Biology subjects

Grube, M.

Publications and source records attributed to Grube, M..

11 recordsLinked to original sources

bioRxiv2026

Experimental trophic flexibility guides a compartmentalized genome-scale model of red microalgae Galdieria sulphuraria

The thermoacidophilic red microalga Galdieria sulphuraria combines broad organic-carbon utilization with biotechnological robustness. We integrated cultivation data for strain SAG 107.79 with an organelle-resolved genome-scale metabolic model describing autotrophic, mixotrophic and heterotrophic metabolism. Heterotrophic cultures produced 2.29, 2.03 and 2.14 g L-1 biomass on glucose, xylose and their mixture, respectively, while mixed-sugar cultures consumed glucose before xylose. Biomass composition was similar under mixotrophy and heterotrophy, and stationary-phase glucose consumption supported a non-growth-associated maintenance demand of 1.7 mmol ATP gDW-1 h-1. These measurements informed trophic-state-specific biomass objective functions. The final model contains 2,487 reactions, 2,270 compartment-specific metabolites and 1,050 genes. The model reproduced the experimentally scored growth phenotypes, highlighted polyol-associated product capacity under heterotrophy and scored 90% in the archived MEMOTE report. To our knowledge, this is the first experimentally based, organelle-resolved genome-scale metabolic model for G. sulphuraria, providing a quantitative framework linking trophic state and substrate identity with carbon use, flux flexibility and product capacity. A user-friendly supplementary package provides the executable SBML model, modular biomass resources, reproducible scripts, quality reports and underlying experimental data.

systems biology↗

bioRxiv2026

Matched primary-metastasis single-nucleus and spatial profiling of leiomyosarcoma identifies antigen-presenting fibroblasts at the tumor-organ interface

Leiomyosarcoma is an aggressive soft tissue sarcoma that metastasizes preferentially to lung and liver. Because matched primary and metastatic specimens are rarely available, the cellular changes that accompany metastatic progression remain poorly defined. Here we combined single-nucleus RNA sequencing of archival FFPE tissue from four matched primary-metastasis pairs (two lung, two liver metastases; 48,941 nuclei) with imaging-based spatial transcriptomics of an extended tissue microarray cohort of 21 patients (69 cores, 313,218 cells). Malignant cells, not assignable from transcriptomic references alone, were defined by inferred copy number profiles that were concordant with matched DNA methylation arrays and confirmed the clonal origin of each metastasis. Malignant metaprograms were organ-associated, with a stress- and hypoxia-associated program enriched in lung metastases and a proliferative, matrix-remodeling program enriched in liver metastases. Antigen-presenting cancer-associated fibroblasts (apCAFs) were enriched in metastases relative to matched primaries. This shift was reproduced in the spatial cohort (p = 0.001), where apCAFs formed a discrete band at the tumor-organ interface between malignant cells and adjacent parenchyma, whereas they were sparse and randomly distributed in primary tumors. Spatial transcriptomics further resolved the malignant compartment into three histomolecular phenotypes: (i) smooth-muscle-like with myxoid features, (ii) GPNMB with anaplastic features, and (iii) PDGFRB with vessel-rich stroma, each with a concordant immunohistochemical (-SMA, GPNMB, PDGFRB) and morphological correlate. Together, our data provide a matched primary-metastasis reference for leiomyosarcoma, identify apCAFs as a spatially organized, metastasis-associated stromal population, and delineate histomolecular phenotypes recognizable by routine immunohistochemistry, including a GPNMB phenotype potentially amenable to GPNMB-directed therapies.

cancer biology↗

bioRxiv2024

Bleaching as a result of coral optimization in a changing environment

Corals play an essential role in marine ecosystems by creating protective coastal structures and habitats for marine biodiversity. Their symbiotic relationship with various algal species, where corals supply nitrogen in exchange for carbon products, is vital for their survival. However, with some algal species being temperature sensitive, this vital symbiosis is increasingly threatened by global warming, causing significant symbiont losses, potentially leading to coral bleaching and fatal consequences. Here, we model the optimal regulation of algal populations by corals through nitrogen allocation. Two algal species compete for nitrogen: one is effective in carbon supply and rapid growth, and the other is resilient to temperature increases. Our testable analytical solution identifies the optimal total algal population as a function of the current temperature and symbiont composition. The model also determines the relative abundances of the two algal species based on current and historical temperatures. Our findings are consistent with numerous previous observations and experimental studies. The model clarifies how inter-species competition under varying temperature patterns shapes the composition and dynamics of algal species in coral symbiosis. It also clarifies that bleaching occurs when the relatively efficient algae fail to exchange enough carbon products at high temperatures.

ecology↗

bioRxiv2024

The microbiome of the lichen Lobaria pulmonaria varies according to climate in Europe

The Lobaria pulmonaria holobiont comprises algal, fungal, cyanobacterial, and bacterial components. We investigated L. pulmonarias bacterial microbiome in the adaptation of this ecologically sensitive lichen species to diverse climatic conditions. Our central hypothesis posited that microbiome composition and functionality aligns with continental-scale climatic parameters related to temperature and precipitation. We also tested the impact of short-term weather dynamics, sampling season, and algal/fungal genotypes on microbiome variation. Metaproteomics provided insights into compositional and functional changes within the microbiome. Climatic variables explained 41.64% of microbiome variation, surpassing the combined influence of local weather and sampling season at 31.63%. Notably, annual mean temperature and temperature seasonality emerged as significant climatic drivers. Microbiome composition correlated with algal, not fungal genotype, suggesting similar environmental recruitment for the algal partner and microbiome. Differential abundance analyses revealed distinct protein compositions in sub-atlantic lowland and alpine regions, indicating differential microbiome responses to contrasting environmental/climatic conditions. Proteins involved in oxidative and cellular stress were notably different. Our findings highlight microbiome plasticity in adapting to stable climates, with limited responsiveness to short-term fluctuations, offering new insights into climate adaptation in lichen symbiosis.

microbiology↗

bioRxiv2023

Biodiversity in mountain soils above the treeline

Despite the importance of healthy soils for human livelihood, wellbeing, and safety, current gaps in our knowledge and understanding of biodiversity in soil are numerous, undermining conservation efforts. These gaps are particularly wide in mountain regions where healthy soils are especially important for human safety and yet evidence is accumulating of ongoing degradation, posing significant threats to ecosystem functioning and human settlements. To analyse these gaps in detail, we synthesise current research on the global diversity of microorganisms, cryptogams, and invertebrates in mountain soils above the treeline. This synthesis is based on a semi-quantitative survey of the literature and an expert-based analysis. Our work reveals not only deficiencies in geographic cover but also significant gaps in taxonomic coverage, particularly among soil protists and invertebrates, and a lack of (functional and ecological) description of the uncultivated majority of prokaryotes, fungi, and protists. We subsequently build on this overview to highlight opportunities for research on mountain soils as systems of co-occurring species that interact in complex environmental matrices to fulfil critical functions and make essential contributions to life on land. Closing gaps in biodiversity research in mountain soil is crucial to enhance our understanding and to promote laws and guidelines advancing international soil biodiversity conservation targets in mountains. Addressing sparse and biased data, recognizing the impact of environmental changes on mountain ecosystems, and advocating dedicated policies are essential strategies to safeguard mountain soils and their biodiversity. GLOSSARY O_TBL View this table: org.highwire.dtl.DTLVardef@16682fdorg.highwire.dtl.DTLVardef@121b9feorg.highwire.dtl.DTLVardef@139eadeorg.highwire.dtl.DTLVardef@16abd74org.highwire.dtl.DTLVardef@bc3da9_HPS_FORMAT_FIGEXP M_TBL C_TBL

ecology↗

bioRxiv2023

Clinical Significance of the Stromatic Component in Ovarian Cancer: Quantity Over Quality in Outcome Prediction

BackgroundThe tumor stroma is composed of a complex network of non-cancerous cells and extracellular matrix elements that collectively are crucial for cancer progression and treatment response. Within the realm of ovarian cancer, the expression of the stromal gene cluster has been linked to poorer progression-free and overall survival rates. However, in the age of precision medicine and genome sequencing, the notion that the simple measurement of tumor-stroma proportion alone can serve as a biomarker for clinical outcome is a topic that continues to generate controversy and provoke discussion. Our current study reveals that it is the quantity of stroma, rather than its quality, that serves as a clinically significant indicator of patient outcome in ovarian cancer. MethodsThis study leveraged the High-Grade-Serous-Carcinoma (HGSC) cohort of the publicly accessible Cancer Genome Atlas Program (TCGA) along with an independent cohort comprising HGSC clinical specimens in diagnostic and Tissue Microarray formats. Our objective was to investigate the correlation between the Tumor-Stroma-Proportion (TSP) and progression-free survival (PFS), overall survival (OS), and response to chemotherapy. We assessed these associations using H&E-stained slides and tissue microarrays. Our analysis employed semi-parametric models that accounted for age, metastases, and residual disease as controlling factors. ResultsWe found that high TSP (>50% stroma) was associated with significantly shorter progression-free survival (PFS) (p=0.016) and overall survival (OS) (p=0.006). Tumors from patients with chemoresistant tumors were twice as likely to have high TSP as compared to tumors from chemosensitive patients (p=0.012). In tissue microarrays, high TSP was again associated with significantly shorter PFS (p=0.044) and OS (p=0.0001), further confirming our findings. The Area Under the ROC curve for the model predicting platinum was estimated at 0.7644. ConclusionsIn HGSC, TSP was a consistent and reproducible marker of clinical outcome measures, including PFS, OS, and platinum chemoresistance. Assessment of TSP as a predictive biomarker that can be easily implemented and integrated into prospective clinical trial design and adapted to identify, at time of initial diagnosis, patients who are least likely to benefit long-term from conventional platinum-based cytotoxic chemotherapy treatment.

pathology↗

bioRxiv2023

Heterogeneous responsiveness to environmental stimuli

Individuals of a species cope with environmental variability through behavioral adjustments driven by individuals responsiveness to environmental stimuli. Three key empirical observations have been made for many animal species: The coexistence of different degrees of responsiveness within one species; the consistency of an individuals degree of responsiveness across time; and the correlation of an individuals degree of responsiveness across contexts. Taking up key elements of existing approaches, we provide one unifying explanation for all three observations, by identifying a unique evolutionarily stable strategy of an appropriately defined game within a stochastic environment that has all three features. Coexistence is explained by a form of negative frequency dependence. Consistency and correlation is explained through potentially small, individual, differences of states animals have and the resulting differential advantages they can get from it. Our results allow us to identify a variety of testable implications.

animal behavior and cognition↗

bioRxiv2023

Introgressive descent and hypersexuality drive the evolution of sexual parasitism and morphological reduction in a fungal species complex.

Taxonomists consider species as discrete units of biological organization, which are subject to a continuous process of evolutionary change and are connected through their shared ancestry. However, the continuous nature of evolutionary change is difficult to reconcile with the discrete outcome of speciation, especially where species boundaries are permeable. A good example of this inconsistency is the lichen genus Pyrenodesmia, which shows a high morphologic and genetic diversity that that defies systematization by taxonomic or phylogenetic methods. Here we show that hybridization explains the presence of discordant morphs and that European species are interconnected through cross-mating in a single reproductive network, a syngameon, despite which species remain largely distinct and distinguishable. Whole genome data reflect the important role played by genome defense mechanisms in the genomic stabilization of fungal hybrids. The recurrence of Repeat Induced Point mutations (RIP) shapes genomes with islands of suppressed recombination and loss of gene content, which in turn generates a feedback loop reinforcing the lack of reproductive isolation through the loss of heterokaryon incompatibility and a tendency towards morphological reduction.

evolutionary biology↗

bioRxiv2021

Fourier SPoC: A costumised machine-learning analysis pipeline for auditory beat-based entrainment in the MEG

We propose here (the informed use) of a customised, data-driven machine-learning pipeline to analyse magnetoencephalography (MEG) in a theoretical source space, with respect to the processing of a regular beat. This hypothesis- and data-driven analysis pipeline allows us to extract the maximally relevant components in MEG source-space, with respect to the oscillatory power in the frequency band of interest and, most importantly, the beat-related modulation of that power. Our pipeline combines Spatio-Spectral Decomposition as a first step to seek activity in the frequency band of interest (SSD, [1]) with a Source Power Co-modulation analysis (SPoC; [2]), which extracts those components that maximally entrain their activity with the given target function, that is here with the periodicity of the beat in the frequency domain (hence, f-SPoC). MEG data (102 magnetometers) from 28 participants passively listening to a 5-min long regular tone sequence with a 400 ms beat period (the "target function" for SPoC) were segmented into epochs of two beat periods each to guarantee a sufficiently long time window. As a comparison pipeline to SSD and f-SpoC, we carried out a state-of-the-art cluster-based permutation analysis (CBPA, [3]). The time-frequency analysis (TFA) of the extracted activity showed clear regular patterns of periodically occurring peaks and troughs across the alpha and beta band (8-20 Hz) in the f-SPoC but not in the CBPA results, and both the depth and the specificity of modulation to the beat frequency yielded a significant advantage. Future applications of this pipeline will address target the relevance to behaviour and inform analogous analyses in the EEG, in order to finally work toward addressing dysfunctions in beat-based timing and their consequences. Author summaryWhen listening to a regular beat, oscillations in the brain have been shown to synchronise with the frequency of that given beat. This phenomenon is called entrainment and has in previous brain-imaging studies been shown in the form of one peak and trough per beat cycle in a range of frequency bands within 15-25 Hz (beta band). Using machine-learning techniques, we designed an analysis pipeline based on Source-Power Co-Modulation (SPoC) that enables us to extract spatial components in MEG recordings that show these synchronisation effects very clearly especially across 8-20 Hz. This approach requires no anatomical knowledge of the individual or even the average brain, it is purely data driven and can be applied in a hypothesis-driven fashion with respect to the "function" that we expect the brain to entrain with and the frequency band within which we expect to see this entrainment. We here apply our customised pipeline using "f-SPoC" to MEG recordings from 28 participants passively listening to a 5-min long tone sequence with a regular 2.5 Hz beat. In comparison to a cluster-based permutation analysis (CBPA) which finds sensors that show statistically significant power modulations across participants, our individually extracted f-SPoC components find a much stronger and clearer pattern of peaks and troughs within one beat cycle. In future work, this pipeline can be implemented to tackle more complex "target functions" like speech and music, and might pave the way toward rhythm-based rehabilitation strategies.

neuroscience↗

bioRxiv2020

Auditory beat perception is related to speech output fluency in post-stroke aphasia

Aphasia affects at least one third of stroke survivors, and there is increasing awareness that more fundamental deficits in auditory processing might contribute to impaired language performance in such individuals. We performed a comprehensive battery of psychoacoustic tasks assessing the perception of tone pairs and sequences across the domains of pitch, rhythm and timbre in 17 individuals with post-stroke aphasia and 17 controls. At the group level, we showed a significant difference in auditory perception in only one test (Dynamic Modulation detection). At the level of individual differences we demonstrated a correlation between metrical pattern (beat) perception and speech output fluency with strong effect (Spearmans rho = 0.72). This was specific in terms of the auditory tests and dissociated from more basic auditory timing perception, which did not correlate with output fluency. This was also specific in terms of the language and cognitive measures, amongst which phonological, semantic and executive function did not correlate with beat detection. We interpret the data in terms of a requirement for the analysis of the metrical structure of sound to construct fluent output, with both being a function of higher-order "temporal scaffolding". The beat perception task herein allows measurement of timing analysis without any need to account for motor output deficit, and could be a potential clinical tool to examine this. This work suggests strategies to improve fluency after stroke by training in metrical pattern perception.

neuroscience↗

bioRxiv2017

Marine cyanolichens from different littoral zones are associated with distinct bacterial communities

The microbial diversity and function of terrestrial lichens has been well studied, but knowledge about the non-photosynthetic bacteria associated with marine lichens is still scarce. 16S rRNA gene Illumina sequencing was used to assess the culture-independent bacterial diversity in the strictly marine cyanolichen species Lichina pygmaea and Lichina confinis, and the maritime chlorolichen species Xanthoria aureola which occupy different areas on the littoral zone. Inland terrestrial cyanolichens from Austria were also analysed as for the marine lichens to examine further the impact of habitat/lichen species on the associated bacterial communities. The L. confinis and L. pygmaea communities were significantly different from those of the maritime Xanthoria aureola lichen found higher up on the littoral zone and these latter communities were more similar to those of the inland terrestrial lichens. The strictly marine lichens were dominated by the Bacteroidetes phylum accounting for 50% of the sequences, whereas Alphaproteobacteria, notably Sphingomonas, dominated the maritime and the inland terrestrial lichens. Bacterial communities associated with the two Lichina species were significantly different sharing only 33 core OTUs, half of which were affiliated to the Bacteroidetes genera Rubricoccus, Tunicatimonas and Lewinella, suggesting an important role of these species in the marine Lichina lichen symbiosis. Marine cyanolichens showed a higher abundance of OTUs likely affiliated to moderately thermophilic and/or radiation resistant bacteria belonging to the Phyla Chloroflexi, Thermi, and the families Rhodothermaceae and Rubrobacteraceae when compared to those of inland terrestrial lichens. This most likely reflects the exposed and highly variable conditions to which they are subjected daily.

ecology↗