The genome of the toxic invasive species Heracleum sosnowskyi carries an increased number of genes despite absence of recent whole-genome duplications.

Heracleum sosnowskyi, belonging to a group of giant hogweeds, is a plant with large effects on ecosystems and human health. It is an invasive species that contributes to the deterioration of grassland ecosystems. The ability of H. sosnowskyi to produce linear furanocoumarins (FCs), photosensitizing compounds, makes it very dangerous. At the same time, linear FCs are compounds with high pharmaceutical value used in skin disease therapies. Despite this high importance, it has not been the focus of genetic and genomic studies. Here, we report a chromosome-scale assembly of Sosnowsky's hogweed genome. Genomic analysis revealed an unusually high number of genes (55106) in the hogweed genome, in contrast to the 25-35 thousand found in most plants. However, we did not find any traces of recent whole-genome duplications not shared with its confamiliar, Daucus carota (carrot), which has approximately thirty thousand genes. The analysis of the genomic proximity of duplicated genes indicates on tandem duplications as a main reason for this increase. We performed a genome-wide search of the genes of the FC biosynthesis pathway and surveyed their expression in aboveground plant parts. Using a combination of expression data and phylogenetic analysis, we found candidate genes for psoralen synthase and experimentally showed the activity of one of them using a heterologous yeast expression system. These findings expand our knowledge on the evolution of gene space in plants and lay a foundation for further analysis of hogweed as an invasive plant and as a source of FCs.

Characterization of vitamin D metabolism in active acromegaly in the setting of bolus (150,000 IU) cholecalciferol treatment.

PURPOSE: To reveal distinctive features of vitamin D metabolism in patients with active acromegaly compared to healthy individuals, particularly in the setting of cholecalciferol treatment. METHODS: The study group included 34 adults with active acromegaly, and the control group included 30 apparently healthy adults with similar age, sex, and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3, and 7 after the administration. All data were analyzed with nonparametric statistics. RESULTS: Patients with acromegaly had tendency to lower baseline 25(OH)D3 levels (p = 0.05) and lower 25(OH)D3 levels (p < 0.05) during the follow-up. They were also characterized by PTH suppression (lower baseline PTH levels and lower prevalence of secondary hyperparathyroidism), altered production of main vitamin D metabolites (higher 1,25(OH)2D3 and lower 24,25(OH)2D3 levels with corresponding lower 25(ОН)D3/1,25(ОН)2D3 and higher 25(ОН)D3/24,25(ОН)2D3 ratios) as well as concordant biochemical features (higher levels of serum phosphorus and albumin-adjusted calcium levels) throughout the study (p < 0.05). The acromegaly group showed an increase in DBP levels after cholecalciferol intake as opposed to the control group (p < 0.05) and had lower increase in free 25(OH)D levels (p < 0.05). Δ25(OH)D3 was similar between the groups (p > 0.05), showed a negative correlation with the disease activity markers-both IGF-1 levels (r = -0.44, p < 0.05) and fasting GH levels (r = -0.56, p < 0.05)-and lacked correlation with BMI in the acromegaly group (p > 0.05). CONCLUSION: Patients with active acromegaly have dysregulated vitamin D metabolism characterized by higher 1,25(ОН)2D3, lower 24,25(ОН)2D3 and altered DBP production. The response to vitamin D supplementation in acromegaly patients might be influenced by hormonal excess. Obtained results require reproducibility check and further study to develop specific clinical recommendations. TRIAL REGISTRATION: NCT04844164 (release date: April 9, 2021; retrospectively registered).

Regioselective Mono- and Dialkylation of [6,6]-open C60 (CF2 ): Synthetic and Kinetic Aspects.

Alkylation of homofullerene [6,6]-C60 (CF2 )2- dianion with the set of alkyl halides, RX, was established to demonstrate an effect of RX nature on the conversion, product composition, and regioselectivity. The respective C60 (CF2 )RH, C60 (CF2 )R2 and C60 (CF2 )R'R'' compounds were obtained in the reaction with sterically unhindered RX, isolated by HPLC and unequivocally characterized. The kinetic studies evidenced SN 2 mechanism for both alkylation steps, yielding mono- and dialkylated C60 (CF2 ), respectively, and indicated the negative charge localization at the bridgehead carbon atoms as well as a steric hindrance of the CF2 moiety likely to be a key factors for the SN 2 reaction mechanism and observed regioselectivity. The significant difference in the rate constants of the first and the second steps is attributed to the different activation barriers predicted by DFT calculations which makes possible to develop synthetic methods for the regioselective preparation of monoalkylated C60 (CF2 )RH and heterodialkylated C60 (CF2 )R'R'' derivatives.

Stepwise Regioselective Hydrogenation of cis-2-C60 (CF2 )2 Homofullerene with [6,6]-Open/Closed Valence Tautomerism.

The homofullerene compound cis-2-C60 (CF2 )2 , which has an unusual kind of open/closed valence tautomerism undergoes consecutive regioselective hydrogenation at bridgehead carbon atoms upon reduction with Zn/Cu couple in H2 O-toluene mixture. The tautomerism barrier in cis-2-C60 (CF2 )2 is negligible in the neutral state, whereas negative charging both impedes tautomeric transformation and promotes regioselective addition of electrophilic species at the bridgehead carbon atoms. In light of this observation, two novel homofullerene derivatives, mixed [6,6]-open/closed C60 (CF2 )2 H2 and [6,6]-open cis-2-C60 (CF2 )2 H4 , were synthesized and their structures were unambiguously determined by means of single crystal X-ray crystallography and NMR spectroscopy.

Reductive Hydrogenation of Cs -C70 (CF3 )8 and C1 -C70 (CF3 )10.

CF3 -derivatized fullerenes prove once again to be promising scaffolds for regioselective fullerene functionalization: now with the smallest possible addends-hydrogen atoms. Hydrogenation of Cs -C70 (CF3 )8 and C1 -C70 (CF3 )10 by means of reduction with Zn/Cu couple in the presence of water proceeds regioselectively, yielding only one major isomer of C70 (CF3 )8 H2 and only two for C70 (CF3 )10 H2 , whose addition patterns are combined in the only abundant isomer of C70 (CF3 )10 H4 . The observed selectivity is governed by the electronic structure of trifluoromethylated substrates. Interestingly, we discovered that Clar's theory can be utilized to predict the regiochemistry of functionalization, and we look forward to testing it on forthcoming cases of derivatization of pre-functionalized fullerene building blocks.