Pluripotency factors functionally premark cell-type-restricted enhancers in ES cells.

Enhancers for embryonic stem (ES) cell-expressed genes and lineage-determining factors are characterized by conventional marks of enhancer activation in ES cells1-3, but it remains unclear whether enhancers destined to regulate cell-type-restricted transcription units might also have distinct signatures in ES cells. Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells

Two novel mutations of Wiskott–Aldrich syndrome: the molecular prediction of interaction between the mutated WASP L101P with WASP-interacting protein by molecular modeling

AbstractWiskott–Aldrich syndrome (WAS) is an X-linked disorder characterized by eczema, thrombocytopenia and increased susceptibility of infections, with mutations of the WAS gene being responsible for WAS and X-linked thrombocytopenia. Herein, two novel mutations of WAS at T336C on exon 3, and at 1326–1329, a G deletion on exon 10, resulting in L101P missense mutation and frameshift mutation 444 stop, respectively, are reported. The affected patients with either mutation showed severe suppression of WAS protein (WASP) levels, T cell proliferation, and CFSE-labeled T cells division. Because WASP L101 have not shown direct nuclear Overhauser effect (NOE) contact with the WASP-interacting protein (WIP) in NMR spectroscopy, molecular modeling was performed to evaluate the molecular effect of WASP P101 to WIP peptide. It is presumed that P101 induced a conformational change in the Q99 residue of WASP and made the side chain of Q99 move away from the WIP peptide, resulting in disruption of the hydrogen bond between Q99 WASP and Y475 WIP. A possible model for the molecular pathogenesis of WAS has been proposed by analyzing the interactions of WASP and WIP using a molecular modeling study

Estimation of hospital-based HIV seroprevalence as a nationwide scale by novel method; 2002-2008 in Korea

<p>Abstract</p> <p>Background</p> <p>In Korea, approximately 70% of HIV-positive individuals are currently diagnosed in hospitals, while most HIV-positive patients were diagnosed at public health centers in 1980 s and 1990 s. However, there are no reporting systems to identify how many HIV tests are performed in the Korean hospitals different from public health centers and Blood centers. We estimated how many HIV tests were performed in hospitals and analyzed the nationwide hospital-based HIV seroprevalence in the present study.</p> <p>Methods</p> <p>Between 2002 and 2008, data included HIV tests on insurance claims in hospitals and the proportion of computerized insurance claims from the Health Insurance Review and Assessment Services. The number of HIV tests from the survey in the External Quality Assurance Scheme for hospital laboratories was collected to calculate the insurance claim proportion. HIV seroprevalence was estimated using data of tested individuals, including infected individuals. Statistical analysis was confirmed with the 95% confidence interval. Statistical significance was defined at p-values < 0.05.</p> <p>Results</p> <p>The number of HIV tests in hospitals increased from 2.7 million in 2002 to 5.0 million in 2008. The trend of HIV seroprevalence was decrease (1.5-1.3 per 10,000 individuals, P < 0.0028), except in 2002. The number of women tested was greater than men, and the proportion increased in older individuals and in small towns. Men had a higher annual HIV seroprevalence than women (P < 0.0001). The annual seroprevalence decreased in men (P = 0.0037), but was stable in women. The seroprevalence in the 30-39 year age group demonstrated higher than other age groups except 2008.</p> <p>Conclusions</p> <p>The nationwide hospital-based number of HIV tests and seroprevalence were estimated using a new method and seroprevalence trends were identified. This information will facilitate improvement in national HIV prevention strategies.</p

β-Caryophyllene attenuates dextran sulfate sodium-induced colitis in mice via modulation of gene expression associated mainly with colon inflammation

AbstractWe examined the modulatory activity of β-caryophyllene (CA) and gene expression in colitic colon tissues in a dextran sulfate sodium (DSS)-induced colitis model. Experimental colitis was induced by exposing male BALB/c mice to 5% DSS in drinking water for 7 days. CA (30 or 300mg/kg) was administered orally once a day together with DSS. CA administration attenuated the increases in the disease activity index, colon weight/length ratio, inflammation score, and myeloperoxidase activity in DSS-treated mice. Microarray analysis showed that CA administration regulated the expression in colon tissue of inflammation-related genes including those for cytokines and chemokines (Ccl2, Ccl7, Ccl11, Ifitm3, IL-1β, IL-28, Tnfrsf1b, Tnfrsf12a); acute-phase proteins (S100a8, Saa3, Hp); adhesion molecules (Cd14, Cd55, Cd68, Mmp3, Mmp10, Sema6b, Sema7a, Anax13); and signal regulatory proteins induced by DSS. CA significantly suppressed NF-κB activity, which mediates the expression of a different set of genes. These results suggest that CA attenuates DSS-induced colitis, possibly by modulating the expression of genes associated mainly with colon inflammation through inhibition of DSS-induced NF-κB activity

Phylogenetic relationships between different raccoon dog (Nyctereutes procyonoides) populations based on four nuclear and Y genes

© 2020, The Genetics Society of Korea.Background: The raccoon dog (Nyctereutes procyonoides), endemic to East Asia, is classified as six subspecies according to their geographical distribution including a population introduced to Europe. Studies on phylogenetic relationship or population genetics in both native and introduced areas have been carried out recently. Lately, opinions that Japanese raccoon dogs should be classified as a different species were asserted based on several studies using karyotypes, morphometric characters, mtDNA, and microsatellites analysis. However, no data pertaining to the nuclear DNA (nDNA) or Y chromosome are available. Objective: To estimate the relationship among the species using different genes is necessary in understanding of the history of this species. Method: Therefore, we investigated nDNA and Y chromosomes in our study to define relationships: (1) between continental raccoon dog populations, (2) between original and introduced groups, and (3) between continental and Japanese groups. Results: The analysis of four nuclear (CHRNA1, VTN, TRSP, WT1) and ZFY genes indicated that there had been no genetic differentiation among the continental populations. However, significant differences were observed between continental and Japanese raccoon dogs in VTN and ZFY genes implying genetic differentiation has been going between them. Conclusion: To better understand the phylogenetic relationship among raccoon dog populations, further study will be necessary.N