Abstract Background Reported prevalence of emotional distress in cancer patients varies widely across studies. The present study determined prevalence of anxiety and depression (separated for ...presence of symptoms versus clinical levels) in a large, representative sample of cancer patients after diagnosis. Method During the years 2004–2009, 10,153 consecutive patients were routinely screened with the Psychosocial Screen for Cancer questionnaire at two major cancer centers. Results Patients' mean age was 59 years and 45% were men. Across cancer types, 19.0% of patients showed clinical levels of anxiety and another 22.6% had subclinical symptoms. Further, 12.9% of patients reported clinical symptoms of depression and an additional 16.5% described subclinical symptoms. Analyses by cancer type revealed significant differences such that patients with lung, gynecological, or hematological cancer reported the highest levels of distress at the time point of cancer diagnosis. As expected, women showed higher rates of anxiety and depression, and for some cancer types the prevalence was two to three times higher than that seen for men. In some cancer types emotional distress was inversely related to age. Patients younger than 50 and women across all cancer types revealed either subclinical or clinical levels of anxiety in over 50% of cases. Limitations Findings describe levels of emotional distress after diagnosis but cannot inform about trajectories of anxiety and depression over time. Conclusion Given that levels of anxiety and depression varied widely by cancer type, gender, and age, these results inform which cancer patients are most likely in need of psychosocial support.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Diploid hybrids of Saccharomyces cerevisiae and its closest relative, Saccharomyces paradoxus, are viable, but the sexual gametes they produce are not. One of several possible causes of this gamete ...inviability is incompatibility between genes from different species--such incompatible genes are usually called "speciation genes." In diploid F1 hybrids, which contain a complete haploid genome from each species, the presence of compatible alleles can mask the effects of (recessive) incompatible speciation genes. But in the haploid gametes produced by F1 hybrids, recessive speciation genes may be exposed, killing the gametes and thus preventing F1 hybrids from reproducing sexually. Here I present the results of an experiment to detect incompatibilities that kill hybrid gametes. I transferred nine of the 16 S. paradoxus chromosomes individually into S. cerevisiae gametes and tested the ability of each to replace its S. cerevisiae homeolog. All nine chromosomes were compatible, producing nine viable haploid strains, each with 15 S. cerevisiae chromosomes and one S. paradoxus chromosome. Thus, none of these chromosomes contain speciation genes that were capable of killing the hybrid gametes that received them. This is a surprising result that suggests that such speciation genes do not play a major role in yeast speciation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Genome-wide sequence divergence between populations can cause hybrid sterility through the action of the anti-recombination system, which rejects crossover repair of double strand breaks between ...nonidentical sequences. Because crossovers are necessary to ensure proper segregation of homologous chromosomes during meiosis, the reduced recombination rate in hybrids can result in high levels of nondisjunction and therefore low gamete viability. Hybrid sterility in interspecific crosses of Saccharomyces yeasts is known to be associated with such segregation errors, but estimates of the importance of nondisjunction to postzygotic reproductive isolation have been hampered by difficulties in accurately measuring nondisjunction frequencies. Here, we use spore-autonomous fluorescent protein expression to quantify nondisjunction in both interspecific and intraspecific yeast hybrids. We show that segregation is near random in interspecific hybrids. The observed rates of nondisjunction can explain most of the sterility observed in interspecific hybrids through the failure of gametes to inherit at least one copy of each chromosome. Partially impairing the anti-recombination system by preventing expression of the RecQ helicase SGS1 during meiosis cuts nondisjunction frequencies in half. We further show that chromosome loss through nondisjunction can explain nearly all of the sterility observed in hybrids formed between two populations of a single species. The rate of meiotic nondisjunction of each homologous pair was negatively correlated with chromosome size in these intraspecific hybrids. Our results demonstrate that sequence divergence is not only associated with the sterility of hybrids formed between distantly related species but may also be a direct cause of reproductive isolation in incipient species.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Prisoner's Dilemma and polymorphism in yeast SUC genes Greig, Duncan; Travisano, Michael
Proceedings - Royal Society. Biological sciences/Proceedings - Royal Society. Biological Sciences,
02/2004, Volume:
271, Issue:
Suppl 3
Journal Article
Peer reviewed
Open access
The SUC multigene family of the single-celled yeast Saccharomyces cerevisiae is polymorphic, with genes varying both in number and activity. All of the genes encode invertase, an enzyme that is ...secreted to digest sucrose outside of the cell. This communal endeavour creates the potential for individual cells to defect (cheat) by stealing the sugar digested by their neighbours without contributing the enzyme themselves. We measured the fitness of a defector, with a deleted suc2 gene, relative to an otherwise isogenic cooperator, with a functional SUC2 gene. We manipulated the level of social interaction within the community by varying the population density and found that the defector is less fit than the cooperator at low levels of sociality but more fit in dense communities. We propose that selection for antisocial cheating causes SUC polymorphism in nature. The infamous Prisoner's Dilemma game shows that social behaviour is generally unstable, and the success of both cooperation and defection can vary continuously in time and space. The variation in SUC genes reflects constant adaptation to an ever-changing biotic environment that is a consequence of the instability of cooperation. It is interesting that social interactions can have a direct effect on molecular evolution, even in an organism as simple as yeast.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Is a group best off if everyone co-operates? Theory often considers this to be so (e.g. the "conspiracy of doves"), this understanding underpinning social and economic policy. We observe, however, ...that after competition between "cheat" and "co-operator" strains of yeast, population fitness is maximized under co-existence. To address whether this might just be a peculiarity of our experimental system or a result with broader applicability, we assemble, benchmark, dissect, and test a systems model. This reveals the conditions necessary to recover the unexpected result. These are 3-fold: (a) that resources are used inefficiently when they are abundant, (b) that the amount of co-operation needed cannot be accurately assessed, and (c) the population is structured, such that co-operators receive more of the resource than the cheats. Relaxing any of the assumptions can lead to population fitness being maximized when cheats are absent, which we experimentally demonstrate. These three conditions will often be relevant, and hence in order to understand the trajectory of social interactions, understanding the dynamics of the efficiency of resource utilization and accuracy of information will be necessary.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increased species richness does not always cause increased ecosystem function. Instead, richness can influence individual species with positive or negative ecosystem effects. We investigated richness ...and function in fermenting wine, and found that richness indirectly affects ecosystem function by altering the ecological dominance of Saccharomyces cerevisiae. While S. cerevisiae generally dominates fermentations, it cannot dominate extremely species-rich communities, probably because antagonistic species prevent it from growing. It is also diluted from species-poor communities, allowing yeasts with lower functional impacts to dominate. We further investigated the impacts of S. cerevisiae and its competitors in high- and low-functioning wine communities, focusing on glucose consumption as an ecosystem function. S. cerevisiae is a keystone species because its presence converts low-functioning communities to communities with the same function as S. cerevisiae monocultures. Thus, even within the same ecosystem, species richness has both positive and negative effects on function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Models of mRNA translation usually presume that transcripts are linear; upon reaching the end of a transcript each terminating ribosome returns to the cytoplasmic pool before initiating anew on a ...different transcript. A consequence of linear models is that faster translation of a given mRNA is unlikely to generate more of the encoded protein, particularly at low ribosome availability. Recent evidence indicates that eukaryotic mRNAs are circularized, potentially allowing terminating ribosomes to preferentially reinitiate on the same transcript. Here we model the effect of ribosome reinitiation on translation and show that, at high levels of reinitiation, protein synthesis rates are dominated by the time required to translate a given transcript. Our model provides a simple mechanistic explanation for many previously enigmatic features of eukaryotic translation, including the negative correlation of both ribosome densities and protein abundance on transcript length, the importance of codon usage in determining protein synthesis rates, and the negative correlation between transcript length and both codon adaptation and 5' mRNA folding energies. In contrast to linear models where translation is largely limited by initiation rates, our model reveals that all three stages of translation-initiation, elongation, and termination/reinitiation-determine protein synthesis rates even at low ribosome availability.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Signaling peptides enable communication between cells, both within and between individuals, and are therefore key to the control of complex physiological and behavioral responses. Since their small ...sizes prevent direct transmission to secretory pathways, these peptides are often produced as part of a larger polyprotein comprising precursors for multiple related or identical peptides; the physiological and behavioral consequences of this unusual gene structure are not understood. Here, we show that the number of mature-pheromone-encoding repeats in the yeast α-mating-factor gene MFα1 varies considerably between closely related isolates of both Saccharomyces cerevisiae and its sister species Saccharomyces paradoxus. Variation in repeat number has important phenotypic consequences: Increasing repeat number caused higher pheromone production and greater competitive mating success. However, the magnitude of the improvement decreased with increasing repeat number such that repeat amplification beyond that observed in natural isolates failed to generate more pheromone, and could actually reduce sexual fitness. We investigate multiple explanations for this pattern of diminishing returns and find that our results are most consistent with a translational trade-off: Increasing the number of encoded repeats results in more mature pheromone per translation event, but also generates longer transcripts thereby reducing the rate of translation-a phenomenon known as length-dependent translation. Length-dependent translation may be a powerful constraint on the evolution of genes encoding repetitive or modular proteins, with important physiological and behavioral consequences across eukaryotes.