Histone methylation is now realized to be a pivotal regulator of gene transcription. Although recent studies have shed light on a trans-histone regulatory pathway that controls H3 Lys 4 and H3 Lys 79 methylation in Saccharomyces cerevisiae, the regulatory pathway that affects Set2-mediated H3 Lys 36 methylation is unknown. To determine the functions of Set2, and identify factors that regulate its site of methylation, we genomically tagged Set2 and identified its associated proteins. Here, we show that Set2 is associated with Rbp1 and Rbp2, the two largest subunits of RNA polymerase II (RNA pol II). Moreover, we find that this association is specific for the interaction of Set2 with the hyperphosphorylated form of RNA pol II. We further show that deletion of the RNA pol II C-terminal domain (CTD) kinase Ctk1, or partial deletion of the CTD, results in a selective abolishment of H3 Lys 36 methylation, implying a pathway of Set2 recruitment to chromatin and a role for H3 Lys 36 methylation in transcription elongation. In support, chromatin immunoprecipitation assays demonstrate the presence of Set2 methylation in the coding regions, as well as promoters, of genes regulated by Ctk1 or Set2. These data document a new link between histone methylation and the transcription apparatus and uncover a regulatory pathway that is selective for H3 Lys 36 methylation.

The minimum AI value in a PVI segment is independently predictive of reconnection of that segment at repeat electrophysiology study. Higher AI and FTI values are required for anterior/roof segments than for posterior/inferior segments to prevent reconnection.

Background Catheter ablation for persistent atrial fibrillation (AF) is associated with less favorable outcomes than for paroxysmal AF. Substrate modification is often added to pulmonary vein isolation (PVI) to try to improve success rates. Recent studies have shown improved clinical outcomes with use of regional ablation index (AI) targets for PVI. We hypothesized that prospective use of AI-guided PVI in persistent AF patients would result in a low rate of PV reconnection at repeat electrophysiology study and that a high success rate can be achieved with durable PVI alone. Methods Forty consecutive patients with persistent AF underwent AI-guided PVI with target values of 550 for anterior and 400 for posterior left atrial regions, followed by a protocol-mandated repeat procedure after 2 months. Patients were monitored for atrial tachyarrhythmia recurrence via daily plus symptom-initiated ECG recordings for 12 months. Recurrence was defined as ≥30 seconds of any atrial tachyarrhythmia after a 3-month blanking period. Results PV reconnection was seen at repeat electrophysiology study in 22% of patients, affecting 7% of PVs. Ablation on the intervenous carina was required in 44% patients to achieve durable PVI. Atrial tachyarrhythmia recurrence was documented in 8 (20%) patients, only one of whom had PV reconnection at repeat study. At 12 months, 38/40 (95%) patients were in sinus rhythm, with 4 (10%) patients having started antiarrhythmic drugs. Higher body mass index and excess alcohol consumption were the only significant factors associated with atrial tachyarrhythmia recurrence. Conclusions Use of AI targets results in a high level of durable PVI. A good clinical outcome can be achieved in the great majority of persistent AF patients with AI-guided PVI alone. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02628730.

The operation of European Works Councils (EWCs) is taking management and employee representatives in MNCs into uncharted territory. In particular, for companies headquartered in Anglo-Saxon economies there is little domestic tradition of statutory employee consultation. Drawing on comparative case studies, this article investigates the impact of EWCs on the process and outcomes of corporate-level management decision-making in UK and US-based MNCs. Variation in EWC impact arises from the interaction of structural factors, such as business focus, management organisation and pre-existing industrial relations arrangements, and agency factors, including management policy and the cohesion of employee representatives. Copyright Blackwell Publishing Ltd/London School of Economics 2004.

Background: Cdc14 phosphatases help control mitosis by dephosphorylating sites (Ser/Thr-Pro) targeted by cyclin-dependent kinases (Cdks). Results: Cdc14 family phosphatases strongly prefer phosphoserine over phosphothreonine at Cdk sites. Conclusion: By discriminating among Cdk sites, Cdc14 may participate in setting the order and timing of Cdk substrate dephosphorylation. Significance: Mechanisms governing the timing of Cdk site dephosphorylation are crucial for proper coordination of late mitotic events.