Notes

Two brand new species of Thyronectria via Mediterranean sea Europe.
Fish, particularly marine species, are considered as the major source of long-chain polyunsaturated fatty acids (LC-PUFA) in the human diet. The extent to which fish can synthesize LC-PUFA varies with species and is regulated by dietary fatty acids and ambient salinity. Therefore, to enable fish to produce more LC-PUFA, comprehending the mechanisms underlying the regulation of LC-PUFA biosynthesis is necessary. Here, the regulatory roles of miR-145 were investigated in the marine teleost rabbitfish Siganus canaliculatus. The hepatic abundance of miR-145 was lower in rabbitfish reared in low salinity (10 ppt) in comparison with that of those cultured in seawater (32 ppt), while the opposite pattern was observed for the transcripts of the transcription factor hepatocyte nuclear factor 4 alpha (Hnf4α), known to affect rabbitfish LC-PUFA biosynthesis. Rabbitfish hnf4α was identified as a target of miR-145 by luciferase reporter assays, and overexpression of miR-145 in the S. canaliculatus hepatocyte line (SCHL) markedly reduced the expression of Hnf4α and its target genes involved in LC-PUFA biosynthesis, namely, Δ4 fads2, Δ6Δ5 fads2, and elovl5. The opposite pattern was observed when miR-145 was knocked down in SCHL cells, with these effects being attenuated by subsequent hnf4α knockdown. Moreover, increasing endogenous Hnf4α by the knockdown of miR-145 increased the expression of LC-PUFA biosynthesis genes and enhanced the synthesis of LC-PUFA in both SCHL cells and rabbitfish in vivo. This is the first report to identify miR-145 as a key effector of LC-PUFA biosynthesis by targeting hnf4α, providing a novel insight into the mechanisms of the regulation of LC-PUFA biosynthesis in vertebrates.Binding hot spots are regions of proteins that, due to their potentially high contribution to the binding free energy, have high propensity to bind small molecules. We present benchmark sets for testing computational methods for the identification of binding hot spots with emphasis on fragment-based ligand discovery. Each protein structure in the set binds a fragment, which is extended into larger ligands in other structures without substantial change in its binding mode. Structures of the same proteins without any bound ligand are also collected to form an unbound benchmark. We also discuss a set developed by Astex Pharmaceuticals for the validation of hot and warm spots for fragment binding. The set is based on the assumption that a fragment that occurs in diverse ligands in the same subpocket identifies a binding hot spot. Since this set includes only ligand-bound proteins, we added a set with unbound structures. All four sets were tested using FTMap, a computational analogue of fragment screening experiments to form a baseline for testing other prediction methods, and differences among the sets are discussed.Antibiotic resistance in bacteria is a major global threat and a leading cause for healthcare-related morbidity and mortality. Resistant biofilm infections are particularly difficult to treat owing to the protective biofilm matrix, which decreases both antibiotic efficacy and clearance by the host. Novel antimicrobial agents that are capable of eradicating resistant infections are greatly needed to combat the rise of antibiotic-resistant bacteria, particularly in patients with cystic fibrosis who are frequently colonized by multidrug-resistant species. Our research group has developed nitric oxide-releasing biopolymers as alternatives to conventional antibiotics. Here, we show that nitric oxide acts as a broad-spectrum antibacterial agent while also improving the efficacy of conventional antibiotics when delivered sequentially. Alone, nitric oxide kills a broad range of bacteria in planktonic and biofilm form without engendering resistance. In combination with conventional antibiotics, nitric oxide increases bacterial susceptibility to multiple classes of antibiotics and slows the development of antibiotic resistance. We anticipate that the use of nitric oxide in combination with antibiotics may improve the outcome of patients with refractory infections, particularly those that are multidrug-resistant.Mutations in KPC-2 and KPC-3 β-lactamase can confer resistance to the β-lactam/β-lactamase inhibitor antibacterial intravenous drug combination ceftazidime-avibactam, introduced in 2015. Avibactam was the first of the diazabicyclooctane class of non-β-lactam β-lactamase inhibitors to be approved for clinical use. The orally bioavailable prodrug ETX0282 of the diazabicyclooctane β-lactamase inhibitor ETX1317 is in clinical development in combination with the oral β-lactam prodrug cefpodoxime proxetil for use against complicated urinary tract infections. We investigated the effects of 3 ceftazidime-avibactam resistance mutations in KPC-3 (V240G, D179Y, and D179Y/T243M) on the ability of ETX1317 to overcome KPC-3-induced cefpodoxime resistance. Isogenic Escherichia coli strains, each expressing the wild-type or a mutant KPC-3 at similar levels, retained susceptibility to cefpodoxime-ETX1317 (12) with essentially identical minimal inhibitory concentrations of 0.125-0.25 μg/mL cefpodoxime. The KPC-3 mutations had little or no effect on the kinact/Ki values for inhibition by each of 3 diazabicyclooctanes avibactam, durlobactam (ETX2514), and ETX1317. The KM values for hydrolysis of cefpodoxime were similar for all 4 variants, but the kcat values of the D179Y and D179Y/T243M variants were much lower than those of the wild-type and V240G mutant enzymes. All 4 KPC-3 variants formed stable, reversibly covalent complexes with ETX1317, but dissociation of ETX1317 was much slower from the D179Y and D179Y/T243M mutants than from the wild-type and V240G mutant enzymes. Thus, the KPC-3 variants examined here that cause resistance to ceftazidime-avibactam do not cause resistance to cefpodoxime-ETX1317.The study investigates the spatial pattern of black carbon (BC) at a high spatial resolution in Augsburg, Germany. Sixty two walks were performed to assess the concentrations of equivalent black carbon (eBC), ultraviolet particulate matter (UVPM), and equivalent brown carbon (eBrC) in different seasons and at different times of the day with a mobile platform (i.e., trolley). Along with BC measurements, images of street microenvironments were recorded. Meteorological parameters, including temperature, relative humidity, and wind speed, were monitored. The BC concentrations showed significant spatial heterogeneity and diurnal variations peaking in the morning and at night. The highest BC concentrations were observed near dense traffic. read more The correlations between BC and street views (buildings, roads, cars, and vegetation) were weak but highly significant. Moreover, meteorological factors also influenced the BC concentration. A model based on street view images and meteorological data was developed to examine the driving factors of the spatial variability of BC concentrations at a higher spatial resolution as different microenvironments based on traffic density.
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