Beschreibung: Peroxisomes are proposed to play an important role in the regulation of systemic inflammation; however, the functional role of these organelles in inflammatory responses of myeloid immune cells is largely unknown. In this article, we demonstrate that the nonclassical peroxisome proliferator 4-phenyl butyric acid is an efficient inducer of peroxisomes in various models of murine macrophages, such as primary alveolar and peritoneal macrophages and the macrophage cell line RAW264.7, but not in primary bone marrow–derived macrophages. Further, proliferation of peroxisomes blocked the TLR4 ligand LPS-induced proinflammatory response, as detected by the reduced induction of the proinflammatory protein cyclooxygenase (COX)-2 and the proinflammatory cytokines TNF-α, IL-6, and IL-12. In contrast, disturbing peroxisome function by knockdown of peroxisomal gene Pex14 or Mfp2 markedly increased the LPS-dependent upregulation of the proinflammatory proteins COX-2 and TNF-α. Specifically, induction of peroxisomes did not affect the upregulation of COX-2 at the mRNA level, but it reduced the half-life of COX-2 protein, which was restored by COX-2 enzyme inhibitors but not by proteasomal and lysosomal inhibitors. Liquid chromatography–tandem mass spectrometry analysis revealed that various anti-inflammatory lipid mediators (e.g., docosahexaenoic acid) were increased in the conditioned medium from peroxisome-induced macrophages, which blocked LPS-induced COX-2 upregulation in naive RAW264.7 cells and human primary peripheral blood–derived macrophages. Importantly, LPS itself induced peroxisomes that correlated with the regulation of COX-2 during the late phase of LPS activation in macrophages. In conclusion, our findings identify a previously unidentified role for peroxisomes in macrophage inflammatory responses and suggest that peroxisomes are involved in the physiological cessation of macrophage activation.

Beschreibung: The oncogenic Ras/MAPK pathway is evolutionarily conserved across metazoans. Yet, almost all our knowledge on this pathway comes from studies using single genetic backgrounds, whereas mutational effects can be highly background dependent. Therefore, we lack insight in the interplay between genetic backgrounds and the Ras/MAPK-signaling pathway. Here, we used a Caenorhabditis elegans RIL population containing a gain-of-function mutation in the Ras/MAPK-pathway gene let-60 and measured how gene expression regulation is affected by this mutation. We mapped eQTL and found that the majority (~73%) of the 1516 detected cis -eQTL were not specific for the let-60 mutation, whereas most (~76%) of the 898 detected trans -eQTL were associated with the let-60 mutation. We detected six eQTL trans -bands specific for the interaction between the genetic background and the mutation, one of which colocalized with the polymorphic Ras/MAPK modifier amx-2 . Comparison between transgenic lines expressing allelic variants of amx-2 showed the involvement of amx-2 in 79% of the trans -eQTL for genes mapping to this trans -band. Together, our results have revealed hidden loci affecting Ras/MAPK signaling using sensitized backgrounds in C. elegans . These loci harbor putative polymorphic modifier genes that would not have been detected using mutant screens in single genetic backgrounds.

Beschreibung: The Hawaiian strain ( CB4856 ) of Caenorhabditis elegans is one of the most divergent from the canonical laboratory strain N2 and has been widely used in developmental, population, and evolutionary studies. To enhance the utility of the strain, we have generated a draft sequence of the CB4856 genome, exploiting a variety of resources and strategies. When compared against the N2 reference, the CB4856 genome has 327,050 single nucleotide variants (SNVs) and 79,529 insertion–deletion events that result in a total of 3.3 Mb of N2 sequence missing from CB4856 and 1.4 Mb of sequence present in CB4856 but not present in N2 . As previously reported, the density of SNVs varies along the chromosomes, with the arms of chromosomes showing greater average variation than the centers. In addition, we find 61 regions totaling 2.8 Mb, distributed across all six chromosomes, which have a greatly elevated SNV density, ranging from 2 to 16% SNVs. A survey of other wild isolates show that the two alternative haplotypes for each region are widely distributed, suggesting they have been maintained by balancing selection over long evolutionary times. These divergent regions contain an abundance of genes from large rapidly evolving families encoding F-box, MATH, BATH, seven-transmembrane G-coupled receptors, and nuclear hormone receptors, suggesting that they provide selective advantages in natural environments. The draft sequence makes available a comprehensive catalog of sequence differences between the CB4856 and N2 strains that will facilitate the molecular dissection of their phenotypic differences. Our work also emphasizes the importance of going beyond simple alignment of reads to a reference genome when assessing differences between genomes.

Beschreibung: This dataset includes surface 3D stereoscopic Digital Image Correlation (3D stereo DIC) images and videos of 10 analogue models on crustal scale rifting with a rotational component. In addition, this dataset provides CT imagery of four analogue models that have been analyzed by means of Digital Volume Correlation (DVC) applied on X-Ray computed tomography volumes. Data of CT scanned models also includes slices of the volumetric displacement set for each displacement component. Using a brittle-viscous two-layer setup, the experiments focused on surface rift propagation, internal viscous flow driven by a horizontal pressure gradient and the interaction of internal and surface deformation. All experiments were performed at the Tectonic Modelling Laboratory of the University of Bern (UB). 3D stereo DIC analyses were performed at the GFZ German Research Centre for Geosciences (GFZ) and DVC analyses were performed at the Royal Holloway University London (RHUL). All models consist of a two-layer brittle-viscous set up with a total thickness of 6 cm. Thickness variations in brittle and ductile layers are expressed by the ratio RBD = brittle layer thickness/ductile layer thickness, which ranges from RBD = 0.5 to RBD = 2. The model set up lies on top of a 5 cm thick foam base with a trapezoidal shape with a height of 900 mm and a pair of bases with widths of 310 mm and 350 mm at the far ends, respectively. The foam block is sliced into segments such that 7 interlayered 0.5 cm thick plexiglass bars prevent foam collapse under the model weight. Before model construction, the foam-plexiglass assemblage is placed between longitudinal side walls. The experimental set-up is such that rotational extension in one part of the model domain is separated from rotational shortening in the other part of the model domain by a vertical rotation axis (Fig. 1). During the model run, the foam homogeneously expands in the domain undergoing extension and homogeneously contracts in the domain undergoing shortening. The applied velocity for all models is 10 mm/h and refers to the divergence of the sidewalls furthest away from the rotation axis which decreases linearly towards the rotation axis. This results in a maximum displacement of 40 mm at the outermost circular segment after a total run time of 4h.

Beschreibung: This data set includes the results of digital image correlation of ten brittle-viscous experiments on crustal extension and four benchmark experiments performed at the Tectonic Modelling Lab of the University of Bern (UB). The experiments demonstrate the differences in rift development in orthogonal versus rotation extension. Detailed descriptions of the experiments and monitoring techniques can be found in Zwaan et al. (2019) to which this data set is supplementary. Additional background information concerning the general modelling approach are available in Zwaan et al. (2016). The data presented here consist of movies displaying digital image correlation (DIC) derived surface and internal displacement fields as well as profiles of the lateral cumulative surface displacements. Digital photographs of the experimental surface and digital image cross section of the computed CT-scans were analyzed with DIC (Adam et al., 2005, 2013) techniques to quantify displacements in the image plane at high precision (〈0.1 mm). DIC was undertaken with the software DaVis 8.0 (LaVision) applying 2D-DIC (FFT-legacy) multipass processing with a final interrogation window size of 32x32 (CT: 12x12) pixels and 50% (CT: 25%) overlap.

Beschreibung: This dataset provides friction data from ring-shear tests (RST) for a quartz sand (“A”). This material is used in various types of analogue experiments in Tectonic Modelling Lab of the University of Bern as an analogue for brittle layers in the crust or lithosphere. The material has been characterized by means of internal friction coefficients μ and cohesions C. Three sub-datasets represent a systematic increase of the sieving height from 10 cm to 20 cm to 30 cm into a shear cell of type No. 1, following the same protocol. This dataset shows that packing density of quartz sand is dependent on the chosen sieving height. However, the effect of the sieving height on internal friction coefficients μ as well as cohesion C is minor and thus negligible in sandbox experiments. According to our analysis the material shows for a sieving height of 10 cm a Mohr-Coulomb behaviour characterized by a linear failure envelope and peak, dynamic and reactivation friction coefficients of μP = 0.70, μD = 0.60 and μR = 0.65, respectively. Cohesions C are in the order of 40 – 80 Pa.

Beschreibung: This dataset provides friction data from ring-shear tests (RST) for a corundum sand (“NKF120”). This material is used in various types of analogue experiments in Tectonic Modelling Lab of the University of Bern as an analogue for brittle layers in the crust or lithosphere. The material has been characterized by means of internal friction coefficients μ and cohesions C. Three sub-datasets represent a systematic increase of the sieving height from 10 cm to 20 cm to 30 cm into a shear cell of type No. 1, following the same protocol. This dataset shows that packing density of corundum sand is dependent on the chosen sieving height. However, the effect of the sieving height on internal friction coefficients μ as well as cohesion C is minor and thus negligible in sandbox experiments. According to our analysis the material shows for a sieving height of 10 cm a Mohr-Coulomb behaviour characterized by a linear failure envelope and peak, dynamic and reactivation friction coefficients of μP = 0.75, μD = 0.64 and μR = 0.68, respectively. Cohesions C are in the order of 70 – 105 Pa.

Beschreibung: This dataset provides results from rheological tests of glucose syrup from two suppliers tested within the EPOS Multi-scale Laboratories (MSL) trans-national access (TNA) program 2019 at the Laboratory of Experimental Tectonics (LET), Univ. Roma TRE, Italy. Syrups Glucowheat 45/81 (GW45) and Glucowheat 60/79 (GW60) are produced by Blattmann Schweiz AG, Switzerland (2019 batch). Syrups GlucoSweet 44 (GS44) and GlucoSweet 62 (GS62) are produced by ADEA (Amidi Destrini ed Affini), Italy (2019 batch) . The four tested glucose syrups are labeled according to their DE value (dextrose equivalent value). For tested products from Blattmann Schweiz AG, the second number refers to the weight percentage of dry substance. Glucose syrup GS44 is used in full lithospheric scale analogue experiments at the Tectonic Modelling Lab (TecLab) at the University of Bern, Switzerland as a low-viscosity material simulating the asthenospheric mantle lithosphere to provide isostatic equilibration. The materials have been analyzed using a MCR301 Rheometer (Anton Paar) equipped with parallel plates geometry and rotational regime . To prevent the evaporation of the samples during the measurements, an external water-lock device has been used.

Beschreibung: This dataset includes surface 3D stereoscopic Digital Image Correlation (3D stereo DIC) images and videos of 9 analogue models on crustal scale rifting with a rotational component. Using a brittle-viscous two-layer setup, the experiments focused on near-surface fault growth, rift segment interaction and rift propagation. All experiments were performed at the Tectonic Modelling Laboratory of the University of Bern (UB). All models consist of a two-layer brittle-viscous set up with a total thickness of 6 cm. Thickness variations in ductile and brittle layers are expressed by the ratio RBD = brittle layer thickness/ductile layer thickness, which ranges from RBD = 1 to RBD = 3. The model set up lies on top of a 5 cm thick foam base with a trapezoidal shape with a height of 900 mm and a pair of bases of 310 mm and 350 mm. The foam block is sliced into segments such that 7 interlayered 0.5 cm thick plexiglass bars prevent foam collapse under the model weight. The foam base is initially compressed between the longitudinal side walls and homogeneously expands during the rotational opening. Applied velocities refer to the divergence of the sidewalls at the outermost point (i.e., furthest away from the rotation axis) and decrease linearly towards the rotation axis. These velocities vary from 10 mm/h over a total run time of 4 h up to 40 mm/h over a total run time of one hour, resulting in identical total extension of ca 13% (given an initial model width of 31 cm) for all models. Detailed descriptions of the experiments as well as monitoring techniques can be found in Schmid et al. (2021).

Beschreibung: This data set includes the results of digital image correlation of ten brittle-viscous experiments on crustal extension and four benchmark experiments performed at the Tectonic Modelling Lab of the University of Bern (UB). The experiments demonstrate the differences in rift development in orthogonal versus rotation extension. Detailed descriptions of the experiments and monitoring techniques can be found in Zwaan et al. (2019) to which this data set is supplementary. Additional background information concerning the general modelling approach are available in Zwaan et al. (2016).. The data presented here consist of movies displaying digital image correlation (DIC) derived surface and internal displacement fields as well as profiles of the lateral cumulative surface displacements. Digital photographs of the experimental surface and digital image cross section of the computed CT-scans were analyzed with DIC (Adam et al., 2005, 2013) techniques to quantify displacements in the image plane at high precision (〈0.1 mm). DIC was undertaken with the software DaVis 8.0 (LaVision) applying 2D-DIC (FFT-legacy) multipass processing with a final interrogation window size of 32x32 (CT: 12x12) pixels and 50% (CT: 25%) overlap.