Actigraphy-based assessment of circadian rhythmicity and sleep in patients with Usher syndrome type 2a: A case-control study.

This study aimed to improve our understanding of sleep problems as a comorbidity of hereditary deaf-blindness due to Usher syndrome type 2a. Fifteen patients with Usher syndrome type 2a with a conclusive genetic diagnosis and 15 unaffected controls participated in comprehensive sleep and activity assessments for 2 weeks, using the MotionWatch 8 actigraph and consensus sleep diary. Various sleep parameters including sleep opportunity window, sleep latency, sleep efficiency, and self-reported sleep quality were analysed.

foxe1 mutant zebrafish show indications of a hypothyroid phenotype and increased sensitivity to ethanol for craniofacial malformations.

Background: FOXE1 mutations in humans are associated with cleft palate and hypothyroidism. We previously developed a foxe1 mutant zebrafish demonstrating mineralization defects in larvae. In the present study, we investigate the thyroid status and skeletal phenotype of adult foxe1 mutants.

Melatonin as an anti-stress signal: effects on an acute stress model and direct actions on interrenal tissue in goldfish.

Background: Melatonin is a key hormone in regulation of circadian rhythms, and involved in many rhythmic functions, such as feeding and locomotor activity. Melatonin reportedly counteracts stress responses in many vertebrates, including fish. However, targets for this action of melatonin and underlying mechanisms remain unknown.

Evaluation of Sleep Quality and Fatigue in Patients with Usher Syndrome Type 2a.

Purpose: To study the prevalence, level, and nature of sleep problems and fatigue experienced by Usher syndrome type 2a (USH2a) patients.

Design: Cross-sectional study.

Participants: Fifty-six genetically confirmed Dutch patients with syndromic USH2a and 120 healthy controls.

Precise targeting for 3D cryo-correlative light and electron microscopy volume imaging of tissues using a FinderTOP.

Cryo-correlative light and electron microscopy (cryoCLEM) is a powerful strategy to high resolution imaging in the unperturbed hydrated state. In this approach fluorescence microscopy aids localizing the area of interest, and cryogenic focused ion beam/scanning electron microscopy (cryoFIB/SEM) allows preparation of thin cryo-lamellae for cryoET. However, the current method cannot be accurately applied on bulky (3D) samples such as tissues and organoids.

Disruption of the gene in zebrafish reveals conserved functions in development of the craniofacial skeleton and the thyroid.

Mutations in the FOXE1 gene are implicated in cleft palate and thyroid dysgenesis in humans. To investigate whether zebrafish could provide meaningful insights into the etiology of developmental defects in humans related to FOXE1, we generated a zebrafish mutant that has a disruption in the nuclear localization signal in the foxe1 gene, thereby restraining nuclear access of the transcription factor. We characterized skeletal development and thyroidogenesis in these mutants, focusing on embryonic and larval stages.

Targeting fibroblast growth factor receptors causes severe craniofacial malformations in zebrafish larvae.

Background And Objective: A key pathway controlling skeletal development is fibroblast growth factor (FGF) and FGF receptor (FGFR) signaling. Major regulatory functions of FGF signaling are chondrogenesis, endochondral and intramembranous bone development. In this study we focus on , as mutations in this gene are found in patients with craniofacial malformations.

Branchial nitrogen cycle symbionts can remove ammonia in fish gills.

Knowledge of the mechanisms by which fish excrete their metabolic nitrogenous waste and insights into nitrogen cycling in aquaculture systems is of utmost importance to improve the sustainable commercial production of fish. In fish, most nitrogenous waste is excreted via the gills as ammonia, a potentially toxic nitrogenous compound. In this study; activity assays, physiological experiments, molecular analysis and microscopy were used to show that the gills of fish harbor a unique combination of hitherto overlooked nitrogen-cycle microorganisms that can theoretically detoxify excreted ammonia by converting it into inert dinitrogen gas.

Long-lasting effects of dexamethasone on immune cells and wound healing in the zebrafish.

This study assessed the lasting impact of dexamethasone (DEX) exposure during early development on tissue repair capacity at later life stages (5, 14, and 24 days post fertilization [dpf]) in zebrafish larvae. Using the caudal fin amputation model, we show that prior exposure to DEX significantly delays but does not prevent wound healing at all life stages studied. DEX-induced impairments on wound healing were fully restored to normal levels with longer post amputation recovery time.

Scales tell a story on the stress history of fish.

Fish faced with stressful stimuli launch an endocrine stress response through activation of the hypothalamic-pituitary-interrenal (HPI-) axis to release cortisol into the blood. Scientifically validated biomarkers to capture systemic cortisol exposure over longer periods of time are of utmost importance to assess chronic stress in governmental, wildlife, aquaculture and scientific settings. Here we demonstrate that cortisol in scales of common carp (Cyprinus carpio L.

Identification of novel osteogenic compounds by an ex-vivo sp7:luciferase zebrafish scale assay.

Tight interactions among different cell types contributing to bone formation are of key importance in the maintenance of bone homeostasis. Based on the high similarity in responses to (anti)osteogenic signals between zebrafish scales and mammalian bone, we developed and validated a model to screen large numbers of compounds using ex-vivo cultured scales of a sp7:luciferase transgenic zebrafish. This model combines the high predictive value of explant cultures with quick, sensitive, and quantifiable readout converging the effects via various pathways including WNT-signaling, to SP7/osterix promoter activity.

Corticotropin-releasing factor-binding protein (CRF-BP) inhibits CRF- and urotensin-I-mediated activation of CRF receptor-1 and -2 in common carp.

Corticotropin-releasing factor-binding protein (CRF-BP) is considered a key determinant for CRF receptor (CRF-R) activation by CRF and several related peptides. Earlier studies have shown that the CRF system is highly conserved in gene structures throughout evolution, yet little is known about the evolutionary conservation of its biological functions. Therefore, we address the functional properties of CRF-BP and CRF-Rs in a teleost fish (common carp; Cyprinus carpio L.

Arachidonic acid enhances turnover of the dermal skeleton: studies on zebrafish scales.

In fish nutrition, the ratio between omega-3 and omega-6 poly-unsaturated fatty acids influences skeletal development. Supplementation of fish oils with vegetable oils increases the content of omega-6 fatty acids, such as arachidonic acid in the diet. Arachidonic acid is metabolized by cyclooxygenases to prostaglandin E2, an eicosanoid with effects on bone formation and remodeling.

Recombinant human leptin attenuates stress axis activity in common carp (Cyprinus carpio L.).

Proper functioning of the endocrine stress axis requires communication between the stress axis and other regulatory mechanisms. We here describe an intimate interplay between the stress axis and recombinant human leptin (rhLeptin) in a teleostean fish, the common carp Cyprinus carpio. Restraint stress (by netting up to 96h) increased plasma cortisol but did not affect hepatic leptin expression.

Subfunctionalization of POMC paralogues in Senegalese sole (Solea senegalensis).

The precursor protein proopiomelanocortin (POMC) gives rise to a variety of biologically active peptides through cell-specific posttranslational processing. Two transcripts of pomc were found in the flatfish Solea senegalensis (ssePOMC-A and ssePOMC-B), that most likely represent subfunctionalized paralogues: ssePOMC-A lacks the N-terminal cleavage site for β-MSH, whereas ssePOMC-B cannot yield ACTH and completely lacks the opioid consensus sequence in the β-END region. An analysis of nucleotide substitution rates shows that the POMC-derived peptides possess well-conserved regions under purifying selection, except the β-END derived from POMC-B, which has undergone positive selection.

Trpv5/6 is vital for epithelial calcium uptake and bone formation.

Calcium is an essential ion serving a multitude of physiological roles. Aside from its role as a second messenger, it is an essential component of the vertebrate bone matrix. Efficient uptake and storage of calcium are therefore indispensable for all vertebrates.

Matrix metalloproteinases in osteoclasts of ontogenetic and regenerating zebrafish scales.

Matrix metalloproteinases (MMPs) are key enzymes in the turnover of extracellular matrix in health, disease, development and regeneration. We have studied zebrafish scale regeneration to ascertain the role of MMP-2 and MMP-9 in these processes. Scales were plucked from the surface of anaesthetised adult male zebrafish, and the scales that regenerated in the scale pocket were recovered at various time points after plucking.

Zebrafish development and regeneration: new tools for biomedical research.

Basic research in pattern formation is concerned with the generation of phenotypes and tissues. It can therefore lead to new tools for medical research. These include phenotypic screening assays, applications in tissue engineering, as well as general advances in biomedical knowledge.

Corticotropin-releasing factor (CRF) and CRF-binding protein expression in and release from the head kidney of common carp: evolutionary conservation of the adrenal CRF system.

Corticotropin-releasing factor (CRF) plays a central role in the regulation of the stress axis. In mammals, CRF as well as its receptors and its CRF-binding protein (CRF-BP) are expressed in a variety of organs and tissues outside the central nervous system. One of these extrahypothalamic sites is the adrenal gland, where the paracrine actions of adrenal CRF influence cortical steroidogenesis and adrenal blood flow.

Central and peripheral interleukin-1beta and interleukin-1 receptor I expression and their role in the acute stress response of common carp, Cyprinus carpio L.

In fish, the hypothalamus-pituitary-interrenal axis (HPI-axis), the equivalent of the hypothalamus-pituitary-adrenal axis (HPA-axis) in mammals, is activated during stress and leads to production and release of cortisol by the interregnal cells in the head kidney. In mammals, the cytokine interleukin-1beta (IL-1beta) takes a key position in the innate immune and inflammatory responses and influences the HPA-axis. In fish, studies that address the effects of cytokines on HPI-axis activation are limited.

Molecular biology and physiology of the melanocortin system in fish: a review.

The melanocortin system consists of melanocortin peptides derived from the proopiomelanocortin gene (in particular adrenocorticotropic hormone, ACTH, and melanocyte-stimulating hormones, MSH) and five melanocortin receptor subtypes (MC1R-MC5R). Knowledge of the melanocortin system in fish is still limited, but information on the receptor part of the system is very rapidly growing. The melanocortin receptors (MCRs) have been recently cloned from several species of fish.

CRF and stress in fish.

The endocrine stress response is pivotal in vertebrate physiology. The stress hormone cortisol-the end product of the endocrine stress axis-(re-)directs energy flows for optimal performance under conditions where homeostasis may be or become at risk. Key players in the continuous adaptation process are corticotropin-releasing factor (CRF) from the hypothalamic nucleus preopticus (NPO), pituitary adrenocorticotropic hormone (ACTH) and cortisol produced by the interrenal cells in the headkidney (adrenal equivalent of fish).

Characterization of an iodothyronine 5'-deiodinase in gilthead seabream (Sparus auratus) that is inhibited by dithiothreitol.

Iodothyronine deiodinases catalyze the conversion of the thyroid prohormone T(4) to T(3) by outer ring deiodination (ORD) of the iodothyronine molecule. The catalytic cycle of deiodinases is considered to be critically dependent on a reducing thiol cosubstrate that regenerates the selenoenzyme to its native state. The endogenous cosubstrate has still not been firmly identified; in studies in vitro the sulfhydryl reagent dithiothreitol (DTT) is commonly used to activate ORD.

Regulation of the stress response in early vertebrates.

The acute stress response is a key regulatory system for the maintenance of homeostatic equilibrium that is activated upon an imminent or ongoing disturbance of the "milieu interieur". In general, the stress response in bony fish is similar to that of mammals. The recent cloning and characterization of corticotropin-releasing hormone-binding protein (CRH-BP) in carp (Cyprinus carpio L.