4,560 research outputs found
Potential distribution range of invasive plant species in Spain
No full textSuccess of invasive species has been frequently estimated as the present distribution range size in the introduced region. However, the present distribution range is only a picture of the invasion for a given time step and do not inform on the potential distribution range of the species. Based on niche-based models we used climatic, geographic and landscape information on the present distribution range for 78 major plant invaders in Spain to estimate and map their potential distribution range. We found a positive relationship between present and potential distribution of species. Most of the species have not yet occupied half of their potential distribution range. Sorghum halepense and Amaranthus retroflexus have the widest potential distribution range. Sorghum halepense and Robinia pseudoacacia have the highest relative occupancy (i.e. proportion of potential distribution range currently occupied). Species with a larger minimum residence time have, on average, higher relative occupancy. Our study warns managers that it might be only a matter of time that currently localized invasive species reach their potential area of distribution
LC-API/MS in Drug Metabolism and Pharmacokinetic Studies
No full textThe use of API interfaces with quadrupole mass spectrometers has been shown to give rise to good sensitivity, selectivity, and robustness for the interfacing of LC to MS. Since their introduction in the 1990s the technique has rapidly become widespread, but at the outset of this research programme, there were still a number of problems associated with it, particularly when dealing with complex sample matrices. The aim of this research programme was to study illustrative examples of the kinds of problems associated with the analysis of biological samples using LC-API-MS in an attempt to arrive at strategies which could be employed to eliminate, or at least compensate for, the problems.
Commonly reported problems include the occurrence of matrix effects - a change in response of the target analyte(s) as a result of the presence in the samples of co /late eluting interferences. An investigation which compared ESI with APCI ionisation illustrated a significant drawback in the accepted methodology for the elimination of matrix effects.
Optimal LC conditions for a number of assays may use non-MS-friendly mobile phases. A simple and convenient solution to this problem was found to be the post column addition of organic modifier, which reproducibly and reliably enhanced sensitivity. This approach was initially used for a range of dihydropyridine calcium channel blockers and was subsequently applied to a range of chiral compounds from different therapeutic groups to illustrate that this was applicable as a generic technique for increasing sensitivity (typically by around an order of magnitude) in low organic mobile phases.
Strategies to develop and validate methods for the determination of endogenous analytes in a biological fluid were investigated. This involved the use of a surrogate matrix, to develop a method for the determination of endogenous testosterone in human serum and the use of non-matrix calibration standards for the successful development and validation of a method for the analysis of indolyl 3 acryloylglycine (IAG) in human urine.
As a result of observations suggesting promotion of ionisation of deltamethrin in liver tissue sample extracts, it was postulated that this was due to the presence of high concentrations of surfactants. After confirming the effect, a series of systematic investigations were performed to attempt to understand the mechanism to be able to utilise this as a general method for the enhancement of signal with low sensitivity analytes. It was found that the type of surfactant and concentration used was directly associated with an increased (or decreased) response.
Although there remain a number of problems associated with the use of LC-API-MS, the work undertaken for this thesis has successfully demonstrated a number of techniques that can be applied to overcome these problems. Knowledge of the nature of the sample undergoing analysis, the required analytical conditions, and where required careful application of one of the techniques described will ensure that a robust method can be readily developed
Book No. 423; Township 23S, Range 09E, Assessor Parcel Map MS 79-38, South 1/2 of Northeast 1/4 and Portion of North 1/2 of Southeast 1/4 of Section 25 - May 1979
No full textAssessor parcel map MS 79-38, South 1/2 of Northeast 1/4 and Portion of North 1/2 of Southeast 1/4 of Section 25 in Township 23S, Range 09E, Monterey County, California.https://digitalcommons.csumb.edu/hornbeck_cgb_14/1608/thumbnail.jp
Multi-Segment Direct Inject nano-ESI-LTQ-FT-ICR-MS/MS For Protein Identification
No full textAbstract Reversed phase high performance liquid chromatography (HPLC) interfaced to electrospray tandem mass spectrometry (MS/MS) is commonly used for the identification of peptides from proteolytically cleaved proteins embedded in a polyacrylamide gel matrix as well as for metabolomics screening. HPLC separations are time consuming (30-60 min average), costly (columns and mobile phase reagents), and carry the risk of column carry over between samples. The use of a chip-based nano-ESI platform (Advion NanoMate) based on replaceable nano-tips for sample introduction eliminates sample cross-contamination, provides unchanging sample matrix, and enhances spray stability with attendant increases in reproducibility. Recent papers have established direct infusion nano-ESI-MS/MS utilizing the NanoMate for protein identification of gel spots based on full range MS scans with data dependent MS/MS. In a full range scan, discontinuous ion suppression due to sample matrix can impair identification of putative mass features of interest in both the proteomic and metabolomic workflows. In the current study, an extension of an established direct inject nano-ESI-MS/MS method is described that utilizes the mass filtering capability of an ion-trap for ion packet separation into four narrow mass ranges (50 amu overlap) with segment specific dynamic data dependent peak inclusion for MS/MS fragmentation (total acquisition time of 3 minutes). Comparison of this method with a more traditional nanoLC-MS/MS based protocol utilizing solvent/sample stream splitting to achieve nanoflow demonstrated comparable results for protein identification from polyacrylamide gel matrices. The advantages of this method include full automation, lack of cross-contamination, low cost, and high throughput.</p
Inter-laboratory reproducibility of fast gas chromatography-electron impact-time of flight mass spectrometry (GC-EI-TOF/MS) based plant metabolomics
No full textThe application of gas chromatography¿mass spectrometry (GC¿MS) to the `global¿ analysis of metabolites in complex samples (i.e. metabolomics) has now become routine. The generation of these data-rich profiles demands new strategies in data mining and standardisation of experimental and reporting aspects across laboratories. As part of the META-PHOR project¿s (METAbolomics for Plants Health and OutReach: http://www.meta-phor.eu/) priorities towards robust technology development, a GC¿MS ring experiment based upon three complex matrices (melon, broccoli and rice) was launched. All sample preparation, data processing, multivariate analyses and comparisons of major metabolite features followed standardised protocols, identical models of GC (Agilent 6890N) and TOF/MS (Leco Pegasus III) were also employed. In addition comprehensive GC×GC¿TOF/MS was compared with 1 dimensional GC¿TOF/MS. Comparisons of the paired data from the various laboratories were made with a single data processing and analysis method providing an unbiased assessment of analytical method variants and inter-laboratory reproducibility. A range of processing and statistical methods were also assessed with a single exemplary dataset revealing near equal performance between them. Further investigations of long-term reproducibility are required, though the future generation of global and valid metabolomics databases offers much promis
SALDI-MS of real world samples
No full textSurface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) is a method of mass spectrometry, ideal for the low mass range, as it reduces fragmentation and helps with clarity of sample analysis. Projected applications of this technology can be seen in medical and drug research.
• Quinine is a small, organic biomolecule (molecular weight 325 g/mol) that is derived from the bark of the cinchona plant. Native to the Americas, is historically used as an anti-malaria, but in recent years has emerged in drug analyses of heroin. Dealers dilute the sample in quinine, which has a similar bitter taste, as a way to conserve supply.
Due to its variety of functional groups and reactive units, quinine has many side effects. As of April 2019, the FDA limits quinine to 83ppm in beverage samples. Coupled with its increased use in illegal drugs and its regulated recreational use, a new, quick and easy method of detection is needed for its analysis.
• Quinine is commonly found dissolved in carbonated beverages to make tonic water.
• Transition metal oxide (TMOs) nanoparticles are used in SALDI-MS because they require minimal sample preparation, have large surface area to sample rations (which helps with desorption/ionization), and they are compatible with a wide range of different samples
Impacts of climate driven range changes on the genetics and morphology of butterflies
No full textThis thesis studied the genetic responses of butterflies to climate induced distribution shifts in terms of patterns of genetic diversity at expanding and contracting range margins, the relative importance of genes versus environment on adaptations to dispersal and local adaptation to temperature during range expansion.
Loss of genetic diversity during range expansion in Pararge aegeria was confirmed using neutral genetic markers (AFLPs). High reductions of genetic diversity were discovered at the range margin relative to the distribution core. Range margin populations exhibit a nearly 50% reduction in neutral genetic diversity, and lower genetic divergence between sites.
The contracting southern range margin of the butterfly Erebia aethiops has not suffered a reduction in genetic diversity relative to the distribution core. As genetic diversity remains relatively high population extinction is unlikely to be exacerbated by inbreeding or reduced fitness from low genetic diversity during range contraction.
Contrary to results from laboratory reared butterflies, wild male P. aegeria do not have significant differences in flight morphology between core and margin sites. This suggests developmental influences suppress the expression of genetic adaptations to dispersal. Wild butterflies also represent a smaller range of phenotypes possibly indicating balancing selection on morphological traits.
Little to no evidence for local adaptation to temperature is apparent at the expanding range margin of P. aegeria. Neither was there evidence for reduced fitness due to lower genetic diversity, as F2 butterflies from core sites had poorer survival rates than the less genetically diverse margin sites.
This study found that neutral genetic diversity is unlikely to affect species during distribution shifts as even high losses during distribution expansion do not appear to affect survival rates. Also adaptation to dispersal and temperature may be limited during range expansion both by environmental constraints and limited selection pressure respectively
Early ADMET profiling of anti-inflammatory alkaloids using validated LC-MS/MS methods
No full textNatural products provide an important and unique source of new lead compounds for drug discovery. Approximately 50% of all new chemical entities are inspired by nature. In the search of novel anti-inflammatory compounds in the ancient medicinal plant Isatis tinctoria, tryptanthrin, indirubin, and (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolin-2-one (indolinone) were identified as pharmacologically active constituents. They inhibit, at low µM to nM concentrations, cyclo-oxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) catalyzed leukotriene synthesis, cyclin-dependent kinase (CDK), glycogensynthase kinase-3b (GSK), and mast cell degranulation. While the molecular modes of action of these alkaloids are not yet fully understood, their unique pharmacological profiles, structural drug-like properties, and low cytotoxicity render these molecules promising anti-inflammatory leads. To further evaluate the potential of these alkaloids as novel anti-inflammatory and anti-allergic leads, an assessment of their ADMET properties was warranted. For exact quantification of the compounds, LC-MS/MS methods were developed and validated according to current regulatory guidelines.
To get a first prognostic picture for the in vivo performance of our compounds, a pilot PK study was performed in male Sprague Dawley rats after intravenous administration at a concentration of 2 mg/kg b.w.. Tryptanthrin and indirubin showed a half-life (t1/2) of around 40 min, while indolinone was quickly eliminated (t1/2 = 4 min).
As most of the drugs are preferentially administered orally, the gastrointestinal tract (GIT) represents the major site of drug absorption. Human colon carcinoma cells (Caco-2 cells) serve as the method of choice to predict human drug absorption across the intestinal wall in vitro. To study the permeability of the three compounds across the epithelial monolayer, the alkaloids were screened at concentrations of 5-10 µM in the Caco-2 assay. As efflux transporters can greatly impact the in vivo absorption and, thus, the bioavailability of a drug candidate, the compounds were tested for possible P-glycoprotein (P-gp) interaction. Therefore, the alkaloids were co-incubated with the P-gp inhibitor verapamil (50 µM). Active efflux was assessed by calculating the efflux ratio (ER) from bidirectional assays. Due to high lipophilicity of indirubin, the compound precipitated in the transporter buffer and was thus excluded for further investigations in aqueous solutions. Tryptanthrin displayed a high permeability (Papp > 32.0 x 10-6 cm/s) across the cell monolayer. The efflux ratio below 2 (< 1.12) and the unchanged Papp values in presence of the P-glycoprotein (P-gp) inhibitor verapamil indicated that tryptanthrin was not involved in P-gp mediated efflux. In the Caco-2 assay, the recovery of indolinone was low, pointing to possibly extensive phase II metabolism. Further investigation by a high-resolution mass spectrometry (HR-MS) system revealed the formation of two sulfate and two glucuronide conjugates for indolinone.
Another well-known biological barrier in the human body is the blood-brain barrier (BBB). To evaluate the BBB permeation potential of tryptanthrin and indolinone, the compounds were tested in three cell-based human and animal BBB models. Data obtained with the human and animal BBB models showed good correlation and were indicative of a high BBB permeation potential of tryptanthrin and indolinone. Furthermore, active-mediated efflux was evaluated by calculating the ER from bidirectional assays. The ERs below 2 suggested that both compounds were not involved in active-mediated efflux.
Besides P-gp, another critical anti-target in drug development is the human ether-a-go-go (hERG) potassium channel. In the late 1990s, an increasing number of non-cardiovascular drugs have been withdrawn from the market due to cardiotoxic side-effects linked to hERG blocking. Since then, regulatory agencies insist on acquiring experimental hERG data of drug candidates before moving into clinical trials. Possible cardiotoxic liability of the compounds was assessed in vitro, by measurement of an inhibitory effect on hERG tail currents in stably transfected HEK 293 cells using the patch-clamp technique. Slight hERG inhibition was found for tryptanthrin (IC50 of 22 µM) and indolinone (IC50 of 25 µM).
Data obtained from the in vitro assays were corroborated by in silico predictions. For tryptanthrin and indolinone, all criteria for high human oral absorption and passive BBB penetration were met. In addition, the slight hERG inhibition found for tryptanthrin and indolinone in vitro could be confirmed by in silico predictions
SIMULTANEOUS DETERMINATION OF SIX PHENOLIC COMPOUNDS IN GUANXIN II PRESCRIPTION BY HPLC/MS/MS
No full textAn HPLC method coupled with triple quadrupole mass spectrometry (MS/MS) was applied to the determination of tanshinone IIA (TanllA), salvianolic acid B (SA-B), protocatechuic acid (PA), protocatechuic aldehyde (PAH), paeoniflorin (PF), and ferulic acid (FA) in Guanxinll prescription. These six compounds were analyzed simultaneously with YMC ODS-AQ column by using an aqueous mobile phase (containing 0.1% acetic acid) modified by methanol in a gradient program. The flow rate was 0.30 mL/min. Triple quadrupole mass spectrometry was optimized in both positive and negative ion multiple reaction monitoring modes for the simultaneous quantitative analysis of the two different types of active components by using a time-segment program. The method gave recoveries of 98.9-102.5% with relative standard deviations of 1.14-2.09% for the spiked herb samples. Limits of detection (LODs) ranged from 0.21 to 4.28 ng/mL and all the compounds showed good linearity in a relatively wide concentration range. The results indicated that HPLC-MS/MS provided rapid and sensitive analysis of six bioactive markers in GuanxinII prescription for quality control and authentication.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000304301600002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Biochemical Research MethodsChemistry, AnalyticalSCI(E)EI0ARTICLE6757-7673
The Timing of Feedback to Early Visual Cortex in the Perception of Long-Range Apparent Motion
No full textWhen 2 visual stimuli are presented one after another in different locations, they are often perceived as one, but moving object. Feedback from area human motion complex hMT/V5+ to V1 has been hypothesized to play an important role in this illusory perception of motion. We measured event-related responses to illusory motion stimuli of varying apparent motion (AM) content and retinal location using Electroencephalography. Detectable cortical stimulus processing started around 60-ms poststimulus in area V1. This component was insensitive to AM content and sequential stimulus presentation. Sensitivity to AM content was observed starting around 90 ms post the second stimulus of a sequence and most likely originated in area hMT/V5+. This AM sensitive response was insensitive to retinal stimulus position. The stimulus sequence related response started to be sensitive to retinal stimulus position at a longer latency of 110 ms. We interpret our findings as evidence for feedback from area hMT/V5+ or a related motion processing area to early visual cortices (V1, V2, V3)
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