Yeast thioredoxin reductase Trr1p controls TORC1-regulated processes

The thioredoxin system plays a predominant role in the control of cellular redox status. Thioredoxin reductase fuels the system with reducing power in the form of NADPH. The TORC1 complex promotes growth and protein synthesis when nutrients, particularly amino acids, are abundant. It also represses catabolic processes, like autophagy, which are activated during starvation. We analyzed the impact of yeast cytosolic thioredoxin reductase TRR1 deletion under different environmental conditions. It shortens chronological life span and reduces growth in grape juice fermentation. TRR1 deletion has a global impact on metabolism during fermentation. As expected, it reduces oxidative stress tolerance, but a compensatory response is triggered, with catalase and glutathione increasing. Unexpectedly, TRR1 deletion causes sensitivity to the inhibitors of the TORC1 pathway, such as rapamycin. This correlates with low Tor2p kinase levels and indicates a direct role of Trr1p in its stability. Markers of TORC1 activity, however, suggest increased TORC1 activity. The autophagy caused by nitrogen starvation is reduced in the trr1Δ mutant. Ribosomal protein Rsp6p is dephosphorylated in the presence of rapamycin. This dephosphorylation diminishes in the TRR1 deletion strain. These results show a complex network of interactions between thioredoxin reductase Trr1p and the processes controlled by TOR

Study protocol: a double blind placebo controlled trial examining the effect of domperidone on the composition of breast milk [NCT00308334]

BACKGROUND: Domperidone, a drug that enhances upper gastric motility, is an anti-dopaminergic medication that also elevates prolactin levels. It has been shown to safely increase the milk supply of lactating women. To date, researchers have analyzed the effects of domperidone on lactating woman with respect to the quantity of their milk production, adverse effects, and drug levels in the breast milk. However, the effect of domperidone on the macronutrient composition of breast milk has not been studied and current guidelines for fortification of human milk for premature infants do not distinguish between those women using or those not using domperidone. The purpose of this study is to evaluate the effect of domperidone (given to lactating mothers of very preterm infants) on the macronutrient composition of breast milk. METHODS/DESIGN: Mothers of infants delivered at less than 31 weeks gestation, who are at least 3 weeks postpartum, and experiencing lactational failure despite non-pharmacological interventions, will be randomized to receive domperidone (10 mg three times daily) or placebo for a 14-day period. Breast milk samples will be obtained the day prior to beginning treatment and on days 4, 7 and 14. The macronutrient (protein, fat, carbohydrate and energy) and macromineral content (calcium, phosphorus and sodium) will be analyzed and compared between the two groups. Additional outcome measures will include milk volumes, serum prolactin levels (measured on days 0, 4, and 10), daily infant weights and breastfeeding rates at 2 weeks post study completion and at discharge. Forty-four participants will be recruited into the study. Analysis will be carried out using the intention to treat approach. DISCUSSION: If domperidone causes significant changes to the nutrient content of breast milk, an alteration in feeding practices for preterm infants may need to be made in order to optimize growth, nutrition and neurodevelopment outcomes

A Versatile Protocol to Generate Translocations in Yeast Genomes Using CRISPR/Cas9

International audienc

Fertility assessment in hybrids between monobrachially homologous Rb races of the house mouse from the island of Madeira: implications for modes of chromosomal evolution

The speciation model of divergence by monobrachially homologous fusions (that is, with one arm in common) benefits from a wide conceptual acceptance, because heterozygotes between populations carrying such fusions suffer from high levels of meiotic dysfunction. The same meiotic configurations can also be generated by WART (whole-arm reciprocal translocation), rearrangements that are known to occur in mammals. Estimating the disadvantage of heterozygotes carrying monobrachially homologous fusions is required to evaluate the relevance of this mode of chromosomal evolution in diversification and speciation. House mice are an excellent study models because chromosomal races exist carrying monobrachially homologous fusions, and WARTs have been documented in this species. The fertility of heterozygote mice carrying the smallest number of monobrachially homologous fusions (that is, a chain of four chromosomes, C4) was investigated in laboratory-bred hybrids between two parapatric chromosomal races from the island of Madeira. Meiotic nondisjunction analyses and histological sections of testes showed that aneuploidy (16.7%) and germ cell death (50.9%) rates reached significantly higher mean values in hybrids than in homozygotes. In females, however, the histological analysis of ovarian follicle parameters revealed no significant differences between hybrid and homozygous individuals. Overall, the reproductive assays indicated that these C4-carrying hybrids were not sterile but showed an approximately 50% decrease in fertility compared to homozygous parental mice. Implications for modes of chromosomal evolution involving monobrachially homologous fusions are discussed