Complete Inactivation of Sebum-Producing Genes Parallels the Loss of Sebaceous Glands in Cetacea

Publisher's version (útgefin grein)Genomes are dynamic biological units, with processes of gene duplication and loss triggering evolutionary novelty. The mammalian skin provides a remarkable case study on the occurrence of adaptive morphological innovations. Skin sebaceous glands (SGs), for instance, emerged in the ancestor of mammals serving pivotal roles, such as lubrication, waterproofing, immunity, and thermoregulation, through the secretion of sebum, a complex mixture of various neutral lipids such as triacylglycerol, free fatty acids, wax esters, cholesterol, and squalene. Remarkably, SGs are absent in a few mammalian lineages, including the iconic Cetacea. We investigated the evolution of the key molecular components responsible for skin sebum production: Dgat2l6, Awat1, Awat2, Elovl3, Mogat3, and Fabp9. We show that all analyzed genes have been rendered nonfunctional in Cetacea species (toothed and baleen whales). Transcriptomic analysis, including a novel skin transcriptome from blue whale, supports gene inactivation. The conserved mutational pattern found in most analyzed genes, indicates that pseudogenization events took place prior to the diversification of modern Cetacea lineages. Genome and skin transcriptome analysis of the common hippopotamus highlighted the convergent loss of a subset of sebum-producing genes, notably Awat1 and Mogat3. Partial loss profiles were also detected in non-Cetacea aquatic mammals, such as the Florida manatee, and in terrestrial mammals displaying specialized skin phenotypes such as the African elephant, white rhinoceros and pig. Our findings reveal a unique landscape of “gene vestiges” in the Cetacea sebum-producing compartment, with limited gene loss observed in other mammalian lineages: suggestive of specific adaptations or specializations of skin lipids.This work was supported by Project No. 031342 cofinanced by COMPETE 2020, Portugal 2020 and the European Union through the ERDF, and by Fundac¸a~o para a Cie^ncia e a Tecnologia through national funds. R.R.F. thanks the Danish National Research Foundation for its support of the Center for Macroecology, Evolution, and Climate (grant DNRF96). We acknowledge the various Cetacea genome consortiums for genome sequencing and assemblies. We also thank Gısli Vikingsson at the Marine and Freshwater Research Institute in Iceland for lending us the Larsen gun and to North Sailing whale watching for the use of their zodiac.Peer Reviewe

Religious experience and aesthetic experience in plastic artists : perspectives from the psychology of religion

Pode a experiência religiosa ser substituída pela experiência estética? Os estudiosos se dividem na resposta. Situando a pergunta no quadro de referência conceitual e epistemológico que distingue entre religião substantiva e religião funcional, levantamos a hipótese de que não há substituição substantiva, mas pode haver substituição funcional entre essas experiências. Levantamos a hipótese ulterior de que a experiência estética pode ser uma experiência do sagrado. As hipóteses foram examinadas com os dados obtidos em entrevistas com oito renomados artistas plásticos, por ocasião da 23ª Bienal de São Paulo, em 1996. Os dados revelaram diferenças, continuidades e analogias entre arte e religião assim como entre arte e sagrado, que permitiram reconhecer em alguns casos substituição funcional da religião pela arte, principalmente se dotada da densidade do sagrado.ABSTRACT Can aesthetic experience replace religious experience? Researchers are quite divided about this issue. From a conceptual and epistemological framework that distinguishes between substantive and functional religion, we formulated the hypothesis that there is not a substantive replacement, but there can be a functional replacement of religious experience by an aesthetic experience. We also considered the additional hypothesis that aesthetic experience can be an experience of the sacred. The hypotheses were examined with the help of interviews with eight well known Brazilian artists, by the time of the 23rd Biennial International Exhibition of Arts of São Paulo, 1996. The data revealed differences, continuities, and analogies between art and religion and between art and the sacred, that allowed to identify in some cases a functional replacement of religion by art, especially if art was endowed with the density of the sacred

Retinoic acid regulates avian lung branching through a molecular network

Retinoic acid (RA) is of major importance during vertebrate embryonic development and its levels need to be strictly regulated otherwise congenital malformations will develop. Through the action of specific nuclear receptors, named RAR/RXR, RA regulates the expression of genes that eventually influence proliferation and tissue patterning. RA has been described as crucial for different stages of mammalian lung morphogenesis, and as part of a complex molecular network that contributes to precise organogenesis; nonetheless, nothing is known about its role in avian lung development. The current report characterizes, for the first time, the expression pattern of RA signaling members (stra6, raldh2, raldh3, cyp26a1, rar alpha, and rar beta) and potential RA downstream targets (sox2, sox9, meis1, meis2, tgf beta 2, and id2) by in situ hybridization. In the attempt of unveiling the role of RA in chick lung branching, in vitro lung explants were performed. Supplementation studies revealed that RA stimulates lung branching in a dose-dependent manner. Moreover, the expression levels of cyp26a1, sox2, sox9, rar beta, meis2, hoxb5, tgf beta 2, id2, fgf10, fgfr2, and shh were evaluated after RA treatment to disclose a putative molecular network underlying RA effect. In situ hybridization analysis showed that RA is able to alter cyp26a1, sox9, tgf beta 2, and id2 spatial distribution; to increase rar beta, meis2, and hoxb5 expression levels; and has a very modest effect on sox2, fgf10, fgfr2, and shh expression levels. Overall, these findings support a role for RA in the proximal-distal patterning and branching morphogenesis of the avian lung and reveal intricate molecular interactions that ultimately orchestrate branching morphogenesis.The authors would like to thank Ana Lima for slide sectioning and Rita Lopes for contributing to the initiation of this project. This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the Project POCI-01-0145-FEDER-007038; and by the Project NORTE-01-0145- FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Melatonin antiproliferative effects require active mitochondrial function in embryonal carcinoma cells

Although melatonin oncostatic and cytotoxic effects have been described in different types of cancer cells, the specific mechanisms leading to its antitumoral effects and their metabolic context specificity are still not completely understood. Here, we evaluated the effects of melatonin in P19 embryonal carcinoma stem cells (CSCs) and in their differentiated counterparts, cultured in either high glucose medium or in a galactose (glucose-free) medium which leads to glycolytic suppression and increased mitochondrial metabolism. We found that highly glycolytic P19 CSCs were less susceptible to melatonin antitumoral effects while cell populations relying on oxidative metabolism for ATP production were more affected. The observed antiproliferative action of melatonin was associated with an arrest at S-phase, decreased oxygen consumption, down-regulation of BCL-2 expression and an increase in oxidative stress culminating with caspase-3-independent cell death. Interestingly, the combined treatment of melatonin and dichloroacetate had a synergistic effect in cells grown in the galactose medium and resulted in an inhibitory effect in the highly resistant P19 CSCs. Melatonin appears to exert its antiproliferative activity in P19 carcinoma cells through a mitochondrially-mediated action which in turn allows the amplification of the effects of dichloroacetate, even in cells with a more glycolytic phenotype

Religious experience and aesthetic experience in plastic artists: perspectives from the psychology of religion / Experiência religiosa e experiência estética em artistas plásticos: perspectivas da psicologia da religião

Can aesthetic experience replace religious experience? Researchers are quite divided about this issue. From a conceptual and epistemological framework that distinguishes between substantive and functional religion, we formulated the hypothesis that there is not a substantive replacement, but there can be a functional replacement of religious experience by an aesthetic experience. We also considered the additional hypothesis that aesthetic experience can be an experience of the sacred. The hypotheses were examined with the help of interviews with eight well known Brazilian artists, by the time of the 23rd Biennial International Exhibition of Arts of São Paulo, 1996. The data revealed differences, continuities, and analogies between art and religion and between art and the sacred, that allowed to identify in some cases a functional replacement of religion by art, especially if art was endowed with the density of the sacred

Chemical constituents of Salacia elliptica (celastraceae).

The chemical investigation of Salacia elliptica allowed to the isolation of 20 constituents: two polyols, one xanthone, a mixture of long chain hydrocarbons, one carboxylic acid, one polymer, two steroidal compounds, one aromatic ester and eleven pentacyclic triterpenes. These triterpenes include 3?-stearyloxy-oleanane, 3?-stearyloxy-ursane, one seco-friedelane, and eight compounds of the friedelane serie. The chemical structure and the relative configuration of a new triterpene 1,3-dioxo-16?-hydroxyfriedelane (15) were established through 1H and 13C NMR including 2D experiments (HMBC, HMQC, COSY and NOESY) and herein reported for the first time

The pressure pan evolution of human erythrovirus B19 in the Amazon

This study was supported by CNPq, MCT and FAPESP projects 00/04205-06 and 00/11511-06-VGDN program. ELD and PMAZ hold a PQ-CNPq scholarship. CMR and FLM hold a CAPES scholarshipMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Micobiologia. Laboratório de Virologia Clinica. São Paulo, SP, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Universidade de São Paulo USP. Departamento de Microbiologia. Laboratório de Evolução Molecular e Bioinformática. São Paulo, SP, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Universidade de São Paulo USP. Departamento de Microbiologia. Laboratório de Evolução Molecular e Bioinformática. São Paulo, SP, Brazil.Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Micobiologia. Laboratório de Virologia Clinica. São Paulo, SP, Brazil.Instituto Adolfo Lutz. São Paulo, SP, Brazil.University of San Marcos. Lima, Peru.The Pennsylvania State University. Department of Biology. Center for Infectious Disease Dynamics. University Park, PA, USA.Universidade de São Paulo USP. Departamento de Microbiologia. Laboratório de Evolução Molecular e Bioinformática. São Paulo, SP, Brazil.To understand the evolutionary dynamics of human parvovirus B19, we analyzed VP1 and VP2 gene sequences of B19 sampled from Belém (Amazon), the city of São Paulo, Brazil and globally. Our analysis revealed a strikingly different pattern of evolutionary change for those viral lineages introduced into Belém, which exhibited a higher rate of nonsynonymous substitutions compared to those viruses sampled from other locations. We propose that difference this is due to the high prevalence of B19 in Belem (up to 85 per cent) compared to other locations (prevalenceÆs of approximately 50 per cent), which imposes a more intense selection pressure. Hence, those B19 lineages introduced into Belem experienced an elevated rate of amino acid change, driven by positive selection, in order to generate serial re-infections in a small web of transmission, which can be thought of as an evolutionary "pressure pan

Promoting a significant increase in the photoluminescence quantum yield of terbium(III) complexes by ligand modification

Two discrete mononuclear complexes, [Tb(bbpen)(NO3)] (I) and [Tb(bbppn)(NO3)] (II), for which H 2 bbpen = N,N'-bis(2-hydroxybenzyl)-N,N'-bis(pyridin-2-ylmethyl)ethylenediamine and H 2 bbppn = N,N'-bis(2-hydroxylbenzyl)-N,N'-bis(pyridin-2-ylmethyl)-1,2-propanediamine, were synthesized and characterized by FTIR, Raman, and photoluminescence (PL, steady-state and time-resolved modes) spectroscopy. The attachment of a methyl group to the ethylenediamine portion of the ligand backbone differentiates II from I and acts as a determining feature to both the structural and optical properties of the former. The single-crystal X-ray structure of H 2 bbppn is described here for the first time, while that of complex II has been redetermined in the monoclinic C2 space group in light of new diffraction data. In II, selective crystallization leads to spontaneous resolution of enantiomeric molecules in different crystals. Absolute emission quantum yields (ϕ) and luminescence excited-state lifetimes (at room temperature and 11 K) were measured for both complexes. Despite their similar molecular structures, I and II exhibit remarkably different ϕ values of 21 ± 2% and 67 ± 7%, respectively, under UV excitation at room temperature. Results of quantum-mechanical (DFT and TD-DFT) calculations and experimental PL measurements also performed for H 2 bbpen and H 2 bbppn confirmed that both ligands are suitable to work as "antennas" for TbIII. Considering the 5D4 lifetime profiles and the significantly higher absolute quantum yield of II, it appears that thermally active nonradiative pathways present in I are minimized in II due to differences in the conformation of the ethylenediamine bridge