Biology subjects

Sauer, F.

Publications and source records attributed to Sauer, F..

4 recordsLinked to original sources

bioRxiv2025

Spatiotemporal mapping of microscale stiffness during collagen polymerization and crosslinking by optical multifrequency time-harmonic elastography

Optical multifrequency time-harmonic elastography (OMTHE) was used for rapid mechanical characterization of extra-cellular matrix-derived collagen networks at micrometer resolution. OMTHE was optimized for point-wise shear wave excitation in small sample volumes and compared to tabletop magnetic resonance elastography (ttMRE) and optical intensity changes. Dynamic stiffening due to the fluid-gel transition during collagen polymerization and chemical crosslinking using glutaraldehyde was tracked by shear waves speed (SWS) at vibration frequencies between 3 and 10 kHz and frame rates up to 4 kHz. During collagen polymerization, after an initial lag phase, SWS increased on average 6 {+/-} 3 min earlier than optical density, suggesting that a load-bearing percolating fiber network was established before fibril thickening enhanced light scattering. In contrast, chemical crosslinking showed a lag-free, diffusion-driven SWS increase from 1.7 {+/-} 0.4 m/s to 2.5 {+/-} 0.5 m/s, matching the relative SWS change from ground-truth ttMRE. In conclusion, OMTHE provides a unique research tool that quantifies biomechanical property changes in small biological samples with spatiotemporal resolutions of micrometers and seconds. Key Results- Point-excitation OMTHE at microscopic resolution maps dynamic stiffness changes in collagen gels during polymerization and crosslinking at high frame rates. - Polymerization and crosslinking of collagen show distinct time courses with polymerization being in the order of minutes ahead of crosslinking. - Collagen stiffening due to polymerization precedes changes in optical density as seen by light microscopy.

biophysics↗

bioRxiv2024

Demographic responses to climatic changes during the Final Palaeolithic in Europe

The European Final Palaeolithic witnessed marked changes in almost all societal domains. Despite a rich body of evidence, our knowledge of palaeodemographic processes and regional population dynamics still needs to be improved. In this study, we present regionally differentiated estimates of absolute numbers and population densities for the Greenland Interstadial 1d-a (GI-1d-a; 14-12.7 ka BP) and the Greenland Stadial 1 (GS-1; 12.7-11.6 ka BP) for Southern, Western, Northern and Central Europe. The data were obtained by applying the Cologne Protocol, a geostatistical approach for estimating prehistoric population size and density, to a newly compiled dataset of Final Palaeolithic sites. On a large spatio-temporal scale, we observe a shift of the main areas of human occupation from the Franco-Cantabrian region, which was intensely occupied during most phases of the preceding Upper Palaeolithic, to regions north of the Alps. At smaller scales, we observe divergent regional trends in the Final Palaeolithic meta-population: during GI 1d-a, a decreasing population in southwestern Europe and an increasing population in north-eastern Central Europe. For the first time since the dispersal of anatomically modern humans into Europe, we see that Central Europe becomes the dominant demographic growth area. Subsequently, the climatic cooling of GS-1 coincides with a pronounced population decline in most parts of the study area. An apparent increase in population density occurs only in north-eastern Central Europe and north-eastern Italy. Our estimates suggest that the total population was reduced by half. Similar results, with a relationship between decreasing temperatures and decreasing populations, have already been observed for the late phase of the Gravettian, when populations were reduced to only one third of those estimated for the early phase. Yet, in contrast to the collapse of local populations during the late Gravettian, the increase in population densities in Central Europe during GS-1 indicates population movements eastwards, possibly in response to deteriorating climatic conditions, particularly in western regions during the Younger Dryas.

ecology↗

bioRxiv2024

A trimeric USP11/USP7/TCEAL1 complex stabilizes RNAPII during early transcription to sustain oncogenic gene expression

During early transcription, RNA polymerase II (RNAPII) undergoes a series of structural transitions controlled by cyclin-dependent kinases. Whether protein ubiquitylation and proteasomal degradation affect the fate of RNAPII close to promoters is less well understood. Here we show that the deubiquitylating enzyme USP11 and its heterodimeric partner USP7 form a trimeric complex with TCEAL1, a member of the poorly understood TCEAL (TCEA/TFIIS-like) protein family. TCEAL1 shares sequence homology with the RNAPII interaction domain of the TCEA/TFIIS elongation factor, which controls the fate of backtracked RNAPII. TCEAL1 stabilizes complexes of USP11 with USP7 and with RNAPII. TCEAL1 is recruited to core promoters when transcription elongation is blocked and globally enhances the chromatin association of RNAPII during early transcription. Mechanistically, the USP11/USP7/TCEAL1 complex competes with TFIIS for binding to core promoters and protects RPB8, an essential subunit of RNAPII, from degradation, likely preventing excessive TFIIS-mediated transcript cleavage and RNAPII disassembly. In neuroblastoma and other tumors, TCEAL1-dependent genes define a TGF beta-dependent gene expression program that is characteristic for mesenchymal and invasive tumor cell types, suggesting that the USP11/USP7/TCEAL1 trimer stabilizes RNAPII during early transcription to support a critical oncogenic gene expression program (190 words).

cancer biology↗

bioRxiv2024

Trapped in translocation: Stalling of XPD on a crosslinked DNA substrate

The super family 2 (SF2) helicase XPD is a central component of the general transcription factor II H (TFIIH) which is essential for transcription and nucleotide excision DNA repair (NER)1. Within these two processes XPDs helicase function is vital for NER but not for transcription initiation, where XPD only acts as a scaffold for other factors 2. We deciphered one of the most enigmatic steps in XPD helicase action: the active separation of dsDNA and its stalling upon approaching an interstrand crosslink, one of the most severe DNA damages in the cell, using cryo EM. Furthermore, the structure clearly shows how dsDNA is separated and reveals a highly unusual involvement of the Arch domain in active dsDNA separation. Combined with mutagenesis and biochemical analyses, we identify distinct functional residues important for helicase activity. Surprisingly, those areas also affect core TFIIH translocase activity, revealing a yet unencountered function of XPD within the TFIIH scaffold. Importantly, our structure provides a basis for XPD damage recognition and further suggests how the NER bubble could be formed, leading to a model for the location of the XPG nuclease relative to the excised damage.

biochemistry↗