Biology subjects

Ott, T.

Publications and source records attributed to Ott, T..

At least 19 recordsLinked to original sources

bioRxiv2026

A cross-kingdom interactome predicted by AlphaFold3 reveals a DNF2-centered interface required for symbiotic accommodation

Legumes convert atmospheric nitrogen into ammonium through symbiotic bacteria housed in root nodules, yet the molecular interactions between rhizobial and host proteins inside nodules remain poorly understood. Here we employed AlphaFold3 to construct a cross-kingdom interactome between Medicago truncatula and its symbiont Sinorhizobium meliloti. Screening more than 217,000 protein pairs yielded 7,137 putative interactions, providing a valuable resource for the broader symbiosis community. Within this network, we focused on DEFECTIVE IN NITROGEN FIXATION 2 (DNF2), a host protein required for rhizobial persistence within nodules. We showed that DNF2 localizes to the peribacteroid space and associates with previously uncharacterized secreted rhizobial proteins (SRPs), suggesting it may function as a hub for host-symbiont communication. Notably, knockout of two DNF2-interacting proteins, SRP86 and SRP485, results in white, nitrogen-fixation-deficient nodules with abnormal symbiosomes and elevated expression of senescence-associated genes, closely phenocopying the dnf2 loss-of-function mutant. Together, our findings define a DNF2-SRP molecular framework underlying symbiotic accommodation, and illustrate the potential of AI-guided interactome mapping to uncover molecular mechanisms of plant-microbe interactions with relevance to sustainable agriculture.

plant biology↗

bioRxiv2026

Psilocybin collapses visual change detection and drives cortical dynamics toward a state of surprise

Psilocybin profoundly alters visual perception, yet the neuronal mechanisms underlying these effects remain unclear. Here we combined large-scale Neuropixels recordings with cell-type specific optogenetics in head-fixed mice performing a visual change-detection task. Psilocybin severely impaired task performance without overt motor deficits. In cortex, the drug modestly suppressed activity of layer 5 neurons while preserving representations of image identity. By contrast, psilocybin imposed a 4-Hz oscillation on visually evoked activity that preferentially affected neurons encoding image change rather than image identity. Under psilocybin, expected image repetitions aberrantly recruited change-encoding ensembles and shifted cortical population dynamics towards trajectories normally evoked by genuine stimulus changes. These effects were strongest in somatostatin-expressing (SST) interneurons in visual cortex. The strength of this modulation depended on image structure and was greatest for images with clear, continuous contours, which preferentially recruited change-encoding ensembles. These findings demonstrate that psilocybin drives internally generated cortical surprise signals, providing a circuit mechanism for altered perception in the acute psychedelic state.

neuroscience↗

bioRxiv2026

Brain-wide reconfiguration of burst firing by psilocybin reveals 5-HT2A-dependent circuit dynamics

Psilocybin produces rapid and lasting therapeutic effects, yet how 5-HT2A receptor activation reshapes brain-wide circuit dynamics during acute drug administration remains poorly understood. Using simultaneous multi-region Neuropixels recordings of 46,360 single units from 35 mice, together with scalp electroencephalography (EEG), pupillometry, and locomotion monitoring, we provide a brain-wide, single-unit and field-potential characterization of psilocybin's acute effects, with pharmacological dissection using the 5-HT2A antagonist ketanserin. Psilocybin selectively reconfigured burst coding, rather than mean firing rate, across cortical, thalamic, and hippocampal circuits: burst firing decreased in hippocampal CA1-CA3 and was bidirectionally modulated in the thalamus, with the reticular nucleus bursting more and first-order geniculate nuclei bursting less. Critically, most of these burst effects were abolished by ketanserin, consistent with at least partial 5-HT2A receptor dependence. These data suggest that the psychedelic state is not simply a matter of how much neurons fire, but of how they fire, pointing to a region-specific, 5-HT2A-associated reconfiguration of burst coding that may underlie the acute phenomenology of the psilocybin experience.

neuroscience↗

bioRxiv2026

Specialised root hair cells facilitate rhizobial infection

Legumes establish symbiotic partnerships with soil bacteria that convert atmospheric nitrogen into plant-available forms. Symbiotic bacteria enter through root hairs following recognition by cell surface receptors that help identify compatible symbionts. However, many root hairs express these receptors, and it has long remained unclear why only a small fraction become infected. Here, we use single-cell transcriptomics to show that legumes pre-specify a rare root hair population for infection before bacterial contact. These susceptible root hairs represent less than one percent of the total, express infection-associated genes prior to encountering symbionts and are conserved in distantly related legumes. Their abundance is regulated by the hormone ethylene and correlates with infection capacity. Our findings reveal that root hair cells do not respond uniformly to symbionts but are instead transcriptionally specialised in advance to control infection entry points. This pre-specification provides a mechanism to balance symbiotic benefits against pathogen infection risks and may exemplify a more general strategy used by multicellular hosts to spatially restrict microbial access.

plant biology↗

bioRxiv2026

The compartmentalized activity of a legume subtilase SBT12a allows symbiosome stabilization

The stabilization of rhizobia in specialized organelles, called symbiosomes, is an evolutionary hallmark for maintaining high rates of nitrogen fixation in legumes. This is achieved by releasing thousands of bacteria from nodular infection threads within in a single plant cell, which poses a great challenge for the host to keep control over these differentiated bacteria. Considering the importance of proteolytic degradation of antimicrobial proteins or generation of symbiosis-promoting peptides, proteolytic activity may represent a key regulatory system. Indeed, we identified the Medicago truncatula subtilisin-like protease (subtilase, SBT) 12a acting as a novel regulator of symbiosome functionality and maintenance. Loss-of-function mutations in SBT12a led to severe symbiotic defects with nodules of sbt12a being characterized by high level induction of defense/senescence-related genes. Using untargeted proteomic High-efficiency Undecanal-based N-Termini EnRichment (HUNTER) we identified and individually confirmed specific SBT12a target proteins that are involved in plant defense responses and symbiosome maintenance. This positions SBT12a as a central host factor controlling symbiosome performance.

plant biology↗

bioRxiv2025

The Lotus japonicus alpha Expansin EXPA1 is recruited during intracellular and intercellular rhizobial colonization

Most legumes establish a mutualistic association with rhizobia, a group of nitrogen-fixing bacteria. In Lotus japonicus, the symbiotic colonization occurs intracellularly, via root-hair infection threads by Mesorhizobium loti, or intercellularly, with Agrobacterium pusense IRBG74. In both mechanisms, cell wall remodeling is presumably an essential process. In plants, alpha-Expansins (EXPA) promote cell wall loosening by non-enzymatically triggering a pH-dependent relaxation. In this study, we show that LjEXPA1, is critical for the intracellular and intercellular symbiotic program in L. japonicus. Promoter activity and subcellular localization analyses revealed that EXPA1 is recruited at essential compartments and structures of epidermal and cortical cells in both mechanisms of rhizobial infection, such as the infection chambers, infection pockets and transcellular infection threads. Additionally, EXPA1-YFP abundantly accumulated in dividing cortical cells during nodule formation. The expression profile of EXPA1 correlates with the symbiotic phenotype observed in homozygous mutants disrupted in the EXPA1 gene (expA1-1 and expA1-2). Infection thread formation and intercellular colonization was drastically reduced in expA1-1 and expA1-2 mutants, respect to wild type plants. Similarly, nodule formation was significantly reduced in these mutants after M. loti or IRBG74 inoculation. Our results indicate that non-enzymatic cell wall remodeling by the alpha Expansin EXPA1 is crucial for the successful establishment of Lotus-rhizobia symbiosis, regardless of the infection mechanism.

plant biology↗

bioRxiv2025

Filamentous growth, cell envelope architecture, and surface appendages of a member of the Chloroflexota, Litorilinea aerophila

Litorilinea aerophila, a filamentous bacterium of the phylum Chloroflexota (class Caldilineae), exhibits unique morphological and cell envelope features that challenge traditional bacterial models. Initially described as Gram-negative, Chloroflexota are increasingly considered as monoderm, lacking a true outer membrane. In this study, we investigated the growth behaviour, cell morphology, and cell appendages of Litorilinea aerophila using light microscopy, cryo-electron tomography, and structural biology. Dry weight-based growth assays revealed a prolonged lag phase (~40 h) followed by exponential and stationary phases. Light and fluorescence microscopy revealed irregular indentations along cell filaments, accompanied by a diffuse distribution of DNA, indicating a multicellular organization. Thin-section electron microscopy confirmed septa formation, and in late growth stages, filaments became shorter with more defined indentations and membrane vesicle release. Next to the already characterised bacterial archaellum of Litorilinea aerophila, two additional types of surface appendages were identified: (i) pilus-like structures consistent with Tad pili, and (ii) grappling hook like structures. These findings contribute to the understanding of cell envelope diversity, growth, and surface structures in filamentous Chloroflexota.

microbiology↗

bioRxiv2025

Cellulose Synthase Complex and Remorin Nanodomains Mediate Stress Resilience Through Cell Wall-Plasma Membrane Attachments

HighlightsO_LIThe plasma membrane forms attachments to the plant cell wall that are revealed by hyperosmotic shock and correlate with tolerance to stress. C_LIO_LICellulose Synthase Complex (CSC) clusters and REMORIN (REM) nanodomains localize to cell wall-plasma membrane attachment sites. C_LIO_LICSC density at the plasma membrane determines the extent of cell wall-plasma membrane attachment under hyperosmotic stress. C_LIO_LIREMs rapidly form nanodomains under hyperosmotic stress and are associated with SHOU4/4L, CSC exocytosis inhibitors that limit CSC density at the plasma membrane. C_LI The outer cell surface of an organism is the frontline for detecting and responding to environmental stimuli. In plants, this interface consists of the plasma membrane that lies beneath the cell wall and remains associated with it through attachment sites. These wall-membrane attachments become evident upon hyperosmotic shock, when severe water loss causes the membrane to retract from the wall. Despite their long-standing observation, the molecular identity and function of these attachments remain poorly understood. Here, we identified two mechanisms governing wall-membrane attachments: one dependent on the Cellulose Synthase Complex (CSC), whose density at the plasma membrane positively correlates with resistance to hyperosmotic stress, and the other on REMORIN (REM), which acts antagonistically to the CSC mechanism. Using proximity-labeling proteomics, we identified SHOU4/4L as REM-associated proteins that mediate this antagonism. Together, our findings reveal how wall-membrane attachments are patterned to mediate plant cell resilience under water stress.

plant biology↗

bioRxiv2025

From Smartphone Images to Musculoskeletal Models: Personalized Inertial Parameter Estimation

Every human body is different, however, current movement analysis does not reflect that, as it heavily relies on generic musculoskeletal models. Usually, these models are scaled to match the participants body segment lengths and body weight, but not taking individual body shape into account. This can lead to errors in the estimation of joint forces and torques, which are important to accurately estimate musculoskeletal variables. Thus, we developed a method to estimate body segment inertial parameters based on body hulls acquired via smartphone pictures. From the body hull, we infer the skeletal shape and pose, and then estimate the distribution of bone, lean, and fatty tissues. We then segment the body hull and assign each tissue type a density, which is used to calculate the body segment inertial parameters. To allow for the use of our method with existing data, we also introduce two new generic musculoskeletal models, which are based on the average standing body shapes. Validation using MRI-derived ground-truth models shows that our method creates participant-specific musculoskeletal models that are closer to the MRI-derived ground truth than scaled generic models. Additionally, we performed lab-based gait experiments to evaluate the effect of our method on residual forces and joint moments, where we found that our method leads to a reduction of residual forces of up to 14.9 % and a reduction of metabolic cost of up to 12.8 % when compared to generic musculoskeletal models. Our new generic models show similar joint moment outcomes, but less reduction of residual forces than the personalized models.

bioengineering↗

bioRxiv2025

The SAFE Labs Handbook: community-driven commitments for group leaders to improve lab culture

Creating positive and equitable lab environments has become a growing priority for the scientific community and funders of scientific research. Research institutions typically respond to this need by providing mandatory or optional training opportunities for their staff. However, there is no established resource for group leaders to improve their lab culture with concrete action points for implementation. Here, we introduce the SAFE Labs Handbook: a collection of thirty "commitments" which can be verifiably actioned without requiring institutional support. These commitments were collaboratively developed by thirteen group leaders in life sciences, from institutions across eight countries, instigated through the 2024 SAFE Labs workshop. The importance of each commitment has been scored by more than 200 researchers, at various career stages, from more than twenty countries. Even though all commitments were rated as significantly important by scientists from all career stages, implementation rates were notably low (< 25%). Lab members reported higher importance scores than group leaders, with large divergences indicating where group leaders may underestimate the potential impact on lab culture. Indeed, the overall implementation rate was correlated with importance score for group leaders, but not lab members. Strikingly, more than 95% of group leaders said they would consider implementing the handbook commitments. Given the high importance-scores and low-implementation rates, the SAFE Labs Handbook represents a unique, community-driven tool with significant potential to improve lab culture on a global scale.

scientific communication and education↗

bioRxiv2025

The Parkinsons disease associated Leucine-rich repeat kinase 2 affects expression of Transferrin receptor 1 and phosphorylation of key signaling proteins in human iPSC-derived dopaminergic neurons

Several variants in the Leucine-rich repeat kinase 2 (LRRK2) gene account for familiar and sporadic late-onset Parkinsons disease (PD). LRRK2 is a large, multifunctional kinase involved in different intracellular pathways crucial for homeostasis and cell survival. One of the poorly understood mechanisms of Parkinsonism is the iron accumulation in Substantia nigra pars compacta (SNc). Transferrin receptor 1 (TfR) plays a significant role for iron uptake into the cell. Here, we investigated the expression of TfR in human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (hDANs) generated from PD patients carrying the LRRK2 p.G2019S form and found dysregulated TfR levels. In addition, we found gene status depending variations of LRRK2 expression in differentiated hDANs, while neuronal progenitor cells (NPCs) did not display these changes. This suggests an unknown regulatory mechanism of LRRK2 expression during dopaminergic differentiation. Further investigations showed dysregulated phosphorylation of the PD-associated GSK-3{beta} und the key signaling factor Akt.

neuroscience↗

bioRxiv2024

Bounded optimality of time investments in rats, mice, and humans

Time is our scarcest resource. Allocating time optimally presents a universal challenge for all organisms because the future benefits of time investments are uncertain. We developed a normative framework for assessing bounded optimality in time allocation, emphasizing the accuracy of future predictions, independent of subjective costs and benefits. In a common decision task across humans, rats, and mice, we varied uncertainty by titrating ambiguous sensory evidence and measured the time each subject was willing to invest post-decision. We observed that all species and subjects invested more time when they were more likely to be correct, which reflected a statistical confidence of uncertain evidence. Time allocation strategy approached the lower bound of optimality, indicating an accurate decision-by-decision assessment of confidence in the likelihood that waiting will pay off - independent of the subjective payoff values and time costs. We demonstrate that an elementary algorithm based on a drift-diffusion process algorithm can implement this optimal time investment strategy. These results illuminate the computational mechanisms governing rational time investment, showing that humans, rats, and mice can maximize payoffs via confidence-guided time allocation. HighlightsO_LIComputational and behavioral framework to assess bounded optimality of investments. C_LIO_LIHumans, rats, and mice invest more time to obtain more likely payoffs, in proportion to statistical confidence. C_LIO_LITime investment was close to optimal model predictions, reflecting bounded optimality of investments under uncertainty. C_LIO_LIBounded-optimal time investment may be an evolutionary ancient adaptive behavioral strategy. C_LI

animal behavior and cognition↗

bioRxiv2024

MMP21 behaves as a fluid flow transported morphogen to impart laterality during development

Heterotaxy (HTX) is frequently caused by deleterious variants in the gene encoding Matrix metallopeptidase 21 (MMP21). However, the underlying pathomechanism has not been ascertained. In this study, we report on a novel HTX-associated MMP21 knockout allele in humans and investigate the peptidases role during laterality development using Xenopus embryos as animal model. The targeted inactivation of mmp21 in f0 mutant Xenopus successfully phenocopied the human HTX condition, yet the cilia-driven leftward fluid flow, which initiates asymmetric gene activity at the left-right organizer (LRO), was unaltered in mmp21 null frogs. Instead, our analysis of downstream events revealed that flow response, the left-sided repression of dand5, could not take place. Remarkably, gain-of-function experiments demonstrated that Mmp21 spreads over LRO cells and triggers flow response. Additionally, Mmp21 functions upstream of Cirop, another metallopeptidase, which we found specifically localized to LRO cilia. Thus, our findings suggest that Mmp21 may be the long-sought morphogen, which is actively transported by the leftward fluid flow to Cirop-laden cilia, in order to specify the left side of the embryo.

developmental biology↗

bioRxiv2024

Effects of parity and early pregnancy on peripheral blood leukocytes in dairy cattle

Subfertility remains a major problem in the dairy industry. Only 35-40% of high-yielding dairy cows and 55-65% of nonlactating heifers become pregnant after their first service. The immune system plays a critical role in the establishment of pregnancy. However, it can also create challenges for embryo survival and contribute to reduced fertility. We conducted 2 separate experiments to characterize changes in subsets of peripheral blood leukocytes (PBL) and their phenotype over the estrous cycle and early pregnancy in heifers and cows. We used flow cytometry and RT-qPCR to assess protein and mRNA expression of molecules important for immune function. We observed that monocytes and T cells were most affected by pregnancy status in heifers, whereas, CD8+ lymphocytes and natural killer (NK) cells were most affected during early pregnancy in cows. Changes in immune parameters measured appeared to be greater in heifers than cows including changes in expression of numerous immune function molecules. To test the hypothesis, we conducted a third experiment to simultaneously analyze the immunological responses to pregnancy between cows and heifers. We observed that cows had greater expression of proinflammatory cytokines and molecules associated with leukocyte migration and phagocytosis compared to heifers. Moreover, animals that failed to become pregnant showed altered expression of anti-inflammatory molecules. Overall, these findings support the hypothesis that early pregnancy signaling alters the proportions and functions of peripheral blood immune cells and differences between cows and heifers may yield insight into the reduced fertility of mature lactating dairy cows. Interpretative summaryIn dairy farming, 35-40% of high-yielding cows and 55-65% of nonlactating heifers conceive after their initial service. The immune system plays a crucial role in protecting cows from diseases and facilitating pregnancy establishment. This study investigates immune adaptation in bovine pregnancy by analyzing changes in immune cell populations and the expression of immunoregulatory molecules in the blood of heifers and lactating cows during early pregnancy. The findings support the hypothesis that early pregnancy signaling alters the proportions and functions of peripheral blood immune cells, offering insights into reduced fertility in mature lactating dairy cows.

immunology↗

bioRxiv2024

Effects of conceptus proteins on endometrium and blood leukocytes of dairy cattle using transcriptome and meta-analysis

This study investigates the short and long-term effects of IFNT and PAG on the transcriptome of endometrium and blood leukocytes. Holstein heifers received intrauterine infusions of one of the following treatments: 20 mL of a 200 g/mL bovine serum albumin solution (BSA; vehicle) from day 14 to 16 of the estrous cycle (BSA), vehicle + 10 g/mL of IFNT from day 14 to 16 (IFNT3), vehicle + 10 g/mL of IFNT from day 14 to 19 (IFNT6), and vehicle + 10 g/mL of IFNT from day 14 to 16 followed by vehicle + 10 g/mL of IFNT + 5 g/mL of PAG from day 17 to 19 (IFNT+PAG). RNA-seq analysis was performed in endometrial biopsies and blood leukocytes collected after treatments. Acute IFNT signaling in the endometrium (IFNT3 vs BSA), induced differentially expressed genes (DEG) associated with interferon activation, immune response, inflammation, cell death, and inhibited vesicle transport and extracellular matrix remodeling. Prolonged IFNT signaling (IFNT6 vs IFNT3) altered gene expression related to cell invasion, retinoic acid signaling, and embryo implantation. In contrast, PAG induced numerous DEG in blood leukocytes but only 4 DEG in the endometrium. In blood leukocytes, PAG stimulated genes involved in development and TGFB signaling while inhibiting interferon signaling and cell migration. Overall, IFNT is a primary regulator of endometrial gene expression, while PAG predominantly affected the transcriptome of circulating immune cells during early pregnancy. Further research is essential to fully grasp the roles of identified DEG in both the endometrium and blood leukocytes. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=70 SRC="FIGDIR/small/591148v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@b51110org.highwire.dtl.DTLVardef@173433dorg.highwire.dtl.DTLVardef@4368e5org.highwire.dtl.DTLVardef@19bd118_HPS_FORMAT_FIGEXP M_FIG C_FIG Main findingsO_LIAcute IFNT signaling in the endometrium activates genes involved in inflammation while inhibiting vesicle transport in cells and ECM remodeling. C_LIO_LIProlonged IFNT signaling in the endometrium regulates genes involved in cell invasion and retinoic acid signaling. C_LIO_LIPAG alter gene expression in blood leukocytes more than in endometrium and may stimulate leukocyte differentiation while inhibiting leukocyte extravasation. C_LI

physiology↗

bioRxiv2023

Interdependence of a kinase and its cognate substrate plasma membrane nanoscale dynamics underlies Arabidopsis response to viral infection

Plant viruses represent a risk to agricultural production and as only a few treatments exist, it is urgent to identify resistance mechanisms and factors. In plant immunity, plasma membrane (PM)-localized proteins play an essential role in sensing the extracellular threat presented by bacteria, fungi or herbivores. Viruses are intracellular pathogens and as such the role of the plant PM in detection and resistance against viruses is often overlooked. We investigated the role of the partially PM-bound Calcium-dependent protein kinase 3 (CPK3) in viral infection and we discovered that it displayed a specific ability to hamper viral propagation over CPK isoforms that are involved in immune response to extracellular pathogens. More and more evidence support that the lateral organization of PM proteins and lipids underlies signal transduction in plants. We showed here that CPK3 diffusion in the PM is reduced upon activation as well as upon viral infection and that such immobilization depended on its substrate, Remorin (REM1.2), a scaffold protein. Furthermore, we discovered that the viral infection induced a CPK3-dependent increase of REM1.2 PM diffusion. Such interdependence was also observable regarding viral propagation. This study unveils a complex relationship between a kinase and its substrate that contrasts with the commonly described co-stabilisation upon activation while it proposes a PM-based mechanism involved in decreased sensitivity to viral infection in plants.

plant biology↗

bioRxiv2023

Competence for transcellular infection in the root cortex involves a post-replicative, cell-cycle exit decision in Medicago truncatula

During root nodule symbiosis (RNS), cell-division activity is re-initiated and sustained in the root cortex to create a hospitable cellular niche. Such temporary and spatially confined site is required to render host cells compatible with the intracellular progression of rhizobia. Although it has been suggested that early infection events might involve a pre-mitotic cell-cycle arrest, this process has not been dissected with cellular resolution. Here, we show that a dual-colour Medicago histone reporter robustly identifies cells with different mitotic or endoreduplication activities in the root cortex. By imaging deep root tissues, we found that a confined trajectory of cortical cells that are transcellularly passed by infection threads are in a stage of the cell-cycle that is distinct from directly adjacent cells. Distinctive features of infected cells include nuclear widening and large-scale chromatin rearrangements consistent with a cell-cycle exit prior to differentiation. Using a combination of fluorescent reporters demarcating cell-cycle phase progression, we confirmed that a reduced proliferation potential and modulating the G2/M transition, a process possibly controlled by the NF-YA1 transcription factor, mark the success of rhizobial delivery to nodule cells.

plant biology↗

bioRxiv2022

Transcellular progression of infection threads in Medicago truncatula roots is controlled by locally confined cell wall modifications

The root nodule symbiosis with its global impact on nitrogen fertilization of soils is characterized by an intracellular colonization of legume roots by rhizo-bacteria. While the symbionts are initially taken up by morphologically adapted root hairs, rhizobia persistently progress within a membrane-confined infection thread through several root cortical and later nodular cell layers. Throughout this transcellular passaging, rhizobia have to repeatedly pass host plasma membranes and cell walls. Here, we genetically dissected this essential process and describe the concerted action of the symbiosis-specific pectin methyl esterase SyPME and the pectate lyase NPL at the infection thread and transcellular passage sites. Their coordinated function mediates spatially confined pectin alterations in the cell-cell interface that result in the establishment of an apoplastic compartment where bacteria are temporarily released into and taken up from the subjacent cell. This process allows successful intracellular progression of infection threads through the entire root cortical tissue.

plant biology↗