Remobilization and deformation of surficial subaqueous slope sediments create turbidites and soft sediment deformation structures, which are common features in many depositional records. Palaeoseismic studies have used seismically‐induced turbidites and soft sediment deformation structures preserved in sedimentary sequences to reconstruct recurrence patterns and – in some cases – allow quantifying rupture location and magnitude of past earthquakes. However, current understanding of earthquake‐triggered remobilization and deformation lacks studies targeting where these processes take place, the subaqueous slope and involving direct comparison of sedimentary fingerprint with well‐documented historical earthquakes. This study investigates the sedimentary imprint of six megathrust earthquakes with varying rupture characteristics in 17 slope sediment cores from two Chilean lakes, Riñihue and Calafquén, and evaluates how it links to seismic intensity, peak ground acceleration, bracketed duration and slope angle. Centimetre‐scale stratigraphic gaps ranging from ca 1 to 20 cm – caused by remobilization of surficial slope sediment – were identified using high‐resolution multi‐proxy core correlation of slope to basin cores, and six types of soft sediment deformation structures ranging from ca 1 to 25 cm thickness using high‐resolution three‐dimensional X‐ray computed tomography data. Stratigraphic gaps occur on slope angles of ≥2.3°, whereas deformation already occurs from slope angle 0.2°. The thickness of both stratigraphic gaps and soft sediment deformation structures increases with slope angle, suggesting that increased gravitational shear stress promotes both surficial remobilization and deformation. Seismic shaking is the dominant trigger for surficial remobilization and deformation at the studied lakes. Total remobilization depth correlates best with bracketed duration and is highest in both lakes for the strongest earthquakes (M_w ca 9.5). In lake Riñihue, soft sediment deformation structure thickness and type correlate best with peak ground acceleration providing the first field‐based evidence of progressive soft sediment deformation structure development with increasing peak ground acceleration for soft sediment deformation structures caused by Kelvin‐Helmholtz instability. The authors propose that long duration and low frequency content of seismic shaking favours surficial remobilization, whereas ground motion amplitude controls Kelvin‐Helmholtz instability‐related soft sediment deformation structure development.

Background: Calcific aortic valve disease (CAVD) is characterized by a phenotypic switch of valvular interstitial cells to bone-forming cells. Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors at the interface between innate immunity and tissue repair. Type I interferons (IFNs) are not only crucial for an adequate antiviral response but also implicated in bone formation. We hypothesized that the accumulation of endogenous TLR3 ligands in the valvular leaflets may promote the generation of osteoblast-like cells through enhanced type I IFN signaling. Methods: Human valvular interstitial cells isolated from aortic valves were challenged with mechanical strain or synthetic TLR3 agonists and analyzed for bone formation, gene expression profiles, and IFN signaling pathways. Different inhibitors were used to delineate the engaged signaling pathways. Moreover, we screened a variety of potential lipids and proteoglycans known to accumulate in CAVD lesions as potential TLR3 ligands. Ligand-receptor interactions were characterized by in silico modeling and verified through immunoprecipitation experiments. Biglycan ( Bgn ), Tlr3 , and IFN-α/β receptor alpha chain ( Ifnar1 )–deficient mice and a specific zebrafish model were used to study the implication of the biglycan (BGN)-TLR3-IFN axis in both CAVD and bone formation in vivo. Two large-scale cohorts (GERA [Genetic Epidemiology Research on Adult Health and Aging], n=55 192 with 3469 aortic stenosis cases; UK Biobank, n=257 231 with 2213 aortic stenosis cases) were examined for genetic variation at genes implicated in BGN-TLR3-IFN signaling associating with CAVD in humans. Results: Here, we identify TLR3 as a central molecular regulator of calcification in valvular interstitial cells and unravel BGN as a new endogenous agonist of TLR3. Posttranslational BGN maturation by xylosyltransferase 1 (XYLT1) is required for TLR3 activation. Moreover, BGN induces the transdifferentiation of valvular interstitial cells into bone-forming osteoblasts through the TLR3-dependent induction of type I IFNs. It is intriguing that Bgn ^−/− , Tlr3 ^−/− , and Ifnar1 ^−/− mice are protected against CAVD and display impaired bone formation. Meta-analysis of 2 large-scale cohorts with >300 000 individuals reveals that genetic variation at loci relevant to the XYLT1–BGN–TLR3–interferon-α/β receptor alpha chain (IFNAR) 1 pathway is associated with CAVD in humans. Conclusions: This study identifies the BGN-TLR3-IFNAR1 axis as an evolutionarily conserved pathway governing calcification of the aortic valve and reveals a potential therapeutic target to prevent CAVD.

Vascular calcification is common in chronic kidney disease (CKD) and associated with increased cardiovascular mortality. Aldosterone has been implicated as an augmenting factor in the progression of vascular calcification. The present study further explored putative beneficial effects of aldosterone inhibition by the mineralocorticoid receptor antagonist spironolactone on vascular calcification in CKD. Serum calcification propensity was determined in serum samples from the MiREnDa trial, a prospective, randomized controlled clinical trial to investigate efficacy and safety of spironolactone in maintenance hemodialysis patients. Experiments were conducted in mice with subtotal nephrectomy and cholecalciferol treatment, and in calcifying primary human aortic smooth muscle cells (HAoSMCs). Serum calcification propensity was improved by spironolactone treatment in patients on hemodialysis from the MiREnDa trial. In mouse models and HAoSMCs, spironolactone treatment ameliorated vascular calcification and expression of osteogenic markers. These observations support a putative benefit of spironolactone treatment in CKD-associated vascular calcification. Further research is required to investigate possible improvements in cardiovascular outcomes by spironolactone and whether the benefits outweigh the risks in patients with CKD.

Over the past decade, there has been growing interest in the sedimentological community to use micro X‐ray computed tomography to analyse microfacies in sediment cores. However, little attention has been paid to the application of micro‐computed tomography in lithified deposits, even though this can allow their texture to be characterised in three dimensions, providing key information about sedimentary structures. A novel application of micro‐computed tomography in lithified sediment‐gravity flow deposits is presented with the objective of characterising their internal 3D sedimentary structures. This technique is applied to three deep‐marine sandstones showing different compositional properties: Cretaceous Gosau Group (Austria), Eocene Hecho Group (Spain) and the Oligocene Annot Formation (France). From micro‐computed tomography data the size of particles and their distribution throughout the sample is reconstructed in 3D permitting a better visualisation of sedimentary textures. Particle distributions computed from micro‐computed tomography are similar to those computed from thin section image analysis, corroborating the reliability of the micro‐computed tomography to evaluate grain‐size trends. Micro‐computed tomography is complemented with micro‐X‐ray fluorescence and thin section petrographic analyses. In cases where mineral composition or grain size are homogeneous or matrix and grains have similar mineral composition, sedimentary structures do not appear visible from micro‐X‐ray fluorescence or thin section analyses. By separating particles based on their computed tomography density, it is possible to isolate the coarsest fraction, highlighting the sedimentary structures. This study demonstrates (i) the potential of micro‐computed tomography in analyses of sedimentary structures from outcrop data and (ii) the importance of the mineralogical composition and degree of grain sorting in assessing the origin of structureless deposits. Considering the importance of visualising sedimentary structures when interpreting depositional processes, micro‐computed tomography is a new and reliable tool to assess the physical properties of sandstones and to analyse their internal 3D sedimentary structures.

Delta-like homolog 1 (Dlk1), an inhibitor of adipogenesis, controls the cell fate of adipocyte progenitors. Experimental data presented here identify two independent regulatory mechanisms, transcriptional and translational, by which Ifrd1 (TIS7) and its orthologue Ifrd2 (SKMc15) regulate Dlk1 levels. Mice deficient in both Ifrd1 and Ifrd2 (dKO) had severely reduced adipose tissue and were resistant to high-fat diet-induced obesity. Wnt signaling, a negative regulator of adipocyte differentiation, was significantly upregulated in dKO mice. Elevated levels of the Wnt/β-catenin target protein Dlk1 inhibited the expression of adipogenesis regulators Pparg and Cebpa, and fatty acid transporter Cd36. Although both Ifrd1 and Ifrd2 contributed to this phenotype, they utilized two different mechanisms. Ifrd1 acted by controlling Wnt signaling and thereby transcriptional regulation of Dlk1. On the other hand, distinctive experimental evidence showed that Ifrd2 acts as a general translational inhibitor significantly affecting Dlk1 protein levels. Novel mechanisms of Dlk1 regulation in adipocyte differentiation involving Ifrd1 and Ifrd2 are based on experimental data presented here.

Objective: Repeated computed tomography (CT) is essential for diagnosis, surgical planning and follow-up in patients with middle and inner ear pathology. Dose reduction to “as low as diagnostically acceptable” (ALADA) is preferable but challenging. We aimed to compare the diagnostic quality of images of subtle temporal bone structures produced with low doses (LD) and reference protocols (RP). Methods: Two formalin-fixed human cadaver heads were scanned using a 64-slice CT scanner and cone-beam CT (CBCT). The protocols were: RP (120 kV, 250 mA, CTDIvol 83.72 mGy), LD1 (100 kV, 80 mA, CTDIvol 26.79 mGy), LD2 (100 kV, 35 mA, CTDIvol 7.66 mGy), LD3 (80 kV, 40 mA, CTDIvol 4.82 mGy), and CBCT standard protocol. Temporal bone structures were assessed using a 5-point scale. Results: A median score of ≥2 was achieved with protocols such as the tendons of m. tensor tympani (RP/LD1/LD2/CBCT) and m. stapedius (CBCT), the incudostapedial joint (RP/LD1/CBCT), the incudomalleolar joint (RP/LD1/LD2/CBCT), the stapes feet (RP/LD1/CBCT), the stapes head (RP/LD1/LD2/CBCT), the tympanic membrane (RP/LD1/LD2/CBCT), the lamina spiralis ossea (none), the chorda tympani (RP/LD1/CBCT), and the modiolus (RP/LD1/LD2/CBCT). Adaptive statistical iterative reconstructions did not show advantages over the filtered back projection. Conclusions: LD protocols using a CTDIvol of 7.66 mGy may be sufficient for the identification of temporal bone structures.