Structural insights into how DEK nucleosome binding facilitates H3K27 trimethylation in chromatin.

Structural diversity of the nucleosome affects chromatin conformations and regulates eukaryotic genome functions. Here we identify DEK, whose function is unknown, as a nucleosome-binding protein. In embryonic neural progenitor cells, DEK colocalizes with H3 K27 trimethylation (H3K27me3), the facultative heterochromatin mark.

FRET analysis of the unwrapping of nucleosomal DNA containing a sequence characteristic of the + 1 nucleosome.

Sequence-dependent mechanical properties of DNA could play essential roles in nuclear processes by affecting histone-DNA interactions. Previously, we found that the DNA entry site of the first nucleosomes from the transcription start site (+ 1 nucleosome) in budding yeast enriches AA/TT steps, but not the exit site, and the biased presence of AA/TT in the entry site was associated with the transcription levels of yeast genes. Because AA/TT is a rigid dinucleotide step, we considered that AA/TT causes DNA unwrapping.

Structural insights into how Cas9 targets nucleosomes.

The CRISPR-associated endonuclease Cas9 derived from prokaryotes is used as a genome editing, which targets specific genomic loci by single guide RNAs (sgRNAs). The eukaryotes, the target of genome editing, store their genome DNA in chromatin, in which the nucleosome is a basic unit. Despite previous structural analyses focusing on Cas9 cleaving free DNA, structural insights into Cas9 targeting of DNA within nucleosomes are limited, leading to uncertainties in understanding how Cas9 operates in the eukaryotic genome.

Contributions of histone tail clipping and acetylation in nucleosome transcription by RNA polymerase II.

The N-terminal tails of histones protrude from the nucleosome core and are target sites for histone modifications, such as acetylation and methylation. Histone acetylation is considered to enhance transcription in chromatin. However, the contribution of the histone N-terminal tail to the nucleosome transcription by RNA polymerase II (RNAPII) has not been clarified.

The Limited Effect of a History of COVID-19 on Antibody Titers and Adverse Reactions Following BNT162b2 Vaccination: A Single-Center Prospective Study.

The need for, and ideal frequency of, the vaccination against coronavirus disease 2019 (COVID-19) of previously infected individuals have not yet been sufficiently evaluated. The aim of this study was to examine the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody status and adverse reactions after vaccination among medical staff with or without a history of COVID-19. A single-center prospective study was performed at Fukuoka University Chikushi Hospital.

Effective connectivity and criminal sentencing decisions: dynamic causal models in laypersons and legal experts.

This magnetic resonance imaging study is designed to obtain relevant implications for criminal justice and explores the effective connectivity underlying expertise. Laypersons and experts considered sentences for remorseful and remorseless defendants, respectively, with and without mitigation, in hypothetical murder cases. Two groups revealed no differential activation.

Pelvic organ prolapse and Japanese lifestyle: prevalence and risk factors in Japan.

Introduction And Hypothesis: Little is known about the prevalence of pelvic organ prolapse (POP). We aimed to evaluate the prevalence of POP and identify its risk factors in Japan.

Methods: This was a single-centre, cross-sectional study.

Acetylation-modulated communication between the H3 N-terminal tail domain and the intrinsically disordered H1 C-terminal domain.

Linker histones (H1s) are key structural components of the chromatin of higher eukaryotes. However, the mechanisms by which the intrinsically disordered linker histone carboxy-terminal domain (H1 CTD) influences chromatin structure and gene regulation remain unclear. We previously demonstrated that the CTD of H1.

A randomized, double-blind, placebo-controlled, phase 3 study of tivantinib in Japanese patients with MET-high hepatocellular carcinoma.

A previous randomized phase 2 study of hepatocellular carcinoma revealed that the c-Met inhibitor tivantinib as second-line treatment significantly prolonged progression-free survival in a subpopulation whose tumor samples highly expressed c-Met (MET-high). Accordingly, this phase 3 study was conducted to evaluate the efficacy of tivantinib as a second-line treatment for Japanese patients with MET-high hepatocellular carcinoma. This randomized, double-blind, placebo-controlled study was conducted at 60 centers in Japan.

Individual feedback and monitoring of endoscopist performance improves the adenoma detection rate in screening colonoscopy: a prospective case-control study.

Background And Purpose: Previous reports have suggested that a longer withdrawal time (WT) during colonoscopy led to an improved adenoma detection rate (ADR); however, there are few controlled studies that substantiated monitoring WT as an educational method. We aimed to validate a feedback and monitoring system to improve the ADR in screening colonoscopy in a prospective case-control setting.

Methods: After collecting data in the pre-feedback period (3.

Quality Indicators for the Detection of Helicobacter pylori-Negative Early Gastric Cancer: A Retrospective Observational Study.

Background/aims: While Helicobacter pylori (HP)-negative gastric cancer is frequently reported, little is known about the predictors for detecting HP-negative early gastric cancer (EGC). We aimed to evaluate the predictors for the detection of HP-negative EGC.

Methods: We retrospectively reviewed 13,477 consecutive asymptomatic cases where upper endoscopy was performed by nine physicians from April 2017 to March 2019 and analyzed the detection rate of high-risk lesions (HRLs), including EGC, tubular adenoma, and lymphoma, according to the status of HP infection.

Human pursuance of equality hinges on mental processes of projecting oneself into the perspectives of others and into future situations.

In the pursuance of equality, behavioural scientists disagree about distinct motivators, that is, consideration of others and prospective calculation for oneself. However, accumulating data suggest that these motivators may share a common process in the brain whereby perspectives and events that did not arise in the immediate environment are conceived. To examine this, we devised a game imitating a real decision-making situation regarding redistribution among income classes in a welfare state.

Computed tomograpy evaluation of morphological changes, clinical response and survival in colorectal cancer liver metastasis treated by regorafenib: A case report.

Pathological response to preoperative chemotherapy was recently found to be correlated with improved survival and has been proposed as a new outcome end-point following resection of liver metastases from colorectal cancer (CRC). It was demonstrated that, particularly after therapy with bevacizumab, CRC liver metastases decreased in size and underwent distinct morphological changes on computed tomography (CT). However, morphological changes in response to treatment with regorafenib have not yet been reported.

Combination therapy with zoledronic acid and cetuximab effectively suppresses growth of colorectal cancer cells regardless of KRAS status.

Targeted molecular therapy is an effective anticancer strategy. Anti-EGFR monoclonal antibodies such as cetuximab (CTX) have been approved for the treatment of various malignancies, including colorectal cancer (CRC) with wild-type KRAS. However, their efficacy in patients with KRAS mutations has not been established.

Metastatic seminoma in the duodenum: diagnosis with endoscopy followed by successful treatment.

Seminomas rarely metastasize to the gastrointestinal tract. In general, these lesions metastasize to the lungs or retroperitoneal lymph nodes. A 34-year-old Japanese man who had undergone orchiectomy for seminoma two years earlier experienced shortness of breath and tarry stools.

Phase I clinical trial of peptide vaccination with URLC10 and VEGFR1 epitope peptides in patients with advanced gastric cancer.

Peptide vaccine treatment has attracted attention in recent years as a new therapy option for chemotherapy‑resistant, advanced, unresectable cancer. The safety of peptide vaccination with HLA-A*2402-restricted URLC10-A24-177 and VEGFR1-A12-9 1084 epitope peptides (fixed 2-mg dose) was investigated in a phase I clinical trial of patients with advanced gastric cancer who were refractory to chemotherapy. We determined the HLA genotype of the subjects after enrollment, results of which were held by the evaluation committee and kept from both patients and investigators until completion of the study.

Neural correlate of human reciprocity in social interactions.

Reciprocity plays a key role maintaining cooperation in society. However, little is known about the neural process that underpins human reciprocity during social interactions. Our neuroimaging study manipulated partner identity (computer, human) and strategy (random, tit-for-tat) in repeated prisoner's dilemma games and investigated the neural correlate of reciprocal interaction with humans.

Varicella-zoster virus ORF49 functions in the efficient production of progeny virus through its interaction with essential tegument protein ORF44.

The ORF49 tegument protein of varicella-zoster virus (VZV) is one of the core gene products that is conserved among herpesvirus family members. Although ORF49 is known to be a cell-tropic factor, its detailed functions remain elusive. ORF44 is another core gene product reported to be essential, although its characterization and detailed functional analysis have not been reported.

Repression of Factor VIII Inhibitor Development with Apoptotic Factor VIII-expressing Embryonic Stem Cells.

Development of factor VIII (fVIII)-neutralizing antibodies, called inhibitors, is a challenging problem in the management of hemophilia A patients. We explored the possibility of pretreatment with apoptotic fVIII-expressing embryonic stem (ES) cells to prevent the development of fVIII inhibitors. Murine ES cells integrated with the human F8 gene were differentiated into embryoid bodies, dissociated to a single cell suspension, subjected to hypo-osmotic shock to induce apoptosis, and intraperitoneally injected into hemophilia A mice.

Extracellular signal-regulated kinase and Akt activation play a critical role in the process of hepatocyte growth factor-induced epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) has recently been studied to elucidate mechanisms of the liver metastatic process. We investigated EMT in the process of liver metastasis and the effects of chemotherapy on EMT cells as therapeutic strategy for colorectal liver metastasis. We used the CT26 murine colorectal carcinoma cell line to create an in vivo mouse liver metastasis model.

Decreased FANCJ caused by 5FU contributes to the increased sensitivity to oxaliplatin in gastric cancer cells.

Background: Oxaliplatin is effective against many types of cancer, and the combination of 5-fluorouracil (5FU) and oxaliplatin is synergistically effective against gastric cancer, as well as colon cancer. The FANCJ protein is one of the Fanconi anemia (FA) gene products, and its interaction with the tumor suppressor BRCA1 is required for DNA double-strand break (DSB) repair. FANCJ also functions in interstrand crosslinks (ICLs) repair by linking to mismatch repair protein complex MLH1-PMS2 (MutLα).

Interferon-gamma-mediated tissue factor expression contributes to T-cell-mediated hepatitis through induction of hypercoagulation in mice.

Unlabelled: Concanavalin A (Con A) treatment induces severe hepatitis in mice in a manner dependent on T cells, interferon (IFN)-gamma, and tumor necrosis factor (TNF). Treatment with the anticoagulant heparin protects against hepatitis, despite healthy production of IFN-γ and TNF. Here, we investigated molecular and cellular mechanisms for hypercoagulation-mediated hepatitis.

Novel cell culture-adapted genotype 2a hepatitis C virus infectious clone.

Although the recently developed infectious hepatitis C virus system that uses the JFH-1 clone enables the study of whole HCV viral life cycles, limited particular HCV strains have been available with the system. In this study, we isolated another genotype 2a HCV cDNA, the JFH-2 strain, from a patient with fulminant hepatitis. JFH-2 subgenomic replicons were constructed.