Genomic Profiling of Lung Adenocarcinoma in Never-Smokers.

Purpose: Approximately 10%-40% of patients with lung cancer report no history of tobacco smoking (never-smokers). We analyzed whole-exome and RNA-sequencing data of 160 tumor and normal lung adenocarcinoma (LUAD) samples from never-smokers to identify clinically actionable alterations and gain insight into the environmental and hereditary risk factors for LUAD among never-smokers.

Methods: We performed whole-exome and RNA-sequencing of 88 and 69 never-smoker LUADs.

Brd4-bound enhancers drive cell-intrinsic sex differences in glioblastoma.

Sex can be an important determinant of cancer phenotype, and exploring sex-biased tumor biology holds promise for identifying novel therapeutic targets and new approaches to cancer treatment. In an established isogenic murine model of glioblastoma (GBM), we discovered correlated transcriptome-wide sex differences in gene expression, H3K27ac marks, large Brd4-bound enhancer usage, and Brd4 localization to Myc and p53 genomic binding sites. These sex-biased gene expression patterns were also evident in human glioblastoma stem cells (GSCs).

Circulating Tumor DNA Profiling in Small-Cell Lung Cancer Identifies Potentially Targetable Alterations.

Purpose: Patients with SCLC rarely undergo biopsies at relapse. When pursued, tissue obtained can be inadequate for molecular testing, posing a challenge in identifying potentially targetable alterations in a clinically meaningful time frame. We examined the feasibility of circulating tumor DNA (ctDNA) testing in identifying potentially targetable alterations in SCLC.

Single-Cell RNA-Seq Uncovers a Robust Transcriptional Response to Morphine by Glia.

Molecular and behavioral responses to opioids are thought to be primarily mediated by neurons, although there is accumulating evidence that other cell types play a prominent role in drug addiction. To investigate cell-type-specific opioid responses, we performed single-cell RNA sequencing (scRNA-seq) of the nucleus accumbens of mice following acute morphine treatment. Differential expression analysis uncovered unique morphine-dependent transcriptional responses by oligodendrocytes and astrocytes.

An optimized, broadly applicable piggyBac transposon induction system.

The piggyBac (PB) transposon has been used in a number of biological applications. The insertion of PB transposons into the genome can disrupt genes or regulatory regions, impacting cellular function, so for many experiments it is important that PB transposition is tightly controlled. Here, we systematically characterize three methods for the post-translational control of the PB transposon in four cell lines.

Instabilities and waves in thin films of living fluids.

We formulate the thin-film hydrodynamics of a suspension of polar self-driven particles and show that it is prone to several instabilities through the interplay of activity, polarity, and the existence of a free surface. Our approach extends, to self-propelling systems, the work of Ben Amar and Cummings [Phys. Fluids 13 1160 (2001)10.

Entropic compression of interacting DNA loops.

We solve a model for the equilibrium folding of DNA via the formation of randomly placed (nonspecific) loops. We find that the loop rearrangement entropy drives a significant reduction in loop size as more loops form. The reduction of the most probable loop size occurs over a wide range of forces and is enhanced by interloop cooperativity, indicating that it should be observable in single DNA experiments.

Formation of loops in DNA under tension.

We study the formation of loops along a DNA molecule under applied tension, as might occur in single-DNA micromanipulation experiments with proteins which are able to simultaneously bind two DNA sites. We consider the case of "bare" DNA in the loop, which forms a "teardrop" shape, and the case where a single DNA-bending protein produces a "kink" in the middle of the loop; the presence of a right-angle kink in the loop reduces its bending energy by a factor of 3. Using the bending energy plus an estimate of the free energies associated with fluctuations and the elasticity of the extended nonlooped DNA, we obtain a probability distribution for loops as a function of loop size and force.

Self-organized pattern formation in motor-microtubule mixtures.

We model the stable self-organized patterns obtained in the nonequilibrium steady states of mixtures of molecular motors and microtubules. In experiments [Nédélec et al., Nature (London) 389, 305 (1997); Surrey et al.

Two-component fluid membranes near repulsive walls: Linearized hydrodynamics of equilibrium and nonequilibrium states.

We study the linearized hydrodynamics of a two-component fluid membrane near a repulsive wall, using a model that incorporates curvature-concentration coupling as well as hydrodynamic interactions. This model is a simplified version of a recently proposed one [J.-B.