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Pedersen, S.

Publications and source records attributed to Pedersen, S..

9 recordsLinked to original sources

Effects of gamebird release on the non-gamebird dietary diversity and composition of red foxes (Vulpes vulpes) in Southern England

The red fox, Vulpes vulpes, is abundant in England and can exert limiting effects on their avian and mammalian prey. Large-scale gamebird releases in the UK may be sustaining high predator numbers, leading to greater predation on other prey species, especially once gamebird stocks are depleted. However, little is known how gamebird release affects the broader diet of the red fox. Here we used DNA metabarcoding to assess the diet of foxes from 18 agricultural estates in Southern England, 10 of which released large numbers of gamebirds (red-legged partridges - Alectoris rufus, and common pheasants - Phasianus colchicus) and 8 which did not. Scats were collected over one year, allowing for seasonal investigation of the foxes' diet. We investigated the vertebrate species consumed and compared the non-gamebird dietary diversity and composition between release and non-release estates and across seasons. The field vole (Microtus agrestis) was found to be the most frequently predated species overall. Brown hares and field voles were detected more on release sites, while bank voles and dog faeces were detected more on non-release sites. We found little evidence that foxes predate ground nesting birds or other species of concern. The dietary diversity was significantly lower on estates that released gamebirds, and this difference was most notable during the post-shoot, spring months (February to April). On both estate types, diversity was highest in the summer months. The altered predatory behaviour due to gamebird release is likely to affect the populations of the non-game prey of the red fox and this should be considered when designing policies regarding gamebird management and biodiversity conservation. Alternative predation combined with predator control may be reducing predation pressure on non-game prey where gamebirds are released, but high fox density elsewhere likely results in higher predation pressure on a wide range of species.

ecology↗

Immunogenomic profiling of circulating T cells in pediatric cancer patients during standard-of-care

While pediatric cancer patients receive intensive chemotherapy, its impact on peripheral T cells and subsequently to disease outcomes are not fully characterized. Here, we assessed T-cell dynamics during treatment, identifying associations with outcomes through immune phenotyping and T-cell Receptor (TCR) sequencing in pediatric solid and hematologic malignancies. We show that while levels of immune checkpoint proteins (PD-1, LAG3, and TIM3) at baseline were highest in lymphomas compared to other cancer groups, they increased significantly in response to therapy in all cancers. Levels of Central Memory (CM) T cells increased in leukemias and solid tumors, while naive T cells and cell-free TCR diversity decreased in lymphomas. By combining immune cell and TCR repertoire features across all timepoints, we proposed the Dynamic Immunogenomic Score (DIS) to measure patient-specific effects of therapy on the peripheral T-cell population. Higher DIS was associated with high-risk cancer types and logistic regression analysis revealed it may predict incidence of relapse in leukemia patients. TCR specificity analysis revealed patient-specific clonal dynamics and differential detection of virally-associated TCRs in cancer patients compared to healthy individuals. Our results highlight the potential of early upfront immunogenomic profiling in identifying high-risk patients that may be predictive in light of emerging cellular immunotherapies.

cancer biology↗

Non-canonical induction of autophagy increases adeno-associated virus type 2 (AAV2) transduction efficiency

Adeno-associated virus (AAV) serotypes infect a wide range of cell types, making this member of the parvovirus family a versatile tool in gene therapy. Infection as well as transduction is set in motion by means of specific receptors in conjunction with trafficking pathways, particularly endocytosis, a main cell entry pathway of non-enveloped viruses. Here, we report that efficacy of transduction is enhanced upon treating cells with hyperosmotic sucrose, a known blocker of clathrin-mediated endocytosis, through the non-canonical induction of autophagy. This mechanism of autophagy induction, however, is different from the previously reported AAV2-mediated induction of autophagy, which relies on a canonical, phosphoinositide 3-kinase class III (PI3K-III) complex-dependent pathway and appears to be dependent on the virus intrinsic secreted phospholipase A2 (sPLA2) domain, particularly its catalytic center activity. IMPORTANCEAdeno-associated virus (AAV) vectors are among the most frequently applied virus-based delivery vehicles for gene therapy. Lack of pathogenicity for humans, availability of a huge number of AAV serotypes differing in their cellular tropism, and the mainly episomal persistence of AAV vector genomes are clear advantages of these biological nanoparticles. By exploring non-pharmacological inducers of autophagy, we provide evidence for a potent and easy to apply strategy to significantly improve the efficacy of recombinant AAV-based gene delivery in hepatic and structural cells. Besides, our data also demonstrate the importance of autophagy for AAV2 infection and vector-mediated transduction in non-hepatic cells.

microbiology↗

Visual Perception of 3D Space and Shape In Time - Part IV: 3D Shape Recognition by 3D Rotation

Human vision has a remarkable ability to recognize complex 3D objects such as faces that appear at any size and 3D orientations at any 3D location. If we initially memorize a face only with a normalized size upfront at the object center, the direct comparison between the one-sized memory and an incoming new image would demand tremendous mental frame translations in 7D. How can we perform such a demanding task so promptly as we experience it in our daily lives? This paper specifically addresses the recognition of human faces with arbitrary 3D orientation in the [Roll, Yaw, Pitch] axes. According to our new model of NHT (Neural Holography Tomography), space is represented by time utilizing the phase of the alpha brainwave. This principle should be applicable to any mental rotation in 3D; thus, it predicts that extra time is required to perceive a rotated face to revolve it back to upright by the constant-speed alpha wave. To assess this hypothesis, we designed a reaction time (RT) experiment, where participants were first asked to memorize sets of upright unfamiliar faces. Following the memorization phase, similar stimuli with a wide range of rotating faces in 3D were presented, and RTs were recorded. As expected, the memorized upfront face was the fastest RT. The excess of the RT was observed proportional to the rotating angle in all [Roll, Yaw, Pitch] axes. Roll had the flattest slope, whereas upper Pitch was the steepest. We suspect that Roll is the swiftest mental operation because it can be conducted by the linear frame translation on the log-polar retinotopy of the visual cortex.

neuroscience↗

Molecular and cellular architecture of the larval sensory organ in the cnidarian Nematostella vectensis

The apical pole of eumetazoan ciliated larvae acts as a neurosensory structure and is principally composed of sensory-secretory cells. Cnidarians like the sea anemone Nematostella vectensis are the only non-bilaterian group to evolve ciliated larvae with a neural integrated sensory organ that is likely homologous to bilaterians. Here, we uncovered the molecular signature of the larval sensory organ in Nematostella by generating a transcriptome of the apical tissue. We characterised the cellular identity of the apical domain by integrating larval single-cell data with the apical transcriptome and further validated this through in-situ hybridisation. We discovered that the apical domain comprises a minimum of 6 distinct cell types, including apical cells, neurons, peripheral flask-shaped gland/secretory cells, and undifferentiated cells. By profiling the spatial expression of neuronal genes, we showed that the apical region has a unique neuronal signature distinct from the rest of the body. By combining the planula cilia proteome with the apical transcriptome data, we revealed the sheer complexity of the non-motile apical tuft. Overall, we present comprehensive spatial/molecular data on the Nematostella larval sensory organ and open new directions for elucidating the functional role of the apical organ and larval nervous system.

evolutionary biology↗

De novo assembly, annotation, and comparative analysis of 26 diverse maize genomes

We report de novo genome assemblies, transcriptomes, annotations, and methylomes for the 26 inbreds that serve as the founders for the maize nested association mapping population. The data indicate that the number of pan-genes exceeds 103,000 and that the ancient tetraploid character of maize continues to degrade by fractionation to the present day. Excellent contiguity over repeat arrays and complete annotation of centromeres further reveal the locations and internal structures of major cytological landmarks. We show that combining structural variation with SNPs can improve the power of quantitative mapping studies. Finally, we document variation at the level of DNA methylation, and demonstrate that unmethylated regions are enriched for cis-regulatory elements that overlap QTL and contribute to changes in gene expression. One sentence summaryA multi-genome analysis of maize reveals previously unknown variation in gene content, genome structure, and methylation.

genomics↗

Characterising pre-clinical sub-phenotypic models of Acute Respiratory Distress Syndrome: an experimental ovine study.

The Acute Respiratory Distress Syndrome (ARDS) describes a heterogenous population of patients with acute severe respiratory failure. However, contemporary advances have begun to identify distinct sub-phenotypes that exist within its broader envelope. These sub-phenotypes have varied outcomes and respond differently to several previously studied interventions. A more precise understanding of their pathobiology and an ability to prospectively identify them, may allow for the development of precision therapies in ARDS. Historically, animal models have played a key role in translational research, although few studies have so far assessed either the ability of animal models to replicate these sub-phenotypes or investigated the presence of sub-phenotypes within animal models. Here, in three ovine models of ARDS, using combinations of oleic acid and intravenous, or intratracheal lipopolysaccharide, we demonstrate the presence of sub-phenotypes which qualitatively resemble those found in clinical cohorts. Principal Components Analysis and partitional clustering reveal two clusters, differentiated by markers of shock, inflammation, and lung injury. This study provides the first preliminary evidence of ARDS phenotypes in pre-clinical models and develops a methodology for investigating this phenomenon in future studies.

physiology↗

Effect of Sequence Depth and Length in Long-read Assembly of the Maize Inbred NC358

Recent improvements in the quality and yield of long-read data and scaffolding technology have made it possible to rapidly generate reference-quality assemblies for complex genomes. Still, generating these assemblies is costly, and an assessment of critical sequence depth and read length to obtain high-quality assemblies is important for allocating limited resources. To this end, we have generated eight independent assemblies for the complex genome of the maize inbred line NC358 using PacBio datasets ranging from 20-75x genomic depth and N50 read lengths of 11-21 kb. Assemblies with 30x or less depth and N50 read length of 11 kb were highly fragmented, with even the low-copy genic fraction of the genome showing degradation at 20x depth. Distinct sequence-quality thresholds were observed for complete assembly of genes, transposable elements, and highly repetitive genomic features such as telomeres, heterochromatic knobs and centromeres. This study provides a useful resource allocation reference to the community as long-read technologies continue to mature.

genomics↗

Absolute quantification of translational regulation and burden using combined sequencing approaches

Translation of mRNAs into proteins is a key cellular process. Ribosome binding sites and stop codons provide signals to initiate and terminate translation, while stable secondary mRNA structures can induce translational recoding events. Fluorescent proteins are commonly used to characterize such elements but require the modification of a parts natural context and allow only a few parameters to be monitored concurrently. Here, we develop an approach that combines ribosome profiling (Ribo-seq) with quantitative RNA sequencing (RNA-seq) to enable the high-throughput characterization of genetic parts controlling translation in absolute units. We simultaneously measure 743 translation initiation rates and 746 termination efficiencies across the Escherichia coli transcriptome, in addition to translational frameshifting induced at a stable RNA pseudoknot structure. By analyzing the transcriptional and translational response, we discover that sequestered ribosomes at the pseudoknot contribute to a {sigma}32-mediated stress response, codon-specific pausing, and a drop in translation initiation rates across the cell. Our work demonstrates the power of integrating global approaches towards a comprehensive and quantitative understanding of gene regulation and burden in living cells.

synthetic biology↗