A5081370735- Zebrafish Biomedical Research Applications
- Neurogenesis and neuroplasticity mechanisms
- Developmental Biology and Gene Regulation
- Axon Guidance and Neuronal Signaling
- Nerve injury and regeneration
- Psychiatric care and mental health services
- Congenital heart defects research
- Organ Transplantation Techniques and Outcomes
- Neuroinflammation and Neurodegeneration Mechanisms
- Liver Disease and Transplantation
- Health and Medical Studies
- RNA modifications and cancer
- Renal Transplantation Outcomes and Treatments
- Neurogenetic and Muscular Disorders Research
- Cerebrospinal fluid and hydrocephalus
- RNA Research and Splicing
- Psychology, Coaching, and Therapy
- Genomics and Chromatin Dynamics
- Spinal Cord Injury Research
- Fetal and Pediatric Neurological Disorders
- MicroRNA in disease regulation
- Schizophrenia research and treatment
- Animal Genetics and Reproduction
- Neurobiology and Insect Physiology Research
- Advanced Neuroimaging Techniques and Applications
Klinik und Poliklinik für Psychiatrie und Psychotherapie
1992-2025
University Hospital Leipzig
2023-2025
University of Edinburgh
2015-2024
Universität Ulm
2004-2024
Discovery Centre
2019-2024
TU Dresden
2021-2024
Gesundheitsamt
2024
Berlin-Brandenburger Centrum für Regenerative Therapien
2023
Mott MacDonald (United Kingdom)
2017-2022
The University of Sydney
2009-2021
The trimeric Sec61/SecY complex is a protein-conducting channel (PCC) for secretory and membrane proteins. Although Sec complexes can form oligomers, it has been suggested that single copy may serve as an active PCC. We determined subnanometer-resolution cryo-electron microscopy structures of eukaryotic ribosome-Sec61 complexes. In combination with biochemical data, we found in both idle states, the not oligomeric interacts mainly via two cytoplasmic loops universal ribosomal adaptor site....
Abstract Spinal cord injury leads to a massive response of innate immune cells in non-regenerating mammals, but also successfully regenerating zebrafish. However, the role successful regeneration is poorly defined. Here we show that inhibiting inflammation reduces and promoting it accelerates axonal spinal-lesioned zebrafish larvae. Mutant analyses peripheral macrophages, not neutrophils or microglia, are necessary for repair. Macrophage-less irf8 mutants prolonged with elevated levels Tnf-α...
Using axonal tracers, we characterized the neurons projecting from brain to spinal cord as well terminal fields of ascending projections in adult zebrafish with unlesioned or transected cords. Twenty distinct nuclei were found project cord. These similar those closely related goldfish, except that additionally parvocellular preoptic nucleus, medial octavolateralis and nucleus tangentialis, but not facial lobe, projected zebrafish. Terminal axons, visualized by anterograde tracing, seen...
The α-2,8-linked polysialic acid (PSA) modification of the neural cell adhesion molecule (NCAM) modulates morphogenetic interactions. PSA is strongly expressed during development and generally down-regulated in adult. However, it remains prominent some areas brain, e.g., hippocampus. We assayed functional role(s) synaptic plasticity hippocampus two experimental paradigms by removing with endoneuraminidase NE (endo-N) an enzyme which specifically cleaves acid. (1) acquisition retention...
The mammalian spinal cord does not regenerate motor neurons that are lost as a result of injury or disease. Here we demonstrate adult zebrafish, which show functional regeneration, capable neuron regeneration. After lesion, the ventricular zone shows widespread increase in proliferation, including slowly proliferating olig2-positive (olig2 + ) ependymo-radial glial progenitor cells. Lineage tracing olig2:green fluorescent protein transgenic fish indicates these cells switch from gliogenic...
Background: Concerns are frequently expressed that working might worsen the mental health of people with severe illness (SMI). Several studies Individual Placement and Support (IPS), however, have found associations between better nonvocational outcomes. IPS has been to double return work SMI in 6 European countries. Aims: To explore separately IPS, returning work, clinical social Methods: Patients (n = 312) a randomized controlled trial centers were followed up for 18 months. Results: There...
Genome-wide association studies identified noncoding SNPs associated with type 2 diabetes and obesity in linkage disequilibrium (LD) blocks encompassing HHEX-IDE introns of CDKAL1 FTO [Sladek R, et al. (2007) Nature 445:881–885; Steinthorsdottir V, Nat. Genet 39:770–775; Frayling TM, Science 316:889–894]. We show that these LD contain highly conserved elements overlap the genomic regulatory transcription factor genes HHEX , SOX4 IRX3 . report human risk drive expression endoderm or pancreas...
Recently our laboratory described an efficient method for generating retroviral provirus insertions in the zebrafish germ line, and we showed that induce embryonic mutations at a frequency of roughly one mutant per 70 insertions. To date have isolated four insertional mutants and, using proviruses as molecular tag, cloned genes disrupted three them. The all lie within or just 5' first coding exon, point opposite transcriptional orientation from gene, disrupt transcription. Here present...
Adult fish, in contrast to mammals, are capable of regenerating axonal tracts as well cells and even entire tissues the central nervous system (CNS). The zebrafish is a powerful genetic model for studies on developing CNS now emerging regeneration model. Here we review recent progress adult paradigms ranging from re-growth models those tissue regeneration. Moreover, tools that have become available elucidate factors contributing successful Since many molecular pathways shared between it...
The autosomal recessive neurodegenerative disease spinal muscular atrophy (SMA) results from low levels of survival motor neuron (SMN) protein; however, it is unclear how reduced SMN promotes SMA development. Here, we determined that ubiquitin-dependent pathways regulate neuromuscular pathology in SMA. Using mouse models SMA, observed widespread perturbations ubiquitin homeostasis, including ubiquitin-like modifier activating enzyme 1 (UBA1). physically interacted with UBA1 neurons, and...
Abstract The inhibitory extracellular matrix in a spinal lesion site is major impediment to axonal regeneration mammals. In contrast, the zebrafish allows substantial axon re-growth, leading recovery of movement. However, little known about regulation and composition growth-promoting matrix. Here we demonstrate that activity Wnt/β-catenin pathway fibroblast-like cells pivotal for re-growth functional recovery. signaling induces expression col12a1a/b deposition Collagen XII, which necessary...
Protein synthesis in all living organisms occurs on ribonucleoprotein particles, called ribosomes. Despite the universality of this process, eukaryotic ribosomes are significantly larger size than their bacterial counterparts due part to presence 80 r proteins rather 54 bacteria. Using cryoelectron microscopy reconstructions a translating plant ( Triticum aestivum ) 80S ribosome at 5.5-Å resolution, together with 6.1-Å map Saccharomyces cerevisiae ribosome, we have localized and modeled...
Abstract Background Although the mechanisms underlying brain patterning and regionalization are very much conserved, morphology of different regions is extraordinarily variable across vertebrate phylogeny. This especially manifest in telencephalon, where most dramatic variation seen between ray-finned fish, which have an everted all other vertebrates, evaginated telencephalon. The that generate these distinct morphologies not well understood. Results Here we study morphogenesis zebrafish...
In adult zebrafish, relatively quiescent progenitor cells show lesion-induced generation of motor neurons. Developmental neuron from the spinal domain (pMN) sharply declines already at 48 hours post-fertilisation (hpf). After that, mostly oligodendrocytes are generated same domain. We demonstrate here that within after a lesion or specific genetic ablation neurons 72 hpf, pMN reverts to expense oligodendrogenesis. contrast, dorsal Pax2-positive interneurons was not altered. Larval...
Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report to date largest genome-wide association study (GWAS) identify genetic risk factors for diverticular disease.Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases 419 135 controls European descent. Associations were replicated in sample 3893 2829...
Adult zebrafish, in contrast to mammals, regrow axons descending from the brainstem after spinal cord transection. L1.1, a homolog of mammalian recognition molecule L1, is upregulated by neurons during axon regrowth. However, its functional relevance for regeneration unclear. Here, we show with novel morpholino-based approach that reducing L1.1 protein expression leads impaired locomotor recovery as well reduced regrowth and synapse formation supraspinal origin This indicates contributes...
Murine retroviral vectors carrying an enhancer detection cassette were used to generate 95 transgenic lines of fish in which reporter expression is observed distinct patterns during embryonic development. We mapped 65 insertion sites the as yet unfinished zebrafish genome sequence. Many integrations map close previously known developmental genes, including transcription factors Pax, Hox, Sox, Pou, Otx, Emx, zinc-finger and bHLH gene families. In most cases, activated provirus located in, or...
We analyzed changes in the expression of mRNAs for axonal growth-promoting cell recognition molecules L1.1, L1.2, and neural adhesion molecule (NCAM) after a rostral (proximal) or caudal (distal) spinal cord transection adult zebrafish. One class cerebrospinal projection nuclei (represented by nucleus medial longitudinal fascicle, intermediate reticular formation, magnocellular octaval nucleus) showed robust regenerative response both types lesions as determined retrograde tracing and/or...
In contrast to mammals, the spinal cord of adult zebrafish has capacity reinitiate generation motor neurons after a lesion. Here we show that genes involved in neuron development, i.e., ventral morphogen sonic hedgehog (shha), as well transcription factors nkx6.1 and pax6, together with Tg(olig2:egfp) transgene, are expressed unlesioned zebrafish. Expression is found ependymoradial glial cells lining central canal ventrodorsal positions match expression domains these developing neural tube....