Biology subjects

Bacher, S.

Publications and source records attributed to Bacher, S..

5 recordsLinked to original sources

bioRxiv2023

PURA Syndrome-causing mutations impair PUR-domain integrity and affect P-body association

Mutations in the human PURA gene cause the neuro-developmental PURA syndrome. In contrast to several other mono-genetic disorders, almost all reported mutations in this nucleic acid binding protein result in the full disease penetrance. In this study, we observed that patient mutations across PURA impair its previously reported co-localization with processing bodies. These mutations either destroyed the folding integrity, RNA binding or dimerization of PURA. We also solved the crystal structures of the N- and C-terminal PUR domains of human PURA and combined them with molecular dynamics simulations and NMR measurements. The observed unusually high dynamics and structural promiscuity of PURA indicated that this protein is particularly susceptible to mutations impairing its structural integrity. It offers an explanation why even conservative mutations across PURA result in the full penetrance of symptoms in patients with PURA syndrome.

molecular biology↗

bioRxiv2022

European scenarios for future biological invasions

O_LIInvasive alien species are one of the major threats to global biodiversity, ecosystem integrity, natures contribution to people and human health. While scenarios about potential future developments have been available for other global change drivers for quite some time, we largely lack an understanding of how biological invasions might unfold in the future across spatial scales. C_LIO_LIBased on previous work on global invasion scenarios, we developed a workflow to downscale global scenarios to a regional and policy-relevant context. We applied this workflow at the European scale to create four European scenarios of biological invasions until 2050 that consider different environmental, socio-economic and socio-cultural trajectories, namely the European Alien Species Narratives (Eur-ASNs). C_LIO_LIWe compared the Eur-ASNs with their previously published global counterparts (Global-ASNs), assessing changes in 26 scenario variables. This assessment showed a high consistency between global and European scenarios in the logic and assumptions of the scenario variables. However, several discrepancies in scenario variable trends were detected that could be attributed to scale differences. This suggests that the workflow is able to capture scale-dependent differences across scenarios. C_LIO_LIWe also compared the Global- and Eur-ASNs with the widely used Global and European Shared Socioeconomic Pathways (SSPs), a set of scenarios developed in the context of climate change to capture different future socio-economic trends. Our comparison showed considerable divergences in the scenario space occupied by the different scenarios, with overall larger differences between the ASNs and SSPs than across scales (global vs. European) within the scenario initiatives. C_LIO_LIGiven the differences between the ASNs and SSPs, it seems that the SSPs do not adequately capture the scenario space relevant to understanding the complex future of biological invasions. This underlines the importance of developing independent, but complementary, scenarios focused on biological invasions. The downscaling workflow we presented and implemented here provides a tool to develop such scenarios across different regions and contexts. This is a major step towards an improved understanding of all major drivers of global change including biological invasions. C_LI

ecology↗

bioRxiv2022

A scenario-guided strategy for the future management of biological invasions

Future dynamics of biological invasions are highly uncertain because they depend on multiple environmental, societal and socio-economic drivers. We adopted a qualitative scenario approach to explore the future of invasive alien species (IAS) in Europe and created an overall strategy for their management that considers different plausible future developments. The scenarios and strategy were developed during two online workshops with a multidisciplinary team of experts. First, we downscaled four global scenarios of biological invasions to the European level. Second, we developed a management strategy structured into 19 goals that cover a broad array of IAS-related topics (i.e. policy, research, public awareness and biosecurity), and provided solutions for achieving these goals considering the European scenarios. Third, we identified four interrelated recommendations around which any long-term strategy for managing IAS in Europe can be structured: (i) a European biosecurity regime, (ii) a dedicated communication strategy, (iii) data standardization and management tools, and (iv) a monitoring and assessment system. Finally, we identified the feasibility of the IAS management strategy, finding strong differences among the four scenarios. High levels of technological development, public environmental awareness, and effectiveness of IAS policies facilitated the implementation of the overall management strategy. Together, our results indicate that it is time for a new management of biological invasions in Europe based on a more integrative perspective across sectors and countries to be better prepared for future challenges.

ecology↗

bioRxiv2022

Depletion of the RNA-binding protein PURA triggers changes in posttranscriptional gene regulation and loss of P-bodies

The RNA-binding protein PURA has been implicated in the rare, monogenetic, neurodevelopmental disorder PURA Syndrome. PURA binds both DNA and RNA and has been associated with various cellular functions. Only little is known about its main cellular roles and the molecular pathways affected upon PURA depletion. Here, we show that PURA is predominantly located in the cytoplasm, where it binds to thousands of mRNAs. Many of these transcripts change abundance in response to PURA depletion. The encoded proteins suggest a role for PURA in immune responses, mitochondrial function, autophagy and processing (P)-body activity. Intriguingly, reduced PURA levels decrease the expression of the integral P-body components LSM14A and DDX6 and strongly affect P-body formation in human cells. Furthermore, PURA knockdown results in stabilization of P-body-enriched transcripts, whereas other mRNAs decrease. Hence, reduced PURA levels, as reported in patients with PURA Syndrome, influence the formation and composition of this phase-separated RNA processing machinery. Our study proposes PURA Syndrome as a new model to study the tight connection between P-body-associated RNA regulation and neurodevelopmental disorders. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/479353v2_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@5712f9org.highwire.dtl.DTLVardef@9eb133org.highwire.dtl.DTLVardef@83b7b2org.highwire.dtl.DTLVardef@1912e5c_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2021

Alternative futures for global biological invasions

Scenario analysis has emerged as a key tool to analyze complex and uncertain future socio-ecological developments. However, current global scenarios (narratives of how the world may develop) have neglected biological invasions, a major threat to biodiversity and the economy. We used a novel participatory process to develop a diverse set of global biological invasion scenarios spanning a wide breadth of plausible global futures through 2050. We adapted the widely used "two axes" scenario analysis approach to develop four families of four scenarios each, resulting in 16 scenarios that were later clustered into four contrasting sets of futures. Our analysis highlighted that socio-economic developments and changes in sustainability policies and lifestyle have the potential to shape biological invasions, in addition to well-known ecological drivers, such as climate and human land use change. Our scenarios align fairly well with the recently developed shared socio-economic pathways, but the factors that drive differences in biological invasions are underrepresented there. Including these factors in global scenarios and models is essential to adequately consider biological invasions in global environmental assessments, and obtain a more integrative picture of future socio-ecological developments.

ecology↗