Enhanced flavour profiles through radicicol induced genomic variation in the lager yeasts, Saccharomyces pastorianus.

The yeasts, Saccharomyces pastorianus, are hybrids of Saccharomyces cerevisiae and Saccharomyces eubayanus and have acquired traits from the combined parental genomes such as ability to ferment a range of sugars at low temperatures and to produce aromatic flavour compounds, allowing for the production of lager beers with crisp, clean flavours. The polyploid strains are sterile and have reached an evolutionary bottleneck for genetic variation. Here we describe an accelerated evolution approach to obtain lager yeasts with enhanced flavour profiles. As the relative expression of orthologous alleles is a significant contributor to the transcriptome during fermentation, we aimed to induce genetic variation by altering the S. cerevisiae to S. eubayanus chromosome ratio. Aneuploidy was induced through the temporary inhibition of the cell's stress response and strains with increased production of aromatic amino acids via the Shikimate pathway were selected by resistance to amino acid analogues. Genomic changes such as gross chromosomal rearrangements, chromosome loss and chromosome gain were detected in the characterised mutants, as were single-nucleotide polymorphisms in ARO4, encoding for DAHP synthase, the catalytic enzyme in the first step of the Shikimate pathway. Transcriptome analysis confirmed the upregulation of genes encoding enzymes in the Ehrlich pathway and the concomitant increase in the production of higher alcohols and esters such as 2-phenylethanol, 2-phenylethyl acetate, tryptophol, and tyrosol. We propose that the polyploid nature of S. pastorianus genomes is an advantageous trait supporting opportunities for genetic alteration in otherwise sterile strains.

Aneuploidy influences the gene expression profiles in Saccharomyces pastorianus group I and II strains during fermentation.

The lager yeasts, Saccharomyces pastorianus, are hybrids of Saccharomyces cerevisiae and Saccharomyces eubayanus and are divided into two broad groups, Group I and II. The two groups evolved from at least one common hybridisation event but have subsequently diverged with Group I strains losing many S. cerevisiae chromosomes while the Group II strains retain both sub-genomes. The complex genomes, containing orthologous alleles from the parental chromosomes, pose interesting questions regarding gene regulation and its impact on the fermentation properties of the strains. Superimposed on the presence of orthologous alleles are complexities of gene dosage due to the aneuploid nature of the genomes. We examined the contribution of the S. cerevisiae and S. eubayanus alleles to the gene expression patterns of representative Group I and II strains during fermentation. We show that the relative expression of S. cerevisiae and S. eubayanus orthologues is positively correlated with gene copy number. Despite the reduced S. cerevisiae content in the Group I strain, S. cerevisiae orthologues contribute to biochemical pathways upregulated during fermentation which may explain the retention of specific chromosomes in the strain. Conversely, S. eubayanus genes are significantly overrepresented in the upregulated gene pool in the Group II strain. Comparison of the transcription profiles of the strains during fermentation identified both common and unique gene expression patterns, with gene copy number being a dominant contributory factor. Thus, the aneuploid genomes create complex patterns of gene expression during fermentation with gene dosage playing a crucial role both within and between strains.

Moving the needle on health inequities: principles and tactics for effective cross-sector population health networks.

PURPOSE OF REVIEW: To summarize elements of cross-sector population health networks to support systems and policy change to achieve equitable access to health services and healthy development opportunities for young children and families, allowing everyone to have a fair and just opportunity to be as healthy as possible. RECENT FINDINGS: The principles and tactics of Equity and Inclusion, Readiness, Joint Planning, Governance, and Data can guide cross-sector networks in effectively supporting communities in addressing health inequities. These principles are not linear or siloed, but rather, they overlap and reinforce each other. The principles require equity and the participation of community members to be central in all aspects of cross-sector network work. SUMMARY: By building strong relationships among community partners, cross-sector population health networks can ensure the network is not a short-term, transactional one-time project, but rather, a sustained collaboration through enduring processes and infrastructure. Networks can gain a fuller understanding of the needs and assets of a community through engagement and leadership by community members than they could gather from data and surveys alone. This approach to serving a community by making members equal partners in the effort helps to place equity at the center of a network's focus, as does embedding equity-related decision-making tools and processes into daily operations of the network. If cross-sector networks build resilient, inclusive structures and procedures, they can utilize them to quickly pivot and adjust to emerging needs or respond to crisis.

Pragmatic lifestyle intervention in patients recovering from colon cancer: a randomized controlled pilot study.

OBJECTIVE: To investigate the feasibility of a pragmatic lifestyle intervention in patients who had recently completed surgery and chemotherapy for colon cancer and to obtain preliminary data of its impact on important health outcomes. DESIGN: A prospective, randomized, controlled pilot trial. SETTING: University rehabilitation facility. PARTICIPANTS: Eighteen (N=18) colon cancer survivors (mean age=69y; range, 52-80y), Dukes stage A to C. INTERVENTIONS: Participants were randomized 6 to 24 months postoperatively to either a 12-week program of combined exercise and dietary advice or standard treatment. MAIN OUTCOME MEASURES: Exercise and dietary behavior, fatigue, health-related quality of life (QOL), aerobic exercise tolerance, functional capacity, muscle strength, and anthropometery were assessed at baseline and immediately after the intervention. RESULTS: Adherences to supervised and independent exercise during the intervention were 90% and 94%, respectively, and there was low attrition (6%). The lifestyle intervention elicited improvements in exercise behavior (P=.068), fatigue (P=.005), aerobic exercise tolerance (P=.010), chair sit-to-stand performance (P=.003), and waist-to-hip ratio (P=.002). A positive change in dietary fiber intake (P=.044) was also observed in the intervention group. No change in QOL was observed (P=.795). CONCLUSIONS: These preliminary results suggest that a pragmatic lifestyle intervention implemented 6 to 24 months after primary treatment for colon cancer was feasible. We observed a significant impact on dietary behavior, fatigue, aerobic exercise tolerance, functional capacity, and waist-to-hip ratio. These findings need to be confirmed with a larger-scale definitive randomized controlled trial.