Classical dendritic cells mediate fibrosis directly via the retinoic acid pathway in severe eye allergy

Fibrosis is a shared end-stage pathway to lung, liver, and heart failure. In the ocular mucosa (conjunctiva), fibrosis leads to blindness in trachoma, pemphigoid, and allergy. The indirect fibrogenic role of DCs via T cell activation and inflammatory cell recruitment is well documented. However, here we demonstrate that DCs can directly induce fibrosis. In the mouse model of allergic eye disease (AED), classical CD11b(+) DCs in the ocular mucosa showed increased activity of aldehyde dehydrogenase (ALDH), the enzyme required for retinoic acid synthesis. In vitro, CD11b(+) DC-derived ALDH was associated with 9-cis-retinoic acid ligation to retinoid x receptor (RXR), which induced conjunctival fibroblast activation. In vivo, stimulating RXR led to rapid onset of ocular mucosal fibrosis, whereas inhibiting ALDH activity in DCs or selectively depleting DCs markedly reduced fibrosis. Collectively, these data reveal a profibrotic ALDH-dependent pathway by DCs and uncover a role for DC retinoid metabolism

Aldehyde dehydrogenase inhibition blocks mucosal fibrosis in human and mouse ocular scarring

Mucous membrane pemphigoid (MMP) is a systemic mucosal scarring disease, commonly causing blindness, for which there is no antifibrotic therapy. Aldehyde dehydrogenase (ALDH) family 1 is upregulated in both ocular MMP (OMMP) conjunctiva and cultured fibroblasts. Application of the ALDH metabolite, retinoic acid (RA), to normal human conjunctival fibroblasts in vitro induced a diseased phenotype. Conversely, application of ALDH inhibitors, including disulfiram, to OMMP fibroblasts in vitro restored their functionality to that of normal controls. ALDH1 is also upregulated in the mucosa of the mouse model of scarring allergic eye disease, used here as a surrogate for OMMP, in which topical application of disulfiram decreased fibrosis in vivo. These data suggest that progressive scarring in OMMP results from ALDH/RA fibroblast autoregulation, that the ALDH1 subfamily has a central role in immune-mediated ocular mucosal scarring, and that ALDH inhibition with disulfiram is a potential, and readily translatable, antifibrotic therapy

Hundreds of genetic barcodes of the species-rich hydroid superfamily Plumularioidea (Cnidaria, Medusozoa) provide a guide toward more reliable taxonomy

Marine hydroids are important benthic components of shallow and deep waters worldwide, but their taxonomy is controversial because diagnostic morphological characters to categorize taxa are limited. Their genetic relationships are also little investigated. We tested taxonomic hypotheses within the highly speciose superfamily Plumularioidea by integrating a classical morphological approach with DNA barcoding of the 16S and COI mitochondrial markers for 659 and 196 specimens of Plumularioidea, respectively. Adding Genbank sequences, we inferred systematic relationships among 1,114 plumularioids, corresponding to 123 nominal species and 17 novel morphospecies in five families of Plumularioidea. We found considerable inconsistencies in the systematics of nominal families, genera and species. The families Kirchenpaueriidae and Plumulariidae were polyphyletic and the Halopterididae paraphyletic. Most genera of Plumularioidea are not monophyletic. Species diversity is considerably underestimated. Within our study, at least 10% of the morphologically-distinctive morphospecies are undescribed, and about 40% of the overall species richness is represented by cryptic species. Convergent evolution and morphological plasticity therefore blur systematic relationships. Additionally, cryptic taxa occur frequently in sympatry or parapatry, complicating correspondence with type material of described species. Sometimes conspecificity of different morphotypes was found. The taxonomy of hydroids requires continued comprehensive revision.This work relied on several hydrozoan samples collected from various sites, with the aid of many people. Supplementary Table S1 refers many of the people involved in the collection and/or preservation of the samples. C.J.M. acknowledges his great buddy-divers Jaime N.-Ruiz (CIMAR, Univ. Costa Rica), Axel Calderon, Nathaniel Chu, Eleni Petrou (STRI, Smiths. Inst.), Hanae Spathias, Karen Koltes (at the Belize station, Smith. Inst.), Freya Sommer (Hopkins Marine Station), Remilson Ferreira ('Costa Norte', Sao Tome), Frederico Cardigos (DOP, Univ. Azores) and others that assisted the dives. C.J.M. also acknowledges Rita Castillo (CIMAR, Univ. Costa Rica), Plinio Gondola, Ligia Calderon, Laura Geyer, Maria Castillo (STRI, Smiths. Inst.), Gregory Ruiz (SERC, Smiths. Inst.), Paul Greenhall, William Keel (MSC, Smith. Inst.), Manuel Enes, Valentina Matos (IMAR/DOP, Univ. Azores), Filipe Porteiro, Joao Goncalves (OKEANOS/IMAR, Univ. Azores), Marina Cunha, Ascensao Ravara (CESAM, Univ. Aveiro), Shirley Pomponi (Harbor Branch, Florida Atlantic Univ.), Estrela Matilde (Fundacao Principe Trust), Monica Albuquerque, Ines Tojeira (EMEPC), Diana Carvalho (Nat. Mus. Nat. Hist., Lisbon) and many others colleagues that facilitated the morphologic classifications and deposition of the samples. Peter Schuchert (Mus. d'Hist. Nat. Geneve) kindly provided some DNA extractes. Todd Kincaid and his team of GUE divers (Project Baseline - Azores) collected valuable samples from unusual depths. Joana Boavida (CIIMAR, Univ. Algarve) facilitated some samples of the 'DeepReefs' project. Jim Drewery (Marine Scotland Science Inst.) also provided few samples. Dale Calder (Royal Ontario Museum) provided some bibliography to C.J.M. and discussed/resolved some dubios taxonomic classifications. Colleagues at the L.A.B. (NMNH, Smith. Inst.) were very supportive. The APC fees for open access publication were supported by a program of the Regional Government of the Azores ("Apoio ao funcionamento e gestao dos centros de I&D regionais: 2018 - DRCT-medida 1

Development of a fish cell culture model to investigate the impact of fish oil replacement on lipid peroxidation

Fish oils are rich in omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA), predominantly 20:5n-3 and 22:6n-3, whereas vegetable oils contain abundant C18-PUFA, predominantly 18:3n-3 or 18:2n-6. We hypothesized that replacement of fish oils with vegetable oils would increase the oxidative stability of fish lipids. Here we have used the FHM cell line to test this hypothesis. The FHM cells were readily able to synthesize 20:5n-3 and 24:6n-3 from 18:3n-3 but 22:6n-3 synthesis was negligible. Also, they were readily able to synthesize 20:3n-6 from 18:2n-6 but 20:4n-6 synthesis was negligible. Mitochondrial β-oxidation was greatest for 18:3n-3 and 20:5n-3 and the rates for 16:0, 18:2n-6, 22:6n-3 and 18:1n-9 were significantly lower. Fatty acid incorporation was predominantly into phospholipids (79-97%) with very little incorporation into neutral lipids. Increasing the fatty acid concentration in the growth medium substantially increased the concentrations of 18:3n-3 and 18:2n-6 in the cell phospholipids but this was not the case for 20:5n-3 or 22:6n-3. When they were subjected to oxidative stress, the FHM cells supplemented with either 20:5n-3 or 22:6n-3 (as compared with 18:3n-3 or saturated fatty acids) exhibited significantly higher levels of thiobarbituric reactive substances (TBARS) indicating higher levels of lipid peroxidation. The results are discussed in relation to the effects of fatty acid unsaturation on the oxidative stability of cellular lipids and the implications for sustainable aquaculture

Environmental Control of Phase Transition and Polyp Survival of a Massive-Outbreaker Jellyfish

A number of causes have been proposed to account for the occurrence of gelatinous zooplankton (both jellyfish and ctenophore) blooms. Jellyfish species have a complex life history involving a benthic asexual phase (polyp) and a pelagic sexual phase (medusa). Strong environmental control of jellyfish life cycles is suspected, but not fully understood. This study presents a comprehensive analysis on the physicochemical conditions that control the survival and phase transition of Cotylorhiza tuberculata; a scyphozoan that generates large outbreaks in the Mediterranean Sea. Laboratory experiments indicated that the influence of temperature on strobilation and polyp survival was the critical factor controlling the capacity of this species to proliferate. Early life stages were less sensitive to other factors such as salinity variations or the competitive advantage provided by zooxanthellae in a context of coastal eutrophication. Coherently with laboratory results, the presence/absence of outbreaks of this jellyfish in a particular year seems to be driven by temperature. This is the first time the environmental forcing of the mechanism driving the life cycle of a jellyfish has been disentangled via laboratory experimentation. Projecting this understanding to a field population under climatological variability results in a pattern coherent with in situ records