Researchers from Peru, Brazil, and elsewhere describe population genetic features and potential genetic adaptations found in individuals from Native American populations in the Andes and the Amazon. Based on genetic profiles for individuals from 18 different populations in Peru, the team narrowed in on related genetic clusters in the Andean highlands that were distinct from populations in the lowland Amazon region, which appeared to reflect differences in population histories, prior migration events, and exposures to distinct environmental features, particularly altitude and climate. For example, the authors note that "longitudinal gene flow between the northern coast of Peru, Andes, and Amazonia accompanied cultural and socioeconomic interactions revealed by archeology. This pattern recapitulates the environmental and cultural differentiation between the fertile north, where altitudes are lower, and the arid south, where the Andes are higher, acting as a genetic barrier between the sharply different environments of the Andes and Amazonia."
Investigators in Korea look at lipid metabolism shifts that appear to help some gastric cancer cells dodge an iron-reliant, lipid peroxidation-regulated form of necrosis known as ferroptosis. Using array-based expression profiling, protein interaction assays, lipid labeling, liquid chromatography-tandem mass spec, and other approaches, the team tracked specific lipid and enzyme levels, along with related DNA methylation features, in a suite of gastric cancer cell lines with a spectrum of ferroptosis sensitivities. "[W]e found that the expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells, leading to ferroptosis sensitization," they write, adding that intestinal-type gastric cancers lacking specific fatty acids appear to have enhanced ferroptosis sensitivity when supplemented with them.
A team from the University of Naples and other centers in Italy focuses on a heat shock protein 70 (HSP70) inhibitor that shows promise for treating some symptoms of a copper homeostasis condition called Wilson disease. The researchers used proteomic assays, fluorescent protein labeling, and other pharmacoproteomic approaches to search for protein interaction changes associated with the ATP7B mutations behind Wilson disease. Their subsequent bioinformatic analyses hinted that the US Food and Drug Administration-approved drug domperidone is structurally similar to a known HSP70 inhibitor and may bolster the stability of ATP7B gene products containing a Wilson disease-related substitution known as H1069Q. "Our findings suggest that HSP70-mediated degradation can be safely targeted with domperidone to rescue [endoplasmic reticulum]-retained ATP7B mutants and, hence, to counter the onset of Wilson disease," the authors report.