Biology subjects

Rosenthal, G.

Publications and source records attributed to Rosenthal, G..

9 recordsLinked to original sources

bioRxiv2026

Ultrasensitive detection of neuronal DNA using genome-wide non-CG methylation patterns

Methylation-based liquid biopsies can identify the tissue origins of circulating cell-free DNA (cfDNA). A major constraint on the sensitivity of these assays is the limited number of cell-type-specific CpG markers. Here we exploit the high abundance of non-CpG (CpH) methylation in neurons to enable ultrasensitive detection of neuronal DNA. We show that neurons carry 100-fold higher CpH methylation than other tissues, in which apparent CpH methylation largely reflects experimental artifacts. Using a computational criterion to identify cfDNA molecules carrying clusters of methylated CpA sites, we detect neuronal DNA at proportions as low as 20 parts per million. Analysis of 231 samples from 163 individuals revealed minimal neuronal cfDNA in the plasma of healthy subjects; elevated levels in patients with measles or acute neurological conditions; strikingly high levels in brain-dead donors, indicating extensive ongoing neuronal death; and the highest levels in the cerebrospinal fluid of patients in a neurological intensive care unit. These findings establish genome-wide, fragment-level analysis of non-CpG methylation as an ultrasensitive approach for blood-based monitoring of brain injury and disease.

genomics↗

bioRxiv2026

Female reproductive fluid evolves rapidly to favor conspecific sperm

Avoiding fertilization with genetically incompatible partners, whether too similar or too divergent, is a central challenge for sexually reproducing organisms. Selection can favor mechanisms acting before and after mating, with postmating processes potentially compensating for constraints on premating choice. In the postmating context, female reproductive fluid (FRF) can modulate sperm performance and bias fertilization outcomes, but its contribution to reproductive isolation remains unclear. We tested whether FRF mediates discrimination against heterospecific and related sperm in two naturally hybridizing sister species of swordtails, Xiphophorus birchmanni and X. malinche, that diverge in premating behavior towards heterospecifics. Effects of FRF differed sharply between species. In X. malinche, FRF enhanced the velocity of conspecific sperm relative to heterospecifics, consistent with postmating discrimination against hybridization. In contrast, FRF in X. birchmanni did not favor conspecific sperm. Evidence for inbreeding avoidance was weaker, and we found no indication of a trade-off between discrimination against genetically similar and dissimilar sperm. These results show that female reproductive fluid can serve as a rapidly evolving axis of reproductive isolation through postmating female choice.

evolutionary biology↗

bioRxiv2022

ReSurveyGermany: Vegetation-plot time-series over the past hundred years in Germany

Vegetation-plot resurvey data are a main source of information on terrestrial biodiversity change, with records reaching back more than one century. Although more and more data from re-sampled plots have been published, there is not yet a comprehensive open-access dataset available for analysis. Here, we compiled and harmonised vegetation-plot resurvey data from Germany covering almost 100 years. We show the distribution of the plot data in space, time and across habitat types of the European Nature Information System (EUNIS). In addition, we include metadata on geographic location, plot size and vegetation structure. The data allow calculating temporal biodiversity change at the community scale and reach back further into the past than most comparable data yet available. They also enable tracking changes in the incidence and distribution of individual species across Germany. In summary, the data come at a level of detail that holds promise for broadening our understanding of the mechanisms and drivers behind plant diversity change over the last century.

ecology↗

bioRxiv2021

Genomic insights into variation in thermotolerance between hybridizing swordtail fishes

Understanding how organisms adapt to changing environments is a core focus of research in evolutionary biology. One common mechanism is adaptive introgression, which has received increasing attention as a potential route to rapid adaptation in populations struggling in the face of ecological change, particularly global climate change. However, hybridization can also result in deleterious genetic interactions that may limit the benefits of adaptive introgression. Here, we used a combination of genome-wide quantitative trait locus mapping and differential gene expression analyses between the swordtail fish species Xiphophorus malinche and X. birchmanni to study the consequences of hybridization on thermotolerance. While these two species are adapted to different thermal environments, we document a complicated architecture of thermotolerance in hybrids. We identify a region of the genome that contributes to reduced thermotolerance in individuals heterozygous for X. malinche and X. birchmanni ancestry, as well as widespread misexpression in hybrids of genes that respond to thermal stress in the parental species, particularly in the circadian clock pathway. We also show that a previously mapped hybrid incompatibility between X. malinche and X. birchmanni contributes to reduced thermotolerance in hybrids. Together, our results highlight the challenges of understanding the impact of hybridization on complex ecological traits and its potential impact on adaptive introgression.

evolutionary biology↗

bioRxiv2019

From a deep learning model back to the brain - inferring morphological markers and their relation to aging

We present a Deep Learning framework for the prediction of chronological age from structural MRI scans. Previous findings associate an overestimation of brain age with neurodegenerative diseases and higher mortality rates. However, the importance of brain age prediction goes beyond serving as biomarkers for neurological disorders. Specifically, utilizing convolutional neural network (CNN) analysis to identify brain regions contributing to the prediction can shed light on the complex multivariate process of brain aging. Previous work examined methods to attribute pixel/voxel-wise contributions to the prediction in a single image, resulting in explanation maps that were found noisy and unreliable. To address this problem, we developed an inference framework for combining these maps across subjects, thus creating a population-based rather than a subject-specific map. We applied this method to a CNN ensemble trained on predicting subjects age from raw T1 brain images of 10,176 subjects. Evaluating the model on an untouched test set resulted in mean absolute error of 3.07 years and a correlation between chronological and predicted age of r=0.98. Using the inference method, we revealed that cavities containing CSF, previously found as general atrophy markers, had the highest contribution for age prediction. Comparing maps derived from different models within the ensemble allowed to assess differences and similarities in brain regions utilized by the model. We showed that this method substantially increased the replicability of explanation maps, converged with results from voxel-based morphometry age studies and highlighted brain regions whose volumetric variability contributed the most to the prediction.\n\nHighlightsO_LICNNs ensemble is shown to estimate \"brain age\" from sMRI with an MAE of [~]3.1 years\nC_LIO_LIA novel framework enables to highlight brain regions contributing to the prediction\nC_LIO_LIThis framework results in explanation maps showing consistency with the literature\nC_LIO_LIAs sample size increases, these maps show higher inter-sample replicability\nC_LIO_LICSF cavities reflecting general atrophy were found as a prominent aging biomarker\nC_LI

neuroscience↗

bioRxiv2019

Long-term vegetation change in species-rich Nardus grasslands of central Germany caused by eutrophication, recovery from acidification and management change

QuestionsThe impact of environmental changes on species-rich Nardus grasslands has been documented from the Atlantic biogeographic region but not from Central Europe. Which patterns and trends of community change in species-rich Nardus grassland of the Continental biogeographic region occurred in past decades? Are patterns and trends similar across areas within the Continental biographic region of Germany? Do they correspond to identified changes in the Atlantic biogeographic region of Europe? LocationEast Hesse Highlands, Germany MethodsIn 2012/15, we re-surveyed vegetation releves on quasi-permanent plots originally surveyed between 1971 and 1986/87 and re-measured soil parameters. We tested for differences in species frequency and abundance, mean Ellenberg indicator values, diversity measures and soil variables. Nitrogen and sulphur deposition data were analysed to evaluate effects of atmospheric pollutants. We used regression analyses to identify the contribution of environmental drivers to changes in species composition. ResultsWe found significant increases in soil pH, Ellenberg R and N values, species of agricultural grasslands and grassland fallows. C:N ratio, Nardus grassland specialists and low-nutrient indicators declined, while changes in species composition relate to changes in pH and management. There was a strong decrease in sulphur and a moderate increase in nitrogen deposition. Local patterns in atmospheric depositions did not correlate with local changes in species composition and soil parameters. ConclusionThe findings indicate significant overall eutrophication, a trend towards less acidic conditions, and insufficient management and abandonment. This is widely consistent across study areas and correspond to recent reports on vegetation changes and recovery from acidification in the Atlantic biogeographic region. We strongly assume reduction in sulphur deposition during recent decades to be a major driver of these changes combined with increased nitrogen deposition and reduced management intensity. This suggests a large-scale validity of processes triggering changes in Nardus grasslands across Western and Central Europe. NomenclatureThe nomenclature follows the German taxonomic reference list (GermanSL version 1.3) of Jansen & Dengler (2008).

ecology↗

bioRxiv2017

Natural selection interacts with the local recombination rate to shape the evolution of hybrid genomes

While hybridization between species is increasingly appreciated to be a common occurrence, little is known about the forces that govern the subsequent evolution of hybrid genomes. We considered this question in three independent, naturally-occurring hybrid populations formed between swordtail fish species Xiphophorus birchmanni and X. malinche. To this end, we built a fine-scale genetic map and inferred patterns of local ancestry along the genomes of 690 individuals sampled from the three populations. In all three cases, we found hybrid ancestry to be more common in regions of high recombination and where there is linkage to fewer putative targets of selection. These same patterns are also apparent in a reanalysis of human-Neanderthal admixture. Our results lend support to models in which ancestry from the \"minor\" parental species persists only where it is rapidly uncoupled from alleles that are deleterious in hybrids, and show the retention of hybrid ancestry to be at least in part predictable from genomic features. Our analyses further indicate that in swordtail fish, the dominant source of selection on hybrids stems from deleterious combinations of epistatically-interacting alleles.\n\nOne sentence summaryThe persistence of hybrid ancestry is predictable from local recombination rates, in three replicate hybrid populations as well as in humans.

evolutionary biology↗

bioRxiv2017

Adolescent Tuning Of Association Cortex In Human Structural Brain Networks

Motivated by prior data on local cortical shrinkage and intracortical myelination, we predicted age-related changes in topological organisation of cortical structural networks during adolescence. We estimated structural correlation from magnetic resonance imaging measures of cortical thickness at 308 regions in a sample of N=297 healthy participants, aged 14-24 years. We used a novel sliding-window analysis to measure age-related changes in network attributes globally, locally and in the context of several community partitions of the network. We found that the strength of structural correlation generally decreased as a function of age. Association cortical regions demonstrated a sharp decrease in nodal degree (hubness) from 14 years, reaching a minimum at approximately 19 years, and then levelling off or even slightly increasing until 24 years. Greater and more prolonged age-related changes in degree of cortical regions within the brain network were associated with faster rates of adolescent cortical myelination and shrinkage. The brain regions that demonstrated the greatest age-related changes were concentrated within prefrontal modules. We conclude that human adolescence is associated with biologically plausible changes in structural imaging markers of brain network organization, consistent with the concept of tuning or consolidating anatomical connectivity between frontal cortex and the rest of the connectome.

neuroscience↗

bioRxiv2017

Altered topology of neural circuits in congenital prosopagnosia

Using a novel fMRI-based inter-subject functional correlation (ISFC) approach, which isolates stimulus-locked inter-regional correlation patterns, we compared the cortical topology of the neural circuit for face processing in participants with congenital prosopagnosia (CP) and matched controls. Whereas the anterior temporal lobe served as the major network hub for face processing in controls, this was not the case for the CPs. Instead, this group evinced hyper-connectivity in posterior regions of the visual cortex, mostly associated with the lateral occipital and the inferior temporal cortices. Moreover, the extent to which the network organization was atypical differed as a function of the severity of the face recognition deficit. These results offer new insights into the perturbed cortical topology in CP, which may serve as the underlying neural basis of the behavioral deficits typical of this disorder. The approach adopted here has the potential to uncover altered topologies in other neurodevelopmental disorders, as well.\n\nSignificance StatementCongenital prosopagnosia (CP; face blindness), a developmental deficit in face recognition, is thought to affect up to 3% of the population. Understanding its neural basis is challenging as there is no obvious deficit on conventional structural or functional MRI scans. Using an innovative, fMRI-based inter-subject correlation approach geared towards tracking inter-regional stimulus-locked brain activation, the present study uncovers marked topological differences in a distributed brain network of higher-order visual regions in CP relative to controls. Alteration in topology also differs as a function of the severity of the deficit. These findings shed new light on the neural perturbations underlying CP, and the analytic approach we have adopted may have utility in elucidating the neural basis of other neurodevelopmental disorders such as dyslexia or amusia.

neuroscience↗