YOGY: a web-based, integrated database to retrieve protein orthologs and associated Gene Ontology terms

We present YOGY a web-based resource for orthologous proteins from nine eukaryotic organisms: Homo sapiens, Mus musculus, Rattus norvegicus, Arabidopsis thaliana, Drosophila melanogaster, Caenorhabditis elegans, Plasmodium falciparum, Schizosaccharomyces pombe and Saccharomyces cerevisiae. Using a gene name from any of these organisms as a query, this database provides comprehensive, combined information on orthologs in other species using data from five independent resources: KOGs, Inparanoid, HomoloGene, OrthoMCL and a table of curated fission and budding yeast orthologs. Associated Gene Ontology (GO) terms of orthologs can also be retrieved for functional inference. Integrating these different and complementary datasets provides a straightforward tool to identify known and predicted orthologs of proteins from a variety of species. This resource should be useful for bench scientists looking for functional clues for their genes of interest as well as for curators looking for information that can be transferred based on orthology and for rapidly identifying the relevant GO terms as an aid to literature curation. YOGY is accessible online at

Global expression changes resulting from loss of telomeric DNA in fission yeast

BACKGROUND: Schizosaccharomyces pombe cells lacking the catalytic subunit of telomerase (encoded by trt1(+)) lose telomeric DNA and enter crisis, but rare survivors arise with either circular or linear chromosomes. Survivors with linear chromosomes have normal growth rates and morphology, but those with circular chromosomes have growth defects and are enlarged. We report the global gene-expression response of S. pombe to loss of trt1(+). RESULTS: Survivors with linear chromosomes had expression profiles similar to cells with native telomeres, whereas survivors with circular chromosomes showed continued upregulation of core environmental stress response (CESR) genes. In addition, survivors with circular chromosomes had altered expression of 51 genes compared to survivors with linear chromosomes, providing an expression signature. S. pombe progressing through crisis displayed two waves of altered gene expression. One coincided with crisis and consisted of around 110 genes, 44% of which overlapped with the CESR. The second was synchronized with the emergence of survivors and consisted of a single class of open reading frames (ORFs) with homology both to RecQ helicases and to dh repeats at centromeres targeted for heterochromatin formation via an RNA interference (RNAi) mechanism. Accumulation of transcript from the ORF was found not only in trt1(- )cells, but also in dcr1(- )and ago1(- )RNAi mutants, suggesting that RNAi may control its expression. CONCLUSIONS: These results demonstrate a correlation between a state of cellular stress, short telomeres and growth defects in cells with circular chromosomes. A putative new RecQ helicase was expressed as survivors emerged and appears to be transcriptionally regulated by RNAi, suggesting that this mechanism operates at telomeres

The longevity and reversibility of quiescence in Schizosaccharomyces pombe are dependent upon the HIRA histone chaperone

Quiescence (G0) is a reversible non-dividing state that facilitates cellular survival in adverse conditions. Here, we demonstrate that the HIRA histone chaperone complex is required for the reversibility and longevity of nitrogen starvation-induced quiescence in Schizosaccharomyces pombe. The HIRA protein, Hip1 is not required for entry into G0 or the induction of autophagy. Although hip1Δ cells retain metabolic activity in G0, they rapidly lose the ability to resume proliferation. After a short period in G0 (1 day), hip1Δ mutants can resume cell growth in response to the restoration of a nitrogen source but do not efficiently reenter the vegetative cell cycle. This correlates with a failure to induce the expression of MBF transcription factor-dependent genes that are critical for S phase. In addition, hip1Δ G0 cells rapidly progress to a senescent state in which they can no longer re-initiate growth following nitrogen source restoration. Analysis of a conditional hip1 allele is consistent with these findings and indicates that HIRA is required for efficient exit from quiescence and prevents an irreversible cell cycle arrest

CSL protein regulates transcription of genes required to prevent catastrophic mitosis in fission yeast.

For every eukaryotic cell to grow and divide, intricately coordinated action of numerous proteins is required to ensure proper cell-cycle progression. The fission yeast Schizosaccharomyces pombe has been instrumental in elucidating the fundamental principles of cell-cycle control. Mutations in S. pombe 'cut' (cell untimely torn) genes cause failed coordination between cell and nuclear division, resulting in catastrophic mitosis. Deletion of cbf11, a fission yeast CSL transcription factor gene, triggers a 'cut' phenotype, but the precise role of Cbf11 in promoting mitotic fidelity is not known. We report that Cbf11 directly activates the transcription of the acetyl-coenzyme A carboxylase gene cut6, and the biotin uptake/biosynthesis genes vht1 and bio2, with the former two implicated in mitotic fidelity. Cbf11 binds to a canonical, metazoan-like CSL response element (GTGGGAA) in the cut6 promoter. Expression of Cbf11 target genes shows apparent oscillations during the cell cycle using temperature-sensitive cdc25-22 and cdc10-M17 block-release experiments, but not with other synchronization methods. The penetrance of catastrophic mitosis in cbf11 and cut6 mutants is nutrient-dependent. We also show that drastic decrease in biotin availability arrests cell proliferation but does not cause mitotic defects. Taken together, our results raise the possibility that CSL proteins play conserved roles in regulating cell-cycle progression, and they could guide experiments into mitotic CSL functions in mammals

Fission stories: using PomBase to understand Schizosaccharomyces pombe biology

PomBase (www.pombase.org), the model organism database (MOD) for the fission yeast Schizosaccharomyces pombe, supports research within and beyond the S. pombe community by integrating and presenting genetic, molecular, and cell biological knowledge into intuitive displays and comprehensive data collections. With new content, novel query capabilities, and biologist-friendly data summaries and visualization, PomBase also drives innovation in the MOD community

C. elegans feed yolk to their young in a form of primitive lactation

The nematode Caenorhabditis elegans exhibits rapid senescence that is promoted by the insulin/IGF-1 signalling (IIS) pathway via regulated processes that are poorly understood. IIS also promotes production of yolk for egg provisioning, which in post-reproductive animals continues in an apparently futile fashion, supported by destructive repurposing of intestinal biomass that contributes to senescence. Here we show that post-reproductive mothers vent yolk which can be consumed by larvae and promotes their growth. This implies that later yolk production is not futile; instead vented yolk functions similarly to milk. Moreover, yolk venting is promoted by IIS. These findings suggest that a self-destructive, lactation-like process effects resource transfer from postreproductive C. elegans mothers to offspring, in a fashion reminiscent of semelparous organisms that reproduce in a single, suicidal burst. That this process is promoted by IIS provides insights into how and why IIS shortens lifespan in C. elegans

The Impact of COVID-19 on Mental Healthcare Utilization in Switzerland Was Strongest Among Young Females—Retrospective Study in 2018–2020

Objectives: To provide a thorough assessment of the impact of the COVID-19 pandemic on the utilization of inpatient and outpatient mental healthcare in Switzerland. Methods: Retrospective cohort study using nationwide hospital data (n > 8 million) and claims data from a large Swiss health insurer (n > 1 million) in 2018–2020. Incidence proportions of different types of psychiatric inpatient admissions, psychiatric consultations, and psychotropic medication claims were analyzed using interrupted time series models for the general population and for the vulnerable subgroup of young people. Results: Inpatient psychiatric admissions in the general population decreased by 16.2% (95% confidence interval: −19.2% to −13.2%) during the first and by 3.9% (−6.7% to −0.2%) during the second pandemic shutdown, whereas outpatient mental healthcare utilization was not substantially affected. We observed distinct patterns for young people, most strikingly, an increase in mental healthcare utilization among females aged <20 years. Conclusion: Mental healthcare provision for the majority of the population was largely maintained, but special attention should be paid to young people. Our findings highlight the importance of monitoring mental healthcare utilization among different populations

PomBase 2015: updates to the fission yeast database.

PomBase (http://www.pombase.org) is the model organism database for the fission yeast Schizosaccharomyces pombe. PomBase provides a central hub for the fission yeast community, supporting both exploratory and hypothesis-driven research. It provides users easy access to data ranging from the sequence level, to molecular and phenotypic annotations, through to the display of genome-wide high-throughput studies. Recent improvements to the site extend annotation specificity, improve usability and allow for monthly data updates. Both in-house curators and community researchers provide manually curated data to PomBase. The genome browser provides access to published high-throughput data sets and the genomes of three additional Schizosaccharomyces species (Schizosaccharomyces cryophilus, Schizosaccharomyces japonicus and Schizosaccharomyces octosporus)

Hidden in plain sight: What remains to be discovered in the eukaryotic proteome?

The first decade of genome sequencing stimulated an explosion in the characterization of unknown proteins. More recently, the pace of functional discovery has slowed, leaving around 20% of the proteins even in well-studied model organisms without informative descriptions of their biological roles. Remarkably, many uncharacterized proteins are conserved from yeasts to human, suggesting that they contribute to fundamental biological processes. To fully understand biological systems in health and disease, we need to account for every part of the system. Unstudied proteins thus represent a collective blind spot that limits the progress of both basic and applied biosciences. We use a simple yet powerful metric based on Gene Ontology (GO) biological process terms to define characterized and uncharacterized proteins for human, budding yeast, and fission yeast. We then identify a set of conserved but unstudied proteins in S. pombe , and classify them based on a combination of orthogonal attributes determined by large-scale experimental and comparative methods. Finally, we explore possible reasons why these proteins remain neglected and propose courses of action to raise their profile and thereby reap the benefits of completing the catalog of proteins' biological roles

PomBase 2018: user-driven reimplementation of the fission yeast database provides rapid and intuitive access to diverse, interconnected information

PomBase (www.pombase.org), the model organism database for the fission yeast Schizosaccharomyces pombe, has undergone a complete redevelopment, resulting in a more fully integrated, better-performing service. The new infrastructure supports daily data updates as well as fast, efficient querying and smoother navigation within and between pages. New pages for publications and genotypes provide routes to all data curated from a single source and to all phenotypes associated with a specific genotype, respectively. For ontology-based annotations, improved displays balance comprehensive data coverage with ease of use. The default view now uses ontology structure to provide a concise, non-redundant summary that can be expanded to reveal underlying details and metadata. The phenotype annotation display also offers filtering options to allow users to focus on specific areas of interest. An instance of the JBrowse genome browser has been integrated, facilitating loading of and intuitive access to, genome-scale datasets. Taken together, the new data and pages, along with improvements in annotation display and querying, allow users to probe connections among different types of data to form a comprehensive view of fission yeast biology. The new PomBase implementation also provides a rich set of modular, reusable tools that can be deployed to create new, or enhance existing, organism-specific databases