Poly(ADP-ribose) polymerase-1 (PARP1) and p53 labelling index correlates with tumour grade in meningiomas

Meningiomas are one of the most frequent intracranial tumours, with 13 histological types and three grades according to the 2007 WHO Classification of Tumours of the Central Nervous System. p53, as one of the most potent tumour suppressor proteins, plays a role in nearly 50% of human tumours. Poly(ADP-ribose) polymerase (PARP) is a DNA repair enzyme with high ATP demand. It plays a role in apoptosis by activating an apoptosis inducing factor, and in necrosis by consuming NAD+ and ATP. Only PARP1 has been investigated in detail in tumours out of the 17 members of the PARP superfamily; however, its role has not been studied in meningiomas yet. The aim of this study was to determine the role of p53 and PARP1 in meningiomas of different grade and to establish whether there is any correlation between the p53 and PARP1 expression. Both PARP1 and p53 have been expressed in all examined meningiomas. PARP1 labelled grade II tumours with a higher intensity as compared to grade I and III neoplasms, respectively. An increased p53 expression was noted in grade III meningiomas. There was no statistical correlation between p53 and PARP1 expression. Our data indicate that both PARP1 and p53 activation is a feature in meningiomas of higher grade, PARP1 overexpression being an early, whereas p53 overexpression, a late event in tumour progression

Structural Diversity and Bioactivities of Peptaibol Compounds From the Longibrachiatum Clade of the Filamentous Fungal Genus Trichoderma

This study examined the structural diversity and bioactivity of peptaibol compounds produced by species from the phylogenetically separated Longibrachiatum Clade of the filamentous fungal genus Trichoderma, which contains several biotechnologically, agriculturally and clinically important species. HPLC-ESI-MS investigations of crude extracts from 17 species of the Longibrachiatum Clade (T. aethiopicum, T. andinense, T. capillare, T. citrinoviride, T. effusum, T. flagellatum, T. ghanense, T. konilangbra, T. longibrachiatum, T. novae-zelandiae, T. pinnatum, T. parareesei, T. pseudokoningii, T. reesei, T. saturnisporum, T. sinensis, and T. orientale) revealed several new and recurrent 20-residue peptaibols related to trichobrachins, paracelsins, suzukacillins, saturnisporins, trichoaureocins, trichocellins, longibrachins, hyporientalins, trichokonins, trilongins, metanicins, trichosporins, gliodeliquescins, alamethicins and hypophellins, as well as eight 19-residue sequences from a new subfamily of peptaibols named brevicelsins. Non-ribosomal peptide synthetase genes were mined from the available genome sequences of the Longibrachiatum Clade. Their annotation and product prediction were performed in silico and revealed full agreement in 11 out of 20 positions regarding the amino acids predicted based on the signature sequences and the detected amino acids incorporated. Molecular dynamics simulations were performed for structural characterization of four selected peptaibol sequences: paracelsins B, H and their 19-residue counterparts brevicelsins I and IV. Loss of position R6 in brevicelsins resulted in smaller helical structures with higher atomic fluctuation for every residue than the structures formed by paracelsins. We observed the formation of highly bent, almost hairpin-like, helical structures throughout the trajectory, along with linear conformation. Bioactivity tests were performed on the purified peptaibol extract of T. reesei on clinically and phytopathologically important filamentous fungi, mammalian cells, and Arabidopsis thaliana seedlings. Porcine kidney cells and boar spermatozoa proved to be sensitive to the purified peptaibol extract. Peptaibol concentrations = 0.3mg ml-1 deterred the growth of A. thaliana. However, negative effects to plants were not detected at concentrations below 0.1 mg ml(-1), which could still inhibit plant pathogenic filamentous fungi, suggesting that those peptaibols reported here may have applications for plant protection