Angiogenic Factors Stimulate Growth of Adult Neural Stem Cells

The ability to grow a uniform cell type from the adult central nervous system (CNS) is valuable for developing cell therapies and new strategies for drug discovery. The adult mammalian brain is a source of neural stem cells (NSC) found in both neurogenic and non-neurogenic zones but difficulties in culturing these hinders their use as research tools.Here we show that NSCs can be efficiently grown in adherent cell cultures when angiogenic signals are included in the medium. These signals include both anti-angiogenic factors (the soluble form of the Notch receptor ligand, Dll4) and pro-angiogenic factors (the Tie-2 receptor ligand, Angiopoietin 2). These treatments support the self renewal state of cultured NSCs and expression of the transcription factor Hes3, which also identifies the cancer stem cell population in human tumors. In an organotypic slice model, angiogenic factors maintain vascular structure and increase the density of dopamine neuron processes.We demonstrate new properties of adult NSCs and a method to generate efficient adult NSC cultures from various central nervous system areas. These findings will help establish cellular models relevant to cancer and regeneration

Strategies and results of field emission scanning electron microscopy (FE-SEM) in the study of parasitic protozoa

11 p. : il.Field emission scanning electron microscopy (FE-SEM) provides a range of strategies for investigating the structural organization of biological systems, varying from isolated macromolecules to tissue organization and whole organisms. This review covers some of the results so far obtained using FE-SEM observation and various protocols of sample fixation to analyze the structural organization of parasitic protozoa and their interaction with host cells. The employment of FE-SEM can be broadened through the use of gold-labeled molecules or tracers, gradual extraction by detergents, and cleavage techniques. These analyses provide significant contributions to the characterization of these organisms concerning ultrastructure, cytoskeleton, motility and intracellular behavior

Heterogeneity in the sensitivity of microtubules of Giardia lamblia to the herbicide oryzalin

8 p. : il.Giardia lamblia is a protozoan that inhabits the small intestine of vertebrates, attaching to the epithelial cells by means of cytoskeletal elements. G. lamblia trophozoites possess several microtubular structures, namely the adhesive disc, the median body, the funis and the four pairs of flagella. Several drugs that target cytoskeletal proteins have been used in the study of cytoskeletal function and dynamics. In this work, we used oryzalin, which binds to α-tubulin, as a tool to study the Giardia cytoskeleton. The trophozoites were treated with oryzalin, and its effects were analysed by immunofluorescency, transmission and scanning electron microscopies. Oryzalin inhibited Giardia proliferation. Treated cells were not able to complete cell division and had flagella showing extensive shortening. Strikingly, the drug did not interfere with the adhesive disc, in contrast to what happens when other drugs are used

Sox2 Acts through Sox21 to Regulate Transcription in Pluripotent and Differentiated Cells

SummarySox2 is an important transcriptional regulator in embryonic and adult stem cells [1–4]. Recently, Sox2 was identified as an oncogene in many endodermal cancers, including colon cancer [5–8]. There is great interest in how Sox2 cooperates with other transcription factors to regulate stem cell renewal, differentiation, and reprogramming [9]. However, we still lack a general understanding of Sox2 transcriptional action. To determine transcriptional partners of Sox2 in adult cells, we generated mice where gene expression could be induced by an externally applied stimulus. We analyzed the consequences in the intestine where cell turnover is rapid. Sox2 expression, but not Oct4, specifically increased the numbers of stem cells and repressed Cdx2, a master regulator of endodermal identity. In vivo studies demonstrated that Sox21, another member of the SoxB gene family, was a specific, immediate, and cell-autonomous target of Sox2 in intestinal stem cells. In vitro experiments showed that Sox21 was sufficient to repress Cdx2 in colon cancer cells and in pluripotent stem cells. Sox21 was also specifically induced by Sox2 in fibroblasts and inhibition of Sox21 blocked reprogramming to the pluripotent state. These results show that transcriptional induction of Sox21 is a rapid and general mediator of the effects of Sox2 on cell identity in a wide range of cell types

Sofosbuvir protects Zika virus-infected mice from mortality, preventing short- and long-term sequelae

Submitted by Sandra Infurna ([email protected]) on 2017-10-17T12:58:25Z No. of bitstreams: 1 andre_ferreira_etal_IOC_2017.pdf: 1574700 bytes, checksum: 1cbe13c85078c5cb11c6954145f48296 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-10-17T13:16:07Z (GMT) No. of bitstreams: 1 andre_ferreira_etal_IOC_2017.pdf: 1574700 bytes, checksum: 1cbe13c85078c5cb11c6954145f48296 (MD5)Made available in DSpace on 2017-10-17T13:16:07Z (GMT). No. of bitstreams: 1 andre_ferreira_etal_IOC_2017.pdf: 1574700 bytes, checksum: 1cbe13c85078c5cb11c6954145f48296 (MD5) Previous issue date: 2017Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biologia. Rio de Janeiro, RJ, BrasilBMK Consortium: Blanver Farmoquímica Ltda; Microbiológica Química e Farmacêutica Ltda, Karin Bruning & Cia. Ltda. Taboão da Serra, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil. / Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças Negligenciadas. Rio de Janeiro, RJ, Brasil.Zika virus (ZIKV) causes significant public health concerns because of its association with congenital malformations, neurological disorders in adults, and, more recently, death. Considering the necessity to mitigate ZIKV-associated diseases, antiviral interventions are an urgent necessity. Sofosbuvir, a drug in clinical use against hepatitis C virus (HCV), is among the FDA-approved substances endowed with anti-ZIKV activity. In this work, we further investigated the in vivo activity of sofosbuvir against ZIKV. Neonatal Swiss mice were infected with ZIKV (2 × 10(7) PFU) and treated with sofosbuvir at 20 mg/kg/day, a concentration compatible with pre-clinical development of this drug. We found that sofosbuvir reduced acute levels of ZIKV from 60 to 90% in different anatomical compartments, such as the blood plasma, spleen, kidney, and brain. Early treatment with sofosbuvir doubled the percentage and time of survival of ZIKV-infected animals. Sofosbuvir also prevented the acute neuromotor impairment triggered by ZIKV. In the long-term behavioural analysis of ZIKV-associated sequelae, sofosbuvir prevented loss of hippocampal- and amygdala-dependent memory. Our results indicate that sofosbuvir inhibits ZIKV replication in vivo, which is consistent with the prospective necessity of antiviral drugs to treat ZIKV-infected individuals

MOESM1 of The availability of the embryonic TGF-β protein Nodal is dynamically regulated during glioblastoma multiforme tumorigenesis

Additional file 1: Figure S1. Nodal immunostaining changes along the development of the oncospheres. (a) Small sphere showing only cells that with a symmetrical Nodal distribution in the cytoplasm. (b) Large sphere comprised by cells with distinct Nodal distributions. (c–e) Nodal immunostaining (red) in OB1 stem cells placed at the top of oncospheres is localized to the cell membrane (green, phalloidin, asterisk). (f–h) Cells located at the lateral edge of oncospheres harboring different heights presented Nodal immunostaining symmetrically distributed in the cytoplasm of cells. (i–l) Cells directly attached to the substrate also presented a symmetrical distribution of Nodal. (e, h, k, l) Optical slices projected on the YZ axis showing a virtual reconstruction of the oncosphere