Identification of Y-Box Binding Protein 1 As a Core Regulator of MEK/ERK Pathway-Dependent Gene Signatures in Colorectal Cancer Cells

Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. Numerous candidate genes involved in disease and in factors of predictive, as well as of prognostic, value have been deduced from such molecular portraits, e.g. in cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. To identify regulators of transcriptome alterations, we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase pathway, computational prediction of regulatory elements in promoters of co-regulated genes, chromatin-based and functional cellular assays. We identified commonly co-regulated, proliferation-associated target genes that respond to the MAPK pathway. We recognized E2F and NFY transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of Y-box binding protein 1 (YBX1) by reporter gene, gel shift, and chromatin immunoprecipitation assays. We also validated the MAPK-dependent gene signature in colorectal cancers and provided evidence for the association of YBX1 with poor prognosis in colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated target genes are involved in executing malignant properties

The OpenMolcas Web: A Community-Driven Approach to Advancing Computational Chemistry

The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations

Facial nerve function in carcinoma of the parotid gland

Aim: To analyse, for patients with carcinoma of the parotid gland, the prognostic value for treatment outcome of the function of the facial nerve (NVII), and determining facial nerve dysfunction after treatment. Methods and materials: In a retrospective study of the Dutch head and Neck cooperative group (NWHHT), data of 324 patients with parotid carcinoma were analysed. The function of N VII before treatment was intact in 77%, partially and completely impaired in 14% and 7%, respectively Eighty-eight percent of the patients were treated surgically, and 77% of them were treated by a combination of postoperative radiotherapy In 21% NVII was sacrificed, a reconstruction was performed in one of three. Results: Independent risk factors for N VII dysfunction before treatment were tumour localisation, positive neck nodes at presentation, pain, increasing age, and perineural invasion. Regional, not local, control was significantly impaired for complete facial paralysis. N VII dysfunction was an independent factor for disease free survival, and was 69%, 37% and 13% for normal, partially and completely impaired function, respectively. After treatment 22% of the patients experienced a partial paralysis, and 13% of the patients experienced a complete parlysis of N VII. Conclusion: For patients with parotid carcinoma, facial nerve function before treatment is a strong prognostic factor for disease free survival. (c) 2006 Elsevier Ltd. All rights reserved