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1.
Environ Geochem Health ; 45(8): 6675-6692, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37354254

RESUMEN

Determining the geochemical background for heavy metals is vital in soil management activities. Although many statistical methods for geochemical background determination have been proposed, the multi-population problem of geochemical data, primarily regional ones, derived mainly from mixing multiple populations belonging to various geological sources or processes, needs to be better addressed. In this study, the Expectation-Maximization (EM) algorithm was employed to separate multiple populations in a 1:250,000 scale regional geochemical data set of soils in a lithologically complex region in the north of Changchun, China. The data set included 3746 surface soil samples analyzed for SiO2, K2O, Al2O3, CaO, La, Rb, Y, Ti, Ce, V, Cr, and As. The potential high-risk areas of As and Cr were determined before and after the separation of multiple populations. The comparison results show that the EM clustering method can efficiently separate multiple populations and determine soil geochemical background more reasonably, thus eliminating false contamination that is easily misidentified and better revealing concealed contamination that is challenging to detect.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Suelo , Dióxido de Silicio , Contaminantes del Suelo/análisis , Monitoreo del Ambiente/métodos , Metales Pesados/análisis , Análisis por Conglomerados , China , Medición de Riesgo
2.
Anticancer Drugs ; 2020 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-32976214

RESUMEN

T-cell acute lymphoblastic leukemia (T-ALL) is the most prevalent malignancy in children. Long non-coding RNAs are being found to have relevance to the pathogenesis of pediatric T-ALL. However, the function of cyclin-dependent kinase inhibitor 2B anti-sense RNA 1 (CDKN2B-AS1) in pediatric T-ALL progression and chemoresistance has not been illuminated. The levels of CDKN2B-AS1, miR-335-3p and tumor necrosis factor receptor-associated factor 5 (TRAF5) were assessed by quantitative real-time PCR. Cell proliferation and the 50% inhibitory concentration (IC50) value were detected using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetr-azolium assay. Cell cycle and apoptosis were evaluated by flow cytometry. Western blot analysis was performed to measure protein expression. Targeted interactions among CDKN2B-AS1, miR-335-3p and TRAF5 were determined by the dual-luciferase reporter and RNA immunoprecipitation assays. Animal studies were conducted to observe the function of CDKN2B-AS1 in vivo. Our data indicated that CDKN2B-AS1 was highly expressed in pediatric T-ALL peripheral blood mononuclear cells and cells, and high CDKN2B-AS1 level was associated with adriamycin (ADR) resistance. CDKN2B-AS1 depletion hindered T-ALL/ADR cell proliferation and cell cycle progression, and promoted cell apoptosis and ADR sensitivity in vitro. Moreover, CDKN2B-AS1 knockdown repressed tumor growth and enhanced ADR sensitivity in vivo. CDKN2B-AS1 sequestered miR-335-3p, and CDKN2B-AS1 depletion exerted regulatory effect in T-ALL/ADR cell progression by up-regulating miR-335-3p. TRAF5 was a direct target of miR-335-3p, and TRAF5 mediated the regulation of miR-335-3p in T-ALL cell behaviors. Furthermore, CDKN2B-AS1 positively modulated TRAF5 expression through sponging miR-335-3p. The current work suggested that CDKN2B-AS1 knockdown repressed the progression and enhanced ADR sensitivity of pediatric T-ALL at least partly through targeting miR-335-3p/TRAF5 axis, highlighting a promising therapeutic target for the treatment of pediatric T-ALL patients.

3.
Proc Natl Acad Sci U S A ; 111(33): 12031-6, 2014 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-25092299

RESUMEN

Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a growing class of natural products that are found in all domains of life. These compounds possess vast structural diversity and have a wide range of biological activities, promising a fertile ground for exploring novel natural products. One challenging aspect of RiPP research is the difficulty of structure determination due to their architectural complexity. We here describe a method for automated structural characterization of RiPPs by tandem mass spectrometry. This method is based on the combined analysis of multiple mass spectra and evaluation of a collection of hypothetical structures predicted based on the biosynthetic gene cluster and molecular weight. We show that this method is effective in structural characterization of complex RiPPs, including lanthipeptides, glycopeptides, and azole-containing peptides. Using this method, we have determined the structure of a previously structurally uncharacterized lanthipeptide, prochlorosin 1.2, and investigated the order of the posttranslational modifications in three biosynthetic systems.


Asunto(s)
Productos Biológicos/química , Péptidos/química , Ribosomas/metabolismo , Espectrometría de Masas en Tándem/métodos , Secuencia de Aminoácidos , Productos Biológicos/metabolismo , Datos de Secuencia Molecular , Estructura Molecular , Péptidos/metabolismo
4.
Sci Total Environ ; 918: 170695, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38331274

RESUMEN

The "background" is an essential index for identifying anthropogenic inputs and potential ecological risks of soil heavy metals. However, the lithology of bedrock can cause significant spatial variation in the natural background of soil elements, posing considerable difficulties in estimating background values. In this study, an attempt was made to calculate the natural background through regression analysis of soil chemical composition, and reasonably evaluate the impact of lithology. A total of 1771 surface soil samples were collected from the Songhua River Basin, China, for chemical composition analysis, and the partial least square regression (PLSR) method was employed to establish the relationship between heavy metals (As, Hg, Cr, Cd, Pb, Cu, Zn, and Ni) and soil chemical composition/environmental parameters (SiO2, Al2O3, TFe2O3, MgO, CaO, K2O, Na2O, La, Y, Zr, V, Sc, Sr, Li and pH). The result shows that As, Cr, Pb, Cu, Zn, and Ni have significant linear relationships with soil chemical composition. Each of these six heavy metals obtained 1771 regression background values; some were higher than the uniform background value obtained from the boxplot, while others were lower. The regression background values recognized not only subtle anthropogenic inputs and potential ecological risks in low-background regions but also spurious contamination in high-background areas. All these indicate that the PLSR method can effectively improve the determination accuracy of the natural background of soil heavy metals. More attention should be paid to the serious anthropogenic inputs appearing in some places of the study area.

5.
PLoS Biol ; 8(3): e1000339, 2010 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-20351769

RESUMEN

Lantibiotic synthetases are remarkable biocatalysts generating conformationally constrained peptides with a variety of biological activities by repeatedly utilizing two simple posttranslational modification reactions: dehydration of Ser/Thr residues and intramolecular addition of Cys thiols to the resulting dehydro amino acids. Since previously reported lantibiotic synthetases show no apparent homology with any other known protein families, the molecular mechanisms and evolutionary origin of these enzymes are unknown. In this study, we present a novel class of lanthionine synthetases, termed LanL, that consist of three distinct catalytic domains and demonstrate in vitro enzyme activity of a family member from Streptomyces venezuelae. Analysis of individually expressed and purified domains shows that LanL enzymes install dehydroamino acids via phosphorylation of Ser/Thr residues by a protein kinase domain and subsequent elimination of the phosphate by a phosphoSer/Thr lyase domain. The latter has sequence homology with the phosphothreonine lyases found in various pathogenic bacteria that inactivate host mitogen activated protein kinases. A LanC-like cyclase domain then catalyzes the addition of Cys residues to the dehydro amino acids to form the characteristic thioether rings. We propose that LanL enzymes have evolved from stand-alone protein Ser/Thr kinases, phosphoSer/Thr lyases, and enzymes catalyzing thiol alkylation. We also demonstrate that the genes for all three pathways to lanthionine-containing peptides are widespread in Nature. Given the remarkable efficiency of formation of lanthionine-containing polycyclic peptides and the latter's high degree of specificity for their cognate cellular targets, it is perhaps not surprising that (at least) three distinct families of polypeptide sequences have evolved to access this structurally and functionally diverse class of compounds.


Asunto(s)
Alanina/análogos & derivados , Proteínas Bacterianas , Bacteriocinas/metabolismo , Isoenzimas , Ligasas , Sulfuros/metabolismo , Alanina/química , Alanina/metabolismo , Secuencia de Aminoácidos , Bacterias/clasificación , Bacterias/enzimología , Bacterias/genética , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Bacteriocinas/química , Evolución Molecular , Isoenzimas/química , Isoenzimas/genética , Isoenzimas/metabolismo , Ligasas/química , Ligasas/genética , Ligasas/metabolismo , Datos de Secuencia Molecular , Estructura Molecular , Familia de Multigenes , Filogenia , Conformación Proteica , Procesamiento Proteico-Postraduccional , ARN Ribosómico 16S/genética , Alineación de Secuencia , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Streptomyces/enzimología , Streptomyces/genética , Sulfuros/química
6.
Proc Natl Acad Sci U S A ; 107(23): 10430-5, 2010 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-20479271

RESUMEN

Our understanding of secondary metabolite production in bacteria has been shaped primarily by studies of attached varieties such as symbionts, pathogens, and soil bacteria. Here we show that a strain of the single-celled, planktonic marine cyanobacterium Prochlorococcus-which conducts a sizable fraction of photosynthesis in the oceans-produces many cyclic, lanthionine-containing peptides (lantipeptides). Remarkably, in Prochlorococcus MIT9313 a single promiscuous enzyme transforms up to 29 different linear ribosomally synthesized peptides into a library of polycyclic, conformationally constrained products with highly diverse ring topologies. Genes encoding this system are found in variable abundances across the oceans-with a hot spot in a Galapagos hypersaline lagoon-suggesting they play a habitat- and/or community-specific role. The extraordinarily efficient pathway for generating structural diversity enables these cyanobacteria to produce as many secondary metabolites as model antibiotic-producing bacteria, but with much smaller genomes.


Asunto(s)
Biocatálisis , Péptidos Cíclicos/biosíntesis , Fitoplancton/metabolismo , Prochlorococcus/metabolismo , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Secuencia Conservada , Ciclización , Genoma Bacteriano , Datos de Secuencia Molecular , Familia de Multigenes , Fitoplancton/química , Fitoplancton/genética , Prochlorococcus/química , Prochlorococcus/genética , Alineación de Secuencia
7.
Front Microbiol ; 14: 1247222, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38029153

RESUMEN

Addressing the current antibiotic-resistance challenge would be aided by the identification of compounds with novel mechanisms of action. Epilancin 15X, a lantibiotic produced by Staphylococcus epidermidis 15 × 154, displays antimicrobial activity in the submicromolar range against a subset of pathogenic Gram-positive bacteria. S. epidermidis is a common member of the human skin or mucosal microbiota. We here investigated the mechanism of action of epilancin 15X. The compound is bactericidal against Staphylococcus carnosus as well as Bacillus subtilis and appears to kill these bacteria by membrane disruption. Structure-activity relationship studies using engineered analogs show that its conserved positively charged residues and dehydroamino acids are important for bioactivity, but the N-terminal lactyl group is tolerant of changes. Epilancin 15X treatment negatively affects fatty acid synthesis, RNA translation, and DNA replication and transcription without affecting cell wall biosynthesis. The compound appears localized to the surface of bacteria and is most potent in disrupting the membranes of liposomes composed of negatively charged membrane lipids in a lipid II independent manner. Epilancin 15X does not elicit a LiaRS response in B. subtilis but did upregulate VraRS in S. carnosus. Treatment of S. carnosus or B. subtilis with epilancin 15X resulted in an aggregation phenotype in microscopy experiments. Collectively these studies provide new information on epilancin 15X activity.

8.
J Am Chem Soc ; 133(8): 2338-41, 2011 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-21114289

RESUMEN

Lantipeptides are ribosomally synthesized and posttranslationally modified peptides containing thioether cross-links. We describe the preparation of seven different lantipeptides in Escherichia coli and demonstrate that this methodology can be used to incorporate nonproteinogenic amino acids.


Asunto(s)
Escherichia coli/metabolismo , Péptidos/metabolismo , Procesamiento Proteico-Postraduccional , Aminoácidos/química , Péptidos/química , Conformación Proteica , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Compuestos de Sulfhidrilo/química , Compuestos de Sulfhidrilo/metabolismo
9.
J Biol Dyn ; 14(1): 269-288, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32281489

RESUMEN

In this paper, Melnikov analysis of chaos in a simple SIR model with periodically or stochastically modulated nonlinear incidence rate and the effect of periodic and bounded noise on the chaotic motion of SIR model possessing homoclinic orbits are detailed investigated. Based on homoclinic bifurcation, necessary conditions for possible chaotic motion as well as sufficient condition are derived by the random Melnikov theorem, and to establish the threshold of bounded noise amplitude for the onset of chaos.


Asunto(s)
Enfermedades Transmisibles/epidemiología , Susceptibilidad a Enfermedades/epidemiología , Dinámicas no Lineales , Procesos Estocásticos , Humanos , Incidencia , Modelos Biológicos
10.
Artículo en Inglés | MEDLINE | ID: mdl-29119058

RESUMEN

For in vivo imaging, the short-wavelength infrared region (SWIR; 1000-2000 nm) provides several advantages over the visible and near-infrared regions: general lack of autofluorescence, low light absorption by blood and tissue, and reduced scattering. However, the lack of versatile and functional SWIR emitters has prevented the general adoption of SWIR imaging by the biomedical research community. Here, we introduce a class of high-quality SWIR-emissive indium-arsenide-based quantum dots (QDs) that are readily modifiable for various functional imaging applications, and that exhibit narrow and size-tunable emission and a dramatically higher emission quantum yield than previously described SWIR probes. To demonstrate the unprecedented combination of deep penetration, high spatial resolution, multicolor imaging and fast-acquisition-speed afforded by the SWIR QDs, we quantified, in mice, the metabolic turnover rates of lipoproteins in several organs simultaneously and in real time as well as heartbeat and breathing rates in awake and unrestrained animals, and generated detailed three-dimensional quantitative flow maps of the mouse brain vasculature.

11.
Lab Chip ; 15(15): 3232-41, 2015 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-26126496

RESUMEN

We study microreactors with internal fields of posts as typical examples of structured microreactors to elucidate flow fields and their implications for mass transfer. Laser-induced fluorescence (LIF) visualization combined with image analysis is used to systematically quantify key features such as interfacial area, phase holdup and the characteristics of the post-wetting layer. The subsequent mass transport analysis yields insight into how the posts contribute to the overall enhanced mass transfer performance compared to open channels, and provides predictions of mass transfer performance under varying operating conditions. Computational fluid dynamic (CFD) simulations of multiphase flow using the volume-of-fluid (VOF) method are in good agreement with experimentally observed multiphase flows.


Asunto(s)
Reactores Biológicos , Microfluídica , Modelos Teóricos
12.
Biomicrofluidics ; 8(4): 044102, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25379087

RESUMEN

A technique for visualizing and quantifying reactive mixing for laminar and turbulent flow in a microscale chemical reactor using confocal-based microscopic laser induced fluorescence (confocal µ-LIF) was demonstrated in a microscale multi-inlet vortex nanoprecipitation reactor. Unlike passive scalar µ-LIF, the reactive µ-LIF technique is able to visualize and quantify micromixing effects. The confocal imaging results indicated that the flow in the reactor was laminar and steady for inlet Reynolds numbers of 10, 53, and 93. Mixing and reaction were incomplete at each of these Reynolds numbers. The results also suggested that although mixing by diffusion was enhanced near the midplane of the reactor at Rej = 53 and 93 due to very thin bands of acidic and basic fluid forming as the fluid spiraled towards the center of the reactor, near the top, and bottom walls of the reactor, the lower velocities due to fluid friction with the walls hindered the formation of these thin bands, and, thus, resulted in large regions of unmixed and unreacted fluid. At Rej = 240, the flow was turbulent and unsteady. The mixing and reaction processes were still found to be incomplete even at this highest Reynolds number. At the reactor midplane, the flow images at Rej = 240 showed unmixed base fluid near the center of the reactor, suggesting that just as in the Rej = 53 and 93 cases, lower velocities near the top and bottom walls of the reactor hinder the mixing and rection of the acidic and basic streams. Ensemble averages of line-scan profiles for the Rej = 240 were then calculated to provide statistical quantification of the microscale mixing in the reactor. These results further demonstrate that even at this highest Reynolds number investigated, mixing and reaction are incomplete. Visualization and quantification of micromixing using this reactive µ-LIF technique can prove useful in the validation of computational fluid dynamics models of micromixing within microscale chemical reactors.

13.
Chem Commun (Camb) ; 48(89): 10966-8, 2012 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-23034674

RESUMEN

We report the heterologous production of Ala(0)actagardine in E. coli by co-expression of the substrate peptide GarA and its modification enzymes GarM and GarO. The activity of GarO, a luciferase-like monooxygenase that introduces the unique sulfoxide group of actagardine, was also investigated in vitro.


Asunto(s)
Bacteriocinas/biosíntesis , Escherichia coli , Secuencia de Aminoácidos , Escherichia coli/metabolismo , Datos de Secuencia Molecular , Péptidos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
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