ADA2 regulates inflammation and hematopoietic stem cell emergence via the A2bR pathway in zebrafish.

Deficiency of adenosine deaminase 2 (DADA2) is an inborn error of immunity caused by loss-of-function mutations in the adenosine deaminase 2 (ADA2) gene. Clinical manifestations of DADA2 include vasculopathy and immuno-hematological abnormalities, culminating in bone marrow failure. A major gap exists in our knowledge of the regulatory functions of ADA2 during inflammation and hematopoiesis, mainly due to the absence of an ADA2 orthologue in rodents. Exploring these mechanisms is essential for understanding disease pathology and developing new treatments. Zebrafish possess two ADA2 orthologues, cecr1a and cecr1b, with the latter showing functional conservation with human ADA2. We establish a cecr1b-loss-of-function zebrafish model that recapitulates the immuno-hematological and vascular manifestations observed in humans. Loss of Cecr1b disrupts hematopoietic stem cell specification, resulting in defective hematopoiesis. This defect is caused by induced inflammation in the vascular endothelium. Blocking inflammation, pharmacological modulation of the A2r pathway, or the administration of the recombinant human ADA2 corrects these defects, providing insights into the mechanistic link between ADA2 deficiency, inflammation and immuno-hematological abnormalities. Our findings open up potential therapeutic avenues for DADA2 patients.

Protocol for the analysis of hematopoietic lineages in the whole kidney marrow of adult zebrafish.

The whole kidney marrow (WKM) is the site for hematopoiesis in the adult zebrafish. Here, we present a protocol for analyzing hematopoietic lineages in the WKM of adult zebrafish. We describe steps for the isolation of hematopoietic cells from the WKM, the downstream analysis of total marrow cellularity, and analysis of cell populations by flow cytometry. We then detail procedures for May-Grünwald-Giemsa staining for analysis of cellular morphology and phenotyping. For complete details on the use and execution of this protocol, please refer to Mahony et al.1.

Lineage skewing and genome instability underlie marrow failure in a zebrafish model of GATA2 deficiency.

Inherited bone marrow failure associated with heterozygous mutations in GATA2 predisposes toward hematological malignancies, but the mechanisms remain poorly understood. Here, we investigate the mechanistic basis of marrow failure in a zebrafish model of GATA2 deficiency. Single-cell transcriptomics and chromatin accessibility assays reveal that loss of gata2a leads to skewing toward the erythroid lineage at the expense of myeloid cells, associated with loss of cebpa expression and decreased PU.1 and CEBPA transcription factor accessibility in hematopoietic stem and progenitor cells (HSPCs). Furthermore, gata2a mutants show impaired expression of npm1a, the zebrafish NPM1 ortholog. Progressive loss of npm1a in HSPCs is associated with elevated levels of DNA damage in gata2a mutants. Thus, Gata2a maintains myeloid lineage priming through cebpa and protects against genome instability and marrow failure by maintaining expression of npm1a. Our results establish a potential mechanism underlying bone marrow failure in GATA2 deficiency.

La temática salud en los estudios sobre los currículos de educación física del Estado de São Paulo: Una revisión integrativa

El objetivo de este artículo fue realizar una revisión integradora de la literatura brasileña para verificar cómo las cuestiones de salud son abordadas en los estudios sobre propuestas curriculares de educación física en el estado de São Paulo. Se revisaron las bases de datos (LILACS, Biblioteca Digital Brasileña de Tesis y Disertaciones (BDTD) y Catálogo de Tesis y Disertaciones de Capes). Como criterio de selección los estudios se asignaron con base en los elementos de análisis (período del plan de estudios relacionado con la salud, concepción del plan de estudios sobre salud, contenidos sobre salud y coherencia entre concepción y contenido) divididos en tres categorías: 1. Descripción superficial del tema salud; 2. Temática salud ignorada y 3. Descripción detallada de la temática salud. Se identificaron 439 fuentes, luego de la selección, se realizó la revisión integrativa incluyendo 24 estudios. Se encontró que en 11 hablan superficialmente sobre la salud, en cuatro la tratan de forma específica y detallada y en nueve estudios ignoran la temática salud. En los periodos 1970-1989 y 1990-1999, sólo se identificaron dos estudios. De ellos, sólo uno se centró en detalle en los elementos de análisis identificados por nuestro estudio. De todos los autores que hablan superficialmente de salud o de PS entre 2000 y 2014, la oposición al currículo tradicional es clara. Para los autores que hablaron en detalle sobre la salud, es evidente la importancia de los contenidos identificados para la PS en las escuelas.

SUMMARY The objective of this review was to perform an integrative review of the Brazilian literature on how health issues are included in the curriculum of physical education in the state of Sao Paulo. Data bases of LILACS, Digital library of thesis in Brazil were reviewed. We selected studies that included health issues divided into three categories; superficial description of the topic, ignored health issues and detailed description of health issues. We identified 439 sources including 24 studies. In eleven of them a superficial cover was detected, four covered the issues in depth and nine ignored the issue. Two studies were identified in the 1970-1989 and 1990-1999 periods. Just one of them centered in health topics. Authors who covered health issues superficially between 2000-2014 opposed to traditional curriculum. Those who covered in more detail health topics talk about the importance of including these concepts in the schools.

Epigenetic Regulation of Endothelial Cell Lineages During Zebrafish Development-New Insights From Technical Advances.

Epigenetic regulation is integral in orchestrating the spatiotemporal regulation of gene expression which underlies tissue development. The emergence of new tools to assess genome-wide epigenetic modifications has enabled significant advances in the field of vascular biology in zebrafish. Zebrafish represents a powerful model to investigate the activity of cis-regulatory elements in vivo by combining technologies such as ATAC-seq, ChIP-seq and CUT&Tag with the generation of transgenic lines and live imaging to validate the activity of these regulatory elements. Recently, this approach led to the identification and characterization of key enhancers of important vascular genes, such as gata2a, notch1b and dll4. In this review we will discuss how the latest technologies in epigenetics are being used in the zebrafish to determine chromatin states and assess the function of the cis-regulatory sequences that shape the zebrafish vascular network.

In the spotlight: the role of TGFß signalling in haematopoietic stem and progenitor cell emergence.

Haematopoietic stem and progenitor cells (HSPCs) sustain haematopoiesis by generating precise numbers of mature blood cells throughout the lifetime of an individual. In vertebrates, HSPCs arise during embryonic development from a specialised endothelial cell population, the haemogenic endothelium (HE). Signalling by the Transforming Growth Factor ß (TGFß) pathway is key to regulate haematopoiesis in the adult bone marrow, but evidence for a role in the formation of HSPCs has only recently started to emerge. In this review, we examine recent work in various model systems that demonstrate a key role for TGFß signalling in HSPC emergence from the HE. The current evidence underpins two seemingly contradictory views of TGFß function: as a negative regulator of HSPCs by limiting haematopoietic output from HE, and as a positive regulator, by programming the HE towards the haematopoietic fate. Understanding how to modulate the requirement for TGFß signalling in HSC emergence may have critical implications for the generation of these cells in vitro for therapeutic use.

Hapln1b, a central organizer of the ECM, modulates kit signaling to control developmental hematopoiesis in zebrafish.

During early vertebrate development, hematopoietic stem and progenitor cells (HSPCs) are produced in hemogenic endothelium located in the dorsal aorta, before they migrate to a transient niche where they expand to the fetal liver and the caudal hematopoietic tissue, in mammals and zebrafish, respectively. In zebrafish, previous studies have shown that the extracellular matrix (ECM) around the aorta must be degraded to enable HSPCs to leave the aortic floor and reach blood circulation. However, the role of the ECM components in HSPC specification has never been addressed. In this study, hapln1b, a key component of the ECM, was specifically expressed in hematopoietic sites in the zebrafish embryo. Gain- and loss-of-function experiments all resulted in the absence of HSPCs in the early embryo, showing that hapln1b is necessary, at the correct level, to specify HSPCs in the hemogenic endothelium. Furthermore, the expression of hapln1b was necessary to maintain the integrity of the ECM through its link domain. By combining functional analyses and computer modeling, we showed that kitlgb interacts with the ECM to specify HSPCs. The findings show that the ECM is an integral component of the microenvironment and mediates the cytokine signaling that is necessary for HSPC specification.

Essential role for Gata2 in modulating lineage output from hematopoietic stem cells in zebrafish.

The differentiation of hematopoietic stem cells (HSCs) is tightly controlled to ensure a proper balance between myeloid and lymphoid cell output. GATA2 is a pivotal hematopoietic transcription factor required for generation and maintenance of HSCs. GATA2 is expressed throughout development, but because of early embryonic lethality in mice, its role during adult hematopoiesis is incompletely understood. Zebrafish contains 2 orthologs of GATA2: Gata2a and Gata2b, which are expressed in different cell types. We show that the mammalian functions of GATA2 are split between these orthologs. Gata2b-deficient zebrafish have a reduction in embryonic definitive hematopoietic stem and progenitor cell (HSPC) numbers, but are viable. This allows us to uniquely study the role of GATA2 in adult hematopoiesis. gata2b mutants have impaired myeloid lineage differentiation. Interestingly, this defect arises not in granulocyte-monocyte progenitors, but in HSPCs. Gata2b-deficient HSPCs showed impaired progression of the myeloid transcriptional program, concomitant with increased coexpression of lymphoid genes. This resulted in a decrease in myeloid-programmed progenitors and a relative increase in lymphoid-programmed progenitors. This shift in the lineage output could function as an escape mechanism to avoid a block in lineage differentiation. Our study helps to deconstruct the functions of GATA2 during hematopoiesis and shows that lineage differentiation flows toward a lymphoid lineage in the absence of Gata2b.

Multi-elemental composition of white and dark muscles in swordfish.

Concentrations of 16 elements (K, Na, Mg, Ca, Fe, Zn, Hg, Se, As, Cu, Cd, Mn, Ni, Cr, Pb and Co) were determined in dorsal white and dark muscle of Xiphias gladius, sampled at various positions of a single swordfish and at the same position of eight specimens. Hg was quantified by thermal decomposition atomic absorption spectrometry (LECO AMA-254) and the rest of the elements by inductively coupled plasma optical emission spectrometry (ICP OES) or mass spectrometry (ICP MS). Element partitioning differed in dark and white muscle. Dark muscle was particularly enriched in Fe (median 13 times) and Cu (9) and moderately enhanced in Se, Mn, Zn and Cd (2.8-4.0). Dark:white ratios of the potentially toxic elements (As, Cr, Hg, Ni and Pb) varied from 0.9 to 1.4, pointing to a similar distribution between the two muscles types and indicating no additional risk in the consumption of dark muscle.

Can water remediated by manganese spinel ferrite nanoparticles be safe for marine bivalves?

In the last few years the use of nanoparticles (NPs) such as the manganese spinel ferrite (MnFe2O4) has been increasing, with a vast variety of applications including water remediation from pollutants as metal(oid)s. Although an increasing number of studies already demonstrated the potential toxicity of NPs towards aquatic systems and inhabiting organisms, there is still scarce information on the potential hazard of the remediated water using NPs. The present study aimed to evaluate the ecotoxicological safety of Pb contaminated seawater remediated with MnFe2O4, NPs, assessing the toxicity induced in mussels Mytilus galloprovincialis exposed to contaminated seawater and to water that was remediated using MnFe2O4, NPs. The results obtained demonstrated that seawater contaminated with Pb, NPs or the mixture of both (Pb + NPs) induced higher toxicity in mussels compared to organisms exposed to Pb, NPs and Pb + NPs after the remediation process. In particular, higher metabolic depression, oxidative stress and neurotoxicity were observed in mussels exposed to contaminated seawater in comparison to mussels exposed to remediated seawater.

Toxic impacts of rutile titanium dioxide in Mytilus galloprovincialis exposed to warming conditions.

Climate change is leading to a gradual increase in the ocean temperature, which can cause physiological and biochemical impairments in aquatic organisms. Along with the environmental changes, the presence of emerging pollutants such as titanium dioxide (TiO2) in marine coastal systems has also been a topic of concern, especially considering the interactive effects that both factors may present to inhabiting organisms. In the present study, it has been assessed the effects of the presence in water of particles of rutile, the most common polymorph of TiO2, in Mytilus galloprovincialis, under actual and predicted warming conditions. Organisms were exposed to different concentrations of rutile (0, 5, 50, 100 µg/L) at control (18 ± 1.0 °C) and increased (22 ± 1.0 °C) temperatures. Histopathological and biochemical changes were evaluated in mussels after 28 days of exposure. Histopathological examination revealed similar alterations on mussels' gills and digestive glands with increasing rutile concentrations at both temperatures. Biochemical markers showed that contaminated mussels have an unchanged metabolic capacity at 18 °C, which increased at 22 °C. Although antioxidant defences were activated in contaminated organisms at 22 °C, cellular damage was still observed. Overall, our findings showed that histopathological impacts occurred after rutile exposure regardless of the temperature, while biochemical alterations were only significantly noticeable when temperature was enhanced to 22 °C. Thus, this study demonstrated that temperature rise may significantly enhance the sensitivity of bivalves towards emerging pollutants.

Deletion of a conserved Gata2 enhancer impairs haemogenic endothelium programming and adult Zebrafish haematopoiesis.

Gata2 is a key transcription factor required to generate Haematopoietic Stem and Progenitor Cells (HSPCs) from haemogenic endothelium (HE); misexpression of Gata2 leads to haematopoietic disorders. Here we deleted a conserved enhancer (i4 enhancer) driving pan-endothelial expression of the zebrafish gata2a and showed that Gata2a is required for HE programming by regulating expression of runx1 and of the second Gata2 orthologue, gata2b. By 5 days, homozygous gata2aΔi4/Δi4 larvae showed normal numbers of HSPCs, a recovery mediated by Notch signalling driving gata2b and runx1 expression in HE. However, gata2aΔi4/Δi4 adults showed oedema, susceptibility to infections and marrow hypo-cellularity, consistent with bone marrow failure found in GATA2 deficiency syndromes. Thus, gata2a expression driven by the i4 enhancer is required for correct HE programming in embryos and maintenance of steady-state haematopoietic stem cell output in the adult. These enhancer mutants will be useful in exploring further the pathophysiology of GATA2-related deficiencies in vivo.

Genotyping and Quantification of In Situ Hybridization Staining in Zebrafish.

In situ hybridization (ISH) is an important technique that enables researchers to study mRNA distribution in situ and has been a critical technique in developmental biology for decades. Traditionally, most gene expression studies relied on visual evaluation of the ISH signal, a method that is prone to bias, particularly in cases where sample identities are known a priori. We have previously reported on a method to circumvent this bias and provide a more accurate quantification of ISH signals. Here, we present a simple guide to apply this method to quantify the expression levels of genes of interest in ISH-stained embryos and correlate that with their corresponding genotypes. The method is particularly useful to quantify spatially restricted gene expression signals in samples of mixed genotypes and it provides an unbiased and accurate alternative to the traditional visual scoring methods.

Biochemical and histopathological impacts of rutile and anatase (TiO2 forms) in Mytilus galloprovincialis.

Titanium dioxide (TiO2) particles have been widely used in various industrial applications and consumer products. Due to their large production and use, they will eventually enter into aquatic environments. Once in the aquatic environment TiO2 particles may interact with the organisms and induce toxic effects. Since the most common crystallographic forms of TiO2 are rutile and anatase, the present study evaluated the effect of these two forms of TiO2 particles in Mytilus galloprovincialis. For this, mussels were exposed to different concentrations of rutile and anatase particles (0, 5, 50, 100 µg/L) for twenty-eight days. Ti concentrations, histopathological alterations and biochemical effects were evaluated. Similar Ti concentrations were found in mussels exposed to rutile and anatase, with the highest values in mussels exposed to the highest exposure concentration. Histopathological results demonstrated that both forms of TiO2 induced alterations on gills and digestive glands along the increasing exposure gradient. Biochemical markers showed that mussels exposed to rutile maintained their metabolic capacity (assessed by the activity of the Electron Transport System, ETS), while anatase increased the metabolism of mussels. Mussels exposed to rutile increased their detoxifying defences which, due to the low tested concentrations, were sufficient to avoid cellular damage. On the other hand, mussels exposed to anatase suffered cellular damages despite the increase of the antioxidant defences which may be related to the high ETS activity. Both rutile and anatase particles were toxic to M. galloprovincialis, being the highest oxidative stress exerted by the crystalline form anatase.

The roles and controls of GATA factors in blood and cardiac development.

GATA factors play central roles in the programming of blood and cardiac cells during embryonic development. Using the experimentally accessible Xenopus and zebrafish models, we report observations regarding the roles of GATA-2 in the development of blood stem cells and GATA-4, -5, and -6 in cardiac development. We show that blood stem cells develop from the dorsal lateral plate mesoderm and GATA-2 is required at multiple stages. Firstly, GATA-2 is required to make the cells responsive to VEGF-A signalling by driving the synthesis of its receptor, FLK-1/KDR. This leads to differentiation into the endothelial cells that form the dorsal aorta. GATA-2 is again required for the endothelial-to-haematopoietic transition that takes place later in the floor of the dorsal aorta. GATA-2 expression is dependent on BMP signalling for each of these inputs into blood stem cell programming. GATA-4, -5, and -6 work together to ensure the specification of cardiac cells during development. We have demonstrated redundancy within the family and also some evolution of the functions of the different family members. Interestingly, one of the features that varies in evolution is the timing of expression relative to other key regulators such as Nkx2.5 and BMP. We show that the GATA factors, Nkx2.5 and BMP regulate each other and it would appear that what is critical is the mutually supportive network of expression rather than the order of expression of each of the component genes. In Xenopus and zebrafish, the cardiac mesoderm is adjacent to an anterior population of cells giving rise to blood and endothelium. This population is not present in mammals and we have shown that, like the cardiac population, the blood and endothelial precursors require GATA-4, -5, and -6 for their development. Later, blood-specific or cardiac-specific regulators determine the ultimate fate of the cells, and we show that these regulators act cross-antagonistically. Fibroblast growth factor (FGF) signalling drives the cardiac fate, and we propose that the anterior extension of the FGF signalling field during evolution led to the recruitment of the blood and endothelial precursors into the heart field ultimately resulting in a larger four chambered heart. Zebrafish are able to successfully regenerate their hearts after injury. To understand the pathways involved, with a view to determining why humans cannot do this, we profiled gene expression in the cardiomyocytes before and after injury, and compared those proximal to the injury with those more distal. We were able to identify an enhancement of the expression of regulators of the canonical Wnt pathway proximal to the injury, suggesting that changes in Wnt signalling are responsible for the repair response to injury.

Impacto do Modelo de Calgary na Capacitação Familiar: Perspetiva da Enfermagem de Saúde Familiar / Impact of the Calgary Model on Family Empowerment: A Family Health Nursing Perspective

Segundo Hanson & Kaakinen (2005) cada sistema familiar apresenta características num determinado momento com o intuito de manter o equilíbrio funcional. Para melhor responder às exigências e movimentos de mudança a família não deve manter o mesmo funcionamento. O presente estudo propôs-se perceber em que medida a implementação de uma consulta de enfermagem familiar estruturada, baseada no Modelo de Calagary, aleado ao Modelo Circumplexo de Olson, influi na capacitação familiar. O estudo, caracterizado como quantitativo, descritivo e inferencial, do tipo pré-teste, pós-teste com grupo de controlo, envolveu 26 famílias. A implementação de uma consulta de enfermagem estruturada, tendo por base os constructos referidos anteriormente, permitiu potenciar a capacitação das potencialidades familiares e, subsequentemente, promover a resiliência familiar, pelo melhoramento funcional ao nível das dimensões coesão e adaptabilidade familiares.

According to Hanson & Kaakinen (2005) each family system presents characteristics at a certain moment in order to maintain functional balance. To better respond to the demands and movements of change, the family should not maintain the same functioning all the time. The present study aimed to understand to what extent the implementation of a structured family nursing consultation, based on the Calagary Model, combined with the Olson Circumplex Model, influences family empowerment. The study, characterized as quantitative, descriptive and inferential, as pretest, posttest with control group, involved 26 families. The implementation of a structured nursing consultation, based on the aforementioned constructs, allowed the empowerment of family potentialities and, subsequently, to promote family resilience through functional improvement of cohesion and family adaptability.

Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium.

Haematopoietic stem cells are generated from the haemogenic endothelium (HE) located in the floor of the dorsal aorta (DA). Despite being integral to arteries, it is controversial whether HE and arterial endothelium share a common lineage. Here, we present a transgenic zebrafish runx1 reporter line to isolate HE and aortic roof endothelium (ARE)s, excluding non-aortic endothelium. Transcriptomic analysis of these populations identifies Runx1-regulated genes and shows that HE initially expresses arterial markers at similar levels to ARE. Furthermore, runx1 expression depends on prior arterial programming by the Notch ligand dll4. Runx1-/- mutants fail to downregulate arterial genes in the HE, which remains integrated within the DA, suggesting that Runx1 represses the pre-existing arterial programme in HE to allow progression towards the haematopoietic fate. These findings strongly suggest that, in zebrafish, aortic endothelium is a precursor to HE, with potential implications for pluripotent stem cell differentiation protocols for the generation of transplantable HSCs.

The influence of temperature and salinity on the impacts of lead in Mytilus galloprovincialis.

Mussels, such as the marine bivalve Mytilus galloprovincialis are sentinels for marine pollution but they are also excellent bioindicators under laboratory conditions. For that, in this study we tested the modulation of biochemical responses under realistic concentrations of the toxic metal Lead (Pb) in water for 28 days under different conditions of salinity and temperature, including control condition (temperature 17 ± 1.0 °C and salinity 30 ± 1.0) as well as those within the range expected to occur due to climate change predictions (± 5 in salinity and + 4 °C in temperature). A comprehensive set of biomarkers was applied to search on modulation of biochemical responses in terms of energy metabolism, energy reserves, oxidative stress and damage occurrence in lipids, proteins as well as neurotoxicity signs. The application of an integrative Principal Coordinates Ordination (PCO) tool was successful and demonstrated that Pb caused an increase in the detoxification activity mainly evidenced by glutathione S-transferases and that the salinities 25 and 35 were, even in un-exposed mussels, responsible for cell damage seen as increased levels of lipid peroxidation (at salinity 25) and oxidised proteins (at salinity 35).

Universal fluorescence module for intraoperative fluorescein angiography-a technical report.

BACKGROUND: Even in specialized centers, suboptimal aneurysm clipping can be as high as 12%. Intraoperative fluorescence angiography with indocyanine green and, more recently, fluorescein sodium have been shown to be a good method for intraoperative flow assessment. However, the cost with the apparatus it entails limits its widespread use. We have developed a low-cost universal fluorescence module (FM) designed to visualize fluorescein and perform intraoperative angiography. The purpose of this paper is to describe this device as well as to present our early experience with its use in the treatment of cerebral aneurysms. METHOD: A FM was designed and built using a cyan-blue narrow bandpass (460 to 490 nm) excitation filter and a yellow-orange longpass (blocking wavelengths under 520 nm) barrier filter mounted on a 3D-printed holding tray in a specific disposition to perfectly match the light source and the objective lens of the surgical microscope. It allowed switching from white light to fluorescence mode in a simple and sterile fashion. Its perfect attachment to the microscope was possible by reusing the lens fittings extracted from used original drape sets that would otherwise be discarded. Four patients underwent aneurysm clipping using the FM at two institutions from April to September 2018. RESULTS: A bright green fluorescence against a dark background was observed after intravenous bolus of fluorescein. Blood vessels became obviously distinct from non-contrast-filled structures such as clipped aneurysms and the brain. Vascular anatomy could be appreciated without any distortion, including perforating arteries. CONCLUSIONS: Intraoperative fluorescence angiography was successfully performed with the use of this universal FM after intravenous injection of fluorescein sodium. This simple and low-cost device may be useful in resource-limited centers, where other sorts of intraoperative angiography are not available.

Remediation of arsenic from contaminated seawater using manganese spinel ferrite nanoparticles: Ecotoxicological evaluation in Mytilus galloprovincialis.

In the last decade different approaches have been applied for water remediation purposes, including the use of nanoparticles (NPs) to remove metals and metalloids from water. Although studies have been done on the toxic impacts of such NPs, very scarce information is available on the impacts of water after decontamination when discharged into aquatic environments. As such, in the present study we aimed to evaluate the ecotoxicological safety of seawater previously contaminated with arsenic (As) and remediated by using manganese-ferrite (MnFe2O4-NPs) NPs. For this, mussels Mytilus galloprovincialis were exposed for 28 days to different conditions, including clean seawater (control), As (1000 µg L-1) contaminated and remediated (As 70 µg L-1) seawater, water containing MnFe2O4- NPs (50 mg L-1) with and without the presence of As. At the end of exposure, concentrations of As in mussels tissues were quantified and biomarkers related to mussels' metabolism and oxidative stress status were evaluated. Results revealed that mussels exposed to water contaminated with As and to As + NPs accumulated significantly more As (between 62% and 76% more) than those exposed to remediated seawater. Regarding biomarkers, our findings demonstrated that in comparison to remediated seawater (conditions a, b, c) mussels exposed to contaminated seawater (conditions A, B, C) presented significantly lower metabolic activity, lower expenditure of energy reserves, activation of antioxidant and biotransformation defences, higher lipids and protein damages and greater AChE inhibition. Furthermore, organisms exposed to As, NPs or As + NPs revealed similar biochemical effects, both before and after water decontamination. In conclusion, the present study suggests that seawater previously contaminated with As and remediated by MnFe2O4-NPs presented significantly lower toxicity than As contaminated water, evidencing the potential use of these NPs to remediate seawater contaminated with As and its safety towards marine systems after discharges to these environments.