TcdB of Clostridioides difficile Mediates RAS-Dependent Necrosis in Epithelial Cells

A Clostridioides difficile infection (CDI) is the most common nosocomial infection worldwide. The main virulence factors of pathogenic C. difficile are TcdA and TcdB, which inhibit small Rho-GTPases. The inhibition of small Rho-GTPases leads to the so-called cytopathic effect, a reorganization of the actin cytoskeleton, an impairment of the colon epithelium barrier function and inflammation. Additionally, TcdB induces a necrotic cell death termed pyknosis in vitro independently from its glucosyltransferases, which are characterized by chromatin condensation and ROS production. To understand the underlying mechanism of this pyknotic effect, we conducted a large-scale phosphoproteomic study. We included the analysis of alterations in the phosphoproteome after treatment with TcdA, which was investigated for the first time. TcdA exhibited no glucosyltransferase-independent necrotic effect and was, thus, a good control to elucidate the underlying mechanism of the glucosyltransferase-independent effect of TcdB. We found RAS to be a central upstream regulator of the glucosyltransferase-independent effect of TcdB. The inhibition of RAS led to a 68% reduction in necrosis. Further analysis revealed apolipoprotein C-III (APOC3) as a possible crucial factor of CDI-induced inflammation in vivo.     

Säurekatalysierte Umsetzungen von Aromaten mit Alkanen und Cycloalkanen. IX. Alkylierungen mit 2,2,4-Trimethylpentan (Isooctan)

Acid-catalyzed Reactions of Aromatic Hydrocarbons with Alkanes and Cycloalkanes. IX. Alkylations with 2,2,4-Trimethylpentane (Isooctane) The non-conventional alkylation of benzene, toluene, ethyl- and isopropylbenzene, fluoro- and chlorobenzene with 2,2,4-trimethylpentane in the presence of acid catalysts is described. The composition of the rather complex reaction mixtures is determined by gas-liquid chromatography and mass spectrometry, tert. butylarenes being the main products beside alkylsubstituted indanes and tetralines. Their formation is interpreted as a competition between fragmentation and isomerization of the alkylating agent. By use of trifluoromethanesulfonic acid or combinations of catalysts from HF or HSO₃F with variant metallic fluorides at lower temperatures the selectivity of the reaction may be partially raised.     

Correlation of III/V semiconductor etch results with physical parameters of high-density reactive plasmas excited by electron cyclotron resonance

Reactive ion etching is the interaction of reactive plasmas with surfaces. To obtain a detailed understanding of this process, significant properties of reactive composite low-pressure plasmas driven by electron cyclotron resonance (ECR) were investigated and compared with the radial uniformity of the etch rate. The determination of the electronic properties of chlorine-and hydrogen-containing plasmas enabled the understanding of the pressure-dependent behavior of the plasma density and provided better insights into the electronic parameters of reactive etch gases. From the electrical evaluation of I(V ) characteristics obtained using a Langmuir probe, plasmas of different compositions were investigated. The standard method of Druyvesteyn to derive the electron energy distribution functions by the second derivative of the I(V ) characteristics was replaced by a mathematical model which has been evolved to be more robust against noise, mainly, because the first derivative of the I(V ) characteristics is used. Special attention was given to the power of the energy dependence in the exponent. In particular, for plasmas that are generated by ECR with EM modes, the existence of Maxwellian distribution functions is not to be taken as a self-evident fact, but the bi-Maxwellian distribution was proven for Ar-and Kr-stabilized plasmas. In addition to the electron temperature, the global uniform discharge model has been shown to be useful for calculating the neutral gas temperature. To what extent the invasive method of using a Langmuir probe could be replaced with the non-invasive optical method of emission spectroscopy, particularly actinometry, was investigated, and the resulting data exhibited the same relative behavior as the Langmuir data. The correlation with etchrate data reveals the large chemical part of the removal process—most striking when the data is compared with etching in pure argon. Although the relative amount of the radial variation of plasma density and etch rate is approximately ±5%, the etch rate shows a slightly concave shape in contrast to the plasma density.     

Laser flash photolysis studies on homo-and copolymers of phenylisopropenyl ketone and of pivalophenone in solution

Benzene solutions of poly(phenylisopropenyl ketone) (PPIK), of copolymers of PIK and styrene and of phenyl-t-butyl ketone (pivalophenone) were irradiated with light flashes (duration 25 nsec) at wavelength 347 nm. The spectra observed at the end of the flash were attributed to the triplet state (T-T-spectra). A fraction of the triplets in the polymers was deactivated by T-T annihilation, as evidenced by lifetimes decreasing with increasing absorbed dose rate. Upon extrapolation to zero intensity the following triplet decay rate constants K_T were obtained:

$\text{(1.0 ± 0.1) 10}{}^7\text{sec}{}^{\mathrm{?}}\text{(}\text{PPIK}\text{),}$

$\text{(8 ± 1) 10}{}^6\text{sec}{}^{\mathrm{?1}}\text{(}\text{CPStPlK12}\text{), (6 ± 1) 10}{}^6\text{sec}{}^{\mathrm{?1}}\text{(}\text{CPStPlK3.7}\text{)}$

$\text{(3 ± 1) 10}{}^6\text{sec}{}^{\mathrm{?1}}\text{(}\text{CPStPlK1}\text{)}$

$\text{(2.5 ± 0.2) 10}{}^6\text{sec}{}^{\mathrm{?1}}\text{(}\text{pivalophenone}\text{)}$

.In PPIK and pivalophenone the dominant chemical route of triplet deactivation is α-cleavage. The relatively high k_T value found with PPIK is presumably due to next neighbour interaction. In copolymers with a high content of isolated PIK units type I processes (α-cleavage) become less probable due to weak next neighbour influence. Thus type II processes dominate in copolymers although being slower than type I processes in homo PPIK. The rate constant of the reaction of PIK triplets in homo PPIK with 2-propanol in benzene solution is (2.0 ± 0.2)10⁶ l/mol sec, whereas pivalophenone triplets react almost 10 times slower with 2-propanol. The difference is assumed to be due to a rather strong interaction of 2-propanol with ground state as well as with excited pivalophenone.     

Monoclinic Zirconia Bodies by Thermoplastic Ceramic Extrusion

Two ultrafine, undoped ZrO₂ powders with median primary particle sizes of 9 and 25 nm were used to prepare ceramic suspensions for thermoplastic extrusion. The organic vehicle consisted of an industrial-grade poly(ethylene- co -vinyl acetate) (EVA) or polyethylene (PE-HD) and decanoic acid as a dispersing agent. The powder volume loadings achieved were 44% and 52% by volume for the two powders, respectively. The amount of dispersant needed was calculated from a new model based on available chemisorption sites on the powder surface. Mixing and extrusion were conducted using a conventional modular plastic processing unit. Green bodies were dewaxed up to 450°C in an inert atmosphere and sintered to full density in air at 1060° and 1100°C, respectively. Analysis of the ceramic phase content and the microstructure of the bodies is presented.     

Toughness Optimization of SBR Elastomers – Use of Fracture Mechanics Methods for Characterization

Elastomer materials are used in a wide application range and subjected to different loading from which failure of the material results. Because this failure is caused by initiation and propagation of cracks, the application of fracture mechanics methods for the assessment of the material is obvious. A short summary of the methods of technical fracture mechanics including possibilities of determination of crack resistance curves is given. Vulcanizates on the basis of SBR 1500 with various sulfur and carbon black contents were investigated. For describing the crack initiation and crack propagation behavior, several fracture mechanics examination methods were applied. Tear‐analyzer results were used to assess the crack propagation behavior under fatigue‐like loading conditions. Furthermore, for the characterization of the crack resistance of the materials under impact‐like loading conditions, instrumented tensile‐impact tests were performed. To obtain information about the initiation and propagation of a stable crack, quasi‐static fracture mechanics tests were applied. The results of the several tests are discussed in dependence on sulfur and carbon black contents. We found a non‐monotonous behavior of the toughness as a function of carbon black loading. An explanation is given in connection with a percolation‐like transition in filler morphology on larger length scales.

Schematic crack propagation curve for characterizing the fatigue behavior of the vulcanizates recorded in a TFA test.     

SiCN ceramics with controllable carbon nanomaterials for electromagnetic absorption performance

Different kinds of carbon nanomaterials, free carbon (C_free), graphene, and N-containing graphene (NG), in single-source-precursors-derived SiCN ceramics, were in situ generated by modifying polysilazane with divinylbenzene, dopamine hydrochloride and melamine, respectively. Adjusting the carbon source brings phase structure and electromagnetic wave absorption (EMA) properties differences of SiCN/C ceramics. In situ C_free enhances the EMA capacity of SiCN ceramics by improving their electrical conductivity of 9.2 × 10⁻⁴ S/cm. The electrical conductivity of SiCN ceramics with 2D graphene sheets balloons to 2.5 × 10⁻³ S/cm, causing poor impedance match thus leading to a worse EMA performance. In situ NG in SiCN ceramics has a low electrical conductivity of 5.6 × 10⁻⁸ S/cm, making for excellent impedance match. The corrugated NG boosts dielectric loss, interfacial, and dipole polarization. NG-SiCN nanocomposites possess an outstanding EMA performance with RL_min of −61.08 dB and effective absorption bandwidth of 4.05 GHz, which are ∼2.4 times lower and ∼4 times higher than those of SiCN, respectively.     

A Novel Coenzyme A Analogue in the Anaerobic,Sulfate-Reducing,Marine Bacterium Desulfobacula toluolica Tol2T

Coenzyme A (CoA) thioesters are formed during anabolic and catabolic reactions in every organism. Degradation pathways of growth-supporting substrates in bacteria can be predicted by differential proteogenomic studies. Direct detection of proposed metabolites such as CoA thioesters by high-performance liquid chromatography coupled with high-resolution mass spectrometry can confirm the reaction sequence and demonstrate the activity of these degradation pathways. In the metabolomes of the anaerobic sulfate-reducing bacterium Desulfobacula toluolica Tol2^T grown with different substrates various CoA thioesters, derived from amino acid, fatty acid or alcohol metabolism, have been detected. Additionally, the cell extracts of this bacterium revealed a number of CoA analogues with molecular masses increased by 1 dalton. By comparing the chromatographic and mass spectrometric properties of synthetic reference standards with those of compounds detected in cell extracts of D. toluolica Tol2^T and by performing co-injection experiments, these analogues were identified as inosino-CoAs. These CoA thioesters contain inosine instead of adenosine as the nucleoside. To the best of our knowledge, this finding represents the first detection of naturally occurring inosino-CoA analogues.     

SELF-ADHESION HYSTERESIS IN POLYDIMETHYLSILOXANE ELASTOMERS

The interphase between a polyimide and a metal substrate was modeled by depositing phthalic anhydride (PA) onto a silver substrate pretreated with meta-aminothiophenol (m-ATP) and then curing in a mixture of acetic anhydride and pyridine or triethylamine. Surface-enhanced Raman scattering (SERS) and reflection-absorption infrared spectroscopy (RAIR) were used to determine the molecular structure of the interphase. It was found that m-ATP was adsorbed dissociatively onto silver substrates through the thiol groups. The tilt angle for m-ATP molecules adsorbed on silver substrates was determined using RAIR to be approximately 39°. However, there was no preferred rotational angle of the adsorbed APDS molecules about the molecular axes. When PA was deposited onto m-ATP pretreated silver substrates, anhydride groups of PA reacted with amino groups of m-ATP to form amic acids. When PA/m-ATP/Ag samples were chemically cured in acetic anhydride and pyridine or triethylamine, isoimide was the predominant product regardless of the use of pyridine or triethylamine as catalyst. These results were different from those obtained from PA/APDS/Au systems in which imide was the major product in the presence of triethylamine. These differences in the relative composition of cured products between two model systems were explained by the effect of substituents attached to APDS and m-ATP benzene rings.