Biology subjects

Hammerschmidt, K.

Publications and source records attributed to Hammerschmidt, K..

15 recordsLinked to original sources

bioRxiv2025

Erythropoietin alleviates intellectual disability and autism-like behavior of mice caused by Zbtb20 haploinsufficiency, a construct-valid model of Primrose syndrome

Among the known genetic causes of syndromic autism spectrum disorders (ASD) are transcription factor deficiencies. In this regard, haploinsufficiency of the zinc finger and broad complex, tramtrack, bric and brac domain-containing protein 20 (ZBTB20) leads to a prototypical clinical picture, referred to as Primrose syndrome, comprising severe ASD symptoms together with intellectual disability. Here, we present a comprehensive behavioral and phenotypical characterization of Zbtb20+/- mice, a construct valid model of this thus far untreatable human condition. Zbtb20+/- mice exhibit diminished sociability, reduced vocalization, distinct repetitive behaviors, impaired cognitive flexibility, hyperactivity and hypoalgesia. Magnetic resonance imaging reveals increased volumes of hippocampus, cerebellum, brain matter, and whole brain, confirmed by postmortem brain weight measurements. Due to our previous observation of enhanced ZBTB20 expression in CA1 pyramidal neurons upon recombinant human erythropoietin (rhEPO) injections, we anticipated a mitigating effect through rhEPO treatment of Zbtb20 deficiency/Primrose syndrome. Indeed, after three weeks of alternate-day rhEPO injections, a remarkable improvement in the behavioral phenotype was observed. Our results highlight rhEPO as a first promising treatment for Primrose syndrome.

neuroscience↗

bioRxiv2024

Unicellular cyanobacteria rely on sodium energetics to fix N2

Diazotrophic cyanobacteria can thrive in combined nitrogen (N)-limited environments due to their ability to fix nitrogen gas (N2) from the atmosphere. Despite this, they occur in low abundance in N-limited coastal waters, which represents an ecological paradox1-3. One hypothesis is that this is partly due to elevated salinity (> 10 g/L NaCl), which inhibits cyanobacterial N2 fixation2,3. Here we show that N2 fixation in a unicellular coastal cyanobacterium is not inhibited but rather exclusively dependent on sodium (Na+) ions. In N-deficient environments, both N2 fixation and population growth were significantly inhibited at low NaCl concentrations (< 4 g/L). Additional experiments indicated that sodium energetics, rather than proton energetics, is necessary for N2 fixation, as Na+ deficiency resulted in insufficient ATP supply for N2 fixation. We show that this is due to the non-functioning Na+-coupled ATP synthase, which we found to be likely coupled to anaerobic rather than aerobic respiration. Sequence alignment analysis of the ion-coupling site of the ATP synthase revealed a high prevalence of Na+ energetics in cyanobacteria, with all unicellular N2 fixers capable of Na+ energetics. This suggests a critical role for sodium energetics in cyanobacteria. It also raises the possibility that sodium energetics is not as rare as thought, but that we may have underestimated the prevalence and importance of sodium energetics in other organisms. Finally, the low abundance of diazotrophic unicellular cyanobacteria in coastal waters may be due to insufficient NaCl levels to support N2-fixation during periods of growth-supporting high temperatures. This provides another perspective on the regulation of the oceanic N cycle that needs to be considered in times of global climate change. Changes in current patterns could lead to an overlap of periods optimal for N2 fixation and population growth, likely resulting in dense cyanobacterial blooms.

microbiology↗

bioRxiv2023

Bet hedging in a unicellular microalga

AbstractUnderstanding how organisms adapt to unpredictable future environments is a fundamental goal in biology, which becomes even more urgent in an era of rapid climate change. One evolutionary adaptation to randomly fluctuating environments is bet hedging, a strategy that successfully facilitates reproduction and population persistence and has been widely reported from microbes to humans. Empirical evidence for its presence in microalga, one of Earths most important primary producers and carbon sinks, is lacking. Here, we report a bet-hedging strategy in the unicellular microalga Haematococcus pluvialis. In a series of experiments, we show that an isogenic H. pluvialis population reversibly diversifies into hetero-phenotypic mobile and non-mobile subunits, independent of environmental conditions. Mobile cells grow faster but are more susceptible to external stressors, while non-mobile cells hardly grow but are more stress-resistant. This is attributed to dramatic shifts from growth-promoting activities (cell division, photosynthesis) to resilience-promoting cellular metabolic processes, including cell enlargement and aggregation, and accumulation of antioxidant and energy-storaging compounds. Our results provide experimental evidence for bet hedging in microalga, which has implications for their potential to adapt to current and predicted future conditions, and thus for the conservation of ecosystem functions.

ecology↗

bioRxiv2023

Stability of Ecologically Scaffolded Traits During Evolutionary Transitions in Individuality

Evolutionary transitions in individuality (ETIs), such as the emergence of multicellularity, are events in the history of life during which entities at one level of organisation (particles) form collective-level entities that subsequently become individuals in their own right. Recent empirical and theoretical studies advocate the importance of an externally imposed meta-population structure or "ecological scaffold" for the emergence of new levels of individuality. Such a scaffold enables survival and reproduction at the collective level and thus the possibility of selection for beneficial traits on that level. However, a long-standing difficulty for the ecological scaffolding approach has been its inability to adequately explain how collective-level trait values that evolved under scaffolding conditions can be retained once these conditions are lifted. We call this difficulty "the problem of endogenisation." Here, we derive general conditions for the possibility of endogenisation. Key to endogenisation is the existence of a fitness valley that can be circumvented when scaffolding occurs. Using a stochastic meta-population model, we implement two versions of ecological scaffolding (one temporal and one spatial) and study subsequent evolutionary trajectories using the modelling techniques of adaptive dynamics. Our analysis yields several important results. The temporal model reveals that only collective traits based on particle-particle interactions can be endogenised when a temporary scaffold is applied to the entire population. The spatial model shows that, given the presence of an environmental gradient of externally imposed meta-population structure, ecological scaffolding can only occur in a limited "Goldilocks" zone of the environment. Further, if endogenisation conditions are also fulfilled, scaffolded collectives can colonise non-scaffolding areas of the environment. We conjecture that Goldilocks zones could act as initiators of ETIs and help explain the near ubiquity of collective-level individuality even if the conditions that promote it prove to be rare.

evolutionary biology↗

bioRxiv2022

Isolated catatonia-like executive dysfunction in micewith forebrain-specific loss of myelin integrity

A key feature of advanced brain aging includes structural defects of intracortical myelin that are associated with secondary neuroinflammation. A similar pathology is seen in specific myelin mutant mice that model advanced brain aging and exhibit a range of behavioral abnormalities. However, the cognitive assessment of these mutants is problematic because myelin-dependent motor-sensory functions are required for quantitative behavioral readouts. To better understand the role of cortical myelin integrity for higher brain functions, we generated mice lacking Plp1, encoding the major integral myelin membrane protein, selectively in ventricular zone stem cells of the mouse forebrain. In contrast to conventional Plp1 null mutants, subtle myelin defects were restricted to the cortex, hippocampus and underlying callosal tracts. Moreover, forebrain-specific Plp1 mutants exhibited no defect of basic motor-sensory performance at any age tested. Surprisingly, several behavioral alterations reported for conventional Plp1 null mice (Gould et al., 2018) were absent and even social interactions appeared normal. However, with novel behavioral paradigms, we determined catatonia-like symptoms and isolated executive dysfunction in both genders. This suggests that loss of myelin integrity has an impact on cortical connectivity and underlies specific defects of executive function. These observations are likewise relevant for human neuropsychiatric conditions and other myelin-related diseases.

neuroscience↗

bioRxiv2021

Phenotypic plasticity, life cycles and the evolutionary transition to multicellularity

SUMMARYUnderstanding the evolutionary transition to multicellularity is a key problem in evolutionary biology (1-4). While around 25 independent instances of the evolution of multicellular existence are known across the tree of life (5), the ecological conditions that drive such transformations are not well understood. The first known transition to multicellularity occurred approximately 2.5 billion years ago in cyanobacteria (5-7), and todays cyanobacteria are characterized by an enormous morphological diversity, based upon which they have been classified into five sections. They range from single-celled species (section I), unicellular cyanobacteria with packet-like phenotypes, e.g., tetrads (section II) and simple filamentous species (section III) to highly differentiated filamentous ones (sections IV and V) (8-10). The unicellular cyanobacterium Cyanothece sp. ATCC 51142, an isolate from the intertidal zone of the U.S. Gulf Coast (11), has been classified as a section I species, and it phylogenetically clusters with the other N2-fixing unicellular cyanobacteria (12). Here we report a facultative multicellular life cycle for a unicellular cyanobacterium, where multicellular filaments and unicellular stages alternate. In a series of experiments we identify the environmental factors underlying the phenotypic switch between the two morphologies. Then we experimentally confirm that the dissolution of filaments into solitary cells is triggered by changes in the external environment, which in turn is modified by the Cyanothece cells. Finally, using numerical models, we test a number of hypotheses regarding the nature of the environmental cues and the physical mechanisms underlying filament dissolution. While results predict that the observed response can be caused by an excreted compound in the medium, we cannot fully exclude changes in nutrient availability (as in (13,14)). The best-fit modeling results demonstrate a nonlinear effect of the compound, which is characteristic for density-dependent sensing systems (15,16). Further, filament fragmentation is predicted to occur by means of connection cleavage rather than by cell death of every alternate cell, which is corroborated by results from fluorescent and scanning electron microscopy. The phenotypic switch between the single-celled and multicellular morphology constitutes an environmentally dependent life cycle, which likely represents an important step en route to permanent multicellularity.

evolutionary biology↗

bioRxiv2021

Beyond Fitness Decoupling: Tradeoff-breaking during Evolutionary Transitions in Individuality

Evolutionary transitions in individuality (ETIs) involve the formation of Darwinian collectives from Darwinian particles. The transition from cells to multicellular life is a prime example. During an ETI, collectives become units of selection in their own right. However, the underlying processes are poorly understood. One observation used to identify the completion of an ETI is an increase in collective-level performance accompanied by a decrease in particle-level performance, for example measured by growth rate. This seemingly counterintuitive dynamic has been referred to as "fitness decoupling" and has been used to interpret both models and experimental data. Using a mathematical approach, we show this concept to be problematic in that the fitness of particles and collectives can never decouple--calculations of particle and collective fitness performed over appropriate and equivalent time intervals are necessarily the same. By way of solution, we draw attention to the value of mechanistic approaches that emphasise traits, and tradeoffs among traits, as opposed to fitness. This trait-based approach is sufficient to capture dynamics that underpin evolutionary transitions. In addition, drawing upon both experimental and theoretical studies, we show that while early stages of transitions might often involve tradeoffs among particle traits, later--and critical--stages are likely to involve the rupture of such tradeoffs. Thus, tradeoff-breaking stands as a useful marker for ETIs.

evolutionary biology↗

bioRxiv2020

Division of labor and fitness decoupling in evolutionary transitions in individuality

Reproductive division of labor has been proposed to play a key role for evolutionary transitions in individuality (ETIs). This chapter provides a guide to a theoretical model that addresses the role of a tradeoff between life-history traits in selecting for a reproductive division of labor during the transition from unicellular to multicellular organisms. In particular, it focuses on the five key assumptions of the model, namely (1) fitness is viability times fecundity; (2) collective traits are linear functions of their cellular counterparts; (3) there is a tradeoff between cell viability and fecundity; (4) cell contribution to the collective is optimal; and (5) there is an initial reproductive cost in large collectives. Thereafter the chapter contrasts two interpretations of the model in the context of ETIs. Originally, the model was interpreted as showing that during the transition to multicellularity the fitness of the lower-level (the cells) is "transferred" to the higher level (the collective). Despite its apparent intuitiveness, fitness transfer may obscure actual mechanisms in metaphorical language. Thus, an alternative and more conservative interpretation of the model that focuses on cell traits and the evolutionary constraints that link them is advocated. In addition, it allows for pursuing subsequent questions, such as the evolution of development.

evolutionary biology↗

bioRxiv2020

Vocal convergence in the multi-level society of Guinea baboons

The extent to which nonhuman primate vocalizations are amenable to modification through experience is relevant for understanding the substrate from which human speech evolved. We examined the vocal behaviour of Guinea baboons, Papio papio, ranging in the Niokolo Koba National Park in Senegal. Guinea baboons live in a multi-level society, with units nested within parties nested within gangs. We investigated whether the acoustic structure of grunts of 27 male baboons of two gangs varied with party/gang membership and genetic relatedness. Males in this species are philopatric, resulting in increased male relatedness within gangs and parties. Grunts from members were more similar within than across social levels (N = 351 dyads for comparison within and between gangs, and N = 169 dyads within and between parties), but the effect sizes were small. Yet, acoustic similarity did not correlate with genetic relatedness, suggesting that higher amounts of social interactions rather than genetic relatedness promote the observed vocal convergence. We consider this convergence a result of sensory-motor integration and suggest this to be an implicit form of vocal learning shared with humans, in contrast to the goal-directed and intentional explicit form of vocal learning unique to human speech acquisition.

animal behavior and cognition↗

bioRxiv2020

Analysis of an experimental transition in individuality challenges the need to assign traits to levels

Major evolutionary transitions in individuality, at any level of the biological hierarchy, occur when groups participate in Darwinian processes as units of selection in their own right. Identifying transitions in individuality can be problematic because apparent selection at one level of the biological hierarchy may be a by-product of selection occurring at another level. Here we discuss approaches to this "levels-of-selection" problem and apply them to a previously published experimental exploration of the evolutionary transition to multicellularity. In these experiments groups of the bacterium Pseudomonas fluorescens were required to reproduce via life cycles involving soma- and germline-like phases. The rate of transition between the two cell types was a focus of selection, and might be regarded as a property of groups, cells, or even genes. By examining the experimental data under several established philosophical frameworks, we argue that in the Pseudomonas experiments, bacterial groups acquired Darwinian properties sufficient to allow the evolution of traits adaptive at the group level.

evolutionary biology↗

bioRxiv2019

Microbial traits and the realized niche in a simple metaorganism

Organisms and their resident microbial communities - the microbiome - form a complex and mostly stable ecosystem. It is known that the composition of the microbiome and bacterial species abundances can have a major impact on host health and Darwinian fitness, but the processes that lead to these microbial patterns have not yet been identified. We here apply the niche concept and trait-based approaches as a first step in understanding the patterns underlying microbial community assembly and structure in the simple metaorganism Hydra. We find that the carrying capacities in single associations do not reflect microbiota densities as part of the community, indicating a discrepancy between the fundamental and realized niche. Whereas in most cases, the realized niche is smaller than the fundamental one, as predicted by theory, the opposite is observed for Hydra’s two main bacterial colonizers. Both, Curvibacter sp. and Duganella sp. benefit from association with the other members of the microbiome and reach higher fractions as compared to when they are the only colonizer. This cannot be linked to any particular trait that is relevant for interacting with the host or by the utilization of specific nutrients but is most likely determined by metabolic interactions between the individual microbiome members.Competing Interest StatementThe authors have declared no competing interest.View Full Text

ecology↗

bioRxiv2019

Fitness effects of host-bacterial interactions - the microbial perspective

Organisms and their resident microbial communities form a complex and mostly stable ecosystem. It is known that the specific composition and abundance of certain bacterial species affect host health and fitness, but the processes that lead to these microbial patterns are unknown. We investigate this by deconstructing the simple microbiome of the freshwater polyp Hydra. We contrast the performance of its two main bacterial associates, Curvibacter and Duganella, on germ free hosts with two in vitro environments over time. We show that interactions within the microbiome but also the host environment lead to the observed species frequencies and abundances. More specifically, we find that both microbial species can only stably coexist in the host environment, whereas Duganella outcompetes Curvibacter in both in vitro environments irrespective of initial starting frequencies. While Duganella seems to benefit through secretions of Curvibacter, its competitive effect on Curvibacter depends upon direct contact. The competition might potentially be mitigated through the spatial structure of the two microbial species on the host, which would explain why both species stably coexist on the host. Interestingly, the fractions of both species on the host do not match the fractions reported previously nor the overall microbiome carrying capacity as reported in this study. Both observations indicate that the rare microbial community members might be relevant for achieving the native community composition and carrying capacity. Our study highlights that for dissecting microbial interactions the specific environmental conditions need to be replicated, a goal difficult to achieve with in vitro systems. ImportanceThis work studies microbial interactions within the microbiome of the simple cnidarian, Hydra, and investigates whether microbial species coexistence and community stability depends on the host environment. We find that the outcome of the interaction between the two most dominant bacterial species in Hydras microbiome differs depending on the environment and only results in a stable coexistence in the host context. The interactive ecology between the host, the two most dominant microbes, but also the less abundant members of the microbiome, are critically important for achieving the native community composition. This indicates that the metaorganism environment needs to be taken into account when studying microbial interactions.

ecology↗

bioRxiv2019

A chronology of multicellularity evolution in cyanobacteria

The transition from unicellular to multicellular organisms is one of the most significant events in the history of life. Key to this process is the emergence of Darwinian individuality at the higher level: groups must become single entities capable of reproduction for selection to shape their evolution. Evolutionary transitions in individuality are characterized by cooperation between the lower level entities and by division of labor. Theory suggests that division of labor may drive the transition to multicellularity by eliminating the trade-off between two incompatible processes that cannot be performed simultaneously in one cell. Here we examine the evolution of the most ancient multicellular transition known today, that of cyanobacteria, where we reconstruct the sequence of ecological and phenotypic trait evolution. Our results show that the prime driver of multicellularity in cyanobacteria was the expansion in metabolic capacity offered by nitrogen fixation, which was accompanied by the emergence of the filamentous morphology and succeeded by a reproductive life cycle. This was followed by the progression of multicellularity into higher complexity in the form of differentiated cells and patterned multicellularity. Significance StatementThe emergence of multicellularity is a major evolutionary transition. The oldest transition, that of cyanobacteria, happened more than 3 to 3.5 billion years ago. We find N2 fixation to be the prime driver of multicellularity in cyanobacteria. This innovation faced the challenge of incompatible metabolic processes since the N2 fixing enzyme (nitrogenase) is sensitive to oxygen, which is abundantly found in cyanobacteria cells performing photosynthesis. At the same time, N2-fixation conferred an adaptive benefit to the filamentous morphology as cells could divide their labour into performing either N2-fixation or photosynthesis. This was followed by the culmination of complex multicellularity in the form of differentiated cells and patterned multicellularity.

evolutionary biology↗

bioRxiv2018

Meta-population structure and the evolutionary transition to multicellularity

AO_SCPLOWBSTRACTC_SCPLOWThe evolutionary transition to multicellularity has occurred on numerous occasions, but transitions to complex life forms are rare. While the reasons are unclear, relevant factors include the intensity of within-versus between-group selection that are likely to have shaped the course of life cycle evolution. A highly structured environment eliminates the possibility of mixing between evolving lineages, thus ensuring strong competition between groups. Less structure intensifies competition within groups, decreasing opportunity for group-level evolution. Here, using populations of the bacterium Pseudomonas fluorescens, we report the results of experiments that explore the effect of lineage mixing on the evolution of nascent multicellular groups. Groups were propagated under regimes requiring reproduction via a life cycle replete with developmental and dispersal (propagule) phases, but in one treatment lineages never mixed, whereas in a second treatment, cells from different lineages experienced intense competition during the dispersal phase. The latter treatment favoured traits promoting cell growth at the expense of traits underlying group fitness - a finding that is supported by results from a mathematical model. Together our results show that the transition to multicellularity benefits from ecological conditions that maintain discreteness not just of the group (soma) phase, but also of the dispersal (germline) phase.

evolutionary biology↗

bioRxiv2018

Classification of mouse ultrasonic vocalizations using deep learning

Vocalizations are a widespread means of communication in the animal kingdom. Mice use a large repertoire of ultrasonic vocalizations (USVs) in different social contexts, for instance courtship, territorial dispute, dominance and mother-pup interaction. Previous studies have pointed to differences in the USVs in different context, sexes, strains and individuals, however, in many cases the outcomes of the analyses remained inconclusive.\n\nWe here provide a more general approach to automatically classify USVs using deep neural networks (DNN). We classified the sex of the emitting mouse (C57Bl/6) based on the vocalizations spectrogram, reaching unprecedented performance (~84% correct) in comparison with other techniques (Support Vector Machines: 64%, Ridge regression: 52%). Vocalization characteristics of individual mice only contribute mildly, and sex-only classification reaches ~78%. The performance can only partially be explained by a set of classical shape features, with duration, volume and bandwidth being the most useful predictors. Splitting estimation into two DNNs, from spectrograms to features (57-82%) and features to sex (67%) does not reach the single-step performance.\n\nIn summary, the emitters sex can be successfully predicted from their spectrograms using DNNs, excelling over other classification techniques. In contrast to previous research, this suggests that male and female vocalizations differ in their spectrotemporal structure, recognizable even in single vocalizations.

bioinformatics↗