[New methods at the transition from research to routine diagnostics].

Background: Pathology, traditionally focused on classification and diagnosis, is continuously evolving through new technologies. Advances in proteomics, epigenetics, tissue staining, and 3D imaging expand the possibilities of classical morphology.

Aim Of The Study: The aim of this study was to investigate how modern technologies can improve diagnostic accuracy and therapy selection and how they can be integrated into pathologic routine diagnostics.

Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) displays a high degree of spatial subtype heterogeneity and co-existence, linked to a diverse microenvironment and worse clinical outcome. However, the underlying mechanisms remain unclear. Here, by combining preclinical models, multi-center clinical, transcriptomic, proteomic, and patient bioimaging data, we identify an interplay between neoplastic intrinsic AP1 transcription factor dichotomy and extrinsic macrophages driving subtype co-existence and an immunosuppressive microenvironment.

The proximity-based protein interactome and regulatory logics of the transcription factor p65 NF-κB/RELA.

The protein interactome of p65/RELA, the most active subunit of the transcription factor (TF) NF-κB, has not been previously determined in living cells. Using p65-miniTurbo fusion proteins and biotin tagging, we identify >350 RELA interactors from untreated and IL-1α-stimulated cells, including many TFs (47% of all interactors) and >50 epigenetic regulators belonging to different classes of chromatin remodeling complexes. A comparison with the interactomes of two point mutants of p65 reveals that the interactions primarily require intact dimerization rather than DNA-binding properties.

Age-associated changes in transcriptional elongation and their effects on homeostasis.

Cellular homeostasis declines with age due to the declining fidelity of biosynthetic processes and the accumulation of molecular damage. Yet, it remains largely elusive how individual processes are affected during aging and what their specific contribution to age-related functional decline is. This review discusses a series of recent publications that has shown that transcription elongation is compromised during aging due to increasing DNA damage, stalling of RNA polymerase II (RNAPII), erroneous transcription initiation in gene bodies, and accelerated RNAPII elongation.

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.