Biology subjects

Fink, P.

Publications and source records attributed to Fink, P..

5 recordsLinked to original sources

bioRxiv2025

Imbalanced Brain Connectome: A Novel Link between Functional Somatic Disorders, Multiple Chemical Sensitivity, and Post-COVID patients

This study aimed to investigate and assess shared patterns of structural brain connectivity across three clinical populations. Despite significant advancements in neuroimaging, structural connectivity alterations have been underexplored in functional somatic disorders (FSDs), multiple chemical sensitivity (MCS), and post-COVID-19 conditions (PC). Clinical observations suggest that olfactory symptoms may represent a missing link between these three patient groups. Using diffusion-weighted MRI and voxel-based probabilistic tractography, structural connectivity was analysed in 57 females (MCS: 16, FSD: 15, PC: 11, and 15 matched healthy controls). Independent-sample t-tests (with FDR correction) and permutation testing were applied to assess group-level differences, particularly in inter- and intra-hemispheric connectivity. A marked decrease in inter-hemispheric connectivity was observed in patients (70.9%) compared with controls (29.1%; p < 0.001). The finding was consistent across all diagnostic groups. These alterations remained stable following reanalysis and aggregation, reliably distinguishing patients from controls. No significant differences were found in intra-hemispheric connectivity across the patient groups. Additionally, out of 12 predefined interregional connections, ten showed significant alterations in at least one patient group. The findings reveal robust and consistent reduced inter-hemispheric connectivity in patients with MCS, FSD, and PC, highlighting a potentially shared neurobiological signature among the patient groups.

neuroscience↗

bioRxiv2024

AI-aided chronic mixture risk assessment along a small European river reveals multiple sites at risk and pharmaceuticals being the main risk drivers

The vast amount of registered chemicals leads to a high diversity of substances occurring in the environment and the creation of new substances outpaces chemical risk assessment as well as monitoring strategies. Hence, risk assessment strategies need to be modified ensuring that they remain aligned with the rapid development and marketing of new substances. Here we performed a longitudinal chronic mixture risk assessment considering a real-world case study scenario with diverse anthropogenic impact types characterised by different land uses along a river in Central Germany. We sampled river water using large-volume solid phase extraction at six selected sampling sites. Following chemical analysis using liquid chromatography-high resolution mass spectrometry, we quantified 192 substances. For 34% of them, we obtained empirical chronic effect data for freshwater organisms. Furthermore, we used the open-source artificial intelligence (AI) model TRIDENT to predict chronic toxicity for all substances. A multi-scenario mixture risk assessment was conducted for three taxonomic groups, using the concentration-addition concept and considering various hazard and exposure scenarios. The results showed that the chronic risk estimates for all taxonomic groups were considerably higher when the empirical data was amended with data from in silico modelling. We identified hot spots of chemical pollution and our analysis indicated that fish were the most vulnerable taxonomic group, with pharmaceuticals being the most relevant risk drivers. Our study exemplifies the application of an AI model to predict chronic risk for aquatic organisms in combination with the consideration of multiple risk scenarios, that may complement future risk assessment strategies. HighlightsO_LI192 organic chemicals were quantified in six surface water samples along a river. C_LIO_LIMultiple hazard and exposure scenarios were considered in mixture risk assessment. C_LIO_LIArtificial intelligence was used to fill data gaps and predict chronic ecotoxicity. C_LIO_LIFish were identified as the most vulnerable taxonomic group for chronic toxicity. C_LIO_LIPharmaceuticals were the most prevalent mixture risk drivers. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/623722v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1836b85org.highwire.dtl.DTLVardef@107eeaaorg.highwire.dtl.DTLVardef@1c60caaorg.highwire.dtl.DTLVardef@16995d0_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2024

Structural elements of cyanobacterial co-factor-independent phosphoglycerate mutase that mediate regulation by PirC

The 2,3-bisphosphoglycerate-independent phosphoglycerate mutase (iPGAM) has been identified as a crucial regulating key point in the carbon storage metabolism of cyanobacteria. Upon nitrogen starvation, the iPGAM is inhibited by the PII-interacting regulator PirC, released from its interaction partner PII due to elevated 2-oxoglutarate levels. In-silico analysis of 338 different iPGAMs revealed a deep-rooted distinctive evolution of iPGAMs in cyanobacteria. Remarkably, cyanobacterial iPGAMs possess a unique loop structure and an extended C-terminus. Our analysis suggests that iPGAM forms a complex with three individual PirC monomers. Complex affinity is affected by the unique loop and the C-terminal structural elements. A C-terminal truncated enzyme showed loss of control by PirC and two-fold increased enzymatic activity compared to the iPGAM-WT. By contrast, deleting the loop structure drastically reduced the activity of this variant. By replacing the WT iPGAM in Synechocystis with different iPGAM variants, in which these structural elements were deleted, it became apparent that deletion of the C-terminal element showed a similar overproduction of polyhydroxybutyrate as deletion of the iPGAM-regulator PirC. However, in contrast to the latter, these strains showed higher over-all biomass accumulation, making them a better chassis for a production strain for PHB or other valuable substances than the PirC-deficient mutant. These findings significantly contribute to our understanding of the metabolic pathways in cyanobacteria and open up new avenues for further research in this field, inspiring future investigations and discoveries. ImportanceThe primordial cyanobacteria were responsible for developing oxygenic photo-synthesis early in evolution. Through endosymbiosis, they further evolved into the chloroplasts found in the plant kingdom. Many metabolic pathways within chloroplasts originated from cyanobacteria. However, differences emerged during their long separate evolution, providing insights into the endosymbiotic process. In the metabolic pathways involving fixed CO2, the co-factor-independent phosphoglycerate mutase (iPGAM) plays a crucial role by directing the first CO2 fixation product, 3-phosphoglycerate, towards critical anabolic path-ways. Our findings reveal a distinct evolution of iPGAM within oxygenic photo-synthetic organisms. We have identified two specific segments in cyanobacterial iPGAMs that tightly control the cellular carbon/nitrogen state through a specific protein interactor (PiC). This understanding of iPGAM has allowed us to engineer cyanobacterial strains with altered carbon fluxes. Since cyanobacteria can directly convert CO2 into valuable products, our results demonstrate a novel approach for developing a chassis for biotechnical use.

microbiology↗

bioRxiv2024

A novel recombinant PHB production platform in filamentous cyanobacteria avoiding nitrogen starvation while preserving cell viability

During the past decades, the importance of developing sustainable, carbon dioxide (CO2)-neutral and biodegradable alternatives to conventional plastic has become evident in the context of global pollution issues. Therefore, heterotrophic bacteria such as Cupriavidus sp. have been intensively explored for the synthesis of the biodegradable polymer polyhydroxybutyrate (PHB). PHB is also naturally produced by a variety of phototrophic cyanobacteria, which only need sunlight and CO2, thereby allowing a CO2 negative, eco-friendly synthesis of this polymer. However, a major drawback of the use of cyanobacteria is the need of a two-stage production process, since relevant amount of PHB synthesis only occurs after transferring the cultures to conditions of nitrogen starvation, which hinders continuous, large-scale production. This study aimed at generating, by means of genetic engineering, a cyanobacterium that continuously produces PHB in large amounts. We choose a genetically amenable filamentous cyanobacterium of the genus Nostoc sp., which is a diazotrophic cyanobacterium, capable of atmospheric nitrogen (N2) fixation but naturally does not produce PHB. We transformed this Nostoc strain with various constructs containing the PHB synthesis operon from Cupriavidus necator H16. In fact, while the transformants initially produced PHB, the PHB-producing strains rapidly lost cell viability. Therefore, we next attempted further optimization of the biosynthetic gene cluster. Finally, we succeeded in stabilized PHB production, whilst simultaneously avoiding decreasing cell viability. In conclusion, the recombinant Nostoc strain constructed in the present work constitutes the first example of a continuous and stable PHB production platform in cyanobacteria, which has been decoupled from nitrogen starvation and, hence, harbours great potential for sustainable, industrial PHB production.

microbiology↗

bioRxiv2019

Fatty acid bioconversion in harpacticoid copepods in a changing environment: a transcriptomic approach

By 2100, global warming is predicted to significantly reduce the capacity of marine primary producers for long-chain polyunsaturated fatty acid (LC-PUFA) synthesis. Primary consumers such as harpacticoid copepods (Crustacea) might mitigate the resulting adverse effects on the food web by increased LC-PUFA bioconversion. Here, we present a high-quality de novo transcriptome assembly of the copepod Platychelipus littoralis, exposed to changes in both temperature (+3{degrees}C) and dietary LC-PUFA availability. Using this transcriptome, we detected multiple transcripts putatively encoding for LC-PUFA-bioconverting front-end fatty acid desaturases and elongases, and performed phylogenetic analyses to identify their relationship with sequences of other (crustacean) taxa. While temperature affected the absolute fatty acid concentrations in copepods, LC-PUFA levels remained unaltered even when copepods were fed a LC-PUFA-deficient diet. While this suggests plasticity of LC-PUFA bioconversion within P. littoralis, none of the putative front-end desaturase or elongase transcripts were differentially expressed under the applied treatments. Nevertheless, the transcriptome presented here provides a sound basis for future ecophysiological research on harpacticoid copepods.

ecology↗