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1.

Introduction

Aqueous–methanol mixtures have successfully been applied to extract a broad range of metabolites from plant tissue. However, a certain amount of material remains insoluble.

Objectives

To enlarge the metabolic compendium, two ionic liquids were selected to extract the methanol insoluble part of trunk from Betula pendula.

Methods

The extracted compounds were analyzed by LC/MS and GC/MS.

Results

The results show that 1-butyl-3-methylimidazolium acetate (IL-Ac) predominantly resulted in fatty acids, whereas 1-ethyl-3-methylimidazolium tosylate (IL-Tos) mostly yielded phenolic structures. Interestingly, bark yielded more ionic liquid soluble metabolites compared to interior wood.

Conclusion

From this one can conclude that the application of ionic liquids may expand the metabolic snapshot.
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2.

Background and Aims

It was previously demonstrated that stolons of Fragaria vesca respond to patches of varying nutrient quality; however, the mechanism of patch-detection remained unknown. Here we provide support for a process by which F. vesca perceives nutrient-rich patches, consistent with nutrient foraging prior to rooting.

Methods

Volatile organic compounds (VOCs) emitted from unsterilized and sterilized field substrates were collected and analyzed by stir-bar headspace extraction gas chromatography-mass spectrometry using a method modified for soil and litter systems. Selected compounds were chosen to represent unsterilized and sterilized field substrates. These synthetic volatile compound mixtures were then applied to neutral substrate to test the ability of F. vesca to choose between unsterilized versus sterilized substrates.

Results

Primary stolons exhibited chemotropism towards unsterilized (natural) substrates and grew away from the sterilized volatile substrates when the alternate choice was a negative control. We conclude that the presence of carboxylic acids tends to stimulate stolon elongation and chemotropism while aldehydes, ketones and monoterpenes tend to suppress it.

Conclusions

We provide evidence that developing stolons of F. vesca forage for nutrient-rich patches via volatile cues similar to those emitted from the soil through microflora activity.
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3.

Background

With the advances in the next-generation sequencing technologies, researchers can now rapidly examine the composition of samples from humans and their surroundings. To enhance the accuracy of taxonomy assignments in metagenomic samples, we developed a method that allows multiple mismatch probabilities from different genomes.

Results

We extended the algorithm of taxonomic assignment of metagenomic sequence reads (TAMER) by developing an improved method that can set a different mismatch probability for each genome rather than imposing a single parameter for all genomes, thereby obtaining a greater degree of accuracy. This method, which we call TADIP (Taxonomic Assignment of metagenomics based on DIfferent Probabilities), was comprehensively tested in simulated and real datasets. The results support that TADIP improved the performance of TAMER especially in large sample size datasets with high complexity.

Conclusions

TADIP was developed as a statistical model to improve the estimate accuracy of taxonomy assignments. Based on its varying mismatch probability setting and correlated variance matrix setting, its performance was enhanced for high complexity samples when compared with TAMER.
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4.

Introduction

Actinomycetes produce the majority of the antibiotics currently in clinical use. The efficiency of antibiotic production is affected by multiple factors such as nutrients, pH, temperature and growth phase. Finding the optimal harvesting time is crucial for successful isolation of the desired bioactive metabolites from actinomycetes, but for this conventional chemical analysis has limitations due to the metabolic complexity.

Objectives

This study explores the utility of NMR-based metabolomics for (1) optimizing fermentation time for the production of known and/or unknown bioactive compounds produced by actinomycetes; (2) elucidating the biosynthetic pathway for microbial natural products; and (3) facilitating the biotransformation of nature-abundant chemicals.

Method

The aqueous culture broth of actinomycete Streptomyces sp. MBT76 was harvested every 24 h for 5 days and each broth was extracted by ethyl acetate. The extracts were analyzed by 1H NMR spectroscopy and the data were compared with principal component analysis (PCA) and orthogonal projection to latent structures (OPLS) analysis. Antimicrobial test were performed by agar diffusion assay.

Results

The secondary metabolites production by Streptomyces sp. MBT76 was growth phase-dependent. Isocoumarins (19), undecylprodiginine (10), streptorubin B (11), 1H-pyrrole-2-carboxamide (12), acetyltryptamine (13), and fervenulin (14) were identified, and their optimal production time was determined in crude extracts without tedious chromatographic fractionation. Of these compounds, 5,6,7,8-tetramethoxyl-3-methyl-isocoumarin (9) is as a novel compound, which was most likely synthesized by a type I iterative polyketide synthase (PKS) encoded by the icm gene cluster. Multivariate data analysis of the 1H NMR spectra showed that acetyltryptamine (13) and tri-methoxylated isocoumarins (7 and 8) were the major determinants of antibiotic activity during later time points. The methoxylation was exploited to allow bioconversion of exogenously added genistein into a suite of methoxylated isoflavones (1518). Methoxylation increased the antimicrobial efficacy of isocoumarins, but decreased that of the isoflavones.

Conclusion

Our results show the applicability of NMR-based metabolic profiling to streamline microbial biotransformation and to determine the optimal harvesting time of actinomycetes for antibiotic production.
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5.

Introduction

Climate change is a major concern for the scientific community, demanding novel information about the effects of environmental stressors on living organisms. Metabolic profiling is required for achieving the most extensive possible range of compounds and their concentration changes on stressed conditions.

Objectives

Individuals of the crustacean species Daphnia magna were exposed to three different abiotic factors linked to global climate change: high salinity, high temperature levels and hypoxia. Advanced chemometric tools were used to characterize the metabolites affected by the exposure.

Method

An exploratory analysis of gas chromatography-mass spectrometry (GCMS) data was performed to discriminate between control and exposed daphnid samples. Due to the complexity of these GCMS data sets, a comprehensive untargeted analysis of the full scan data was performed using multivariate curve resolution-alternating least squares (MCR-ALS) method. This approach enabled to resolve most of the metabolite signals from interference peaks caused by derivatization reactions. Metabolites with significant changes in their peak areas were tentatively identified and the involved metabolic pathways explored.

Results

D. magna metabolic biomarkers are proposed for the considered physical factors. Metabolites related with energy metabolic pathways including some amino acids, carbohydrates, organic acids and nucleosides were identified as potential biomarkers of the investigated treatments.

Conclusions

The proposed untargeted GCMS metabolomics strategy and multivariate data analysis tools were useful to investigate D. magna metabolome under environmental stressed conditions.
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6.

Background

Genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) confer increased risk of developing late-onset Alzheimer’s Disease (LOAD) and other neurodegenerative disorders. Recent studies provided insight into the multifaceted roles of TREM2 in regulating extracellular β-amyloid (Aβ) pathology, myeloid cell accumulation, and inflammation observed in AD, yet little is known regarding the role of TREM2 in regulating intracellular microtubule associated protein tau (MAPT; tau) pathology in neurodegenerative diseases and in AD, in particular.

Results

Here we report that TREM2 deficiency leads to accelerated and exacerbated hyperphosphorylation and aggregation of tau in a humanized mouse model of tauopathy. TREM2 deficiency also results, indirectly, in dramatic widespread dysregulation of neuronal stress kinase pathways.

Conclusions

Our results suggest that deficiency of microglial TREM2 leads to heightened tau pathology coupled with widespread increases in activated neuronal stress kinases. These findings offer new insight into the complex, multiple roles of TREM2 in regulating Aβ and tau pathologies.
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7.

Background

Among the reported potential agents to treat the epilepsy, sulphonamides are important and their significance cannot be ignored. A series of substituted 4-amino-benzene sulfonamides were designed, keeping in view the structural requirement of pharmacophore.

Methods

Lipinski rule of five has been calculated; failure to Lipinski rule was not observed. Docking was performed through AutoDock Vina. Molecules have been screened out through docking. Compounds were synthesized and characterized through IR, 1HNMR, 13C NMR, Mass and elemental analysis. The anticonvulsant activity of the synthesized compounds was assessed using the Maximal Electroshock Seizure (MES) model. In-silico biological activity spectrum, toxicological studies, predicted oral rats LD50 were performed.

Results

Docking studies showed good interaction with lyase (Oxo-acid) - human carbonic anhydrase-I (1AZM). The in-silico studies proved them to be with good drug-likeness properties, especially 4-(3-Acetyl-phenylamino)-methyl)-benzenesulfonamide (2g). These results revealed that the synthesized compounds (1a-1c, 2a-2q) exhibited promising anticonvulsant effect against MES model for inhibition of Lyase- Human Carbonic Anhydrase-I.

Conclusion

After investigating all the results, the compound 4-(3-Acetyl-phenylamino)-methyl)-benzenesulfonamide (2g) is found to be best in the series. A comparatively good activity of compound 2g suggests us that sulphonamide can be leads to further optimization for building potent and chemically diversified anti-convulsant agents.
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8.

Background

Many vector-borne diseases co-circulate, as the viruses from the same family are also transmitted by the same vector species. For example, Zika and dengue viruses belong to the same Flavivirus family and are primarily transmitted by a common mosquito species Aedes aegypti. Zika outbreaks have also commonly occurred in dengue-endemic areas, and co-circulation and co-infection of both viruses have been reported. As recent immunological cross-reactivity studies have confirmed that convalescent plasma following dengue infection can enhance Zika infection, and as global efforts of developing dengue and Zika vaccines are intensified, it is important to examine whether and how vaccination against one disease in a large population may affect infection dynamics of another disease due to antibody-dependent enhancement.

Methods

Through a conceptual co-infection dynamics model parametrized by reported dengue and Zika epidemic and immunological cross-reactivity characteristics, we evaluate impact of a hypothetical dengue vaccination program on Zika infection dynamics in a single season when only one particular dengue serotype is involved.

Results

We show that an appropriately designed and optimized dengue vaccination program can not only help control the dengue spread but also, counter-intuitively, reduce Zika infections. We identify optimal dengue vaccination coverages for controlling dengue and simultaneously reducing Zika infections, as well as the critical coverages exceeding which dengue vaccination will increase Zika infections.

Conclusion

This study based on a conceptual model shows the promise of an integrative vector-borne disease control strategy involving optimal vaccination programs, in regions where different viruses or different serotypes of the same virus co-circulate, and convalescent plasma following infection from one virus (serotype) can enhance infection against another virus (serotype). The conceptual model provides a first step towards well-designed regional and global vector-borne disease immunization programs.
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9.

Background

In population association studies, standard methods of statistical inference assume that study subjects are independent samples. In genetic association studies, it is therefore of interest to diagnose undocumented close relationships in nominally unrelated study samples.

Results

We describe the R package CrypticIBDcheck to identify pairs of closely-related subjects based on genetic marker data from single-nucleotide polymorphisms (SNPs). The package is able to accommodate SNPs in linkage disequibrium (LD), without the need to thin the markers so that they are approximately independent in the population. Sample pairs are identified by superposing their estimated identity-by-descent (IBD) coefficients on plots of IBD coefficients for pairs of simulated subjects from one of several common close relationships.

Conclusions

The methods implemented in CrypticIBDcheck are particularly relevant to candidate-gene association studies, in which dependent SNPs cluster in a relatively small number of genes spread throughout the genome. The accommodation of LD allows the use of all available genetic data, a desirable property when working with a modest number of dependent SNPs within candidate genes. CrypticIBDcheck is available from the Comprehensive R Archive Network (CRAN).
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10.

Background

We test whether traditional ecological knowledge (TEK) about how to make an item predicts a person’s skill at making it among the Tsimane’ (Bolivia). The rationale for this research is that the failure to distinguish between knowledge and skill might account for some of the conflicting results about the relationships between TEK, human health, and economic development.

Methods

We test the association between a commonly-used measure of individual knowledge (cultural consensus analysis) about how to make an arrow or a bag and a measure of individual skill at making these items, using ordinary least-squares regression. The study consists of 43 participants from 3 villages.

Results

We find no association between our measures of knowledge and skill (core model, p?>?0.5,?R 2 ?=?.132).

Conclusions

While we cannot rule out the possibility of a real association between these phenomena, we interpret our findings as support for the claim that researchers should distinguish between methods to measure knowledge and skill when studying trends in TEK.
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11.

Background

In 2009, an outbreak of dengue caused high fatality in Sri Lanka. We conducted 5 autopsies of clinically suspected myocarditis cases at the General Hospital, Peradeniya to describe the histopathology of the heart and other organs.

Methods

The diagnosis of dengue was confirmed with specific IgM and IgG ELISA, HAI and RT-PCR techniques. The histology was done in tissue sections stained with hematoxylin and eosin.

Results

Of the 319 cases of dengue fever, 166(52%) had severe infection. Of them, 149 patients (90%) had secondary dengue infection and in 5 patients, DEN-1 was identified as the causative serotype. The clinical diagnosis of myocarditis was considered in 45(27%) patients. The autopsies were done in 5 patients who succumbed to shock (3 females and 2 males) aged 13- 31 years. All had pleural effusions, ascites, bleeding patches in tissue planes and histological evidence of myocarditis. The main histological findings of the heart were interstitial oedema with inflammatory cell infiltration and necrosis of myocardial fibers. One patient had pericarditis. The concurrent pulmonary abnormalities were septal congestion, pulmonary haemorrhage and diffuse alveolar damage; one case showed massive necrosis of liver.

Conclusions

The histology supports occurrence of myocarditis in dengue infection.
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12.

Objective

To produce (S)-3-hydroxy-1-(3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-4-(2,4,5-trifluorophenyl)butan-1-one (S)-1 from 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro [1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-one (2) by microbial bioreduction.

Results

A new isolate of Pseudomonas pseudoalcaligenes reduced enantioselectively prochiral ketone 2 to chiral alcohol (S)-1. Whole cells of the bacterium were tolerant towards 20 % (v/v) DMSO and 10 g 2/l. Under the optimal conditions, the preparative-scale bioreduction yielded (S)-1 at 90 % yield and >99 % ee. Cells could be re-used with the yield and ee of product being 45 % and >99 %, respectively, after five cycles.

Conclusion

Bioreduction using whole cells of P. pseudoalcaligenes is an attractive approach to produce (S)-1, as a chiral intermediate of the anti-diabetic drug, sitagliptin.
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13.

Key message

The resistance of durum wheat to the Wheat spindle streak mosaic virus (WSSMV) is controlled by two main QTLs on chromosomes 7A and 7B, with a huge epistatic effect.

Abstract

Wheat spindle streak mosaic virus (WSSMV) is a major disease of durum wheat in Europe and North America. Breeding WSSMV-resistant cultivars is currently the only way to control the virus since no treatment is available. This paper reports studies of the inheritance of WSSMV resistance using two related durum wheat populations obtained by crossing two elite cultivars with a WSSMV-resistant emmer cultivar. In 2012 and 2015, 354 recombinant inbred lines (RIL) were phenotyped using visual notations, ELISA and qPCR and genotyped using locus targeted capture and sequencing. This allowed us to build a consensus genetic map of 8568 markers and identify three chromosomal regions involved in WSSMV resistance. Two major regions (located on chromosomes 7A and 7B) jointly explain, on the basis of epistatic interactions, up to 43% of the phenotypic variation. Flanking sequences of our genetic markers are provided to facilitate future marker-assisted selection of WSSMV-resistant cultivars.
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14.
Zhou  Xinrui  Yin  Rui  Kwoh  Chee-Keong  Zheng  Jie 《BMC genomics》2018,19(10):936-154

Background

The evolution of influenza A viruses leads to the antigenic changes. Serological diagnosis of the antigenicity is usually labor-intensive, time-consuming and not suitable for early-stage detection. Computational prediction of the antigenic relationship between emerging and old strains of influenza viruses using viral sequences can facilitate large-scale antigenic characterization, especially for those viruses requiring high biosafety facilities, such as H5 and H7 influenza A viruses. However, most computational models require carefully designed subtype-specific features, thereby being restricted to only one subtype.

Methods

In this paper, we propose a Context-FreeEncoding Scheme (CFreeEnS) for pairs of protein sequences, which encodes a protein sequence dataset into a numeric matrix and then feeds the matrix into a downstream machine learning model. CFreeEnS is not only free from subtype-specific selected features but also able to improve the accuracy of predicting the antigenicity of influenza. Since CFreeEnS is subtype-free, it is applicable to predicting the antigenicity of diverse influenza subtypes, hopefully saving the biologists from conducting serological assays for highly pathogenic strains.

Results

The accuracy of prediction on each subtype tested (A/H1N1, A/H3N2, A/H5N1, A/H9N2) is over 85%, and can be as high as 91.5%. This outperforms existing methods that use carefully designed subtype-specific features. Furthermore, we tested the CFreeEnS on the combined dataset of the four subtypes. The accuracy reaches 84.6%, much higher than the best performance 75.1% reported by other subtype-free models, i.e. regional band-based model and residue-based model, for predicting the antigenicity of influenza. Also, we investigate the performance of CFreeEnS when the model is trained and tested on different subtypes (i.e. transfer learning). The prediction accuracy using CFreeEnS is 84.3% when the model is trained on the A/H1N1 dataset and tested on the A/H5N1, better than the 75.2% using a regional band-based model.

Conclusions

The CFreeEnS not only improves the prediction of antigenicity on datasets with only one subtype but also outperforms existing methods when tested on a combined dataset with four subtypes of influenza viruses.
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15.

Background

The introduction of the dengue virus (DENV) in Nepal is recent, first reports date back to 2004 from a Japanese traveller and limited information is available about DENV infection in the Nepali population. Within a decade after the first DENV detection, it is now endemic in multiple districts of Nepal with approximately 11.2 million people residing in the Terai belt being at risk of DENV infection. Sporadic cases of DENV infection have been reported every year for the past decade during the monsoon season, mainly in the Terai region.

Methods

Medline/Embase/Cochrane databases were reviewed for reports on the burden of dengue infection, diagnostic methods, and national surveillance.

Results

Four outbreaks were reported since 2004 including the diagnosis of all serotypes in 2006 and predominance of a single serotype in 2010 (DENV-1), 2013 (DENV-2), and 2016 (DENV-1). The clinical diagnoses showed a predominance of dengue fever while 4/917 (0.4%), 8/642 (1.2%) and 8/1615 (0.4%) dengue haemorrhagic fever/dengue shock syndrome cases were identified during the outbreaks in 2010, 2013 and 2016, respectively. The number of cases reported in males was significantly higher (67.4%) than in females. Disease occurrence was primarily found in the Terai region until 2010 and was increasingly detected in the Hilly region in 2016.

Conclusion

In Nepal currently weak diagnostic facilities, very limited research on mosquitoes vectors, and poor surveillance of dengue leading to inappropriate detection and control of DENV. We surmise that improved basic research and epidemiological training courses for local scientists and laboratory personal at national and international level will help better understand the evolution and distribution of DENV transmission and its eventual control.
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16.
17.

Background

We have previously shown that many chronic, inflammatory diseases are accompanied, and possibly partly caused or exacerbated, by various coagulopathies, manifested as anomalous clots in the form of ‘dense matted deposits’. More recently, we have shown that these clots can be amyloid in nature, and that the plasma of healthy controls can be induced to form such clots by the addition of tiny amounts of bacterial lipopolysaccharide or lipoteichoic acid. Type 2 diabetes (T2D) is also accompanied by raised levels of LPS.

Methods

We use superresolution and confocal microscopies to investigate the amyloid nature of clots from healthy and T2D individuals.

Results

We show here, with the established stain thioflavin T and the novel stains Amytracker? 480 and 680, that the clotting of plasma from type 2 diabetics is also amyloid in nature, and that this may be prevented by the addition of suitable concentrations of LPS-binding protein.

Conclusion

This implies strongly that there is indeed a microbial component to the development of type 2 diabetes, and suggests that LBP might be used as treatment for it and its sequelae.
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18.

Key message

Mutation of BSH1 leads to brittle sheath phenotype and reduction of very-long-chain fatty acids and their derivatives in wax.

Abstract

The cell wall plays an important role in plant mechanical strength. Several brittle culm mutants have been identified and characterized in rice. Here, we characterized an anther culture-derived rice brittle sheath mutant, named bsh1 and isolated BSH1 via map-based strategy. BSH1 encodes OsCYP96B4 protein, which was localized on ER membrane in the protoplast transient assay. BSH1 is mainly expressed in developing vascular tissues and the cells in which cell wall secondary thickening is occurring. Mutation in bsh1 causes changes in cell wall composition by affecting the expression of cell wall-related genes. Moreover, bsh1 shows reduced amounts of very-long-chain fatty acids and their derivatives in wax rather than the medium-chain fatty acids. In summary, BSH1 functions mainly in secondary cell wall formation, and probably in wax biosynthesis in an unidentified mechanism.
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19.

Background and aims

Although the role of microbial iron respiration in tidal marshes has been recognized for decades, the effect of rhizosphere processes on dissimilatory ferric iron reduction (FeR) is poorly known. Herein, we examined the FeR surrounding the root zone of three tidal marsh plants.

Methods

Using in situ rhizoboxes, we accurately separated rhizobox soil as one rhizosphere zone, and three bulk soil zones. Dissimilatory and sulfidic-mediated FeR were quantified by accumulation of non-sulfidic Fe(II) and Fe sulfides over time, respectively.

Results

The rates of dissimilatory FeR attained 42.5 μmol Fe g?1 d?1 in the rhizosphere, and logarithmically declined by up to 19.1 μmol Fe g?1 d?1 in the outer bulk soil. The rates of sulfidic-mediated FeR were less than 2 μmol Fe g?1 d?1 among all zones. Poorly crystalline Fe(III), DOC and DON, porewater Fe2+, and SO42? were all enriched in the rhizosphere, whereas non-sulfidic Fe(II) and Fe sulfides gradually accumulated away from the roots. Iron reducers (Geobacter, Bacillus, Shewanella, and Clostridium) had higher populations in the rhizosphere than in the bulk soil. Higher rates of dissimilatory FeR were observed in the Phragmites australis and Spartina alterniflora rhizoboxes than in the Cyperus malaccensis rhizoboxes.

Conclusions

The radial change pattern of dissimilatory FeR rates were determined by allocation of poorly crystalline Fe(III) and dissolved organic carbon. The interspecies difference of rhizosphere dissimilatory FeR was associated with the root porosity and aerenchyma of the tidal marsh plants.
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20.

Key message

This review gives a comprehensive overview of adaptations of mangrove root system to the adverse environmental conditions and summarizes the ecological importance of mangrove root to the ecosystem.

Abstract

In plants, the first line of defense against abiotic stress is in their roots. If the soil surrounding the plant root is healthy and biologically diverse, the plant will have a higher chance to survive in stressful conditions. Different plant species have unique adaptations when exposed to a variety of abiotic stress conditions. None of the responses are identical, even though plants have become adapted to the exact same environment. Mangrove plants have developed complex morphological, anatomical, physiological, and molecular adaptations allowing survival and success in their high-stress habitat. This review briefly depicts adaptive strategies of mangrove roots with respect to anatomy, physiology, biochemistry and also the major advances recently made at the genetic and genomic levels. Results drawn from the different studies on mangrove roots have further indicated that specific patterns of gene expression might contribute to adaptive evolution of mangroves under high salinity. We also review crucial ecological contributions provided by mangrove root communities to the ecosystem including marine fauna.
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