Biology subjects

Hartmann, F.

Publications and source records attributed to Hartmann, F..

15 recordsLinked to original sources

bioRxiv2026

A multi-omics approach to maize (Zea mays) tassel development

The development of the male inflorescence in maize (Zea mays L.) is a complex and highly regulated process that is essential for reproductive success and yield. To gain a comprehensive understanding of the regulatory programs involved in tassel formation, including the initial specification of anther cell types, the transcriptomes, small RNAs (sRNAs), and proteomes were profiled at four developmental stages (0.5-2.0 cm). The RNAseq analysis indicates dynamic shifts in gene expression underlying the transition from indeterminate meristems to organ initiation and germinal cell determination by 2.0 cm. Complementing these data, sRNA sequencing uncovered 182 microRNAs (miRNAs) with distinct temporal patterns. A core set of 126 miRNAs was expressed throughout tassel development, while others displayed strong stage-specific enrichment. Notably, families of miRNAs that target auxin signaling were dynamically regulated, suggesting fine-tuning of hormone signaling in relation to meristem activity. Later stages were enriched for miR2275 and miR11969, which previously have both been associated with meiocytes, indicating the onset of reproductive sRNA pathways during the early stages of anther differentiation. Together, these datasets provide a broad overview of tassel development and form a backbone to enrich existing RNAseq and single cell RNAseq data sets of specific steps in tassel and initial anther development, while also adding new data on sRNA expression.

plant biology↗

bioRxiv2025

Protective and pathogenic antibody responses from a primate Shigella outbreak inform vaccine design

There is currently no approved vaccine for Shigella spp., a leading cause of diarrhea that are increasingly resistant to antimicrobials. Shigella vaccine development is complicated in part by an incomplete understanding of the structural and molecular determinants of immunity. To address this, we isolated monoclonal antibodies (mAbs) against candidate Shigella vaccine antigens using samples from a Shigella flexneri outbreak in a non-human primate (NHP) research facility. We found that antibodies targeting the Shigella O-antigen (O-Ag) can undergo significant affinity maturation (>10%) to acquire broad cross-reactivity across S. flexneri serotypes. We also found that the virulence-associated type III secretion system (T3SS) proteins IpaD and IpaB elicit moderate T cell and robust antibody responses. T3SS antibodies either inhibit, or - surprisingly - enhance bacterial virulence in vitro and in vivo depending on their epitope specificity. These findings provide key insights into protective and deleterious immune responses against Shigella that directly inform vaccine immunogen design.

immunology↗

bioRxiv2025

Characterization of the maize (Zea mays)-Ustilago maydis interaction in a warming climate

Maize is among the most grown crops worldwide. Concurrently, infections with Ustilago maydis, causing corn smut disease, occur in all major growing regions. This is accompanied by loss of biomass, yields, and silage quality. As global warming increases, modeling analysis predicts an increase in pathogen infestation. Nevertheless, there are no maize lines resistant to U. maydis and no effective fungicides available. Based on the evaluation of climate data for the State of Bavaria (Germany), maize-U. maydis infection trials and RNAseq analysis were conducted on a variety of maize cultivars under different temperature conditions generating a large phenotypic and transcriptomic dataset to determine the influence of temperature changes and differences in plant susceptibility. Even a minimal increase in temperature resulted in increased symptoms and significant variances in expression. Infection-gene expression association analysis followed by in vivo tests identified GIBBERELLIC ACID STIMULATED TRANSCRIPT-LIKE4 (GSL4) and{gamma} -aminobutyric acid as important factors for the infection.

plant biology↗

bioRxiv2025

Uridine Metabolism as a Targetable Metabolic Achilles' Heel for chemo-resistant B-ALL

Relapse continues to limit survival for patients with B-cell acute lymphoblastic leukemia (B-ALL). Previous studies have independently implicated activation of B-cell developmental signaling pathways and increased glucose consumption with chemo-resistance and relapse risk. Here, we connect these observations, demonstrating that B-ALL cells with active signaling, defined by high expression of phosphorylated ribosomal protein S6 ("pS6+ cells"), are metabolically unique and glucose dependent. Isotope tracing and metabolic flux analysis confirm that pS6+ cells are highly glycolytic and notably sensitive to glucose deprivation, relying on glucose for de novo nucleotide synthesis. Uridine, but not purine or pyrimidine, rescues pS6+ cells from glucose deprivation, highlighting uridine is essential for their survival. Active signaling in pS6+ cells drives uridine production through activating phosphorylation of carbamoyl phosphate synthetase (CAD), the enzyme catalyzing the initial steps of uridine synthesis. Inhibition of signaling abolishes glucose dependency and CAD phosphorylation in pS6+ cells. Primary pS6+ cells demonstrate high expression of uridine synthesis proteins, including dihydroorotate dehydrogenase (DHODH), the rate-limiting catalyst of de novo uridine synthesis. Gene expression demonstrates that increased expression of DHODH is associated with relapse and inferior event-free survival after chemotherapy. Further, the majority of B-ALL genomic subtypes demonstrate activity of DHODH. Inhibiting DHODH using BAY2402232 effectively kills pS6+ cells in vitro, with its IC50 correlated with the strength of pS6 signaling across 14 B-ALL cell lines and patient-derived xenografts (PDX). In vivo DHODH inhibition prolongs survival and decreases leukemia burden in pS6+ B-ALL cell line and PDX models. These findings link active signaling to uridine dependency in B-ALL cells and an associated risk of relapse. Targeting uridine synthesis through DHODH inhibition offers a promising therapeutic strategy for chemo-resistant B-ALL as a novel therapeutic approach for resistant disease.

cancer biology↗

bioRxiv2025

Temporal and spatial composition of the tumor microenvironment predicts response to immune checkpoint inhibition

Immune checkpoint inhibition (ICI) has fundamentally changed cancer treatment. However, only a minority of patients with metastatic triple negative breast cancer (TNBC) benefit from ICI, and the determinants of response remain largely unknown. To better understand the factors influencing patient outcome, we assembled a longitudinal cohort with tissue from multiple timepoints, including primary tumor, pre-treatment metastatic tumor, and on-treatment metastatic tumor from 117 patients treated with ICI (nivolumab) in the phase II TONIC trial. We used highly multiplexed imaging to quantify the subcellular localization of 37 proteins in each tumor. To extract meaningful information from the imaging data, we developed SpaceCat, a computational pipeline that quantifies features from imaging data such as cell density, cell diversity, spatial structure, and functional marker expression. We applied SpaceCat to 678 images from 294 tumors, generating more than 800 distinct features per tumor. Spatial features were more predictive of patient outcome, including features like the degree of mixing between cancer and immune cells, the diversity of the neighboring immune cells surrounding cancer cells, and the degree of T cell infiltration at the tumor border. Non-spatial features, including the ratio between T cell subsets and cancer cells and PD-L1 levels on myeloid cells, were also associated with patient outcome. Surprisingly, we did not identify robust predictors of response in the primary tumors. In contrast, the metastatic tumors had numerous features which predicted response. Some of these features, such as the cellular diversity at the tumor border, were shared across timepoints, but many of the features, such as T cell infiltration at the tumor border, were predictive of response at only a single timepoint. We trained multivariate models on all of the features in the dataset, finding that we could accurately predict patient outcome from the pre-treatment metastatic tumors, with improved performance using the on-treatment tumors. We validated our findings in matched bulk RNA-seq data, finding the most informative features from the on-treatment samples. Our study highlights the importance of profiling sequential tumor biopsies to understand the evolution of the tumor microenvironment, elucidating the temporal and spatial dynamics underlying patient responses and underscoring the need for further research on the prognostic role of metastatic tissue and its utility in stratifying patients for ICI.

cancer biology↗

bioRxiv2024

SusC/D-like proteins in Gammaproteobacteria that utilize fructans

Fructans are ubiquitous in terrestrial ecosystems, however, these glycans are unexplored in the marine environment. We have discovered that the Antarctic gammaproteobacterium Pseudoalteromonas distincta is highly adapted to the degradation of fructose-containing substrates. This is enabled by proteins encoded in several genomic regions, including a fructan polysaccharide utilization locus (PUL). In addition to a glycoside hydrolase from family 32 (GH32), the fructan PUL encodes two proteins that have been described as specific for Bacteroidota and were previously unknown for Gammaproteobacteria: a glycan-binding SusD-like protein and a SusC-like TonB-dependent transporter (TBDT), which work as a complex in glycan import. Proteome analyses and biochemistry results suggest that the SusC/D-like proteins of P. distincta shuttle small-sized inulin-type fructans directly into the cell, where they are degraded by a periplasmic exo-active GH32. A SusD-like protein could provide a competitive adavantage in the absence of extracelluar endo-active inulinases. Comparative genomics identified further SusC/D-like proteins in Gammaproteobacteria, most of which are co-encoded with GH32s, indicative of fructan PULs, and are frequently associated with the marine habitat. Our study thus shows the first known exception to the paradigm that only Bacteroidota use SusC/D-like proteins. It further suggests that fructans contribute to the marine glycan pool.

molecular biology↗

bioRxiv2024

Learning tissue representation by identification of persistent local patterns in spatial omics data

Spatial omics data provide rich molecular and structural information on tissues. Their analysis provides insights into local heterogeneity of tissues and holds promise to improve patient stratification by association of clinical observations with refined tissue representations. We introduce Kasumi, a method for the identification of spatially localized neighborhood patterns of intra- and intercellular relationships that are persistent across samples and conditions. The tissue representation based on these patterns can facilitate translational tasks, as we show for stratification of cancer patients for disease progression and response to treatment using data from different experimental platforms. On these tasks Kasumi outperforms related approaches and offers explanations of spatial coordination and relationships at the cell-type or marker level. We show that persistent patterns comprise regions of different sizes and that non-abundant, localized relationships in the tissue are strongly associated with unfavorable outcomes.

bioinformatics↗

bioRxiv2023

Autophagy counters inflammation-driven glycolytic impairment in aging hematopoietic stem cells

Aging of the hematopoietic system promotes various blood, immune and systemic disorders and is largely driven by hematopoietic stem cell (HSC) dysfunction (1). Autophagy is central for the benefits associated with activation of longevity signaling programs (2), and for HSC function and response to nutrient stress (3,4). With age, a subset of HSCs increases autophagy flux and preserves some regenerative capacity, while the rest fail to engage autophagy and become metabolically overactivated and dysfunctional (4). However, the signals that promote autophagy in old HSCs and the mechanisms responsible for the increased regenerative potential of autophagy-activated old HSCs remain unknown. Here, we demonstrate that autophagy activation is an adaptive survival response to chronic inflammation in the aging bone marrow (BM) niche (5). We find that inflammation impairs glucose metabolism and suppresses glycolysis in aged HSCs through Socs3-mediated impairment of AKT/FoxO-dependent signaling. In this context, we show that inflammation-mediated autophagy engagement preserves functional quiescence by enabling metabolic adaptation to glycolytic impairment. Moreover, we demonstrate that transient autophagy induction via a short-term fasting/refeeding paradigm normalizes glucose uptake and glycolytic flux and significantly improves old HSC regenerative potential. Our results identify inflammation-driven glucose hypometabolism as a key driver of HSC dysfunction with age and establish autophagy as a targetable node to reset old HSC glycolytic and regenerative capacity. One-Sentence SummaryAutophagy compensates for chronic inflammation-induced metabolic deregulation in old HSCs, and its transient modulation can reset old HSC glycolytic and regenerative capacity.

cell biology↗

bioRxiv2023

The statistics of natural shapes predict high-level aftereffects in human vision

Shape perception is essential for numerous everyday behaviors from object recognition to grasping and handling objects. Yet how the brain encodes shape remains poorly understood. Here, we probed shape representations using visual aftereffects--perceptual distortions that occur following extended exposure to a stimulus--to resolve a long-standing debate about shape encoding. We implemented contrasting low-level and high-level computational models of neural adaptation, which made precise and distinct predictions about the illusory shape distortions the observers experience following adaptation. Directly pitting the predictions of the two models against one another revealed that the perceptual distortions are driven by high-level shape attributes derived from the statistics of natural shapes. Our findings suggest that the diverse shape attributes thought to underlie shape encoding (e.g., curvature distributions, skeletons, aspect ratio) are the result of a visual system that learns to encode natural shape geometries based on observing many objects.

neuroscience↗

bioRxiv2022

A method to estimate contact regions between hands and objects during human multi-digit grasping

In order to grasp an object successfully, we must select appropriate contact regions for our hands on the surface of the object. However, identifying such regions is challenging. Here, we describe a workflow to estimate contact regions from marker-based tracking data. Participants grasp real objects, while we track the 3D position of both the objects and the hand including the fingers joints. We first determine joint Euler angles from a selection of tracked markers positioned on the back of the hand. Then, we use state-of-the-art hand mesh reconstruction algorithms to generate a mesh model of the participants hand in the current pose and 3D position. Using objects that were either 3D printed, or 3D scanned--and are thus available as both real objects and mesh data--allows us to co-register the hand and object meshes. In turn, this allows us to estimate approximate contact regions by calculating intersections between the hand mesh and the co-registered 3D object mesh. The method may be used to estimate where and how humans grasp objects under a variety of conditions. Therefore, the method could be of interest to researchers studying visual and haptic perception, motor control, human-computer interaction in virtual and augmented reality, and robotics. SUMMARYWhen we grasp an object, multiple regions of the fingers and hand typically make contact with the objects surface. Reconstructing such contact regions is challenging. Here, we present a method for approximately estimating contact regions, by combining marker-based motion capture with existing deep learning-based hand mesh reconstruction.

neuroscience↗

bioRxiv2022

Magnitude and kinetics of the human immune cell response associated with severe dengue progression by single-cell proteomics

Approximately five million dengue virus-infected patients, particularly children, progress to a potentially life-threatening severe dengue (SD) infection annually. To identify the immune features and temporal dynamics underlying SD progression, we performed deep immune profiling by mass cytometry of PBMCs collected longitudinally from SD progressors (SDp) and uncomplicated dengue (D) patients. While D is characterized by early activation of innate immune responses, in SDp there is rapid expansion and activation of IgG-secreting plasma cells and memory and regulatory T cells. Concurrently, SDp, particularly children, demonstrate increased proinflammatory NK cells, inadequate expansion of CD16+ monocytes, and high expression of the Fc{gamma}R, CD64 on myeloid cells, yet diminished antigen presentation. Syndrome-specific determinants include suppressed dendritic cell abundance in shock/hemorrhage vs. enriched plasma cell expansion in organ impairment. This study reveals uncoordinated immune responses in SDp and provides insights into SD pathogenesis in humans with potential implications for prediction and treatment.

immunology↗

bioRxiv2022

Stepwise recombination suppression around the mating-type locus in the fungus Schizothecium tetrasporum (Ascomycota, Sordariales)

Recombination is often suppressed at sex-determining loci in plants and animals, and at self-incompatibility or mating-type loci in plants and fungi. In fungal ascomycetes, recombination suppression around the mating-type locus is associated with pseudo-homothallism, i.e., the production of self-fertile dikaryotic sexual spores carrying the two opposite mating types. This has been well studied in two species complexes from different families of Sordariales: Podospora anserina and Neurospora tetrasperma. However, it is unclear whether this intriguing convergent association holds in other species. We show here that Schizothecium tetrasporum, a fungus from a third family in the order Sordariales, also produces mostly self-fertile dikaryotic spores carrying the two opposite mating types. This was due to a high frequency of second meiotic division segregation at the mating-type locus, indicating the occurrence of a single and systematic crossing-over event between the mating-type locus and the centromere, as in P. anserina. The mating-type locus has the typical Sordariales organization, plus a MAT1-1-1 pseudogene in the MAT1-2 haplotype. High-quality genome assemblies of opposite mating types and segregation analyses revealed a suppression of recombination in a region of 1.3 Mb around the mating-type locus. We detected three evolutionary strata, displaying a stepwise extension of recombination suppression, but no rearrangement or transposable element accumulation in the non-recombining region. Our findings indicate a convergent evolution of self-fertile dikaryotic sexual spores across multiple ascomycete fungi. The particular pattern of meiotic segregation at the mating-type locus was associated with recombination suppression around this locus, that had extended stepwise. This association is consistent with a recently proposed mechanism of deleterious allele sheltering through recombination suppression around a permanently heterozygous locus. AUTHOR SUMMARYRecombination allows faster adaptation and the purging of deleterious mutation but is often paradoxically lacking in sex chromosomes. It has been recently recognized that recombination can also be suppressed on fungal mating-type chromosomes, but the evolutionary explanation and the proximal mechanism of this phenomenon remain unclear. By studying here the sexual biology of a poorly studied mold living in rabbit dung, we reveal a striking convergence in three distant fungal lineages of an independently evolved association between the production of self-fertile sexual spores (carrying two nuclei with opposite mating types), a particular segregation of the mating-type locus and the lack of recombination on mating-type chromosomes, having evolved stepwise. Such a convergent association suggests causal relationships and will contribute to unveil the evolutionary causes of recombination suppression. Graphical summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=174 SRC="FIGDIR/small/500756v2_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1cea706org.highwire.dtl.DTLVardef@378c41org.highwire.dtl.DTLVardef@d90297org.highwire.dtl.DTLVardef@1391c74_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

bioRxiv2020

Chronic oxytocin-driven alternative splicing of CRFR2α induces anxiety

Recently, oxytocin (OXT) has generated considerable interest as potential treatment for psychiatric disorders, including general anxiety disorder or autism spectrum disorder. Therefore, knowledge on the involved molecular processes downstream of OXT receptor (OXTR) activation is indispensable. We reveal that alternative splicing of corticotropin releasing factor receptor 2 (CRFR2) parallels increased anxiety-like behavior following chronic OXT treatment, contrasting the well-known anxiolysis of acute OXT. In detail, chronic OXT shifts the splicing ratio between membrane-bound (mCRFR2) and soluble CRFR2 (sCRFR2) in favor of the latter via ERK1/2-MEF2A signaling. Targeted manipulations of Crfr2 splicing mimic the effect of chronic OXT, confirming its role in the regulation of anxiety-like behavior. Furthermore, chronic OXT triggers cytoplasmic distribution and extracellular release of sCRFR2 into the cerebrospinal fluid, with sCRFR2 levels positively correlating with anxiety-like behavior. Concluding, the dichotomy between anxiolytic mCRFR2 and anxiogenic sCRFR2 is the basis for the deleterious effects of chronic OXT on anxiety. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/255844v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1b50691org.highwire.dtl.DTLVardef@1c22efborg.highwire.dtl.DTLVardef@19a772eorg.highwire.dtl.DTLVardef@69af7_HPS_FORMAT_FIGEXP M_FIG C_FIG

animal behavior and cognition↗

bioRxiv2020

The complex genomic basis of rapid convergent adaptation to pesticides across continents in a fungal plant pathogen

Convergent evolution leads to identical phenotypic traits in different species or populations. Convergence can be driven by standing variation allowing selection to favor identical alleles in parallel or the same mutations can arise independently. However, the molecular basis of such convergent adaptation remains often poorly resolved. Pesticide resistance in agricultural ecosystems is a hallmark of convergence in phenotypic traits. Here, we analyze the major fungal pathogen Zymoseptoria tritici causing serious losses on wheat and with parallel fungicide resistance emergence across continents. We sampled three population pairs each from a different continent spanning periods early and late in the application of fungicides. To identify causal loci for resistance, we combined knowledge from molecular genetics work and performed genome-wide association studies (GWAS) on a global set of isolates. We discovered yet unknown factors in azole resistance including membrane stability functions. We found strong support for the hotspot model of resistance evolution with parallel changes in a small set of loci but additional loci showed more population-specific allele frequency changes. Genome-wide scans of selection showed that half of all known resistance loci were overlapping a selective sweep region. Hence, the application of fungicides was one of the major selective agents acting on the pathogen over the past decades. Furthermore, loci identified through GWAS showed the highest overlap with selective sweep regions underlining the importance to map phenotypic trait variation in evolving populations. Our population genomic analyses showed that both de novo mutations and gene flow likely contributed to the parallel emergence of resistance.

evolutionary biology↗

bioRxiv2020

An image-computable model of human visual shape similarity

Shape is a defining feature of objects. Yet, no image-computable model accurately predicts how similar or different shapes appear to human observers. To address this, we developed a model ( ShapeComp), based on over 100 shape features (e.g., area, compactness, Fourier descriptors). When trained to capture the variance in a database of >25,000 animal silhouettes, ShapeComp predicts human shape similarity judgments almost perfectly (r2>0.99) without fitting any parameters to human data. To test the model, we created carefully selected arrays of complex novel shapes using a Generative Adversarial Network trained on the animal silhouettes, which we presented to observers in a wide range of tasks. Our findings show that human shape perception is inherently multidimensional and optimized for comparing natural shapes. ShapeComp outperforms conventional metrics, and can also be used to generate perceptually uniform stimulus sets, making it a powerful tool for investigating shape and object representations in the human brain.

neuroscience↗