Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.

Tracking non-genetic evolution from primary to metastatic ccRCC: TRACERx Renal.

While the key aspects of genetic evolution and their clinical implications in clear cell renal-cell carcinoma (ccRCC) are well-documented, how genetic features co-evolve with the phenotype and tumor microenvironment (TME) remains elusive. Here, through joint genomic-transcriptomic analysis of 243 samples from 79 patients recruited to the TRACERx Renal study, we identify pervasive non-genetic intratumor heterogeneity, with over 40% not attributable to genetic alterations. By integrating tumor transcriptomes and phylogenetic structures, we observe convergent evolution to specific phenotypic traits, including cell proliferation, metabolic reprogramming and overexpression of putative cGAS-STING repressors amid high aneuploidy.

Nanoscale imaging and control of altermagnetism in MnTe.

Nanoscale detection and control of the magnetic order underpins a spectrum of condensed-matter research and device functionalities involving magnetism. The key principle involved is the breaking of time-reversal symmetry, which in ferromagnets is generated by an internal magnetization. However, the presence of a net magnetization limits device scalability and compatibility with phases, such as superconductors and topological insulators.

Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking.

Transition metals function as structural and catalytic cofactors for a large diversity of proteins and enzymes that collectively comprise the metalloproteome. Metallostasis considers all cellular processes, notably metal sensing, metalloproteome remodeling, and trafficking (or allocation) of metals that collectively ensure the functional integrity and adaptability of the metalloproteome. Bacteria employ both protein and RNA-based mechanisms that sense intracellular transition metal bioavailability and orchestrate systems-level outputs that maintain metallostasis.