ORCID Profile
0000-0003-3844-0143
Current Organisation
Peter MacCallum Cancer Centre
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Publisher: Cold Spring Harbor Laboratory
Date: 22-08-2019
DOI: 10.1101/744300
Abstract: In order to study the adaptation scope of the fish respiratory organ and the O 2 metabolism due to endurance training, we subjected adult zebrafish ( Danio rerio ) to endurance exercise for 5 weeks. After the training period, the swimmer group showed a significant increase in swimming performance, body weight and length. In scanning electron microscopy of the gills, the average length of centrally located primary filaments appeared significantly longer in the swimmer than in the non-trained control group (+6.1%, 1639 µ m vs. 1545 µ m, p=0.00043) and the average number of secondary filaments increased significantly (+7.7%, 49.27 vs. 45.73, p=9e-09). Micro-computed tomography indicated a significant increase in the gill volume (p=0.048) by 11.8% from 0.490 mm 3 to 0.549 mm 3 . The space-filling complexity dropped significantly (p=0.0088) by 8.2% from 38.8% to 35.9%., i.e. making the gills of the swimmers less compact. Respirometry after 5 weeks showed a significantly higher oxygen consumption (+30.4%, p=0.0081) of trained fish during exercise compared to controls. Scanning electron microscopy revealed different stages of new secondary filament budding, which happened at the tip of the primary lamellae. Using BrdU we could confirm that the growth of the secondary filaments took place mainly in the distal half and the tip and for primary filaments mainly at the tip. We conclude that the zebrafish respiratory organ - unlike the mammalian lung - has a high plasticity, and after endurance training increases its volume and changes its structure in order to facilitate O 2 uptake. Adult zebrafish show an increase of their gill volume after endurance training, likely to adjust for the increased oxygen demand measured with respirometry during swimming.
Publisher: Public Library of Science (PLoS)
Date: 05-02-2020
Publisher: Cold Spring Harbor Laboratory
Date: 26-07-2023
DOI: 10.1101/2023.07.24.550437
Abstract: The liver is a remarkable organ that can regenerate in response to injury. Depending on the extent of injury, the liver can undergo compensatory hyperplasia or fibrosis. Despite decades of research, the molecular mechanisms underlying these processes are poorly understood. Here, we developed a new model to study liver regeneration based on cryoinjury. To visualise liver regeneration at cellular resolution, we adapted the CUBIC tissue-clearing approach. Hepatic cryoinjury induced a localised necrotic and apoptotic lesion characterised by inflammation and infiltration of innate immune cells. Following this initial phase, we observed fibrosis, which resolved as regeneration re-established homeostasis in 30 days. Importantly, this approach enables the comparison of healthy and injured parenchyma with an in idual animal, providing unique advantages to previous models. In summary, the hepatic cryoinjury model provides a fast and reproducible method for studying the cellular and molecular pathways underpinning fibrosis and liver regeneration.
Publisher: BMJ
Date: 26-04-2019
Publisher: MDPI AG
Date: 02-03-2020
Abstract: Type 2 diabetes mellitus (T2DM) is a chronic progressive disease characterized by insulin resistance and insufficient insulin secretion to maintain normoglycemia. The majority of T2DM patients bear amyloid deposits mainly composed of islet amyloid polypeptide (IAPP) in their pancreatic islets. These—originally β-cell secretory products—extracellular aggregates are cytotoxic for insulin-producing β-cells and are associated with β-cell loss and inflammation in T2DM advanced stages. Due to the absence of T2DM preventive medicaments and the presence of only symptomatic drugs acting towards increasing hormone secretion and action, we aimed at establishing a novel disease-modifying therapy targeting the cytotoxic IAPP deposits in order to prevent the development of T2DM. We generated a vaccine based on virus-like particles (VLPs), devoid of genomic material, coupled to IAPP peptides inducing specific antibodies against aggregated, but not monomeric IAPP. Using a mouse model of islet amyloidosis, we demonstrate in vivo that our vaccine induced a potent antibody response against aggregated, but not soluble IAPP, strikingly preventing IAPP depositions, delaying onset of hyperglycemia and the induction of the associated pro-inflammatory cytokine Interleukin 1β (IL-1β). We offer the first cost-effective and safe disease-modifying approach targeting islet dysfunction in T2DM, preventing pathogenic aggregates without disturbing physiological IAPP function.
Publisher: Cold Spring Harbor Laboratory
Date: 07-06-2019
DOI: 10.1101/662536
Abstract: During heart regeneration in the zebrafish, fibrotic tissue is replaced by newly formed cardiomyocytes derived from pre-existing ones. It is unclear whether the heart is comprised of several cardiomyocyte populations bearing different capacity to replace lost myocardium. Here, using sox10 genetic fate mapping, we identified a subset of pre-existent cardiomyocytes in the adult zebrafish heart with a distinct gene expression profile that expanded massively after cryoinjury. Genetic ablation of sox10 + cardiomyocytes severely impaired cardiac regeneration revealing that they play a crucial role for heart regeneration.
Publisher: Public Library of Science (PLoS)
Date: 28-06-2017
No related grants have been discovered for Marcos Sande-Melon.