Biology subjects

Andersen, O.

Publications and source records attributed to Andersen, O..

7 recordsLinked to original sources

bioRxiv2025

Changes in DNA Methylation During Anoxia and Reoxygenation in Crucian Carp Brain

Oxygen is essential for cellular metabolism, and its absence poses a severe risk to vertebrates. However, the crucian carp (Carassius carassius) can survive without oxygen for months due to physiological adaptations. This study investigates the role of epigenomic regulation, specifically DNA methylation, in response to anoxia and subsequent reoxygenation. Brain samples from crucian carp subjected to normoxia, anoxia, and reoxygenation (n = 4 per condition) were analyzed through transcriptome (mRNA) and whole-genome bisulfite sequencing. Results revealed a notable transcriptional response to anoxia, with 1,265 differentially expressed genes (DEGs) identified compared to normoxia. Using the machine-learning-based MethylScore, we found 14 genes with differentially methylated regions (DMRs) during anoxia. These DMR-associated genes did not meet the strict DEGs criteria (adjusted p-value < 0.05; absolute log2fold-change > 0.38), but 17 genes exhibited differences in mRNA abundance when focusing solely on DMRs. DMRs were primarily located within transcriptional start sites, and analysis of protein products revealed that genes involved in transcription regulation, protein trafficking, and signal transduction were differentially methylated and expressed under varying conditions. This study advances our understanding of epigenomic regulation in oxygen deprivation and highlights the potential in exploring alternative epigenomic mechanisms.

physiology↗

bioRxiv2025

The Alzheimer's-Associated SORL1 p.Y1816C Variant Impairs APP Sorting, Axonal Trafficking, and Neuronal Activity in iPSC-Derived Brain Models

BackgroundSORL1, encoding the sorting receptor SORLA, is now recognized as the fourth autosomal dominant Alzheimers disease (AD) gene. Loss of SORLA function is known to disrupt endosomal trafficking and enhance amyloidogenic APP processing, two key aspects of the onset and progression of AD. However, the pathogenic consequences of disrupted endolysosomal pathways, deregulated protein sorting, as well as the effects of specific SORL1 missense variants on human neuronal function, still remain understudied. MethodsOur investigations were performed using two complementary human iPSC-derived models: 2D NGN2-induced neurons and 3D cerebral organoids established from isogenic wild-type (WT), SORL1 p.Y1816C (KI) missense variant, and SORL1 knock-out (KO) cells. We analyzed SORLA maturation and ectodomain shedding, APP localization, and amyloid-{beta} secretion. Endosomal morphology and neuritic swellings were assessed via electron microscopy, while axonal transport of APP and Rab5+ endosomes was evaluated through live-cell imaging. Neuronal network activity was measured using multielectrode array recordings. ResultsOur results demonstrate that the p.Y1816C variant leads to impaired SORLA maturation and reduced shedding, without affecting neuronal or organoid differentiation. Notably, we show an ultrastructure of endosomes, including their content, and demonstrate that both KO and KI models exhibit early endosome enlargement, increased APP retention in endosomes, elevated A{beta}40/42 secretion, and amyloid-{beta} deposition in 3D organoids. Importantly, we identified previously uncharacterized functional consequences of abolished SORLA activity, including axonal swellings and significantly impaired transport of Rab5+ endosomes and APP, characterized by deregulated velocities, directionality of transport, and increased stalling. Additionally, we discovered that both KO and p.Y1816C KI neurons exhibit abnormal electrophysiological activity, including increased spontaneous firing, burst frequency, and network synchrony. ConclusionsOur study defines the mechanistic consequences of the SORL1 p.Y1816C variant and demonstrates its pathogenicity in human neurons. Importantly, we also identify novel roles for SORLA in maintaining axonal transport homeostasis and regulating neuronal excitability, expanding its functional relevance beyond endosomal APP processing. These findings reinforce the central role of endosomal trafficking disruption in AD and support the use of isogenic human models for evaluating AD risk variants.

neuroscience↗

bioRxiv2023

Production of sterile Atlantic salmon by germ cell ablation with antisense oligonucleotides

Cultivation of sterile-only fish in aquaculture offers multiple benefits of environmental, economical, and social value. A reliable method for efficient sterilization without affecting fish welfare and performance traits would have significant impact on fish production practices. Here, we demonstrate sterilization of Atlantic salmon embryos by targeting the dead end gene with antisense oligonucleotides. Successful gene knock down and sterilization was achieved only when using Gapmer oligonucleotides and not with morpholino oligos. Germ cell-depleted embryos developed into morphologically normal male and female salmon with rudimentary gonads devoid of gametes.

developmental biology↗

bioRxiv2019

A nanopore based chromosome-level assembly representing Atlantic cod from the Celtic Sea.

Currently available genome assemblies for Atlantic cod (Gadus morhua) have been constructed using DNA from fish belonging to the Northeast Arctic Cod (NEAC) population; a migratory population feeding in the cold Barents Sea. These assemblies have been crucial for the development of genetic markers which have been used to study population differentiation and adaptive evolution in Atlantic cod, pinpointing four discrete islands of genomic divergence located on linkage groups 1, 2, 7 and 12. In this paper, we present a high-quality reference genome from a male Atlantic cod representing a southern population inhabiting the Celtic sea. Structurally, the genome assembly (gadMor_Celtic) was produced from long-read nanopore data and has a combined contig size of 686 Mb with a N50 of 10 Mb. Integrating contigs with genetic linkage mapping information enabled us to construct 23 chromosome sequences which mapped with high confidence to the latest NEAC population assembly (gadMor3) and allowed us to characterize in detail large chromosomal inversions on linkage groups 1, 2, 7 and 12. In most cases, inversion breakpoints could be located within single nanopore contigs. Our results suggest the presence of inversions in Celtic cod on linkage groups 6, 11 and 21, although these remain to be confirmed. Further, we identified a specific repetitive element that is relatively enriched at predicted centromeric regions. Our gadMor_Celtic assembly provides a resource representing a southern cod population which is complementary to the existing northern population based genome assemblies and represents the first step towards developing pan-genomic resources for Atlantic cod.

genomics↗

bioRxiv2019

Increased serological response against human herpesvirus 6A is associated with risk for multiple sclerosis

Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses.\n\nA novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8742 persons with MS and 7215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further.\n\nThe IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9x10-22), and increased risk of future MS (OR = 2.22, p = 2x10-5). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, p = 6x10-6). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6x10-11). The association did not differ between MS subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody responses were located to the Human Leukocyte Antigen (HLA) region and the strongest association for IE1A was the DRB1*13:01-DQA1*01:03-DQB1*06:03 haplotype while the main association for IE1B was DRB1*13:02-DQA1*01:02-DQB1*06:04.\n\nIn conclusion a role for HHV-6A in MS etiology is supported by an increased serological response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA genes.

immunology↗

bioRxiv2018

Intense and sustained pain reduces cortical responses to auditory stimuli: implications for the interpretation of Heterotopic Noxious Conditioning Stimulation in humans

Phasic pain stimuli are inhibited when they are applied concomitantly with a conditioning tonic stimulus at another body location (Heterotopic Noxious Conditioning Stimulation, HNCS). While this effect is thought to rely on a spino-bulbo-spinal mechanism in animals (Diffuse Noxious Inhibitory Controls, DNIC), the underlying neurophysiology in humans may further involve other pathways. In this study, we investigated the role of supraspinal mechanisms in HNCS by presenting auditory stimuli during a conditioning tonic painful stimulus (the Cold Pressor Test, CPT). Considering that auditory stimuli are not conveyed through the spinal cord, any changes in brain responses to auditory stimuli during HNCS can be ascribed entirely to supraspinal mechanisms. High-density electroencephalography (EEG) was recorded during HNCS and auditory stimuli were administered in three blocks, before, during, and after HNCS. Nociceptive Withdrawal Reflexes (NWRs) were recorded at the same time points to investigate spinal processing. Our results showed that AEPs were significantly reduced during HNCS. Moreover, the amplitude of the NWR was significantly diminished during HNCS in most participants. Given that spinal and supraspinal mechanisms operate concomitantly during HNCS, the possibility of isolating their individual contributions to DNIC-like effects in humans is questionable. We conclude that the net effects of HCNS cannot be measured independently from attentional/cognitive influences.

neuroscience↗

bioRxiv2018

A zinc knuckle gene on the Y chromosome (zkY) determines sex in Atlantic cod (Gadus morhua)

The genetic mechanisms determining sex in teleost fishes are highly variable, ranging from a single gene to complex patterns of polygenic regulation. The master sex determining gene has only been identified in very few species and there is no information about the gene in the superorder Paracanthopterygii that includes the codfishes, toadfishes and anglerfishes. Here we characterize a male-specific region of 9 kb on linkage group 11 in Atlantic cod (Gadus morhua) harboring a single gene named zkY for zinc knuckle on the Y chromosome. A diagnostic PCR test of phenotypically sexed males and females of Atlantic cod confirmed the sex-specific nature of the Y-sequence. We searched for autosomal gene copies of zkY and identified twelve highly similar genes, of which eight (zk1-zk8) code for proteins containing the zinc knuckle motif. 3D structure modelling suggests that the amino acid changes observed in six of the eight copies might influence the putative RNA-binding specificity. Cod zkY and the autosomal proteins zk1 and zk2 possess an identical zinc knuckle structure, but only the Y-specific gene zkY was expressed at high levels in the developing larvae before the onset of sex differentiation. We propose that cod zkY functions as the master masculinization gene by coding for a suppressor of germ cell division in males. PCR amplification of Y-sequences in Arctic cod (Arctogadus glacialis) and Greenland cod (Gadus macrocephalus ogac) suggests that this novel sex determining mechanism emerged in codfishes more than 7.5 million years ago.\n\nAuthor SummaryStudying the diverse sex determining genes in teleost fish may contribute to increase our understanding of sex chromosome evolution in vertebrates. To date, no sex determinant is known for the superorder Paracanthopterygii, comprising about 1340 species, including the commercially important Atlantic cod. In this study we characterize a Y-specific region of 9 kb on linkage group 11 containing a single gene named zkY for zinc knuckle on the Y chromosome. The gene is transcribed at high levels in larvae before commencement of sex differentiation and encodes a novel zinc knuckle protein that putatively binds RNA target sequences. We propose that cod zkY suppresses germ cell proliferation in the developing males by interacting with the germ-cell specific RNA regulatory network.

genetics↗