Gis1 and Rph1 Regulate Glycerol and Acetate Metabolism in Glucose Depleted Yeast Cells

Aging in organisms as diverse as yeast, nematodes, and mammals is delayed by caloric restriction, an effect mediated by the nutrient sensing TOR, RAS/cAMP, and AKT/Sch9 pathways. The transcription factor Gis1 functions downstream of these pathways in extending the lifespan of nutrient restricted yeast cells, but the mechanisms involved are still poorly understood. We have used gene expression microarrays to study the targets of Gis1 and the related protein Rph1 in different growth phases. Our results show that Gis1 and Rph1 act both as repressors and activators, on overlapping sets of genes as well as on distinct targets. Interestingly, both the activities and the target specificities of Gis1 and Rph1 depend on the growth phase. Thus, both proteins are associated with repression during exponential growth, targeting genes with STRE or PDS motifs in their promoters. After the diauxic shift, both become involved in activation, with Gis1 acting primarily on genes with PDS motifs, and Rph1 on genes with STRE motifs. Significantly, Gis1 and Rph1 control a number of genes involved in acetate and glycerol formation, metabolites that have been implicated in aging. Furthermore, several genes involved in acetyl-CoA metabolism are downregulated by Gis1

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Effects of family-based treatment on adolescent outpatients treated for anorexia nervosa in the Eating Disorder Unit of Helsinki University Hospital

Abstract Background Family therapy for adolescent anorexia nervosa (AN) has stronger evidence of efficacy in comparison with individual therapy, and family-based treatment (FBT) is the most evaluated in numerous randomized clinical trials. However, few studies have focused on how FBT performs outside of research settings. The current study is the first to assess clinical outcomes of FBT for adolescent AN in Finland, in a specialized outpatient clinic. Aim The naturalistic outcome of outpatient FBT for adolescent AN was investigated. Methods Fifty-two female patients and their families who received FBT at a tertiary eating disorders unit participated in the study. Data on their pre-treatment parameters, treatment details, and condition at the end of treatment (EOT) was collected from their medical records. Results At EOT, a majority (61.5%) had achieved a full weight restoration [percentage of expected body weight (%EBW) ≥ 95%]. Participants with an %EBW ≥ 95 at EOT had a significantly higher pre-treatment %EBW than those with an EBW < 95% at EOT. Participants with an EBW ≥ 95% at EOT showed significantly higher total weight gain during the treatment period, a higher rate of regular menstrual periods at EOT, significantly lower rates of dietary restrictions, and less cognitive or behavioral symptoms of the eating disorder overall, compared to participants who did not achieve a normal body weight. In 22 cases (42.3%), there was no need for further treatment at the end of FBT. Participants who needed further treatment after FBT, compared to those who did not, showed significantly higher rates of psychiatric comorbidity, history of mental health treatment, and need for psychopharmacological treatment. Conclusions In this naturalistic study, and in line with previous studies, FBT for AN appeared to be an effective and sometimes sufficient intervention, especially for patients with milder weight deficit and less severe psychiatric comorbidities. The results show that FBT can be successfully implemented in Finland and suggest that training more ED clinicians in FBT would be beneficial. Trial registration: The study was retrospectively registered on February 8th, 2023, in ClinicalTrials.gov Protocol Registration and Results System, identifier: NCT05734573