Exome sequencing in multiplex families with left-sided cardiac defects has high yield for disease gene discovery.

Congenital heart disease (CHD) is a common group of birth defects with a strong genetic contribution to their etiology, but historically the diagnostic yield from exome studies of isolated CHD has been low. Pleiotropy, variable expressivity, and the difficulty of accurately phenotyping newborns contribute to this problem. We hypothesized that performing exome sequencing on selected individuals in families with multiple members affected by left-sided CHD, then filtering variants by population frequency, in silico predictive algorithms, and phenotypic annotations from publicly available databases would increase this yield and generate a list of candidate disease-causing variants that would show a high validation rate.

Synonymous variants that disrupt messenger RNA structure are significantly constrained in the human population.

Background: The role of synonymous single-nucleotide variants in human health and disease is poorly understood, yet evidence suggests that this class of "silent" genetic variation plays multiple regulatory roles in both transcription and translation. One mechanism by which synonymous codons direct and modulate the translational process is through alteration of the elaborate structure formed by single-stranded mRNA molecules. While tools to computationally predict the effect of non-synonymous variants on protein structure are plentiful, analogous tools to systematically assess how synonymous variants might disrupt mRNA structure are lacking.

Pathoadaptive Alteration of Biofilm Formation in Response to the Gallbladder Environment.

Typhoid fever, a human-specific disease, is primarily caused by the pathogen serovar Typhi. It is estimated that 3 to 5% of people infected with typhoid fever become chronic carriers. Studies have demonstrated that a mechanism of chronic carriage involves biofilm formation on gallstone surfaces.

Selective benzylic C-H monooxygenation mediated by iodine oxides.

A method for the selective monooxdiation of secondary benzylic C-H bonds is described using an -oxyl catalyst and a hypervalent iodine species as a terminal oxidant. Combinations of ammonium iodate and catalytic -hydroxyphthalimide (NHPI) were shown to be effective in the selective oxidation of -butylbenzene directly to 1-phenylbutyl acetate in high yield (86%). This method shows moderate substrate tolerance in the oxygenation of substrates containing secondary benzylic C-H bonds, yielding the corresponding benzylic acetates in good to moderate yield.

Systemic, renal, and colonic effects of intravenous and enteral rehydration in horses.

Background: Intravenous (IV) and intragastric (IG) administration of fluid therapy are commonly used in equine practice, but there are limited data on the systemic, renal, and enteric effects.

Hypothesis: IV fluid administration will increase intestinal and fecal hydration in a rate-dependent manner after hypertonic dehydration, but will be associated with significant urinary water and electrolyte loss. Equivalent volumes of IG plain water will result in comparatively greater intestinal hydration with less renal loss.