Biology subjects

Schäfer, L.

Publications and source records attributed to Schäfer, L..

3 recordsLinked to original sources

bioRxiv2026

The chemistry of families: Linking body odor composition to olfactory perception

Body odors inform human kin recognition. However, underlying chemical mechanisms and how they relate to body odor perception are still unclear. The present study therefore simultaneously examined perceptual body odor similarity according to human raters, its chemical basis and the link between the two in human families. The study included 33 raters who assessed body odors collected from 60 odor donors belonging to 15 biological families. Each family comprised a mother, a father and one adolescent same-sex sibling-dyad (8 sister dyads, 7 brother dyads). Body odor sampling was conducted with cotton pads for presentation to human raters and with thermal desorption (TD) tubes for Gas Chromatography-Mass Spectrometry (GC-MS) analysis. Relatedness and sex predicted perceived body odor similarity in parent-offspring versus unrelated control dyads. Analyses of chemical profiles revealed greater body odor similarity within families than between unrelated individuals. Parallel to the perceptual results, relatedness and sex predicted chemical similarity based on whole odor profiles. Finally, a machine-learning prediction model integrating perceptual and chemical data, revealed a small but significant positive association between chemical similarity of body odor and perceived olfactory similarity according to human raters, suggesting that odor perception is partly informed by chemical characteristics. Overall, the present study extends our understanding of human chemosensory communication and supports the notion of a family-specific olfactory signature.

ecology↗

bioRxiv2024

Coupling the role of lipids to the conformational dynamics of the ABC transporter P-gp

The ATP-binding cassette (ABC) transporter P-glycoprotein (P-gp) is a multidrug efflux pump that is overexpressed in a variety of cancers and associated with the drug resistance phenomenon. P-gp structures were previously determined in detergent and in nanodiscs, in which different transmembrane helix conformations were found, "straight" and "kinked", respectively, indicating a possible role of the lipid environment on the P-gp structural ensemble. Here, we investigate the dynamic conformational ensembles and protein-lipid interactions of the two human P-gp inward-open conformers (straight and kinked) employing all-atom molecular dynamics simulations in asymmetric multicomponent lipid bilayers that mimic the highly specialized hepatocyte membrane in which P-gp is expressed. The two conformers are found to differ in terms of the accessibility of the substrate cavity. The MD simulations show how cholesterol and different lipid species wedge, snorkel, and partially enter within the cavity of the straight P-gp conformer solved in detergent. However, the access to the cavity of kinked P-gp conformer solved in nanodiscs is restricted. Furthermore, the volume and dynamic fluctuations of the substrate cavity largely differ between the two P-gp structures, and are modulated by the presence (or absence) of cholesterol in the membrane and/or of ATP. From the mechanistic perspective, our findings indicate that the straight conformer likely precedes the kinked conformer in the functional working cycle of P-pg, with the latter conformation representing a post substrate-bound state. The inaccessibility of the main transmembrane cavity in the kinked conformer might be crucial in preventing substrate disengagement and transport withdrawal. Remarkably, in our unbiased MD simulations, one transmembrane portal helix (TM10) of the straight conformer underwent a spontaneous conformational transition to a kinked conformation, underlining the relevance of both conformations in a native phospholipid environment and revealing structural descriptors defining the transition between two P-gp conformers.

biophysics↗

bioRxiv2021

Altered fibrin clot structure contributes to thrombosis risk in severe COVID-19

The high incidence of thrombotic events suggests a possible role of the contact system pathway in COVID-19 pathology. Here, we demonstrate altered levels of factor XII (FXII) and its activation products in two independent cohorts of critically ill COVID-19 patients in comparison to patients suffering from severe acute respiratory distress syndrome due to influenza virus (ARDS-influenza). Compatible with this data, we report rapid consumption of FXII in COVID-19, but not in ARDS-influenza, plasma. Interestingly, the kaolin clotting time was not prolonged in COVID-19 as compared to ARDS-influenza. Using confocal and electron microscopy, we show that increased FXII activation rate, in conjunction with elevated fibrinogen levels, triggers formation of fibrinolysis-resistant, compact clots with thin fibers and small pores in COVID-19. Accordingly, we observed clot lysis in 30% of COVID-19 patients and 84% of ARDS-influenza subjects. Analysis of lung tissue sections revealed wide-spread extra- and intra-vascular compact fibrin deposits in COVID-19. Together, our results indicate that elevated fibrinogen levels and increased FXII activation rate promote thrombosis and thrombolysis resistance via enhanced thrombus formation and stability in COVID-19.

biochemistry↗