatory responses by its cytokine-like activity and is, therefore, a target of anti-inflammatory therapies. Here we identified HMGB1 as a novel metformin-binding protein by affinity purification using a biotinylated metformin analogue. Metformin directly bound to the C-terminal acidic tail of HMGB1. Both in vitro and in vivo, metformin inhibited inflammatory responses induced by full-length HMGB1 but not by HMGB1 lacking the acidic tail. In an acetaminophen-induced acute liver injury model in which HMGB1 released from injured cells exacerbates the initial injury, metformin effectively reduced liver injury and had no additional inhibitory effects when the extracellular HMGB1 was blocked by anti-HMGB1-neutralizing antibody. In summary, we report for the first time that metformin suppresses inflammation by inhibiting the extracellular activity of HMGB1. Because HMGB1 plays a major role in inflammation, our results suggest possible new ways to manage HMGB1-induced inflammation

Tumor size and proliferative marker geminin levels associated with SUVmax levels on PET for breast cancers

It has been well established that maximum standardized uptake value (SUVmax) for 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) is clinically useful for evaluating treatment efficacy as well as predicting prognosis of breast cancer patients. Although SUVmax reflects increased glucose uptake and metabolism possibly induced by activation of growth factor signaling or TP53 dysfunction, tumor characteristics of SUVmax-high breast cancers remain to be elucidated. For the present study, we used immunohistochemical staining to investigate expressions of phospho-ribosomal protein S6 (pS6, downstream molecule of phosphatidyl inositol 3-kinase/Akt/mammalian target of the rapamycin/S6K pathway) and phosphor-p44/42 mitogen-activated protein kinase (pMAPK). Expression levels of TP53 and proliferative marker geminin as well as Ki67 were also examined by means of immunostaining in 163 invasive breast cancers. Cutoff values were set at 10% for pS6, 20% for pMAPK and TP53, and 4% for geminin. The SUVmax levels were significantly higher in the pS6-positive (p = 0.0173), TP53-positive (p = 0.0207) and geminin-high cancers (p2cm and geminin-high showed SUVmax-high, while only 6 of 49 (12.2%) breast cancers ≤2cm in size and with low geminin levels were SUVmax-high. In conclusion, we could determine that breast cancers with a large tumor and a geminin-high rather than Ki67- high proliferative marker were significantly associated with high levels of SUVmax. These findings may signify that SUVmax reflects tumor characteristics with high proliferative activity but not activation of mTOR/S6K and MAPK pathways or increased glucose metabolism due to dysfunction of TP53

Qualitative investigation of the factors that generate ambivalent feelings in women who give birth after receiving negative results from non-invasive prenatal testing

Background: Women who receive negative results from non-invasive prenatal genetic testing (NIPT) may find that they later have mixed or ambivalent feelings, for example, feelings of accepting NIPT and regretting undergoing the test. This study aimed to investigate the factors generating ambivalent feelings among women who gave birth after having received negative results from NIPT. Methods: A questionnaire was sent to women who received a negative NIPT result, and a contents analysis was conducted focusing on ambivalent expressions for those 1562 women who responded the questionnaire. The qualitative data gathered from the questionnaire were analyzed using the N-Vivo software package. Results: Environmental factors, genetic counseling-related factors, and increased anticipatory anxiety, affected the feeling of ambivalence among pregnant women. Furthermore, pregnant women desired more information regarding the detailed prognosis for individuals with Down syndrome and living with them and/or termination, assuming the possibility that they were positive. Conclusions: Three major interrelated factors affected the feeling of ambivalence in women. Highlighting and discussing such factors during genetic counseling may resolve some of these ambivalences, thereby enhancing the quality of decisions made by pregnant women