As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra- and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium. While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.
Halogen bonding is a recently rediscovered secondary interaction that shows potential to become a complementary molecular tool to hydrogen bonding in rational drug design and in material sciences. Whereas hydrogen bond symmetry has been the subject of systematic studies for decades, the understanding of the analogous three-center halogen bonds is yet in its infancy. The isotopic perturbation of equilibrium (IPE) technique with (13)C NMR detection was applied to regioselectively deuterated pyridine complexes to investigate the symmetry of [N-I-N](+) and [N-Br-N](+) halogen bonding in solution. Preference for a symmetric arrangement was observed for both a freely adjustable and for a conformationally restricted [N-X-N](+) model system, as also confirmed by computation on the DFT level. A closely attached counterion is shown to be compatible with the preferred symmetric arrangement. The experimental observations and computational predictions reveal a high energetic gain upon formation of symmetric, three-center four-electron halogen bonding. Whereas hydrogen bonds are generally asymmetric in solution and symmetric in the crystalline state, the analogous bromine and iodine centered halogen bonds prefer symmetric arrangement in solution.
Here we report a case of Covid-19-related acute necrotizing encephalopathy (ANE) where SARS-CoV-2 RNA was found in cerebrospinal fluid (CSF) 19 days after symptom onset after testing negative twice. Even though monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurological function deteriorated into coma. Magnetic resonance imaging of the brain showed pathological signal symmetrically in central thalami, subinsular regions, medial temporal lobes and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light (NfL) and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein (GFAp), were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received intravenous immunoglobulins (IVIG) and plasma exchange (PLEX). Her neurological status improved and she was extubated four weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected Covid-19 and neurological symptoms.
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