Marc Muller

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Verified

Marc verified their affiliation via an institutional email.

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• PhD in Biochemistry
• Maître de Recherche/ Senior Assistant Professor (Retired) at University of Liège

Tartrazine (E102) is a controversial coloring agent whose potential impacts on human health are not fully understood. Our study reveals the vascular disrupting effects of tartrazine (TTZ) on developing zebrafish embryos in vivo and on human umbilical vein endothelial cells in vitro. The dye was shown to cause dose-dependent hemorrhages in zebrafish...

"Persistent organic pollutants (POPs)" have a plethora of deleterious effects on humans and the environment due to their bioaccumulative, persistent, and mimicking properties. Individually, each of these chemicals has been tested and its effects measured, however they are rather found as parts of complex mixtures of which we do not fully grasp the...

Zebrafish are now widely used to study skeletal development and bone-related diseases. To that end, understanding osteoblast differentiation and function, the expression of essential transcription factors, signaling molecules, and extracellular matrix proteins is crucial. We isolated Sp7-expressing osteoblasts from 4-day-old larvae using a fluoresc...

The high temperature sex reversal process leading to functional phenotypic masculinization during development has been widely described in Nile tilapia (Oreochromis n iloticus) under laboratory or aquaculture conditions and in the wild. In this study, we selected five wild populations of O. niloticus from different river basins in Benin and produce...

Osteoarthritis is a degenerative articular disease affecting mainly aging animals and people. The extracellular matrix protein Efemp1 was previously shown to have higher turn-over and increased secretion in the blood serum, urine, and subchondral bone of knee joints in osteoarthritic patients. Here, we use the zebrafish as a model system to investi...

Detecting skeletal or bone-related deformities in model and aquaculture fish is vital for numerous biomedical studies. In biomedical research, model fish with bone-related disorders are potential indicators of various chemically induced toxins in their environment or poor dietary conditions. In aquaculture, skeletal deformities are affecting fish h...

DAF-FM DA is widely used as a live staining compound to show the presence of nitric oxide (NO) in cells. Applying this stain to live zebrafish embryos is known to indicate early centers of bone formation, but the precise (cellular) location of the signal has hitherto not been revealed. Using sections of zebrafish embryos live-stained with DAF-FM DA...

Evaluating the risks and benefits of using traditional medicinal plants is of utmost importance for a huge fraction of the human population, in particular in Northern Vietnam. Zebrafish are increasingly used as a simple vertebrate model for testing toxic and physiological effects of compounds, especially on development. Here, we tested 12 ethanolic...

Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis (OA), and osteomodulin (OMD), a proteoglycan involved in extracellular matrix mineralization, is associated with the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used Omd knockout and overexpressing...

Background Osteoarthritis (OA) is associated with metabolic and structural changes in all joint tissues. Subchondral bone sclerosis, cartilage degradation, and synovial inflammation are the main hallmarks of OA [1–3]. OMD is a keratan sulfate proteoglycan, a member of the small leucine-rich proteoglycan (SLRP) family. OMD was first identified in bo...

Persistent organic pollutants (POPs) are posing major environmental and health threats due to their stability, ubiquity, and bioaccumulation. Most of the numerous studies of these compounds deal with single chemicals, although real exposures always consist of mixtures. Thus, using different tests, we screened the effects on zebrafish larvae caused...

In this paper we perform an empirical evaluation of variants of deep learning methods to automatically localize anatomical landmarks in bioimages of fishes acquired using different imaging modalities (microscopy and radiography). We compare two methodologies namely heatmap based regression and multivariate direct regression, and evaluate them in co...

Wnt signaling is a key regulator of osteoblast differentiation and mineralization in humans and animals, mediated by the canonical Wnt/β-catenin and noncanonical signaling pathways. Both pathways are crucial in regulating osteoblastogenesis and bone formation. The zebrafish silberblick (slb) carries a mutation in wnt11f2, a gene that contributes to...

Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis (OA) and Osteomodulin (OMD), a proteoglycan involved in extracellular matrix mineralization, is associated to the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used knock-out and overexpressing male m...

The rising concerns about controversial food additives’ potential hazardous properties require extensive yet animal-minimized testing strategies. Zebrafish embryos are the ideal in vivo model representing both human and environmental health. In this study, we exposed zebrafish embryos to eight controversial food additives. Our results indicate that...

Medicinal plants play important roles in traditional medicine, and numerous compounds among them have been recognized for their antimicrobial activity. However, little is known about the potential of Vietnamese medicinal plants for antifungal activity. In this study, we examined the antagonistic activity of twelve medicinal plant species collected...

Endophytes can generate a cornucopia of marvelous bioactive secondary metabolites useful for mankind but their biodiversity and associations with host plants are still elusive. In this study, we explored the culturable endophytic microorganisms associated with 14 medicinal plants that are of high socio-economic value and/or reportedly endemic to no...

Zebrafish larvae, especially gene-specific mutants and transgenic lines, are increasingly used to study vertebrate skeletal development and human pathologies such as osteoporosis, osteopetrosis and osteoarthritis. Probiotics have been recognized in recent years as a prophylactic treatment for various bone health issues in humans. Here, we present t...

Monogenic early-onset osteoporosis (EOOP) is a rare disease defined by low bone mineral density (BMD) that results in increased risk of fracture in children and young adults. Although several causative genes have been identified, some of the EOOP causation remains unresolved. Whole-exome sequencing revealed a de novo heterozygous loss-of-function m...

In this paper, we propose variants of deep learning methods to segment head and operculum of the zebrafish larvae in microscopy images. In the first approach, we used a three-class model to jointly segment head and operculum area of zebrafish larvae from background. In the second, two-step, approach, we first trained binary segmentation model to se...

Porcine epidemic diarrhea virus (PEDV) causes diarrhea in pigs leading to severe illnesses and high mortality rates. The development of medicinal agents to treat PEDV infection is therefore crucial. In this study, antiviral activities against PEDV of ethanol and aqueous extracts of 17 Vietnamese traditional medicinal plants were evaluated using the...

In this study, we showed that crude extract of Anisomeles indica (AI-EtE) expressed its toxicity to HeLa cells with an IC50 dose of 38.8 µg/mL and to zebrafish embryos with malformations, lethality and hatching inhibition at 72-hpf at doses higher than 75 µg/mL. More interestingly, flow cytometry revealed that AI-EtE significantly promoted the numb...

Abstract Ethnopharmacological relevance Clerodendrum cyrtophyllum Turcz has been used in traditional medicine for the treatment of various diseases. In spite of its therapeutic applications, research on its toxicity and teratogenicity is still limited. Aim of the study The study aimed to investigate the developmental toxicity of the ethanol extrac...

High mitochondrial DNA (mtDNA) copy numbers are essential for oogenesis and embryogenesis and correlate with fertility of oocytes and viability of embryos. To understand the pathology and mechanisms associated with low mtDNA copy numbers, we knocked down mitochondrial transcription factor A (tfam), a regulator of mtDNA replication, during early zeb...

Prioritizing chemicals posing threats to drinking water resources is crucial for legislation considering the cost of water treatment, remediation, and monitoring. We profiled in vitro potential endocrine disrupting activities (both agonistic and antagonistic) of 18 contaminants most prevalent in Walloon raw water resources intended for drinking wat...

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and several other environment/food-borne toxic compounds induce their toxicity via the aryl hydrocarbon receptor (AhR). AhR is also modulated by various endogenous ligands e.g. highly potent tryptophan (Trp)-derivative FICZ (6-formylindolo[3,2-b]carbazole) and natural ligands abundant in the human diet e.g...

The aryl hydrocarbon receptor (AhR) mediates cellular signals in vertebrates and invertebrates with its main transcriptional regulatory function being the up-regulation of cytochrome P450 family 1 (CYP1) of metabolizing enzymes. Although several chemicals have been reported as antagonists of AhR expression, knowledge gaps exist on the chemical-stru...

Ethnopharmacological relevance Clerodendrum cyrtophyllum Turcz, a plant belonging to the Verbenaceae family, has been used in traditional medicine for the treatment of various inflammatory diseases in many Asian countries. Aim of the study: The study aimed to evaluate anti-inflammatory properties of the ethanol extract from Clerodendrum cyrthophyll...

The aryl hydrocarbon receptor (AhR) plays an important role in several biological processes such as reproduction, immunity and homoeostasis. However, little is known on the chemical-structural and physicochemical features that influence the activity of AhR antagonistic modulators. In the present report, in vitro AhR antagonistic activity evaluation...

The extracellular matrix can trigger cellular responses through its composition and structure. Major extracellular matrix components are the proteoglycans, which are composed of a core protein associated with glycosaminoglycans, among which the small leucine-rich proteoglycans (SLRPs) are the largest family. This review highlights how the codon usa...

High mitochondrial DNA (mtDNA) copy numbers are essential for oogenesis and embryogenesis and correlate with fertility of oocytes and viability of embryos. To understand the pathology and mechanisms associated with low mtDNA copy numbers, we knocked down mitochondrial transcription factor A ( Tfam ), a regulator of mtDNA replication, during early z...

Introduction: Human exposure to persistent organic pollutants (POPs) has been linked to genitourinary health-related conditions such as decreased sperm quality, hypospadias, and prostate cancer (PCa). Conventional risk assessment of POPs focuses on individual compounds. However, in real life, individuals are exposed to many compounds simultaneousl...

While humans are exposed to mixtures of persistent organic pollutants (POPs), their risk assessment is usually based on a chemical-by-chemical approach. To assess the health effects associated with mixed exposures, knowledge on mixture toxicity is required. Several POPs are potential ligands of the Aryl hydrocarbon receptor (AhR), which involves in...

There are errors the Funding statement. The correct Funding statement is as follows: RN is a Ph.D. grant holder from FRIA-FNRS (Fond pour la Formation et la Recherche dans l’Industrie et dans l’Agriculture). MM is a "Maître de Recherche" at the "Fonds National de Recherche Scientifique". This study was supported by ULiège-ARC program (Actions de Re...

Nile tilapia (Oreochromis niloticus) is an African freshwater fish that displays a genetic sex determination system (XX|XY) where high temperatures (above 32°C to 36.5°C) induce masculinization. In Nile tilapia, the thermosensitive period was reported from 10 to 30 days post fertilization. In their natural environment, juveniles may encounter high...

Male proportion and survival rates. Male proportion (%) and post-treatment survival rates (%) at 40 dpf for all progenies and treatments (control and thermal continuums and thermal control). (DOCX)

In laboratory fish research, the zebrafish Danio rerio (Cyprinidae) represents the equivalent of the mouse in mammalian research. This species has become a major model for studies in developmental and behavioural genetics, neurophysiology, biomedicine, ecotoxicology, and behavioural and evolutionary ecology. To meet the need for accurate and reprod...

Different mechanisms are involved in high temperature-induced masculinization among teleost fishes. These mechanisms need to be investigated in African catfish, a species with a XX/XY genetic sex determinism that can be overridden by high temperature (HT). The influence of HT on the three main sex steroid hormones (testosterone– T, 17β-estradiol –...

The detection of anatomical landmarks in bioimages is a necessary but tedious step for geometric morphometrics studies in many research domains. We propose variants of a multi-resolution tree-based approach to speed-up the detection of landmarks in bioimages. We extensively evaluate our method variants on three different datasets (cephalometric, ze...

Although the involvement of Ser/Arg-rich (SR) proteins in RNA metabolism is well documented, their role in vertebrate development remains elusive. We, therefore, elected to take advantage of the zebrafish model organism to study the SR genes' functions using the splicing morpholino (sMO) microinjection and the programmable site-specific nucleases....

Of all pathogenic mitochondrial DNA (mtDNA) mutations in humans, ~25% is de novo, although the occurrence in oocytes has never been directly assessed. We used next generation sequencing to detect point mutations directly in the mtDNA of 3-15 individual mature oocytes and three somatic tissues from eight zebrafish females. Various statistical and bi...

Reporter gene assays incorporating nuclear receptors (estrogen, androgen, thyroid β and PPARγ2) have been implemented to assess the endocrine activity of 13 mycotoxins and their mixtures. As expected, zearalenone and its metabolites α-zearalenol and β- zearalenol turned out to have the strongest estrogenic potency (EC50 8,7 10-10 ± 0,8; 3,1 10-11 ±...

We studied the mtDNA bottleneck in zebrafish to elucidate size, timing, and variation in germline and non-germline cells. Mature zebrafish oocytes contain, on average, 19.0 × 106 mtDNA molecules with high variation between oocytes. During embryogenesis, the mtDNA copy number decreases to ∼170 mtDNA molecules per primordial germ cell (PGC), a number...

Physiological modifications in near weightlessness, as experienced by astronauts during space flight, have been the subject of numerous studies. Various animal models have been used on space missions or in microgravity simulation on ground to understand the effects of gravity on living animals. Here, we used the zebrafish larvae as a model to study...

In the last few years, the advent of metal halide perovskite solar cells has revolutionized the prospects of next-generation photovoltaics. As this technology is maturing at an exceptional rate, research on its environmental impact is becoming increasingly relevant.

Intensive development of organometal halide perovskite solar cells has lead to a dramatic surge in power conversion efficiency up to 20%. Unfortunately, the most efficient perovskite solar cells all contain lead (Pb), which is an unsettling flaw that leads to severe environmental concerns and is therefore a stumbling block envisioning their large-s...

Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic and developmental studies. Our understanding of the physiological consequences of altered gravity in an entire organism is still incomplete. We used altered gravity and drug treatment experiments to evaluate their effects specifically on bone formation and...

Thirteen individual organochlorine compounds at 3 concentrations (80, 400, and 2000 ng/mL culture medium), as well as mixtures, were assayed for the estrogen receptor (ER) activation or inhibition, using a luciferase reporter gene assay (RGA). None of the PCB 138, 153, or 180 or their mixture induced a response in the RGA. o,p󸀠-DDT was the most pot...

Bone morphogenetic proteins (BMPs) control many developmental and physiological processes, including skeleton formation and homeostasis. Previous studies in zebrafish revealed the crucial importance of proper BMP signaling before 48 h post-fertilization (hpf) for cartilage formation in the skull. Here, we focus on the involvement of the BMP pathway...

Zebrafish is increasingly used to assess biological properties of chemical substances and thus is becoming a specific tool for toxicological and pharmacological studies. The effects of chemical substances on embryo survival and development are generally evaluated manually through microscopic observation by an expert and documented by several typica...

Several in vivo stainings, such as Calcein, Alizarin Red and Quercetin are commonly used to visualize ossification in living teleost specimen. These staining techniques represent important tools for bone research in fish, but do not visualize cartilage. In the present study, we show that nitric oxide (NO) labelling by DAF-FM DA visualizes both bone...

One of the major challenges when testing drug candidates targeted at a specific pathway in whole animals is the discrimination between specific effects and unwanted, off-target effects. Here we used the zebrafish to define several developmental defects caused by impairment of Egf signaling, a major pathway of interest in tumor biology. We inactivat...

Cranial cartilage derives mainly from cranial neural crest cells and its formation requires fibroblast growth factor (Fgf) signaling for early differentiation and survival of developing chondrocytes as well as patterning of the endodermal pouches. Here, we investigate the role of Fgf receptors in chondrocyte maturation at later stages, beyond 24hpf...

The cartilaginous elements forming the pharyngeal arches of the zebrafish derive from cranial neural crest cells. Their proper differentiation and patterning are regulated by reciprocal interactions between neural crest cells and surrounding endodermal, ectodermal and mesodermal tissues. In this study, we show that the endodermal factors Runx3 and...

Double fluorescent in situ hybridization for sox9a (Cy3, red) and egr1 (FITC, green) in 72 hpf larvae. Lateral view, anterior to the right, the movie proceeds from the right side going to the center of the embryo. sox9a is expressed in pharyngeal cartilage cells and egr1 is expressed in pharyngeal endoderm. sox9a and egr1 mRNAs never colocalize and...

Double fluorescent in situ hybridization for sox9b (Cy3, red) and egr1 (FITC, green) at 72 hpf. Lateral view, anterior to the right, the movie proceeds from the right side going to the center of the embryo. sox9b and egr1 are expressed in pharyngeal endoderm cells and colocalize in the same expression domains. (MP4)

casanova mutants, lacking endoderm, do not express sox9b or fsta at 48 hpf. Lateral views of in situ hybridizations (A–D) with indicated markers, anterior to the left. Scale bars 100 µm. Homozygous cas−/− do not express fsta (A,B) nor sox9b (C,D) compared to wild-type or heterozygous cas+/−. Pharyngeal endoderm (pe), otic vesicle (ov). (TIF)

Double fluorescent in situ hybridization for fli1 (Cy3, red) and egr1 (FITC, green) in 47 hpf zebrafish embryos. Lateral view, anterior to the left, the movie proceeds from the left side going to the center of the embryo. fli1 is expressed in cranial neural crest cells (pharyngeal cartilage precursor cells) and in endothelium. fli1 displays the cha...

Double fluorescent in situ hybridization for fli1 (Cy3, red) and egr1 (FITC, green) at 4 dpf. Lateral view, anterior to the right, the movie proceeds from the right side going to the center of the embryo. fli1 is expressed in pharyngeal cartilages and in endothelium. Egr1 is expressed in the phrayngeal endoderm and oral epithelium. fli1 and egr1 mR...

casanova mutants, lacking endoderm, do not express egr1 at 48 hpf. Single in situ hybridization for egr1 in casanova mutants. Lateral (A,B) and dorsal (C,D) views, anterior to the left. Scale bars 100 µm. (A,C) Wild-type or heterozygous cas+/− express egr1 in the pharyngeal endoderm (pe). (B,D) Homozygous cas−/− do not express egr1 in the pharyngea...

Here we show the cloning and characterization of a novel homolog of prepro C-RFa cDNA from Cyprinus carpió. The deduced preprohormone precursor of 115 amino acids leads to a mature bioactive peptide of 20 amino acids with identical sequence to other teleost C-RFa. Modeling of the mature C-RFa peptide highlighted significant similarity to homologous...

Standard toxicological assays using the zebrafish model system evaluate lethality and teratogenicity upon exposure during the first 2days after fertilization. We tested the biological effects of several widely used drugs on zebrafish by acute treatment for 24h starting at late embryonic stages, between 48 and 72h post-fertilization. For 4 out of 6...

The pituitary is a complex gland comprising different cell types each secreting specific hormones. The extensive network of signaling molecules and transcription factors required for determination and terminal differentiation of specific cell types is still not fully understood. The SRY-like HMG-box (SOX) transcription factor Sox4 plays important r...

Constructed wetland systems (CWS) have been used as a low cost bio-filtration system to treat farm wastewater. While studies have shown that CWS are efficient in removing organic compounds and pathogens, there is limited data on the presence of hormones in this type of treatment system. The objective of this study was to evaluate the ability of the...

Here we show the cloning and characterization of a novel homolog of prepro C-RFa cDNA from Cyprinus carpió. The deduced preprohormone precursor of 115 amino acids leads to a mature bioactive peptide of 20 amino acids with identical sequence to other teleost C-RFa. Modeling of the mature C-RFa peptide highlighted significant similarity to homologous...

The increasing availability and use of sports supplements is of concern as highlighted by a number of studies reporting endocrine disruptor contamination in such products. The health food supplement market, including sport supplements, is growing across the Developed World. Therefore, the need to ensure the quality and safety of sport supplements f...

The mycotoxin zearalenone (ZEN) is a secondary metabolite of fungi which is produced by certain species of the genus Fusarium and can occur in cereals and other plant products. Reporter gene assays incorporating natural steroid receptors and the H295R steroidogenesis assay have been implemented to assess the endocrine disrupting activity of ZEN and...

This chapter introduces the main topics of research that have benefited so far from the space environment (reduced gravity, ambient radiation, vacuum, etc.), and provides an outlook for future research development. By convention, it is split into two fields: physical sciences/engineering and life sciences. Physical science and engineering studies c...

Zebrafish were proposed as an alternative to mammalian models to assess the efficacy and toxicity of antileukemic drugs. Due to the limited number of transgenic zebrafish leukemia models, we explored human leukemic cell xenograft in zebrafish embryos. Human leukemic cell lines and blast cells sorted from patients with acute myelogenous leukemia wer...

In many biological studies, scientists assess effects of experimental conditions by visual inspection of microscopy images. They are able to observe whether a protein is expressed or not, if cells are going through normal cell cycles, how organisms evolve in different experimental conditions, etc. But, with the large number of images acquired in hi...

Zebrafish is increasingly used to assess biological properties of chemical substances and thus becomes a specific tool for toxicological and pharmacological studies. The effects of chemical substances on embryo development are generally evaluated manually through microscopic observation by an expert and documented by several typical photographs. Id...