A Comparative Study on the Lysosomal Cation Channel TMEM175 Using Automated Whole-Cell Patch-Clamp, Lysosomal Patch-Clamp, and Solid Supported Membrane-Based Electrophysiology: Functional Characterization and High-Throughput Screening Assay Development.

The lysosomal cation channel TMEM175 is a Parkinson's disease-related protein and a promising drug target. Unlike whole-cell automated patch-clamp (APC), lysosomal patch-clamp (LPC) facilitates physiological conditions, but is not yet suitable for high-throughput screening (HTS) applications. Here, we apply solid supported membrane-based electrophysiology (SSME), which enables both direct access to lysosomes and high-throughput electrophysiological recordings.

Robust genomic copy number predictor of pan cancer metastasis.

Copy number alterations(CNAs) are the most common genetic changes observed in many cancers, reflecting the innate chromosomal instability of this disorder. Yet, how these alterations affect gene function to promote metastases across different tumor types has not been established. In this study, we developed a pan-cancer metastasis potential score (panMPS) based on observed CNAs.

Utilization of the 21-Gene Recurrence Score in a Diverse Breast Cancer Patient Population: Development of a Clinicopathologic Model to Predict High-Risk Scores and Response to Neoadjuvant Chemotherapy.

Introduction: The 21-gene expression profile [Oncotype DX Recurrence Score (RS)] stratifies benefit from adjuvant chemotherapy in hormone receptor (HR)-positive, HER2/neu-negative, node-negative breast cancer. It is not routinely applied to predict neoadjuvant chemotherapy (NACT) response; data in diverse patient populations also are limited. We developed a statistical model based on standard clinicopathologic features to identify high-risk cases (RS > 30) and then evaluated ability of predicted high RS to predict for NACT downstaging.

Scarless and site-directed mutagenesis in Salmonella enteritidis chromosome.

Background: A variety of techniques have been described which introduce scarless, site-specific chromosomal mutations. These techniques can be applied to make point mutations or gene deletions as well as insert heterologous DNA into bacterial vectors for vaccine development. Most methods use a multi-step approach that requires cloning and/or designing repeat sequences to facilitate homologous recombination.

An open-label study of adjunctive modafinil in patients with sedation related to serotonergic antidepressant therapy.

Objective: In patients with major depressive disorder (MDD), excessive sleepiness and fatigue not only are major components of the disorder, but also may occur as side effects of antidepressant therapy. In addition, sedation may be a consequence of antidepressant regimens. The novel wake-promoting agent modafinil improves wakefulness and reduces fatigue across a variety of clinical disorders.