Biology subjects

Schaefer, H.

Publications and source records attributed to Schaefer, H..

13 recordsLinked to original sources

bioRxiv2026

The alpine Edelweiss genome reveals a recent allotetraploid origin and localized subgenome dominance

Few plants symbolize the European Alps as profoundly as Edelweiss (Leontopodium nivale subsp. alpinum), yet its evolutionary origin and genomic constitution has remained elusive. We present a haplotype-resolved, chromosome-scale assembly of an L. n. alpinum accession from the Central Alps. The 3.15-Gb genome resolved 48 chromosomes in four phased sets with balanced gene and repeat landscapes. Phylogenomics partitioned these sets into two progenitor-derived subgenomes, DE and FG, demonstrating an allotetraploid origin. Comparison with the diploid subspecies L. n. nivale from Southern European Mountains (Appennines) linked DE to this sampled southern lineage, whereas FG derives from another distinct, unresolved diploid progenitor. Chloroplast genomes placed the plastid split between central Alps and Apennine samples in the recent Pleistocene, approximately 20,000 years ago, and LTR insertion-age profiles revealed recent retrotransposon activity consistent with genome shock following allopolyploidization. Although the subgenomes are broadly balanced,large inversions and elevated divergence concentrate on three chromosome groups. On Chromosome 3, structural complexity coincides with FG hypermethylation and DE-biased expression, revealing localized subgenome dominance. Together, these results support previous studies that suggested a westward expansion from the Asian centre of Leontopodium diversity, followed by differentiation and hybridization of closely related European lineages. Our assembly positions Edelweiss as an alpine model for recent allotetraploidy and enables genomic studies of demography, selection and high-alpine adaptation.

evolutionary biology↗

bioRxiv2026

A semi-automated tool for improving Assessments and Lab Tests data annotation in ImmPort

Public data sharing in immunological and clinical research is essential for transparency, reproducibility, and secondary analysis. However, many datasets in repositories such as ImmPort lack sufficient structured data to enable reuse. ImmPort's Assessments and Lab Tests templates -- which capture critical clinical information -- are often incomplete or omitted due to their complexity and the manual effort required. To address this challenge, an application with a graphical user interface requiring no programming was developed to facilitate population of these templates. The tool streamlines the submission process by reducing time and complexity for data contributors while ensuring template formatting. It integrates ImmPort files, study-specific data files, and a curated data dictionary to automate the mapping of study variables to the required fields within each template. The tool was evaluated on seven ImmPort studies with diverse designs. It successfully generated submission-ready templates that passed ImmPort's internal validation and will be incorporated into the repository. By improving the feasibility and completeness of templates, this approach enhances the quality, findability, and reusability of data within ImmPort.

immunology↗

bioRxiv2026

Before auxin distribution matters: Prepatterning of the Arabidopsis embryo axis by MPK6-dependent AUX/IAA8 phosphorylation

In growth and development of plants, the signaling molecule auxin plays an instrumental role. Many patterning processes are controlled by auxin signaling in a self-organizing matter. After fertilization, such a patterning process needs to be started for the first time during plant life. Contrary to previous models, we show that the first differential auxin response that separates embryonic from extra-embryonic development in the two zygotic daughter cells happens independently of a detectable auxin gradient. Instead, differential phosphorylation of the transcriptional inhibitor Aux/IAA8 by MAP kinase signaling leads to differences in auxin sensitivity between the two daughter cells, initiating embryonic development in the apical cell. IAA8 phosphorylation in the basal cell prevents proteasomal degradation, suppressing canonical auxin responses, which initiates extra-embryonic development. MAP kinase signaling therefore precedes auxin gradients and prepatterns the apical-basal axis independently of an auxin gradient.

plant biology↗

bioRxiv2026

Ancient DNA reveals early use of melons in China's Song Dynasty

Melon (Cucumis melo L.) domestication is thought to have occurred independently once in Northeast Africa and twice in India, but archaeobotanical seed remains point to a possible additional domestication in China. Because Cucumis seeds are difficult to diagnose morphologically, genomic data from archaeological material are needed to evaluate these scenarios and reconstruct ancient melon traits. We sequenced two Song Dynasty melon seeds from Shuomen Gugang (China), recovering 4.6x and 1.7x nuclear genome coverage. Nuclear and chloroplast analyses place both seeds within cultivated C. melo from China, supporting introduction from the broader Asian domestication pool rather than independent Chinese domestication. To assess whether these seeds carried traits associated with sweet dessert melons, we examined loci underlying fruit phenotypes. Neither seed carried alleles for orange flesh; one harbored an allele linked to yellow/orange peel, the other possessed alleles associated with green flesh and reduced acidity. Since wild melons are monoecious, the presence of the derived andromonoecy allele in one seed, associated with rounder fruit shape, suggests early selection on fruit morphology. Together, these findings indicate that Song Dynasty melons were likely consumed as fresh or culinary fruits rather than as sweet dessert melons. Their flesh coloration resonates with Song-period aesthetic sensibilities, exemplified by jade-green celadon ceramics frequently crafted in melon-shaped forms. By anchoring East Asian archaeobotanical remains within modern melon genomic variation, this study provides a temporal framework for melon dispersal into China and shows how ancient genomics can illuminate past crop use.

evolutionary biology↗

bioRxiv2023

A novel phylogenomics pipeline reveals complex pattern of reticulate evolution in Cucurbitales

High-throughput sequencing data, such as target capture, RNA-Seq, genome skimming, and high-depth whole genome sequencing, are used for phylogenomic analyses. Integrating these mixed data types into a single phylogenomic dataset requires several bioinformatic tools and significant computational resources. Here, we present CAPTUS, a novel pipeline to analyze mixed data efficiently. CAPTUS assembles these data types, searches for loci of interest, and produces paralog-filtered alignments. If reference target loci are not available for the studied taxon, CAPTUS can also be used to discover new putative homologs via sequence clustering. Compared to other software, CAPTUS allows the recovery of a greater number of more complete loci across more species. We apply CAPTUS to assemble a comprehensive dataset, comprising the four types of sequencing data for the angiosperm order Cucurbitales, a clade of about 3,100 species in eight mainly tropical plant families, including begonias (Begoniaceae) and gourds (Cucurbitaceae). Our phylogenomic results support the currently accepted circumscription of Cucurbitales except for the position of the holoparasitic Apodanthaceae, which group with Rafflesiaceae in Malpighiales. A subset of mitochondrial gene regions supports the earlier divergence of Apodanthaceae in Cucurbitales. However, the nuclear regions and majority of mitochondrial regions place Apodanthaceae in Malpighiales. Within Cucurbitaceae, we confirm the monophyly of all currently accepted tribes but also reveal hybridization and incomplete lineage sorting both in Cucurbitales and within Cucurbitaceae. We show that contradicting results among earlier phylogenetic studies in Cucurbitales can be reconciled when accounting for gene tree conflict and demonstrate the efficiency of CAPTUS for complex datasets.

bioinformatics↗

bioRxiv2023

Therapeutic Prime/Pull Vaccination of HSV-2 Infected Guinea Pigs with the Ribonucleotide Reductase 2 (RR2) Protein and CXCL11 Chemokine Boosts Antiviral Local Tissue-Resident and Effector Memory CD4+ and CD8+ T Cells and Protects Against Recurrent Genital Herpes

Following acute herpes simplex virus type 2 (HSV-2) infection, the virus undergoes latency in sensory neurons of the dorsal root ganglia (DRG). Intermittent virus reactivation from latency and shedding in the vaginal mucosa (VM) causes recurrent genital herpes. While T-cells appear to play a role in controlling virus reactivation and reducing the severity of recurrent genital herpes, the mechanisms for recruiting these T-cells into DRG and VM tissues remain to be fully elucidated. The present study investigates the effect of CXCL9, CXCL10, and CXCL11 T-cell-attracting chemokines on the frequency and function of DRG- and VM-resident CD4+ and CD8+ T cells and its effect on the frequency and severity of recurrent genital herpes. HSV-2 latent-infected guinea pigs were immunized intramuscularly with the HSV-1 RR2 protein (Prime) and subsequently treated intravaginally with the neurotropic adeno-associated virus type 8 (AAV-8) expressing CXCL9, CXCL10, or CXCL11 T-cell-attracting chemokines (Pull). Compared to the RR2 therapeutic vaccine alone, the RR2/CXCL11 prime/pull therapeutic vaccine significantly increased the frequencies of functional tissue-resident (TRM cells) and effector (TEM cells) memory CD4+ and CD8+ T cells in both DRG and VM tissues. This was associated with less virus shedding in the healed genital mucosal epithelium and reduced frequency and severity of recurrent genital herpes. These findings confirm the role of local DRG- and VM-resident CD4+ and CD8+ TRM and TEM cells in reducing virus reactivation shedding and the severity of recurrent genital herpes and propose the novel prime/pull vaccine strategy to protect against recurrent genital herpes. IMPORTANCEThe present study investigates a novel prime/pull therapeutic vaccine strategy to protect against recurrent genital herpes in the guinea pig model. HSV-2 infected guinea pigs were vaccinated using a recombinantly expressed herpes tegument protein-RR2 (prime), followed by intravaginal treatment with the neurotropic adeno-associated virus type 8 (AAV-8) expressing CXCL9, CXCL10, or CXCL11 T-cell-attracting chemokines (pull). The RR2/CXCL11 prime/pull therapeutic vaccine elicited a significant reduction in virus shedding in the vaginal mucosa and decreased the severity and frequency of recurrent genital herpes. This protection was associated with increased frequencies of functional tissue-resident (TRM cells) and effector (TEM cells) memory CD4+ and CD8+ T cells infiltrating latently infected DRG tissues and the healed regions of the vaginal mucosa. These findings shed light on the role of tissue-resident (TRM cells) and effector (TEM cells) memory CD4+ and CD8+ T cells in DRG and vaginal mucosa (VM) tissues in protection against recurrent genital herpes and propose the prime/pull therapeutic vaccine strategy in combating genital herpes. TWEETA therapeutic RR2/CXCL11 prime/pull vaccine reduced recurrent genital herpes more effectively than therapeutic vaccination with a subunit HSV RR2 antigen alone.

immunology↗

bioRxiv2023

Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome (LTCS) patients

Deep metabolomic, proteomic and immunologic phenotyping of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients have matched a wide diversity of clinical symptoms with potential biomarkers for coronavirus disease 2019 (COVID-19). Within here, several studies described the role of metabolites, lipoproteins and inflammation markers during infection and in recovered patients. In fact, after SARS-CoV-2 viral infection almost 20-30% of patients experience persistent symptoms even after 12 weeks of recovery which has been defined as long-term COVID-19 syndrome (LTCS). Emerging evidence revealed that a dysregulated immune system and persisting inflammation could be one of the key drivers of LTCS. However, how these small biomolecules such as metabolites, lipoprotein, cytokines and chemokines altogether govern pathophysiology is largely underexplored. Thus, a clear understanding how these parameters into an integrated fashion could predict the disease course may help to stratify LTCS patients from acute COVID-19 or recovered specimen and would help to elucidate a potential mechanistic role of these biomolecules during the disease course. Here, we report an integrated analysis of blood serum and plasma by in vitro diagnostics research NMR spectroscopy and flow cytometry-based cytokine quantification in a total of 125 individuals (healthy controls (HC; n=73), recovered (n=12), acute (n=7) and LTCS (n=33)). We identified that in LTCS patients lactate and pyruvate were significantly different from either healthy controls or acute COVID-19 patients. Further correlational analysis of cytokines and metabolites indicated that creatine, glutamine, and high-density lipoprotein (HDL) phospholipids were distributed differentially amongst patients or individuals. Of note, triglycerides and several lipoproteins (apolipoproteins Apo-A1 and A2) in LTCS patients demonstrate COVID-19-like alterations compared to HC. Interestingly, LTCS and acute COVID-19 samples were distinguished mostly by their creatinine, phenylalanine, succinate, 3-hydroxybutyrate (3-HB) and glucose concentrations, illustrating an imbalanced energy metabolism. Most of the cytokines and chemokines were present at low levels in LTCS patients compared with HC except IL-18 chemokine, which tended to be higher in LTCS patients and correlated positively with several amino acids (creatine, histidine, leucine, and valine), metabolites (lactate and 3-HB) and lipoproteins. The identification of these persisting plasma metabolites, lipoprotein and inflammation alterations will help to better stratify LTCS patients from other diseases and could help to predict ongoing severity of LTCS patients. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/523998v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@ecdeacorg.highwire.dtl.DTLVardef@10f0f80org.highwire.dtl.DTLVardef@1c2ddaborg.highwire.dtl.DTLVardef@672120_HPS_FORMAT_FIGEXP M_FIG C_FIG Layman summary & significance of the researchAlmost 20-30% of individuals infected with the SARS-CoV-2 virus regardless of hospitalization status experience long-term COVID-19 syndrome (LTCS). It is devasting for millions of individuals worldwide and hardly anything is known about why some people experience these symptoms even after 3 to 12 months after the acute phase. In this, we attempted to understand whether dysregulated metabolism and inflammation could be contributing factors to the ongoing symptoms in LTCS patients. Total blood triglycerides and the Cory cycle metabolites (lactate and pyruvate) were significantly higher, lipoproteins (Apo-A1 and A2) were drastically lower in LTCS patients compared to healthy controls. Correlation analysis revealed that either age or gender are positively correlated with several metabolites (citrate, glutamate, 3-hydroxybutyrate, glucose) and lipoproteins (Apo-A1, HDL Apo-A1, LDL triglycerides) in LTCS patients. Several cytokines and chemokines were also positively correlated with metabolites and lipoproteins thus, dysregulation in metabolism and inflammation could be a potential contributory factor for LTCS symptoms.

immunology↗

bioRxiv2022

A Prime/Pull RR2/CXCL11 Therapeutic Vaccine that Bolsters the Number and Function of Dorsal Root Ganglia Tissue-Resident HSV-Specific CD8+ TRM Cells Protects Latently Infected Guinea Pigs from Recurrent Genital Herpes

Reactivation of herpes simplex virus type 2 (HSV-2) from latently infected dorsal root ganglia (DRG) and subsequent virus shedding in the genital tract trigger recurrent genital herpes. Memory CD8+ T cells play a critical role in preventing HSV-2 reactivation from latently infected DRG, thus reducing recurrent genital lesions. The role of T-cell attracting chemokines in promoting CD8+ T cell protective immunity in recurrent genital herpes remains to be fully elucidated. In this study, we investigated whether and how the CXCL11/CXCR3 pathway affects the frequency and function of DRG-resident CD8+ T cells and the severity of recurrent genital herpes. Latently infected guinea pigs were primed with the HSV-1 RR2 protein, delivered intramuscularly with CpG/Alum adjuvants, and the induced T cells were "pulled" from the periphery into the latently infected DRG using T-cell attracting CXCL11 chemokine, delivered to DRG. In the guinea pigs that received the prime/pull vaccine, we detected a significant increase in both the number and function of tissue-resident IFN-{gamma}+CD103+CD44+CXCR3+CD8+ TRM cells that infiltrated healed sites of the vaginal mucosa (VM) and DRG tissues. This was associated with a significant decrease in virus shedding and a reduction in both the severity and frequency of recurrent genital herpes lesions. In contrast, in the guinea pigs that received the RR2 vaccine alone, we detected fewer functional CD8+ TRM cells and no reduction in the severity of recurrent genital herpes. These findings highlight the role of the CXCL11/CXCR3 chemokine pathway in shaping tissue-resident CD8+ TRM cell protective immunity against recurrent genital herpes. IMPORTANCERecurrent genital herpes is a common sexually transmitted disease worldwide. Currently, no FDA-approved therapeutic vaccines are available. In the present study, we used HSV-2 latently infected guinea pig to investigate a novel therapeutic prime/pull vaccine strategy based on priming T cells systemically, with a recombinantly expressed herpes envelope and tegument protein RR2 and "pulling" primed T cells into the tissues of latently infected ganglia with the T-cell-attracting chemokine, CXCL11. We discovered that this RR2/CXCL11 prime/pull vaccine elicited a significant reduction in virus shedding and a decrease in both the severity and frequency of recurrent genital herpes sores. This protection correlated with increased numbers of functional tissue-resident IFN-{gamma}+CD103+CD44+CXCR3+CD8+ TRM cells that infiltrate healed sites of the VM tissues and DRG. Our findings shed light on the role of TRM cells in protection against recurrent genital herpes and propose the prime/pull therapeutic vaccine as a new strategy against genital herpes. TWEETThe present study presents a novel RR2/CXCL11 prime/pull therapeutic vaccine that elicited a significant reduction in virus shedding and a decrease in both the severity and frequency of recurrent genital herpes sores.

immunology↗

bioRxiv2021

Tree phyllospheres are a habitat for diverse populations of CO-oxidising bacteria

BackgroundCarbon monoxide (CO) is a naturally occurring and ubiquitous trace gas in the atmosphere. As a product of combustion processes, it can reach concentrations in the mg/m3 range in urban areas, contributing to air pollution. Aerobic CO-degrading microorganisms have been identified previously and are thought to remove ~370 Tg of CO in soils and oceans per year. Based on the presence of genes encoding subunits of the enzyme carbon monoxide dehydrogenase in metagenomes, a large fraction of soil bacteria may have the potential for CO degradation. The activity and diversity of CO-degrading microorganisms in above ground habitats such as the phyllosphere has not been addressed, however, and their potential role in global CO cycling remains unknown. ResultsMonitoring of CO-degradation in leaf washes of two common British trees, Ilex aquifolium and Crataegus monogyna, demonstrated CO uptake in all samples investigated. Leaf washes of I. aquifolium had significantly higher CO oxidation rates than those of C. monogyna. A diverse range of bacterial taxa were identified as candidate CO-oxidising taxa based on high-throughput sequencing and multivariate statistical analysis of 16S rRNA amplicon data, as well as functional diversity analysis based on coxL, the gene encoding the large subunit of CO-dehydrogenase. Candidate CO-oxidising taxa included a range of Rhizobiales and Burkholderiales, of which the Burkholderiales OTUs were abundant colonisers of the phyllosphere at the time of sampling, as indicated by 16S rRNA gene sequencing. In addition, an estimated 12.4% of leaf OTUs in samples of this study contained coxL homologues, based on their predicted genomes. We also mined data of publicly available phyllosphere metagenomes for genes encoding subunits of CO-dehydrogenase which indicated that, on average, 25% of phyllosphere bacteria contained CO-dehydrogenase gene homologues. A CO-oxidising Phyllobacteriaceae strain was isolated from phyllosphere samples which contains genes encoding both CODH as well as a RuBisCO. ConclusionsThe phyllosphere, a vast microbial habitat, supports diverse and potentially abundant CO-oxidising bacteria. These findings identify tree phyllosphere bacteria as a potential sink for atmospheric CO and highlight the need for a more detailed assessment of phyllosphere microbial communities in the global cycle of CO.

microbiology↗

bioRxiv2021

Genetic diversification of persistent Mycobacterium abscessus within Cystic Fibrosis patients

Mycobacterium (M.) abscessus infections in Cystic Fibrosis (CF) patients cause a deterioration of lung function. Treatment of these multidrug-resistant pathogens is associated with severe side-effects, while frequently unsuccessful. Insight on M. abscessus genomic evolvement during chronic lung infection would be beneficial for improving treatment strategies. A longitudinal study enrolling 42 CF patients was performed at a CF center in Berlin, Germany, to elaborate phylogeny and genomic diversification of in-patient M. abscessus. Eleven of the 42 CF patients were infected with M. abscessus. Global human-transmissible M. abscessus cluster strains were isolated from five of these 11 patients. Phylogenetic analysis of 88 genomes from isolates of the 11 patients excluded occurrence of M. abscessus transmission among members of the study group. Genome sequencing and variant analysis of 30 isolates from 11 serial respiratory samples collected over four years from a chronically infected patient demonstrated accumulation of gene mutations. In total, 53 genes exhibiting non-synonymous variations were identified. Enrichment analysis emphasized genes involved in synthesis of glycopeptidolipids, genes from the embABC (arabinosyltransferase) operon, betA (glucose-methanol-choline oxidoreductase) and choD (cholesterol oxidase). Genetic diversity evolved in a variety of virulence- and resistance-associated genes. The strategy of M. abscessus populations in chronic lung infection is not clonal expansion of dominant variants, but to sustain simultaneously a wide range of genetic variants facilitating adaptation of the population to changing living conditions in the lung. Genomic diversification during chronic infection requires increased attention when new control strategies against M. abscessus infections are explored.

genomics↗

bioRxiv2021

Tree phylogenetic diversity supports nature's contributions to people, but is at risk from human population growth

There is growing evidence for a link between biodiversity and ecosystem function, and for a correlation between human population and the species diversity of plants and animals in a region. Here, we suggest these relationships might not be independent. Using a comprehensive phylogeny of southern African trees and structural equation modelling, we show that human population density correlates with tree phylogenetic diversity and show that this relationship is stronger than the correlation with species richness alone. Further, we demonstrate that areas high in phylogenetic diversity support a greater diversity of ecosystem goods and services, indicating that the evolutionary processes responsible for generating variation among living organisms are also key to the provisioning of natures contributions to people. Our results raise the intriguing possibility that the history of human settlement in southern Africa may have been shaped, in part, by the evolutionary history of its tree flora. However, the correlation between human population and tree diversity generates a conflict between people and nature. Our study suggests that future human population growth may threaten the contributions to people provided by intact and phylogenetically diverse ecosystems.

ecology↗

bioRxiv2017

Bioinformatics analysis quantifies neighborhood preferences of cancer cells in Hodgkin lymphoma.

MotivationHodgkin lymphoma is a tumor of the lymphatic system and represents one of the most frequent lymphoma in the Western world. It is characterized by Hodgkin cells and Reed-Sternberg cells, which exhibit a broad morphological spectrum. The cells are visualized by immunohistochemical staining of tissue sections. In pathology, tissue images are mainly manually evaluated, relying on the expertise and experience of pathologists. Computational quantification methods become more and more essential to evaluate tissue images. In particular, the distribution of cancer cells is of great interest.\n\nResultsHere, we systematically quantified and investigated cancer cell properties and their spatial neighborhood relations by applying statistical analyses to whole slide images of Hodgkin lymphoma and lymphadenitis, which describes a non-cancerous inflammation of the lymph node. We differentiated cells by their morphology and studied the spatial neighborhood relation of more than 400,000 immunohistochemically stained cells. We found that, according to their morphological features, the cells exhibited significant preferences for and aversions to cells of specific profiles as nearest neighbor. We quantified differences between Hodgkin lymphoma and lymphadenitis concerning the neighborhood relations of cells and the sizes of cells. The approach can easily be applied to other cancer types.\n\nContactina.koch@bioinformatik.uni-frankfurt.de

bioinformatics↗

bioRxiv2017

Mutation rates in seeds and seed-banking influence substitution rates across the angiosperm phylogeny

1) BackgroundSeed-banking (the ability to persist in the soil over many generations) is usually considered as a dormant stage where genotypes are \"stored\" as a bet-hedging strategy in response to unpredictable environments. However, seed dormancy may instead have consequences for the integrity of the DNA and generate novel mutations.\n\n2) MethodsWe address this paradox by building phylogenies based on the plastomes and nuclear ITS of species belonging to ten angiosperm clades. In each clade, the substitution rate (branch-length) of a seed-banking species is compared with that of a closely-related non-seed-banking species.\n\n3) ResultsSeed-banking species show as high or higher substitution rates than non-seedbanking species, and therefore mutations occur in dormant seeds at a rate at least as high as in above-ground plants. Moreover, seed born mutations have the same probability to reach fixation as those from above ground. Our results are robust to differences in selection, generation time, and polymorphism.\n\n4) ConclusionsMutations occurring in seeds, and thus seed-banking, affect the population diversity of plant species, and are observable at the macro-evolutionary scale. Our study has consequences for seed storage projects, since the stored seeds are likely to accumulate mutations at a higher rate than previously thought.

evolutionary biology↗