TGF-β and RAS jointly unmask primed enhancers to drive metastasis.

Epithelial-to-mesenchymal transitions (EMTs) and extracellular matrix (ECM) remodeling are distinct yet important processes during carcinoma invasion and metastasis. Transforming growth factor β (TGF-β) and RAS, signaling through SMAD and RAS-responsive element-binding protein 1 (RREB1), jointly trigger expression of EMT and fibrogenic factors as two discrete arms of a common transcriptional response in carcinoma cells. Here, we demonstrate that both arms come together to form a program for lung adenocarcinoma metastasis and identify chromatin determinants tying the expression of the constituent genes to TGF-β and RAS inputs.

TPPU_DSF: A Web Application to Calculate Thermodynamic Parameters Using DSF Data.

Here we present TPPU_DSF (https://maciasnmr.net/tppu_dsf/). This is a free and open-source web application that opens, converts, fits, and calculates the thermodynamic parameters of protein unfolding from standard differential scanning fluorimetry (DSF) data in an automated manner.

HTSDSF Explorer, A Novel Tool to Analyze High-throughput DSF Screenings.

The identification of new drugs for novel therapeutic targets requires the screening of libraries containing tens of thousands of compounds. While experimental screenings are assisted by high-throughput technologies, in target-based biophysical assays, such as differential scanning fluorimetry (DSF), the analysis steps must be calculated manually, often combining several software packages. To simplify the determination of the melting temperature (T) of the target and the change induced by ligand binding (ΔT), we developed the HTSDSF explorer, a versatile, all-in-one, user-friendly application suite.

Preparing Graduate Students for Community Engagement in Health Services Research.

The purpose of this paper is to shed light on the importance of didactic and experiential training in community engagement for students conducting Health Services Research (HSR) in pharmacy. The incorporation of community-based learning (CBL) courses can be beneficial for graduate students because they provide an opportunity to gain important skills in stakeholder engagement and developing sustainable research partnerships. Early exposure and mentorship of graduate students through CBL courses could minimize the risk of students entering communities in their future careers with harmful tactics such as stereotypes and implicit biases.

Unveiling the dimer/monomer propensities of Smad MH1-DNA complexes.

Smad transcription factors are the main downstream effectors of the Transforming growth factor β superfamily (TGFβ) signalling network. The DNA complexes determined here by X-ray crystallography for the Bone Morphogenetic Proteins (BMP) activated Smad5 and Smad8 proteins reveal that all MH1 domains bind [GGC(GC)|(CG)] motifs similarly, although TGFβ-activated Smad2/3 and Smad4 MH1 domains bind as monomers whereas Smad1/5/8 form helix-swapped dimers. Dimers and monomers are also present in solution, as revealed by NMR.