Biology subjects

Jensen, B.

Publications and source records attributed to Jensen, B..

16 recordsLinked to original sources

bioRxiv2026

Danish profile of soft rot Pectobacteriaceae; A three-year field sampling study proving several clonal clades of soft rot isolates across diverse locations implicating a common origin

Soft rot Pectobacteriaceae (SRP) are among the most economically important plant pathogenic bacteria and are especially known to be problematic in potato production. The epidemiology of disease transmission has been investigated for almost a century, and several aspects have been highlighted as plausible infection routes. However, it is generally accepted that the major source of disease is the latently infected mother tuber, but several parameters are still influencing disease prevalence including contaminated equipment, soil water status as well as temperature. Management of the disease is limited to hygiene practices, dry storage and seed certification systems but several studies have also proven biocontrol agents such as bacteriophages (phages) as promising tools. Despite the severity of SRP on potato production, little is known about the genetic diversity of SRPs in Denmark, and since only few isolates are available, the possibility to design a broadly effective phage cocktail is limited. Here we describe a three-year field study utilizing an agri-citizen science approach where Danish farmers provided symptomatic potato plants or tubers, together with metadata such as date, location, potato variety and origin. By using whole genome sequencing (Illumina and Nanopore) together with metadata we were able to investigate and monitor the epidemiological disease spread across the country using 103 complete genomes, sampled across all three years. In this study we provide epidemiological evidence of disease origins and a suite of phages that could be used as a biocontrol tool for early disease intervention. Our results revealed several clonal clades across diverse locations (SNPs < 20) which strongly indicate common origin. A total of 17 Pectobacterium phages were tested and did target > 80% of clonal clades. Based on the clonality across the soft rot isolates we propose the possibility to set in early on using phages targeting strains relevant for soft rot development, with the possibility of a surveillance program together with customizing the phage preference.

microbiology↗

bioRxiv2026

TBX5 dosage governs ventricular cardiomyocyte maturation, specialization and dedifferentiation in vivo

Variation in transcription factor (TF) activity modulates traits and disease susceptibility, yet how such variation translates into cellular phenotype and organ function in vivo is not well established. We utilized AAV-mediated gene delivery to express the dosage-sensitive TF TBX5 across a physiologically plausible range in postnatal ventricular cardiomyocytes. Transcriptomic profiling revealed that TBX5 dosage-dependent cardiomyocyte states changed gradually and often non-monotonically across the TBX5 dosage spectrum. The lowest dosages induced cardiomyocyte hypertrophy and upregulated gene programs governing oxidative metabolism, calcium handling, and contractility. In contrast, mid-to-high dosages induced a ventricular conduction system-like transcriptional profile. Supraphysiological dosages triggered cardiomyocyte dedifferentiation, characterized by cardiomyocyte size reduction, cell cycle re-entry, metabolic reprogramming, and impaired ventricular ejection fraction. Furthermore, the ventricular state of an Nppa-Nppb deficiency model characterized by cardiac hypertrophy and reduced Tbx5 expression was partially normalized by TBX5 delivery. By defining the non-linear relationship of TBX5 activity level, cardiomyocyte state and cardiac function, our study reveals how TF dosage regulates the transitions from physiological maturation to specialized lineage acquisition and dedifferentiation at the cell and organ level in vivo.

developmental biology↗

bioRxiv2026

Homothallic or heterothallic? A genomic investigation into the sexual capabilities of the ascomycete fungus Clonostachys rosea

Modes of reproduction and sexual strategies strongly influence the genetic diversity and evolutionary potential of a species. The ascomycete fungus Clonostachys rosea is reported to be homothallic (sexually self-fertile), although a rapid decay of genome-wide linkage disequilibrium is also reported, something that is not in line with an obligate homothallic mode of reproduction. To investigate this phenomenon, we identified the mating-type (MAT1) locus in 66 genome-sequenced C. rosea strains under the hypothesis that each strain contains genes from both MAT1 idiomorphs. Eleven strains indeed contained both MAT1-1 and MAT1-2 genes, suggesting homothallism. However, most strains harboured either MAT1-1 or MAT1-2 genes and co-existed in North America, Europe and China, suggesting heterothallism. The MAT1 locus of heterothallic strains was highly conserved, and the linkage disequilibrium half decay distance was 1050 bp, suggesting sexual outcrossing. The presence of conserved MAT1-1 or MAT1-2 idiomorphs in strains of other Clonostachys species shows that heterothallism is likely the ancestral state. A phylogenetic analysis of 2800 single-copy orthologous genes revealed that homothallic and heterothallic strains separated in two well-supported clades, indicating a single lineage of homothallic C. rosea, likely originating in South America, followed by intercontinental dispersal. Homothallic C. rosea strains displayed higher nucleotide diversity than heterothallic strains, indicating a lack of outcrossing. This unique case of both homothallic and heterothallic lineages within the same species provides an opportunity to study the genomic consequences of selfing in very closely related strains.

evolutionary biology↗

bioRxiv2024

In Situ-Crosslinked Zippersomes Enhance Cardiac Repair by Increasing Accumulation and Retention

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction, but their therapeutic efficacy is limited by inefficient accumulation at the target site. A non-invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post-infarct cardiac regeneration. Here we show that EVs decorated with the next-generation of high-affinity heterodimerizing leucine zippers, termed high-affinity (HiA) Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited [~]7-fold enhanced accumulation within the infarcted myocardium in mice after three days and continued to be retained up to day 21, surpassing the performance of unmodified EVs. After myocardial infarction in mice, high-affinity Zippersomes increase the ejection fraction by 53% and 100% compared with unmodified EVs and PBS, respectively. This notable improvement in cardiac function played a crucial role in restoring healthy heart performance. High-affinity Zippersomes also robustly decrease infarct size by 52% and 60% compared with unmodified EVs and PBS, respectively, thus representing a promising platform for non-invasive vesicle delivery to the infarcted heart. Translational Impact StatementTherapeutic delivery to the heart remains inefficient and poses a bottleneck in modern drug delivery. Surgical application and intramyocardial injection of therapeutics carry high risks for most heart attack patients. To address these limitations, we have developed a non-invasive strategy for efficient cardiac accumulation of therapeutics using in situ crosslinking. Our approach achieves high cardiac deposition of therapeutics without invasive intramyocardial injections. Patients admitted with myocardial infarction typically receive intravenous access, which would allow painless administration of Zippersomes alongside standard of care.

bioengineering↗

bioRxiv2023

The smooth-walled human RVOT contains trabeculations that cause conduction delay.

AimsThe right ventricular outflow tract (RVOT) is the outlet from the right ventricle and is the initiating substrate of life-threatening arrhythmias. While the luminal wall of the RVOT is often assumed to be without the complex trabecular meshwork that characterizes the right ventricular free wall, the anatomy of the RVOT is an understudied subject. Our aim was to investigate whether trabeculations occur in the RVOT and to assess whether this impacts electrical propagation. Methods & ResultsWe used high-resolution MRI and serial sectioning to reconstruct the macroscopic details of the human RVOT and identified cases exhibiting much trabeculation. The smooth lumen of the RVOT varied between 9% and 23% of the total RV anterior surface (N=11). Histological analysis on additional six hearts indicated that the RVOT compact layer is thinner when trabeculations are present. RNA sequencing of four human donor hearts revealed enrichment in the subendocardial region of 88 genes associated with cardiac conduction and trabeculations (P adjusted<0.05). Finally, we selected two human donor hearts showing trabeculations in the RVOT from which we generated wedge preparation and performed optical and electrical mapping. The trabecular regions demonstrated high degree of fractionation when compared to non-trabeculated regions, which coincided with delayed activation. ConclusionTrabeculations are found in the RVOT, and their extent varies among individuals. This impacts on the thickness of the compact wall in the RVOT, restricting the depth of tissue at which clinical interventions can be performed, as well as influencing electrical propagation and possible arrhythmogenicity.

physiology↗

bioRxiv2023

The changing morphology of the ventricular walls of mouse and human with increasing gestation.

That the highly trabeculated ventricular walls of the developing embryos transforms to the arrangement during the fetal stages, when the mural architecture is dominated by the thickness of the compact myocardium, has been explained by coalescence of trabeculations, often erroneously described as "compaction". Recent data, however, supports differential rates of growth of the trabecular and compact layers as the major driver of change. Here, these processes were assessed quantitatively and morphologically using a larger dataset than has previously been available of mouse hearts from embryonic day 10.5 to postnatal day 3, supported by images from human hearts. The volume of the trabecular layer increased throughout development, in contrast to what would be expected had there been "compaction". During the embryonic-fetal transition, fast growth of the compact layer diminished the proportion of trabeculations. Similarly, great expansion of the central cavity reduced the proportion that intertrabecular recesses make of the total cavity. Using the median value of left ventricular trabeculation, we provided illustrations for each gestational day so as to provide pictorial evidence of the changes. The illustrations confirmed a pronounced growth of the compact wall, and prominence of the central cavity. This corresponds, in morphological terms, to a reduction in the extent of the trabecular layer. Similar observations were made in the human hearts. We conclude that it is a period of comparatively slow growth of the trabecular layer, rather than so-called compaction, that is the major determinant of the changing morphology of the ventricular walls of both mouse and human.

developmental biology↗

bioRxiv2023

ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97

The t(X,17) chromosomal translocation, generating the ASPSCR1-TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCC), frustrating efforts to identify therapeutic targets for these rare cancers. Proteomic analysis showed that VCP/p97, an AAA+ ATPase with known segregase function, was strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1-TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1-TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology. Specifically, VCP co-distributed with ASPSCR1-TFE3 across chromatin in association with enhancers genome-wide. VCP presence, its hexameric assembly, and its enzymatic function orchestrated the oncogenic transcriptional signature of ASPSCR1-TFE3, by facilitating assembly of higher-order chromatin conformation structures as demonstrated by HiChIP. Finally, ASPSCR1-TFE3 and VCP demonstrated co-dependence for cancer cell proliferation and tumorigenesis in vitro and in ASPS and RCC mouse models, underscoring VCPs potential as a novel therapeutic target.

cancer biology↗

bioRxiv2023

Trabeculations of the porcine and human cardiac ventricles are different in number but similar in total volume.

An intricate meshwork of trabeculations lines the luminal side of cardiac ventricles. Compaction, a developmental process, is thought to reduce trabeculations by adding them to the neighboring compact wall which is then enlarged. When pig, a plausible cardiac donor for xenotransplantation, is compared to human, the ventricular walls appear to have fewer trabeculations. We hypothesized the trabecular volume is proportionally smaller in pig than in human. Macroscopically, we observed in sixteen pig hearts that the ventricular walls harbor few but large trabeculations. Close inspection revealed a high number of tiny trabeculations, a few hundred, within the recesses of the large trabeculations. While tiny, these were still larger than embryonic trabeculations and even when considering their number, the total tally of trabeculations in pig was much fewer than in human. Volumetrics based on high-resolution MRI of additional six pig hearts compared to six human hearts, revealed the left ventricles were not significantly differently trabeculated (21.5 versus 22.8%, respectively), and the porcine right ventricles were only slightly less trabeculated (42.1 versus 49.3%, respectively). We then analyzed volumetrically ten pig embryonic hearts from gestational day 14 to 35. The trabecular and compact layer always grew, as did the intertrabecular recesses, in contrast to what compaction predicts. The proportions of the trabecular and compact layers changed substantially, nonetheless, due to differences in their growth rate rather than compaction. In conclusion, processes that affect the trabecular morphology do not necessarily affect the proportion of trabecular-to-compact myocardium and they are then distinct from compaction.

developmental biology↗

bioRxiv2023

Laterality defect of the heart in non-teleost fish

Dextrocardia is a rare congenital malformation in humans in which most of the heart mass is positioned in the right hemithorax rather than on the left. The heart itself may be normal and dextrocardia is sometimes diagnosed during non-related explorations. A few reports have documented atypical positions of the cardiac chambers in farmed teleost fish. Here, we report the casual finding of a left-right mirrored heart ventricle in a 85 cm long spiny dogfish (Squalus acanthias) that was caught in the wild. Macroscopic observations showed an outflow tract originating from the left side of the ventricular mass, rather than from the right. Internal inspection revealed the normal structures, including a looped cavity on the inner curvature of which was a large trabeculation, or the bulboventricular fold. MRI data acquired at 0.7 mm isotropic resolution and subsequent 3D-modeling revealed the atrioventricular canal was to the right of the bulboventricular fold, rather than on the left. The atrium and sinus venosus had the normal midline position and gross shape. Spurred by finding of the left-right mirrored shark ventricle, we revisit our previously published material on farmed Adriatic sturgeon (Acipenser naccarii), a non-teleost bony fish. We found several alevins with inverted (L-loop) hearts, amounting to an approximate incidence of 1-2 %. Additionally, an adult sturgeon measuring 90 cm in length showed abnormal topology of the cardiac chambers, but normal position of the abdominal organs. In conclusion, left-right mirrored hearts, a setting that resembles human dextrocardia, can occur in both farmed and wild non-teleost fish.

zoology↗

bioRxiv2022

The capacity to configure the hymenophore is not confined to the pore field in Oak mazegill (Daedalea quercina, Polyporales)

Configuring of the hymenophore of basidiocarps of Polyporales is thought to happen in the pore field immediately behind the basidiocarp margin. Basidiocarp growth is not restricted to the margin, however. Here, the importance of the pore field was assessed from observations on naturally occurring Oak mazegill (Polyporales, Daedalea quercina) basidiocarps and tested by experimental perturbations in natural habitats that were monitored for two years. Oak mazegill was chosen because the formed hymenophore has a unique and stable combination of poroid and lamellate features. Whether the pore field is required for basidiocarp growth was tested in ten basidiocarps in which one side was resected. New growth was observed in six basidiocarps and it occurred equally from the cut hymenophore and the intact pore field. New formation of hymenophore and pileus even occurred in seven out of ten basidiocarps that had the entire pore field resected. Whether the hymenophore is configured permanently, was tested on 54 basidiocarps on ten trunks that were turned upside-down. A new hymenophore grew through the old pileus, often far from the pore field, and its hymenophore configuration was invariably poroid despite the old hymenophore had lamellate features. In 48 experimentally banded basidiocarps, new hymenophore grew in the insertion hole of the band despite this being far from the pore field. The banded basidiocarps grew at an average rate of 5 mm per year. In conclusion, the capacity to configure the hymenophore is not confined to the pore field and it may be broadly present in the basidiocarp. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/503585v1_ufig1.gif" ALT="Figure 1"> View larger version (90K): org.highwire.dtl.DTLVardef@1d5eefdorg.highwire.dtl.DTLVardef@3d2709org.highwire.dtl.DTLVardef@cdd068org.highwire.dtl.DTLVardef@2d636f_HPS_FORMAT_FIGEXP M_FIG Graphical abstract. The configuring of the hymenophore of polypore fungi is thought to be driven by the pore field immediately behind the basidiocarp margin. The experiments on Oak mazegill basidiocarps reported here, including the complete resection of the margin and its pore field, do not support this notion. They suggest instead that the capacity to form the hymenophore is broadly present in the basidiocarp. C_FIG

microbiology↗

bioRxiv2022

Anatomy of the heart of the leatherback turtle

Non-crocodylian reptiles have hearts with a single ventricle, which is partially separated by a muscular ridge that provide some separation of blood flows. An exceptional situation exists in monitor lizards and pythons, where the ventricular left side generates a much higher systolic blood pressure than the right side, thus resembling mammals and birds. This functional division of the ventricle depends on a large muscular ridge and may relate to high metabolic demand. The large leatherback turtle (<1000 kg), with its active ocean-going lifestyle and elevated body temperatures, may have similar adaptations. Here, we report on the anatomy the hearts of two leatherback turtles. One stranded in Ballum, Denmark in 2020, and was examined in detail, supplemented by observations and photos of an additional stranding specimen from Canada. The external morphology of the leatherback heart resembles that of other turtles, but it is large. We made morphometric measurements of the Ballum heart and created an interactive 3D model using high resolution MRI. The volume of the ventricle was 950 ml, from a turtle of 300 kg, which is almost twice as large as in other reptiles. The Ballum heart was compared to MRI scans of the hearts of a tortoise, a python, and a monitor lizard. Internally, the leatherback heart is typical of non-crocodylian reptiles, and did not contain the well-developed septation found in pythons and monitor lizards. We conclude that if leatherback turtles have exceptional circulation needs, they are sustained with a relatively large but otherwise typical non-crocodylian reptile heart.

evolutionary biology↗

bioRxiv2021

Anatomy of the Heart with the Highest Heart Rate

Shrews occupy the lower extreme of the seven orders of magnitude mammals range in size. Their hearts are large relative to body weight and heart rate can exceed a thousand beats a minute. To investigate whether cardiac traits that are typical mammalian scale to these extremes, we assessed the heart of three species of shrew (genus Sorex) following the sequential segmental analysis developed for human hearts. Using micro-computed tomography we describe the overall structure and find, in agreement with previous studies, a large and elongate ventricle. The atrial and ventricular septums and the atrioventricular and arterial valves are typically mammalian. The ventricular walls comprise mostly compact myocardium and especially the right ventricle has few trabeculations on the luminal side. A developmental process of compaction is thought to reduce trabeculations in mammals, but in embryonic shrews the volume of trabeculations increase for every gestational stage, only slower than the compact volume. By expression of Hcn4, we identify a sinus node and an atrioventricular conduction axis which is continuous with the ventricular septal crest. Outstanding traits include pulmonary venous sleeve myocardium that reaches farther into the lungs than in any other mammals. Typical proportions of coronary arteries-to-aorta do not scale and the shrew coronary arteries are proportionally enormous, presumably to avoid the high resistance to blood flow of narrow vessels. In conclusion, most cardiac traits do scale to the miniscule shrews. The shrew heart, nevertheless, stands out by its relative size, elongation, proportionally large coronary vessels, and extent of pulmonary venous myocardium.

zoology↗

bioRxiv2020

The nuclear receptor RORα preserves cardiomyocyte mitochondrial function by regulating mitophagy through caveolin-3

Preserving optimal mitochondrial function is critical in the heart, which is the most ATP-avid organ in the body. Recently, we showed that global deficiency of the nuclear receptor ROR in the "staggerer" (RORsg/sg) mouse exacerbates angiotensin II-induced cardiac hypertrophy and compromises cardiomyocyte mitochondrial function. The mechanisms underlying these observations have not been defined. Here we present evidence that ROR regulates cardiomyocyte mitophagy using pharmacological and genetic gain- and loss-of-function tools, including a novel cardiomyocyte-specific ROR knockout mouse. Cardiomyocyte ROR is upregulated by hypoxia and the loss of ROR blunts hypoxia-induced mitophagy and broadly compromises mitochondrial function. We show that ROR is a direct transcriptional regulator of the mitophagy mediator caveolin-3 in cardiomyocytes and that increased expression of ROR increases caveolin-3 abundance and enhances mitophagy. Knockdown of ROR impairs cardiomyocyte mitophagy, but this defect can be rescued by caveolin-3 overexpression. Collectively, these findings reveal a novel role for ROR in regulating mitophagy through caveolin-3 and expand our currently limited understanding of the mechanisms underlying ROR-mediated cardioprotection.

molecular biology↗

bioRxiv2020

The mechanism underlying J-waves and T-waves in the electrocardiogram of mice and zebra finches

Brief cardiac cycles are required to achieve high heart rates as seen in endothermic animals. A main determinant of the cardiac cycle is the repolarization phase of the cardiac action potential, which is visible in the ECG as a T-wave. In mammals with high heart rates - such as rodents - the repolarization phase is short and the ECG is characterized by a positive deflection following the QRS-complex, the J-wave. It is unclear whether birds with high heart rates show similar ECG characteristics. Here we study cardiac repolarization and the ECG in the zebra finch which has high heart rates. In ex vivo hearts of zebra finch (N=5) and mouse (N=5), pseudo-ECGs and optical action potentials were measured. In both species, total ventricular activation was fast with QRS durations shorter than 10ms. Ventricular activation progressed from the left to the right ventricle in zebra finch whereas the activation pattern was apex-to-base in mouse. In both species, phase 1 early repolarization followed the activation front, causing a positive J-wave in the pseudo-ECG. In zebra finch, late repolarization was directed from the right ventricle to the left ventricle, whereas late repolarization was directed opposite in mouse. Accordingly, on the zebra finch ECG, the J-wave and the T-wave have the same direction, whereas in the mouse the J-wave and the T-wave are discordant. Our findings demonstrate early repolarization and the associated J-wave are not restricted to mammals and that they also occur within birds. Early repolarization may have evolved by convergence in association with high heart rates. Summary statementZebra finches are small birds with high heart rates. Similar to small rodents, the zebra finch ECG contains a J-wave, which is caused by early repolarization

physiology↗

bioRxiv2019

Heart development in the lizards (Varanidae) with the greatest extent of ventricular septation

Among lizards, only monitor lizards (Varanidae) have a functionally divided cardiac ventricle. This enables them to sustain higher systemic blood pressures and higher metabolic rates than other reptiles of similar size. The division results from the concerted action of three partial septa, which may have homology to the full ventricular septum of mammals and archosaurs. Homology, however has only been inferred from anatomical comparisons of hearts of adult monitors whereas gene expression during heart development has not been studied. We show in developing monitors that the partial septa that separate the left and right ventricle, the muscular ridge and bulbuslamelle, express the evolutionary conserved transcription factors Tbx5, Irx1 and Irx2, orthologues of which mark the full ventricular septum. Compaction of embryonic trabeculae contributes to the formation of these septa. The septa are positioned, however, to the right of the atrioventricular junction and they do not partake in the separation of incoming atrial blood streams. Instead, the vertical septum within the left ventricle separates the atrial blood streams. It expresses Tbx3 and Tbx5, which orchestrate the formation of the electrical conduction axis of the full ventricular septum. These patterns of expression are more pronounced in monitors than in other lizards, and are associated with a deep electrical activation near the vertical septum, contrasting the primitive base-to-apex activation of other lizards. We conclude that current concepts of ventricular septum formation apply well to the monitor septa and that there is evolutionary conservation of ventricular septum formation among amniote vertebrates.

evolutionary biology↗

bioRxiv2018

Little variation in the morphology of the atria across 13 orders of birds

Mammals and birds acquired high performance hearts and endothermy during their independent evolution from amniotes with many reptile characters. A literature review shows that the variation in atrial morphology is greater in mammals than in ectothermic reptiles. We therefore hypothesized that the transition from ectothermy to endothermy associated with greater variation in cardiac structure. We tested the hypothesis in birds, by assessing the variation in 15 characters in hearts from 13 orders of birds. Hearts were assessed by gross morphology and histology, and we focused on the atria as they have multiple features that lend themselves to quantification. We found bird hearts to have multiple features in common with ectothermic reptiles (synapomorphies), for instance the presence of three sinus horns. Convergent features were shared with crocodylians and mammals, such as the cranial offset of the left atrioventricular junction. Other convergent features like the compact organization of the atrial walls were shared with mammals only. Sinus myocardium expressing Isl1 was node-like (Mallard), thickened (chicken), or anatomically indistinct from surrounding myocardium (Lesser redpoll). Some features were distinctively avian (apomorphies), including the presence of a left atrial antechamber, and the ventral merger of the left and right atrium, which was found in parrots and passerine birds. Most features, however, exhibited little variation. For instance, there were always three systemic veins and two pulmonary veins, whereas among mammals there are 2-3 and 1-7, respectively. Our findings suggest that the transition to high cardiac performance does not necessarily lead to greater variation in cardiac structure.

evolutionary biology↗