Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas.

B cells have the unique property to somatically alter their immunoglobulin (IG) genes by V(D)J recombination, somatic hypermutation (SHM) and class-switch recombination (CSR). Aberrant targeting of these mechanisms is implicated in lymphomagenesis, but the mutational processes are poorly understood. By performing whole genome and transcriptome sequencing of 181 germinal center derived B-cell lymphomas (gcBCL) we identified distinct mutational signatures linked to SHM and CSR.

Defective homologous recombination DNA repair as therapeutic target in advanced chordoma.

Chordomas are rare bone tumors with few therapeutic options. Here we show, using whole-exome and genome sequencing within a precision oncology program, that advanced chordomas (n = 11) may be characterized by genomic patterns indicative of defective homologous recombination (HR) DNA repair and alterations affecting HR-related genes, including, for example, deletions and pathogenic germline variants of BRCA2, NBN, and CHEK2. A mutational signature associated with HR deficiency was significantly enriched in 72.

Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories.

Identifying the earliest somatic changes in prostate cancer can give important insights into tumor evolution and aids in stratifying high- from low-risk disease. We integrated whole genome, transcriptome and methylome analysis of early-onset prostate cancers (diagnosis ≤55 years). Characterization across 292 prostate cancer genomes revealed age-related genomic alterations and a clock-like enzymatic-driven mutational process contributing to the earliest mutations in prostate cancer patients.

Patient-specific molecular alterations are associated with metastatic clear cell renal cell cancer progressing under tyrosine kinase inhibitor therapy.

The availability of tyrosine kinase inhibitors (TKI) during the past ten years has led to improved response and overall survival of patients suffering from metastatic clear cell renal cell carcinoma (ccRCC). However, most of these tumors will eventually progress due to resistance evolving under therapy. The objective of this pilot study was to determine whether molecular alterations in ccRCC tissues sampled over the course of the disease might be suggestive of potential therapies.

OTP: An automatized system for managing and processing NGS data.

The One Touch Pipeline (OTP) is an automation platform managing Next-Generation Sequencing (NGS) data and calling bioinformatic pipelines for processing these data. OTP handles the complete digital process from import of raw sequence data via alignment of sequencing reads to identify genomic events in an automated and scalable way. Three major goals are pursued: firstly, reduction of human resources required for data management by introducing automated processes.

Cloud prediction of protein structure and function with PredictProtein for Debian.

We report the release of PredictProtein for the Debian operating system and derivatives, such as Ubuntu, Bio-Linux, and Cloud BioLinux. The PredictProtein suite is available as a standard set of open source Debian packages. The release covers the most popular prediction methods from the Rost Lab, including methods for the prediction of secondary structure and solvent accessibility (profphd), nuclear localization signals (predictnls), and intrinsically disordered regions (norsnet).

Serum levels of brain-derived neurotrophic factor are unchanged after transcranial direct current stimulation in treatment-resistant depression.

Background: Brain-derived neurotrophic factor (BDNF) plays an important role in differentiation and repair of neurons in the adult brain. BDNF serum levels have been found to be lower in depressed patients than in healthy subjects. In a couple of studies, effective antidepressant treatment including electroconvulsive therapy led to an increase in BDNF serum levels.

Evaluation of sham transcranial direct current stimulation for randomized, placebo-controlled clinical trials.

Background: Transcranial direct current stimulation (tDCS) has been investigated as therapeutic intervention in various psychiatric and neurologic disorders. As placebo responses to technical interventions may be pronounced in many clinical conditions, it is important to thoroughly develop placebo conditions which meet the requirements for application in randomized double-blind controlled trials.

Objective: The two-part experiment reported here aims at evaluating a new sham tDCS condition in healthy subjects and device operators.

Transcranial direct current stimulation in a patient with therapy-resistant major depression.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) has been reported to exert significant antidepressant effects in patients with major depression. Several recent studies found an improvement of depressive symptoms in drug-free patients. Here we report the case of a 66-year-old female patient suffering from recurrent major depressive episodes who underwent anodal tDCS of the left dorsolateral PFC over 4 weeks as an add-on treatment to a stable antidepressant medication.

Visualization of the endopelvic fascia by transrectal three-dimensional ultrasound.

The aim of our pilot study was to explore the feasibility of visualizing the endopelvic fascia by transrectal three-dimensional (3D) ultrasound. Transrectal 3D ultrasound was performed in 12 nulliparous women and 11 women with a history of vaginal delivery. A 6-10 MHz volume probe was used to examine the suburethral anterior vaginal wall.

Age-related alterations in the protein expression profile of C57BL/6J mouse pituitaries.

The aim of our study was to monitor the protein expression profile in pituitary glands of healthy C57BL/6J mice during aging. Pituitary glands of 4-week old (immature), 3-month old (mature), and >25-month old mice were analysed by proteomic tools such as two-dimensional electrophoresis and N-terminal micro-sequencing. A change was detected in the expression of growth hormone after sexual maturation.