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Abstract Small-scale fisheries provide income and food security to local peoples around the world. In the Brazilian Amazon, the pescada (Plagioscion squamosissimus) is among the fishes that contributes most to catches in small-scale fisheries. Our main goal was to evaluate the abundance, size, relevance to small-scale fisheries and trophic ecology of P. squamosissimus in the Tapajós and Tocantins rivers, in the Brazilian Amazon. We combined data from fishers’ local ecological knowledge (LEK) and fish sampling. We expected that fishers in the Tapajós River, less altered by anthropic changes, would cite a higher abundance, larger size and more prey and predators of P. squamosissimus. We interviewed 61 and 33 fishers and sampled fish in nine and five sites in the Tapajós and Tocantins rivers, respectively. The comparison between fishers’ citations and fish sampled indicated a higher relevance of P. squamosissimus to fishers in the Tapajós River, where this fish had an average larger size and where the fishers mentioned more food items. This pattern could be partially related to the history of anthropogenic changes in the Tocantins River. These results indicated that P. squamosissimus is a generalist fish, which could be resilient to fishing and environmental pressures.

The PI Launchpad attempts to provide an entry level explanation of the process of space mission development for new Principal Investigators (PIs). In particular, PI launchpad has a focus on building teams, making partnerships, and science concept maturity for a space mission concept, not necessarily technical or engineering practices. Here we briefly summarize the goals of the PI Launchpad workshops and present some results from the workshops held in 2019 and 2021. The workshop attempts to describe the current process of space mission development (i.e. space-based telescopes and instrument platforms, planetary missions of all types, etc.), covering a wide range of topics that a new PI may need to successfully develop a team and write a proposal. It is not designed to replace real experience but to provide an easily accessible resource for potential PIs who seek to learn more about what it takes to submit a space mission proposal, and what the first steps to take can be. The PI Launchpad was created in response to the high barrier to entry for early career or any scientist who is unfamiliar with mission design. These barriers have been outlined in several recent papers and reports, and are called out in recent space science Decadal reports.

Trophic levels can be applied to describe the ecological role of organisms in food webs and assess changes in ecosystems. Stable isotopes analysis can assist in the understanding of trophic interactions and use of food resources by aquatic organisms. The local ecological knowledge (LEK) of fishers can be an alternative to advance understanding about fish trophic interactions and to construct aquatic food webs, especially in regions lacking research capacity. The objectives of this study are: to calculate the trophic levels of six fish species important to fishing by combining data from stable isotopes analysis and fishers’ LEK in two clear water rivers (Tapajós and Tocantins) in the Brazilian Amazon; to compare the trophic levels of these fish between the two methods (stable isotopes analysis and LEK) and the two rivers; and to develop diagrams representing the trophic webs of the main fish prey and predators based on fisher’s LEK. The fish species studied were Pescada (Plagioscion squamosissimus), Tucunaré (Cichla pinima), Piranha (Serrasalmus rhombeus), Aracu (Leporinus fasciatus), Charuto (Hemiodus unimaculatus), and Jaraqui (Semaprochilodus spp.). A total of 98 interviews and 63 samples for stable isotopes analysis were carried out in both rivers. The average fish trophic levels did not differ between the stable isotopes analysis and the LEK in the Tapajós, nor in the Tocantins Rivers. The overall trophic level of the studied fish species obtained through the LEK did not differ from data obtained through the stable isotopes analysis in both rivers, except for the Aracu in the Tapajós River. The main food items consumed by the fish according to fishers’ LEK did agree with fish diets as described in the biological literature. Fishers provided useful information on fish predators and feeding habits of endangered species, such as river dolphin and river otter. Collaboration with fishers through LEK studies can be a viable approach to produce reliable data on fish trophic ecology to improve fisheries management and species conservation in tropical freshwater environments and other regions with data limitations.

The protein infusion of basic fibroblast growth factor-2 (FGF-2) and platelet derived growth factor-BB (PDGF-BB) have been shown to promote the formation of a stable and functional vascular network in small and large animal models of ischemia. Here, we sought to determine whether a similar effect could be obtained using a gene-therapy-based strategy with nonviral vectors. Rats underwent a surgical procedure to create hindlimb ischemia and were injected with a combination of plasmids that expressed FGF-2 and PDGF-BB. Anatomical and functional parameters of the angiogenesis and arteriogenesis response were evaluated after 4 weeks. The results were compared with rats injected with plasmids that expressed a reporter gene or the extensively studied vascular endothelial growth factor (VEGF165) alone. Treatment with the FGF-2/PDGF-BB combination increased the angiogenesis and arteriogenesis response compared with the empty plasmid, and it was as effective as VEGF165. In terms of safety, the combination allowed the use of a 50% lower individual dose of each plasmid and in addition promoted the formation of more stable vessels than VEGF165. In conclusion, the dual gene transfer of FGF-2 and PDGF-BB using nonviral vectors is safe and effective in promoting the formation of a functional vascular network in a rodent model of hindlimb ischemia. [ABSTRACT FROM AUTHOR]

Antisense oligonucleotide (ASO) gapmers downregulate gene expression by inducing enzyme-dependent degradation of targeted RNA and represent a promising therapeutic platform for addressing previously undruggable genes. Unfortunately, their therapeutic application, particularly that of the more potent chemistries (e.g., locked-nucleic-acid-containing gapmers), has been hampered by their frequent hepatoxicity, which could be driven by hybridization-mediated interactions. An early de-risking of this liability is a crucial component of developing safe, ASO-based drugs. To rank ASOs based on their effect on the liver, we have developed an acute screen in the mouse that can be applied early in the drug development cycle. A single-dose (3-day) screen with streamlined endpoints (i.e., plasma transaminase levels and liver weights) was observed to be predictive of ASO hepatotoxicity ranking established based on a repeat-dose (15 day) study. Furthermore, to study the underlying mechanisms of liver toxicity, we applied transcriptome profiling and pathway analyses and show that adverse in vivo liver phenotypes correlate with the number of potent, hybridization-mediated off-target effects (OTEs). We propose that a combination of in silico OTE predictions, streamlined in vivo hepatotoxicity screening, and a transcriptome-wide selectivity screen is a valid approach to identifying and progressing safer compounds. Keywords: antisense oligonucleotides, ASOs, off-target effects, OTEs, hepatotoxicity, locked nucleic acids, LNA, gene silencing, RNArcher, selectivity

Esta intervención tiene como objetivo problematizar y proponer algunas reflexiones sobre las implicancias, aportes y resultados de las participaciones de tesistas e investigadores en el sistema judicial, específicamente, en los juicios por crímenes de lesa humanidad. Buscamos aportar a problematizar, reconocer las voces y los objetivos de los distintos actores presentes en una escena judicial específica, el proceso oral y público y la condena la Fuerza de Tareas 5 de la Armada Argentina por las violaciones a los derechos humanos cometidas por durante la última dictadura militar (1976-1983) en el cordón industrial de las localidades bonaerenses de Berisso y Ensenada y en la región del Río Santiago. Intentaremos reflexionar sobre como en dicha oportunidad el ámbito judicial fue receptivo y sirvió a la materialización de una reivindicación colectiva y de clase al componer una forma ampliada de reparación, económica, simbólica y moral, para un colectivo de trabajadores.

Considerando que, junto con varios equipos profesionales, la intervención consiste en varios tipos de conocimientos especializados para resolver un tema específico, nuestros propósitos fueron: (a) verificar cuál la perspectiva del equipo multiprofesional acerca de la contribución específica del profesional del Educación Física; (b) identificar la auto-evaluación de los profesionales de la Educación Física junto a la realización del trabajo multi-profesional; y (c) comprobar el entendimiento de los miembros del equipo sobre losaspectos necesarios para subsidiar su intervención. El estudio fue realizado con ocho profesionales. Se utilizó la entrevista semi-estructurada y el análisis de contenido con las categorías establecidas a priori. En el contexto investigado las interacciones profesionales son conflictivos y competitivas, con la subordinación a la zona dominante (medicina), así como la jerarquización de las profisiones secundarias en el sector de la salud.

O campo de trabalho em educação física oferece, atualmente, desafi os gerados pelas mudanças estabelecidas nas relações de trabalho, com o usuário e entre outros grupos profi ssionais. As noções de competência e qualidade dos serviços prestados são exigências freqüentes e geram uma busca crescente por melhor formação profi ssional e responsabilidade sobre as tarefas especifi cas da área, bem como, uma preocupação com as questões éticas da intervenção profissional em educação física. O objetivo desse estudo foi compreender como o profissional de educação física descreve e interpreta as conseqüências de sua intervenção profi ssional, a partir da perspectiva do erro. As informações foram obtidas através de entrevista semi-estruturada, realizada com 11 profi ssionais que atuavam fora do âmbito escolar, com formação profi ssional variando entre 7 e 25 anos. O tratamento dos dados seguiu as características da análise de conteúdo, com o estabelecimento a posteriori das categorias de análise, a saber: (1) Formação Acadêmica e Identidade Profi ssional, que engloba as características e circunstâncias da formação, identidade e cultura profi ssional e (2) Intervenção profi ssional e Credencialismo: engloba os aspectos ligados ao processo de legitimação e credenciamento profi ssional. A pesquisa permitiu considerar que os profi ssionais de educação física expressam algumas preocupações com a qualidade dos serviços oferecidos na área, entretanto, não defi nem com clareza como se constitui o erro profissional na área, e também não avaliam as conseqüências de sua intervenção profissional a partir dessa perspectiva. ABSTRACT Employment in the area of Physical Education offers a series of challenges that have been created by changes established in relationships at work, with the user and with other professional groups. Notions of competence and quality of the services rendered are common demands and generate an increasing search for better professional education and responsibility for tasks specifi c to the area, as well as a concern with the ethical factors of professional intervention in physical education. The purpose of this study was to understand how physical education professionals describe and interpret the consequences of their professional intervention, based on the error perspective. Information was obtained by means of a semi-structure interview, conducted with 11 professionals who were not part of the school system, and who had 7 – 25 years of professional education. The data treatment followed the characteristics of the content analysis, establishing later the analysis categories, namely: 1) Academic Education and Professional Identity, which includes the characteristics and circumstances of professional education, identity and culture and 2) Professional intervention and Accreditation, which includes aspects connected to professional legitimacy and the accreditation process. This study allowed us to consider that, while Physical Education professionals are concerned with the quality of the services offered in the area, they do not clearly defi ne what constitutes a professional error in the area, and neither do they evaluate the consequences of their professional intervention based on this perspective.

Cold storage (CS) can induce a physiological disorder known as chilling injury (CI) in nectarine fruits. The main symptom is mealiness that is perceived as non-juicy fruit by consumers. Postharvest treatments such as controlled atmosphere (CA; a high CO2 concentration and low O2) have been used under cold conditions to avoid this disorder. With the objective of exploring the mechanisms involved in the CA effect on mealiness prevention, we analyzed transcriptomic changes under six conditions of ‘Red Pearl’ nectarines by RNA-Seq. Our analysis included just harvested nectarines, juicy non-stored fruits, fruits affected for CI after CS and fruits stored in a combination of CA plus CS without CI phenotype. Nectarines stored in cold conditions combined with CA treatment resulted in less mealiness; we obtained 21.6% of juice content compared with just CS fruits (7.7%; mealy flesh). RNA-Seq data analyses were carried out to study the gene expression for different conditions assayed. During ripening, we detected that nectarines exposed to CA treatment expressed a similar number of genes compared with fruits that were not exposed to cold conditions. Firm fruits have more differentially expressed genes than soft fruits, which suggest that most important changes occur during CS. On the other hand, gene ontology analysis revealed enrichment mainly in metabolic and cellular processes. Differentially expressed genes analysis showed that low O2 concentrations combined with cold conditions slows the metabolic processes more than just the cold storage, resulting mainly in the suppression of primary metabolism and cold stress response. This is a significant step toward unraveling the molecular mechanism that explains the effectiveness of CA as a tool to prevent CI development on fruits.

El objetivo de ese estudio fue verificar el punto de vista de los docentes de uno curso de formación profesional sobre: (a) ¿Como se catacteriza la intervención professional en Educación Física?; (b) ¿Que elementos devem compone-los? (c) ¿y como esos elementos devem ser articulados por los professionais de Educación Física? Para eso, utilizamos la abordagem qualitativa y a partir de los dados obtenidos en la entrevista semi-estructurada, empleamos la análisis de contenido con las categorías préestablecidas á priori sobre (a) mercado de trabajo, (b) conocimientos, habilidades, actitudes a ser desarrolladas durante la graduación (c) sistema de avaliación, (d) visión de la graduación en Educación Física. Se pudo considerar que, a pesar del grupo estudiado expresar algunas preocupaciones importantes con relación à valoración de los conocimientos venidos de las asignaturas-madre, habilidades motoras y de investigación científica, los puntos de vista manifestados en este estudio en no permitieron definir claramente, ni caracterizar los elementos que deben componer la acción profesional en Educación Física.

Many species of amphibians have suffered serious population declines. Several factors contribute separately or jointly to these declines. However, the reduction of an available habitat due to human expansion is still the main cause, and roads are a major mean for this expansion. Both the construction phase and the subsequent use of roads have negative consequences for amphibians. We reviewed the literature on the subject within the Neotropical context. To this end, the paper begins with a summary of recent reviews and proceeds through an analysis of sampling methods used in roadkill studies, mitigation measures and the Neotropical scenario and concludes with several suggestions to guide future studies. More attention will be given to roadkills, which is one of the primary impacts on wildlife that is caused by roads. Even in the Neotropical zone most studies are foot-based, the richness and abundance of amphibians affected are higher in regions outside the Neotropics. One possible explanation is that in the other regions, the proportion of studies exclusively on amphibians is bigger. Regarding mitigation measures, most studies only indicates what should be used, but do not implement or evaluate their effectiveness.

Neural encoding of abstract rules in the audition of newborn infants has been recently demonstrated in several studies using event-related potentials (ERPs). In the present study the neural encoding of Western music chords was investigated in newborn infants. Using ERPs, we examined whether the categorizations of major versus minor and consonance versus dissonance are present at the level of the change-related mismatch response (MMR). Using an oddball paradigm, root minor, dissonant and inverted major chords were presented in a context of consonant root major chords. The chords were transposed to several different frequency levels, so that the deviant chords did not include a physically deviant frequency that could result in an MMR without categorization. The results show that the newborn infants were sensitive to both dissonant and minor chords but not to inverted major chords in the context of consonant root major chords. While the dissonant chords elicited a large positive MMR, the minor chords elicited a negative MMR. This indicates that the two categories were processed differently. The results suggest newborn infants are sensitive to Western music categorizations, which is consistent with the authors’ previous studies in adults and school-aged children.

In recent years, there has been increasing interest in matrix-type influence on forest fragments. Terrestrial amphibians are good bioindicators for this kind of research because of low vagility and high philopatry. This study compared richness, abundance, and species composition of terrestrial amphibians through pitfall traps in two sets of semideciduous seasonal forest fragments in southeastern Brazil, according to the predominant surrounding matrix (sugar cane and pasture). There were no differences in richness, but fragments surrounded by sugar cane had the lowest abundance of amphibians, whereas fragments surrounded by pastures had greater abundance. The most abundant species, Rhinella ornata, showed no biometric differences between fragment groups but like many other amphibians sampled showed very low numbers of individuals in fragments dominated by sugar cane fields. Our data indicate that the sugar cane matrix negatively influences the community of amphibians present in fragments surrounded by this type of land use.

While the association between coronavirus disease-19 (COVID-19) and neutrophils extracellular traps (NETs) is recognized, uncertainties remain regarding its precise onset, timing of resolution and target therapy. To assess changes in inflammatory and NET markers during the first week of COVID-19 hospitalization, and the association with disease severity. "In vitro" experiments investigated the effect of antiplatelets, anticoagulants, and cyclic nucleotide stimulators on NETs release. Prospective cohort study, changes in interleukin (IL)-6, IL-8, IL-17, TNF-α, RANTES, PF4, and citrullinated-H3 (citH3) levels within each outcome group was evaluated using ANOVA. Differences between moderately ill, critically ill, and non-survivors were determined using Kruskal-Wallis and logistic regression. Healthy neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) or COVID-19 sera and treated with unfractionated heparin (UFH), low molecular weight heparin (LMWH), aspirin (ASA), ticagrelor, cinaciguat, sildenafil, and milrinone. The proportion of NETosis was assessed using IncuCyte Cell Imager. Of the 125 patients, 40.8% had moderate COVID-19, 40.8% had critical COVID-19 but recovered, and 18.4% died. From admission to hospitalization day 8, IL-6 levels decreased in moderately and critically ill, but not in non-survivors, while citH3 levels increased in critically ill and non-survivors. IL-6, IL-8, and TNF-α levels were associated with critical and fatal COVID-19. The release of NETs by neutrophils stimulated with PMA or COVID-19 sera was decreased in the presence of ASA, UFH, LMWH and cyclic nucleotide stimulators in a dose-dependent manner. In the first week of hospitalization, NET markers rose later than inflammatory markers in severe COVID-19 cases. Cyclic nucleotide stimulators, ASA and heparin may emerge as treatment approaches as they may modulate NETosis., Competing Interests: Declarations Conflict of interest The authors declare no conflict of interest. Generative AI and AI-assisted technologies in the writing process During the preparation of this work the author(s) used https://www.deepl.com/ in order to correct grammatical errors in the text. After using this tool, the authors reviewed and edited the content as needed and took full responsibility for the content of the publication. Informed consent The study was conducted in compliance with the Helsinki Declaration. A waiver of the Informed Consent was granted based on the emergence of the pandemic, the observational nature of the study, the utilization of data obtained from medical records, and the use of residual samples. The study ensured the deidentification of patient records. In addition, patients diagnosed with COVID-19 were isolated, and access to the patients and their relatives was restricted to healthcare personnel., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Declaration of competing interests The authors declare the following conflicts of interest (past 36 months): F.N.A.: member of the International Society on Thrombosis and Haemostasis (ISTH) Council and Vice-Chair of the ISTH Guideline and Guidance Committee; research funding (investigator-initiated studies, paid to university) from Bayer, Daiichi-Sankyo, and Sanofi; and consultancy fees (paid to university) from Boston Scientific. D.D.M.: member of the ISTH Council and consultant to the National Bleeding Disorders Foundation, the American Society of Hematology, and Believe Ltd on matters related to future research and workforce development in the areas of hematology and inherited bleeding disorders. A.C.: serves on the advisory board of Novo Nordisk and has received honoraria from Novo Nordisk, Grifols, Takeda, and Roche. E.V.D.P.: medical consultant for the area of the Brazilian Ministry of Health responsible for the national program of hereditary bleeding disorders. S.M.: member of the ISTH Council and reports participation in advisory or educational activities with AbbVie, Bayer, Astra Zeneca, Alveron (Advisory Board), Hemab, Norgine, Sanofi, Synapse, and Viatris; all honoraria are being paid to her institution. Y.F.-Y, T.S., and C.S. report no conflict of interest.

Coagulation activation in immunothrombosis involves various pathways distinct from classical hemostasis, offering potential therapeutic targets to control inflammation-induced hypercoagulability while potentially sparing hemostasis. The Angiopoietin/Tie2 pathway, previously linked to embryonic angiogenesis and sepsis-related endothelial barrier regulation, was recently associated with coagulation activation in sepsis and COVID-19. This study explores the connection between key mediators of the Angiopoietin/Tie2 pathway and coagulation activation. The study included COVID-19 patients with hypoxia and healthy controls. Blood samples were processed to obtain platelet-free plasma, and frozen until analysis. Extracellular vesicles (EVs) in plasma were characterized and quantified using flow cytometry, and their tissue factor (TF) procoagulant activity was measured using a kinetic chromogenic method. Several markers of hemostasis were assessed. Levels of ANGPT1, ANGPT2, and soluble Tie2 correlated with markers of coagulation and platelet activation. EVs from platelets and endothelial cells were increased in COVID-19 patients, and a significant increase in TF + EVs derived from endothelial cells was observed. In addition, ANGPT2 levels were associated with TF expression and activity in EVs. In conclusion, we provide further evidence for the involvement of the Angiopoietin/Tie2 pathway in the coagulopathy of COVID-19 mediated in part by release of EVs as a potential source of TF activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Barbosa, de Lima, Peachazepi Moraes, Borba-Junior, Huber, Santos, Bombassaro, Dertkigil, Ilich, Key, Annichino-Bizzacchi, Orsi, Mansour, Velloso and De Paula.)

SARS-CoV-2 and other sarbecoviruses continue to threaten humanity, highlighting the need to characterize common mechanisms of viral immune evasion for pandemic preparedness. Cytotoxic lymphocytes are vital for antiviral immunity and express NKG2D, an activating receptor conserved among mammals that recognizes infection-induced stress ligands (e.g., MIC-A/B). We found that SARS-CoV-2 evades NKG2D recognition by surface downregulation of MIC-A/B via shedding, observed in human lung tissue and COVID-19 patient serum. Systematic testing of SARS-CoV-2 proteins revealed that ORF6, an accessory protein uniquely conserved among sarbecoviruses, was responsible for MIC-A/B downregulation via shedding. Further investigation demonstrated that natural killer (NK) cells efficiently killed SARS-CoV-2-infected cells and limited viral spread. However, inhibition of MIC-A/B shedding with a monoclonal antibody, 7C6, further enhanced NK-cell activity toward SARS-CoV-2-infected cells. Our findings unveil a strategy employed by SARS-CoV-2 to evade cytotoxic immunity, identify the culprit immunevasin shared among sarbecoviruses, and suggest a potential novel antiviral immunotherapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Data on availability, affordability, and accessibility is key for the planning of global strategies to reduce the burden of venous thromboembolism (VTE)., Objectives: A survey was conducted for the 10th anniversary of World Thrombosis Day to assess the availability of VTE therapies worldwide and challenges in uniform implementation., Methods: We gathered information on the approval status, availability, utilization, occurrence of shortages, and spread of medical and interventional therapies for VTE. Furthermore, we collected information by accessing or contacting national or continental medicines agencies, manufacturers or distributors, and online drug repositories., Results: We obtained data from a total of 69 countries: 33 countries in Europe, 19 in Asia, 7 in the Americas, 9 in Africa, and 1 in Oceania. Unfractionated heparin, low-molecular-weight heparin, and vitamin K antagonists were available in almost all countries, but shortages were recorded in 13%, 19%, and 15% of them, respectively. Direct oral anticoagulants were available in approximately three-quarters of the surveyed countries. At least one parenteral medication for heparin-induced thrombocytopenia was available in 57% of countries and a shortage was reported in 9% of these. Shortage of thrombolytics was recorded in 50% of countries. Overall, at least one type of catheter-directed therapy system was approved for use in 77% of countries and available in 23% of surveyed institutions. Our findings revealed notable geographic disparities in the worldwide availability of VTE therapies, the access to which appeared to be limited by economic and geopolitical factors., Conclusion: We anticipate that this comprehensive information will play a pivotal role in highlighting the shortcomings of VTE therapies and the lack of homogeneous availability globally., Competing Interests: Declaration of competing interests C.A. received honoraria for lectures and participation in advisory boards from Bayer, BMS/Pfizer, Daiichi Sankyo, and Sanofi. L.A.C. research institution has received honoraria from Bayer, BMS-Pfizer Alliance, The Academy for Continued Advancement in Healthcare Education, Amag Pharmaceutical, LEO Pharma, Sanofi, Valeo Pharma, and Servier. L.A.C. holds a Tier 2 research Chair in Thrombosis and Anticoagulation Safety from the University of Ottawa. S.B. received institutional grants from Sanofi, Concept Medical, Bayer, Medtronic, Boston Scientific, Bard, Novartis, and Daiichi Sankyo and honoraria for advisory boards or lectures from Boston Scientific, Penumbra, Viatris, Bayer, Sanofi. S.A.M., R.M.F., G.C.M., E.V.D.P., M.D., M.C.G.E., L.H., P.S., C.M.S., and M.T.S. report no conflicts of interest., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Heme is a fundamental molecule for several biological processes, but when released in the extracellular space such as in hemolytic diseases, it can be toxic to cells and tissues. Hemopexin (HPX) is a circulating protein responsible for removing free heme from the circulation, whose levels can be severely depleted in conditions such as sickle cell diseases. Accordingly, increasing HPX levels represents an attractive strategy to mitigate the deleterious effects of heme in these conditions. Gene transfer of liver-produced proteins with adeno-associated virus (AAV) has been shown to be an effective and safety strategy in animal and human studies mainly in hemophilia. Here, we report the feasibility of increasing HPX levels using an AAV8 vector expressing human HPX (hHPX). C57Bl mice were injected with escalating doses of our vector, and expression was assessed by enzyme immunoassay (ELISA), Western blot, and quantitative polymerase chain reaction (qPCR). In addition, the biological activity of transgenic hHPX was confirmed using two different models of heme challenge consisting of serial heme injections or phenylhydrazine-induced hemolysis. Sustained expression of hHPX was confirmed for up to 26 weeks in plasma. Expression was dose-dependent and not associated with clinical signs of toxicity. hHPX levels were significantly reduced by heme infusions and phenylhydrazine-induced hemolysis. No clinical toxicity or laboratory signs of liver damage were observed in preliminary short-term heme challenge studies. Our results confirm that long-term expression of hHPX is feasible and safe in mice, even in the presence of heme overload. Additional studies are needed to explore the effect of transgenic HPX protein in animal models of chronic hemolysis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.