RESUMO
The current concept of epigenetic repression is based on one repressor unit corresponding to one silent gene. This notion, however, cannot adequately explain concurrent silencing of multiple loci observed in large chromosome regions. The long-range epigenetic silencing (LRES) can be a frequent occurrence throughout the human genome. To comprehensively characterize the influence of estrogen signaling on LRES, we analyzed transcriptome, methylome, and estrogen receptor alpha (ESR1)-binding datasets from normal breast epithelia and breast cancer cells. This "omics" approach uncovered 11 large repressive zones (range, 0.35 approximately 5.98 megabases), including a 14-gene cluster located on 16p11.2. In normal cells, estrogen signaling induced transient formation of multiple DNA loops in the 16p11.2 region by bringing 14 distant loci to focal ESR1-docking sites for coordinate repression. However, the plasticity of this free DNA movement was reduced in breast cancer cells. Together with the acquisition of DNA methylation and repressive chromatin modifications at the 16p11.2 loci, an inflexible DNA scaffold may be a novel determinant used by breast cancer cells to reinforce estrogen-mediated repression.
Assuntos
Neoplasias da Mama/metabolismo , Cromossomos Humanos Par 16 , Epigênese Genética/fisiologia , Estrogênios/fisiologia , Inativação Gênica , Animais , Sítios de Ligação , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Células Cultivadas , Metilação de DNA , Receptor alfa de Estrogênio/metabolismo , Estrogênios/metabolismo , Feminino , Humanos , Glândulas Mamárias Humanas/citologia , Glândulas Mamárias Humanas/metabolismo , Família MultigênicaRESUMO
Elpidium is the most common ostracod genus occurring in phytotelmata in the Neotropical region, with distributions ranging from Florida, USA in the north to Rio Grande do Sul, Brazil in the south. However, the genus remains poorly known both in terms of diversity and of the distributional pattern of its species. Here, we describe six new species of Elpidium, E. oxumae n. sp., E. cordiforme n. sp., E. picinguabaense n. sp., E. eriocaularum n. sp., E. higutiae n. sp., E. purium n. sp., all from phytotelm environments in the Brazilian Atlantic rain forest. In addition, we discuss the distributional pattern and endemicity levels of Elpidium species in the light of these new taxonomic results and argue about possible misunderstandings on the distribution of the type species E. bromeliarum.
Assuntos
Crustáceos , Animais , BrasilRESUMO
Elpidium species exclusively inhabiting confined and temporary environments, such as those of tank-bromeliads, are a source of interesting and diverse studies on taxonomy, evolution and ecology, to name a few. However, despite its great diversity of species or potential for study, this genus (and other phytotelm members) has been poorly studied. In the last years, however, description of Elpidium species increased from six before 2013 to 11 today. This study is an effort to keep uncovering its great diversity and to go further in order to deeply understand the genus Elpidium. To this end, this study describes another species in the genus, Elpidium litoreum sp. nov., and proposes a phylogenetic reconstruction of it based on morphological characters. Our results point to the monophyly of Elpidium and puts Intrepidocythere ibipora as its sister-group. Although the phylogeny revealed some interesting relations, it also exposed some incongruities that ultimately demonstrate how superficial the current knowledge about the genus is. All these questions are discussed in detail. We see this work as at the same time an effort to better understand Elpidium and a stimulus to other researches to turn their attention to the historically neglected phytotelmata community.
RESUMO
Elpidium ostracods are known by their very particular niche (water accumulated in tank-bromeliads), their relatively low dispersal ability and their dependency on amphibians for dispersal and colonization of new bromeliads. All these characteristics make the genus an interesting group for evolutionary, ecological and even taxonomic studies. However, the diversity of the group remains poorly studied. Here, we describe three new species of Elpidium, Elpidium littlei n. sp., Elpidium heberti n. sp. and Elpidium wolfi n. sp., and re-describe Elpidium laesslei, all from Jamaica. These species are characterized by a copulatory process with separated ejaculatory duct and distal glans, a feature so far unique within the genus. Each species can, in turn, be diagnosed by soft part and carapace morphology, most notably comparing hemipenis, valve ornamentation and degree of sexual dimorphism. The observed morphological diversity of Elpidium is discussed in relation to previous genetic estimates that suggested an even higher diversity in Jamaica. We point to intraspecific variation and lack of complete morphological descriptions as possible explanations. We also reaffirm the need of multidisciplinary studies in order to do more objective and secure taxonomic classifications in future studies.
Assuntos
Evolução Biológica , Crustáceos , Animais , Ecologia , Jamaica , Caracteres SexuaisRESUMO
Fungi from the widely distributed genus Trichoderma are of great biotechnological interest, being currently used in a vast range of applications. Here, we report that high-molecular weight fraction (HWF) derived from Trichoderma asperelloides ethanolic extract exhibits antibiotic activity against staphylococcal biofilms. The antibacterial and anti-biofilm properties of T. asperelloides extracts were evaluated by well-established assays in Staphylococcus aureus ATCC strains (29213 and 6538) and in one clinical isolate from bovine mastitis. The HWF from T. asperelloides eradicated S. aureus by causing substantial matrix de-structuring and biomass reduction (p < 10-5) at concentrations as low as 2.3 µg mL-1. Additionally, we present ultra-structure analysis by the use of scanning electron microscopy as well as transmission microscopy, which showed that T. asperelloides killed cells through cell wall and membrane disturbance. Remarkably, the HWF from T. asperelloides killed S. aureus and eradicated its biofilms in a greater performance than gentamicin (p < 10-5), a known potent antibiotic against S. aureus. Our results indicate that extract from T. asperelloides may represent a promising candidate for the development of new antibiotics against gram-positive bacteria.
Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Etanol/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Trichoderma/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Biofilmes/crescimento & desenvolvimento , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Staphylococcus aureus/citologiaRESUMO
There is evidence that in the human breast there is a stem cell population that can give rise to many different cell types and have the unique potential to divide asymmetrically. In this way stem cells maintain the stem cell pool and simultaneously generate committed cells that reconstitute the organ for example for preparing the breast for a new pregnancy after the involution from a previous pregnancy and lactation process. In addition to the in vivo models of mammary morphogenesis there are in vitro systems that are more amenable to study in critically determined conditions the ductulogenic pattern of growth of the breast epithelia. Primary mammary epithelial cells grown in collagen matrix are able to form tree-like structures resembling in vivo ductulogenesis. The human breast epithelial cells MCF-10F formed tubules when grown in type I collagen and we demonstrated that treatment of these cells with 17ß-estradiol (E(2)) induces phonotypical changes indicative of neoplastic transformation. The transformation of MCF-10F by E(2) is associated with impaired ductal morphogenesis by altering the stem cells unique potential to divide asymmetrically inducing formation of solid masses mimicking intraductal carcinoma that progress to invasive and tumorigenic phenotype. In the present work we present evidence for the mechanism of cell asymmetry leading to normal ductulogenesis and how the normal stem cell is transformed to cancer stem cell by altering this process. Furthermore, we demonstrate that the carcinogenic agent, in this case E(2), induces a defect in the asymmetric cell division program of the normal mammary stem cell.