168 research outputs found

    A transcriptomic approach to the metabolism of tetrapyrrolic photosensitizers in a marine annelid

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    Funding Information: Funding: The authors also acknowledge DPGM (the Portuguese General Directorate for Marine Policy) for funding the MARVEN project (ref. FA_05_2017_007). The Portuguese Foundation for Science and Technology (FCT) funded project WormALL (PTDC/BTA-BTA/28650/2017), which includes the contract attributed to M.D. and the fellowship attributed to A.P.R. UCIBIO and LAQV are financed by national funds from FCT, UID/Multi/04378/2020 and UID/QUI/50006/2020, respectively. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.The past decade has seen growing interest in marine natural pigments for biotechnological applications. One of the most abundant classes of biological pigments is the tetrapyrroles, which are prized targets due their photodynamic properties; porphyrins are the best known examples of this group. Many animal porphyrinoids and other tetrapyrroles are produced through heme metabolic pathways, the best known of which are the bile pigments biliverdin and bilirubin. Eulalia is a marine Polychaeta characterized by its bright green coloration resulting from a remarkably wide range of greenish and yellowish tetrapyrroles, some of which have promising photodynamic properties. The present study combined metabolomics based on HPLC-DAD with RNA-seq transcriptomics to investigate the molecular pathways of porphyrinoid metabolism by comparing the worm’s proboscis and epidermis, which display distinct pigmentation patterns. The results showed that pigments are endogenous and seemingly heme-derived. The worm possesses homologs in both organs for genes encoding enzymes involved in heme metabolism such as ALAD, FECH, UROS, and PPOX. However, the findings also indicate that variants of the canonical enzymes of the heme biosynthesis pathway can be species-and organ-specific. These differences between molecular networks contribute to explain not only the differential pigmentation patterns between organs, but also the worm’s variety of novel endogenous tetrapyrrolic compounds.publishersversionpublishe

    Light-Mediated Toxicity of Porphyrin-Like Pigments from a Marine Polychaeta

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    PTDC/MAR BIO/01132014 PTDC/BTA-BTA/28650/2017 UID/Multi/04378/2020 UID/QUI/50006/2020 ref. FA_05_2017_007Porphyrins and derivatives form one of the most abundant classes of biochromes. They result from the breakdown of heme and have crucial physiological functions. Bilins are well-known representatives of this group that, besides significant antioxidant and anti-mutagenic properties, are also photosensitizers for photodynamic therapies. Recently, we demonstrated that the Polychaeta Eulalia viridis, common in the Portuguese rocky intertidal, holds a high variety of novel greenish and yellowish porphyrinoid pigments, stored as granules in the chromocytes of several organs. On the follow-up of this study, we chemically characterized pigment extracts from the worm's skin and proboscis using HPLC and evaluated their light and dark toxicity in vivo and ex vivo using Daphnia and mussel gill tissue as models, respectively. The findings showed that the skin and proboscis have distinct patterns of hydrophilic or even amphiphilic porphyrinoids, with some substances in common. The combination of the two bioassays demonstrated that the extracts from the skin exert higher dark toxicity, whereas those from the proboscis rapidly exert light toxicity, then becoming exhausted. One particular yellow pigment that is highly abundant in the proboscis shows highly promising properties as a natural photosensitizer, revealing that porphyrinoids from marine invertebrates are important sources of these high-prized bioproducts.publishersversionpublishe

    In Vivo Transplantation of Human Intestinal Organoids Enhances Select Tight Junction Gene Expression

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    BACKGROUND: Short bowel syndrome is a potentially fatal condition with inadequate management options. Tissue-engineered small intestine (TESI) is a promising solution, but confirmation of TESI function will be crucial before human application. We sought to define intestinal epithelial barrier function in human intestinal organoid (HIO)-derived TESI. MATERIALS AND METHODS: HIOs were generated in vitro from human embryonic stem cells. After 1 mo, HIOs were collected for analysis or transplanted into the kidney capsule of immunocompromised mice. Transplanted HIOs (tHIOs) were harvested for analysis at 4 or 8 wk. Reverse transcription quantitative polymerase chain reaction and immunofluorescent staining were performed for tight junction components: claudin 3 (CLDN3), claudin 15 (CLDN15), occludin (OCLN), and zonula occludens-1, or tight junction protein-1 (TJP1/ZO-1). RESULTS: Four-week-old tHIOs demonstrated significantly (P \u3c 0.05) higher levels of CLDN15 (6x), OCLN (4x), and TJP1/ZO-1 (3x) normalized to GAPDH than in vitro HIOs. Eight-week-old tHIOs demonstrated significantly (P \u3c 0.05) higher expression levels of CLDN3 (26x), CLDN15 (29x), OCLN (4x), and TJP1/ZO-1 (5x) than in vitro HIOs. There was no significant difference in expression of these tight junction components between 4- and 8-week-old tHIOs. Immunofluorescent staining revealed the presence of claudin 3, claudin 15, occludin, and zonula occludens-1 in both in vitro HIOs and tHIOs; however, the morphology appeared more mature in tHIOs. CONCLUSIONS: In vitro HIOs have lower levels of tight junction mRNA, and tight junction proteins appear morphologically immature. Transplantation facilitates maturation of the HIOs and enhances select tight junction gene expression

    Main roads to melanoma

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    The characterization of the molecular mechanisms involved in development and progression of melanoma could be helpful to identify the molecular profiles underlying aggressiveness, clinical behavior, and response to therapy as well as to better classify the subsets of melanoma patients with different prognosis and/or clinical outcome. Actually, some aspects regarding the main molecular changes responsible for the onset as well as the progression of melanoma toward a more aggressive phenotype have been described. Genes and molecules which control either cell proliferation, apoptosis, or cell senescence have been implicated. Here we provided an overview of the main molecular changes underlying the pathogenesis of melanoma. All evidence clearly indicates the existence of a complex molecular machinery that provides checks and balances in normal melanocytes. Progression from normal melanocytes to malignant metastatic cells in melanoma patients is the result of a combination of down- or up-regulation of various effectors acting on different molecular pathways

    The pitfalls of plural valuation

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    This paper critically examines the current political context in which valuation studies of nature are undertaken. It challenges the belief that somehow, more and technically better valuation will drive the societal change toward more just and sustainable futures. Instead, we argue that current and proposed valuation practices risk to continue to overrepresent the values of those who hold power and dominate the valuation space, and to perpetuate the discrimination of the views and values of nondominant stakeholders. In tackling this politically sensitive issue, we define a political typology of valuations, making explicit the roles of power and discrimination. This is done to provide valuation professionals and other actors with a simple framework to determine if valuation actions and activities are constructive, inclusive, resolve injustices and enable systemic change, or rather entrench the status quo or aggravate existing injustices. The objective is to buttress actors in their decisions to support, accept, improve, oppose, or reject such valuations
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