A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci

<p>Abstract</p> <p>Background</p> <p>Chromatin structure at a given site can differ between chromosome copies in a cell, and such imbalances in chromatin structure have been shown to be important in understanding the molecular mechanisms controlling several disease loci. Human genetic variation, DNA methylation, and disease have been intensely studied, uncovering many sites of allele-specific DNA methylation (ASM). However, little is known about the genome-wide occurrence of sites of allele-specific histone modification (ASHM) and their relationship to human disease. The aim of this study was to investigate the extent and characteristics of sites of ASHM in human embryonic stem cells (hESCs).</p> <p>Results</p> <p>Using a statistically rigorous protocol, we investigated the genomic distribution of ASHM in hESCs, and their relationship to sites of allele-specific expression (ASE) and DNA methylation. We found that, although they were rare, sites of ASHM were substantially enriched at loci displaying ASE. Many were also found at known imprinted regions, hence sites of ASHM are likely to be better markers of imprinted regions than sites of ASM. We also found that sites of ASHM and ASE in hESCs colocalize at risk loci for developmental syndromes mediated by deletions, providing insights into the etiology of these disorders.</p> <p>Conclusion</p> <p>These results demonstrate the potential importance of ASHM patterns in the interpretation of disease loci, and the protocol described provides a basis for similar studies of ASHM in other cell types to further our understanding of human disease susceptibility.</p

I Going Away. I Going Home. : Austin Clarke\u27s Leaving this Island Place

Austin Clarke’s “Leaving This Island Place” is one of scores of Caribbean autobiographical works that focus on a bright, young, lower-class islander leaving his/her small island place and setting out on “Eldorado voyages.” The narrative of that journey away from home to Europe or Canada or the United States and the later efforts to return may be said to be the Caribbean story, as suggested in the subtitle of Wilfred Cartey’s study of Caribbean literature, Whispers from the Caribbean: I Going Away, I Going Home, which argues that while in Caribbean literature there is much movement away, there is also a body of literature in which “the notion of ‘away’ and images of movement out are replaced by images of return” (xvi). Traditionally, however, the first autobiographical works, such as George Lamming’s In the Castle of My Skin, V. S. Naipaul’s A House for Mr. Biswas, Merle Hodge’s Crick Crack, Monkey, Jamaica Kincaid’s Annie John, Michelle Cliff’s No Telephone to Heaven, Edwidge Danticat’s Breath, Eyes, Memory, and Elizabeth Nunez’s Beyond the Limbo Silence, have focused on the childhood in the Caribbean and the journey away—or at least the preparation for that journey. Such is the case with Clarke’s “Leaving This Island Place.

Prediction of free-ion activities and ionic equilibria in bovine milk

The electrolytes in milk are essential as nutrients and for osmotic balance and have been well characterised at normal milk concentrations. When milk is concentrated by evaporation or reverse osmosis, the concentration of ions can easily exceed solubility limits. The main objective of this work was to be able to accurately predict ions association, activity and solubility in concentrated bovine milk. The Mean Spherical Approximation (MSA) method was used to calculate free-ion activity coefficients as it contained terms that enhanced accuracy at higher concentrations. This approach led to a system of over 80 non-linear equations for equilibria, electroneutrality and conservation, that was solved using Newton’s method. Significant problems were encountered due to incomplete definitions of variables and units in chemical literature. The Gibbs–Duhem relationship was used with numerical integration to determine water activities from free-ion activities, thus enabling some validation using data for binary systems. The predicted pH was also used for validation. The results were considered satisfactory given the impossibility of obtaining accurate data for even the simplest multi-components systems

Effect of viscosity on electrical conductivity in liquid foods

The electrical conductivities of foods affect their heating with ohmic heating and microwaves, and are required for electrical tomography studies. A range of model foods consisting of solutions of sodium carboxymethyl cellulose (NaCMC), NaCMC + sugars, concentrated skim milk, whey protein and viscous sugar solutions, with various amounts of electrolytes were prepared. The electrical conductivity was measured using a parallel plate sensor connected to an RCL meter using an a.c. voltage. The conductivity was found to increase with concentration, but was reduced by the effects of viscosity on ion mobility. The conductivity was closely related to bulk viscosity for sugar solutions following the modified Walden equation, but was unrelated to the viscosity of NaCMC solutions. Instead an “ion-diffusion” viscosity was defined and calculated from the electrical conductivity data, and this was found to relate well to the expected viscosity of the solution to which ions are exposed at a molecular scale

Electrical conductivity of viscous liquid foods

The electrical conductivities of foods are used for quality assurance, electrical tomography studies and are required for effective simulation of electrical heating processes such as ohmic and microwave heating. Solutions containing milk solids, whey proteins, sugars and sodium carboxymethyl cellulose (NaCMC), with and without electrolytes were prepared and tested. The electrical conductivity was measured using an RCL meter connected to a parallel plate probe. At low concentrations the conductivity increased with concentration, but in some viscous solutions the reduced ion mobility caused a drop in conductivity. The conductivity of sugar solutions could be related to following the modified Walden equation, but that of NaCMC solutions was not influenced by the bulk viscosity. Instead an ion “diffusion viscosity” was defined and calculated from the conductivity. It was found to correspond to the likely viscosity of the solution at a molecular scale

Comparison of a Conjugate Heat Transfer Scheme using the Lattice Boltzmann Method

The Lattice Boltzmann method (LBM) is a collision based computational fluid dynamics method used as an alternative to more traditional finite difference and finite element methods, in that LBM is built to take advantage of parallel systems. In the present case, LBM is used to model three-dimensional transient conjugate heat transfer within a box containing a solid fin. A comparison of different implementation methods for conjugate heat transfer has been carried out to determine their applicability. The geometry modelled was input as a stereolithography file, which may be generated easily by a range of packages, such as SolidWorks. From the simple box and fin geometry trialed, the solution method can easily be adapted to evaluate the suitability of structured packings for packed bed reactors, or other solid-fluid systems

A comparison between laboratory and industrial fouling of reverse osmosis membranes used to concentrate milk

© 2018 Reverse osmosis with polyamide spiral wound membranes is used to concentrate milk to reduce its volume before transport to processing facilities. The main aim of this work was to identify the cause of unusually low flux through a membrane that had been used in an industrial facility. The fluxes of new and used industrial membranes were measured using a flat-sheet cross-flow laboratory system. It was found that the fouling characteristics of laboratory fouled membranes were entirely different from the industrial membrane. The laboratory membranes could be restored to a high flux with a regime of water flushing, caustic and acid. FTIR showed no significant build-up on the membrane. In contrast the industrial membrane could not be cleaned in this manner. FTIR and FT-Raman showed species associated with milk lipids. Cleaning by solvent extraction using a two-phase mixture of water, isopropanol and cyclohexane increased the flux from 1% to almost 50% of the value of a new membrane. Analysis of the solvent-extracted material indicated the presence of phospholipids with a relatively high concentration of sphingomyelin. It was concluded that the laboratory experiments did not mimic industrial processes and an effective industrial cleaning system was not found