Continuous Monitoring and Future Projection of Ocean Warming, Acidification, and Deoxygenation on the Subarctic Coast of Hokkaido, Japan

As the ocean absorbs excessive anthropogenic CO2 and ocean acidification proceeds, it is thought to be harder for marine calcifying organisms, such as shellfish, to form their skeletons and shells made of calcium carbonate. Recent studies have suggested that various marine organisms, both calcifiers and non-calcifiers, will be affected adversely by ocean warming and deoxygenation. However, regardless of their effects on calcifiers, the spatiotemporal variability of parameters affecting ocean acidification and deoxygenation has not been elucidated in the subarctic coasts of Japan. This study conducted the first continuous monitoring and future projection of physical and biogeochemical parameters of the subarctic coast of Hokkaido, Japan. Our results show that the seasonal change in biogeochemical parameters, with higher pH and dissolved oxygen (DO) concentration in winter than in summer, was primarily regulated by water temperature. The daily fluctuations, which were higher in the daytime than at night, were mainly affected by daytime photosynthesis by primary producers and respiration by marine organisms at night. Our projected results suggest that, without ambitious commitment to reducing CO2 and other greenhouse gas emissions, such as by following the Paris Agreement, the impact of ocean warming and acidification on calcifiers along subarctic coasts will become serious, exceeding the critical level of high temperature for 3 months in summer and being close to the critical level of low saturation state of calcium carbonate for 2 months in mid-winter, respectively, by the end of this century. The impact of deoxygenation might often be prominent assuming that the daily fluctuation in DO concentration in the future is similar to that at present. The results also suggest the importance of adaptation strategies by local coastal industries, especially fisheries, such as modifying aquaculture styles

Lattice instability and elastic dispersion due to the rattling motion in the type-I clathrate Ba_8Ga_<16>Sn_<30>

To investigate the off-center rattling motion and its charge-carrier dependence in type-I clathrate compounds, we carried out ultrasonic measurements on type-I Ba8Ga16Sn30 and a reference compound, K8Ga8Sn38. We found elastic softening of C44 originating from a lattice instability due to the off-center rattling motion of Ba atom in Ba8Ga16Sn30. Elastic softening below 1 K suggests that the lattice instability remains at very low temperatures. We also found ultrasonic dispersion which has no mode selectivity. No-mode-selective ultrasonic dispersion in Ba8Ga16Sn30 would be caused by a strong electron-phonon coupling. No charge-carrier dependence is observed between n-type and p-type Ba8Ga16Sn30. The significant softening on the bulk modulus in Ba8Ga16Sn30 contrasts to the continuous hardening in K8Ga8Sn38, indicating the central role of the rattling motion in the softening

A Multicenter, Open-label, Clinical Trial to Assess the Effectiveness and Safety of Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced-intensity Conditioning in Relapsed/refractory Anaplastic Large-cell Lymphoma in Children

No standard treatment for relapsed or refractory anaplastic large-cell lymphoma (ALCL) has been established. This study is a multicenter, open-label trial to examine the effectiveness and safety of transplantation with reduced-intensity conditioning (RIC) for patients under 20 years old with relapsed or refractory ALCL. We defined RIC as the administration of fludarabine (30 mg/m2/day) for five days plus melphalan (70 mg/m2/day) for two days and total body irradiation at 4 Gy, followed by allogeneic hematopoietic stem cell transplantation

A comparative simulation study of coupled THM processes and their effect on fractured rock permeability around nuclear waste repositories

This paper presents an international, multiple-code, simulation study of coupled thermal, hydrological, and mechanical (THM) processes and their effect on permeability and fluid flow in fractured rock around heated underground nuclear waste emplacement drifts. Simulations were conducted considering two types of repository settings: (a) open emplacement drifts in relatively shallow unsaturated volcanic rock, and (b) backfilled emplacement drifts in deeper saturated crystalline rock. The results showed that for the two assumed repository settings, the dominant mechanism of changes in rock permeability was thermal-mechanically-induced closure (reduced aperture) of vertical fractures, caused by thermal stress resulting from repository-wide heating of the rock mass. The magnitude of thermal-mechanically-induced changes in permeability was more substantial in the case of an emplacement drift located in a relatively shallow, low-stress environment where the rock is more compliant, allowing more substantial fracture closure during thermal stressing. However, in both of the assumed repository settings in this study, the thermal-mechanically-induced changes in permeability caused relatively small changes in the flow field, with most changes occurring in the vicinity of the emplacement drifts

A comparative simulation study of coupled THM processes and their effect on fractured rock permeability around nuclear waste repositories

Abstract This paper presents an international, multiple-code, simulation study of coupled thermal, hydrological, and mechanical (THM) processes and their effect on permeability and fluid flow in fractured rock around heated underground nuclear waste emplacement drifts. Simulations were conducted considering two types of repository settings: (a) open emplacement drifts in relatively shallow unsaturated volcanic rock, and (b) backfilled emplacement drifts in deeper saturated crystalline rock. The results showed that for the two assumed repository settings, the dominant mechanism of changes in rock permeability was thermalmechanically-induced closure (reduced aperture) of vertical fractures, caused by thermal stress resulting from repository-wide heating of the rock mass. The magnitude of thermal-mechanically-induced changes in permeability was more substantial in the case of an emplacement drift located in a relatively shallow, low-stress environment where the rock is more compliant, allowing more substantial fracture closure during thermal stressing. However, in both of the assumed repository settings in this study, the thermalmechanically induced changes in permeability caused relatively small changes in the flow field, with most changes occurring in the vicinity of the emplacement drifts

E3 Ubiquitin Ligase Synoviolin Is Involved in Liver Fibrogenesis

Chronic hepatic damage leads to liver fibrosis, which is characterized by the accumulation of collagen-rich extracellular matrix. However, the mechanism by which E3 ubiquitin ligase is involved in collagen synthesis in liver fibrosis is incompletely understood. This study aimed to explore the involvement of the E3 ubiquitin ligase synoviolin (Syno) in liver fibrosis.The expression and localization of synoviolin in the liver were analyzed in CCl(4)-induced hepatic injury models and human cirrhosis tissues. The degree of liver fibrosis and the number of activated hepatic stellate cells (HSCs) was compared between wild type (wt) and Syno(+/-) mice in the chronic hepatic injury model. We compared the ratio of apoptosis in activated HSCs between wt and Syno(+/-) mice. We also analyzed the effect of synoviolin on collagen synthesis in the cell line from HSCs (LX-2) using siRNA-synoviolin and a mutant synoviolin in which E3 ligase activity was abolished. Furthermore, we compared collagen synthesis between wt and Syno(-/-) mice embryonic fibroblasts (MEF) using quantitative RT-PCR, western blotting, and collagen assay; then, we immunohistochemically analyzed the localization of collagen in Syno(-/-) MEF cells.In the hepatic injury model as well as in cirrhosis, synoviolin was upregulated in the activated HSCs, while Syno(+/-) mice developed significantly less liver fibrosis than in wt mice. The number of activated HSCs was decreased in Syno(+/-) mice, and some of these cells showed apoptosis. Furthermore, collagen expression in LX-2 cells was upregulated by synoviolin overexpression, while synoviolin knockdown led to reduced collagen expression. Moreover, in Syno(-/-) MEF cells, the amounts of intracellular and secreted mature collagen were significantly decreased, and procollagen was abnormally accumulated in the endoplasmic reticulum.Our findings demonstrate the importance of the E3 ubiquitin ligase synoviolin in liver fibrosis

The Effect of Interim FDG-PET-guided Response-Adapted Therapy in Pediatric Patients with Hodgkin’s Lymphoma (HL-14) : Protocol for a Phase II Study

This trial enrolls patients with untreated Hodgkin’s lymphoma aged<20 years at diagnosis and examines the effects of omitting radiation therapy if the FDG-positron emission tomography (PET) findings after two completed cycles of combination chemotherapy are negative. It thereby aims to determine whether patients who truly require radiation therapy can be identified by FDG-PET. If so, this modality could be used to omit radiation therapy for all other patients, decreasing the risk of serious long-term complications without affecting survival rates. The outcomes of patients for whom FDG-PET is used to assess early treatment response will also be determined

Abnormally High Levels of Virus-Infected IFN-γ+CCR4+CD4+CD25+ T Cells in a Retrovirus-Associated Neuroinflammatory Disorder

BACKGROUND:Human T-lymphotropic virus type 1 (HTLV-1) is a human retrovirus associated with both HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic neuroinflammatory disease, and adult T-cell leukemia (ATL). The pathogenesis of HAM/TSP is known to be as follows: HTLV-1-infected T cells trigger a hyperimmune response leading to neuroinflammation. However, the HTLV-1-infected T cell subset that plays a major role in the accelerated immune response has not yet been identified. PRINCIPAL FINDINGS:Here, we demonstrate that CD4(+)CD25(+)CCR4(+) T cells are the predominant viral reservoir, and their levels are increased in HAM/TSP patients. While CCR4 is known to be selectively expressed on T helper type 2 (Th2), Th17, and regulatory T (Treg) cells in healthy individuals, we demonstrate that IFN-gamma production is extraordinarily increased and IL-4, IL-10, IL-17, and Foxp3 expression is decreased in the CD4(+)CD25(+)CCR4(+) T cells of HAM/TSP patients as compared to those in healthy individuals, and the alteration in function is specific to this cell subtype. Notably, the frequency of IFN-gamma-producing CD4(+)CD25(+)CCR4(+)Foxp3(-) T cells is dramatically increased in HAM/TSP patients, and this was found to be correlated with disease activity and severity. CONCLUSIONS:We have defined a unique T cell subset--IFN-gamma(+)CCR4(+)CD4(+)CD25(+) T cells--that is abnormally increased and functionally altered in this retrovirus-associated inflammatory disorder of the central nervous system

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection