Impacts of land cover data selection and trait parameterisation on dynamic modelling of species' range expansion

Peer reviewedPublisher PD

Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs.

Post-transcriptional control of gene expression is mediated by the interaction of RNA-binding proteins with their cognate mRNAs that specifically regulate their stability, localization and translation. mRNA-binding proteins are multifunctional and it has been proposed therefore that a combinatorial RNA-binding protein code exists that allows specific protein sub-complexes to control cytoplasmic gene expression under a range of pathophysiological conditions. We show that polypyrimidine tract-binding protein (PTB) is central to one such complex that forms in apoptotic cells. Thus, during apoptosis initiated by TNF-related apoptosis inducing ligand there is a change in the repertoire of RNA-binding proteins with which PTB interacts. We show that altering the cellular levels of PTB and its binding partners, either singly or in combination, is sufficient to directly change the rates of apoptosis with increased expression of PTB, YBX1, PSF and NONO/p54(nrb) accelerating this process. Mechanistically, we show that these proteins post-transcriptionally regulate gene expression, and therefore apoptotic rates, by interacting with and stimulating the activity of RNA elements (internal ribosome entry segments) found in mRNAs that are translated during apoptosis. Taken together, our data show that PTB function is controlled by a set of co-recruited proteins and importantly provide further evidence that it is possible to dictate cell fate by modulating cytoplasmic gene expression pathways alone

Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation.

Eukaryotic translation initiation factor 4E (eIF4E) is considered as the corner stone in the cap-dependent translation initiation machinery. Its role is to recruit mRNA to the ribosome through recognition of the 5'-terminal mRNA cap structure (m7GpppN, where G is guanosine, N is any nucleotide). eIF4E is implicated in cell transformation, tumourigenesis, and angiogenesis by facilitating translation of oncogenic mRNAs; it is thus regarded as an attractive anticancer drug target. We have used two approaches to design cap-binding inhibitors of eIF4E by modifying the N7-substituent of m7GMP and replacing the phosphate group with isosteres such as squaramides, sulfonamides, and tetrazoles, as well as by structure-based virtual screening aimed at identifying non-nucleotide cap-binding antagonists. Phosphomimetic nucleotide derivatives and highly ranking virtual hits were evaluated in a series of in vitro and cell-based assays to identify the first non-nucleotide eIF4E cap-binding inhibitor with activities in cell-based assays, N-[(5,6-dihydro-6-oxo-1,3-dioxolo[4,5-g]quinolin-7-yl)methyl]-N'-(2-methyl-propyl)-N-(phenyl-methyl)thiourea (14), including down-regulation of oncogenic proteins and suppression of RNA incorporation into polysomes. Although we did not observe cellular activity with any of our modified m7GMP phosphate isostere compounds, we obtained X-ray crystallography structures of three such compounds in complex with eIF4E, 5'-deoxy-5'-(1,2-dioxo-3-hydroxycyclobut-3-en-4-yl)amino-N7-methyl-guanosine (4a), N7-3-chlorobenzyl-5'-deoxy-5'-(1,2-dioxo-3-hydroxy-cyclobut-3-en-4-yl)amino-guanosine (4f), and N7-benzyl-5'-deoxy-5'-(trifluoromethyl-sulfamoyl)guanosine (7a). Collectively, the data we present on structure-based design of eIF4E cap-binding inhibitors should facilitate the optimisation of such compounds as potential anticancer agents

Design of nucleotide-mimetic and non-nucleotide inhibitors of the translation initiation factor eIF4E: Synthesis, structural and functional characterisation.

Eukaryotic translation initiation factor 4E (eIF4E) is considered as the corner stone in the cap-dependent translation initiation machinery. Its role is to recruit mRNA to the ribosome through recognition of the 5'-terminal mRNA cap structure (m7GpppN, where G is guanosine, N is any nucleotide). eIF4E is implicated in cell transformation, tumourigenesis, and angiogenesis by facilitating translation of oncogenic mRNAs; it is thus regarded as an attractive anticancer drug target. We have used two approaches to design cap-binding inhibitors of eIF4E by modifying the N7-substituent of m7GMP and replacing the phosphate group with isosteres such as squaramides, sulfonamides, and tetrazoles, as well as by structure-based virtual screening aimed at identifying non-nucleotide cap-binding antagonists. Phosphomimetic nucleotide derivatives and highly ranking virtual hits were evaluated in a series of in vitro and cell-based assays to identify the first non-nucleotide eIF4E cap-binding inhibitor with activities in cell-based assays, N-[(5,6-dihydro-6-oxo-1,3-dioxolo[4,5-g]quinolin-7-yl)methyl]-N'-(2-methyl-propyl)-N-(phenyl-methyl)thiourea (14), including down-regulation of oncogenic proteins and suppression of RNA incorporation into polysomes. Although we did not observe cellular activity with any of our modified m7GMP phosphate isostere compounds, we obtained X-ray crystallography structures of three such compounds in complex with eIF4E, 5'-deoxy-5'-(1,2-dioxo-3-hydroxycyclobut-3-en-4-yl)amino-N7-methyl-guanosine (4a), N7-3-chlorobenzyl-5'-deoxy-5'-(1,2-dioxo-3-hydroxy-cyclobut-3-en-4-yl)amino-guanosine (4f), and N7-benzyl-5'-deoxy-5'-(trifluoromethyl-sulfamoyl)guanosine (7a). Collectively, the data we present on structure-based design of eIF4E cap-binding inhibitors should facilitate the optimisation of such compounds as potential anticancer agents

Beta diversity patterns reveal positive effects of farmland abandonment on moth communities

Farmland abandonment and the accompanying natural succession are largely perceived as unwanted amongst many European conservationists due to alleged negative effects on biodiversity levels. Here, we test this assumption by analysing alpha, beta and gamma diversity patterns of macro-moth communities in habitats on an ecological succession gradient, from extensively managed meadows to scrub-encroached and wooded sites. Macro-moths were light-trapped at 84 fixed circular sampling sites arranged in a semi-nested design within the National Park of Peneda-Gerês, NW-Portugal. In total, we sampled 22825 individuals belonging to 378 species. Alpha, beta and gamma diversity patterns suggest that farmland abandonment is likely to positively affect both overall macro-moth diversity and forest macro-moth diversity, and to negatively affect species diversity of non-forest macro-moth species. Our results also show that spatial habitat heterogeneity is important to maintain gamma diversity of macromoths, especially for rare non-forest species and habitat specialistsinfo:eu-repo/semantics/publishedVersio

Sää- ja ilmastoriskit Suomessa - Kansallinen arvio

Tähän raporttiin on koottu ajantasainen arvio sään ja ilmaston aiheuttamista riskeistä eri toimialoille Suomessa. Arviossa otettiin huomioon sekä muuttuvan ilmaston että yhteiskunnallisen kehityksen vaikutus riskin muodostumiseen nykyhetkessä ja tulevaisuudessa. Sää- ja ilmastoriskejä pyrittiin hahmottamaan vaaratekijän (riskiä aiheuttava sääilmiö), altistumisen (riskin kohteen sijainti) ja haavoittuvuuden (riskin kohteen ominaisuudet) yhdistelmänä. Sääilmiöt aiheuttavat Suomessa riskejä jo nykyilmastossa. Muun muassa rajuilmat, helleaallot ja rankkasateet aiheuttavat taloudellisia ja terveydellisiä vaikutuksia sekä yleistä haittaa. Tulevaisuudessa riskit muuttuvat ilmastonmuutoksen muuttaessa haitallisia sääilmiöitä. Ilmastonmuutos tuo vähitellen kasvavia riskejä erityisesti ekosysteemeille ja infrastruktuurille. Muualla maailmalla tapahtuvat ilmastonmuutoksen vaikutukset voivat heijastua epäsuorasti Suomeen globaalien tavara-, energia-, raha- ja ihmisvirtojen kautta. Näiden riskien systemaattinen arviointi on vasta aloitettu. Raportin tavoitteena on tukea yhteiskunnan riskeihin varautumista ja ilmastonmuutokseen sopeutumista eri hallinnon tasoilla ja toimialoilla. Arvio perustuu pääosin kirjallisuudesta löytyviin tutkimuksiin ja selvityksiin sekä asiantuntija-arvioihin. Työ tehtiin “Sää- ja ilmastoriskien arviointi ja toimintamallit” (SIETO)- hankkeessa vuosina 2017–2018