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Candida albicans, a normal member of the human microbiome and an opportunistic fungal pathogen, undergoes several morphological transitions. One of these transitions is white-opaque switching, where C. albicans alternates between 2 stable cell types with distinct cellular and colony morphologies, metabolic preferences, mating abilities, and interactions with the innate immune system. White-to-opaque switching is regulated by mating type; it is repressed by the a1/α2 heterodimer in a/α cells, but this repression is lifted in a/a and α/α mating type cells (each of which are missing half of the repressor). The widely used C. albicans reference strain, SC5314, is unusual in that white-opaque switching is completely blocked when the cells are a/α; in contrast, most other C. albicans a/α strains can undergo white-opaque switching at an observable level. In this paper, we uncover the reason for this difference. We show that, in addition to repression by the a1/α2 heterodimer, SC5314 contains a second block to white-opaque switching: 4 transcription regulators of filamentous growth are upregulated in this strain and collectively suppress white-opaque switching. This second block is missing in the majority of clinical strains, and, although they still contain the a1/α2 heterodimer repressor, they exhibit a/α white-opaque switching at an observable level. When both blocks are absent, white-opaque switching occurs at very high levels. This work shows that white-opaque switching remains intact across a broad group of clinical strains, but the precise way it is regulated and therefore the frequency at which it occurs varies from strain to strain., Competing Interests: Conflicts of interest ADJ is a cofounder of BioSynesis, Inc., a company developing diagnostics and therapeutics for biofilm infections. MBL is a consultant for BioSynesis, Inc. No funding for this research was provided by BioSynesis, Inc. and/or by any grants to BioSynesis, Inc. Neither BioSynesis, Inc., nor agencies funding BioSynesis, Inc., played any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

An unusual feature of the opportunistic pathogen Candida albicans is its ability to switch stochastically between two distinct, heritable cell types called white and opaque. Here, we show that only opaque cells, in response to environmental signals, massively upregulate a specific group of secreted proteases and peptide transporters, allowing exceptionally efficient use of proteins as sources of nitrogen. We identify the specific proteases [members of the secreted aspartyl protease ( SAP ) family] needed for opaque cells to proliferate under these conditions, and we identify four transcriptional regulators of this specialized proteolysis and uptake program. We also show that, in mixed cultures, opaque cells enable white cells to also proliferate efficiently when proteins are the sole nitrogen source. Based on these observations, we suggest that one role of white-opaque switching is to create mixed populations where the different phenotypes derived from a single genome are shared between two distinct cell types., (Copyright © 2020 by the Genetics Society of America.)

In all organisms, the majority of traits vary continuously between individuals. Explaining the genetic basis of quantitative trait variation requires comprehensively accounting for genetic and nongenetic factors as well as their interactions. The growth of microbial cells can be characterized by a lag duration, an exponential growth phase, and a stationary phase. Parameters that characterize these growth phases can vary among genotypes (phenotypic variation), environmental conditions (phenotypic plasticity), and among isogenic cells in a given environment (phenotypic variability). We used a high-throughput microscopy assay to map genetic loci determining variation in lag duration and exponential growth rate in growth rate-limiting and nonlimiting glucose concentrations, using segregants from a cross of two natural isolates of the budding yeast, Saccharomyces cerevisiae We find that some quantitative trait loci (QTL) are common between traits and environments whereas some are unique, exhibiting gene-by-environment interactions. Furthermore, whereas variation in the central tendency of growth rate or lag duration is explained by many additive loci, differences in phenotypic variability are primarily the result of genetic interactions. We used bulk segregant mapping to increase QTL resolution by performing whole-genome sequencing of complex mixtures of an advanced intercross mapping population grown in selective conditions using glucose-limited chemostats. We find that sequence variation in the high-affinity glucose transporter HXT7 contributes to variation in growth rate and lag duration. Allele replacements of the entire locus, as well as of a single polymorphic amino acid, reveal that the effect of variation in HXT7 depends on genetic, and allelic, background. Amplifications of HXT7 are frequently selected in experimental evolution in glucose-limited environments, but we find that HXT7 amplifications result in antagonistic pleiotropy that is absent in naturally occurring variants of HXT7 Our study highlights the complex nature of the genotype-to-phenotype map within and between environments., (Copyright © 2017 by the Genetics Society of America.)

In microbial populations, growth initiation and proliferation rates are major components of fitness and therefore likely targets of selection. We used a high-throughput microscopy assay, which enables simultaneous analysis of tens of thousands of microcolonies, to determine the sources and extent of growth rate variation in the budding yeast (Saccharomyces cerevisiae) in different glucose environments. We find that cell growth rates are regulated by the extracellular concentration of glucose as proposed by Monod (1949), but that significant heterogeneity in growth rates is observed among genetically identical individuals within an environment. Yeast strains isolated from different geographic locations and habitats differ in their growth rate responses to different glucose concentrations. Inheritance patterns suggest that the genetic determinants of growth rates in different glucose concentrations are distinct. In addition, we identified genotypes that differ in the extent of variation in growth rate within an environment despite nearly identical mean growth rates, providing evidence that alleles controlling phenotypic variability segregate in yeast populations. We find that the time to reinitiation of growth (lag) is negatively correlated with growth rate, yet this relationship is strain-dependent. Between environments, the respirative activity of individual cells negatively correlates with glucose abundance and growth rate, but within an environment respirative activity and growth rate show a positive correlation, which we propose reflects differences in protein expression capacity. Our study quantifies the sources of genetic and nongenetic variation in cell growth rates in different glucose environments with unprecedented precision, facilitating their molecular genetic dissection.

An essential property of all cells is the ability to exit from active cell division and persist in a quiescent state. For single-celled microbes this primarily occurs in response to nutrient deprivation. We studied the genetic requirements for survival of Saccharomyces cerevisiae when starved for either of two nutrients: phosphate or leucine. We measured the survival of nearly all nonessential haploid null yeast mutants in mixed populations using a quantitative sequencing method that estimates the abundance of each mutant on the basis of frequency of unique molecular barcodes. Starvation for phosphate results in a population half-life of 337 hr whereas starvation for leucine results in a half-life of 27.7 hr. To measure survival of individual mutants in each population we developed a statistical framework that accounts for the multiple sources of experimental variation. From the identities of the genes in which mutations strongly affect survival, we identify genetic evidence for several cellular processes affecting survival during nutrient starvation, including autophagy, chromatin remodeling, mRNA processing, and cytoskeleton function. In addition, we found evidence that mitochondrial and peroxisome function is required for survival. Our experimental and analytical methods represent an efficient and quantitative approach to characterizing genetic functions and networks with unprecedented resolution and identified genotype-by-environment interactions that have important implications for interpretation of studies of aging and quiescence in yeast.

The aim of the present study was to examine the effects of music relaxation on insomnia and emotional measures in people living with schizophrenia. Twenty-four people living with schizophrenia participated in the study. The study involved a 7-day running-in no-treatment period, followed by a 7-day experimental period. Treatment consisted of music relaxation played at bedtime. During each of these periods, participants' sleep was continuously monitored with a wrist actigraph, and participants completed a wide spectrum of questionnaires. Results showed an improvement in sleep latency and sleep efficiency after the music relaxation was played. Likewise, music relaxation was shown to improve participants' total psychopathology score (PANSS) as well as their level of depression. Moreover, a significant correlation was found between reduction in level of situational anxiety and improvement in sleep efficiency. The findings suggest the beneficial effect of music relaxation as a treatment both for insomnia and for emotional measures in people living with schizophrenia.

A large percentage of older people suffer from chronic insomnia, affecting many aspects of life quality and well-being. Although insomnia is most often treated with medication, a growing number of studies demonstrate the efficiency of various relaxation techniques. The present study had three aims: first, to compare two relaxation techniques--music relaxation and progressive muscular relaxation--on various objective and subjective measures of sleep quality; second, to examine the effect of these techniques on anxiety and depression; and finally, to explore possible relationships between the efficiency of both techniques and personality variables. Fifteen older adults took part in the study. Following one week of base-line measurements of sleep quality, participants followed one week of music relaxation and one week of progressive muscular relaxation before going to sleep. Order of relaxation techniques was controlled. Results show music relaxation was more efficient in improving sleep. Sleep efficiency was higher after music relaxation than after progressive muscular relaxation. Moreover, anxiety was lower after music relaxation. Progressive muscular relaxation was related to deterioration of sleep quality on subjective measures. Beyond differences between the relaxation techniques, extraverts seemed to benefit more from both music and progressive muscular relaxation. The advantage of non-pharmacological means to treat insomnia, and the importance of taking individual differences into account are discussed.

Previous studies have demonstrated the benefits of music therapy in Alzheimer's patients, focusing either on improvement of healthy cognitive and social skills, or reduction of agitation symptoms. The present study examined the effect of background music on both positive and negative behaviors, during a time in which patients were not occupied with any structured activity. Twenty eight participants were observed both with and without stimulative, familiar background music. Results showed both a significant increase in positive social behaviors and a significant decrease in negative behaviors related to agitation when music is played. Results demonstrate the contribution of music to enhancing general positive functioning in elderly patients with dementia, and reducing negative behaviors typical of their condition.