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Bertelsen, M. F.

Publications and source records attributed to Bertelsen, M. F..

8 recordsLinked to original sources

Spatial navigation through evolution: a single-cell atlas of the mammalian entorhinal cortex

Spatial navigation is a fundamental mammalian ability, supported by the entorhinal cortex (EC), a structurally conserved yet functionally diverse region across mammalian species. However, how molecular signaling underlies both shared and species-specific navigational strategies remains unclear. Here, we present a cross-species single-cell atlas of the EC from human, Hamadryas baboon, mouse, and Egyptian fruit bat - species spanning distinct evolutionary lineages and navigational demands, including true 3D navigation in bats. Using this resource, we identify conserved principal neuron populations as well as species-specific innovations, including mixed-layer or functional identities and fruit bat-specific subtypes. GABAergic interneurons neurons show strong conservation of somatostatin (SST) and parvalbumin (PV) families, while VIP GABAergic neurons exhibit pronounced species-specific divergence, with an expanded repertoire in primates. Integration with whole-brain diffusion tensor imaging reveals conserved and species-specific connectivity between the EC, hippocampus, and sensory cortices. Major species-specific cellular innovations were further validated using orthogonal histological approaches, confirming their anatomical and laminar organization. Overall, this atlas provides a comparative framework available for the research community to dissect the molecular, cellular, and circuit principles underlying conserved and specialized spatial navigation across mammals.

neuroscience↗

New high accuracy diagnostics for avian Aspergillus fumigatus infection using Nanopore methylation sequencing of host cell-free DNA and machine learning prediction

Avian aspergillosis is a detrimental fungal infection affecting wild and domestic birds yet sensitive antemortem diagnostics for early clinical infections are lacking. Here we present new diagnostics for Aspergillus fumigatus (Af) infection developed from cell-free DNA (cfDNA) methylation markers. Broiler chickens were experimentally infected with either Af, a non-Af agent (Escherichia coli or Gallibacterium anatis) or assigned as controls. Oxford Nanopore (ONT) sequencing was performed on serum cfDNA (n = 124), and machine learning (ML) models were trained on infection-specific markers. Three tests were developed: A High Accuracy test for best performance (sensitivity: 100%, specificity: 89.2%) and robustness (ROC-AUC: 0.92) as well as Fast- and In situ tests for rapid turnaround and methylation PCR. Diagnostic accuracies were 92.3%, 82.7%, and 73.1%, respectively. In conclusion, new tests using on ML- and host cfDNA methylation markers demonstrated high diagnostic performance comparable to microbial cfDNA (mcfDNA) tests but without concern for environmental contamination. Key highlightsO_LIWe present three new high accuracy diagnostic tests for Aspergillus fumigatus infection in chickens that use methylation markers from serum cell-free DNA (cfDNA). C_LIO_LIDifferentially methylated cfDNA regions (DMRs) were detected by Oxford Nanopore sequencing (ONT) in experimentally infected chickens and used as markers to train machine learning (ML) models for development of three diagnostic tests. C_LIO_LIThe highest accuracy was found with 83 markers of 10 kilobases (KB) using the glmnet algorithm for the ML model, which classified 92.3% blinded samples correctly. C_LIO_LIA Fast test designed for cheap <1h sequencing using adaptive sampling could correctly classify 82.7% samples with 22 markers using a random forest (rf) model. C_LIO_LIAn In situ test with only four markers, envisioned for use in a simple methylation-specific PCR (MSP-PCR) assay, could correctly classify 73.1% blinded samples. C_LIO_LIReference values with associated probabilities of infection were calculated for each of the three tests and are presented for further evaluation. C_LI

microbiology↗

Comparative neuroimaging of the carnivoran brain: Neocortical sulcal anatomy

Carnivorans are an important study object for comparative neuroscience, as they exhibit a wide range of behaviours, ecological adaptations, and social structures. Previous studies have mainly examined relative brain size, but a comprehensive understanding of brain diversity requires the investigation of other aspects of their neuroanatomy. Here, we obtained primarily post-mortem brain scans from twenty-six species of the order Carnivora, spanning across eight families with diverse representatives and including additional individuals for selected species, to create the largest Carnivoran brain collection to date. We then reconstructed their cortical surfaces, and examined neocortical sulcal anatomy to establish a framework for systematic inter-species comparisons. We observed distinct regional variations in sulcal anatomy, potentially related to the species behaviour and ecology. Arctoidea species with pronounced forepaw dexterity exhibited complex sulcal configurations in the presumed somatosensory cortex but low sulcal complexity in the presumed visual and auditory occipitotemporal cortex. Canidae had the largest number of unique major sulci with a unique sulcus in the occipital cortex and highly social canids featuring an additional frontal cortex sulcus. We also observed differentially complex occipito-temporal sulcal patterns in Felidae and Canidae, indicative of changes in auditory and visual areas that may be related to foraging strategies and social behaviour. In conclusion, this study presents an inventory of the sulcal anatomy of a number of rarely studied carnivoran brains including detailed digital atlases and establishes a framework and novel avenues for further investigations employing a variety of neuroimaging modalities to reveal more about carnivoran brain diversity.

neuroscience↗

Comparing the limbic-frontal connectome across the primate order: conservation of connections and implications for translational neuroscience

The interaction of the limbic system and frontal cortex of the primate brain is important in many affective behaviors. For this reason, it is heavily implicated in a number of psychiatric conditions. This system is often studied in the macaque monkey, the most largely-used non-human primate model species. However, how evolutionary conserved this system is and how well results obtained in any model species translate to the human can only be understood by studying its organization across the primate order. Here, we present an investigation of the topology of limbic-frontal connections across seven species, representing all major branches of the primate family tree. We show that dichotomous organization of amydalofugal and uncinate connections with frontal cortex is conserved across all species. Subgenual connectivity of the cingulum bundle, however, seems less prominent in prosimian and New World monkey brains. These results inform both translational neuroscience and primate brain evolution.

neuroscience↗

Airborne environmental DNA for terrestrial vertebrate community monitoring

Assessing and studying the distribution, ecology, diversity and movements of species is key in understanding environmental and anthropogenic effects on natural ecosystems. Although environmental DNA is rapidly becoming the tool of choice to assess biodiversity 1-3 there are few eDNA sample types that effectively capture terrestrial vertebrate diversity and those that do can be laborious to collect, require special permits and contain PCR inhibitory substances, which can lead to detection failure. Thus there is an urgent need for novel environmental DNA approaches for efficient and cost-effective large-scale routine monitoring of terrestrial vertebrate diversity. Here we show that DNA metabarcoding of airborne environmental DNA filtered from air can be used to detect a wide range of local vertebrate taxa. We filtered air at three localities in Copenhagen Zoo, detecting mammal, bird, amphibian and reptile species present in the zoo or its immediate surroundings. Our study demonstrates that airDNA has the capacity to complement and extend existing terrestrial vertebrate monitoring methods and could form the cornerstone of programs to assess and monitor terrestrial communities, for example in future global next generation biomonitoring frameworks 4,5.

molecular biology↗

The Digital Brain Bank: an open access platform for post-mortem datasets

Post-mortem MRI provides the opportunity to acquire high-resolution datasets to investigate neuroanatomy, and validate the origins of image contrast through microscopy comparisons. We introduce the Digital Brain Bank (open.win.ox.ac.uk/DigitalBrainBank), a data release platform providing open access to curated, multimodal post-mortem neuroimaging datasets. Datasets span three themes - Digital Neuroanatomist: datasets for detailed neuroanatomical investigations; Digital Brain Zoo: datasets for comparative neuroanatomy; Digital Pathologist: datasets for neuropathology investigations. The first Digital Brain Bank release includes twenty one distinctive whole-brain diffusion MRI datasets for structural connectivity investigations, alongside microscopy and complementary MRI modalities. This includes one of the highest-resolution whole-brain human diffusion MRI datasets ever acquired, whole-brain diffusion MRI in fourteen non-human primate species, and one of the largest post-mortem whole-brain cohort imaging studies in neurodegeneration. The Digital Brain Bank is the culmination of our labs investment into post-mortem MRI methodology and MRI-microscopy analysis techniques. This manuscript provides a detailed overview of our work with post-mortem imaging to date, including the development of diffusion MRI methods to image large post-mortem samples, including whole, human brains. Taken together, the Digital Brain Bank provides crossscale, cross-species datasets facilitating the incorporation of post-mortem data into neuroimaging studies.

neuroscience↗

ATRIOVENTRICULAR NODAL FUNCTION, ATRIAL FIBRILLATION AND VENTRICULAR TACHYCARDIA IN GIRAFFES

Unique cardiovascular adaptations in giraffes (Giraffa Camelopardalis reticulata) have been the focus of numerous investigations for almost a century. The vertical distance between the heart and brain impose high pressure on the giraffe left ventricle leading to thickening that exceeds heart in other mammals. Yet, cardiovascular function appears to be unimpacted by these morphologic differences. Physiologically adapted atrioventricular conduction may contribute to these unique cardiovascular characteristics. Atrioventricular (AV) function was assessed to determine whether physiologically adapted AV intervals might optimize the delay between atrial and ventricular contractions. Using ambulatory and intracardiac recordings, we report a longer PR interval in giraffes than predicted by allometric scaling. Slow ventricular response during atrial fibrillation further supports species-specific atrioventricular adaptations.

zoology↗

The microbiome of captive hamadryas baboon

Hamadryas baboon is a highly social primate that lives in complex multilevel societies exhibiting a wide range of group behaviors akin to humans. Here, we report the comprehensive 16s rRNA gene analyses of group-living baboon microbiota across different body sites. Additionally, we compared the baboon and human microbiome of the oral cavity, gut and vagina. Our analyses show that the baboon microbiome is distinct from the human and baboon cohabitants share similar microbial profiles in multiple body sites. The oral, gut and vagina shared more bacterial ASVs in group-living baboons than in humans. The shared ASVs in baboons had significantly positive correlations, suggesting a potential bacterial exchange throughout the body. No significant differences in baboon gut microbiome composition within the maternity line and between maternity lines were detected, suggesting that the offspring acquire their gut microbiota primarily through bacterial exchange among cohabitants. Besides, Lactobacillus was not so predominant in baboon vagina as in the human vagina but was the most abundant genus in baboon gut. These data and findings can form the basis of future microbiome studies in baboons and be used as a reference to research where the microbiome is expected to impact human modeling with baboons.

microbiology↗