タービダイトにもとづいた混濁流の挙動の復元－安野層と日本海溝の例

京都大学新制・課程博士博士(理学)甲第24174号理博第4865号京都大学大学院理学研究科地球惑星科学専攻(主査)准教授 成瀬 元, 准教授 堤 昭人, 教授 野口 高明学位規則第4条第1項該当Doctor of ScienceKyoto UniversityDFA

The poly(ADP-ribosyl)ation of BRD4 mediated by PARP1 promoted pathological cardiac hypertrophy

The bromodomain and extraterminal (BET) family member BRD4 is pivotal in the pathogenesis of cardiac hypertrophy. BRD4 induces hypertrophic gene expression by binding to the acetylated chromatin, facilitating the phosphorylation of RNA polymerases II (Pol II) and leading to transcription elongation. The present study identified a novel post-translational modification of BRD4: poly(ADP-ribosyl)ation (PARylation), that was mediated by poly(ADP-ribose)polymerase-1 (PARP1) in cardiac hypertrophy. BRD4 silencing or BET inhibitors JQ1 and MS417 prevented cardiac hypertrophic responses induced by isoproterenol (ISO), whereas overexpression of BRD4 promoted cardiac hypertrophy, confirming the critical role of BRD4 in pathological cardiac hypertrophy. PARP1 was activated in ISO-induced cardiac hypertrophy and facilitated the development of cardiac hypertrophy. BRD4 was involved in the prohypertrophic effect of PARP1, as implied by the observations that BRD4 inhibition or silencing reversed PARP1-induced hypertrophic responses, and that BRD4 overexpression suppressed the anti-hypertrophic effect of PARP1 inhibitors. Interactions of BRD4 and PARP1 were observed by co-immunoprecipitation and immunofluorescence. PARylation of BRD4 induced by PARP1 was investigated by PARylation assays. In response to hypertrophic stimuli like ISO, PARylation level of BRD4 was elevated, along with enhanced interactions between BRD4 and PARP1. By investigating the PARylation of truncation mutants of BRD4, the C-terminal domain (CTD) was identified as the PARylation modification sites of BRD4. PARylation of BRD4 facilitated its binding to the transcription start sites (TSS) of hypertrophic genes, resulting in enhanced phosphorylation of RNA Pol II and transcription activation of hypertrophic genes. The present findings suggest that strategies targeting inhibition of PARP1-BRD4 might have therapeutic potential for pathological cardiac hypertrophy

Mixed methods to explore factors associated with the decline of patients in the methadone maintenance treatment program in Shanghai, China

BACKGROUND: This study was to characterize the Methadone Maintenance Treatment (MMT) in Shanghai, China, and to explore factors associated with the decline of patients in MMT during 2005-2016. METHODS: Both qualitative and quantitative methods were used in this study. Based on the data from Shanghai Centers for Disease Control (CDC), we described the changes in the number of patients who received MMT, and new enrollment each year from 2005 to 2016. Focus groups were conducted with 22 patients, and in-depth interviews were conducted with 9 service providers. RESULTS: Quantitative data demonstrate that the number of new enrollment began to decline in 2009, and the number of patients receiving MMT began to decline in 2012. The main reasons for dropout include (1) discontinuing medication due to unknown reasons (25%), (2) criminal activities other than drug-related crimes (20%), (3) relapse to heroin use (16%), and (4) physical disease (10%). Qualitative assessment results indicate that the major reasons for the decline of patients in MMT are as follows: (1) the increase of Amphetamine-type stimulants (ATS) use in recent years, (2) limited knowledge about MMT in both patients and MMT staff, (3) complicated enrollment criteria, and (4) discrimination against drug use. CONCLUSION: Various reasons to explain the decline of patients in MMT in Shanghai, China, were identified. Government agencies, service providers, and other stakeholders need to work together and overcome identified barriers to support MMT programs in China

Lattice and Collective Effects for PEP-X

This is a more comprehensive report of the accelerator physics in the white paper 'PEP-X Light Source at SLAC'. A new light source called 'PEP-X' would reside in the 2.2-km PEP-II tunnel. It has a hybrid lattice where two of its six arcs contain DBA cells that provide a total of 30 straight sections for insertion device beam lines and the remaining arcs contain TME cells for an extremely low emittance. Using 90 meter damping wigglers the horizontal emittance at 4.5 GeV is further reduced to 0.1 nm-rad. Many collective effects including intra-beam scattering, Touschek lifetime, and fast ion instability are studied. We expect that PEP-X will produce photon beams having brightnesses near 10{sup 22} (ph/s/mm{sup 2}/mrad{sup 2}/0.1% BW) at 10 keV and 10{sup 21} at 35 keV

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Comparative single-cell genomics of Atribacterota JS1 in the Japan Trench hadal sedimentary biosphere

Deep-sea and subseafloor sedimentary environments host heterotrophic microbial communities that contribute to Earth’s carbon cycling. However, the potential metabolic functions of individual microorganisms and their biogeographical distributions in hadal ocean sediments remain largely unexplored. In this study, we conducted single-cell genome sequencing on sediment samples collected from six sites (7,445–8,023 m water depth) along an approximately 500 km transect of the Japan Trench during the International Ocean Discovery Program Expedition 386. A total of 1,886 single-cell amplified genomes (SAGs) were obtained, offering comprehensive genetic insights into sedimentary microbial communities in surface sediments (<1 m depth) above the sulfate-methane transition zone along the Japan Trench. Our genome data set included 269 SAGs from Atribacterota JS1, the predominant bacterial clade in these hadal environments. Phylogenetic analysis classified SAGs into nine distinct phylotypes, whereas metagenome-assembled genomes were categorized into only two phylotypes, advancing JS1 diversity coverage through a single cell-based approach. Comparative genomic analysis of JS1 lineages from different habitats revealed frequent detection of genes related to organic carbon utilization, such as extracellular enzymes like clostripain and α-amylase, and ABC transporters of oligopeptide from Japan Trench members. Furthermore, specific JS1 phylotypes exhibited a strong correlation with in situ methane concentrations and contained genes involved in glycine betaine metabolism. These findings suggest that the phylogenomically diverse and novel Atribacterota JS1 is widely distributed in Japan Trench sediment, playing crucial roles in carbon cycling within the hadal sedimentary biosphere

Inverse Analysis of Experimental Scale Turbidity Currents Using Deep Learning Neural Networks

Despite the importance of turbidity currents in environmental and resource geology, their flow conditions and mechanisms are not well understood. This study proposes and verifies a novel method for the inverse analysis of turbidity currents using a deep learning neural network (DNN) with numerical and flume experiment data sets. Numerical data sets of turbidites were generated with a forward model. Then, the DNN model was trained to find the functional relationship between flow conditions and turbidites by processing the numerical data sets. The performance of the trained DNN model was evaluated with 2, 000 numerical test data sets and five experiment data sets. Inverse analysis results on numerical test data sets indicated that flow conditions can be reconstructed from depositional characteristics of turbidites. For experimental turbidites, spatial distributions of grain size and thickness were consistent with the sample values. Concerning hydraulic conditions, flow depth, layer-averaged velocity, and flow duration were reconstructed with a certain level of deviation. The reconstructed flow depth and duration had percent errors less than 36.0% except for one experiment, which had an error of 193% in flow duration. The flow velocity was reconstructed with percent errors 2.38%–73.7%. Greater discrepancies between the measured and reconstructed values of flow concentration (1.79%–300%) were observed relative to the former three parameters, which may be attributed to difficulties in measuring the flow concentration during experiments. Although the DNN model did not provide perfect reconstruction, it proved to be a significant advance for the inverse analysis of turbidity currents

The Ten Relationships in Rural Land Circulation

The ten relationships during land circulation are discussed. Among them, the relationship between peasant household and government indicates that government should only carry out its service and regulatory functions and farmers should be the main body of land circulation, because peasants usually have no discourse power during land circulation. In the relationship between land ownership and contracting management right, we mainly discuss the transfer of land contracting management right and point out that land contracting management right within a certain period is the object of land circulation. In the relationship between land circulation and deepening reform, land circulation is only an approach to develop scale management and to deepen the reform. Land circulation can be accelerated only by vigorously developing secondary and tertiary industries and speeding up the transfer of rural surplus labor force. In the relationship between land circulation and land reform, it is pointed out that China at present is not suitable for a new land reform. In the relationship between the land contract with time limit and the contract system and private ownership system, contract system and private ownership system are unsuitable for China at present; and we should continue to insist on the land contract with time limit. In the relationship between land circulation and economic development, land circulation is a natural process without enforceability. Otherwise, it may hinder the development of rural economy. In the relationship between enterprise and peasant household, land circulation should be held among peasants and companies and enterprises can participate in it. The relationship between land circulation and agriculture business performance points out that land circulation should adapt to the local situation. Relationship between land circulation and land loss and annexation shows that land circulation must adhere to the moderate principle and prevent land loss of peasants into a handful of persons. And the relationship between small peasant economy and agricultural modernization indicates that economic model of small peasant economy may not be an obstacle to the modernization of agriculture