Filling the Gaps in the Kirromycin Biosynthesis: Deciphering the Role of Genes Involved in Ethylmalonyl-CoA Supply and Tailoring Reactions

Kirromycin is the main product of the soil-dwelling Streptomyces collinus Tü 365. The elucidation of the biosynthetic pathway revealed that the antibiotic is synthesised via a unique combination of trans-/cis-AT type I polyketide synthases and non-ribosomal peptide synthetases (PKS I/NRPS). This was the first example of an assembly line integrating the three biosynthetic principles in one pathway. However, information about other enzymes involved in kirromycin biosynthesis remained scarce.\ua0In this study, genes encoding tailoring enzymes KirM, KirHVI, KirOI, and KirOII, and the putative crotonyl-CoA reductase/carboxylase KirN were deleted, complemented, and the emerged products analysed by HPLC-HRMS and MS/MS. Derivatives were identified in mutants ΔkirM, ΔkirHVI, ΔkirOI, and ΔkirOII. The products of ΔkirOI, ΔkirOII, and kirHVI were subjected to 2D-NMR for structure elucidation. Our results enabled functional assignment of those enzymes, demonstrating their involvement in kirromycin tailoring. In the ΔkirN mutant, the production of kirromycin was significantly decreased. The obtained data enabled us to clarify the putative roles of the studied enzymes, ultimately allowing us to fill many of the missing gaps in the biosynthesis of the complex antibiotic. Furthermore, this collection of mutants can serve as a toolbox for generation of new kirromycins

Using SDRT to analyze pathological conversations. Logicality, rationality and pragmatic deviances

International audienceSchizophrenia is well-known among mental illnesses for the severity of the thought dis- orders it involves, and for their widespread and spectacular manifestations ranging from deviant social behavior to delusion, not to mention affective and sensory distortions. Confronted with such a pathological con- versation, any "ordinary" speaker intuitively feels that there are some incoherencies or discontinuities. The aim of this research is to account for these using both pragmatics and formal semantics. Linguistics, especially semantics and pragmatics, is thus central to this work

Differential effects of lung inflammation on insulin resistance in humans and mice

BACKGROUND: The rates of obesity, its associated diseases, and allergies are raising at alarming rates in most countries. House dust mites (HDM) are highly allergenic and exposure often associates with an urban sedentary indoor lifestyle, also resulting in obesity. The aim of this study was to investigate the epidemiological association and physiological impact of lung inflammation on obesity and glucose homeostasis. METHODS: Epidemiological data from 2207 adults of the population-based KORA FF4 cohort were used to test associations between asthma and rhinitis with metrics of body weight and insulin sensitivity. To obtain functional insights, C57BL/6J mice were intranasally sensitized and challenged with HDM and simultaneously fed with either low-fat or high-fat diet for 12 weeks followed by a detailed metabolic and biochemical phenotyping of the lung, liver, and adipose tissues. RESULTS: We found a direct association of asthma with insulin resistance but not body weight in humans. In mice, co-development of obesity and HDM-induced lung inflammation attenuated inflammation in lung and perigonadal fat, with little impact on body weight, but small shifts in the composition of gut microbiota. Exposure to HDM improved glucose tolerance, reduced hepatosteatosis, and increased energy expenditure and basal metabolic rate. These effects associate with increased activity of thermogenic adipose tissues independent of uncoupling protein 1. CONCLUSIONS: Asthma associates with insulin resistance in humans, but HDM challenge results in opposing effects on glucose homeostasis in mice due to increased energy expenditure, reduced adipose inflammation, and hepatosteatosis

Present and future of high-temperature superconductor quantum-based voltage standards

This paper presents a brief overview of the current state-of-the-art of Josephson junctions for Quantum-based Voltage Standards fabricated with High-Temperature Superconductors (HTS). A short introduction on the history and technical evolution of Low Temperature Superconductors (LTS) technology is provided for non-specialists. Then HTS technology is summarized and discussed in the context of quantum voltage standard applications. Finally, the two most promising technologies: bicrystal and Focused Helium-Ion Beam junctions are discussed with more detail, analyzing strength, limitations and perspectives in both cases

Feasibility studies of the time-like proton electromagnetic form factor measurements with PANDA at FAIR

The possibility of measuring the proton electromagnetic form factors in the time-like region at FAIR with the \PANDA detector is discussed. Detailed simulations on signal efficiency for the annihilation of $\bar p +p$ into a lepton pair as well as for the most important background channels have been performed. It is shown that precision measurements of the differential cross section of the reaction $\bar p +p \to e^++ e^-$ can be obtained in a wide angular and kinematical range. The individual determination of the moduli of the electric and magnetic proton form factors will be possible up to a value of momentum transfer squared of $q^2\simeq 14$ (GeV/c)$^2$. The total $\bar p +p\to e^++e^-$ cross section will be measured up to $q^2\simeq 28$ (GeV/c)$^2$. The results obtained from simulated events are compared to the existing data. Sensitivity to the two photons exchange mechanism is also investigated.Comment: 12 pages, 4 tables, 8 figures Revised, added details on simulations, 4 tables, 9 figure

7-Chloro-4-[(E)-N′-(4-fluoro­benzyl­idene)hydrazin­yl]quinoline monohydrate

The mol­ecule of the title hydrate, C16H11ClFN3·H2O, is slightly twisted, as indicated by the dihedral angle of 9.55 (10)° formed between the quinoline ring system and the benzene ring. The conformation about the C=N double bond is E, and the amine-H atom is oriented towards the quinoline residue. In the crystal structure, the water mol­ecule accepts an N—H⋯O and makes two O—H⋯Nquinoline hydrogen bonds, generating a two-dimensional array in the ab plane, which is further stabilized by C—H⋯O inter­actions. The most significant contacts between layers are of the type C—H⋯F

Feasibility studies of time-like proton electromagnetic form factors at PANDA at FAIR

Simulation results for future measurements of electromagnetic proton form factors at \PANDA (FAIR) within the PandaRoot software framework are reported. The statistical precision with which the proton form factors can be determined is estimated. The signal channel $\bar p p \to e^+ e^-$ is studied on the basis of two different but consistent procedures. The suppression of the main background channel, $\textit{i.e.}$ $\bar p p \to \pi^+ \pi^-$, is studied. Furthermore, the background versus signal efficiency, statistical and systematical uncertainties on the extracted proton form factors are evaluated using two different procedures. The results are consistent with those of a previous simulation study using an older, simplified framework. However, a slightly better precision is achieved in the PandaRoot study in a large range of momentum transfer, assuming the nominal beam conditions and detector performance

Study of J/ψJ/\psi and ψ(3686)→Σ(1385)0Σˉ(1385)0\psi(3686)\rightarrow\Sigma(1385)^{0}\bar\Sigma(1385)^{0} and Ξ0Ξˉ0\Xi^0\bar\Xi^{0}

We study the decays of $J/\psi$ and $\psi(3686)$ to the final states $\Sigma(1385)^{0}\bar\Sigma(1385)^{0}$ and $\Xi^0\bar\Xi^{0}$ based on a single baryon tag method using data samples of $(1310.6 \pm 7.0) \times 10^{6}$ $J/\psi$ and $(447.9 \pm 2.9) \times 10^{6}$ $\psi(3686)$ events collected with the BESIII detector at the BEPCII collider. The decays to $\Sigma(1385)^{0}\bar\Sigma(1385)^{0}$ are observed for the first time. The measured branching fractions of $J/\psi$ and $\psi(3686)\rightarrow\Xi^0\bar\Xi^{0}$ are in good agreement with, and much more precise, than the previously published results. The angular parameters for these decays are also measured for the first time. The measured angular decay parameter for $J/\psi\rightarrow\Sigma(1385)^{0}\bar\Sigma(1385)^{0}$, $\alpha =-0.64 \pm 0.03 \pm 0.10$, is found to be negative, different to the other decay processes in this measurement. In addition, the "12\% rule" and isospin symmetry in the $J/\psi$ and $\psi(3686)\rightarrow\Xi\bar\Xi$ and $\Sigma(1385)\bar{\Sigma}(1385)$ systems are tested.Comment: 11 pages, 7 figures. This version is consistent with paper published in Phys.Lett. B770 (2017) 217-22

Observation of an anomalous line shape of the η′π+π−\eta^{\prime}\pi^{+}\pi^{-} mass spectrum near the ppˉp\bar{p} mass threshold in J/ψ→γη′π+π−J/\psi\rightarrow\gamma\eta^{\prime}\pi^{+}\pi^{-}

Using $1.09\times10^{9}$ $J/\psi$ events collected by the BESIII experiment in 2012, we study the $J/\psi\rightarrow\gamma\eta^{\prime}\pi^{+}\pi^{-}$ process and observe a significant abrupt change in the slope of the $\eta^{\prime}\pi^{+}\pi^{-}$ invariant mass distribution at the proton-antiproton ($p\bar{p}$) mass threshold. We use two models to characterize the $\eta^{\prime}\pi^{+}\pi^{-}$ line shape around $1.85~\text{GeV}/c^{2}$: one which explicitly incorporates the opening of a decay threshold in the mass spectrum (Flatt\'{e} formula), and another which is the coherent sum of two resonant amplitudes. Both fits show almost equally good agreement with data, and suggest the existence of either a broad state around $1.85~\text{GeV}/c^{2}$ with strong couplings to $p\bar{p}$ final states or a narrow state just below the $p\bar{p}$ mass threshold. Although we cannot distinguish between the fits, either one supports the existence of a $p\bar{p}$ molecule-like state or bound state with greater than $7\sigma$ significance