A pathogenic role for germline PTEN variants which accumulate into the nucleus.

The PTEN gene encodes a master regulator protein that exerts essential functions both in the cytoplasm and in the nucleus. PTEN is mutated in the germline of both patients with heterogeneous tumor syndromic diseases, categorized as PTEN hamartoma tumor syndrome (PHTS), and a group affected with autism spectrum disorders (ASD). Previous studies have unveiled the functional heterogeneity of PTEN variants found in both patient cohorts, making functional studies necessary to provide mechanistic insights related to their pathogenicity. Here, we have functionally characterized a PTEN missense variant [c.49C>G; p.(Gln17Glu); Q17E] associated to both PHTS and ASD patients. The PTEN Q17E variant displayed partially reduced PIP3-catalytic activity and normal stability in cells, as shown using S. cerevisiae and mammalian cell experimental models. Remarkably, PTEN Q17E accumulated in the nucleus, in a process involving the PTEN N-terminal nuclear localization sequence. The analysis of additional germline-associated PTEN N-terminal variants illustrated the existence of a PTEN N-terminal region whose targeting in disease causes PTEN nuclear accumulation, in parallel with defects in PIP3-catalytic activity in cells. Our findings highlight the frequent occurrence of PTEN gene mutations targeting PTEN N-terminus whose pathogenicity may be related, at least in part, with the retention of PTEN in the nucleus. This could be important for the implementation of precision therapies for patients with alterations in the PTEN pathway

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

Bioprospection of Trichoderma spp. involved in phosphate solubilization and biological control of Sclerotinia sclerotiorum in soybean

Os efeitos nocivos resultantes do uso de fertilizantes e agrotóxicos ao meio ambiente e a saúde humana estimulam a busca por estratégias que contribuam para uma agricultura mais sustentável. No Brasil, aspectos envolvendo a disponibilidade de fósforo e a presença de uma gama de patógenos de solo estão entre os principais fatores limitantes para a produção agrícola. O uso de microrganismos específicos para auxiliar na absorção de fósforo pela planta e como agentes de biocontrole vêm sendo uma estratégia promissora. Fungos do gênero Trichoderma encontram-se entre os agentes de controle biológico e solubilizadores de fosfato conhecidos e empregados mundialmente. Além do controle de fitopatógenos, melhoram o desenvolvimento e a produção de diversas espécies de plantas de importância econômica. O presente trabalho busca selecionar Trichoderma spp. capazes de solubilizar fósforo e de suprimir a atividade do fitopatógeno Sclerotinia sclerotiorum, agente etiológico do mofo branco. Além disso, avaliou- se um consórcio de Trichoderma spp. para uma possível formulação de um inoculante para soja. Dessa forma, foram avaliados 251 isolados de Trichoderma providos de solos da floresta Amazônica, em condições de laboratório e casa de vegetação. Plantas de soja foram cultivadas em solo com um gradiente de fosfato de rocha Bayóvar e de superfosfato triplo. A presença dos dois isolados de Trichoderma spp. (AMS 34.39 e AMS 31.15) apresentaram respostas positivas na promoção de crescimento das plantas, de 2,1 a 41,1%, considerando as fontes e níveis de fósforo em relação ao tratamento sem a presença de Trichoderma. O experimento de controle biológico selecionou três estirpes com potencial em controlar S. sclerotiorum em condições de casa de vegetação, não apresentando plantas com sintomas do mofo branco. E por fim, a aplicação do consórcio de Trichoderma spp. mostrou resultados positivos, auxiliando na absorção de fósforo em 39,6 a 49%, com possibilidade de um novo inoculante para a cultura da soja. A aplicação do consórcio não alterou a comunidade bacteriana do solo, mas estimulou os grupos envolvidos na solubilização de fosfato.The harmful effects resulting from the use of fertilizers and pesticides to the environment and human health stimulate the search for strategies that contribute to a more sustainable agriculture. In Brazil, aspects involving the availability of phosphorus and the presence of soil pathogens are the main limiting factors for agricultural production. The use of specific microorganisms to aid in the phosphorus absorption by the plant and as well as biocontrol agents has been a promising strategy. Fungi of the genus Trichoderma are found among biological control agents and phosphate solubilizers known and used worldwide. In addition to the control of phytopathogens, they improve the development and production of several species of economic importance. The aim of this work is to select Trichoderma spp. capable of solubilizing phosphorus and suppressing the activity of the phytopathogen Sclerotinia sclerotiorum, a fungus that causes the white mold. In addition, it was evaluated a consortium of Trichoderma spp. for a possible formulation of a soybean inoculant. In this way, 251 isolates of Trichoderma, from the Amazon forest soils, were evaluated in experiments under laboratory and greenhouse conditions. Soybean plants were grown in soil with a gradient of Bayovar rock phosphate and triple superphosphate. The presence of the two isolates of Trichoderma spp. (AMS 34.39 and AMS 31.15) showed positive responses in promoting plant growth, from 2.1 to 41.1%, considering the sources and levels of phosphorus in relation to the treatment without the presence of Trichoderma. The biological control experiment selected three strains with the potential to control S. sclerotiorum under greenhouse conditions, with no plants showing symptoms of white mold. And finally, the application of the consortium of Trichoderma spp. showed positive results, helping in the absorption of phosphorus in 39.6 to 49%, with the possibility of a new inoculant for soybean culture. The application of the consortium did not alter the soil bacterial community, but stimulated the groups involved in phosphate solubilization

Impact of the soil humidity on structure of the bacterial communities and on the enzymatic activities in soils of the Caatinga and Atlantic Forest

As comunidades microbianas regulam a ciclagem de nutrientes no solo. O impacto das mudanças climáticas sobre estas poderia alterar a estrutura, a função e provocar um desequilíbrio dos nutrientes no ambiente. O principal objetivo desse trabalho foi estudar o impacto da umidade sobre a diversidade e atividades enzimáticas das comunidades bacterianas em microcosmos compostos por solos dos biomas Caatinga e Mata Atlântica. Amostras de solo foram coletadas nos seguintes estados brasileiros: Bahia, Pernambuco e São Paulo totalizando quatro pontos de coleta, com um ponto em cada estado e dois pontos no estado de São Paulo. As amostras de solo dos dois biomas, foram incubadas em microcosmos, com três ciclos de umidade (60 %- 30 %, umidade relativa) e para cada ciclo de umidade, foram construídas uma biblioteca do gene 16S rRNA. Nas análises de alfa diversidade, foram calculados os índices PD (diversidade filogenética baseado nos ramos da árvore filogenética) e Shannon. Para avaliar a beta diversidade foi utilizado o índice Bray-Curts (índice de similaridade baseado nos grupos dominantes) e a distância UniFrac. Simultaneamente, cada uma das amostras de cada tratamento foi analisada para as seguintes atividades enzimáticas: fosfatase ácida e alcalina, arilsulfatase, desidrogenase, celulase, amilase, urease e fitase. Os resultados aqui obtidos mostraram que os filos Acidobacteria, Proteobacteria e Chloroflexi foram mais abundantes nos solos da Mata Atlântica e Actinobacteria, Proteobacteria, Chloroflexi e Acidobacteria nos solos da Caatinga, considerando a característica em estudo do efeito adverso do estresse hídrico. As classes mais prevalentes na Mata Atlântica foram Acidobacteria, Alphaproteobacteria, Betaproteobacteria e Gammaproteobacteria. Enquanto que para a Caatinga, as classes prevalentes foram Ktedonobacteria, Actinobacteria-6 e Betaproteobacteria. No que diz respeito ao estresse hídrico sobre as atividades enzimáticas, os dados demonstraram efeito significativo para todos os solos amostrados, exceto para a enzima fitase. Por correlação entre as OTUs e as enzimas observou-se que grupos específicos foram correlacionados positivamente com a atividade das enzimas e com C e N total nos solos estudados. Estes resultados indicam que os ciclos de umidade afetam a distribuição taxonômica das comunidades bacterianas e as funções enzimáticas.The microbial communities regulate the nutrient cycling in the soil. The impact of climate change on could alter the structure and function and cause an imbalance of nutrients in the environment. The main aim of this work was to study the impact of the soil humidity on diversity and enzymatic activities of bacterial communities in microcosms compounds soils of the Biosphere biomes of Caatinga and Atlantic Forest. Soil samples were collected in the following Brazilian states: Bahia, Pernambuco and Sao Paulo totaling four collection points, with a point in each state and two points in São Paulo. The soils samples of the two Biomes, were incubated in microcosms, with three humidity cycles (60% - 30% relative humidity) and for each humidity cycle, was constructed a 16S rRNA gene library. In the analyzes of alpha diversity, the PD indices were calculated (based on phylogenetic diversity branches of the phylogenetic tree) and Shannon and to test the beta diversity we used the Bray-Curts index (similarity index based on the dominant groups) and the distance UniFrac. Simultaneously, each soil sample of each treatment was analyzed for the following enzymatic activities: acid and alkaline phosphatase, arylsulfatase, dehydrogenase, cellulase, amylase, urease and phytase. The results herein obtained showed that the Phyla Acidobacteria, Proteobacteria and Chloroflexi were more abundant in the soils at Atlantic Forest, and Actinobacteria, Proteobacteria, Chloroflexi and Acidobacteria in the soils of Caatinga, considering the studied trait of the adverse effect of water stress. The most prevalent classes in the Atlantic Forest were Acidobacteria, Alphaproteobacteria, Betaproteobacteria and Gammaproteobacteria. While for the Caatinga, the prevalent classes were Ktedonobacteria, Actinobacteria-6 and Betaproteobacteria. In regard to the hydric stress on the enzymatic activities, the data showed significant effects for all sampling soils, except for the enzyme phytase. By correlations between OTUs and enzymes it was observed that specific groups were positively correlated with the activity of the enzymes and carbon and total nitrogen in the studied soils. These results indicate that humidity cycle affects the taxonomic distribution of bacterial communities and the enzymatic functions

Ticagrelor Increases SIRT1 and HES1 mRNA Levels in Peripheral Blood Cells from Patients with Stable Coronary Artery Disease and Chronic Obstructive Pulmonary Disease

Ticagrelor is a powerful P2Y12inhibitor with pleiotropic effects in the cardiovascularsystem. Consistently, we have reported that in patients with stable coronary artery disease (CAD) andconcomitant chronic obstructive pulmonary disease (COPD) who underwent percutaneous coronaryintervention (PCI), 1-month treatment with ticagrelor was superior in improving biological markersof endothelial function, compared with clopidogrel. The objective of this study was to investigate themechanisms underlying these beneficial effects of ticagrelor by conducting molecular analyses ofRNA isolated from peripheral blood cells of these patients. We determined mRNAs levels of markersof inflammation and oxidative stress, such asRORγt(T helper 17 cells marker),FoxP3(regulatoryT cells marker),NLRP3,ICAM1,SIRT1, Notch ligandsJAG1andDLL4,andHES1, a Notch targetgene. We found that 1-month treatment with ticagrelor, but not clopidogrel, led to increased levels ofSIRT1andHES1mRNAs. In patients treated with ticagrelor or clopidogrel, we observed a negativecorrelation among changes in bothSIRT1andHES1mRNA and serum levels of Epidermal GrowthFactor (EGF), a marker of endothelial dysfunction found to be reduced by ticagrelor treatment inour previous study. In conclusion, we report that in stable CAD/COPD patients ticagrelor positivelyregulatesHES1andSIRT1, two genes playing a protective role in the context of inflammation andoxidative stress. Our observations confirm and expand previous studies showing that the beneficialeffects of ticagrelor in stable CAD/COPD patients may be, at least in part, mediated by its capacity toreduce systemic inflammation and oxidative stres

Evaluation of E6 and E7 mRNA expression in HPV DNA positive breast cancer

Several studies have suggested a possible role for HPV in the pathogenesis of the breast cancer. We investigated the presence of the HPV DNA in breast cancers and non malignant disease breast tissues by the use of a standard HPV detection method (INNO-Lipa HPV), in order to detect HPV DNA in metastatic nodes, to investigate a possible cervical HPV co-infection, and to evaluate the E6/E7 mRNA expression in HPV DNA positive breast cancer tissues. The rate of HPV infection was significantly higher in the cancer group than in controls (9/31 vs 0/12, p = 0.04). One out of eight metastatic axillary nodes was positive for HPV infection; 2/3 of the positive HPV breast cancer patients were co-infected at the cervical site. The role of the virus in breast oncogenesis is still unclear, since our analysis failed in demonstrating the expression of viral E6 and E7 in positive HPV positive breast tumor tissues