Hierarchical structure of physical Yukawa couplings from matter field K\"ahler metric

We study the impacts of matter field K\"ahler metric on physical Yukawa couplings in string compactifications. Since the K\"ahler metric is non-trivial in general, the kinetic mixing of matter fields opens a new avenue for realizing a hierarchical structure of physical Yukawa couplings, even when holomorphic Yukawa couplings have the trivial structure. The hierarchical Yukawa couplings are demonstrated by couplings of pure untwisted modes on toroidal orbifolds and their resolutions in the context of heterotic string theory with standard embedding. Also, we study the hierarchical couplings among untwisted and twisted modes on resolved orbifolds.Comment: 25 pages, 6 figures, v2: published versio

Flavor, CP and Metaplectic Modular Symmetries in Type IIB Chiral Flux Vacua

We examine symmetries of chiral four-dimensional vacua of Type IIB flux compactifications with vanishing superpotential $W=0$. We find that the ${\cal N}=1$ supersymmetric MSSM-like and Pati-Salam vacua possess enhanced discrete symmetries in the effective action below the mass scale of stabilized complex structure moduli and dilaton. Furthermore, a generation number of quarks/leptons is small on these vacua where the flavor, CP and metaplectic modular symmetries are described in the framework of eclectic flavor symmetry.Comment: 30 pages, 5 figure

Novel moduli space in modular flavor models : a case study for modular T′T' seesaw model with hidden SU(2)SU(2) gauge symmetry

We study flavor phenomenologies in a basis of a double covering of modular $A_4$ group with a hidden $SU(2)$ symmetry, in which we work on regions at nearby two fixed points and three special points. These special points of $SL(2,\mathbb{Z})$ moduli space are statistically favored in flux compactifications of Type IIB string theory. Neutrino masses are approximately obtained by using the seesaw mechanism due to our two additional symmetries. We perform chi square numerical analysis for each of the fixed/special points in the normal and inverted hierarchies and demonstrate predictions for each case. Then, we briefly discuss the possible signature of hidden gauge bosons at collider experiments from the hidden $SU(2)$ symmetry.Comment: 28 pages, 10 figures, 2 table

Analysis of the anti-tumor mechanism of BRD4 inhibition in hepatocellular carcinoma

Bromodomain and extra terminal (BET) family proteins, which include BRD4, are readers of histone acetyl-lysines and key regulators of gene transcription. BRD4 inhibitors exert anti-tumor effects in various cancers, including hepatocellular carcinoma (HCC). We investigated the mechanism underlying the antitumor effects of BRD4 inhibition in HCC. We first tested the effects of the BRD4 inhibitor JQ1 in a series of 9 HCC cell lines and found that it strongly suppressed HCC cell proliferation by inducing cell cycle arrest and apoptosis. Gene expression microarray analysis revealed that JQ1 also induced marked changes in the gene expression profiles of HCC cells, and genes associated with cell cycle and apoptosis were significantly enriched among the affected genes. Notably, a number of cancer-related genes, including BCAT1, DDR1, GDF15, FANCD2, SENP1 and TYRO3, were strongly suppressed by JQ1 in HCC cells. We also confirmed BRD4 bound within the promoter regions of these genes, which suggests they are targets of BRD4 in HCC cells. JQ1 thus appears to exert its anti-tumor effects in HCC by suppressing multiple BRD4 target genes

Unstable bodyweight and incident type 2 diabetes mellitus: A meta-analysis

Aims/IntroductionThe present meta-analysis aimed to clarify the association of unstable bodyweight with the risk of type 2 diabetes mellitus, an association that has been controversial among longitudinal studies.Materials and MethodsAn electronic literature search using EMBASE and MEDLINE was followed up to 31 August 2016. The relative risks (RRs) of type 2 diabetes mellitus in individuals with unstable bodyweight were pooled using the inverse variance method.ResultsEight studies were eligible for the meta-analysis. The median duration of measurements of weight change and follow-up years for ascertaining type 2 diabetes mellitus were 13.5 and 9.4 years, respectively. The pooled RR for the least vs most stable category was 1.33 (95% confidence interval 1.12–1.57). Between-study heterogeneity was statistically significant (P = 0.048). Whether type 2 diabetes mellitus was ascertained by blood testing explained 66.0% of the variance in the logarithm of RR (P = 0.02). In three studies in which blood testing was carried out, type 2 diabetes mellitus risk was not significant (RR 1.06, 95% confidence interval 0.91–1.25). Furthermore, publication bias that inflated type 2 diabetes mellitus risk was statistically detected by Egger\u27s test (P = 0.09).ConclusionsUnstable bodyweight might be modestly associated with the elevated risk of type 2 diabetes mellitus; although serious biases, such as diagnostic suspicion bias and publication bias, made it difficult to assess this association

Quantitative Relationship Between Cumulative Risk Alleles Based on Genome-Wide Association Studies and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

Many epidemiological studies have assessed the genetic risk of having undiagnosed or of developing type 2 diabetes mellitus (T2DM) using several single nucleotide polymorphisms (SNPs) based on findings of genome-wide association studies (GWAS). However, the quantitative association of cumulative risk alleles (RAs) of such SNPs with T2DM risk has been unclear. The aim of this meta-analysis is to review the strength of the association between cumulative RAs and T2DM risk. Systematic literature searches were conducted for cross-sectional or longitudinal studies that examined odds ratios (ORs) for T2DM in relation to genetic profiles. Logarithm of the estimated OR (log OR) of T2DM for 1 increment in RAs carried (1-ΔRA) in each study was pooled using a random-effects model. There were 46 eligible studies that included 74,880 cases among 249,365 participants. In 32 studies with a cross-sectional design, the pooled OR for T2DM morbidity for 1-ΔRA was 1.16 (95% confidence interval [CI], 1.13–1.19). In 15 studies that had a longitudinal design, the OR for incident T2DM was 1.10 (95% CI, 1.08–1.13). There was large heterogeneity in the magnitude of log OR (P < 0.001 for both cross-sectional studies and longitudinal studies). The top 10 commonly used genes significantly explained the variance in the log OR (P = 0.04 for cross-sectional studies; P = 0.006 for longitudinal studies). The current meta-analysis indicated that carrying 1-ΔRA in T2DM-associated SNPs was associated with a modest risk of prevalent or incident T2DM, although the heterogeneity in the used genes among studies requires us to interpret the results with caution

On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10’s of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation

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