Meroterpenoids are mixed polyketide-terpenoid natural products with a broad range of biological activities. Herein, we present the structures of four new meroterpenoid antibiotics, merochlorins A-D, produced by the marine bacterium Streptomyces sp. strain CNH-189, which possess novel chemical skeletons unrelated to known bacterial agents. Draft genome sequencing, mutagenesis, and heterologous biosynthesis in the genome-minimized model actinomycete Streptomyces coelicolor provided the 57.6 kb merochlorin gene cluster that contains two genes encoding rare bacterial vanadium-dependent haloperoxidase (VHPO) genes. Pathway expression of two different fosmid clones that differ largely by the presence or absence of the VHPO gene mcl40 resulted in the differential biosynthesis of merochlorin C, suggesting that Mcl40 catalyzes an unprecedented 15-membered chloronium-induced macrocyclization reaction converting merochlorin D to merochlorin C. 相似文献
Temporal information provided by cochlear implants enables successful speech perception in quiet, but limited spectral information precludes comparable success in voice perception. Talker identification and speech decoding by young hearing children (5-7 yr), older hearing children (10-12 yr), and hearing adults were examined by means of vocoder simulations of cochlear implant processing. In Experiment 1, listeners heard vocoder simulations of sentences from a man, woman, and girl and were required to identify the talker from a closed set. Younger children identified talkers more poorly than older listeners, but all age groups showed similar benefit from increased spectral information. In Experiment 2, children and adults provided verbatim repetition of vocoded sentences from the same talkers. The youngest children had more difficulty than older listeners, but all age groups showed comparable benefit from increasing spectral resolution. At comparable levels of spectral degradation, performance on the open-set task of speech decoding was considerably more accurate than on the closed-set task of talker identification. Hearing children's ability to identify talkers and decode speech from spectrally degraded material sheds light on the difficulty of these domains for child implant users. 相似文献
We study boundedness properties of a class ofmultiparameter paraproducts on the dual space of the dyadic Hardy space Hd1 (T N), the dyadic product BMO space BMOd (T N). For this, we introduce a notion of logarithmic mean oscillation on the polydisc. We also obtain a result on the boundedness of iterated commutators on BMO [0, 1]N). 相似文献
A papillary‐structured collagen fibril membrane is created, mimicking the 3D‐architecture of the human papillary dermis. Primary human keratinocytes cultured to confluency on papillar‐structured films are compared to keratinocytes cultured on flat membranes. Microscopical evaluation reveals the presence of morphologically distinct cells at the base of the papillar structures that are not observed on flat membranes. Gene expression microarrays and RT‐qPCR indicate that these cells are in a more proliferative/migrational state, whereas cells on flat membranes have a more differentiated expression profile. Immunohistochemical stainings confirm these results. In conclusion, specific collagen architecture can direct keratinocyte behavior, and this may be used to further improve skin regeneration.
Vacuolar ATPases are a potential therapeutic target because of their involvement in a variety of severe diseases such as osteoporosis or cancer. Archazolide A (1) and related analogs have been previously identified as selective inhibitors of V-ATPases with potency down to the subnanomolar range. Herein we report on the determination of the ligand binding mode by a combination of molecular docking, molecular dynamics simulations, and biochemical experiments, resulting in a sound model for the inhibitory mechanism of this class of putative anticancer agents. The binding site of archazolides was confirmed to be located in the equatorial region of the membrane-embedded V(O)-rotor, as recently proposed on the basis of site-directed mutagenesis. Quantification of the bioactivity of a series of archazolide derivatives, together with the docking-derived binding mode of archazolides to the V-ATPase, revealed favorable ligand profiles, which can guide the development of a simplified archazolide analog with potential therapeutic relevance. 相似文献
The aim of this work is to report phase equilibrium data for the binary systems (CO2 + α-humulene) and (CO2 + trans-caryophyllene), and for the ternary system (CO2 + α-humulene + trans-caryophyllene). Results from literature show that α-humulene and trans-caryophyllene are the main compounds responsible for the anti-inflammatory and anti-allergic characteristics attributed to the medicinal plant Cordia verbenacea D.C., hence giving importance to the phase behaviour investigation performed in this work. Phase equilibrium experiments were performed in a high-pressure, variable-volume view cell over the temperature range of T = (303 to 343) K and pressures up to 20 MPa. (Liquid + liquid) and (vapour + liquid + liquid) equilibrium were observed at T = 303 K, while (vapour + liquid) phase transitions were verified to occur from T = (313 to 343) K, for all systems studied. Thermodynamic modelling was performed using the Peng–Robinson equation of state and the classical quadratic mixing rules, with a satisfactory agreement between experimental and calculated values. 相似文献
Alkene content determinations in fluid catalytic cracking (FCC) liquid products were performed by means of normal-phase high-performance liquid chromatography (NP-HPLC) with diode array detection (UV/DAD). Separation of alkenes from aromatic hydrocarbons was performed on amino-modified silica gel column with n-heptane as mobile phase. The column has a little affinity to alkenes and saturated hydrocarbons and a pronounced affinity to aromatic compounds. The problem of alkenes and saturates co-elution on this column type was overcome with the detection system, UV/DAD, sensitive and selective to alkenes, while saturates are inactive in UV field. Total alkene content was determined as a sum of mono- and dialkene groups quantified by external standard method. Validation and verification of the developed method proved their applicability. The following criteria were used to validate the HPLC–DAD method: selectivity, linearity, precision, limits of detection and quantification. Alkene contents were quantified with the external standard method of wide calibration range, so both low and high alkene contents can be determined by the single calibration. Correlation coefficients were higher than 0.99. Precision was evaluated as repeatability and intermediary precision with relative standard deviations less than 5%. Some structural investigation of alkene groups was performed to confirm the assumption. Proposed method was compared with certified NMR method. Six commercial motor gasoline samples were analyzed by these two methods. Obtained results indicate good agreement between alkene content determined by both methods. The developed method was applied to the determination of alkene content in liquid FCC products in the boiling range from 70 °C to 190 °C. 相似文献