Leptin receptor signaling regulates protein synthesis pathways and neuronal differentiation in pluripotent stem cells

The role of leptin receptor (OB-R) signaling in linking pluripotency with growth and development and the consequences of dysfunctional leptin signaling on progression of metabolic disease is poorly understood. Using a global unbiased proteomics approach we report that embryonic fibroblasts (MEFs) carrying the db/db mutation exhibit metabolic abnormalities, while their reprogrammed induced pluripotent stem cells (iPSCs) show altered expression of proteins involved in embryonic development. An upregulation in expression of eukaryotic translation initiation factor 4e (Eif4e) and Stat3 binding to the Eif4e promoter was supported by enhanced protein synthesis in mutant iPSCs. Directed differentiation of db/db iPSCs toward the neuronal lineage showed defects. Gene editing to correct the point mutation in db/db iPSCs using CRISPR-Cas9, restored expression of neuronal markers and protein synthesis while reversing the metabolic defects. These data imply a direct role for OB-R in regulating metabolism in embryonic fibroblasts and key developmental pathways in iPSCs.publishedVersio

Hydrothermal dolomitization of basinal deposits controlled by a synsedimentary fault system in Triassic extensional setting, Hungary

Dolomitization of relatively thick carbonate successions occurs via an effective fluid circulation mechanism, since the replacement process requires a large amount of Mg-rich fluid interacting with the CaCO3 precursor. In the western end of the Neotethys, fault-controlled extensional basins developed during the Late Triassic spreading stage. In the Buda Hills and Danube-East blocks, distinct parts of silica and organic matter-rich slope and basinal deposits are dolomitized. Petrographic, geochemical, and fluid inclusion data distinguished two dolomite types: (1) finely to medium crystalline and (2) medium to coarsely crystalline. They commonly co-occur and show a gradual transition. Both exhibit breccia fabric under microscope. Dolomite texture reveals that the breccia fabric is not inherited from the precursor carbonates but was formed during the dolomitization process and under the influence of repeated seismic shocks. Dolomitization within the slope and basinal succession as well as within the breccia zones of the underlying basement block is interpreted as being related to fluid originated from the detachment zone and channelled along synsedimentary normal faults. The proposed conceptual model of dolomitization suggests that pervasive dolomitization occurred not only within and near the fault zones. Permeable beds have channelled the fluid towards the basin centre where the fluid was capable of partial dolomitization. The fluid inclusion data, compared with vitrinite reflectance and maturation data of organic matter, suggest that the ascending fluid was likely hydrothermal which cooled down via mixing with marine-derived pore fluid. Thermal gradient is considered as a potential driving force for fluid flow

Mid-Crustal Focused Fluid Movement: Thermal Consequences and Silica Transport

Numerical models have been constructed to assess the thermal consequences and silica transport that would result if water released by regional metamorphic dehydration or cooling plutons were focused into large-scale (10 km) fracture zones. Two fracture zone model geometries have been considered, in one the fracture zone is planar, and in the other the fracture zone is radially symmetric. In both models dispersion and collection of fluids is simulated. The model results indicate that for planar or radially symmetric fracture zones, hydrothermal flow rates must approach 0.1 g/s (per m crack length) or 1 kg/s, respectively, to produce significant thermal effects. Given that regional metamorphic fluid fluxes are probably < 10−9 kg/m2−s, generation of a thermal ano-maly by fluids released during metamorphic dehydration into a planar fracture zone requires an unrealistic degree of lateral flow (>50 km). The collection area required to produce a detectable heating effect about a radially symmetric fracture zone is smaller (a radius of ∼ ∼ 15 km), but also implausibly large. These scales suggest tha

Acoustic and petrophysical properties of mechanically compacted overconsolidated sands: part 1 – experimental results

This paper part one is set out to lay primary observations of experimental compaction measurements to form the basis for rock physics modelling in paper part two. P‐ and S‐wave velocities and corresponding petrophysical (porosity and density) properties of seven unconsolidated natural sands with different mineralogical compositions and textures are reported. The samples were compacted in a uniaxial strain configuration from 0.5 up to 30 MPa effective stresses. Each sand sample was subjected to three loading cycles to study the influence of stress reduction on acoustic velocities and rock physical properties with the key focus on simulating a complex burial history with periods of uplift. Results show significant differences in rock physical properties between normal compaction and overconsolidation (unloaded and reloaded). The differences observed for total porosity, density, and P‐ and S‐wave velocities are attributed to irrecoverable permanent deformation. Microtextural differences affect petrophysical, acoustic, elastic and mechanical properties, mostly during normal consolidation but are less significant during unloading and reloading. Different pre‐consolidation stress magnitudes, stress conditions (isotropic or uniaxial) and mineral compositions do not significantly affect the change in porosity and velocities during unloading as a similar steep velocity–porosity gradient is observed. The magnitude of change in the total porosity is low compared to the associated change in P‐ and S‐wave velocities during stress release. This can be explained by the different sensitivity of the porosity and acoustic properties (velocities) to the change in stress. Stress reduction during unloading yields maximum changes in the total porosity, P‐ and S‐wave velocities of 5%, 25%, and 50%, respectively. These proportions constitute the basis for the following empirical (approximation) correlations: Δϕ ∼ ±5 ΔVP and ΔVP ∼ ±2ΔVS. The patterns observed in the experiments are similar to well log data from the Barents Sea. Applications to rock physics modelling and reservoir monitoring are reported in a companion paper.acceptedVersio