Structural Transition of Vacancy-Solute Complexes in Al-Mg-Si Alloys

To theoretically examine the structural transition of vacancy–solute complexes in Al–Mg–Si alloys, we performed first-principles calculations for layered vacancy–solute complexes with additional Mg atoms. The central Mg atom in the additional Mg layer shifted to the Si layer with the increase in the number of Mg atoms to weaken the repulsive Mg–Mg interaction and to form Mg–Si bonds. When five Mg atoms were added to the layered vacancy–solute complex, the central Mg atom completely shifted to the Si layer, and a Mg vacancy was formed in the Mg layer, which indicated that the β″-eye is formed upon the addition of Mg atoms. We reproduced β″-eye formation from a solid solution with a vacancy using first-principles-based Monte Carlo simulations. Once the β″-eye was formed on the layered vacancy–solute complex, the process can be repeated by the formation of alternate Mg and Si layers along [010] β″. These results clearly indicate that the layered vacancy–solute complex plays an important role in β″-eye formation.

Observed Defects of Swiss Cheese Based on the Microbiome Contribution to the Production of Organic Acids

The United States Department of Agriculture downgrades on the order of 17% of all Swiss cheese produced in the United States due to defects. Many of these defects are related to improper eye formation, number, distribution, or size; leading to an industry loss of over $69 million per annum. The microbiome in Swiss-type cheeses plays a significant role in eye development due to production of organic acids and gaseous emissions contingent on bacterial abundance and phenotype. The relationship between bacteria and the organic acids they produce leading to Swiss cheese defects can be correlated using Next-generation sequencing and high-performance liquid chromatography coupled with UV-Vis and mass spectrometry, respectively. From two processing facilities, Next-generation sequencing identified bacterial genera Lactobacillus and Propionibacterium to be associated with split/cracked cheese defects, and Clostridium sensu stricto 12, Propionibacterium, and Lactobacillus to be associated with irregular Eye formation/distribution (or collapsed eye formation) defects in Swiss cheese. Also identified through Next-generation sequencing was the genera "Candidatus Berkiella", Propionibacterium, and Lactobacillus to be associated with blind defects in Swiss cheese. Chromatographic separation and identification of organic acids provided evidence that lower levels of acetic and propionic acids were found in the split/cracked cheese samples; lower abundance of acetic, lactic, propionic and butyric acids were found in blind cheese samples (while a higher abundance of citric acid was found); and lower concentrations of citric, acetic, and propionic acids were found in irregular eye distribution samples. From these data, it can be concluded that Swiss cheese monitoring for bacteria in the genera Lactobacillus, Propionibacterium, Clostridium sensu stricto 12, and "Candidatus Berkiella" can be used as a predictor of three types of cheese defects before and during long storage times leading to inferior product resulting in losses to the processor while organic acid monitoring results proved to be inconclusive.

A hypomorphic cystathionine ß-synthase gene contributes to cavefish eye loss by disrupting optic vasculature

Vestigial structures are key indicators of evolutionary descent, but the mechanisms underlying their development are poorly understood. This study examines vestigial eye formation in the teleost Astyanax mexicanus, which consists of a sighted surface-dwelling morph and multiple populations of blind cave morphs. Cavefish embryos initially develop eyes, but they subsequently degenerate and become vestigial structures embedded in the head. The mutated genes involved in cavefish vestigial eye formation have not been characterized. Here we identify cystathionine ß-synthase a (cbsa), which encodes the key enzyme of the transsulfuration pathway, as one of the mutated genes responsible for eye degeneration in multiple cavefish populations. The inactivation of cbsa affects eye development by increasing the transsulfuration intermediate homocysteine and inducing defects in optic vasculature, which result in aneurysms and eye hemorrhages. Our findings suggest that localized modifications in the circulatory system may have contributed to the evolution of vestigial eyes in cavefish.

Developmentally regulated Tcf7l2 splice variants mediate transcriptional repressor functions during eye formation

Tcf7l2 mediates Wnt/β-Catenin signalling during development and is implicated in cancer and type-2 diabetes. The mechanisms by which Tcf7l2 and Wnt/β-Catenin signalling elicit such a diversity of biological outcomes are poorly understood. Here, we study the function of zebrafish tcf7l2 alternative splice variants and show that only variants that include exon five or an analogous human tcf7l2 variant can effectively provide compensatory repressor function to restore eye formation in embryos lacking tcf7l1a/tcf7l1b function. Knockdown of exon five specific tcf7l2 variants in tcf7l1a mutants also compromises eye formation, and these variants can effectively repress Wnt pathway activity in reporter assays using Wnt target gene promoters. We show that the repressive activities of exon5-coded variants are likely explained by their interaction with Tle co-repressors. Furthermore, phosphorylated residues in Tcf7l2 coded exon5 facilitate repressor activity. Our studies suggest that developmentally regulated splicing of tcf7l2 can influence the transcriptional output of the Wnt pathway.