Our results demonstrate that the SCML2/USP7 complex constitutes a novel molecular pathway in modulating the

epigenetic state of sex chromosomes during male meiosis.”
“The best way to assess the response to chemoradiotherapy of locally advanced oesophageal carcinomas is not known. We used F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT to evaluate the metabolic response during chemoradiotherapy and tried to correlate this response to survival.\n\nPatients with biopsy-proven oesophageal carcinoma underwent FDG PET/CT with evaluation of the standardized uptake value (SUV) before any treatment (SUV1) and during chemoradiotherapy after two cycles of 5-fluorouracil (FU)/cisplatin and 20 Gy (SUV2). Metabolic response was defined as 1-(SUV2/SUV1). Surgery was discussed after 40 Gy and three cycles PF-6463922 nmr of chemotherapy. GSK1120212 in vivo Results of interim PET were not considered for the therapeutic decision.\n\nAmong 72 patients who underwent a first FDG PET/CT before any treatment, 59 (82 %) could receive the second FDG PET/CT examination. Median survival was 22.2 months with 1-year and 2-year survivals

of 70 and 46 %, respectively. Nineteen patients (32 %) underwent surgery. Mean SUV1 and SUV2 were 12.3 +/- 6.2 and 6 +/- 4.1, respectively (p < 0.001). Using a cut-off for metabolic response of 50 %, sensitivity and specificity for survival were 0.7 and 0.58. The 2-year overall survival of good responders was 62 % as compared to 27 % for poor metabolic responders. A multivariate analysis was performed, including T and N stages, surgery, histology and metabolic response: only metabolic response was significantly (p = 0.009) associated with 2-year survival.\n\nEarly evaluation of metabolic response had

a great prognostic value and could help identify good responders to chemoradiotherapy.”
“The order and timing of cell-cycle events is controlled by changing substrate specificity and different activity thresholds of cyclin-dependent kinases (CDKs). However, it is not understood how a single protein kinase can trigger hundreds of switches in a sufficiently time-resolved fashion. We show that cyclin-Cdk1-Cks1-dependent phosphorylation of multisite targets in Saccharomyces cerevisiae is controlled by key substrate parameters including distances between phosphorylation sites, distribution DAPT cost of serines and threonines as phosphoacceptors and positioning of cyclin-docking motifs. The component mediating the key interactions in this process is Cks1, the phosphoadaptor subunit of the cyclin-Cdk1-Cks1 complex. We propose that variation of these parameters within networks of phosphorylation sites in different targets provides a wide range of possibilities for differential amplification of Cdk1 signals, thus providing a mechanism to generate a wide range of thresholds in the cell cycle.”
“CD4(+)CD25(+) regulatory T cells (Tregs) play a crucial role in controlling immune responses.