Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers and may have application as a non-invasive biomarker of disease

Large chromosomal regions can be suppressed in cancer cells as denoted by hypermethylation of neighbouring CpG islands and downregulation of most genes within the region. We have analysed the extent and prevalence of long-range epigenetic silencing at 2q14.2 (the first and best characterised example of coordinated epigenetic remodelling) and investigated its possible applicability as a non-invasive diagnostic marker of human colorectal cancer using different approaches and biological samples. Hypermethylation of at least one of the CpG islands analysed (EN1, SCTR, INHBB) occurred in most carcinomas (90%), with EN1 methylated in 73 and 40% of carcinomas and adenomas, respectively. Gene suppression was a common phenomenon in all the tumours analysed and affected both methylated and unmethylated genes. Detection of methylated EN1 using bisulfite treatment and melting curve (MC) analysis from stool DNA in patients and controls resulted in a predictive capacity of, 44% sensitivity in positive patients (27% of overall sensitivity) and 97% specificity. We conclude that epigenetic suppression along 2q14.2 is common to most colorectal cancers and the presence of a methylated EN1 CpG island in stool DNA might be used as biomarker of neoplastic disease

Mammalian Otolin: A Multimeric Glycoprotein Specific to the Inner Ear that Interacts with Otoconial Matrix Protein Otoconin-90 and Cerebellin-1

The mammalian otoconial membrane is a dense extracellular matrix containing bio-mineralized otoconia. This structure provides the mechanical stimulus necessary for hair cells of the vestibular maculae to respond to linear accelerations and gravity. In teleosts, Otolin is required for the proper anchoring of otolith crystals to the sensory maculae. Otoconia detachment and subsequent entrapment in the semicircular canals can result in benign paroxysmal positional vertigo (BPPV), a common form of vertigo for which the molecular basis is unknown. Several cDNAs encoding protein components of the mammalian otoconia and otoconial membrane have recently been identified, and mutations in these genes result in abnormal otoconia formation and balance deficits.Here we describe the cloning and characterization of mammalian Otolin, a protein constituent of otoconia and the otoconial membrane. Otolin is a secreted glycoprotein of ∼70 kDa, with a C-terminal globular domain that is homologous to the immune complement C1q, and contains extensive posttranslational modifications including hydroxylated prolines and glycosylated lysines. Like all C1q/TNF family members, Otolin multimerizes into higher order oligomeric complexes. The expression of otolin mRNA is restricted to the inner ear, and immunohistochemical analysis identified Otolin protein in support cells of the vestibular maculae and semi-circular canal cristae. Additionally, Otolin forms protein complexes with Cerebellin-1 and Otoconin-90, two protein constituents of the otoconia, when expressed in vitro. Otolin was also found in subsets of support cells and non-sensory cells of the cochlea, suggesting that Otolin is also a component of the tectorial membrane.Given the importance of Otolin in lower organisms, the molecular cloning and biochemical characterization of the mammalian Otolin protein may lead to a better understanding of otoconial development and vestibular dysfunction

Featuring I···N Halogen Bond and Weaker Interactions in Iodoperfluoroalkylimidazoles: An Experimental and Theoretical Charge Density Study

The experimental charge density distribution of two new iodoperfluoroalkylimidazole derivatives has been determined with the aspherical atom model against single-crystal X-ray diffracted intensities and analyzed by means of the Bader Quantum Theory of Atoms In Molecules. The compounds self-assemble in the solid state forming infinite chains through strong I···N halogen bonds. The topological and energetic features of these interactions have been determined and compared with those of a previously reported I···N interaction formed by an iodoperfluoroarene derivative, allowing elucidation of the role of hybridization of the carbon atom bonded to the halogen atom in the nature of the halogen bonding interaction. The weaker interactions present in the crystal structures have been investigated as well, with particular attention to F···F interactions. They have also been analyzed through the Interacting Quantum Atoms approach in order to elucidate their role in stabilizing the crystal structure

Electronic and geometric structure effects on one-electron oxidation of first-row transition metals in the same ligand framework

Developing new transition metal catalysts requires understanding of how both metal and ligand properties determine reactivity. Since metal complexes bearing ligands of the Py5 family (2,6-bis-[(2-pyridyl)methyl] pyridine) have been employed in many fields in the past 20 years, we set out here to understand their redox properties by studying a series of base metal ions (M = Mn, Fe, Co, and Ni) within the Py5OH (pyridine-2,6-diylbis[di-(pyridin-2-yl)methanol]) variant. Both reduced (M-II) and the one-electron oxidized (M-III) species were carefully characterized using a combination of X-ray crystallography, X-ray absorption spectroscopy, cyclic voltammetry, and density-functional theory calculations. The observed metal-ligand interactions and electrochemical properties do not always follow consistent trends along the periodic table. We demonstrate that this observation cannot be explained by only considering orbital and geometric relaxation, and that spin multiplicity changes needed to be included into the DFT calculations to reproduce and understand these trends. In addition, exchange reactions of the sixth ligand coordinated to the metal, were analysed. Finally, by including published data of the extensively characterised Py5OMe (pyridine-2,6-diylbis[di-(pyridin-2-yl)methoxymethane])complexes, the special characteristics of the less common Py5OH ligand were extracted. This comparison highlights the non-innocent effect of the distal OH functionalization on the geometry, and consequently on the electronic structure of the metal complexes. Together, this gives a complete analysis of metal and ligand degrees of freedom for these base metal complexes, while also providing general insights into how to control electrochemical processes of transition metal complexes

From gloom to doom: Financial loss and negative affect prime risk averse preferences

© Springer Science+Business Media, LLC, part of Springer Nature 2019. The final publication is available at Springer via https://doi.org/10.1007/s12144-019-00507-3. The final publication is available at Springer via https://doi.org/10.1007/s12144-019-00507-3Previous research has shown that risk preferences are sensitive to the financial domain in which they are framed. In the present study we explore whether the effect of valence priming on risk taking is moderated by the financial context under consideration. A total of 260 participants completed an online questionnaire where risky choices were elicited for seven different financial scenarios. Participants were allocated to different valence (neutral, positive or negative) and arousal (low or high) priming conditions. Two factors were extracted: Factor 1 (Negative) included insurance and possibility of loss, whilst Factor 2 (Positive) included the remaining five scenarios (investment, salary, pension, possibility of gain, and mortgage). Moreover, only negative priming—regardless of arousal level—influenced people’s risky choices by inducing more risk-averse behavior; this effect was confined only to loss and insurance domains. The findings call into question the generalizability of priming effects on different financial context and show that the effects of priming on financial risk taking are sensitive to the financial context under consideration.Peer reviewe