Infection of Human Coronary Artery Endothelial Cells by Group B Streptococcus Contributes to Dysregulation of Apoptosis, Hemostasis, and Innate Immune Responses

Early onset sepsis due to group B streptococcus leads to neonatal morbidity, increased mortality, and long-term neurological deficencies. Interaction between septicemic GBS and confluent monolayers of human coronary artery endothelial cells (HCAECs) was analyzed by genome wide expression profiling. In total, 124 genes were differentially expressed (89 upregulated, 35 downregulated) based on a more than 3-fold difference to control HCAEC. Regulated genes are involved in apoptosis, hemostasis, oxidative stress response, infection, and inflammation. Regulation of selected genes and proteins identified in the gene array analysis was confirmed by Real-time RT-PCR assay (granulocyte chemotactic protein 2), ELISA (urokinase, cyclooxygenase 2, granulocyte chemotactic protein 1), and western blotting (Heme oxygenase1, BCL2 interacting protein) at various time points between 4 and 24 hours. These results indicate that GBS infection might influence signalling pathways leading to impaired function of the innate immune system and hemorrhagic and inflammatory complications during GBS sepsis

Designing a model for the global energy system—GENeSYS-MOD : an application of the Open-Source Energy Modeling System (OSeMOSYS)

This paper develops a path for the global energy system up to 2050, presenting a new application of the open-source energy modeling system (OSeMOSYS) to the community. It allows quite disaggregate energy and emission analysis: Global Energy System Model (GENeSYS-MOD) uses a system of linear equations of the energy system to search for lowest-cost solutions for a secure energy supply, given externally defined constraints, mainly in terms of CO2-emissions. The general algebraic modeling system (GAMS) version of OSeMOSYS is updated to the newest version and, in addition, extended and enhanced to include e.g., a modal split for transport, an improved trading system, and changes to storages. The model can be scaled from small-scale applications, e.g., a company, to cover the global energy system. The paper also includes an application of GENeSYS-MOD to analyze decarbonization scenarios at the global level, broken down into 10 regions. Its main focus is on interdependencies between traditionally segregated sectors: electricity, transportation, and heating; which are all included in the model. Model calculations suggests that in order to achieve the 1.5–2 C target, a combination of renewable energy sources provides the lowest-cost solution, solar photovoltaic being the dominant source. Average costs of electricity generation in 2050 are about 4 cents/kWh (excluding infrastructure and transportation costs).DFG, 325093850, Open Access Publizieren 2017 - 2018 / Technische Universität Berli

Designing a global energy system based on 100% renewables for 2050 - GENeSYS-MOD: An application of the open-source energy modelling system (OSeMOSYS)

This paper develops a path for the global energy system up to 2050, presenting a new application of the open source energy systems model OSeMOSYS to the community. It allows quite disaggregate energy and emission analysis: GENeSYS-MOD (Global Energy System Model) uses a system of linear equations of the energy system to search for lowestcost solutions for a secure energy supply, given externally defined constraints, mainly in terms of CO2-emissions. The General Algebraic Modeling System (GAMS) version of OSeMOSYS is updated to the newest version and, in addition, extended and enhanced to include e.g. a modal split for transport, an improved trading system, and changes to storages. The model can be scaled from small-scale applications, e.g. a company, to cover the global energy system. The paper also includes an application of GENeSYS-MOD to analyze decarbonization scenarios at the global level, broken down into 10 regions. Its main focus is on interdependencies between traditionally segregated sectors: electricity, transportation, and heating. Model calculations suggests that in order to achieve the 1.5ê-2ê C target, a combination of renewable energy sources provides the lowest-cost solution, solar photovoltaic being the dominant source. Average costs of electricity generation in 2050 are about 4 €cents/kWh (excluding infrastructure and transportation costs)

GRHydro: a new open-source general-relativistic magnetohydrodynamics code for the Einstein toolkit

We present the new general-relativistic magnetohydrodynamics (GRMHD) capabilities of the Einstein toolkit, an open-source community-driven numerical relativity and computational relativistic astrophysics code. The GRMHD extension of the toolkit builds upon previous releases and implements the evolution of relativistic magnetized fluids in the ideal MHD limit in fully dynamical spacetimes using the same shock-capturing techniques previously applied to hydrodynamical evolution. In order to maintain the divergence-free character of the magnetic field, the code implements both constrained transport and hyperbolic divergence cleaning schemes. We present test results for a number of MHD tests in Minkowski and curved spacetimes. Minkowski tests include aligned and oblique planar shocks, cylindrical explosions, magnetic rotors, Alfvén waves and advected loops, as well as a set of tests designed to study the response of the divergence cleaning scheme to numerically generated monopoles. We study the code's performance in curved spacetimes with spherical accretion onto a black hole on a fixed background spacetime and in fully dynamical spacetimes by evolutions of a magnetized polytropic neutron star and of the collapse of a magnetized stellar core. Our results agree well with exact solutions where these are available and we demonstrate convergence. All code and input files used to generate the results are available on http://einsteintoolkit.org. This makes our work fully reproducible and provides new users with an introduction to applications of the code

D,L-Lysine-Acetylsalicylate + Glycine (LASAG) Reduces SARS-CoV-2 Replication and Shows an Additive Effect with Remdesivir

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease-19 (COVID-19) is still challenging healthcare systems and societies worldwide. While vaccines are available, therapeutic strategies are developing and need to be adapted to each patient. Many clinical approaches focus on the repurposing of approved therapeutics against other diseases. However, the efficacy of these compounds on viral infection or even harmful secondary effects in the context of SARS-CoV-2 infection are sparsely investigated. Similarly, adverse effects of commonly used therapeutics against lifestyle diseases have not been studied in detail. Using mono cell culture systems and a more complex chip model, we investigated the effects of the acetylsalicylic acid (ASA) salt D,L-lysine-acetylsalicylate + glycine (LASAG) on SARS-CoV-2 infection in vitro. ASA is commonly known as Aspirin ® and is one of the most frequently used medications worldwide. Our data indicate an inhibitory effect of LASAG on SARS-CoV-2 replication and SARS-CoV-2-induced expression of pro-inflammatory cytokines and coagulation factors. Remarkably, our data point to an additive effect of the combination of LASAG and the antiviral acting drug remdesivir on SARS-CoV-2 replication in vitro

Noncovalent Functionalization and Passivation of Black Phosphorus with Optimized Perylene Diimides for Hybrid Field Effect Transistors

Amongst the different existing methods to passivate black phosphorus (BP) from environmental degradation, the noncovalent functionalization with perylene diimides (PDI) has been postulated as one of the most promising routes because it allows preserving its electronic properties. This work describes the noncovalent functionalization and outstanding environmental protection of BP with tailor made PDI having peri-amide aromatic side chains, which include phenyl and naphthyl groups, exhibiting a significantly increased molecule-BP interaction. These results are rationalized by density functional theory (DFT) calculations showing that the adsorption energies are mainly governed by van der Waals (vdW) interactions and increase concomitantly with the aromatic character of the side chains. The resulting hybrids are thoroughly characterized showing enhanced ambient and thermal stabilities. Last but not least, hybrid organic-inorganic BP-PDI field effect transistors (FETs) are studied for the first time showing the usefulness of PDI derivatives as efficient passivation layers while obtaining improved values of electron mobilities. These results pave the way for the use of optimized PDIs by molecular engineering to preserve the electronic properties of BP FETs, using straightforward wet chemical approaches

Identification of a regulatory pathway inhibiting adipogenesis via RSPO2

Healthy adipose tissue remodeling depends on the balance between de novo adipogenesis from adipogenic progenitor cells and the hypertrophy of adipocytes. De novo adipogenesis has been shown to promote healthy adipose tissue expansion, which confers protection from obesity-associated insulin resistance. Here, we define the role and trajectory of different adipogenic precursor subpopulations and further delineate the mechanism and cellular trajectory of adipogenesis, using single-cell RNA-sequencing datasets of murine adipogenic precursors. We identify Rspo2 as a functional regulator of adipogenesis, which is secreted by a subset of CD142$^{+}$ cells to inhibit maturation of early progenitors through the receptor Lgr4. Increased circulating RSPO2 in mice leads to adipose tissue hypertrophy and insulin resistance and increased RSPO2 levels in male obese individuals correlate with impaired glucose homeostasis. Taken together, these findings identify a complex cellular crosstalk that inhibits adipogenesis and impairs adipose tissue homeostasis

Osteocytes Serve as a Reservoir for Intracellular Persisting Staphylococcus aureus Due to the Lack of Defense Mechanisms

Chronic staphylococcal osteomyelitis can persist for long time periods causing bone destruction. The ability of Staphylococcus aureus to develop chronic infections is linked to its capacity to invade and replicate within osteoblasts and osteocytes and to switch to a dormant phenotype called small colony variants. Recently, osteocytes were described as a main reservoir for this pathogen in bone tissue. However, the mechanisms involved in the persistence of S. aureus within these cells are still unknown. Here, we investigated the interaction between S. aureus and osteoblasts or osteocytes during infection. While osteoblasts are able to induce a strong antimicrobial response and eliminate intracellular S. aureus , osteocytes trigger signals to recruit immune cells and enhance inflammation but fail an efficient antimicrobial activity to clear the bacterial infection. Moreover, we found that extracellular signals from osteocytes enhance intracellular bacterial clearance by osteoblasts. Even though both cell types express Toll-like receptor (TLR) 2, the main TLR responsible for S. aureus detection, only osteoblasts were able to increase TLR2 expression after infection. Additionally, proteomic analysis indicates that reduced intracellular bacterial killing activity in osteocytes is related to low antimicrobial peptide expression. Nevertheless, high levels of lipid mediators and cytokines were secreted by osteocytes, suggesting that they can contribute to inflammation. Taken together, our results demonstrate that osteocytes contribute to severe inflammation observed in osteomyelitis and represent the main niche for S. aureus persistence due to their poor capacity for intracellular antimicrobial response