3D-Epigenomic Regulation of Gene Transcription in Hepatocellular Carcinoma.

The fundamental cause of transcription dysregulation in hepatocellular carcinoma (HCC) remains elusive. To investigate the underlying mechanisms, comprehensive 3D-epigenomic analyses are performed in cellular models of THLE2 (a normal hepatocytes cell line) and HepG2 (a hepatocellular carcinoma cell line) using integrative approaches for chromatin topology, genomic and epigenomic variation, and transcriptional output. Comparing the 3D-epigenomes in THLE2 and HepG2 reveal that most HCC-associated genes are organized in complex chromatin interactions mediated by RNA polymerase II (RNAPII). Incorporation of genome-wide association studies (GWAS) data enables the identification of non-coding genetic variants that are enriched in distal enhancers connecting to the promoters of HCC-associated genes via long-range chromatin interactions, highlighting their functional roles. Interestingly, CTCF binding and looping proximal to HCC-associated genes appear to form chromatin architectures that overarch RNAPII-mediated chromatin interactions. It is further demonstrated that epigenetic variants by DNA hypomethylation at a subset of CTCF motifs proximal to HCC-associated genes can modify chromatin topological configuration, which in turn alter RNAPII-mediated chromatin interactions and lead to dysregulation of transcription. Together, the 3D-epigenomic analyses provide novel insights of multifaceted interplays involving genetics, epigenetics, and chromatin topology in HCC cells

Mucosal-associated invariant T cells augment immunopathology and gastritis in chronic helicobacter pyloriInfection

Mucosal-associated invariant T (MAIT) cells produce inflammatory cytokines and cytotoxic granzymes in response to by-products of microbial riboflavin synthesis. Although MAIT cells are protective against some pathogens, we reasoned that they might contribute to pathology in chronic bacterial infection. We observed MAIT cells in proximity to Helicobacter pylori bacteria in human gastric tissue, and so, using MR1-tetramers, we examined whether MAIT cells contribute to chronic gastritis in a mouse H. pylori SS1 infection model. Following infection, MAIT cells accumulated to high numbers in the gastric mucosa of wild-type C57BL/6 mice, and this was even more pronounced in MAIT TCR transgenic mice or in C57BL/6 mice where MAIT cells were preprimed by Ag exposure or prior infection. Gastric MAIT cells possessed an effector memory Tc1/Tc17 phenotype, and were associated with accelerated gastritis characterized by augmented recruitment of neutrophils, macrophages, dendritic cells, eosinophils, and non-MAIT T cells and by marked gastric atrophy. Similarly treated MR1−/− mice, which lack MAIT cells, showed significantly less gastric pathology. Thus, we demonstrate the pathogenic potential of MAIT cells in Helicobacter-associated immunopathology, with implications for other chronic bacterial infections

Hermitian-Randić matrix and Hermitian-Randić energy of mixed graphs

Abstract Let M be a mixed graph and H ( M ) $H(M)$ be its Hermitian-adjacency matrix. If we add a Randić weight to every edge and arc in M, then we can get a new weighted Hermitian-adjacency matrix. What are the properties of this new matrix? Motivated by this, we define the Hermitian-Randić matrix R H ( M ) = ( r h ) k l $R_{H}(M)=(r_{h})_{kl}$ of a mixed graph M, where ( r h ) k l = − ( r h ) l k = i d k d l $(r_{h})_{kl}=-(r_{h})_{lk}=\frac{\mathbf{i}}{\sqrt {d_{k}d_{l}}}$ ( i = − 1 $\mathbf{i}=\sqrt{-1}$ ) if ( v k , v l ) $(v_{k},v_{l})$ is an arc of M, ( r h ) k l = ( r h ) l k = 1 d k d l $(r_{h})_{kl}=(r_{h})_{lk}=\frac{1}{\sqrt{d_{k}d_{l}}}$ if v k v l $v_{k}v_{l}$ is an undirected edge of M, and ( r h ) k l = 0 $(r_{h})_{kl}=0$ otherwise. In this paper, firstly, we compute the characteristic polynomial of the Hermitian-Randić matrix of a mixed graph. Furthermore, we give bounds on the Hermitian-Randić energy of a general mixed graph. Finally, we give some results about the Hermitian-Randić energy of mixed trees

Sufficient Spectral Radius Conditions for Hamilton-Connectivity of k-Connected Graphs

We present two new sufficient conditions in terms of the spectral radius ρ(G) guaranteeing that a k-connected graph G is Hamilton-connected, unless G belongs to a collection of exceptional graphs. We use the Bondy–Chvátal closure to characterize these exceptional graphs