Biology subjects

Rauch, C.

Publications and source records attributed to Rauch, C..

9 recordsLinked to original sources

bioRxiv2026

The proposed Baltic Sea endemic green alga Monostroma balticum represents a foliose morphotype of Ulva intestinalis (Ulvales, Ulvophyceae).

Green algae in Ulva, Monostroma and similar genera are notoriously difficult to identify morphologically, due to high phenotypic plasticity and the presence of cryptic species - which has historically resulted in a challenging taxonomy, poorly resolved species boundaries, and potentially numerous invalid species descriptions. DNA-based specimen identification, especially combined with analysis of historical herbarium voucher DNA, has huge potential in resolving many unresolved taxonomical problems in these algae. One such example is Monostroma balticum, which has been described as foliose, monostromatic green seaweed known only free-floating, and reported to be endemic to the Baltic Sea. Previous studies have highlighted major uncertainty in the status of this taxon. We conducted an extensive sampling campaign of monostromatic green algae across the Baltic Sea to molecularly, morphologically and ecologically characterise this enigmatic taxon. Additionally, we investigated original exciccate material of M. balticum by using a museomic approach. We show that Monostroma balticum represents a monostromatic, foliose morphotype of the cosmopolitan and ubiquitous species Ulva intestinalis. This foliose growth form is seen in low salinity conditions, and, so far, reported only from the inner basin of the Baltic Sea. Our work shows that using morphology- and DNA-based museomic approaches for contemporary and historical specimens is a powerful combination to resolve long-standing taxonomical uncertainties and to produce new biodiversity information, even in relatively well-studied regions.

plant biology↗

bioRxiv2026

Glycine betaine-mediated transcriptional stimulation links its catabolism and vitamin B12 biosynthesis in Rhizobiaceae

Glycine betaine (GB) is a trimethylated ammonium compound widely used as a compatible solute, and serves as a carbon, nitrogen, and methyl group source in many members of the Rhizobiaceae. GB is critical for high-level vitamin B2 production, a cofactor synthesized exclusively by microorganisms. Vitamin B2 formation requires multiple methylation steps. In the industrial vitamin B2 production strain Pseudomonas denitrificans, GB has been shown to serve as a methyl group donor through its successive demethylation to glycine and to provide the carbon backbone for the universal porphyrin precursor 5-aminolevulinic acid. Moreover, previous proteomics studies have revealed increased levels of vitamin B2 biosynthetic enzymes in the presence of GB. However, it has remained unclear at what level of gene expression this regulation occurs. Here, using promoter-reporter fusions in the vitamin B2 overproducer Ensifer adhaerens LU2703 and in the low-producer Sinorhizobium meliloti 102F34, we demonstrate that GB activates promoters of both its own catabolic pathway and of major cob operons. Two of these operons encode the complete set of S-adenosylmethionine-dependent methyltransferases required for corrin ring biosynthesis, the foundational, rate-limiting stage in vitamin B12 production. Stimulation of cobE and cobH promoters as well as vitamin B2 production yields followed sigmoidal dose-response curves with saturation in a similar concentration range, suggesting a tight coupling between GB supply and biosynthetic output. Our findings uncover a novel regulatory layer in vitamin B2 biosynthesis and provide promoter-probe set-ups for further exploration of GB-mediated transcriptional control.

microbiology↗

bioRxiv2026

Dynamic expression range expansion of ECF sigma factor-dependent synthetic regulons by promoter context engineering

Alternative {sigma} factors enable bacteria to reprogram transcription in response to environmental cues and provide powerful tools for synthetic gene regulation. Extracytoplasmic function (ECF) {sigma} factors have recently been implemented as orthogonal transcriptional switches in several bacteria, including the -proteobacterium Sinorhizobium meliloti. Here, we investigated how promoter sequence context influences the activity and specificity of heterologous ECF-dependent core promoters. Combining ECF core promoters from Pseudomonas syringae and Escherichia coli with flanking sequences derived from strong promoters of S. meliloti and other proteobacteria increased promoter activity by up to 45-fold while preserving {sigma} factor specificity. We identified a short upstream AT motif, resembling a minimal UP element, as a key determinant of promoter strength. Targeted mutagenesis confirmed its role in supporting transcription initiation. Engineering promoter-flanking sequences together with the AT motif generated promoter libraries spanning up to a 75-fold range of activities. Importantly, promoter activity hierarchies were maintained within synthetic multi-gene regulons controlled by a single ECF master regulator, demonstrating modular and predictable gene expression. Our results establish promoter environment engineering as a robust strategy for expanding the dynamic range of orthogonal ECF regulatory systems and facilitate the scalable design of synthetic transcriptional programs in bacteria.

synthetic biology↗

bioRxiv2025

Genomic Informational Field Theory (GIFT) to map complex traits in small sample sizes

Genome-wide association studies (GWAS) are commonly used to investigate the genetic basis of complex traits. However, to be adequately powered they typically require large sample sizes to provide precise inferences. To address this challenge, this paper introduces GIFT, a novel data analytic method that enhances the power of genetic analyses, enabling the use of smaller datasets without compromising precision. In a small cohort of 157 ponies, GIFT was applied to examine the complex trait of "height at withers", comparing its performance to traditional GWAS. GIFT enabled the identification genetic loci linked to insulin physiology validating, in turn, a long-standing hypothesis that "height at withers" is associated with insulin physiology in equids, potentially promoting equine metabolic syndrome (EMS). By redefining correlations between single nucleotide polymorphisms (SNPs), GIFT provides new insights into linkage disequilibrium and reveals underlying gene network structures. This, in turn, enables the distinction between core and peripheral genes within these networks. By reducing the time and cost associated with large-scale genotype-phenotype mapping studies without sacrificing statistical robustness, GIFT broadens access to quantitative genetic research, allowing smaller-scale studies to investigate the genetic architecture of complex traits with greater resolution. NEW & NOTEWORTHYInferring genotype-phenotype associations typically require large sample sizes, limiting many genetic studies. GIFT, a novel data analytics tool, overcomes this by enabling accurate association mapping in small datasets. We further show how GIFTs extended framework infers linkage disequilibrium and gene networks, distinguishing core from peripheral genes involved in complex traits. This advancement enhances understanding of biological architecture and enables high-resolution genetic research in limited cohorts, offering a powerful, cost-effective alternative to traditional large-scale approaches.

genetics↗

bioRxiv2024

PPARgamma, a key modulator of metabolic reprogramming, stemness and chemoresistance associated with retrodifferentiation in human hepatocellular carcinomas

Human hepatocellular carcinomas (HCCs) with cancer stem cell (CSC) features are a subclass of therapeutically challenging cancers. We recently showed that retrodifferentiation of hepatic cancer cells into CSC-like cells leads to metabolic reprogramming and chemoresistance. The molecular mechanisms whereby differentiated cancer cells switch towards a CSC phenotype are poorly understood. By studying metabolic reprogramming associated with HCC cell plasticity, we identified an unsuspected role of peroxisome proliferator-activated receptor (PPAR){gamma} in hepatic CSC phenotype acquisition. Gene expression and metabolic analyses performed throughout cell differentiation/retrodifferentiation process of human HepaRG and HBG-BC2 HCC cells show that metabolic reprogramming in hepatic CSCs is associated with fragmented mitochondrial network, decreased respiration, de novo lipogenesis, fatty acid oxidation, but increased glycolysis and lipid storage. Mitochondrial genes downregulated in HepaRG-CSCs are also downregulated in the STEM HCC subclass. While PPAR is the main isoform in differentiated hepatic cells, we find high PPAR{gamma} expression in hepatic CSCs. Accordingly, nuclear localization of PPAR{gamma} is detected in human HCC tumors and PPAR{gamma}high/PPARlow expression is associated with the STEM HCC subclass and a poor outcome in human HCC cohorts. PPAR{gamma} silencing or/and inhibition of its target gene pyruvate dehydrogenase kinase 4 reactivates cell respiration, increases reactive oxygen species production and sensitizes hepatic CSCs to chemotherapy. Conversely, PPAR activation synergizes with chemotherapy to induce cell death. Targeting PPAR{gamma}, a key regulator of metabolic reprogramming and stemness in hepatic CSCs, or modulating the PPAR{gamma}/PPAR balance that finely tunes the differentiation/retrodifferentiation process in HCC deserves further investigation for antitumor therapy. Implications heading and statementPPAR{gamma}, a key regulator of metabolic reprogramming and stemness in hepatic CSC, reduces oxidative phosphorylation and reactive oxygen species production, therefore contributing to HCC chemoresistance.

cancer biology↗

bioRxiv2024

The drug disposition in the Spleen: A novel study of CYP and UGT-mediated drug metabolism.

Understanding the fate of a drug, its disposition and pharmacokinetics as it reaches the site of action is key to any pharmaceutical research and development. The emerging role of the spleen in its involvement in regulating the immune system has garnered interest in new immunotherapeutic strategies. Using novel precision immunotherapeutic drugs that will potentially engage with the host immune system to specifically target and eliminate diseased cells, makes this approach a better alternative to conventional therapies. The spleen poses as a potential immunotherapeutic target and confirmation of drugs reaching its site of action requires monitoring enzymes that engages with xenobiotics like drugs. The pig was selected as the model for human based on the close homology conveyed between pig and human using a phylogenetic construction of Cytochrome P450s (CYP450) and UDP-glucuronosyltransferases (UGT) in both species. Moreover, an RNAseq transcriptome analysis between the human spleen, pig liver and spleen tissues were obtained from a next generation sequencing (NGS) to identify genes associated with drug metabolism. Immunofluorescence and Western Blot analysis was carried out to determine the protein expression of metabolizing CYP450s and UGTs in pig spleen. Therefore, drug substrates and their metabolites known in human liver were investigated in pig spleen to determine the functional expression of CYP450s and UGTs. Promising in-vitro results has demonstrated the expression of these metabolic enzymes at a functional level from observations showing elimination of drug substrates and the apparent metabolites formed. Monitoring the enzyme activities would also indicate uptake of these substrates in splenocytes, confirm that the spleen can metabolize drugs, and provide further insight into therapeutic or toxic related implications from drug interactions.

pharmacology and toxicology↗

bioRxiv2024

Investigative power of Genomic Informational Field Theory (GIFT) relative to GWAS for genotype-phenotype mapping

Identifying associations between phenotype and genotype is the fundamental basis of genetic analyses. Inspired by frequentist probability and the work of R.A. Fisher, genome-wide association studies (GWAS) extract information using averages and variances from genotype-phenotype datasets. Averages and variances are legitimated upon creating distribution density functions obtained through the grouping of data into categories. However, as data from within a given category cannot be differentiated, the investigative power of such methodologies is limited. Genomic Informational Field Theory (GIFT) is a method specifically designed to circumvent this issue. The way GIFT proceeds is opposite to that of GWAS. Whilst GWAS determines the extent to which genes are involved in phenotype formation (bottom-up approach), GIFT determines the degree to which the phenotype can select microstates (genes) for its subsistence (top-down approach). Doing so requires dealing with new genetic concepts, a.k.a. genetic paths, upon which significance levels for genotype-phenotype associations can be determined. By using different datasets obtained in ovis aries related to bone growth (Dataset-1) and to a series of linked metabolic and epigenetic pathways (Dataset-2), we demonstrate that removing the informational barrier linked to categories enhances the investigative and discriminative powers of GIFT, namely that GIFT extracts more information than GWAS. We conclude by suggesting that GIFT is an adequate tool to study how phenotypic plasticity and genetic assimilation are linked. NEW & NOTEWORTHYThe genetic basis of complex traits remains challenging to investigate using classic GWASs. Given the success of gene editing technologies this point needs to be addressed urgently since there can only be useful editing technologies if precise genotype-phenotype mapping information is available initially. GIFT is a new mapping method designed to increase the investigative power of biological/medical datasets suggesting, in turn, the need to rethink the conceptual bases of quantitative genetics.

genetics↗

bioRxiv2022

FIT-GWA: A new method for the genetic analysis of small gene effects, high precision in phenotype measurements and small sample sizes.

Small gene effects involved in complex/omnigenic traits remain costly to analyse using current genome-wide association methods (GWAS) because of the number of individuals required to return meaningful association(s), a.k.a. study power. Inspired by field theory in physics, we provide a different method called Genomic Informational Field Theory (GIFT). In contrast to GWAS, GIFT assumes that the phenotype is measured precisely enough and/or the number of individuals in the population is too small to permit the creation of categories. To extract information, GIFT uses the information contained in the cumulative sums difference of gene microstates between two configurations: (i) when the individuals are taken at random without information on phenotype values, and (ii) when individuals are ranked as a function of their phenotypic value. The difference in the cumulative sum is then attributed to the emergence of phenotypic fields. We demonstrate that GIFT recovers GWAS, that is, Fishers theory, when the phenotypic fields are linear (first order). However, unlike GWAS, GIFT demonstrates how the variance of microstate distribution density functions can also be involved in genotype-phenotype associations when the phenotypic fields are quadratic (second order). Using genotype-phenotype simulations based on Fishers theory as a toy model, we illustrate the application of the method with a small sample size of 1000 individuals.

genetics↗

bioRxiv2021

Postsynaptic plasticity of cholinergic synapses underlies the induction and expression of appetitive memories in Drosophila

In vertebrates, several forms of memory-relevant synaptic plasticity involve postsynaptic rearrangements of glutamate receptors. In contrast, previous work indicates that Drosophila and other invertebrates store memories using presynaptic plasticity of cholinergic synapses. Here, we provide evidence for postsynaptic plasticity at cholinergic output synapses from the Drosophila mushroom bodies (MBs). We find that the nicotinic acetylcholine receptor (nAChR) subunit 5 is required within specific MB output neurons (MBONs) for appetitive memory induction, but is dispensable for aversive memories. In addition, nAChR 2 subunits mediate memory expression and likely functions downstream of 5 and the postsynaptic scaffold protein Dlg. We show that postsynaptic plasticity traces can be induced independently of the presynapse, and that in vivo dynamics of 2 nAChR subunits are changed both in the context of associative and non-associative memory formation, underlying different plasticity rules. Therefore, regardless of neurotransmitter identity, key principles of postsynaptic plasticity support memory storage across phyla.

neuroscience↗