Co-expression of adjacent genes in yeast cannot be simply attributed to shared regulatory system

<p>Abstract</p> <p>Background</p> <p>Adjacent gene pairs in the yeast genome have a tendency to express concurrently. Sharing of regulatory elements within the intergenic region of those adjacent gene pairs was often considered the major mechanism responsible for such co-expression. However, it is still in debate to what extent that common transcription factors (TFs) contribute to the co-expression of adjacent genes. In order to resolve the evolutionary aspect of this issue, we investigated the conservation of adjacent pairs in five yeast species. By using the information for TF binding sites in promoter regions available from the MYBS database <url>http://cg1.iis.sinica.edu.tw/~mybs/</url>, the ratios of TF-sharing pairs among all the adjacent pairs in yeast genomes were analyzed. The levels of co-expression in different adjacent patterns were also compared.</p> <p>Results</p> <p>Our analyses showed that the proportion of adjacent pairs conserved in five yeast species is relatively low compared to that in the mammalian lineage. The proportion was also low for adjacent gene pairs with shared TFs. Particularly, the statistical analysis suggested that co-expression of adjacent gene pairs was not noticeably associated with the sharing of TFs in these pairs. We further proposed a case of the PAC (polymerase A and C) and RRPE (rRNA processing element) motifs which co-regulate divergent/bidirectional pairs, and found that the shared TFs were not significantly relevant to co-expression of divergent promoters among adjacent genes.</p> <p>Conclusion</p> <p>Our findings suggested that the commonly shared <it>cis</it>-regulatory system does not solely contribute to the co-expression of adjacent gene pairs in yeast genome. Therefore we believe that during evolution yeasts have developed a sophisticated regulatory system that integrates both TF-based and non-TF based mechanisms(s) for concurrent regulation of neighboring genes in response to various environmental changes.</p

Systematic review and meta-analysis of depression, anxiety, and suicidal ideation among Ph.D. students

Abstract University administrators and mental health clinicians have raised concerns about depression and anxiety among Ph.D. students, yet no study has systematically synthesized the available evidence in this area. After searching the literature for studies reporting on depression, anxiety, and/or suicidal ideation among Ph.D. students, we included 32 articles. Among 16 studies reporting the prevalence of clinically significant symptoms of depression across 23,469 Ph.D. students, the pooled estimate of the proportion of students with depression was 0.24 (95% confidence interval [CI], 0.18–0.31; I2 = 98.75%). In a meta-analysis of the nine studies reporting the prevalence of clinically significant symptoms of anxiety across 15,626 students, the estimated proportion of students with anxiety was 0.17 (95% CI, 0.12–0.23; I2 = 98.05%). We conclude that depression and anxiety are highly prevalent among Ph.D. students. Data limitations precluded our ability to obtain a pooled estimate of suicidal ideation prevalence. Programs that systematically monitor and promote the mental health of Ph.D. students are urgently needed

Emerging Two-Dimensional Crystallization of Cucurbit[8]uril Complexes: From Supramolecular Polymers to Nanofibers.

The binding of imidazolium salts to cucurbit[8]uril, CB[8], triggers a stepwise self-assembly process with semiflexible polymer chains and crystalline nanostructures as early- and late-stage species, respectively. In such a process, which involves the crystallization of the host-guest complexes, the guest plays a critical role in directing self-assembly toward desirable morphologies. These include platelet-like aggregates and two-dimensional (2D) fibers, which, moreover, exhibit viscoelastic and lyotropic properties. Our observations provide a deeper understanding of the self-assembly of CB[8] complexes, with fundamental implications in the design of functional 2D systems and crystalline materials.EPSRC (reference no. EP/ G060649/1), ERC Starting Investigator Grant (project no. 240629, ASPiRe) Next Generation Fellowship from the Walters-Kundert Foundation. MINE- CO, the FSE and the FEDER for funding through projects RYC-2015-18471 (Ramoń y Cajal program) and CTQ2017- 84087-R. Royal Society University Research Fellowship UF160152. EPSRC CDT in Nanoscience and Nanotechnology (NanoDTC), grant number EP/L015978/1

Processing and turnover of the Hedgehog protein in the endoplasmic reticulum

Autocatalytic processing of the Hedgehog ligand from its precursor protein relies on protein disulfide isomerase and ER-associated degradation

Homeless pregnant women in the city of Santos, São Paulo, Brazil: reflections and challenges to public policies

O estudo teve como objetivo investigar o cotidiano de gestantes em situação de rua e sua relação com as políticas públicas na cidade de Santos, litoral do Estado de São Paulo. A coleta de dados foi feita através do registro e estudo de narrativas de memórias de vida. A análise deu-se pelo agrupamento temático de trechos das narrativas, sendo identificadas quatro principais categorias: vida na rua; cuidado e gestação; projetos futuros; e rede pública de serviços. As narrativas revelam mulheres com capacidade criativa para desejar uma vida melhor a partir da possibilidade de ter um filho. Entretanto, a condição social em que vivem, envolvendo a luta diária pela sobrevivência e, em alguns casos, a dependência química dificultam o planejamento de estratégias que transformem o desejo em um projeto de vida. Dessa forma, na maioria das vezes perdem a guarda de seus filhos. Embora conheçam os serviços públicos, quase sempre os acessam apenas em casos de urgência. Não se identificaram na rede de serviços assistenciais - pública e do terceiro setor - programas focados na questão da gestante em situação de rua, ainda que o Brasil já viva, atualmente, histórias de famílias que têm a situação de rua como experiência intergeracional. Os resultados apontam para a necessidade de constituição de políticas intersetoriais, voltadas para gestantes em situação de rua.The study aimed to investigate the daily routine of homeless pregnant women and their relation to public policies in the city of Santos, State of São Paulo. Data was collected through the record and study of narratives of life memories. The analysis was conducted through the thematic grouping of excerpts of narratives, and four main categories were identified: life on the street; care and pregnancy; future projects; and public services. The narratives reveal women with creative ability to desire a better life based on the possibility of having a child. However, the social condition in which they live, which involves the daily struggle for survival and, in some cases, drug addiction, hinders the planning of strategies to transform the desire into a life project. Thus, most of them lose custody of their children. Although they know the public services, they go to them only in emergencies, mostly. We have not identified, in the network of care services - public and third sector -, programs focusing on the issue of homeless pregnant women, even though Brazil already witnesses, today, stories of families who have the homeless situation as an intergenerational experience. The results point to the need of making intersectoral policies targeted at homeless pregnant women

Moderators of the effect of therapeutic exercise for knee and hip osteoarthritis: a systematic review and individual participant data meta-analysis

Background Many international clinical guidelines recommend therapeutic exercise as a core treatment for knee and hip osteoarthritis. We aimed to identify individual patient-level moderators of the effect of therapeutic exercise for reducing pain and improving physical function in people with knee osteoarthritis, hip osteoarthritis, or both. Methods We did a systematic review and individual participant data (IPD) meta-analysis of randomised controlled trials comparing therapeutic exercise with non-exercise controls in people with knee osteoathritis, hip osteoarthritis, or both. We searched ten databases from March 1, 2012, to Feb 25, 2019, for randomised controlled trials comparing the effects of exercise with non-exercise or other exercise controls on pain and physical function outcomes among people with knee osteoarthritis, hip osteoarthritis, or both. IPD were requested from leads of all eligible randomised controlled trials. 12 potential moderators of interest were explored to ascertain whether they were associated with short-term (12 weeks), medium-term (6 months), and long-term (12 months) effects of exercise on self-reported pain and physical function, in comparison with non-exercise controls. Overall intervention effects were also summarised. This study is prospectively registered on PROSPERO (CRD42017054049). Findings Of 91 eligible randomised controlled trials that compared exercise with non-exercise controls, IPD from 31 randomised controlled trials (n=4241 participants) were included in the meta-analysis. Randomised controlled trials included participants with knee osteoarthritis (18 [58%] of 31 trials), hip osteoarthritis (six [19%]), or both (seven [23%]) and tested heterogeneous exercise interventions versus heterogeneous non-exercise controls, with variable risk of bias. Summary meta-analysis results showed that, on average, compared with non-exercise controls, therapeutic exercise reduced pain on a standardised 0–100 scale (with 100 corresponding to worst pain), with a difference of –6·36 points (95% CI –8·45 to –4·27, borrowing of strength [BoS] 10·3%, between-study variance [τ2] 21·6) in the short term, –3·77 points (–5·97 to –1·57, BoS 30·0%, τ2 14·4) in the medium term, and –3·43 points (–5·18 to –1·69, BoS 31·7%, τ2 4·5) in the long term. Therapeutic exercise also improved physical function on a standardised 0–100 scale (with 100 corresponding to worst physical function), with a difference of –4·46 points in the short term (95% CI –5·95 to –2·98, BoS 10·5%, τ2 10·1), –2·71 points in the medium term (–4·63 to –0·78, BoS 33·6%, τ2 11·9), and –3·39 points in the long term (–4·97 to –1·81, BoS 34·1%, τ2 6·4). Baseline pain and physical function moderated the effect of exercise on pain and physical function outcomes. Those with higher self-reported pain and physical function scores at baseline (ie, poorer physical function) generally benefited more than those with lower self-reported pain and physical function scores at baseline, with the evidence most certain in the short term (12 weeks). Interpretation There was evidence of a small, positive overall effect of therapeutic exercise on pain and physical function compared with non-exercise controls. However, this effect is of questionable clinical importance, particularly in the medium and long term. As individuals with higher pain severity and poorer physical function at baseline benefited more than those with lower pain severity and better physical function at baseline, targeting individuals with higher levels of osteoarthritis-related pain and disability for therapeutic exercise might be of merit