The Orphan Nuclear Estrogen Receptor–Related Receptor α (Errα) Is Expressed Throughout Osteoblast Differentiation and Regulates Bone Formation in Vitro

The orphan nuclear estrogen receptor–related receptor α (ERRα), is expressed by many cell types, but is very highly expressed by osteoblastic cells in which it transactivates at least one osteoblast-associated gene, osteopontin. To study the putative involvement of ERRα in bone, we first assessed its expression in rat calvaria (RC) in vivo and in RC cells in vitro. ERRα mRNA and protein were expressed at all developmental stages from early osteoprogenitors to bone-forming osteoblasts, but protein was most abundant in mature cuboidal osteoblasts. To assess a functional role for ERRα in osteoblast differentiation and bone formation, we blocked its expression by antisense oligonucleotides in either proliferating or differentiating RC cell cultures and found inhibition of cell growth and a proliferation-independent inhibition of differentiation. On the other hand, ERRα overexpression in RC cells increased differentiation and maturation of progenitors to mature bone-forming cells. Our findings show that ERRα is highly expressed throughout the osteoblast developmental sequence and plays a physiological role in differentiation and bone formation at both proliferation and differentiation stages. In addition, we found that manipulation of receptor levels in the absence of known ligand is a fruitful approach for functional analysis of this orphan receptor and identification of potential target genes

Experimental Investigation on Static and Dynamic Bulk Moduli of Dry and Fluid-Saturated Porous Sandstones

Knowledge of pressure-dependent static and dynamic moduli of porous reservoir rocks is of key importance for evaluating geological setting of a reservoir in geo-energy applications. We examined experimentally the evolution of static and dynamic bulk moduli for porous Bentheim sandstone with increasing confining pressure up to about 190 MPa under dry and water-saturated conditions. The static bulk moduli (K-s) were estimated from stress-volumetric strain curves while dynamic bulk moduli (K-d) were derived from the changes in ultrasonic P- and S- wave velocities (similar to 1 MHz) along different traces, which were monitored simultaneously during the entire deformation. In conjunction with published data of other porous sandstones (Berea, Navajo and Weber sandstones), our results reveal that the ratio between dynamic and static bulk moduli (K-d/K-s) reduces rapidly from about 1.5 - 2.0 at ambient pressure to about 1.1 at high pressure under dry conditions and from about 2.0 - 4.0 to about 1.5 under water-saturated conditions, respectively. We interpret such a pressure-dependent reduction by closure of narrow (compliant) cracks, highlighting thatK(d)/K(s)is positively correlated with the amount of narrow cracks. Above the crack closure pressure, where equant (stiff) pores dominate the void space,K-d/K(s)is almost constant. The enhanced difference between dynamic and static bulk moduli under water saturation compared to dry conditions is possibly caused by high pore pressure that is locally maintained if measured using high-frequency ultrasonic wave velocities. In our experiments, the pressure dependence of dynamic bulk modulus of water-saturated Bentheim sandstone at effective pressures above 5 MPa can be roughly predicted by both the effective medium theory (Mori-Tanaka scheme) and the squirt-flow model. Static bulk moduli are found to be more sensitive to narrow cracks than dynamic bulk moduli for porous sandstones under dry and water-saturated conditions

Methyl 5-[N,N-bis­(methoxy­carbonyl­meth­yl)amino]-4-cyano-2-methoxy­carbonyl-3-thio­phene­ethan­o­ate

In the title compound, C16H18N2O8S, derived from ranelic acid, there is a highly substituted thio­phene ring. The crystal structure involves inter­molecular C—H⋯O and C—H⋯S hydrogen bonds

Strain Partitioning and Frictional Behavior of Opalinus Clay During Fault Reactivation

The Opalinus Clay (OPA) formation is considered a suitable host rock candidate for nuclear waste storage. However, the sealing integrity and long-term safety of OPA are potentially compromised by pre-existing natural or artificially induced faults. Therefore, characterizing the mechanical behavior and microscale deformation mechanisms of faults and the surrounding rock is relevant for predicting repository damage evolution. In this study, we performed triaxial tests using saw-cut samples of the shaly and sandy facies of OPA to investigate the influence of pressure and mineral composition on the deformation behavior during fault reactivation. Dried samples were hydrostatically pre-compacted at 50 MPa and then deformed at constant strain rate, drained conditions and confining pressures (pc) of 5–35 MPa. Mechanical data from triaxial tests was complemented by local strain measurements to determine the relative contribution of bulk deformation and fault slip, as well as by acoustic emission (AE) monitoring, and elastic P-wave velocity measurements using ultrasonic transmissions. With increasing pc, we observe a transition from brittle deformation behavior with highly localized fault slip to semi-brittle behavior characterized by non-linear strain hardening with increasing delocalization of deformation. We find that brittle localization behavior is limited by pc at which fault strength exceeds matrix yield strength. AEs were only detected in tests performed on sandy facies samples, and activity decreased with increasing pc. Microstructural analysis of deformed samples revealed a positive correlation between increasing pc and gouge layer thickness. This goes along with a change from brittle fragmentation and frictional sliding to the development of shear zones with a higher contribution of cataclastic and granular flow. Friction coefficient at fault reactivation is only slightly higher for the sandy (µ ~ 0.48) compared to the shaly facies (µ ~ 0.4). Slide-hold-slide tests performed after ~ 6 mm axial shortening suggest stable creeping and long-term weakness of faults at the applied conditions. Our results demonstrate that the mode of fault reactivation highly depends on the present stress field and burial history

Preparatory Slip in Laboratory Faults: Effects of Roughness and Load Point Velocity

Aseismic slip may occur during a long preparatory phase preceding earthquakes, and what controls it remains poorly understood. In this study, we explored the role of load point velocity and surface roughness on slow slip during the preparatory stage prior to stick-slip events. To that end, we conducted displacement-rate controlled friction experiments by imposing varying load point velocities on sawcut granite samples with different surface roughness at a confining pressure of 35 MPa. We measured the average slip along the fault with the recorded far-field displacements and strain changes, while acoustic emission sensors and local strain gages were used to capture local slip variations. We found that the average amount of aseismic slip during the preparatory stage increases with roughness, whereas precursory slip duration decreases with increased load point velocity. These results reveal a complex slip pattern on rough faults which leads to dynamic ruptures at high load point velocities

Geotechnical controls on erodibility in fluvial impact erosion

Bedrock incision by rivers is commonly driven by the impacts of moving bedload particles. The speed of incision is modulated by rock properties, which is quantified within a parameter known as erodibility that scales the erosion rate to the erosive action of the flow. Although basic models for the geotechnical controls on rock erodibility have been suggested, large scatter and trends in the remaining relationships indicate that they are incompletely understood. Here, we conducted dedicated laboratory experiments measuring erodibility using erosion mills. In parallel, we measured uniaxial compressive strength, tensile strength, Young's modulus, bulk density, and the Poisson's ratio for the tested lithologies. We find that under the same flow conditions, erosion rates of samples from the same lithology can vary by a factor of up to 60. This indicates that rock properties that may vary over short distances within the same rock can exert a strong control on its erosional properties. The geotechnical properties of the tested lithologies are strongly cross-correlated, preventing a purely empirical determination of their controls on erodibility. The currently prevailing model predicts that erosion rates should scale linearly with Young's modulus and inversely with the square of the tensile strength. We extend this model using first-principle physical arguments, taking into account the geotechnical properties of the impactor. The extended model provides a better description of the data than the existing model. Yet, the fit is far from satisfactory. We suggest that the ratio of mineral grain size to the impactor diameter presents a strong control on erodibility that has not been quantified so far. We also discuss how our laboratory results upscale to real landscapes and long timescales. For both a revised stream power incision model and a sediment-flux-dependent incision model, we suggest that long-term erosion rates scale linearly with erodibility and that, within this theoretical framework, relative laboratory measurements of erodibility can be applied at the landscape scale.</p

A novel hybrid material with calcium and strontium release capability

The preparation of PDMS–TEOS–CaO hybrid materials by sol–gel techniques has been widely described in previous works. Calcium nitrate is the most common source of calcium used in these preparations. However, to remove possible toxic nitrate by-products a thermal treatment is necessary at temperatures above 500 1C, which leads to the degradation of the polymeric components of the hybrids. Strontium has already shown some promising results in the therapeutic area, being used in cases of osteoporosis and low bone density. In this study a new potential bioactive hybrid material was prepared, by sol–gel techniques, using calcium acetate as a novel calcium source. Also, for the first time, incorporation of strontium in a PDMS–TEOS hybrid system was evaluated. Samples were characterized before and after immersion in Kokubo’s Simulated Body Fluid (SBF) by SEM, EDS, ICP and FT-IR spectroscopy

Identification of novel TMPRSS2:ERG mechanisms in prostate cancer metastasis: involvement of MMP9 and PLXNA2

International audienceProstate cancer (PCa) is one of the major public health problems in Western countries. Recently, the TMPRSS2:ERG gene fusion, which results in the aberrant expression of the transcription factor ERG, has been shown to be the most common gene rearrangement in PCa. Previous studies have determined the contributions of this fusion in PCa disease initiation and/or progression in vitro and in vivo. In this study on TMPRSS2:ERG regulation in PCa, we used an androgen receptor and TMPRSS2:ERG fusion double-negative PCa cell model: PC3c. In three cell clones with different TMPRSS2:ERG expression levels, ectopic expression of the fusion resulted in significant induction of cell migration and invasion in a dose-dependent manner. In agreement with this phenotype, high-throughput microarray analysis revealed that a set of genes, functionally associated with cell motility and invasiveness, were deregulated in a dose-dependent manner in TMPRSS2:ERG-expressing cells. Importantly, we identified increased MMP9 (Metalloproteinase 9) and PLXNA2 (Plexin A2) expression in TMPRSS2:ERG-positive PCa samples, and their expression levels were significantly correlated with ERG expression in a PCa cohort. In line with these findings, there was evidence that TMPRSS2:ERG directly and positively regulates MMP9 and PLXNA2 expression in PC3c cells. Moreover, PLXNA2 upregulation contributed to TMPRSS2:ERG-mediated enhancements of PC3c cell migration and invasion. Furthermore, and importantly, PLXNA2 expression was upregulated in metastatic PCa tumors compared with localized primary PCa tumors. This study provides novel insights into the role of the TMPRSS2:ERG fusion in PCa metastasis