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1.
Sci Total Environ ; 945: 173950, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38879021

ABSTRACT

Neonicotinoids are the top-selling insecticides worldwide. Because of their method of use, mainly to coat seeds, neonicotinoids have been found to widely contaminate the environment. Their high toxicity has been shown to be a major concern in terms of impact on biodiversity, and the use of these insecticides has been associated with population declines of species in different countries. Despite the widespread recognition of the risk of neonicotinoids to biodiversity, their temporal and spatial use remains poorly known in many countries. Yet this information is essential to address the potential impacts of these pesticides on biodiversity and to inform measures to establish protected areas or biodiversity restoration. The present study relied a large publicly available dataset to characterise the temporal and spatial use in France of imidacloprid, the most widely used neonicotinoid worldwide, as well as analysed water contamination surveys between 2005 and 2022 to assess the contamination of the environment. The results show that imidacloprid was the main neonicotinoid used in France over the study period. This use was spatially structured, with higher use in northern and western France, particularly related to cereal and beet crops area. The water contamination survey indicated that imidacloprid has widely contaminated the environment and consequently increased the risk to biodiversity, especially in counties crossed by the Loire, Seine and Vilaine rivers. This risk increased between 2005 and 2018 due to the higher use of imidacloprid and decreased sharply after 2018 due to its ban, although it was reauthorized by derogation for sugar beet in 2021. This study is the first assessment of imidacloprid pressure on biodiversity in France and shows the spatial and temporal correlation between agricultural practices and the freshwater contamination level. These results will help to identify priority areas for mitigation and restoration measures.


Subject(s)
Environmental Monitoring , Insecticides , Neonicotinoids , Nitro Compounds , Neonicotinoids/analysis , France , Nitro Compounds/analysis , Insecticides/analysis , Biodiversity , Water Pollutants, Chemical/analysis , Spatio-Temporal Analysis
2.
Curr Opin Biotechnol ; 87: 103098, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38452572

ABSTRACT

Natural products represent an inestimable source of valuable compounds for human health. Notably, those produced by plants remain challenging to access due to their low production. Potential shortages of plant-derived biopharmaceuticals caused by climate change or pandemics also regularly tense the market trends. Thus, biotechnological alternatives of supply based on synthetic biology have emerged. These innovative strategies mostly rely on the use of engineered microbial systems for compound synthesis. In this regard, yeasts remain the easiest-tractable eukaryotic models and a convenient chassis for reconstructing whole biosynthetic routes for the heterologous production of plant-derived metabolites. Here, we highlight the recent discoveries dedicated to the bioproduction of new-to-nature compounds in yeasts and provide an overview of emerging strategies for optimising bioproduction.


Subject(s)
Biological Products , Biological Products/metabolism , Plants/metabolism , Biotechnology/methods , Synthetic Biology , Yeasts/metabolism , Metabolic Engineering/methods , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/genetics , Humans
3.
Proc Natl Acad Sci U S A ; 120(49): e2300861120, 2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38011572

ABSTRACT

Increasing landscape heterogeneity has been suggested to be an important strategy to strengthen natural pest control in crops, especially through enhancing the amount of seminatural habitats. Increasing crop diversity is also a promising strategy to complement or replace seminatural habitat when seminatural habitat is scarce. However, their relative or possibly interactive effects on pest and weed infestation remain poorly investigated, and the role of different types of seminatural habitats has been understudied. Using an extensive sampling effort in 974 arable fields across 7 y, we evaluated the separate and interactive effects of crop diversity (seven arable crop types) and the amount of four types of seminatural habitats (meadows, hay, forests, and hedgerows) in the landscape on pest and weed control. Meadows and crop diversity, respectively, supported insect pest and weed control services in agricultural landscapes through a complementarity effect. Crop diversity increased weed seed predation rate (by 16%) and reduced weed infestation (by 6%), whereas long-term grasslands (to a much higher degree than hay or woody habitats) increased insect pest predation rates (by 23%) and reduced pest infestation (by 19%) in most arable crops. Our results demonstrate that diversification of the agricultural landscape requires long-term grasslands as well as improved crop diversity to ensure the delivery of efficient pest and weed control services.


Subject(s)
Agriculture , Grassland , Animals , Agriculture/methods , Ecosystem , Crops, Agricultural , Insecta
4.
Synth Syst Biotechnol ; 8(2): 224-226, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36936387

ABSTRACT

Synthetic biology is constantly making progress for producing compounds on demand. Recently, Yocum and collaborators have developed an outstanding approach based on the anchoring of biosynthetic enzymes to the peroxisomal membrane. This allowed access to an untapped resource of acetyl-CoA and stimulated the synthesis of a valuable polyketide.

5.
Biochem Biophys Res Commun ; 649: 79-86, 2023 03 15.
Article in English | MEDLINE | ID: mdl-36758482

ABSTRACT

Glutathione transferases are detoxification enzymes with multifaceted roles, including a role in the metabolism and scavenging of nitric oxide (NO) compounds in cells. Here, we explored the ability of Trametes versicolor glutathione transferases (GSTs) from the Omega class (TvGSTOs) to bind metal-nitrosyl compounds. TvGSTOs have been studied previously for their ligandin role and are interesting models to study protein‒ligand interactions. First, we determined the X-ray structure of the TvGSTO3S isoform bound to the dinitrosyl glutathionyl iron complex (DNGIC), a physiological compound involved in the storage of nitric oxide. Our results suggested a different binding mode compared to the one previously described in human GST Pi 1 (GSTP1). Then, we investigated the manner in which TvGSTO3S binds three nonphysiological metal-nitrosyl compounds with different metal cores (iron, ruthenium and osmium). We assayed sodium nitroprusside, a well-studied vasodilator used in cases of hypertensive crises or heart failure. Our results showed that the tested GST can bind metal-nitrosyls at two distinct binding sites. Thermal shift analysis with six isoforms of TvGSTOs identified TvGSTO6S as the best interactant. Using the Griess method, TvGSTO6S was found to improve the release of nitric oxide from sodium nitroprusside in vitro, whereas the effects of human GST alpha 1 (GSTA1) and GSTP1 were moderate. Our results open new structural perspectives for understanding the interactions of glutathione transferases with metal-nitrosyl compounds associated with the biochemical mechanisms of NO uptake/release in biological systems.


Subject(s)
Nitric Oxide , Trametes , Humans , Nitric Oxide/metabolism , Nitroprusside/pharmacology , Trametes/metabolism , Glutathione Transferase/metabolism , Iron/metabolism , Glutathione/metabolism
6.
Plants (Basel) ; 11(9)2022 Apr 20.
Article in English | MEDLINE | ID: mdl-35567119

ABSTRACT

Plant ß-glucanases are enzymes involved in the synthesis, remodelling and turnover of cell wall components during multiple physiological processes. Based on the type of the glycoside bond they cleave, plant ß-glucanases have been grouped into three categories: (i) ß-1,4-glucanases degrade cellulose and other polysaccharides containing 1,4-glycosidic bonds to remodel and disassemble the wall during cell growth. (ii) ß-1,3-glucanases are responsible for the mobilization of callose, governing the symplastic trafficking through plasmodesmata. (iii) ß-1,3-1,4-glucanases degrade mixed linkage glucan, a transient wall polysaccharide found in cereals, which is broken down to obtain energy during rapid seedling growth. In addition to their roles in the turnover of self-glucan structures, plant ß-glucanases are crucial in regulating the outcome in symbiotic and hostile plant-microbe interactions by degrading non-self glucan structures. Plants use these enzymes to hydrolyse ß-glucans found in the walls of microbes, not only by contributing to a local antimicrobial defence barrier, but also by generating signalling glucans triggering the activation of global responses. As a counterpart, microbes developed strategies to hijack plant ß-glucanases to their advantage to successfully colonize plant tissues. This review outlines our current understanding on plant ß-glucanases, with a particular focus on the latest advances on their roles in adaptative responses.

7.
J Clin Med ; 11(7)2022 Mar 30.
Article in English | MEDLINE | ID: mdl-35407528

ABSTRACT

Diffusion weighted imaging (DWI) constitutes a major functional parameter performed in Magnetic Resonance Imaging (MRI). The DW sequence is performed by acquiring a set of native images described by their b-values, each b-value representing the strength of the diffusion MR gradients specific to that sequence. By fitting the data with models describing the motion of water in tissue, an apparent diffusion coefficient (ADC) map is built and allows the assessment of water mobility inside the tissue. The high cellularity of tumors restricts the water diffusion and decreases the value of ADC within tumors, which makes them appear hypointense on ADC maps. The role of this sequence now largely exceeds its first clinical apparitions in neuroimaging, whereby the method helped diagnose the early phases of cerebral ischemic stroke. The applications extend to whole-body imaging for both neoplastic and non-neoplastic diseases. This review emphasizes the integration of DWI in the genitourinary system imaging by outlining the sequence's usage in female pelvis, prostate, bladder, penis, testis and kidney MRI. In gynecologic imaging, DWI is an essential sequence for the characterization of cervix tumors and endometrial carcinomas, as well as to differentiate between leiomyosarcoma and benign leiomyoma of the uterus. In ovarian epithelial neoplasms, DWI provides key information for the characterization of solid components in heterogeneous complex ovarian masses. In prostate imaging, DWI became an essential part of multi-parametric Magnetic Resonance Imaging (mpMRI) to detect prostate cancer. The Prostate Imaging-Reporting and Data System (PI-RADS) scoring the probability of significant prostate tumors has significantly contributed to this success. Its contribution has established mpMRI as a mandatory examination for the planning of prostate biopsies and radical prostatectomy. Following a similar approach, DWI was included in multiparametric protocols for the bladder and the testis. In renal imaging, DWI is not able to robustly differentiate between malignant and benign renal tumors but may be helpful to characterize tumor subtypes, including clear-cell and non-clear-cell renal carcinomas or low-fat angiomyolipomas. One of the most promising developments of renal DWI is the estimation of renal fibrosis in chronic kidney disease (CKD) patients. In conclusion, DWI constitutes a major advancement in genitourinary imaging with a central role in decision algorithms in the female pelvis and prostate cancer, now allowing promising applications in renal imaging or in the bladder and testicular mpMRI.

8.
Br J Radiol ; 94(1120): 20200931, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33481641

ABSTRACT

OBJECTIVES: The aim of this pilot study was to investigate in two rectal cancer patients undergoing neoadjuvant chemo-radiotherapy (nCRT) the implant feasibility and dosimetric benefit in sexual organ-sparing of an injectable, absorbable, radiopaque hydrogel spacer. METHODS: Two rectal cancer patients (one male and one female) underwent hydrogel implant between rectum and vagina/prostate before nCRT and curative surgery. A CT scan was performed before and after injection and a comparative dosimetric study was performed testing a standard (45/50 Gy) and a dose escalated (46/55.2 Gy) schedule. RESULTS: In both patients, the spacer implant in the recto-prostatic or recto-vaginal space was feasible and well tolerated. For the male, the dosimetric benefit with spacer was minimal for sexual organs. For the female however, doses delivered to the vagina were significantly reduced with spacer with a mean reduction of more than 5 Gy for both regimens. CONCLUSIONS: For organ preservation protocols and selected sexually active female patients, use of hydrogel spacers can be considered to spare sexual organs from the high radiotherapy dose levels. ADVANCES IN KNOWLEDGE: For females with advanced rectal tumor, a spacer implant between the rectum and the vagina before nCRT is feasible and reduces doses delivered to the vagina.


Subject(s)
Hydrogels/administration & dosage , Organs at Risk/diagnostic imaging , Radiation Injuries/prevention & control , Rectal Neoplasms/radiotherapy , Tomography, X-Ray Computed/methods , Aged , Feasibility Studies , Female , Humans , Male , Middle Aged , Pilot Projects , Prostate/diagnostic imaging , Vagina/diagnostic imaging
9.
Fungal Genet Biol ; 148: 103506, 2021 03.
Article in English | MEDLINE | ID: mdl-33450403

ABSTRACT

The Omega class of glutathione transferases (GSTs) forms a distinct class within the cytosolic GST superfamily because most of them possess a catalytic cysteine residue. The human GST Omega 1 isoform was first characterized twenty years ago, but it took years of work to clarify the roles of the human isoforms. Concerning the kingdom of fungi, little is known about the cellular functions of Omega glutathione transferases (GSTOs), although they are widely represented in some of these organisms. In this study, we re-assess the phylogeny and the classification of GSTOs based on 240 genomes of mushroom-forming fungi (Agaricomycetes). We observe that the number of GSTOs is not only extended in the order of Polyporales but also in other orders such as Boletales. Our analysis leads to a new classification in which the fungal GSTOs are divided into two Types A and B. The catalytic residue of Type-A is either cysteine or serine, while that of Type-B is cysteine. The present study focuses on Trametes versicolor GSTO isoforms that possess a catalytic cysteine residue. Transcriptomic data show that Type-A GSTOs are constitutive enzymes while Type-B are inducible ones. The crystallographic analysis reveals substantial structural differences between the two types while they have similar biochemical profiles in the tested conditions. Additionally, these enzymes have the ability to bind antioxidant molecules such as wood polyphenols in two possible binding sites as observed from X-ray structures. The multiplication of GSTOs could allow fungal organisms to adapt more easily to new environments.


Subject(s)
Agaricales/genetics , Fungal Proteins/chemistry , Fungal Proteins/genetics , Gene Expression Profiling , Genetic Variation , Glutathione Transferase/chemistry , Glutathione Transferase/genetics , Phylogeny , Agaricales/chemistry , Agaricales/metabolism , Binding Sites , Crystallography, X-Ray , Fungal Proteins/classification , Fungal Proteins/metabolism , Glutathione Transferase/classification , Glutathione Transferase/metabolism , Models, Molecular , Protein Conformation
10.
Evol Appl ; 13(9): 2206-2221, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33005219

ABSTRACT

Root-knot nematodes, Meloidogyne spp., are soil-borne polyphagous pests with major impact on crop yield worldwide. Resistant crops efficiently control avirulent root-knot nematodes, but favour the emergence of virulent forms. Since virulence is associated with fitness costs, susceptible crops counter-select virulent root-knot nematodes. In this study, we identify optimal rotation strategies between susceptible and resistant crops to control root-knot nematodes and maximize crop yield. We developed an epidemiological model describing the within-season dynamics of avirulent and virulent root-knot nematodes on susceptible or resistant plant root-systems, and their between-season survival. The model was fitted to experimental data and used to predict yield-maximizing rotation strategies, with special attention to the impact of epidemic severity and genetic parameters. Crop rotations were found to be efficient under realistic parameter ranges. They were characterized by low ratios of resistant plants and were robust to parameter uncertainty. Rotations provide significant gain over resistant-only strategies, especially under intermediate fitness costs and severe epidemic contexts. Switching from the current general deployment of resistant crops to custom rotation strategies could not only maintain or increase crop yield, but also preserve the few and valuable R-genes available.

11.
J Nat Prod ; 83(10): 2960-2966, 2020 10 23.
Article in English | MEDLINE | ID: mdl-33001642

ABSTRACT

Glutathione transferases comprise a large class of multifunctional enzymes, some involved in detoxification pathways. Since these enzymes are able to interact with potentially toxic molecules, they could be used as targets to screen for compounds with biological activity. To test this hypothesis, glutathione transferases (GSTs) from the white-rot fungus Trametes versicolor have been used to screen for antifungal molecules from a library of tropical wood extracts. The interactions between a set of six GSTs from the omega class and 116 extracts from 21 tropical species were quantified using a high-throughput thermal shift assay. A correlation between these interactions and the antifungal properties of the tested extracts was demonstrated. This approach has been extended to the fractionation of an Andira coriacea extract and led to the detection of maackiain and lapachol in this wood. Altogether, the present results supported the hypothesis that such detoxification enzymes could be used to detect biologically active molecules.


Subject(s)
Glutathione Transferase , Antifungal Agents , Glutathione , Molecular Structure , Polyporaceae , Trametes , Wood
12.
Biosci Rep ; 40(10)2020 10 30.
Article in English | MEDLINE | ID: mdl-32970113

ABSTRACT

Sinorhizobium meliloti is a nitrogen-fixing bacterium forming symbiotic nodules with the legume Medicago truncatula. S. meliloti possesses two BolA-like proteins (BolA and YrbA), the function of which is unknown. In organisms where BolA proteins and monothiol glutaredoxins (Grxs) are present, they contribute to the regulation of iron homeostasis by bridging a [2Fe-2S] cluster into heterodimers. A role in the maturation of iron-sulfur (Fe-S) proteins is also attributed to both proteins. In the present study, we have performed a structure-function analysis of SmYrbA showing that it coordinates diverse divalent metal ions (Fe2+, Co2+, Ni2+, Cu2+ and Zn2+) using His32 and His67 residues, that are also used for Fe-S cluster binding in BolA-Grx heterodimers. It also possesses the capacity to form heterodimers with the sole monothiol glutaredoxin (SmGrx2) present in this species. Using cellular approaches analyzing the metal tolerance of S. meliloti mutant strains inactivated in the yrbA and/or bolA genes, we provide evidence for a connection of YrbA with the regulation of iron homeostasis. The mild defects in M. truncatula nodulation reported for the yrbA bolA mutant as compared with the stronger defects in nodule development previously observed for a grx2 mutant suggest functions independent of SmGrx2. These results help in clarifying the physiological role of BolA-type proteins in bacteria.


Subject(s)
Bacterial Proteins/metabolism , Cations, Divalent/metabolism , Metals/metabolism , Sinorhizobium meliloti/metabolism , Amino Acid Sequence/genetics , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Circular Dichroism , Conserved Sequence/genetics , Histidine/genetics , Histidine/metabolism , Medicago truncatula/microbiology , Sinorhizobium meliloti/genetics , Structure-Activity Relationship
13.
Microb Biotechnol ; 13(5): 1673-1677, 2020 09.
Article in English | MEDLINE | ID: mdl-32212309

ABSTRACT

The natural durability of wood species, defined as their inherent resistance to wood-destroying agents, is a complex phenomenon depending on many biotic and abiotic factors. Besides the presence of recalcitrant polymers, the presence of compounds with antimicrobial properties is known to be important to explain wood durability. Based on the advancement in our understanding of fungal detoxification systems, a reverse chemical ecology approach was proposed to explore wood natural durability using fungal glutathione transferases. A set of six glutathione transferases from the white-rot Trametes versicolor were used as targets to test wood extracts from seventeen French Guiana neotropical species. Fluorescent thermal shift assays quantified interactions between fungal glutathione transferases and these extracts. From these data, a model combining this approach and wood density significantly predicts the wood natural durability of the species tested previously using long-term soil bed tests. Overall, our findings confirm that detoxification systems could be used to explore the chemical environment encountered by wood-decaying fungi and also wood natural durability.


Subject(s)
Trametes , Wood , Polyporaceae
15.
Nephrol Dial Transplant ; 35(6): 937-945, 2020 06 01.
Article in English | MEDLINE | ID: mdl-30608554

ABSTRACT

BACKGROUND: Kidney cortical interstitial fibrosis (IF) is highly predictive of renal prognosis and is currently assessed by the evaluation of a biopsy. Diffusion magnetic resonance imaging (MRI) is a promising tool to evaluate kidney fibrosis via the apparent diffusion coefficient (ADC), but suffers from inter-individual variability. We recently applied a novel MRI protocol to allow calculation of the corticomedullary ADC difference (ΔADC). We here present the validation of ΔADC for fibrosis assessment in a cohort of 164 patients undergoing biopsy and compare it with estimated glomerular filtration rate (eGFR) and other plasmatic parameters for the detection of fibrosis. METHODS: This monocentric cross-sectional study included 164 patients undergoing renal biopsy at the Nephrology Department of the University Hospital of Geneva between October 2014 and May 2018. Patients underwent diffusion-weighted imaging, and T1 and T2 mappings, within 1 week after biopsy. MRI results were compared with gold standard histology for fibrosis assessment. RESULTS: Absolute cortical ADC or cortical T1 values correlated poorly to IF assessed by the biopsy, whereas ΔADC was highly correlated to IF (r=-0.52, P < 0.001) and eGFR (r = 0.37, P < 0.01), in both native and allograft patients. ΔT1 displayed a lower, but significant, correlation to IF and eGFR, whereas T2 did not correlate to IF nor to eGFR. ΔADC, ΔT1 and eGFR were independently associated with kidney fibrosis, and their combination allowed detection of extensive fibrosis with good specificity. CONCLUSION: ΔADC is better correlated to IF than absolute cortical or medullary ADC values. ΔADC, ΔT1 and eGFR are independently associated to IF and allow the identification of patients with extensive IF.


Subject(s)
Diffusion Magnetic Resonance Imaging/methods , Fibrosis/diagnosis , Kidney Cortex/pathology , Kidney Diseases/diagnosis , Kidney Medulla/pathology , Cross-Sectional Studies , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Pilot Projects , ROC Curve
16.
Proc Biol Sci ; 286(1912): 20191550, 2019 10 09.
Article in English | MEDLINE | ID: mdl-31594515

ABSTRACT

Nature-based agriculture that reduces dependency on chemical inputs requires using ecological principles for sustainable agro-ecosystems, aiming to balance ecology, economics and social justice. There is growing evidence that pollinator-dependent crops with high insect, particularly bee, pollination service can give higher yields. However, the interacting effects between insect pollination and agricultural inputs on crop yields and farm economics remain to be established to reconcile food production with biodiversity conservation. We quantified individual and combined effects of pesticides, insect pollination and soil quality on oilseed rape (Brassica napus L.) yield and gross margin, using a total of 294 farmers' fields surveyed between 2013 and 2016. We show that yield and gross margins are greater (15-40%) in fields with higher pollinator abundance than in fields with reduced pollinator abundance. This effect is, however, strongly reduced by pesticide use. Greater yields may be achieved by either increasing agrochemicals or increasing bee abundance, but crop economic returns were only increased by the latter, because pesticides did not increase yields while their costs reduced gross margins.


Subject(s)
Bees/physiology , Pesticides , Pollination , Agriculture , Animals , Biodiversity , Brassica napus , Crop Production , Crops, Agricultural , Ecosystem , Insecta
17.
Med Oncol ; 36(8): 67, 2019 Jun 12.
Article in English | MEDLINE | ID: mdl-31190232

ABSTRACT

To evaluate the diagnostic performance of a whole-body 18F-choline (FCH) hybrid PET/MRI for prostate cancer patients at biochemical relapse after radical prostatectomy (RP) compared to pelvic multiparametric MRI (mpMRI), one of the standard imaging modality for this patient population. From 2010 to 2016, 58 whole-body FCH PET/MRI studies with mpMRI acquisitions were performed in 53 prostate cancer patients relapsing after curative RP. Median PSA and PSA doubling time (PSA DT) at PET study were 1.5 ng/ml and 6.5 months, respectively. The overall positivity rate of FCH PET/MRI was 58.6% (n = 34), dropping to 44% in patients with a PSA ≤ 2 ng/ml (n = 36). Median PSA values in positive and negative PET/MRI studies were 2.2 ng/ml and 0.8 ng/ml, respectively, with no differences in PSA DT (6.5 vs. 6.6 months). A PSA value ≥ 1.5 ng/ml was a significant predictor of positivity on PET/MRI studies. Compared to PET, mpMRI identified more local relapses (17 vs. 14, p = 0.453) while PET outperformed whole-body Dixon MRI for regional (16 vs. 9, p = 0.016) and distant (12 vs. 6, p = 0.031) metastases. Compared to pelvic mpMRI, the treatment approach turned out to be influenced more frequently using whole-body FCH hybrid PET/MRI studies (58.6% vs. 38%). In prostate cancer patients with biochemical recurrence after RP, whole-body FCH PET/MRI achieved a higher detection rate of nodal/distant metastases compared to pelvic mpMRI alone, increasing the change of treatment strategy by more than 20%.


Subject(s)
Neoplasm Recurrence, Local/diagnostic imaging , Prostatic Neoplasms/diagnostic imaging , Aged , Aged, 80 and over , Choline/analogs & derivatives , Fluorine Radioisotopes , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Multimodal Imaging/methods , Neoplasm Staging , Positron Emission Tomography Computed Tomography/methods , Prospective Studies , Prostatectomy , Prostatic Neoplasms/surgery , Radiopharmaceuticals , Whole Body Imaging/methods
18.
Protein Sci ; 28(6): 1143-1150, 2019 06.
Article in English | MEDLINE | ID: mdl-30972861

ABSTRACT

Trametes versicolor glutathione transferase Omega 3S (TvGSTO3S) catalyzes the conjugation of isothiocyanates (ITC) with glutathione (GSH). Previously, this isoform was investigated in depth both biochemically and structurally. Structural analysis of complexes revealed the presence of a GSH binding site (G site) and a deep hydrophobic binding site (H site) able to bind plant polyphenols. In the present study, crystals of apo TvGSTO3S were soaked with glutathionyl-phenethylthiocarbamate, the product of the reaction between GSH and phenethyl isothiocyanate (PEITC). On the basis of this crystal structure, we show that the phenethyl moiety binds in a new site at loop ß2 -α2 while the glutathionyl part exhibits a particular conformation that occupies both the G site and the entrance to the H site. This binding mode is allowed by a conformational change of the loop ß2 -α2 at the enzyme active site. It forms a hydrophobic slit that stabilizes the phenethyl group at a distinct site from the previously described H site. Structural comparison of TvGSTO3S with drosophila DmGSTD2 suggests that this flexible loop could be the region that binds PEITC for both isoforms. These structural features are discussed in a catalytic context.


Subject(s)
Glutathione Transferase/chemistry , Glutathione/biosynthesis , Isothiocyanates/metabolism , Trametes/enzymology , Binding Sites , Biocatalysis , Glutathione/chemistry , Glutathione Transferase/metabolism , Isothiocyanates/chemistry , Models, Molecular , Molecular Structure
19.
Eur Radiol ; 29(9): 4776-4782, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30747299

ABSTRACT

OBJECTIVES: Distinguishing between kidney stones and phleboliths can constitute a diagnostic challenge in patients undergoing unenhanced low-dose CT (LDCT) for acute flank pain. We sought to investigate the accuracy of radiomics and a machine-learning classifier in differentiating between kidney stones and phleboliths on LDCT. METHODS: Radiomics features were extracted following a semi-automatic segmentation of kidney stones and phleboliths for two independent consecutive cohorts of patients undergoing LDCT for acute flank pain. Radiomics features from the first cohort of patients (n = 369) were ultimately used to train a machine-learning model designed to distinguish kidney stones (n = 211) from phleboliths (n = 201). Classification performance was assessed on the second independent cohort (i.e., testing set) (kidney stones n = 24; phleboliths n = 23) using positive and negative predictive values (PPV and NPV), area under the receiver operating curves (AUC), and permutation testing. RESULTS: Our machine-learning classification model trained on radiomics features achieved an overall accuracy of 85.1% on the independent testing set, with an AUC of 0.902, PPV of 81.5%, and NPV of 90.0%. Classification accuracy was significantly better than chance on permutation testing (p < 0.05, permutation p value). CONCLUSION: Radiomics and machine learning enable accurate differentiation between kidney stones and phleboliths on LDCT in patients presenting with acute flank pain. KEY POINTS: • Combining a machine-learning algorithm with radiomics features extracted for abdominopelvic calcification on LDCT offers a highly accurate method for discriminating phleboliths from kidney stones. • Our radiomics and machine-learning model proved robust for CT acquisition and reconstruction protocol when tested in comparison with an external independent cohort of patients with acute flank pain. • The high performance of the radiomics-based automatic classification model in differentiating phleboliths from kidney stones indicates its potential as a future diagnostic tool for equivocal abdominopelvic calcifications in the setting of suspected renal colic.


Subject(s)
Kidney Calculi/diagnostic imaging , Lithiasis/diagnostic imaging , Machine Learning , Tomography, X-Ray Computed/methods , Acute Pain/etiology , Adult , Aged , Aged, 80 and over , Algorithms , Diagnosis, Differential , Female , Flank Pain/etiology , Humans , Male , Middle Aged , Young Adult
20.
Acad Radiol ; 26(7): e150-e160, 2019 07.
Article in English | MEDLINE | ID: mdl-30076081

ABSTRACT

RATIONALE AND OBJECTIVES: To assess both the complete aorta and coronary artery disease (CAD) using low iodine contrast computed-tomography angiography before transcatheter aortic valve replacement. MATERIALS AND METHODS: 84 patients underwent computed-tomography angiography before transcatheter aortic valve replacement: 42 with standard iodine injection protocol (P1:120 mL); 42 with a low dose iodine injection protocol (P2:60 mL). Mean attenuation and subjective image quality were rated at different levels of the aorta, iliac and coronary arteries. Sensitivity, specificity, negative and positive predictive values for depiction of CAD were calculated according to the coronary angiography. RESULTS: Mean attenuation was significantly higher in P1 for the ascending aorta (p < 0.001). No significant difference was observed regarding image quality of the aortic valve (p = 0.876), the ascending aorta (p = 0.306), or the abdominal aorta (p = 1.0). Diagnostic image quality of coronary arteries was excellent for P1 and P2 (94.6% vs 96.5%, p = 0.08). Sensitivity, specificity, negative and positive predictive values, and accuracy for depiction of CAD were excellent for P1 and P2 (100% vs 100%; 79% vs 86%, 70% vs 87%, 100% vs 100% and 86% vs 93%) without significant differences (p = 0.93; p = 0.58; p = 0.90; p = 1.0; p = 0.74), respectively. CONCLUSION: Despite a difference in aortic mean attenuation, a reduced iodine injection protocol showed similar image quality and detection of CAD in comparison with a standard injection protocol.


Subject(s)
Computed Tomography Angiography/methods , Contrast Media , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Radiographic Image Enhancement/methods , Transcatheter Aortic Valve Replacement , Aged, 80 and over , Aorta/diagnostic imaging , Coronary Artery Disease/surgery , Female , Humans , Iodine , Male , Preoperative Care/methods , Retrospective Studies
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