Western North Pacific Integrated Physical-Biogeochemical Ocean Observation Experiment (INBOX): Part 3. Mesoscale variability of dissolved oxygen concentrations observed by multiple floats during S1-INBOX

As part of the interdisciplinary project S1-INBOX (Western North Pacific Integrated Physical-Biogeochemical Ocean Observation Experiment conducted around the S1 biogeochemical mooring site), we used data from more than 18 floats and a biogeochemical mooring S1 (near 30° N, 145° E) to investigate temporal and spatial changes in the shallow oxygen maximum (SOM) associated with a mesoscale cyclonic eddy. On the northern edge of the cyclonic eddy, patches (linear dimensions of 20–40 km) with relatively high oxygen concentrations were observed around the SOM. The patterns of the oxygen concentrations reflected the fact that changes of the depths of the isopycnal surfaces were caused by small disturbances associated with the eddy structure along the eddy edge. The implication is that nutrient-rich water was supplied by upward isopycnal heaving at the edge of the eddy and contributed to the formation of the high-oxygen patches. As relatively high oxygen concentrations on the same isopycnal surfaces at greater depths were sometimes observed in the region downstream of the high-oxygen patches, we suggest that the patches were advected to the downstream region. The high-oxygen water seemed to extend into the eddy core from its edge. Ageostrophic secondary circulation around the edge of the eddy might have contributed to maintenance of the high oxygen concentrations in the eddy core, and these high oxygen concentrations may have been formed during spin-up of the eddy by heaving of isopycnal surfaces

Efficiency of Mixing Forced by Unsteady Shear Flow

The dependence of mixing efficiency on time-varying forcing is studied by direct numerical simulation (DNS) of Kelvin–Helmholtz (KH) instability. Time-dependent forcing fields are designed to reproduce a wavelike oscillation by solving the equations of motion in a tilted coordinate frame and allowing the tilt angle to vary in time. Mixing efficiency Γ is defined as the ratio of potential energy gain to dissipation, both averaged over one forcing cycle and first examined via parameters characterizing waves: the minimum Richardson number Riₘᵢₙ and the normalized frequency of the forcing ω/N. The effect of Reynolds number Re₀ and the initial random disturbance amplitude b are also examined. In the experiments presented, Γ varies between 0.21 and 0.36 and is controlled by the timing of two events: the emergence of KH billows and the arrival of the deceleration of the mean shear by the wavelike forcing. Here, Γ is higher than a canonical value of 0.2 when the deceleration phase of the forcing suppresses the less efficient turbulence after breakdown of KH billows. However, when Riₘᵢₙ and ω/N are small, KH billows start to develop before Riₘᵢₙ is achieved. Therefore, the forcing accelerates the mean shear and thereby sustains turbulence after the breakdown of KH billows. The canonical value is then reproduced in the DNS. Although larger values of Re₀ and b intensify the development of KH billows and modify Γ, this effect is less significant when forcing fields act to sustain turbulence. The time-averaged Thorpe scale and Ozmidov scale are also used to see how mixing is modified by forcing fields and compared with past microstructure measurements. It is found that DNS also corresponds to past observations if the forcing accelerates the mean shear to sustain turbulence

Western North Pacific Integrated Physical-Biogeochemical Ocean Observation Experiment (INBOX): Part 2. Biogeochemical responses to eddies and typhoons revealed from the S1 mooring and shipboard measurements

An interdisciplinary project called S1-INBOX (Western North Pacific Integrated PhysicalBiogeochemical Ocean Observation Experiment conducted around the S1 biogeochemical mooring site) was carried out during the summer of 2011 in the oligotrophic, subtropical North Pacific Ocean near biogeochemical mooring S1 (30° N, 145° E). Results from the S1 mooring during S1-INBOX revealed a large export flux at a depth of 200 m, a high chlorophyll a concentration in the deep chlorophyll maximum layer, and a high potential photochemical efficiency of photosystem II. These phenomena were associated with vertical uplift of isopycnal surfaces at the edge of a cyclonic eddy and a transition from the cyclonic eddy to an anticyclonic eddy. Shipboard biogeochemical surveys conducted during oligotrophic conditions in July 2011 revealed that the phytoplankton community in these waters was dominated by small species that are responsive to intermittent supplies of nutrients. Surface wind forcing because of Typhoons MA-ON and SONCA may have generated near-inertial oscillations. Diapycnal mixing associated with near-inertial waves was also related to high export fluxes, the indication being that propagation of near-inertial internal waves and subsequent mixing may have been important to biogeochemical phenomena during S1-INBOX

Western North Pacific Integrated Physical-Biogeochemical Ocean Observation Experiment (INBOX): Part 1.Specifications and chronology of the S1-INBOX floats

An interdisciplinary project called the Western North Pacific Integrated Physical-Biogeochemical Ocean Observation Experiment (INBOX) has been conducted since 2011. In the oligotrophic subtropics south of the Kuroshio Extension near biogeochemical mooring S1 (30° N, 145° E), 18 floats, each with a dissolved oxygen sensor, have been deployed in a 150 × 150 km square area. With the horizontal (30 km) and temporal (2 days) resolution of the data, we observed an upper ocean structure associated with mesoscale eddies and ocean responses to atmospheric forcing. The data set obtained from the S1-INBOX study was used to elucidate the impacts of physical processes on biogeochemical phenomena. This article is the first in a series of articles: specific information about the floats and a chronology of events are provided

Neutrino Masses in the Supersymmetric Standard Model with Right-Handed Neutrinos and Spontaneous R-Parity Violation

We propose an extension of the supersymmetric standard model with right-handed neutrinos and a singlet Higgs field, and study the neutrino masses in this model. The Majorana masses for the right-handed neutrinos are generated around the supersymmetry breaking scale through the vacuum expectation value of the singlet Higgs field. This model may induce spontaneous R-parity violation via the vacuum expectation value of the right-handed sneutrino. In the case, the effective theory is similar to a bilinear R-parity violating model. There are two sources for the neutrino masses: one is this bilinear R-parity breaking effect, and the other is the ordinary seesaw effect between left- and right-handed neutrinos. Combining these two effects, the hierarchical neutrino mass pattern arises even when the neutrino Yukawa matrices are not hierarchical. We acquire appropriate masses and mixings to explain both the solar and atmospheric neutrino oscillations.Comment: 22pages, RevTeX, 3 ps figures; a reference adde

Functional and genomic characterization of patient‐derived xenograft model to study the adaptation to mTORC1 inhibitor in clear cell renal cell carcinoma

Resistance to the mechanistic target of rapamycin (mTOR) inhibitors, which are a standard treatment for advanced clear cell renal cell carcinoma (ccRCC), eventually develops in most cases. In this study, we established a patient-derived xenograft (PDX) model which acquired resistance to the mTOR inhibitor temsirolimus, and explored the underlying mechanisms of resistance acquisition. Temsirolimus was administered to PDX model mice, and one cohort of PDX models acquired resistance after repeated passages. PDX tumors were genetically analyzed by whole-exome sequencing and detected several genetic alterations specific to resistant tumors. Among them, mutations in ANKRD12 and DNMT1 were already identified in the early passage of a resistant PDX model, and we focused on a DNMT1 mutation as a potential candidate for developing the resistant phenotype. While DNMT1 expression in temsirolimus-resistant tumors was comparable with the control tumors, DNMT enzyme activity was decreased in resistant tumors compared with controls. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated heterozygous knockdown of DNMT1 in the temsirolimus-sensitive ccRCC (786-O) cell line was shown to result in a temsirolimus-resistant phenotype in vitro and in vivo. Integrated gene profiles using methylation and microarray analyses of PDX tumors suggested a global shift for the hypomethylation status including promotor regions, and showed the upregulation of several molecules that regulate the mTOR pathway in temsirolimus-resistant tumors. Present study showed the feasibility of PDX model to explore the mechanisms of mTOR resistance acquisition and suggested that genetic alterations, including that of DNMT1, which alter the methylation status in cancer cells, are one of the potential mechanisms of developing resistance to temsirolimus

Single ingestion of soy β-conglycinin induces increased postprandial circulating FGF21 levels exerting beneficial health effects

Soy protein β-conglycinin has serum lipid-lowering and anti-obesity effects. We showed that single ingestion of β-conglycinin after fasting alters gene expression in mouse liver. A sharp increase in fibroblast growth factor 21 (FGF21) gene expression, which is depressed by normal feeding, resulted in increased postprandial circulating FGF21 levels along with a significant decrease in adipose tissue weights. Most increases in gene expressions, including FGF21, were targets for the activating transcription factor 4 (ATF4), but not for peroxisome proliferator-activated receptor α. Overexpression of a dominant-negative form of ATF4 significantly reduced β-conglycinin-induced increases in hepatic FGF21 gene expression. In FGF21-deficient mice, β-conglycinin effects were partially abolished. Methionine supplementation to the diet or primary hepatocyte culture medium demonstrated its importance for activating liver or hepatocyte ATF4-FGF21 signaling. Thus, dietary β-conglycinin intake can impact hepatic and systemic metabolism by increasing the postprandial circulating FGF21 levels.UTokyo Research掲載「大豆のタンパク質1回摂取で代謝を改善する因子が急増」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/single-ingestion-of-soy-protein-improves-metabolism.htmlUTokyo Research "Single ingestion of soy protein improves metabolism" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/single-ingestion-of-soy-protein-improves-metabolism.htm

Comparison of cellular characteristics between human hepatoma cell lines with wild-type p53 and those with mutant-type p53 gene

Characteristics of human hepatoma cell lines with the wild-type p53 were compared with those of human hepatoma cell lines with the mutant-type p53. The p21 protein located downstream of p53 was expressed in cell lines with the wild-type p53 but was not expressed in cell lines with the mutant-type p53. As to other tumor suppressor genes such as p16 and p27, there was no difference in their expression between both types of cell lines. In addition, no marked difference was observed in the activities of CDK2 and CDK4 between cell lines with the wild-type and the mutant-type p53. Phosphorylated Rb protein was detected in all cell lines except the HLE line, indicating that this cell line may have a deletion of and/or a mutation of the Rb gene. These results indicate that abnormalities of tumor suppressor genes other than p53, p16, p27, and Rb may be involved in hepatocarcinogenesis. The population doubling time of the wild-type p53 cells was significantly longer than that of the mutant p53 cells. Neither type of cell line showed a specific chromosome distribution which would indicate karyotype instability. The cell lines expressing the wild-type p53 produced tumors at lower frequency than those with the mutant p53 gene. Although there was no significant difference in effects of TGF-&#946;1, EGF, cholera toxin, and db-cAMP on cell growth between the two types of cells, all three cell lines with the wild-type p53 were resistant to cytotoxicity of TNF-&#945;, while two of the three with the mutant p53 were very sensitive to its cytotoxic effects.</p

Ad4BP/SF-1 regulates cholesterol synthesis to boost the production of steroids

Housekeeping metabolic pathways such as glycolysis are active in all cell types. In addition, many types of cells are equipped with cell-specific metabolic pathways. To properly perform their functions, housekeeping and cell-specific metabolic pathways must function cooperatively. However, the regulatory mechanisms that couple metabolic pathways remain largely unknown. Recently, we showed that the steroidogenic cell-specific nuclear receptor Ad4BP/ SF-1, which regulates steroidogenic genes, also regulates housekeeping glycolytic genes. Here, we identify cholesterogenic genes as the targets of Ad4BP/SF-1. Further, we reveal that Ad4BP/SF-1 regulates Hummr, a candidate mediator of cholesterol transport from endoplasmic reticula to mitochondria. Given that cholesterol is the starting material for steroidogenesis and is synthesized from acetyl-CoA, which partly originates from glucose, our results suggest that multiple biological processes involved in synthesizing steroid hormones are governed by Ad4BP/SF-1. To our knowledge, this study provides the first example where housekeeping and cell-specific metabolism are coordinated at the transcriptional level.This work was supported by Grants 16H05142 (K.M.), 17H06427 (K.M.), 16K08593 (T.B.), and 17J03270 (M.I.) from the Japan Society for the Promotion of Science (JSPS) KAKENHI; The Uehara Memorial Foundation (K.M.); Takeda Science Foundation (T.B.); The Shin-Nihon of Advanced Medical Research (T.B.).Supplementary information accompanies this paper at https://doi.org/10.1038/s42003-018-0020-z

Dynamical Doublet-Triplet Higgs Mass Splitting

We propose a new mechanism towards the solution to the doublet-triplet Higgs mass splitting problem in the supersymmetric grand unified theory. Our model is based on the gauge group $SU(5)_H \times SU(5)_{GUT}$, where $SU(5)_H$ and $SU(5)_{GUT}$ are a new strong gauge interaction and the ordinary grand unified gauge group, respectively. The doublet-triplet Higgs mass splitting is realized through the quantum deformation of moduli space caused by the strong $SU(5)_H$ gauge dynamics. The low energy description of our model is given by the minimal supersymmetric standard model.Comment: 9 pages, LaTeX, the version to be published in Phys. Rev. D. (some typographical errors have been corrected