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Two major challenges in proteomics are the large number of proteins and their broad dynamic range in the cell. We exploited the abundance-dependent Michaelis-Menten kinetics of trypsin digestion to selectively digest and deplete abundant proteins with a method we call DigDeAPr. We validated the depletion mechanism with known yeast protein abundances, and we observed greater than threefold improvement in low-abundance human-protein identification and quantitation metrics. This methodology should be broadly applicable to many organisms, proteases and proteomic pipelines.
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http://dx.doi.org/10.1038/nmeth.2250 | DOI Listing |
Cephalalgia
September 2025
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, USA.
Migraine is a complex neurological disorder involving multiple neuropeptides that modulate nociceptive and sensory pathways. The most studied peptide is calcitonin gene-related peptide (CGRP), which is a well-established migraine trigger and therapeutic target. Recently, another peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), has emerged as an alternative target for migraine therapeutics.
View Article and Find Full Text PDFAdv Healthc Mater
September 2025
State Key Laboratory of Southwestern Chinese Medicine Resources, College of Modern Chinese Medicine Industry, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation, damage, and disability. Activated fibroblast-like synoviocytes (FLSs), abundant in RA synovium, crucially facilitate disease progression. These activated FLSs drive RA pathogenesis by upregulating adhesion molecules, proinflammatory cytokines, chemokines, and major histocompatibility complex class II (MHC-II).
View Article and Find Full Text PDFInt J Cosmet Sci
September 2025
Givaudan Active Beauty, Research and Development, Givaudan France SAS, Argenteuil, France.
Objective: Porphyrins are ubiquitous metabolites and are constitutive of the bacterial metabolome of healthy skin. Their consideration has until now been limited to their pro-inflammatory activity in acne vulgaris. The present work suggests a new role for these molecules in the onset of skin ageing.
View Article and Find Full Text PDFNature
September 2025
Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Würzburg, Germany.
Bacteriophages are the most abundant entities on earth and exhibit vast genetic and phenotypic diversity. Exploitation of this largely unexplored molecular space requires identification and functional characterization of genes that act at the phage-host interface. So far, this has been restricted to few model phage-host systems that are amenable to genetic manipulation.
View Article and Find Full Text PDFOncogene
September 2025
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Pancreatic cancer is a highly aggressive malignancy with a dismal prognosis, characterized by a complex tumor microenvironment that promotes immunosuppression and limits the efficacy of immune checkpoint blockade (ICB) therapy. Fibroblast activation protein (FAP) is overexpressed in the tumor stroma and represents a promising target for therapeutic intervention. Here, we developed a novel antibody-drug conjugate (ADC) targeting FAP, and investigated its anti-tumor activity and ability to enhance ICB efficacy in pancreatic cancer.
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