The dia-PASEF technology uses ion mobility separation to reduce signal interferences and increase sensitivity in proteomic experiments. Here we present a two-dimensional peak-picking algorithm and generation of optimized spectral libraries, as well as take advantage of neural network-based processing of dia-PASEF data. Our computational platform boosts proteomic depth by up to 83% compared to previous work, and is specifically beneficial for fast proteomic experiments and those with low sample amounts. It quantifies over 5300 proteins in single injections recorded at 200 samples per day throughput using Evosep One chromatography system on a timsTOF Pro mass spectrometer and almost 9000 proteins in single injections recorded with a 93-min nanoflow gradient on timsTOF Pro 2, from 200 ng of HeLa peptides. A user-friendly implementation is provided through the incorporation of the algorithms in the DIA-NN software and by the FragPipe workflow for spectral library generation.

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.

Two mononuclear Cu II complexes with tetrapeptides incorporating a L-2,3-diaminopropionic acid (dap) branching unit are reported to undergo PCET and catalyse water oxidation. C-terminal His extension of dap (L = 2GH) instead of Gly (L = 3G) lowers the pK a for Cu III H À2 L (9.36 vs. 9.98) and improves the TOF at pH 11 (53 vs. 24 s À1 ).Reactions requiring the synchronous transfer of multiple protons and electrons become energetically viable under mild conditions through the catalytic promotion of proton-coupled electron transfer (PCET) mechanisms that help circumventing high-energy intermediates. 1 Splitting water into its elements, which attracts growing attention as a prospective renewable tool to generate H 2 as an energy carrier, 2-4 ranks among reactions where PCET is of critical importance. Water oxidation catalysts (WOCs) can improve the efficiency of the oxidative half-reaction: 2H 2 O -O 2 + 4H + + 4e À , which has long been considered the bottleneck of the water splitting process. Bioinspired, homogeneous WOCs (Fe, 5 Co, 6 Ru, 7 or Ir 8 ), although inherently less robust than heterogeneous catalysts, 9 represent a meaningful source of mechanistic insight into the multiple proton and electron-transfer events associated with O 2 formation. A growing number of studies conclude that PCET helps in stabilising high-valent MQO or M-O intermediates by preventing charge accumulation upon oxidation and, as a consequence these intermediates can complete the O-O bond formation step. 10 Cu has rich oxygen chemistry, 11 yet, homogeneous WOCs involving this metal appeared only recently, when surprisingly robust Cu II complexes with 2,2 0 -bipyridine (bpy, TOF B 100 s À1 at pH 13) 12 and subsequently, with triglycylglycine (GGGG, or H-Gly-Gly-Gly-Gly-OH, TOF = 33 s À1