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Biology subjects

Veronesi, G.

Publications and source records attributed to Veronesi, G..

5 recordsLinked to original sources

A multidisciplinary analysis of the as-isolated Escherichia coli SufBC2D complex reveals the presence of two new iron-sulfur clusters

Iron-sulfur (Fe-S) clusters are essential inorganic cofactors dedicated to a wide range of biological functions including electron transfer and catalysis. Specialized multi-protein machineries present in all types of organisms support their biosynthesis. These machineries encompass a scaffold protein on which Fe-S clusters are assembled before being transferred to cellular targets. Here, we describe the first characterization of the native Fe-S cluster of the anaerobically purified SufBC2D scaffold from Escherichia coli by XAS, Mossbauer, UV-visible absorption and EPR spectroscopy. Interestingly, we propose that SufBC2D harbors two types of Fe-S cluster, a [2Fe-2S] cluster with an unprecedented usual coordination and a previously unreported [3Fe-3S] cluster. These data combined with mutagenesis and biochemistry allow to propose ligands for these clusters. These results support the hypothesis that both SufB and SufD are involved in Fe-S cluster ligation and are discussed in the context of Fe-S cluster biogenesis where both [2Fe-2S] and [4Fe-4S] clusters need to mature cellular Fe-S protein targets.

biochemistry↗

Subcellular architecture and metabolic connection in the planktonic photosymbiosis between Collodaria (radiolarians) and their microalgae

Photosymbiosis is widespread and ecologically important in the oceanic plankton but remains poorly studied. Here, we used multimodal subcellular imaging to investigate the photosymbiosis between colonial Collodaria and their microalga dinoflagellate (Brandtodinium) collected in surface seawaters. We showed that this symbiosis is a very dynamic system whereby symbionts interact with different host cells via extracellular vesicles within the "greenhouse-like" colony. 3D electron microscopy revealed that the volume of the photosynthetic apparatus (plastid and pyrenoid) of the microalgae increased in symbiosis compared to free-living while the mitochondria volume was similar. Stable isotope probing coupled with NanoSIMS showed that carbon and nitrogen were assimilated and stored in the symbiotic microalga in starch granules and purine crystals, respectively. Nitrogen was also allocated to the algal nucleus (nucleolus). After 3 hours, low 13C and 15N transfer was detected in the host Golgi. Metal mapping revealed that intracellular iron concentration was similar in free-living and symbiotic microalgae (ca 40 ppm) and two-fold higher in the host, whereas copper concentration increased in symbiotic microalgae (up to 6900 ppm) and was detected in the host cell and extracellular vesicles. Sulfur mapping also pinpointed the importance of this nutrient for the algal metabolism. This study, which revealed subcellular changes of the morphology and nutrient homeostasis in symbiotic microalgae, improves our understanding on the metabolism of this widespread and abundant oceanic symbiosis and paves the way for more studies to investigate the metabolites exchanged.

ecology↗

Correlative transmission electron microscopy and high-resolution hard X-ray fluorescence microscopy of cell sections to measure trace elements concentrations at the organelle level

Metals are essential to all forms of life and their concentration and distribution in the organisms are tightly regulated. Indeed, in their free form, metal ions are toxic. Therefore, an excess of physiologic metal ions or the uptake of non-physiologic metal ions can be highly detrimental for the organisms. It is thus fundamental to understand metals distribution and dynamics in physiologic or disrupted conditions, for instance in metal-related pathologies or upon environmental exposure to metals. Elemental imaging techniques can serve this purpose, by allowing the visualization and the quantification of metal species in a tissue or down to the interior of a cell. Among these techniques, synchrotron radiation-based X-ray fluorescence (SR-XRF) microscopy is the most sensitive to date, and great progresses were made to reach spatial resolutions as low as 20x20 nm2. Until recently, 2D XRF mapping was used on whole cells, thus summing up the signal from the whole thickness of the cell. In the last two years, we have developed a methodology to work on thin cell sections, in order to analyze the metal content at the level of the organelle. Herein, we propose a correlative method to couple SR-XRF to electron microscopy, with the aim to quantify the elemental content in an organelle of interest. As a proof-of-concept, the technique was applied to the analysis of mitochondria from hepatocytes exposed to silver nanoparticles. It was thus possible to identify mitochondria with higher concentration of Ag(I) ions compared to the surrounding cytosol. The versatility of the method makes it suitable to answer a large panel of biological questions, for instance related to metal homeostasis in biological organisms.

cell biology↗

Visualization of silver nanoparticle intracellular trafficking revealed nuclear translocation of silver ions leading to nuclear receptor impairment

The impact on human health of the increasing use of silver nanoparticles (AgNPs) in medical devices remains understudied, even though AgNP-containing dressings are known to release silver in the bloodstream leading to accumulation and slow clearance in the liver. Cellular studies have shown the intracellular dissolution of AgNPs within endo-lysosomes followed by Ag(I) binding to biomolecular thiolate-containing molecules. However, the precise subcellular distribution of Ag(I) and the nature of the disrupted physiological pathways remained unknown. Novel imaging approaches enabled us to visualize the trafficking of AgNP-containing lysosomes towards a perinuclear location and a direct nuclear transfer of Ag(I) species with accumulation in the nucleoli. These Ag(I) species impaired nuclear receptor activity, disrupting critical mechanisms of liver physiology in very low dose exposure scenarios, thus justifying further research into defining a framework for the safe use of AgNPs.

pharmacology and toxicology↗

Education and coronary heart disease: a Mendelian randomization study

ObjectivesTo determine whether educational attainment is a causal risk factor in the development of coronary heart disease.\n\nDesignMendelian randomization study, where genetic data are used as proxies for education, in order to minimize confounding. A two-sample design was applied, where summary level genetic data was analysed from two publically available consortia.\n\nSettingIn the main analysis, we analysed genetic data from two large consortia (CARDIoGRAM and SSGAC), comprising of 112 cohorts from predominantly high-income countries. In addition, we also analysed genetic data from 7 additional large consortia, in order to identify putative causal mediators.\n\nParticipantsThe main analysis was of 589 377 men and women, predominantly of European origin.\n\nExposureA one standard deviation increase in the genetic predisposition towards higher education (i.e. 3.6 years of additional schooling). This was measured by 162 genetic variants that have been previously associated with education.\n\nMain outcomeCombined fatal and nonfatal coronary heart disease (63 746 events).\n\nResults3.6 years of additional education lowered the risk of coronary heart disease by a third (odds ratio = 0.67, 95% confidence interval [CI], 0.59 to 0.77, p=0.01). Equivalent increases in education were also causally associated with reductions in smoking, BMI and improvements in blood lipid profiles.\n\nConclusionsMore time spent in education is causally associated with a large reduction in the risk of coronary heart disease. This may be partly explained by changes to smoking, BMI and a blood lipids. These findings offer support for policy interventions that increase education, in order to also reduce the burden of cardiovascular disease.

epidemiology↗