Follow this and additional works at: https://newprairiepress.org/fgr This work is licensed under a Creative Commons Attribution-Share Alike 4.0 License. Recommended Citation Recommended CitationBruchez, J. J., J. Eberle, and V.E. Russo (1993) "Regulatory sequences involved in the translation of Neurospora crassa mRNA: Kozak sequences and stop codons," Fungal Genetics Reports: Vol. 40, Article 3. https://doi. Abstract AbstractWe have analyzed the sequences of 77 nuclear genes of N. crassa thought to be transcribed by RNA polymerase II (References 1-72) which should represent virtually all of the presently published nuclear gene sequences for this fungus.

The protein MucR from Brucella abortus has been described as a transcriptional regulator of many virulence genes. It is a member of the Ros/MucR family comprising proteins that control the expression of genes important for the successful interaction of α-proteobacteria with their eukaryotic hosts. Despite clear evidence of the role of MucR in repressing virulence genes, no study has been carried out so far demonstrating the direct interaction of this protein with the promoter of its target gene babR encoding a LuxR-like regulator repressing virB genes. In this study, we show for the first time the ability of MucR to bind the promoter of babR in electrophoretic mobility shift assays demonstrating a direct role of MucR in repressing this gene. Furthermore, we demonstrate that MucR can bind the virB gene promoter. Analyses by RT-qPCR showed no significant differences in the expression level of virB genes in Brucella abortus CC092 lacking MucR compared to the wild-type Brucella abortus strain, indicating that MucR binding to the virB promoter has little impact on virB gene expression in B. abortus 2308. The MucR modality to bind the two promoters analyzed supports our previous hypothesis that this is a histone-like protein never found before in Brucella.

The transcription factor CCCTC-binding factor (CTCF) modulates pleiotropic functions mostly related to gene expression regulation. The role of CTCF in large scale genome organization is also well established. A unifying model to explain relationships among many CTCF-mediated activities involves direct or indirect interactions with numerous protein cofactors recruited to specific binding sites. The co-association of CTCF with other architectural proteins such as cohesin, chromodomain helicases, and BRG1, further supports the interplay between master regulators of mammalian genome folding. Here, we report a comprehensive LC-MS/MS mapping of the components of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex co-associated with CTCF including subunits belonging to the core, signature, and ATPase modules. We further show that the localization patterns of representative SWI/SNF members significantly overlap with CTCF sites on transcriptionally active chromatin regions. Moreover, we provide evidence of a direct binding of the BRK-BRG1 domain to the zinc finger motifs 4–8 of CTCF, thus, suggesting that these domains mediate the interaction of CTCF with the SWI/SNF complex. These findings provide an updated view of the cooperative nature between CTCF and the SWI/SNF ATP-dependent chromatin remodeling complexes, an important step for understanding how these architectural proteins collaborate to shape the genome.

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Background Atrial fibrillation patients with a history of major bleeding (MB) are at high risk of future bleeding events; this history was an exclusion criterion in pivotal phase 3 trials of anticoagulation for stroke prevention. Real-world edoxaban effectiveness and safety in patients with a history of MB were analysed from the global ETNA programme. Purpose To compare edoxaban effectiveness and safety in AF patients with or without an MB history. Methods The Global ETNA-AF programme (EU: NCT02944019, Japan: UMIN000017011, South Korea/Taiwan: NCT02951039) integrates data from multiple prospective, observational, noninterventional regional studies of AF patients treated with edoxaban for stroke prevention. This snapshot analysis summarises global baseline characteristics and 2-year annualised rates of all-cause death, cardiovascular death, stroke (haemorrhagic, ischaemic, any), and bleeding (including MB, major gastrointestinal bleeding [MGIB], intracranial haemorrhage [ICH], clinically relevant nonmajor bleeding, and any bleeding) in patients with or without MB history. Results Data from 27,333 patients (479 with MB history and 26,854 without) from Europe, Japan, South Korea, and Taiwan were analysed. Patients with MB history were significantly older (P<0.0001) and more likely to be ≥75 years of age (P=0.0003), to be male (P=0.024), and to have a lower body weight and creatinine clearance (P<0.0001 for both) (Table). Globally, antiplatelet use was significantly higher in patients with MB history compared with patients without (P=0.005). Patients with MB history were more likely to have previously diagnosed heart failure (HF, P=0.001) and to receive 30 mg vs 60 mg edoxaban at baseline (P<0.0001). Hazard ratios for effectiveness and safety outcomes are shown in the Figure. Patients with MB history had significantly higher annualised rates of all-cause death (5.7% vs 3.1%; P<0.0001), ischaemic stroke (1.8% vs 0.7%; P=0.002), and any stroke (3.1% vs 0.9%; P<0.0001) than patients without MB history. Patients with MB history also had significantly higher annualised rates of MB (3.6% vs 1.0%; P<0.0001), MGIB (1.5% vs 0.5%; P=0.001), ICH (1.5% vs 0.3%; P<0.0001), fatal bleeding (0.9% vs 0.2%; P<0.0001), and fatal ICH (0.5% vs 0.1%; P=0.0002). Among patients with MB history, the annualised rate of ICH did not differ between patients with ICH history (1.42%/yr) vs without (1.65%/yr); whereas the annualised rate of MGIB was significantly higher in patients with MGIB history vs without (4.14%/yr vs 1.08%/yr; P=0.0337). Conclusions Patients with AF receiving edoxaban and who have a history of MB are more likely elderly, male, and have comorbidities, including HF. These patients are also more susceptible to any adverse cardiovascular event. ICH event rates were not higher in patients with prior ICH than those with non-ICH major bleedings, whereas history of MGIB was associated with a high risk of MGIB recurrence. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo