Biology subjects

Krause, S.

Publications and source records attributed to Krause, S..

At least 19 recordsLinked to original sources

bioRxiv2025

Intrinsic specificity of a 'core' Tip60 acetyltransferase complex in Drosophila

The lysine acetyltransferase Tip60 (KAT5) regulates gene expression through acetylation of histone N-terminal tail domains. We determined the intrinsic substrate selectivity of a recombinant, 4-subunit TIP60 core module from Drosophila melanogaster with synthetic nucleosome arrays. We compared matched arrays of nucleosomes containing either the replication-dependent histone H2A, or the variant H2A.V (H2A.Z in mammals), a prominent substrate of Tip60. Targeted mass spectrometry allowed to quantify acetylation of individual lysines in histones H2A, H2A.V and H4. Overall, H4 and H2A/H2A.V were equally well acetylated. The analysis comprehensively identified selected sites of acetylation, their relative acetylation levels, diacetylation patterns and revealed surprisingly different acetylation rates of individual lysines. We also applied this defined acetylation system to evaluate the effectiveness and selectivity of a TIP60 inhibitor, NU9056. Remarkably, the inhibitor shows variable effectiveness at different acetylation sites. Knowledge about the intrinsic substrate selectivity of Tip60 is a prerequisite for a mechanistic understanding of the enzymes mode of action.

biochemistry↗

bioRxiv2025

Evaluation of visual performance for RCS rats: A tailor-made OMR setup via DeepLabCut and PsychoPy with a customized algorithm

In this study, we developed an optimized optomotor response (OMR) setup for rats based on existing commercial systems and introduced a novel method that integrates DeepLabCut, PsychoPy, and custom algorithms to automate OMR performance evaluation in rats. Our primary findings revealed the optimal spatial frequency (SF) and grating velocity for pigmented Royal College of Surgeons (RCS) and wild-type (WT) rats. The RCS rats, a model for retinal degeneration, displayed normal OMR performance at postnatal days 30 (P30) and 50 (P50), but a significant decline was observed at 3 months. In most rats aged 6 and 12 months, the percentage of correct responses (PoC) was 50%, indicating blindness. The high efficiency and reproducibility of our non-invasive OMR test, along with its suitability for post-surgical and retinal degeneration models, underscores its potential for broad applications in visual performance evaluation.

neuroscience↗

bioRxiv2024

Better and faster collective decisions by larger fish shoals in the wild

Studies on collective cognition have provided many examples of decision-making benefits in terms of animals sharing information about predators, prey or resources in their environment. It has been shown how the efficient spread of adaptive information within groups can provide benefits which increase with group size. Little is known, however, to which extent groups also amplify maladaptive information such as false alarms and whether such costs reduce or even nullify the above benefits. Here, we investigated fish shoals in the wild that responded collec-tively with escape dives when attacked by birds. We analysed the response of shoals in reac-tion to hard-to-detect bird attacks and similar but harmless flybys as a function of shoal size. With increasing shoal size fish increasingly detected predator attacks (true positives) while their false alarms remained constant. Therefore, larger shoals became better at correctly clas-sifying potentially dangerous stimuli rather than becoming more sensitive to all stimuli poten-tially related to attacks. In addition, decision time decreased with increasing shoal size. Larger shoals were thus able to mitigate two major trade-offs inherent in solitary decision making: the trade-off between true and false positives and the trade-off between speed and accuracy. We report performance increases at shoal sizes of tens of thousands of fish and pose chal-lenges for the modelling of the underlying mechanisms.

animal behavior and cognition↗

bioRxiv2023

Physical interaction between MSL2 and CLAMP assures direct cooperativity and prevents competition at composite binding sites

MSL2, the DNA-binding subunit of the Drosophila dosage compensation complex, cooperates with the ubiquitous protein CLAMP to bind MSL recognition elements (MREs) on the X chromosome. We explore the nature of the cooperative binding to these GA-rich, composite se-quence elements in reconstituted naive embryonic chromatin. We found that the cooperativity requires physical interaction between both proteins. Remarkably, disruption of this interaction does not lead to indirect, nucleosome-mediated cooperativity as expected, but to competition. The protein interaction apparently not only increases the affinity for composite binding sites, but also locks both proteins in a defined dimeric state that prevents competition. High Affinity Sites of MSL2 on the X chromosome contain variable numbers of MREs. We find that the cooperation between MSL2/CLAMP is not influenced by MRE clustering or arrangement, but happens largely at the level of individual MREs. The sites where MSL2/CLAMP bind strongly in vitro locate to all chromosomes and show little overlap to an expanded set of X-chromosomal MSL2 in vivo binding sites generated by CUT&RUN. Apparently, the intrinsic MSL2/CLAMP cooperativity is limited to a small selection of potential sites in vivo. This restriction must be due to components missing in our reconstitution, such as roX2 lncRNA.

molecular biology↗

bioRxiv2022

Photoelectrochemical imaging of action potentials for single cardiomyocytes through contact force manipulation of organoids

Accurate monitoring of cardiomyocyte action potentials (APs) is essential to understand disease propagation and for trials of novel therapeutics. Patch clamp techniques offer gold standard measurements in this field, but are notoriously difficult to operate and only provide measurements of a single cell. Here we propose photoelectrochemical imaging (PEI), in conjunction with a setup for controlling the contact force between the cardiomyocyte organoids and the sensor surface, for measuring APs with high sensitivity. The method was validated through the use of drugs, and the results successfully visualized the expected electrophysiological changes to the APs. PEI allows for several cells to be monitored simultaneously, opening further research to the electrophysiological interactions of adjoining cells. This method expands the applications of PEI to three-dimensional geometries and provides the fields of stem cell research, drug trials and heart disease modelling with an invaluable tool to further investigate the role of APs.

biophysics↗

bioRxiv2022

Ephemeral Resource Availability Makes Wild Guppies More Social

Sociality can facilitate the discovery of novel resources, yet it can also entail costs, including increased competition, aggression, sexual harassment and disease transmission. Selection should therefore favour social flexibility as a response to changes in resource conditions, allowing individuals to adjust their social associations optimally. Quantifying these social adjustments and how they allow individuals to benefit in dynamically changing resource environments can provide insight into the adaptive capacity of wild animal populations. We experimentally studied social flexibility in wild guppies (Poecilia reticulata) by examining their fission-fusion dynamics. Using mixed-sex sets of individually marked fish, we manipulated recent foraging experience by presenting them with unpredictable, ephemeral food patches or control patches in the wild. Guppies exposed to ephemeral food patches significantly increased their sociality, doubling the proportion of time spent social compared to controls. This shift was driven by an increase in the probability of starting social contact and a decrease in the probability of ending social contact. Stronger increases in sociality were associated with individuals more often locating ephemeral food patches, mediated by foraging motivation. Importantly, increased sociality was not merely the result of local aggregation, as exposure to ephemeral food patches increased, rather than reduced, spatial activity. And stronger spatial activity did not result in more time spent social. In a second experiment, fish were briefly presented with food patches they could see and smell but not actually consume. Again, fish increased their level of sociality compared to control, indicating that the observed social response was not merely driven by satiation-related changes in activity budgets. Together, our results highlight the adaptive and dynamic nature of fission-fusion social systems and support the view that wild animals adaptively shape their social environment in response to fluctuations in resource variability.

animal behavior and cognition↗

bioRxiv2021

A scalable, clinically severe pig model for Duchenne muscular dystrophy

Large animal models for Duchenne muscular dystrophy (DMD) are crucial for preclinical evaluation of novel diagnostic procedures and treatment strategies. Pigs cloned from male cells lacking DMD exon 52 (DMD{Delta}52) resemble molecular, clinical and pathological hallmarks of DMD, but cannot be propagated by breeding due to death before sexual maturity. Therefore, female DMD+/- carriers were generated. A single founder animal had 11 litters with 29 DMDY/-, 34 DMD+/- as well as 36 male and 29 female wild-type (WT) offspring. Breeding with F1 and F2 DMD+/- carriers resulted in additional 114 DMDY/- piglets. The majority of them survived for 3-4 months, providing large cohorts for experimental studies. Pathological investigations and proteome studies of skeletal muscles and myocardium confirmed the resemblance of human disease mechanisms. Importantly, DMDY/- pigs reveal progressive fibrosis of myocardium and increased expression of connexin-43, associated with significantly reduced left ventricular fractional shortening and ejection fraction already at age 3 months. Furthermore, behavioral tests provided evidence for impaired cognitive ability of DMDY/- pigs. Our breeding cohort of DMD{Delta}52 pigs and standardized tissue repositories from DMDY/- pigs, DMD+/- carriers, and WT littermate controls provide important resources for studying DMD disease mechanisms and for testing novel diagnostic procedures and treatment strategies.

pathology↗

bioRxiv2021

Unraveling the critical growth factors for stable cultivation of (nano-sized) Micrarchaeota

Micrarchaeota are members of the archaeal DPANN superphylum. These so far poorly characterized archaea have been found to have reduced genomes and likely depend on interactions with host organisms for growth and survival. Here we report on the enrichment of the first stable co-culture of a member of the Micrarchaeota together with its host, as well as the isolation of the latter. Electron microscopic analysis suggest that growth is dependent on the physical interaction of the two organisms within a biofilm. The interaction seems to be ensured by the necessity to grow in form of a biofilm. Furthermore, transcriptomic analyses indicate a shift towards biofilm formation of the host as a result of co-cultivation. Finally, genomic, metabolomic, extracellular polymeric substance (EPSs) and lipid content analyses reveal that the Micrarchaeon symbiont relies on the acquisition of metabolites from its host and thereby provide first insights into the basis of symbiont-host interactions.

microbiology↗

bioRxiv2020

Causal evidence for the adaptive benefits of social foraging in the wild

Sociality is a fundamental organizing principle across taxa, thought to come with a suite of adaptive benefits. However, making causal inferences about these adaptive benefits requires experimental manipulation of the social environment, which is rarely feasible in the field. Here we manipulated the number of conspecifics in Trinidadian guppies (Poecilia reticulata) in the wild, and quantified how this affected a key benefit of sociality, social foraging, by investigating several components of foraging success. As adaptive benefits of social foraging may differ between sexes, we studied males and females separately, expecting females, the more social and risk-averse sex, to benefit more from conspecifics than males. Conducting over 1,600 foraging trials, we found that in both sexes, increasing the number of conspecifics led to faster detection of novel food patches and a higher probability of feeding following detection of the patch, resulting in greater individual resource consumption. The slope of the latter relationship differed between the sexes, with males unexpectedly exhibiting a stronger social benefit. Our study provides rare causal evidence for the adaptive benefits of social foraging in the wild, and highlights that sex differences in sociality do not necessarily imply an unequal ability to profit from the presence of others.

animal behavior and cognition↗

bioRxiv2020

Drosophila SWR1 and NuA4 complexes are defined by DOMINO isoforms

Histone acetylation and deposition of H2A.Z variant are integral aspects of active transcription. In Drosophila, the single DOMINO chromatin regulator complex is thought to combine both activities via an unknown mechanism. Here we show that alternative isoforms of the DOMINO nucleosome remodeling ATPase, DOM-A and DOM-B, directly specify two distinct multi-subunit complexes. Both complexes are necessary for transcriptional regulation but through different mechanisms. The DOM-B complex incorporates H2A.V (the fly ortholog of H2A.Z) genome-wide in an ATP-dependent manner, like the yeast SWR1 complex. The DOM-A complex, instead, functions as an ATP-independent histone acetyltransferase complex similar to the yeast NuA4, targeting lysine 12 of histone H4. Our work provides an instructive example of how different evolutionary strategies lead to similar functional separation. In yeast and humans, nucleosome remodeling and histone acetyltransferase complexes originate from gene duplication and paralog specification. Drosophila generates the same diversity by alternative splicing of a single gene. HighlightsO_LIIsoforms of DOMINO dictate the formation of distinct complexes C_LIO_LIDOM-B complex is the Drosophila SWR1 and incorporates H2A.V genome-wide C_LIO_LIDOM-A complex acetylates H4K12 and is the Drosophila NuA4 C_LI

molecular biology↗

bioRxiv2019

JASPer controls interphase histone H3S10 phosphorylation by chromosomal kinase JIL-1 in Drosophila

In flies, the chromosomal kinase JIL-1 is responsible for most interphase histone H3S10 phosphorylation and has been proposed to protect active chromatin from acquiring heterochromatic marks, like dimethylated histone H3K9 (H3K9me2) and HP1. Here, we show that JIL-1s targeting to chromatin depends on a new PWWP domain-containing protein JASPer (JIL-1 Anchoring and Stabilizing Protein). The JASPer-JIL-1 (JJ)-complex is the major form of the kinase in vivo and is targeted to active genes and telomeric transposons via binding of the PWWP domain of JASPer to H3K36me3 nucleosomes. Put in place, the complex modulates the transcriptional output. JIL-1 and JJ-complex depletion in cycling cells lead to small changes in H3K9me2 distribution at active genes and telomeric transposons. Finally, we identified many new interactors of the endogenous JJ-complex and propose that JIL-1 not only prevents heterochromatin formation, but also coordinates chromatin-based regulation in the transcribed part of the genome.

molecular biology↗

bioRxiv2018

Females facilitate male patch discovery in a wild fish population

When individuals are more socially responsive to one sex than the other, the benefits they get from foraging socially are likely to depend on the sex composition of the social environment. We tested this hypothesis by performing experimental manipulations of guppy, Poecilia reticulata, sex compositions in the wild. Males found fewer novel food patches in the absence of females than in mixed-sex compositions, while female patch discovery did not differ between compositions. We argue that these results were driven by sex-dependent mechanisms of social association: Markov chain-based fission-fusion modeling revealed that males reduced sociality when females were absent, while less social individuals found fewer patches. Females were similarly social with or without males. Finally, males, but not females, preferred to join females over males at patches. Our findings reveal the relevance of considering how individual and population-level traits interact in shaping the adaptive value of social living in the wild.

animal behavior and cognition↗

bioRxiv2018

Social networks in the presence and absence of visual cues

We compared the social dynamics of two populations of the live-bearing Atlantic molly (Poecilia mexicana) that live in adjacent habitats with very different predator regimes: cave mollies that inhabit a low-predation environment inside a sulfidic cave with a low density of predatory water bugs (Belostoma sp.), and mollies that live directly outside the cave (henceforth called \"surface\" mollies) in a high-predation environment with a high density of fish-eating birds. We filmed the social interactions of marked fish in both environments and analysed their social network dynamics using a Markov model under two different fish densities of 12 and 6 fish per 0.36 m2. As expected, surface mollies spent overall much more time social than cave mollies. This difference in overall social time was a result of surface mollies being less likely to discontinue social contact (once they had a social partner) and being more likely to resume social contact (once alone) than cave mollies. Interestingly surface mollies were also less likely to leave a current social partner than cave mollies. At low density, mollies (in both environments) were expected to show reduced social encounters which should dramatically change their social dynamics. Surface mollies, however, displayed an ability to maintain their social dynamics at low density (primarily by reducing the convex polygon spanned by the group) which was not observed in cave mollies. Despite the fact that we only compared two populations, our data provide a mechanistic explanation for density compensations of social dynamics that have also been observed in other fish species and give an example of how comparisons between the social dynamics of different populations can be made that go beyond conventional network analyses.

animal behavior and cognition↗

bioRxiv2018

Factor cooperation for chromosome discrimination in Drosophila

Transcription regulators select their genomic binding sites from a large pool of similar, non-functional sequences. Although general principles that allow such discrimination are known, the complexity of DNA elements often precludes a prediction of functional sites.\n\nThe process of dosage compensation in Drosophila allows exploring the rules underlying binding site selectivity. The male-specific-lethal (MSL) Dosage Compensation Complex selectively binds to some 300 X-chromosomal High Affinity Sites (HAS) containing GA-rich MSL recognition elements (MREs), but disregards thousands of other MRE sequences in the genome. The DNA-binding subunit MSL2 alone identifies a subset of MREs, but fails to recognize most MREs within HAS. The Chromatin-linked adaptor for MSL proteins (CLAMP) also interacts with many MREs genome-wide and promotes DCC binding to HAS. Using genome-wide DNA-immunoprecipitation we describe extensive cooperativity between both factors, depending on the nature of the binding sites. These are explained by physical interaction between MSL2 and CLAMP. In vivo, both factors cooperate to compete with nucleosome formation at HAS. The male-specific MSL2 thus synergises with a ubiquitous GA-repeat binding protein for refined X/autosome discrimination.

molecular biology↗

bioRxiv2018

Individual- and population-level drivers of consistent foraging success across environments

Individual foraging is under strong natural selection. Yet, whether individuals differ consistently in their foraging success across environments, and which individual and population-level traits might drive such differences, is largely unknown. We addressed this question in a field experiment, conducting over 1,100 foraging trials with nine subpopulations of guppies, Poecilia reticulata, translocating them across environments in the wild. A-priori, we determined the individual social phenotypes. We show that individuals consistently differed in reaching food, but not control, patches across environments. Social individuals reached more food patches than less social ones and males reached more food patches than females. Overall, individuals were, however, more likely to join females at patches than males, which explains why individuals in subpopulations with relatively more females reached, on average, more food patches. Our results provide rare evidence for individual differences in foraging success across environments, driven by individual and population level (sex ratio) traits.

animal behavior and cognition↗

bioRxiv2018

Hierarchical optimization for the efficient parametrization of ODE models

Mathematical models are nowadays important tools for analyzing dynamics of cellular processes. The unknown model parameters are usually estimated from experimental data. These data often only provide information about the relative changes between conditions, hence, the observables contain scaling parameters. The unknown scaling parameters and corresponding noise parameters have to be inferred along with the dynamic parameters. The nuisance parameters often increase the dimensionality of the estimation problem substantially and cause convergence problems. In this manuscript, we propose a hierarchical optimization approach for estimating the parameters for ordinary differential equation (ODE) models from relative data. Our approach restructures the optimization problem into an inner and outer subproblem. These subproblems possess lower dimensions than the original optimization problem, and the inner problem can be solved analytically. We evaluated accuracy, robustness, and computational efficiency of the hierarchical approach by studying three signaling pathways. The proposed approach achieved better convergence than the standard approach and required a lower computation time. As the hierarchical optimization approach is widely applicable, it provides a powerful alternative to established approaches.

systems biology↗

bioRxiv2017

Machine-assisted cultivation and analysis of biofilms

Biofilms are the natural form of life of the majority of microorganisms. These multispecies consortia are intensively studied not only for their effects on health and environment but also because they have an enormous potential as tools for biotechnological processes. Further exploration and exploitation of these complex systems will benefit from technical solutions that enable integrated, machine-assisted cultivation and analysis. We here introduce a microfluidic platform, where readily available microfluidic chips are connected by automated liquid handling with analysis instrumentation, such as fluorescence detection, microscopy, chromatography and optical coherence tomography. The system is operable under oxic and anoxic conditions, allowing for different gases as feeding sources and offers high spatiotemporal resolution in the analysis of metabolites and biofilm composition. We demonstrate the platforms performance by monitoring the self-organized separation of mixed cultures along autonomously created gradients, the productivity of biofilms along the microfluidic channel and the enrichment of microbial nanoorganisms.

microbiology↗

bioRxiv2017

A functional connectome phenotyping dataset including cognitive state and personality measures

The dataset enables exploration of higher-order cognitive faculties, self-generated mental experience, and personality features in relation to the intrinsic functional architecture of the brain. We provide multimodal magnetic resonance imaging (MRI) data and a broad set of state and trait phenotypic assessments: mind-wandering, personality traits, and cognitive abilities. Specifically, 194 healthy participants (between 20 and 75 years of age) filled out 31 questionnaires, performed 7 tasks, and reported 4 probes of in-scanner mind-wandering. The scanning session included four 15.5-min resting-state functional MRI runs using a multiband EPI sequence and a high-resolution structural scan using a 3D MP2RAGE sequence. This dataset constitutes one part of the MPI-Leipzig Mind-Brain-Body database.

neuroscience↗