Metastatic site influences driver gene function in pancreatic cancer.

Driver gene mutations can increase the metastatic potential of the primary tumor, but their role in sustaining tumor growth at metastatic sites is poorly understood. A paradigm of such mutations is inactivation of - a transcriptional effector of TGFβ signaling - which is a hallmark of multiple gastrointestinal malignancies. inactivation mediates TGFβ's remarkable anti- to pro-tumorigenic switch during cancer progression and can thus influence both tumor initiation and metastasis.

High-throughput evaluation of genetic variants with prime editing sensor libraries.

Tumor genomes often harbor a complex spectrum of single nucleotide alterations and chromosomal rearrangements that can perturb protein function. Prime editing has been applied to install and evaluate genetic variants, but previous approaches have been limited by the variable efficiency of prime editing guide RNAs. Here we present a high-throughput prime editing sensor strategy that couples prime editing guide RNAs with synthetic versions of their cognate target sites to quantitatively assess the functional impact of endogenous genetic variants.

Lake surface cooling drives littoral-pelagic exchange of dissolved gases.

The extent of littoral influence on lake gas dynamics remains debated in the aquatic science community due to the lack of direct quantification of lateral gas transport. The prevalent assumption of diffusive horizontal transport in gas budgets fails to explain anomalies observed in pelagic gas concentrations. Here, we demonstrate through high-frequency measurements in a eutrophic lake that daily convective horizontal circulation generates littoral-pelagic advective gas fluxes one order of magnitude larger than typical horizontal fluxes used in gas budgets.

Somatic mouse models of gastric cancer reveal genotype-specific features of metastatic disease.

Metastatic gastric carcinoma is a highly lethal cancer that responds poorly to conventional and molecularly targeted therapies. Despite its clinical relevance, the mechanisms underlying the behavior and therapeutic response of this disease are poorly understood owing, in part, to a paucity of tractable models. Here we developed methods to somatically introduce different oncogenic lesions directly into the murine gastric epithelium.