Transcription processes compete with loop extrusion to homogenize promoter and enhancer dynamics.

The spatiotemporal configuration of genes with distal regulatory elements is believed to be crucial for transcriptional control, but full mechanistic understanding is lacking. We combine simultaneous live tracking of pairs of genomic loci and nascent transcripts with molecular dynamics simulations to assess the gene and its enhancer. We find that both loci exhibit more constrained mobility than control sequences due to stalled cohesin at CCCTC-binding factor sites.

Targeting NTRK1 Enhances Immune Checkpoint Inhibitor Efficacy in NTRK1 Wild-Type Non-Small Cell Lung Cancer.

Treatment of non-small cell lung cancer (NSCLC) has drastically changed in recent years owing to the robust anticancer effects of immune checkpoint inhibitors (ICI). However, only 20% of the patients with NSCLC benefit from ICIs, highlighting the need to uncover the mechanisms mediating resistance. By analyzing the overall survival (OS) and mutational profiles of 424 patients with NSCLC who received ICI treatments between 2015 and 2021, we determined that patients carrying a loss-of-function mutation in neurotrophic tyrosine kinase receptor 1 (NTRK1) had a prolonged OS when compared with patients with wild-type NTRK1.

P16 and HPV status in head and neck sarcomas and sarcomatoid carcinomas.

Human papillomavirus (HPV)-positive oropharyngeal carcinoma is a distinct type of head and neck carcinoma with improved prognosis. p16 immunostaining is often used as a surrogate marker for HPV infection in this particular setting. The aim of this study is to estimate the prevalence of p16 staining and HPV infection in head and neck sarcomatoid carcinomas as well as head and neck sarcomas.

Systematic analysis of electronic barrier heights and widths for concerted proton transfer in cyclic hydrogen bonded clusters: (HF), (HCl) and (HO) where = 3, 4, 5.

The MP2 and CCSD(T) methods are paired with correlation consistent basis sets as large as aug-cc-pVQZ to optimize the structures of the cyclic minima for (HF), (HCl) and (HO) where = 3-5, as well as the corresponding transition states (TSs) for concerted proton transfer (CPT). MP2 and CCSD(T) harmonic vibrational frequencies confirm the nature of each minimum and TS. Both conventional and explicitly correlated CCSD(T) computations are employed to assess the electronic dissociation energies and barrier heights for CPT near the complete basis (CBS) limit for all 9 clusters.

Spinal magnetic stimulation to treat chronic back pain: a feasibility study in veterans.

Chronic low back pain represents a significant societal problem leading to increased healthcare costs and quality of life. This study was designed to evaluate the feasibility and effectiveness of non-invasive spinal electromagnetic simulation (SEMS) to treat nonspecific chronic low back pain (CLBP). A single-site prospective study was conducted to evaluate SEMS in reducing pain and improving disability.