Expression variability of co-regulated genes differentiates Saccharomyces cerevisiae strains

Background: Saccharomyces cerevisiae (Baker’s yeast) is found in diverse ecological niches and is characterized by high adaptive potential under challenging environments. In spite of recent advances on the study of yeast genome diversity, little is known about the underlying gene expression plasticity. In order to shed new light onto this biological question, we have compared transcriptome profiles of five environmental isolates, clinical and laboratorial strains at different time points of fermentation in synthetic must medium, during exponential and stationary growth phases. Results: Our data unveiled diversity in both intensity and timing of gene expression. Genes involved in glucose metabolism and in the stress response elicited during fermentation were among the most variable. This gene expression diversity increased at the onset of stationary phase (diauxic shift). Environmental isolates showed lower average transcript abundance of genes involved in the stress response, assimilation of nitrogen and vitamins, and sulphur metabolism, than other strains. Nitrogen metabolism genes showed significant variation in expression among the environmental isolates. Conclusions: Wild type yeast strains respond differentially to the stress imposed by nutrient depletion, ethanol accumulation and cell density increase, during fermentation of glucose in synthetic must medium. Our results support previous data showing that gene expression variability is a source of phenotypic diversity among closely related organisms.Fundação para a Ciência e TecnologiaThe authors wish to thank Adega Cooperativa da Bairrada, Cantanhede, Portugal, for providing the commercial strains

Comparative transcriptomic analysis reveals similarities and dissimilarities in saccharomyces cerevisiae wine strains response to nitrogen availability

Nitrogen levels in grape-juices are of major importance in winemaking ensuring adequate yeast growth and fermentation performance. Here we used a comparative transcriptome analysis to uncover wine yeasts responses to nitrogen availability during fermentation. Gene expression was assessed in three genetically and phenotypically divergent commercial wine strains (CEG, VL1 and QA23), under low (67 mg/L) and high nitrogen (670 mg/L) regimes, at three time points during fermentation (12h, 24h and 96h). Two-way ANOVA analysis of each fermentation condition led to the identification of genes whose expression was dependent on strain, fermentation stage and on the interaction of both factors. The high fermenter yeast strain QA23 was more clearly distinct from the other two strains, by differential expression of genes involved in flocculation, mitochondrial functions, energy generation and protein folding and stabilization. For all strains, higher transcriptional variability due to fermentation stage was seen in the high nitrogen fermentations. A positive correlation between maximum fermentation rate and the expression of genes involved in stress response was observed. The finding of common genes correlated with both fermentation activity and nitrogen up-take underlies the role of nitrogen on yeast fermentative fitness. The comparative analysis of genes differentially expressed between both fermentation conditions at 12h, where the main difference was the level of nitrogen available, showed the highest variability amongst strains revealing strain-specific responses. Nevertheless, we were able to identify a small set of genes whose expression profiles can quantitatively assess the common response of the yeast strains to varying nitrogen conditions. The use of three contrasting yeast strains in gene expression analysis prompts the identification of more reliable, accurate and reproducible biomarkers that will facilitate the diagnosis of deficiency of this nutrient in the grape-musts and the development of strategies to optimize yeast performance in industrial fermentations

Risk Model-Based Lung Cancer Screening and Racial and Ethnic Disparities in the US

Importance The revised 2021 US Preventive Services Task Force (USPSTF) guidelines for lung cancer screening have been shown to reduce disparities in screening eligibility and performance between African American and White individuals vs the 2013 guidelines. However, potential disparities across other racial and ethnic groups in the US remain unknown. Risk model–based screening may reduce racial and ethnic disparities and improve screening performance, but neither validation of key risk prediction models nor their screening performance has been examined by race and ethnicity.Objective To validate and recalibrate the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 2012 (PLCOm2012) model—a well-established risk prediction model based on a predominantly White population—across races and ethnicities in the US and evaluate racial and ethnic disparities and screening performance through risk-based screening using PLCOm2012 vs the USPSTF 2021 criteria.Design, Setting, and Participants In a population-based cohort design, the Multiethnic Cohort Study enrolled participants in 1993-1996, followed up through December 31, 2018. Data analysis was conducted from April 1, 2022, to May 19. 2023. A total of 105 261 adults with a smoking history were included.Exposures The 6-year lung cancer risk was calculated through recalibrated PLCOm2012 (ie, PLCOm2012-Update) and screening eligibility based on a 6-year risk threshold greater than or equal to 1.3%, yielding similar eligibility as the USPSTF 2021 guidelines.Outcomes Predictive accuracy, screening eligibility-incidence (E-I) ratio (ie, ratio of the number of eligible to incident cases), and screening performance (sensitivity, specificity, and number needed to screen to detect 1 lung cancer).Results Of 105 261 participants (60 011 [57.0%] men; mean [SD] age, 59.8 [8.7] years), consisting of 19 258 (18.3%) African American, 27 227 (25.9%) Japanese American, 21 383 (20.3%) Latino, 8368 (7.9%) Native Hawaiian/Other Pacific Islander, and 29 025 (27.6%) White individuals, 1464 (1.4%) developed lung cancer within 6 years from enrollment. The PLCOm2012-Update showed good predictive accuracy across races and ethnicities (area under the curve, 0.72-0.82). The USPSTF 2021 criteria yielded a large disparity among African American individuals, whose E-I ratio was 53% lower vs White individuals (E-I ratio: 9.5 vs 20.3; P < .001). Under the risk-based screening (PLCOm2012-Update 6-year risk ≥1.3%), the disparity between African American and White individuals was substantially reduced (E-I ratio: 15.9 vs 18.4; P < .001), with minimal disparities observed in persons of other minoritized groups, including Japanese American, Latino, and Native Hawaiian/Other Pacific Islander. Risk-based screening yielded superior overall and race and ethnicity–specific performance to the USPSTF 2021 criteria, with higher overall sensitivity (67.2% vs 57.7%) and lower number needed to screen (26 vs 30) at similar specificity (76.6%).Conclusions The findings of this cohort study suggest that risk-based lung cancer screening can reduce racial and ethnic disparities and improve screening performance across races and ethnicities vs the USPSTF 2021 criteria

Molecular analysis of the genes involved in aroma synthesis in the species S. cerevisiae, S. kudriavzevii and S. bayanus var. uvarum in winemaking conditions

The Saccharomyces genus is the main yeast involved in wine fermentations to play a crucial role in the production and release of aromatic compounds. Despite the several studies done into the genome-wide expression analysis using DNA microarray technology in wine S. cerevisiae strains, this is the first to investigate other species of the Saccharomyces genus. This research work investigates the expression of the genes involved in flavor compound production in three different Saccharomyces species (S. cerevisiae, S. bayanus var. uvarum and S. kudriavzevii ) under low (12°C) and moderate fermentation temperatures (28°C). The global genes analysis showed that 30% of genes appeared to be differently expressed in the three cryophilic strains if compared to the reference strain (mesophilic S. cerevisiae), suggesting a very close cold adaptation response. Remarkable differences in the gene expression level were observed when comparing the three species, S. cerevisiae, S. bayanus var. uvarum and S. kudriavzevii, which will result in different aroma profiles. Knowledge of these differences in the transcriptome can be a tool to help modulate aroma to create wines with the desired aromatic traits. © 2014 Gamero et al.AGL2009-12673-CO2-01, AGL2012-39937-C02-01 and from the Spanish Government and PROMETEO grant (Project PROMETEO/2009/019) from the Generalitat Valenciana to A. Querol. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer Reviewe

The Survival Impact of Second Primary Lung Cancer in Patients With Lung Cancer

Abstract Background Lung cancer survivors have a high risk of developing second primary lung cancer (SPLC), but little is known about the survival impact of SPLC diagnosis. Methods We analyzed data from 138 969 patients in the Surveillance, Epidemiology, and End Results (SEER), who were surgically treated for initial primary lung cancer (IPLC) in 1988-2013. Each patient was followed from the date of IPLC diagnosis to SPLC diagnosis (for those with SPLC) and last vital status through 2016. We performed multivariable Cox regression to evaluate the association between overall survival and SPLC diagnosis as a time-varying predictor. To investigate potential effect modification, we tested interaction between SPLC and IPLC stage. Using data from the Multiethnic Cohort Study (MEC) (n = 1540 IPLC patients with surgery), we evaluated the survival impact of SPLC by smoking status. All statistical tests were 2-sided. Results A total of 12 115 (8.7%) patients developed SPLC in SEER over 700 421 person-years of follow-up. Compared with patients with single primary lung cancer, those with SPLC had statistically significantly reduced overall survival (hazard ratio [HR] = 2.12, 95% confidence interval [CI] = 2.06 to 2.17; P &amp;lt; .001). The effect of SPLC on reduced survival was more pronounced among patients with early stage IPLC vs advanced-stage IPLC (HR = 2.14, 95% CI = 2.08 to 2.20, vs HR = 1.43, 95% CI = 1.21 to 1.70, respectively; Pinteraction &amp;lt; .001). Analysis using MEC data showed that the effect of SPLC on reduced survival was statistically significantly larger among persons who actively smoked at initial diagnosis vs those who formerly or never smoked (HR = 2.31, 95% CI = 1.48 to 3.61, vs HR = 1.41, 95% CI = 0.98 to 2.03, respectively; Pinteraction = .04). Conclusions SPLC diagnosis is statistically significantly associated with decreased survival in SEER and MEC. Intensive surveillance targeting patients with early stage IPLC and active smoking at IPLC diagnosis may lead to a larger survival benefit. </jats:sec

Adaptation of yeasts Saccharomyces cerevisiae and Brettanomyces bruxellensis to winemaking conditions: a comparative study of stress genes expression

International audienceBrettanomyces is the major microbial cause for wine spoilage worldwide and causes significant economic losses. Like Saccharomyces cerevisiae, it is well adapted to winemaking, but molecular pathways involved in this acclimatization are still unknown. In this work, we report a time-scale comparison between the two yeasts coping with alcoholic fermentation. Orthologs of some well-characterized stress genes of S. cerevisiae were searched by sequence alignment in the Dekkera/Brettanomyces partial genome; nine genes were finally selected on the basis on their similarity and involvement in adaptation to wine. Transcript analysis during a model grape juice fermentation indicates that a subset of genes (i.e., ATP1, ERG6, VPS34) shows peculiar expression patterns in Brettanomyces bruxellensis but also that some common regulations of stress response exist between the two yeasts, although with different timing (i.e., for MSN4, SNF1, HSP82, NTH1). This suggests that B. bruxellensis efficient survival in such challenging conditions is due to mechanisms unique to it, together with a conserved yeast stress response. This study, although limited by the poor genetic data available on B. bruxellensis, provides first insights into its gene expression remodeling in winemaking and opens new frames for further investigations