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Sample records for basal progenitor progeny

  1. Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny

    PubMed Central

    Davis, Felicity M.; Lloyd-Lewis, Bethan; Harris, Olivia B.; Kozar, Sarah; Winton, Douglas J.; Muresan, Leila; Watson, Christine J.

    2016-01-01

    The mammary gland undergoes cycles of growth and regeneration throughout reproductive life, a process that requires mammary stem cells (MaSCs). Whilst recent genetic fate-mapping studies using lineage-specific promoters have provided valuable insights into the mammary epithelial hierarchy, the true differentiation potential of adult MaSCs remains unclear. To address this, herein we utilize a stochastic genetic-labelling strategy to indelibly mark a single cell and its progeny in situ, combined with tissue clearing and 3D imaging. Using this approach, clones arising from a single parent cell could be visualized in their entirety. We reveal that clonal progeny contribute exclusively to either luminal or basal lineages and are distributed sporadically to branching ducts or alveoli. Quantitative analyses suggest that pools of unipotent stem/progenitor cells contribute to adult mammary gland development. Our results highlight the utility of tracing a single cell and reveal that progeny of a single proliferative MaSC/progenitor are dispersed throughout the epithelium. PMID:27779190

  2. Lung epithelial tip progenitors integrate glucocorticoid- and STAT3-mediated signals to control progeny fate

    PubMed Central

    Laresgoiti, Usua; Rao, Chandrika; Brady, Jane L.; Richardson, Rachel V.; Batchen, Emma J.; Chapman, Karen E.

    2016-01-01

    Insufficient alveolar gas exchange capacity is a major contributor to lung disease. During lung development, a population of distal epithelial progenitors first produce bronchiolar-fated and subsequently alveolar-fated progeny. The mechanisms controlling this bronchiolar-to-alveolar developmental transition remain largely unknown. We developed a novel grafting assay to test if lung epithelial progenitors are intrinsically programmed or if alveolar cell identity is determined by environmental factors. These experiments revealed that embryonic lung epithelial identity is extrinsically determined. We show that both glucocorticoid and STAT3 signalling can control the timing of alveolar initiation, but that neither pathway is absolutely required for alveolar fate specification; rather, glucocorticoid receptor and STAT3 work in parallel to promote alveolar differentiation. Thus, developmental acquisition of lung alveolar fate is a robust process controlled by at least two independent extrinsic signalling inputs. Further elucidation of these pathways might provide therapeutic opportunities for restoring alveolar capacity. PMID:27578791

  3. UbC-StarTrack, a clonal method to target the entire progeny of individual progenitors

    PubMed Central

    Figueres-Oñate, María; García-Marqués, Jorge; López-Mascaraque, Laura

    2016-01-01

    Clonal cell analysis defines the potential of single cells and the diversity they can produce. To achieve this, we have developed a novel adaptation of the genetic tracing strategy, UbC-StarTrack, which attributes a specific and unique color-code to single neural precursors, allowing all their progeny to be tracked. We used integrable fluorescent reporters driven by a ubiquitous promoter in PiggyBac-based vectors to achieve inheritable and stable clonal cell labeling. In addition, coupling this to an inducible Cre-LoxP system avoids the expression of non-integrated reporters. To assess the utility of this system, we first analyzed images of combinatorial expression of fluorescent reporters in transfected cells and their progeny. We also validated the efficiency of the UbC-StarTrack to trace cell lineages through in vivo, in vitro and ex vivo strategies. Finally, progenitors located in the lateral ventricles were targeted at embryonic or postnatal stages to determine the diversity of neurons and glia they produce, and their clonal relationships. In this way we demonstrate that UbC-StarTrack can be used to identify all the progeny of a single cell and that it can be employed in a wide range of contexts. PMID:27654510

  4. Cortical ventricular zone progenitors and their progeny maintain spatial relationships and radial patterning during preplate development indicating an early protomap.

    PubMed

    O'Leary, Dennis D M; Borngasser, Douglass

    2006-07-01

    The graded expression of transcription factors by progenitors in the ventricular zone (VZ) confers positional or area identity that is inherited by subplate (SP) neurons and governs their expression of guidance molecules for thalamocortical axons and other properties required for cortical area specification. This mechanism would be most efficient if VZ progenitors and their SP neuronal progeny maintain neighbor relationships during the generation of the preplate (PP), the precursor of the SP. Therefore, a major goal of this study is to determine whether progenitors in the cortical VZ and their progeny maintain neighbor relationships during the genesis of the neocortical PP. We used time-lapse video microscopy to follow the movements of VZ progenitors and the radial movement of their progeny and distribution in the PP in whole-mount or slice cortical explants from embryonic rats at stages when PP neurons are generated. We show that labeled VZ cells proliferate and have a strong tendency to retain neighbor relationships within the VZ and that their neuronal progeny move superficially along a radial column to form the overlying PP; during this process, their neuronal progeny also retain neighbor relationships and thereby form the PP in spatial register with the VZ progenitors that generate them. This behavior differs from that reported at later stages of cortical development, when cortical plate (CP) neurons are generated, and considerable dispersion is evident among both cells within the VZ and neuronal progeny as they migrate from the VZ to the CP. However, our findings show that at the early stage of cortical development, when PP/SP neurons are generated, the VZ is, at a cellular level, a "protomap" of the PP/SP.

  5. The evolution of basal progenitors in the developing non-mammalian brain

    PubMed Central

    Nomura, Tadashi; Ohtaka-Maruyama, Chiaki; Yamashita, Wataru; Wakamatsu, Yoshio; Murakami, Yasunori; Calegari, Federico; Suzuki, Kunihiro; Gotoh, Hitoshi; Ono, Katsuhiko

    2016-01-01

    The amplification of distinct neural stem/progenitor cell subtypes during embryogenesis is essential for the intricate brain structures present in various vertebrate species. For example, in both mammals and birds, proliferative neuronal progenitors transiently appear on the basal side of the ventricular zone of the telencephalon (basal progenitors), where they contribute to the enlargement of the neocortex and its homologous structures. In placental mammals, this proliferative cell population can be subdivided into several groups that include Tbr2+ intermediate progenitors and basal radial glial cells (bRGs). Here, we report that basal progenitors in the developing avian pallium show unique morphological and molecular characteristics that resemble the characteristics of bRGs, a progenitor population that is abundant in gyrencephalic mammalian neocortex. Manipulation of LGN (Leu-Gly-Asn repeat-enriched protein) and Cdk4/cyclin D1, both essential regulators of neural progenitor dynamics, revealed that basal progenitors and Tbr2+ cells are distinct cell lineages in the developing avian telencephalon. Furthermore, we identified a small population of subapical mitotic cells in the developing brains of a wide variety of amniotes and amphibians. Our results suggest that unique progenitor subtypes are amplified in mammalian and avian lineages by modifying common mechanisms of neural stem/progenitor regulation during amniote brain evolution. PMID:26732839

  6. Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion.

    PubMed

    Florio, Marta; Albert, Mareike; Taverna, Elena; Namba, Takashi; Brandl, Holger; Lewitus, Eric; Haffner, Christiane; Sykes, Alex; Wong, Fong Kuan; Peters, Jula; Guhr, Elaine; Klemroth, Sylvia; Prüfer, Kay; Kelso, Janet; Naumann, Ronald; Nüsslein, Ina; Dahl, Andreas; Lachmann, Robert; Pääbo, Svante; Huttner, Wieland B

    2015-03-27

    Evolutionary expansion of the human neocortex reflects increased amplification of basal progenitors in the subventricular zone, producing more neurons during fetal corticogenesis. In this work, we analyze the transcriptomes of distinct progenitor subpopulations isolated by a cell polarity-based approach from developing mouse and human neocortex. We identify 56 genes preferentially expressed in human apical and basal radial glia that lack mouse orthologs. Among these, ARHGAP11B has the highest degree of radial glia-specific expression. ARHGAP11B arose from partial duplication of ARHGAP11A (which encodes a Rho guanosine triphosphatase-activating protein) on the human lineage after separation from the chimpanzee lineage. Expression of ARHGAP11B in embryonic mouse neocortex promotes basal progenitor generation and self-renewal and can increase cortical plate area and induce gyrification. Hence, ARHGAP11B may have contributed to evolutionary expansion of human neocortex.

  7. Msx1-Positive Progenitors in the Retinal Ciliary Margin Give Rise to Both Neural and Non-neural Progenies in Mammals.

    PubMed

    Bélanger, Marie-Claude; Robert, Benoit; Cayouette, Michel

    2017-01-23

    In lower vertebrates, stem/progenitor cells located in a peripheral domain of the retina, called the ciliary margin zone (CMZ), cooperate with retinal domain progenitors to build the mature neural retina. In mammals, it is believed that the CMZ lacks neurogenic potential and that the retina develops from one pool of multipotent retinal progenitor cells (RPCs). Here we identify a population of Msx1-expressing progenitors in the mouse CMZ that is both molecularly and functionally distinct from RPCs. Using genetic lineage tracing, we report that Msx1 progenitors have unique developmental properties compared with RPCs. Msx1 lineages contain both neural retina and non-neural ciliary epithelial progenies and overall generate fewer photoreceptors than classical RPC lineages. Furthermore, we show that the endocytic adaptor protein Numb regulates the balance between neural and non-neural fates in Msx1 progenitors. These results uncover a population of CMZ progenitors, distinct from classical RPCs, that also contributes to mammalian retinogenesis.

  8. Hedgehog signaling promotes basal progenitor expansion and the growth and folding of the neocortex

    PubMed Central

    Wang, Lei; Hou, Shirui; Han, Young-Goo

    2016-01-01

    The unique mental abilities of humans are rooted in the immensely expanded and folded neocortex, which reflects the expansion of neural progenitors, especially basal progenitors including basal radial glia (bRGs, also called outer RGs) and intermediate progenitor cells (IPCs). Here, we show that constitutively active Shh signaling expanded bRGs and IPCs and induced folding in the otherwise smooth mouse neocortex, whereas the loss of Shh signaling decreased the number of bRGs and IPCs and the size of the neocortex. SHH signaling was strongly active in the human fetal neocortex but not in the mouse embryonic neocortex, and blocking SHH signaling in human cerebral organoids decreased the number of bRGs. Mechanistically, Shh signaling increased the initial generation and self-renewal of bRGs as well as increasing IPC proliferation. Thus, robust SHH signaling in the human fetal neocortex may contribute to bRG and IPC expansion and neocortical growth and folding. PMID:27214567

  9. A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification

    PubMed Central

    Florio, Marta; Namba, Takashi; Pääbo, Svante; Hiller, Michael; Huttner, Wieland B.

    2016-01-01

    The gene ARHGAP11B promotes basal progenitor amplification and is implicated in neocortex expansion. It arose on the human evolutionary lineage by partial duplication of ARHGAP11A, which encodes a Rho guanosine triphosphatase–activating protein (RhoGAP). However, a lack of 55 nucleotides in ARHGAP11B mRNA leads to loss of RhoGAP activity by GAP domain truncation and addition of a human-specific carboxy-terminal amino acid sequence. We show that these 55 nucleotides are deleted by mRNA splicing due to a single C→G substitution that creates a novel splice donor site. We reconstructed an ancestral ARHGAP11B complementary DNA without this substitution. Ancestral ARHGAP11B exhibits RhoGAP activity but has no ability to increase basal progenitors during neocortex development. Hence, a single nucleotide substitution underlies the specific properties of ARHGAP11B that likely contributed to the evolutionary expansion of the human neocortex. PMID:27957544

  10. Inducible knockout of Mef2a, -c, and -d from nestin-expressing stem/progenitor cells and their progeny unexpectedly uncouples neurogenesis and dendritogenesis in vivo

    PubMed Central

    Latchney, Sarah E.; Jiang, Yindi; Petrik, David P.; Eisch, Amelia J.; Hsieh, Jenny

    2015-01-01

    Myocyte enhancer factor (Mef)-2 transcription factors are implicated in activity-dependent neuronal processes during development, but the role of MEF2 in neural stem/progenitor cells (NSPCs) in the adult brain is unknown. We used a transgenic mouse in which Mef2a, -c, and -d were inducibly deleted in adult nestin-expressing NSPCs and their progeny. Recombined cells in the hippocampal granule cell layer were visualized and quantified by yellow fluorescent protein (YFP) expression. In control mice, postmitotic neurons expressed Mef2a, -c, and -d, whereas type 1 stem cells and proliferating progenitors did not. Based on this expression, we hypothesized that Mef2a, -c, and -d deletion in adult nestin-expressing NSPCs and their progeny would result in fewer mature neurons. Control mice revealed an increase in YFP+ neurons and dendrite formation over time. Contrary to our hypothesis, inducible Mef2 KO mice also displayed an increase in YFP+ neurons over time—but with significantly stunted dendrites—suggesting an uncoupling of neuron survival and dendritogenesis. We also found non–cell-autonomous effects after Mef2a, -c, and -d deletion. These in vivo findings indicate a surprising functional role for Mef2a, -c, and -d in cell- and non–cell-autonomous control of adult hippocampal neurogenesis that is distinct from its role during development.—Latchney, S. E., Jiang, Y., Petrik, D. P., Eisch, A. J., Hsieh, J. Inducible knockout of Mef2a, -c, and -d from nestin-expressing stem/progenitor cells and their progeny unexpectedly uncouples neurogenesis and dendritogenesis in vivo. PMID:26286136

  11. Characterization of Lgr5+ progenitor cell transcriptomes in the apical and basal turns of the mouse cochlea.

    PubMed

    Waqas, Muhammad; Guo, Luo; Zhang, Shasha; Chen, Yan; Zhang, Xiaoli; Wang, Lei; Tang, Mingliang; Shi, Haibo; Bird, Phillip I; Li, Huawei; Chai, Renjie

    2016-07-05

    Lgr5+ supporting cells (SCs) are enriched hair cell (HC) progenitors in the cochlea, and several studies have shown a difference in the proliferation and HC regeneration ability of SCs between the apical and basal turns. However, the detailed differences between the transcriptomes of the apical and basal Lgr5+ SCs have not yet been investigated. We found that when isolated by FACS, Lgr5+ cells from the apex generated significantly more HCs and had significantly higher proliferation and mitotic HC regeneration ability compared to those from the base. Next, we used microarray analysis to determine the transcriptome expression profiles of Lgr5+ progenitors from the apex and the base. We first analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors from the apex and the base. Then we analyzed the cell cycle genes and the transcription factors that might regulate the proliferation and differentiation of Lgr5+ progenitors. Lastly, to further analyze the role of differentially expressed genes and to gain an overall view of the gene network in cochlear HC regeneration, we created a protein-protein interaction network. Our datasets suggest the possible genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these genes might provide new therapeutic targets for HC regeneration in the future.

  12. Characterization of Lgr5+ progenitor cell transcriptomes in the apical and basal turns of the mouse cochlea

    PubMed Central

    Zhang, Shasha; Chen, Yan; Zhang, Xiaoli; Wang, Lei; Tang, Mingliang; Shi, Haibo; Bird, Phillip I.; Li, Huawei; Chai, Renjie

    2016-01-01

    Lgr5+ supporting cells (SCs) are enriched hair cell (HC) progenitors in the cochlea, and several studies have shown a difference in the proliferation and HC regeneration ability of SCs between the apical and basal turns. However, the detailed differences between the transcriptomes of the apical and basal Lgr5+ SCs have not yet been investigated. We found that when isolated by FACS, Lgr5+ cells from the apex generated significantly more HCs and had significantly higher proliferation and mitotic HC regeneration ability compared to those from the base. Next, we used microarray analysis to determine the transcriptome expression profiles of Lgr5+ progenitors from the apex and the base. We first analyzed the genes that were enriched and differentially expressed in Lgr5+ progenitors from the apex and the base. Then we analyzed the cell cycle genes and the transcription factors that might regulate the proliferation and differentiation of Lgr5+ progenitors. Lastly, to further analyze the role of differentially expressed genes and to gain an overall view of the gene network in cochlear HC regeneration, we created a protein-protein interaction network. Our datasets suggest the possible genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors, and these genes might provide new therapeutic targets for HC regeneration in the future. PMID:27070092

  13. Smoking-Associated Disordering of the Airway Basal Stem/Progenitor Cell Metabotype

    PubMed Central

    Deeb, Ruba S.; Walters, Matthew S.; Strulovici-Barel, Yael; Chen, Qiuying; Gross, Steven S.

    2016-01-01

    The airway epithelium is a complex pseudostratified multicellular layer lining the tracheobronchial tree, functioning as the primary defense against inhaled environmental contaminants. The major cell types of the airway epithelium include basal, intermediate columnar, ciliated, and secretory. Basal cells (BCs) are the proliferating stem/progenitor population that differentiate into the other specialized cell types of the airway epithelium during normal turnover and repair. Given that cigarette smoke delivers thousands of xenobiotics and high levels of reactive molecules to the lung epithelial surface, we hypothesized that cigarette smoke broadly perturbs BC metabolism. To test this hypothesis, primary airway BCs were isolated from healthy nonsmokers (n = 11) and healthy smokers (n = 7) and assessed by global metabolic profiling by liquid chromatography–mass spectrometry. The analysis identified 52 significant metabolites in BCs differentially expressed between smokers and nonsmokers (P < 0.05). These changes included metabolites associated with redox pathways, energy production, and inflammatory processes. Notably, BCs from smokers exhibited altered levels of the key enzyme cofactors/substrates nicotinamide adenine dinucleotide, flavin adenine dinucleotide, acetyl coenzyme A, and membrane phospholipid levels. Consistent with the high burden of oxidants in cigarette smoke, glutathione levels were diminished, whereas 3-nitrotyrosine levels were increased, suggesting that protection of airway epithelial cells against oxidative and nitrosative stress is significantly compromised in smoker BCs. It is likely that this altered metabotype is a reflection of, and likely contributes to, the disordered biology of airway BCs consequent to the stress cigarette smoking puts on the airway epithelium. PMID:26161876

  14. Protein profile of basal prostate epithelial progenitor cells--stage-specific embryonal antigen 4 expressing cells have enhanced regenerative potential in vivo.

    PubMed

    Höfner, Thomas; Klein, Corinna; Eisen, Christian; Rigo-Watermeier, Teresa; Haferkamp, Axel; Sprick, Martin R

    2016-04-01

    The long-term propagation of basal prostate progenitor cells ex vivo has been very difficult in the past. The development of novel methods to expand prostate progenitor cells in vitro allows determining their cell surface phenotype in greater detail. Mouse (Lin(-)Sca-1(+) CD49f(+) Trop2(high)-phenotype) and human (Lin(-) CD49f(+) TROP2(high)) basal prostate progenitor cells were expanded in vitro. Human and mouse cells were screened using 242 anti-human or 176 antimouse monoclonal antibodies recognizing the cell surface protein profile. Quantitative expression was evaluated at the single-cell level using flow cytometry. Differentially expressed cell surface proteins were evaluated in conjunction with the known CD49f(+)/TROP2(high) phenotype of basal prostate progenitor cells and characterized by in vivo sandwich-transplantation experiments using nude mice. The phenotype of basal prostate progenitor cells was determined as CD9(+)/CD24(+)/CD29(+)/CD44(+)/CD47(+)/CD49f(+)/CD104(+)/CD147(+)/CD326(+)/Trop2(high) of mouse as well as human origin. Our analysis revealed several proteins, such as CD13, Syndecan-1 and stage-specific embryonal antigens (SSEAs), as being differentially expressed on murine and human CD49f(+) TROP2(+) basal prostate progenitor cells. Transplantation experiments suggest that CD49f(+) TROP2(high) SSEA-4(high) human prostate basal progenitor cells to be more potent to regenerate prostate tubules in vivo as compared with CD49f(+) TROP2(high) or CD49f(+) TROP2(high) SSEA-4(low) cells. Determination of the cell surface protein profile of functionally defined murine and human basal prostate progenitor cells reveals differentially expressed proteins that may change the potency and regenerative function of epithelial progenitor cells within the prostate. SSEA-4 is a candidate cell surface marker that putatively enables a more accurate identification of the basal PESC lineage.

  15. In vitro keratinocyte expansion for cell transplantation therapy is associated with differentiation and loss of basal layer derived progenitor population.

    PubMed

    Esteban-Vives, Roger; Young, Matt; Over, Patrick; Schmelzer, Eva; Corcos, Alain; Ziembicki, Jenny; Gerlach, Jörg

    2015-06-01

    An alternative approach for traditional clinical mesh grafting in burn wound treatment is the use of expanded autologous keratinocytes in suspension or sheets that are cultured over 2-4 weeks in a remote service facility. While a wound reepithelialization has been described, the functional and aesthetic outcome is under debate. Cell isolation from split-skin donor tissue aims to preserve the valuable stem cell progenitors from the basal epidermal layer and to provide patients with a rapid wound reepithelialization and a satisfying outcome. While the presence of epidermal progenitors in the cell graft is thought to enable an improved epidermal surface post reepithelialization, we investigated a feasible clinical approach involving cultured versus noncultured epidermal cells comparing the α6int(high)/K15(high)/FSC(low)/SSC(low) and α6int(high)/K5(high)/FSC(low)/SSC(low) keratinocyte progenitor subpopulations before and after in vitro culture process. Our results show a significant increase of cell size during in vitro passaging and a decrease of progenitor markers linked to a gradual differentiation. A provision of the regenerative epidermal progenitors, isolated from the split-skin biopsy and applied directly onto the wound in an on-site setting of isolation and cell spray grafting in the operation room, could be of interest when choosing options for skin wound care with autologous cells.

  16. CLoNe is a new method to target single progenitors and study their progeny in mouse and chick.

    PubMed

    García-Moreno, Fernando; Vasistha, Navneet A; Begbie, Jo; Molnár, Zoltán

    2014-04-01

    Cell lineage analysis enables us to address pivotal questions relating to: the embryonic origin of cells and sibling cell relationships in the adult body; the contribution of progenitors activated after trauma or disease; and the comparison across species in evolutionary biology. To address such fundamental questions, several techniques for clonal labelling have been developed, each with its shortcomings. Here, we report a novel method, CLoNe that is designed to work in all vertebrate species and tissues. CLoNe uses a cocktail of labelling, targeting and transposition vectors that enables targeting of specific subpopulations of progenitor types with a combination of fluorophores resulting in multifluorescence that describes multiple clones per specimen. Furthermore, transposition into the genome ensures the longevity of cell labelling. We demonstrate the robustness of this technique in mouse and chick forebrain development, and show evidence that CLoNe will be broadly applicable to study clonal relationships in different tissues and species.

  17. Analysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors.

    PubMed

    Edri, Reuven; Yaffe, Yakey; Ziller, Michael J; Mutukula, Naresh; Volkman, Rotem; David, Eyal; Jacob-Hirsch, Jasmine; Malcov, Hagar; Levy, Carmit; Rechavi, Gideon; Gat-Viks, Irit; Meissner, Alexander; Elkabetz, Yechiel

    2015-03-23

    Decoding heterogeneity of pluripotent stem cell (PSC)-derived neural progeny is fundamental for revealing the origin of diverse progenitors, for defining their lineages, and for identifying fate determinants driving transition through distinct potencies. Here we have prospectively isolated consecutively appearing PSC-derived primary progenitors based on their Notch activation state. We first isolate early neuroepithelial cells and show their broad Notch-dependent developmental and proliferative potential. Neuroepithelial cells further yield successive Notch-dependent functional primary progenitors, from early and midneurogenic radial glia and their derived basal progenitors, to gliogenic radial glia and adult-like neural progenitors, together recapitulating hallmarks of neural stem cell (NSC) ontogeny. Gene expression profiling reveals dynamic stage-specific transcriptional patterns that may link development of distinct progenitor identities through Notch activation. Our observations provide a platform for characterization and manipulation of distinct progenitor cell types amenable for developing streamlined neural lineage specification paradigms for modelling development in health and disease.

  18. Adult interfollicular tumour-initiating cells are reprogrammed into an embryonic hair follicle progenitor-like fate during basal cell carcinoma initiation.

    PubMed

    Youssef, Khalil Kass; Lapouge, Gaëlle; Bouvrée, Karine; Rorive, Sandrine; Brohée, Sylvain; Appelstein, Ornella; Larsimont, Jean-Christophe; Sukumaran, Vijayakumar; Van de Sande, Bram; Pucci, Doriana; Dekoninck, Sophie; Berthe, Jean-Valery; Aerts, Stein; Salmon, Isabelle; del Marmol, Véronique; Blanpain, Cédric

    2012-12-01

    Basal cell carcinoma, the most frequent human skin cancer, arises from activating hedgehog (HH) pathway mutations; however, little is known about the temporal changes that occur in tumour-initiating cells from the first oncogenic hit to the development of invasive cancer. Using an inducible mouse model enabling the expression of a constitutively active Smoothened mutant (SmoM2) in the adult epidermis, we carried out transcriptional profiling of SmoM2-expressing cells at different times during cancer initiation. We found that tumour-initiating cells are massively reprogrammed into a fate resembling that of embryonic hair follicle progenitors (EHFPs). Wnt/ β-catenin signalling was very rapidly activated following SmoM2 expression in adult epidermis and coincided with the expression of EHFP markers. Deletion of β-catenin in adult SmoM2-expressing cells prevents EHFP reprogramming and tumour initiation. Finally, human basal cell carcinomas also express genes of the Wnt signalling and EHFP signatures.

  19. The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice

    PubMed Central

    Ju, Xiang-Chun; Hou, Qiong-Qiong; Sheng, Ai-Li; Wu, Kong-Yan; Zhou, Yang; Jin, Ying; Wen, Tieqiao; Yang, Zhengang; Wang, Xiaoqun; Luo, Zhen-Ge

    2016-01-01

    Cortical expansion and folding are often linked to the evolution of higher intelligence, but molecular and cellular mechanisms underlying cortical folding remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental duplications during hominoid evolution, but its role in brain development has not been explored. Here, we found that expression of TBC1D3 in ventricular cortical progenitors of mice via in utero electroporation caused delamination of ventricular radial glia cells (vRGs) and promoted generation of self-renewing basal progenitors with typical morphology of outer radial glia (oRG), which are most abundant in primates. Furthermore, down-regulation of TBC1D3 in cultured human brain slices decreased generation of oRGs. Interestingly, localized oRG proliferation resulting from either in utero electroporation or transgenic expression of TBC1D3, was often found to underlie cortical regions exhibiting folding. Thus, we have identified a hominoid gene that is required for oRG generation in regulating the cortical expansion and folding. DOI: http://dx.doi.org/10.7554/eLife.18197.001 PMID:27504805

  20. Evidence of progenitor cells of glandular and myoepithelial cell lineages in the human adult female breast epithelium: a new progenitor (adult stem) cell concept.

    PubMed

    Boecker, Werner; Buerger, Horst

    2003-10-01

    Although experimental data clearly confirm the existence of self-renewing mammary stem cells, the characteristics of such progenitor cells have never been satisfactorily defined. Using a double immunofluorescence technique for simultaneous detection of the basal cytokeratin 5, the glandular cytokeratins 8/18 and the myoepithelial differentiation marker smooth muscle actin (SMA), we were able to demonstrate the presence of CK5+ cells in human adult breast epithelium. These cells have the potential to differentiate to either glandular (CK8/18+) or myoepithelial cells (SMA+) through intermediary cells (CK5+ and CK8/18+ or SMA+). We therefore proceeded on the assumption that the CK5+ cells are phenotypically and behaviourally progenitor (committed adult stem) cells of human breast epithelium. Furthermore, we furnish evidence that most of these progenitor cells are located in the luminal epithelium of the ductal lobular tree. Based on data obtained in extensive analyses of proliferative breast disease lesions, we have come to regard usual ductal hyperplasia as a progenitor cell-derived lesion, whereas most breast cancers seem to evolve from differentiated glandular cells. Double immunofluorescence experiments provide a new tool to characterize phenotypically progenitor (adult stem) cells and their progenies. This model has been shown to be of great value for a better understanding not only of normal tissue regeneration but also of proliferative breast disease. Furthermore, this model provides a new tool for unravelling further the regulatory mechanisms that govern normal and pathological cell growth.

  1. Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain.

    PubMed

    Pilaz, Louis-Jan; McMahon, John J; Miller, Emily E; Lennox, Ashley L; Suzuki, Aussie; Salmon, Edward; Silver, Debra L

    2016-01-06

    Embryonic neocortical development depends on balanced production of progenitors and neurons. Genetic mutations disrupting progenitor mitosis frequently impair neurogenesis; however, the link between altered mitosis and cell fate remains poorly understood. Here we demonstrate that prolonged mitosis of radial glial progenitors directly alters neuronal fate specification and progeny viability. Live imaging of progenitors from a neurogenesis mutant, Magoh(+/-), reveals that mitotic delay significantly correlates with preferential production of neurons instead of progenitors, as well as apoptotic progeny. Independently, two pharmacological approaches reveal a causal relationship between mitotic delay and progeny fate. As mitotic duration increases, progenitors produce substantially more apoptotic progeny or neurons. We show that apoptosis, but not differentiation, is p53 dependent, demonstrating that these are distinct outcomes of mitotic delay. Together our findings reveal that prolonged mitosis is sufficient to alter fates of radial glia progeny and define a new paradigm to understand how mitosis perturbations underlie brain size disorders such as microcephaly.

  2. NTPDase2 and purinergic signaling control progenitor cell proliferation in neurogenic niches of the adult mouse brain.

    PubMed

    Gampe, Kristine; Stefani, Jennifer; Hammer, Klaus; Brendel, Peter; Pötzsch, Alexandra; Enikolopov, Grigori; Enjyoji, Keiichi; Acker-Palmer, Amparo; Robson, Simon C; Zimmermann, Herbert

    2015-01-01

    Nerve cells are continuously generated from stem cells in the adult mammalian subventricular zone (SVZ) and hippocampal dentate gyrus. We have previously noted that stem/progenitor cells in the SVZ and the subgranular layer (SGL) of the dentate gyrus express high levels of plasma membrane-bound nucleoside triphosphate diphosphohydrolase 2 (NTPDase2), an ectoenzyme that hydrolyzes extracellular nucleoside diphosphates and triphosphates. We inferred that deletion of NTPDase2 would increase local extracellular nucleoside triphosphate concentrations perturbing purinergic signaling and boosting progenitor cell proliferation and neurogenesis. Using newly generated mice globally null for Entpd2, we demonstrate that NTPDase2 is the major ectonucleotidase in these progenitor cell-rich areas. Using BrdU-labeling protocols, we have measured stem cell proliferation and determined long-term survival of cell progeny under basal conditions. Brains of Entpd2 null mice revealed increased progenitor cell proliferation in both the SVZ and the SGL. However, this occurred without noteworthy alterations in long-term progeny survival. The hippocampal stem cell pool and the pool of the intermediate progenitor type-2 cells clearly expanded. However, substantive proportions of these proliferating cells were lost during expansion at around type-3 stage. Cell loss was paralleled by decreases in cAMP response element-binding protein phosphorylation in the doublecortin-positive progenitor cell population and by an increase in labeling for activated caspase-3 levels. We propose that NTPDase2 has functionality in scavenging mitogenic extracellular nucleoside triphosphates in neurogenic niches of the adult brain, thereby acting as a homeostatic regulator of nucleotide-mediated neural progenitor cell proliferation and expansion.

  3. Sustained Pax6 Expression Generates Primate-like Basal Radial Glia in Developing Mouse Neocortex

    PubMed Central

    Mora-Bermúdez, Felipe; Taverna, Elena; Haffner, Christiane; Fu, Jun; Anastassiadis, Konstantinos; Stewart, A. Francis; Huttner, Wieland B.

    2015-01-01

    The evolutionary expansion of the neocortex in mammals has been linked to enlargement of the subventricular zone (SVZ) and increased proliferative capacity of basal progenitors (BPs), notably basal radial glia (bRG). The transcription factor Pax6 is known to be highly expressed in primate, but not mouse, BPs. Here, we demonstrate that sustaining Pax6 expression selectively in BP-genic apical radial glia (aRG) and their BP progeny of embryonic mouse neocortex suffices to induce primate-like progenitor behaviour. Specifically, we conditionally expressed Pax6 by in utero electroporation using a novel, Tis21–CreERT2 mouse line. This expression altered aRG cleavage plane orientation to promote bRG generation, increased cell-cycle re-entry of BPs, and ultimately increased upper-layer neuron production. Upper-layer neuron production was also increased in double-transgenic mouse embryos with sustained Pax6 expression in the neurogenic lineage. Strikingly, increased BPs existed not only in the SVZ but also in the intermediate zone of the neocortex of these double-transgenic mouse embryos. In mutant mouse embryos lacking functional Pax6, the proportion of bRG among BPs was reduced. Our data identify specific Pax6 effects in BPs and imply that sustaining this Pax6 function in BPs could be a key aspect of SVZ enlargement and, consequently, the evolutionary expansion of the neocortex. PMID:26252244

  4. Sustained Pax6 Expression Generates Primate-like Basal Radial Glia in Developing Mouse Neocortex.

    PubMed

    Wong, Fong Kuan; Fei, Ji-Feng; Mora-Bermúdez, Felipe; Taverna, Elena; Haffner, Christiane; Fu, Jun; Anastassiadis, Konstantinos; Stewart, A Francis; Huttner, Wieland B

    2015-08-01

    The evolutionary expansion of the neocortex in mammals has been linked to enlargement of the subventricular zone (SVZ) and increased proliferative capacity of basal progenitors (BPs), notably basal radial glia (bRG). The transcription factor Pax6 is known to be highly expressed in primate, but not mouse, BPs. Here, we demonstrate that sustaining Pax6 expression selectively in BP-genic apical radial glia (aRG) and their BP progeny of embryonic mouse neocortex suffices to induce primate-like progenitor behaviour. Specifically, we conditionally expressed Pax6 by in utero electroporation using a novel, Tis21-CreERT2 mouse line. This expression altered aRG cleavage plane orientation to promote bRG generation, increased cell-cycle re-entry of BPs, and ultimately increased upper-layer neuron production. Upper-layer neuron production was also increased in double-transgenic mouse embryos with sustained Pax6 expression in the neurogenic lineage. Strikingly, increased BPs existed not only in the SVZ but also in the intermediate zone of the neocortex of these double-transgenic mouse embryos. In mutant mouse embryos lacking functional Pax6, the proportion of bRG among BPs was reduced. Our data identify specific Pax6 effects in BPs and imply that sustaining this Pax6 function in BPs could be a key aspect of SVZ enlargement and, consequently, the evolutionary expansion of the neocortex.

  5. A radon progeny deposition model

    SciTech Connect

    Rielage, Keith; Elliott, Steven R; Hime, Andrew; Guiseppe, Vincente E; Westerdale, S.

    2010-12-01

    The next generation low-background detectors operating underground aim for unprecedented low levels of radioactive backgrounds. Although the radioactive decays of airborne radon (particularly {sup 222}Rn) and its subsequent progeny present in an experiment are potential backgrounds, also problematic is the deposition of radon progeny on detector materials. Exposure to radon at any stage of assembly of an experiment can result in surface contamination by progeny supported by the long half life (22 y) of {sup 210}Pb on sensitive locations of a detector. An understanding of the potential surface contamination from deposition will enable requirements of radon-reduced air and clean room environments for the assembly of low background experiments. It is known that there are a number of environmental factors that govern the deposition of progeny onto surfaces. However, existing models have not explored the impact of some environmental factors important for low background experiments. A test stand has been constructed to deposit radon progeny on various surfaces under a controlled environment in order to develop a deposition model. Results from this test stand and the resulting deposition model are presented.

  6. A Radon Progeny Deposition Model

    SciTech Connect

    Guiseppe, V. E.; Elliott, S. R.; Hime, A.; Rielage, K.; Westerdale, S.

    2011-04-27

    The next generation low-background detectors operating underground aim for unprecedented low levels of radioactive backgrounds. Although the radioactive decays of airborne radon (particularly {sup 222}Rn) and its subsequent progeny present in an experiment are potential backgrounds, also problematic is the deposition of radon progeny on detector materials. Exposure to radon at any stage of assembly of an experiment can result in surface contamination by progeny supported by the long half life (22 y) of {sup 210}Pb on sensitive locations of a detector. An understanding of the potential surface contamination from deposition will enable requirements of radon-reduced air and clean room environments for the assembly of low background experiments. It is known that there are a number of environmental factors that govern the deposition of progeny onto surfaces. However, existing models have not explored the impact of some environmental factors important for low background experiments. A test stand has been constructed to deposit radon progeny on various surfaces under a controlled environment in order to develop a deposition model. Results from this test stand and the resulting deposition model are presented.

  7. Tracing the fate of limbal epithelial progenitor cells in the murine cornea.

    PubMed

    Di Girolamo, N; Bobba, S; Raviraj, V; Delic, N C; Slapetova, I; Nicovich, P R; Halliday, G M; Wakefield, D; Whan, R; Lyons, J G

    2015-01-01

    Stem cell (SC) division, deployment, and differentiation are processes that contribute to corneal epithelial renewal. Until now studying the destiny of these cells in a living mammal has not been possible. However, the advent of inducible multicolor genetic tagging and powerful imaging technologies has rendered this achievable in the translucent and readily accessible murine cornea. K14CreER(T2)-Confetti mice that harbor two copies of the Brainbow 2.1 cassette, yielding up to 10 colors from the stochastic recombination of fluorescent proteins, were used to monitor K-14(+) progenitor cell dynamics within the corneal epithelium in live animals. Multicolored columns of cells emerged from the basal limbal epithelium as they expanded and migrated linearly at a rate of 10.8 µm/day toward the central cornea. Moreover, the permanent expression of fluorophores, passed on from progenitor to progeny, assisted in discriminating individual clones as spectrally distinct streaks containing more than 1,000 cells within the illuminated area. The centripetal clonal expansion is suggestive that a single progenitor cell is responsible for maintaining a narrow corridor of corneal epithelial cells. Our data are in agreement with the limbus as the repository for SC as opposed to SC being distributed throughout the central cornea. This is the first report describing stem/progenitor cell fate determination in the murine cornea using multicolor genetic tracing. This model represents a powerful new resource to monitor SC kinetics and fate choice under homeostatic conditions, and may assist in assessing clonal evolution during corneal development, aging, wound-healing, disease, and following transplantation.

  8. Exploration of the functional hierarchy of the basal layer of human epidermis at the single-cell level using parallel clonal microcultures of keratinocytes.

    PubMed

    Fortunel, Nicolas O; Cadio, Emmanuelle; Vaigot, Pierre; Chadli, Loubna; Moratille, Sandra; Bouet, Stéphan; Roméo, Paul-Henri; Martin, Michèle T

    2010-04-01

    The basal layer of human epidermis contains both stem cells and keratinocyte progenitors. Because of this cellular heterogeneity, the development of methods suitable for investigations at a clonal level is dramatically needed. Here, we describe a new method that allows multi-parallel clonal cultures of basal keratinocytes. Immediately after extraction from tissue samples, cells are sorted by flow cytometry based on their high integrin-alpha 6 expression and plated individually in microculture wells. This automated cell deposition process enables large-scale characterization of primary clonogenic capacities. The resulting clonal growth profile provided a precise assessment of basal keratinocyte hierarchy, as the size distribution of 14-day-old clones ranged from abortive to highly proliferative clones containing 1.7 x 10(5) keratinocytes (17.4 cell doublings). Importantly, these 14-day-old primary clones could be used to generate three-dimensional reconstructed epidermis with the progeny of a single cell. In long-term cultures, a fraction of highly proliferative clones could sustain extensive expansion of >100 population doublings over 14 weeks and exhibited long-term epidermis reconstruction potency, thus fulfilling candidate stem cell functional criteria. In summary, parallel clonal microcultures provide a relevant model for single-cell studies on interfollicular keratinocytes, which could be also used in other epithelial models, including hair follicle and cornea. The data obtained using this system support the hierarchical model of basal keratinocyte organization in human interfollicular epidermis.

  9. Basal Cell Carcinoma

    MedlinePlus

    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  10. Basal cell cancer (image)

    MedlinePlus

    Basal cell cancer is a malignant skin tumor involving cancerous changes of basal skin cells. Basal cell skin cancers ... biopsy is needed to prove the diagnosis of basal cell carcinoma. Treatment varies depending on the size, depth, and ...

  11. Nonhereditary enhancement of progeny growth

    NASA Technical Reports Server (NTRS)

    Khan, Amir S.; Fiorotto, Marta L.; Hill, Leigh-Anne; Malone, P. Brandon; Cummings, Kathleen K.; Parghi, Deena; Schwartz, Robert J.; Smith, Roy G.; Draghia-Akli, Ruxandra

    2002-01-01

    The im electroporated injection of a protease-resistant GH-releasing hormone cDNA into rat dams at 16 d gestation resulted in enhanced long-term growth of the F(1) offspring. The offspring were significantly heavier by 2 wk of age, and the difference was sustained to 10 wk of age. Consistent with their augmented growth, the plasma IGF-I concentration of the F(1) progeny was increased significantly. The pituitary gland of the offspring was significantly heavier and contained an increased number of somatotrophs and PRL-secreting cells, which is indicative of modification of cell lineage differentiation. These unique findings demonstrate that enhanced GH-releasing hormone expression in pregnant dams can result in intergenerational growth promotion by altering development of the pituitary gland in the offspring.

  12. Progenitor Cell Fate Decisions in Mammary Tumorigenesis

    DTIC Science & Technology

    2013-03-01

    luminal progenitors contributing to transformation of ER- luminal and basal cells and development of treatment resistant breast cancer . We previously...proliferate and metastasize. Decreased DNA damage repair or altered epigenetic marks can dramatically affect the cellular composition of these tumors

  13. Progenitor Cells in Proximal Airway Epithelial Development and Regeneration

    PubMed Central

    Lynch, Thomas J.; Engelhardt, John F.

    2015-01-01

    Multiple distinct epithelial domains are found throughout the airway that are distinguishable by location, structure, function, and cell-type composition. Several progenitor cell populations in the proximal airway have been identified to reside in confined microenvironmental niches including the submucosal glands (SMGs), which are embedded in the tracheal connective tissue between the surface epithelium and cartilage, and basal cells that reside within the surface airway epithelium (SAE). Current research suggests that regulatory pathways that coordinate development of the proximal airway and establishment of progenitor cell niches may overlap with pathways that control progenitor cell responses during airway regeneration following injury. SMGs have been shown to harbor epithelial progenitor cells, and this niche is dysregulated in diseases such as cystic fibrosis. However, mechanisms that regulate progenitor cell proliferation and maintenance within this glandular niche are not completely understood. Here we discuss glandular progenitor cells during development and regeneration of the proximal airway and compare properties of glandular progenitors to those of basal cell progenitors in the SAE. Further investigation into glandular progenitor cell control will provide a direction for interrogating therapeutic interventions to correct aberrant conditions affecting the SMGs in diseases such as cystic fibrosis, chronic bronchitis, and asthma. PMID:24818588

  14. Fate mapping by piggyBac transposase reveals that neocortical GLAST+ progenitors generate more astrocytes than Nestin+ progenitors in rat neocortex.

    PubMed

    Siddiqi, Faez; Chen, Fuyi; Aron, Abraham W; Fiondella, Christopher G; Patel, Komal; LoTurco, Joseph J

    2014-02-01

    Progenitors within the neocortical ventricular zone (VZ) first generate pyramidal neurons and then astrocytes. We applied novel piggyBac transposase lineage tracking methods to fate-map progenitor populations positive for Nestin or glutamate and aspartate transpoter (GLAST) promoter activities in the rat neocortex. GLAST+ and Nestin+ progenitors at embryonic day 13 (E13) produce lineages containing similar rations of neurons and astrocytes. By E15, the GLAST+ progenitor population diverges significantly to produce lineages with 5-10-fold more astrocytes relative to neurons than generated by the Nestin+ population. To determine when birth-dated progeny within GLAST+ and Nestin+ populations diverge, we used a Cre/loxP fate-mapping system in which plasmids are lost after a cell division. By E18, birth-dated progeny of GLAST+ progenitors give rise to 2-3-fold more neocortical astrocytes than do Nestin+ progenitors. Finally, we used a multicolor clonal labeling method to show that the GLAST+ population labeled at E15 generates astrocyte progenitors that produce larger, spatially restricted, clonal clusters than the Nestin+ population. This study provides in vivo evidence that by mid-corticogenesis (E15), VZ progenitor populations have significantly diversified in terms of their potential to generate astrocytes and neurons.

  15. Spatiotemporal analyses of neural lineages after embryonic and postnatal progenitor targeting combining different reporters

    PubMed Central

    Figueres-Oñate, Maria; García-Marqués, Jorge; Pedraza, Maria; De Carlos, Juan Andrés; López-Mascaraque, Laura

    2015-01-01

    Genetic lineage tracing with electroporation is one of the most powerful techniques to target neural progenitor cells and their progeny. However, the spatiotemporal relationship between neural progenitors and their final phenotype remain poorly understood. One critical factor to analyze the cell fate of progeny is reporter integration into the genome of transfected cells. To address this issue, we performed postnatal and in utero co-electroporations of different fluorescent reporters to label, in both cerebral cortex and olfactory bulb, the progeny of subventricular zone neural progenitors. By comparing fluorescent reporter expression in the adult cell progeny, we show a differential expression pattern within the same cell lineage, depending on electroporation stage and cell identity. Further, while neuronal lineages arise from many progenitors in proliferative zones after few divisions, glial lineages come from fewer progenitors that accomplish many cell divisions. Together, these data provide a useful guide to select a strategy to track the cell fate of a specific cell population and to address whether a different proliferative origin might be correlated with functional heterogeneity. PMID:25852461

  16. BMP-driven NRF2 activation in esophageal basal cell differentiation and eosinophilic esophagitis

    PubMed Central

    Jiang, Ming; Ku, Wei-Yao; Zhou, Zhongren; Dellon, Evan S.; Falk, Gary W.; Nakagawa, Hiroshi; Wang, Mei-Lun; Liu, Kuancan; Wang, Jun; Katzka, David A.; Peters, Jeffrey H.; Lan, Xiaopeng; Que, Jianwen

    2015-01-01

    Tissue homeostasis requires balanced self-renewal and differentiation of stem/progenitor cells, especially in tissues that are constantly replenished like the esophagus. Disruption of this balance is associated with pathological conditions, including eosinophilic esophagitis (EoE), in which basal progenitor cells become hyperplastic upon proinflammatory stimulation. However, how basal cells respond to the inflammatory environment at the molecular level remains undetermined. We previously reported that the bone morphogenetic protein (BMP) signaling pathway is critical for epithelial morphogenesis in the embryonic esophagus. Here, we address how this pathway regulates tissue homeostasis and EoE development in the adult esophagus. BMP signaling was specifically activated in differentiated squamous epithelium, but not in basal progenitor cells, which express the BMP antagonist follistatin. Previous reports indicate that increased BMP activity promotes Barrett’s intestinal differentiation; however, in mice, basal progenitor cell–specific expression of constitutively active BMP promoted squamous differentiation. Moreover, BMP activation increased intracellular ROS levels, initiating an NRF2-mediated oxidative response during basal progenitor cell differentiation. In both a mouse EoE model and human biopsies, reduced squamous differentiation was associated with high levels of follistatin and disrupted BMP/NRF2 pathways. We therefore propose a model in which normal squamous differentiation of basal progenitor cells is mediated by BMP-driven NRF2 activation and basal cell hyperplasia is promoted by disruption of BMP signaling in EoE. PMID:25774506

  17. Dosimetry of inhaled radon and thoron progeny

    SciTech Connect

    James, A.C.

    1994-06-01

    This chapter reviews recent developments in modeling doses received by lung tissues, with particular emphasis on application of ICRP`s new dosimetric model of the respiratory tract for extrapolating to other environments the established risks from exposure to radon progeny in underground mines. Factors discussed include: (1) the influence of physical characteristics of radon progeny aerosols on dose per unit exposure, e.g., the unattached fraction, and the activity-size distributions of clustered and attached progeny; (2) the dependence of dose on breathing rate, and on the exposed subject (man, woman or child); (3) the variability of dose per unit exposure in a home when exposure is expressed in terms of potential {alpha} energy or radon gas concentration; (4) the comparative dosimetry of thoron progeny; and (5) the effects of air-cleaning on lung dose. Also discussed is the apparent discrepancy between lung cancer risk estimates derived purely from dosimetry and the lung cancer incidence observed in the epidemiological studies of radon-exposed underground miners. Application of ICRP`s recommended risk factors appears to overestimate radon lung-cancer risk for miners by a factor of three. ``Normalization`` of the calculated effective dose is therefore needed, at least for {alpha} dose from radon and thoron progeny, in order to obtain a realistic estimate of lung cancer risk.

  18. Integrin αvβ3 and thyroid hormones promote expansion of progenitors in embryonic neocortex.

    PubMed

    Stenzel, Denise; Wilsch-Bräuninger, Michaela; Wong, Fong Kuan; Heuer, Heike; Huttner, Wieland B

    2014-02-01

    Neocortex expansion during evolution is associated with the enlargement of the embryonic subventricular zone, which reflects an increased self-renewal and proliferation of basal progenitors. In contrast to human, the vast majority of mouse basal progenitors lack self-renewal capacity, possibly due to lack of a basal process contacting the basal lamina and downregulation of cell-autonomous production of extracellular matrix (ECM) constituents. Here we show that targeted activation of the ECM receptor integrin αvβ3 on basal progenitors in embryonic mouse neocortex promotes their expansion. Specifically, integrin αvβ3 activation causes an increased cell cycle re-entry of Pax6-negative, Tbr2-positive intermediate progenitors, rather than basal radial glia, and a decrease in the proportion of intermediate progenitors committed to neurogenic division. Interestingly, integrin αvβ3 is the only known cell surface receptor for thyroid hormones. Remarkably, tetrac, a thyroid hormone analog that inhibits the binding of thyroid hormones to integrin αvβ3, completely abolishes the intermediate progenitor expansion observed upon targeted integrin αvβ3 activation, indicating that this expansion requires the binding of thyroid hormones to integrin αvβ3. Convergence of ECM and thyroid hormones on integrin αvβ3 thus appears to be crucial for cortical progenitor proliferation and self-renewal, and hence for normal brain development and the evolutionary expansion of the neocortex.

  19. Lgr5-EGFP marks taste bud stem/progenitor cells in posterior tongue.

    PubMed

    Yee, Karen K; Li, Yan; Redding, Kevin M; Iwatsuki, Ken; Margolskee, Robert F; Jiang, Peihua

    2013-05-01

    Until recently, reliable markers for adult stem cells have been lacking for many regenerative mammalian tissues. Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5) has been identified as a marker for adult stem cells in intestine, stomach, and hair follicle; Lgr5-expressing cells give rise to all types of cells in these tissues. Taste epithelium also regenerates constantly, yet the identity of adult taste stem cells remains elusive. In this study, we found that Lgr5 is strongly expressed in cells at the bottom of trench areas at the base of circumvallate (CV) and foliate taste papillae and weakly expressed in the basal area of taste buds and that Lgr5-expressing cells in posterior tongue are a subset of K14-positive epithelial cells. Lineage-tracing experiments using an inducible Cre knockin allele in combination with Rosa26-LacZ and Rosa26-tdTomato reporter strains showed that Lgr5-expressing cells gave rise to taste cells, perigemmal cells, along with self-renewing cells at the bottom of trench areas at the base of CV and foliate papillae. Moreover, using subtype-specific taste markers, we found that Lgr5-expressing cell progeny include all three major types of adult taste cells. Our results indicate that Lgr5 may mark adult taste stem or progenitor cells in the posterior portion of the tongue.

  20. Progeny from dedifferentiated adipocytes display protracted adipogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Progeny of adipofibroblast cells, derived from mature bovine adipocytes, were used to determine their ability to redifferentiate into lipid-assimilating adipocytes. Traditional cell biology methods were used, including the expression of adipogenic markers such as PPAR'. When exposed to medium supple...

  1. SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development.

    PubMed

    Azim, Eiman; Jabaudon, Denis; Fame, Ryann M; Macklis, Jeffrey D

    2009-10-01

    The neuronal diversity of the CNS emerges largely from controlled spatial and temporal segregation of cell type-specific molecular regulators. We found that the transcription factor SOX6 controls the molecular segregation of dorsal (pallial) from ventral (subpallial) telencephalic progenitors and the differentiation of cortical interneurons, regulating forebrain progenitor and interneuron heterogeneity. During corticogenesis in mice, SOX6 and SOX5 were largely mutually exclusively expressed in pallial and subpallial progenitors, respectively, and remained mutually exclusive in a reverse pattern in postmitotic neuronal progeny. Loss of SOX6 from pallial progenitors caused their inappropriate expression of normally subpallium-restricted developmental controls, conferring mixed dorsal-ventral identity. In postmitotic cortical interneurons, loss of SOX6 disrupted the differentiation and diversity of cortical interneuron subtypes, analogous to SOX5 control over cortical projection neuron development. These data indicate that SOX6 is a central regulator of both progenitor and cortical interneuron diversity during neocortical development.

  2. Nevoid basal cell carcinoma syndrome

    MedlinePlus

    NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic condition. The gene linked to the syndrome is known as PTCH (" ...

  3. Imaging basal ganglia function

    PubMed Central

    BROOKS, DAVID J.

    2000-01-01

    In this review, the value of functional imaging for providing insight into the role of the basal ganglia in motor control is reviewed. Brain activation findings in normal subjects and Parkinson's disease patients are examined and evidence supporting the existence for functionally independent distributed basal ganglia-frontal loops is presented. It is argued that the basal ganglia probably act to focus and filter cortical output, optimising the running of motor programs. PMID:10923986

  4. Dendritic cell potentials of early lymphoid and myeloid progenitors.

    PubMed

    Manz, M G; Traver, D; Miyamoto, T; Weissman, I L; Akashi, K

    2001-06-01

    It has been proposed that there are at least 2 classes of dendritic cells (DCs), CD8alpha(+) DCs derived from the lymphoid lineage and CD8alpha(-) DCs derived from the myeloid lineage. Here, the abilities of lymphoid- and myeloid-restricted progenitors to generate DCs are compared, and their overall contributions to the DC compartment are evaluated. It has previously been shown that primitive myeloid-committed progenitors (common myeloid progenitors [CMPs]) are efficient precursors of both CD8alpha(+) and CD8alpha(-) DCs in vivo. Here it is shown that the earliest lymphoid-committed progenitors (common lymphoid progenitors [CLPs]) and CMPs and their progeny granulocyte-macrophage progenitors (GMPs) can give rise to functional DCs in vitro and in vivo. CLPs are more efficient in generating DCs than their T-lineage descendants, the early thymocyte progenitors and pro-T cells, and CMPs are more efficient DC precursors than the descendant GMPs, whereas pro-B cells and megakaryocyte-erythrocyte progenitors are incapable of generating DCs. Thus, DC developmental potential is preserved during T- but not B-lymphoid differentiation from CLP and during granulocyte-macrophage but not megakaryocyte-erythrocyte development from CMP. In vivo reconstitution experiments show that CLPs and CMPs can reconstitute CD8alpha(+) and CD8alpha(-) DCs with similar efficiency on a per cell basis. However, CMPs are 10-fold more numerous than CLPs, suggesting that at steady state, CLPs provide only a minority of splenic DCs and approximately half the DCs in thymus, whereas most DCs, including CD8alpha(+) and CD8alpha(-) subtypes, are of myeloid origin. (Blood. 2001;97:3333-3341)

  5. Luminal progenitors restrict their lineage potential during mammary gland development.

    PubMed

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-02-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.

  6. Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development

    PubMed Central

    Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

    2015-01-01

    The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes. PMID:25688859

  7. A Twist2-dependent progenitor cell contributes to adult skeletal muscle.

    PubMed

    Liu, Ning; Garry, Glynnis A; Li, Stephen; Bezprozvannaya, Svetlana; Sanchez-Ortiz, Efrain; Chen, Beibei; Shelton, John M; Jaichander, Priscilla; Bassel-Duby, Rhonda; Olson, Eric N

    2017-03-01

    Skeletal muscle possesses remarkable regenerative potential due to satellite cells, an injury-responsive stem cell population located beneath the muscle basal lamina that expresses Pax7. By lineage tracing of progenitor cells expressing the Twist2 (Tw2) transcription factor in mice, we discovered a myogenic lineage that resides outside the basal lamina of adult skeletal muscle. Tw2(+) progenitors are molecularly and anatomically distinct from satellite cells, are highly myogenic in vitro, and can fuse with themselves and with satellite cells. Tw2(+) progenitors contribute specifically to type IIb/x myofibres during adulthood and muscle regeneration, and their genetic ablation causes wasting of type IIb myofibres. We show that Tw2 expression maintains progenitor cells in an undifferentiated state that is poised to initiate myogenesis in response to appropriate cues that extinguish Tw2 expression. Tw2-expressing myogenic progenitors represent a previously unrecognized, fibre-type-specific stem cell involved in postnatal muscle growth and regeneration.

  8. Calibration of CR-39-based thoron progeny device.

    PubMed

    Fábián, F; Csordás, A; Shahrokhi, A; Somlai, J; Kovács, T

    2014-07-01

    Radon isotopes and their progenies have proven significant role in respiratory tumour formation. In most cases, the radiological effect of one of the radon isotopes (thoron) and its progenies has been neglected together with its measurement technique; however, latest surveys proved that thoron's existence is expectable in flats and in workplace in Europe. Detectors based on different track detector measurement technologies have recently spread for measuring thoron progenies; however, the calibration is not yet completely elaborated. This study deals with the calibration of the track detector measurement method suitable for measuring thoron progenies using different devices with measurement techniques capable of measuring several progenies (Pylon AB5 and WLx, Sarad EQF 3220). The calibration factor values related to the thoron progeny monitors, the measurement uncertainty, reproducibility and other parameters were found using the calibration chamber. In the future, the effects of the different parameters (aerosol distribution, etc.) will be determined.

  9. Basal Cell Carcinoma

    PubMed Central

    Lanoue, Julien

    2016-01-01

    Basal cell carcinoma is the most commonly occurring cancer in the world and overall incidence is still on the rise. While typically a slow-growing tumor for which metastases is rare, basal cell carcinoma can be locally destructive and disfiguring. Given the vast prevalence of this disease, there is a significant overall burden on patient well-being and quality of life. The current mainstay of basal cell carcinoma treatment involves surgical modalities, such as electrodessication and curettage, excision, cryosurgery, and Mohs micrographic surgery. Such methods are typically reserved for localized basal cell carcinoma and offer high five-year cure rates, but come with the risk of functional impairment, disfigurement, and scarring. Here, the authors review the evidence and indications for nonsurgical treatment modalities in cases where surgery is impractical, contraindicated, or simply not desired by the patient. PMID:27386043

  10. Resident vascular progenitor cells.

    PubMed

    Torsney, Evelyn; Xu, Qingbo

    2011-02-01

    Homeostasis of the vessel wall is essential for maintaining its function, including blood pressure and patency of the lumen. In physiological conditions, the turnover rate of vascular cells, i.e. endothelial and smooth muscle cells, is low, but markedly increased in diseased situations, e.g. vascular injury after angioplasty. It is believed that mature vascular cells have an ability to proliferate to replace lost cells normally. On the other hand, recent evidence indicates stem/progenitor cells may participate in vascular repair and the formation of neointimal lesions in severely damaged vessels. It was found that all three layers of the vessels, the intima, media and adventitia, contain resident progenitor cells, including endothelial progenitor cells, mesenchymal stromal cells, Sca-1+ and CD34+ cells. Data also demonstrated that these resident progenitor cells could differentiate into a variety of cell types in response to different culture conditions. However, collective data were obtained mostly from in vitro culture assays and phenotypic marker studies. There are many unanswered questions concerning the mechanism of cell differentiation and the functional role of these cells in vascular repair and the pathogenesis of vascular disease. In the present review, we aim to summarize the data showing the presence of the resident progenitor cells, to highlight possible signal pathways orchestrating cell differentiation toward endothelial and smooth muscle cells, and to discuss the data limitations, challenges and controversial issues related to the role of progenitors. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".

  11. Light-induced Notch activity controls neurogenic and gliogenic potential of neural progenitors.

    PubMed

    Kim, Kyung-Tai; Song, Mi-Ryoung

    2016-10-28

    Oscillations in Notch signaling are essential for reserving neural progenitors for cellular diversity in developing brains. Thus, steady and prolonged overactivation of Notch signaling is not suitable for generating neurons. To acquire greater temporal control of Notch activity and mimic endogenous oscillating signals, here we adopted a light-inducible transgene system to induce active form of Notch NICD in neural progenitors. Alternating Notch activity saved more progenitors that are prone to produce neurons creating larger number of mixed clones with neurons and progenitors in vitro, compared to groups with no light or continuous light stimulus. Furthermore, more upper layer neurons and astrocytes arose upon intermittent Notch activity, indicating that dynamic Notch activity maintains neural progeny and fine-tune neuron-glia diversity.

  12. Post-injury niches induce temporal shifts in progenitor fates to direct lesion repair after spinal cord injury

    PubMed Central

    Sellers, Drew L.; Maris, Don O.; Horner, Philip J.

    2009-01-01

    Progenitors that express NG2-proteoglycan are the predominant self-renewing cell within the CNS. NG2-progenitors replenish oligodendrocyte populations within the intact stem-cell niche, and cycling NG2-cells are among the first cells to react to CNS insults. We investigated the role of NG2-progenitors after spinal cord injury (SCI) and how bone morphogen protein (BMP) signals remodel the progressive post-injury niche. Progeny labeled by an NG2-specific reporter virus undergo a coordinated shift in differentiation profile. NG2-progeny born 24-hours post-injury (PI) produce scar-forming astrocytes and transient populations of novel phagocytic astrocytes shown to contain denatured myelin within cathepsin-D labeled endosomes, but NG2-progenitors born 7-days PI differentiate into oligodendrocytes and express myelin on processes that wrap axons. Analysis of spinal cord mRNA shows a temporal-shift in the niche-transcriptome of ligands that affect post-injury remodeling and direct progenitor differentiation. We conclude that NG2-progeny are diverse lineages that obey progressive-cues after trauma to replenish the injured niche. PMID:19458241

  13. Evaluation of antioxidant compounds and total sugar content in a nectarine [Prunus persica (L.) Batsch] progeny.

    PubMed

    Abidi, Walid; Jiménez, Sergio; Moreno, María Ángeles; Gogorcena, Yolanda

    2011-01-01

    Epidemiological studies suggest that consumption of fruit rich in phenolic compounds is associated with health-protective effects due to their antioxidant properties. For these reasons quality evaluation has become an important issue in fruit industry and in breeding programs. Phytochemical traits such as total phenolics, flavonoids, anthocyanins, L-ascorbic acid, sugar content and relative antioxidant capacity (RAC) were analyzed over four years in flesh fruit of an F1 population "Venus" × "Big Top" nectarines. Other traits such as harvesting date, yield, fruit weight, firmness, soluble solids concentration (SSC), pH, titratable acidity (TA) and ripening index (RI) were also determined in the progeny. Results showed high variability among genotypes for all analyzed traits. Total phenolics and flavonoids showed significant positive correlations with RAC implying that both are important antioxidant bioactive compounds in peaches. We found genotypes with enhanced antioxidant capacity and a better performance than progenitors, and in consequence the best marketability.

  14. Evaluation of Antioxidant Compounds and Total Sugar Content in a Nectarine [Prunus persica (L.) Batsch] Progeny

    PubMed Central

    Abidi, Walid; Jiménez, Sergio; Moreno, María Ángeles; Gogorcena, Yolanda

    2011-01-01

    Epidemiological studies suggest that consumption of fruit rich in phenolic compounds is associated with health-protective effects due to their antioxidant properties. For these reasons quality evaluation has become an important issue in fruit industry and in breeding programs. Phytochemical traits such as total phenolics, flavonoids, anthocyanins, L-ascorbic acid, sugar content and relative antioxidant capacity (RAC) were analyzed over four years in flesh fruit of an F1 population “Venus” × “Big Top” nectarines. Other traits such as harvesting date, yield, fruit weight, firmness, soluble solids concentration (SSC), pH, titratable acidity (TA) and ripening index (RI) were also determined in the progeny. Results showed high variability among genotypes for all analyzed traits. Total phenolics and flavonoids showed significant positive correlations with RAC implying that both are important antioxidant bioactive compounds in peaches. We found genotypes with enhanced antioxidant capacity and a better performance than progenitors, and in consequence the best marketability. PMID:22072927

  15. Age-dependent lung dosimetry of radon progeny

    SciTech Connect

    Hofmann, W.; Martonen, T.B.; Menache, M.G.

    1988-02-01

    Two morphometric models differing in the tracheobronchial region, were compared in the present paper: Model 1 is based on the adult morphology of Weibel, assuming that all bronchial airways grow in equal proportion; while Model 2 adopts the adult structure proposed by Yeh and Schum, using measured airway dimensions in the right upper lobe as a function of age. Tidal volume and respiratory frequency also vary with age: while the breathing frequency decreases with rising age, tidal volume increases. Radiation doses in each bronchial airway generation were computed for the deep lying basal cells as well as for the more uniformly distributed serous (SMGS) cells, which are currently assumed to be the progenitor cells for bronchial carcinomas. Radiation doses to both target cells were significantly higher in the newborn than in the adult, for all simulated breathing patterns, showing the highest relative increase in upper bronchial airways. Comparing both tracheobronchial growth models, Model 1 predicts higher doses at early ages, but produced lower doses in the adult lung.

  16. Environmental factors unveil dormant developmental capacities in multipotent progenitors of the trunk neural crest.

    PubMed

    Coelho-Aguiar, Juliana M; Le Douarin, Nicole M; Dupin, Elisabeth

    2013-12-01

    The neural crest (NC), an ectoderm-derived structure of the vertebrate embryo, gives rise to the melanocytes, most of the peripheral nervous system and the craniofacial mesenchymal tissues (i.e., connective, bone, cartilage and fat cells). In the trunk of Amniotes, no mesenchymal tissues are derived from the NC. In certain in vitro conditions however, avian and murine trunk NC cells (TNCCs) displayed a limited mesenchymal differentiation capacity. Whether this capacity originates from committed precursors or from multipotent TNCCs was unknown. Here, we further investigated the potential of TNCCs to develop into mesenchymal cell types in vitro. We found that, in fact, quail TNCCs exhibit a high ability to differentiate into myofibroblasts, chondrocytes, lipid-laden adipocytes and mineralizing osteoblasts. In single cell cultures, both mesenchymal and neural cell types coexisted in TNCC clonal progeny: 78% of single cells yielded osteoblasts together with glial cells and neurons; moreover, TNCCs generated heterogenous clones with adipocytes, myofibroblasts, melanocytes and/or glial cells. Therefore, alike cephalic NCCs, early migratory TNCCs comprised multipotent progenitors able to generate both mesenchymal and melanocytic/neural derivatives, suggesting a continuum in NC developmental potentials along the neural axis. The skeletogenic capacity of the TNC, which was present in the exoskeletal armor of the extinct basal forms of Vertebrates and which persisted in the distal fin rays of extant teleost fish, thus did not totally disappear during vertebrate evolution. Mesenchymal potentials of the TNC, although not fulfilled during development, are still present in a dormant state in Amniotes and can be disclosed in in vitro culture. Whether these potentials are not expressed in vivo due to the presence of inhibitory cues or to the lack of permissive factors in the trunk environment remains to be understood.

  17. Comparative analysis of radon, thoron and thoron progeny concentration measurements.

    PubMed

    Janik, Miroslaw; Tokonami, Shinji; Kranrod, Chutima; Sorimachi, Atsuyuki; Ishikawa, Tetsuo; Hosoda, Masahiro; McLaughlin, James; Chang, Byung-Uck; Kim, Yong Jae

    2013-07-01

    This study examined correlations between radon, thoron and thoron progeny concentrations based on surveys conducted in several different countries. For this purpose, passive detectors developed or modified by the National Institute of Radiological Sciences (NIRS) were used. Radon and thoron concentrations were measured using passive discriminative radon-thoron detectors. Thoron progeny measurements were conducted using the NIRS-modified detector, originally developed by Zhuo and Iida. Weak correlations were found between radon and thoron as well as between thoron and thoron progeny. The statistical evaluation showed that attention should be paid to the thoron equilibrium factor for calculation of thoron progeny concentrations based on thoron measurements. In addition, this evaluation indicated that radon, thoron and thoron progeny were independent parameters, so it would be difficult to estimate the concentration of one from those of the others.

  18. Specialized progenitors and regeneration.

    PubMed

    Reddien, Peter W

    2013-03-01

    Planarians are flatworms capable of regenerating all body parts. Planarian regeneration requires neoblasts, a population of dividing cells that has been studied for over a century. Neoblast progeny generate new cells of blastemas, which are the regenerative outgrowths at wounds. If the neoblasts comprise a uniform population of cells during regeneration (e.g. they are all uncommitted and pluripotent), then specialization of new cell types should occur in multipotent, non-dividing neoblast progeny cells. By contrast, recent data indicate that some neoblasts express lineage-specific transcription factors during regeneration and in uninjured animals. These observations raise the possibility that an important early step in planarian regeneration is the specialization of neoblasts to produce specified rather than naïve blastema cells.

  19. Physiology of Continuous Bone Marrow Culture Derived Permanent Granulocyte-Macrophage Progenitor Cells

    DTIC Science & Technology

    1983-08-01

    capable of differentiating to mature neutrophillic granulocytes and granulocyte-macrophage progenitor cells . Several T- cell lines including K45, JURKAT...CEM, K230 have been screened for produc- tion of Interleukin-3 by assay of supernatant from cell lines for proliferation of mouse IL-3 dependent...hematopoietic progeni- tor cell lines Lines 45 and 230 produce low levels of activity. "In contrast, IL-2 (T- cell growth factor) dependent human T- cell

  20. Life beyond the Basal.

    ERIC Educational Resources Information Center

    Grey, Jeanne; Carbone, Carole

    1987-01-01

    Reading is a tool for learning. The goal for the teaching of reading must be to produce lovers of reading. A holistic approach should replace exclusive dependence on basal readers. Effective methods are the following: (1) language experience approach; (2) word banks; (3) pattern books; (4) sustained silent reading; and (5) directed…

  1. Isolated rat cortical progenitor cells are maintained in division in vitro by membrane-associated factors.

    PubMed

    Temple, S; Davis, A A

    1994-04-01

    Ventricular zone cells in the developing CNS undergo extensive cell division in vivo and under certain conditions in vitro. The culture conditions that promote cell division have been studied to determine the role that contact with cell membrane associated factors play in the proliferation of these cells. Progenitor cells have been taken from the ventricular zone of developing rat cerebral cortex and placed into microwells. Small clusters of these cells can generate large numbers of neurons and non-neuronal progeny. In contrast, single progenitor cells largely cease division, approximately 90% acquiring neuron-like characteristics by 1 day in vitro. DiI-labeled, single cells from embryonic day 14 cortex plated onto clusters of unmarked progenitor cells have a significantly higher probability (approximately 3-fold) of maintaining a progenitor cell phenotype than if plated onto the plastic substratum around 100 microns away from the clusters. Contact with purified astrocytes also promotes the progenitor cell phenotype, whereas contact with meningeal fibroblasts or balb3T3 cells promotes their differentiation. Membrane homogenates from cortical astrocytes stimulate significantly more incorporation of BrdU by E14 cortical progenitor cells than membrane homogenates from meningeal fibroblasts. These data indicate that the proliferation of rat cortical progenitor cells can be maintained by cell-type specific, membrane-associated factors.

  2. Restriction of transgene expression to the B-lymphoid progeny of human lentivirally transduced CD34+ cells.

    PubMed

    Moreau, Thomas; Bardin, Florence; Imbert, Jean; Chabannon, Christian; Tonnelle, Cécile

    2004-07-01

    Development of gene transfer strategies will necessitate improved efficiency and control of transduction and transgene expression. We here provide evidence that targeting expression of the GFP reporter gene to the B-lymphoid progeny of genetically modified human hematopoietic progenitor cells can be achieved through the insertion of regulatory sequences from the human CD19 gene promoter into a lentiviral vector. Based on a bioinformatics approach, three human CD19-derived sequences were designed and inserted into a self-inactivated lentiviral vector backbone upstream of the GFP gene: S.CD19 (230 bp), M.CD19 (464 bp), and L.CD19 (1274 bp). These new lentiviral vectors efficiently transduced cord blood CD34(+) cells. The M.CD19 and especially L.CD19 sequences preferentially targeted GFP expression to in vitro and in vivo differentiated CD19(+) progeny; moreover, transgene expression was detected from the CD34(+) pro/pre-B cell to the mature peripheral IgM(+) B cell stage. In contrast, GFP expression was weak or absent in primary T-lymphoid and uncommitted progenitor cells or in erythroid, natural killer, or myeloid differentiated cells. Such B-lineage-specific lentiviral vectors may be useful for correcting inherited disorders that affect B-lymphoid cells or for deciphering the transcriptional program that controls B cell commitment and differentiation.

  3. Earmuff restricts progenitor cell potential by attenuating the competence to respond to self-renewal factors

    PubMed Central

    Janssens, Derek H.; Komori, Hideyuki; Grbac, Daniel; Chen, Keng; Koe, Chwee Tat; Wang, Hongyan; Lee, Cheng-Yu

    2014-01-01

    Despite expressing stem cell self-renewal factors, intermediate progenitor cells possess restricted developmental potential, which allows them to give rise exclusively to differentiated progeny rather than stem cell progeny. Failure to restrict the developmental potential can allow intermediate progenitor cells to revert into aberrant stem cells that might contribute to tumorigenesis. Insight into stable restriction of the developmental potential in intermediate progenitor cells could improve our understanding of the development and growth of tumors, but the mechanisms involved remain largely unknown. Intermediate neural progenitors (INPs), generated by type II neural stem cells (neuroblasts) in fly larval brains, provide an in vivo model for investigating the mechanisms that stably restrict the developmental potential of intermediate progenitor cells. Here, we report that the transcriptional repressor protein Earmuff (Erm) functions temporally after Brain tumor (Brat) and Numb to restrict the developmental potential of uncommitted (immature) INPs. Consistently, endogenous Erm is detected in immature INPs but undetectable in INPs. Erm-dependent restriction of the developmental potential in immature INPs leads to attenuated competence to respond to all known neuroblast self-renewal factors in INPs. We also identified that the BAP chromatin-remodeling complex probably functions cooperatively with Erm to restrict the developmental potential of immature INPs. Together, these data led us to conclude that the Erm-BAP-dependent mechanism stably restricts the developmental potential of immature INPs by attenuating their genomic responses to stem cell self-renewal factors. We propose that restriction of developmental potential by the Erm-BAP-dependent mechanism functionally distinguishes intermediate progenitor cells from stem cells, ensuring the generation of differentiated cells and preventing the formation of progenitor cell-derived tumor-initiating stem cells. PMID

  4. Dosimetry of radium-223 and progeny

    SciTech Connect

    Fisher, D.R.; Sgouros, G.

    1999-01-01

    Radium-223 is a short-lived (11.4 d) alpha emitter with potential applications in radioimmunotherapy of cancer. Radium-223 can be complexed and linked to protein delivery molecules for specific tumor-cell targeting. It decays through a cascade of short-lived alpha- and beta-emitting daughters with emission of about 28 MeV of energy through complete decay. The first three alpha particles are essentially instantaneous. Photons associated with Ra-223 and progeny provide the means for tumor and normal-organ imaging and dosimetry. Two beta particles provide additional therapeutic value. Radium-223 may be produced economically and in sufficient amounts for widescale application. Many aspects of the chemistry of carrier-free isotope preparation, complexation, and linkage to the antibody have been developed and are being tested. The radiation dosimetry of a Ra-223-labeled antibody shows favorable tumor to normal tissue dose ratios for therapy. The 11.4-d half-life of Ra-223 allows sufficient time for immunoconjugate preparation, administration, and tumor localization by carrier antibodies before significant radiological decay takes place. If 0.01 percent of a 37 MBq (1 mCi) injection deposits in a one gram tumor mass, and if the activity is retained with a typical effective half-time (75 h), the absorbed dose will be 163 mGy MBq{sup {minus}1} (600 rad mCi{sup {minus}1}) administered. 49 refs., 5 figs., 2 tabs.

  5. Aging neural progenitors lose competence to respond to mitogenic Notch signaling

    PubMed Central

    Farnsworth, Dylan R.; Bayraktar, Omer Ali; Doe, Chris Q.

    2015-01-01

    Drosophila neural stem cells (neuroblasts) are a powerful model system for investigating stem cell self-renewal, specification of temporal identity, and progressive restriction in competence. Notch signaling is a conserved cue that is an important determinant of cell fate in many contexts across animal development; for example mammalian T cell differentiation in the thymus and neuroblast specification in Drosophila are both regulated by Notch signaling. However, Notch also functions as a mitogen, and constitutive Notch signaling potentiates T cell leukemia as well as Drosophila neuroblast tumors. While the role of Notch signaling has been studied in these and other cell types, it remains unclear how stem cells and progenitors change competence to respond to Notch over time. Notch is required in type II neuroblasts for normal development of their transit amplifying progeny, intermediate neural progenitors (INPs). Here we find that aging INPs lose competence to respond to constitutively active Notch signaling. Moreover, we show that reducing the levels of the old INP temporal transcription factor Eyeless/Pax6 allows Notch signaling to promote the de-differentiation of INP progeny into ectopic INPs, thereby creating a proliferative mass of ectopic progenitors in the brain. These findings provide a new system for studying progenitor competence, and identify a novel role for the conserved transcription factor Eyeless/Pax6 in blocking Notch signaling during development. PMID:26585279

  6. Efficiency Analysis and Comparison of Different Radon Progeny Measurement Methods

    PubMed Central

    Zhang, Lei

    2013-01-01

    Radon exposure to the public contributes more than half of all the radiation doses caused by natural radiation; accurate measurement of radon progeny is quite essential for the dose evaluation of radon exposure in environment. For the purpose of establishing a radon progeny standard and controlling measurement quality of commercial devices, it is quite important to analyze the efficiency of different measurement methods and determine which would be the most appropriate for radon progeny measurements. Through theoretical analysis and experimental measurement, some commonly used measurement methods were compared in this study and the development trends of those methods were reviewed. Results show that for radon progeny measurement, the spectroscopic analysis method is better than the gross count method, while least-square calculation methods is better than traditional three-count or five-count method. Multiperiod counting of α plus β spectrum as well as using weighted least-square calculation method might be the best choice for accurate measurement on radon progeny in standard radon chamber when calibrating commercial radon progeny monitors. PMID:24385873

  7. Emergence of neuronal diversity from patterning of telencephalic progenitors.

    PubMed

    Azzarelli, Roberta; Hardwick, Laura J A; Philpott, Anna

    2015-01-01

    During central nervous system (CNS) development, hundreds of distinct neuronal subtypes are generated from a single layer of multipotent neuroepithelial progenitor cells. Within the rostral CNS, initial regionalization of the telencephalon marks the territories where the cerebral cortex and the basal ganglia originate. Subsequent refinement of the primary structures determines the formation of domains of differential gene expression, where distinct fate-restricted progenitors are located. To understand how diversification of neural progenitors and neurons is achieved in the telencephalon, it is important to address early and late patterning events in this context. In particular, important questions include: How does the telencephalon become specified and regionalized along the major spatial axes? Within each region, are the differences in neuronal subtypes established at the progenitor level or at the postmitotic stage? If distinct progenitors exist that are committed to subtype-specific neuronal lineages, how does the diversification emerge? What is the contribution of positional and temporal cues and how is this information integrated into the intrinsic programs of cell identity? WIREs For further resources related to this article, please visit the WIREs website.

  8. Expression of TCR-Vβ peptides by murine bone marrow cells does not identify T-cell progenitors.

    PubMed

    Abbey, Janice L; Karsunky, Holger; Serwold, Thomas; Papathanasiou, Peter; Weissman, Irving L; O'Neill, Helen C

    2015-08-01

    Germline transcription has been described for both immunoglobulin and T-cell receptor (TCR) genes, raising questions of their functional significance during haematopoiesis. Previously, an immature murine T-cell line was shown to bind antibody to TCR-Vβ8.2 in absence of anti-Cβ antibody binding, and an equivalent cell subset was also identified in the mesenteric lymph node. Here, we investigate whether germline transcription and cell surface Vβ8.2 expression could therefore represent a potential marker of T-cell progenitors. Cells with the TCR phenotype of Vβ8.2(+) Cβ(-) are found in several lymphoid sites, and among the lineage-negative (Lin(-)) fraction of hematopoietic progenitors in bone marrow (BM). Cell surface marker analysis of these cells identified subsets reflecting common lymphoid progenitors, common myeloid progenitors and multipotential progenitors. To assess whether the Lin(-) Vβ8.2(+) Cβ(-) BM subset contains hematopoietic progenitors, cells were sorted and adoptively transferred into sub-lethally irradiated recipients. No T-cell or myeloid progeny were detected following introduction of cells via the intrathymic or intravenous routes. However, B-cell development was detected in spleen. This pattern of restricted in vivo reconstitution disputes Lin(-) Vβ8.2(+) Cβ(-) BM cells as committed T-cell progenitors, but raises the possibility of progenitors with potential for B-cell development.

  9. Characterization of nonmalignant and malignant prostatic stem/progenitor cells by Hoechst side population method.

    PubMed

    Mimeault, Murielle; Batra, Surinder K

    2009-01-01

    Recent technical progress in the field of cancer stem/progenitor cell research revealed that these malignant cells may provide critical roles for primary tumor growth, metastases at distant tissues and organs, treatment resistance, and disease relapse. The precise molecular oncogenic events that frequently occur in cancer stem/progenitor cells and their early progenies during the early and late stages of cancer progression as well as their contribution to the treatment resistance and disease recurrence remain poorly defined. This lack of information on the deregulated gene products that may be involved in the malignant transformation of tissue-resident adult stem/progenitor cells into highly tumorigenic and/or migrating cancer stem/progenitor cells emphasizes the urgent need to perform future investigations. Toward this direction, we describe in this book chapter the characterization of nonmalignant and malignant prostatic stem/progenitor cells from well-established cell lines by Hoechst side population method. This novel approach should help to establish novel in vitro and in vivo models of human cancer stem/progenitor cell mimicking more closely the genetic and phenotypic changes occurring during the different stages of prostate carcinogenesis and disease progression in clinical settings. Of therapeutic interest, the identification of new biomarkers and molecular targets specific to these prostatic cancer-initiating cells should also help to develop more effective diagnostic and prognostic tests and chemopreventive and therapeutic treatments for the patients diagnosed at early and late stages of disease progression.

  10. Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments†

    PubMed Central

    Nelson, Celeste M.; Villadsen, Rene; Fridriksdottir, Agla; Ruth, Jason R.; Stampfer, Martha R.; Petersen, Ole W.

    2010-01-01

    In adult tissues, multi-potent progenitor cells are some of the most primitive members of the developmental hierarchies that maintain homeostasis. That progenitors and their more mature progeny share identical genomes, suggests that fate decisions are directed by interactions with extrinsic soluble factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells. Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell–cell versus cell–ECM interactions, as well as constellations of signaling molecules; and these were used in conjunction with physiologically relevant 3 dimensional human breast cultures. Both immortalized and primary human breast progenitors were analyzed. We report on the functional ability of those proteins of the mammary gland that maintain quiescence, maintain the progenitor state, and guide progenitor differentiation towards myoepithelial and luminal lineages. PMID:20023793

  11. Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments

    SciTech Connect

    LaBarge, Mark A; Nelson, Celeste M; Villadsen, Rene; Fridriksdottir, Agla; Ruth, Jason R; Stampfer, Martha R; Petersen, Ole W; Bissell, Mina J

    2008-09-19

    In adult tissues, multi-potent progenitor cells are some of the most primitive members of the developmental hierarchies that maintain homeostasis. That progenitors and their more mature progeny share identical genomes, suggests that fate decisions are directed by interactions with extrinsic soluble factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells. Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well as constellations of signaling molecules; and these were used in conjunction with physiologically relevant 3 dimensional human breast cultures. Both immortalized and primary human breast progenitors were analyzed. We report on the functional ability of those proteins of the mammary gland that maintain quiescence, maintain the progenitor state, and guide progenitor differentiation towards myoepithelial and luminal lineages.

  12. Biokinetic models for radiocesium and its progeny

    SciTech Connect

    Leggett, Richard Wayne

    2013-01-01

    Over the next few years the International Commission on Radiological Protection (ICRP) will publish a series of reports containing updated biokinetic and dosimetric models and dose coefficients for occupational intake of radionuclides. The biokinetic modeling scheme continues a trend in modern ICRP reports toward physiologically realistic descriptions of the time-dependent behavior of absorbed radionuclides and ingrowing chain members. This paper proposes systemic biokinetic models for cesium isotopes and their chain members for use in these ICRP reports and examines dosimetric implications of the proposed models. Comparisons of A = tissue dose per unit input to blood based on current ICRP models for workers (ICRP Publication 68, 1994) with B = corresponding values based on the proposed biokinetic models (but using dosimetry models of Publication 68) yields the following ranges of ratios B:A for tissues addressed in current ICRP documents: 0.5-25 for 130Cs (T1/2 = 29.2 min), 0.6-9.5 for 134mCs (2.9 h), 0.8-2.2 for 129Cs (32.1 h), 0.7-1.7 for 131Cs (9.69 d), 0.8-1.3 for 136Cs (13.2 d), 0.7-1.1 for 134Cs (2.06 y), 0.5-1.9 for 137Cs (30.2 y), and 0.2-3.7 for 135Cs (2.3x106 y). The large differences in estimated tissue dose for some tissues and cesium isotopes, particularly short-lived isotopes, result mainly from differences in model predictions of the time-dependent distributions of cesium in the body. For example, the proposed and current ICRP models for cesium predict peak kidney contents of ~22% and ~0.4%, respectively, following intravenous injection of stable cesium. Based on the proposed models for cesium and its progeny, the only dosimetrically significant chain members of cesium isotopes are 137mBa, which represents 32-85% of the estimated tissue doses from injected 137Cs, and 134Cs, which represents 4-53% of the estimated tissue doses from injected 134mCs.

  13. Attachment of radon progeny to cigarette-smoke aerosols

    SciTech Connect

    Biermann, A.H.; Sawyer, S.R.

    1995-05-01

    The daughter products of radon gas are now recognized as a significant contributor to radiation exposure to the general public. It is also suspected that a synergistic effect exists with the combination cigarette smoking and radon exposure. We have conducted an experimental investigation to determine the physical nature of radon progeny interactions with cigarette smoke aerosols. The size distributions of the aerosols are characterized and attachment rates of radon progeny to cigarette-smoke aerosols are determined. Both the mainstream and sidestream portions of the smoke aerosol are investigated. Unattached radon progeny are very mobile and, in the presence of aerosols, readily attach to the particle surfaces. In this study, an aerosol chamber is used to contain the radon gas, progeny and aerosol mixture while allowing the attachment process to occur. The rate of attachment is dependent on the size distribution, or diffusion coefficient, of the radon progeny as well as the aerosol size distribution. The size distribution of the radon daughter products is monitored using a graded-screen diffusion battery. The diffusion battery also enables separation of the unattached radon progeny from those attached to the aerosol particles. Analysis of the radon decay products is accomplished using alpha spectrometry. The aerosols of interest are size fractionated with the aid of a differential mobility analyzer and cascade impactor. The measured attachment rates of progeny to the cigarette smoke are compared to those found in similar experiments using an ambient aerosol. The lowest attachment coefficients observed, {approximately}10{sup {minus}6} cm{sup 3}/s, occurred for the ambient aerosol. The sidestream and mainstream smoke aerosols exhibited higher attachment rates in that order. The results compared favorably with theories describing the coagulation process of aerosols.

  14. Human basal body basics.

    PubMed

    Vertii, Anastassiia; Hung, Hui-Fang; Hehnly, Heidi; Doxsey, Stephen

    2016-01-01

    In human cells, the basal body (BB) core comprises a ninefold microtubule-triplet cylindrical structure. Distal and subdistal appendages are located at the distal end of BB, where they play indispensable roles in cilium formation and function. Most cells that arrest in the G0 stage of the cell cycle initiate BB docking at the plasma membrane followed by BB-mediated growth of a solitary primary cilium, a structure required for sensing the extracellular environment and cell signaling. In addition to the primary cilium, motile cilia are present in specialized cells, such as sperm and airway epithelium. Mutations that affect BB function result in cilia dysfunction. This can generate syndromic disorders, collectively called ciliopathies, for which there are no effective treatments. In this review, we focus on the features and functions of BBs and centrosomes in Homo sapiens.

  15. Regulation of development of rat stem and progenitor Leydig cells by activin.

    PubMed

    Li, L; Wang, Y; Li, X; Liu, S; Wang, G; Lin, H; Zhu, Q; Guo, J; Chen, H; Ge, H-S; Ge, R-S

    2017-01-01

    Stem Leydig cells have been demonstrated to differentiate into adult Leydig cells via intermediate stages of progenitor and immature Leydig cells. However, the exact regulatory mechanisms are unclear. We hypothesized that the development of stem or progenitor Leydig cells depends upon locally produced growth factors. Microarray analysis revealed that the expression levels of activin type I receptor (Acvr1) and activin A receptor type II-like 1 (Acvrl1) were stem > progenitor = immature = adult Leydig cells. This indicates that their ligand activin might play an important role in stem and progenitor Leydig cell proliferation and differentiation. When seminiferous tubules were incubated with 1 or 10 ng/mL activin A for 3 days, it concentration-dependently increased EdU incorporation into stem Leydig cells by up to 20-fold. When progenitor Leydig cells were incubated with 1 or 10 ng/mL activin A for 2 days, it concentration-dependently increased (3) H-thymidine incorporation into progenitor Leydig cells by up to 200%. Real-time PCR analysis showed that activin A primarily increased Pcna expression but reduced Star, Hsd3b1, and Cyp17a1 expression levels. Activin A also significantly inhibited the basal and luteinizing hormone-stimulated androgen production. In conclusion, activin A primarily stimulates the proliferation of stem and progenitor Leydig cells, but inhibits the differentiation of stem and progenitor Leydig cells into the Leydig cell lineage in rat testis.

  16. Paracrine Met signaling triggers epithelial–mesenchymal transition in mammary luminal progenitors, affecting their fate

    PubMed Central

    Di-Cicco, Amandine; Petit, Valérie; Chiche, Aurélie; Bresson, Laura; Romagnoli, Mathilde; Orian-Rousseau, Véronique; Vivanco, Maria dM; Medina, Daniel; Faraldo, Marisa M; Glukhova, Marina A; Deugnier, Marie-Ange

    2015-01-01

    HGF/Met signaling has recently been associated with basal-type breast cancers, which are thought to originate from progenitor cells residing in the luminal compartment of the mammary epithelium. We found that ICAM-1 efficiently marks mammary luminal progenitors comprising hormone receptor-positive and receptor-negative cells, presumably ductal and alveolar progenitors. Both cell populations strongly express Met, while HGF is produced by stromal and basal myoepithelial cells. We show that persistent HGF treatment stimulates the clonogenic activity of ICAM1-positive luminal progenitors, controlling their survival and proliferation, and leads to the expression of basal cell characteristics, including stem cell potential. This is accompanied by the induction of Snai1 and Snai2, two major transcription factors triggering epithelial–mesenchymal transition, the repression of the luminal-regulatory genes Elf5 and Hey1, and claudin down-regulation. Our data strongly indicate that paracrine Met signaling can control the function of luminal progenitors and modulate their fate during mammary development and tumorigenesis. DOI: http://dx.doi.org/10.7554/eLife.06104.001 PMID:26165517

  17. Modeling surface backgrounds from radon progeny plate-out

    SciTech Connect

    Perumpilly, G.; Guiseppe, V. E.; Snyder, N.

    2013-08-08

    The next generation low-background detectors operating deep underground aim for unprecedented low levels of radioactive backgrounds. The surface deposition and subsequent implantation of radon progeny in detector materials will be a source of energetic background events. We investigate Monte Carlo and model-based simulations to understand the surface implantation profile of radon progeny. Depending on the material and region of interest of a rare event search, these partial energy depositions can be problematic. Motivated by the use of Ge crystals for the detection of neutrinoless double-beta decay, we wish to understand the detector response of surface backgrounds from radon progeny. We look at the simulation of surface decays using a validated implantation distribution based on nuclear recoils and a realistic surface texture. Results of the simulations and measured α spectra are presented.

  18. Maternal dietary lipids alter bone chemical composition, mechanical properties, and histological characteristics of progeny of Japanese quail.

    PubMed

    Liu, D; Veit, H P; Wilson, J H; Denbow, D M

    2003-03-01

    This study evaluated the effects of maternal dietary lipids on chemical components and mechanical and histological properties of tibia in progeny of Japanese quail fed different dietary lipids. Laying hens were fed a basal diet containing either soybean oil (SBO), hydrogenated soybean oil (HSBO), chicken fat (CF), or menhaden fish oil (FO) at 50 g/kg of the diet. The various maternal dietary lipid treatments did not affect growth of progeny at any developmental stage. There were no differences in tibial length, diameter, or collagen content. Tibial percentage ash was significantly higher in newly hatched progeny from hens fed the FO and HSBO diets. The levels of tibial deoxypyridinoline and total pyridinium crosslinks were higher in the FO and HSBO groups at hatch. At 7 d of age, the tibial deoxypyridinoline links remained higher in the FO group compared to the CF and SBO groups. Likewise, progeny from hens consuming the FO or HSBO diet had higher tibial shear force and stiffness at 7 and 14 d of age. There were no pronounced differences in tibial fracture energy and deflection among treatments. Maternal FO or HSBO enlarged the cartilaginous proliferative and hypertrophic zones of the tibial proximal end in newly hatched quail, which was accompanied by a thicker cortical bone in the diaphysis. However, the width of the hypertrophic zones tended to be smaller in these two groups coupled with improvement in trabecular density and cortical thickness in the proximal end and cortical density in the diaphysis at 3 wk of age. These results suggest that maternal dietary lipids altered bone development by influencing organic matrix quality and mineralization in embryos.

  19. Assessing the deposition of radon progeny from a uranium glass necklace.

    PubMed

    Hansen, M F; Moss, G R

    2015-06-01

    Could jewellery made from uranium glass beads pose an increased risk to skin cancer? The literature Eatough (Alpha-particle dosimetry for the basal layer of the skin and the radon progeny (218)Po and (214)Po. Phys. Med. Biol. 1997; 42: 1899-1911.) suggests that the alphas from the short-lived radon daughters, (218)Po and (214)Po, may reach the basal layer of the epidermis, which is believed to be important in the induction of skin cancers. The deposition of the alphas from the (218)Po and (214)Po daughters was investigated using PADC detector material. The expectation would be that no alpha particles would penetrate through the dead skin layer, assuming the average of 70 microns used in radiation protection, but the skin around the collar bone could potentially be thinner than the assumed average. It should be noticed that by inserting a slice of pig skin in between the necklace and the PADC, no great excess of alpha tracks were seen after 1 week of exposure in the freezer. There was, however, a clear signal through the pig skin from beta particles, confirming the potential of a uranium bead necklace posing a health risk.

  20. Vismodegib in basal cell carcinoma.

    PubMed

    Amaria, R N; Bowles, D W; Lewis, K D; Jimeno, A

    2012-07-01

    Vismodegib is a novel, small-molecule inhibitor of smoothened, a key component of the hedgehog signaling pathway. Increased hedgehog pathway signaling is critical in the development of hereditary and spontaneous basal cell carcinomas of the skin, and has been implicated in the development of a number of other tumors. In preclinical models, vismodegib demonstrated potent antitumor activity in hedgehog-dependent tumors, particularly basal cell carcinomas. Clinically, phase I and II studies showed dramatic anticancer activity in patients with advanced basal cell carcinomas. In January 2012, vismodegib was approved by the FDA for the treatment of unresectable or metastatic basal cell carcinomas of the skin.

  1. Microdosimetry of radon progeny: Application to risk assessment

    SciTech Connect

    Fisher, D.R.; Hui, T.E.; James, A.C. ); Bond, V.P. )

    1990-01-01

    We developed methods for calculating radiation doses to individual cells and cell nuclei of human bronchial epithelium from radon and progeny for specified levels of exposure, breathing rates, equilibrium factors, unattached fraction of progeny, and other factors that are important in radon dosimetry. If we also know which cells are likely precursors for cancer, and we also know their locations in the respiratory tract, we then may calculate the statistical probability that these cells are irradiated by alpha particles, the number of single alpha-particle hits, and the spectrum of doses delivered as a probability density in specific energy.

  2. Notch Stimulates Both Self-Renewal and Lineage Plasticity in a Subset of Murine CD9High Committed Megakaryocytic Progenitors

    PubMed Central

    Chaabouni, Azza; Chazaud, Bénédicte; Morlé, François

    2016-01-01

    This study aimed at reinvestigating the controversial contribution of Notch signaling to megakaryocytic lineage development. For that purpose, we combined colony assays and single cells progeny analyses of purified megakaryocyte-erythroid progenitors (MEP) after short-term cultures on recombinant Notch ligand rDLL1. We showed that Notch activation stimulated the SCF-dependent and preferential amplification of Kit+ erythroid and bipotent progenitors while favoring commitment towards the erythroid at the expense of megakaryocytic lineage. Interestingly, we also identified a CD9High MEP subset that spontaneously generated almost exclusively megakaryocytic progeny mainly composed of single megakaryocytes. We showed that Notch activation decreased the extent of polyploidization and maturation of megakaryocytes, increased the size of megakaryocytic colonies and surprisingly restored the generation of erythroid and mixed colonies by this CD9High MEP subset. Importantly, the size increase of megakaryocytic colonies occurred at the expense of the production of single megakaryocytes and the restoration of colonies of alternative lineages occurred at the expense of the whole megakaryocytic progeny. Altogether, these results indicate that Notch activation is able to extend the number of divisions of MK-committed CD9High MEPs before terminal maturation while allowing a fraction of them to generate alternative lineages. This unexpected plasticity of MK-committed progenitors revealed upon Notch activation helps to better understand the functional promiscuity between megakaryocytic lineage and hematopoietic stem cells. PMID:27089435

  3. Colonization of the satellite cell niche by skeletal muscle progenitor cells depends on Notch signals.

    PubMed

    Bröhl, Dominique; Vasyutina, Elena; Czajkowski, Maciej T; Griger, Joscha; Rassek, Claudia; Rahn, Hans-Peter; Purfürst, Bettina; Wende, Hagen; Birchmeier, Carmen

    2012-09-11

    Skeletal muscle growth and regeneration rely on myogenic progenitor and satellite cells, the stem cells of postnatal muscle. Elimination of Notch signals during mouse development results in premature differentiation of myogenic progenitors and formation of very small muscle groups. Here we show that this drastic effect is rescued by mutation of the muscle differentiation factor MyoD. However, rescued myogenic progenitors do not assume a satellite cell position and contribute poorly to myofiber growth. The disrupted homing is due to a deficit in basal lamina assembly around emerging satellite cells and to their impaired adhesion to myofibers. On a molecular level, emerging satellite cells deregulate the expression of basal lamina components and adhesion molecules like integrin α7, collagen XVIIIα1, Megf10, and Mcam. We conclude that Notch signals control homing of satellite cells, stimulating them to contribute to their own microenvironment and to adhere to myofibers.

  4. Production of human glucocerebrosidase in mice after retroviral gene transfer into multipotential hematopoietic progenitor cells

    SciTech Connect

    Correll, P.H.; Fink, J.K.; Brady, R.O.; Perry, L.K.; Karlsson, S. )

    1989-11-01

    The human glucocerebrosidase (GC) gene has been transferred efficiently into spleen colony-forming unit (CFU-S) multipotential hematopoietic progenitor cells, and production of human GC RNA and protein has been achieved in transduced CFU-S colonies. High-titer retroviral vectors containing the human GC cDNA were constructed. Four vectors were compared with respect to gene-transfer efficiency into CFU-S progenitors. One vector (G vector) required high concentrations of interleukins 3 and 6 during stimulation and coculture for efficient transduction of CFU-S progenitors. The remaining three vectors (NTG, GTN, and GI vectors) transduced these progenitors at infection frequencies approaching 100% using low concentrations of hematopoietic growth factors to simulate cell division prior to and during the infection. Vectors using the viral long terminal repeat enhancer/promoter to drive the human GC cDNA produced high levels of human GC RNA in the progeny of CFU-S progenitors after gene transfer. All three vectors producing human GC RNA in CFU-S colonies can generate human GC as detected by immunochemical analysis of CFU-S colonies. The capacity of the viral long terminal repeat and the internal thymidine kinase promoter to direct synthesis of RNA in transduced bone marrow and spleen cells 5 months after bone marrow transplantation reflected the performance of these promoters in NTG-transduced CFU-S colonies.

  5. SOX6 controls dorsal-ventral progenitor parcellation and interneuron diversity during neocortical development

    PubMed Central

    Azim, Eiman; Jabaudon, Denis; Fame, Ryann; Macklis, Jeffrey D.

    2010-01-01

    Summary The extraordinary neuronal diversity of the central nervous system emerges largely from controlled spatial and temporal segregation of cell type-specific molecular regulators. Here, we report that the transcription factor SOX6 controls the molecular segregation of dorsal (pallial) from ventral (subpallial) telencephalic progenitors, and the differentiation of cortical interneurons, regulating forebrain progenitor and interneuron heterogeneity. During corticogenesis in mice, SOX6 and highly related SOX5 expression is largely mutually exclusive in pallial and subpallial progenitors, respectively, and remains mutually exclusive in a reverse pattern in postmitotic neuronal progeny. Loss of SOX6 from pallial progenitors causes their inappropriate expression of normally subpallium-restricted developmental controls, conferring mixed dorsal-ventral identity. In postmitotic cortical interneurons, loss of SOX6 dramatically disrupts the differentiation and diversity of cortical interneuron subtypes, analogous to SOX5 control over cortical projection neuron development. These data reveal SOX6 as a novel transcription factor regulator of both progenitor and cortical interneuron diversity during neocortical development. PMID:19657336

  6. Distinct FAK activities determine progenitor and mammary stem cell characteristics

    PubMed Central

    Luo, Ming; Zhao, Xiaofeng; Chen, Song; Liu, Suling; Wicha, Max S.; Guan, Jun-Lin

    2013-01-01

    Mammary stem (MaSCs) and progenitor cells are important for mammary gland development and maintenance and may give rise to mammary cancer stem cells (MaCSCs). Yet there remains limited understanding of how these cells contribute to tumorigenesis. Here we show that conditional deletion of focal adhesion kinase (FAK) in embryonic mammary epithelial cells (MaECs) decreases luminal progenitors (LPs) and basal MaSCs, reducing their colony-forming and regenerative potentials in a cell autonomous manner. Loss of FAK kinase activity in MaECs specifically impaired LP proliferation and alveologenesis, whereas a kinase-independent activity of FAK supported ductal invasion and basal MaSC activity. Deficiency in LPs suppressed tumorigenesis and MaCSC formation in a mouse model of breast cancer. In contrast to the general inhibitory effect of FAK attenuation, inhibitors of FAK kinase preferentially inhibited proliferation and tumorsphere formation of LP-like, but not MaSC-like, human breast cancer cells. Our findings establish distinct kinase dependent and independent activities of FAK that differentially regulate LPs and basal MaSCs. We suggest that targeting these distinct functions may tailor therapeutic strategies to address breast cancer heterogeneity more effectively. PMID:23832665

  7. Control of indoor radon and radon progeny concentrations

    SciTech Connect

    Sextro, R.G.

    1985-05-01

    There are three general categories of techniques for the control of radon and radon progeny concentrations in indoor air - restriction of radon entry, reduction of indoor radon concentrations by ventilation or air cleaning, and removal of airborne radon progeny. The predominant radon entry process in most residences appears to be pressure driven flow of soil gas through cracks or other openings in the basement, slab, or subfloor. Sealing these openings or ventilation of the subslab or subfloor space are methods of reducing radon entry rates. Indoor radon concentrations may be reduced by increased ventilation. The use of charcoal filters for removal of radon gas in the indoor air by adsorption has also been proposed. Concentrations of radon progeny, which are responsible for most of the health risks associated with radon exposures, can be controlled by use of electrostatic or mechanical filtration. Air circulation can also reduce radon progeny concentrations in certain cases. This paper reviews the application and limitations of each of these control measures and discusses recent experimental results.

  8. Adversity before Conception Will Affect Adult Progeny in Rats

    ERIC Educational Resources Information Center

    Shachar-Dadon, Alice; Schulkin, Jay; Leshem, Micah

    2009-01-01

    The authors investigated whether adversity in a female, before she conceives, will influence the affective and social behavior of her progeny. Virgin female rats were either undisturbed (controls) or exposed to varied, unpredictable, stressors for 7 days (preconceptual stress [PCS]) and then either mated immediately after the end of the stress…

  9. Thoron and thoron progeny measurements in German clay houses.

    PubMed

    Gierl, S; Meisenberg, O; Feistenauer, P; Tschiersch, J

    2014-07-01

    In recent years, elevated thoron concentrations were found in houses built of unfired clay. In this study experiments were carried out in 17 traditional and modern clay houses in Germany to obtain an overview of indoor thoron in such houses. Long-term measurements over an 8-week period were performed using a newly developed Unattended Battery-Operated Progeny Measurement Device (UBPM) for measuring thoron progeny. This instrument uses a high-voltage electric field to precipitate radon and thoron progeny on nuclear track detectors. Additional active and passive measurements of radon, thoron and their progeny were performed. The equilibrium equivalent thoron concentration was found to be between 2 and 10 Bq m(-3). Gas concentrations were found to be between 20 and 160 Bq m(-3) for radon and between 10 and 90 Bq m(-3) for thoron 20 cm from the wall. The thoron exposure contributes significantly to the inhalation dose of the dwellers (0.6-4 mSv a(-1)).

  10. Expression of ezrin in subventricular zone neural stem cells and their progeny in adult and developing mice.

    PubMed

    Moon, Younghye; Kim, Joo Yeon; Choi, So Yoen; Cho, Hyo Min; Kim, Hyun; Sun, Woong

    2013-03-01

    Ezrin is a member of the ezrin-radixin-moesin (ERM) family of proteins, which link the cytoskeleton and cell membrane. ERM proteins are involved in pivotal cellular functions including cell-matrix recognition, cell-cell communication, and cell motility. Several recent studies have shown that ERM proteins are expressed in specific cell types of the adult rostral migratory stream (RMS). In this study, we found that ERM proteins are expressed highly in the early postnatal RMS and the ventricular zone of embryonic cerebral cortex, suggesting that these proteins may be expressed by neural progenitors. Furthermore, whereas ezrin previously was found to be expressed exclusively by astrocytes of the adult RMS, we found that ezrin-expressing cells also expressed the markers for indicating neuroblasts in vivo and in vitro, and that ezrin expression by neuroblasts decreases progressively as neuroblasts migrate. Using in vitro differentiation of adult neural stem cells, we found that ezrin is expressed by neural stem cells and their progeny (neuroblasts and astrocytes), but not by oligodendrocytic progeny. Collectively our findings demonstrate that adult neural stem cells and neuroblasts express ezrin and that ezrin may be involved in intracellular actin remodeling.

  11. PET imaging of adoptive progenitor cell therapies.

    SciTech Connect

    Gelovani, Juri G.

    2008-05-13

    Objectives. The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive “tracking” of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to

  12. Transplantation of Defined Populations of Differentiated Human Neural Stem Cell Progeny

    PubMed Central

    Fortin, Jeff M.; Azari, Hassan; Zheng, Tong; Darioosh, Roya P.; Schmoll, Michael E.; Vedam-Mai, Vinata; Deleyrolle, Loic P.; Reynolds, Brent A.

    2016-01-01

    Many neurological injuries are likely too extensive for the limited repair capacity of endogenous neural stem cells (NSCs). An alternative is to isolate NSCs from a donor, and expand them in vitro as transplantation material. Numerous groups have already transplanted neural stem and precursor cells. A caveat to this approach is the undefined phenotypic distribution of the donor cells, which has three principle drawbacks: (1) Stem-like cells retain the capacity to proliferate in vivo. (2) There is little control over the cells’ terminal differentiation, e.g., a graft intended to replace neurons might choose a predominantly glial fate. (3) There is limited ability of researchers to alter the combination of cell types in pursuit of a precise treatment. We demonstrate a procedure for differentiating human neural precursor cells (hNPCs) in vitro, followed by isolation of the neuronal progeny. We transplanted undifferentiated hNPCs or a defined concentration of hNPC-derived neurons into mice, then compared these two groups with regard to their survival, proliferation and phenotypic fate. We present evidence suggesting that in vitro-differentiated-and-purified neurons survive as well in vivo as their undifferentiated progenitors, and undergo less proliferation and less astrocytic differentiation. We also describe techniques for optimizing low-temperature cell preservation and portability. PMID:27030542

  13. High-field magnetic white dwarfs as the progeny of early-type stars?

    NASA Astrophysics Data System (ADS)

    Dobbie, P. D.; Külebi, B.; Casewell, S. L.; Burleigh, M. R.; Parker, Q. A.; Baxter, R.; Lawrie, K. A.; Jordan, S.; Koester, D.

    2013-01-01

    We present an analysis of the newly resolved components of two hot, double-degenerate systems, SDSS J074853.07+302543.5 + J074852.95+302543.4 and SDSS J150813.24+394504.9 + J150813.31+394505.6 (CBS 229). We confirm that each system has widely separated components (a > 100 au) consisting of a H-rich, non-magnetic white dwarf and a H-rich, high-field magnetic white dwarf (HFMWD). The masses of the non-magnetic degenerates are found to be larger than typical of field white dwarfs. We use these components to estimate the total ages of the binaries and demonstrate that both magnetic white dwarfs are the progeny of stars with Minit > 2 M⊙. We briefly discuss the traits of all known hot, wide, magnetic + non-magnetic double degenerates in the context of HFMWD formation theories. These are broadly consistent (chance probability, P ≈ 0.065) with HFMWDs forming primarily from early-type stars and, in the most succinct interpretation, link their magnetism to the fields of their progenitors. Our results do not, however, rule out that HFMWDs can form through close binary interactions and studies of more young, wide double degenerates are required to reach firm conclusions on these formation pathways.

  14. Multicolor immunofluorescence reveals that p63- and/or K5-positive progenitor cells contribute to normal breast epithelium and usual ductal hyperplasia but not to low-grade intraepithelial neoplasia of the breast.

    PubMed

    Boecker, Werner; Stenman, Göran; Schroeder, Tina; Schumacher, Udo; Loening, Thomas; Stahnke, Lisa; Löhnert, Catharina; Siering, Robert Michael; Kuper, Arthur; Samoilova, Vera; Tiemann, Markus; Korsching, Eberhard; Buchwalow, Igor

    2017-03-16

    We contend that knowledge about the cellular composition of normal breast epithelium is a prerequisite for understanding proliferative breast disease. Against this background, we used multicolor immunofluorescence to study normal breast epithelium and two types of intraepithelial proliferative breast lesion for expression of the p63, basal keratin K5, glandular keratin K8/18, SMA, ER-alpha, and Ki67. We studied eight normal breast epithelium samples, 12 cases of usual ductal hyperplasia, and 33 cases of low-grade intraepithelial neoplasia (9 flat epithelial atypia, 14 low-grade ductal carcinoma in situ and 10 cases of lobular neoplasia). Usual ductal hyperplasia showed striking similarity to normal luminal breast epithelium including p63+ and/or K5+ luminal progenitor cells and the full spectrum of luminal progeny cells. In normal breast epithelium and usual ductal hyperplasia, expression of ER-alpha was associated with lack of expression of the proliferation antigen Ki67. In contrast, we found in both types of low-grade intraepithelial neoplasia robust expression of keratin K8/18 and a positive association between ER-alpha and Ki67 expression. However, these lesions were consistently negative for p63 and/or K5. Our observational study supports the view that usual ductal hyperplasia and low-grade intraepithelial neoplasia are different entities rather than part of a spectrum of the same disease. We propose a new operational model of cell differentiation that may serve to better understand correlations between normal breast epithelium and proliferative breast diseases. From our data we conclude that p63+ and/or K5+ progenitor cells contribute to maintenance of normal epithelium and usual ductal hyperplasia, but not to low-grade intraepithelial neoplasia of the breast.

  15. Defining the nature of human pluripotent stem cell progeny.

    PubMed

    Patterson, Michaela; Chan, David N; Ha, Iris; Case, Dana; Cui, Yongyan; Van Handel, Ben; Mikkola, Hanna Ka; Lowry, William E

    2012-01-01

    While it is clear that human pluripotent stem cells (hPSCs) can differentiate to generate a panoply of various cell types, it is unknown how closely in vitro development mirrors that which occurs in vivo. To determine whether human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) make equivalent progeny, and whether either makes cells that are analogous to tissue-derived cells, we performed comprehensive transcriptome profiling of purified PSC derivatives and their tissue-derived counterparts. Expression profiling demonstrated that hESCs and hiPSCs make nearly identical progeny for the neural, hepatic, and mesenchymal lineages, and an absence of re-expression from exogenous reprogramming factors in hiPSC progeny. However, when compared to a tissue-derived counterpart, the progeny of both hESCs and hiPSCs maintained expression of a subset of genes normally associated with early mammalian development, regardless of the type of cell generated. While pluripotent genes (OCT4, SOX2, REX1, and NANOG) appeared to be silenced immediately upon differentiation from hPSCs, genes normally unique to early embryos (LIN28A, LIN28B, DPPA4, and others) were not fully silenced in hPSC derivatives. These data and evidence from expression patterns in early human fetal tissue (3-16 weeks of development) suggest that the differentiated progeny of hPSCs are reflective of very early human development (< 6 weeks). These findings provide support for the idea that hPSCs can serve as useful in vitro models of early human development, but also raise important issues for disease modeling and the clinical application of hPSC derivatives.

  16. Lineage tracing of resident tendon progenitor cells during growth and natural healing.

    PubMed

    Dyment, Nathaniel A; Hagiwara, Yusuke; Matthews, Brya G; Li, Yingcui; Kalajzic, Ivo; Rowe, David W

    2014-01-01

    Unlike during embryogenesis, the identity of tissue resident progenitor cells that contribute to postnatal tendon growth and natural healing is poorly characterized. Therefore, we utilized 1) an inducible Cre driven by alpha smooth muscle actin (SMACreERT2), that identifies mesenchymal progenitors, 2) a constitutively active Cre driven by growth and differentiation factor 5 (GDF5Cre), a critical regulator of joint condensation, in combination with 3) an Ai9 Cre reporter to permanently label SMA9 and GDF5-9 populations and their progeny. In growing mice, SMA9+ cells were found in peritendinous structures and scleraxis-positive (ScxGFP+) cells within the tendon midsubstance and myotendinous junction. The progenitors within the tendon midsubstance were transiently labeled as they displayed a 4-fold expansion from day 2 to day 21 but reduced to baseline levels by day 70. SMA9+ cells were not found within tendon entheses or ligaments in the knee, suggesting a different origin. In contrast to the SMA9 population, GDF5-9+ cells extended from the bone through the enthesis and into a portion of the tendon midsubstance. GDF5-9+ cells were also found throughout the length of the ligaments, indicating a significant variation in the progenitors that contribute to tendons and ligaments. Following tendon injury, SMA9+ paratenon cells were the main contributors to the healing response. SMA9+ cells extended over the defect space at 1 week and differentiated into ScxGFP+ cells at 2 weeks, which coincided with increased collagen signal in the paratenon bridge. Thus, SMA9-labeled cells represent a unique progenitor source that contributes to the tendon midsubstance, paratenon, and myotendinous junction during growth and natural healing, while GDF5 progenitors contribute to tendon enthesis and ligament development. Understanding the mechanisms that regulate the expansion and differentiation of these progenitors may prove crucial to improving future repair strategies.

  17. Circulating Progenitor Cells and Scleroderma

    PubMed Central

    2010-01-01

    Scleroderma (systemic sclerosis) is a disease of unknown origins that involves tissue ischemia and fibrosis in the skin and internal organs such as the lungs. The tissue ischemia is due to a lack of functional blood vessels and an inability to form new blood vessels. Bone marrow–derived circulating endothelial progenitor cells play a key role in blood vessel repair and neovascularization. Scleroderma patients appear to have defects in the number and function of circulating endothelial progenitor cells. Scleroderma patients also develop fibrotic lesions, possibly as the result of tissue ischemia. Fibroblast-like cells called fibrocytes that differentiate from a different pool of bone marrow–derived circulating progenitor cells seem to be involved in this process. Manipulating the production, function, and differentiation of circulating progenitor cells represents an exciting new possibility for treating scleroderma. PMID:18638425

  18. MT1-MMP and Type II Collagen Specify Skeletal Stem Cells and Their Bone and Cartilage Progeny

    PubMed Central

    Szabova, Ludmila; Yamada, Susan S.; Wimer, Helen; Chrysovergis, Kaliopi; Ingvarsen, Signe; Behrendt, Niels; Engelholm, Lars H.

    2009-01-01

    Skeletal formation is dependent on timely recruitment of skeletal stem cells and their ensuing synthesis and remodeling of the major fibrillar collagens, type I collagen and type II collagen, in bone and cartilage tissues during development and postnatal growth. Loss of the major collagenolytic activity associated with the membrane-type 1 matrix metalloproteinase (MT1-MMP) results in disrupted skeletal development and growth in both cartilage and bone, where MT1-MMP is required for pericellular collagen dissolution. We show here that reconstitution of MT1-MMP activity in the type II collagen–expressing cells of the skeleton rescues not only diminished chondrocyte proliferation, but surprisingly, also results in amelioration of the severe skeletal dysplasia associated with MT1-MMP deficiency through enhanced bone formation. Consistent with this increased bone formation, type II collagen was identified in bone cells and skeletal stem/progenitor cells of wildtype mice. Moreover, bone marrow stromal cells isolated from mice expressing MT1-MMP under the control of the type II collagen promoter in an MT1-MMP–deficient background showed enhanced bone formation in vitro and in vivo compared with cells derived from nontransgenic MT1-MMP–deficient littermates. These observations show that type II collagen is not stringently confined to the chondrocyte but is expressed in skeletal stem/progenitor cells (able to regenerate bone, cartilage, myelosupportive stroma, marrow adipocytes) and in the chondrogenic and osteogenic lineage progeny where collagenolytic activity is a requisite for proper cell and tissue function. PMID:19419317

  19. Asymmetric cell division of stem and progenitor cells during homeostasis and cancer.

    PubMed

    Gómez-López, Sandra; Lerner, Robin G; Petritsch, Claudia

    2014-02-01

    Stem and progenitor cells are characterized by their ability to self-renew and produce differentiated progeny. A fine balance between these processes is achieved through controlled asymmetric divisions and is necessary to generate cellular diversity during development and to maintain adult tissue homeostasis. Disruption of this balance may result in premature depletion of the stem/progenitor cell pool, or abnormal growth. In many tissues, including the brain, dysregulated asymmetric divisions are associated with cancer. Whether there is a causal relationship between asymmetric cell division defects and cancer initiation is as yet not known. Here, we review the cellular and molecular mechanisms that regulate asymmetric cell divisions in the neural lineage and discuss the potential connections between this regulatory machinery and cancer.

  20. sup 222 Rn, sup 222 Rn progeny and sup 220 Rn progeny as atmospheric tracers of air masses at the Mauno Loa Observatory

    SciTech Connect

    Hutter, A.R.; George, A.C.; Maiello, M.L.; Fisenne, I.M.; Larsen, R.J.; Beck, H.L.; Wilson, F.C.

    1990-03-01

    {sup 222}Rn, {sup 222}Rn progeny and {sup 220}Rn progeny concentrations in air were measured at the Mauna Loa Observatory (MLO) in Hawaii during March 1989 in order to investigate the feasibility of using them as atmospheric tracers to help determine local air mass flow patterns. Charcoal traps, cooled to dry ice temperatures, were used to collect {sup 222}Rn, which was subsequently measured in pulse ionization chambers at the Environmental Measurements Laboratory (EML). {sup 222}Rn progeny and {sup 220}Rn progeny for 37 samples were measured at the Observatory by sampling high volumes of air through filters, which were counted for up to 11 h in alpha scintillation counters. Individual progeny concentrations were calculated using both least squares and maximum likelihood techniques. In general, {sup 222}Rn progeny and {sup 220}Rn progeny concentrations were low when free tropospheric air was present (downslope and tradewind conditions), and consistently higher when surface air from the island broke through the trade wind inversion layer (upslope conditions). The data suggest that {sup 222}Rn, {sup 222}Rn progeny, or {sup 220}Rn progeny monitoring may provide new and useful information to help indicate the different air flow patterns present at MLO. 17 refs., 5 figs., 2 tabs.

  1. Ovarian monocyte progenitor cells: phenotypic and functional characterization.

    PubMed

    Pascual, Cherry J; Sanberg, Paul R; Chamizo, Wilfredo; Haraguchi, Soichi; Lerner, Danika; Baldwin, Margi; El-Badri, Nagwa S

    2005-04-01

    Leukocytes of the macrophage lineage are abundant in the ovarian tissues and have an important function in both follicular development and regression of postovulatory follicles. In this study, we tested the hypothesis that continuous production of macrophages in the ovarian stroma is maintained by a resident population of progenitors. We established a long-term culture of ovarian follicular stromal cells from BALB/c and green fluorescent protein-transgenic (GFP-TG) C57BL/6 mice. Nonadherent cells were collected and tested for hematopoietic function in vitro and in vivo. Histological and ultrastructural analyses revealed a homogenous population of monocyte-like rounded cells. Nonadherent cells continued to proliferate in culture for several months without senescence. When plated at very low density in methylcellulose, these cells formed colonies consisting of monocyte-like cells. Ovarian monocyte-like cells reacted with CD45, CD11b, CD11c, and Ly6-Gr-1 cell surface markers. A distinct CD45low population within these cells reacted with CD117 (C-kit) surface marker, suggestive of a primitive hematopoietic progenitor. Fifty thousand nonadherent cells failed to provide radioprotection to lethally irradiated mice and thus were not considered to be equivalent to pluripotent hematopoietic stem cells. Ovarian nonadherent stromal cells were positive for alkaline phosphatase but lacked embryonic cell antigens stage-specific embryonic antigen (SSEA-1) and Oct-4. We conclude that in the ovaries, a higher requirement for macrophages is provided by a resident stromal population of progenitors whose progeny is restricted to the production of cells of the monocyte-macrophage lineage.

  2. Frequent Gene Products and Molecular Pathways Altered in Prostate Cancer– and Metastasis-Initiating Cells and Their Progenies and Novel Promising Multitargeted Therapies

    PubMed Central

    Mimeault, Murielle; Batra, Surinder K

    2011-01-01

    Recent gene expression profiling analyses and gain- and loss-of-function studies performed with distinct prostate cancer (PC) cell models indicated that the alterations in specific gene products and molecular pathways often occur in PC stem/progenitor cells and their progenies during prostate carcinogenesis and metastases at distant sites, including bones. Particularly, the sustained activation of epidermal growth factor receptor (EGFR), hedgehog, Wnt/β-catenin, Notch, hyaluronan (HA)/CD44 and stromal cell–derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) during the epithelial-mesenchymal transition (EMT) process may provide critical functions for PC progression to locally invasive, metastatic and androgen-independent disease states and treatment resistance. Moreover, an enhanced glycolytic metabolism in PC stem/progenitor cells and their progenies concomitant with the changes in their local microenvironment, including the induction of tumor hypoxia and release of diverse soluble factors by tumor myofibroblasts, also may promote the tumor growth, angiogenesis and metastases. More particularly, these molecular transforming events may cooperate to upregulate Akt, nuclear factor (NF)-κB, hypoxia-inducible factors (HIFs) and stemness gene products such as Oct3/4, Sox2, Nanog and Bmi-1 in PC cells that contribute to their acquisition of high self-renewal, tumorigenic and invasive capacities and survival advantages during PC progression. Consequently, the molecular targeting of these deregulated gene products in the PC- and metastasis-initiating cells and their progenies represent new promising therapeutic strategies of great clinical interest for eradicating the total PC cell mass and improving current antihormonal treatments and docetaxel-based chemotherapies, thereby preventing disease relapse and the death of PC patients. PMID:21607288

  3. Monitoring of short-lived radon progeny in mines.

    PubMed

    Skubacz, K; Bywalec, T

    2003-01-01

    Obligatory measurements of the potential alpha energy concentration of short-lived radon progeny have been performing in the Polish underground mines since 1989. In consideration of economic aspects, an attempt was made from the very beginning to combine it with measurements of the dust concentration. Therefore the developed measuring units were an integral part of the dust samplers complying with the requirements of the State Mining Authority to apply them in underground mines. This way the developed devices could fulfil two measurement tasks simultaneously: measurement of the dust concentration and potential alpha energy concentration of short-lived radon progeny. The new device based on the thermoluminescence detectors is able to cooperate with the dust samplers made by the SKC company and equipped with a cyclone making it possible to operate them constantly for one working day. The lower limit of detection was equal about 0.04 microJ m(-3) at a 95% confidence level and 1 h pumping.

  4. Progeny Clustering: A Method to Identify Biological Phenotypes

    PubMed Central

    Hu, Chenyue W.; Kornblau, Steven M.; Slater, John H.; Qutub, Amina A.

    2015-01-01

    Estimating the optimal number of clusters is a major challenge in applying cluster analysis to any type of dataset, especially to biomedical datasets, which are high-dimensional and complex. Here, we introduce an improved method, Progeny Clustering, which is stability-based and exceptionally efficient in computing, to find the ideal number of clusters. The algorithm employs a novel Progeny Sampling method to reconstruct cluster identity, a co-occurrence probability matrix to assess the clustering stability, and a set of reference datasets to overcome inherent biases in the algorithm and data space. Our method was shown successful and robust when applied to two synthetic datasets (datasets of two-dimensions and ten-dimensions containing eight dimensions of pure noise), two standard biological datasets (the Iris dataset and Rat CNS dataset) and two biological datasets (a cell phenotype dataset and an acute myeloid leukemia (AML) reverse phase protein array (RPPA) dataset). Progeny Clustering outperformed some popular clustering evaluation methods in the ten-dimensional synthetic dataset as well as in the cell phenotype dataset, and it was the only method that successfully discovered clinically meaningful patient groupings in the AML RPPA dataset. PMID:26267476

  5. Radon progeny in hydrometeors at the earth's surface.

    PubMed

    Voltaggio, M

    2012-07-01

    During atmospheric thermal inversions, dew and hoarfrost concentrate gamma emitting radionuclides of the short-lived (222)Rn progeny ((214)Pb and (214)Bi), causing an increase in the total natural gamma background from the ground. To highlight this phenomenon, a volcanic zone of high (222)Rn flux was studied during the winter season 2010-11. High-specific short-lived radon progeny activities up to 122 Bq g(-1) were detected in hydrometeors forming at the earth's surface (ESHs), corresponding to a mean increase of up to 17 % of the normal gamma background value. A theoretical model, depending on radon flux from soil and predicting the radon progeny concentrations in hydrometeors forming at the ESHs is presented. The comparison between model and field data shows a good correspondence. Around nuclear power plants or in nuclear facilities that use automatic NaI or CsI total gamma spectroscopy systems for monitoring radioactive contamination, hydrometeors forming at the ESHs in sites with a high radon flux could represent a relevant source of false alarms of radioactive contamination.

  6. Mesenchymal progenitor cells for the osteogenic lineage.

    PubMed

    Ono, Noriaki; Kronenberg, Henry M

    2015-09-01

    Mesenchymal progenitors of the osteogenic lineage provide the flexibility for bone to grow, maintain its function and homeostasis. Traditionally, colony-forming-unit fibroblasts (CFU-Fs) have been regarded as surrogates for mesenchymal progenitors; however, this definition cannot address the function of these progenitors in their native setting. Transgenic murine models including lineage-tracing technologies based on the cre-lox system have proven to be useful in delineating mesenchymal progenitors in their native environment. Although heterogeneity of cell populations of interest marked by a promoter-based approach complicates overall interpretation, an emerging complexity of mesenchymal progenitors has been revealed. Current literatures suggest two distinct types of bone progenitor cells; growth-associated mesenchymal progenitors contribute to explosive growth of bone in early life, whereas bone marrow mesenchymal progenitors contribute to the much slower remodeling process and response to injury that occurs mainly in adulthood. More detailed relationships of these progenitors need to be studied through further experimentation.

  7. Expanded Hematopoietic Progenitor Cells Reselected for High Aldehyde Dehydrogenase Activity Demonstrate Islet Regenerative Functions.

    PubMed

    Seneviratne, Ayesh K; Bell, Gillian I; Sherman, Stephen E; Cooper, Tyler T; Putman, David M; Hess, David A

    2016-04-01

    Human umbilical cord blood (UCB) hematopoietic progenitor cells (HPC) purified for high aldehyde dehydrogenase activity (ALDH(hi) ) stimulate islet regeneration after transplantation into mice with streptozotocin-induced β cell deletion. However, ALDH(hi) cells represent a rare progenitor subset and widespread use of UCB ALDH(hi) cells to stimulate islet regeneration will require progenitor cell expansion without loss of islet regenerative functions. Here we demonstrate that prospectively purified UCB ALDH(hi) cells expand efficiently under serum-free, xeno-free conditions with minimal growth factor supplementation. Consistent with the concept that ALDH-activity is decreased as progenitor cells differentiate, kinetic analyses over 9 days revealed the frequency of ALDH(hi) cells diminished as culture time progressed such that total ALDH(hi) cell number was maximal (increased 3-fold) at day 6. Subsequently, day 6 expanded cells (bulk cells) were sorted after culture to reselect differentiated progeny with low ALDH-activity (ALDH(lo) subset) from less differentiated progeny with high ALDH-activity (ALDH(hi) subset). The ALDH(hi) subset retained primitive cell surface marker coexpression (32.0% ± 7.0% CD34(+) /CD38(-) cells, 37.0% ± 6.9% CD34(+) /CD133(+) cells), and demonstrated increased hematopoietic colony forming cell function compared with the ALDH(lo) subset. Notably, bulk cells or ALDH(lo) cells did not possess the functional capacity to lower hyperglycemia after transplantation into streptozotocin-treated NOD/SCID mice. However, transplantation of the repurified ALDH(hi) subset significantly reduced hyperglycemia, improved glucose tolerance, and increased islet-associated cell proliferation and capillary formation. Thus, expansion and delivery of reselected UCB cells that retain high ALDH-activity after short-term culture represents an improved strategy for the development of cellular therapies to enhance islet regeneration in situ.

  8. Effect of calving distribution on beef cattle progeny performance.

    PubMed

    Funston, R N; Musgrave, J A; Meyer, T L; Larson, D M

    2012-12-01

    Records collected between 1997 and 2010 were used to determine the effect of calving period on heifer (n = 1,019) and steer (n = 771) progeny from the Gudmundsen Sandhills Laboratory, Whitman, NE. Progeny were classified as being born in the first, second, or third 21-d period of the spring calving season within year. Heifer birth BW was lightest (P < 0.01) for heifers born in the first period. Birth to weaning ADG tended (P = 0.10) to be least for heifers born in the first calving period; however, weaning BW decreased (P = 0.03) with advancing calving period. Weaning to prebreeding ADG tended (P = 0.07) to be least for heifers born in the first period; however, prebreeding BW was greatest (P < 0.01) for calves born in the first period. Heifer ADG from the beginning of the breeding season to pregnancy diagnosis was greater (P = 0.03) for heifers born in the third vs. first calving period. Heifers cycling at the beginning of the breeding season decreased (P < 0.01) with advancing calving date (70, 58, and 39%, respectively) and 45 d pregnancy rates were lowest (P = 0.02) for heifers born in the third calving period (90, 86, and 78%, respectively). Birth date of the first calf of the heifer and birth BW decreased (P < 0.01) if the heifer was born in the first calving period. First calf progeny had the greatest (P ≤ 0.10) weaning BW if born to a heifer born in the first calving period. As steer calving period advanced, weaning BW decreased (P < 0.01). Calving period did not affect (P = 0.81) feedlot ADG. As calving period advanced, HCW, marbling score, and yield grade decreased (P < 0.01). The percentage of steers grading USDA small marbling was not affected (P = 0.13) by calving period; however, the percentage of steers grading USDA modest marbling or greater and the total carcass value declined (P ≤ 0.01) as calving period advanced. Heifer calves born during the first 21 d of the spring calving season had greater weaning, prebreeding, and precalving BW; greater

  9. Mated Progeny Production Is a Biomarker of Aging in Caenorhabditis elegans

    PubMed Central

    Pickett, Christopher L.; Dietrich, Nicholas; Chen, Junfang; Xiong, Chengjie; Kornfeld, Kerry

    2013-01-01

    The relationships between reproduction and aging are important for understanding the mechanisms of aging and evaluating evolutionary theories of aging. To investigate the effects of progeny production on reproductive and somatic aging, we conducted longitudinal studies of Caenorhabditis elegans hermaphrodites. For mated wild-type animals that were not sperm limited and survived past the end of the reproductive period, high levels of cross-progeny production were positively correlated with delayed reproductive and somatic aging. In this group of animals, individuals that generated more cross progeny also reproduced and lived longer than individuals that generated fewer cross progeny. These results indicate that progeny production does not accelerate reproductive or somatic aging. This longitudinal study demonstrated that cumulative cross progeny production through day four is an early-stage biomarker that is a positive predictor of longevity. Furthermore, in mated animals, high levels of early cross progeny production were positively correlated with high levels of late cross progeny production, indicating that early progeny production does not accelerate reproductive aging. The relationships between progeny production and aging were further evaluated by comparing self-fertile hermaphrodites that generated relatively few self progeny with mated hermaphrodites that generated many cross progeny. The timing of age-related somatic degeneration was similar in these groups, suggesting progeny production does not accelerate somatic aging. These studies rigorously define relationships between progeny production, reproductive aging, and somatic aging and identify new biomarkers of C. elegans aging. These results indicate that some mechanisms or pathways control age-related degeneration of both reproductive and somatic tissues in C. elegans. PMID:24142929

  10. BABA-primed defense responses to Phytophthora infestans in the next vegetative progeny of potato

    PubMed Central

    Floryszak-Wieczorek, Jolanta; Arasimowicz-Jelonek, Magdalena; Abramowski, Dariusz

    2015-01-01

    The transcript of the PR1 gene accumulation as an informative marker of systemic acquired resistance (SAR) was analyzed in β-aminobutyric acid (BABA) primed potato in the short-lasting (3 days) and long-lasting (28 days) time periods after induction and in the vegetative descendants of primed plants derived from tubers and from in vitro seedlings. BABA pretreatment resulted either in minimal or no PR1 gene expression, but sequential treatment with BABA followed by virulent Phytophthora infestans provided data on the imprint of post-stress information and its duration until fertilization, in the form of an enhanced PR1 transcript accumulation and a transient increase of basal resistance to the late blight disease. The primed state for defense of the susceptible potato cultivar was transmitted to its vegetative progeny as a potentiated PR1 mRNA accumulation following challenge inoculation. However, variation was observed between vegetative accessions of the BABA-primed potato genotype in responsiveness to disease. In contrast to plants derived from tubers, potato propagated through in vitro seedlings largely lost inducible resistance traits, although itretained primed PR1 gene expression. PMID:26528308

  11. Expression of ZNF396 in basal cell carcinoma.

    PubMed

    Bai, Juncheng; Kito, Yusuke; Okubo, Hiroshi; Nagayama, Tomoko; Takeuchi, Tamotsu

    2014-05-01

    Zfp191 represses differentiation and keeps various cells in the stem/progenitor stage. Here, we report that a Zfp191 homolog protein, ZNF396, is expressed in basal cell carcinoma (BCC) and possibly represses the expression of a Notch system effector molecule, Hes1 (hairy and enhancer of split-1), and prevents BCC cells from undergoing Notch-mediated squamous cell differentiation. ZNF396 immunoreactivity was found in the nucleus of 35 of 38 cutaneous BCC and 4 of 74 squamous cell carcinoma tissue specimens. In non-tumorous epidermal tissues, ZNF396 immunoreactivity was restricted in basal cells. siRNA-mediated silencing of ZNF396 induced the expression of Notch2, Hes1, and involucrin in cultured BCC cells. Finally, we found that siRNA-mediated silencing of ZNF396 gene inhibited the proliferation of TE354.T basal cell carcinoma cells. ZNF396 might repress Notch-Hes1 signaling axis and prevent tumor cells from undergoing squamous differentiation in BCC.

  12. Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development

    PubMed Central

    Mora-Bermúdez, Felipe; Badsha, Farhath; Kanton, Sabina; Camp, J Gray; Vernot, Benjamin; Köhler, Kathrin; Voigt, Birger; Okita, Keisuke; Maricic, Tomislav; He, Zhisong; Lachmann, Robert; Pääbo, Svante; Treutlein, Barbara; Huttner, Wieland B

    2016-01-01

    Human neocortex expansion likely contributed to the remarkable cognitive abilities of humans. This expansion is thought to primarily reflect differences in proliferation versus differentiation of neural progenitors during cortical development. Here, we have searched for such differences by analysing cerebral organoids from human and chimpanzees using immunohistofluorescence, live imaging, and single-cell transcriptomics. We find that the cytoarchitecture, cell type composition, and neurogenic gene expression programs of humans and chimpanzees are remarkably similar. Notably, however, live imaging of apical progenitor mitosis uncovered a lengthening of prometaphase-metaphase in humans compared to chimpanzees that is specific to proliferating progenitors and not observed in non-neural cells. Consistent with this, the small set of genes more highly expressed in human apical progenitors points to increased proliferative capacity, and the proportion of neurogenic basal progenitors is lower in humans. These subtle differences in cortical progenitors between humans and chimpanzees may have consequences for human neocortex evolution. DOI: http://dx.doi.org/10.7554/eLife.18683.001 PMID:27669147

  13. Field investigation of surface-deposited radon progeny as a possible predictor of the airborne radon progeny dose rate.

    PubMed

    Sun, Kainan; Steck, Daniel J; Field, R William

    2009-08-01

    The quantitative relationships between radon gas concentration, the surface-deposited activities of various radon progeny, the airborne radon progeny dose rate, and various residential environmental factors were investigated through actual field measurements in 38 selected Iowa houses occupied by either smokers or nonsmokers. Airborne dose rate was calculated from unattached and attached potential alpha energy concentrations (PAECs) using two dosimetric models with different activity-size weighting factors. These models are labeled Pdose and Jdose, respectively. Surface-deposited 218Po and 214Po were found significantly correlated to radon, unattached PAEC, and both airborne dose rates (p < 0.0001) in nonsmoking environments. However, deposited 218Po was not significantly correlated to the above parameters in smoking environments. In multiple linear regression analysis, natural logarithm transformation was performed for airborne dose rate as the dependent variable, as well as for radon and deposited 218Po and 214Po as predictors. An interaction effect was found between deposited 214Po and an obstacle in front of the Retrospective Reconstruction Detector (RRD) in predicting dose rate (p = 0.049 and 0.058 for Pdose and Jdose, respectively) for nonsmoking environments. After adjusting for radon and deposited radon progeny effects, the presence of either cooking, usage of a fireplace, or usage of a ceiling fan significantly, or marginally significantly, reduced the Pdose to 0.65 (90% CI 0.42-0.996), 0.54 (90% CI 0.28-1.02), and 0.66 (90% CI 0.45-0.96), respectively. For Jdose, only the usage of a ceiling fan significantly reduced the dose rate to 0.57 (90% CI 0.39-0.85). In smoking environments, deposited 218Po was a significant negative predictor for Pdose (RR 0.68, 90% CI 0.55-0.84) after adjusting for long-term 222Rn and environmental factors. A significant decrease of 0.72 (90% CI 0.64-0.83) in the mean Pdose was noted, after adjusting for the radon and radon

  14. In vitro culture of stress erythroid progenitors identifies distinct progenitor populations and analogous human progenitors

    PubMed Central

    Xiang, Jie; Wu, Dai-Chen; Chen, Yuanting

    2015-01-01

    Tissue hypoxia induces a systemic response designed to increase oxygen delivery to tissues. One component of this response is increased erythropoiesis. Steady-state erythropoiesis is primarily homeostatic, producing new erythrocytes to replace old erythrocytes removed from circulation by the spleen. In response to anemia, the situation is different. New erythrocytes must be rapidly made to increase hemoglobin levels. At these times, stress erythropoiesis predominates. Stress erythropoiesis is best characterized in the mouse, where it is extramedullary and utilizes progenitors and signals that are distinct from steady-state erythropoiesis. In this report, we use an in vitro culture system that recapitulates the in vivo development of stress erythroid progenitors. We identify cell-surface markers that delineate a series of stress erythroid progenitors with increasing maturity. In addition, we use this in vitro culture system to expand human stress erythroid progenitor cells that express analogous cell-surface markers. Consistent with previous suggestions that human stress erythropoiesis is similar to fetal erythropoiesis, we demonstrate that human stress erythroid progenitors express fetal hemoglobin upon differentiation. These data demonstrate that similar to murine bone marrow, human bone marrow contains cells that can generate BMP4-dependent stress erythroid burst-forming units when cultured under stress erythropoiesis conditions. PMID:25608563

  15. Abundant occurrence of basal radial glia in the subventricular zone of embryonic neocortex of a lissencephalic primate, the common marmoset Callithrix jacchus.

    PubMed

    Kelava, Iva; Reillo, Isabel; Murayama, Ayako Y; Kalinka, Alex T; Stenzel, Denise; Tomancak, Pavel; Matsuzaki, Fumio; Lebrand, Cécile; Sasaki, Erika; Schwamborn, Jens C; Okano, Hideyuki; Huttner, Wieland B; Borrell, Víctor

    2012-02-01

    Subventricular zone (SVZ) progenitors are a hallmark of the developing neocortex. Recent studies described a novel type of SVZ progenitor that retains a basal process at mitosis, sustains expression of radial glial markers, and is capable of self-renewal. These progenitors, referred to here as basal radial glia (bRG), occur at high relative abundance in the SVZ of gyrencephalic primates (human) and nonprimates (ferret) but not lissencephalic rodents (mouse). Here, we analyzed the occurrence of bRG cells in the embryonic neocortex of the common marmoset Callithrix jacchus, a near-lissencephalic primate. bRG cells, expressing Pax6, Sox2 (but not Tbr2), glutamate aspartate transporter, and glial fibrillary acidic protein and retaining a basal process at mitosis, occur at similar relative abundance in the marmoset SVZ as in human and ferret. The proportion of progenitors in M-phase was lower in embryonic marmoset than developing ferret neocortex, raising the possibility of a longer cell cycle. Fitting the gyrification indices of 26 anthropoid species to an evolutionary model suggested that the marmoset evolved from a gyrencephalic ancestor. Our results suggest that a high relative abundance of bRG cells may be necessary, but is not sufficient, for gyrencephaly and that the marmoset's lissencephaly evolved secondarily by changing progenitor parameters other than progenitor type.

  16. Epidermal growth factor receptor activity is necessary for mouse basal cell proliferation

    PubMed Central

    Brechbuhl, Heather M.; Li, Bilan; Smith, Russell W.

    2014-01-01

    ERB family receptors (EGFR, ERB-B2, ERB-B3, and ERB-B4) regulate epithelial cell function in many tissue types. In the human airway epithelium, changes in ERB receptor expression are associated with epithelial repair defects. However, the specific role(s) played by ERB receptors in repair have not been determined. We aimed to determine whether ERB receptors regulate proliferation of the tracheobronchial progenitor, the basal cell. Receptor tyrosine kinase arrays were used to evaluate ERB activity in normal and naphthalene (NA)-injured mouse trachea and in air-liquid interface cultures. Roles for epidermal growth factor (EGF), EGFR, and ERB-B2 in basal cell proliferation were evaluated in vitro. NA injury and transgenic expression of an EGFR-dominant negative (DN) receptor were used to evaluate roles for EGFR signaling in vivo. EGFR and ERB-B2 were active in normal and NA-injured trachea and were the only active ERB receptors detected in proliferating basal cells in vitro. EGF was necessary for basal cell proliferation in vitro. The EGFR inhibitor, AG1478, decreased proliferation by 99, and the Erb-B2 inhibitor, AG825, decreased proliferation by ∼66%. In vivo, EGFR-DN expression in basal cells significantly decreased basal cell proliferation after NA injury. EGF and EGFR are necessary for basal cell proliferation. The EGFR/EGFR homo- and the EGFR/ERB-B2 heterodimer account for ∼34 and 66%, respectively, of basal cell proliferation in vitro. Active EGFR is necessary for basal cell proliferation after NA injury. We conclude that EGFR activation is necessary for mouse basal cell proliferation and normal epithelial repair. PMID:25217659

  17. Children's Literature in the Basals.

    ERIC Educational Resources Information Center

    O'Brien, Maureen A.

    Three basal reading series, levels kindergarten through grade three, were studied to categorize the types of literature each contained. The following series were analyzed: "The Headway Program" (Open Court Publishing Company), "Series r Macmillan Reading," and "Basics in Reading" (Scott, Foresman and Company). It was…

  18. Teachers Reflect Standards in Basals

    ERIC Educational Resources Information Center

    Gewertz, Catherine

    2012-01-01

    Dozens of teachers and literacy specialists from across the country hunkered down in Baltimore at round tables, with laptops, pens, and paper, intent on rewriting the collections that wield tremendous influence over the way millions of U.S. children learn literacy skills: the big-name basal readers. Hailing from 18 school districts in 11 states,…

  19. Alveolar progenitor cells develop in mouse mammary glands independent of pregnancy and lactation.

    PubMed

    Booth, Brian W; Boulanger, Corinne A; Smith, Gilbert H

    2007-09-01

    We have previously described pluripotent, parity-induced mammary epithelial cells (PI-MEC) marked by Rosa26-lacZ expression in the mammary glands of parous females. PI-MEC act as lobule-limited epithelial stem/progenitor cells. To determine whether parity is necessary to generate PI-MEC, we incubated mammary explant cultures from virgin mice in vitro with insulin alone (I), hydrocortisone alone (H), prolactin alone (Prl), or a combination of these lactogenic hormones (IHPrl). Insulin alone activated the WAP-Cre gene. Hydrocortisone and prolactin alone did not. Any combination of hormones that included insulin was effective. Only I, H and Prl together were able to induce secretory differentiation and milk protein synthesis. In addition, EGF, IGF-2 and IGF-1 added individually produced activated (lacZ(+)) PI-MEC in explant cultures. Neither estrogen nor progesterone induced WAP-Cre expression in the explants. None of these positive initiators of WAP-Cre expression in PI-MEC were effective in mammospheres or two-dimensional cultures of mammary epithelium, indicating the indispensability of epithelial-stromal interaction in PI-MEC activation. Like PI-MEC, lacZ(+) cells from virgin explants proliferated and contributed progeny to mammospheres in vitro and to epithelial outgrowths in vivo after transplantation. LacZ(+) cells induced in virgin mouse mammary explants were multipotent (like PI-MEC) in impregnated hosts producing lacZ(+) mammary alveolar structures comprised of both myoepithelial and luminal progeny. These data demonstrate PI-MEC, a mammary epithelial sub-population of lobule-limited progenitor cells, are present in nulliparous female mice before parity and, like the PI-MEC observed following parity, are capable of proliferation, self-renewal and the capacity to produce progeny of diverse epithelial cell fates.

  20. Possible promotion of neuronal differentiation in fetal rat brain neural progenitor cells after sustained exposure to static magnetism.

    PubMed

    Nakamichi, Noritaka; Ishioka, Yukichi; Hirai, Takao; Ozawa, Shusuke; Tachibana, Masaki; Nakamura, Nobuhiro; Takarada, Takeshi; Yoneda, Yukio

    2009-08-15

    We have previously shown significant potentiation of Ca(2+) influx mediated by N-methyl-D-aspartate receptors, along with decreased microtubules-associated protein-2 (MAP2) expression, in hippocampal neurons cultured under static magnetism without cell death. In this study, we investigated the effects of static magnetism on the functionality of neural progenitor cells endowed to proliferate for self-replication and differentiate into neuronal, astroglial, and oligodendroglial lineages. Neural progenitor cells were isolated from embryonic rat neocortex and hippocampus, followed by culture under static magnetism at 100 mT and subsequent determination of the number of cells immunoreactive for a marker protein of particular progeny lineages. Static magnetism not only significantly decreased proliferation of neural progenitor cells without affecting cell viability, but also promoted differentiation into cells immunoreactive for MAP2 with a concomitant decrease in that for an astroglial marker, irrespective of the presence of differentiation inducers. In neural progenitors cultured under static magnetism, a significant increase was seen in mRNA expression of several activator-type proneural genes, such as Mash1, Math1, and Math3, together with decreased mRNA expression of the repressor type Hes5. These results suggest that sustained static magnetism could suppress proliferation for self-renewal and facilitate differentiation into neurons through promoted expression of activator-type proneural genes by progenitor cells in fetal rat brain.

  1. B Lineage–specific Regulation of V(D)J Recombinase Activity Is Established in Common Lymphoid Progenitors

    PubMed Central

    Borghesi, Lisa; Hsu, Lih-Yun; Miller, Juli P.; Anderson, Michael; Herzenberg, Leonard; Herzenberg, Leonore; Schlissel, Mark S.; Allman, David; Gerstein, Rachel M.

    2004-01-01

    Expression of V(D)J recombinase activity in developing lymphocytes is absolutely required for initiation of V(D)J recombination at antigen receptor loci. However, little is known about when during hematopoietic development the V(D)J recombinase is first active, nor is it known what elements activate the recombinase in multipotent hematopoietic progenitors. Using mice that express a fluorescent transgenic V(D)J recombination reporter, we show that the V(D)J recombinase is active as early as common lymphoid progenitors (CLPs) but not in the upstream progenitors that retain myeloid lineage potential. Evidence of this recombinase activity is detectable in all four progeny lineages (B, T, and NK, and DC), and rag2 levels are the highest in progenitor subsets immediately downstream of the CLP. By single cell PCR, we demonstrate that V(D)J rearrangements are detectable at IgH loci in ∼5% of splenic natural killer cells. Finally, we show that recombinase activity in CLPs is largely controlled by the Erag enhancer. As activity of the Erag enhancer is restricted to the B cell lineage, this provides the first molecular evidence for establishment of a lineage-specific transcription program in multipotent progenitors. PMID:14769852

  2. Genetic Divergence in Eucalyptus camaldulensis Progenies in the Savanna Biome in Mato Grosso, Brazil

    PubMed Central

    Brito da Costa, Reginaldo; da Silva, Jeane Cabral; Skowronski, Leandro; Constantino, Michel; Pistori, Hemerson; Pinto, Jannaína Velasques da Costa

    2016-01-01

    Assessing the parental genetic differences and their subsequent prediction of progeny performance is an important first step to assure the efficiency of any breeding program. In this study, we estimate the genetic divergence in Eucalyptus camaldulensis based on the morphological traits of 132 progenies grown in a savanna biome. Thus, a field experiment was performed using a randomized block design and five replications to compare divergences in total height, commercial height, diameter at breast height, stem form and survival rate at 48 months. Tocher’s clustering method was performed using the Mahalanobis and Euclidian distances. The Mahalanobis distance seemed more reliable for the assessed parameters and clustered all of the progenies into fourteen major groups. The most similar progenies (86 accessions) were clustered into Group I, while the most dissimilar (1 progeny) represented Group XIV. The divergence analysis indicated that promising crosses could be made between progenies allocated in different groups for high genetic divergence and for favorable morphological traits. PMID:27681225

  3. Estimation of Radiological Dose From Progeny of 222Rn and 220Rn Using DTPS/DRPS and Wire-Mesh-Capped Progeny Sensors

    PubMed Central

    Jakhu, Rajan; Bangotra, Pargin; Mittal, Harish Mohan

    2016-01-01

    Radon (222Rn) and its decay products are the major sources of natural radiation exposure to general population. The activity concentrations of unattached and attached short-lived 222Rn and thoron (220Rn) progeny in indoor environment of some dwellings of the Jalandhar and Kapurthala districts of Punjab had been calculated using the deposition-based progeny sensors (DRPS/DTPS) and wire-mesh-capped (DRPS/DTPS) progeny sensors. The observed concentration of attached 222Rn and 220Rn progeny showed the variation from 5 to 21 Bq·m−3 and 0.3 to 1.7 Bq·m−3, respectively. The activity concentration of the unattached 222Rn and 220Rn progeny varies from 1 to 5 Bq·m−3 and 0.1 to 0.6 Bq·m−3, respectively. The average unattached fraction of 222Rn and 220Rn progeny is 0.2 and 0.1. The average value of the indoor aerosol concentration attachment rate of 222Rn and 220Rn progeny is 2251 cm−3, 24 ms−1, and 617 ms−1. Relation among the unattached fraction and attachment rate is established, and the obtained results of dose conversion factors show the significance of the nano-sized 222Rn decay products in 222Rn dosimetry. PMID:27994523

  4. Estimation of Radiological Dose From Progeny of (222)Rn and (220)Rn Using DTPS/DRPS and Wire-Mesh-Capped Progeny Sensors.

    PubMed

    Mehra, Rohit; Jakhu, Rajan; Bangotra, Pargin; Mittal, Harish Mohan

    2016-01-01

    Radon ((222)Rn) and its decay products are the major sources of natural radiation exposure to general population. The activity concentrations of unattached and attached short-lived (222)Rn and thoron ((220)Rn) progeny in indoor environment of some dwellings of the Jalandhar and Kapurthala districts of Punjab had been calculated using the deposition-based progeny sensors (DRPS/DTPS) and wire-mesh-capped (DRPS/DTPS) progeny sensors. The observed concentration of attached (222)Rn and (220)Rn progeny showed the variation from 5 to 21 Bq·m(-3) and 0.3 to 1.7 Bq·m(-3), respectively. The activity concentration of the unattached (222)Rn and (220)Rn progeny varies from 1 to 5 Bq·m(-3) and 0.1 to 0.6 Bq·m(-3), respectively. The average unattached fraction of (222)Rn and (220)Rn progeny is 0.2 and 0.1. The average value of the indoor aerosol concentration attachment rate of (222)Rn and (220)Rn progeny is 2251 cm(-3), 24 ms(-1), and 617 ms(-1). Relation among the unattached fraction and attachment rate is established, and the obtained results of dose conversion factors show the significance of the nano-sized (222)Rn decay products in (222)Rn dosimetry.

  5. Maternal Hypothyroxinemia-Induced Neurodevelopmental Impairments in the Progeny.

    PubMed

    Min, Hui; Dong, Jing; Wang, Yi; Wang, Yuan; Teng, Weiping; Xi, Qi; Chen, Jie

    2016-04-01

    Maternal hypothyroxinemia can induce neurodevelopmental impairments in the developing fetus. We here review recent studies on the epidemiology and molecular mechanisms associated with this important public health issue. In 2011, the American Thyroid Association defined maternal hypothyroxinemia as low serum free thyroxine (FT4) levels (<5th or <10th percentile) existing in conjunction with normal serum free triiodothyronine (FT3) or thyroid stimulating hormone (TSH) levels during pregnancy. Compared to clinical or subclinical hypothyroidism, hypothyroxinemia is more commonly found in pregnant women. Hypothyroxinemia usually ensues in response to several factors, such as mild iodine deficiency, environmental endocrine disrupters, or certain thyroid diseases. Unequivocal evidence demonstrates that maternal hypothyroxinemia leads to negative effects on fetal brain development, increasing the risks for cognitive deficits and poor psychomotor development in resulting progeny. In support of this, rodent models provide direct evidence of neurodevelopmental damage induced by maternal hypothyroxinemia, including dendritic and axonal growth limitation, neural abnormal location, and synaptic function alteration. The neurodevelopmental impairments induced by hypothyroxinemia suggest an independent role of T4. Increasing evidence indicates that adequate thyroxine is required for the mothers in order to protect against the abnormal brain development in their progeny.

  6. Parental age influences developmental stability of the progeny in Drosophila

    PubMed Central

    Colines, Betina; Rodríguez, Nahuel Cabrera; Hasson, Esteban R.; Carreira, Valeria; Frankel, Nicolás

    2015-01-01

    The stochastic nature of biochemical processes is a source of variability that influences developmental stability. Developmental instability (DI) is often estimated through fluctuating asymmetry (FA), a parameter that deals with within-individual variation in bilateral structures. A relevant goal is to shed light on how environment, physiology and genotype relate to DI, thus providing a more comprehensive view of organismal development. Using Drosophila melanogaster isogenic lines, we investigated the effect of parental age, parental diet and offspring heterozygosity on DI. In this work, we have uncovered a clear relationship between parental age and offspring asymmetry. We show that asymmetry of the progeny increases concomitantly with parental age. Moreover, we demonstrate that enriching the diet of parents mitigates the effect of age on offspring symmetry. We show as well that increasing the heterozygosity of the progeny eliminates the effect of parental age on offspring symmetry. Taken together, our results suggest that diet, genotype and age of the parents interact to determine offspring DI in wild populations. These findings provide us with an avenue to understand the mechanisms underlying DI. PMID:25673675

  7. Accumulation of differentiating intestinal stem cell progenies drives tumorigenesis

    PubMed Central

    Zhai, Zongzhao; Kondo, Shu; Ha, Nati; Boquete, Jean-Philippe; Brunner, Michael; Ueda, Ryu; Lemaitre, Bruno

    2015-01-01

    Stem cell self-renewal and differentiation are coordinated to maintain tissue homeostasis and prevent cancer. Mutations causing stem cell proliferation are traditionally the focus of cancer studies. However, the contribution of the differentiating stem cell progenies in tumorigenesis is poorly characterized. Here we report that loss of the SOX transcription factor, Sox21a, blocks the differentiation programme of enteroblast (EB), the intestinal stem cell progeny in the adult Drosophila midgut. This results in EB accumulation and formation of tumours. Sox21a tumour initiation and growth involve stem cell proliferation induced by the unpaired 2 mitogen released from accumulating EBs generating a feed-forward loop. EBs found in the tumours are heterogeneous and grow towards the intestinal lumen. Sox21a tumours modulate their environment by secreting matrix metalloproteinase and reactive oxygen species. Enterocytes surrounding the tumours are eliminated through delamination allowing tumour progression, a process requiring JNK activation. Our data highlight the tumorigenic properties of transit differentiating cells. PMID:26690827

  8. MEASUREMENT OF RADON, THORON AND THEIR PROGENY CONCENTRATIONS IN THE DWELLINGS OF PAURI GARHWAL, UTTARAKHAND, INDIA.

    PubMed

    Joshi, Veena; Dutt, Sanjay; Yadav, Manjulata; Mishra, Rosaline; Ramola, R C

    2016-10-01

    It is well known that inhalation of radon, thoron and their progeny contributes more than 50 % of natural background radiation dose to human being. The time-integrated passive measurements of radon, thoron and their progeny concentrations were carried out in the dwellings of Pauri Garhwal, Uttarakhand, India. The measurements of radon and thoron concentrations were performed by LR-115 detector-based single-entry pin-hole dosemeter, while for the measurement of progeny concentrations, LR-115 deposition-based direct radon and thoron progeny sensors technique was used. The experimental techniques and results obtained are discussed in detail.

  9. Genetic predisposition directs breast cancer phenotype by dictating progenitor cell fate

    PubMed Central

    Proia, Theresa A.; Keller, Patricia J.; Gupta, Piyush B.; Klebba, Ina; Jones, Ainsley D.; Sedic, Maja; Gilmore, Hannah; Tung, Nadine; Naber, Stephen P.; Schnitt, Stuart; Lander, Eric S.; Kuperwasser, Charlotte

    2011-01-01

    Women with inherited mutations in the BRCA1 gene have increased risk of developing breast cancer, but also exhibit a predisposition for the development of aggressive basal-like breast tumors. We report here that breast epithelial cells derived from patients harboring deleterious mutations in BRCA1 (BRCA1mut/+) give rise to tumors with increased basal differentiation relative to cells from BRCA1+/+ patients. Molecular analysis of disease-free breast tissues from BRCA1mut/+ patients revealed defects in progenitor cell lineage commitment even before cancer incidence. Moreover, we discovered that the transcriptional repressor Slug is an important functional regulator of human breast progenitor cell lineage commitment and differentiation and that it is aberrantly expressed in BRCA1mut/+ tissues. Slug expression is necessary for increased basal-like phenotypes prior to and following neoplastic transformation. These findings demonstrate that the genetic background of patient populations, in addition to affecting incidence rates, significantly impacts progenitor cell fate commitment and, therefore, tumor phenotype. PMID:21295272

  10. Altered gene products involved in the malignant reprogramming of cancer stem/progenitor cells and multitargeted therapies.

    PubMed

    Mimeault, Murielle; Batra, Surinder K

    2014-10-01

    Recent studies in the field of cancer stem cells have revealed that the alterations in key gene products involved in the epithelial-mesenchymal transition (EMT) program, altered metabolic pathways such as enhanced glycolysis, lipogenesis and/or autophagy and treatment resistance may occur in cancer stem/progenitor cells and their progenies during cancer progression. Particularly, the sustained activation of diverse developmental cascades such as hedgehog, epidermal growth factor receptor (EGFR), Wnt/β-catenin, Notch, transforming growth factor-β (TGF-β)/TGF-βR receptors and/or stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) can play critical functions for high self-renewal potential, survival, invasion and metastases of cancer stem/progenitor cells and their progenies. It has also been observed that cancer cells may be reprogrammed to re-express different pluripotency-associated stem cell-like markers such as Myc, Oct-3/4, Nanog and Sox-2 along the EMT process and under stressful and hypoxic conditions. Moreover, the enhanced expression and/or activities of some drug resistance-associated molecules such as Bcl-2, Akt/molecular target of rapamycin (mTOR), nuclear factor-kappaB (NF-κB), hypoxia-inducible factors (HIFs), macrophage inhibitory cytokine-1 (MIC-1) and ATP-binding cassette (ABC) multidrug transporters frequently occur in cancer cells during cancer progression and metastases. These molecular events may cooperate for the survival and acquisition of a more aggressive and migratory behavior by cancer stem/progenitor cells and their progenies during cancer transition to metastatic and recurrent disease states. Of therapeutic interest, these altered gene products may also be exploited as molecular biomarkers and therapeutic targets to develop novel multitargeted strategies for improving current cancer therapies and preventing disease relapse.

  11. Altered gene products involved in the malignant reprogramming of cancer stem/progenitor cells and multitargeted therapies

    PubMed Central

    Mimeault, Murielle; Batra, Surinder K.

    2013-01-01

    Recent studies in the field of cancer stem cells have revealed that the alterations in key gene products involved in the epithelial-mesenchymal transition (EMT) program, altered metabolic pathways such as enhanced glycolysis, lipogenesis and/or autophagy and treatment resistance may occur in cancer stem/progenitor cells and their progenies during cancer progression. Particularly, the sustained activation of diverse developmental cascades such as hedgehog, epidermal growth factor receptor (EGFR), Wnt/β-catenin, Notch, transforming growth factor-β (TGF-β)/TGF-βR receptors and/or stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) can play critical functions for high self-renewal potential, survival, invasion and metastases of cancer stem/progenitor cells and their progenies. It has also been observed that cancer cells may be reprogrammed to re-express different pluripotency-associated stem cell-like markers such as Myc, Oct-3/4, Nanog and Sox-2 along the EMT process and under stressful and hypoxic conditions. Moreover, the enhanced expression and/or activities of some drug resistance-associated molecules such as Bcl-2, Akt/molecular target of rapamycin (mTOR), nuclear factor-kappaB (NF-κB), hypoxia-inducible factors (HIFs), macrophage inhibitory cytokine-1 (MIC-1) and ATP-binding cassette (ABC) multidrug transporters frequently occur in cancer cells during cancer progression and metastases. These molecular events may cooperate for the survival and acquisition of a more aggressive and migratory behavior by cancer stem/progenitor cells and their progenies during cancer transition to metastatic and recurrent disease states. Of therapeutic interest, these altered gene products may also be exploited as molecular biomarkers and therapeutic targets to develop novel multitargeted strategies for improving current cancer therapies and preventing disease relapse. PMID:23994756

  12. Great promise of tissue-resident adult stem/progenitor cells in transplantation and cancer therapies.

    PubMed

    Mimeault, Murielle; Batra, Surinder K

    2012-01-01

    Recent progress in tissue-resident adult stem/progenitor cell research has inspired great interest because these immature cells from your own body can act as potential, easily accessible cell sources for cell transplantation in regenerative medicine and cancer therapies. The use of adult stem/progenitor cells endowed with a high self-renewal ability and multilineage differentiation potential, which are able to regenerate all the mature cells in the tissues from their origin, offers great promise in replacing non-functioning or lost cells and regenerating diseased and damaged tissues. The presence of a small subpopulation of adult stem/progenitor cells in most tissues and organs provides the possibility of stimulating their in vivo differentiation, or of using their ex vivo expanded progenies for cell-replacement and gene therapies with multiple applications in humans without a high-risk of graft rejection and major side effects. Among the diseases that could be treated by adult stem cell-based therapies are hematopoietic and immune disorders, multiple degenerative disorders such as Parkinson's and Alzheimer's diseases, Types 1 and 2 diabetes mellitus as well as skin, eye, liver, lung, tooth and cardiovascular disorders. In addition, a combination of the current cancer treatments with an adjuvant treatment consisting of an autologous or allogeneic adult stem/progenitor cell transplantation also represents a promising strategy for treating and even curing diverse aggressive, metastatic, recurrent and lethal cancers. In this chapter, we reviewed the most recent advancements on the characterization of phenotypic and functional properties of adult stem/progenitor cell types found in bone marrow, heart, brain and other tissues and discussed their therapeutic implications in the stem cell-based transplantation therapy.

  13. Spontaneous Calcium Oscillations Regulate Human Cardiac Progenitor Cell Growth

    PubMed Central

    Ferreira-Martins, João; Rondon-Clavo, Carlos; Tugal, Derin; Korn, Justin A; Rizzi, Roberto; Padin-Iruegas, Maria Elena; Ottolenghi, Sergio; De Angelis, Antonella; Urbanek, Konrad; Iwata, Noriko; D’Amario, Domenico; Hosoda, Toru; Leri, Annarosa; Kajstura, Jan; Anversa, Piero; Rota, Marcello

    2009-01-01

    Rationale The adult heart possesses a pool of progenitor cells stored in myocardial niches but the mechanisms involved in the activation of this cell compartment are currently unknown. Objective Ca2+ promotes cell growth raising the possibility that changes in intracellular Ca2+ initiate division of c-kit-positive human cardiac progenitor cells (hCPCs) and determine their fate. Methods and Results Ca2+ oscillations were identified in hCPCs and these events occurred independently from coupling with cardiomyocytes or the presence of extracellular Ca2+. These findings were confirmed in the heart of transgenic mice in which EGFP was under the control of the c-kit-promoter. Ca2+ oscillations in hCPCs were regulated by the release of Ca2+ from the ER through activation of inositol 1,4,5-triphosphate receptors (IP3Rs) and the re-uptake of Ca2+ by the sarco/endoplasmic reticulum Ca2+ pump (SERCA). IP3Rs and SERCA were highly expressed in hCPCs while ryanodine receptors were not detected. Although Na+-Ca2+ exchanger, store-operated Ca2+-channels and plasma membrane Ca2+-pump were present and functional in hCPCs, they had no direct effects on Ca2+ oscillations. Conversely, Ca2+ oscillations and their frequency markedly increased with ATP and histamine which activated purinoceptors and histamine-1 receptors highly expressed in hCPCs. Importantly, Ca2+ oscillations in hCPCs were coupled with the entry of cells into the cell cycle and BrdUrd incorporation. Induction of Ca2+ oscillations in hCPCs prior to their intramyocardial delivery to infarcted hearts was associated with enhanced engraftment and expansion of these cells promoting the generation of a large myocyte progeny. Conclusion IP3R-mediated Ca2+ mobilization control hCPC growth and their regenerative potential. PMID:19745162

  14. Airway Progenitor Clone Formation Is Enhanced by Y-27632-Dependent Changes in the Transcriptome.

    PubMed

    Reynolds, Susan D; Rios, Cydney; Wesolowska-Andersen, Agata; Zhuang, Yongbin; Pinter, Mary; Happoldt, Carrie; Hill, Cynthia L; Lallier, Scott W; Cosgrove, Gregory P; Solomon, George M; Nichols, David P; Seibold, Max A

    2016-09-01

    The application of conditional reprogramming culture (CRC) methods to nasal airway epithelial cells would allow more wide-spread incorporation of primary airway epithelial culture models into complex lung disease research. In this study, we adapted the CRC method to nasal airway epithelial cells, investigated the growth advantages afforded by this technique over standard culture methods, and determined the cellular and molecular basis of CRC cell culture effects. We found that the CRC method allowed the production of 7.1 × 10(10) cells after 4 passages, approximately 379 times more cells than were generated by the standard bronchial epithelial growth media (BEGM) method. These nasal airway epithelial cells expressed normal basal cell markers and could be induced to form a mucociliary epithelium. Progenitor cell frequency was significantly higher using the CRC method in comparison to the standard culture method, and progenitor cell maintenance was dependent on addition of the Rho-kinase inhibitor Y-27632. Whole-transcriptome sequencing analysis demonstrated widespread gene expression changes in Y-27632-treated basal cells. We found that Y-27632 treatment altered expression of genes fundamental to the formation of the basal cell cytoskeleton, cell-cell junctions, and cell-extracellular matrix (ECM) interactions. Importantly, we found that Y-27632 treatment up-regulated expression of unique basal cell intermediate filament and desmosomal genes. Conversely, Y-27632 down-regulated multiple families of protease/antiprotease genes involved in ECM remodeling. We conclude that Y-27632 fundamentally alters cell-cell and cell-ECM interactions, which preserves basal progenitor cells and allows greater cell amplification.

  15. Effect of dam parity on litter performance, transfer of passive immunity, and progeny microbial ecology.

    PubMed

    Carney-Hinkle, E E; Tran, H; Bundy, J W; Moreno, R; Miller, P S; Burkey, T E

    2013-06-01

    Litter performance and progeny health status may be decreased in progeny derived from primiparous sows but improve with increasing parity. The objective was to evaluate litter performance, the production and passive transfer of Ig, and fecal microbial populations in progeny derived from first parity (P1) compared with fourth parity (P4) dams. Litter performance was recorded for P1 (n = 19) and P4 (n = 24) dams including number of pigs/litter (total born, born live, stillbirths, mummified fetuses, prewean mortality, and pigs weaned) and average litter and piglet BW at birth (d 0), d 7, d 14, and at weaning (average d 19). Blood samples were collected from all dams on d 90 and 114 of gestation and d 0 of lactation. Colostrum and milk samples were collected from each dam on d 0, 7, and 14 of lactation for quantification of IgG and IgA. Blood and fecal samples were collected from each litter (n = 6 pigs/litter) on d 1, 7, and 14 after parturition. Circulating IgG and IgA concentrations were quantified in all blood samples. Denaturing gradient gel electrophoresis (DGGE) was used to characterize similarity and diversity of fecal microbes among progeny. Progeny of P1 dams had decreased average litter BW at d 7 (25.7 vs. 30.0 kg; P < 0.03) and decreased average piglet BW throughout the experiment (d 0, 7, 14, and 19; P < 0.001) compared with P4 progeny. No parity × day interactions were observed with respect to immunoglobulin or microbial analyses. Concentrations of IgA tended to be greater (P = 0.09) in samples of colostrum and milk obtained from P4 compared with P1 dams. Serum IgG concentrations were greater (P < 0.02) in P4 progeny compared with P1 progeny. Results of DGGE revealed that P1 progeny had increased (P < 0.001) microbial similarity on d 7 and decreased (P < 0.03) microbial similarity on d 14 compared with P4 progeny. Progeny of P1 dams tended (P = 0.07) to have a greater Shannon's diversity index compared with P4 progeny on d 1, and P1 progeny had a greater

  16. Retinoid signaling in control of progenitor cell differentiation during mouse development

    PubMed Central

    Duester, Gregg

    2013-01-01

    The vitamin A metabolite retinoic acid (RA) serves as a ligand for nuclear RA receptors that control differentiation of progenitor cells important for vertebrate development. Genetic studies in mouse embryos deficient for RA-generating enzymes have been invaluable for deciphering RA function. RA first begins to act during early organogenesis when RA generated in trunk mesoderm begins to function as a diffusible signal controlling progenitor cell differentiation. In neuroectoderm, RA functions as an instructive signal to stimulate neuronal differentiation of progenitor cells in the hindbrain and spinal cord. RA is not required for early neuronal differentiation of the forebrain, but at later stages RA stimulates neuronal differentiation in forebrain basal ganglia. RA also acts as a permissive signal for differentiation by repressing fibroblast growth factor (FGF) signaling in differentiated cells as they emerge from progenitor populations in the caudal progenitor zone and second heart field. In addition, RA signaling stimulates differentiation of spermatogonial germ cells and induces meiosis in male but not female gonads. A more complete understanding of the normal functions of RA signaling during development will guide efforts to use RA as a differentiation agent for therapeutic purposes. PMID:23973941

  17. Retinoid signaling in control of progenitor cell differentiation during mouse development.

    PubMed

    Duester, Gregg

    2013-12-01

    The vitamin A metabolite retinoic acid (RA) serves as a ligand for nuclear RA receptors that control differentiation of progenitor cells important for vertebrate development. Genetic studies in mouse embryos deficient for RA-generating enzymes have been invaluable for deciphering RA function. RA first begins to act during early organogenesis when RA generated in trunk mesoderm begins to function as a diffusible signal controlling progenitor cell differentiation. In neuroectoderm, RA functions as an instructive signal to stimulate neuronal differentiation of progenitor cells in the hindbrain and spinal cord. RA is not required for early neuronal differentiation of the forebrain, but at later stages RA stimulates neuronal differentiation in forebrain basal ganglia. RA also acts as a permissive signal for differentiation by repressing fibroblast growth factor (FGF) signaling in differentiated cells as they emerge from progenitor populations in the caudal progenitor zone and second heart field. In addition, RA signaling stimulates differentiation of spermatogonial germ cells and induces meiosis in male but not female gonads. A more complete understanding of the normal functions of RA signaling during development will guide efforts to use RA as a differentiation agent for therapeutic purposes.

  18. PROGENITORS OF RECOMBINING SUPERNOVA REMNANTS

    SciTech Connect

    Moriya, Takashi J.

    2012-05-01

    Usual supernova remnants have either ionizing plasma or plasma in collisional ionization equilibrium, i.e., the ionization temperature is lower than or equal to the electron temperature. However, the existence of recombining supernova remnants, i.e., supernova remnants with ionization temperature higher than the electron temperature, has been recently confirmed. One suggested way to have recombining plasma in a supernova remnant is to have a dense circumstellar medium at the time of the supernova explosion. If the circumstellar medium is dense enough, collisional ionization equilibrium can be established in the early stage of the evolution of the supernova remnant and subsequent adiabatic cooling, which occurs after the shock wave gets out of the dense circumstellar medium, makes the electron temperature lower than the ionization temperature. We study the circumstellar medium around several supernova progenitors and show which supernova progenitors can have a circumstellar medium dense enough to establish collisional ionization equilibrium soon after the explosion. We find that the circumstellar medium around red supergiants (especially massive ones) and the circumstellar medium dense enough to make Type IIn supernovae can establish collisional ionization equilibrium soon after the explosion and can evolve to become recombining supernova remnants. Wolf-Rayet stars and white dwarfs have the possibility to be recombining supernova remnants but the fraction is expected to be very small. As the occurrence rate of the explosions of red supergiants is much higher than that of Type IIn supernovae, the major progenitors of recombining supernova remnants are likely to be red supergiants.

  19. Gamma-Ray Burst Progenitors

    NASA Astrophysics Data System (ADS)

    Levan, Andrew; Crowther, Paul; de Grijs, Richard; Langer, Norbert; Xu, Dong; Yoon, Sung-Chul

    2016-12-01

    We review our current understanding of the progenitors of both long and short duration gamma-ray bursts (GRBs). Constraints can be derived from multiple directions, and we use three distinct strands; (i) direct observations of GRBs and their host galaxies, (ii) parameters derived from modelling, both via population synthesis and direct numerical simulation and (iii) our understanding of plausible analog progenitor systems observed in the local Universe. From these joint constraints, we describe the likely routes that can drive massive stars to the creation of long GRBs, and our best estimates of the scenarios that can create compact object binaries which will ultimately form short GRBs, as well as the associated rates of both long and short GRBs. We further discuss how different the progenitors may be in the case of black hole engine or millisecond-magnetar models for the production of GRBs, and how central engines may provide a unifying theme between many classes of extremely luminous transient, from luminous and super-luminous supernovae to long and short GRBs.

  20. Transgenerational effects of neonatal hypoxia-ischemia in progeny.

    PubMed

    Infante, Smitha K; Rea, Harriett C; Perez-Polo, J R

    2013-10-01

    Neonatal hypoxia-ischemia (HI) affects 60% of low birth weight infants and up to 40% of preterm births. Cell death and brain injury after HI have been shown to cause long-lasting behavioral deficits. By using a battery of behavioral tests on second generation 3-week-old rodents, we found that neonatal HI is associated with behavioral outcomes in the progeny of HI-affected parents. Our results suggest an epigenetic transfer mechanism of some of the neurological symptoms associated with neonatal HI. Elucidating the transfer of brain injury to the next generation after HI calls attention to the risks associated with HI injury and the need for proper treatment to reverse these effects. Assessing the devastating extent of HI's reach serves as a cautionary tale to the risks associated with neonatal HI, and provides an incentive to create improved therapeutic measures to treat HI.

  1. Dedifferentiated adipocyte-derived progeny cells (DFAT cells)

    PubMed Central

    Wei, Shengjuan; Zan, Linsen; Hausman, Gary J; Rasmussen, Theodore P; Bergen, Werner G; Dodson, Michael V

    2013-01-01

    Analyses of mature adipocytes have shown that they possess a reprogramming ability in vitro, which is associated with dedifferentiation. The subsequent dedifferentiated fat cells (DFAT cells) are multipotent and can differentiate into adipocytes and other cell types as well. Mature adipocytes can be easily obtained by biopsy, and the cloned progeny cells are homogeneous in vitro. Therefore, DFAT cells (a new type of stem cell) may provide an excellent source of cells for tissue regeneration, engineering and disease treatment. The dedifferentiation of mature adipocytes, the multipotent capacity of DFAT cells and comparisons and contrasts with mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPS) are discussed in this review. PMID:23991357

  2. Pattern of Neurogenesis and Identification of Neuronal Progenitor Subtypes during Pallial Development in Xenopus laevis

    PubMed Central

    Moreno, Nerea; González, Agustín

    2017-01-01

    The complexity of the pallium during evolution has increased dramatically in many different respects. The highest level of complexity is found in mammals, where most of the pallium (cortex) shows a layered organization and neurons are generated during development following an inside-out order, a sequence not observed in other amniotes (birds and reptiles). Species-differences may be related to major neurogenetic events, from the neural progenitors that divide and produce all pallial cells. In mammals, two main types of precursors have been described, primary precursor cells in the ventricular zone (vz; also called radial glial cells or apical progenitors) and secondary precursor cells (called basal or intermediate progenitors) separated from the ventricle surface. Previous studies suggested that pallial neurogenetic cells, and especially the intermediate progenitors, evolved independently in mammalian and sauropsid lineages. In the present study, we examined pallial neurogenesis in the amphibian Xenopus laevis, a representative species of the only group of tetrapods that are anamniotes. The pattern of pallial proliferation during embryonic and larval development was studied, together with a multiple immunohistochemical analysis of putative progenitor cells. We found that there are two phases of progenitor divisions in the developing pallium that, following the radial unit concept from the ventricle to the mantle, finally result in an outside-in order of mature neurons, what seems to be the primitive condition of vertebrates. Gene expressions of key transcription factors that characterize radial glial cells in the vz were demonstrated in Xenopus. In addition, although mitotic cells were corroborated outside the vz, the expression pattern of markers for intermediate progenitors differed from mammals.

  3. RADON PROGENY AS AN EXPERIMENTAL TOOL FOR DOSIMETRY OF NANOAEROSOLS

    SciTech Connect

    Ruzer, Lev; Ruzer, Lev S.; Apte, Michael G.

    2008-02-25

    The study of aerosol exposure and dosimetry measurements and related quantitation of health effects are important to the understanding of the consequences of air pollution, and are discussed widely in the scientific literature. During the last 10 years the need to correlate aerosol exposure and biological effects has become especially important due to rapid development of a new, revolutionary industry ?-- nanotechnology. Nanoproduct commerce is predicted to top $1 trillion by 2015. Quantitative assessment of aerosol particle behavior in air and in lung deposition, and dosimetry in different parts of the lung, particularly for nanoaerosols, remains poor despite several decades of study. Direct measurements on humans are still needed in order to validate the hollow cast, animal studies, and lung deposition modeling. We discuss here the use of nanoscale radon decay products as an experimental tool in the study of local deposition and lung dosimetry for nanoaerosols. The issue of the safe use of radon progeny in such measurements is discussed based on a comparison of measured exposure in 3 settings: general population, miners, and in a human experiment conducted at the Paul Scherer Institute (PSI) in Switzerland. One of the properties of radon progeny is that they consist partly of 1 nm radioactive particles called unattached activity; having extremely small size and high diffusion coefficients, these particles can be potentially useful as radioactive tracers in the study of nanometer-sized aerosols. We present a theoretical and experimental study of the correlation between the unattached activity and aerosol particle surface area, together with a description of its calibration and method for measurement of the unattached fraction.

  4. Hematopoietic progenitor cell regulation by CD4+CD25+ T cells.

    PubMed

    Urbieta, Maite; Barao, Isabel; Jones, Monica; Jurecic, Roland; Panoskaltsis-Mortari, Angela; Blazar, Bruce R; Murphy, William J; Levy, Robert B

    2010-06-10

    CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) possess the capacity to modulate both adaptive and innate immune responses. We hypothesized that Tregs could regulate hematopoiesis based on cytokine effector molecules they can produce. The studies here demonstrate that Tregs can affect the differentiation of myeloid progenitor cells. In vitro findings demonstrated the ability of Tregs to inhibit the differentiation of interleukin-3 (IL-3)/stem cell factor (colony-forming unit [CFU]-IL3)-driven progenitor cells. Inhibitory effects were mediated by a pathway requiring cell-cell contact, major histocompatibility complex class II expression on marrow cells, and transforming growth factor-beta. Importantly, depletion of Tregs in situ resulted in enhanced CFU-IL3 levels after bone marrow transplantation. Cotransplantation of CD4(+)FoxP3(+)(gfp) Tregs together with bone marrow was found to diminish CFU-IL3 responses after transplantation. To address the consequence of transplanted Tregs on differentiated progeny from these CFU 2 weeks after hematopoietic stem cell transplantation, peripheral blood complete blood counts were performed and examined for polymorphonuclear leukocyte content. Recipients of cotransplanted Tregs exhibited diminished neutrophil counts. Together, these findings illustrate that both recipient and donor Tregs can influence hematopoietic progenitor cell activity after transplantation and that these cells can alter responses outside the adaptive and innate immune systems.

  5. Lineage specification of Flk-1+ progenitors is associated with divergent Sox7 expression in cardiopoiesis

    PubMed Central

    Nelson, Timothy J; Chiriac, Anca; Faustino, Randolph S; Crespo-Diaz, Ruben J; Behfar, Atta; Terzic, Andre

    2009-01-01

    SUMMARY Embryonic stem cell differentiation recapitulates the diverse phenotypes of a developing embryo, traceable according to markers of lineage specification. At gastrulation, the vascular endothelial growth factor (VEGF) receptor, Flk-1 (KDR), identifies a mesoderm-restricted potential of embryonic stem cells. The multi-lineage propensity of Flk-1+ progenitors mandates the mapping of fate-modifying co-factors in order to stratify differentiating cytotypes and predict lineage competency. Here, Flk-1 based selection of early embryonic stem cell progeny separated a population depleted of pluripotent (Oct4, Sox2) and endoderm (Sox17) markers. The gene expression profile of the Flk-1+ population was notable for a significant upregulation in the vasculogenic Sox7 transcription factor, which overlapped with the emergence of primordial cardiac transcription factors GATA-4, Myocardin and Nkx2.5. Sorting the parental Flk-1+ pool with the chemokine receptor CXCR4 to enrich the cardiopoietic subpopulation uncovered divergent Sox7 expression, with a 7-fold induction in non-cardiac compared to cardiac progenitors. Bioinformatic resolution sequestered a framework gene expression relationships between Sox transcription factor family members and the Flk-1/CXCR4 axes with significant integration of β-catenin signaling. Thus, differential Sox7 gene expression presents a novel biomarker profile, and possible regulatory switch, to distinguish cardiovascular pedigrees within Flk-1+ multi-lineage progenitors. PMID:19272523

  6. Human embryonic hemopoiesis. Kinetics of progenitors and precursors underlying the yolk sac----liver transition.

    PubMed Central

    Migliaccio, G; Migliaccio, A R; Petti, S; Mavilio, F; Russo, G; Lazzaro, D; Testa, U; Marinucci, M; Peschle, C

    1986-01-01

    Human embryonic development involves transition from yolk sac (YS) to liver (L) hemopoiesis. We report the identification of pluripotent, erythroid, and granulo-macrophage progenitors in YS, L, and blood from human embryos. Furthermore, comprehensive studies are presented on the number of hemopoietic progenitors and precursors, as well as of other cell types, in YS, L, and blood at precisely sequential stages in embryos and early fetuses (i.e., at 4.5-8 wk and 9-10 wk postconception, respectively). Our results provide circumstantial support to a monoclonal hypothesis for human embryonic hemopoiesis, based on migration of stem and early progenitor cells from a generation site (YS) to a colonization site (L) via circulating blood. The YS----L transition is associated with development of the differentiation program in proliferating stem cells: their erythroid progeny shows, therefore, parallel switches of multiple parameters, e.g., morphology (megaloblasts----macrocytes) and globin expression (zeta----alpha, epsilon----gamma). Images PMID:3722384

  7. Adult Olfactory Bulb Interneuron Phenotypes Identified by Targeting Embryonic and Postnatal Neural Progenitors

    PubMed Central

    Figueres-Oñate, Maria; López-Mascaraque, Laura

    2016-01-01

    Neurons are generated during embryonic development and in adulthood, although adult neurogenesis is restricted to two main brain regions, the hippocampus and olfactory bulb. The subventricular zone (SVZ) of the lateral ventricles generates neural stem/progenitor cells that continually provide the olfactory bulb (OB) with new granule or periglomerular neurons, cells that arrive from the SVZ via the rostral migratory stream. The continued neurogenesis and the adequate integration of these newly generated interneurons is essential to maintain homeostasis in the olfactory bulb, where the differentiation of these cells into specific neural cell types is strongly influenced by temporal cues. Therefore, identifying the critical features that control the generation of adult OB interneurons at either pre- or post-natal stages is important to understand the dynamic contribution of neural stem cells. Here, we used in utero and neonatal SVZ electroporation along with a transposase-mediated stable integration plasmid, in order to track interneurons and glial lineages in the OB. These plasmids are valuable tools to study the development of OB interneurons from embryonic and post-natal SVZ progenitors. Accordingly, we examined the location and identity of the adult progeny of embryonic and post-natally transfected progenitors by examining neurochemical markers in the adult OB. These data reveal the different cell types in the olfactory bulb that are generated in function of age and different electroporation conditions. PMID:27242400

  8. Feedback control of growth, differentiation, and morphogenesis of pancreatic endocrine progenitors in an epithelial plexus niche

    PubMed Central

    Bankaitis, Eric D.; Bechard, Matthew E.; Wright, Christopher V.E.

    2015-01-01

    In the mammalian pancreas, endocrine cells undergo lineage allocation upon emergence from a bipotent duct/endocrine progenitor pool, which resides in the “trunk epithelium.” Major questions remain regarding how niche environments are organized within this epithelium to coordinate endocrine differentiation with programs of epithelial growth, maturation, and morphogenesis. We used EdU pulse-chase and tissue-reconstruction approaches to analyze how endocrine progenitors and their differentiating progeny are assembled within the trunk as it undergoes remodeling from an irregular plexus of tubules to form the eventual mature, branched ductal arbor. The bulk of endocrine progenitors is maintained in an epithelial “plexus state,” which is a transient intermediate during epithelial maturation within which endocrine cell differentiation is continually robust and surprisingly long-lived. Within the plexus, local feedback effects derived from the differentiating and delaminating endocrine cells nonautonomously regulate the flux of endocrine cell birth as well as proliferative growth of the bipotent cell population using Notch-dependent and Notch-independent influences, respectively. These feedback effects in turn maintain the plexus state to ensure prolonged allocation of endocrine cells late into gestation. These findings begin to define a niche-like environment guiding the genesis of the endocrine pancreas and advance current models for how differentiation is coordinated with the growth and morphogenesis of the developing pancreatic epithelium. PMID:26494792

  9. Examining Dictionary Instruction in Basal Readers.

    ERIC Educational Resources Information Center

    Fisher, Peter J. L.; And Others

    This study explored the nature of dictionary instruction in several basal reading series. Three basal reading series from major academic publishers (Scott Foresman, Ginn, and Holt) with 1989 copyrights, were selected for detailed analysis. Results indicated that even where the professed aim of the basal reading series was to incorporate dictionary…

  10. The basal ganglia and apraxia.

    PubMed

    Pramstaller, P P; Marsden, C D

    1996-02-01

    Ever since Liepmann's original descriptions at the beginning of the century apraxia has usually been attributed to damage confined to the cerebral cortex and/or cortico-cortical connecting pathways. However, there have been suggestions that apraxia can be due to deep subcortical lesions, which raises the question as to whether damage to the basal ganglia or thalamus can cause apraxia. We therefore analysed 82 cases of such 'deep' apraxias reported in the literature. These reports consisted of a small number (n=9) of cases studied neuropathologically, and a much larger group (n=73) in which CT or MRI was used to identify the size and extent of the lesion. The reports were subdivided into (i) those with small isolated lesions which involved nuclei of the basal ganglia or thalamus only, and not extending to involve periventricular or peristriatal white matter; (ii) those with large lesions which involved two or more of the nuclei, or one or more of these deep structures plus damage to closely adjacent areas including the internal capsule, periventricular or peristriatal white matter; and (iii) lesions sparing basal ganglia and thalamus but involving adjacent white matter. The main conclusions to be drawn from this meta-analysis are that lesions confined to the basal ganglia (putamen, caudate nucleus and globus pallidus) rarely, if ever, cause apraxia. Lesions affecting the lenticular nucleus or putamen nearly always intruded into the adjacent lateral white matter to involve association fibres, in particular those of the superior longitudinal fasciculus and frontostriatal connections. Apraxia occurred with deep lesions of the basal ganglia apparently sparing white matter in only eight out of the 82 cases. Apraxia was most commonly seen when there were lesions in the lenticular nucleus or putamen (58 out of 72 cases) with additional involvement of capsular, and particularly of periventricular or peristriatal, white matter. Lesions of the globus pallidus (no cases) or

  11. Evaluation of indoor aerosol control devices and their effects on radon progeny concentrations. Revision

    SciTech Connect

    Sextro, R.G.; Offermann, F.J.; Nazaroff, W.W.; Nero, A.V.; Revzan, K.L.; Yater, J.

    1984-11-01

    Eleven portable air cleaning devices have been evaluated for control of indoor concentrations of respirable particles, and their concomitant effects on radon progeny concentrations have been investigated. The experiments were conducted in a room-size chamber using cigarette smoke and radon injection from an external source. Of the devices examined the electrostatic precipitators and extended surface filters had significant particle removal rates, while the particle removal rates for several small panel-filters, an ion-generator, and a pair of mixing fans were found to be essentially negligible. The evaluation of radon progeny control produced similar results; the air cleaners which were effective in removing particles were also effective in reducing radon progeny concentrations. At the low particle concentrations, deposition of the unattached radon progeny on room surfaces was found to be a significant removal mechanism. Deposition rates of attached and unattached progeny have been estimated from these data, and were used to calculate the equilibrium factors for total and unattached progeny concentrations as a function of particle concentration. While particle removal reduces total airborne radon progeny concentrations, the relative alpha decay dose to the lungs appears to change very little as the particle concentration decreases due to the greater radiological importance of unattached progeny.

  12. Cell cycle regulation of hematopoietic stem or progenitor cells.

    PubMed

    Hao, Sha; Chen, Chen; Cheng, Tao

    2016-05-01

    The highly regulated process of blood production is achieved through the hierarchical organization of hematopoietic stem cell (HSC) subsets and their progenies, which differ in self-renewal and differentiation potential. Genetic studies in mice have demonstrated that cell cycle is tightly controlled by the complex interplay between extrinsic cues and intrinsic regulatory pathways involved in HSC self-renewal and differentiation. Deregulation of these cellular programs may transform HSCs or hematopoietic progenitor cells (HPCs) into disease-initiating stem cells, and can result in hematopoietic malignancies such as leukemia. While previous studies have shown roles for some cell cycle regulators and related signaling pathways in HSCs and HPCs, a more complete picture regarding the molecular mechanisms underlying cell cycle regulation in HSCs or HPCs is lacking. Based on accumulated studies in this field, the present review introduces the basic components of the cell cycle machinery and discusses their major cellular networks that regulate the dormancy and cell cycle progression of HSCs. Knowledge on this topic would help researchers and clinicians to better understand the pathogenesis of relevant blood disorders and to develop new strategies for therapeutic manipulation of HSCs.

  13. Migraine attacks the Basal Ganglia

    PubMed Central

    2011-01-01

    Background With time, episodes of migraine headache afflict patients with increased frequency, longer duration and more intense pain. While episodic migraine may be defined as 1-14 attacks per month, there are no clear-cut phases defined, and those patients with low frequency may progress to high frequency episodic migraine and the latter may progress into chronic daily headache (> 15 attacks per month). The pathophysiology of this progression is completely unknown. Attempting to unravel this phenomenon, we used high field (human) brain imaging to compare functional responses, functional connectivity and brain morphology in patients whose migraine episodes did not progress (LF) to a matched (gender, age, age of onset and type of medication) group of patients whose migraine episodes progressed (HF). Results In comparison to LF patients, responses to pain in HF patients were significantly lower in the caudate, putamen and pallidum. Paradoxically, associated with these lower responses in HF patients, gray matter volume of the right and left caudate nuclei were significantly larger than in the LF patients. Functional connectivity analysis revealed additional differences between the two groups in regard to response to pain. Conclusions Supported by current understanding of basal ganglia role in pain processing, the findings suggest a significant role of the basal ganglia in the pathophysiology of the episodic migraine. PMID:21936901

  14. Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons.

    PubMed

    Goldstein, Bradley J; Goss, Garrett M; Hatzistergos, Konstantinos E; Rangel, Erika B; Seidler, Barbara; Saur, Dieter; Hare, Joshua M

    2015-01-01

    The olfactory epithelium houses chemosensory neurons, which transmit odor information from the nose to the brain. In adult mammals, the olfactory epithelium is a uniquely robust neuroproliferative zone, with the ability to replenish its neuronal and non-neuronal populations due to the presence of germinal basal cells. The stem and progenitor cells of these germinal layers, and their regulatory mechanisms, remain incompletely defined. Here we show that progenitor cells expressing c-Kit, a receptor tyrosine kinase marking stem cells in a variety of embryonic tissues, are required for maintenance of the adult neuroepithelium. Mouse genetic fate-mapping analyses show that embryonically, a c-Kit(+) population contributes to olfactory neurogenesis. In adults under conditions of normal turnover, there is relatively sparse c-Kit(+) progenitor cell (ckPC) activity. However, after experimentally induced neuroepithelial injury, ckPCs are activated such that they reconstitute the neuronal population. There are also occasional non-neuronal cells found to arise from ckPCs. Moreover, the selective depletion of the ckPC population, utilizing temporally controlled targeted diphtheria toxin A expression, results in failure of neurogenesis after experimental injury. Analysis of this model indicates that most ckPCs reside among the globose basal cell populations and act downstream of horizontal basal cells, which can serve as stem cells. Identification of the requirement for olfactory c-Kit-expressing progenitors in olfactory maintenance provides new insight into the mechanisms involved in adult olfactory neurogenesis. Additionally, we define an important and previously unrecognized site of adult c-Kit activity.

  15. Modeling Renal Progenitors – Defining the Niche

    PubMed Central

    Tanigawa, Shunsuke; Perantoni, Alan O.

    2016-01-01

    Significant recent advances in methodologies for the differentiation of pluripotent stem cells to renal progenitors as well as the definition of niche conditions for sustaining those progenitors have dramatically enhanced our understanding of their biology and developmental programing, prerequisites for establishing viable approaches to renal regeneration. In this article, we review the evolution of culture techniques and models for the study of metanephric development, describe the signaling mechanisms likely to be driving progenitor self-renewal, and discuss current efforts to generate de novo functional tissues, providing in depth protocols and niche conditions for the stabilization of the nephronic Six2+ progenitor. PMID:26856661

  16. Osterix-cre labeled progenitor cells contribute to the formation and maintenance of the bone marrow stroma.

    PubMed

    Liu, Yaling; Strecker, Sara; Wang, Liping; Kronenberg, Mark S; Wang, Wen; Rowe, David W; Maye, Peter

    2013-01-01

    We have carried out fate mapping studies using Osterix-EGFPCre and Osterix-CreERt animal models and found Cre reporter expression in many different cell types that make up the bone marrow stroma. Constitutive fate mapping resulted in the labeling of different cellular components located throughout the bone marrow, whereas temporal fate mapping at E14.5 resulted in the labeling of cells within a region of the bone marrow. The identity of cell types marked by constitutive and temporal fate mapping included osteoblasts, adipocytes, vascular smooth muscle, perineural, and stromal cells. Prolonged tracing of embryonic precursors labeled at E14.5dpc revealed the continued existence of their progeny up to 10 months of age, suggesting that fate mapped, labeled embryonic precursors gave rise to long lived bone marrow progenitor cells. To provide further evidence for the marking of bone marrow progenitors, bone marrow cultures derived from Osterix-EGFPCre/Ai9 mice showed that stromal cells retained Cre reporter expression and yielded a FACS sorted population that was able to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and into osteoblasts, adipocytes, and perivascular stromal cells after transplantation. Collectively, our studies reveal the developmental process by which Osterix-Cre labeled embryonic progenitors give rise to adult bone marrow progenitors which establish and maintain the bone marrow stroma.

  17. FatJ acts via the Hippo mediator Yap1 to restrict the size of neural progenitor cell pools

    PubMed Central

    Van Hateren, Nick J.; Das, Raman M.; Hautbergue, Guillaume M.; Borycki, Anne-Gaëlle; Placzek, Marysia; Wilson, Stuart A.

    2011-01-01

    The size, composition and functioning of the spinal cord is likely to depend on appropriate numbers of progenitor and differentiated cells of a particular class, but little is known about how cell numbers are controlled in specific cell cohorts along the dorsoventral axis of the neural tube. Here, we show that FatJ cadherin, identified in a large-scale RNA interference (RNAi) screen of cadherin genes expressed in the neural tube, is localised to progenitors in intermediate regions of the neural tube. Loss of function of FatJ promotes an increase in dp4-vp1 progenitors and a concomitant increase in differentiated Lim1+/Lim2+ neurons. Our studies reveal that FatJ mediates its action via the Hippo pathway mediator Yap1: loss of downstream Hippo components can rescue the defect caused by loss of FatJ. Together, our data demonstrate that RNAi screens are feasible in the chick embryonic neural tube, and show that FatJ acts through the Hippo pathway to regulate cell numbers in specific subsets of neural progenitor pools and their differentiated progeny. PMID:21521736

  18. A survey of immunohistochemical biomarkers for basal-like breast cancer against a gene expression profile gold standard.

    PubMed

    Won, Jennifer R; Gao, Dongxia; Chow, Christine; Cheng, Jinjin; Lau, Sherman Y H; Ellis, Matthew J; Perou, Charles M; Bernard, Philip S; Nielsen, Torsten O

    2013-11-01

    Gene expression profiling of breast cancer delineates a particularly aggressive subtype referred to as 'basal-like', which comprises ∼15% of all breast cancers, afflicts younger women and is refractory to endocrine and anti-HER2 therapies. Immunohistochemical surrogate definitions for basal-like breast cancer, such as the clinical ER/PR/HER2 triple-negative phenotype and models incorporating positive expression for CK5 (CK5/6) and/or EGFR are heavily cited. However, many additional biomarkers for basal-like breast cancer have been described in the literature. A parallel comparison of 46 proposed immunohistochemical biomarkers of basal-like breast cancer was performed against a gene expression profile gold standard on a tissue microarray containing 42 basal-like and 80 non-basal-like breast cancer cases. Ki67 and PPH3 were the most sensitive biomarkers (both 92%) positively expressed in the basal-like subtype, whereas CK14, IMP3 and NGFR were the most specific (100%). Among biomarkers surveyed, loss of INPP4B (a negative regulator of phosphatidylinositol signaling) was 61% sensitive and 99% specific with the highest odds ratio (OR) at 108, indicating the strongest association with basal-like breast cancer. Expression of nestin, a common marker of neural progenitor cells that is also associated with the triple-negative/basal-like phenotype and poor breast cancer prognosis, possessed the second highest OR at 29 among the 46 biomarkers surveyed, as well as 54% sensitivity and 96% specificity. As a positively expressed biomarker, nestin possesses technical advantages over INPP4B that make it a more ideal biomarker for identification of basal-like breast cancer. The comprehensive immunohistochemical biomarker survey presented in this study is a necessary step for determining an optimized surrogate immunopanel that best defines basal-like breast cancer in a practical and clinically accessible way.

  19. Characterization of thrombopoietin (TPO)-responsive progenitor cells in adult mouse bone marrow with in vivo megakaryocyte and erythroid potential.

    PubMed

    Ng, Ashley P; Kauppi, Maria; Metcalf, Donald; Di Rago, Ladina; Hyland, Craig D; Alexander, Warren S

    2012-02-14

    Hematopoietic progenitor cells are the progeny of hematopoietic stem cells that coordinate the production of precise numbers of mature blood cells of diverse functional lineages. Identification of cell-surface antigen expression associated with hematopoietic lineage restriction has allowed prospective isolation of progenitor cells with defined hematopoietic potential. To clarify further the cellular origins of megakaryocyte commitment, we assessed the in vitro and in vivo megakaryocyte and platelet potential of defined progenitor populations in the adult mouse bone marrow. We show that megakaryocytes arise from CD150(+) bipotential progenitors that display both platelet- and erythrocyte-producing potential in vivo and that can develop from the Flt3(-) fraction of the pregranulocyte-macrophage population. We define a bipotential erythroid-megakaryocyte progenitor population, the CD150(+)CD9(lo)endoglin(lo) fraction of Lin(-)cKit(+)IL7 receptor alpha(-)FcγRII/III(lo)Sca1(-) cells, which contains the bulk of the megakaryocyte colony-forming capacity of the bone marrow, including bipotential megakaryocyte-erythroid colony-forming capacity, and can generate both erythrocytes and platelets efficiently in vivo. This fraction is distinct from the CD150(+)CD9(hi)endoglin(lo) fraction, which contains bipotential precursors with characteristics of increased megakaryocytic maturation, and the CD150(+)CD9(lo)endoglin(hi) fraction, which contains erythroid lineage-committed cells. Finally, we demonstrate that bipotential erythroid-megakaryocyte progenitor and CD150(+)CD9(hi)endoglin(lo) cells are TPO-responsive and that the latter population specifically expands in the recovery from thrombocytopenia induced by anti-platelet serum.

  20. Neural progenitor number is regulated by nuclear factor-kappaB p65 and p50 subunit-dependent proliferation rather than cell survival.

    PubMed

    Young, Kaylene M; Bartlett, Perry F; Coulson, Elizabeth J

    2006-01-01

    The number of cells generated by a proliferating stem or precursor cell can be influenced both by proliferation and by the degree of cell death/survival of the progeny generated. In this study, the extent to which cell survival controls progenitor number was examined by comparing the growth characteristics of neurosphere cultures derived from mice lacking genes for the death-inducing Bcl-2 homologue Hara Kiri (Hrk), apoptosis-associated protein 1 (Apaf1), or the prosurvival nuclear factor-kappaB (NFkappaB) subunits p65, p50, or c-rel. We found no evidence that Hrk or Apaf1, and by inference the mitochondrial cell death pathway, are involved in regulating the number of neurosphere-derived progeny. However, we identified the p65p50 NFkappaB dimer as being required for the normal growth and expansion of neurosphere cultures. Genetic loss of both p65 and p50 NFkappaB subunits resulted in a reduced number of progeny but an increased proportion of neurons. No effect on cell survival was observed. This suggests that the number and fate of neural progenitor cells are more strongly regulated by cell cycle control than survival.

  1. Early growth performance of full-sib Acacia auriculiformis x Acacia mangium F1 hybrid progenies at three different sites

    NASA Astrophysics Data System (ADS)

    Shah Aimin, Atirah Abdullah; Abdullah, Mohd Zaki; Muhammad, Norwati; Ratnam, Wickneswari

    2014-09-01

    Field trials of 14 full sib Acacia auriculiformis x Acacia mangium F1 hybrid progenies were evaluated for growth performance at three sites (Bintulu, Mentakab and Segamat). Results indicated that there were significant differences (p> 0.05) for diameter breast height (Dbh) and total height (Ht) among the progenies and different sites. Superior progenies have been identified for future tree selection and improvement.

  2. Levels of thoron and progeny in high background radiation area of southeastern coast of Odisha, India.

    PubMed

    Ramola, R C; Gusain, G S; Rautela, B S; Sagar, D V; Prasad, G; Shahoo, S K; Ishikawa, T; Omori, Y; Janik, M; Sorimachi, A; Tokonami, S

    2012-11-01

    Exposure to radon, (222)Rn, is assumed to be the most significant source of natural radiation to human beings in most cases. It is thought that radon and its progeny are major factors that cause cancer. The presence of thoron, (220)Rn, was often neglected because it was considered that the quantity of thoron in the environment is less than that of radon. However, recent studies have shown that a high thoron concentration was found in some regions and the exposure to (220)Rn and its progeny can equal or several time exceed that of (220)Rn and its progeny. The results of thoron and its progeny measurements in the houses of high background radiation area (HBRA) of the southeastern coast of Odisha, India presented here. This area is one of the high background radiation areas in India with a large deposit of monazite sand which is the probable source of thoron. Both active and passive methods were employed for the measurement of thoron and its progeny in cement, brick and mud houses in the study area. Thoron concentration was measured using RAD-7 and Raduet. A CR-39 track detector was employed for the measurement of environmental thoron progeny, both in active and passive modes. Thoron and its progeny concentrations were found to be comparatively high in the area. A comparison between the results obtained with various techniques is presented in this paper.

  3. p300/β-Catenin Interactions Regulate Adult Progenitor Cell Differentiation Downstream of WNT5a/Protein Kinase C (PKC)*

    PubMed Central

    Rieger, Megan E.; Zhou, Beiyun; Solomon, Nicola; Sunohara, Mitsuhiro; Li, Changgong; Nguyen, Cu; Liu, Yixin; Pan, Jie-hong; Minoo, Parviz; Crandall, Edward D.; Brody, Steven L.; Kahn, Michael; Borok, Zea

    2016-01-01

    Maintenance of stem/progenitor cell-progeny relationships is required for tissue homeostasis during normal turnover and repair. Wnt signaling is implicated in both maintenance and differentiation of adult stem/progenitor cells, yet how this pathway serves these dichotomous roles remains enigmatic. We previously proposed a model suggesting that specific interaction of β-catenin with either of the homologous Kat3 co-activators, p300 or CREB-binding protein, differentially regulates maintenance versus differentiation of embryonic stem cells. Limited knowledge of endogenous mechanisms driving differential β-catenin/co-activator interactions and their role in adult somatic stem/progenitor cell maintenance versus differentiation led us to explore this process in defined models of adult progenitor cell differentiation. We focused primarily on alveolar epithelial type II (AT2) cells, progenitors of distal lung epithelium, and identified a novel axis whereby WNT5a/protein kinase C (PKC) signaling regulates specific β-catenin/co-activator interactions to promote adult progenitor cell differentiation. p300/β-catenin but not CBP/β-catenin interaction increases as AT2 cells differentiate to a type I (AT1) cell-like phenotype. Additionally, p300 transcriptionally activates AT1 cell-specific gene Aqp-5. IQ-1, a specific inhibitor of p300/β-catenin interaction, prevents differentiation of not only primary AT2 cells, but also tracheal epithelial cells, and C2C12 myoblasts. p300 phosphorylation at Ser-89 enhances p300/β-catenin interaction, concurrent with alveolar epithelial cell differentiation. WNT5a, a traditionally non-canonical WNT ligand regulates Ser-89 phosphorylation and p300/β-catenin interactions in a PKC-dependent manner, likely involving PKCζ. These studies identify a novel intersection of canonical and non-canonical Wnt signaling in adult progenitor cell differentiation that has important implications for targeting β-catenin to modulate adult progenitor cell

  4. Multi-parametric approach towards the assessment of radon and thoron progeny exposures

    SciTech Connect

    Mishra, Rosaline E-mail: rosaline.mishra@gmail.com; Sapra, B. K.; Mayya, Y. S.

    2014-02-15

    Conventionally, the dosimetry is carried out using radon and thoron gas concentration measurements and doses have been assigned using assumed equilibrium factors for the progeny species, which is inadequate pertaining to the variations in equilibrium factors and possibly due to significant thoron. In fact, since the true exposures depend upon the intricate mechanisms of progeny deposition in the lung, therefore an integrated approach for the assessment of progeny is essential. In this context, the recently developed deposition based progeny concentration measurement techniques (DTPS: Direct Thoron progeny sensors and DRPS: Direct Radon progeny sensors) appear to be best suited for radiological risk assessments both among occupational workers and general study populations. DTPS and DRPS consist of aluminized mylar mounted LR115 type passive detectors, which essentially detects the alpha particles emitted from the deposited progeny atoms on the detector surface. It gives direct measure of progeny activity concentrations in air. DTPS has a lower limit of detection limit of 0.1 Bq/m{sup 3} whereas that for DRPS is 1 Bq/m{sup 3}, hence are perfectly suitable for indoor environments. These DTPS and DRPS can be capped with 200-mesh type wire-screen to measure the coarse fraction of the progeny concentration and the corresponding coarse fraction deposition velocities as well as the time integrated fine fraction. DTPS and DRPS can also be lodged in an integrated sampler wherein the wire-mesh and filter-paper are arranged in an array in flow-mode, to measure the fine and coarse fraction concentration separately and simultaneously. The details are further discussed in the paper.

  5. Maternal Diet and Insulin-Like Signaling Control Intergenerational Plasticity of Progeny Size and Starvation Resistance

    PubMed Central

    2016-01-01

    Maternal effects of environmental conditions produce intergenerational phenotypic plasticity. Adaptive value of these effects depends on appropriate anticipation of environmental conditions in the next generation, and mismatch between conditions may contribute to disease. However, regulation of intergenerational plasticity is poorly understood. Dietary restriction (DR) delays aging but maternal effects have not been investigated. We demonstrate maternal effects of DR in the roundworm C. elegans. Worms cultured in DR produce fewer but larger progeny. Nutrient availability is assessed in late larvae and young adults, rather than affecting a set point in young larvae, and maternal age independently affects progeny size. Reduced signaling through the insulin-like receptor daf-2/InsR in the maternal soma causes constitutively large progeny, and its effector daf-16/FoxO is required for this effect. nhr-49/Hnf4, pha-4/FoxA, and skn-1/Nrf also regulate progeny-size plasticity. Genetic analysis suggests that insulin-like signaling controls progeny size in part through regulation of nhr-49/Hnf4, and that pha-4/FoxA and skn-1/Nrf function in parallel to insulin-like signaling and nhr-49/Hnf4. Furthermore, progeny of DR worms are buffered from adverse consequences of early-larval starvation, growing faster and producing more offspring than progeny of worms fed ad libitum. These results suggest a fitness advantage when mothers and their progeny experience nutrient stress, compared to an environmental mismatch where only progeny are stressed. This work reveals maternal provisioning as an organismal response to DR, demonstrates potentially adaptive intergenerational phenotypic plasticity, and identifies conserved pathways mediating these effects. PMID:27783623

  6. [Obtaining transgenic rice plants and their progenies using Agrobacterium tumefaciens].

    PubMed

    Yin, Z C; Yang, F; Xu, Y; Li, B J

    1998-12-01

    Rice (Oriza sativa L.) suspension cells of Taipei 309 were co-cultivated with A. tumefaciens stran EHA101 harbouring binary vector pBYT2 for 3 days in the presence of vir inducer, 100 mumol/L acetosyringone (AS). After 2 months of continuous selection, 17 stable hygromycin-resistant, GUS-positive calli were recovered from 364 suspension cell clusters co-cultivated with A. tumefaciens. 10 putative transgenic R0 plants obtained from 8 tansformed calli and their progenies were analyzed for the integration and expression of foreign genes. Southern blot analysis of R0 and R1 generations indicated that foreign genes had been stably integrated in the genome of transgenic rice and sexually transmitted. One of the transgenic lines showed 5 copies of T-DNA integration, while the others had only one copy. Histochemical staining observation and fluorometric assay of GUS activity in transgenic rice cells and plants showed ubiquitin promoter from maize was highly effective in driving the expression of gus reporter gene in transgenic rice cells. GUS protein and its activity were also investigated through ndPAGE-X-Gluc staining assay, and it was found that the GUS protein in transgenic rice cells was smaller in size than the standard GUS protein (Sigma Co. G0786) but as large as that from E.coli HB101 (pBI121). This study suggested that Agrobacterium-mediated transformation of plant is an efficient and reliable method to introduce foreign genes into rice.

  7. Parentage verification in field progeny testing program of Mehsana buffalo.

    PubMed

    Jakhesara, S J; Rank, D N; Kansara, J D; Parikh, R C; Patel, V M; Vataliya, P H; Solanki, J V

    2012-12-01

    The present study was undertaken to construct a multiplex microsatellite panel for parentage testing in Mehsana buffalo (Bubalus bubalis). The study was based on a total of 212 Mehsana buffalos (100 dams, 100 daughters, and 12 sires). Genomic DNA was extracted from blood and semen samples. A panel of 10 microsatellite markers (CSSM61, ILSTS29, ILSTS17, ILSTS28, CSSM57, CSSM22, ILSTS61, CSSM8, ETH152, and ILSTS11) was amplified in a single multiplex reaction and analyzed by capillary electrophoresis on an automated DNA sequencer. The expected heterozygosity ranged from 0.642 to 0.833 (mean 0.762). The total exclusion probability using 10 microsatellite loci with 1 known parent was 0.993. Seven out of 10 microsatellite loci revealed relatively high polymorphic information content (>0.7). Eighty-one daughters out of 100 daughters qualified by compatibility according to Mendelism. The results suggest that multiplex microsatellite panel is a fast, robust, reliable, and economic tool to verify the parentage as well as to assign the putative sire to daughters under progeny testing with very high accuracy and hence can be used in routine parentage testing.

  8. Impact of progesterone on stem/progenitor cells in the human breast.

    PubMed

    Hilton, Heidi N; Clarke, Christine L

    2015-06-01

    The epithelium of the human breast is made up of a branching ductal-lobular system, which is lined by a single layer of luminal cells surrounded by a contractile basal cell layer. The co-ordinated development of stem/progenitor cells into these luminal and basal cells is fundamentally important for breast morphogenesis. The ovarian steroid hormone, progesterone, is critical in driving proliferation and normal breast development, yet progesterone analogues have also been shown to be a major driver of breast cancer risk. Studies in recent years have revealed an important role for progesterone in stimulating the mammary stem cell compartment in the mouse mammary gland, and growing evidence supports the notion that progesterone also stimulates progenitor cells in both the normal human breast and in breast cancer cells. As changes in cell type composition are one of the hallmark features of breast cancer progression, these observations have critical implications in discerning the mechanisms of how progesterone increases breast cancer risk. This review summarises recent work regarding the impact of progesterone action on the stem/progenitor cell compartment of the human breast.

  9. Notch1-induced mammary tumor development is cyclin D1-dependent and correlates with expansion of pre-malignant multipotent duct-limited progenitors.

    PubMed

    Ling, H; Sylvestre, J-R; Jolicoeur, P

    2010-08-12

    Members of the Notch family are involved in the development of breast cancer in animal models and in humans. In young transgenic mice, expressing intracellular activated Notch1 (N1(IC)) in mammary cells, we found that CD24(+) CD29(high) progenitor cells had enhanced survival, and were expanded through a cyclin D1-dependent pathway. This expansion positively correlated with the later cyclin D1-dependent formation of basal-like ductal tumors. This expanded population exhibited abnormal differentiation skewed toward the basal cells, showed signs of pre-malignancy (low PTEN/p53 and high c-myc) and contained stem cells with impaired self-renewal in vivo, and more numerous multipotent, ductal-restricted progenitors. Our data suggest that N1(IC) can favor transformation of progenitor cells early in life through a cyclin D1-dependent pathway.

  10. Enhanced genetic modification of adult growth factor mobilized peripheral blood hematopoietic stem and progenitor cells with rapamycin.

    PubMed

    Li, Lijing; Torres-Coronado, Mónica; Gu, Angel; Rao, Anitha; Gardner, Agnes M; Epps, Elizabeth W; Gonzalez, Nancy; Tran, Chy-Anh; Wu, Xiwei; Wang, Jin-Hui; DiGiusto, David L

    2014-10-01

    Genetic modification of adult human hematopoietic stem and progenitor cells (HSPCs) with lentiviral vectors leads to long-term gene expression in the progeny of the HSPCs and has been used to successfully treat several monogenic diseases. In some cases, the gene-modified cells have a selective growth advantage over nonmodified cells and eventually are the dominant engrafted population. However, in disease indications for which the gene-modified cells do not have a selective advantage, optimizing transduction of HSPC is paramount to successful stem cell-based gene therapy. We demonstrate here that transduction of adult CD34+ HSPCs with lentiviral vectors in the presence of rapamycin, a widely used mTORC1 inhibitor, results in an approximately threefold increase in stable gene marking with minimal effects on HSPC growth and differentiation. Using this approach, we have demonstrated that we can enhance the frequency of gene-modified HSPCs that give rise to clonogenic progeny in vitro without excessive increases in the number of vector copies per cell or changes in integration pattern. The genetic marking of HSPCs and expression of transgenes is durable, and transplantation of gene-modified HSPCs into immunodeficient mice results in high levels of gene marking of the lymphoid and myeloid progeny in vivo. The prior safe clinical history of rapamycin in other applications supports the use of this compound to generate gene-modified autologous HSPCs for our HIV gene therapy clinical trials.

  11. BASAL BODIES, BUT NOT CENTRIOLES, IN NAEGLERIA

    PubMed Central

    Fulton, Chandler; Dingle, Allan D.

    1971-01-01

    Amebae of Naegleria gruberi transform into flagellates whose basal bodies have the typical centriole-like structure. The amebae appear to lack any homologous structure, even during mitosis. Basal bodies are constructed during transformation and, in cells transforming synchronously at 25°C, they are first seen about 10 min before flagella are seen. No structural precursor for these basal bodies has been found. These observations are discussed in the light of hypotheses about the continuity of centrioles. PMID:4942778

  12. Photodynamic therapy for basal cell carcinoma.

    PubMed

    Fargnoli, Maria Concetta; Peris, Ketty

    2015-11-01

    Topical photodynamic therapy is an effective and safe noninvasive treatment for low-risk basal cell carcinoma, with the advantage of an excellent cosmetic outcome. Efficacy of photodynamic therapy in basal cell carcinoma is supported by substantial research and clinical trials. In this article, we review the procedure, indications and clinical evidences for the use of photodynamic therapy in the treatment of basal cell carcinoma.

  13. Functional Neuroanatomy of the Basal Ganglia

    PubMed Central

    Lanciego, José L.; Luquin, Natasha; Obeso, José A.

    2012-01-01

    The “basal ganglia” refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions. Proposed more than two decades ago, the classical basal ganglia model shows how information flows through the basal ganglia back to the cortex through two pathways with opposing effects for the proper execution of movement. Although much of the model has remained, the model has been modified and amplified with the emergence of new data. Furthermore, parallel circuits subserve the other functions of the basal ganglia engaging associative and limbic territories. Disruption of the basal ganglia network forms the basis for several movement disorders. This article provides a comprehensive account of basal ganglia functional anatomy and chemistry and the major pathophysiological changes underlying disorders of movement. We try to answer three key questions related to the basal ganglia, as follows: What are the basal ganglia? What are they made of? How do they work? Some insight on the canonical basal ganglia model is provided, together with a selection of paradoxes and some views over the horizon in the field. PMID:23071379

  14. beta-Chemokine production by neural and glial progenitor cells is enhanced by HIV-1 Tat: effects on microglial migration.

    PubMed

    Hahn, Yun Kyung; Vo, Phu; Fitting, Sylvia; Block, Michelle L; Hauser, Kurt F; Knapp, Pamela E

    2010-07-01

    Human immunodeficiency virus (HIV)-1 neuropathology results from collective effects of viral proteins and inflammatory mediators on several cell types. Significant damage is mediated indirectly through inflammatory conditions promulgated by glial cells, including microglia that are productively infected by HIV-1, and astroglia. Neural and glial progenitors exist in both developing and adult brains. To determine whether progenitors are targets of HIV-1, a multi-plex assay was performed to assess chemokine/cytokine expression after treatment with viral proteins transactivator of transcription (Tat) or glycoprotein 120 (gp120). In the initial screen, ten analytes were basally released by murine striatal progenitors. The beta-chemokines CCL5/regulated upon activation, normal T cell expressed and secreted, CCL3/macrophage inflammatory protein-1alpha, and CCL4/macrophage inflammatory protein-1beta were increased by 12-h exposure to HIV-1 Tat. Secreted factors from Tat-treated progenitors were chemoattractive towards microglia, an effect blocked by 2D7 anti-CCR5 antibody pre-treatment. Tat and opiates have interactive effects on astroglial chemokine secretion, but this interaction did not occur in progenitors. gp120 did not affect chemokine/cytokine release, although both CCR5 and CXCR4, which serve as gp120 co-receptors, were detected in progenitors. We postulate that chemokine production by progenitors may be a normal, adaptive process that encourages immune inspection of newly generated cells. Pathogens such as HIV might usurp this function to create a maladaptive state, especially during development or regeneration, when progenitors are numerous.

  15. Multipotent neural stem cells generate glial cells of the central complex through transit amplifying intermediate progenitors in Drosophila brain development.

    PubMed

    Viktorin, Gudrun; Riebli, Nadia; Popkova, Anna; Giangrande, Angela; Reichert, Heinrich

    2011-08-15

    The neural stem cells that give rise to the neural lineages of the brain can generate their progeny directly or through transit amplifying intermediate neural progenitor cells (INPs). The INP-producing neural stem cells in Drosophila are called type II neuroblasts, and their neural progeny innervate the central complex, a prominent integrative brain center. Here we use genetic lineage tracing and clonal analysis to show that the INPs of these type II neuroblast lineages give rise to glial cells as well as neurons during postembryonic brain development. Our data indicate that two main types of INP lineages are generated, namely mixed neuronal/glial lineages and neuronal lineages. Genetic loss-of-function and gain-of-function experiments show that the gcm gene is necessary and sufficient for gliogenesis in these lineages. The INP-derived glial cells, like the INP-derived neuronal cells, make major contributions to the central complex. In postembryonic development, these INP-derived glial cells surround the entire developing central complex neuropile, and once the major compartments of the central complex are formed, they also delimit each of these compartments. During this process, the number of these glial cells in the central complex is increased markedly through local proliferation based on glial cell mitosis. Taken together, these findings uncover a novel and complex form of neurogliogenesis in Drosophila involving transit amplifying intermediate progenitors. Moreover, they indicate that type II neuroblasts are remarkably multipotent neural stem cells that can generate both the neuronal and the glial progeny that make major contributions to one and the same complex brain structure.

  16. Damage to Olfactory Progenitor Cells Is Involved in Cigarette Smoke-Induced Olfactory Dysfunction in Mice.

    PubMed

    Ueha, Rumi; Ueha, Satoshi; Kondo, Kenji; Sakamoto, Takashi; Kikuta, Shu; Kanaya, Kaori; Nishijima, Hironobu; Matsushima, Kouji; Yamasoba, Tatsuya

    2016-03-01

    Exposure to cigarette smoke is a major cause of olfactory dysfunction. However, the underlying mechanisms by which cigarette smoke interferes with the highly regenerative olfactory nerve system remain unclear. To investigate whether cigarette smoke induces olfactory dysfunction by disrupting cell proliferation and cell survival in the olfactory epithelium (OE), we developed a mouse model of smoking that involved intranasal administration of a cigarette smoke solution (CSS). Immunohistological analyses and behavioral testing showed that CSS administration during a period of 24 days reduced the number of olfactory marker protein-positive mature olfactory receptor neurons (ORNs) in the OE and induced olfactory dysfunction. These changes coincided with a reduction in the number of SOX2(+) ORN progenitors and Ki-67(+) proliferating cells in the basal layer of the OE, an increase in the number of caspase-3(+) apoptotic cells, and an increase in the expression of mRNA for the inflammatory cytokines IL-1β and IL-6. Notably, the proliferating ORN progenitor population recovered after cessation of treatment with CSS, resulting in the subsequent restoration of mature ORN numbers and olfaction. These results suggest that SOX2(+) ORN progenitors are targets of CSS-induced impairment of the OE, and that by damaging the ORN progenitor population and increasing ORN death, CSS exposure eventually overwhelms the regenerative capacity of the epithelium, resulting in reduced numbers of mature ORNs and olfactory dysfunction.

  17. Precommitment low-level Neurog3 expression defines a long-lived mitotic endocrine-biased progenitor pool that drives production of endocrine-committed cells.

    PubMed

    Bechard, Matthew E; Bankaitis, Eric D; Hipkens, Susan B; Ustione, Alessandro; Piston, David W; Yang, Yu-Ping; Magnuson, Mark A; Wright, Christopher V E

    2016-08-15

    The current model for endocrine cell specification in the pancreas invokes high-level production of the transcription factor Neurogenin 3 (Neurog3) in Sox9(+) bipotent epithelial cells as the trigger for endocrine commitment, cell cycle exit, and rapid delamination toward proto-islet clusters. This model posits a transient Neurog3 expression state and short epithelial residence period. We show, however, that a Neurog3(TA.LO) cell population, defined as Neurog3 transcriptionally active and Sox9(+) and often containing nonimmunodetectable Neurog3 protein, has a relatively high mitotic index and prolonged epithelial residency. We propose that this endocrine-biased mitotic progenitor state is functionally separated from a pro-ductal pool and endows them with long-term capacity to make endocrine fate-directed progeny. A novel BAC transgenic Neurog3 reporter detected two types of mitotic behavior in Sox9(+) Neurog3(TA.LO) progenitors, associated with progenitor pool maintenance or derivation of endocrine-committed Neurog3(HI) cells, respectively. Moreover, limiting Neurog3 expression dramatically increased the proportional representation of Sox9(+) Neurog3(TA.LO) progenitors, with a doubling of its mitotic index relative to normal Neurog3 expression, suggesting that low Neurog3 expression is a defining feature of this cycling endocrine-biased state. We propose that Sox9(+) Neurog3(TA.LO) endocrine-biased progenitors feed production of Neurog3(HI) endocrine-committed cells during pancreas organogenesis.

  18. Changes to DNA methylation and homologous recombination frequency in the progeny of stressed plants.

    PubMed

    Migicovsky, Zoë; Kovalchuk, Igor

    2013-02-01

    Plants undergo changes in response to biotic and abiotic stresses that help them adjust and survive. Some of these changes may even be passed on to progeny and eventually lead to adaptive evolution. Transgenerational changes in response to stress include alterations in DNA methylation and changes in homologous recombination frequency (HRF). The progeny of plants that were stressed often show elevated HRF as well as genomic hypermethylation, although specific loci that are beneficial in times of stress may be hypomethylated. One of the possible mechanisms responsible for passing the memory to the progeny involves small interfering RNAs; Dicer-like proteins, DCL2 and DCL3, are in part required for this process. However, while epigenetic modifications are often present in the untreated progeny of stressed plants, they are not usually sustained for multiple unexposed generations. Still, transgenerational inheritance of such changes has already begun to provide evidence for an important role of epigenetics in enhancing stress resistance.

  19. Alternatives for evaluating daughter performance of progeny-test bulls between official evaluations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In August 2007, USDA changed from calculating official genetic evaluations quarterly to triannually to coincide with the schedule for international evaluations. Industry cooperators requested that unofficial interim evaluations be initiated between official evaluations for progeny-test (PT) bulls to...

  20. [Genetic polymorphism of clones and their seed progeny in the scotch pine clone plantation].

    PubMed

    Korshikov, I I; Demkovich, A E

    2010-01-01

    Genetic variation at 12 allozyme loci (10 of them being polymorphic ones) has been studied in the archive-clone plantation of 23 Pinus sylvestris plus-trees and their seed progeny in the south-east of Ukraine. More than a half of clones had 4-8 heterozygous loci, whereas their seed progeny was marked by a lower variation than maternal trees. Seed progeny was obtained at a high outcrossing rate (t(m) = 95%). The clone progeny was characterized by a high percentage of abnormal allele segregation in megagametophytes. There was also a high frequency of significant deviation in distribution of seed embryo genotypes from the theoretically expected one according to the Hardy-Weinberg law.

  1. Pseudohypoparathyroidism with basal ganglia calcification

    PubMed Central

    Song, Cheng-Yuan; Zhao, Zhen-Xiang; Li, Wei; Sun, Cong-Cong; Liu, Yi-Ming

    2017-01-01

    Abstract Rationale: Parkinsonism can be secondary to many internal diseases, in some certain conditions, it seems that the clinical manifestations of parkinsonism presenting reversible. We report a case of patient with parkinsonism secondary to pseudohypoparathyroidism, who improved markedly after the supplement of serum calcium. Patient concerns and diagnoses: A 52-year-old woman with acute parkinsonism was diagnosed as pseudohypoparathyroidism after the conducting of brain computed tomography, laboratory examinations, and gene detection. The son of the patient was also examined and was diagnosed as pseudohypoparathyroidism, who had ever complained of the history of epilepsy. The clinical manifestations of parkinsonism of the patient was reevaluated after the supplement of serum calcium according to the diagnosis. Interventions and outcomes: The brain computed tomography revealed the basal ganglia calcification of the patient, accompanying by serum hypocalcemia and hyperphosphatemia. Loss of function mutation also confirmed the diagnosis. Five days after the therapy targeting at correction of serum hypocalcemia, the patient improved greatly in dyskinesia. Lessons: This study reported a patient presenting as acute reversible parkinsonism, who was finally diagnosed as pseudohypoparathyroidism. It indicated us that secondary parkinsonism should be carefully differentiated for its dramatic treatment effect. And the family history of seizures might be an indicator for the consideration of pseudohypoparathyroidism. PMID:28296742

  2. Progenitors of Supernovae Type Ia

    NASA Astrophysics Data System (ADS)

    Toonen, S.; Nelemans, G.; Bours, M.; Portegies Zwart, S.; Claeys, J.; Mennekens, N.; Ruiter, A.

    2013-01-01

    Despite the significance of Type Ia supernovae (SNeIa) in many fields in astrophysics, SNeIa lack a theoretical explanation. The standard scenarios involve thermonuclear explosions of carbon/oxygen white dwarfs approaching the Chandrasekhar mass; either by accretion from a companion or by a merger of two white dwarfs. We investigate the contribution from both channels to the SNIa rate with the binary population synthesis (BPS) code SeBa in order to constrain binary processes such as the mass retention efficiency of WD accretion and common envelope evolution. We determine the theoretical rates and delay time distribution of SNIa progenitors and in particular study how assumptions affect the predicted rates.

  3. Campylobacter epidemiology from breeders to their progeny in Eastern Spain.

    PubMed

    Ingresa-Capaccioni, S; Jiménez-Trigos, E; Marco-Jiménez, F; Catalá, P; Vega, S; Marin, C

    2016-03-01

    While horizontal transmission is a route clearly linked to the spread of Campylobacter at the farm level, few studies support the transmission of Campylobacter spp. from breeder flocks to their offspring. Thus, the present study was carried out to investigate the possibility of vertical transmission. Breeders were monitored from the time of housing day-old chicks, then throughout the laying period (0 to 60 wk) and throughout their progeny (broiler fattening, 1 to 42 d) until slaughter. All samples were analyzed according with official method ISO 10272:2006. Results revealed that on breeder farms, Campylobacter isolation started from wk 16 and reached its peak at wk 26, with 57.0% and 93.2% of positive birds, respectively. After this point, the rate of positive birds decreased slightly to 86.0% at 60 wk. However, in broiler production all day-old chicks were found negative for Campylobacter spp, and the bacteria was first isolated at d 14 of age (5.0%), with a significant increase in detection during the fattening period with 62% of Campylobacter positive animals at the end of the production cycle. Moreover, non-positive sample was determined from environmental sources. These results could be explained because Campylobacter may be in a low concentration or in a non-culturable form, as there were several studies that successfully detected Campylobacter DNA, but failed to culture. This form can survive in the environment and infect successive flocks; consequently, further studies are needed to develop more modern, practical, cost-effective and suitable techniques for routine diagnosis.

  4. High Correlated Paternity Leads to Negative Effects on Progeny Performance in Two Mediterranean Shrub Species

    PubMed Central

    Nora, Sofia; Aparicio, Abelardo; Albaladejo, Rafael G.

    2016-01-01

    Anthropogenic habitat deterioration can promote changes in plant mating systems that subsequently may affect progeny performance, thereby conditioning plant recruitment for the next generation. However, very few studies yet tested mating system parameters other than outcrossing rates; and the direct effects of the genetic diversity of the pollen received by maternal plants (i.e. correlated paternity) has often been overlooked. In this study, we investigated the relation between correlated paternity and progeny performance in two common Mediterranean shrubs, Myrtus communis and Pistacia lentiscus. To do so, we collected open-pollinated progeny from selected maternal plants, calculated mating system parameters using microsatellite genotyping and conducted sowing experiments under greenhouse and field conditions. Our results showed that some progeny fitness components were negatively affected by the high correlated paternity of maternal plants. In Myrtus communis, high correlated paternity had a negative effect on the proportion and timing of seedling emergence in the natural field conditions and in the greenhouse sowing experiment, respectively. In Pistacia lentiscus, seedling emergence time under field conditions was also negatively influenced by high correlated paternity and a progeny survival analysis in the field experiment showed greater mortality of seedlings from maternal plants with high correlated paternity. Overall, we found effects of correlated paternity on the progeny performance of Myrtus communis, a self-compatible species. Further, we also detected effects of correlated paternity on the progeny emergence time and survival in Pistacia lentiscus, an obligate outcrossed species. This study represents one of the few existing empirical examples which highlight the influence that correlated paternity may exert on progeny performance in multiple stages during early seedling growth. PMID:27835658

  5. Control of respirable particles and radon progeny with portable air cleaners

    SciTech Connect

    Offermann, F.J.; Sextro, R.G.; Fisk, W.J.; Nazaroff, W.W.; Nero, A.V.; Revzan, K.L.; Yater, J.

    1984-02-01

    Eleven portable air cleaning devices have been evaluated for control of indoor concentrations of respirable particles and radon progeny. Following injection of cigarette smoke and radon in a room-size chamber, decay rates for particles and radon progeny concentrations were measured with and without air cleaner operation. Particle concentrations were obtained for total number concentration and for number concentration by particle size. In tests with no air cleaner the natural decay rate for cigarette smoke was observed to be 0.2 hr/sup -1/. Air cleaning rates for particles were found to be negligible for several small panel-filters, a residential ion-generator, and a pair of mixing fans. The electrostatic precipitators and extended surface filters tested had significant particle removal rates, and a HEPA-type filter was the most efficient air cleaner. The evaluation of radon progeny control produced similar results; the air cleaners which were effective in removing particles were also effective in removing radon progeny. At low particle concentrations plateout of the unattached radon progeny is an important removal mechanism. Based on data from these tests, the plateout rate for unattached progeny was found to be 15 hr/sup -1/. The unattached fraction and the overall removal rate due to deposition of attached and unattached nuclides have been estimated for each radon decay product as a function of particle concentration. While air cleaning can be effective in reducing total radon progeny, concentrations of unattached radon progeny can increase with increasing air cleaning. 39 references, 26 figures, 9 tables.

  6. The Influence of Radon (Gas and Progeny) and Weather Conditions on Ambient Dose Equivalent Rate.

    PubMed

    Márquez, J L; Benito, G; Saez, J C; Navarro, N; Alvarez, A; Quiñones, J

    2016-08-13

    The purpose of this study is to identify the influence of radon (gas and progeny) on the ambient dose equivalent rate measured at the reference station ESMERALDA, where continuous measurements of the ambient dose equivalent rate (every 10 min) combined with activity concentration measurements of radon gas and radon progeny as well as meteorological parameters have been collected. This study has been performed using a correlation study based on a principal components analysis and the Spearman's rank correlation coefficient.

  7. The hESC line Envy expresses high levels of GFP in all differentiated progeny.

    PubMed

    Costa, Magdaline; Dottori, Mirella; Ng, Elizabeth; Hawes, Susan M; Sourris, Koula; Jamshidi, Pegah; Pera, Martin F; Elefanty, Andrew G; Stanley, Edouard G

    2005-04-01

    Human embryonic stem cells (hESCs) have been advanced as a potential source of cells for use in cell replacement therapies. The ability to identify hESCs and their differentiated progeny readily in transplantation experiments will facilitate the analysis of hESC potential and function in vivo. We have generated a hESC line designated 'Envy', in which robust levels of green fluorescent protein (GFP) are expressed in stem cells and all differentiated progeny.

  8. Prorenin receptor is critical for nephron progenitors.

    PubMed

    Song, Renfang; Preston, Graeme; Kidd, Laura; Bushnell, Daniel; Sims-Lucas, Sunder; Bates, Carlton M; Yosypiv, Ihor V

    2016-01-15

    Deficient nephrogenesis is the major factor contributing to renal hypoplasia defined as abnormally small kidneys. Nephron induction during kidney development is driven by reciprocal interactions between progenitor cells of the cap mesenchyme (CM) and the ureteric bud (UB). The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump H(+)-ATPase. Global loss of PRR is lethal in mice and PRR mutations are associated with a high blood pressure, left ventricular hypertrophy and X-linked mental retardation in humans. To circumvent lethality of the ubiquitous PRR mutation in mice and to determine the potential role of the PRR in nephrogenesis, we generated a mouse model with a conditional deletion of the PRR in Six2(+) nephron progenitors and their epithelial derivatives (Six2(PRR-/-)). Targeted ablation of PRR in Six2(+) nephron progenitors caused a marked decrease in the number of developing nephrons, small cystic kidneys and podocyte foot process effacement at birth, and early postnatal death. Reduced congenital nephron endowment resulted from premature depletion of nephron progenitor cell population due to impaired progenitor cell proliferation and loss of normal molecular inductive response to canonical Wnt/β-catenin signaling within the metanephric mesenchyme. At 2 months of age, heterozygous Six2(PRR+/-) mice exhibited focal glomerulosclerosis, decreased kidney function and massive proteinuria. Collectively, these findings demonstrate a cell-autonomous requirement for the PRR within nephron progenitors for progenitor maintenance, progression of nephrogenesis, normal kidney development and function.

  9. The interface between glial progenitors and gliomas

    PubMed Central

    Canoll, Peter

    2009-01-01

    The mammalian brain and spinal cord contain heterogeneous populations of cycling, immature cells. These include cells with stem cell-like properties as well as progenitors in various stages of early glial differentiation. This latter population is distributed widely throughout gray and white matter and numerically represents an extremely large cell pool. In this review, we discuss the possibility that the glial progenitors that populate the adult CNS are one source of gliomas. Indeed, the marker phenotypes, morphologies, and migratory properties of cells in gliomas strongly resemble glial progenitors in many ways. We review briefly some salient features of normal glial development and then examine the similarities and differences between normal progenitors and cells in gliomas, focusing on the phenotypic plasticity of glial progenitors and the responses to growth factors in promoting proliferation and migration of normal and glioma cells, and discussing known mutational changes in gliomas in the context of how these might affect the proliferative and migratory behaviors of progenitors. Finally, we will discuss the “cancer stem cell” hypothesis in light of the possibility that glial progenitors can generate gliomas. PMID:18784926

  10. Study of corneal epithelial progenitor origin and the Yap1 requirement using keratin 12 lineage tracing transgenic mice

    PubMed Central

    Kasetti, Ramesh Babu; Gaddipati, Subhash; Tian, Shifu; Xue, Lei; Kao, Winston W.-Y.; Lu, Qingxian; Li, Qiutang

    2016-01-01

    Key issues in corneal epithelium biology are the mechanism for corneal epithelium stem cells to maintain the corneal epithelial homeostasis and wound healing responses, and what are the regulatory molecular pathways involved. There are apparent discrepancies about the locations of the progenitor populations responsible for corneal epithelial self-renewal. We have developed a genetic mouse model to trace the corneal epithelial progenitor lineages during adult corneal epithelial homeostasis and wound healing response. Our data revealed that the early corneal epithelial progenitor cells expressing keratin-12 originated from limbus, and gave rise to the transit amplifying cells that migrated centripetally to differentiate into corneal epithelial cells. Our results support a model that both corneal epithelial homeostasis and wound healing are mainly maintained by the activated limbal stem cells originating form limbus, but not from the corneal basal epithelial layer. In the present study, we further demonstrated the nuclear expression of transcriptional coactivator YAP1 in the limbal and corneal basal epithelial cells and its essential role for maintaining the high proliferative potential of those corneal epithelial progenitor cells in vivo. PMID:27734924

  11. Parental Age Affects Somatic Mutation Rates in the Progeny of Flowering Plants1

    PubMed Central

    Singh, Amit Kumar; Bashir, Tufail; Sailer, Christian; Gurumoorthy, Viswanathan; Ramakrishnan, Anantha Maharasi; Dhanapal, Shanmuhapreya; Grossniklaus, Ueli; Baskar, Ramamurthy

    2015-01-01

    In humans, it is well known that the parental reproductive age has a strong influence on mutations transmitted to their progeny. Meiotic nondisjunction is known to increase in older mothers, and base substitutions tend to go up with paternal reproductive age. Hence, it is clear that the germinal mutation rates are a function of both maternal and paternal ages in humans. In contrast, it is unknown whether the parental reproductive age has an effect on somatic mutation rates in the progeny, because these are rare and difficult to detect. To address this question, we took advantage of the plant model system Arabidopsis (Arabidopsis thaliana), where mutation detector lines allow for an easy quantitation of somatic mutations, to test the effect of parental age on somatic mutation rates in the progeny. Although we found no significant effect of parental age on base substitutions, we found that frameshift mutations and transposition events increased in the progeny of older parents, an effect that is stronger through the maternal line. In contrast, intrachromosomal recombination events in the progeny decrease with the age of the parents in a parent-of-origin-dependent manner. Our results clearly show that parental reproductive age affects somatic mutation rates in the progeny and, thus, that some form of age-dependent information, which affects the frequency of double-strand breaks and possibly other processes involved in maintaining genome integrity, is transmitted through the gametes. PMID:25810093

  12. Selection of inbred maize (Zea mays L.) progenies by topcrosses conducted in contrasting environments.

    PubMed

    Rodrigues, C S; Pacheco, C A P; Guedes, M L; Pinho, R G V; Castro, C R

    2016-09-23

    The aim of this study was to identify inbred progenies of S0:1 maize (Zea mays L.) plants that were efficient at a low level of technology and responsive at a high level of technology through the use of topcrosses. Two contrasting environments were created using two levels of base fertilization and topdressing, so that the levels of nitrogen, phosphorus, and potassium were applied four times higher in one environment than in the other. We used S0:1 progenies derived from commercial hybrids in topcrosses with two testers (an elite line from the flint heterotic group and an elite line from the dent heterotic group). The progenies and three controls were evaluated in an augmented block design in Nossa Senhora das Dores, SE, Brazil in the 2010 crop season. The average grain yield in the high-technological level was 21.44% greater than that in the low-technological level. There were no changes in progeny behavior in the two technological levels for grain yield. The testers did not differ in the average grain yield of the progenies at the two technological levels. Therefore, it is possible to select progenies derived from commercial hybrids that have an efficient response to fertilization.

  13. Thoron ( 220Rn) progeny reduction by an air cleaner of the polarized media filter type

    NASA Astrophysics Data System (ADS)

    Bigu, J.

    1993-02-01

    The effect of an air cleaner on 220Rn progeny atmospheres has been studied in a Radon/Thoron Test Facility (RTTF) of the walk-in type. The air cleaner consists basically of a fan and a special filter material sandwiched between two metal screens, to which an electric field is applied. The filter is of the polarized media type and uses fibreglass as material. The fan and filter system are housed in a metal case. Air is drawn from the back of the case by means of the fan and forced through the "electrical" filter where removal of the 220Rn progeny occurs. Radon-220 progeny "depleted" air is discharged at the top of the device. Tests were conducted in 220Rn/ 220Rn progeny atmospheres when the air cleaner was operating, and when it was turned off. Very pronounced effects were observed during the operation of the device, namely: a dramatic decrease in the 220Rn progeny concentrations and the total aerosol concentration, as well as a large increase in the 220Rn progeny unattached fractions and the plate-out of these radionuclides on the walls of the RTTF. The air cleaner has potential in industrial applications, which should be explored.

  14. Evaluation of progenies from the fifth reciprocal recurrent selection cycle in maize.

    PubMed

    Alves, N B; Pádua, J M V; Dias, K O G; Diniz, R P; Guedes, M L; Cardoso, G A; Souza, J C

    2015-07-27

    The objective of this study was to evaluate the performance of 119 full sib progenies of the fifth cycle of reciprocal recurrent selection (RRS) derived from of Universidade Federal de Lavras maize breeding program. The experiment was carried out in an 11 x 11 triple lattice design at two locations (Lavras, Lambari). The plots consisted of two rows of 3 m, with four plants per 1 m and 0.60 meters of spacing between lines. The grain yield was obtained as kg/plot through weighing of husked ears. The contrast between progenies and controls was not significant, indicating there were no significant differences among the average grain yields of the progenies and controls. When considering the joint analysis, heritability was 64.2%; however, this estimate did not differ from the values estimated for each location separately. Estimates of genetic and phenotypic variance among progenies ranged from 0.21 to 0.28 and 0.30 to 0.47, respectively. Estimates of selection gain, for 10% selection intensity, indicated gains of 16% in the joint analysis of the two locations. The progenies of the fifth cycle of RRS had high average grain yield, associated with high variability. In comparison to the average grain yields exhibited by the controls, it was concluded that the progenies have the potential to be commercially exploited.

  15. Progenitor's Signatures in Type Ia Supernova Remnants

    NASA Astrophysics Data System (ADS)

    Chiotellis, A.; Kosenko, D.; Schure, K. M.; Vink, J.

    2013-01-01

    The remnants of Type Ia supernovae (SNe Ia) can provide important clues about their progenitor histories. We discuss two well-observed supernova remnants (SNRs) that are believed to have resulted from SNe Ia, and use various tools to shed light on the possible progenitor histories. We find that Kepler's SNR is consistent with a symbiotic binary progenitor consisting of a white dwarf and an AGB star. Our hydrosimulations can reproduce the observed kinematic and morphological properties. For Tycho's remnant we use the characteristics of the X-ray spectrum and kinematics to show that the ejecta has likely interacted with dense circumstellar gas.

  16. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

    PubMed

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

  17. Ezh2 represses the basal cell lineage during lung endoderm development.

    PubMed

    Snitow, Melinda E; Li, Shanru; Morley, Michael P; Rathi, Komal; Lu, Min Min; Kadzik, Rachel S; Stewart, Kathleen M; Morrisey, Edward E

    2015-01-01

    The development of the lung epithelium is regulated in a stepwise fashion to generate numerous differentiated and stem cell lineages in the adult lung. How these different lineages are generated in a spatially and temporally restricted fashion remains poorly understood, although epigenetic regulation probably plays an important role. We show that the Polycomb repressive complex 2 component Ezh2 is highly expressed in early lung development but is gradually downregulated by late gestation. Deletion of Ezh2 in early lung endoderm progenitors leads to the ectopic and premature appearance of Trp63+ basal cells that extend the entire length of the airway. Loss of Ezh2 also leads to reduced secretory cell differentiation. In their place, morphologically similar cells develop that express a subset of basal cell genes, including keratin 5, but no longer express high levels of either Trp63 or of standard secretory cell markers. This suggests that Ezh2 regulates the phenotypic switch between basal cells and secretory cells. Together, these findings show that Ezh2 restricts the basal cell lineage during normal lung endoderm development to allow the proper patterning of epithelial lineages during lung formation.

  18. Organic and inorganic selenium: III. Ewe and progeny performance.

    PubMed

    Stewart, W C; Bobe, G; Pirelli, G J; Mosher, W D; Hall, J A

    2012-12-01

    Selenium is an essential micronutrient in sheep, and deficiency can limit lamb growth and survival. To evaluate how different chemical forms of Se administered to mature ewes at comparative dosages affect ewe and progeny performance, 240 ewes were divided into 8 treatment groups (n = 30 each) and drenched weekly with no Se; at the maximum FDA-allowed concentration with inorganic Na-selenite or organic Se-yeast (4.9 mg Se/wk); with inorganic Na-selenate (8.95 mg Se/wk); or with inorganic Na-selenite and organic Se-yeast at supranutritional concentrations (14.7 and 24.5 mg Se/wk, respectively). The treatment period started approximately 2 wk before breeding and lasted for 62.5 wk. Ewes of the no-Se and Se-yeast groups continued treatments for another 21 to 24 wk through a second lambing season. Chemical form or dosage of Se did not affect ewe reproductive performance based on proportion of ewes lambing in each treatment group, or number of lambs born, nursed, or weaned per ewe (all P > 0.10). Ewes receiving the highest supplementation rate of Se-yeast at 24.5 mg Se/wk had higher BCS (scale 1 to 5) at the end of yr 1 (2.95 vs. 2.66; P = 0.05) than ewes receiving Se-yeast at 4.9 mg Se/wk. Performance was better in lambs from ewes receiving Se-yeast at 24.5 mg Se/wk than in lambs from ewes receiving Se-yeast at 4.9 mg Se/wk or no Se. In yr 1, lambs from ewes receiving Se-yeast at 24.5 vs. 4.9 mg Se/wk were heavier at 120 d of age (37.0 vs. 34.2 kg; P = 0.05). In yr 2, lambs from ewes receiving Se-yeast at 24.5 mg Se/wk were or tended to be heavier at 60 d of age than lambs from ewes receiving no Se (21.2 vs. 19.0 kg; P = 0.04) or lambs from ewes receiving Se-yeast at 4.9 mg Se/wk (19.2 kg; P = 0.09). This effect was more pronounced in ewes raising multiple lambs. We conclude that supranutritional supplementation of ewes with Se-yeast at 24.5 mg Se/wk improves lamb growth and ewe health without negatively affecting reproductive performance.

  19. Behavioral and neurobiological studies on the male progeny of maternal rats exposed to chronic unpredictable stress before pregnancy.

    PubMed

    Li, Haihong; Zhang, Lei; Fang, Zeman; Lin, Linyun; Wu, Cairu; Huang, Qingjun

    2010-01-22

    Studies have shown that maternal chronic stress or depression is linked to an increased risk for affective disorders in progeny. However, the impact of maternal chronic stress before pregnancy on their progeny in animal models has not been well studied. We investigated the behaviors and the neurobiology in 60-day-old male progeny of maternal rats exposed to a 21-day chronic unpredictable stress (CUS) before pregnancy, with male progeny of unstressed maternal rats as the control. Sucrose consumption test showed that both sucrose intake and sucrose consumption percentage of the CUS progeny were lower than those of the control progeny (P<0.05). The number of times crossing the removed hidden platform in the CUS progeny was significantly fewer than that in the control progeny in Morris water maze test (P<0.05). The level of 5-hydroxytryptamine (5-HT) in the hypothalamus was reduced but the level of norepinephrine (NE) in the hippocampus was increased in CUS progeny when compared to the control (P<0.05). Western blotting showed that the relative level of phosphorylated CREB (P-CREB) in the CUS progeny was lower than that in the control progeny (P<0.05). There were significant positive correlations between sucrose consumption percentage and the level of 5-HT in hypothalamus P<0.05) or the level of P-CREB in hippocampus (P<0.05). In conclusion, depression or stressful events before pregnancy was also associated with high risk of depression in progeny, and the down-regulation of P-CREB in the hippocampus might be one of the mechanisms underlying depression in the CUS progeny.

  20. Murine leukemia virus infects early bone marrow progenitors in immunocompetent mice.

    PubMed

    Tumas-Brundage, K M; Garret, W; Blank, K; Prystowsky, M B

    1996-10-15

    Chronic murine leukemia viruses (MuLVs) are retroviruses which induce leukemias/lymphomas after long latency periods. The induction of leukemia by MuLVs is complex, requiring multiple steps beginning with infection of an appropriate target cell. A number of investigators have proposed a bone marrow-thymus axis in the development of retrovirus induced T-cell lymphoma in which cells are initially infected in the bone marrow. These bone marrow cells or their progeny migrate to the thymus during the disease process. In our system using adult, immunocompetent BALB.K mice infected with E-55(+) MuLV, a similar pattern is seen; integrated virus is initially detectable in the bone marrow and spleen and only later in the thymus. In order to better understand the leukemic process, we analyzed the bone marrow from adult, immunocompetent BALB.K mice infected with the E-55(+) MuLV in bone marrow colony assays. The results from these assays demonstrate that either a pluripotent progenitor cell or an early progenitor cell is a target in the bone marrow for the virus.

  1. Circulating Vascular Progenitor Cells in Moyamoya Disease

    PubMed Central

    Kang, Hyun-Seung; Wang, Kyu-Chang

    2015-01-01

    Various approaches have been attempted in translational moyamoya disease research. One promising material for modeling and treating this disease is vascular progenitor cells, which can be acquired and expanded from patient peripheral blood. These cells may provide a novel experimental model and enable us to obtain insights regarding moyamoya disease pathogenesis. We briefly present the recent accomplishments in regard to the studies of vascular progenitor cells in moyamoya disease. PMID:26180610

  2. Metastatic Basal cell carcinoma accompanying gorlin syndrome.

    PubMed

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  3. The Basal Ganglia-Circa 1982

    NASA Technical Reports Server (NTRS)

    Mehler, William R.

    1981-01-01

    Our review has shown that recent studies with the new anterograde and retrograde axon transport methods have confirmed and extended our knowledge of the projection of the basal ganglia and clarified their sites of origin. They have thrown new light on certain topographic connectional relationships and revealed several new reciprocal connections between constituent nuclei of the basal ganglia. Similarly, attention has been drawn to the fact that there have also been many new histochemical techniques introduced in recent years that are now providing regional biochemical overlays for connectional maps of the central nervous system, especially regions in, or interconnecting with, the basal ganglia. However, although these new morphological biochemical maps are very complex and technically highly advanced, our understanding of the function controlled by the basal ganglia still remains primitive. The reader who is interested in some new ideas of the functional aspects of the basal ganglia is directed to Nauta's proposed conceptual reorganization of the basal ganglia telencephalon and to Marsden's more clinically orientated appraisal of the unsolved mysteries of the basal ganglia participation in the control of movement.

  4. Inhalation dose due to radon, thoron, and progenies in dwellings of a hill station.

    PubMed

    Sivakumar, R

    2017-02-01

    The general public spends a major portion of their time in an indoor environment and hence receives a considerable amount of radiation. Knowledge about indoor radiation is important in order to arrive at the actual effective dose received by residents. The indoor radon, thoron, and progeny concentrations observed in the present study were found to vary with seasons of a given year. The highest and lowest indoor average radon, thoron, and progeny levels were observed during winter and summer seasons, respectively. The concentrations of indoor radon, thoron, and progenies were found to vary with the type of houses. The highest (222)Rn, (220)Rn, and progeny concentrations were observed in mud houses and the lowest values were recorded in wooden houses. The indoor (222)Rn concentration correlated well with concentration of its grandparent (238)U in underlying soil with a correlation coefficient of 0.87. The correlation between indoor (220)Rn and (232)Th in the underlying soil was found to be 0.64. The estimated effective doses received by the general public in the present study due to indoor radon and thoron were 1.49 ± 0.49 and 1.30 ± 0.53 mSv/year, respectively. The annual effective doses due to radon and thoron progenies were estimated as 0.76 ± 0.27 and 0.47 ± 0.23 mSv/year, respectively. The contributions from (222)Rn, (220)Rn, and corresponding progenies to the annual effective doses received were 37, 32, 19, and 12%, respectively. The general public living in the study area receives an inhalation dose of 4.02 mSv/year due to indoor radon, thoron, and progenies, which were found to be less than the action limit of ICRP 2009.

  5. TBX1 regulates epithelial polarity and dynamic basal filopodia in the second heart field.

    PubMed

    Francou, Alexandre; Saint-Michel, Edouard; Mesbah, Karim; Kelly, Robert G

    2014-11-01

    Elongation of the vertebrate heart occurs by progressive addition of second heart field (SHF) cardiac progenitor cells from pharyngeal mesoderm to the poles of the heart tube. The importance of these cells in the etiology of congenital heart defects has led to extensive research into the regulation of SHF deployment by signaling pathways and transcription factors. However, the basic cellular features of these progenitor cells, including epithelial polarity, cell shape and cell dynamics, remain poorly characterized. Here, using immunofluorescence, live imaging and embryo culture, we demonstrate that SHF cells constitute an atypical, apicobasally polarized epithelium in the dorsal pericardial wall, characterized by apical monocilia and dynamic actin-rich basal filopodia. We identify the 22q11.2 deletion syndrome gene Tbx1, required in the SHF for outflow tract development, as a regulator of the epithelial properties of SHF cells. Cell shape changes in mutant embryos include increased circularity, a reduced basolateral membrane domain and impaired filopodial activity, and are associated with elevated aPKCζ levels. Activation of aPKCζ in embryo culture similarly impairs filopodia activity and phenocopies proliferative defects and ectopic differentiation observed in the SHF of Tbx1 null embryos. Our results reveal that epithelial and progenitor cell status are coupled in the SHF, identifying control of cell shape as a regulatory step in heart tube elongation and outflow tract morphogenesis.

  6. [Basal cell carcinoma with matrical differentiation].

    PubMed

    Goldman-Lévy, Gabrielle; Frouin, Eric; Soubeyran, Isabelle; Maury, Géraldine; Guillot, Bernard; Costes, Valérie

    2015-04-01

    Basal cell carcinoma with matrical differentiation is a very rare variant of basal cell carcinoma. To our knowledge, less than 30 cases have been reported. This tumor is composed of basaloid lobules showing a differentiation toward the pilar matrix cells. Recently, it has been demonstrated that beta-catenin would interfer with physiopathogenesis of matrical tumors, in particular pilomatricomas, but also basal cell carcinomas with matrical differentiation. This is a new case, with immunohistochemical and molecular analysis of beta-catenin, in order to explain its histogenesis.

  7. Potential for amelioration of aflatoxin B1-induced immunotoxic effects in progeny of White Leghorn breeder hens co-exposed to vitamin E.

    PubMed

    Khan, Wajid Arshad; Khan, Muhammad Zargham; Khan, Ahrar; Ul Hassan, Zahoor; Saleemi, Muhammad Kashif

    2014-01-01

    This study was designed to evaluate the protective activity of Vitamin E (Vit E) on the immunotoxic effects induced by aflatoxin B1 (AFB1) in the progeny of breeder hens. For this purpose, 192 White Leghorn (WL) layer breeder hens were divided into 12 groups (A-L) and then fed test diets for either 1, 2 or 3 weeks. Group A was kept on basal feed (2900 Kcal/kg metabolizable energy) and served as control, while group B was offered a feed supplemented with Vit E at 100 mg/Kg. Groups C-G were offered feed containing 0.1, 0.5, 2.5, 5.0, and 10.0 mg/Kg AFB1, respectively, whereas groups H-L were offered the same dietary levels of AFB1 along with 100 mg/Kg Vit E supplementation. Hatching eggs were shifted to an incubator on a weekly basis to get progeny chicks. Hatched chicks in each group were maintained on basal ration and then subjected to different immunological assays. Lymphoproliferative responses (against PHA-P), antibody titers (against SRBC), oxidative damage to RBC, as well as phagocytic and nitrite production potential of the peritoneal macrophages from the chicks, were all adversely impacted by hen exposure to the higher doses of AFB1 or by increased intake (time) by the hens at a given dose of the toxin. No consistent ameliorative effects from Vit E were noted in these studies, i.e. effects seen against lower AFB1 doses were no longer apparent with the highest doses of AFB1. As such, for now it can be concluded that, with this particular single dose level of Vit E, AFB1-associated immunotoxic effects in progeny chicks can potentially be mitigated by dietary intake of Vit E by their hen dams. However, this is clearly an outcome that is driven by the level of the mycotoxin present in the feed. Future studies need to examine what impact higher Vit E doses than those employed herein might have in these ameliorative outcomes.

  8. p130Cas alters the differentiation potential of mammary luminal progenitors by deregulating c-Kit activity.

    PubMed

    Tornillo, Giusy; Elia, Angela Rita; Castellano, Isabella; Spadaro, Michela; Bernabei, Paola; Bisaro, Brigitte; Camacho-Leal, Maria Del Pilar; Pincini, Alessandra; Provero, Paolo; Sapino, Anna; Turco, Emilia; Defilippi, Paola; Cabodi, Sara

    2013-07-01

    It has recently been proposed that defective differentiation of mammary luminal progenitors predisposes to basal-like breast cancer. However, the molecular and cellular mechanisms involved are still unclear. Here, we describe that the adaptor protein p130Cas is a crucial regulator of mouse mammary epithelial cell (MMEC) differentiation. Using a transgenic mouse model, we show that forced p130Cas overexpression in the luminal progenitor cell compartment results in the expansion of luminal cells, which aberrantly display basal cell features and reduced differentiation in response to lactogenic stimuli. Interestingly, MMECs overexpressing p130Cas exhibit hyperactivation of the tyrosine kinase receptor c-Kit. In addition, we demonstrate that the constitutive c-Kit activation alone mimics p130Cas overexpression, whereas c-Kit downregulation is sufficient to re-establish proper differentiation of p130Cas overexpressing cells. Overall, our data indicate that high levels of p130Cas, via abnormal c-Kit activation, promote mammary luminal cell plasticity, thus providing the conditions for the development of basal-like breast cancer. Consistently, p130Cas is overexpressed in human triple-negative breast cancer, further suggesting that p130Cas upregulation may be a priming event for the onset of basal-like breast cancer.

  9. alpha-Radiation dose at bronchial bifurcations of smokers from indoor exposure to radon progeny.

    PubMed Central

    Martell, E A

    1983-01-01

    Synergistic interactions of indoor radon progeny with the cigarette smoking process have been evaluated experimentally. Smoking enhances the air concentration of submicron particles and attached radon decay products. Fractionation in burning cigarettes gives rise to the association of radon progeny with large particles in mainstream cigarette smoke, which are selectively deposited in "hot spots" at bronchial bifurcations. Because smoke tars are resistant to dissolution in lung fluid, attached radon progeny undergo substantial radioactive decay at bifurcations before clearance. Radon progeny inhaled during normal breathing between cigarettes make an even larger contribution to the alpha-radiation dose at bifurcations. Progressive chemical and radiation damage to the epithelium at bifurcations gives rise to prolonged retention of insoluble 210Pb-enriched smoke particles produced by tobacco trichome combustion. The high incidence of lung cancer in cigarette smokers is attributed to the cumulative alpha-radiation dose at bifurcations from indoor radon and thoron progeny--218Po, 214Po, 212Po, and 212Bi--plus that from 210Po in 210Pb-enriched smoke particles. It is estimated that a carcinogenic alpha-radiation dose of 80-100 rads (1 rad = 0.01 J/kg = 0.01 Gy) is delivered to approximately equal to 10(7) cells (approximately equal to 10(6) cells at individual bifurcations) of most smokers who die of lung cancer. PMID:6572389

  10. Analyses of muscular dystrophy and Con A deficiency traits in testcross progeny of chickens.

    PubMed

    Kline, K; Sanders, B G

    1984-01-01

    Hereditary muscular dystrophic chickens of the Storrs strain possess two genetic disorders, muscular dystrophy (MD) and a deficient concanavalin A (Con A), a T-cell mitogen, mediated splenic lymphocyte blastogenic response. A possible amelioration of the MD phenotype in MD chickens expressing normal Con A was postulated on the basis of progeny segregating for these two traits in F2 genetic analyses. To test this possibility, testcross progeny were examined for segregation of MD and Con A deficiency traits, and for the degree of muscle destruction and Con A deficiency. The data show both traits to be inherited independently as autosomal recessive traits, and do not support any phenotypic modifications occurring in chickens expressing MD with normal Con A. In the testcross progeny, the Con A deficiency disorder is equally deficient in normal and MD progeny, and the degree of muscle destruction as measured by serum creatine phosphokinase levels is equally great in MD chickens with or without the Con A deficiency trait. The reduced numbers of MD chickens in the testcross progeny can be accounted for by chance and probably reflect losses during in ovo development.

  11. Mixed models for selection of Jatropha progenies with high adaptability and yield stability in Brazilian regions.

    PubMed

    Teodoro, P E; Bhering, L L; Costa, R D; Rocha, R B; Laviola, B G

    2016-08-19

    The aim of this study was to estimate genetic parameters via mixed models and simultaneously to select Jatropha progenies grown in three regions of Brazil that meet high adaptability and stability. From a previous phenotypic selection, three progeny tests were installed in 2008 in the municipalities of Planaltina-DF (Midwest), Nova Porteirinha-MG (Southeast), and Pelotas-RS (South). We evaluated 18 families of half-sib in a randomized block design with three replications. Genetic parameters were estimated using restricted maximum likelihood/best linear unbiased prediction. Selection was based on the harmonic mean of the relative performance of genetic values method in three strategies considering: 1) performance in each environment (with interaction effect); 2) performance in each environment (with interaction effect); and 3) simultaneous selection for grain yield, stability and adaptability. Accuracy obtained (91%) reveals excellent experimental quality and consequently safety and credibility in the selection of superior progenies for grain yield. The gain with the selection of the best five progenies was more than 20%, regardless of the selection strategy. Thus, based on the three selection strategies used in this study, the progenies 4, 11, and 3 (selected in all environments and the mean environment and by adaptability and phenotypic stability methods) are the most suitable for growing in the three regions evaluated.

  12. Dose estimation derived from the exposure to radon, thoron and their progeny in the indoor environment

    PubMed Central

    Ramola, R. C.; Prasad, Mukesh; Kandari, Tushar; Pant, Preeti; Bossew, Peter; Mishra, Rosaline; Tokonami, S.

    2016-01-01

    The annual exposure to indoor radon, thoron and their progeny imparts a major contribution to inhalation doses received by the public. In this study, we report results of time integrated passive measurements of indoor radon, thoron and their progeny concentrations that were carried out in Garhwal Himalaya with the aim of investigating significant health risk to the dwellers in the region. The measurements were performed using recently developed LR-115 detector based techniques. The experimentally determined values of radon, thoron and their progeny concentrations were used to estimate total annual inhalation dose and annual effective doses. The equilibrium factors for radon and thoron were also determined from the observed data. The estimated value of total annual inhalation dose was found to be 1.8 ± 0.7 mSv/y. The estimated values of the annual effective dose were found to be 1.2 ± 0.5 mSv/y and 0.5 ± 0.3 mSv/y, respectively. The estimated values of radiation doses suggest no important health risk due to exposure of radon, thoron and progeny in the study area. The contribution of indoor thoron and its progeny to total inhalation dose ranges between 13–52% with mean value of 30%. Thus thoron cannot be neglected when assessing radiation doses. PMID:27499492

  13. Dose estimation derived from the exposure to radon, thoron and their progeny in the indoor environment

    NASA Astrophysics Data System (ADS)

    Ramola, R. C.; Prasad, Mukesh; Kandari, Tushar; Pant, Preeti; Bossew, Peter; Mishra, Rosaline; Tokonami, S.

    2016-08-01

    The annual exposure to indoor radon, thoron and their progeny imparts a major contribution to inhalation doses received by the public. In this study, we report results of time integrated passive measurements of indoor radon, thoron and their progeny concentrations that were carried out in Garhwal Himalaya with the aim of investigating significant health risk to the dwellers in the region. The measurements were performed using recently developed LR-115 detector based techniques. The experimentally determined values of radon, thoron and their progeny concentrations were used to estimate total annual inhalation dose and annual effective doses. The equilibrium factors for radon and thoron were also determined from the observed data. The estimated value of total annual inhalation dose was found to be 1.8 ± 0.7 mSv/y. The estimated values of the annual effective dose were found to be 1.2 ± 0.5 mSv/y and 0.5 ± 0.3 mSv/y, respectively. The estimated values of radiation doses suggest no important health risk due to exposure of radon, thoron and progeny in the study area. The contribution of indoor thoron and its progeny to total inhalation dose ranges between 13–52% with mean value of 30%. Thus thoron cannot be neglected when assessing radiation doses.

  14. Synaptic organisation of the basal ganglia

    PubMed Central

    BOLAM, J. P.; HANLEY, J. J.; BOOTH, P. A. C.; BEVAN, M. D.

    2000-01-01

    The basal ganglia are a group of subcortical nuclei involved in a variety of processes including motor, cognitive and mnemonic functions. One of their major roles is to integrate sensorimotor, associative and limbic information in the production of context-dependent behaviours. These roles are exemplified by the clinical manifestations of neurological disorders of the basal ganglia. Recent advances in many fields, including pharmacology, anatomy, physiology and pathophysiology have provided converging data that have led to unifying hypotheses concerning the functional organisation of the basal ganglia in health and disease. The major input to the basal ganglia is derived from the cerebral cortex. Virtually the whole of the cortical mantle projects in a topographic manner onto the striatum, this cortical information is ‘processed’ within the striatum and passed via the so-called direct and indirect pathways to the output nuclei of the basal ganglia, the internal segment of the globus pallidus and the substantia nigra pars reticulata. The basal ganglia influence behaviour by the projections of these output nuclei to the thalamus and thence back to the cortex, or to subcortical ‘premotor’ regions. Recent studies have demonstrated that the organisation of these pathways is more complex than previously suggested. Thus the cortical input to the basal ganglia, in addition to innervating the spiny projection neurons, also innervates GABA interneurons, which in turn provide a feed-forward inhibition of the spiny output neurons. Individual neurons of the globus pallidus innervate basal ganglia output nuclei as well as the subthalamic nucleus and substantia nigra pars compacta. About one quarter of them also innervate the striatum and are in a position to control the output of the striatum powerfully as they preferentially contact GABA interneurons. Neurons of the pallidal complex also provide an anatomical substrate, within the basal ganglia, for the synaptic

  15. Epidemiology of basal-like breast cancer.

    PubMed

    Millikan, Robert C; Newman, Beth; Tse, Chiu-Kit; Moorman, Patricia G; Conway, Kathleen; Dressler, Lynn G; Smith, Lisa V; Labbok, Miriam H; Geradts, Joseph; Bensen, Jeannette T; Jackson, Susan; Nyante, Sarah; Livasy, Chad; Carey, Lisa; Earp, H Shelton; Perou, Charles M

    2008-05-01

    Risk factors for the newly identified "intrinsic" breast cancer subtypes (luminal A, luminal B, basal-like and human epidermal growth factor receptor 2-positive/estrogen receptor-negative) were determined in the Carolina Breast Cancer Study, a population-based, case-control study of African-American and white women. Immunohistochemical markers were used to subtype 1,424 cases of invasive and in situ breast cancer, and case subtypes were compared to 2,022 controls. Luminal A, the most common subtype, exhibited risk factors typically reported for breast cancer in previous studies, including inverse associations for increased parity and younger age at first full-term pregnancy. Basal-like cases exhibited several associations that were opposite to those observed for luminal A, including increased risk for parity and younger age at first term full-term pregnancy. Longer duration breastfeeding, increasing number of children breastfed, and increasing number of months breastfeeding per child were each associated with reduced risk of basal-like breast cancer, but not luminal A. Women with multiple live births who did not breastfeed and women who used medications to suppress lactation were at increased risk of basal-like, but not luminal A, breast cancer. Elevated waist-hip ratio was associated with increased risk of luminal A in postmenopausal women, and increased risk of basal-like breast cancer in pre- and postmenopausal women. The prevalence of basal-like breast cancer was highest among premenopausal African-American women, who also showed the highest prevalence of basal-like risk factors. Among younger African-American women, we estimate that up to 68% of basal-like breast cancer could be prevented by promoting breastfeeding and reducing abdominal adiposity.

  16. Neural Progenitors Adopt Specific Identities by Directly Repressing All Alternative Progenitor Transcriptional Programs.

    PubMed

    Kutejova, Eva; Sasai, Noriaki; Shah, Ankita; Gouti, Mina; Briscoe, James

    2016-03-21

    In the vertebrate neural tube, a morphogen-induced transcriptional network produces multiple molecularly distinct progenitor domains, each generating different neuronal subtypes. Using an in vitro differentiation system, we defined gene expression signatures of distinct progenitor populations and identified direct gene-regulatory inputs corresponding to locations of specific transcription factor binding. Combined with targeted perturbations of the network, this revealed a mechanism in which a progenitor identity is installed by active repression of the entire transcriptional programs of other neural progenitor fates. In the ventral neural tube, sonic hedgehog (Shh) signaling, together with broadly expressed transcriptional activators, concurrently activates the gene expression programs of several domains. The specific outcome is selected by repressive input provided by Shh-induced transcription factors that act as the key nodes in the network, enabling progenitors to adopt a single definitive identity from several initially permitted options. Together, the data suggest design principles relevant to many developing tissues.

  17. Immunomodulation in progeny from thymectomized primiparous mice exposed to benzo(a)pyrene during mid-pregnancy.

    PubMed

    Wolisi, G O; Majekodunmi, J; Bailey, G B; Urso, P

    2001-05-01

    Previous studies have shown that Benzo(a)pyrene (B(a)P3) given to non-thymectomized (NTX) female mice alters expression of T cell subsets and suppresses cell mediated immunity (CMI) and humoral immunity (HI) in the progeny. Thus, maternal exposure to B(a)P may influence changes in progeny immune status. To understand how maternal cellular and humoral factors influence embryonic development of progeny immunity, adult female mice were thymectomized (TX) at 6 weeks, mated and injected with 150 microg B(a)P)/g body weight at 12 days of pregnancy. After B(a)P exposure, the following studies were performed: (A) Maternal reproductive capacity and survival rate of progeny; (B) Detection of T cells in progeny thymus; (C) Functional characteristics of progeny thymus or spleen. Maternal thymectomy and B(a)P exposure reduced average litter size by 40%. Serological sensitivity of thymus cells with anti-Thyl + complement occurred at a higher dilution of mAb in progeny from TX mothers exposed to B(a)P, suggesting that B(a)P-thymectomy led to increased sensitivity of developing thymocytes to mAb plus complement. Progeny from TX mothers exposed to B(a)P showed enhanced thymic CMI, but suppressed splenic CMI and HI. Thus, thymectomy prevents CMI immunosuppression by B(a)P, while HI is still suppressed. These results indicate that the maternal thymus is necessary for incurring the effect of B(a)P on progeny CMI.

  18. Identification of a locus in arabidopsis controlling both the expression of rhizobacteria-mediated induced systemic resistance (ISR) and basal resistance against Pseudomonas syringae pv. tomato.

    PubMed

    Ton, J; Pieterse, C M; Van Loon, L C

    1999-10-01

    Selected nonpathogenic rhizobacteria with biological disease control activity are able to elicit an induced systemic resistance (ISR) response that is phenotypically similar to pathogen-induced systemic acquired resistance (SAR). Ten ecotypes of Arabidopsis thaliana were screened for their potential to express rhizobacteria-mediated ISR and pathogen-induced SAR against the leaf pathogen Pseudomonas syringae pv. tomato DC3000 (Pst). All ecotypes expressed SAR. However, of the 10 ecotypes tested, ecotypes RLD and Wassilewskija (Ws) did not develop ISR after treatment of the roots with nonpathogenic Pseudomonas fluorescens WCS417r bacteria. This nonresponsive phenotype was associated with relatively high susceptibility to Pst infection. The F1 progeny of crosses between the non-responsive ecotypes RLD and Ws on the one hand, and the responsive ecotypes Columbia (Col) and Landsberg erecta (Ler) on the other hand, were fully capable of expressing ISR and exhibited a relatively high level of basal resistance, similar to that of their WCS417r-responsive parent. This indicates that the potential to express ISR and the relatively high level of basal resistance against Pst are both inherited as dominant traits. Analysis of the F2 and F3 progeny of a Col x RLD cross revealed that inducibility of ISR and relatively high basal resistance against Pst cosegregate in a 3:1 fashion, suggesting that both resistance mechanisms are monogenically determined and genetically linked. Neither the responsiveness to WCS417r nor the relatively high level of basal resistance against Pst were complemented in the F1 progeny of crosses between RLD and Ws, indicating that RLD and Ws are both affected in the same locus, necessary for the expression of ISR and basal resistance against Pst. The corresponding locus, designated ISR1, was mapped between markers B4 and GL1 on chromosome 3. The observed association between ISR and basal resistance against Pst suggests that rhizobacteria-mediated ISR

  19. Study of the atmospheric chemistry of radon progeny in laboratory and real indoor atmospheres

    SciTech Connect

    Hopke, P.K.

    1992-07-01

    This report covers the second year of the 28 month grant current grant to Clarkson University to study the chemical and physical behavior of the polonium 218 atom immediately following its formation by the alpha decay of radon. Because small changes in size for activity result in large changes in the delivered dose per unit exposure, this behavior must be understood if the exposure to radon progeny and it dose to the cells in the respiratory tract are to be fully assessed. Two areas of radon progeny behavior are being pursued; laboratory studies under controlled conditions to better understand the fundamental physical and chemical process that affect the progeny's atmospheric behavior and studies in actual indoor environments to develop a better assessment of the exposure of the occupants of that space to the size and concentration of the indoor radioactive aerosol. This report describes the progress toward achieving these objectives.

  20. Comparative study of various techniques for environmental radon, thoron and progeny measurements.

    PubMed

    Ramola, R C; Prasad, Mukesh; Rawat, Mukesh; Dangwal, Anoop; Gusain, G S; Mishra, Rosaline; Sahoo, S K; Tokonami, S

    2015-11-01

    Long-term average concentrations of radon, thoron and progeny were measured in normal and high background radiation areas in India using different techniques. Radon, thoron and progeny concentrations were measured using Raduet, Pin-Hole dosimeter, deposition-based CR-39 and deposition-based direct radon/thoron progeny sensor (DRPS/DTPS) detector system. All these techniques were used at a same time inside an individual dwelling. Radon concentration was recorded higher than thoron concentration in Garhwal Homes (NBRA) while thoron concentration was found relatively higher in the houses of Chhatarpur area (HBRA) in Odisha, India. The values measured with the CR-39 detector-based technique were found comparable with the values measured with the LR-115 detector-based technique. The comparisons of results using various techniques and their usefulness in radiation measurements are discussed in detail.

  1. Fast determination of radon progeny concentrations. Report No. MRL 90-142(TR)

    SciTech Connect

    Bigu, J.; Edwardson, E.

    1990-01-01

    A technical evaluation of four Rn222 progeny measuring instruments (the Pylon WL-1000C, the MDA IWLM-811, the MIMIL IIM, and the EDA WLM-30) was conducted under laboratory controlled conditions and at several locations in an underground uranium mine. The laboratory evaluation consisted of a thorough study of the behaviour and performance of the instruments under a wide variety of environmental conditions, such as Rn222 gas concentration, Rn222 progeny concentration, temperature, relative humidity, aerosol concentration, and gamma-field exposure. The readings of the instruments were compared with the Thomas-Tsivoglou method, a widely accepted Rn222 progeny concentration measuring method. The instruments were rated according to accuracy, convenience of use, reliability, and ease of operation.

  2. AFLP marking and polymorphism among progenies of Gymnema sylvestre: an important medicinal plant of India.

    PubMed

    Osman, Magda Abbaker; Dhawan, Sunita Singh; Bahl, Janak Raj; Darokar, Mahendra P; Khanuja, Suman P S

    2011-11-01

    The level of polymorphism among twelve selected progenies of Gymnema sylvestre was investigated through AFLP markers by multiplexing PCR reactions using 64 (8x8) primer combinations. Fourteen primer combinations were selected as the most suitable combination for G. sylvestre. Analysis of the 12 progenies with these 14 primer pairs produced 1689 fragments of which 972 (57.5%) were polymorphic and 485 (28.7%) were unique to a particular genotype. The number of fragments produced by individual primer pairs was in the range of 55 to 225. Out of these, polymorphic fragments were in the range of 34 (E-ACC/M-CAC) to 157 (E-AGG/M-CAG) and unique bands observed were 8 (E-ACC / M-CAC) to 69 (E-AGG/M-CAC). Different primer combinations detected different levels of polymorphism, ranging from 33% (E-AGG/ M-CAC) to 69.8% (E-AGG/ M-CAC). From the observations, it appears that the primer combinations E-AGG/M-CAC, E-AGG/CTG, E-AGG/CAG and E-ACA/CAT were the most informative for the detection of polymorphism among the progenies compared with others, since they produced a high number of unique fragments. The similarity coefficient ranged from 0.212 to 0.731. High similarity was observed between progeny S8 and S9 (73%) and high divergence between progenies S3 and S11. Among the selected progeny, S9 was found to be the most similar to the parent (63%), while genotype S11 was the most distant (36.9%).

  3. STELLAR BINARY COMPANIONS TO SUPERNOVA PROGENITORS

    SciTech Connect

    Kochanek, Christopher S.

    2009-12-20

    For typical models of binary statistics, 50%-80% of core-collapse supernova (ccSN) progenitors are members of a stellar binary at the time of the explosion. Independent of any consequences of mass transfer, this has observational consequences that can be used to study the binary properties of massive stars. In particular, the secondary companion to the progenitor of a Type Ib/c SN is frequently (approx50%) the more optically luminous star since the high effective temperatures of the stripped progenitors make it relatively easy for a lower luminosity, cooler secondary to emit more optical light. Secondaries to the lower mass progenitors of Type II SN will frequently produce excess blue emission relative to the spectral energy distribution of the red primary. Available data constrain the models weakly. Any detected secondaries also provide an independent lower bound on the progenitor mass and, for historical SN, show that it was not a Type Ia event. Bright ccSN secondaries have an unambiguous, post-explosion observational signature-strong, blueshifted, relatively broad absorption lines created by the developing SN remnant (SNR). These can be used to locate historical SN with bright secondaries, confirm that a source is a secondary, and, potentially, measure abundances of ccSN ejecta. Luminous, hot secondaries will re-ionize the SNR on timescales of 100-1000 yr that are faster than re-ionization by the reverse shock, creating peculiar H II regions due to the high metallicity and velocities of the ejecta.

  4. Hematopoietic stem cells and progenitors of chronic myeloid leukemia express leukemia-associated antigens: implications for the graft-versus-leukemia effect and peptide vaccine-based immunotherapy

    PubMed Central

    Yong, Agnes S. M.; Keyvanfar, Keyvan; Eniafe, Rhoda; Savani, Bipin N.; Rezvani, Katayoun; Sloand, Elaine M.; Goldman, John M.; Barrett, A. John

    2008-01-01

    The cure of chronic myeloid leukemia (CML) patients following allogeneic stem cell transplantation (SCT) is attributed to graft-versus-leukemia (GVL) effects targeting alloantigens and/or leukemia-associated antigens (LAA) on leukemia cells. To assess the potential of LAA-peptide vaccines in eliminating leukemia in CML patients, we measured WT1, PR3, ELA2 and PRAME expression in CD34+ progenitor subpopulations in CML patients and compared them with minor histocompatibility antigens (mHAgs) HA1 and SMCY. All CD34+ subpopulations expressed similar levels of mHAgs irrespective of disease phase, suggesting that in the SCT setting, mHAgs are the best target for GVL. Furthermore, WT1 was consistently overexpressed in advanced phase (AdP) CML in all CD34+ subpopulations, and mature progenitors of chronic phase (CP) CML compared to healthy individuals. PRAME overexpression was limited to more mature AdP-CML progenitors only. Conversely, only CP-CML progenitors had PR3 overexpression, suggesting that PR1-peptide vaccines are only appropriate in CP-CML. Surface expression of WT1 protein in the most primitive hematopoietic stem cells in AdP-CML suggest that they could be targets for WT1 peptide-based vaccines, which in combination with PRAME, could additionally improve targeting differentiated progeny, and benefit patients responding suboptimally to tyrosine kinase inhibitors, or enhance GVL effects in SCT patients. PMID:18548092

  5. A family business: stem cell progeny join the niche to regulate homeostasis.

    PubMed

    Hsu, Ya-Chieh; Fuchs, Elaine

    2012-01-23

    Stem cell niches, the discrete microenvironments in which the stem cells reside, play a dominant part in regulating stem cell activity and behaviours. Recent studies suggest that committed stem cell progeny become indispensable components of the niche in a wide range of stem cell systems. These unexpected niche inhabitants provide versatile feedback signals to their stem cell parents. Together with other heterologous cell types that constitute the niche, they contribute to the dynamics of the microenvironment. As progeny are often located in close proximity to stem cell niches, similar feedback regulations may be the underlying principles shared by different stem cell systems.

  6. Radon, thoron and their progeny levels in some dwellings of northern Haryana, India using SSNTDs

    NASA Astrophysics Data System (ADS)

    Saini, R. S.; Nain, Mahabir; Chauhan, R. P.; Kishore, Nawal; Chakarvarti, S. K.

    2009-08-01

    Radon pollution is an important global problem of radiation hygiene. Radon and its progeny are the major contributors in the radiation dose received by general population of the world. Keeping this in mind the environmental monitoring of radon, thoron and their progeny in some dwellings of northern part of Haryana state of India has been carried out. The radon-thoron twin dosimeter cups were used for the study. The aim of the study is the possible health risk assessment in the dwellings under consideration.

  7. Neurobehavioral Effects of Sodium Tungstate Exposure on Rats and Their Progeny

    DTIC Science & Technology

    2007-06-30

    Neurobehavioral Effects of Sodium Tungstate Expo sure on Rats and Their Progeny S.M. McInturf ALYNV. Bekkedal A. Olabisi D. Arfsten E. Wilfong IL...20071116226 Neurobehavioral Effects of Sodium Tungstate Exposure on Rats and. Their Progeny S.M. McInturf M.Y.V. Bekkedal A. Olabisi D. Arfsten E...days of daily tungsten exposure via drinking water. Sprague-Dawley rats were orally dosed with diH20 vehicle, 5 or 125 mg/kg/day of sodium tungstate for

  8. Neuropeptides: developmental signals in placode progenitor formation.

    PubMed

    Lleras-Forero, Laura; Tambalo, Monica; Christophorou, Nicolas; Chambers, David; Houart, Corinne; Streit, Andrea

    2013-07-29

    Few families of signaling factors have been implicated in the control of development. Here, we identify the neuropeptides nociceptin and somatostatin, a neurotransmitter and neuroendocrine hormone, as a class of developmental signals in both chick and zebrafish. We show that signals from the anterior mesendoderm are required for the formation of anterior placode progenitors, with one of the signals being somatostatin. Somatostatin controls ectodermal expression of nociceptin, and both peptides regulate Pax6 in lens and olfactory progenitors. Consequently, loss of somatostatin and nociceptin signaling leads to severe reduction of lens formation. Our findings not only uncover these neuropeptides as developmental signals but also identify a long-sought-after mechanism that initiates Pax6 in placode progenitors and may explain the ancient evolutionary origin of neuropeptides, predating a complex nervous system.

  9. Endothelial progenitor cells in cardiovascular diseases

    PubMed Central

    Lee, Poay Sian Sabrina; Poh, Kian Keong

    2014-01-01

    Endothelial dysfunction has been associated with the development of atherosclerosis and cardiovascular diseases. Adult endothelial progenitor cells (EPCs) are derived from hematopoietic stem cells and are capable of forming new blood vessels through a process of vasculogenesis. There are studies which report correlations between circulating EPCs and cardiovascular risk factors. There are also studies on how pharmacotherapies may influence levels of circulating EPCs. In this review, we discuss the potential role of endothelial progenitor cells as both diagnostic and prognostic biomarkers. In addition, we look at the interaction between cardiovascular pharmacotherapies and endothelial progenitor cells. We also discuss how EPCs can be used directly and indirectly as a therapeutic agent. Finally, we evaluate the challenges facing EPC research and how these may be overcome. PMID:25126384

  10. Disruption of cell-matrix interactions by heparin enhances mesenchymal progenitor adipocyte differentiation

    SciTech Connect

    Luo Weijun; Shitaye, Hailu; Friedman, Michael; Bennett, Christina N.; Miller, Joshua; MacDougald, Ormond A.; Hankenson, Kurt D.

    2008-11-01

    Differentiation of marrow-derived mesenchymal progenitors to either the osteoblast or adipocyte lineage is reciprocally regulated. Factors that promote osteoblastogenesis inhibit adipogenesis, while adipogenic factors are inhibitory to osteoblast differentiation. Heparin, a soluble glycosaminoglycan, inhibits bone formation in vivo and osteoblast cell differentiation and function in vitro, and has been shown to promote adipocyte differentiation. To elucidate the role that heparin plays in the adipogenic induction of murine mesenchymal progenitors, we studied immortalized marrow stromal cells (IM-MSC), the MSC cell line, ST2, and 3T3L1 pre-adipocytes. Heparin alone was not sufficient to induce adipogenesis, but enhanced the induction under a variety of adipogenic cocktails. This effect was both dose- and time-dependent. Heparin showed a positive effect at concentrations > 0. 1 {mu}g/ml when applied before day 3 during the induction course. Heparin's effect on adipogenesis was independent of cell proliferation, cell density, and extracellular lipid. This effect is likely related to the unique structure of heparin because another polyanionic glycosaminoglycan, dextran sulfate, did not promote adipogenic differentiation. Heparin treatment altered morphology and adhesion characteristics of progenitor cells, resulting in cell rounding and aggregation. As well, heparin counteracted the known inhibitory effect of fibronectin on adipogenesis and decreased basal focal adhesion kinase and paxillin phosphorylation. We conclude that heparin-mediated disruption of cell-matrix adhesion enhances adipogenic potential.

  11. Laminin regulates postnatal oligodendrocyte production by promoting oligodendrocyte progenitor survival in the subventricular zone.

    PubMed

    Relucio, Jenne; Menezes, Michael J; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi; Colognato, Holly

    2012-10-01

    The laminin family of extracellular matrix proteins are expressed broadly during embryonic brain development, but are enriched at ventricular and pial surfaces where laminins mediate radial glial attachment during corticogenesis. In the adult brain, however, laminin distribution is restricted, yet is found within the vascular basal lamina and associated fractones of the ventricular zone (VZ)-subventricular zone (SVZ) stem cell niche, where laminins regulate adult neural progenitor cell proliferation. It remains unknown, however, if laminins regulate the wave of oligodendrogenesis that occurs in the neonatal/early postnatal VZ-SVZ. Here we report that Lama2, the gene that encodes the laminin α2-subunit, regulates postnatal oligodendrogenesis. At birth, Lama2-/- mice had significantly higher levels of dying oligodendrocyte progenitor cells (OPCs) in the OPC germinal zone of the dorsal SVZ. This translated into fewer OPCs, both in the dorsal SVZ well as in an adjacent developing white matter tract, the corpus callosum. In addition, intermediate progenitor cells that give rise to OPCs in the Lama2-/- VZ-SVZ were mislocalized and proliferated nearer to the ventricle surface. Later, delays in oligodendrocyte maturation (with accompanying OPC accumulation), were observed in the Lama2-/- corpus callosum, leading to dysmyelination by postnatal day 21. Together these data suggest that prosurvival laminin interactions in the developing postnatal VZ-SVZ germinal zone regulate the ability, or timing, of oligodendrocyte production to occur appropriately.

  12. Extrastriatal Dopaminergic Circuits of the Basal Ganglia

    PubMed Central

    Rommelfanger, Karen S.; Wichmann, Thomas

    2010-01-01

    The basal ganglia are comprised of the striatum, the external and internal segment of the globus pallidus (GPe and GPi, respectively), the subthalamic nucleus (STN), and the substantia nigra pars compacta and reticulata (SNc and SNr, respectively). Dopamine has long been identified as an important modulator of basal ganglia function in the striatum, and disturbances of striatal dopaminergic transmission have been implicated in diseases such as Parkinson's disease (PD), addiction and attention deficit hyperactivity disorder. However, recent evidence suggests that dopamine may also modulate basal ganglia function at sites outside of the striatum, and that changes in dopaminergic transmission at these sites may contribute to the symptoms of PD and other neuropsychiatric disorders. This review summarizes the current knowledge of the anatomy, functional effects and behavioral consequences of the dopaminergic innervation to the GPe, GPi, STN, and SNr. Further insights into the dopaminergic modulation of basal ganglia function at extrastriatal sites may provide us with opportunities to develop new and more specific strategies for treating disorders of basal ganglia dysfunction. PMID:21103009

  13. Animal models relevant to human prostate carcinogenesis underlining the critical implication of prostatic stem/progenitor cells

    PubMed Central

    Mimeault, Murielle; Batra, Surinder K.

    2012-01-01

    Recent development of animal models relevant to human prostate cancer (PC) etiopathogenesis has provided important information on the specific functions provided by key gene products altered during disease initiation and progression to locally invasive, metastatic and hormone-refractory stages. Especially, the characterization of transgenic mouse models has indicated that the inactivation of distinct tumor suppressor proteins such as phosphatase tensin homolog deleted on chromosome 10 (PTEN), Nkx3.1, p27KIP1 and p53 and retinoblastoma (pRb) may cooperate for the malignant transformation of prostatic stem/progenitor cells into PC stem/progenitor cells and tumor development and metastases. Moreover, the sustained activation of diverse oncogenic signaling elements, including epidermal growth factor receptor (EGFR), sonic hedgehog, Wnt/β-catenin, c-Myc, Akt and nuclear factor-kappaB (NF-κB) also may contribute to the acquisition of more aggressive and hormone-refractory phenotypes by PC stem/progenitor cells and their progenies during disease progression. Importantly, it has also been shown that an enrichment of PC stem/progenitor cells expressing stem cell-like markers may occur after androgen deprivation therapy and docetaxel treatment in the transgenic mouse models of PC suggesting the critical implication of these immature PC cells in treatment resistance, tumor re-growth and disease recurrence. Of clinical interest, the molecular targeting of distinct gene products altered in PC cells by using different dietary compounds has also been shown to counteract PC initiation and progression in animal models supporting their potential use as chemopreventive or chemotherapeutic agents for eradicating the total tumor cell mass, improving current anti-hormonal and chemotherapies and preventing disease relapse. PMID:21396984

  14. GRHL2 coordinates regeneration of a polarized mucociliary epithelium from basal stem cells

    PubMed Central

    Gao, Xia; Bali, Aman S.; Randell, Scott H.

    2015-01-01

    Pseudostratified airway epithelium of the lung is composed of polarized ciliated and secretory cells maintained by basal stem/progenitor cells. An important question is how lineage choice and differentiation are coordinated with apical–basal polarity and epithelial morphogenesis. Our previous studies indicated a key integrative role for the transcription factor Grainyhead-like 2 (Grhl2). In this study, we present further evidence for this model using conditional gene deletion during the regeneration of airway epithelium and clonal organoid culture. We also use CRISPR/Cas9 genome editing in primary human basal cells differentiating into organoids and mucociliary epithelium in vitro. Loss of Grhl2 inhibits organoid morphogenesis and the differentiation of ciliated cells and reduces the expression of both notch and ciliogenesis genes (Mcidas, Rfx2, and Myb) with distinct Grhl2 regulatory sites. The genome editing of other putative target genes reveals roles for zinc finger transcription factor Znf750 and small membrane adhesion glycoprotein in promoting ciliogenesis and barrier function as part of a network of genes coordinately regulated by Grhl2. PMID:26527742

  15. GRHL2 coordinates regeneration of a polarized mucociliary epithelium from basal stem cells.

    PubMed

    Gao, Xia; Bali, Aman S; Randell, Scott H; Hogan, Brigid L M

    2015-11-09

    Pseudostratified airway epithelium of the lung is composed of polarized ciliated and secretory cells maintained by basal stem/progenitor cells. An important question is how lineage choice and differentiation are coordinated with apical-basal polarity and epithelial morphogenesis. Our previous studies indicated a key integrative role for the transcription factor Grainyhead-like 2 (Grhl2). In this study, we present further evidence for this model using conditional gene deletion during the regeneration of airway epithelium and clonal organoid culture. We also use CRISPR/Cas9 genome editing in primary human basal cells differentiating into organoids and mucociliary epithelium in vitro. Loss of Grhl2 inhibits organoid morphogenesis and the differentiation of ciliated cells and reduces the expression of both notch and ciliogenesis genes (Mcidas, Rfx2, and Myb) with distinct Grhl2 regulatory sites. The genome editing of other putative target genes reveals roles for zinc finger transcription factor Znf750 and small membrane adhesion glycoprotein in promoting ciliogenesis and barrier function as part of a network of genes coordinately regulated by Grhl2.

  16. Identification of triple-negative and basal-like canine mammary carcinomas using four basal markers.

    PubMed

    Kim, N H; Lim, H Y; Im, K S; Kim, J H; Sur, J-H

    2013-05-01

    Molecular-based classification of canine mammary carcinomas (CMCs) has been a recent research focus. In human breast cancer, triple-negative and basal-like phenotypes are distinct molecular subgroups that are known for their poor prognosis, but these tumours are not yet well defined in the dog. The aim of this study was to determine whether CMCs include triple-negative and basal-like phenotypes by immunohistochemical assessment of expression of the oestrogen receptor (OR), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and four basal markers, cytokeratin (CK) 14, CK5/6, p63 and the epidermal growth factor receptor (EGFR). In this study of 241 CMCs, 45 triple-negative tumours (OR(-), PR(-) and HER2(-)) were identified and this phenotype was associated with an unfavourable prognosis. In these tumours, the expression of CK14, CK5/6 and EGFR was related to clinicopathological parameters, while the expression of p63 was not relevant. The majority of the triple-negative tumours were of the basal-like phenotype, given that 75.6% of them expressed more than two basal markers. However, three of the basal markers were not uniformly expressed; therefore, the proportion of the basal-like phenotype was altered on the basis of the selection of the markers. Although both triple-negative and basal-like phenotypes are distinct entities in CMC, further study is needed to differentiate one from the other.

  17. Basal Forebrain Cholinergic System and Memory.

    PubMed

    Blake, M G; Boccia, M M

    2017-02-18

    Basal forebrain cholinergic neurons constitute a way station for many ascending and descending pathways. These cholinergic neurons have a role in eliciting cortical activation and arousal. It is well established that they are mainly involved in cognitive processes requiring increased levels of arousal, attentive states and/or cortical activation with desynchronized activity in the EEG. These cholinergic neurons are modulated by several afferents of different neurotransmitter systems. Of particular importance within the cortical targets of basal forebrain neurons is the hippocampal cortex. The septohippocampal pathway is a bidirectional pathway constituting the main septal efferent system, which is widely known to be implicated in every memory process investigated. The present work aims to review the main neurotransmitter systems involved in modulating cognitive processes related to learning and memory through modulation of basal forebrain neurons.

  18. Basal cell carcinoma of the nail unit.

    PubMed

    Forman, Seth B; Ferringer, Tammie C; Garrett, Algin B

    2007-05-01

    We report a case of a 70-year-old white male with a basal cell carcinoma of the left thumb nail unit. Excision of the tumor via Mohs micrographic surgery was completed in 2 stages. The defect was repaired with a full thickness skin graft. Five months later the nail unit healed without complications. Prior to this report, 21 cases of basal cell carcinoma have been reported in the world literature. This case, as well as the prior reports, are reviewed with a focus on time to diagnosis, location, excisional technique, and method of repair.

  19. Development of calibration facility for radon and its progenies at NIM (China).

    PubMed

    Liang, J C; Zheng, P H; Yang, Z J; Liu, H R; Zhang, M; Li, Z S; Zhang, L; Guo, Q J

    2015-11-01

    Accurate measurement of radon and its progenies is the basis to control the radon dose and reduce the risk of lung cancer caused. The precise calibration of measuring instrument is an important part of the quality control of measurements of the concentration of radon and radon progenies. To establish Chinese national standards and realise reliable calibrations of measuring instrument for radon and its progenies, a radon chamber with regulation capability of environmental parameters, aerosol and radon concentrations was designed and constructed at National Institute of Metrology (NIM). The chamber has a total volume of ∼20 m(3) including an exposure volume of 12.44 m(3). The radon concentration can be controlled from 12 Bq m(-3) to the maximum of 232 kBq m(-3). The regulation range of temperature, relative humidity and aerosol are 0.66 -44.39°C, 16.4 -95 %RH and 10(2) -10(6) cm(-3), respectively. The main advantages of the NIM radon chamber with respect to maintaining a stable concentration and equilibrium factor of radon progenies in a wide range through automatic regulation and control of radon and aerosol are described.

  20. Indoor radon progeny aerosol size measurements in urban, suburban, and rural regions

    SciTech Connect

    Tu, K.W.; Knutson, E.O.; George, A.C. )

    1991-01-01

    By using direct and indirect methods, the authors conducted size distribution measurements of radon progeny particles in a variety of indoor environments in urban, suburban, and rural areas. The radon progeny particle size distribution owing to indoor activities has two definable source categories: (1) gas combustion from stoves and kerosene heaters - particles were found to be smaller than 0.1 {mu}m in diameter, mostly in the range 0.02-0.08 {mu}m; and (2) cigarette smoking and food frying - particles were found to be larger, in the size range 0.1-0.2 {mu}m. The radon progeny particle size distribution, without significant indoor activities, such as cooking, was found to be larger in rural areas than in urban or suburban areas. The modal diameters of the size spectra in the rural areas were two to three times larger than those in urban or suburban areas, around 0.3-0.4 bs. 0.1-0.2 {mu}m. Results obtained by applying the attachment theory to the measured number-weighted size spectra from an electrical aerosol size analyzer support this finding. These results, if confirmed by more extensive studies, will be useful for the assessment of the risk from the inhalation of radon progeny in various indoor environments.

  1. Progeny Review: An Alternative Approach for Examining the Replication of Intervention Studies in Special Education

    ERIC Educational Resources Information Center

    Therrien, William J.; Mathews, Hannah M.; Hirsch, Shanna Eisner; Solis, Michael

    2016-01-01

    Despite the importance of replication for building an evidence base, there has been no formal examination to date of replication research in special education. In this review, we examined the extent and nature of replication of intervention research in special education using an "article progeny" approach and a three-pronged definition…

  2. Effect of late gestation bodyweight change and condition score on progeny feedlot performance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inadequate nutrient intake during late gestation can cause cow BW loss and influence cow reproductive performance and subsequent productivity of steer progeny. Therefore, a 7-yr study with a 3 × 3 arrangement of treatments was conducted at Corona Range and Livestock Research Center, Corona, NM to e...

  3. Reproduction and progeny growth in rats fed clinoptilolite in the presence or absence of dietary cadmium

    SciTech Connect

    Pond, W.G.; Yen, J.T.

    1983-12-01

    The purposes of the experiment reported were to determine the effects of long-term ingestion of clinoptilolite on reproduction in female rats and on the postnatal development of their progeny and to ascertain whether or not clinoptilolite offers protection against the toxic effects of long-term Cd ingestion.

  4. Filter for on-line air monitor unaffected by radon progeny and method of using same

    DOEpatents

    Phillips, Terrance D.; Edwards, Howard D.

    1999-01-01

    An apparatus for testing air having contaminants and radon progeny therein. The apparatus includes a sampling box having an inlet for receiving the air and an outlet for discharging the air. The sampling box includes a filter made of a plate of sintered stainless steel. The filter traps the contaminants, yet allows at least a portion of the radon progeny to pass therethrough. A method of testing air having contaminants and radon progeny therein. The method includes providing a testing apparatus that has a sampling box with an inlet for receiving the air and an outlet for discharging the air, and has a sintered stainless steel filter disposed within said sampling box; drawing air from a source into the sampling box using a vacuum pump; passing the air through the filter; monitoring the contaminants trapped by the filter; and providing an alarm when a selected level of contaminants is reached. The filter traps the contaminants, yet allows at least a portion of the radon progeny to pass therethrough.

  5. Aneuploid progenies of triploid hybrids between diploid and tetraploid loach Misgurnus anguillicaudatus in China.

    PubMed

    Li, Ya-Juan; Gao, Yang-Chun; Zhou, He; Ma, Hai-Yan; Lin, Zhong-Qiao; Ma, Tian-Yu; Sui, Yi; Arai, Katsutoshi

    2016-10-01

    Triploid Chinese loach, Misgurnus anguillicaudatus, hybrids between tetraploids from Hubei Province and diploids from Liaoning Province were mated with either diploid wild-type or triploid hybrids to analyze viability and ploidy of the resultant progenies. Both triploid males and females generated fertile gametes, but progenies from the crosses using gametes of triploid hybrids did not survive beyond the larval stages. In crosses between wild-type diploid females and triploid hybrid males, embryos ranging from 2.2n to 2.6n were predominant with a mode of either 2.4n (chromosome numbers 59, 60, 61) or 2.5n (chromosome numbers 62, 63). Those from the crosses between triploid hybrid females and diploid males gave a modal ploidy level at approximately 2.5n in one case, but a shift to a higher ploidy level was observed in other embryos. In the progenies between triploid hybrid females and males, the ploidy level at approximately 3.0n (chromosome numbers 74, 75, 76) was most frequent. The cytogenetic results of the progenies suggest the production of aneuploid gametes with a modal ploidy level at approximately 1.5n in triploid hybrids. However, a shift to higher chromosome numbers in gametes was observed in certain cases, suggesting the involvement of mortality selection of gametes and/or zygotes with lower chromosome numbers.

  6. Does nutrition-related stress carry over to spruce budworm, Choristoneura fumiferana (Lepidoptera: Tortricidae) progeny?

    PubMed

    Carisey, N; Bauce, E

    2002-04-01

    Three different patterns of feeding of sixth-instar spruce budworm, Choristoneura fumiferana Clemens were simulated in the laboratory. Larvae were fed artificial diets whose nitrogen and total soluble sugar contents varied according to levels similar to those found in three types of balsam fir, Abies balsamea (L.) Miller foliage (current-year foliage from middle and lower crown sections and one-year-old foliage). The biological performance of offspring was studied according to the nutrition of their parents. Although food quality had no impact on pupal weight of female parents and individual mean egg weight, progeny fitness was influenced by parental nutrition. Old foliage simulated diet, poor in nitrogen, clearly affected the early larval development of progeny, especially the percent of egg hatch and first-instar survival. Lower crown current-year foliage simulated diet, with low total soluble sugar content, reduced the first-instar survival of the progeny. However, the selective pressure exerted by low food qualities on the parental generation and on the early stages of their progenies resulted in C. fumiferana populations having higher tolerance to starvation and higher survival after the diapause period. These results highlighted the potentially direct and indirect effects of C. fumiferana parental nutrition on the next generation. The patterns of feeding of parental generations would appear to affect the quality and size of subsequent populations through several selections on the different life-history stages of both generations.

  7. Biochemical evaluation of triploid progenies of diploid × tetraploid breeding populations of Camellia for genotypes rich in catechin and caffeine.

    PubMed

    Das, Sourabh Kumar; Sabhapondit, Santanu; Ahmed, Giasuddin; Das, Sudripta

    2013-06-01

    To verify the quality of triploid varieties of Camellia tea species at the secondary metabolite level, we tested caffeine and catechin profiles of 97 F(1) segregating progenies in two breeding populations with a common tetraploid parent and diploid parents of two geographic and varietal origins. Catechin and caffeine levels of the triploid progenies were quantified and compared against their diploid parent. Some of the progenies showed better performance than their diploid parent. Most of the progenies of the diploid C. sinensis × tetraploid cross showed heterosis for caffeine and EGCG. Progenies of the C. assamica subsp. lasiocalyx × tetraploid cross showed heterosis for +C, EC, EGC, and TC. The genomic contributions of the diploid parent seem to be the main factor in the variation between the two populations. Our studies showed quantitative enhancement of some of the quality-related parameters in tea, providing a platform to refocus on this classical breeding approach for developing quality cultivars in tea.

  8. Radon: Chemical and physical states of radon progeny. Final technical report

    SciTech Connect

    Castleman, A.W. Jr.

    1996-12-31

    The evolving chemical and physical form of radon progeny influence their transport to the bioreceptor and the extent to which that receptor can take up these species into various tissues. When first born following radioactive decay processes, the potentially deleterious radon progeny undergo various physical and chemical transformations as they transcend from a highly charged to a neutral state, and interact with various constituents of the environment. These transformations impact on the extent to which the radon progeny become associated with aerosol particles on the one hand, and their ultimate chemical form that is available for uptake in the biosystem, on the other. The program, which originally commenced in 1987, dealt with the basic chemistry and physics of radon progeny and hence impacted on several themes of importance to the DOE/OHER radon program. One of these is dose response, which is governed by the physical forms of the radon progeny, their transport to the bioreceptor and the chemical forms that govern their uptake. The second theme had to do with cellular responses, one of the major issues motivating the work. It is well known that various sizes of ions and molecules are selectively transported across cell membrane to differing degrees. This ultimately has to do with their chemical and physical forms, charge and size. The overall objective of the work was threefold: (1) quantifying the mechanisms and rates of the chemical and physical transformation; (2) ascertaining the ultimate chemical forms, and (3) determining the potential interactions of these chemical species with biological functional groups to ascertain their ultimate transport and incorporation within cells.

  9. The Progenitors of Type Ia Supernova

    NASA Astrophysics Data System (ADS)

    Tout, C. A.

    2005-08-01

    Type Ia supernovae are identified as exploding degenerate stars. Their luminosity is due to the radioactive decay of about a solar mass of 56Ni through 56Co to 56Fe. As such they are a major source of iron in the inter-stellar medium. Although it is generally accepted that a degenerate carbon/oxygen white dwarf explodes as it accretes material from a binary companion, the progenitors of type Ia supernovae have not been categorically identified. We discuss the various possible progenitors in detail and indicate theoretical and observational difficulties with each possibility. It may well be that the true nature of the progenitors has not yet even been conceived of. We look at why population synthesis fails to help distinguish and consider how the advent of population nucleosynthesis may change this. When used as universal standard candles SNe Ia are calibrated with the Phillips relation between absolute luminosity and light curve shape. This must therefore be valid at all redshifts and so both the absolute luminosity and the light curve decay must only depend on a single major property of the progenitors. We report on the latest understanding of this relation and find little to justify its universality beyond the local empirical evidence. A major effect on the absolute luminosities is the neutron to proton ratio at the time of the explosion because this determines the fraction of iron group elements made up of 56Ni.

  10. Single Degenerate Progenitors of Type Ia Supernovae

    NASA Astrophysics Data System (ADS)

    Bours, Madelon; Toonen, Silvia; Nelemans, Gijs

    2013-01-01

    There is a general agreement that Type Ia supernovae correspond to the thermonuclear runaway of a white dwarf (WD) in a compact binary. The details of these progenitor systems are still unclear. Using the population synthesis code SeBa and several assumption for the WD retention efficiency, we estimate the delay times and supernova rates for the single degenerate scenario.

  11. Direct Conversion of Fibroblasts to Megakaryocyte Progenitors.

    PubMed

    Pulecio, Julian; Alejo-Valle, Oriol; Capellera-Garcia, Sandra; Vitaloni, Marianna; Rio, Paula; Mejía-Ramírez, Eva; Caserta, Ilaria; Bueren, Juan A; Flygare, Johan; Raya, Angel

    2016-10-11

    Current sources of platelets for transfusion are insufficient and associated with risk of alloimmunization and blood-borne infection. These limitations could be addressed by the generation of autologous megakaryocytes (MKs) derived in vitro from somatic cells with the ability to engraft and differentiate in vivo. Here, we show that overexpression of a defined set of six transcription factors efficiently converts mouse and human fibroblasts into MK-like progenitors. The transdifferentiated cells are CD41(+), display polylobulated nuclei, have ploidies higher than 4N, form MK colonies, and give rise to platelets in vitro. Moreover, transplantation of MK-like murine progenitor cells into NSG mice results in successful engraftment and further maturation in vivo. Similar results are obtained using disease-corrected fibroblasts from Fanconi anemia patients. Our results combined demonstrate that functional MK progenitors with clinical potential can be obtained in vitro, circumventing the use of hematopoietic progenitors or pluripotent stem cells.

  12. Targeting human oligodendrocyte progenitors for myelin repair.

    PubMed

    Dietz, Karen C; Polanco, Jessie J; Pol, Suyog U; Sim, Fraser J

    2016-09-01

    Oligodendrocyte development has been studied for several decades, and has served as a model system for both neurodevelopmental and stem/progenitor cell biology. Until recently, the vast majority of studies have been conducted in lower species, especially those focused on rodent development and remyelination. In humans, the process of myelination requires the generation of vastly more myelinating glia, occurring over a period of years rather than weeks. Furthermore, as evidenced by the presence of chronic demyelination in a variety of human neurologic diseases, it appears likely that the mechanisms that regulate development and become dysfunctional in disease may be, in key ways, divergent across species. Improvements in isolation techniques, applied to primary human neural and oligodendrocyte progenitors from both fetal and adult brain, as well as advancements in the derivation of defined progenitors from human pluripotent stem cells, have begun to reveal the extent of both species-conserved signaling pathways and potential key differences at cellular and molecular levels. In this article, we will review the commonalities and differences in myelin development between rodents and man, describing the approaches used to study human oligodendrocyte differentiation and myelination, as well as heterogeneity within targetable progenitor pools, and discuss the advances made in determining which conserved pathways may be both modeled in rodents and translate into viable therapeutic strategies to promote myelin repair.

  13. The progenitors of subluminous type Ia supernovae

    SciTech Connect

    Howell, D. Andrew

    2001-02-01

    We find that spectroscopically peculiar subluminous SNe Ia come from an old population. Of the thirteen subluminous SNe Ia known, nine are found in E/S0 galaxies, and the remainder are found in early-type spirals. The probability that this is a chance occurrence is only 0.1%. The finding that subluminous SNe Ia are associated with an older stellar population indicates that for a sufficiently large lookback time (already accessible in current high redshift searches) they will not be found. Due to a scarcity in old populations, hydrogen and helium main sequence stars and He red giant stars that undergo Roche lobe overflow are unlikely to be the progenitors of subluminous SNe Ia. Earlier findings that overluminous SNe Ia (DELTA m{sub 15} (B) < 0.94) come from a young progenitor population are confirmed. The fact that subluminous SNe Ia and overluminous SNe Ia come from different progenitor populations and also have different properties is a prediction of the CO white dwarf merger progenitor scenario.

  14. Selection of transduced CD34+ progenitors and enzymatic correction of cells from Gaucher patients, with bicistronic vectors.

    PubMed Central

    Migita, M; Medin, J A; Pawliuk, R; Jacobson, S; Nagle, J W; Anderson, S; Amiri, M; Humphries, R K; Karlsson, S

    1995-01-01

    -granulocyte/macrophage, and CFU-mix hematopoietic colonies, demonstrating their ability to differentiate into these myeloid lineages in vitro. The transduced, sorted progenitors raised the GC enzyme levels in their progeny cells manyfold compared with untransduced CD34+ progenitors. Collectively, this demonstrates the development of high titer, selectable bicistronic vectors that allow isolation of transduced hematopoietic progenitors and cells that have been metabolically corrected. Images Fig. 2 Fig. 3 PMID:8618847

  15. SUPERNOVA REMNANT PROGENITOR MASSES IN M31

    SciTech Connect

    Jennings, Zachary G.; Williams, Benjamin F.; Dalcanton, Julianne J.; Gilbert, Karoline M.; Fouesneau, Morgan; Weisz, Daniel R.; Murphy, Jeremiah W.; Dolphin, Andrew E. E-mail: adolphin@raytheon.com

    2012-12-10

    Using Hubble Space Telescope photometry, we age-date 59 supernova remnants (SNRs) in the spiral galaxy M31 and use these ages to estimate zero-age main-sequence masses (M{sub ZAMS}) for their progenitors. To accomplish this, we create color-magnitude diagrams (CMDs) and employ CMD fitting to measure the recent star formation history of the regions surrounding cataloged SNR sites. We identify any young coeval population that likely produced the progenitor star, then assign an age and uncertainty to that population. Application of stellar evolution models allows us to infer the M{sub ZAMS} from this age. Because our technique is not contingent on identification or precise location of the progenitor star, it can be applied to the location of any known SNRs. We identify significant young star formation around 53 of the 59 SNRs and assign progenitor masses to these, representing a factor of {approx}2 increase over currently measured progenitor masses. We consider the remaining six SNRs as either probable Type Ia candidates or the result of core-collapse progenitors that have escaped their birth sites. In general, the distribution of recovered progenitor masses is bottom-heavy, showing a paucity of the most massive stars. If we assume a single power-law distribution, dN/dM{proportional_to}M{sup {alpha}}, then we find a distribution that is steeper than a Salpeter initial mass function (IMF) ({alpha} = -2.35). In particular, we find values of {alpha} outside the range -2.7 {>=} {alpha} {>=} -4.4 to be inconsistent with our measured distribution at 95% confidence. If instead we assume a distribution that follows a Salpeter IMF up to some maximum mass, then we find that values of M{sub Max} > 26 are inconsistent with the measured distribution at 95% confidence. In either scenario, the data suggest that some fraction of massive stars may not explode. The result is preliminary and requires more SNRs and further analysis. In addition, we use our distribution to estimate a

  16. Stem and progenitor cells of the mammalian olfactory epithelium: Taking poietic license.

    PubMed

    Schwob, James E; Jang, Woochan; Holbrook, Eric H; Lin, Brian; Herrick, Daniel B; Peterson, Jesse N; Hewitt Coleman, Julie

    2017-03-01

    The capacity of the olfactory epithelium (OE) for lifelong neurogenesis and regeneration depends on the persistence of neurocompetent stem cells, which self-renew as well as generating all of the cell types found within the nasal epithelium. This Review focuses on the types of stem and progenitor cells in the epithelium and their regulation. Both horizontal basal cells (HBCs) and some among the population of globose basal cells (GBCs) are stem cells, but the two types plays vastly different roles. The GBC population includes the basal cells that proliferate in the uninjured OE and is heterogeneous with respect to transcription factor expression. From upstream in the hierarchy to downstream, GBCs encompass 1) Sox2(+) /Pax6(+) stem-like cells that are totipotent and self-renew over the long term, 2) Ascl1(+) transit-amplifying progenitors with a limited capacity for expansive proliferation, and 3) Neurog1(+) /NeuroD1(+) immediate precursor cells that make neurons directly. In contrast, the normally quiescent HBCs are activated to multipotency and proliferate when sustentacular cells are killed, but not when only OSNs die, indicating that HBCs are reserve stem cells that respond to severe epithelial injury. The master regulator of HBC activation is the ΔN isoform of the transcription factor p63; eliminating ΔNp63 unleashes HBC multipotency. Notch signaling, via Jagged1 ligand on Sus cells and Notch1 and Notch2 receptors on HBCs, is likely to play a major role in setting the level of p63 expression. Thus, ΔNp63 becomes a potential therapeutic target for reversing the neurogenic exhaustion characteristic of the aged OE. J. Comp. Neurol. 525:1034-1054, 2017. © 2016 Wiley Periodicals, Inc.

  17. Preparation of Primary Myogenic Precursor Cell/Myoblast Cultures from Basal Vertebrate Lineages

    PubMed Central

    Froehlich, Jacob Michael; Seiliez, Iban; Gabillard, Jean-Charles; Biga, Peggy R.

    2014-01-01

    Due to the inherent difficulty and time involved with studying the myogenic program in vivo, primary culture systems derived from the resident adult stem cells of skeletal muscle, the myogenic precursor cells (MPCs), have proven indispensible to our understanding of mammalian skeletal muscle development and growth. Particularly among the basal taxa of Vertebrata, however, data are limited describing the molecular mechanisms controlling the self-renewal, proliferation, and differentiation of MPCs. Of particular interest are potential mechanisms that underlie the ability of basal vertebrates to undergo considerable postlarval skeletal myofiber hyperplasia (i.e. teleost fish) and full regeneration following appendage loss (i.e. urodele amphibians). Additionally, the use of cultured myoblasts could aid in the understanding of regeneration and the recapitulation of the myogenic program and the differences between them. To this end, we describe in detail a robust and efficient protocol (and variations therein) for isolating and maintaining MPCs and their progeny, myoblasts and immature myotubes, in cell culture as a platform for understanding the evolution of the myogenic program, beginning with the more basal vertebrates. Capitalizing on the model organism status of the zebrafish (Danio rerio), we report on the application of this protocol to small fishes of the cyprinid clade Danioninae. In tandem, this protocol can be utilized to realize a broader comparative approach by isolating MPCs from the Mexican axolotl (Ambystomamexicanum) and even laboratory rodents. This protocol is now widely used in studying myogenesis in several fish species, including rainbow trout, salmon, and sea bream1-4. PMID:24835774

  18. Basal ganglia hemorrhage related to lightning strike.

    PubMed

    Ozgun, B; Castillo, M

    1995-01-01

    We describe a case of bilateral basal ganglia hemorrhage after a lightning strike to the head documented by a CT scan. Review of the literature shows this to be the most common brain imaging finding that can be attributed to a lightning strike. Several mechanistic theories are discussed, with the most plausible one being related to preferential conduction pathways through the brain.

  19. Teaching Social Studies Using Basal Readers.

    ERIC Educational Resources Information Center

    Garcia, Jesus; Logan, John W.

    1983-01-01

    A lesson, "Harriet Tubman: A Most Successful Conductor," illustrates how to employ a basal reader in social studies instruction in the elementary grades. This approach offers students a relevant curriculum, greater opportunities for concept development, practice in skills areas, and activities that offer greater opportunity to master…

  20. Parallel basal ganglia circuits for decision making.

    PubMed

    Hikosaka, Okihide; Ghazizadeh, Ali; Griggs, Whitney; Amita, Hidetoshi

    2017-02-02

    The basal ganglia control body movements, mainly, based on their values. Critical for this mechanism is dopamine neurons, which sends unpredicted value signals, mainly, to the striatum. This mechanism enables animals to change their behaviors flexibly, eventually choosing a valuable behavior. However, this may not be the best behavior, because the flexible choice is focused on recent, and, therefore, limited, experiences (i.e., short-term memories). Our old and recent studies suggest that the basal ganglia contain separate circuits that process value signals in a completely different manner. They are insensitive to recent changes in value, yet gradually accumulate the value of each behavior (i.e., movement or object choice). These stable circuits eventually encode values of many behaviors and then retain the value signals for a long time (i.e., long-term memories). They are innervated by a separate group of dopamine neurons that retain value signals, even when no reward is predicted. Importantly, the stable circuits can control motor behaviors (e.g., hand or eye) quickly and precisely, which allows animals to automatically acquire valuable outcomes based on historical life experiences. These behaviors would be called 'skills', which are crucial for survival. The stable circuits are localized in the posterior part of the basal ganglia, separately from the flexible circuits located in the anterior part. To summarize, the flexible and stable circuits in the basal ganglia, working together but independently, enable animals (and humans) to reach valuable goals in various contexts.

  1. TEMPORAL VARIABILITY IN BASAL ISOPRENE EMISSION FACTOR

    EPA Science Inventory

    Seasonal variability in basal isoprene emission factor (micrograms C /g hr or nmol/ m2 sec, leaf temperature at 30 degrees C and photosynthetically active radiation (PAR) at 1000 micromol/ m2 sec) was studied during the 1998 growing season at Duke Forest in the North Carolina Pie...

  2. Basal Ganglia Germinoma in an Adult.

    PubMed

    Vialatte de Pémille, Clément; Bielle, Franck; Mokhtari, Karima; Kerboua, Esma; Alapetite, Claire; Idbaih, Ahmed

    2016-08-01

    Intracranial germinoma is a rare primary brain cancer, usually located within the midline and mainly affecting Asian pediatric patients. Interestingly, we report here the peculiar case of a young North-African adult patient suffering from a basal ganglia germinoma without the classical ipsilateral cerebral hemiatrophy associated with this location.

  3. Basal Textbooks and the Social Studies

    ERIC Educational Resources Information Center

    Ediger, Marlow

    2010-01-01

    Basal textbooks are rather popular for social studies teachers to use in the classroom setting. There are selected reasons for this occurring. They do provide beginning and new teachers a framework for ongoing lessons and units of study. The accompanying Manual provides suggestions for learning activities for learners to pursue. Evaluation…

  4. Proximity Interactions among Basal Body Components in Trypanosoma brucei Identify Novel Regulators of Basal Body Biogenesis and Inheritance

    PubMed Central

    Dang, Hung Quang; Zhou, Qing; Rowlett, Veronica W.; Hu, Huiqing; Lee, Kyu Joon; Margolin, William

    2017-01-01

    ABSTRACT The basal body shares similar architecture with centrioles in animals and is involved in nucleating flagellar axonemal microtubules in flagellated eukaryotes. The early-branching Trypanosoma brucei possesses a motile flagellum nucleated from the basal body that consists of a mature basal body and an adjacent pro-basal body. Little is known about the basal body proteome and its roles in basal body biogenesis and flagellar axoneme assembly in T. brucei. Here, we report the identification of 14 conserved centriole/basal body protein homologs and 25 trypanosome-specific basal body proteins. These proteins localize to distinct subdomains of the basal body, and several of them form a ring-like structure surrounding the basal body barrel. Functional characterization of representative basal body proteins revealed distinct roles in basal body duplication/separation and flagellar axoneme assembly. Overall, this work identified novel proteins required for basal body duplication and separation and uncovered new functions of conserved basal body proteins in basal body duplication and separation, highlighting an unusual mechanism of basal body biogenesis and inheritance in this early divergent eukaryote. PMID:28049148

  5. Origin of hemopoietic stromal progenitor cells in chimeras

    SciTech Connect

    Chertkov, J.L.; Drize, N.J.; Gurevitch, O.A.; Samoylova, R.S.

    1985-12-01

    Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice.

  6. Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches.

    PubMed

    Peterson, Shelby C; Eberl, Markus; Vagnozzi, Alicia N; Belkadi, Abdelmadjid; Veniaminova, Natalia A; Verhaegen, Monique E; Bichakjian, Christopher K; Ward, Nicole L; Dlugosz, Andrzej A; Wong, Sunny Y

    2015-04-02

    Basal cell carcinoma (BCC) is characterized by frequent loss of PTCH1, leading to constitutive activation of the Hedgehog pathway. Although the requirement for Hedgehog in BCC is well established, the identity of disease-initiating cells and the compartments in which they reside remain controversial. By using several inducible Cre drivers to delete Ptch1 in different cell compartments in mice, we show here that multiple hair follicle stem cell populations readily develop BCC-like tumors. In contrast, stem cells within the interfollicular epidermis do not efficiently form tumors. Notably, we observed that innervated Gli1-expressing progenitors within mechanosensory touch dome epithelia are highly tumorigenic. Sensory nerves activate Hedgehog signaling in normal touch domes, while denervation attenuates touch dome-derived tumors. Together, our studies identify varying tumor susceptibilities among different stem cell populations in the skin, highlight touch dome epithelia as "hot spots" for tumor formation, and implicate cutaneous nerves as mediators of tumorigenesis.

  7. Galactic constraints on supernova progenitor models

    NASA Astrophysics Data System (ADS)

    Acharova, I. A.; Gibson, B. K.; Mishurov, Yu. N.; Kovtyukh, V. V.

    2013-09-01

    Aims: To estimate the mean masses of oxygen and iron ejected per each type of supernovae (SNe) event from observations of the elemental abundance patterns in the Galactic disk and constrain the relevant SNe progenitor models. Methods: We undertake a statistical analysis of the radial abundance distributions in the Galactic disk within a theoretical framework for Galactic chemical evolution which incorporates the influence of spiral arms. This framework has been shown to recover the non-linear behaviour in radial gradients, the mean masses of oxygen and iron ejected during SNe explosions to be estimated, and constraints to be placed on SNe progenitor models. Results: (i) The mean mass of oxygen ejected per core-collapse SNe (CC SNe) event (which are concentrated within spiral arms) is ~0.27 M⊙; (ii) the mean mass of iron ejected by tardy Type Ia SNe (SNeIa, whose progenitors are older/longer-lived stars with ages ≳100 Myr and up to several Gyr, which do not concentrate within spiral arms) is ~0.58 M⊙; (iii) the upper mass of iron ejected by prompt SNeIa (SNe whose progenitors are younger/shorter-lived stars with ages ≲100 Myr, which are concentrated within spiral arms) is ≤0.23 M⊙ per event; (iv) the corresponding mean mass of iron produced by CC SNe is ≤0.04 M⊙ per event; (v) short-lived SNe (core-collapse or prompt SNeIa) supply ~85% of the Galactic disk's iron. Conclusions: The inferred low mean mass of oxygen ejected per CC SNe event implies a low upper mass limit for the corresponding progenitors of ~23 M⊙, otherwise the Galactic disk would be overabundant in oxygen. This inference is the consequence of the non-linear dependence between the upper limit of the progenitor initial mass and the mean mass of oxygen ejected per CC SNe explosion. The low mean mass of iron ejected by prompt SNeIa, relative to the mass produced by tardy SNeIa (~2.5 times lower), prejudices the idea that both sub-populations of SNeIa have the same physical nature. We

  8. Metastatic giant basal cell carcinoma: a case report

    PubMed Central

    Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M’rabti, Hind; Errihani, Hassan

    2016-01-01

    Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy. PMID:27795755

  9. Metastatic giant basal cell carcinoma: a case report.

    PubMed

    Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M'rabti, Hind; Errihani, Hassan

    2016-01-01

    Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy.

  10. MicroRNA-21 coordinates human multipotent cardiovascular progenitors therapeutic potential.

    PubMed

    Richart, Adèle; Loyer, Xavier; Néri, Tui; Howangyin, Kiave; Guérin, Coralie L; Ngkelo, Anta; Bakker, Wineke; Zlatanova, Ivana; Rouanet, Marie; Vilar, José; Lévy, Bernard; Rothenberg, Marc; Mallat, Ziad; Pucéat, Michel; Silvestre, Jean-Sébastien

    2014-11-01

    Published clinical trials in patients with ischemic diseases show limited benefit of adult stem cell-based therapy, likely due to their restricted plasticity and commitment toward vascular cell lineage. We aim to uncover the potent regenerative ability of MesP1/stage-specific embryonic antigen 1 (SSEA-1)-expressing cardiovascular progenitors enriched from human embryonic stem cells (hESCs). Injection of only 10(4) hESC-derived SSEA-1(+) /MesP1(+) cells, or their progeny obtained after treatment with VEGF-A or PDGF-BB, was effective enough to enhance postischemic revascularization in immunodeficient mice with critical limb ischemia (CLI). However, the rate of incorporation of hESC-derived SSEA-1(+) /MesP1(+) cells and their derivatives in ischemic tissues was modest. Alternatively, these cells possessed a unique miR-21 signature that inhibited phosphotase and tensin homolog (PTEN) thereby activating HIF-1α and the systemic release of VEGF-A. Targeting miR-21 limited cell survival and inhibited their proangiogenic capacities both in the Matrigel model and in mice with CLI. We next assessed the impact of mR-21 in adult angiogenesis-promoting cells. We observed an impaired postischemic angiogenesis in miR-21-deficient mice. Notably, miR-21 was highly expressed in circulating and infiltrated monocytes where it targeted PTEN/HIF-1α/VEGF-A signaling and cell survival. As a result, miR-21-deficient mice displayed an impaired number of infiltrated monocytes and a defective angiogenic phenotype that could be partially restored by retransplantation of bone marrow-derived cells from wild-type littermates. hESC-derived SSEA-1(+) /MesP1(+) cells progenitor cells are powerful key integrators of therapeutic angiogenesis in ischemic milieu and miR-21 is instrumental in this process as well as in the orchestration of the biological activity of adult angiogenesis-promoting cells.

  11. BDNF +/− Mice Exhibit Deficits in Oligodendrocyte Lineage Cells of the Basal Forebrain

    PubMed Central

    VonDran, Melissa W.; Clinton-Luke, Patricia; Honeywell, Jean Z.; Dreyfus, Cheryl F.

    2009-01-01

    Previous work indicated that BDNF, through the trkB receptor, increases DNA synthesis in oligodendrocyte progenitor cells (OPCs) and differentiation of post-mitotic oligodendrocytes (OLGs) of the basal forebrain (BF). In the present studies, BDNF knockout animals were used to investigate BDNF’s effects on OLG lineage cells (OLCs) in vivo. OLCs of the BF were found to express the trkB receptor, suggesting they are responsive to BDNF. Immunohistochemistry using NG2 and CC1 antibodies was utilized to examine numbers of NG2+ OPCs and CC1+ post-mitotic BF OLGs. In the embryo (E17), BDNF −/− animals display reduced NG2+ cells. This reduction was also observed in BDNF +/− mice at E17 and at postnatal day 1 (P1), P14 and adult, suggesting that BDNF plays a role in OPC development. BDNF +/− mice do not exhibit deficits in numbers of CC1+ OLGs. However, myelin basic protein (MBP), myelin associated glycoprotein (MAG), and proteolipid protein (PLP) are reduced in BDNF +/− mice, suggesting that BDNF plays a role in differentiation. These data indicate that progenitor cells and myelin proteins may be affected in vivo by a decrease in BDNF. PMID:20091777

  12. Learning Reward Uncertainty in the Basal Ganglia

    PubMed Central

    Bogacz, Rafal

    2016-01-01

    Learning the reliability of different sources of rewards is critical for making optimal choices. However, despite the existence of detailed theory describing how the expected reward is learned in the basal ganglia, it is not known how reward uncertainty is estimated in these circuits. This paper presents a class of models that encode both the mean reward and the spread of the rewards, the former in the difference between the synaptic weights of D1 and D2 neurons, and the latter in their sum. In the models, the tendency to seek (or avoid) options with variable reward can be controlled by increasing (or decreasing) the tonic level of dopamine. The models are consistent with the physiology of and synaptic plasticity in the basal ganglia, they explain the effects of dopaminergic manipulations on choices involving risks, and they make multiple experimental predictions. PMID:27589489

  13. Insulin pumps: Beyond basal-bolus.

    PubMed

    Millstein, Richard; Becerra, Nancy Mora; Shubrook, Jay H

    2015-12-01

    Insulin pumps are a major advance in diabetes management, making insulin dosing easier and more accurate and providing great flexibility, safety, and efficacy for people who need basal-bolus insulin therapy. They are the preferred treatment for people with type 1 diabetes and many with type 2 diabetes who require insulin. This article reviews the basics of how insulin pumps work, who benefits from a pump, and how to manage inpatients and outpatients on insulin pumps.

  14. Basal hydraulic conditions of Ice Stream B

    NASA Technical Reports Server (NTRS)

    Engelhardt, Hermann; Kamb, Barclay

    1993-01-01

    Fifteen boreholes have been drilled to the base of Ice Stream B in the vicinity of UpB Camp. The boreholes are spread over an area of about 500 x 1000 m. Several till cores were retrieved from the bottom of the 1000-m-deep holes. Laboratory tests using a simple shear box revealed a yield strength of basal till of 2 kPa. This agrees well with in-situ measurements using a shear vane. Since the average basal shear stress of Ice Stream B with a surface slope of 0.1 degree is about 20 kPa, the ice stream cannot be supported by till that weak. Additional support for this conclusion comes from the basal water pressure that has been measured in all boreholes as soon as the hot water drill reached bottom. In several boreholes, the water pressure has been continuously monitored; in two of them, over several years. The water pressure varies but stays within 1 bar of flotation where ice overburden pressure and water pressure are equal. The ratio of water and overburden pressure lies between 0.986 and 1.002. This is an extremely high value as compared to other fast-moving ice masses; e.g., Variegated Glacier in surge has a ratio of 0.8, and Columbia Glacier - a fast-moving tidewater glacier - has a ratio of 0.9. It implies that water flow under the glacier occurs in a thin film and not in conduits that would drain away water too rapidly. It also implies that basal sliding must be very effective. Water flow under the glacier was measured in a salt-injection experiment where a salt pulse was released at the bottom of a borehole while 60 m down-glacier, the electrical resistance was measured between two other boreholes. A flow velocity of 7 mm/s was obtained.

  15. RFamide peptides in agnathans and basal chordates.

    PubMed

    Osugi, Tomohiro; Son, You Lee; Ubuka, Takayoshi; Satake, Honoo; Tsutsui, Kazuyoshi

    2016-02-01

    Since a peptide with a C-terminal Arg-Phe-NH2 (RFamide peptide) was first identified in the ganglia of the venus clam in 1977, RFamide peptides have been found in the nervous system of both invertebrates and vertebrates. In vertebrates, the RFamide peptide family includes gonadotropin-inhibitory hormone (GnIH), neuropeptide FF (NPFF), prolactin-releasing peptide (PrRP), pyroglutamylated RFamide peptide/26RFamide peptide (QRFP/26RFa), and kisspeptins (kiss1 and kiss2). They are involved in important functions such as the release of hormones, regulation of sexual or social behavior, pain transmission, reproduction, and feeding. In contrast to tetrapods and jawed fish, the information available on RFamide peptides in agnathans and basal chordates is limited, thus preventing further insights into the evolution of RFamide peptides in vertebrates. In this review, we focus on the previous research and recent advances in the studies on RFamide peptides in agnathans and basal chordates. In agnathans, the genes encoding GnIH, NPFF, and PrRP precursors and the mature peptides have been identified in lamprey (Petromyzon marinus) and hagfish (Paramyxine atami). Putative kiss1 and kiss2 genes have also been found in the genome database of lamprey. In basal chordates, namely, in amphioxus (Branchiostoma japonicum), a common ancestral form of GnIH and NPFF genes and their mature peptides, as well as the ortholog of the QRFP gene have been identified. The studies revealed that the number of orthologs of vertebrate RFamide peptides present in agnathans and basal chordates is greater than expected, suggesting that the vertebrate RFamide peptides might have emerged and expanded at an early stage of chordate evolution.

  16. Interneuron Progenitor Transplantation to Treat CNS Dysfunction

    PubMed Central

    Chohan, Muhammad O.; Moore, Holly

    2016-01-01

    Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field. PMID:27582692

  17. POPULATION SYNTHESIS AND GAMMA RAY BURST PROGENITORS

    SciTech Connect

    C. L. FREYER

    2000-12-11

    Population synthesis studies of binaries are always limited by a myriad of uncertainties from the poorly understood effects of binary mass transfer and common envelope evolution to the many uncertainties that still remain in stellar evolution. But the importance of these uncertainties depends both upon the objects being studied and the questions asked about these objects. Here I review the most critical uncertainties in the population synthesis of gamma-ray burst progenitors. With a better understanding of these uncertainties, binary population synthesis can become a powerful tool in understanding, and constraining, gamma-ray burst models. In turn, as gamma-ray bursts become more important as cosmological probes, binary population synthesis of gamma-ray burst progenitors becomes an important tool in cosmology.

  18. Human progenitor cells for bone engineering applications.

    PubMed

    de Peppo, G M; Thomsen, P; Karlsson, C; Strehl, R; Lindahl, A; Hyllner, J

    2013-06-01

    In this report, the authors review the human skeleton and the increasing burden of bone deficiencies, the limitations encountered with the current treatments and the opportunities provided by the emerging field of cell-based bone engineering. Special emphasis is placed on different sources of human progenitor cells, as well as their pros and cons in relation to their utilization for the large-scale construction of functional bone-engineered substitutes for clinical applications. It is concluded that, human pluripotent stem cells represent a valuable source for the derivation of progenitor cells, which combine the advantages of both embryonic and adult stem cells, and indeed display high potential for the construction of functional substitutes for bone replacement therapies.

  19. Noninvasive Imaging of Administered Progenitor Cells

    SciTech Connect

    Steven R Bergmann, M.D., Ph.D.

    2012-12-03

    The objective of this research grant was to develop an approach for labeling progenitor cells, specifically those that we had identified as being able to replace ischemic heart cells, so that the distribution could be followed non-invasively. In addition, the research was aimed at determining whether administration of progenitor cells resulted in improved myocardial perfusion and function. The efficiency and toxicity of radiolabeling of progenitor cells was to be evaluated. For the proposed clinical protocol, subjects with end-stage ischemic coronary artery disease were to undergo a screening cardiac positron emission tomography (PET) scan using N-13 ammonia to delineate myocardial perfusion and function. If they qualified based on their PET scan, they would undergo an in-hospital protocol whereby CD34+ cells were stimulated by the administration of granulocytes-colony stimulating factor (G-CSF). CD34+ cells would then be isolated by apharesis, and labeled with indium-111 oxine. Cells were to be re-infused and subjects were to undergo single photon emission computed tomography (SPECT) scanning to evaluate uptake and distribution of labeled progenitor cells. Three months after administration of progenitor cells, a cardiac PET scan was to be repeated to evaluate changes in myocardial perfusion and/or function. Indium oxine is a radiopharmaceutical for labeling of autologous lymphocytes. Indium-111 (In-111) decays by electron capture with a t{sub ½} of 67.2 hours (2.8 days). Indium forms a saturated complex that is neutral, lipid soluble, and permeates the cell membrane. Within the cell, the indium-oxyquinolone complex labels via indium intracellular chelation. Following leukocyte labeling, ~77% of the In-111 is incorporated in the cell pellet. The presence of red cells and /or plasma reduces the labeling efficacy. Therefore, the product needed to be washed to eliminate plasma proteins. This repeated washing can damage cells. The CD34 selected product was a 90

  20. Loss of Telomeres in the Progeny of Human Lymphocytes Exposed to Energetic Heavy Ions

    NASA Technical Reports Server (NTRS)

    Cucinotta, F.A.; George, K.; Durante, M.

    2006-01-01

    We have used cross-species multi-color banding (RxFISH) combined with telomere FISH probes, to measure chromosomal aberrations in the progeny of human peripheral blood lymphocytes exposed to ionizing radiation. Accelerated iron particles (energy 1 GeV/nucleon) induced many more terminal deletions than the same dose of gamma-rays. We found that truncated chromosomes without telomeres could be transmitted for at least three cell cycles following exposure, and represented about 10% of all aberrations observed in the progeny of cells exposed to iron ions. High energy heavy ions generate the most significant health risk for human space exploration and the results suggest that telomere loss may be the leading mechanism for their high efficiency in the induction of late effects.

  1. Effect of age on generation of progeny from antigen-stimulated human lymphocytes.

    PubMed

    Sohnle, P G; Collins-Lech, C; Huhta, K E

    1982-01-01

    Numerous studies have shown the proliferative response to various mitogenic stimuli of peripheral blood lymphocytes from elderly humans to be impaired. The present investigation examined the termination phase of antigen-stimulated proliferative responses of lymphocytes from elderly and young subjects. In both groups, the responding lymphocytes appeared to stop proliferating and enter the resting stage of the cell cycle when a certain total number of progeny had been generated, suggesting the phenomenon of density-dependent regulation of growth. Lymphocytes from elderly subjects stopped proliferating when significantly fewer progeny had been generated than did those from young subjects. The data suggest, therefore, that lymphocytes from elderly humans may have increased sensitivity to one or more of the factors which cause density-dependent inhibition of growth.

  2. [Autosegregation of enzyme loci in agamospermous progenies of triploid plants of sugar beet (Beta vulgaris L.)].

    PubMed

    Levites, E V; Kirikovich, S S

    2011-07-01

    The ratios of the phenotypic classes of glucosephosphate isomerase (GP12) and malate dehydrogenase (MDH1 and MDH2) were studied in agamospermous progenies of triploid sugar beet plants. The ratio of the phenotypic classes of these enzymes corresponds to the calculations based on the assumption of polyteny of chromosomes carrying alleles of the enzyme loci accompanied by the loss of extra copies of the alleles in the first division of a cell entering embryogenesis. An increase in the gene dosage due to polyteny leads to the appearance in the progeny with a definite frequency of alleles that were absent in the original parental plant. The notions of meiotic autosegregation and mitotic autosegregation characteristic of meiotic and mitotic agamospermy are introduced, as well as the term locus polygenotype characterizing not only the allelic composition and the number of chromosomes, but also the number of chromatids carrying alleles of the marker locus in the cell before its entry into embryogenesis.

  3. Variability of cell wall polysaccharides composition and hemicellulose enzymatic profile in an apple progeny.

    PubMed

    Galvez-Lopez, D; Laurens, F; Quéméner, B; Lahaye, M

    2011-12-01

    The genetic variability of apple cell walls polysaccharides chemical composition and structure was assessed in a progeny of 141 individuals harvested over 2 years. The variability of the hemicelluloses oligosaccharides released by glucanase was analyzed by MALDI-TOF MS. The genetic contribution was distinguished from harvest year as well as from parental crossing patterns and scab resistance selection. Results showed that harvest year had a major impact on cell wall polysaccharide composition and structure. Within each harvest, genetic effect impact more significantly cell wall polysaccharide chemistry than does reciprocal crossing or early scab selection. Uronic acids, glucose, galactose and xylose contents as well as some glucomannan and xyloglucan structures have a high heritability. This first cell wall chemotyping of an apple progeny opens the way for future searches of genetic markers for the chemical variability of cell wall polysaccharides.

  4. Mapping Quantitative Trait Loci Controlling Milk Production in Dairy Cattle by Exploiting Progeny Testing

    PubMed Central

    Georges, M.; Nielsen, D.; Mackinnon, M.; Mishra, A.; Okimoto, R.; Pasquino, A. T.; Sargeant, L. S.; Sorensen, A.; Steele, M. R.; Zhao, X.; Womack, J. E.; Hoeschele, I.

    1995-01-01

    We have exploited ``progeny testing'' to map quantitative trait loci (QTL) underlying the genetic variation of milk production in a selected dairy cattle population. A total of 1,518 sires, with progeny tests based on the milking performances of > 150,000 daughters jointly, was genotyped for 159 autosomal microsatellites bracketing 1645 centimorgan or approximately two thirds of the bovine genome. Using a maximum likelihood multilocus linkage analysis accounting for variance heterogeneity of the phenotypes, we identified five chromosomes giving very strong evidence (LOD score >/= 3) for the presence of a QTL controlling milk production: chromosomes 1, 6, 9, 10 and 20. These findings demonstrate that loci with considerable effects on milk production are still segregating in highly selected populations and pave the way toward marker-assisted selection in dairy cattle breeding. PMID:7713441

  5. Ependymal stem cells divide asymmetrically and transfer progeny into the subventricular zone when activated by injury.

    PubMed

    Gleason, D; Fallon, J H; Guerra, M; Liu, J-C; Bryant, P J

    2008-09-22

    Evidence is presented to show that cells of the ependymal layer surrounding the ventricles of the mammalian (rat) forebrain act as neural stem cells (NSCs), and that these cells can be activated to divide by a combination of injury and growth factor stimulation. Several markers of asymmetric cell division (ACD), a characteristic of true stem cells, are expressed asymmetrically in the ependymal layer but not in the underlying subventricular zone (SVZ), and when the brain is treated with a combination of local 6-hydroxydopamine (6-OHDA) with systemic delivery of transforming growth factor-alpha (TGFalpha), ependymal cells divide asymmetrically and transfer progeny into the SVZ. The SVZ cells then divide as transit amplifying cells (TACs) and their progeny enter a differentiation pathway. The stem cells in the ependymal layer may have been missed in many previous studies because they are usually quiescent and divide only in response to strong stimuli.

  6. [Assessment of the impact of GMO of plant origin on rat progeny development in 3 generations].

    PubMed

    Tyshko, N V; Zhminchenko, V M; Pashorina, V A; Seliaskin, K E; Saprykin, V P; Utembaeva, N T; Tutel'ian, V A

    2011-01-01

    The publication presents the results of assessment of impact of genetically modified (GM) maize Liberty Link on prenatal and postnatal development of progeny of 3 generations of Wistar rats. A total of 630 adult animals and 2837 pups were used in the experiment. The animals were divided into 5 groups which got the diets with inclusion of maize: the animals of the experimental group got the diet with the GM-maize, animals of the control group - with near isogenic conventional analogue of the GM-maize, animals of the 1st, 2nd and 3rd reference groups - conventional varieties of maize ROSS 144 MV, ROSS 197 MVW, Dokuchayevskaya 250 MV respectively. The maize was included in the diet at maximum possible level not violating the balance of basic nutrients. Analysis of the data obtained during the study did not reveal any impact of GM-maize on rat progeny development.

  7. Genetic manipulation of Aspergillus nidulans: meiotic progeny for genetic analysis and strain construction.

    PubMed

    Todd, Richard B; Davis, Meryl A; Hynes, Michael J

    2007-01-01

    The multicellular microbial eukaryote Aspergillus nidulans is an excellent model for the study of a wide array of biological processes. Studies in this system contribute significantly to understanding fundamental biological principles and are relevant for biotechnology and industrial applications, as well as human, animal and plant fungal pathogenesis. A. nidulans is easily manipulated using classical and molecular genetics. Here, we describe the storage and handling of A. nidulans and procedures for genetic crossing, progeny analysis and growth testing. These procedures are used for Mendelian analysis of segregation of alleles to show whether a mutant phenotype segregates as a single gene and independent assortment of genes to determine the linkage relationship between genes. Meiotic crossing is used for construction of multiple mutant strains for genetic analysis. Genetic crossing and analysis of progeny can be undertaken in 2-3 weeks and growth testing takes 2-3 days.

  8. The portable device for continual measurement of radon progenies on filter using the detector Timepix.

    PubMed

    Bulanek, Boris; Hulka, Jiri; Jilek, Karel; Stekl, Ivan

    2015-06-01

    In this article, a portable device was presented for continual measuring of equilibrium equivalent concentration (EEC) of (222)Rn based on the Timepix detector with 300-µm-thick active layer. In order to have a portable device, a filtration head was developed for collecting short-lived radon progenies attached on aerosols. The short-lived progenies are estimated from analysing alphas from decay of (218,214)Po from Millipore filter after termination of filtration. Comparison with beta measurement was done as well. The dependence of EEC on an air flow and filtration time was studied. The low-level detection limit for EEC was estimated from the last 10 min of 3-h decay measurement and was found in the range of 40-70 Bq m(-3). EEC was measured in National Radiation Protection Institute radon chamber, and results were compared with the commercial detector Fritra4.

  9. A Novel Molecular and Functional Stemness Signature Assessing Human Cord Blood-Derived Endothelial Progenitor Cell Immaturity

    PubMed Central

    Pascaud, Juliette; Driancourt, Catherine; Boyer-Di-Ponio, Julie; Uzan, Georges

    2016-01-01

    Endothelial Colony Forming Cells (ECFCs), a distinct population of Endothelial Progenitor Cells (EPCs) progeny, display phenotypic and functional characteristics of endothelial cells while retaining features of stem/progenitor cells. Cord blood-derived ECFCs (CB-ECFCs) have a high clonogenic and proliferative potentials and they can acquire different endothelial phenotypes, this requiring some plasticity. These properties provide angiogenic and vascular repair capabilities to CB-ECFCs for ischemic cell therapies. However, the degree of immaturity retained by EPCs is still confused and poorly defined. Consequently, to better characterize CB-ECFC stemness, we quantified their clonogenic potential and demonstrated that they were reprogrammed into induced pluripotent stem cells (iPSCs) more efficiently and rapidly than adult endothelial cells. Moreover, we analyzed the transcriptional profile of a broad gene panel known to be related to stem cells. We showed that, unlike mature endothelial cells, CB-ECFCs expressed genes involved in the maintenance of embryonic stem cell properties such as DNMT3B, GDF3 or SOX2. Thus, these results provide further evidence and tools to appreciate EPC-derived cell stemness. Moreover this novel stem cell transcriptional signature of ECFCs could help better characterizing and ranging EPCs according to their immaturity profile. PMID:27043207

  10. Oscillators and Oscillations in the Basal Ganglia

    PubMed Central

    Wilson, Charles J.

    2015-01-01

    What is the meaning of an action potential? There must be different answers for neurons that oscillate spontaneously, firing action potentials even in the absence of any synaptic input, and those driven to fire from a resting membrane potential. In spontaneously firing neurons, the occurrence of the next action potential is guaranteed. Only variations in its timing can carry the message. Among cells of this type are all those making up the deeper nuclei of the basal ganglia, including both segments of the globus pallidus, the substantia nigra, and the subthalamic nucleus. These cells receive thousands of excitatory and inhibitory synaptic inputs, but no input is required to maintain the firing of the cells; they fire at approximately the same rate when the synapses are silenced. Instead, synaptic inputs produce brief changes in spike timing and firing rate. The interactions among oscillating cells within and among the basal ganglia nuclei produce a complex resting pattern of activity. Normally, this pattern is highly irregular and decorrelates the network, so that the firing of each cell is statistically independent of the others. This maximizes the potential information that may be transmitted by the basal ganglia to its target structures. In Parkinson’s disease, the resting pattern of activity is dominated by a slow oscillation shared by all the neurons. Treatment with deep brain stimulation may gain its therapeutic value by disrupting this shared pathological oscillation, and restoring independent action by each neuron in the network. PMID:25449134

  11. Vesicular transport of progeny parvovirus particles through ER and Golgi regulates maturation and cytolysis.

    PubMed

    Bär, Séverine; Rommelaere, Jean; Nüesch, Jürg P F

    2013-09-01

    Progeny particles of non-enveloped lytic parvoviruses were previously shown to be actively transported to the cell periphery through vesicles in a gelsolin-dependent manner. This process involves rearrangement and destruction of actin filaments, while microtubules become protected throughout the infection. Here the focus is on the intracellular egress pathway, as well as its impact on the properties and release of progeny virions. By colocalization with cellular marker proteins and specific modulation of the pathways through over-expression of variant effector genes transduced by recombinant adeno-associated virus vectors, we show that progeny PV particles become engulfed into COPII-vesicles in the endoplasmic reticulum (ER) and are transported through the Golgi to the plasma membrane. Besides known factors like sar1, sec24, rab1, the ERM family proteins, radixin and moesin play (an) essential role(s) in the formation/loading and targeting of virus-containing COPII-vesicles. These proteins also contribute to the transport through ER and Golgi of the well described analogue of cellular proteins, the secreted Gaussia luciferase in absence of virus infection. It is therefore likely that radixin and moesin also serve for a more general function in cellular exocytosis. Finally, parvovirus egress via ER and Golgi appears to be necessary for virions to gain full infectivity through post-assembly modifications (e.g. phosphorylation). While not being absolutely required for cytolysis and progeny virus release, vesicular transport of parvoviruses through ER and Golgi significantly accelerates these processes pointing to a regulatory role of this transport pathway.

  12. Impact of the 235U series on doses from intakes of natural uranium and decay progeny.

    PubMed

    Lowe, L M

    1997-10-01

    The doses from 235U series radionuclides have often been ignored in dose assessments involving natural uranium and progeny. This is due to the relatively low abundance of 235U in natural uranium (less than 5% on an activity basis). However, inclusion of the 235U series radionuclides, especially 227Ac and 231Pa, in dose calculations can have a substantial impact on estimated inhalation doses.

  13. Dosimetry of localized accumulations of cigarette smoke and radon progeny at bifurcations

    SciTech Connect

    Martonen, T.B.; Hofmann, W.

    1991-01-01

    The work focuses upon deposition and clearance processes affecting cigarette smoke particles and radon progeny within surrogate airway models, replica casts and the human lung. As shall be demonstrated, 'cloud motion' for mainstream cigarette smoke can produce locations of enhanced deposition not experienced with dilute aerosols composed of like-sized particles. These sites of concentrated deposits occur at airway bifurcations, especially at the inclusive carinal ridges.

  14. Morphological and physiological responses of two coffee progenies to soil water availability.

    PubMed

    Dias, Paulo C; Araujo, Wagner L; Moraes, Gustavo A B K; Barros, Raimundo S; DaMatta, Fábio M

    2007-12-01

    Drought is a major environmental constraint affecting growth and production of coffee. The effects of water supply on growth, biomass allocation, water relations, and gas exchange in two coffee progenies representing drought-tolerant (Siriema) and drought-sensitive (Catucaí) genotypes were compared. They were grown in 12-L pots until 4-months old, when they were submitted to two watering treatments for 60 d: plants receiving either 100% transpired water (control plants) or a fraction (about 40%) of the amount of water transpired by control plants (drought-stressed plants). Under control conditions, Siriema grew faster than Catucaí. Regardless of the watering regimes and progenies, relative growth rate (RGR) was positively correlated both with net assimilation rate (NAR) and long-term water-use efficiency (WUE), but not with differences in biomass allocation. Both progenies responded to drought stress through (i) similar decreases in both RGR and NAR with marginal, if any, changes in allocation; (ii) decreases in leaf water potential, which occurred to a greater extent in Catucaí than in Siriema, even though they have showed similar abilities to adjust osmotically and elastically; (iii) similar reductions in net photosynthesis due mainly to nonstomatal factors; and (iv) decreases in transpiration rate coupled with increased long-term WUE. However, the lower transpiration rate and the higher long-term WUE as found in Siriema relative to Catucaí under control conditions persisted under drought conditions. Overall, the major differences between these progenies were largely associated with differences in plant water use, which was likely related to the improved water status of Siriema. The possible implications of selecting coffee genotypes for high WUE are discussed.

  15. Prediction of Lung Cells Oncogenic Transformation for Induced Radon Progeny Alpha Particles Using Sugarscape Cellular Automata

    PubMed Central

    Baradaran, Samaneh; Maleknasr, Niaz; Setayeshi, Saeed; Akbari, Mohammad Esmaeil

    2014-01-01

    Background Alpha particle irradiation from radon progeny is one of the major natural sources of effective dose in the public population. Oncogenic transformation is a biological effectiveness of radon progeny alpha particle hits. The biological effects which has caused by exposure to radon, were the main result of a complex series of physical, chemical, biological and physiological interactions. The cellular and molecular mechanisms for radon-induced carcinogenesis have not been clear yet. Methods Various biological models, including cultured cells and animals, have been found useful for studying the carcinogenesis effects of radon progeny alpha particles. In this paper, sugars cape cellular automata have been presented for computational study of complex biological effect of radon progeny alpha particles in lung bronchial airways. The model has included mechanism of DNA damage, which has been induced alpha particles hits, and then formation of transformation in the lung cells. Biomarkers were an objective measure or evaluation of normal or abnormal biological processes. In the model, the metabolism rate of infected cell has been induced alpha particles traversals, as a biomarker, has been followed to reach oncogenic transformation. Results The model results have successfully validated in comparison with “in vitro oncogenic transformation data” for C3H 10T1/2 cells. This model has provided an opportunity to study the cellular and molecular changes, at the various stages in radiation carcinogenesis, involving human cells. Conclusion It has become well known that simulation could be used to investigate complex biomedical systems, in situations where traditional methodologies were difficult or too costly to employ. PMID:25250147

  16. Endothelial Progenitors: A Consensus Statement on Nomenclature.

    PubMed

    Medina, Reinhold J; Barber, Chad L; Sabatier, Florence; Dignat-George, Francoise; Melero-Martin, Juan M; Khosrotehrani, Kiarash; Ohneda, Osamu; Randi, Anna M; Chan, Jerry K Y; Yamaguchi, Teruhide; Van Hinsbergh, Victor W M; Yoder, Mervin C; Stitt, Alan W

    2017-03-10

    Endothelial progenitor cell (EPC) nomenclature remains ambiguous and there is a general lack of concordance in the stem cell field with many distinct cell subtypes continually grouped under the term "EPC." It would be highly advantageous to agree standards to confirm an endothelial progenitor phenotype and this should include detailed immunophenotyping, potency assays, and clear separation from hematopoietic angiogenic cells which are not endothelial progenitors. In this review, we seek to discourage the indiscriminate use of "EPCs," and instead propose precise terminology based on defining cellular phenotype and function. Endothelial colony forming cells and myeloid angiogenic cells are examples of two distinct and well-defined cell types that have been considered EPCs because they both promote vascular repair, albeit by completely different mechanisms of action. It is acknowledged that scientific nomenclature should be a dynamic process driven by technological and conceptual advances; ergo the ongoing "EPC" nomenclature ought not to be permanent and should become more precise in the light of strong scientific evidence. This is especially important as these cells become recognized for their role in vascular repair in health and disease; and, in some cases, progress toward use in cell therapy. © Stem Cells Translational Medicine 2017.

  17. Transient nuclear Prospero induces neural progenitor quiescence

    PubMed Central

    Lai, Sen-Lin; Doe, Chris Q

    2014-01-01

    Stem cells can self-renew, differentiate, or enter quiescence. Understanding how stem cells switch between these states is highly relevant for stem cell-based therapeutics. Drosophila neural progenitors (neuroblasts) have been an excellent model for studying self-renewal and differentiation, but quiescence remains poorly understood. In this study, we show that when neuroblasts enter quiescence, the differentiation factor Prospero is transiently detected in the neuroblast nucleus, followed by the establishment of a unique molecular profile lacking most progenitor and differentiation markers. The pulse of low level nuclear Prospero precedes entry into neuroblast quiescence even when the timing of quiescence is advanced or delayed by changing temporal identity factors. Furthermore, loss of Prospero prevents entry into quiescence, whereas a pulse of low level nuclear Prospero can drive proliferating larval neuroblasts into quiescence. We propose that Prospero levels distinguish three progenitor fates: absent for self-renewal, low for quiescence, and high for differentiation. DOI: http://dx.doi.org/10.7554/eLife.03363.001 PMID:25354199

  18. Neuregulin 1 Type II-ErbB Signaling Promotes Cell Divisions Generating Neurons from Neural Progenitor Cells in the Developing Zebrafish Brain.

    PubMed

    Sato, Tomomi; Sato, Fuminori; Kamezaki, Aosa; Sakaguchi, Kazuya; Tanigome, Ryoma; Kawakami, Koichi; Sehara-Fujisawa, Atsuko

    2015-01-01

    Post-mitotic neurons are generated from neural progenitor cells (NPCs) at the expense of their proliferation. Molecular and cellular mechanisms that regulate neuron production temporally and spatially should impact on the size and shape of the brain. While transcription factors such as neurogenin1 (neurog1) and neurod govern progression of neurogenesis as cell-intrinsic mechanisms, recent studies show regulatory roles of several cell-extrinsic or intercellular signaling molecules including Notch, FGF and Wnt in production of neurons/neural progenitor cells from neural stem cells/radial glial cells (NSCs/RGCs) in the ventricular zone (VZ). However, it remains elusive how production of post-mitotic neurons from neural progenitor cells is regulated in the sub-ventricular zone (SVZ). Here we show that newborn neurons accumulate in the basal-to-apical direction in the optic tectum (OT) of zebrafish embryos. While neural progenitor cells are amplified by mitoses in the apical ventricular zone, neurons are exclusively produced through mitoses of neural progenitor cells in the sub-basal zone, later in the sub-ventricular zone, and accumulate apically onto older neurons. This neurogenesis depends on Neuregulin 1 type II (NRG1-II)-ErbB signaling. Treatment with an ErbB inhibitor, AG1478 impairs mitoses in the sub-ventricular zone of the optic tectum. Removal of AG1478 resumes sub-ventricular mitoses without precedent mitoses in the apical ventricular zone prior to basal-to-apical accumulation of neurons, suggesting critical roles of ErbB signaling in mitoses for post-mitotic neuron production. Knockdown of NRG1-II impairs both mitoses in the sub-basal/sub-ventricular zone and the ventricular zone. Injection of soluble human NRG1 into the developing brain ameliorates neurogenesis of NRG1-II-knockdown embryos, suggesting a conserved role of NRG1 as a cell-extrinsic signal. From these results, we propose that NRG1-ErbB signaling stimulates cell divisions generating neurons from

  19. Inheritance of nitrogen use efficiency in inbred progenies of tropical maize based on multivariate diallel analysis.

    PubMed

    Guedes, Fernando Lisboa; Diniz, Rafael Parreira; Balestre, Marcio; Ribeiro, Camila Bastos; Camargos, Renato Barbosa; Souza, João Cândido

    2014-01-01

    The objective of our study was to characterize and determine the patterns of genetic control in relation to tolerance and efficiency of nitrogen use by means of a complete diallel cross involving contrasting inbred progenies of tropical maize based on a univariate approach within the perspective of a multivariate mixed model. Eleven progenies, previously classified regarding the tolerance and responsiveness to nitrogen, were crossed in a complete diallel cross. Fifty-five hybrids were obtained. The hybrids and the progenies were evaluated at two different nitrogen levels, in two locations. The grain yield was measured as well as its yield components. The heritability values between the higher and lower nitrogen input environment did not differ among themselves. It was observed that the general combining ability values were similar for both approaches univariate and multivariate, when it was analyzed within each location and nitrogen level. The estimate of variance of the specific combining ability was higher than general combining ability estimate and the ratio between them was 0.54. The univariate and multivariate approaches are equivalent in experiments with good precision and high heritability. The nonadditive genetic effects exhibit greater quantities than the additive genetic effects for the genetic control of nitrogen use efficiency.

  20. Inheritance of Nitrogen Use Efficiency in Inbred Progenies of Tropical Maize Based on Multivariate Diallel Analysis

    PubMed Central

    Guedes, Fernando Lisboa; Diniz, Rafael Parreira; Balestre, Marcio; Ribeiro, Camila Bastos; Camargos, Renato Barbosa; Souza, João Cândido

    2014-01-01

    The objective of our study was to characterize and determine the patterns of genetic control in relation to tolerance and efficiency of nitrogen use by means of a complete diallel cross involving contrasting inbred progenies of tropical maize based on a univariate approach within the perspective of a multivariate mixed model. Eleven progenies, previously classified regarding the tolerance and responsiveness to nitrogen, were crossed in a complete diallel cross. Fifty-five hybrids were obtained. The hybrids and the progenies were evaluated at two different nitrogen levels, in two locations. The grain yield was measured as well as its yield components. The heritability values between the higher and lower nitrogen input environment did not differ among themselves. It was observed that the general combining ability values were similar for both approaches univariate and multivariate, when it was analyzed within each location and nitrogen level. The estimate of variance of the specific combining ability was higher than general combining ability estimate and the ratio between them was 0.54. The univariate and multivariate approaches are equivalent in experiments with good precision and high heritability. The nonadditive genetic effects exhibit greater quantities than the additive genetic effects for the genetic control of nitrogen use efficiency. PMID:25587575

  1. Study on the influence of CR-39 detector size on radon progeny detection in indoor environments

    SciTech Connect

    Pereira, L. A.; Hadler, J. C.; Lixandrão F, A. L.; Guedes, S.; Takizawa, R. H.

    2014-11-11

    It is well known that radon daughters up to {sup 214}Po are the real contaminants to be considered in case of indoor radon contamination. Assemblies consisting of 6 circular bare sheets of CR-39, a nuclear track detector, with radius varying from 0.15 to 1.2 cm were exposed far from any material surface for periods of approximately 6 months in 13 different indoor rooms (7 workplaces and 6 dwellings), where ventilation was moderate or poor. It was observed that track density was as greater as smaller was the detector radius. Track density data were fitted using an equation deduced based on the assumption that the behavior of radon and its progeny in the air was described by Fick's Law, i.e., when the main mechanism of transport of radon progeny in the air is diffusion. As many people spend great part of their time in closed or poorly ventilated environments, the confirmation they present equilibrium between radon and its progeny is an interesting start for dosimetric calculations concerning this contamination.

  2. Multivariate analysis to determine the genetic distance among backcross papaya (Carica papaya) progenies.

    PubMed

    Ramos, H C C; Pereira, M G; Gonçalves, L S A; Berilli, A P C G; Pinto, F O; Ribeiro, E H

    2012-05-14

    Morpho-agronomic and molecular (RAPD and ISSR markers) data were used to evaluate genetic distances between papaya backcross progenies in order to help identify agronomically superior genotypes. Thirty-two papaya progenies were evaluated based on 15 morpho-agronomic characteristics, 20 ISSR and 19 RAPD primers. Manhattan, Jaccard and Gower distances were used to estimate differences based on continuous and binary data and combined analyses, respectively. Except for production, there were significant differences in the continuous variables among the genotypes. The molecular analysis revealed 193 dominant markers (ISSR and RAPD), being 53 polymorphic loci. Among the various clusters that were generated, the one based on a combined analysis of morpho-agronomic and molecular data gave the highest cophenetic correlation (0.72) compared to individual analysis, consistently allocating the progenies into six groups. We found that the Gower algorithm was more coherent in the discrimination of the genotypes, demonstrating that a combination of molecular and agronomic data is valuable for studies of genetic dissimilarity in papaya.

  3. Analysis of radon and thoron progeny measurements based on air filtration.

    PubMed

    Stajic, J M; Nikezic, D

    2015-02-01

    Measuring of radon and thoron progeny concentrations in air, based on air filtration, was analysed in order to assess the reliability of the method. Changes of radon and thoron progeny activities on the filter during and after air sampling were investigated. Simulation experiments were performed involving realistic measuring parameters. The sensitivity of results (radon and thoron concentrations in air) to the variations of alpha counting in three and five intervals was studied. The concentration of (218)Po showed up to be the most sensitive to these changes, as was expected because of its short half-life. The well-known method for measuring of progeny concentrations based on air filtration is rather unreliable and obtaining unrealistic or incorrect results appears to be quite possible. A simple method for quick estimation of radon potential alpha energy concentration (PAEC), based on measurements of alpha activity in a saturation regime, was proposed. Thoron PAEC can be determined from the saturation activity on the filter, through beta or alpha measurements.

  4. Erythrocyte alloantigens in the Storrs strain of hereditary muscular dystrophic chickens and segregating testcross progeny.

    PubMed

    Sanders, B G; Kline, K; Briles, W E

    1981-01-01

    The Storrs strain of muscular dystrophic chickens were typed for erythrocyte alloalleles at 10 loci, including the B locus. Gene fixation is present at five loci and expression of the predominate alloantigen varied in frequency from 0.53 to 0.91 at the other five loci tested. The Storrs strain of muscular dystrophic chickens are not fixed at the B locus, expressing the B2/B2 allelic combination 81 percent of the time and B2/B23 the remaining percentage. Testcross progeny segregating for the muscular dystrophy trait did not show any alloantigen associations at the 10 loci examined. No association of the MD train with a particular B genotype could be ascertained. CPK levels as a measure of muscle destruction in the muscular dystrophic testcross progeny segregating at the B locus did not reveal an association with any B haplotype. Serum IgG levels and low Con A response in muscular dystrophic testcross progeny also were not associated with any specific B locus alloantigen combinations. The possibility remains that the establishment of a pathological index for muscular dystrophy in MD chickens may reveal an association with the B locus.

  5. Impact of haze-fog days to radon progeny equilibrium factor and discussion of related factors.

    PubMed

    Hou, Changsong; Shang, Bing; Zhang, Qingzhao; Cui, Hongxing; Wu, Yunyun; Deng, Jun

    2015-11-01

    The equilibrium factor F between radon and its short-lived progenies is an important parameter to estimate radon exposure of humans. Therefore, indoor and outdoor concentrations of radon and its short-lived radon progeny were measured in Beijing area using a continuously measuring device, in an effort to obtain information on the F value. The results showed that the mean values of F were 0.58 ± 0.13 (0.25-0.95, n = 305) and 0.52 ± 0.12 (0.31-0.91, n = 64) for indoor and outdoor, respectively. The indoor F value during haze-fog days was higher than the typical value of 0.4 recommended by the United Nations Scientific Committee on the Effects of Atomic Radiation, and it was also higher than the values of 0.47 and 0.49 reported in the literature. A positive correlation was observed between indoor F values and PM2.5 concentrations (R (2) = 0.71). Since 2013, owing to frequent heavy haze-fog events in Beijing and surrounding areas, the number of the days with severe pollution remains at a high level. Future studies on the impact of the ambient fine particulate matter on indoor radon progeny equilibrium factor F could be important.

  6. Optimization of the Timepix chip to measurement of radon, thoron and their progenies.

    PubMed

    Janik, Miroslaw; Ploc, Ondrej; Fiederle, Michael; Procz, Simon; Kavasi, Norbert

    2016-01-01

    Radon and thoron as well as their short-lived progenies are decay products of the radium and thorium series decays. They are the most important radionuclide elements with respect to public exposure. To utilize the semiconductor pixel radiation Timepix chip for the measurement of active and real-time alpha particles from radon, thoron and their progenies, it is necessary to check the registration and visualization of the chip. An energy check for radon, thoron and their progenies, as well as for (241)Am and(210)Po sources, was performed using the radon and thoron chambers at NIRS (National Institute of Radiological Sciences). The check found an energy resolution of 200 keV with a 14% efficiency as well as a linear dependency between the channel number (cluster volume) and the energy. The coefficient of determination r(2) of 0.99 for the range of 5 to 9 MeV was calculated. In addition, an offset for specific Timepix configurations between pre-calibration for low energy from 6 to 60 keV, and the actual calibration for alpha particles with energies from 4000 to 9000 keV, was detected.

  7. Morphology of respiratory tract lesions in rats exposed to radon progeny

    SciTech Connect

    Dagle, G.E.; Cross, F.T.; Gies, R.A.

    1992-12-31

    We will discuss the morphologic features of lesions in the respiratory tract of rats exposed to radon and radon progeny. Groups of male Wister rats were exposed to from 10 to 1000 working levels (WL) of radon progeny in the presence of less than 1 to about 15 mg m{sup {minus}3} uranium ore dust. Cumulative exposures ranged from 20 to approximately 10,000 working level months (WLM). Higher exposure levels produced radiation pneumonitis characterized by interstitial fibrosis, associated with alveolar epithelial cell hyperplasia and accumulations of alveolar macrophages containing phagocytosed uranium ore dust. Nodular fibrosis and alveolar proteinosis were correlated with deposits of uranium ore dust. Vesicular emphysema also occurred at higher exposure levels. Pulmonary adenomatosis appeared to be a preneoplastic lesion; it was composed of nodular proliferation of bronchioloalveolar epithelium without disruption of the general architecture of the parenchyma. At exposure levels where rats lived longer than 1 y, lung tumors and a few tumors of the nasal cavity developed. The principal lung tumors were pulmonary adenomas, bronchioloalveolar carcinomas, papillary adenocarcinomas, epidermoid carcinomas, and adenosquamous carcinomas. Occasionally, malignant mesotheliomas and sarcomas were also present. The malignant lung tumors were characterized by invasion and occasionally metastasized to regional lymph nodes. Lower exposure rates produced more tumors, generally of different histologic types, and more fatal tumors than higher exposure rates. The similarity to relationships of human radon progeny exposure as far as incidence and types of lung tumors establish the validity of this animal model for studying radon carcinogenesis in humans.

  8. Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny.

    PubMed

    Wimmer, M E; Briand, L A; Fant, B; Guercio, L A; Arreola, A C; Schmidt, H D; Sidoli, S; Han, Y; Garcia, B A; Pierce, R C

    2017-02-21

    Paternal environmental perturbations including exposure to drugs of abuse can produce profound effects on the physiology and behavior of offspring via epigenetic modifications. Here we show that adult drug-naive male offspring of cocaine-exposed sires have memory formation deficits and associated reductions in NMDA receptor-mediated hippocampal synaptic plasticity. Reduced levels of the endogenous NMDA receptor co-agonist d-serine were accompanied by increased expression of the d-serine degrading enzyme d-amino acid oxidase (Dao1) in the hippocampus of cocaine-sired male progeny. Increased Dao1 transcription was associated with enrichment of permissive epigenetic marks on histone proteins in the hippocampus of male cocaine-sired progeny, some of which were enhanced near the Dao1 locus. Finally, hippocampal administration of d-serine reversed both the memory formation and synaptic plasticity deficits. Collectively, these results demonstrate that paternal cocaine exposure produces epigenetic remodeling in the hippocampus leading to NMDA receptor-dependent memory formation and synaptic plasticity impairments only in male progeny, which has significant implications for the male descendants of chronic cocaine users.Molecular Psychiatry advance online publication, 21 February 2017; doi:10.1038/mp.2017.8.

  9. Epiboly generates the epidermal basal monolayer and spreads the nascent mammalian skin to enclose the embryonic body

    PubMed Central

    Panousopoulou, Eleni; Hobbs, Carl; Mason, Ivor; Green, Jeremy B. A.

    2016-01-01

    ABSTRACT Epiboly is a morphogenetic process that is employed in the surface ectoderm of anamniotes during gastrulation to cover the entire embryo. We propose here that mammals also utilise this process to expand the epidermis and enclose the body cavity and spinal cord with a protective surface covering. Our data supports a model whereby epidermal spreading is driven by the primary establishment of the epidermal basal progenitor monolayer through radial cell intercalation of a multi-layered epithelium towards the basal lamina. By using a suspension organotypic culture strategy, we find that this process is fibronectin-dependent and autonomous to the skin. The radial cell rearrangements that drive epidermal spreading also require ROCK activity but are driven by cell protrusions and not myosin II contractility. Epidermal progenitor monolayer formation and epidermal spreading are delayed in Crash mice, which possess a dominant mutation in Celsr1, an orthologue of the core planar cell polarity (PCP) Drosophila protein Flamingo (also known as Stan). We observe a failure of ventral enclosure in Crash mutants suggesting that defective epidermal spreading might underlie some ventral wall birth defects. PMID:26989131

  10. Adrenomedullary progenitor cells: Isolation and characterization of a multi-potent progenitor cell population.

    PubMed

    Vukicevic, Vladimir; Rubin de Celis, Maria Fernandez; Pellegata, Natalia S; Bornstein, Stefan R; Androutsellis-Theotokis, Andreas; Ehrhart-Bornstein, Monika

    2015-06-15

    The adrenal is a highly plastic organ with the ability to adjust to physiological needs by adapting hormone production but also by generating and regenerating both adrenocortical and adrenomedullary tissue. It is now apparent that many adult tissues maintain stem and progenitor cells that contribute to their maintenance and adaptation. Research from the last years has proven the existence of stem and progenitor cells also in the adult adrenal medulla throughout life. These cells maintain some neural crest properties and have the potential to differentiate to the endocrine and neural lineages. In this article, we discuss the evidence for the existence of adrenomedullary multi potent progenitor cells, their isolation and characterization, their differentiation potential as well as their clinical potential in transplantation therapies but also in pathophysiology.

  11. Basal cell nevus syndrome - close-up of palm (image)

    MedlinePlus

    ... skeletal abnormalities. Skin manifestations include pits in the palms and soles, and numerous basal cell carcinomas. This ... close-up of the pits found in the palm of an individual with basal cell nevus syndrome.

  12. Direct evidence for interaction between human erythroid progenitor cells and a hemoglobin switching activity present in fetal sheep serum.

    PubMed Central

    Stamatoyannopoulos, G; Nakamoto, B; Kurachi, S; Papayannopoulou, T

    1983-01-01

    An activity that induces Hb F to Hb A switching in human cells is present in fetal sheep serum. To test directly the role of cell-to-environment interactions in hemoglobin switching and to define the level of erythroid cell differentiation at which this activity operates, colony transfer experiments were done. Clones grown in the presence of switching activity-containing medium (fetal sheep serum) or control medium (fetal calf serum) were transferred, at the 16- to 30-cell stage, to either fetal sheep serum or fetal calf serum plates and Hb F synthesis was determined in the fully mature erythroid bursts. Fetal calf serum-to-fetal calf serum transfers produced colonies with the high Hb F levels characteristic of undisturbed fetal calf serum-grown clones. Fetal sheep serum-to-fetal calf serum transfers resulted in significant decrease in Hb F synthesis, revealing an interaction between hemoglobin switching activity and cells at an early stage of progenitor cell development. The reduction of Hb F synthesis in fetal calf serum-to-fetal sheep serum transfers indicated that hemoglobin switching activity interacts with cells at later stages of progenitor cell development. Maximal decrease in Hb F synthesis was observed in fetal sheep serum-to-fetal sheep serum transfers, indicating that optimal effects on Hb switching are obtained when the environment that induces Hb switching is present throughout the development of progenitor cells. By splitting single early clones into two parts and transferring them to either a fetal sheep serum or a fetal calf serum environment, these interactions were further demonstrated in the progeny of a single erythroid burst-forming unit. Since all clone transfers were done on cell-free plates, the results of fetal calf serum-to-fetal sheep serum and of fetal sheep serum-to-fetal sheep serum transfers indicated that the switching activity does not require helper cells for its action. These studies show directly that (i) Hb F synthesis is

  13. Porcine Skin-Derived Progenitor (SKP) Spheres and Neurospheres: Distinct “Stemness” Identified by Microarray Analysis

    PubMed Central

    Zhao, Ming-Tao; Whitworth, Kristin M.; Lin, Hui; Zhang, Xia; Isom, S. Clay; Dobbs, Kyle B.; Bauer, Bethany; Zhang, Yong

    2010-01-01

    Abstract Skin-derived progenitors (SKP) are neural crest derived and can generate neural and mesodermal progeny in vitro, corresponding to the multipotency of neural crest stem cells. Likewise, neural stem/progenitor cells (displaying as neurospheres) have the capacity of self-renewing, and can produce most phenotypes in the nervous system. Both form spheres when cultured with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Although the “stemness” of neural stem/progenitor cells has been extensively investigated, the molecular comparison of SKP spheres and neurospheres has not been elucidated. Here, SKP spheres and neurospheres from the same individual porcine fetuses were isolated with the same culture medium, and the multipotency was tested by in vitro differentiation assays. Microarray analysis was used to illustrate the “stemness” of SKP spheres and neurospheres. The upregulated genes that were in common in the SKP spheres and neurospheres are involved in ribosome, tight junction, gap junction, cell communication, calcium signaling, ErbB signaling, JAK–STAT signaling, MAPK signaling, etc. The differentially expressed genes between SKP spheres and neurospheres are mainly involved in ECM–receptor interaction and the transforming growth factor-beta (TGF-β) signaling pathway. Finally, treatment with leukemia inhibitory factor (LIF) or MEK inhibitor results in a distinctive impact on the “stemness” and differentiation genes of SKP spheres and neurospheres. Thus, the cell-intrinsic genetic program may contribute to the innate “stemness” of SKP spheres and neurospheres in a similar local microenvironment. PMID:20694160

  14. Mesenchymal Stem and Progenitor Cells in Normal and Dysplastic Hematopoiesis—Masters of Survival and Clonality?

    PubMed Central

    Pleyer, Lisa; Valent, Peter; Greil, Richard

    2016-01-01

    Myelodysplastic syndromes (MDS) are malignant hematopoietic stem cell disorders that have the capacity to progress to acute myeloid leukemia (AML). Accumulating evidence suggests that the altered bone marrow (BM) microenvironment in general, and in particular the components of the stem cell niche, including mesenchymal stem cells (MSCs) and their progeny, play a pivotal role in the evolution and propagation of MDS. We here present an overview of the role of MSCs in the pathogenesis of MDS, with emphasis on cellular interactions in the BM microenvironment and related stem cell niche concepts. MSCs have potent immunomodulatory capacities and communicate with diverse immune cells, but also interact with various other cellular components of the microenvironment as well as with normal and leukemic stem and progenitor cells. Moreover, compared to normal MSCs, MSCs in MDS and AML often exhibit altered gene expression profiles, an aberrant phenotype, and abnormal functional properties. These alterations supposedly contribute to the “reprogramming” of the stem cell niche into a disease-permissive microenvironment where an altered immune system, abnormal stem cell niche interactions, and an impaired growth control lead to disease progression. The current article also reviews molecular targets that play a role in such cellular interactions and possibilities to interfere with abnormal stem cell niche interactions by using specific targeted drugs. PMID:27355944

  15. Zika virus infection induces mitosis abnormalities and apoptotic cell death of human neural progenitor cells

    PubMed Central

    Souza, Bruno S. F.; Sampaio, Gabriela L. A.; Pereira, Ciro S.; Campos, Gubio S.; Sardi, Silvia I.; Freitas, Luiz A. R.; Figueira, Claudio P.; Paredes, Bruno D.; Nonaka, Carolina K. V.; Azevedo, Carine M.; Rocha, Vinicius P. C.; Bandeira, Antonio C.; Mendez-Otero, Rosalia; dos Santos, Ricardo Ribeiro; Soares, Milena B. P.

    2016-01-01

    Zika virus (ZIKV) infection has been associated with severe complications both in the developing and adult nervous system. To investigate the deleterious effects of ZIKV infection, we used human neural progenitor cells (NPC), derived from induced pluripotent stem cells (iPSC). We found that NPC are highly susceptible to ZIKV and the infection results in cell death. ZIKV infection led to a marked reduction in cell proliferation, ultrastructural alterations and induction of autophagy. Induction of apoptosis of Sox2+ cells was demonstrated by activation of caspases 3/7, 8 and 9, and by ultrastructural and flow cytometry analyses. ZIKV-induced death of Sox2+ cells was prevented by incubation with the pan-caspase inhibitor, Z-VAD-FMK. By confocal microscopy analysis we found an increased number of cells with supernumerary centrosomes. Live imaging showed a significant increase in mitosis abnormalities, including multipolar spindle, chromosome laggards, micronuclei and death of progeny after cell division. FISH analysis for chromosomes 12 and 17 showed increased frequency of aneuploidy, such as monosomy, trisomy and polyploidy. Our study reinforces the link between ZIKV and abnormalities in the developing human brain, including microcephaly. PMID:28008958

  16. Early molecular events during retinoic acid induced differentiation of neuromesodermal progenitors

    PubMed Central

    Cunningham, Thomas J.; Colas, Alexandre

    2016-01-01

    ABSTRACT Bipotent neuromesodermal progenitors (NMPs) residing in the caudal epiblast drive coordinated body axis extension by generating both posterior neuroectoderm and presomitic mesoderm. Retinoic acid (RA) is required for body axis extension, however the early molecular response to RA signaling is poorly defined, as is its relationship to NMP biology. As endogenous RA is first seen near the time when NMPs appear, we used WNT/FGF agonists to differentiate embryonic stem cells to NMPs which were then treated with a short 2-h pulse of 25 nM RA or 1 µM RA followed by RNA-seq transcriptome analysis. Differential expression analysis of this dataset indicated that treatment with 25 nM RA, but not 1 µM RA, provided physiologically relevant findings. The 25 nM RA dataset yielded a cohort of previously known caudal RA target genes including Fgf8 (repressed) and Sox2 (activated), plus novel early RA signaling targets with nearby conserved RA response elements. Importantly, validation of top-ranked genes in vivo using RA-deficient Raldh2−/− embryos identified novel examples of RA activation (Nkx1-2, Zfp503, Zfp703, Gbx2, Fgf15, Nt5e) or RA repression (Id1) of genes expressed in the NMP niche or progeny. These findings provide evidence for early instructive and permissive roles of RA in controlling differentiation of NMPs to neural and mesodermal lineages. PMID:27793834

  17. Hematopoietic stem and progenitor cells acquire distinct DNA-hypermethylation during in vitro culture.

    PubMed

    Weidner, Carola Ingrid; Walenda, Thomas; Lin, Qiong; Wölfler, Monika Martina; Denecke, Bernd; Costa, Ivan Gesteira; Zenke, Martin; Wagner, Wolfgang

    2013-11-28

    Hematopoietic stem and progenitor cells (HPCs) can be maintained in vitro, but the vast majority of their progeny loses stemness during culture. In this study, we compared DNA-methylation (DNAm) profiles of freshly isolated and culture-expanded HPCs. Culture conditions of CD34(+) cells - either with or without mesenchymal stromal cells (MSCs) - had relatively little impact on DNAm, although proliferation is greatly increased by stromal support. However, all cultured HPCs - even those which remained CD34(+) - acquired significant DNA-hypermethylation. DNA-hypermethylation occurred particularly in up-stream promoter regions, shore-regions of CpG islands, binding sites for PU.1, HOXA5 and RUNX1, and it was reflected in differential gene expression and variant transcripts of DNMT3A. Low concentrations of DNAm inhibitors slightly increased the frequency of colony-forming unit initiating cells. Our results demonstrate that HPCs acquire DNA-hypermethylation at specific sites in the genome which is relevant for the rapid loss of stemness during in vitro manipulation.

  18. Membranes replace irradiated blast cells as growth requirement for leukemic blast progenitors in suspension culture

    SciTech Connect

    Nara, N.; McCulloch, E.A.

    1985-11-01

    The blast cells of acute myeloblastic leukemia (AML) may be considered as a renewal population, maintained by blast stem cells capable of both self-renewal and the generation of progeny with reduced or absent proliferative potential. This growth requires that two conditions be met: first, the cultures must contain growth factors in media conditioned either by phytohemagglutinin (PHA)-stimulated mononuclear leukocytes (PHA-LCM), or by cells of the continuous bladder carcinoma line HTB9 (HTB9-CM). Second, the cell density must be maintained at 10(6) blasts/ml; this may be achieved by adding irradiated cells to smaller numbers of intact blasts. The authors are concerned with the mechanism of the feeding function. They present evidence that (a) cell-cell contact is required. (b) Blasts are heterogeneous in respect to their capacity to support growth. (c) Fractions containing membranes from blast cells will substitute for intact cells in promoting the generation of new blast progenitors in culture. (d) This membrane function may be specific for AML blasts, since membranes from blasts of lymphoblastic leukemia or normal marrow cells were inactive.

  19. Rapidly rotating second-generation progenitors for the 'blue hook' stars of ω Centauri.

    PubMed

    Tailo, Marco; D'Antona, Francesca; Vesperini, Enrico; Di Criscienzo, Marcella; Ventura, Paolo; Milone, Antonino P; Bellini, Andrea; Dotter, Aaron; Decressin, Thibaut; D'Ercole, Annibale; Caloi, Vittoria; Capuzzo-Dolcetta, Roberto

    2015-07-16

    Horizontal branch stars belong to an advanced stage in the evolution of the oldest stellar galactic population, occurring either as field halo stars or grouped in globular clusters. The discovery of multiple populations in clusters that were previously believed to have single populations gave rise to the currently accepted theory that the hottest horizontal branch members (the 'blue hook' stars, which had late helium-core flash ignition, followed by deep mixing) are the progeny of a helium-rich 'second generation' of stars. It is not known why such a supposedly rare event (a late flash followed by mixing) is so common that the blue hook of ω Centauri contains approximately 30 per cent of the horizontal branch stars in the cluster, or why the blue hook luminosity range in this massive cluster cannot be reproduced by models. Here we report that the presence of helium core masses up to about 0.04 solar masses larger than the core mass resulting from evolution is required to solve the luminosity range problem. We model this by taking into account the dispersion in rotation rates achieved by the progenitors, whose pre-main-sequence accretion disk suffered an early disruption in the dense environment of the cluster's central regions, where second-generation stars form. Rotation may also account for frequent late-flash-mixing events in massive globular clusters.

  20. Autumn frost hardiness in Norway spruce plus tree progeny and trees of the local and transferred provenances in central Sweden.

    PubMed

    Hannerz, Mats; Westin, Johan

    2005-09-01

    Reforestation with provenances from locations remote from the planting site (transferred provenances) or the progeny of trees of local provenances selected for superior form and vigor (plus trees) offer alternative means to increase yield over that obtained by the use of seed from unselected trees of the local provenance. Under Swedish conditions, Norway spruce (Picea abies (L.) Karst.) of certain transferred provenances generally has an advantage in productivity relative to the local provenance comparable to that of progeny of plus trees. The aim of this study was to explore the extent to which productivity gains achieved by provenance transfer or the use of plus tree progeny are associated with reductions in autumn frost hardiness, relative to that of trees of the local provenance. In a field trial with 19-year-old trees in central Sweden, bud hardiness was tested on four occasions during the autumn of 2002. Trees of the local provenance were compared with trees of a south Swedish provenance originating 3 degrees of latitude to the south, a Belarusian provenance and the progeny of plus trees of local origin. The Belarusian provenance was the least hardy and the local provenance the most hardy, with plus tree progeny and the south Swedish provenance being intermediate in hardiness. Both the Belarusian provenance and the plus tree progeny were significantly taller than trees of the other populations. Within provenances, tree height was negatively correlated with autumn frost hardiness. Among the plus tree progeny, however, no such correlation between tree height and autumn frost hardiness was found. It is concluded that although the gain in productivity achieved by provenance transfer from Belarus was comparable to that achieved by using the progeny of plus trees of the local provenance, the use of trees of the Belarus provenance involved an increased risk of autumn frost damage because of later hardening.

  1. Regulation of the nascent brain vascular network by neural progenitors.

    PubMed

    Santhosh, Devi; Huang, Zhen

    2015-11-01

    Neural progenitors are central players in the development of the brain neural circuitry. They not only produce the diverse neuronal and glial cell types in the brain, but also guide their migration in this process. Recent evidence indicates that neural progenitors also play a critical role in the development of the brain vascular network. At an early stage, neural progenitors have been found to facilitate the ingression of blood vessels from outside the neural tube, through VEGF and canonical Wnt signaling. Subsequently, neural progenitors directly communicate with endothelial cells to stabilize nascent brain vessels, in part through down-regulating Wnt pathway activity. Furthermore, neural progenitors promote nascent brain vessel integrity, through integrin αvβ8-dependent TGFβ signaling. In this review, we will discuss the evidence for, as well as questions that remain, regarding these novel roles of neural progenitors and the underlying mechanisms in their regulation of the nascent brain vascular network.

  2. Traumatic bilateral basal ganglia hematoma: A report of two cases

    PubMed Central

    Bhargava, Pranshu; Grewal, Sarvpreet Singh; Gupta, Bharat; Jain, Vikas; Sobti, Harman

    2012-01-01

    Traumatic Basal ganglia hemorrhage is relatively uncommon. Bilateral basal ganglia hematoma after trauma is extremely rare and is limited to case reports. We report two cases of traumatic bilateral basal ganglia hemorrhage, and review the literature in brief. Both cases were managed conservatively. PMID:23293672

  3. Influence of air flow on the behavior of thoron and its progeny in a traditional Japanese house

    SciTech Connect

    Ma, Jizeng; Doi, Masahiro; Kobayashi, Sadayoshi

    1997-01-01

    Air flow influence on the spatial distribution of thoron ({sup 220}Rn) concentration in a typical Japanese traditional house was investigated at various indoor air flow levels. The effect of air flow on the behavior of both thoron and radon progeny were examined simultaneously. Measurements were carried out by using two types of passive monitors, the radon-thoron discriminative monitor and the Radtrak monitor. Thoron and radon progeny were measured by filter grab sampling with ZnS scintillation counting. Under static condition, a horizontal distribution with greatly varied thoron concentrations was found as reported by previous studies. Under turbulent conditions, thoron concentrations in the middle of the room increased and the concentration gradient of thoron gas became lower. An obvious vertical distribution of thoron was also observed. Prominent diurnal variation of radon progeny concentrations was observed whereas that of thoron progeny concentrations was not. Concentration of thoron progeny changed little at different air flow levels, although the thoron gas level at the middle of the room varied significantly. The influence of air flows on detection efficiencies of the two types of thoron monitors were also checked. The mechanism of behavioral change of thoron and its progeny in turbulent atmosphere is discussed. 18 refs., 7 figs.

  4. Transfusion Support for ABO-Incompatible Progenitor Cell Transplantation

    PubMed Central

    Kopko, Patricia M.

    2016-01-01

    Summary ABO-incompatible transplants comprise up to 50% of allogeneic progenitor cell transplants. Major, minor and bidirectional ABO-incompatible transplants each have unique complications that can occur, including hemolysis at the time of progenitor cell infusion, hemolysis during donor engraftment, passenger lymphocyte syndrome, delayed red blood cell engraftment, and pure red cell aplasia. Appropriate transfusion support during the different phases of the allogeneic progenitor cell transplant process is an important part of ABO-incompatible transplantation. PMID:27022318

  5. Dopamine release in the basal ganglia

    PubMed Central

    Rice, Margaret E.; Patel, Jyoti C.; Cragg, Stephanie J.

    2011-01-01

    Dopamine (DA) is a key transmitter in the basal ganglia, yet DA transmission does not conform to several aspects of the classic synaptic doctrine. Axonal DA release occurs through vesicular exocytosis and is action-potential and Ca2+ dependent. However, in addition to axonal release, DA neurons in midbrain exhibit somatodendritic release, by an incompletely understood, but apparently exocytotic mechanism. Even in striatum, axonal release sites are controversial, with evidence for DA varicosities that lack postsynaptic specialization, and largely extrasynaptic DA receptors and transporters. Moreover, DA release is often assumed to reflect a global response to a population of activities in midbrain DA neurons, whether tonic or phasic, with precise timing and specificity of action governed by other basal ganglia circuits. This view has been reinforced by anatomical evidence showing dense axonal DA arbors throughout striatum, and a lattice network formed by DA axons and glutamatergic input from cortex and thalamus. Nonetheless, localized DA transients are seen in vivo using voltammetric methods with high spatial and temporal resolution. Mechanistic studies using similar methods in vitro have revealed local regulation of DA release by other transmitters and modulators, as well as by proteins known to be disrupted in Parkinson’s disease and other movement disorders. Notably, the actions of most other striatal transmitters on DA release also do not conform to the synaptic doctrine, with the absence of direct synaptic contacts for glutamate, GABA and aceylcholie (ACh) on striatal DA axons. Overall, the findings reviewed here indicate that DA signaling in the basal ganglia is sculpted by cooperation between the timing and pattern of DA input and those of local regulatory factors. PMID:21939738

  6. Short communication: Initial evidence supporting existence of potential rumen epidermal stem and progenitor cells.

    PubMed

    Yohe, T T; Tucker, H L M; Parsons, C L M; Geiger, A J; Akers, R M; Daniels, K M

    2016-09-01

    The bovine rumen epidermis is a keratinized multilayered tissue that experiences persistent cell turnover. Because of this constant cell turnover, epidermal stem cells and their slightly more differentiated daughter cells, epidermal progenitor cells, must exist in the stratum basale of rumen epidermis. To date, these 2 epidermal cell populations and any unique cellular markers they may possess remain completely uncharacterized in the bovine rumen. An important first step in this new research area is the demonstration of the relative abundance and existence of markers for these cells in rumen tissue. A related second step is to document rumen epidermal proliferative responses to an extrinsic signal such as nutrient concentration within the rumen. The objectives of this experiment were to evaluate the extrinsic effect of diet on (1) gene expression of 6 potential rumen epidermal stem or progenitor cell markers and (2) rumen epidermal cell proliferation within the stratum basale. Twelve preweaned Holstein heifers were fed either a restricted diet (R) or an enhanced diet (EH). Animals on R received a milk replacer (MR) diet fed at 0.44kg of powder dry matter (DM)/d (20.9% crude protein, 29.8% fat, DM basis) and EH received MR at 1.08kg of powder dry matter/d (28.9% crude protein, 26.2% fat, DM basis). All calves had access to a 20% crude protein starter and were weaned during wk 7 of the experiment. Lifetime DM intake was 0.73kg of DM/calf per day for R (5.88 Mcal of net energy/calf per day) and 1.26kg of DM/calf per day for EH (10.68 Mcal of net energy/calf per day). Twenty-four hours before slaughter heifers received an intravenous dose of 5-bromo-2'-deoxyuridine to label proliferating cells. Heifers were slaughtered at 8 wk of age, and rumen samples from the ventral sac region were obtained and stored in RNA preservative and processed for routine histology. Quantitative real-time reverse transcriptase PCR was used to analyze relative abundance of genes. Candidate

  7. Fractionation of a Basal Magma Ocean

    NASA Astrophysics Data System (ADS)

    Laneuville, M.; Hernlund, J. W.; Labrosse, S.

    2014-12-01

    Earth's magnetic field is thought to be sustained by dynamo action in a convecting metallic outer core since at least 3.45 Ga (Tarduno et al., 2010). Convection induces an isentropic temperature gradient that drains 13±3 TW of heat from the core by thermal conduction (de Koker et al., 2012; Pozzo et al., 2012; Gomi et al., 2013), and suggests that Earth's core has cooled by ˜1,000 K or more since Earth's formation (Gomi et al., 2013). However, models of Earth's initial thermal evolution following a giant-impact predict rapid cooling to the mantle melting temperature (e.g., Solomatov, 2007). In order to understand how the core could have retained enough heat to explain the age of the geodynamo, we relax a key assumption of the basal magma ocean model of (Labrosse et al., 2007) to allow for the possibility that the magma is stably stratified. Recent giant impact simulations suggest extensive core-mantle mixing (Saitoh and Makino, 2013), which could have produced such a large stratified magma layer at the core-mantle boundary. In the presence of a stable density gradient, heat transfer through the basal magma ocean occurs through conduction and therefore delays heat loss from the core. Partitioning of iron in the liquid phase upon crystallization changes the density profile and triggers convection in the upper part of the basal magma ocean. Our hypothesis suggests that early core cooling is dominated by the diffusion timescale through the basal magma ocean, and predicts a delayed onset of the geodynamo (i.e, during the late Headean/early Archean). This model can therefore be falsified if the existence of a geomagnetic field can be inferred from magnetization of inclusions in Hadean zircons. N. de Koker et al., Proc. Natl. Acad. Sci. 190, 4070-4073 (2012).H. Gomi et al., Phys. Earth Planet. Inter. 224, 88-103 (2013).S. Labrosse et al., Nature 450, 866-869 (2007).M. Pozzo et al., Nature 485, 355-358 (2012).T. Saitoh and J. Makino. Astrophys. J. 768, 44 (2013).V

  8. Mössbauer spectroscopy of Basal Ganglia

    NASA Astrophysics Data System (ADS)

    Miglierini, Marcel; Lančok, Adriana; Kopáni, Martin; Boča, Roman

    2014-10-01

    Chemical states, structural arrangement, and magnetic features of iron deposits in biological tissue of Basal Ganglia are characterized. The methods of SQUID magnetometry and electron microscopy are employed. 57Fe Mössbauer spectroscopy is used as a principal method of investigation. Though electron microscopy has unveiled robust crystals (1-3 μm in size) of iron oxides, they are not manifested in the corresponding 57Fe Mössbauer spectra. The latter were acquired at 300 K and 4.2 K and resemble ferritin-like behavior.

  9. The Basal Ganglia and Adaptive Motor Control

    NASA Astrophysics Data System (ADS)

    Graybiel, Ann M.; Aosaki, Toshihiko; Flaherty, Alice W.; Kimura, Minoru

    1994-09-01

    The basal ganglia are neural structures within the motor and cognitive control circuits in the mammalian forebrain and are interconnected with the neocortex by multiple loops. Dysfunction in these parallel loops caused by damage to the striatum results in major defects in voluntary movement, exemplified in Parkinson's disease and Huntington's disease. These parallel loops have a distributed modular architecture resembling local expert architectures of computational learning models. During sensorimotor learning, such distributed networks may be coordinated by widely spaced striatal interneurons that acquire response properties on the basis of experienced reward.

  10. Advanced treatment for basal cell carcinomas.

    PubMed

    Atwood, Scott X; Whitson, Ramon J; Oro, Anthony E

    2014-07-01

    Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists.

  11. Mössbauer spectroscopy of Basal Ganglia

    SciTech Connect

    Miglierini, Marcel; Lančok, Adriana; Kopáni, Martin; Boča, Roman

    2014-10-27

    Chemical states, structural arrangement, and magnetic features of iron deposits in biological tissue of Basal Ganglia are characterized. The methods of SQUID magnetometry and electron microscopy are employed. {sup 57}Fe Mössbauer spectroscopy is used as a principal method of investigation. Though electron microscopy has unveiled robust crystals (1-3 μm in size) of iron oxides, they are not manifested in the corresponding {sup 57}Fe Mössbauer spectra. The latter were acquired at 300 K and 4.2 K and resemble ferritin-like behavior.

  12. Advanced Treatment for Basal Cell Carcinomas

    PubMed Central

    Atwood, Scott X.; Whitson, Ramon J.; Oro, Anthony E.

    2014-01-01

    Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists. PMID:24985127

  13. Defining human dendritic cell progenitors by multiparametric flow cytometry

    PubMed Central

    Breton, Gaëlle; Lee, Jaeyop; Liu, Kang; Nussenzweig, Michel C

    2015-01-01

    Human dendritic cells (DCs) develop from progressively restricted bone marrow (BM) progenitors: these progenitor cells include granulocyte, monocyte and DC progenitor (GMDP) cells; monocyte and DC progenitor (MDP) cells; and common DC progenitor (CDP) and DC precursor (pre-DC) cells. These four DC progenitors can be defined on the basis of the expression of surface markers such as CD34 and hematopoietin receptors. In this protocol, we describe five multiparametric flow cytometry panels that can be used as a tool (i) to simultaneously detect or phenotype the four DC progenitors, (ii) to isolate DC progenitors to enable in vitro differentiation or (iii) to assess the in vitro differentiation and proliferation of DC progenitors. The entire procedure from isolation of cells to flow cytometry can be completed in 3–7 h. This protocol provides optimized antibody panels, as well as gating strategies, for immunostaining of BM and cord blood specimens to study human DC hematopoiesis in health, disease and vaccine settings. PMID:26292072

  14. Nutritional regulation of stem and progenitor cells in Drosophila

    PubMed Central

    Shim, Jiwon; Gururaja-Rao, Shubha; Banerjee, Utpal

    2013-01-01

    Stem cells and their progenitors are maintained within a microenvironment, termed the niche, through local cell-cell communication. Systemic signals originating outside the niche also affect stem cell and progenitor behavior. This review summarizes studies that pertain to nutritional effects on stem and progenitor cell maintenance and proliferation in Drosophila. Multiple tissue types are discussed that utilize the insulin-related signaling pathway to convey nutritional information either directly to these progenitors or via other cell types within the niche. The concept of systemic control of these cell types is not limited to Drosophila and may be functional in vertebrate systems, including mammals. PMID:24255094

  15. Spatial distribution and characterization of non-apical progenitors in the zebrafish embryo central nervous system

    PubMed Central

    Norris, Joseph

    2017-01-01

    Studies of non-apical progenitors (NAPs) have been largely limited to the developing mammalian cortex. They are postulated to generate the increase in neuron numbers that underlie mammalian brain expansion. Recently, NAPs have also been reported in the retina and central nervous system of non-mammalian species; in the latter, however, they remain poorly characterized. Here, we characterize NAP location along the zebrafish central nervous system during embryonic development, and determine their cellular and molecular characteristics and renewal capacity. We identified a small population of NAPs in the spinal cord, hindbrain and telencephalon of zebrafish embryos. Live-imaging analysis revealed at least two types of mitotic behaviour in the telencephalon: one NAP subtype retains the apical attachment during division, while another divides in a subapical position disconnected from the apical surface. All NAPs observed in spinal cord lost apical contact prior to mitoses. These NAPs express HuC and produce two neurons from a single division. Manipulation of Notch activity reveals that neurons and NAPs in the spinal cord use similar regulatory mechanisms. This work suggests that the majority of spinal NAPs in zebrafish share characteristics with basal progenitors in mammalian brains. PMID:28148823

  16. Sirt1 regulates glial progenitor proliferation and regeneration in white matter after neonatal brain injury

    PubMed Central

    Jablonska, Beata; Gierdalski, Marcin; Chew, Li-Jin; Hawley, Teresa; Catron, Mackenzie; Lichauco, Arturo; Cabrera-Luque, Juan; Yuen, Tracy; Rowitch, David; Gallo, Vittorio

    2016-01-01

    Regenerative processes in brain pathologies require the production of distinct neural cell populations from endogenous progenitor cells. We have previously demonstrated that oligodendrocyte progenitor cell (OPC) proliferation is crucial for oligodendrocyte (OL) regeneration in a mouse model of neonatal hypoxia (HX) that reproduces diffuse white matter injury (DWMI) of premature infants. Here we identify the histone deacetylase Sirt1 as a Cdk2 regulator in OPC proliferation and response to HX. HX enhances Sirt1 and Sirt1/Cdk2 complex formation through HIF1α activation. Sirt1 deacetylates retinoblastoma (Rb) in the Rb/E2F1 complex, leading to dissociation of E2F1 and enhanced OPC proliferation. Sirt1 knockdown in culture and its targeted ablation in vivo suppresses basal and HX-induced OPC proliferation. Inhibition of Sirt1 also promotes OPC differentiation after HX. Our results indicate that Sirt1 is an essential regulator of OPC proliferation and OL regeneration after neonatal brain injury. Therefore, enhancing Sirt1 activity may promote OL recovery after DWMI. PMID:27991597

  17. Lacrimal Gland Repair Using Progenitor Cells.

    PubMed

    Gromova, Anastasia; Voronov, Dmitry A; Yoshida, Miya; Thotakura, Suharika; Meech, Robyn; Dartt, Darlene A; Makarenkova, Helen P

    2017-01-01

    In humans, the lacrimal gland (LG) is the primary contributor to the aqueous layer of the tear film. Production of tears in insufficient quantity or of inadequate quality may lead to aqueous-deficiency dry eye (ADDE). Currently there is no cure for ADDE. The development of strategies to reliably isolate LG stem/progenitor cells from the LG tissue brings great promise for the design of cell replacement therapies for patients with ADDE. We analyzed the therapeutic potential of epithelial progenitor cells (EPCPs) isolated from adult wild-type mouse LGs by transplanting them into the LGs of TSP -1(-/-) mice, which represent a novel mouse model for ADDE. TSP-1(-/-) mice are normal at birth but progressively develop a chronic form of ocular surface disease, characterized by deterioration, inflammation, and secretory dysfunction of the lacrimal gland. Our study shows that, among c-kit-positive epithelial cell adhesion molecule (EpCAM(+) ) populations sorted from mouse LGs, the c-kit(+) dim/EpCAM(+) /Sca1 (-) /CD34 (-) /CD45 (-) cells have the hallmarks of an epithelial cell progenitor population. Isolated EPCPs express pluripotency factors and markers of the epithelial cell lineage Runx1 and EpCAM, and they form acini and ducts when grown in reaggregated three-dimensional cultures. Moreover, when transplanted into injured or "diseased" LGs, they engraft into acinar and ductal compartments. EPCP-injected TSP-1(-/-) LGs showed reduction of cell infiltration, differentiation of the donor EPCPs within secretory acini, and substantial improvement in LG structural integrity and function. This study provides the first evidence for the effective use of adult EPCP cell transplantation to rescue LG dysfunction in a model system. Stem Cells Translational Medicine 2017;6:88-98.

  18. Lacrimal Gland Repair Using Progenitor Cells.

    PubMed

    Gromova, Anastasia; Voronov, Dmitry A; Yoshida, Miya; Thotakura, Suharika; Meech, Robyn; Dartt, Darlene A; Makarenkova, Helen P

    2016-08-15

    : In humans, the lacrimal gland (LG) is the primary contributor to the aqueous layer of the tear film. Production of tears in insufficient quantity or of inadequate quality may lead to aqueous-deficiency dry eye (ADDE). Currently there is no cure for ADDE. The development of strategies to reliably isolate LG stem/progenitor cells from the LG tissue brings great promise for the design of cell replacement therapies for patients with ADDE. We analyzed the therapeutic potential of epithelial progenitor cells (EPCPs) isolated from adult wild-type mouse LGs by transplanting them into the LGs of TSP-1(-/-) mice, which represent a novel mouse model for ADDE. TSP-1(-/-) mice are normal at birth but progressively develop a chronic form of ocular surface disease, characterized by deterioration, inflammation, and secretory dysfunction of the lacrimal gland. Our study shows that, among c-kit-positive epithelial cell adhesion molecule (EpCAM(+)) populations sorted from mouse LGs, the c-kit(+)dim/EpCAM(+)/Sca1(-)/CD34(-)/CD45(-) cells have the hallmarks of an epithelial cell progenitor population. Isolated EPCPs express pluripotency factors and markers of the epithelial cell lineage Runx1 and EpCAM, and they form acini and ducts when grown in reaggregated three-dimensional cultures. Moreover, when transplanted into injured or "diseased" LGs, they engraft into acinar and ductal compartments. EPCP-injected TSP-1(-/-) LGs showed reduction of cell infiltration, differentiation of the donor EPCPs within secretory acini, and substantial improvement in LG structural integrity and function. This study provides the first evidence for the effective use of adult EPCP cell transplantation to rescue LG dysfunction in a model system.

  19. Bone Marrow Stress Decreases Osteogenic Progenitors.

    PubMed

    Ng, Adeline H; Baht, Gurpreet S; Alman, Benjamin A; Grynpas, Marc D

    2015-11-01

    Age-related bone loss may be a result of declining levels of stem cells in the bone marrow. Using the Col2.3Δtk (DTK) transgenic mouse, osteoblast depletion was used as a source of marrow stress in order to investigate the effects of aging on osteogenic progenitors which reside in the marrow space. Five-month-old DTK mice were treated with one or two cycles of ganciclovir to conditionally ablate differentiated osteoblasts, whereas controls were saline-treated. Treatment cycles were two weeks in length followed by four weeks of recovery. All animals were sacrificed at 8 months of age; bone marrow stromal cells (BMSCs) were harvested for cell culture and whole bones were excised for bone quality assessment. Colony-forming unit (CFU) assays were conducted to investigate the osteogenic potential of BMSC in vitro, and RNA was extracted to assess the expression of osteoblastic genes. Bone quality assessments included bone histomorphometry, TRAP staining, microcomputed tomography, and biomechanical testing. Osteoblast depletion decreased CFU-F (fibroblast), CFU-ALP (alkaline phosphatase), and CFU-VK (von Kossa) counts and BMSC osteogenic capacity in cell culture. Ex vivo, there were no differences in bone mineral density of vertebrae or femurs between treatment groups. Histology showed a decrease in bone volume and bone connectivity with repeated osteoblast depletion; however, this was accompanied by an increase in bone formation rate. There were no notable differences in osteoclast parameters or observed bone marrow adiposity. We have developed a model that uses bone marrow stress to mimic age-related decrease in osteogenic progenitors. Our data suggest that the number of healthy BMSCs and their osteogenic potential decline with repeated osteoblast depletion. However, activity of the remaining osteoblasts increases to compensate for this loss in progenitor osteogenic potential.

  20. Basal cell nevus syndrome or Gorlin syndrome.

    PubMed

    Thalakoti, Srikanth; Geller, Thomas

    2015-01-01

    Basal cell nevus syndrome (BCNS) or Gorlin syndrome is a rare neurocutaneous syndrome sometimes known as the fifth phacomatosis, inherited in autosomal dominant fashion with complete penetrance and variable expressivity. Gorlin syndrome is characterized by development of multiple basal cell carcinomas (BCCs), jaw cysts, palmar or plantar pits, calcification of falx cerebri, various developmental skeletal abnormalities such as bifid rib, hemi- or bifid vertebra and predisposition to the development of various tumors. BCNS is caused by a mutation in the PTCH1 gene localized to 9q22.3. Its estimated prevalence varies between 1/55600 and 1/256000 with an equal male to female ratio. The medulloblastoma variant seen in Gorlin syndrome patients is of the desmoplastic type, characteristically presenting during the first 3 years of life. Therefore, children with desmoplastic medulloblastoma should be carefully screened for other features of BCNS. Radiation therapy for desmoplastic medulloblastoma should be avoided in BCNS patients as it may induce development of invasive BCCs and other tumors in the skin area exposed to radiation. This syndrome is a multisystem disorder so involvement of multiple specialists with a multimodal approach to detect and treat various manifestations at early stages will reduce the long-term sequelae and severity of the condition. Life expectancy is not significantly altered but morbidity from complications and cosmetic scarring can be substantial.

  1. Multiphoton imaging of basal cell carcinoma (BCC)

    NASA Astrophysics Data System (ADS)

    Cicchi, R.; Carli, P.; Massi, D.; Sestini, S.; Stambouli, D.; Pavone, F. S.

    2006-02-01

    We used two-photon microscopy towards the imaging of cutaneous basal cell carcinoma (BCC). Our aim was to evaluate the morphology of BCC using two-photon fluorescence excitation and to establish a correlation with histopathology. We built a custom two-photon microscope and we measured the system capabilities. The system allowed to perform a preliminary measurement on a fresh human skin tissue sample. A human skin tissue sample of BCC excised during dermatological surgery procedures were used. The clinical diagnosis of BCC was confirmed by subsequent histopathological examination. The sample was imaged using endogenous tissue fluorescence within 2-3 hours from the excision with a two photon laser scanning fluorescence microscope. The acquired images allowed an obvious discrimination of the neoplastic areas toward normal tissue, based on morphological differences and aberrations of the intensity of the fluorescence signal. Our results showed that BCC tissue has a more homogeneous structure in comparison to normal tissue as well as a higher fluorescent response. The images obtained by two photon microscopy were further compared to the images acquired by an optical microscope after the conventional histopathological examination on one part of the respective sample. Our suggested method may represent a new diagnostic tool that improves the diagnostic accuracy of clinical examination alone, enabling the accurate discrimination of basal cell carcinoma from normal tissue.

  2. Evolution of basal deuterostome nervous systems.

    PubMed

    Holland, Linda Z

    2015-02-15

    Understanding the evolution of deuterostome nervous systems has been complicated by the by the ambiguous phylogenetic position of the Xenocoelomorpha (Xenoturbellids, acoel flat worms, nemertodermatids), which has been placed either as basal bilaterians, basal deuterostomes or as a sister group to the hemichordate/echinoderm clade (Ambulacraria), which is a sister group of the Chordata. None of these groups has a single longitudinal nerve cord and a brain. A further complication is that echinoderm nerve cords are not likely to be evolutionarily related to the chordate central nervous system. For hemichordates, opinion is divided as to whether either one or none of the two nerve cords is homologous to the chordate nerve cord. In chordates, opposition by two secreted signaling proteins, bone morphogenetic protein (BMP) and Nodal, regulates partitioning of the ectoderm into central and peripheral nervous systems. Similarly, in echinoderm larvae, opposition between BMP and Nodal positions the ciliary band and regulates its extent. The apparent loss of this opposition in hemichordates is, therefore, compatible with the scenario, suggested by Dawydoff over 65 years ago, that a true centralized nervous system was lost in hemichordates.

  3. Progenitor endothelial cell involvement in Alzheimer's disease

    SciTech Connect

    Budinger, Thomas F.

    2003-05-01

    There is compelling evidence that endothelial cells of the brain and periphery are dysfunctional in Alzheimer's Disease. There is evidence for a fundamental defect in, or abnormal aging of, endothelial progenitor cells in atherosclerosis. The possibility that endothelial cell defects are a primary cause for Alzheimer's Disease or other dementias can be researched by molecular and cell biology studies as well as cell trafficking studies using recently demonstrated molecular imaging methods. The evidence for abnormal endothelial function and the methods to explore this hypothesis are presented.

  4. High porosity of basal till at Burroughs glacier, southeastern Alaska

    SciTech Connect

    Ronnert, L.; Mickelson, D.M. )

    1992-09-01

    Debris-rich basal ice at Burroughs glacier, southeastern Alaska, has 60 vol% to 70 vol% debris. Recently deposited basal till exceeds 60 vol% sediment with 30% to almost 40% porosity. Where basal ice is very rich in debris, basal till is deposited through melt out with only slight compaction of the debris. Porosity this high in till is commonly associated with subglacially deforming and dilated sediment. However, the recently deposited basal melt-out till at Burroughs glacier has not been deformed after deposition, but has porosity values similar to tills elsewhere interpreted to be subglacially deforming and dilated in an unfrozen state. High porosity can occur in basal melt-out till deposited directly by basal melt out.

  5. Basal stem cells contribute to squamous cell carcinomas in the oral cavity.

    PubMed

    Tang, Xiao-Han; Scognamiglio, Theresa; Gudas, Lorraine J

    2013-05-01

    The cells of origin of oral cavity squamous cell carcinoma (OCSCC) are unknown. We used a cell lineage tracing approach (adult K14-CreER(TAM); ROSA26 mice transiently treated with tamoxifen) to identify and track normal epithelial stem cells (SCs) in mouse tongues by X-gal staining and to determine if these cells become neoplastically transformed by treatment with a carcinogen, 4-nitroquinoline 1-oxide (4-NQO). Here, we show that in normal tongue epithelia, X-gal(+) cells formed thin columns throughout the entire epithelium 12 weeks after tamoxifen treatment, indicating that the basal layer contains long-lived SCs that produce progeny by asymmetric division to maintain homeostasis. Carcinogen treatment results in a ~10-fold reduction in the total number of X-gal(+) clonal cell populations and horizontal expansion of X-gal(+) clonal cell columns, a pattern consistent with symmetric division of some SCs. Finally, X-gal(+) SCs are present in papillomas and invasive OCSCCs, and these long-lived X-gal(+) SCs are the cells of origin of these tumors. Moreover, the resulting 4-NQO-induced tumors are multiclonal. These findings provide insights into the identity of the initiating cells of oral cancer.

  6. Murine and Human Tissue-Engineered Esophagus Form from Sufficient Stem/Progenitor Cells and Do Not Require Microdesigned Biomaterials

    PubMed Central

    Spurrier, Ryan Gregory; Speer, Allison L.; Hou, Xiaogang; El-Nachef, Wael N.

    2015-01-01

    Purpose: Tissue-engineered esophagus (TEE) may serve as a therapeutic replacement for absent foregut. Most prior esophagus studies have favored microdesigned biomaterials and yielded epithelial growth alone. None have generated human TEE with mesenchymal components. We hypothesized that sufficient progenitor cells might only require basic support for successful generation of murine and human TEE. Materials and Methods: Esophageal organoid units (EOUs) were isolated from murine or human esophagi and implanted on a polyglycolic acid/poly-l-lactic acid collagen-coated scaffold in adult allogeneic or immune-deficient mice. Alternatively, EOU were cultured for 10 days in vitro prior to implantation. Results: TEE recapitulated all key components of native esophagus with an epithelium and subjacent muscularis. Differentiated suprabasal and proliferative basal layers of esophageal epithelium, muscle, and nerve were identified. Lineage tracing demonstrated that multiple EOU could contribute to the epithelium and mesenchyme of a single TEE. Cultured murine EOU grew as an expanding sphere of proliferative basal cells on a neuromuscular network that demonstrated spontaneous peristalsis in culture. Subsequently, cultured EOU generated TEE. Conclusions: TEE forms after transplantation of mouse and human organ-specific stem/progenitor cells in vivo on a relatively simple biodegradable scaffold. This is a first step toward future human therapies. PMID:25298083

  7. A review of lung-to-blood absorption rates for radon progeny.

    PubMed

    Marsh, J W; Bailey, M R

    2013-12-01

    The International Commission on Radiological Protection (ICRP) Publication 66 Human Respiratory Tract Model (HRTM) treats clearance of materials from the respiratory tract as a competitive process between absorption into blood and particle transport to the alimentary tract and lymphatics. The ICRP recommended default absorption rates for lead and polonium (Type M) in ICRP Publication 71 but stated that the values were not appropriate for short-lived radon progeny. This paper reviews and evaluates published data from volunteer and laboratory animal experiments to estimate the HRTM absorption parameter values for short-lived radon progeny. Animal studies showed that lead ions have two phases of absorption: ∼10 % absorbed with a half-time of ∼15 min, the rest with a half-time of ∼10 h. The studies also indicated that some of the lead ions were bound to respiratory tract components. Bound fractions, f(b), for lead were estimated from volunteer and animal studies and ranged from 0.2 to 0.8. Based on the evaluations of published data, the following HRTM absorption parameter values were derived for lead as a decay product of radon: f(r) = 0.1, s(r) = 100 d(-1), s(s) = 1.7 d(-1), f(b) = 0.5 and s(b) = 1.7 d(-1). Effective doses calculated assuming these absorption parameter values instead of a single absorption half-time of 10 h with no binding (as has generally been assumed) are only a few per cent higher. However, as there is some conflicting evidence on the absorption kinetics for radon progeny, dose calculations have been carried out for different sets of absorption parameter values derived from different studies. The results of these calculations are discussed.

  8. Determination of rain age via {gamma} rays from accreted radon progeny

    SciTech Connect

    Greenfield, M. B.; Ito, N.; Iwata, A.; Kubo, K.; Ishigaki, M.; Komura, K.

    2008-10-01

    The relative {gamma} ray activities from {sup 214}Pb and {sup 214}Bi condensed from precipitation are used to determine its 'age', the average time the accreted activity has been removed from secular equilibrium. A verifiable assumption that radon progeny on/in the surface/volume of droplets mostly remains in secular equilibrium until they begin their descent, enables estimates of their transit times to ground of typically a few tens of minutes. This agrees well with the time expected for the activity on the surface of droplets to reach the ground from heights of a few kilometers. The half lives of {gamma} activities from {sup 214}Bi and {sup 214}Pb, 19.7 and 26.9 min, respectively, are on the same scale as transit time to ground and close enough to each other to measure ratios of activities from secular equilibrium (1.00) to transient equilibrium (3.88) within a few hundreds of minutes. The ratio of {gamma} count rates is independent of knowledge of either initial activity or any systematic errors and thus limited only by the uncertainty from counting statistics, which from condensates of 5-30 l of rain viewed with 2{pi} solid angle by a 50% efficient, high-resolution Ge detector is only a few percent. These ratios fit extremely well to known theoretical curves, which cannot only be used to date rain but can also be extrapolated backward to determine radon progeny activities in rain prior to its descent, knowledge of which may facilitate further studies using radon progeny as tracers.

  9. An historical overview of radon and its progeny: applications and health effects.

    PubMed

    Mc Laughlin, J

    2012-11-01

    Since its discovery by Dorn in 1900, studies of radon and its progeny have contributed to such diverse scientific fields as meteorology, geophysics, mineral exploration and radiation health effects. In addition to terrestrial scientific studies of radon, NASA missions in recent decades have yielded data on the behaviour of radon and its progeny on the Moon and on Mars. Radon has been used therapeutically for ∼100 y in the form of radon seeds for the irradiation of malignant tumours. It is, however, for its negative health effects that radon is better and more justifiably known. The causal role of radon and, in particular, its progeny in the elevated incidence of lung cancer in underground uranium miners was established in the 1950s. It is of historical interest to note that the fatal lung disease of silver miners in Saxony and Bohemia in the 16th century, was undoubtedly lung cancer caused by the high levels of radon in the mines. In recent decades there has been an ever-growing interest in the public health effects of exposure to radon in homes. Extensive radon epidemiological studies both of underground miners and of the general public in recent decades have quantified the lung cancer risks from radon exposure. Radon was classified in 1988 by International Agency for Research on Cancer as a human carcinogen and in 2009 the World Health Organization identified radon as the second cause of lung cancer globally after smoking. Radon control strategies are used by many governments to control and reduce the risk to public health from radon.

  10. Molecular Characterization of the Complete Genome of Three Basal-BR Isolates of Turnip mosaic virus Infecting Raphanus sativus in China

    PubMed Central

    Zhu, Fuxiang; Sun, Ying; Wang, Yan; Pan, Hongyu; Wang, Fengting; Zhang, Xianghui; Zhang, Yanhua; Liu, Jinliang

    2016-01-01

    Turnip mosaic virus (TuMV) infects crops of plant species in the family Brassicaceae worldwide. TuMV isolates were clustered to five lineages corresponding to basal-B, basal-BR, Asian-BR, world-B and OMs. Here, we determined the complete genome sequences of three TuMV basal-BR isolates infecting radish from Shandong and Jilin Provinces in China. Their genomes were all composed of 9833 nucleotides, excluding the 3′-terminal poly(A) tail. They contained two open reading frames (ORFs), with the large one encoding a polyprotein of 3164 amino acids and the small overlapping ORF encoding a PIPO protein of 61 amino acids, which contained the typically conserved motifs found in members of the genus Potyvirus. In pairwise comparison with 30 other TuMV genome sequences, these three isolates shared their highest identities with isolates from Eurasian countries (Germany, Italy, Turkey and China). Recombination analysis showed that the three isolates in this study had no “clear” recombination. The analyses of conserved amino acids changed between groups showed that the codons in the TuMV out group (OGp) and OMs group were the same at three codon sites (852, 1006, 1548), and the other TuMV groups (basal-B, basal-BR, Asian-BR, world-B) were different. This pattern suggests that the codon in the OMs progenitor did not change but that in the other TuMV groups the progenitor sequence did change at divergence. Genetic diversity analyses indicate that the PIPO gene was under the highest selection pressure and the selection pressure on P3N-PIPO and P3 was almost the same. It suggests that most of the selection pressure on P3 was probably imposed through P3N-PIPO. PMID:27271614

  11. Molecular Characterization of the Complete Genome of Three Basal-BR Isolates of Turnip mosaic virus Infecting Raphanus sativus in China.

    PubMed

    Zhu, Fuxiang; Sun, Ying; Wang, Yan; Pan, Hongyu; Wang, Fengting; Zhang, Xianghui; Zhang, Yanhua; Liu, Jinliang

    2016-06-04

    Turnip mosaic virus (TuMV) infects crops of plant species in the family Brassicaceae worldwide. TuMV isolates were clustered to five lineages corresponding to basal-B, basal-BR, Asian-BR, world-B and OMs. Here, we determined the complete genome sequences of three TuMV basal-BR isolates infecting radish from Shandong and Jilin Provinces in China. Their genomes were all composed of 9833 nucleotides, excluding the 3'-terminal poly(A) tail. They contained two open reading frames (ORFs), with the large one encoding a polyprotein of 3164 amino acids and the small overlapping ORF encoding a PIPO protein of 61 amino acids, which contained the typically conserved motifs found in members of the genus Potyvirus. In pairwise comparison with 30 other TuMV genome sequences, these three isolates shared their highest identities with isolates from Eurasian countries (Germany, Italy, Turkey and China). Recombination analysis showed that the three isolates in this study had no "clear" recombination. The analyses of conserved amino acids changed between groups showed that the codons in the TuMV out group (OGp) and OMs group were the same at three codon sites (852, 1006, 1548), and the other TuMV groups (basal-B, basal-BR, Asian-BR, world-B) were different. This pattern suggests that the codon in the OMs progenitor did not change but that in the other TuMV groups the progenitor sequence did change at divergence. Genetic diversity analyses indicate that the PIPO gene was under the highest selection pressure and the selection pressure on P3N-PIPO and P3 was almost the same. It suggests that most of the selection pressure on P3 was probably imposed through P3N-PIPO.

  12. Development of a Progeny Marker for Steelhead; A Thesis submitted to Oregon State University.

    SciTech Connect

    Shippentower, Gene E.

    2009-04-15

    This study was undertaken to determine if strontium chloride could be used to create a trans-generational otolith mark in steelhead (Oncorhynchus mykiss). I completed two strontium injection trials and a survey of juvenile steelhead from various steelhead hatcheries. The two trials measured Sr:Ca ratios in otoliths in response to injections and the survey measured the natural variation in Sr:Ca ratios in otoliths of juvenile hatchery steelhead in response to the natural variation. In 2003, adult female Wallowa River, Oregon O. mykiss, were captured at the hatchery and evenly divided between a control group and two treatment groups. These females received an intraperitoneal injection of 1cc/500 g of body weight of a physiologically isotonic solution (0.9% saline) containing concentrations of 0 (control), 1000, or 5000 parts per million (ppm) of strontium chloride hexahydrate (SrCl2* 6H2O). Females were housed in a single outdoor tank until spawned artificially, and a distinct external tag identified each female within each treatment group. In 2004, female steelhead were captured throughout the duration of the adult returns to the Umatilla River basin and injected with 0, 1000, 5000, or 20,000-ppm strontium. In both trials, progeny of fish treated with strontium had significantly higher Sr:Ca ratios in the primordial region of their otoliths as measured using an electron wavelength dispersive microprobe. There was no difference in fertilization rates of eggs and survival rates of fry among treatment groups. Progeny from treated mothers were on average larger than progeny of untreated mothers. The Sr:Ca ratios in otoliths collected from various populations of steelhead were greater than the control values measured in both injections studies. This study suggests that the marking technique works and the utility for such a technique could be used for empirical observations in determining the relative fitness of progeny of adult hatchery origin fish

  13. Dedifferentiated adipocyte-derived progeny cells (DFAT cells): Potential stem cells of adipose tissue.

    PubMed

    Wei, Shengjuan; Zan, Linsen; Hausman, Gary J; Rasmussen, Theodore P; Bergen, Werner G; Dodson, Michael V

    2013-07-01

    Analyses of mature adipocytes have shown that they possess a reprogramming ability in vitro, which is associated with dedifferentiation. The subsequent dedifferentiated fat cells (DFAT cells) are multipotent and can differentiate into adipocytes and other cell types as well. Mature adipocytes can be easily obtained by biopsy, and the cloned progeny cells are homogeneous in vitro. Therefore, DFAT cells (a new type of stem cell) may provide an excellent source of cells for tissue regeneration, engineering and disease treatment. The dedifferentiation of mature adipocytes, the multipotent capacity of DFAT cells and comparisons and contrasts with mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPS) are discussed in this review.

  14. Exposure to radon and radon progeny in the indoor environment. Final report

    SciTech Connect

    Socolow, R.H.

    1994-10-01

    This report discusses the work done by the Center for Energy and Environmental Studies at Princeton University as part of the radon research program. It involves radon measurements in various buildings, as well as the use of natural ventilation to mitigate radon levels. The report is divided into four chapters: The use of radon entry rate measurements to understand radon concentration in buildings; Use of natural basement ventilation to control radon in single family dwellings; The effect of natural ventilation on radon and radon progeny levels in houses; and Comparison of natural and forced ventilation for radon mitigation in houses.

  15. Adenoid basal hyperplasia of the uterine cervix: a lesion of reserve cell type, distinct from adenoid basal carcinoma.

    PubMed

    Kerdraon, Olivier; Cornélius, Aurélie; Farine, Marie-Odile; Boulanger, Loïc; Wacrenier, Agnès

    2012-12-01

    Adenoid basal hyperplasia is an underrecognized cervical lesion, resembling adenoid basal carcinoma, except the absence of deep invasion into the stroma. We report a series of 10 cases, all extending less than 1 mm from the basement membrane. Our results support the hypothesis that adenoid basal hyperplasia arises from reserve cells of the cervix. Lesions were found close to the squamocolumnar junction, in continuity with the nearby subcolumnar reserve cells. They shared the same morphology and immunoprofile using a panel of 4 antibodies (keratin 5/6, keratin 14, keratin 7 and p63) designed to differentiate reserve cells from mature squamous cells and endocervical columnar cells. We detected no human papillomavirus infection by in situ hybridization targeting high-risk human papillomavirus, which was concordant with the absence of immunohistochemical p16 expression. We demonstrated human papillomavirus infection in 4 (80%) of 5 adenoid basal carcinoma, which is in the same range as previous studies (88%). Thus, adenoid basal hyperplasia should be distinguished from adenoid basal carcinoma because they imply different risk of human papillomavirus infection and of subsequent association with high-grade invasive carcinoma. In our series, the most reliable morphological parameters to differentiate adenoid basal hyperplasia from adenoid basal carcinoma were the depth of the lesion and the size of the lesion nests. Furthermore, squamous differentiation was rare in adenoid basal hyperplasia and constant in adenoid basal carcinoma. Finally, any mitotic activity and/or an increase of Ki67 labeling index should raise the hypothesis of adenoid basal carcinoma.

  16. Neutrino emission from nearby supernova progenitors

    NASA Astrophysics Data System (ADS)

    Yoshida, Takashi; Takahashi, Koh; Umeda, Hideyuki

    2016-05-01

    Neutrinos have an important role for energy loss process during advanced evolution of massive stars. Although the luminosity and average energy of neutrinos during the Si burning are much smaller than those of supernova neutrinos, these neutrinos are expected to be detected by the liquid scintillation neutrino detector KamLAND if a supernova explosion occurs at the distance of ~100 parsec. We investigate the neutrino emission from massive stars during advanced evolution. We calculate the evolution of the energy spectra of neutrinos produced through electron-positron pair-annihilation in the supernova progenitors with the initial mass of 12, 15, and 20 M ⊙ during the Si burning and core-collapse stages. The neutrino emission rate increases from ~ 1050 s-1 to ~ 1052 s-1. The average energy of electron-antineutrinos is about 1.25 MeV during the Si burning and gradually increases until the core-collapse. For one week before the supernova explosion, the KamLAND detector is expected to observe 12-24 and 6-13 v¯e events in the normal and inverted mass hierarchies, respectively, if a supernova explosion of a 12-20 M ⊙ star occurs at the distance of 200 parsec, corresponding to the distance to Betelgeuse. Observations of neutrinos from SN progenitors have a possibility to constrain the core structure and the evolution just before the core collapse of massive stars.

  17. Type Ia Supernovae: Colors, Rates, and Progenitors

    NASA Astrophysics Data System (ADS)

    Heringer, Epson; Pritchet, Chris; Kezwer, Jason; Graham, Melissa L.; Sand, David; Bildfell, Chris

    2017-01-01

    The rate of type Ia supernovae (SNe Ia) in a galaxy depends not only on stellar mass, but also on star formation history (SFH). Here we show that two simple observational quantities (g ‑ r or u ‑ r host galaxy color, and r-band luminosity), coupled with an assumed delay time distribution (DTD) (the rate of SNe Ia as a function of time for an instantaneous burst of star formation), are sufficient to accurately determine a galaxy’s SN Ia rate, with very little sensitivity to the precise details of the SFH. Using this result, we compare observed and predicted color distributions of SN Ia hosts for the MENeaCS cluster supernova survey, and for the SDSS Stripe 82 supernova survey. The observations are consistent with a continuous DTD, without any cutoff. For old progenitor systems, the power-law slope for the DTD is found to be -{1.50}-0.15+0.19. This result favors the double degenerate scenario for SN Ia, though other interpretations are possible. We find that the late-time slopes of the DTD are different at the 1σ level for low and high stretch supernova, which suggest a single degenerate (SD) scenario for the latter. However, due to ambiguity in the current models’ DTD predictions, SD progenitors can neither be confirmed as causing high stretch supernovae nor ruled out from contributing to the overall sample.

  18. The progenitors of supernovae Type Ia

    NASA Astrophysics Data System (ADS)

    Toonen, Silvia

    2014-09-01

    Despite the significance of Type Ia supernovae (SNeIa) in many fields in astrophysics, SNeIa lack a theoretical explanation. SNeIa are generally thought to be thermonuclear explosions of carbon/oxygen (CO) white dwarfs (WDs). The canonical scenarios involve white dwarfs reaching the Chandrasekhar mass, either by accretion from a non-degenerate companion (single-degenerate channel, SD) or by a merger of two CO WDs (double-degenerate channel, DD). The study of SNeIa progenitors is a very active field of research for binary population synthesis (BPS) studies. The strength of the BPS approach is to study the effect of uncertainties in binary evolution on the macroscopic properties of a binary population, in order to constrain binary evolutionary processes. I will discuss the expected SNeIa rate from the BPS approach and the uncertainties in their progenitor evolution, and compare with current observations. I will also discuss the results of the POPCORN project in which four BPS codes were compared to better understand the differences in the predicted SNeIa rate of the SD channel. The goal of this project is to investigate whether differences in the simulated populations are due to numerical effects or whether they can be explained by differences in the input physics. I will show which assumptions in BPS codes affect the results most and hence should be studied in more detail.

  19. Progenitor Cell Dysfunctions Underlie Some Diabetic Complications

    PubMed Central

    Rodrigues, Melanie; Wong, Victor W.; Rennert, Robert C.; Davis, Christopher R.; Longaker, Michael T.; Gurtner, Geoffrey C.

    2016-01-01

    Stem cells and progenitor cells are integral to tissue homeostasis and repair. They contribute to health through their ability to self-renew and commit to specialized effector cells. Recently, defects in a variety of progenitor cell populations have been described in both preclinical and human diabetes. These deficits affect multiple aspects of stem cell biology, including quiescence, renewal, and differentiation, as well as homing, cytokine production, and neovascularization, through mechanisms that are still unclear. More important, stem cell aberrations resulting from diabetes have direct implications on tissue function and seem to persist even after return to normoglycemia. Understanding how diabetes alters stem cell signaling and homeostasis is critical for understanding the complex pathophysiology of many diabetic complications. Moreover, the success of cell-based therapies will depend on a more comprehensive understanding of these deficiencies. This review has three goals: to analyze stem cell pathways dysregulated during diabetes, to highlight the effects of hyperglycemic memory on stem cells, and to define ways of using stem cell therapy to overcome diabetic complications. PMID:26079815

  20. Red supergiants as type II supernova progenitors

    NASA Astrophysics Data System (ADS)

    Negueruela, Ignacio; Dorda, Ricardo; González-Fernández, Carlos; Marco, Amparo

    2015-08-01

    Recent searches for supernova IIp progenitors in external galaxies have led to the identification of red objects with magnitudes and colours indicative of red supergiants, in most cases implying quite low luminosities and hence masses well below 10Msol. Stellar models, on the other hand, do not predict explosions from objects below 9 Msol. What does our knowledge of local red supergiants tells us about the expected properties of such objects?We have carried out a comprehensive spectroscopic and photometric study of a sample of hundreds of red supergiants in the Milky Way and both Magellanic Clouds. We have explored correlations between different parameters and the position of stars in the HR diagrams of open clusters. At solar metallicty, there is strong evidence for a phase of very heavy mass loss at the end of the red supergiant phase, but the existence of such a phase is still not confirmed at SMC metallicities. Objects of ~ 7Msol, on the other hand, become very dusty in the SMC, and appear as very luminous Miras.Among Milky Way clusters, we find a surprising lack of objects readily identifiable as the expected 7 to 10 Msol red supergiants or AGB stars. We are carrying out an open cluster survey aimed at filling this region of the HR diagram with reliable data. Finally, we will discuss the implications of all this findings for the expected properties of supernova progenitors, as it looks unlikely that typical red supergiants may explode without undergoing further evolution.

  1. Hierarchization of myogenic and adipogenic progenitors within human skeletal muscle.

    PubMed

    Pisani, Didier F; Clement, Noémie; Loubat, Agnès; Plaisant, Magali; Sacconi, Sabrina; Kurzenne, Jean-Yves; Desnuelle, Claude; Dani, Christian; Dechesne, Claude A

    2010-12-01

    Skeletal muscle cells constitute a heterogeneous population that maintains muscle integrity through a high myogenic regenerative capacity. More unexpectedly, this population is also endowed with an adipogenic potential, even in humans, and intramuscular adipocytes have been found to be present in several disorders. We tested the distribution of myogenic and adipogenic commitments in human muscle-derived cells to decipher the cellular basis of the myoadipogenic balance. Clonal analysis showed that adipogenic progenitors can be separated from myogenic progenitors and, interestingly, from myoadipogenic bipotent progenitors. These progenitors were isolated in the CD34(+) population on the basis of the expression of CD56 and CD15 cell surface markers. In vivo, these different cell types have been found in the interstitial compartment of human muscle. In vitro, we show that the proliferation of bipotent myoadipogenic CD56(+)CD15(+) progenitors gives rise to myogenic CD56(+)CD15(-) progenitors and adipogenic CD56(-)CD15(+) progenitors. A cellular hierarchy of muscle and fat progenitors thus occurs within human muscle. These results provide cellular bases for adipogenic differentiation in human skeletal muscle, which may explain the fat development encountered in different muscle pathological situations.

  2. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis

    PubMed Central

    Gehling, Ursula M; Willems, Marc; Schlagner, Kathleen; Benndorf, Ralf A; Dandri, Maura; Petersen, Jörg; Sterneck, Martina; Pollok, Joerg-Matthias; Hossfeld, Dieter K; Rogiers, Xavier

    2010-01-01

    AIM: To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS: Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry. Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1 (SDF-1) were measured using an enzyme linked immunosorbent assay. RESULTS: Progenitor cells with a CD133+/CD45+/CD14+ phenotype were observed in 61% of the patients. Between 1% and 26% of the peripheral blood mononuclear cells (MNCs) displayed this phenotype. Furthermore, a distinct population of c-kit+ progenitor cells (between 1% and 38 % of the MNCs) could be detected in 91% of the patients. Additionally, 18% of the patients showed a population of progenitor cells (between 1% and 68% of the MNCs) that was characterized by expression of breast cancer resistance protein-1. Further phenotypic analysis disclosed that the circulating precursors expressed CXC chemokine receptor 4, the receptor for SDF-1. In line with this finding, elevated plasma levels of SDF-1 were present in all patients and were found to correlate with the number of mobilized CD133+ progenitor cells. CONCLUSION: These data indicate that in humans, liver cirrhosis leads to recruitment of various populations of hematopoietic progenitor cells that display markers of intrahepatic progenitor cells. PMID:20066741

  3. Progenitor cells in arteriosclerosis: good or bad guys?

    PubMed

    Campagnolo, Paola; Wong, Mei Mei; Xu, Qingbo

    2011-08-15

    Accumulating evidence indicates that the mobilization and recruitment of circulating or tissue-resident progenitor cells that give rise to endothelial cells (ECs) and smooth muscle cells (SMCs) can participate in atherosclerosis, neointima hyperplasia after arterial injury, and transplant arteriosclerosis. It is believed that endothelial progenitor cells do exist and can repair and rejuvenate the arteries under physiologic conditions; however, they may also contribute to lesion formation by influencing plaque stability in advanced atherosclerotic plaque under specific pathologic conditions. At the same time, smooth muscle progenitors, despite their capacity to expedite lesion formation during restenosis, may serve to promote atherosclerotic plaque stabilization by producing extracellular matrix proteins. This profound evidence provides support to the hypothesis that both endothelial and smooth muscle progenitors may act as a double-edged sword in the pathogenesis of arteriosclerosis. Therefore, the understanding of the regulatory networks that control endothelial and smooth muscle progenitor differentiation is undoubtedly fundamental both for basic research and for improving current therapeutic avenues for atherosclerosis. We update the progress in progenitor cell study related to the development of arteriosclerosis, focusing specifically on the role of progenitor cells in lesion formation and discuss the controversial issues that regard the origins, frequency, and impact of the progenitors in the disease.

  4. The dermatoscopic universe of basal cell carcinoma.

    PubMed

    Lallas, Aimilios; Apalla, Zoe; Argenziano, Giuseppe; Longo, Caterina; Moscarella, Elvira; Specchio, Francesca; Raucci, Margaritha; Zalaudek, Iris

    2014-07-01

    Following the first descriptions of the dermatoscopic pattern of basal cell carcinoma (BCC) that go back to the very early years of dermatoscopy, the list of dermatoscopic criteria associated with BCC has been several times updated and renewed. Up to date, dermatoscopy has been shown to enhance BCC detection, by facilitating its discrimination from other skin tumors and inflammatory skin diseases. Furthermore, upcoming evidence suggests that the method is also useful for the management of the tumor, since it provides valuable information about the histopathologic subtype, the presence of clinically undetectable pigmentation, the expansion of the tumor beyond clinically visible margins and the response to non-ablative treatments. In the current article, we provide a summary of the traditional and latest knowledge on the value of dermatoscopy for the diagnosis and management of BCC.

  5. A novel NIH/3T3 duplex feeder system to engineer corneal epithelial sheets with enhanced cytokeratin 15-positive progenitor populations.

    PubMed

    Miyashita, Hideyuki; Shimmura, Shigeto; Higa, Kazunari; Yoshida, Satoru; Kawakita, Tetsuya; Shimazaki, Jun; Tsubota, Kazuo

    2008-07-01

    Corneal epithelial cell sheets co-cultivated with feeder cells are used to reconstruct the ocular surface in stem cell-depleted eyes. The present study was conducted to investigate the optimal method of using feeder cells in the interest of preserving progenitor cells in cultivated sheets. We compared the phenotype and secondary colony forming efficiency (CFE) of cell sheets that were engineered using 3T3 feeder cells as a separate layer or as a contact layer. We also devised a novel "duplex feeder" system that consists of two separate layers of feeder cells. After cells reached confluence, cells were cultured at the air-liquid interface to allow full stratification. Stratified sheets were then analyzed using immunohistochemistry and secondary colony formation. Contact feeder cultures and duplex feeder cultures yielded epithelial sheets with small, cuboid basal cells with strong expression of keratin (K)3, K12, and K 15. Furthermore, only duplex feeder layers reproduced the basal K 15, suprabasal K12 limbal phenotype where epithelial stem cells reside. A similar effect was observed when cornea stroma-derived progenitor cells were used as feeder cells. Duplex feeder sheets also produced significantly more secondary colonies than cells dissociated from single layer sheets, suggesting that the duplex feeder system produces transplantable sheets with a higher yield of progenitor cells.

  6. GSK-3 is a master regulator of neural progenitor homeostasis

    PubMed Central

    Kim, Woo-Yang; Wang, Xinshuo; Wu, Yaohong; Doble, Bradley W; Patel, Satish; Woodgett, James R; Snider, William D

    2016-01-01

    The development of the brain requires the exquisite coordination of progenitor proliferation and differentiation to achieve complex circuit assembly. It has been suggested that glycogen synthase kinase 3 (GSK-3) acts as an integrating molecule for multiple proliferation and differentiation signals because of its essential role in the RTK, Wnt and Shh signaling pathways. We created conditional mutations that deleted both the α and β forms of GSK-3 in mouse neural progenitors. GSK-3 deletion resulted in massive hyperproliferation of neural progenitors along the entire neuraxis. Generation of both intermediate neural progenitors and postmitotic neurons was markedly suppressed. These effects were associated with the dysregulation of β-catenin, Sonic Hedgehog, Notch and fibroblast growth factor signaling. Our results indicate that GSK-3 signaling is an essential mediator of homeostatic controls that regulate neural progenitors during mammalian brain development. PMID:19801986

  7. Cytogenetic characterization and fae1 gene variation in progenies from asymmetric somatic hybrids between Brassica napus and Crambe abyssinica.

    PubMed

    Wang, Y P; Snowdon, R J; Rudloff, E; Wehling, P; Friedt, W; Sonntag, K

    2004-08-01

    Sexual progenies of asymmetric somatic hybrids between Brassica napus and Crambe abyssinica were analyzed with respect to chromosomal behavior, fae1 gene introgression, fertility, and fatty-acid composition of the seed. Among 24 progeny plants investigated, 11 plants had 38 chromosomes and were characterized by the occurrence of normal meiosis with 19 bivalents. The other 13 plants had more than 38 chromosomes, constituting a complete chromosomal set from B. napus plus different numbers of additional chromosomes from C. abyssinica. The chromosomes of B. napus and C. abyssinica origin could be clearly discriminated by genomic in situ hybridization (GISH) in mitotic and meiotic cells. Furthermore, meiotic GISH enabled identification of intergenomic chromatin bridges and of asynchrony between the B. napus and C. abyssinca meiotic cycles. Lagging, bridging and late disjunction of univalents derived from C. abyssinica were observed. Analysis of cleaved amplified polymorphic sequence (CAPS) markers derived from the fae1 gene showed novel patterns different from the B. napus recipient in some hybrid offspring. Most of the progeny plants had a high pollen fertility and seed set, and some contained significantly greater amounts of seed erucic acid than the B. napus parent. This study demonstrates that a part of the C. abyssinica genome can be transferred into B. napus via asymmetric hybridization and maintained in sexual progenies of the hybrids. Furthermore, it confirms that UV irradiation improves the fertility of the hybrid and of its sexual progeny via chromosomal elimination and facilitates the introgression of exotic genetic material into crop species.

  8. Fruiting Body Formation of Cordyceps militaris from Multi-Ascospore Isolates and Their Single Ascospore Progeny Strains

    PubMed Central

    Shrestha, Bhushan; Han, Sang-Kuk; Sung, Jae-Mo

    2012-01-01

    Interest in commercial cultivation and product development of Cordyceps species has shown a recent increase. Due to its biochemical and pharmacological effects, Cordyceps militaris, commonly known as orange caterpillar fungus, is being investigated with great interest. Cultivation of C. militaris has been practiced on a large scale in order to fulfill a demand for scientific investigation and product development. Isolates of C. militaris can be easily established from both spores and tissue. For isolation of spores, ascospores released from mature stromata are trapped in sterile medium. Multi-ascospore isolates, as well as combinations of single ascospore strains, are used for production of fruiting bodies. Progeny ascospore strains can be isolated from artificial fruiting bodies, thus, the cycle of fruiting body production can be continued for a long period of time. In this study, we examined fruiting body production from multi-ascospore isolates and their progeny strains for three generations. F1 progeny strains generally produced a larger number of fruiting bodies, compared with their mother multi-ascospore isolates; however, F2 and F3 progeny strains produced fewer fruiting bodies. Optimum preservation conditions could help to increase the vitality of the progeny strains. In order to retain the fruiting ability of the strains, further testing of various methods of preservation and different methods for isolation should be performed. PMID:22870051

  9. Genomic prediction of trait segregation in a progeny population: a case study of Japanese pear (Pyrus pyrifolia)

    PubMed Central

    2013-01-01

    Background In cross breeding, it is important to choose a good parental combination that has high probability of generating offspring with desired characteristics. This study examines a method for predicting the segregation of target traits in a progeny population based on genome-wide markers and phenotype data of parental cultivars. Results The proposed method combines segregation simulation and Bayesian modeling for genomic selection. Marker segregation in a progeny population was simulated based on parental genotypes. Posterior marker effects sampled via Markov Chain Monte Carlo were used to predict the segregation pattern of target traits. The posterior distribution of the proportion of progenies that fulfill selection criteria was calculated and used for determining a promising cross and the necessary size of the progeny population. We applied the proposed method to Japanese pear (Pyrus pyrifolia Nakai) data to demonstrate the method and to show how it works in the selection of a promising cross. Verification using an actual breeding population suggests that the segregation of target traits can be predicted with reasonable accuracy, especially in a highly heritable trait. The uncertainty in predictions was reflected on the posterior distribution of the proportion of progenies that fulfill selection criteria. A simulation study based on the real marker data of Japanese pear cultivars also suggests the potential of the method. Conclusions The proposed method is useful to provide objective and quantitative criteria for choosing a parental combination and the breeding population size. PMID:24028660

  10. Lack of selection for resistance to whirling disease among progeny of Colorado River rainbow trout

    USGS Publications Warehouse

    Ryce, E.K.N.; Zale, A.V.; Nehring, R.B.

    2001-01-01

    We compared the resistance to whirling disease of two groups of Colorado River rainbow trout Oncorhynchus mykiss and a domestic strain of rainbow trout in a controlled laboratory challenge. These three groups represented the progeny of wild rainbow trout known to have recruited (1) during the early years of infestation by Myxobolus cerebralis of the Colorado River or (2) before the presence of M. cerebralis in the system and (3) the Erwin strain of rainbow trout. The severity of whirling disease in each group was dependent on the dose of triactinomyxons of M. cerebralis to which the fish were exposed. Microscopic lesions and spore counts both increased with increasing parasite dose. Survival of the progeny of Colorado fish that recruited before the presence of M. cerebralis in the system was significantly less than was that of the domestic fish exposed to 0 and 1,000 triactinomyxons/fish. The parents that recruited to the system before the presence of M. cerebralis were considerably older than were those used for our domestic strain; this difference in parent age probably resulted in the difference in survival because egg quality decreases with age in rainbow trout. There was no difference in microscopic lesions, spore counts, or swimming performance among the three groups of rainbow trout when exposed at the same parasite level, indicating that there was no difference in resistance to whirling disease among these groups of fish.

  11. RADON AND PROGENY ALPHA-PARTICLE ENERGY ANALYSIS USING NUCLEAR TRACK METHODOLOGY

    SciTech Connect

    Espinosa Garcia, Guillermo; Golzarri y Moreno, Dr. Jose Ignacio; Bogard, James S

    2008-01-01

    A preliminary procedure for alpha energy analysis of radon and progeny using Nuclear Track Methodology (NTM) is described in this paper. The method is based on the relationship between alpha-particle energies deposited in polycarbonate material (CR-39) and the track size developed after a well-established chemical etching process. Track geometry, defined by parameters such as major or minor diameters, track area and overall track length, is shown to correlate with alpha-particle energy over the range 6.00 MeV (218Po) to 7.69 MeV (214Po). Track features are measured and the data analyzed automatically using a digital imaging system and commercial PC software. Examination of particle track diameters in CR-39 exposed to environmental radon reveals a multi-modal distribution. Locations of the maxima in this distribution are highly correlated with alpha particle energies of radon daughters, and the distributions are sufficiently resolved to identify the radioisotopes. This method can be useful for estimating the radiation dose from indoor exposure to radon and its progeny.

  12. Characteristics of indoor radon and its progeny in a Japanese dwelling while using air appliances.

    PubMed

    Pornnumpa, C; Tokonami, S; Sorimachi, A; Kranrod, C

    2015-11-01

    Characteristics of radon and its progeny were investigated in different air conditions by turning four types of indoor air appliances on and off in a two-story concrete Japanese dwelling. The four appliances were air conditioner, air cleaner, gas heater and cooker hood. The measurements were done using two devices: (1) a Si-based semiconductor detector for continuous measurement of indoor radon concentration and (2) a ZnS(Ag) scintillation counting system for equilibrium-equivalent radon concentration. Throughout the entire experiment, the cooker hood was the most effective in decreasing indoor radon concentration over a long period of time and the less effective was the air conditioner, while the air cleaner and gas heater did not affect the concentration of radon. However, the results measured in each air condition will differ according to the lifestyles and activities of the inhabitants. In this study, indoor radon and its progeny in a Japanese dwelling will be characterised by the different air conditions.

  13. Study of the atmospheric chemistry of radon progeny in laboratory and real indoor atmospheres

    SciTech Connect

    Hopke, P.K.

    1990-01-01

    The chemical and physical behavior of the {sup 218}Po atom immediately following its formation by the alpha decay of radon must be understood if the exposure to radon progeny is to be fully assessed. Two areas of radon progeny behavior will be studied; laboratory studies and studies in actual indoor environments. Laboratory studies include: Measure the neutralization rate of {sup 218}Po{sup +}{sub x} in O{sub 2} at low radon concentrations. Determine the formation rates of {center dot}OH, {center dot}O, or other oxidative radicals formed by the radiolysis of air following radon decay. Examine the formation of particles by the radiolytic oxidation of substances and measure the rate of ion-induced nucleation in the sulfuric acid-water vapor system with and without NH{sub 3} additions using a thermal diffusion cloud chamber. Exposure studies include: Initiate measurements of the activity size distribution in actual homes with occupants present; Initiate a prospective study of the utility of measurement of deposited {sup 210}Pb embedded in glass surfaces as a measure of the long-term, integrated exposure of the population to radon, and acquire the components and begin to develop the methodology to determine the hygroscopicity of the indoor aerosol.

  14. Predicting the size of the progeny mapping population required to positionally clone a gene.

    PubMed

    Dinka, Stephen J; Campbell, Matthew A; Demers, Tyler; Raizada, Manish N

    2007-08-01

    A key frustration during positional gene cloning (map-based cloning) is that the size of the progeny mapping population is difficult to predict, because the meiotic recombination frequency varies along chromosomes. We describe a detailed methodology to improve this prediction using rice (Oryza sativa L.) as a model system. We derived and/or validated, then fine-tuned, equations that estimate the mapping population size by comparing these theoretical estimates to 41 successful positional cloning attempts. We then used each validated equation to test whether neighborhood meiotic recombination frequencies extracted from a reference RFLP map can help researchers predict the mapping population size. We developed a meiotic recombination frequency map (MRFM) for approximately 1400 marker intervals in rice and anchored each published allele onto an interval on this map. We show that neighborhood recombination frequencies (R-map, >280-kb segments) extracted from the MRFM, in conjunction with the validated formulas, better predicted the mapping population size than the genome-wide average recombination frequency (R-avg), with improved results whether the recombination frequency was calculated as genes/cM or kb/cM. Our results offer a detailed road map for better predicting mapping population size in diverse eukaryotes, but useful predictions will require robust recombination frequency maps based on sampling more progeny.

  15. Polyploid Titan Cells Produce Haploid and Aneuploid Progeny To Promote Stress Adaptation

    PubMed Central

    Gerstein, Aleeza C.; Fu, Man Shun; Mukaremera, Liliane; Li, Zhongming; Ormerod, Kate L.; Fraser, James A.; Berman, Judith

    2015-01-01

    ABSTRACT Cryptococcus neoformans is a major life-threatening fungal pathogen. In response to the stress of the host environment, C. neoformans produces large polyploid titan cells. Titan cell production enhances the virulence of C. neoformans, yet whether the polyploid aspect of titan cells is specifically influential remains unknown. We show that titan cells were more likely to survive and produce offspring under multiple stress conditions than typical cells and that even their normally sized daughters maintained an advantage over typical cells in continued exposure to stress. Although polyploid titan cells generated haploid daughter cell progeny upon in vitro replication under nutrient-replete conditions, titan cells treated with the antifungal drug fluconazole produced fluconazole-resistant diploid and aneuploid daughter cells. Interestingly, a single titan mother cell was capable of generating multiple types of aneuploid daughter cells. The increased survival and genomic diversity of titan cell progeny promote rapid adaptation to new or high-stress conditions. PMID:26463162

  16. Genetic determinism of anatomical and hydraulic traits within an apple progeny.

    PubMed

    Lauri, Pierre-Éric; Gorza, Olivier; Cochard, Hervé; Martinez, Sébastien; Celton, Jean-Marc; Ripetti, Véronique; Lartaud, Marc; Bry, Xavier; Trottier, Catherine; Costes, Evelyne

    2011-08-01

    The apple tree is known to have an isohydric behaviour, maintaining rather constant leaf water potential in soil with low water status and/or under high evaporative demand. However, little is known on the xylem water transport from roots to leaves from the two perspectives of efficiency and safety, and on its genetic variability. We analysed 16 traits related to hydraulic efficiency and safety, and anatomical traits in apple stems, and the relationships between them. Most variables were found heritable, and we investigated the determinism underlying their genetic control through a quantitative trait loci (QTL) analysis on 90 genotypes from the same progeny. Principal component analysis (PCA) revealed that all traits related to efficiency, whether hydraulic conductivity, vessel number and area or wood area, were included in the first PC, whereas the second PC included the safety variables, thus confirming the absence of trade-off between these two sets of traits. Our results demonstrated that clustered variables were characterized by common genomic regions. Together with previous results on the same progeny, our study substantiated that hydraulic efficiency traits co-localized with traits identified for tree growth and fruit production.

  17. Mapping Quantitative Field Resistance Against Apple Scab in a 'Fiesta' x 'Discovery' Progeny.

    PubMed

    Liebhard, R; Koller, B; Patocchi, A; Kellerhals, M; Pfammatter, W; Jermini, M; Gessler, C

    2003-04-01

    ABSTRACT Breeding of resistant apple cultivars (Malus x domestica) as a disease management strategy relies on the knowledge and understanding of the underlying genetics. The availability of molecular markers and genetic linkage maps enables the detection and the analysis of major resistance genes as well as of quantitative trait loci (QTL) contributing to the resistance of a genotype. Such a genetic linkage map was constructed, based on a segregating population of the cross between apple cvs. Fiesta (syn. Red Pippin) and Discovery. The progeny was observed for 3 years at three different sites in Switzerland and field resistance against apple scab (Venturia inaequalis) was assessed. Only a weak correlation was detected between leaf scab and fruit scab. A QTL analysis was performed, based on the genetic linkage map consisting of 804 molecular markers and covering all 17 chromosomes of apple. With the maximum likelihood-based interval mapping method, eight genomic regions were identified, six conferring resistance against leaf scab and two conferring fruit scab resistance. Although cv. Discovery showed a much stronger resistance against scab in the field, most QTL identified were attributed to the more susceptible parent 'Fiesta'. This indicated a high degree of homozygosity at the scab resistance loci in 'Discovery', preventing their detection in the progeny due to the lack of segregation.

  18. Comparison of remote consequences in Taraxacum officinale seed progeny collected in radioactively or chemically contaminated areas.

    PubMed

    Pozolotina, Vera N; Antonova, Elena V; Bezel, Victor S

    2012-10-01

    We carried out a comparative study of seed progeny taken from the dandelion (Taraxacum officinale s.l.) coenopopulations exposed for a long time to radioactive or chemical contamination originated from the East-Ural radioactive trace zone (EURT) or Nizhniy Tagil metallurgical combine impact zone (NTMC), respectively. Coenopopulations from EURT, NTMC and background areas significantly differ from each other with respect to the qualitative and quantitative composition of allozyme phenes. An analysis of clonal diversity showed the uniqueness of all coenopopulations in terms of their phenogenetics. P-generation seed viability was found to decrease in a similar manner as all types of the industrial stress increased. Studies of F (1)-generation variability in radio- and metal resistance by family analysis showed that seed progeny from EURT impact zone possessed high viability that, however, was accompanied by development of latent injuries resulting in low resistance to additional man-caused impacts. In F (1)-generation originated from NTMC zone, high seed viability was combined with increased resistance to provocative heavy metal and radiation exposure. No significant differences in responses to 'habitual' and 'new' factors, i.e. pre-adaptation effect, were found in samples from the contaminated areas.

  19. Neural stem cell progeny regulate stem cell death in a Notch and Hox dependent manner

    PubMed Central

    Arya, R; Sarkissian, T; Tan, Y; White, K

    2015-01-01

    Cell death is a prevalent, well-controlled and fundamental aspect of development, particularly in the nervous system. In Drosophila, specific neural stem cells are eliminated by apoptosis during embryogenesis. In the absence of apoptosis, these stem cells continue to divide, resulting in a dramatically hyperplastic central nervous system and adult lethality. Although core cell death pathways have been well described, the spatial, temporal and cell identity cues that activate the cell death machinery in specific cells are largely unknown. We identified a cis-regulatory region that controls the transcription of the cell death activators reaper, grim and sickle exclusively in neural stem cells. Using a reporter generated from this regulatory region, we found that Notch activity is required for neural stem cell death. Notch regulates the expression of the abdominalA homeobox protein, which provides important spatial cues for death. Importantly, we show that pro-apoptotic Notch signaling is activated by the Delta ligand expressed on the neighboring progeny of the stem cell. Thus we identify a previously undescribed role for progeny in regulating the proper developmental death of their parental stem cells. PMID:25633198

  20. Qualified testing of single-locus codominant inheritance using single tree progenies.

    PubMed

    Gillet, E M; Gregorius, H R

    2000-09-01

    In forest trees, classical techniques of studying modes of inheritance are usually not feasible due to the difficulty of performing controlled crosses. The limited information on inheritance extractable from readily available data, such as the large progenies collectable from single seed trees, must be compensated by the design of appropriately parameterized models. For this purpose, a system analytic approach is used to develop a new inferential framework for testing a single-locus codominant mode of inheritance of genetic traits using the inferred genotypes within progenies of single trees of inferred heterozygous genotype. Model assumptions are random gametic fusion between the local gamete pools and absence of postzygotic selection; ovule segregation distortion is allowed. The method yields estimates of the allele frequencies in both local gamete pools. Since tests of modes of inheritance must be tests of models rather than of parameters, the utility of the classical statistical testing procedures is limited, particularly concerning the qualification of a sampling method to attain a preassigned level of precision. Consistent application of this principle makes it possible to design qualified sampling methods prior to the actual experiment as well as to specify qualification levels for tests of completed experiments.

  1. Global Expression Profiling of Globose Basal Cells and Neurogenic Progression Within the Olfactory Epithelium

    PubMed Central

    Krolewski, Richard C.; Packard, Adam; Schwob, James E.

    2013-01-01

    Ongoing, lifelong neurogenesis maintains the neuronal population of the olfactory epithelium in the face of piecemeal neuronal turnover and restores it following wholesale loss. The molecular phenotypes corresponding to different stages along the progression from multipotent globose basal cell (GBC) progenitor to differentiated olfactory sensory neuron are poorly characterized. We used the transgenic expression of enhanced green fluorescent protein (eGFP) and cell surface markers to FACS-isolate ΔSox2-eGFP(+) GBCs, Neurog1-eGFP(+) GBCs and immature neurons, and ΔOMP-eGFP(+) mature neurons from normal adult mice. In addition, the latter two populations were also collected 3 weeks after olfactory bulb ablation, a lesion that results in persistently elevated neurogenesis. Global profiling of mRNA from the populations indicates that all stages of neurogenesis share a cohort of >2,100 genes that are upregulated compared to sustentacular cells. A further cohort of >1,200 genes are specifically upregulated in GBCs as compared to sustentacular cells and differentiated neurons. The increased rate of neurogenesis caused by olfactory bulbectomy had little effect on the transcriptional profile of the Neurog1-eGFP(+) population. In contrast, the abbreviated lifespan of ΔOMP-eGFP(+) neurons born in the absence of the bulb correlated with substantial differences in gene expression as compared to the mature neurons of the normal epithelium. Detailed examination of the specific genes upregulated in the different progenitor populations revealed that the chromatin modifying complex proteins LSD1 and coREST were expressed sequentially in upstream ΔSox2-eGFP(+) GBCs and Neurog1-eGFP(+) GBCs/immature neurons. The expression patterns of these proteins are dynamically regulated after activation of the epithelium by methyl bromide lesion. PMID:22847514

  2. Radiation dose due to radon and thoron progeny inhalation in high-level natural radiation areas of Kerala, India.

    PubMed

    Omori, Yasutaka; Tokonami, Shinji; Sahoo, Sarata Kumar; Ishikawa, Tetsuo; Sorimachi, Atsuyuki; Hosoda, Masahiro; Kudo, Hiromi; Pornnumpa, Chanis; Nair, Raghu Ram K; Jayalekshmi, Padmavaty Amma; Sebastian, Paul; Akiba, Suminori

    2017-03-20

    In order to evaluate internal exposure to radon and thoron, concentrations for radon, thoron, and thoron progeny were measured for 259 dwellings located in high background radiation areas (HBRAs, outdoor external dose: 3-5 mGy y(-1)) and low background radiation areas (control areas, outdoor external dose: 1 mGy y(-1)) in Karunagappally Taluk, Kerala, India. The measurements were conducted using passive-type radon-thoron detectors and thoron progeny detectors over two six-month measurement periods from June 2010 to June 2011. The results showed no major differences in radon and thoron progeny concentrations between the HBRAs and the control areas. The geometric mean of the annual effective dose due to radon and thoron was calculated as 0.10 and 0.44 mSv, respectively. The doses were small, but not negligible compared with the external dose in the two areas.

  3. Maternal temperature history activates Flowering Locus T in fruits to control progeny dormancy according to time of year.

    PubMed

    Chen, Min; MacGregor, Dana R; Dave, Anuja; Florance, Hannah; Moore, Karen; Paszkiewicz, Konrad; Smirnoff, Nicholas; Graham, Ian A; Penfield, Steven

    2014-12-30

    Seasonal behavior is important for fitness in temperate environments but it is unclear how progeny gain their initial seasonal entrainment. Plants use temperature signals to measure time of year, and changes to life histories are therefore an important consequence of climate change. Here we show that in Arabidopsis the current and prior temperature experience of the mother plant is used to control germination of progeny seeds, via the activation of the florigen Flowering Locus T (FT) in fruit tissues. We demonstrate that maternal past and current temperature experience are transduced to the FT locus in silique phloem. In turn, FT controls seed dormancy through inhibition of proanthocyanidin synthesis in fruits, resulting in altered seed coat tannin content. Our data reveal that maternal temperature history is integrated through FT in the fruit to generate a metabolic signal that entrains the behavior of progeny seeds according to time of year.

  4. Single Low-Dose Ionizing Radiation Induces Genotoxicity in Adult Zebrafish and its Non-Irradiated Progeny.

    PubMed

    Lemos, J; Neuparth, T; Trigo, M; Costa, P; Vieira, D; Cunha, L; Ponte, F; Costa, P S; Metello, L F; Carvalho, A P

    2017-02-01

    This study investigated to what extent a single exposure to low doses of ionizing radiation can induce genotoxic damage in irradiated adult zebrafish (Danio rerio) and its non-irradiated F1 progeny. Four groups of adult zebrafish were irradiated with a single dose of X-rays at 0 (control), 100, 500 and 1000 mGy, respectively, and couples of each group were allowed to reproduce following irradiation. Blood of parental fish and whole-body offspring were analysed by the comet assay for detection of DNA damage. The level of DNA damage in irradiated parental fish increased in a radiation dose-dependent manner at day 1 post-irradiation, but returned to the control level thereafter. The level of DNA damage in the progeny was directly correlated with the parental irradiation dose. Results highlight the genotoxic risk of a single exposure to low-dose ionizing radiation in irradiated individuals and also in its non-irradiated progeny.

  5. The Progenitor of SN 1987A. [IUE

    NASA Technical Reports Server (NTRS)

    Sonneborn, G.

    1988-01-01

    Spatially resolved IUE spectra (1150 to 2000 A) taken at the position of SN 1987A in March 1987 show that the 12th mag B3 I star Sk -69 deg 202 disappeared. Only the fainter companion stars (Star 2 and Star 3) are present near the site of the supernova. It is concluded that Sk -69 deg 202 exploded to produce SN 1987A. The known characteristics of Sk -69 deg 202 are consistent with the interpretation that the progenitor was a relatively compact star, having a high-velocity low-density stellar wind prior to the outburst. Recent IUE spectra of SN 1987A (May 1988) show no evidence that Sk -69 deg 202 still exists inside the expanding ejecta.

  6. Stem/Progenitor cells in vascular regeneration.

    PubMed

    Zhang, Li; Xu, Qingbo

    2014-06-01

    A series of studies has been presented in the search for proof of circulating and resident vascular progenitor cells, which can differentiate into endothelial and smooth muscle cells and pericytes in animal and human studies. In terms of pluripotent stem cells, including embryonic stem cells, iPS, and partial-iPS cells, they display a great potential for vascular lineage differentiation. Development of stem cell therapy for treatment of vascular and ischemic diseases remains a major challenging research field. At the present, there is a clear expansion of research into mechanisms of stem cell differentiation into vascular lineages that are tested in animal models. Although there are several clinical trials ongoing that primarily focus on determining the benefits of stem cell transplantation in ischemic heart or peripheral ischemic tissues, intensive investigation for translational aspects of stem cell therapy would be needed. It is a hope that stem cell therapy for vascular diseases could be developed for clinic application in the future.

  7. Multipotent pancreas progenitors: Inconclusive but pivotal topic

    PubMed Central

    Jiang, Fang-Xu; Morahan, Grant

    2015-01-01

    The establishment of multipotent pancreas progenitors (MPP) should have a significant impact not only on the ontology of the pancreas, but also for the translational research of glucose-responding endocrine β-cells. Deficiency of the latter may lead to the pandemic type 1 or type 2 diabetes mellitus, a metabolic disorder. An ideal treatment of which would potentially be the replacement of destroyed or failed β-cells, by restoring function of endogenous pancreatic endocrine cells or by transplantation of donor islets or in vitro generated insulin-secreting cells. Thus, considerable research efforts have been devoted to identify MPP candidates in the pre- and post-natal pancreas for the endogenous neogenesis or regeneration of endocrine insulin-secreting cells. In order to advance this inconclusive but critical field, we here review the emerging concepts, recent literature and newest developments of potential MPP and propose measures that would assist its forward progression. PMID:26730269

  8. L1 Retrotransposition in Neural Progenitor Cells.

    PubMed

    Muotri, Alysson R

    2016-01-01

    Long interspersed nucleotide element 1 (LINE-1 or L1) is a family of non-LTR retrotransposons that can replicate and reintegrate into the host genome. L1s have considerably influenced mammalian genome evolution by retrotransposing during germ cell development or early embryogenesis, leading to massive genome expansion. For many years, L1 retrotransposons were viewed as a selfish DNA parasite that had no contribution in somatic cells. Historically, L1s were thought to only retrotranspose during gametogenesis and in neoplastic processes, but recent studies have shown that L1s are extremely active in the mouse, rat, and human neuronal progenitor cells (NPCs). These de novo L1 insertions can impact neuronal transcriptional expression, creating unique transcriptomes of individual neurons, possibly contributing to the uniqueness of the individual cognition and mental disorders in humans.

  9. Basal bodies exhibit polarized positioning in zebrafish cone photoreceptors

    PubMed Central

    Ramsey, Michelle; Perkins, Brian D.

    2012-01-01

    The asymmetric positioning of basal bodies, and therefore cilia, is often critical for proper cilia function. This planar polarity is critical for motile cilia function but has not been extensively investigated for non-motile cilia or for sensory cilia such as vertebrate photoreceptors. Zebrafish photoreceptors form an organized mosaic ideal for investigating cilia positioning. We report that in the adult retina, the basal bodies of red, green-, and blue-sensitive cone photoreceptors localized asymmetrically on the cell edge nearest to the optic nerve. In contrast, no patterning was seen in the basal bodies of ultraviolet-sensitive cones or in rod photoreceptors. The asymmetric localization of basal bodies was consistent in all regions of the adult retina. Basal body patterning was unaffected in the cones of the XOPS-mCFP transgenic line, which lacks rod photoreceptors. Finally, the adult pattern was not seen in 7 day post fertilization (dpf) larvae as basal bodies were randomly distributed in all the photoreceptor subtypes. These results establish the asymmetrical localization of basal bodies in red-, green-, and blue-sensitive cones in adult zebrafish retinas but not in larvae. This pattern suggests an active cellular mechanism regulated the positioning of basal bodies after the transition to the adult mosaic and that rods do not seem to be necessary for the patterning of cone basal bodies. PMID:23171982

  10. Pigmented basal cell carcinoma mimicking a superficial spreading melanoma.

    PubMed

    Hasbún Acuña, Paula; Cullen Aravena, Roberto; Maturana Donaire, César; Ares Mora, Raúl; Porras Kusmanic, Ninoska

    2016-12-20

    Basal cell carcinoma is the most common form of skin cancer, especially in elderly people. Pigmented basal cell carcinoma is a rare subtype and has been described in the literature as a nodular and hyperpigmented lesion; rarely, it can appear as an extensive pigmented plate, which may be clinically indistinguishable from superficial spreading melanoma and Bowen disease. Dermatoscopy has a high sensitivity in the diagnosis of basal cell carcinoma. When Menzies criteria are used; however, the final diagnosis is made by histopathology. The objective of the present report is to analyze the case of a patient with pigmented basal cell carcinoma simulating a superficial spreading melanoma.

  11. Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

    PubMed Central

    Lo Muzio, Lorenzo

    2008-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic

  12. Nevoid basal cell carcinoma syndrome (Gorlin syndrome).

    PubMed

    Lo Muzio, Lorenzo

    2008-11-25

    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5-10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic

  13. Effects of aposymbiotic and symbiotic aphids on parasitoid progeny development and adult oviposition behavior within aphid instars.

    PubMed

    Cheng, Rui-Xia; Meng, Ling; Li, Bao-Ping

    2010-04-01

    This study aims at exploring the potential relationship between aphidiine parasitoid development and the primary endosymbiont in aphids by focusing on specific aphid instars and the relative effects on parasitoid oviposition behavior and progeny development. Lysiphlebus ambiguus (Aphidiidae, Hymenoptera) is a solitary parasitoid of several species of aphids, including Aphis fabae. In this study, A. fabae was treated with antibiotic rifampicin to obtain aposymbiotic hosts and exposed to parasitism. L. ambiguus launched significantly more attacks on symbiotic L(2) (the second instar), aposymbiotic L(3) (the third instar) and L(4) (the forth instar) hosts than on the corresponding hosts at the same age. L. ambiguus also parasitized more L(1) aphids compared with adults irrespective of whether the aphid was asymbiotic or not. Pupa mortality rate of parasitoid progeny was significantly lower from aposymbiotic hosts than from the corresponding symbiotics at all stages. Female-biased parasitoid progeny was produced from aposymbiotic aphids without respect to host ages, but female progeny increased linearly with host ages at parasitism from symbiotic aphids. Body size of parasitoid progeny increased linearly with host instars at parasitism in symbiotic aphids but did not significantly change across host instars in aposymbiotic aphids. The offspring parasitoids turned out to be generally large in body size from attacking aposymbiotic aphids compared with the symbiotics. Development time of egg-to-adult of parasitoid progeny decreased with host instars in both symbiotic and aposymbiotic aphids but was generally much longer in aposymbiotic aphids than in symbiotic aphids. Our study suggests that age or body size of host aphids may not be the only cue exercised by L. ambiguus to evaluate host quality and that offspring parasitoids may be able to compensate for the nutrition stress associated with disruption of primary endosymbiotc bacteria in aposymbiotic aphids.

  14. Progeny from irradiated colorectal cancer cells acquire an EMT-like phenotype and activate Wnt/β-catenin pathway.

    PubMed

    Bastos, Lilian Gonçalves dos Reis; de Marcondes, Priscila Guimarães; de-Freitas-Junior, Julio Cesar Madureira; Leve, Fernanda; Mencalha, André Luiz; de Souza, Waldemir Fernandes; de Araujo, Wallace Martins; Tanaka, Marcelo Neves; Abdelhay, Eliana Saul Furquim Werneck; Morgado-Díaz, José Andrés

    2014-12-01

    Radiotherapy remains a major approach to adjuvant therapy for patients with advanced colorectal cancer, however, the fractionation schedules frequently allow for the repopulation of surviving tumors cells, neoplastic progression, and subsequent metastasis. The aim of the present study was to analyze the transgenerational effects induced by radiation and evaluate whether it could increase the malignant features on the progeny derived from irradiated parental colorectal cancer cells, Caco-2, HT-29, and HCT-116. The progeny of these cells displayed a differential radioresistance as seen by clonogenic and caspase activation assay and had a direct correlation with survivin expression as observed by immunoblotting. Immunofluorescence showed that the most radioresistant progenies had an aberrant morphology, disturbance of the cell-cell adhesion contacts, disorganization of the actin cytoskeleton, and vimentin filaments. Only the progeny derived from intermediary radioresistant cells, HT-29, reduced the E-cadherin expression and overexpressed β-catenin and vimentin with increased cell migration, invasion, and metalloprotease activation as seen by immunoblotting, wound healing, invasion, and metalloprotease activity assay. We also observed that this most aggressive progeny increased the Wnt/β-catenin-dependent TCF/LEF activity and underwent an upregulation of mesenchymal markers and downregulation of E-cadherin, as determined by qRT-PCR. Our results showed that the intermediate radioresistant cells can generate more aggressive cellular progeny with the EMT-like phenotype. The Wnt/β-catenin pathway may constitute an important target for new adjuvant treatment schedules with radiotherapy, with the goal of reducing the migratory and invasive potential of the remaining cells after treatment.

  15. Pannexin 1 regulates postnatal neural stem and progenitor cell proliferation

    PubMed Central

    2012-01-01

    Background Pannexin 1 forms ion and metabolite permeable hexameric channels and is abundantly expressed in the brain. After discovering pannexin 1 expression in postnatal neural stem and progenitor cells we sought to elucidate its functional role in neuronal development. Results We detected pannexin 1 in neural stem and progenitor cells in vitro and in vivo. We manipulated pannexin 1 expression and activity in Neuro2a neuroblastoma cells and primary postnatal neurosphere cultures to demonstrate that pannexin 1 regulates neural stem and progenitor cell proliferation likely through the release of adenosine triphosphate (ATP). Conclusions Permeable to ATP, a potent autocrine/paracine signaling metabolite, pannexin 1 channels are ideally suited to influence the behavior of neural stem and progenitor cells. Here we demonstrate they play a robust role in the regulation of neural stem and progenitor cell proliferation. Endogenous postnatal neural stem and progenitor cells are crucial for normal brain health, and their numbers decline with age. Furthermore, these special cells are highly responsive to neurological injury and disease, and are gaining attention as putative targets for brain repair. Therefore, understanding the fundamental role of pannexin 1 channels in neural stem and progenitor cells is of critical importance for brain health and disease. PMID:22458943

  16. Identification of functional progenitor cells in the pulmonary vasculature

    PubMed Central

    Firth, Amy L.; Yuan, Jason X. -J.

    2012-01-01

    The pulmonary vasculature comprises a complex network of branching arteries and veins all functioning to reoxygenate the blood for circulation around the body. The cell types of the pulmonary artery are able to respond to changes in oxygen tension in order to match ventilation to perfusion. Stem and progenitor cells in the pulmonary vasculature are also involved, be it in angiogenesis, endothelial dysfunction or formation of vascular lesions. Stem and progenitor cells may be circulating around the body, residing in the pulmonary artery wall or stimulated for release from a central niche like the bone marrow and home to the pulmonary vasculature along a chemotactic gradient. There may currently be some controversy over the pathogenic versus therapeutic roles of stem and progenitor cells and, indeed, it is likely both chains of evidence are correct due to the specific influence of the immediate environmental niche a progenitor cell may be in. Due to their great plasticity and a lack of specific markers for stem and progenitor cells, they can be difficult to precisely identify. This review discusses the methodological approaches used to validate the presence of and subtype of progenitors cells in the pulmonary vasculature while putting it in context of the current knowledge of the therapeutic and pathogenic roles for such progenitor cells. PMID:22558524

  17. THE PROGENITOR OF THE TYPE IIb SN 2008ax REVISITED

    SciTech Connect

    Folatelli, Gastón; Bersten, Melina C.; Benvenuto, Omar G.; Kuncarayakti, Hanindyo; Maeda, Keiichi; Nomoto, Ken’ichi

    2015-10-01

    Hubble Space Telescope observations of the site of the supernova (SN) SN 2008ax obtained in 2011 and 2013 reveal that the possible progenitor object detected in pre-explosion images was in fact multiple. Four point sources are resolved in the new, higher-resolution images. We identify one of the sources with the fading SN. The other three objects are consistent with single supergiant stars. We conclude that their light contaminated the previously identified progenitor candidate. After subtraction of these stars, the progenitor appears to be significantly fainter and bluer than previously measured. Post-explosion photometry at the SN location indicates that the progenitor object has disappeared. If single, the progenitor is compatible with a supergiant star of B to mid-A spectral type, while a Wolf–Rayet (W-R) star would be too luminous in the ultraviolet to account for the observations. Moreover, our hydrodynamical modeling shows that the pre-explosion mass was 4–5 M{sub ⊙} and the radius was 30–50 R{sub ⊙}, which is incompatible with a W-R progenitor. We present a possible interacting binary progenitor computed with our evolutionary models that reproduces all the observational evidence. A companion star as luminous as an O9–B0 main-sequence star may have remained after the explosion.

  18. Heterogeneity of basal keratinocytes: nonrandom distribution of thymidine-labeled basal cells in confluent cultures is not a technical artifact

    SciTech Connect

    Milstone, L.M.; LaVigne, J.F.

    1985-06-01

    Basal surface autoradiography of (/sup 3/H)dThd-labeled, confluent, keratinocyte cultures reveals that proliferating cells have a nonrandom, patterned distribution. Unlabeled cells, likewise, appear nonrandomly in clusters. The authors show here that failure to detect DNA synthesis in some basal cells in culture is not an artifact caused either by physical separation of the labeled nuclei from the radiographic emulsion or by a diffusion barrier that would prevent (/sup 3/H)dThd from reaching basal cells.

  19. Reduction of radon progeny concentration by means of an air cleaner. Report no. MRL 90-143(TR)

    SciTech Connect

    Bigu, J.; Edwardson, E.

    1990-01-01

    There are a variety of airborne radionuclides found in working and living environments which at sufficiently elevated concentration levels can pose a potential hazard to human health. This report describes the use of a device which operates on a 'hybrid' technique consisting of air filtration, electrostatic deposition, and turbulent air mixing to reduce the concentration levels of Rn222 progeny levels in air. Experiments were carried out in Rn222/Rn222 progeny atmospheres when the air cleaner was operating and when it was turned off.

  20. Ultrastructure of neurons and interneuronal connections in the sensomotor cortex of progeny of alcohol-addicted rats

    SciTech Connect

    Popova, E.N.

    1985-05-01

    This paper studies the ultrastructure of neurons and interneuronal connections in the sensomotor cortex of the progeny of alcohol-addicted rats. Experiments were carried out on 12 female and four male albino rats; they were given alcohol solutions for 4 months and then mated. The female rats continued to ingest alcohol until the young rats acquired vision. The sensomotor cortex of experimental young rats aged 21 and 30 days and of intact animals of the same age was investigated; the sections were stained with uranyl acetate and studied. It is shown that alcoholic intoxication of females and males causes significant disturbances of the structural organization of the sensomotor cortex in the progeny.

  1. Rippled-pattern basal cell carcinoma.

    PubMed

    Misago, Noriyuki; Tsuruta, Noriko; Narisawa, Yutaka

    2012-07-01

    Basal cell carcinoma (BCC) is the most common malignant cutaneous neoplasm, however, there have been few studies on BCC with a "rippled pattern" so far. We reviewed the 650 BCC specimens from the archives of our institution, and only one example of BCC with a rippled pattern was found. We herein report the histopathological characteristics of this case. Within the lesion, which showed the typical histopathological features of nodular BCC, there was a noticeable area composed of 10-15 basaloid aggregations, which showed the rippled pattern. The rippled pattern was characterized by alternating bands of epithelial cords of spindle-shaped basaloid cells and mucinous spaces. Characteristically, around the rippled-pattern area, neoplastic aggregations with a mucinous reticulated or cystic pattern (pseudo-tubular structures), and many cord-like structures were seen. A review of the published work and the present case suggested that the histopathological characteristics of rippled-pattern BCC are: (i) a nodular type of BCC; (ii) considerably rare; (iii) have frequent intervention by mucinous spaces between the epithelial cords; and (iv) no apparent divergent differentiation with folliculosebaceous-apocrine lineage. The last three characteristics contrasted with those of the rippled-pattern sebaceoma/trichoblastoma. However, neoplastic germinative cells in rippled-pattern BCC may naturally form cord-like structures in a manner similar to rippled-pattern sebaceoma/trichoblastoma.

  2. New basal cell carcinoma susceptibility loci

    PubMed Central

    Stacey, Simon N.; Helgason, Hannes; Gudjonsson, Sigurjon A.; Thorleifsson, Gudmar; Zink, Florian; Sigurdsson, Asgeir; Kehr, Birte; Gudmundsson, Julius; Sulem, Patrick; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R.; Thorisdottir, Kristin; Ragnarsson, Rafn; Fuentelsaz, Victoria; Corredera, Cristina; Gilaberte, Yolanda; Grasa, Matilde; Planelles, Dolores; Sanmartin, Onofre; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Nexø, Bjørn A.; Tjønneland, Anne; Overvad, Kim; Jonasson, Jon G.; Tryggvadottir, Laufey; Johannsdottir, Hrefna; Kristinsdottir, Anna M.; Stefansson, Hreinn; Masson, Gisli; Magnusson, Olafur T.; Halldorsson, Bjarni V.; Kong, Augustine; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Vogel, Ulla; Kumar, Rajiv; Nagore, Eduardo; Mayordomo, José I.; Gudbjartsson, Daniel F.; Olafsson, Jon H.; Stefansson, Kari

    2015-01-01

    In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10−12), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10−9), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10−12) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10−16). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained. PMID:25855136

  3. Basal terraces on melting ice shelves

    NASA Astrophysics Data System (ADS)

    Dutrieux, Pierre; Stewart, Craig; Jenkins, Adrian; Nicholls, Keith W.; Corr, Hugh F. J.; Rignot, Eric; Steffen, Konrad

    2014-08-01

    Ocean waters melt the margins of Antarctic and Greenland glaciers, and individual glaciers' responses and the integrity of their ice shelves are expected to depend on the spatial distribution of melt. The bases of the ice shelves associated with Pine Island Glacier (West Antarctica) and Petermann Glacier (Greenland) have similar geometries, including kilometer-wide, hundreds-of-meter high channels oriented along and across the direction of ice flow. The channels are enhanced by, and constrain, oceanic melt. New meter-scale observations of basal topography reveal peculiar glaciated landscapes. Channel flanks are not smooth, but are instead stepped, with hundreds-of-meters-wide flat terraces separated by 5-50 m high walls. Melting is shown to be modulated by the geometry: constant across each terrace, changing from one terrace to the next, and greatly enhanced on the ~45° inclined walls. Melting is therefore fundamentally heterogeneous and likely associated with stratification in the ice-ocean boundary layer, challenging current models of ice shelf-ocean interactions.

  4. Basal Terraces on Melting Ice Shelves

    NASA Astrophysics Data System (ADS)

    Dutrieux, P.; Stewart, C.; Jenkins, A.; Nicholls, K. W.; Corr, H. F. J.; Rignot, E. J.; Steffen, K.

    2014-12-01

    Ocean waters melt the margins of Antarctic and Greenland glaciers and individualglaciers' responses and the integrity of their ice shelves are expected to depend on thespatial distribution of melt. The bases of the ice shelves associated with Pine IslandGlacier (West Antarctica) and Petermann Glacier (Greenland) have similar geometries,including kilometers-wide, hundreds-of-meter-high channels oriented along and acrossthe direction of ice flow. The channels are enhanced by, and constrain, oceanic melt.New, meter-scale observations of basal topography reveal peculiar glaciated landscapes.Channel flanks are not smooth, but are instead stepped, with hundreds-of-meters-wideflat terraces separated by 5-50 m-high walls. Melting is shown to be modulated by thegeometry: constant across each terrace, changing from one terrace to the next, and greatlyenhanced on the ~45°-inclined walls. Melting is therefore fundamentally heterogeneousand likely associated with stratification in the ice-ocean boundary layer, challengingcurrent models of ice shelf-ocean interactions.

  5. Stomatal architecture and evolution in basal angiosperms.

    PubMed

    Carpenter, Kevin J

    2005-10-01

    Stomatal architecture-the number, form, and arrangement of specialized epidermal cells associated with stomatal guard cells-of 46 species of basal angiosperms representing all ANITA grade families and Chloranthaceae was investigated. Leaf clearings and cuticular preparations were examined with light microscopy, and a sample of 100 stomata from each specimen was coded for stomatal type and five other characters contributing to stomatal architecture. New stomatal types were defined, and many species were examined and illustrated for the first time. Character evolution was examined in light of the ANITA hypothesis using MacClade software. Analysis of character evolution, along with other evidence from this study and evidence from the literature on fossil angiosperms and other seed plant lineages, suggests that the ancestral condition of angiosperms can be described as anomo-stephanocytic, a system in which complexes lacking subdidiaries (anomocytic) intergrade with those having weakly differentiated subsidiaries arranged in a rosette (stephanocytic). From this ancestral condition, tangential divisions of contact cells led to the profusion of different types seen in early fossil angiosperms and Amborellaceae, Austrobaileyales, and derived Chloranthaceae, while the state in Nymphaeales is little modified. Formation of new, derived types by tangential division appears to be a recurrent theme in seed plant evolution.

  6. New basal cell carcinoma susceptibility loci.

    PubMed

    Stacey, Simon N; Helgason, Hannes; Gudjonsson, Sigurjon A; Thorleifsson, Gudmar; Zink, Florian; Sigurdsson, Asgeir; Kehr, Birte; Gudmundsson, Julius; Sulem, Patrick; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R; Thorisdottir, Kristin; Ragnarsson, Rafn; Fuentelsaz, Victoria; Corredera, Cristina; Gilaberte, Yolanda; Grasa, Matilde; Planelles, Dolores; Sanmartin, Onofre; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Nexø, Bjørn A; Tjønneland, Anne; Overvad, Kim; Jonasson, Jon G; Tryggvadottir, Laufey; Johannsdottir, Hrefna; Kristinsdottir, Anna M; Stefansson, Hreinn; Masson, Gisli; Magnusson, Olafur T; Halldorsson, Bjarni V; Kong, Augustine; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Vogel, Ulla; Kumar, Rajiv; Nagore, Eduardo; Mayordomo, José I; Gudbjartsson, Daniel F; Olafsson, Jon H; Stefansson, Kari

    2015-04-09

    In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10(-12)), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10(-9)), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10(-12)) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10(-16)). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained.

  7. [Vismodegib Therapy for Periocular Basal Cell Carcinoma].

    PubMed

    Keserü, M; Green, S; Dulz, S

    2017-01-01

    Background Basal cell carcinoma (BCC) is the commonest periorbital tumour. Mohs' micrographic surgery and secondary reconstruction is the therapeutic gold standard for periorbital BCC. In cases of inoperability for any reason, therapeutic alternatives are needed. Since the approval of vismodegib, an orally administered, targeted BCC therapy is available. Nevertheless there is little information on the use of vismodegib for periorbital BCC. Patients and Methods In a retrospective study, we analysed the data of 4 patients treated with vismodegib since 2014. The patients' mean age before starting therapy was 87 years. The mean maximum tumour diameter was 22.0 mm. Results The median follow-up was 17 months. The median treatment duration was 7.5 months. In 75 % of patients, complete clinical remission of BCC was achieved. In 25 % of patients, interim stabilisation of tumour growth was possible. The most common side effect of therapy was muscle spasm. Conclusion Vismodegib is an effective treatment option for patients with periorbital BCC, in whom surgical treatment is not possible for any reason.

  8. [Basal metabolism during pregnancy: a systematic review].

    PubMed

    Sally, Enilce de Oliveira Fonseca; Anjos, Luiz Antonio dos; Wahrlich, Vivian

    2013-02-01

    Gestational energy expenditure (EE) is the basis for nutritional counseling and body weight control. The objective of this study was to systematically review the behavior of the basal metabolic rate (BMR), the major component of EE, during non gemelar pregnancy of healthy women. Based on the inclusion criteria, 37 articles were identified (24 cohort and 13 cross-sectional studies). Increases in BMR (between 8% and 35%) were observed in most cohort studies and it was related to the duration of follow-up and nutritional status. In the cross-sectionals, the increase in BMR varied from 8% to 28% close to delivery in comparison with the first trimester or post-partum. Lack of information on maternal age, loss of follow-up and short duration of follow-up during the pregnancy were serious limitations in the identified studies. In conclusion, BMR increases during pregnancy, and the increase is more intense after the second trimester. The most reliable data come from the few cohort studies that initiated before pregnancy.

  9. Segregation and Heritability of Male Sterility in Populations Derived from Progeny of Satsuma Mandarin

    PubMed Central

    Goto, Shingo; Yoshioka, Terutaka; Ohta, Satoshi; Kita, Masayuki; Hamada, Hiroko

    2016-01-01

    Male sterility derived from Satsuma mandarin (Citrus unshiu) has been used in Japanese citrus breeding programs to obtain seedless cultivars, which is a desirable trait for consumers. Male sterility has often been evaluated by anther development or pollen fertility; however, the inheritance and heritability of male sterility derived from Satsuma is poorly understood. In this study, we investigated the mode of inheritance and broad-sense heritability of male sterility derived from Satsuma. Initially, we evaluated the total number of pollen grains per anther and apparent pollen fertility, as indicated by lactophenol blue staining, in 15 citrus cultivars and selections to understand the male sterility of Satsuma. The results indicated that male sterility was primarily caused by decreased number of pollen grains per anther in progeny of Satsuma. We also evaluated these traits in three F1 populations (hyuganatsu × ‘Okitsu No. 56’, ‘Okitsu No. 46’ × ‘Okitsu No. 56’ and ‘Okitsu No. 46’ × ‘Kara’), of which the parents are derived from Satsuma. Individuals in these populations showed strong segregation for number of pollen grains per anther. The apparent fertility of pollen also showed segregation but was almost constant at 70%–90%. The estimated broad-sense heritability for the number of pollen grains per anther was as high as 0.898 in the ‘Okitsu No. 46’ × ‘Okitsu No. 56’ and ‘Okitsu No. 46’ × ‘Kara’ populations. These results indicated that the number of pollen grains per anther primarily determined male sterility among progeny of Satsuma, and this trait was inherited by the progeny. Development of DNA markers closely linked to male sterility using the F1 populations of ‘Okitsu No. 46’ × ‘Okitsu No. 56’ and ‘Okitsu No. 46’ × ‘Kara’ is expected to contribute to the breeding of novel seedless citrus cultivars. PMID:27589237

  10. Morphologic changes in basal cells during repair of tracheal epithelium.

    PubMed Central

    Wang, C. Z.; Evans, M. J.; Cox, R. A.; Burke, A. S.; Zhu, Q.; Herndon, D. N.; Barrow, R. E.

    1992-01-01

    Basal cells are differentiated with respect to junctional adhesion mechanisms and play a role in attachment of columnar epithelium to the basal lamina. Although much is known about nonciliated and ciliated cell differentiation during the repair process after injury, little is known about the basal cell. We studied the morphology of basal cells and quantitated junctional adhesion structures during repair of tracheal epithelium exposed to toxic cotton smoke. Ten adult ewes were given a smoke injury to a portion of the upper cervical trachea and were killed at 4, 6, 8, 10, and 18 days after injury for morphometric studies. At 4 days, there was a stratified reparative epithelium over the basal lamina, which was two to four cells in depth. The basal cells were identified by their hemidesmosome (HD) attachment to the basal lamina. Basal cells were about 69% larger than controls and flattened rather than columnar. The amount of HD attachment was 192% greater than controls. In contrast, volume density of cytokeratin filaments had decreased about 47%. Basal cells had returned to normal numbers and size and a columnar shape by day 18. The amount of desmosome (D) and HD attachment and volume density of cytokeratins had also reached control levels by day 18. These data indicate that morphology of basal cells changes during the initial stages of reparative regeneration but returns to normal by 18 days. Morphologic changes appear to reflect changes in size of the cell associated with cell division rather than differentiation of recently divided basal cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1381564

  11. Effect of acyclovir and interferon on human hematopoietic progenitor cells.

    PubMed Central

    Parker, L M; Lipton, J M; Binder, N; Crawford, E L; Kudisch, M; Levin, M J

    1982-01-01

    Continuous in vitro exposure of human bone marrow cells to acyclovir (approximately 200 microM) or human leukocyte interferon (approximately 250 U/ml) caused 50% inhibition of granulocyte colony-forming cell differentiation. Colonies expressed in the presence of either agent were reduced both in size and number. Erythroid progenitors were more resistant than granulocyte progenitors to the antiproliferative effects of acyclovir. Progenitor cells of patients recovering from cytotoxic chemotherapy were no more sensitive to the effects of acyclovir or interferon than were cells obtained from patients before chemotherapy. PMID:6177284

  12. Lineage tracing of neuromesodermal progenitors reveals novel Wnt-dependent roles in trunk progenitor cell maintenance and differentiation.

    PubMed

    Garriock, Robert J; Chalamalasetty, Ravindra B; Kennedy, Mark W; Canizales, Lauren C; Lewandoski, Mark; Yamaguchi, Terry P

    2015-05-01

    In the development of the vertebrate body plan, Wnt3a is thought to promote the formation of paraxial mesodermal progenitors (PMPs) of the trunk region while suppressing neural specification. Recent lineage-tracing experiments have demonstrated that these trunk neural progenitors and PMPs derive from a common multipotent progenitor called the neuromesodermal progenitor (NMP). NMPs are known to reside in the anterior primitive streak (PS) region; however, the extent to which NMPs populate the PS and contribute to the vertebrate body plan, and the precise role that Wnt3a plays in regulating NMP self-renewal and differentiation are unclear. To address this, we used cell-specific markers (Sox2 and T) and tamoxifen-induced Cre recombinase-based lineage tracing to locate putative NMPs in vivo. We provide functional evidence for NMP location primarily in the epithelial PS, and to a lesser degree in the ingressed PS. Lineage-tracing studies in Wnt3a/β-catenin signaling pathway mutants provide genetic evidence that trunk progenitors normally fated to enter the mesodermal germ layer can be redirected towards the neural lineage. These data, combined with previous PS lineage-tracing studies, support a model that epithelial anterior PS cells are Sox2(+)T(+) multipotent NMPs and form the bulk of neural progenitors and PMPs of the posterior trunk region. Finally, we find that Wnt3a/β-catenin signaling directs trunk progenitors towards PMP fates; however, our data also suggest that Wnt3a positively supports a progenitor state for both mesodermal and neural progenitors.

  13. Proposal of a super trait for the optimum selection of popcorn progenies based on path analysis.

    PubMed

    do Amaral Júnior, A T; Dos Santos, A; Gerhardt, I F S; Kurosawa, R N F; Moreira, N F; Pereira, M G; de A Gravina, G; de L Silva, F H

    2016-12-19

    A challenge faced by popcorn breeding programs is the existence of a negative correlation between the two main traits, popping expansion and yield, which hinders simultaneous gains. The objective of this study was to investigate the use of a new variable or super trait, which favors the reliable selection of superior progenies. The super trait 'expanded popcorn volume per hectare' was introduced in the evaluation of 200 full-sib families of the eighth recurrent intrapopulation selection cycle, which were arranged in randomized blocks with three replicates in two environments. Although the inability to obtain simultaneous gains through selection via popping expansion or yield was confirmed, the super trait was positively associated with both yield and popping expansion, allowing simultaneous gains via indirect selection using 'expanded popcorn volume per hectare' as the main trait. This approach is recommended because this super trait can be used in breeding programs to optimize selective gains for the crop.

  14. Recent developments in radon metrology: new aspects in the calibration of radon, thoron and progeny devices.

    PubMed

    Röttger, A; Honig, A

    2011-05-01

    Due to the importance of reliable measurements of radon activity concentration, one of the past developments in metrology was applied to the field of radon, thus meeting two basic needs: (1) the harmonisation of metrology within the scope of the mutual recognition arrangement, an arrangement drawn up by the International Committee of Weights and Measures for the mutual recognition of national standards and of calibrations issued by national metrology institutes and (2) the increased demands of the European Atomic Energy Community (EURATOM) directive, transferred into national radiation protection regulations with regard to natural radioactivity and its quality-assured measurements. This paper gives an overview of typical technical procedures in the radon-measuring technique group of PTB, covering all aspects of reference atmospheres (primary standards) for radon, thoron and their respective progenies.

  15. Transcriptional and post-transcriptional regulation of Drosophila germline stem cells and their differentiating progeny.

    PubMed

    White-Cooper, Helen; Caporilli, Simona

    2013-01-01

    In this chapter we will concentrate on the transcriptional and translational regulations that govern the development and differentiation of male germline cells. Our focus will be on the processes that occur during differentiation, that distinguish the differentiating population of cells from their stem cell parents. We discuss how these defining features are established as cells transit from a stem cell character to that of a fully committed differentiating cell. The focus will be on how GSCs differentiate, via spermatogonia, to spermatocytes. We will achieve this by first describing the transcriptional activity in the differentiating spermatocytes, cataloguing the known transcriptional regulators in these cells and then investigating how the transcription programme is set up by processes in the progentior cells. This process is particularly interesting to study from a stem cell perspective as the male GSCs are unipotent, so lineage decisions in differentiating progeny of stem cells, which occurs in many other stem cell systems, do not impinge on the behaviour of these cells.

  16. Anaphora in Basal Reader Selections: How Frequently Do They Occur?

    ERIC Educational Resources Information Center

    Baumann, James F.

    To determine how frequently various forms of anaphora appear in materials written for children, 1,000-word excerpts were analyzed from the second, fourth, and sixth grade texts of four basal reader series. The basal programs consisted of the "Ginn Reading Program," the "Houghton Mifflin Reading Program,""Scott, Foresman…

  17. Working together: basal ganglia pathways in action selection

    PubMed Central

    Friend, DM; Kravitz, AV

    2014-01-01

    Jin, Tecuapetla, and Costa combined in vivo electrophysiology with optogenetic-identification to examine firing in multiple basal ganglia nuclei during rapid motor sequences. Their results support a model of basal ganglia function in which co-activation of the direct and indirect pathways facilitate appropriate, while inhibiting competing, motor programs. PMID:24816402

  18. A Prognostic Dilemma of Basal Cell Carcinoma with Intravascular Invasion

    PubMed Central

    Niumsawatt, Vachara; Castley, Andrew

    2016-01-01

    Summary: Basal cell carcinoma is the most common malignancy; however, it very rarely metastasizes. Despite the low mortality caused by this cancer, once it spreads, it has dim prognosis. We report a case of basal cell carcinoma with rare intravascular invasion and review the literature for risk factors and management of metastasis. PMID:27757356

  19. Vismodegib resistance in basal cell carcinoma: not a smooth fit.

    PubMed

    Ridky, Todd W; Cotsarelis, George

    2015-03-09

    In this issue of Cancer Cell, two complementary papers by Atwood and colleagues and Sharpe and colleagues show that basal cell carcinomas resistant to the Smoothened (SMO) inhibitor vismodegib frequently harbor SMO mutations that limit drug binding, with mutations at some sites also increasing basal SMO activity.

  20. How Basals Teach Strategies To Derive Word Meaning from Context.

    ERIC Educational Resources Information Center

    Fisher, Peter J. L.; And Others

    A study examined the nature and extent of the instruction, application, and practice in deriving word meanings from context in a variety of basal reading series. Seven major basal reading series at the fourth-grade level (published between 1986 and 1989 and readily available) were analyzed. Results indicated that: (1) the series differed…

  1. Basal cell epithelioma (carcinoma) in children and teenagers

    SciTech Connect

    Rahbari, H.; Mehregan, A.H.

    1982-01-15

    Among over 390,000 routine dermatopathologic specimens there were 85 cases diagnosed as basal cell epithelioma (carcinoma) (BCE) in persons 19 years old or younger. This number was refined to 40 cases de novo BCE in children and teenagers. Basal cell epithelioma unrelated to other conditions is rare in the young and it should be differentiated from similar fibroepithelial growths.

  2. RADON AND PROGENY SOURCED DOSE ASSESSMENT OF SPA EMPLOYEES IN BALNEOLOGICAL SITES.

    PubMed

    Uzun, Sefa Kemal; Demiröz, Işık

    2016-09-01

    This study was conducted in the scope of IAEA project with the name 'Establishing a Systematic Radioactivity Survey and Total Effective Dose Assessment in Natural Balneological Sites' (TUR/9/018), at the Health Physics department of Sarayköy Nuclear Research and Training Center (SANAEM). The aim of this study is estimation of radon and progeny sourced effective dose for the people who are working at the spa facilities by measuring radon activity concentration (RAC) at the ambient air of indoor spa pools and dressing rooms. As it is known, the source of the radon gas is the radium content of the earth crust. Therefore, thermal waters coming from ground may contain dissolved radon and the radon can diffuse water to air. So the ambient air of spa pools can contain serious RAC that depends on a lot of parameters. In this regard, RAC measurements were executed at the 70 spa facilities in Turkey. The measurements were done with both active and passive methods at ambient air of spa pools and dressing rooms. Thus, active measurements were carried out by using the Alphaguard(®) with diffusion mode during half an hour, and passive measurements were carried out by using the humidity resistive CR-39 radon detectors during 2 months. Results show that RAC values at ambient air of spa pools varies between 13 Bq m(-3) and 10 kBq m(-3) Because long-term measurements are more reliable, if it is available, for dose calculations passive radon measurements (with CR-39 detectors) at ambient air of spa pools and dressing rooms were used, otherwise active measurement results were used. With the measurement by the conversion coefficients of ICRP 65 and occupational data of the employees has got from questionary forms, effective dose values were calculated. According to the calculations, spa employees are exposed to annual average dose between 0.05 and 29 mSv because of radon and progeny.

  3. Observations and modelling of thoron and its progeny in the soil-atmosphere-plant system.

    PubMed

    Baldacci, A E; Gattavecchia, E; Kirchner, G

    2010-11-01

    Samples of pasture vegetation, mainly Trifolium pratensis, were collected at the Botanic Garden of the University of Bologna during the period 1998-2000 and measured by gamma-spectrometry for determining thoron progeny. Concentrations of (212)Pb were between 1.5 and 20 Bq m(-2), with individual peaks up to 70 Bq m(-2). Soil samples were collected at the same location and physically characterised. Their chemical composition (particularly Th and U) was determined by X-ray fluorescence spectroscopy. Lead-212 on plants mainly originates from dry and wet deposition of this isotope generated in the lower atmosphere by the decay of its short-lived precursor (220)Rn, which is produced in the upper soil layers as a member of the natural thorium decay chain and exhales into the atmosphere. Concentrations of (220)Rn in the atmosphere depend on (1) the amount of Th present in soil, (2) the radon fraction which escapes from the soil minerals into the soil pore space, (3) its transport into the atmosphere, and (4) its redistribution within the atmosphere. The mobility of radon in soil pore space can vary by orders of magnitude depending on the soil water content, thus being the main factor for varying concentrations of (220)Rn and (212)Pb in the atmosphere. We present a simple model to predict concentrations of thoron in air and its progeny deposited from the atmosphere, which takes into account varying soil moisture contents calculated by the OPUS code. Results of this model show close agreement with our observations.

  4. Effects of soil contamination by trace elements on white poplar progeny: seed germination and seedling vigour.

    PubMed

    Madejón, Paula; Cantos, Manuel; Jiménez-Ramos, María C; Marañón, Teodoro; Murillo, José M

    2015-11-01

    Seed germination is considered a critical phase in plant development and relatively sensitive to heavy metals. White poplar (Populus alba) trees tend to accumulate Cd and Zn in their tissues. We tested if soil contamination can affect P. alba progeny, reduced seed germination and explored the distribution of mineral elements in the seed. For this purpose, fruits and seeds from female P. alba trees were selected from two contaminated and one non-contaminated areas. Seeds from all the sites were germinated using only water or a nutritive solution (in vitro). Concentrations of nutrients and trace elements in the fruits and seeds were analysed. Seedling growth in vitro was also analysed. Finally, a mapping of different elements within the poplar seed was obtained by particle-induced X-ray emission (PIXE). Germination was similar between different progenies, refuting our hypothesis that seeds from a contaminated origin would have reduced germination capacity compared to those from a non-contaminated site. Seedling growth was not affected by the contaminated origin. Cadmium and Zn concentrations in fruits produced by P. alba trees in the contaminated sites were higher than by those from the non-contaminated site. However, the nutritional status of the trees was adequate in both cases. Cd in seedlings was higher in those from contaminated soils although lower than in fruits, indicating a certain exclusion from seeds. Preliminary results of the PIXE technique showed that Al and Zn were distributed uniformly in the seeds (Cd was not detected with this technique), while the nutrients P and S were concentrated in the cotyledons.

  5. Effects of breeder hen age and dietary L-carnitine on progeny embryogenesis.

    PubMed

    Peebles, E D; Kidd, M T; McDaniel, C D; Tanksley, J P; Parker, H M; Corzo, A; Woodworth, J C

    2007-06-01

    1. Ross 308 broiler breeder hens were given diets containing 0 or 25 mg L-carnitine/kg (8 replications per treatment) from 21 weeks of age. 2. Hens were inseminated with semen from Ross broiler breeder males. In a common facility, subsequent progeny hatchability and embryonic mortality at 25, 30, 32, and 38 weeks of breeder age were evaluated. 3. Subsequent egg component weights, incubational egg water loss, progeny embryo growth, and embryo, yolk sac and liver composition through 18 d of incubation at 27, 32, and 38 weeks of breeder age were evaluated. 4. Calculated additions of L-carnitine were in agreement with analysed contents of 3.5 and 31.1 mg free L-carnitine/kg of diet, respectively, and total L-carnitine concentrations increased by 48.6, 21.7, and 10.0% in 0-d yolk, 18-d yolk sac, and 18-d liver samples, respectively, due to the addition of dietary L-carnitine. 5. Supplemental L-carnitine resulted in increased (0.6%) relative 0-d egg yolk weight across weeks 27, 32, and 38, and reduced (0.38%) 18-d yolk sac palmitoleic acid concentration at week 27 without altering embryogenesis. 6. In conclusion, dietary L-carnitine (25 mg/kg of the diet) was deposited in the yolks of broiler breeder hens and was subsequently transferred to the embryonic liver via yolk sac absorption through 18 d of incubation. Furthermore, dietary L-carnitine supplementation increased ovarian follicle yolk deposition in 27-, 32-, and 38-week-old breeder hens, and influenced yolk sac fatty acid beta-oxidation in embryos from 27-week-old breeder hens causing yolk sac palmitoleic acid concentrations to be reduced by 18 d of incubation.

  6. Influence of abnormally high leptin levels during pregnancy on metabolic phenotypes in progeny mice.

    PubMed

    Makarova, Elena N; Chepeleva, Elena V; Panchenko, Polina E; Bazhan, Nadezhda M

    2013-12-01

    Maternal obesity increases the risk of obesity in offspring, and obesity is accompanied by an increase in blood leptin levels. The "yellow" mutation at the mouse agouti locus (A(y)) increases blood leptin levels in C57BL preobese pregnant mice without affecting other metabolic characteristics. We investigated the influence of the A(y) mutation or leptin injection at the end of pregnancy in C57BL mice on metabolic phenotypes and the susceptibility to diet-induced obesity (DIO) in offspring. In both C57BL-A(y) and leptin-treated mice, the maternal effect was more pronounced in male offspring. Compared with males born to control mothers, males born to A(y) mothers displayed equal food intake (FI) but decreased body weight (BW) gain after weaning, equal glucose tolerance, and enhanced FI-to-BW ratios on the standard diet but the same FI and BW on the high-fat diet. Males born to A(y) mothers were less responsive to the anorectic effect of exogenous leptin and less resistant to fasting (were not hyperphagic and gained less weight during refeeding after food deprivation) compared with males born to control mothers. However, all progeny displayed equal hypothalamic expression of Agouti gene-related protein (AgRP), neuropeptide Y (NPY), and proopiomelanocortin (POMC) and equal plasma leptin and glucose levels after food deprivation. Leptin injections in C57BL mice on day 17 of pregnancy decreased BW in both male and female offspring but inhibited FI and DIO only in male offspring. Our results show that hyperleptinemia during pregnancy has sex-specific long-term effects on energy balance regulation in progeny and does not predispose offspring to developing obesity.

  7. A Truncated Nef Peptide from SIVcpz Inhibits the Production of HIV-1 Infectious Progeny

    PubMed Central

    Sabino Cunha, Marcela; Lima Sampaio, Thatiane; Peterlin, B. Matija; Jesus da Costa, Luciana

    2016-01-01

    Nef proteins from all primate Lentiviruses, including the simian immunodeficiency virus of chimpanzees (SIVcpz), increase viral progeny infectivity. However, the function of Nef involved with the increase in viral infectivity is still not completely understood. Nonetheless, until now, studies investigating the functions of Nef from SIVcpz have been conducted in the context of the HIV-1 proviruses. In an attempt to investigate the role played by Nef during the replication cycle of an SIVcpz, a Nef-defective derivative was obtained from the SIVcpzWTGab2 clone by introducing a frame shift mutation at a unique restriction site within the nef sequence. This nef-deleted clone expresses an N-terminal 74-amino acid truncated peptide of Nef and was named SIVcpz-tNef. We found that the SIVcpz-tNef does not behave as a classic nef-deleted HIV-1 or simian immunodeficiency virus of macaques SIVmac. Markedly, SIVcpz-tNef progeny from both Hek-293T and Molt producer cells were completely non-infectious. Moreover, the loss in infectivity of SIVcpz-tNef correlated with the inhibition of Gag and GagPol processing. A marked accumulation of Gag and very low levels of reverse transcriptase were detected in viral lysates. Furthermore, these observations were reproduced once the tNef peptide was expressed in trans both in SIVcpzΔNef and HIV-1WT expressing cells, demonstrating that the truncated peptide is a dominant negative for viral processing and infectivity for both SIVcpz and HIV-1. We demonstrated that the truncated Nef peptide binds to GagPol outside the protease region and by doing so probably blocks processing of both GagPol and Gag precursors at a very early stage. This study demonstrates for the first time that naturally-occurring Nef peptides can potently block lentiviral processing and infectivity. PMID:27399760

  8. Variations in oil palm (Elaeis guineensis Jacq.) progeny response to high aluminium concentrations in solution culture.

    PubMed

    Cristancho, R J A; Hanafi, M M; Omar, S R Syed; Rafii, M Y

    2011-03-01

    Aluminium (Al) phytotoxicity is an important soil constraint that limits crop yield. The objectives of this study were to investigate how growth, physiology, nutrient content and organic acid concentration is affected by Al, and to assess the degree of Al tolerance in different oil palm progeny (OPP). Four OPPs ['A' (Angola dura × Angola dura), 'B' (Nigerian dura × Nigerian dura), 'C' (Deli dura × AVROS pisifera) and 'D' (Deli dura × Dumpy AVROS pisifera)] were grown in different Al concentrations (0, 100 and 200 μm) in aerated Hoagland solution, pH 4.4, for 80 days. We observed a severe reduction (57.5%) in shoot dry weight, and root tips were reduced by 46.5% in 200 μm Al. In 'B' and 'C', the majority of macro- and micronutrients in plants were reduced significantly by 200 μm Al, with Mg being lowered by more than 50% in roots and shoots. The 200 μm Al treatment resulted in a 56.50% reduction in total leaf area, a 20% reduction in net photosynthesis and a 17% reduction in SPAD chlorophyll value in the third leaf. Root tips (0-5 mm) showed a significant increase in oxalic acid content with increasing Al concentration (∼ 5.86-fold); progeny 'A' had the highest concentration of oxalic acid. There was a significant interaction between Al concentration × OPP on total leaf number, root volume, lateral root length, Mg and K in root and shoot tissues, and Ca and N in shoots. The OPPs could be ranked in their tolerance to Al as: 'A' > 'D' > 'B' > 'C'.

  9. Responses of human embryonic stem cells and their differentiated progeny to ionizing radiation

    SciTech Connect

    Zou, Ying; Zhang, Ningzhe; Ellerby, Lisa M.; Davalos, Albert R.; Zeng, Xianmin; Campisi, Judith; Desprez, Pierre-Yves

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer hESCs and their progeny, NSCs and neurons, were exposed to ionizing radiation. Black-Right-Pointing-Pointer Upon irradiation, most hESCs died within 5-7 h. Black-Right-Pointing-Pointer Surviving NSCs underwent senescence and displayed features of astrocytes. Black-Right-Pointing-Pointer Surviving NSCs did not display the secretory phenotype expressed by pure astrocytes. Black-Right-Pointing-Pointer This study is to better understand the stress-responses of hESCs and their progeny. -- Abstract: Human embryonic stem cells (hESCs) hold promise for the treatment of many human pathologies. For example, hESCs and the neuronal stem cells (NSCs) and neurons derived from them have significant potential as transplantation therapies for a variety of neurodegenerative diseases. Two concerns about the use of hESCs and their differentiated derivatives are their ability to function and their ability to resist neoplastic transformation in response to stresses that inevitably arise during their preparation for transplantation. To begin to understand how these cells handle genotoxic stress, we examined the responses of hESCs and derived NSCs and neurons to ionizing radiation (IR). Undifferentiated hESCs were extremely sensitive to IR, with nearly all the cells undergoing cell death within 5-7 h. NSCs and neurons were substantially more resistant to IR, with neurons showing the most resistant. Of interest, NSCs that survived IR underwent cellular senescence and acquired astrocytic characteristics. Unlike IR-treated astrocytes, however, the NSC-derived astrocytic cells that survived IR did not display the typical pro-inflammatory, pro-carcinogenic senescence-associated secretory phenotype. These findings suggest distinct genotoxic stress-responses of hESCs and derived NSC and neuronal populations, and suggest that damaged NSCs, while failing to function, may not cause local inflammation.

  10. CuO Nanoparticle Interaction with Arabidopsis thaliana: Toxicity, Parent-Progeny Transfer, and Gene Expression.

    PubMed

    Wang, Zhenyu; Xu, Lina; Zhao, Jian; Wang, Xiangke; White, Jason C; Xing, Baoshan

    2016-06-07

    CuO nanoparticles (NPs) (20, 50 mg L(-1)) inhibited seedling growth of different Arabidopsis thaliana ecotypes (Col-0, Bay-0, and Ws-2), as well as the germination of their pollens and harvested seeds. For most of growth parameters (e.g., biomass, relative growth rate, root morphology change), Col-0 was the more sensitive ecotype to CuO NPs compared to Bay-0 and Ws-2. Equivalent Cu(2+) ions and CuO bulk particles had no effect on Arabidopsis growth. After CuO NPs (50 mg L(-1)) exposure, Cu was detected in the roots, leaves, flowers and harvested seeds of Arabidopsis, and its contents were significantly higher than that in CuO bulk particles (50 mg L(-1)) and Cu(2+) ions (0.15 mg L(-1)) treatments. Based on X-ray absorption near-edge spectroscopy analysis (XANES), Cu in the harvested seeds was confirmed as being mainly in the form of CuO (88.8%), which is the first observation on the presence of CuO NPs in the plant progeny. Moreover, after CuO NPs exposure, two differentially expressed genes (C-1 and C-3) that regulated root growth and reactive oxygen species generation were identified, which correlated well with the physiological root inhibition and oxidative stress data. This current study provides direct evidence for the negative effects of CuO NPs on Arabidopsis, including accumulation and parent-progeny transfer of the particles, which may have significant implications with regard to the risk of NPs to food safety and security.

  11. Tachykinin regulation of basal synovial blood flow

    PubMed Central

    Ferrell, W R; Lockhart, J C; Karimian, S M

    1997-01-01

    Experiments were performed to investigate the role of endogenously released tachykinins in the regulation of blood flow to the rat knee joint. Synovial perfusion was assessed by laser Doppler perfusion imaging, which permitted spatial measurement of relative changes in perfusion from control (pre drug administration), expressed as the percentage change. Most experiments were performed on the exposed medial aspect of the knee joint capsule.Neither the selective tachykinin NK1 receptor antagonist, FK888, nor the selective tachykinin NK2 receptor antagonist, SR48968, significantly influenced synovial blood flow at doses of 10−12, 10−10 and 10−8 mol. However, topical co-administration of these agents produced significant dose-dependent reductions in basal synovial perfusion of 6.3±4.6, 12.0±3.4 and 19.9±2.6%, respectively; n=29. The non-selective tachykinin NK1/NK2 receptor antagonist, FK224, also produced significant (at 10−10 and 10−8 mol), but less potent, reductions in perfusion of 5.3±4.0, 8.4±2.2 and 5.9±2.8%, respectively; n=25.Topical administration of the α1-, α2-adrenoceptor antagonist phenoxybenzamine elicited a 31.3±6.2% increase in blood flow which was substantially reduced to 10.4±3.8% by co-administration of the FK888 and SR48968 (both at 10−8 mol; n=8–13), suggesting that normally there is sympathetic vasoconstrictor ‘tone' which is opposed by the vasodilator action of endogenous tachykinins.One week after surgical interruption of the nerve supply to the knee joint, co-administration of FK888 and SR48968 (both at 10−8 mol) now produced slight vasodilatation (6.7±4.6%; n=9) which did not differ significantly from vehicle treatment. Depletion of tachykinins from sensory nerve fibres by systemic capsaicin administration also resulted in abolition of the vasoconstrictor effect of FK888 and SR48968 (both at 10−8 mol), with these agents only producing a slight vasodilatation (2.5±5.3%; n=6).By use of a near infra

  12. Basal Autophagy Is Required for Herpes simplex Virus-2 Infection

    PubMed Central

    Yakoub, Abraam M.; Shukla, Deepak

    2015-01-01

    Autophagy is a conserved catabolic process of the cell, which plays an important role in regulating plethora of infections. The role of autophagy in Herpes simplex virus-2 (HSV-2) infection is unknown. Here, we found that HSV-2 does not allow induction of an autophagic response to infection, but maintains basal autophagy levels mostly unchanged during productive infection. Thus, we investigated the importance of basal autophagy for HSV-2 infection, using pharmacological autophagy suppression or cells genetically deficient in an autophagy-essential gene (ATG5). Interference with basal autophagy flux in cells significantly reduced viral replication and diminished the infection. These results indicate that basal autophagy plays an indispensable role required for a productive infection. Importantly, this study draws a sharp distinction between induced and basal autophagy, where the former acts as a viral clearance mechanism abrogating infection, while the latter supports infection. PMID:26248741

  13. Basal Ganglia Mechanisms Underlying Precision Grip Force Control

    PubMed Central

    Prodoehl, Janey; Corcos, Daniel M.; Vaillancourt, David E.

    2009-01-01

    The classic grasping network has been well studied but thus far the focus has been on cortical regions in the control of grasping. Sub-cortically, specific nuclei of the basal ganglia have been shown to be important in different aspects of precision grip force control but these findings have not been well integrated. In this review we outline the evidence to support the hypothesis that key basal ganglia nuclei are involved in parameterizing specific properties of precision grip force. We review literature from different areas of human and animal work that converges to build a case for basal ganglia involvement in the control of precision gripping. Following on from literature showing anatomical connectivity between the basal ganglia nuclei and key nodes in the cortical grasping network, we suggest a conceptual framework for how the basal ganglia could function within the grasping network, particularly as it relates to the control of precision grip force. PMID:19428499

  14. Stem and progenitor cell dysfunction in human trisomies

    PubMed Central

    Liu, Binbin; Filippi, Sarah; Roy, Anindita; Roberts, Irene

    2015-01-01

    Trisomy 21, the commonest constitutional aneuploidy in humans, causes profound perturbation of stem and progenitor cell growth, which is both cell context dependent and developmental stage specific and mediated by complex genetic mechanisms beyond increased Hsa21 gene dosage. While proliferation of fetal hematopoietic and testicular stem/progenitors is increased and may underlie increased susceptibility to childhood leukemia and testicular cancer, fetal stem/progenitor proliferation in other tissues is markedly impaired leading to the characteristic craniofacial, neurocognitive and cardiac features in individuals with Down syndrome. After birth, trisomy 21-mediated premature aging of stem/progenitor cells may contribute to the progressive multi-system deterioration, including development of Alzheimer's disease. PMID:25520324

  15. STUDY OF RADIATION EXPOSURE DUE TO RADON, THORON AND THEIR PROGENY IN THE INDOOR ENVIRONMENT OF RAJPUR REGION OF UTTARAKHAND HIMALAYA.

    PubMed

    Kandari, Tushar; Aswal, Sunita; Prasad, Mukesh; Pant, Preeti; Bourai, A A; Ramola, R C

    2016-10-01

    In the present study, the measurements of indoor radon, thoron and their progeny concentrations have been carried out in the Rajpur region of Uttarakhand, Himalaya, India by using LR-115 solid-state nuclear track detector-based time-integrated techniques. The gas concentrations have been measured by single-entry pin-hole dosemeter technique, while for the progeny concentrations, deposition-based Direct Thoron and Radon Progeny Sensor technique has been used. The radiation doses due to the inhalation of radon, thoron and progeny have also been determined by using obtained concentrations of radon, thoron and their progeny in the study area. The average radon concentration varies from 75 to 123 Bq m(-3) with an overall average of 89 Bq m(-3) The average thoron concentration varies from 29 to 55 Bq m(-3) with an overall average of 38 Bq m(-3) The total annual effective dose received due to radon, thoron and their progeny varies from 2.4 to 4.1 mSv y(-1) with an average of 2.9 mSv y(-1) While the average equilibrium factor for radon and its progeny was found to be 0.39, for thoron and its progeny, it was 0.06.

  16. In vivo generated Citrus exocortis viroid progeny variants display a range of phenotypes with altered levels of replication, systemic accumulation and pathogenicity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Citrus exocortis viroid (CEVd) exists as heterogeneous variants in plant hosts. We inoculated RNA transcripts from a CEVd cDNA clone into protoplasts, seedlings and mature plants of citrus and sequenced 240 in vivo generated progeny variants. Selected progeny variants were further used to evaluate t...

  17. Pine Island Glacier - local flow mechanisms and basal sliding

    NASA Astrophysics Data System (ADS)

    Wilkens, N. M.; Kleiner, T.; Humbert, A.

    2013-12-01

    Pine Island Glacier is a fast moving outlet glacier in the West Antarctic Ice Sheet. Several tributaries feeding the central ice stream characterise the flow field structure of this glacier. In the past decades the glacier has shown acceleration, thinning and a significant grounding line retreat. These ongoing processes are coinciding with a concentrated mass loss in the area around Pine Island Glacier, the Amundsen Sea Embayment. The area is of additional interest due to its retrograde bed slope. The postulated instability of the setting turns the glacier into an even more suitable object for modelling studies. One major challenge encountered when modelling the flow field of Pine Island Glacier is to reproduce the locally varying flow pattern, with its many tributaries. Commonly this difficulty is overcome by inversion for parameters controlling basal sliding. Our study is aimed at connecting basal sliding again to physical parameters. To achieve this we conduct experiments of Pine Island Glacier with the diagnostic 3D full-Stokes model COMice. The model is thermo-mechanically coupled and implemented with the commercial finite-element package COMSOL Multiphysics©. We use remotely sensed surface velocity data to validate our results. In a first step, the model is used to identify dominant local mechanisms that drive the flow of the different tributaries. We identify connections between the basal topography, the basal temperature, the driving stress and the basal roughness distribution. The thus gained information is used to confine basal sliding. Areas with similar qualitative characteristics are identified, and constant-sliding assumptions made for those. Additionally, the basal roughness distribution is matched onto a basal sliding parameter. This way the sliding law is again brought closer to its original meaning. Our results are important for prognostic model experiments, as we connect basal sliding to locally varying basal properties, which might lead to

  18. Two progenitor cells for human oogonia inferred from pedigree data and the X-inactivation imprinting model of the fragile-X syndrome.

    PubMed Central

    Laird, C D; Lamb, M M; Thorne, J L

    1990-01-01

    Laird has proposed that the human fragile-X syndrome is caused by abnormal chromosome imprinting. The analysis presented here supports and extends this proposal. Using published pedigrees that include DNA polymorphism (RFLP) data, we establish that the states of the fragile-X mutation termed "imprinted" and "nonimprinted" usually can be distinguished by the level of cytogenetic expression of the fragile-X chromosome. This information is then used to assess the state of the fragile-X allele in carrier progeny of individual women who inherited a nonimprinted fragile-X chromosome. From this assessment, an estimate is made of the frequency, in individual women, of primary oocytes with an imprinted fragile-X chromosome. The results of this analysis provide additional support for the specific model in which chromosome imprinting occurs in a female in, on average, half of her primary oocytes. This is the expected frequency if X-chromosome inactivation is the initial step in the imprinting of the mutant fragile-X allele. Moreover, this analysis suggests a biological explanation for peculiarities of fragile-X inheritance described by others as "clustering" and the "Sherman paradox." We interpret these peculiarities as consequences of a very small number of oogonial progenitor cells. Two progenitor cells for oogonia is the best integer estimate of the number of such cells at the time of the initial event that leads to chromosome imprinting. PMID:1969225

  19. Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema.

    PubMed

    Doyle, Margaret F; Tracy, Russell P; Parikh, Megha A; Hoffman, Eric A; Shimbo, Daichi; Austin, John H M; Smith, Benjamin M; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R Graham

    2017-01-01

    Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50-79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema.

  20. Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema

    PubMed Central

    Tracy, Russell P.; Parikh, Megha A.; Hoffman, Eric A.; Shimbo, Daichi; Austin, John H. M.; Smith, Benjamin M.; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R. Graham

    2017-01-01

    Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema. PMID:28291826

  1. The Limbal Epithelial Progenitors in the Limbal Niche Environment

    PubMed Central

    Zhang, Yuan; Sun, Hong; Liu, Yongsong; Chen, Shuangling; Cai, Subo; Zhu, Yingting; Guo, Ping

    2016-01-01

    Limbal epithelial progenitors are stem cells located in limbal palisades of vogt. In this review, we present the audience with recent evidence that limbal epithelial progenitors may be a powerful stem cell resource for the cure of human corneal stem cell deficiency. Further understanding of their mechanism may shed lights to the future successful application of stem cell therapy not only to the eye tissue, but also to the other tissues in the human body. PMID:27877075

  2. Characterization of Chromosome Inheritance of the Intergeneric BC2 and BC3 Progeny between Saccharum spp. and Erianthus arundinaceus.

    PubMed

    Huang, Yongji; Wu, Jiayun; Wang, Ping; Lin, Yanquan; Fu, Cheng; Deng, Zuhu; Wang, Qinnan; Li, Qiwei; Chen, Rukai; Zhang, Muqing

    2015-01-01

    Erianthus arundinaceus (E. arundinaceus) has many desirable agronomic traits for sugarcane improvement, such as high biomass, vigor, rationing ability, tolerance to drought, and water logging, as well as resistance to pests and disease. To investigate the introgression of the E. arundinaceus genome into sugarcane in the higher generations, intergeneric BC2 and BC3 progeny generated between Saccharum spp. and E. arundinaceus were studied using the genomic in situ hybridization (GISH) technique. The results showed that the BC2 and BC3 generations resulted from n + n chromosome transmission. Furthermore, chromosome translocation occurred at terminal fragments from the E. arundinaceus chromosome in some progeny of Saccharum spp. and E. arundinaceus. Notably, the translocated chromosomes could be stably transmitted to their progeny. This study illustrates the characterization of chromosome inheritance of the intergeneric BC2 and BC3 progeny between Saccharum spp. and E. arundinaceus. This work could provide more useful molecular cytogenetic information for the germplasm resources of E. arundinaceus, and may promote further understanding of the germplasm resources of E. arundinaceus for sugarcane breeders to accelerate its progress in sugarcane commercial breeding.

  3. Combining ability of S3 progenies for key agronomic traits in popcorn: comparison of testers in top-crosses.

    PubMed

    de Lima, V J; do Amaral Junior, A T; Kamphorst, S H; Pena, G F; Leite, J T; Schmitt, K F M; Vittorazzi, C; de Almeida Filho, J E; Mora, F

    2016-12-02

    The successful development of hybrid cultivars depends on the reliability of estimated combining ability of the parent lines. The objectives of this study were to assess the combining ability of partially inbred S3 families of popcorn derived from the open-pollinated variety UENF 14, via top-crosses with four testers, and to compare the testers for their ability to discriminate the S3 progenies. The experiment was conducted in the 2015/2016 crop season, in an incomplete-block (Lattice) design with three replications. The following agronomic traits were evaluated: average plant height, grain yield (GY), popping expansion (PE), and expanded popcorn volume per hectare. The top-cross hybrid, originating from the BRS-Angela vs S3 progeny 10 combination, was indicated as promising, showing high values for specific combining ability for GY and PE. For the S3 progenies that showed high and positive GCA values for GY and PE, the continuity of the breeding program is recommended, with the advance of self-pollination generations. Fasoulas' differentiation index discriminated the BRS-Angela tester as the most suitable for identifying the superior progenies.

  4. No significant level of inheritable interchromosomal aberrations in the progeny of bystander primary human fibroblasts after alpha particle irradiation

    NASA Astrophysics Data System (ADS)

    Hu, Burong; Zhu, Jiayun; Zhou, Hongning; Hei, Tom K.

    2013-02-01

    A major concern for bystander effects is the probability that normal healthy cells adjacent to the irradiated cells become genomically unstable and undergo further carcinogenesis after therapeutic irradiation or space mission where astronauts are exposed to low dose of heavy ions. Genomic instability is a hallmark of cancer cells. In the present study, two irradiation protocols were performed in order to ensure pure populations of bystander cells and the genomic instability in their progeny were investigated. After irradiation, chromosomal aberrations of cells were analyzed at designated time points using G2 phase premature chromosome condensation (G2-PCC) coupled with Giemsa staining and with multiplex fluorescent in situ hybridization (mFISH). Our Giemsa staining assay demonstrated that elevated yields of chromatid breaks were induced in the progeny of pure bystander primary fibroblasts up to 20 days after irradiation. mFISH assay showed no significant level of inheritable interchromosomal aberrations were induced in the progeny of the bystander cell groups, while the fractions of gross aberrations (chromatid breaks or chromosomal breaks) significantly increased in some bystander cell groups. These results suggest that genomic instability occurred in the progeny of the irradiation associated bystander normal fibroblasts exclude the inheritable interchromosomal aberration.

  5. Identification of steelhead and resident rainbow trout progeny in the Deschutes River, Oregon, revealed with otolith microchemistry

    USGS Publications Warehouse

    Zimmerman, C.E.; Reeves, G.H.

    2002-01-01

    Comparisons of strontium:calcium (Sr:Ca) ratios in otolith primordia and freshwater growth regions were used to identify the progeny of steelhead Oncorhynchus mykiss (anadromous rainbow trout) and resident rainbow trout in the Deschutes River, Oregon. We cultured progeny of known adult steelhead and resident rainbow trout to confirm the relationship between Sr:Ca ratios in otolith primordia and the life history of the maternal parent. The mean (??SD) Sr:Ca ratio was significantly higher in the otolith primordia of the progeny of steelhead (0.001461 ?? 0.00029; n = 100) than in those of the progeny of resident rainbow trout (0.000829 ?? 0.000012; n = 100). We used comparisons of Sr:Ca ratios in the primordia and first-summer growth regions of otoliths to determine the maternal origin of unknown O. mykiss juveniles (n = 272) collected from rearing habitats within the main-stem Deschutes River and tributary rearing habitats and thus to ascertain the relative proportion of each life history morph in each rearing habitat. Resident rainbow trout fry dominated the bi-monthly samples collected from main-stem rearing habitats between May and November 1995. Steelhead fry dominated samples collected from below waterfalls on two tributaries in 1996 and 1998.

  6. [The postnatal development of the progeny of males whose germ cells were irradiated at different stages of spermatogenesis].

    PubMed

    Lepekhin, N P; Palyga, G F

    1995-01-01

    Distinct genetic radiosensitivity of germinal cells of males irradiated during different stages of spermatogenesis with doses of 0.25-5.0 Gy leads to reduction in vital newborn rats number in the first generation progeny and to elevated postnatal mortality rate. These postnatal ontogeny disorders depend on the irradiation dose and spermatogenesis stage for a moment irradiation.

  7. The progeny of Arabidopsis thaliana plants exposed to salt exhibit changes in DNA methylation, histone modifications and gene expression.

    PubMed

    Bilichak, Andriy; Ilnystkyy, Yaroslav; Hollunder, Jens; Kovalchuk, Igor

    2012-01-01

    Plants are able to acclimate to new growth conditions on a relatively short time-scale. Recently, we showed that the progeny of plants exposed to various abiotic stresses exhibited changes in genome stability, methylation patterns and stress tolerance. Here, we performed a more detailed analysis of methylation patterns in the progeny of Arabidopsis thaliana (Arabidopsis) plants exposed to 25 and 75 mM sodium chloride. We found that the majority of gene promoters exhibiting changes in methylation were hypermethylated, and this group was overrepresented by regulators of the chromatin structure. The analysis of DNA methylation at gene bodies showed that hypermethylation in the progeny of stressed plants was primarily due to changes in the 5' and 3' ends as well as in exons rather than introns. All but one hypermethylated gene tested had lower gene expression. The analysis of histone modifications in the promoters and coding sequences showed that hypermethylation and lower gene expression correlated with the enrichment of H3K9me2 and depletion of H3K9ac histones. Thus, our work demonstrated a high degree of correlation between changes in DNA methylation, histone modifications and gene expression in the progeny of salt-stressed plants.

  8. Proliferation of mouse embryonic stem cell progeny and the spontaneous contractile activity of cardiomyocytes are affected by microtopography.

    PubMed

    Biehl, Jesse K; Yamanaka, Satoshi; Desai, Tejal A; Boheler, Kenneth R; Russell, Brenda

    2009-08-01

    The niche in which stem cells reside and differentiate is a complex physicochemical microenvironment that regulates cell function. The role played by three-dimensional physical contours was studied on cell progeny derived from mouse embryonic stem cells using microtopographies created on PDMS (poly-dimethyl-siloxane) membranes. While markers of differentiation were not affected, the proliferation of heterogeneous mouse embryonic stem cell-derived progeny was attenuated by 15 microm-, but not 5 microm-high microprojections. This reduction was reversed by Rho kinase and myosin light chain kinase inhibition, which diminishes the tension generating ability of stress fibers. Purified cardiomyocytes derived from embryonic stem cells also showed significant blunting of proliferation and increased beating rates compared with cells grown on flat substrates. Thus, proliferation of stem cell-derived progeny appears to be regulated by microtopography through tension-generation of contractility in the third-dimension. These results emphasize the importance of topographic cues in the modulation of stem cell progeny behavior.

  9. Analysis of variance components of testcross progenies in an autotetraploid species and consequences for recurrent selection with a tester.

    PubMed

    Gallais, A

    1992-01-01

    For autotetraploid species the development of the concept of test value (value in testcross) leads to a simple description of the variance among testcross progenies. When defining directly genetic effects at the level of the value of the progenies, there is no contribution of triand tetragenic interactions. To estimate additive and dominance variances it is only necessary to have the population of progenies structured in half-sib or full-sib families; it is then possible to determine the presence of epistasis using a two-way mating design. When the theory of recurrent selection is applied dominance variance can be neglected for the prediction of genetic advance in one cycle as well for the development of combined selection when progenies are structured in families. The results are similar to those for diploids with two-locus epistasis. The more efficient scheme consists of the development of pair-crossing in off-season generations (for intercrossing) and simultaneous crossing of each plant to the tester. In comparison to the classical scheme, the relative efficiency of such a scheme is 41%. The use of combined selection will further increase this superiority.

  10. Characterization of Chromosome Inheritance of the Intergeneric BC2 and BC3 Progeny between Saccharum spp. and Erianthus arundinaceus

    PubMed Central

    Wang, Ping; Lin, Yanquan; Fu, Cheng; Deng, Zuhu; Wang, Qinnan; Li, Qiwei; Chen, Rukai; Zhang, Muqing

    2015-01-01

    Erianthus arundinaceus (E. arundinaceus) has many desirable agronomic traits for sugarcane improvement, such as high biomass, vigor, rationing ability, tolerance to drought, and water logging, as well as resistance to pests and disease. To investigate the introgression of the E. arundinaceus genome into sugarcane in the higher generations, intergeneric BC2 and BC3 progeny generated between Saccharum spp. and E. arundinaceus were studied using the genomic in situ hybridization (GISH) technique. The results showed that the BC2 and BC3 generations resulted from n + n chromosome transmission. Furthermore, chromosome translocation occurred at terminal fragments from the E. arundinaceus chromosome in some progeny of Saccharum spp. and E. arundinaceus. Notably, the translocated chromosomes could be stably transmitted to their progeny. This study illustrates the characterization of chromosome inheritance of the intergeneric BC2 and BC3 progeny between Saccharum spp. and E. arundinaceus. This work could provide more useful molecular cytogenetic information for the germplasm resources of E. arundinaceus, and may promote further understanding of the germplasm resources of E. arundinaceus for sugarcane breeders to accelerate its progress in sugarcane commercial breeding. PMID:26196281

  11. Vernalization response of domesticated× wild chickpea progeny is subject to strong genotype by environment interaction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vernalization insensitivity is a key feature of domesticated chickpea and its genetic basis is not well understood. We studied vernalization response among hybrid progeny derived from two domesticated x wild crosses. The wild parents are vernalization sensitive, late flowering genotypes while both d...

  12. Cold storage of the adult stage of Gonatocerus ashmeadi girault: the impact on maternal and progeny quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of storage of adult G. ashmeadi at 2, 5 and 10°C on maternal and the unstored progeny fitness qualities was examined. The maternal generation did not survive 5 d exposure to 2°C and those stored at 10°C survived longer than those held at 5°C. Oviposition of the maternal generation conti...

  13. Identification of cocoa trees combining high yield potential and resistance to diseases in segregating progenies In Ecuador

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diseases and low yielding planting material are the main factors limiting production of “fine” or “flavour” cocoa in Ecuador. This makes it necessary to develop modern varieties capable of overcoming these limitations. During the 1960s and 1970s INIAP tested several progenies from selected crosses...

  14. Simultaneous Visualization of Parental and Progeny Viruses by a Capsid-Specific HaloTag Labeling Strategy.

    PubMed

    Liu, An-An; Zhang, Zhenfeng; Sun, En-Ze; Zheng, Zhenhua; Zhang, Zhi-Ling; Hu, Qinxue; Wang, Hanzhong; Pang, Dai-Wen

    2016-01-26

    Real-time, long-term, single-particle tracking (SPT) provides us an opportunity to explore the fate of individual viruses toward understanding the mechanisms underlying virus infection, which in turn could lead to the development of therapeutics against viral diseases. However, the research focusing on the virus assembly and egress by SPT remains a challenge because established labeling strategies could neither specifically label progeny viruses nor make them distinguishable from the parental viruses. Herein, we have established a temporally controllable capsid-specific HaloTag labeling strategy based on reverse genetic technology. VP26, the smallest pseudorabies virus (PrV) capsid protein, was fused with HaloTag protein and labeled with the HaloTag ligand during virus replication. The labeled replication-competent recombinant PrV harvested from medium can be applied directly in SPT experiments without further modification. Thus, virus infectivity, which is critical for the visualization and analysis of viral motion, is retained to the largest extent. Moreover, progeny viruses can be distinguished from parental viruses using diverse HaloTag ligands. Consequently, the entire course of virus infection and replication can be visualized continuously, including virus attachment and capsid entry, transportation of capsids to the nucleus along microtubules, docking of capsids on the nucleus, endonuclear assembly of progeny capsids, and the egress of progeny viruses. In combination with SPT, the established strategy represents a versatile means to reveal the mechanisms and dynamic global picture of the life cycle of a virus.

  15. Progeny of Osmia lignaria from distinct regions differ in developmental phenology and survival under a common thermal regime.

    PubMed

    Pitts-Singer, Theresa L; Cane, James H; Trostle, Glen

    2014-08-01

    Many insects, including some bees, have extensive subcontinental distributions that can differ in climatic conditions. Within and beyond these distributions, humans intentionally transport beneficial insects, including bees, to non-natal geographic locations. Insects also are experiencing unprecedented climatic change in their resident localities. For solitary bees, we know very little about the adaptive plasticity and geographic variation in developmental physiology that accommodates the different climates experienced within distributional ranges. Osmia lignaria Say (Hymenoptera: Megachilidae) is a widely distributed North American spring-emerging bee being developed as a managed pollinator for tree fruit crops, including almonds. We examined the development and survival of O. lignaria progeny that were descended from populations sourced from southern California, western Washington, and northern Utah, and then were reared together under an hourly and weekly temperature regime simulating those of a California almond-growing region. We found that developmental physiologies of Washington and Utah progeny were generally similar. However, California progeny developed slower, were more metabolically active, and survived better under California conditions than did populations native to regions at higher latitudes. Regardless of geographic origin, cocooned adults managed under prescribed thermal regimes emerged faster and lived longer after wintering. Progeny of parents from different regions exhibited some acclimatory plasticity in developmental phenologies to a novel climatic regime, but overall their responses reflected their geographic origins. This outcome is consistent with their developmental phenologies being largely heritable adaptations to regional climates.

  16. Large volume leukapheresis maximizes the progenitor cell yield for allogeneic peripheral blood progenitor donation.

    PubMed

    Kobbe, G; Soehngen, D; Heyll, A; Fischer, J; Thiele, K P; Aul, C; Wernet, P

    1997-04-01

    We have investigated the efficiency and safety of large volume leukapheresis (LVL) for the collection of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPCs) from healthy donors. In six apheresis sessions in four healthy individuals on a COBE-BCT Spectra cell separator (median processed volume 3.5 X total blood volume, TBV, range 3.3-4.4 X TBV), harvested cells were collected sequentially into three single bags. The collection bags were changed after processing 33%, 66%, and 100% of the prospective apheresis volume, allowing analysis of PBPCs collected at different periods during one harvest. Mononuclear cells (MNCs), CD34+ cells, CD34+ subsets, and lymphocyte subsets were determined in each bag. Substantially more PBPCs were harvested than were in the circulation before G-CSF administration preceding LVL (median 171%, range 69-267%), reflecting progenitor release during the procedure. In donors 1 and 3, the CD34+ cell yields decreased in the third bag to 53% and 42% of that collected in the first bag, whereas the progenitor cell yields in donors 2 and 4 were stable or rose during the procedure, achieving in the third bag 157% and 105% of the number of CD34+ cells collected in the first bag. Minor changes were found in the subsets of CD34+ cells, lymphocytes, and monocytes collected at different periods during a single harvest. LVL was well tolerated. Reversible thombocytopenia developed in all cases. No late effects attributable to LVL or G-CSF were found in the 4 donors and 16 other healthy individuals who have undergone LVL in our institution. We conclude that LVL is safe and maximizes PBPC yields for allogeneic transplantation.

  17. [Genetic diversity revealed by ISSR molecular marker in common wheat, spelt, compactum and progeny of recurrent selection].

    PubMed

    Du, Jin-Kun; Yao, Ying-Yin; Ni, Zhong-Fu; Peng, Hui-Ru; Sun, Qi-Xin

    2002-05-01

    It is important to estimate the genetic diversity between the parents for improving the heterosis of hybrid wheat. In this study, ISSR(inter-simple sequence repeat) marker was used to measure the genetic diversity within and among common wheat (Triticum aestivum L.), spelt (Triticum spelta L.), compactum (Triticum compactum Host.) and progeny of foreign wheat-based recurrent selection, and the possibility of establishing the new heterotic group was also assessed. Forty seven genotypes were used for ISSR analysis, which included 14 common wheat, 10 spelt wheat, 11 compactum and 12 progeny of recurrent selection. Eleven of 33 ISSR primers that can produce distinguishable bands were selected for PCR amplification. A total of 238 bands were amplified, among which 207 (87%) bands were polymorphic. The polymorphic bands amplified by each primer ranged from 11 to 38, with an averaged of 18.8. The percentage of polymorphic band (80.3%) in common wheat was higher than that in progeny of recurrent selection (78.7%), spelt (75.0%) and compactum (74.9%). The 238 polymorphic products were used to calculate Nei's similarity index (GS) and the genetic distance (GD). It was found that the mean genetic distance between different wheat types (0.3115-0.3442) was obviously higher than that within common wheat (0.2743), spelt (0.2351), compactum (0.2622). In addition, progeny of recurrent selection also showed much higher genetic distance with other three wheat types (0.3217, 0.3256, 0.3198). The cluster analysis was performed based on the genetic distance (GD) matrix by using UPGMA method. Common wheat, spelt, compactum and progeny of recurrent selection were classified into four different groups. In this study, ISSR marker was firstly used to assess genetic diversity among common wheat, spelt, compactum and progeny of recurrent selection, and can differentiate the wheat cultivars (lines) that selected from the same cross combination. It was concluded that spelt, compactum and progeny

  18. Constraining the Progenitor Masses of Core Collapse Supernova Remnants

    NASA Astrophysics Data System (ADS)

    Díaz Rodríguez, Mariangelly; Murphy, Jeremiah Wayne; Elwood, Benjamin; Williams, Benjamin F.; Rubin, David

    2016-01-01

    Understanding the progenitor mass distribution of supernova explosions is an important observational constraint of stellar evolution theory. Recently, a novel approach was proposed to significantly increase the number of progenitor masses: characterize the progenitor mass of supernova remnants (SNRs) by age-dating the local stellar population. Preliminary statistical analyses suggested that there is a lack of SNRs around the most massive of massive stars. This suggested that there is a maximum mass for core collapse supernova explosions, or there is a bias against finding SNRs associated with the most massive stars. We test for a bias by considering the distribution of SNRs sizes using a Monte Carlo simulation. We find that the distribution of remnants sizes is the same for low mass progenitors and high mass progenitors. This implies that there is no bias against finding SNRs around the most massive progenitors. Our next step is to apply Bayesian statistical inference and obtain the joint probability for all the parameters involved in the statistical distribution model: the minimum mass, maximum mass, and slope of the mass distribution.

  19. Interstitial stromal progenitors during kidney development: here, there and everywhere.

    PubMed

    Fanni, Daniela; Gerosa, Clara; Vinci, Laura; Ambu, Rossano; Dessì, Angelica; Eyken, Peter Van; Fanos, Vassilios; Faa, Gavino

    2016-12-01

    In recent years, the renal interstitium has been identified as the site of multiple cell types, giving rise to multiple contiguous cellular networks with multiple fundamental structural and functional roles. Few studies have been carried out on the morphological and functional properties of the stromal/interstitial renal cells during the intrauterine life. This work was aimed at reviewing the peculiar features of renal interstitial stem/progenitor cells involved in kidney development. The origin of the renal interstitial progenitor cells remains unknown. During kidney development, besides the Six2 + cells of the cap mesenchyme, a self-renewing progenitor population, characterized by the expression of Foxd1, represents the first actor of the non-nephrogenic lineage. Foxd1 + interstitial progenitors originate the cortical and the renal medullary interstitial progenitors. Here, the most important stromal/interstitial compartments present in the developing human kidney will be analyzed: capsular stromal cells, cortical interstitial cells, medullary interstitial cells, the interstitium inside the renal stem cell niche, Hilar interstitial cells and Ureteric interstitial cells. Data reported here indicate that the different interstitial compartments of the developing kidney are formed by different cell types that characterize the different renal areas. Further studies are needed to better characterize the different pools of renal interstitial progenitors and their role in human nephrogenesis.

  20. Viral disruption of olfactory progenitors is exacerbated in allergic mice.

    PubMed

    Ueha, R; Mukherjee, S; Ueha, S; de Almeida Nagata, D E; Sakamoto, T; Kondo, K; Yamasoba, T; Lukacs, N W; Kunkel, S L

    2014-09-01

    Upper airway viral infection in patients with airway allergy often exacerbates olfactory dysfunction, but the mechanism for this exacerbation remains unclear. Here, we examined the effects of respiratory syncytial virus (RSV) infection, in the presence or absence of airway allergy, on olfactory receptor neurons (ORNs) and their progenitors in mice. Immunohistological analyses revealed that cockroach allergen (CRA)-induced airway allergy alone did not affect the number of OMP(+) mature ORNs and SOX2(+) ORN progenitors. Intranasal RSV line 19 infection in allergy-free mice resulted in a transient decrease in SOX2(+) ORN progenitors without affecting OMP(+) ORNs. In contrast, the RSV-induced decrease in SOX2(+) ORN progenitors was exacerbated and prolonged in allergic mice, which resulted in eventual loss of OMP(+) ORNs. In the allergic mice, reduction of RSV in the olfactory epithelium was delayed as compared with allergy-free mice. These results suggest that ORN progenitors were impaired by RSV infection and that airway allergy exacerbated damage to ORN progenitors by reducing viral clearance.

  1. Characterization of Botulinum Progenitor Toxins by Mass Spectrometry†

    PubMed Central

    Hines, Harry B.; Lebeda, Frank; Hale, Martha; Brueggemann, Ernst E.

    2005-01-01

    Botulinum toxin analysis has renewed importance. This study included the use of nanochromatography-nanoelectrospray-mass spectrometry/mass spectrometry to characterize the protein composition of botulinum progenitor toxins and to assign botulinum progenitor toxins to their proper serotype and strain by using currently available sequence information. Clostridium botulinum progenitor toxins from strains Hall, Okra, Stockholm, MDPH, Alaska, and Langeland and 89 representing serotypes A through G, respectively, were reduced, alkylated, digested with trypsin, and identified by matching the processed product ion spectra of the tryptic peptides to proteins in accessible databases. All proteins known to be present in progenitor toxins from each serotype were identified. Additional proteins, including flagellins, ORF-X1, and neurotoxin binding protein, not previously reported to be associated with progenitor toxins, were present also in samples from several serotypes. Protein identification was used to assign toxins to a serotype and strain. Serotype assignments were accurate, and strain assignments were best when either sufficient nucleotide or amino acid sequence data were available. Minor difficulties were encountered using neurotoxin-associated protein identification for assigning serotype and strain. This study found that combined nanoscale chromatographic and mass spectrometric techniques can characterize C. botulinum progenitor toxin protein composition and that serotype/strain assignments based upon these proteins can provide accurate serotype and, in most instances, strain assignments using currently available information. Assignment accuracy will continue to improve as more nucleotide/amino acid sequence information becomes available for different botulinum strains. PMID:16085839

  2. Characterization of botulinum progenitor toxins by mass spectrometry.

    PubMed

    Hines, Harry B; Lebeda, Frank; Hale, Martha; Brueggemann, Ernst E

    2005-08-01

    Botulinum toxin analysis has renewed importance. This study included the use of nanochromatography-nanoelectrospray-mass spectrometry/mass spectrometry to characterize the protein composition of botulinum progenitor toxins and to assign botulinum progenitor toxins to their proper serotype and strain by using currently available sequence information. Clostridium botulinum progenitor toxins from strains Hall, Okra, Stockholm, MDPH, Alaska, and Langeland and 89 representing serotypes A through G, respectively, were reduced, alkylated, digested with trypsin, and identified by matching the processed product ion spectra of the tryptic peptides to proteins in accessible databases. All proteins known to be present in progenitor toxins from each serotype were identified. Additional proteins, including flagellins, ORF-X1, and neurotoxin binding protein, not previously reported to be associated with progenitor toxins, were present also in samples from several serotypes. Protein identification was used to assign toxins to a serotype and strain. Serotype assignments were accurate, and strain assignments were best when either sufficient nucleotide or amino acid sequence data were available. Minor difficulties were encountered using neurotoxin-associated protein identification for assigning serotype and strain. This study found that combined nanoscale chromatographic and mass spectrometric techniques can characterize C. botulinum progenitor toxin protein composition and that serotype/strain assignments based upon these proteins can provide accurate serotype and, in most instances, strain assignments using currently available information. Assignment accuracy will continue to improve as more nucleotide/amino acid sequence information becomes available for different botulinum strains.

  3. Invited review: mesenchymal progenitor cells in intramuscular connective tissue development.

    PubMed

    Miao, Z G; Zhang, L P; Fu, X; Yang, Q Y; Zhu, M J; Dodson, M V; Du, M

    2016-01-01

    The abundance and cross-linking of intramuscular connective tissue contributes to the background toughness of meat, and is thus undesirable. Connective tissue is mainly synthesized by intramuscular fibroblasts. Myocytes, adipocytes and fibroblasts are derived from a common pool of progenitor cells during the early embryonic development. It appears that multipotent mesenchymal stem cells first diverge into either myogenic or non-myogenic lineages; non-myogenic mesenchymal progenitors then develop into the stromal-vascular fraction of skeletal muscle wherein adipocytes, fibroblasts and derived mesenchymal progenitors reside. Because non-myogenic mesenchymal progenitors mainly undergo adipogenic or fibrogenic differentiation during muscle development, strengthening progenitor proliferation enhances the potential for both intramuscular adipogenesis and fibrogenesis, leading to the elevation of both marbling and connective tissue content in the resulting meat product. Furthermore, given the bipotent developmental potential of progenitor cells, enhancing their conversion to adipogenesis reduces fibrogenesis, which likely results in the overall improvement of marbling (more intramuscular adipocytes) and tenderness (less connective tissue) of meat. Fibrogenesis is mainly regulated by the transforming growth factor (TGF) β signaling pathway and its regulatory cascade. In addition, extracellular matrix, a part of the intramuscular connective tissue, provides a niche environment for regulating myogenic differentiation of satellite cells and muscle growth. Despite rapid progress, many questions remain in the role of extracellular matrix on muscle development, and factors determining the early differentiation of myogenic, adipogenic and fibrogenic cells, which warrant further studies.

  4. Dual Function of Sox1 in Telencephalic Progenitor Cells

    PubMed Central

    Kan, Lixin; Jalali, Ali; Zhao, Li-Ru; Zhou, Xiaojing; McGuire, Tammy; Kazanis, Ilias; Episkopou, Vasso; Bassuk, Alexander G.; Kessler, John A.

    2012-01-01

    The transcription factor, Sox1 has been implicated in the maintenance of neural progenitor cell status, but accumulating evidence suggests that this is only part of its function. This study examined the role of Sox1 expression in proliferation, lineage commitment, and differentiation by telencephalic neural progenitor cells in vitro and in vivo, and further clarified the pattern of Sox1 expression in postnatal and adult mouse brain. Telencephalic neural progenitor cells isolated from Sox1 null embryos formed neurospheres normally, but were specifically deficient in neuronal differentiation. Conversely, overexpression of Sox1 in the embryonic telencephalon in vivo both expanded the progenitor pool and biased neural progenitor cells towards neuronal lineage commitment. Sox1 mRNA and protein were found to be persistently expressed in the postnatal and adult brain in both differentiated and neurogenic regions. Importantly, in differentiated regions Sox1 co-labeled only with neuronal markers. These observations, coupled with previous studies, suggest that Sox1 expression by early embryonic progenitor cells initially helps to maintain the cells in cell cycle, but that continued expression subsequently promotes neuronal lineage commitment. PMID:17719572

  5. [Characterization of hematopoietic progenitor cells during the human embryonic development].

    PubMed

    Coulombel, L; Huyhn, A; Izac, B

    1995-01-01

    In a search for assays that might facilitate identification of pluripotent stem cells with extended potentialities, we analysed the properties of hematopoietic progenitor cells detected in the extraembryonic yolk sac and in the intraembryonic part of human embryos between approximately 28 and 45 days of development. Cells from the yolk sac, the liver rudiment and the remainder of the embryo were plated in semi solid methylcellulose colony-assays supplemented with combinations of cytokines. Large BFU-E-derived colonies as well as granulocytic colonies were detected in every yolk sac sample. Interestingly, progenitor cells were also detected in the intraembryonic part, outside the liver and a subclass of these progenitors were detected that generated large granulomacrophagic colonies capable of generating secondary colonies when replated. These were preferentially located in the embryo. Colony-assays initiated with CD34+ cells sorted from the different tissues confirmed these data. These results first indicate that embryonic progenitors exhibit unique phenotypic features, and second, analysis of the distribution of progenitors between the different tissues may suggest the existence of other sites of hematopoietic production. More detailed analysis of the potentialities of these progenitors should now be assessed in vitro in cocultures assays and in vivo by reconstituting immunodeficient mice.

  6. On the progenitor of the Type IIb supernova 2016gkg

    NASA Astrophysics Data System (ADS)

    Kilpatrick, Charles D.; Foley, Ryan J.; Abramson, Louis E.; Pan, Yen-Chen; Lu, Cicero-Xinyu; Williams, Peter; Treu, Tommaso; Siebert, Matthew R.; Fassnacht, Christopher D.; Max, Claire E.

    2017-03-01

    We present a detection in pre-explosion Hubble Space Telescope (HST) imaging of a point source consistent with being the progenitor star of the Type IIb supernova (SN IIb) 2016gkg. Post-explosion imaging from the Keck adaptive optics system was used to perform relative astrometry between the Keck and HST imaging. We identify a single point source in the HST images coincident with the SN position to 0.89σ. The HST photometry is consistent with the progenitor star being an A0 Ia star with T = 9500 K and log (L/L⊙) = 5.15. We find that the SN 2016gkg progenitor star appears more consistent with binary than single-star evolutionary models. In addition, early-time light-curve data from SN 2016gkg revealed a rapid rise in luminosity within ∼0.4 d of non-detection limits, consistent with models of the cooling phase after shock break-out. We use these data to determine an explosion date of 2016 September 20.15 and progenitor-star radius of log (R/R⊙) = 2.41, which agrees with photometry from the progenitor star. Our findings are also consistent with detections of other SNe IIb progenitor stars, although more luminous and bluer than most other examples.

  7. Progenitors for Ly-1 B cells are distinct from progenitors for other B cells

    PubMed Central

    1985-01-01

    Data from previous multiparameter fluorescence-activated cell sorter (FACS) analysis and sorting studies define a subset of murine B cells that expresses the Ly-1 surface determinant in conjunction with IgM, IgD, Ia, and other typical B cell markers. These Ly-1 B cells are physically and functionally distinct. They express more IgM and less IgD than most other B cells; they are not normally found in lymph node or bone marrow; they are always present at low frequencies (1-5%) in normal spleens, and, as we show here, they comprise about half of the B cells (10-20% of total cells) recovered from the peritoneal cavity in normal mice. Furthermore, most of the commonly studied IgM autoantibodies in normal and autoimmune mice are produced by these Ly-1 B cells, even though they seldom produce antibodies to exogenous antigens such as trinitrophenyl-Ficoll or trinitrophenyl-keyhole limpet hemocyanin. Cell transfer studies presented here demonstrate that the progenitors of Ly-1 B cells are different from the progenitors of the predominant B cell populations in spleen and lymph node. In these studies, we used FACS analysis and functional assays to characterize donor-derived (allotype-marked) B cells present in lethally irradiated recipients 1-2 mo after transfer. Surprisingly, adult bone marrow cells typically used to reconstitute B cells in irradiated recipients selectively failed to reconstitute the Ly-1 B subset. Liver, spleen, and bone marrow cells from young mice, in contrast, reconstituted all B cells (including Ly-1 B), and peritoneal "washout" cells (PerC) from adult mice uniquely reconstituted Ly-1 B. Bone marrow did not block Ly- 1 B development, since PerC and newborn liver still gave rise to Ly-1 B when jointly transferred with marrow. These findings tentatively assign Ly-1 B to a distinct developmental lineage originating from progenitors that inhabit the same locations as other B cell progenitors in young animals, but move to unique location(s) in adults. PMID

  8. The Binary Progenitor of Tycho Brahe's Supernova

    NASA Astrophysics Data System (ADS)

    Ruiz-Lapuente, P.

    2006-08-01

    The brightness of type Ia supernovae, and their homogeneity as a class, makes them powerful tools in cosmology, yet little is known about the progenitor systems of these explosions. They are thought to arise when a white dwarf accretes matter from a companion star, is compressed and undergoes a thermonuclear explosion. Unless the companion star is another white dwarf (in which case it should be destroyed by the mass-transfer process itself), it should survive and show distinguishing properties. Tycho's supernova (SN 1572) provides an opportunity to address observationally the identification of the surviving companion. Here we report a survey of the central region of its remnant, around the position of the explosion, which excludes red giants as the mass donor of the exploding white dwarf. We found a type G0-G2 star, similar to our Sun in surface temperature and luminosity (but lower surface gravity), moving at more than three times the mean velocity of the stars at that distance, which appears to be the surviving companion of the supernova.

  9. Harmine stimulates proliferation of human neural progenitors

    PubMed Central

    Dakic, Vanja; Maciel, Renata de Moraes; Drummond, Hannah; Nascimento, Juliana M.; Trindade, Pablo

    2016-01-01

    Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive) derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A), which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY), and an irreversible selective inhibitor of monoamine oxidase (MAO) but not DYRK1A (pargyline). INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo. PMID:27957390

  10. NFAT restricts osteochondroma formation from entheseal progenitors

    PubMed Central

    Tsang, Kelly; He, Lizhi; Garcia, Roberto A.; Ermann, Joerg; Mizoguchi, Fumitaka; Zhang, Minjie; Aliprantis, Antonios O.

    2016-01-01

    Osteochondromas are common benign osteocartilaginous tumors in children and adolescents characterized by cartilage-capped bony projections on the surface of bones. These tumors often cause pain, deformity, fracture, and musculoskeletal dysfunction, and they occasionally undergo malignant transformation. The pathogenesis of osteochondromas remains poorly understood. Here, we demonstrate that nuclear factor of activated T cells c1 and c2 (NFATc1 and NFATc2) suppress osteochondromagenesis through individual and combinatorial mechanisms. In mice, conditional deletion of NFATc1 in mesenchymal limb progenitors, Scleraxis-expressing (Scx-expressing) tendoligamentous cells, or postnatally in Aggrecan-expressing cells resulted in osteochondroma formation at entheses, the insertion sites of ligaments and tendons onto bone. Combinatorial deletion of NFATc1 and NFATc2 gave rise to larger and more numerous osteochondromas in inverse proportion to gene dosage. A population of entheseal NFATc1- and Aggrecan-expressing cells was identified as the osteochondroma precursor, previously believed to be growth plate derived or perichondrium derived. Mechanistically, we show that NFATc1 restricts the proliferation and chondrogenesis of osteochondroma precursors. In contrast, NFATc2 preferentially inhibits chondrocyte hypertrophy and osteogenesis. Together, our findings identify and characterize a mechanism of osteochondroma formation and suggest that regulating NFAT activity is a new therapeutic approach for skeletal diseases characterized by defective or exaggerated osteochondral growth. PMID:27158674

  11. Developmental origin of postnatal cardiomyogenic progenitor cells

    PubMed Central

    Liu, Yuan-Hung; Lai, Ling-Ping; Huang, Shih-Yun; Lin, Yi-Shuan; Wu, Shinn-Chih; Chou, Chih-Jen; Lin, Jiunn-Lee

    2016-01-01

    Aim: To trace the cell origin of the cells involved in postnatal cardiomyogenesis. Materials & methods: Nkx2.5 enhancer-eGFP (Nkx2.5 enh-eGFP) mice were used to test the cardiomyogenic potential of Nkx2.5 enhancer-expressing cells. By analyzing Cre excision of activated Nkx2.5-eGFP+ cells from different lineage-Cre/Nkx2.5 enh-eGFP/ROSA26 reporter mice, we traced the developmental origin of Nkx2.5 enhancer-expressing cells. Results: Nkx2.5 enhancer-expressing cells could differentiate into striated cardiomyocytes both in vitro and in vivo. Nkx2.5-eGFP+ cells increased remarkably after experimental myocardial infarction (MI). The post-MI Nkx2.5-eGFP+ cells originated from the embryonic epicardial cells, not from the pre-existing cardiomyocytes, endothelial cells, cardiac neural crest cells or perinatal/postnatal epicardial cells. Conclusion: Postnatal Nkx2.5 enhancer-expressing cells are cardiomyogenic progenitor cells and originate from embryonic epicardium-derived cells. PMID:28031967

  12. Oral keratinocyte stem/progenitor cells: specific markers, molecular signaling pathways and potential uses.

    PubMed

    Calenic, Bogdan; Greabu, Maria; Caruntu, Constantin; Tanase, Cristiana; Battino, Maurizio

    2015-10-01

    Oral keratinocyte stem cells reside in the basal layers of the oral epithelium, representing a minor population of cells with a great potential to self-renew and proliferate over the course of their lifetime. As a result of the potential uses of oral keratinocyte stem cells in regenerative medicine and the key roles they play in tissue homeostasis, inflammatory conditions, wound healing and tumor initiation and progression, intense scientific efforts are currently being undertaken to identify, separate and reprogram these cells. Although currently there is no specific marker that can characterize and isolate oral keratinocyte stem cells, several suggestions have been made. Thus, different stem/progenitor-cell subpopulations have been categorized based on combinations of positive and/or negative membrane-surface markers, which include integrins, clusters of differentiation and cytokeratins. Important advances have also been made in understanding the molecular pathways that govern processes such as self-renewal, differentiation, proliferation, wound healing and programmed cell death. A thorough understanding of stem-cell biology and the molecular players that govern cellular fate is paramount in the quest for using stem-cell-derived therapies in the treatment of various oral pathologies. The current review focuses on recent advances in understanding the molecular signaling pathways coordinating the behavior of these cells and in identifying suitable markers used for their isolation and characterization. Special emphasis will also be placed on the roles played by oral keratinocyte stem and progenitor cells in normal and diseased oral tissues and on their potential uses in the fields of general medicine and dentistry.

  13. Identification of Lymphomyeloid Primitive Progenitor Cells in Fresh Human Cord Blood and in the Marrow of Nonobese Diabetic–Severe Combined Immunodeficient (NOD-SCID) Mice Transplanted with Human CD34+ Cord Blood Cells

    PubMed Central

    Robin, Catherine; Pflumio, Françoise; Vainchenker, William; Coulombel, Laure

    1999-01-01

    Transplantation of genetically marked donor cells in mice have unambiguously identified individual clones with full differentiative potential in all lymphoid and myeloid pathways. Such evidence has been lacking in humans because of limitations inherent to clonal stem cell assays. In this work, we used single cell cultures to show that human cord blood (CB) contains totipotent CD34+ cells capable of T, B, natural killer, and granulocytic cell differentiation. Single CD34+ CD19−Thy1+ (or CD38−) cells from fresh CB were first induced to proliferate and their progeny separately studied in mouse fetal thymic organotypic cultures (FTOCs) and cocultures on murine stromal feeder layers. 10% of the clones individually analyzed produced CD19+, CD56+, and CD15+ cells in stromal cocultures and CD4+CD8+ T cells in FTOCs, identifying totipotent progenitor cells. Furthermore, we showed that totipotent clones with similar lymphomyeloid potential are detected in the bone marrow of nonobese diabetic severe combined immunodeficient (NOD-SCID) mice transplanted 4 mo earlier with human CB CD34+ cells. These results provide the first direct demonstration that human CB contains totipotent lymphomyeloid progenitors and transplantable CD34+ cells with the ability to reconstitute, in the marrow of recipient mice, the hierarchy of hematopoietic compartments, including a compartment of functional totipotent cells. These experimental approaches can now be exploited to analyze mechanisms controlling the decisions of such primitive human progenitors and to design conditions for their ampification that can be helpful for therapeutic purposes. PMID:10330439

  14. Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer.

    PubMed

    Shaykhiev, Renat; Wang, Rui; Zwick, Rachel K; Hackett, Neil R; Leung, Roland; Moore, Malcolm A S; Sima, Camelia S; Chao, Ion Wa; Downey, Robert J; Strulovici-Barel, Yael; Salit, Jacqueline; Crystal, Ronald G

    2013-09-01

    Activation of the human embryonic stem cell (hESC) signature genes has been observed in various epithelial cancers. In this study, we found that the hESC signature is selectively induced in the airway basal stem/progenitor cell population of healthy smokers (BC-S), with a pattern similar to that activated in all major types of human lung cancer. We further identified a subset of 6 BC-S hESC genes, whose coherent overexpression in lung adenocarcinoma (AdCa) was associated with reduced lung function, poorer differentiation grade, more advanced tumor stage, remarkably shorter survival, and higher frequency of TP53 mutations. BC-S shared with hESC and a considerable subset of lung carcinomas a common TP53 inactivation molecular pattern which strongly correlated with the BC-S hESC gene expression. These data provide transcriptome-based evidence that smoking-induced reprogramming of airway BC toward the hESC-like phenotype might represent a common early molecular event in the development of aggressive lung carcinomas in humans.

  15. The basal ganglia-circa 1982. A review and commentary.

    PubMed

    Mehler, W R

    1981-01-01

    Our review has shown that recent studies with the new anterograde and retrograde axon transport methods have confirmed and extended our knowledge of the projection of the basal ganglia and clarified their sites of origin. They have thrown new light on certain topographic connectional relationships and revealed several new reciprocal connections between constituent nuclei of the basal ganglia. Similarly, attention has been drawn to the fact that there have also been many new histochemical techniques introduced in recent years that are now providing regional biochemical overlays for connectional maps of the central nervous system, especially regions in, or interconnecting with, the basal ganglia. However, although these new morphological biochemical maps are very complex and technically highly advanced, our understanding of the function controlled by the basal ganglia still remains primitive. The reader who is interested in some new ideas of the functional aspects of the basal ganglia is directed to Nauta's [88] proposed conceptual reorganization of the basal ganglia telencephalon and to Marsden's [72] more clinically orientated appraisal of the unsolved mysteries of the basal ganglia participation in the control of movement.

  16. Basal area growth, carbon isotope discrimination, and intrinsic ...

    EPA Pesticide Factsheets

    Many hectares of intensively managed Douglas-fir (Pseudotsuga menziesii Mirb. Franco) stands in western North America are fertilized with nitrogen to increase growth rates. Understanding the mechanisms of response facilitates prioritization of stands for treatment. The objective of this study was to test the hypothesis that the short-term basal area growth response to a single application of 224 kg N ha-1 as urea was associated with reduced stable carbon isotope discrimination (∆13C) and increased intrinsic water use efficiency (iWUE) in a 20-yr-old plantation of Douglas-fir in the Oregon Coast Range, USA. Increment cores were measured to estimate earlywood, latewood, and total basal area increment over a time series from 1997 to 2015. Stable carbon isotope discrimination and iWUE were estimated using earlywood and latewood stable carbon isotope concentrations in tree-ring holocellulose starting seven years before fertilization in early 2009 and ending seven years after treatment. A highly significant interaction effect between fertilization treatment and year was found for total basal area growth and earlywood basal area increment. Fertilized trees showed significant total basal area growth and earlywood basal area increment in the first (2009) and second (2010) growing seasons after fertilization in 2009. A marginally significant fertilization effect was found for latewood basal area increment only in the first growing season after treatment. A significant i

  17. Interactions between the Midbrain Superior Colliculus and the Basal Ganglia

    PubMed Central

    Redgrave, Peter; Coizet, Veronique; Comoli, Eliane; McHaffie, John G.; Leriche, Mariana; Vautrelle, Nicolas; Hayes, Lauren M.; Overton, Paul

    2010-01-01

    An important component of the architecture of cortico-basal ganglia connections is the parallel, re-entrant looped projections that originate and return to specific regions of the cerebral cortex. However, such loops are unlikely to have been the first evolutionary example of a closed-loop architecture involving the basal ganglia. A phylogenetically older, series of subcortical loops can be shown to link the basal ganglia with many brainstem sensorimotor structures. While the characteristics of individual components of potential subcortical re-entrant loops have been documented, the full extent to which they represent functionally segregated parallel projecting channels remains to be determined. However, for one midbrain structure, the superior colliculus (SC), anatomical evidence for closed-loop connectivity with the basal ganglia is robust, and can serve as an example against which the loop hypothesis can be evaluated for other subcortical structures. Examination of ascending projections from the SC to the thalamus suggests there may be multiple functionally segregated systems. The SC also provides afferent signals to the other principal input nuclei of the basal ganglia, the dopaminergic neurones in substantia nigra and to the subthalamic nucleus. Recent electrophysiological investigations show that the afferent signals originating in the SC carry important information concerning the onset of biologically significant events to each of the basal ganglia input nuclei. Such signals are widely regarded as crucial for the proposed functions of selection and reinforcement learning with which the basal ganglia have so often been associated. PMID:20941324

  18. Expression of the human. beta. -globin gene following retroviral-mediated transfer into multipotential hematopoietic progenitors of mice

    SciTech Connect

    Karlsson, S.; Bodine, D.M.; Perry, L.; Papayannopoulou, T.; Nienhuis, A.W. )

    1988-08-01

    Efficient transfer of the {beta}-globin gene into primitive hematopoietic progenitors was achieved with consistent and significant expression in the progeny of those cells. Retroviral vectors containing the intact genomic human {beta}-globin gene and the neomycin (G418)-resistance (neo{sup R}) gene were constructed. These gave titers of 10{sup 6} or more neo{sup R} colony-forming units/ml when packaged in {psi}2 cells. Mouse bone marrow cells were infected by coculture with producer cells and injected into lethally irradiated animals. Several parameters were varied to enhance infection frequency of colony-forming units, spleen (CFU-S); overall 41% of 116 foci studied contained an intact proviral genome. The human {beta}-globin gene was expressed in 31 of 35 CFU-S-derived spleen colonies that contained the intact vector genome at levels ranging from 1% to 5% of that of the mouse {beta}-globin genes. Infected bone marrow cells were also injected into genetically anemic W/W{sup v} recipients without prior irradiation. Human {beta}-globin chains were detected in circulating erythrocytes by immunofluorescent staining with a specific monoclonal antibody. All animals injected with donor cells that had been cultured in G418 (1 mg/ml) for 48 hr after retroviral infection had circulating erythrocytes containing human {beta}-globin chains between 3 and 8 weeks after transplantation.

  19. Continuous single cell imaging reveals sequential steps of plasmacytoid dendritic cell development from common dendritic cell progenitors

    PubMed Central

    Dursun, Ezgi; Endele, Max; Musumeci, Andrea; Failmezger, Henrik; Wang, Shu-Hung; Tresch, Achim; Schroeder, Timm; Krug, Anne B.

    2016-01-01

    Functionally distinct plasmacytoid and conventional dendritic cells (pDC and cDC) shape innate and adaptive immunity. They are derived from common dendritic cell progenitors (CDPs) in the murine bone marrow, which give rise to CD11c+ MHCII− precursors with early commitment to DC subpopulations. In this study, we dissect pDC development from CDP into an ordered sequence of differentiation events by monitoring the expression of CD11c, MHC class II, Siglec H and CCR9 in CDP cultures by continuous single cell imaging and tracking. Analysis of CDP genealogies revealed a stepwise differentiation of CDPs into pDCs in a part of the CDP colonies. This developmental pathway involved an early CD11c+ SiglecH− pre-DC stage and a Siglec H+ CCR9low precursor stage, which was followed rapidly by upregulation of CCR9 indicating final pDC differentiation. In the majority of the remaining CDP pedigrees however the Siglec H+ CCR9low precursor state was maintained for several generations. Thus, although a fraction of CDPs transits through precursor stages rapidly to give rise to a first wave of pDCs, the majority of CDP progeny differentiate more slowly and give rise to longer lived precursor cells which are poised to differentiate on demand. PMID:27892478

  20. The BAF complex interacts with Pax6 in adult neural progenitors to establish a neurogenic cross-regulatory transcriptional network.

    PubMed

    Ninkovic, Jovica; Steiner-Mezzadri, Andrea; Jawerka, Melanie; Akinci, Umut; Masserdotti, Giacomo; Petricca, Stefania; Fischer, Judith; von Holst, Alexander; Beckers, Johanes; Lie, Chichung D; Petrik, David; Miller, Erik; Tang, Jiong; Wu, Jiang; Lefebvre, Veronique; Demmers, Jeroen; Eisch, Amelia; Metzger, Daniel; Crabtree, Gerald; Irmler, Martin; Poot, Raymond; Götz, Magdalena

    2013-10-03

    Numerous transcriptional regulators of neurogenesis have been identified in the developing and adult brain, but how neurogenic fate is programmed at the epigenetic level remains poorly defined. Here, we report that the transcription factor Pax6 directly interacts with the Brg1-containing BAF complex in adult neural progenitors. Deletion of either Brg1 or Pax6 in the subependymal zone (SEZ) causes the progeny of adult neural stem cells to convert to the ependymal lineage within the SEZ while migrating neuroblasts convert to different glial lineages en route to or in the olfactory bulb (OB). Genome-wide analyses reveal that the majority of genes downregulated in the Brg1 null SEZ and OB contain Pax6 binding sites and are also downregulated in Pax6 null SEZ and OB. Downstream of the Pax6-BAF complex, we find that Sox11, Nfib, and Pou3f4 form a transcriptional cross-regulatory network that drives neurogenesis and can convert postnatal glia into neurons. Taken together, elements of our work identify a tripartite effector network activated by Pax6-BAF that programs neuronal fate.

  1. The expanding universe of disorders of the basal ganglia.

    PubMed

    Obeso, Jose A; Rodriguez-Oroz, Maria C; Stamelou, Maria; Bhatia, Kailash P; Burn, David J

    2014-08-09

    The basal ganglia were originally thought to be associated purely with motor control. However, dysfunction and pathology of different regions and circuits are now known to give rise to many clinical manifestations beyond the association of basal ganglia dysfunction with movement disorders. Moreover, disorders that were thought to be caused by dysfunction of the basal ganglia only, such as Parkinson's disease and Huntington's disease, have diverse abnormalities distributed not only in the brain but also in the peripheral and autonomic nervous systems; this knowledge poses new questions and challenges. We discuss advances and the unanswered questions, and ways in which progress might be made.

  2. The basal ganglia-circa 1982 - A review and commentary

    NASA Technical Reports Server (NTRS)

    Mehler, W. R.

    1981-01-01

    A review is presented of recent studies which utilize new anterograde and retrograde axon transport methods in order to improve knowledge of the projection of the basal ganglia and to clarify their sites of origin. These studies have thrown new light on certain topographic connectional relationships and have revealed several new reciprocal connections between constituent nuclei of the basal ganglia. Also examined are the many new histochemical techniques that are now providing regional biochemical overlays for connectional maps of the central nervous system, especially regions in or interconnecting with the basal ganglia.

  3. The terminal basal mitosis of chicken retinal Lim1 horizontal cells is not sensitive to cisplatin-induced cell cycle arrest.

    PubMed

    Shirazi Fard, Shahrzad; Thyselius, Malin; All-Ericsson, Charlotta; Hallböök, Finn

    2014-01-01

    For proper development, cells need to coordinate proliferation and cell cycle-exit. This is mediated by a cascade of proteins making sure that each phase of the cell cycle is controlled before the initiation of the next. Retinal progenitor cells divide during the process of interkinetic nuclear migration, where they undergo S-phase on the basal side, followed by mitoses on the apical side of the neuroepithelium. The final cell cycle of chicken retinal horizontal cells (HCs) is an exception to this general cell cycle behavior. Lim1 expressing (+) horizontal progenitor cells (HPCs) have a heterogenic final cell cycle, with some cells undergoing a terminal mitosis on the basal side of the retina. The results in this study show that this terminal basal mitosis of Lim1+ HPCs is not dependent on Chk1/2 for its regulation compared to retinal cells undergoing interkinetic nuclear migration. Neither activating nor blocking Chk1 had an effect on the basal mitosis of Lim1+ HPCs. Furthermore, the Lim1+ HPCs were not sensitive to cisplatin-induced DNA damage and were able to continue into mitosis in the presence of γ-H2AX without activation of caspase-3. However, Nutlin3a-induced expression of p21 did reduce the mitoses, suggesting the presence of a functional p53/p21 response in HPCs. In contrast, the apical mitoses were blocked upon activation of either Chk1/2 or p21, indicating the importance of these proteins during the process of interkinetic nuclear migration. Inhibiting Cdk1 blocked M-phase transition both for apical and basal mitoses. This confirmed that the cyclin B1-Cdk1 complex was active and functional during the basal mitosis of Lim1+ HPCs. The regulation of the final cell cycle of Lim1+ HPCs is of particular interest since it has been shown that the HCs are able to sustain persistent DNA damage, remain in the cell cycle for an extended period of time and, consequently, survive for months.

  4. Interleukin-1 regulates proliferation and differentiation of oligodendrocyte progenitor cells.

    PubMed

    Vela, José M; Molina-Holgado, Eduardo; Arévalo-Martín, Angel; Almazán, Guillermina; Guaza, Carmen

    2002-07-01

    Interleukin-1 (IL-1) is a pleiotropic cytokine expressed during normal CNS development and in inflammatory demyelinating diseases, but remarkably little is known about its effect on oligodendroglial cells. In this study we explored the role of IL-1beta in oligodendrocyte progenitors and differentiated oligodendrocytes. The effects of IL-1beta were compared to those of IL-1 receptor antagonist, the specific inhibitor of IL-1 activity, since progenitors and differentiated oligodendrocytes produce IL-1beta and express IL-1 receptors. Unlike other proinflammatory cytokines (TNFalpha and IFNgamma), IL-1beta was not toxic for oligodendrocyte lineage cells. However, this cytokine inhibited proliferation of oligodendrocyte progenitors in the presence of growth factors (PDGF plus bFGF). This was evidenced by a significant decrease in both cells incorporating bromodeoxyuridine (45%) and total cell numbers (57%) after 6 days of treatment. Interestingly, IL-1beta blocked proliferation at the late progenitor/prooligodendrocyte (O4+) stage but did not affect proliferation of early progenitors (A2B5+). Inhibition of proliferation paralleled with promotion of differentiation, as revealed by the increased percentage of R-mab+ cells (6.7-fold). Moreover, when oligodendrocyte progenitors were allowed to differentiate in the absence of growth factors, treatment with IL-1beta promoted maturation to the MBP+ stage (4.2-fold) and survival of differentiating oligodendrocytes (2.1-fold). Regarding intracellular signaling, IL-1beta activated the p38 mitogen-activated protein kinase (MAPK) but not the p42/p44 MAPK and, when combined with growth factors, intensified p38 activation but inhibited the growth-factor-induced p42/p44 activation. IL-1beta also induced a time-dependent inhibition of PFGF-Ralpha gene expression. These results support a role for IL-1beta in promoting mitotic arrest and differentiation of oligodendrocyte progenitors as well as maturation and survival of differentiating

  5. Characterization of hematopoietic progenitors from human yolk sacs and embryos.

    PubMed

    Huyhn, A; Dommergues, M; Izac, B; Croisille, L; Katz, A; Vainchenker, W; Coulombel, L

    1995-12-15

    Hematopoiesis first arises in the extraembryonic yolk sac, and it is generally believed that yolk sac-derived stem cells migrate and seed the fetal liver at approximately week 6 of development in humans. Recently, the identification at day 8.5 to 9 of multipotential stem cells in intraembryonic sites different from the liver suggests that the establishment of hematopoiesis might be more complex than initially believed. In an attempt to understand initial steps of hematopoiesis during human ontogeny, we characterized clonogenic myeloid progenitor cells in human yolk sacs and corresponding embryos at 25 to 50 days of development. Most erythroid colonies derived from the yolk sacs differed from adult marrow-derived progenitors in that they also contained cells of the granulomacrophagic lineage, suggesting that they were pluripotent and exhibited a different response to cytokines. Furthermore, a subclass of nonerythroid progenitors generated very large granulomacrophagic colonies, some of which generated secondary erythroid colonies on replating. Analysis of the distribution of progenitors revealed that in contrast to erythroid progenitors, whose numbers were equally distributed between the yolk sac and the embryo, 80% of the nonerythroid progenitors were found in the embryo at stages II and III. Interestingly, a high proportion of nonerythroid progenitors (including high proliferative potential cells) was present in colony assays initiated with cells remaining after the liver has been removed. These findings were validated in colony assays established with CD34+ cells purified from extraembryonic yolk sacs and intraembryonic tissues. Increased knowledge about the biology of hematopoietic stem cells early in life may help to further understanding of the mechanisms associated with the restriction in proliferative and differentiative potential observed in the adult hematopoietic stem cell compartment.

  6. Comparison of the Transcriptomes of Long-Term Label Retaining-Cells and Control Cells Microdissected from Mammary Epithelium: An Initial Study to Characterize Potential Stem/Progenitor Cells

    PubMed Central

    Choudhary, Ratan K.; Li, Robert W.; Evock-Clover, Christina M.; Capuco, Anthony V.

    2012-01-01

    Background: Previous molecular characterizations of mammary stem cells (MaSC) have utilized fluorescence-activated cell sorting or in vitro cultivation of cells from enzymatically dissociated tissue to enrich for MaSC. These approaches result in the loss of all histological information pertaining to the in vivo locale of MaSC and progenitor cells. Instead, we used laser microdissection to excise putative progenitor cells and control cells from their in situ locations in cryosections and characterized the molecular properties of these cells. MaSC/progenitor cells were identified based on their ability to retain bromodeoxyuridine for an extended period. Results: We isolated four categories of cells from mammary epithelium of female calves: bromodeoxyuridine label retaining epithelial cells (LREC) from basal (LRECb) and embedded layers (LRECe), and epithelial control cells from basal and embedded layers. Enriched expression of genes in LRECb was associated with stem cell attributes and identified WNT, TGF-β, and MAPK pathways of self renewal and proliferation. Genes expressed in LRECe revealed retention of some stem-like properties along with up-regulation of differentiation factors. Conclusion: Our data suggest that LREC in the basal epithelial layer are enriched for MaSC, as these cells showed increased expression of genes that reflect stem cell attributes; whereas LREC in suprabasal epithelial layers are enriched for more committed progenitor cells, expressing some genes that are associated with stem cell attributes along with those indicative of cell differentiation. Our results support the use of DNA label retention to identify MaSC and also provide a molecular profile and novel candidate markers for these cells. Insights into the biology of stem cells will be gained by confirmation and characterization of candidate MaSC markers identified in this study. PMID:23423481

  7. How Are Squamous and Basal Cell Skin Cancers Diagnosed?

    MedlinePlus

    ... and Staging Tests for Basal and Squamous Cell Skin Cancers Most skin cancers are brought to a ... non-cancerous) without the need for a biopsy. Skin biopsy If the doctor thinks that a suspicious ...

  8. Short latency cerebellar modulation of the basal ganglia

    PubMed Central

    Chen, Christopher H.; Fremont, Rachel; Arteaga-Bracho, Eduardo E.; Khodakhah, Kamran

    2014-01-01

    The graceful, purposeful motion of our body is an engineering feat which remains unparalleled in robotic devices using advanced artificial intelligence. Much of the information required for complex movements is generated by the cerebellum and the basal ganglia in conjunction with the cortex. Cerebellum and basal ganglia have been thought to communicate with each other only through slow multi-synaptic cortical loops, begging the question as to how they coordinate their outputs in real time. Here we show in mice that the cerebellum rapidly modulates the activity of the striatum via a disynaptic pathway. Under physiological conditions this short latency pathway is capable of facilitating optimal motor control by allowing the basal ganglia to incorporate time-sensitive cerebellar information and by guiding the sign of cortico-striatal plasticity. Conversely, under pathological condition this pathway relays aberrant cerebellar activity to the basal ganglia to cause