Oleanolic acid but not ursolic acid induces cell death in HepG2 cells under starvation-induced autophagy

Dissertação de mestrado em Genética MolecularCancer incidence is increasing worldwide mainly due to changes in diet, life style and increased lifespan. In particular, liver cancer is the fifth most common cancer in the world and the third most common cause of cancer mortality. Plant phytochemicals are a good and promising source of anticancer compounds. In a previous study, we reported the potential of ursolic acid (UA) to induce cell death and to inhibit proliferation in colorectal cancer cells. This natural triterpenoid, UA, was also shown to activate JNK and to modulate molecular markers of autophagy. In the present study, the ability of two isomer triterpenoids, UA and oleanolic acid (OA), to induce cell death and modulate autophagy in the human hepatocellular carcinoma cell line (HepG2 cells) was tested. For that, the effect of these phytochemicals on cell death was evaluated by MTT assay and propidium iodide staining, in complete and starvation medium. Autophagy markers were evaluated by western blot and fluorescence microscopy. Contrary to our previous data with other cell lines, HepG2 cells were less susceptible to UA and, unexpectedly, OA was a more potent inducer of cell death than UA. Interestingly, starvation-induced autophagy sensitized HepG2 cells to cell death caused by OA, but not by UA. The IC50 of OA decreased from about 50 μM in complete medium to 3.5 μM in starvation medium. Although UA and OA increased the levels of autophagy markers LC3 and p62, as well as the number of acidic vacuoles (as assessed by MDC staining), the cell death induced by OA was not prevented by inhibitors of autophagy and of lysosome proteases. Overall, the results seem to indicate that autophagy is not directly involved in cell death induced by OA. Interestingly, methyl- -cyclodextrin (a polymer able to decrease membrane cholesterol content) prevented OA-induced cell death, which indicates that disruption of cholesterol homeostasis, and in particular in lipid rafts, may be involved in OA effects under starvation conditions. The present results suggest the application of OA as a specific drug for cancer treatment in particular cell physiological conditions, such as under metabolic stress.A incidência do cancro está a aumentar em todo o mundo principalmente devido a alterações da alimentação, do estilo de vida e do aumento da esperança média de vida. Em particular, o cancro do fígado é o quinto cancro mais comum no mundo e a terceira maior causa de morte por cancro. Os fitoquímicos são uma excelente e promissora fonte de compostos anticancerígenos. Num estudo anterior o nosso grupo descreveu o potencial do ácido ursólico (AU) na indução de morte e na inibição da proliferação de células do cancro coloretal. Este triterpenóide de origem natural foi também descrito como ativador da sinalização JNK e modulador de marcadores moleculares de autofagia. No presente trabalho foi testada a capacidade de dois isómeros triterpenóides, o AU e o ácido oleanólico (AO), em induzir morte celular e modular a autofagia numa linha celular do carcinoma hepatocelular humano (células HepG2). Para tal, o efeito destes fitoquímicos na morte celular foi avaliado pelo ensaio de MTT e pela marcação com o iodeto de propídio, tanto em meio completo como em meio com privação de nutrientes. Os marcadores de autofagia foram avaliados por western blot e também por microscopia de fluorescência. Contrariamente a resultados anteriores com outras linhas celulares, as células HepG2 foram menos suscetíveis ao AU, bem como o AO mostrou ser mais potente na indução de morte celular do que o AU. Além disso, a autofagia induzida pela privação de nutrientes suscetibilizou marcadamente as células HepG2 para a morte celular causada pelo AO, e tal já não se verificou com o AU. Nestas condições o IC50 do AO foi de 3,5 μM, enquanto em meio completo era de cerca de 50 μM. Embora, o AU e o AO aumentem os níveis dos marcadores autofágicos LC3 e p62, bem como o número de vacúolos acídicos (avaliado pela marcação com MDC), a morte celular induzida pelo AO não foi prevenida por inibidores de autofagia e nem por inibidores de proteases lisossomais. Em geral, os resultados parecerem indicar que a autofagia não está diretamente envolvida na morte celular induzida pelo AO. No entanto, um polímero capaz de diminuir o conteúdo de colesterol nas membranas celulares, a metil- -ciclodextrina, preveniu a morte celular induzida pelo AO. Este resultado indica-nos que o AO pode induzir uma alteração na homeostasia do colesterol, em particular em domínios lipídicos ricos em colesterol, com efeitos drásticos sob a viabilidade das células quando estas estão sob privação de nutrientes. Estes resultados sugerem-nos que o AO pode ser utilizado no tratamento do cancro em condições fisiológicas específicas, tal como sob stress metabólico.Fundação para a Ciência e Tecnologia (FCT) – Projeto PTDC/QUI-BIQ/101392/200

ATLANTIC EPIPHYTES: a data set of vascular and non-vascular epiphyte plants and lichens from the Atlantic Forest

Epiphytes are hyper-diverse and one of the frequently undervalued life forms in plant surveys and biodiversity inventories. Epiphytes of the Atlantic Forest, one of the most endangered ecosystems in the world, have high endemism and radiated recently in the Pliocene. We aimed to (1) compile an extensive Atlantic Forest data set on vascular, non-vascular plants (including hemiepiphytes), and lichen epiphyte species occurrence and abundance; (2) describe the epiphyte distribution in the Atlantic Forest, in order to indicate future sampling efforts. Our work presents the first epiphyte data set with information on abundance and occurrence of epiphyte phorophyte species. All data compiled here come from three main sources provided by the authors: published sources (comprising peer-reviewed articles, books, and theses), unpublished data, and herbarium data. We compiled a data set composed of 2,095 species, from 89,270 holo/hemiepiphyte records, in the Atlantic Forest of Brazil, Argentina, Paraguay, and Uruguay, recorded from 1824 to early 2018. Most of the records were from qualitative data (occurrence only, 88%), well distributed throughout the Atlantic Forest. For quantitative records, the most common sampling method was individual trees (71%), followed by plot sampling (19%), and transect sampling (10%). Angiosperms (81%) were the most frequently registered group, and Bromeliaceae and Orchidaceae were the families with the greatest number of records (27,272 and 21,945, respectively). Ferns and Lycophytes presented fewer records than Angiosperms, and Polypodiaceae were the most recorded family, and more concentrated in the Southern and Southeastern regions. Data on non-vascular plants and lichens were scarce, with a few disjunct records concentrated in the Northeastern region of the Atlantic Forest. For all non-vascular plant records, Lejeuneaceae, a family of liverworts, was the most recorded family. We hope that our effort to organize scattered epiphyte data help advance the knowledge of epiphyte ecology, as well as our understanding of macroecological and biogeographical patterns in the Atlantic Forest. No copyright restrictions are associated with the data set. Please cite this Ecology Data Paper if the data are used in publication and teaching events. © 2019 The Authors. Ecology © 2019 The Ecological Society of Americ

Participação política no Brasil: ação coletiva e interfaces socioestatais

Essa coletânea reúne alguns trabalhos apresentados e discutidos no “Encontro internacional participação, democracia e políticas públicas: aproximando agendas e agentes”, realizado na Faculdade de Ciências e Letras da Unesp de Araraquara em abril de 2013. O encontro foi organizado pelo Grupo de Pesquisa Participação, Democracia e Políticas Públicas, formado por docentes e pesquisadores ligados ao Departamento de Antropologia, Política e Filosofia e também ao Departamento de Administração Pública desta faculdade. A proposta do encontro partiu do diagnóstico de ambos os departamentos da necessidade de se ampliar os debates que relacionem as temáticas da participação, das políticas públicas e da democracia no Brasil e na América Latina, no atual contexto de insuficiência das instituições políticas calcadas no âmbito da democracia liberal e de uma notória “crise da representação”. O livro foi dividido em três partes, “Ação coletiva e institucionalização: interfaces socioestatais”, que trata dos processos de institucionalização dos movimentos sociais; “Instituições participativas da teoria à implementação: dilemas e desafios”, sobre estratégias de governança; e “Participação como política e a política da participação: difusão, impactos, poder”, sobre políticas públicas e o trabalho das ONGs nas ações governamentais

NEOTROPICAL ALIEN MAMMALS: a data set of occurrence and abundance of alien mammals in the Neotropics

Biological invasion is one of the main threats to native biodiversity. For a species to become invasive, it must be voluntarily or involuntarily introduced by humans into a nonnative habitat. Mammals were among first taxa to be introduced worldwide for game, meat, and labor, yet the number of species introduced in the Neotropics remains unknown. In this data set, we make available occurrence and abundance data on mammal species that (1) transposed a geographical barrier and (2) were voluntarily or involuntarily introduced by humans into the Neotropics. Our data set is composed of 73,738 historical and current georeferenced records on alien mammal species of which around 96% correspond to occurrence data on 77 species belonging to eight orders and 26 families. Data cover 26 continental countries in the Neotropics, ranging from Mexico and its frontier regions (southern Florida and coastal-central Florida in the southeast United States) to Argentina, Paraguay, Chile, and Uruguay, and the 13 countries of Caribbean islands. Our data set also includes neotropical species (e.g., Callithrix sp., Myocastor coypus, Nasua nasua) considered alien in particular areas of Neotropics. The most numerous species in terms of records are from Bos sp. (n = 37,782), Sus scrofa (n = 6,730), and Canis familiaris (n = 10,084); 17 species were represented by only one record (e.g., Syncerus caffer, Cervus timorensis, Cervus unicolor, Canis latrans). Primates have the highest number of species in the data set (n = 20 species), partly because of uncertainties regarding taxonomic identification of the genera Callithrix, which includes the species Callithrix aurita, Callithrix flaviceps, Callithrix geoffroyi, Callithrix jacchus, Callithrix kuhlii, Callithrix penicillata, and their hybrids. This unique data set will be a valuable source of information on invasion risk assessments, biodiversity redistribution and conservation-related research. There are no copyright restrictions. Please cite this data paper when using the data in publications. We also request that researchers and teachers inform us on how they are using the data

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans—anteaters, sloths, and armadillos—have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, 10 anteaters, and 6 sloths. Our data set includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the southern United States, Mexico, and Caribbean countries at the northern portion of the Neotropics, to the austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n = 5,941), and Cyclopes sp. have the fewest (n = 240). The armadillo species with the most data is Dasypus novemcinctus (n = 11,588), and the fewest data are recorded for Calyptophractus retusus (n = 33). With regard to sloth species, Bradypus variegatus has the most records (n = 962), and Bradypus pygmaeus has the fewest (n = 12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other data sets of Neotropical Series that will become available very soon (i.e., Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans data set. Please cite this data paper when using its data in publications. We also request that researchers and teachers inform us of how they are using these data

NEOTROPICAL CARNIVORES: a data set on carnivore distribution in the Neotropics

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non-detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non-governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peer-reviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non-detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio-temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other large-scale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data

Brazilian Flora 2020: Leveraging the power of a collaborative scientific network

International audienceThe shortage of reliable primary taxonomic data limits the description of biological taxa and the understanding of biodiversity patterns and processes, complicating biogeographical, ecological, and evolutionary studies. This deficit creates a significant taxonomic impediment to biodiversity research and conservation planning. The taxonomic impediment and the biodiversity crisis are widely recognized, highlighting the urgent need for reliable taxonomic data. Over the past decade, numerous countries worldwide have devoted considerable effort to Target 1 of the Global Strategy for Plant Conservation (GSPC), which called for the preparation of a working list of all known plant species by 2010 and an online world Flora by 2020. Brazil is a megadiverse country, home to more of the world's known plant species than any other country. Despite that, Flora Brasiliensis, concluded in 1906, was the last comprehensive treatment of the Brazilian flora. The lack of accurate estimates of the number of species of algae, fungi, and plants occurring in Brazil contributes to the prevailing taxonomic impediment and delays progress towards the GSPC targets. Over the past 12 years, a legion of taxonomists motivated to meet Target 1 of the GSPC, worked together to gather and integrate knowledge on the algal, plant, and fungal diversity of Brazil. Overall, a team of about 980 taxonomists joined efforts in a highly collaborative project that used cybertaxonomy to prepare an updated Flora of Brazil, showing the power of scientific collaboration to reach ambitious goals. This paper presents an overview of the Brazilian Flora 2020 and provides taxonomic and spatial updates on the algae, fungi, and plants found in one of the world's most biodiverse countries. We further identify collection gaps and summarize future goals that extend beyond 2020. Our results show that Brazil is home to 46,975 native species of algae, fungi, and plants, of which 19,669 are endemic to the country. The data compiled to date suggests that the Atlantic Rainforest might be the most diverse Brazilian domain for all plant groups except gymnosperms, which are most diverse in the Amazon. However, scientific knowledge of Brazilian diversity is still unequally distributed, with the Atlantic Rainforest and the Cerrado being the most intensively sampled and studied biomes in the country. In times of “scientific reductionism”, with botanical and mycological sciences suffering pervasive depreciation in recent decades, the first online Flora of Brazil 2020 significantly enhanced the quality and quantity of taxonomic data available for algae, fungi, and plants from Brazil. This project also made all the information freely available online, providing a firm foundation for future research and for the management, conservation, and sustainable use of the Brazilian funga and flora