Stratigraphy and Geological Development of the Chichibu Terrane in the Kuraoka district, Miyazaki Prefecture, Kyushu.

The Chichibu Terrane is divided into the Northern, Middle and Southern Belts. This thesis re-examines the stratigraphy of constituents of the Chichibu Terrane of this study area by investigating lithology, mega- and micro-fossils, and clarifying the geotectonic division, and discusses the tectonic development of the Chichibu Terrane from middle to western Kyushu. The Northern Belt is composed of the Lower Jurassic olistostrome facies of the Yurugidake and Mamihara Formations. The constituents of the Middle Belt are the pre-Silurian Kuraoka Igneous Rocks, the Silurian to Devonian Gionyama Formation, "green shist formation", the Upper Permian Kagamiyama, Upper Triassic Murono, Lower Jurassic Kanmuridake, Upper Jurassic Oishi Formations and the Cretaceous neritic sediments. The Southern Belt is divided into the northern unit representing the Lower to Upper Jurassic olistostrome facies and the southern unit of Upper Jurassic to Upper Cretaceous by the Shiraiwayama Thrust (Murata, 1981) trending nearly EW. Most of the Kagamiyama Formation, which had been considered to be of Middle Permian (Saito and Kanbe, 1954), is the Late Permian accretionary complex including exotic blocks of green rocks, chert, serpentinite and rare limestone. The high-pressure and low-temperature type metamorphic rocks of jadeite-glaucophene facies are included in some exotic blocks. Considering the radiolarian assemblage, both on northern and southern margins of the previous Kagamiayama Formation are redefined to be the Lower Jurassic olistostrome facies of the Mamihara Formation (newly named) and the Lower Jurassic well-organized Kanmuridake Formation (newly named). Constituents of the Northern Belt are distributed both on northern and southern sides (northern side: the Mamihara Formation, southern side: the Yurugidake Formation) of the Middle Belt (=Kurosegawa Terrane) in the study area, and the main constituents of Kurosegawa Terrane are considered to form a nappes thrust over the Northern Belt. Such distribution and structural relation are also confirmed in the Yatsushiro district (Miyamoto, 1990; and others) that suggests wider distribution from middle to western Kyushu now largely covered by the Aso pyroclastic flow deposits. The redefined Oishi Formation lies along the southern side of the Gionyama lenticular body which provides exotic blocks of granitic rocks and bluish-green acidic tuff into the apparent lowermost part. The upper part of the formation contains blocks of the Oishi Formation the Upper Permian sandstone, acidic tuff, and the Upper Jurassic sandstone. These exotic blocks are mostly a continental and continental shelf origin with an exception of chert gravels contained within the slump breccia. The Oishi Formation mainly represents a turbidite facies yielding the Early Callovian radiolarian assemblage. Such characteristics of lithofacies indicate that the Oishi Formation was deposited by gravity flow such as turbidity current and subsolifluction down to sedimentary basin during the Late Jurassic, accompanying with breakdown of the Upper Permian and Upper Triassic rocks. The breakdown was most probably caused by thrust movement within the accretionary complex. On the basis of the fossil evidence and lithofacies, the Cretaceous neritic sediments within the Middle and Northern Belts are divided into the correlatives of the Monobegawa Group in Shikoku (the Hauterivian to Lower Barremian Togawa, Barremian Tsubana, Aptian Kasabe, probably Aptian Gokase and Albian Shibanomoto Formations), the Kubo Formation and unconformably overlying Takahata Formation. The bivalve fauna of Kubo Formation (probably Late Albian) is newly found and is not related to the Lower Cretaceous Monobegawa Group of the Chichibu Terrane. However, it includes common taxa with those of the pre-Sotoizumi and Ryoke types of the Inner Zone-faunas in Southwest Japan. These two formations thrust over the formations (Kagamiyama, Mamihara and Togawa Formations) of the Northern and Middle Belts of the Chichibu Terrane, and judging from the bivalves from Kubo Formations, they are probably nappes from the north. The southern unit of the Chichibu Terrane distributed in a south area of the Shiroiwayama Thrust mainly consists of sandstone, shale and alternating beds, containing exotic blocks of limestone, chert and green rocks. The pelitic-matrix of this unit yields radiolarian fossils of younger age than early Late Jurassic. The Albian to Cenomanian radiolarian assemblage correlated with the Holocryptocanium barbui - H. geysersense A-zone (Nakaseko and Nishimura, 1981) or the H. barbui A-zone (Yao, 1984) is obtained from siliceous mudstone, suggesting. This unit is comparable with the lowermost to lower Upper Cretaceous Sakaguchi Formation (Nishizono and Murata, 1983) distributed along the southern margin of the Kannose Zone in Yatsushiro district, while the lithofacies and radiolarian age indicate that the formation can also be correlated with the Hinokage Formation (Imai et al., 1971) of the Morozuka Group of the Shimanto Terrane distributed in a south area of the Butsuzo Tectonic Line. The resemblance between these formations across the Butsuzo Tectonic Line reminds to re-examine the location and the significance of the Butsuzo Tectonic Line

Розробка математичної моделі оцінювання процесу іскріння в індуктивно-ємнісних електричних колах

The brain is one of the most energetically expensive organs in the vertebrate body. Consequently, the high cost of brain development and maintenance is predicted to constrain adaptive brain size evolution (the expensive tissue hypothesis, ETH). Here, we test the ETH in a teleost fish with predominant female mating competition (reversed sex roles) and male pregnancy, the pacific seaweed pipefish Syngnathus schlegeli. The relative size of the brain and other energetically expensive organs (kidney, liver, heart, gut, visceral fat, and ovary/testis) was compared among three groups: pregnant males, nonpregnant males and egg producing females. Brood size in pregnant males was unrelated to brain size or the size of any other organ, whereas positive relationships were found between ovary size, kidney size, and liver size in females. Moreover, we found that the size of energetically expensive organs (brain, heart, gut, kidney, and liver) as well as the amount of visceral fat did not differ between pregnant and nonpregnant males. However, we found marked differences in relative size of the expensive organs between sexes. Females had larger liver and kidney than males, whereas males stored more visceral fat than females. Furthermore, in females we found a negative correlation between brain size and the amount of visceral fat, whereas in males, a positive trend between brain size and both liver and heart size was found. These results suggest that, while the majority of variation in the size of various expensive organs in this species likely reflects that individuals in good condition can afford to allocate resources to several organs, the cost of the expensive brain was visible in the visceral fat content of females, possibly due to the high costs associated with female egg production.Data available from the Dryad Digital Repository: http://dx.doi.org/10.5061/dryad.t25d2</p

Anti-integrin αvβ6 autoantibodies in patients with primary sclerosing cholangitis

[Background] Patients with primary sclerosing cholangitis (PSC) possess autoantibodies against biliary epithelial cells. However, the target molecules remain unknown. [Methods] The sera of patients with PSC and controls were subjected to enzyme-linked immunosorbent assays to detect autoantibodies using recombinant integrin proteins. Integrin αvβ6 expression in the bile duct tissues was examined using immunofluorescence. The blocking activity of the autoantibodies was examined using solid-phase binding assays. [Results] Anti-integrin αvβ6 antibodies were detected in 49/55 (89.1%) patients with PSC and 5/150 (3.3%) controls (P < 0.001), with a sensitivity and specificity of 89.1% and 96.7%, respectively, for PSC diagnosis. When focusing on the presence or absence of IBD, the proportion of the positive antibodies in PSC with IBD was 97.2% (35/36) and that in PSC alone was 73.7% (14/19) (P = 0.008). Integrin αvβ6 was expressed in bile duct epithelial cells. Immunoglobulin (Ig)G from 15/33 patients with PSC blocked integrin αvβ6-fibronectin binding through an RGD (Arg–Gly–Asp) tripeptide motif. [Conclusions] Autoantibodies against integrin αvβ6 were detected in most patients with PSC; anti-integrin αvβ6 antibody may serve as a potential diagnostic biomarker for PSC

レゾルシル酸ラクトンLL-Z1640-2の成人T細胞白血病/リンパ腫に対する治療効果

Adult T-cell leukaemia/lymphoma (ATL) remains incurable. The NF-κB and interferon regulatory factor 4 (IRF4) signalling pathways are among the critical survival pathways for the progression of ATL. TGF-β-activated kinase 1 (TAK1), an IκB kinase-activating kinase, triggers the activation of NF-κB. The resorcylic acid lactone LL-Z1640-2 is a potent irreversible inhibitor of TAK1/extracellular signal-regulated kinase 2 (ERK2). We herein examined the therapeutic efficacy of LL-Z1640-2 against ATL. LL-Z1640-2 effectively suppressed the in vivo growth of ATL cells. It induced in vitro apoptosis and inhibited the nuclear translocation of p65/RelA in ATL cells. The knockdown of IRF4 strongly induced ATL cell death while downregulating MYC. LL-Z1640-2 as well as the NF-κB inhibitor BAY11-7082 decreased the expression of IRF4 and MYC at the protein and mRNA levels, indicating the suppression of the NF-κB-IRF4-MYC axis. The treatment with LL-Z1640-2 also mitigated the phosphorylation of p38 MAPK along with the expression of CC chemokine receptor 4. Furthermore, the inhibition of STAT3/5 potentiated the cytotoxic activity of LL-Z1640-2 against IL-2-responsive ATL cells in the presence of IL-2. Therefore, LL-Z1640-2 appears to be an effective treatment for ATL. Further studies are needed to develop more potent compounds that retain the active motifs of LL-Z1640-2

Identification of an Anti–Integrin αvβ6 Autoantibody in Patients With Ulcerative Colitis

指定難病「潰瘍性大腸炎」の自己抗体発見 --新たな診断や治療開発へ--. 京都大学プレスリリース. 2021-03-09.Background and Aims: Ulcerative colitis is the most frequent type of inflammatory bowel disease and is characterized by colonic epithelial cell damage. Although involvement of autoimmunity has been suggested in ulcerative colitis, specific autoantigens/antibodies have yet to be elucidated. Methods: Using 23 recombinant integrin proteins, we performed enzyme-linked immunosorbent assays on sera from patients with ulcerative colitis and controls. Integrin expression and IgG binding in the colon tissues of patients with ulcerative colitis and controls were examined using immunofluorescence and coimmunoprecipitation, respectively. The blocking activity of autoantibodies was examined using solid-phase binding and cell adhesion assays. Results: Screening revealed that patients with ulcerative colitis had IgG antibodies against integrin αvβ6. In the training and validation groups, 103 of 112 (92.0%) patients with ulcerative colitis and only 8 of 155 (5.2%) controls had anti–integrin αvβ6 antibodies (P < .001), resulting in a sensitivity of 92.0% and a specificity of 94.8% for diagnosing ulcerative colitis. Anti–integrin αvβ6 antibody titers coincided with ulcerative colitis disease activity, and IgG1 was the major subclass. Patient IgG bound to the integrin αvβ6 expressed on colonic epithelial cells. Moreover, IgG of patients with ulcerative colitis blocked integrin αvβ6–fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif and inhibited cell adhesion. Conclusions: A significant majority of patients with ulcerative colitis had autoantibodies against integrin αvβ6, which may serve as a potential diagnostic biomarker with high sensitivity and specificity

Clustering out-of-hospital cardiac arrest patients with non-shockable rhythm by machine learning latent class analysis

[Aim] We aimed to identify subphenotypes among patients with out-of-hospital cardiac arrest (OHCA) with initial non-shockable rhythm by applying machine learning latent class analysis and examining the associations between subphenotypes and neurological outcomes. [Methods] This study was a retrospective analysis within a multi-institutional prospective observational cohort study of OHCA patients in Osaka, Japan (the CRITICAL study). The data of adult OHCA patients with medical causes and initial non-shockable rhythm presenting with OHCA between 2012 and 2016 were included in machine learning latent class analysis models, which identified subphenotypes, and patients who presented in 2017 were included in a dataset validating the subphenotypes. We investigated associations between subphenotypes and 30-day neurological outcomes. [Results] Among the 12, 594 patients in the CRITICAL study database, 4, 849 were included in the dataset used to classify subphenotypes (median age: 75 years, 60.2% male), and 1, 465 were included in the validation dataset (median age: 76 years, 59.0% male). Latent class analysis identified four subphenotypes. Odds ratios and 95% confidence intervals for a favorable 30-day neurological outcome among patients with these subphenotypes, using group 4 for comparison, were as follows; group 1, 0.01 (0.001–0.046); group 2, 0.097 (0.051–0.171); and group 3, 0.175 (0.073–0.358). Associations between subphenotypes and 30-day neurological outcomes were validated using the validation dataset. [Conclusion] We identified four subphenotypes of OHCA patients with initial non-shockable rhythm. These patient subgroups presented with different characteristics associated with 30-day survival and neurological outcomes

Association between serum lactate level during cardiopulmonary resuscitation and survival in adult out-of-hospital cardiac arrest: a multicenter cohort study

We aimed to investigate the association between serum lactate levels during cardiopulmonary resuscitation (CPR) and survival in patients with out-of-hospital cardiac arrest (OHCA). From the database of a multicenter registry on OHCA patients, we included adult nontraumatic OHCA patients transported to the hospital with ongoing CPR. Based on the serum lactate levels during CPR, the patients were divided into four quartiles: Q1 (≤ 10.6 mEq/L), Q2 (10.6–14.1 mEq/L), Q3 (14.1–18.0 mEq/L), and Q4 (> 18.0 mEq/L). The primary outcome was 1-month survival. Among 5226 eligible patients, the Q1 group had the highest 1-month survival (5.6% [74/1311]), followed by Q2 (3.6% [47/1316]), Q3 (1.7% [22/1292]), and Q4 (1.0% [13/1307]) groups. In the multivariable logistic regression analysis, the adjusted odds ratio of Q4 compared with Q1 for 1-month survival was 0.24 (95% CI 0.13–0.46). 1-month survival decreased in a stepwise manner as the quartiles increased (p for trend < 0.001). In subgroup analysis, there was an interaction between initial rhythm and survival (p for interaction < 0.001); 1-month survival of patients with a non-shockable rhythm decreased when the lactate levels increased (p for trend < 0.001), but not in patients with a shockable rhythm (p for trend = 0.72). In conclusion, high serum lactate level during CPR was associated with poor 1-month survival in OHCA patients, especially in patients with non-shockable rhythm

Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization in an Inverse Microemulsion System: Homopolymerization, Chain Extension, and Block Copolymerization

We report the first successful reversible addition-fragmentation chain transfer inverse microemulsion polymerization (RAFT-IMEP). The inverse microemulsion (IME) system conditions were optimized by generating pseudo-three-component phase diagrams. The IME consisted of the hydrophilic monomer N,N-dimethylacrylamide (DMA), water, hexanes, nonionic surfactants, and a cosurfactant. The polymerization kinetics and the living character of RAFT-IMEP, conducted with varying amounts of dispersed aqueous phase, were similar to that observed for aqueous RAFT polymerization of DMA. The colloidal stability during polymerization was also investigated via dynamic light scattering. Decreasing the weight fraction of the dispersed aqueous phase leads to an increase in colloidal stability and a decrease in microemulsion size. An increase in the dispersity of molecular weight is also observed with a decrease in the weight fraction of dispersed aqueous phase. This observation is attributed to uncontrolled polymer that forms during the early stages of RAFT-IMEP. Chain extension or block copolymer formation is accomplished by simple addition of DMA or DEA to the polyDMA macroCTA, demonstrating the potential utility for preparing doubly hydrophilic block copolymers under appropriate RAFT/IMEP conditions