Commensal bacteria are believed to play important roles in human health. The mechanisms by which they affect mammalian physiology are poorly understood; however, bacterial metabolites are likely to be key components of host interactions. Here, we use bioinformatics and synthetic biology to mine the human microbiota for N-acyl amides that interact with G-protein-coupled receptors (GPCRs). We found that N-acyl amide synthase genes are enriched in gastrointestinal bacteria and the lipids they encode interact with GPCRs that regulate gastrointestinal tract physiology. Mouse and cell-based models demonstrate that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands although future studies are needed to define their potential physiologic role in humans. This work suggests that chemical mimicry of eukaryotic signaling molecules may be common among commensal bacteria and that manipulation of microbiota genes encoding metabolites that elicit host cellular responses represents a new small molecule therapeutic modality (microbiome-biosynthetic-gene-therapy).
demand for fresh water has been increasing, caused by the growing
population and industrialization throughout the world. In this study,
we report a capacitive-based desalination system using Prussian blue
materials in a rocking chair desalination battery, which is composed
of sodium nickel hexacyanoferrate (NaNiHCF) and sodium iron HCF (NaFeHCF)
electrodes. In this system, ions are removed not only by charging
steps but also by discharging steps, and it is possible to treat actual
seawater with this system because the Prussian blue material has a
high charge capacity with a reversible reaction of alkaline cations.
Here, we demonstrate a rocking chair desalination battery to desalt
seawater, and the results show that this system has a high desalination
capacity (59.9 mg/g) with efficient energy consumption (0.34 Wh/L
for 40% Na ion removal efficiency).
A direct adaptive state-feedback controller is proposed for highly nonlinear systems. We consider uncertain or ill-defined nonaffine nonlinear systems and employ a neural network (NN) with flexible structure, i.e., an online variation of the number of neurons. The NN approximates and adaptively cancels an unknown plant nonlinearity. A control law and adaptive laws for the weights in the hidden layer and output layer of the NN are established so that the whole closed-loop system is stable in the sense of Lyapunov. Moreover, the tracking error is guaranteed to be uniformly asymptotically stable (UAS) rather than uniformly ultimately bounded (UUB) with the aid of an additional robustifying control term. The proposed control algorithm is relatively simple and requires no restrictive conditions on the design constants for the stability. The efficiency of the proposed scheme is shown through the simulation of a simple nonaffine nonlinear system.
Sungsanpin (1), a new 15-amino-acid peptide, was discovered from a Streptomyces species isolated from deep-sea sediment collected off Jeju Island, Korea. The planar structure of 1 was determined by 1D and 2D NMR spectroscopy, mass spectrometry, and UV spectroscopy. The absolute configurations of the stereocenters in this compound were assigned by derivatizations of the hydrolysate of 1 with Marfey's reagents and 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl isothiocyanate, followed by LC-MS analysis. Careful analysis of the ROESY NMR spectrum and three-dimensional structure calculations revealed that sungsanpin possesses the features of a lasso peptide: eight amino acids (-Gly(1)-Phe-Gly-Ser-Lys-Pro-Ile-Asp(8)-) that form a cyclic peptide and seven amino acids (-Ser(9)-Phe-Gly-Leu-Ser-Trp-Leu(15)) that form a tail that loops through the ring. Sungsanpin is thus the first example of a lasso peptide isolated from a marine-derived microorganism. Sungsanpin displayed inhibitory activity in a cell invasion assay with the human lung cancer cell line A549.
Cantilever sensors have attracted considerable attention over the last decade because of their potential as a highly sensitive sensor platform for high throughput and multiplexed detection of proteins and nucleic acids. A micromachined cantilever platform integrates nanoscale science and microfabrication technology for the label-free detection of biological molecules, allowing miniaturization. Molecular adsorption, when restricted to a single side of a deformable cantilever beam, results in measurable bending of the cantilever. This nanoscale deflection is caused by a variation in the cantilever surface stress due to biomolecular interactions and can be measured by optical or electrical means, thereby reporting on the presence of biomolecules. Biological specificity in detection is typically achieved by immobilizing selective receptors or probe molecules on one side of the cantilever using surface functionalization processes. When target molecules are injected into the fluid bathing the cantilever, the cantilever bends as a function of the number of molecules bound to the probe molecules on its surface. Mass-produced, miniature silicon and silicon nitride microcantilever arrays offer a clear path to the development of miniature sensors with unprecedented sensitivity for biodetection applications, such as toxin detection, DNA hybridization, and selective detection of pathogens through immunological techniques. This article discusses applications of cantilever sensors in cancer diagnosis.
Ohmyungsamycins A and B (1 and 2), which are new cyclic peptides, were isolated from a marine bacterial strain belonging to the Streptomyces genus collected from a sand beach on Jeju, a volcanic island in the Republic of Korea. Based on the interpretation of the NMR, UV, and IR spectroscopic and MS data, the planar structures of 1 and 2 were elucidated as cyclic depsipeptides bearing unusual amino acid units, including N-methyl-4-methoxytrytophan, β-hydroxyphenylalanine, and N,N-dimethylvaline. The absolute configurations of the α-carbons of the amino acid residues were determined using the advanced Marfey's method. The configurations of the additional stereogenic centers at the β-carbons of the threonine, N-methylthreonine, and β-hydroxyphenylalanine units were assigned by GITC (2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocyanate) derivatization and the modified Mosher's method. We have developed a new method utilizing PGME (phenylglycine methyl ester) derivatization coupled with chromatographic analysis to determine the absolute configuration of N,N-dimethylvaline. Our first successful establishment of the absolute configuration of N,N-dimethylvaline using PGME will provide a general and convenient analytical method for determining the absolute configurations of amino acids with fully substituted amine groups. Ohmyungsamycins A and B showed significant inhibitory activities against diverse cancer cells as well as antibacterial effects.
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