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Vest Hicks posted an update 1 week, 2 days ago
Polymers of basic amino acids function as polycationic compounds under physiological conditions and exhibit intriguing biological properties, such as antimicrobial and antiviral activities, immunopotentiating ability, and DNA-binding activity. Poly(ε-L-lysine) (ε-PL) produced by some strains of Streptomyces spp. is a cationic homopolymer of L-lysine linking between ε-amino and α-carboxylic acid functional groups and has been used as a food preservative based on its biocompatibility and biodegradability. An ε-PL-producing strain of Streptomyces sp. USE-33 was found to secrete a novel polycationic substance into its culture broth along with ε-PL. High-performance liquid chromatography analyses and one- and two-dimensional 1H and 13C nuclear magnetic resonance (NMR) experiments, accompanied by NMR titration studies, revealed that the secreted substance was poly[β-(L-diaminopropionyl-L-diaminopropionic acid)], PAP, characterized by an isopeptide backbone linking between the β-amino and α-carboxylic acid groups of L-α,β-diaminopropionic acid (L-Dpr) with pendent L-Dpr residues. PAP had a molecular weight of 500 to 1400, and copolymers composed of the two amino acids L-Dpr and L-lysine were not detected in the producer strain USE-33. The strain coproduced high levels of the two poly(amino acid)s in the presence of glycerol, citrate, and ammonium sulfate at pH 4.0 in a two-stage cultivation procedure. PAP exhibited strong inhibitory activities against several yeasts and weaker activities against bacteria than ε-PL. PAP may share a number of biological functions with ε-PL, and the use of PAP along with ε-PL has potential as a specific and advanced material for technical applications in various fields.Key points• Novel cationic poly(amino acid) was found in an ε-PL-producing Streptomyces species.• The l-α,β-diaminopropionic acid polymer was characterized by a comb-like structure.• The novel poly(amino acid), PAP, exhibited antibacterial and antifungal activities.Neurological morbidity is a growing concern in children with severe bronchiolitis. The aim of the study was to evaluate the frequency of occurrence and the factors associated with seizures in very young infants less then 3 months of age, admitted to a pediatric intensive care unit (PICU) for severe bronchiolitis. We performed a single center retrospective cohort study evaluating occurrence of seizures in infants admitted to the PICU between 2010 and 2018 for severe bronchiolitis. We described characteristics of the patients, laboratory test, brain imaging, and electroencephalogram results, as well as the treatment used. We conducted a multivariable logistic regression to identify factors associated with the occurrence of seizures. A p value less then 0.05 was considered significant. A total of 805 patients were included in the study; 722 (89.6%) were mechanically ventilated. Twenty-six infants (3.2%, 95% confidence interval, 95% CI [2.1%; 4.7%]) had seizures shortly prior to admission or during PICU stay.n in older infants (hyponatremia and mechanical ventilation).A trade-off between reproduction and survival is a characteristic of many organisms. In bacteria, growth is constrained when cellular resources are channelled towards environmental stress protection. At the core of this trade-off in Escherichia coli is RpoS, a sigma factor that diverts transcriptional resources towards general stress resistance. The constancy of RpoS levels in natural isolates is unknown. A uniform RpoS content in E. GsMTx4 ic50 coli would impart a narrow range of resistance properties to the species, whereas a diverse set of RpoS levels in nature should result in a diverse range of stress susceptibilities. We explore the diversity of trade-off settings and phenotypes by measuring the level of RpoS protein in strains of E. coli cohabiting in a natural environment. Strains from a stream polluted with domestic waste were investigated in monthly samples. Analyses included E. coli phylogroup classification, RpoS protein level, RpoS-dependent stress phenotypes and the sequencing of rpoS mutations. The most striking finding was the continuum of RpoS levels, with a 100-fold range of RpoS amounts consistently found in individuals in the stream. Approximately 1.8% of the sampled strains carried null or non-synonymous mutations in rpoS. The natural isolates also exhibited a broad (>100-fold) range of stress resistance responses. Our results are consistent with the view that a multiplicity of survival-multiplication trade-off settings is a feature of the species E. coli. The phenotypic diversity resulting from the trade-off permits bet-hedging and the adaptation of E. coli strains to a very broad range of environments.Cancer metastasis is the leading cause of mortality in cancer patients. Over 70% of lung cancer patients are diagnosed at advanced or metastatic stages, and this results in an increased incidence of mortality. Terrein is a secondary bioactive fungal metabolite isolated from Aspergillus terreus. Numerous studies have demonstrated that terrein has anticancer properties, but in the present study, the cellular mechanisms underlying the inhibition of lung cancer cell metastasis by terrein was investigated for the first time. Using MTT assays, the cytotoxic effects of terrein were first examined in human lung cancer cells (A549 cells) and then compared with its cytotoxic effects in three noncancer control cell lines (Vero kidney, L6 skeletal muscle and H9C2 cardiomyoblast cells). The results indicated that terrein significantly reduced the viability of all these cells but exhibited a different level of toxicity in each cell type; these results revealed a specific concentration range in which the effect of terrein was specific to A549 cells. This significant cytotoxic effect of terrein in A549 cells was verified using LDH assays. It was then demonstrated that terrein attenuated the proliferation of A549 cells using IncuCyte image analysis. Regarding its antimetastatic effects, terrein significantly inhibited A549 cell adhesion, migration and invasion. In addition, terrein suppressed the angiogenic processes of A549 cells, including vascular endothelial growth factor (VEGF) secretion, capillary‑like tube formation and VEGF/VEGFR2 interaction. These phenomena were accompanied by reduced protein levels of integrins, FAK, and their downstream mediators (e.g., PI3K, AKT, mTORC1 and P70S6K). All these data indicated that terrein was able to inhibit all the major metastatic processes in human lung cancer cells, which is crucial for cancer treatment.