Biology subjects

Sartorio, M.

Publications and source records attributed to Sartorio, M..

2 recordsLinked to original sources

bioRxiv2025

Biomarkers in cerebrospinal fluid sediments

Cerebrospinal fluid (CSF) biomarkers for neurodegenerative diseases have been extensively studied over the years. However, CSF samples are routinely centrifuged, and the resulting sediment or pellet is typically discarded to remove cellular debris and high-density particles. This standard practice raises a critical question: could these discarded sediments harbour potential biomarkers relevant to the diagnosis and prognosis of certain brain diseases? In this study, we analysed CSF pellets from various cases and identified, entrapped among undetermined remnants, brain-derived structures such as wasteosomes and psammoma bodies. Furthermore, we observed that disease-relevant proteins can become deposited in the sediment, as is the case for both tau and A{beta}42 in Alzheimers disease or tau in progressive supranuclear palsy disease. These findings suggest that some potential biomarkers might accumulate or be hidden in the sediment and, taken as a whole, the results underscore the need to broaden the scope of biomarker research. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/657984v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1d5b55corg.highwire.dtl.DTLVardef@175ae02org.highwire.dtl.DTLVardef@f30e42org.highwire.dtl.DTLVardef@12d326b_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO C_FIG

neuroscience↗

bioRxiv2023

Dual Membrane-Sspanning Anti-Sigma Factors Regulate Vesiculation in Gut Bacteroidota

Bacteroidota are abundant members of the human gut microbiota that shape the enteric landscape by modulating host immunity and degrading dietary- and host-derived glycans. These processes are at least partially mediated by Outer Membrane Vesicles (OMVs). In this work, we developed a high-throughput screen to identify genes required for OMV biogenesis and its regulation in Bacteroides thetaiotaomicron (Bt). Our screening led us to the identification of a novel family of Dual Membrane-spanning Anti-sigma factors (Dma), which regulate OMV biogenesis in Bt. We employed molecular and multiomic analyses to demonstrate that deletion of Dma1, the founding member of the Dma family, results in hypervesiculation by modulating the expression of NigD1, which belongs to a family of uncharacterized proteins found throughout Bacteroidota. Dma1 has an unprecedented domain organization: it contains a C-terminal {beta}-barrel embedded in the OM; its N-terminal domain interacts with its cognate sigma factor in the cytoplasm, and both domains are tethered via an intrinsically disordered region that traverses the periplasm. Phylogenetic analyses reveal that the Dma family is a unique feature of Bacteroidota. This study provides the first mechanistic insights into the regulation of OMV biogenesis in human gut bacteria.

microbiology↗