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1.
Sci Total Environ ; 941: 173488, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38810748

ABSTRACT

Wildfires strongly alter hydrological processes and surface and groundwater quality in forested environments. The paired-watershed method, consisting of comparing a burnt (altered) watershed with an unburnt (control) watershed, is commonly adopted in studies addressing the hydrological effects of wildfires. This approach requires a calibration period to assess the pre-perturbation differences and relationships between the control and the altered watershed. Unfortunately, in many studies, the calibration phase is lacking due to the unpredictability of wildfires and the large number of processes that should be investigated. So far, no information is available on the possible bias induced by the lack of the calibration period in the paired-watershed method when assessing the hydrological impacts of wildfires. Through a literature review, the consequences of the lack of calibration on the assessment of wildfire hydrological changes were evaluated, along with the most used watershed pairing strategies. The literature analysis showed that if calibration is lacking, misestimation of wildfire impacts is likely, particularly when addressing low-severity or long-term wildfire effects. The Euclidean distance based on physical descriptors (geology, morphology, vegetation) was proposed as a metric of watersheds similarity and tested in mountain watersheds in Central Italy. The Euclidean distance proved to be an effective metric for selecting the most similar watershed pairs. This work raises awareness of biases exerted by lacking calibration in paired-watershed studies and proposes a rigorous and objective methodology for future studies on the hydrological effects of wildfires.

2.
Opt Express ; 22(10): 11570-7, 2014 May 19.
Article in English | MEDLINE | ID: mdl-24921277

ABSTRACT

We report on the resonant Fabry Perot cavity of the PVLAS (Polarization of the Vacuum with LASer) experiment operating at λ = 1064 nm with a record decay time of 2.7 ms, a factor more than two larger than any previously reported optical resonator. This corresponds to a coherence length of 8.1 · 10(5) m. The cavity length is 3.303 m, and the resulting finesse is 770,000.

3.
J Chromatogr A ; 1284: 36-43, 2013 Apr 05.
Article in English | MEDLINE | ID: mdl-23466198

ABSTRACT

The peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily. In the last years novel PPARs ligands have been identified and these include PPARα/γ dual agonists. To rapidly identify novel PPARs dual ligands, a robust binding assay amenable to high-throughput screening toward PPAR isoforms would be desirable. In this work we describe a parallel assay based on the principles of frontal affinity chromatography coupled to mass spectrometry (FAC-MS) that can be used to characterize dual agonists. For this purpose the ligand binding domain of PPARα receptor was immobilized onto the surface of open tubular capillaries to create new PPAR-alpha-OT columns to be used in parallel with PPAR-gamma-OT columns. The two biochromatographic systems were used in both ranking and Kd experiments toward new ureidofibrate-like dual agonists for subtype selectivity ratio determination. In order to validate the system, the Kd values determined by frontal analysis chromatography were compared to the affinity constants obtained by ITC experiments. The results of this study strongly demonstrate the specific nature of the interaction of the ligands with the two immobilized receptor subtypes.


Subject(s)
Chromatography, Affinity/instrumentation , Chromatography, Affinity/methods , Mass Spectrometry/methods , PPAR alpha/chemistry , PPAR gamma/chemistry , Calorimetry , Drug Discovery/methods , Immobilized Proteins/agonists , Immobilized Proteins/chemistry , Immobilized Proteins/metabolism , Ligands , PPAR alpha/agonists , PPAR alpha/metabolism , PPAR gamma/agonists , PPAR gamma/metabolism , Protein Binding , Reproducibility of Results
4.
J Med Chem ; 56(1): 60-72, 2013 Jan 10.
Article in English | MEDLINE | ID: mdl-23171045

ABSTRACT

The preparation of a series of 2-(aryloxy)-3-phenylpropanoic acids, resulting from the introduction of different substituents into the biphenyl system of the previously reported peroxisome proliferator-activated receptor α/γ (PPARα/γ) dual agonist 1, allowed the identification of new ligands with higher potency on PPARα and fine-tuned moderate PPARγ activity. For the most promising stereoisomer (S)-16, X-ray and calorimetric studies in PPARγ revealed, at high ligand concentration, the presence of two molecules simultaneously bound to the receptor. On the basis of these results and docking experiments in both receptor subtypes, a molecular explanation was provided for its different behavior as a full and partial agonist of PPARα and PPARγ, respectively. The effects of (S)-16 on mitochondrial acylcarnitine carrier and carnitine-palmitoyl-transferase 1 gene expression, two key components of the carnitine shuttle system, were also investigated, allowing the hypothesis of a more beneficial pharmacological profile of this compound compared to the less potent PPARα agonist fibrates currently used in therapy.


Subject(s)
Carnitine O-Palmitoyltransferase/metabolism , Membrane Transport Proteins/metabolism , Mitochondrial Proteins/metabolism , PPAR alpha/agonists , PPAR gamma/agonists , Propionates/chemical synthesis , Calorimetry , Carnitine O-Palmitoyltransferase/genetics , Cell Line, Tumor , Crystallography, X-Ray , Humans , Membrane Transport Proteins/genetics , Mitochondrial Proteins/genetics , Molecular Docking Simulation , Propionates/chemistry , Propionates/pharmacology , Protein Conformation , Stereoisomerism , Structure-Activity Relationship , Thermodynamics , Transcriptional Activation , Up-Regulation
5.
J Med Chem ; 55(1): 37-54, 2012 Jan 12.
Article in English | MEDLINE | ID: mdl-22081932

ABSTRACT

A series of ureidofibrate-like derivatives was prepared and assayed for their PPAR functional activity. A calorimetric approach was used to characterize PPARγ-ligand interactions, and docking experiments and X-ray studies were performed to explain the observed potency and efficacy. R-1 and S-1 were selected to evaluate several aspects of their biological activity. In an adipogenic assay, both enantiomers increased the expression of PPARγ target genes and promoted the differentiation of 3T3-L1 fibroblasts to adipocytes. In vivo administration of these compounds to insulin resistant C57Bl/6J mice fed a high fat diet reduced visceral fat content and body weight. Examination of different metabolic parameters showed that R-1 and S-1 are insulin sensitizers. Notably, they also enhanced the expression of hepatic PPARα target genes indicating that their in vivo effects stemmed from an activation of both PPARα and γ. Finally, the capability of R-1 and S-1 to inhibit cellular proliferation in colon cancer cell lines was also evaluated.


Subject(s)
Benzoxazoles/chemistry , Fibric Acids/chemistry , PPAR alpha/metabolism , PPAR gamma/metabolism , Propionates/chemistry , Urea/chemistry , Adipocytes/cytology , Adipocytes/drug effects , Adipocytes/metabolism , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Benzoxazoles/chemical synthesis , Benzoxazoles/pharmacology , Body Weight/drug effects , Calorimetry , Cell Differentiation/drug effects , Cell Line , Cell Line, Tumor , Cell Proliferation/drug effects , Crystallography, X-Ray , Drug Partial Agonism , Drug Screening Assays, Antitumor , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/metabolism , Gene Expression Profiling , Humans , Insulin Resistance , Intra-Abdominal Fat/drug effects , Liver/drug effects , Liver/metabolism , Mice , Mice, Inbred C57BL , Models, Molecular , PPAR alpha/agonists , PPAR alpha/genetics , PPAR gamma/agonists , PPAR gamma/genetics , Propionates/chemical synthesis , Propionates/pharmacology , Stereoisomerism , Structure-Activity Relationship
6.
J Chromatogr A ; 1232: 84-92, 2012 Apr 06.
Article in English | MEDLINE | ID: mdl-22056242

ABSTRACT

In this study we report the development of new chromatographic tools for binding studies based on the gamma isoform ligand binding domain (LBD) of peroxisome proliferator-activated receptor (PPARγ) belonging to the nuclear receptor superfamily of ligand-activated transcription factors. PPARγ subtype plays important roles in the functions of adipocytes, muscles, and macrophages with a direct impact on type 2 diabetes, dyslipidemia, atherosclerosis, and cardiovascular disease. In order to set up a suitable immobilization chemistry, the LBD of PPARγ receptor was first covalently immobilized onto the surface of aminopropyl silica particles to create a PPARγ-Silica column for zonal elution experiments and then onto the surface of open tubular (OT) capillaries to create PPARγ-OT capillaries following different immobilization conditions. The capillaries were used in frontal affinity chromatography coupled to mass spectrometry (FAC-MS) experiments to determine the relative binding affinities of a series of chiral fibrates. The relative affinity orders obtained for these derivatives were consistent with the EC(50) values reported in literature. The optimized PPARγ-OT capillary was validated by determining the K(d) values of two selected compounds. Known the role of stereoselectivity in the binding of chiral fibrates, for the first time a detailed study was carried out by analysing two enantioselective couples on the LBD-PPARγ capillary by FAC and a characteristic two-stairs frontal profile was derived as the result of the two saturation events. All the obtained data indicate that the immobilized form of PPARγ-LBD retained the ability to specifically bind ligands.


Subject(s)
Chromatography, Affinity/methods , Immobilized Proteins/metabolism , Macromolecular Substances/metabolism , Mass Spectrometry/methods , PPAR gamma/metabolism , Binding Sites , Drug Discovery/methods , Hep G2 Cells , Humans , Ligands , Stereoisomerism
7.
Food Addit Contam ; 22(5): 437-42, 2005 May.
Article in English | MEDLINE | ID: mdl-16019815

ABSTRACT

The occurrence of patulin was investigated in 100 conventional and 69 organic fruity foodstuffs samples commercially available in Italy by using an HPLC method with a limit of quantification of 0.5 microg kg(-1). Patulin was detected in 26 (26%) conventional and 31 (45%) organic products with a significantly higher (p<0.01) mean concentration in the organic products (4.78 vs. 1.15 microg kg(-1)). Mean patulin concentrations in conventional apple juices, pear juices, other juices and fruits purees were 3.14, 0.22, 0.19, 0.11 microg kg(-1), respectively, and 7.11, 11.46, 2.10, 0.18 microg kg(-1) in the relevant organic products. Four samples of juices (one conventional and two organic apple, and one organic pear) contained patulin at concentrations above the limit of 50 microg kg(-1), four at concentrations between 10 and 25 microg kg(-1), and the remaining ones below 10 microg kg(-1). Patulin was detected (<1 microg kg(-1)) in only three of the 23 fruity baby food samples tested (homogenized fruits, 11 conventional and 12 organic). Based on the available data on Italian intakes of fruit juices, the estimated daily intakes of patulin, were 0.38 and 1.57 ng kg(-1) body weight (bw) from conventional and organic products, respectively. Estimated daily intakes of patulin for children were higher, 3.41 ng kg(-1) bw from conventional and 14.17 ng kg(-1) bw from organic products, but largely below the provisional maximum tolerable daily intake (PMTDI) of 400 ng kg(-1) bw. Patulin was also found in two samples of organic apple vinegar (<5 microg kg(-1)) and in fresh apples with rotten spots (12 out of 24 samples) with maximum levels at 16,402 and 44,572 microg kg(-1) for conventional and organic apples, respectively.


Subject(s)
Fruit/chemistry , Patulin/analysis , Beverages/analysis , Chromatography, High Pressure Liquid/methods , Eating , Environmental Exposure/adverse effects , Food Contamination/analysis , Food, Organic/analysis , Humans , Italy , Malus/chemistry , Mycotoxins/analysis , Pyrus/chemistry , Risk Assessment/methods
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