DOT1L has emerged as an anticancer target for MLL-associated leukaemias; however, its functional role in solid tumours is largely unknown. Here we identify that DOT1L cooperates with c-Myc and p300 acetyltransferase to epigenetically activate epithelial–mesenchymal transition (EMT) regulators in breast cancer progression. DOT1L recognizes SNAIL, ZEB1 and ZEB2 promoters via interacting with the c-Myc-p300 complex and facilitates lysine-79 methylation and acetylation towards histone H3, leading to the dissociation of HDAC1 and DNMT1 in the regions. The upregulation of these EMT regulators by the DOT1L-c-Myc-p300 complex enhances EMT-induced breast cancer stem cell (CSC)-like properties. Furthermore, in vivo orthotopic xenograft models show that DOT1L is required for malignant transformation of breast epithelial cells and breast tumour initiation and metastasis. Clinically, DOT1L expression is associated with poorer survival and aggressiveness of breast cancers. Collectively, we suggest that cooperative effect of DOT1L and c-Myc-p300 is critical for acquisition of aggressive phenotype of breast cancer by promoting EMT/CSC.

The linear or branched allyl moieties on aromatic rings are well-known as ubiquitous structural motifs found in a range of natural products and medicinally relevant molecules. They also represent an important class of organic intermediates for the transformation of an olefin group into many useful functional groups. Established methods for the installation of allylic groups rely primarily on nucleophilic substitution or transmetalation of aryl metal complexes to allyl electrophiles, Lewis acid-mediated Friedel−Crafts allylation of electron-rich arenes, and Tsuji−Trost allylation reactions with π-allyl species. Complementing previous protocols, the transition metal-catalyzed allylation reactions via C−H activation strategy using various allylic surrogates like allylic acetates, allylic carbonates, allylic phosphonates, allylic halides, allylic alcohols, vinyl oxiranes, allenes, 1,3-dienes, and others have recently emerged as a powerful tool for creating the corresponding allyl, crotyl and prenyl moieties. This review, which includes all reported methods in the literature until the beginning of 2017, focuses on recent progress on direct allylation reactions of aromatic and vinylic C(sp 2 )−H bonds with allylic sources and various transition metal catalysts.

BackgroundStaphylococcus aureus (SA) has peculiar abilities to colonize the skin in atopic dermatitis (AD) patients.ObjectiveWe sought to determine the colonization rates of SA in acute and chronic skin lesions of AD patients, to find any difference in colonization rates according to age and to find the influences of total immunoglobulin E (IgE) and eosinophil counts to the colonization of SA.MethodsWe evaluated the total IgE level and eosinophil counts, and cultured SA from the skin lesions of 687 AD patients (131 acute and 556 chronic skin lesions) and 247 control urticaria patients (July 2009 to November 2010; Samsung Medical Center Dermatology Clinic, Seoul, Korea).ResultsThe SA colonization rates were 74%, 38% and 3% in acute, chronic skin lesions and control skin, respectively, and they were increased with age in AD patients. The colonization rate in chronic skin lesions was higher in the high IgE/eosinophilia groups as compared to the normal IgE/eosinophil groups.ConclusionThe SA colonization rate was higher in AD patients and especially in acute lesions, and had a tendency to increase with age. As the colonization rates were only higher in the high IgE/eosinophilia groups of chronic skin lesions, we suggested that SA may invade the skin through barrier defects in acute skin lesions, but the colonization in chronic lesions may be orchestrated through many different factors.

Purpose -The purpose of this paper is to explore the roles of telepresence and fantasy in an online apparel shopping experience. Online apparel consumers undergo a virtual product experience (telepresence) that simulates the product experience in a brick-and-mortar store. Fantasy entails the pleasurable mental imagery involving product use. Design/methodology/approach -A total of 86 female university students completed a survey after browsing a stimulus web site in a laboratory setting. Path analysis was used to identify hypothesized relationships between telepresence, fantasy, shopping enjoyment, willingness to purchase, and willingness to patronize the online retailer. Findings -Results showed that telepresence influenced consumer fantasy and both telepresence and consumer fantasy led to shopping enjoyment (experiential value). Telepresence, fantasy, and shopping enjoyment directly contributed to willingness to purchase from the online retailer, whereas telepresence, fantasy and shopping enjoyment contributed indirectly to willingness to patronize the online retailer.Research limitations/implications -The study used a sample of female university students in the USA. This limits its generalizability to all consumers. It also examined one web site feature; other features may produce different effects. Practical implications -Findings suggest that business practitioners implement features on their web sites to yield telepresence and fantasy, which may enhance purchase and patronage responses towards their site. Originality/value -This study enhances understanding of two variables requiring further study, telepresence and fantasy, in online apparel shopping experience.

Increase in the number of scattered atypical melanocytes with large hyperchromatic nuclei in a partial nail matrix may provide a diagnostic clue to subungual melanoma in situ in concert with its clinical suspicion.

No abstract

Polycomb protein chromobox homolog 7 (CBX7) is involved in several biologic processes including stem cell regulation and cancer development, but its roles in breast cancer remain unknown. Here, we demonstrate that CBX7 negatively regulates breast tumor initiation. 2 /ESA + cell population and reinforced in vitro self-renewal and in vivo tumor-initiating ability. Similarly, CBX7 overexpression repressed these effects. We also found that CBX7 inhibits the Wnt/b-catenin/T cell factor pathway by enhancing the expression of Dickkopf-1 (DKK-1), a Wnt antagonist. In particular, CBX7 increased DKK-1 transcription by cooperating with p300 acetyltransferase and subsequently enhancing the histone acetylation of the DKK-1 promoter. Furthermore, pharmacologic inhibition of DKK-1 in CBX7-overexpressing cells showed recovery of Wnt signaling and consequent rescue of the CD44 +

Soil metagenome constitutes a reservoir for discovering novel enzymes from the unculturable microbial diversity. From three plant rhizosphere metagenomic libraries comprising a total of 142,900 members of recombinant plasmids, we obtained 14 recombinant fosmids that exhibited lipolytic activity. A selected recombinant plasmid, pFLP-2, which showed maximum lipolytic activity, was further analyzed. DNA sequence analysis of the subclone in pUC119, pELP-2, revealed an open reading frame of 1,191 bp encoding a 397-amino-acid protein. Purified EstD2 exhibited maximum enzymatic activity towards p-nitrophenyl butyrate, indicating that it is an esterase. Purified EstD2 showed optimal activity at 35 °C and at pH 8.0. The K(m) and K(cat) values were determined to be 79.4 μM and 120.5/s, respectively. The esterase exhibited an increase in enzymatic activity in the presence of 15% butanol and 15% methanol. Phylogenetic analysis revealed that the lipolytic protein EstD2 may be a member of a novel family of lipolytic enzymes. Several hypothetical protein homologs of EstD2 were found in the database. A hypothetical protein from Phenylobacterium zucineum HLK1, a close homolog of EstD2, displayed lipolytic activity when the corresponding gene was expressed in Escherichia coli. Our results suggest that the other hypothetical protein homologs of EstD2 might also be members of this novel family.