Role of temperature on nonlinear cardiac dynamics.

Thermal effects affecting spatiotemporal behavior of cardiac tissue are discussed by relating temperature variations to proarrhythmic dynamics in the heart. By introducing a thermoelectric coupling in a minimal model of cardiac tissue, we are able to reproduce experimentally measured dynamics obtained simultaneously from epicardial and endocardial canine right ventricles at different temperatures. A quantitative description of emergent proarrhythmic properties of restitution, conduction velocity, and alternans regimes as a function of temperature is presented. Complex discordant alternans patterns that enhance tissue dispersion consisting of one wave front and three wave backs are described in both simulations and experiments. Possible implications for model generalization are finally discussed

Antimicrobial and plant growth-promoting properties of the cacao endophyte Bacillus subtilis ALB629.

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Active Faulting in Lake Constance (Austria, Germany, Switzerland) Unraveled by Multi-Vintage Reflection Seismic Data

Probabilistic seismic hazard assessments are primarily based on instrumentally recorded and historically documented earthquakes. For the northern part of the European Alpine Arc, slow crustal deformation results in low earthquake recurrence rates and brings up the necessity to extend our perspective beyond the existing earthquake catalog. The overdeepened basin of Lake Constance (Austria, Germany, and Switzerland), located within the North-Alpine Molasse Basin, is investigated as an ideal (neo-) tectonic archive. The lake is surrounded by major tectonic structures and constrained via the North Alpine Front in the South, the Jura fold-and-thrust belt in the West, and the Hegau-Lake Constance Graben System in the North. Several fault zones reach Lake Constance such as the St. Gallen Fault Zone, a reactivated basement-rooted normal fault, active during several phases from the Permo-Carboniferous to the Mesozoic. To extend the catalog of potentially active fault zones, we compiled an extensive 445 km of multi-channel reflection seismic data in 2017, complementing a moderate-size GI-airgun survey from 2016. The two datasets reveal the complete overdeepened Quaternary trough and its sedimentary infill and the upper part of the Miocene Molasse bedrock. They additionally complement existing seismic vintages that investigated the mass-transport deposit chronology and Mesozoic fault structures. The compilation of 2D seismic data allowed investigating the seismic stratigraphy of the Quaternary infill and its underlying bedrock of Lake Constance, shaped by multiple glaciations. The 2D seismic sections revealed 154 fault indications in the Obersee Basin and 39 fault indications in the Untersee Basin. Their interpretative linkage results in 23 and five major fault planes, respectively. One of the major fault planes, traceable to Cenozoic bedrock, is associated with a prominent offset of the lake bottom on the multibeam bathymetric map. Across this area, high-resolution single channel data was acquired and a transect of five short cores was retrieved displaying significant sediment thickness changes across the seismically mapped fault trace with a surface-rupture related turbidite, all indicating repeated activity of a likely seismogenic strike-slip fault with a normal faulting component. We interpret this fault as northward continuation of the St. Gallen Fault Zone, previously described onshore on 3D seismic data

Interaction between SNAI2 and MYOD enhances oncogenesis and suppresses differentiation in Fusion Negative Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is an aggressive pediatric malignancy of the muscle, that includes Fusion Positive (FP)-RMS harboring PAX3/7-FOXO1 and Fusion Negative (FN)-RMS commonly with RAS pathway mutations. RMS express myogenic master transcription factors MYOD and MYOG yet are unable to terminally differentiate. Here, we report that SNAI2 is highly expressed in FN-RMS, is oncogenic, blocks myogenic differentiation, and promotes growth. MYOD activates SNAI2 transcription via super enhancers with striped 3D contact architecture. Genome wide chromatin binding analysis demonstrates that SNAI2 preferentially binds enhancer elements and competes with MYOD at a subset of myogenic enhancers required for terminal differentiation. SNAI2 also suppresses expression of a muscle differentiation program modulated by MYOG, MEF2, and CDKN1A. Further, RAS/MEK-signaling modulates SNAI2 levels and binding to chromatin, suggesting that the differentiation blockade by oncogenic RAS is mediated in part by SNAI2. Thus, an interplay between SNAI2, MYOD, and RAS prevents myogenic differentiation and promotes tumorigenesis

Histone hyperacetylation disrupts core gene regulatory architecture in rhabdomyosarcoma

Core regulatory transcription factors (CR TFs) orchestrate the placement of super-enhancers (SEs) to activate transcription of cell-identity specifying gene networks, and are critical in promoting cancer. Here, we define the core regulatory circuitry of rhabdomyosarcoma and identify critical CR TF dependencies. These CR TFs build SEs that have the highest levels of histone acetylation, yet paradoxically the same SEs also harbor the greatest amounts of histone deacetylases. We find that hyperacetylation selectively halts CR TF transcription. To investigate the architectural determinants of this phenotype, we used absolute quantification of architecture (AQuA) HiChIP, which revealed erosion of native SE contacts, and aberrant spreading of contacts that involved histone acetylation. Hyperacetylation removes RNA polymerase II (RNA Pol II) from core regulatory genetic elements, and eliminates RNA Pol II but not BRD4 phase condensates. This study identifies an SE-specific requirement for balancing histone modification states to maintain SE architecture and CR TF transcription