A nucleosome-free dG-dC-rich sequence element promotes constitutive transcription of the essential yeast RIO1 gene

RIO1 is an essential gene that encodes a protein serine kinase and is transcribed constitutively at a very low level. Transcriptional activation of RIO1 dispenses with a canonical TATA box as well as with classical transactivators or specific DNAbinding factors. Instead, a dGdCrich sequence element, that is located 40 to 48 bp upstream the single site of mRNA initiation, is essential and presumably constitutes the basal promoter. In addition, we demonstrate here that this promoter element comprises a nucleosomefree gap which is centered at the dGdC tract and flanked by two positioned nucleosomes. This element is both, necessary and sufficient, for basal transcription initiation at the RIO1 promoter and, thus, constitutes a novel type of core promoter element

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Distinct Nongenomic Signal Transduction Pathways Controlled by 17β-Estradiol Regulate DNA Synthesis and Cyclin D(1) Gene Transcription in HepG2 Cells

Estrogens induce cell proliferation in target tissues by stimulating progression through the G1 phase of the cell cycle. Activation of cyclin D(1) gene expression is a critical feature of this hormonal action. The existence of rapid/nongenomic estradiol-regulated protein kinase C (PKC-α) and extracellular signal-regulated kinase (ERK) signal transduction pathways, their cross talk, and role played in DNA synthesis and cyclin D(1) gene transcription have been studied herein in human hepatoma HepG2 cells. 17β-Estradiol was found to rapidly activate PKC-α translocation and ERK-2/mitogen-activated protein kinase phosphorylation in this cell line. These actions were independent of each other, preceding the increase of thymidine incorporation into DNA and cyclin D(1) expression, and did not involve DNA binding by estrogen receptor. The results obtained with specific inhibitors indicated that PKC-α pathway is necessary to mediate the estradiol-induced G1-S progression of HepG2 cells, but it does not exert any effect(s) on cyclin D(1) gene expression. On the contrary, ERK-2 cascade was strongly involved in both G1-S progression and cyclin D(1) gene transcription. Deletion of its activating protein-1 responsive element motif resulted in attenuation of cyclin D(1) promoter responsiveness to estrogen. These results indicate that estrogen-induced cyclin D(1) transcription can occur in HepG2 cells independently of the transcriptional activity of estrogen receptor, sustaining the pivotal role played by nongenomic pathways of estrogen action in hormone-induced proliferation