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| 2. |
- Ruilope, LM, et al.
(author)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 5. |
- Heuer, V. B., et al.
(author)
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Temperature limits to deep subseafloor life in the Nankai Trough subduction zone
- 2020
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6521, s. 1230-1234
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Journal article (peer-reviewed)abstract
- Microorganisms in marine subsurface sediments substantially contribute to global biomass. Sediments warmer than 40 degrees C account for roughly half the marine sediment volume, but the processes mediated by microbial populations in these hard-to-access environments are poorly understood. We investigated microbial life in up to 1.2-kilometer-deep and up to 120 degrees C hot sediments in the Nankai Trough subduction zone. Above 45 degrees C, concentrations of vegetative cells drop two orders of magnitude and endospores become more than 6000 times more abundant than vegetative cells. Methane is biologically produced and oxidized until sediments reach 80 degrees to 85 degrees C. In 100 degrees to 120 degrees C sediments, isotopic evidence and increased cell concentrations demonstrate the activity of acetate-degrading hyperthermophiles. Above 45 degrees C, populated zones alternate with zones up to 192 meters thick where microbes were undetectable.
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| 6. |
- Inagaki-Kawata, Y, et al.
(author)
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Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants
- 2020
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 578-
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Journal article (peer-reviewed)abstract
- The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1,995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants.
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| 7. |
- Ito, S, et al.
(author)
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Cdc7 kinase stimulates Aurora B kinase in M-phase
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 18622-
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Journal article (peer-reviewed)abstract
- The conserved serine-threonine kinase, Cdc7, plays a crucial role in initiation of DNA replication by facilitating the assembly of an initiation complex. Cdc7 is expressed at a high level and exhibits significant kinase activity not only during S-phase but also during G2/M-phases. A conserved mitotic kinase, Aurora B, is activated during M-phase by association with INCENP, forming the chromosome passenger complex with Borealin and Survivin. We show that Cdc7 phosphorylates and stimulates Aurora B kinase activity in vitro. We identified threonine-236 as a critical phosphorylation site on Aurora B that could be a target of Cdc7 or could be an autophosphorylation site stimulated by Cdc7-mediated phosphorylation elsewhere. We found that threonines at both 232 (that has been identified as an autophosphorylation site) and 236 are essential for the kinase activity of Aurora B. Cdc7 down regulation or inhibition reduced Aurora B activity in vivo and led to retarded M-phase progression. SAC imposed by paclitaxel was dramatically reversed by Cdc7 inhibition, similar to the effect of Aurora B inhibition under the similar situation. Our data show that Cdc7 contributes to M-phase progression and to spindle assembly checkpoint most likely through Aurora B activation.
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| 8. |
- Wang, J., et al.
(author)
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Final report of the CCQM-K145 : Toxic and essential elements in bovine liver
- 2020
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In: Metrologia. - : IOP Publishing Ltd. - 0026-1394 .- 1681-7575. ; 57:1 A
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Journal article (peer-reviewed)abstract
- Liver plays a major role in metabolism and acts as a source of energy for the body by storing glycogen. With the growing interest and investigation in the biological effects in recent years, it is important and necessary to develop accurate and comparable analytical methods for elements in bio-samples. It has, however, been 10 years since the tissue sample (bovine liver) of CCQM-K49 key comparison. The purpose of CCQM-K145 is to ensure the comparable and traceable measurement results for essential and toxic elements such as P, S, Zn, Mn, Ni, Mo, Sr, Cr, Co, Pb, As and Hg in bovine liver among NMIs and other designated measurement bodies worldwide. The comparison was agreed by IAWG as 6th IAWG Benchmarking Exercise with Zn and Ni as exemplary elements at the meeting in Korea in the early October 2016. The results of CCQM-K145 are expected to cover the measurement capability and support CMCs claiming for inorganic elements in the similar biological tissue materials and food samples. 30 NMIs and DIs registered in CCQM-K145. With respect to the methodology, a variety of techniques such as IDMS, ICP-OES, ICP-MS(non-ID), AAS and NAA were adopted by the participants. For Zn, Ni, Sr, Pb and Hg measurements, most participants chose ID-ICP-MS method, which showed the better performance in terms of consistency and reliability of the measurement results. In aspect of the traceability for the measurement results in CCQM-K145, most participants used their own (in house) CRMs or other NMI's CRMs to guarantee trace to SI unit. Most participants used similar matrix CRMs for quality control or method validation. Base on different statistic way to calculate the reference mass fraction values and associated uncertainties for each measurand, removal of the suspected extreme values, and discussion at the IAWG meetings, the median values are proposed as the KCRV for Zn, Ni, Mn, Mo, Cr, Pb and Hg; the arithmetic mean values are proposed as the KCRV for P, S, Sr, Co and As. In general, the performances of the majority of CCQM-K145 participants are very good, illustrating their measurement capabilities for Zn, Ni, P, S, Mn, Mo, Sr, Cr, As, Co, Pb and Hg in a complex biological tissue matrix. Bovine liver contains many kinds of nutrients and microelements, it can be regarded as a typical representative material of biological tissue and food. In CCQM-K145, the analytes involved alkali metals and transition elements, metalloids/semi-metals and non metals with a range of mass fraction from mg/g to μg/kg. CCQM-K145 also tested the ability of NMIs/DIs to determine elements that were easy to be lost and polluted, and interfered significantly. The chemical pretreatment methods of samples used in the comparison is suitable for general food and biological matrix samples. A variety of measurement methods used in the comparison represent the main instrumental technology for elemental analysis. Therefore, for supporting CMC claim, CCQM-K145 is readily applicable to measurement of more elements in a wide range of biological materials (including liquids and solids) and meat products. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
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| 11. |
- Quétel, C. R., et al.
(author)
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Methylmercury in tuna: demonstrating measurement capabilities and evaluating comparability of results worldwide from the CCQM P-39 comparison
- 2005
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In: Journal of Analytical Atomic Spectrometry. - : Royal Society of Chemistry (RSC). - 0267-9477 .- 1364-5544. ; 20, s. 1058-66
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Journal article (peer-reviewed)abstract
- Six metrology institutes (NMIs) representing at the Comité International des Poids et Mesures (CIPM) 4 Member States of the Metre Convention and 2 international organisations, and 8 expert laboratories selected outside CIPM have compared their capabilities to quantitatively measure methylmercury (MeHg) in a prepared tuna material containing approximately 4.3 mg kg–1 Hg. This comparison was the object of the CIPM–Comité Consultatif pour la Quantité de Matière (CCQM) Pilot Study 39, organised by the Institute for Reference Materials and Measurements (IRMM), from the European Commission—Joint Research Centre. Beside the test material itself, a bottle of the BCR-464 tuna Certified Reference Material (CRM) and an ampoule of IRMM-670, a 202Hg isotope enriched MeHg candidate isotopic CRM, were distributed to all participants, who were free to apply the measurement strategy of their choice. Four, including 1 NMI, relied on external calibration or the method of standard additions, whereas the other 10 implemented an isotope dilution mass spectrometry (IDMS) approach and chose to use the IRMM-670 for their measurements. Alkaline digestion at room temperature (with manual shaking) or high temperature (under sonication, oven or hot plate conditions) was employed by most participants, with hydrochloric acid leaching the second most popular choice. Alkylation (4 phenylations, 4 ethylations and 3 propylations) in the aqueous phase was preferred by a large majority over butylation by the Grignard reaction. All participants were requested to estimate the uncertainty associated with their results and 9 out of 14 stated relative combined uncertainties below 6%(k= 2). Despite this apparent consensus, the perception of which factor caused the largest contribution to this estimation differed among participants because of the differences in the analytical methodologies deployed but also because of wide differences of the concepts of uncertainty estimation. The mixture mode(MM) median, calculated also from the measurement uncertainties stated by the participants, was 1.967 ± 0.204 × 10–5 mol kg–1(95% confidence). Twelve of the results were re-grouped within a range of less than 0.3 × 10–5 mol kg–1(MM median = 1.967 ± 0.162 × 10–5 mol kg–1, 95% confidence): they nearly all (1 exception) overlapped with each other within k= 2 stated uncertainties. For the other 2 results the uncertainty seemed to have been particularly underestimated as they lay, respectively, at more than 20% above and less than –40% below the overall average. The relative standard deviation of the results of 9 laboratories out of the 10 that applied IDMS was about 2.6%. It can be assumed from the degree of equivalence shown by 12 out of 14 study participants that, at present, laboratories worldwide are potentially able to supply accurate results for MeHg in fish-type matrices (containing about 2 × 10–5 mol kg–1) within ±10% uncertainty. This encouraging outcome permitted scheduling of a follow-up CCQM-K43 key comparison for a lower MeHg content level in salmon tissues.
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| 12. |
- de Pablo, Yolanda, et al.
(author)
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Vimentin Phosphorylation Is Required for Normal Cell Division of Immature Astrocytes
- 2019
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In: Cells. - : MDPI AG. - 2073-4409. ; 8:9
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Journal article (peer-reviewed)abstract
- Vimentin (VIM) is an intermediate filament (nanofilament) protein expressed in multiple cell types, including astrocytes. Mice with VIM mutations of serine sites phosphorylated during mitosis (VIMSA/SA) show cytokinetic failure in fibroblasts and lens epithelial cells, chromosomal instability, facilitated cell senescence, and increased neuronal differentiation of neural progenitor cells. Here we report that in vitro immature VIMSA/SA astrocytes exhibit cytokinetic failure and contain vimentin accumulations that co-localize with mitochondria. This phenotype is transient and disappears with VIMSA/SA astrocyte maturation and expression of glial fibrillary acidic protein (GFAP); it is also alleviated by the inhibition of cell proliferation. To test the hypothesis that GFAP compensates for the effect of VIMSA/SA in astrocytes, we crossed the VIMSA/SA and GFAP(-/-) mice. Surprisingly, the fraction of VIMSA/SA immature astrocytes with abundant vimentin accumulations was reduced when on GFAP(-/-) background. This indicates that the disappearance of vimentin accumulations and cytokinetic failure in mature astrocyte cultures are independent of GFAP expression. Both VIMSA/SA and VIM(SA/SA)GFAP(-/-) astrocytes showed normal mitochondrial membrane potential and vulnerability to H2O2, oxygen/glucose deprivation, and chemical ischemia. Thus, mutation of mitotic phosphorylation sites in vimentin triggers formation of vimentin accumulations and cytokinetic failure in immature astrocytes without altering their vulnerability to oxidative stress.
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| 16. |
- Screaton, E., et al.
(author)
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Interactions between deformation and fluids in the frontal thrust region of the NanTroSEIZE transect offshore the Kii Peninsula, Japan : Results from IODP Expedition 316 Sites C0006 and C0007
- 2009
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In: Geochemistry Geophysics Geosystems. - 1525-2027. ; 10, s. Q0AD01-
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Journal article (peer-reviewed)abstract
- Integrated Ocean Drilling Program (IODP) Expedition 316 Sites C0006 and C0007 examined the deformation front of the Nankai accretionary prism offshore the Kii Peninsula, Japan. In the drilling area, the frontal thrust shows unusual behavior as compared to other regions of the Nankai Trough. Drilling results, integrated with observations from seismic reflection profiles, suggest that the frontal thrust has been active since similar to 0.78-0.436 Ma and accommodated similar to 13 to 34% of the estimated plate convergence during that time. The remainder has likely been distributed among out-of-sequence thrusts further landward and/or accommodated through diffuse shortening. Unlike results of previous drilling on the Nankai margin, porosity data provide no indication of undercompaction beneath thrust faults. Furthermore, pore water geochemistry data lack clear indicators of fluid flow from depth. These differences may be related to coarser material with higher permeability or more complex patterns of faulting that could potentially provide more avenues for fluid escape. In turn, fluid pressures may affect deformation. Well-drained, sand-rich material under the frontal thrust could have increased fault strength and helped to maintain a large taper angle near the toe. Recent resumption of normal frontal imbrication is inferred from seismic reflection data. Associated decollement propagation into weaker sediments at depth may help explain evidence for recent slope failures within the frontal thrust region. This evidence consists of seafloor bathymetry, normal faults documented in cores, and low porosities in near surface sediments that suggest removal of overlying material. Overall, results provide insight into the complex interactions between incoming materials, deformation, and fluids in the frontal thrust region.
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| 17. |
- Inagaki, A., et al.
(author)
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Thermal Image Velocimetry
- 2013
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In: Boundary-Layer Meteorology. - : Springer Science and Business Media LLC. - 0006-8314 .- 1573-1472. ; 149:1, s. 1-18
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Journal article (peer-reviewed)abstract
- A method for measuring the two-dimensional distribution of wind velocity vectors near a surface exposed to solar radiation, by tracking brightness temperature images instead of particle images, is proposed. It is based on time-sequential thermography with the algorithm used for particle image velocimetry. This thermal image velocimetry (TIV) was tested on a full-scale building wall covered by polystyrene boards attached side-by-side over a vertically elongated area measuring 22.2 m by 2.73 m. A thermal infrared camera was installed 8 m from the test wall to capture the wall-surface temperature at 30 Hz frequency. A sonic anemometer was also installed 35 mm from the surface used for validation of the TIV. The advection velocity estimated from thermal infrared imagery had a linear relationship with the wind velocity measured by the sonic anemometer, irrespective of the wind speed and direction. This linear slope was multiplied by the advection velocity of the thermal infrared image to rescale it to the wind velocity, and the term 'TIV velocity' was then used. A histogram and power spectra of the TIV velocity showed quantitatively good agreement with the velocity measured by the sonic anemometer, except for the high-frequency region of the spectra, where the TIV velocity was overestimated compared with that of the sonic anemometer. The method was also tested on ground covered by artificial turf to demonstrate its application to a horizontal plane with a wider area, extending for more than 80 m by 60 m.
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| 18. |
- Inagaki, Shunsuke, et al.
(author)
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Effects of adsorbed molecular ordering to the superconductivity of a two-dimensional atomic layer crystal
- 2023
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In: Physical Review Materials. - : American Physical Society. - 2475-9953. ; 7:2
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Journal article (peer-reviewed)abstract
- The effect of 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) adsorption on the physical properties of the two-dimensional (2D) atomic layer superconductor (ALSC) In/Si(111)-(7×3) has been studied by angle-resolved photoelectron spectroscopy, transport measurements, and scanning tunneling microscopy. Hole doping from the adsorbed molecules has been reported to increase the superconducting transition temperature Tc of this ALSC, and the molecular spin tends to decrease it. Owing to its large electron affinity and its nonexistent spin state, the adsorption of PTCDA was expected to increase Tc. However, the PTCDA adsorption dopes only a small number of holes in the In layers and causes a suppression of Tc with a sharp increase in the normal-state sheet resistance followed by an insulating transition. Taking the disordering of the arrangement of PTCDA into account, we conclude that the increase in resistance is due to the localization effect originating from the random potential that is induced by the disordered PTCDA molecules. The present result also indicates the importance of the crystallinity of a 2D molecular film adsorbed on ALSCs.
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| 19. |
- Leger, Michelle M., et al.
(author)
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Organelles that illuminate the origins of Trichomonas hydrogenosomes and Giardia mitosomes
- 2017
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In: NATURE ECOLOGY & EVOLUTION. - : Springer Science and Business Media LLC. - 2397-334X. ; 1:4
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Journal article (peer-reviewed)abstract
- Many anaerobic microbial parasites possess highly modified mitochondria known as mitochondrion-related organelles (MROs). The best-studied of these are the hydrogenosomes of Trichomonas vaginalis and Spironucleus salmonicida, which produce ATP anaerobically through substrate-level phosphorylation with concomitant hydrogen production; and the mitosomes of Giardia intestinalis, which are functionally reduced and lack any role in ATP production. Howewer, to understand the metabolic specializations that these MROs underwent in adaptation to parasitism, data from their free-living relatives are needed. Here, we present a large-scale comparative transcriptomic study of MROs across a major eukaryotic group, Metamonada, examining lineage-specific gain and loss of metabolic functions in the MROs of Trichomonas, Giardia, Spironucleus and their free-living relatives. Our analyses uncover a complex history of ATP production machinery in diplomonads such as Giardia, and their closest relative, Dysnectes; and a correlation between the glycine cleavage machinery and lifestyles. Our data further suggest the existence of a previously undescribed biochemical class of MRO that generates hydrogen but is incapable of ATP synthesis.
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| 20. |
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| 21. |
- Nakazawa, K., et al.
(author)
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Surface properties of dental zirconia ceramics affected by ultrasonic scaling and low-temperature degradation
- 2018
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:9
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Journal article (peer-reviewed)abstract
- Zirconia (3Y-TZP) dental prostheses are widely used in clinical dentistry. However, the effect of ultrasonic scaling performed as a part of professional tooth cleaning on 3Y-TZP dental prostheses, especially in conjunction with low-temperature degradation (LTD), has not been fully investigated. The present study aimed to evaluate the influence of ultrasonic scaling and LTD on the surface properties of 3Y-TZP in relation to bacterial adhesion on the treated surface. 3Y-TZP specimens (4 x 4 x 2 mm) were polished and then subjected to autoclaving at 134 degrees C for 100 h to induce LTD, followed by 10 rounds of ultrasonic scaling using a steel scaler tip for 1 min each. Surface roughness, crystalline structure, wettability, and hardness were analyzed by optical interferometry, X-ray diffraction analysis, contact angle measurement, and nano-indentation technique, respectively. Subsequently, bacterial adhesion onto the treated 3Y-TZP surface was evaluated using Streptococcus mitis and S. oralis. The results demonstrated that the combination of ultrasonic scaling and LTD significantly increased the Sa value (surface roughness parameter) of the polished 3Y-TZP surface from 1.6 nm to 117 nm. LTD affected the crystalline structure, causing phase transformation from the tetragonal to the monoclinic phase, and decreased both the contact angle and surface hardness. However, bacterial adhesion was not influenced by these changes in surface properties. The present study suggests that ultrasonic scaling may be acceptable for debridement of 3Y-TZP dental prostheses because it did not facilitate bacterial adhesion even in the combination with LTD, although it did cause slight roughening of the surface.
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