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Keller, H.

Publications and source records attributed to Keller, H..

7 recordsLinked to original sources

Bacterial dispersal and host specificity shape microbiome strain sharing among great ape species in neighboring zoo exhibits

Animal microbiomes often exhibit host-species-specific structure, which could suggest a shared evolutionary history with their hosts. However, in wild populations this possibility has been difficult to disentangle from geographic or ecological barriers to microbial dispersal, particularly in taxa like non-human primates in which phylogeny and geography are closely related. To investigate microbiome transmission and adaptation in a common environment, the gut microbiomes of zoo-housed great apes were profiled longitudinally for four months. Even in a shared environment, phylogenetic structure emerged in both species- and strain-level microbiome composition. Longitudinal tracking of new strain acquisitions revealed that transmission across exhibits was possible, even between distantly related host species, suggesting that phylogenetic structure emerged in the longer term as different strains survived in different hosts. Comparison to metagenomes from humans and wild great apes revealed little evidence that human keepers, researchers, or zoo guests drive transmission between exhibits. Instead, across-exhibit transmission disproportionately involved spore-forming bacterial genera, possibly suggesting airborne spore transmission as a means of bacterial dispersal. By investigating microbiomes of different host species in a common geographic environment without direct inter-host interaction, this study identifies spatial constraints on transmission, bacterial dispersal ability, and differential survival of bacterial strains in different hosts as factors shaping the gut microbiomes of great apes.

evolutionary biology↗

Deep learning enables quantitative subcellular analysis of plant-microbe interfaces

Specialized host-microbe interfaces are central to cellular interactions in plants. Intracellular structures such as haustoria formed by filamentous pathogens mediate nutrient exchange and effector delivery to host cells. Despite their biological importance, the lack of quantitative frameworks has largely confined the study of these interfaces to qualitative observations, limiting our ability to compare infection strategies, cellular responses, and spatial organization across cells and tissues. Here, we present HFinder, a deep learning-based framework for automated detection, segmentation, and quantitative analysis of plant-microbe interfaces in confocal images. Using an object-centric deep learning approach, HFinder enables robust identification of haustoria, microbial hyphae, and host organelles across diverse imaging conditions and pathosystems. We demonstrate that this framework supports quantitative analyses of subcellular processes at host-microbe interfaces, including effector secretion, perturbation of host cellular processes, and immune receptor accumulation at haustoria. HFinder provides a practical and scalable solution for the systematic digitalization of plant infection imaging data and establishes a general framework for quantitative studies of cellular dynamics at host-microbe contact zones.

cell biology↗

Exercise-Induced Myostimulin Enhances Muscle Function in Health and Disease

Musculoskeletal diseases are a leading contributor to years lived with disability worldwide1,2. While exercise offers significant benefits for people with these conditions, many individuals do not engage in adequate physical activity3. Consequently, there is growing interest in pharmacological interventions that can emulate essential health-promoting effects of exercise4,5. By integrating transcriptomics data of exercised skeletal muscle, we identified C1orf54/C1ORF54 as a novel exercise-responsive gene in mice and humans. We demonstrate that removal of the first sixteen N-terminal amino acids of C1ORF54 gives rise to a previously uncharacterized protein that stimulates the proliferation of muscle precursor cells and which we named myostimulin. Intriguingly, repeated intermittent treatment of mice with recombinant myostimulin boosts maximal isometric strength in mice within a week. Moreover, we have engineered a variant with improved biophysical properties, increased biological activity in vitro and enhanced efficacy in vivo. This variant even accelerates the recovery of muscle strength from axonotmesis, a condition associated with pronounced muscle weakness. Our data ascribe to myostimulin a role for enhancing the regenerative capacity of skeletal muscle and mediating functional adaptations characteristic of sustained resistance training. Therefore, myostimulin could be an innovative, fast acting therapeutic for certain human musculoskeletal diseases, injuries and other disorders that improve with exercise.

physiology↗

Invasion of the stigma by the pollen tube or an oomycete pathogen: striking similarities and differences

The epidermis is the first barrier that protects organisms from surrounding stresses. Similar to the hyphae of filamentous pathogens that penetrate and invade the outer tissues of the host, the pollen germinates and grows a tube within epidermal cells of the stigma. Early responses of the epidermal layer are therefore decisive for the outcome of these two-cell interaction processes. Here, we aim at characterizing and comparing how the papillae of the stigma respond to intrusion attempts, either by hypha of the hemibiotrophic oomycete root pathogen, Phytophthora parasitica or by the pollen tube. We found that P. parasitica spores attach to the papillae and hyphae subsequently invade the entire pistil. Using transmission electron microscopy, we examined in detail the invasive growth characteristics of P. parasitica and found that the hypha passed through the stigmatic cell wall to grow in contact with the plasma membrane, contrary to the pollen tube that advanced engulfed within the two cell wall layers of the papilla. Further quantitative image analysis revealed that the pathogen and the pollen tube trigger reorganization of the endomembrane system (trans Golgi network, late endosome) and the actin cytoskeleton. Some of these remodeling processes are common to both invaders, while others appear to be more specific showing that the stigmatic cells trigger an appropriate response to the invading structure and somehow can recognize the invader that attempts to penetrate.

plant biology↗

A key regulator with a MIF-like domain orchestrates cellular differentiation and virulence in the fungal pathogen Magnaporthe oryzae

MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) is a pleiotropic protein with chemotactic, pro-inflammatory, and growth-promoting activities first discovered in mammals. In parasites, MIF homologs are involved in immune evasion and pathogenesis. Here, we present the first comprehensive analysis of a MIF protein from the devastating plant pathogen Magnaporthe oryzae (Mo). The fungal genome encodes a single MIF protein (MoMIF1) that, unlike the human homolog, harbors multiple low-complexity regions (LCRs) and is unique to Ascomycota. Following infection, MoMIF1 is expressed in the biotrophic phase of the fungus, and is strongly down-regulated during subsequent necrotrophic growth in leaves and roots. We show that MoMIF1 is secreted during plant infection, affects the production of the mycotoxin tenuazonic acid and inhibits plant cell death. Our results show that MoMIF1 is a novel key regulator of fungal virulence that maintains the balance between biotrophy and necrotrophy during the different phases of fungal infection.

plant biology↗

Hidden paths to endless forms most wonderful: Ecology latently shapes evolution of multicellular development in predatory bacteria

Ecological causes of developmental-system evolution, for example from predation, remain under intense investigation. An important open question is the role of latent phenotypes in eco-evo-devo. The predatory bacterium Myxococcus xanthus undergoes aggregative multicellular development upon starvation. Here we use M. xanthus to test whether evolution in several distinct growth environments that do not induce development latently alters developmental phenotypes, including morphology and plasticity, in environments that do induce development. In the MyxoEE-3 evolution experiment, growing M. xanthus populations swarmed across agar surfaces while adapting to distinct conditions varying at factors such as surface stiffness or prey identity. All examined developmental phenotypes underwent extensive and ecologically specific latent evolution, with surface stiffness, prey presence and prey identity all strongly impacting the latent evolution of development. Evolution on hard agar allowed retention of developmental proficiency and extensive stochastic phenotypic radiation, including of reaction norms, with instances of both increased plasticity and canalization. In contrast, evolution on soft agar latently led to systematic loss of development, revealing an ecologically-contingent fitness trade-off between the growth and developmental phases of a multicellular life cycle that is likely determined by details of motility behavior. Similar contingency was observed after evolution during predatory growth in distinct prey environments, with Bacillus subtilis causing greater loss of development and lower stochastic diversification than Escherichia coli. Our results have implications for understanding evolutionary interactions among predation, development and motility in myxobacterial life cycles, and, more broadly, the importance of latent phenotypes for the diversification of developmental systems.

evolutionary biology↗

An oomycete effector impairs autophagy in evolutionary distant organisms and favors host infection

An arsenal of effector proteins from plant pathogenic Phytophthora species manipulates their host from inside the cells. Phytophthora parasitica produces the effector AVH195 during an initial, biotrophic phase of infection. The protein transiently impairs plant immune-associated hypersensitive cell death in Nicotiana. ATG8 Interaction Motifs in the protein indicate that the effector targets the autophagic core machinery. We selected a photosynthetic microalga with a single copy ATG8 gene as an alternative model to dissect AVH195-induced autophagic perturbation. AVH195 slows down autophagic flux in Chlamydomonas reinhardtii thus promoting the accumulation of cargo-rich vesicles. In yeast, membrane-associated AVH195 interacts with ATG8 from Chlamydomonas and with different ATG8 isoforms from Arabidopsis thaliana. The overexpression of Avh195 in Arabidopsis promotes growth of both infecting P. parasitica and Hyaloperonospora arabidopsidis, an obligate biotroph. To our knowledge, this report provides first evidence that an oomycete effector non-selectively targets ATG8 in different organisms from the green lineage to slow down autophagic flux for infection.

plant biology↗