Yeast flocculation is a community-building cell aggregation trait that is an important mechanism of stress resistance and a useful phenotype for brewers; however, it is also a nuisance in many industrial processes, in clinical settings, and in the laboratory. Chemostat-based evolution experiments are impaired by inadvertent selection for aggregation, which we observe in 35% of populations. These populations provide a testing ground for understanding the breadth of genetic mechanisms Saccharomyces cerevisiae uses to flocculate, and which of those mechanisms provide the biggest adaptive advantages. In this study, we employed experimental evolution as a tool to ask whether one or many routes to flocculation are favored, and to engineer a strain with reduced flocculation potential. Using a combination of whole genome sequencing and bulk segregant analysis, we identified causal mutations in 23 independent clones that had evolved cell aggregation during hundreds of generations of chemostat growth. In 12 of those clones, we identified a transposable element insertion in the promoter region of known flocculation gene FLO1, and, in an additional five clones, we recovered loss-of-function mutations in transcriptional repressor TUP1, which regulates FLO1 and other related genes. Other causal mutations were found in genes that have not been previously connected to flocculation. Evolving a flo1 deletion strain revealed that this single deletion reduces flocculation occurrences to 3%, and demonstrated the efficacy of using experimental evolution as a tool to identify and eliminate the primary adaptive routes for undesirable traits.
Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially lifethreatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs.
The ability of yeast to form biofilms contributes to better survival under stressful conditions. We see the impact of yeast biofilms and “flocs” (clumps) in human health and industry, where forming clumps enables yeast to act as a natural filter in brewing and forming biofilms enables yeast to remain virulent in cases of fungal infection. Despite the importance of biofilms in yeast natural isolates, the majority of our knowledge about yeast biofilm genetics comes from work with a few tractable laboratory strains. A new collection of sequenced natural isolates from the Saccharomyces Genome Resequencing Project enabled us to examine the breadth of biofilm-related phenotypes in geographically, ecologically, and genetically diverse strains of Saccharomyces cerevisiae. We present a panel of 31 haploid and 24 diploid strains for which we have characterized six biofilm-related phenotypes: complex colony morphology, complex mat formation, flocculation, agar invasion, polystyrene adhesion, and psuedohyphal growth. Our results show that there is extensive phenotypic variation between and within strains, and that these six phenotypes are primarily uncorrelated or weakly correlated, with the notable exception of complex colony and complex mat formation. We also show that the phenotypic strength of these strains varies significantly depending on ploidy, and the diploid strains demonstrate both decreased and increased phenotypic strength with respect to their haploid counterparts. This is a more complex view of the impact of ploidy on biofilm-related phenotypes than previous work with laboratory strains has suggested, demonstrating the importance and enormous potential of working with natural isolates of yeast.
Polar Mesosphere Summer Echoes (PMSE) occur near the mesopause during the polar summer months. PMSE are primarily studied at VHF, however there have been some detections at higher frequencies. Here, we report on some of the first detections of PMSE with the 450 MHz (67 cm) Poker Flat Advanced Modular Incoherent Scatter Radar (PFISR). Echoes were observed with volume reflectivities (radar scattering cross section per unit volume) near 2–3 × 10−17 m−1. On 11 June 2007, PFISR was operating in a 26‐beam position mode, with look directions spread over an approximately 80 by 80 km2 region at 85 km altitude with elevation angles as low as ∼50°. The measurements showed patchy (tens of kilometer) irregularity regions drifting in from the north, in addition to smaller, more localized structures. There was no evidence for strong aspect sensitivity of these UHF echoes, as PMSE was observed in all look directions with relatively uniform intensity. The observations indicate the presence of fossilized irregularities drifting with the background wind field as well as areas of developing irregularities possibly associated with the presence of active neutral air turbulence.
Yeast flocculation is a community-building cell aggregation trait that is an important mechanism of stress resistance and a useful phenotype for brewers; however, it is also a nuisance in many industrial processes, in clinical settings, and in the laboratory. Chemostat-based evolution experiments are impaired by inadvertent selection for aggregation, which we observe in 35% of populations. These populations provide a testing ground for understanding the breadth of genetic mechanisms Saccharomyces cerevisiae uses to flocculate, and which of those mechanisms provide the biggest adaptive advantages. In this study, we employed experimental evolution as a tool to ask whether one or many routes to flocculation are favored, and to engineer a strain with reduced flocculation potential. Using a combination of whole genome sequencing and bulk segregant analysis, we identified causal mutations in 23 independent clones that had evolved cell aggregation during hundreds of generations of chemostat growth. In 12 of those clones, we identified a transposable element insertion in the promoter region of known flocculation gene FLO1, and, in an additional five clones, we recovered loss-of-function mutations in transcriptional repressor TUP1, which regulates FLO1 and other related genes. Other causal mutations were found in genes that have not been previously connected to flocculation. Evolving a flo1 deletion strain revealed that this single deletion reduces flocculation occurrences to 3%, and demonstrated the efficacy of using experimental evolution as a tool to identify and eliminate the primary adaptive routes for undesirable traits.
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