Biosynthetic Gene Content of the ‘Perfume Lichens’ Evernia prunastri and Pseudevernia furfuracea

Lichen-forming fungi produce a vast number of unique natural products with a wide variety of biological activities and human uses. Although lichens have remarkable potential in natural product research and industry, the molecular mechanisms underlying the biosynthesis of lichen metabolites are poorly understood. Here we use genome mining and comparative genomics to assess biosynthetic gene clusters and their putative regulators in the genomes of two lichen-forming fungi, which have substantial commercial value in the perfume industry, Evernia prunastri and Pseudevernia furfuracea. We report a total of 80 biosynthetic gene clusters (polyketide synthases (PKS), non-ribosomal peptide synthetases and terpene synthases) in E. prunastri and 51 in P. furfuracea. We present an in-depth comparison of 11 clusters, which show high homology between the two species. A ketosynthase (KS) phylogeny shows that biosynthetic gene clusters from E. prunastri and P. furfuracea are widespread across the Fungi. The phylogeny includes 15 genomes of lichenized fungi and all fungal PKSs with known functions from the MIBiG database. Phylogenetically closely related KS domains predict not only similar PKS architecture but also similar cluster architecture. Our study highlights the untapped biosynthetic richness of lichen-forming fungi, provides new insights into lichen biosynthetic pathways and facilitates heterologous expression of lichen biosynthetic gene clusters

Effects of cigarette smoking on carotid and radial artery distensibility

Cigarette smoking acutely induces a marked increase of blood pressure and heart rate. This is accompanied by a marked reduction of radial artery distensibility. Whether this reflects an alteration of arterial mechanics of large elastic arteries as well is not established, however. In this study we addressed the acute effects of smoking on the stiffness of a peripheral medium-sized muscular artery and a large elastic vessel. We studied seven healthy normotensive smokers (age 28 \ub1 7 years, mean \ub1 SEM), in the absence of smoking for at least 24 h. Radial artery (NIUS 02) and carotid artery diameter (WTS) were concomitantly acquired beat-to-beat in the 5 min before, during and after smoking of a cigarette containing 1.2 mg of nicotine. Blood pressure and heart rate were concomitantly recorded by a Finapres device. Radial and carotid artery distensibility were calculated according to the Langewouters and Reneman formulae, respectively. Data were collected for consecutive 30 s periods. Statistical comparisons were performed between the three different phases and, within each phase, between 30 s periods. In five subjects the protocol was repeated after 1 week using a stran rather than a cigarette to obtain data under sham smoking

Climate-specific biosynthetic gene clusters in populations of a lichen-forming fungus

Natural products can contribute to abiotic stress tolerance in plants and fungi. We hypothesize that biosynthetic gene clusters (BGCs), the genomic elements that underlie natural product biosynthesis, display structured differences along elevation gradients. We analysed biosynthetic gene variation in natural populations of the lichen-forming fungus Umbilicaria pustulata. We collected a total of 600 individuals from the Mediterranean and cold-temperate climates. Population genomic analyses indicate that U. pustulata contains three clusters that are highly differentiated between the Mediterranean and cold-temperate populations. One entire cluster is exclusively present in cold-temperate populations, and a second cluster is putatively dysfunctional in all cold-temperate populations. In the third cluster variation is fixed in all cold-temperate populations due to hitchhiking. In these two clusters the presence of consistent allele frequency differences among replicate populations/gradients suggests that selection rather than drift is driving the pattern. We advocate that the landscape of fungal biosynthetic genes is shaped by both positive and hitchhiking selection. We demonstrate, for the first time, the presence of climate-associated BGCs and BGC variations in lichen-forming fungi. While the associated secondary metabolites of the candidate clusters are presently unknown, our study paves the way for targeted discovery of natural products with ecological significance

Climate‐specific biosynthetic gene clusters in populations of a lichen‐forming fungus

Natural products can contribute to abiotic stress tolerance in plants and fungi. We hypothesize that biosynthetic gene clusters (BGCs), the genomic elements that underlie natural product biosynthesis, display structured differences along elevation gradients. We analysed biosynthetic gene variation in natural populations of the lichen-forming fungus Umbilicaria pustulata. We collected a total of 600 individuals from the Mediterranean and cold-temperate climates. Population genomic analyses indicate that U. pustulata contains three clusters that are highly differentiated between the Mediterranean and cold-temperate populations. One entire cluster is exclusively present in cold-temperate populations, and a second cluster is putatively dysfunctional in all cold-temperate populations. In the third cluster variation is fixed in all cold-temperate populations due to hitchhiking. In these two clusters the presence of consistent allele frequency differences among replicate populations/gradients suggests that selection rather than drift is driving the pattern. We advocate that the landscape of fungal biosynthetic genes is shaped by both positive and hitchhiking selection. We demonstrate, for the first time, the presence of climate-associated BGCs and BGC variations in lichen-forming fungi. While the associated secondary metabolites of the candidate clusters are presently unknown, our study paves the way for targeted discovery of natural products with ecological significance

Climate-specific biosynthetic gene clusters in populations of a lichen-forming fungus

Natural products can contribute to abiotic stress tolerance in plants and fungi. We hypothesize that biosynthetic gene clusters (BGCs), the genomic elements that underlie natural product biosynthesis, display structured differences along elevation gradients. We analysed biosynthetic gene variation in natural populations of the lichen-forming fungus Umbilicaria pustulata. We collected a total of 600 individuals from the Mediterranean and cold-temperate climates. Population genomic analyses indicate that U. pustulata contains three clusters that are highly differentiated between the Mediterranean and cold-temperate populations. One entire cluster is exclusively present in cold-temperate populations, and a second cluster is putatively dysfunctional in all cold-temperate populations. In the third cluster variation is fixed in all cold-temperate populations due to hitchhiking. In these two clusters the presence of consistent allele frequency differences among replicate populations/gradients suggests that selection rather than drift is driving the pattern. We advocate that the landscape of fungal biosynthetic genes is shaped by both positive and hitchhiking selection. We demonstrate, for the first time, the presence of climate-associated BGCs and BGC variations in lichen-forming fungi. While the associated secondary metabolites of the candidate clusters are presently unknown, our study paves the way for targeted discovery of natural products with ecological significance

3109G-CSF effects on left ventricular function assessed with standard echocardiographic evaluation (biplane EF) and 2D myocardial strain in patients with STEMI and LV dysfunction

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Reduction of pulmonary pressure values after PGE1 infusion in sclerodermic patients with pulmonary involvment

Pulmonary involvement is a common finding in progressive systemic sclerosis, a generalized autoimmune disorder with an abnormal interstitial collagen accumulation and deterioration of small arteries and capillary vessels. In SS her's an evidence of abnormal vascular tone regulation that is evident in the lung as an increase of arterial pulmonary pressure. Aim of this study was to assess acute effect of PGE1 administration on pulmonary vascular bed-flows affected by sclerodermic alterations evaluating the response of pulmonary arterial pressure and exhaled NO to prostaglandin administration. We studied 10 female normotensive patients (age 60\ub12 yr.) with systemic sclerosis and pulmonary involvement (P) documented with high resolution CT with no evidence or clinical history of cardiovascular or chronic pulmonary disease The data obtained were compared with 10 sclerodermic patients (age 58\ub18 yr.) without pulmonary involvement (NP). All the patients underwent infusion of PGE1 (Alprostadil,60 mcg, 5 days a week for 4 weeks). An echocardiographic evaluation was performed at baseline (B), acutely post-treatment (A) and after 4 weeks stopping therapy (S) to evaluate Right Ventricular Systolic Pressure (RVSP). We also measured left and right ventricle telediastolic and systolic diameters and left ventricular mass were calculated. We also measured transmitralic flows to evaluate diastolic function and the left ventricular ejection fraction (EF%). At the same times we measured exhaled NO concentrations (ppb) with a chemi-luminescence NO gas analyzer device. (\ub7p<0.05 A1 vs B1; 1ep<0.05 S1 vs A1; \ub0p<0.05 B2 vs B1 See the table at the bottom). Our data showed that P patients had increased RVSP values and lower NO concentrations in exhaled air compared to NP. PGE1 infusion is accompanied in these patients by a significant decrease in RVSP values and by a concomitant increase in exhaled NO concentration which both return to B conditions in follow up evaluations. A similar acute increasing trend in NO concentrations with RVSP decrease was observed in NP although it did not reached statistical significance. In conclusion PGE1 infusion may have a favorable effect on pulmunary vassels flows due to an increased of NO sensitivity and production