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Sample records for lineage progression potential

  1. 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.

  2. 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

  3. Calcium receptor expression and function in oligodendrocyte commitment and lineage progression: potential impact on reduced myelin basic protein in CaR-null mice.

    PubMed

    Chattopadhyay, Naibedya; Espinosa-Jeffrey, Araceli; Tfelt-Hansen, Jacob; Yano, Shozo; Bandyopadhyay, Sanghamitra; Brown, Edward M; de Vellis, Jean

    2008-08-01

    Oligodendrocytes develop from oligodendrocyte progenitor cells (OPCs), which in turn arise from a subset of neuroepithelial precursor cells during midneurogenesis. Development of the oligodendrocyte lineage involves a plethora of cell-intrinsic and -extrinsic signals. A cell surface calcium-sensing receptor (CaR) has been shown to be functionally expressed in immature oligodendrocytes. Here, we investigated the expression and function of the CaR during oligodendrocyte development. We show that the order of CaR mRNA expression as assessed by quantitative polymerase chain reaction is mature oligodendrocyte > neuron > astrocyte. We next determined the rank order of CaR expression on inducing specification of neural stem cells to the neuronal, oligodendroglial, or astrocytic lineages and found that the relative levels of CaR mRNA expression are OPC > neuron > astrocytes. CaR mRNA expression in cells at various stages of development along the oligodendrocyte lineage revealed that its expression is robustly up-regulated during the OPC stage and remains high until the premyelinating stage, decreasing thereafter by severalfold in the mature oligodendrocyte. In OPCs, high Ca(2+) acting via the CaR promotes cellular proliferation. We further observed that high Ca(2+) stimulates the mRNA levels of myelin basic protein in preoligodendrocytes, which is also CaR mediated. Finally, myelin basic protein levels were significantly reduced in the cerebellum of CaR-null mice during development. Our results show that CaR expression is up-regulated when neural stem cells are specified to the oligodendrocyte lineage and that activation of the receptor results in OPC expansion and differentiation. We conclude that the CaR may be a novel regulator of oligodendroglial development and function.

  4. Direct and progressive differentiation of human embryonic stem cells into the chondrogenic lineage.

    PubMed

    Gong, Guochun; Ferrari, Deborah; Dealy, Caroline N; Kosher, Robert A

    2010-09-01

    Treatment of common and debilitating degenerative cartilage diseases particularly osteoarthritis is a clinical challenge because of the limited capacity of the tissue for self-repair. Because of their unlimited capacity for self-renewal and ability to differentiate into multiple lineages, human embryonic stem cells (hESCs) are a potentially powerful tool for repair of cartilage defects. The primary objective of the present study was to develop culture systems and conditions that enable hESCs to directly and uniformly differentiate into the chondrogenic lineage without prior embryoid body (EB) formation, since the inherent cellular heterogeneity of EBs hinders obtaining homogeneous populations of chondrogenic cells that can be used for cartilage repair. To this end, we have subjected undifferentiated pluripotent hESCs to the high density micromass culture conditions we have extensively used to direct the differentiation of embryonic limb bud mesenchymal cells into chondrocytes. We report that micromass cultures of pluripotent hESCs undergo direct, rapid, progressive, and substantially uniform chondrogenic differentiation in the presence of BMP2 or a combination of BMP2 and TGF-beta1, signaling molecules that act in concert to regulate chondrogenesis in the developing limb. The gene expression profiles of hESC-derived cultures harvested at various times during the progression of their differentiation has enabled us to identify cultures comprising cells in different phases of the chondrogenic lineage ranging from cultures just entering the lineage to well differentiated chondrocytes. Thus, we are poised to compare the abilities of hESC-derived progenitors in different phases of the chondrogenic lineage for cartilage repair.

  5. Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression

    PubMed Central

    Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Dombrowski, Stephen M.; Miller, Tyler E.; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; von Elverfeldt, Dominik; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.; Bredel, Markus

    2014-01-01

    Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet the role of this process in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily conserved, alternative exons that represent only a minority of the total alternative exons identified. Many of these conserved exons have functional features that influence signaling pathways to profound biological effect. Here, we determined that lineage-specific splicing of a brain-enriched cassette exon in the membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes endosomal targeting of the EGFR oncoprotein, consequently enhancing EGFR signaling during brain tumor progression. ANXA7 exon splicing was mediated by the ribonucleoprotein PTBP1, which is normally repressed during neuronal development. PTBP1 was highly expressed in glioblastomas due to loss of a brain-enriched microRNA (miR-124) and to PTBP1 amplification. The alternative ANXA7 splicing trait was present in precursor cells, suggesting that glioblastoma cells inherit the trait from a potential tumor-initiating ancestor and that these cells exploit this trait through accumulation of mutations that enhance EGFR signaling. Our data illustrate that lineage-specific splicing of a tissue-regulated alternative exon in a constituent of an oncogenic pathway eliminates tumor suppressor functions and promotes glioblastoma progression. This paradigm may offer a general model as to how tissue-specific regulatory mechanisms can reprogram normal developmental processes into oncogenic ones. PMID:24865424

  6. Progress and Potential

    PubMed Central

    Haspel, Richard L.; Olsen, Randall J.; Berry, Anna; Hill, Charles E.; Pfeifer, John D.; Schrijver, Iris; Kaul, Karen L.

    2014-01-01

    Context Genomic medicine is revolutionizing patient care. Physicians in areas as diverse as oncology, obstetrics, and infectious disease have begun using next-generation sequencing assays as standard diagnostic tools. Objective To review the role of pathologists in genomic testing as well as current educational programs and future training needs in genomic pathology. Data Sources Published literature as well as personal experience based on committee membership and genomic pathology curricular design. Conclusion Pathologists, as the directors of the clinical laboratories, must be prepared to integrate genomic testing into their practice. The pathology community has made significant progress in genomics-related education. A continued coordinated and proactive effort will ensure a future vital role for pathologists in the evolving health care system and also the best possible patient care. PMID:24678680

  7. Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential

    PubMed Central

    Bolton, Helen; Graham, Sarah J. L.; Van der Aa, Niels; Kumar, Parveen; Theunis, Koen; Fernandez Gallardo, Elia; Voet, Thierry; Zernicka-Goetz, Magdalena

    2016-01-01

    Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic. PMID:27021558

  8. Transmission and Progression to Disease of Mycobacterium tuberculosis Phylogenetic Lineages in The Netherlands

    PubMed Central

    Verhagen, Lilly M.; Borgdorff, Martien W.; van Soolingen, Dick

    2015-01-01

    The aim of this study was to determine if mycobacterial lineages affect infection risk, clustering, and disease progression among Mycobacterium tuberculosis cases in The Netherlands. Multivariate negative binomial regression models adjusted for patient-related factors and stratified by patient ethnicity were used to determine the association between phylogenetic lineages and infectivity (mean number of positive contacts around each patient) and clustering (as defined by number of secondary cases within 2 years after diagnosis of an index case sharing the same fingerprint) indices. An estimate of progression to disease by each risk factor was calculated as a bootstrapped risk ratio of the clustering index by the infectivity index. Compared to the Euro-American reference, Mycobacterium africanum showed significantly lower infectivity and clustering indices in the foreign-born population, while Mycobacterium bovis showed significantly lower infectivity and clustering indices in the native population. Significantly lower infectivity was also observed for the East African Indian lineage in the foreign-born population. Smear positivity was a significant risk factor for increased infectivity and increased clustering. Estimates of progression to disease were significantly associated with age, sputum-smear status, and behavioral risk factors, such as alcohol and intravenous drug abuse, but not with phylogenetic lineages. In conclusion, we found evidence of a bacteriological factor influencing indicators of a strain's transmissibility, namely, a decreased ability to infect and a lower clustering index in ancient phylogenetic lineages compared to their modern counterparts. Confirmation of these findings via follow-up studies using tuberculin skin test conversion data should have important implications on M. tuberculosis control efforts. PMID:26224845

  9. Transmission and Progression to Disease of Mycobacterium tuberculosis Phylogenetic Lineages in The Netherlands.

    PubMed

    Nebenzahl-Guimaraes, Hanna; Verhagen, Lilly M; Borgdorff, Martien W; van Soolingen, Dick

    2015-10-01

    The aim of this study was to determine if mycobacterial lineages affect infection risk, clustering, and disease progression among Mycobacterium tuberculosis cases in The Netherlands. Multivariate negative binomial regression models adjusted for patient-related factors and stratified by patient ethnicity were used to determine the association between phylogenetic lineages and infectivity (mean number of positive contacts around each patient) and clustering (as defined by number of secondary cases within 2 years after diagnosis of an index case sharing the same fingerprint) indices. An estimate of progression to disease by each risk factor was calculated as a bootstrapped risk ratio of the clustering index by the infectivity index. Compared to the Euro-American reference, Mycobacterium africanum showed significantly lower infectivity and clustering indices in the foreign-born population, while Mycobacterium bovis showed significantly lower infectivity and clustering indices in the native population. Significantly lower infectivity was also observed for the East African Indian lineage in the foreign-born population. Smear positivity was a significant risk factor for increased infectivity and increased clustering. Estimates of progression to disease were significantly associated with age, sputum-smear status, and behavioral risk factors, such as alcohol and intravenous drug abuse, but not with phylogenetic lineages. In conclusion, we found evidence of a bacteriological factor influencing indicators of a strain's transmissibility, namely, a decreased ability to infect and a lower clustering index in ancient phylogenetic lineages compared to their modern counterparts. Confirmation of these findings via follow-up studies using tuberculin skin test conversion data should have important implications on M. tuberculosis control efforts.

  10. Rostral-caudal distribution of Emx1-lineage stem/transit amplifying cells and lineage progression in embryonic cortex depend on Hedgehog signaling.

    PubMed

    Lillien, Laura

    2014-11-01

    Lineage progression of neural precursors to an EGF-responsive state can be promoted by several extrinsic signals, including fibroblast growth factor 2 (FGF2) and Hedgehog (Hh). It has been suggested that EGF-responsive precursors in the embryonic cerebral cortex originate in the ventral telencephalon in an FGF-dependent manner and migrate dorsally. To determine whether cortical EGF-responsive cells originate locally from dorsal precursors, we marked these precursors using Emx1-cre and the cre reporter Z/EG and observed a local origin for EGF-responsive cells. We also found a rostral-caudal difference in the abundance of self-renewing, neurogenic Emx1-lineage precursors, with more present rostrally. Deleting the Hh receptor smoothened in Emx-1 lineage cells impaired their progression to an EGF-responsive state. Moreover, loss of smoothened increased the proportion of neurogenic, self-renewing Emx1-lineage cells in caudal regions of cortex, eliminating their asymmetric distribution. Our results support the idea that Hh signaling promotes lineage progression of stem/transit amplifying cells, particularly in caudal regions of the embryonic cortex, leading to rostral-caudal differences in the abundance of neurogenic, self-renewing precursors. © 2014 Wiley Periodicals, Inc.

  11. The Earliest Thymic T Cell Progenitors Sustain B Cell and Myeloid Lineage Potentials

    PubMed Central

    Luc, Sidinh; Luis, Tiago C.; Boukarabila, Hanane; Macaulay, Iain C.; Buza-Vidas, Natalija; Bouriez-Jones, Tiphaine; Lutteropp, Michael; Woll, Petter S.; Loughran, Stephen J.; Mead, Adam J.; Hultquist, Anne; Brown, John; Mizukami, Takuo; Matsuoka, Sahoko; Ferry, Helen; Anderson, Kristina; Duarte, Sara; Atkinson, Deborah; Soneji, Shamit; Domanski, Aniela; Farley, Alison; Sanjuan-Pla, Alejandra; Carella, Cintia; Patient, Roger; de Bruijn, Marella; Enver, Tariq; Nerlov, Claus; Blackburn, Clare; Godin, Isabelle; Jacobsen, Sten Eirik W.

    2012-01-01

    The stepwise commitment from hematopoietic stem cells in the bone marrow (BM) to T lymphocyte-restricted progenitors in the thymus represents a paradigm for understanding the requirement for distinct extrinsic cues during different stages of lineage restriction from multipotent to lineage restricted progenitors. However, the commitment stage at which progenitors migrate from the BM to the thymus remains unclear. Here we provide functional and molecular evidence at the single cell level that the earliest progenitors in the neonatal thymus possessed combined granulocyte-monocyte, T and B lymphocyte, but not megakaryocyte-erythroid lineage potential. These potentials were identical to those of thymus-seeding progenitors in the BM, which were closely related at the molecular level. These findings establish the distinct lineage-restriction stage at which the T lineage commitment transits from the BM to the remote thymus. PMID:22344248

  12. Widespread Occurrence of Secondary Lipid Biosynthesis Potential in Microbial Lineages

    PubMed Central

    Shulse, Christine N.; Allen, Eric E.

    2011-01-01

    Bacterial production of long-chain omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), is constrained to a narrow subset of marine γ-proteobacteria. The genes responsible for de novo bacterial PUFA biosynthesis, designated pfaEABCD, encode large, multi-domain protein complexes akin to type I iterative fatty acid and polyketide synthases, herein referred to as “Pfa synthases”. In addition to the archetypal Pfa synthase gene products from marine bacteria, we have identified homologous type I FAS/PKS gene clusters in diverse microbial lineages spanning 45 genera representing 10 phyla, presumed to be involved in long-chain fatty acid biosynthesis. In total, 20 distinct types of gene clusters were identified. Collectively, we propose the designation of “secondary lipids” to describe these biosynthetic pathways and products, a proposition consistent with the “secondary metabolite” vernacular. Phylogenomic analysis reveals a high degree of functional conservation within distinct biosynthetic pathways. Incongruence between secondary lipid synthase functional clades and taxonomic group membership combined with the lack of orthologous gene clusters in closely related strains suggests horizontal gene transfer has contributed to the dissemination of specialized lipid biosynthetic activities across disparate microbial lineages. PMID:21629834

  13. Progression to active tuberculosis, but not transmission, varies by M. tuberculosis lineage in The Gambia

    PubMed Central

    de Jong, Bouke C.; Hill, Philip C.; Aiken, Alex; Awine, Timothy; Antonio, Martin; Adetifa, Ifedayo M.; Jackson-Sillah, Dolly J.; Fox, Annette; DeRiemer, Kathryn; Gagneux, Sebastien; Borgdorff, Martien W.; McAdam, Keith P.W.J.; Corrah, Tumani; Small, Peter M.; Adegbola, Richard A.

    2008-01-01

    Considerable variability exists in the outcome of M. tuberculosis infection. We hypothesized that M. africanum was less likely than M. tuberculosis to transmit and progress to tuberculosis disease. In a cohort study of tuberculosis patients and their household contacts in the Gambia, we categorized 1,808 HIV negative tuberculosis contacts according to exposure to M. tuberculosis or to M. africanum. A positive skin test indicated transmission and development of tuberculosis during 2 years of follow-up indicated progression to disease. Transmission was similar, but progression to disease was significantly lower in contacts exposed to M. africanum than to M. tuberculosis (1.0% vs 2.9%; Hazard Ratio (HR) 3.1, 95% CI 1.1–8.7). Within M. tuberculosis sensu stricto, contacts exposed to a Beijing family strain were most likely to progress to disease (5.6%; HR 6.7 (2.0–22) relative to M. africanum). M. africanum and M. tuberculosis transmit equally well to household contacts, but contacts exposed to M. africanum are less likely to progress to tuberculosis disease than those exposed to M. tuberculosis. The variable rate of progression by lineage suggests that TB variability matters in clinical settings and should be taken into account in studies evaluating tuberculosis vaccines and treatment regimens for latent tuberculosis infection. PMID:18702608

  14. Role of Mitochondrial Metabolism in the Control of Early Lineage Progression and Aging Phenotypes in Adult Hippocampal Neurogenesis.

    PubMed

    Beckervordersandforth, Ruth; Ebert, Birgit; Schäffner, Iris; Moss, Jonathan; Fiebig, Christian; Shin, Jaehoon; Moore, Darcie L; Ghosh, Laboni; Trinchero, Mariela F; Stockburger, Carola; Friedland, Kristina; Steib, Kathrin; von Wittgenstein, Julia; Keiner, Silke; Redecker, Christoph; Hölter, Sabine M; Xiang, Wei; Wurst, Wolfgang; Jagasia, Ravi; Schinder, Alejandro F; Ming, Guo-Li; Toni, Nicolas; Jessberger, Sebastian; Song, Hongjun; Lie, D Chichung

    2017-02-08

    Precise regulation of cellular metabolism is hypothesized to constitute a vital component of the developmental sequence underlying the life-long generation of hippocampal neurons from quiescent neural stem cells (NSCs). The identity of stage-specific metabolic programs and their impact on adult neurogenesis are largely unknown. We show that the adult hippocampal neurogenic lineage is critically dependent on the mitochondrial electron transport chain and oxidative phosphorylation machinery at the stage of the fast proliferating intermediate progenitor cell. Perturbation of mitochondrial complex function by ablation of the mitochondrial transcription factor A (Tfam) reproduces multiple hallmarks of aging in hippocampal neurogenesis, whereas pharmacological enhancement of mitochondrial function ameliorates age-associated neurogenesis defects. Together with the finding of age-associated alterations in mitochondrial function and morphology in NSCs, these data link mitochondrial complex function to efficient lineage progression of adult NSCs and identify mitochondrial function as a potential target to ameliorate neurogenesis-defects in the aging hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Lineage-specific function of Engrailed-2 in the progression of chronic myelogenous leukemia to T-cell blast crisis.

    PubMed

    Abollo-Jiménez, Fernando; Campos-Sánchez, Elena; Toboso-Navasa, Amparo; Vicente-Dueñas, Carolina; González-Herrero, Inés; Alonso-Escudero, Esther; González, Marcos; Segura, Víctor; Blanco, Oscar; Martínez-Climent, José Angel; Sánchez-García, Isidro; Cobaleda, César

    2014-01-01

    In hematopoietic malignancies, oncogenic alterations interfere with cellular differentiation and lead to tumoral development. Identification of the proteins regulating differentiation is essential to understand how they are altered in malignancies. Chronic myelogenous leukemia (CML) is a biphasic disease initiated by an alteration taking place in hematopoietic stem cells. CML progresses to a blast crisis (BC) due to a secondary differentiation block in any of the hematopoietic lineages. However, the molecular mechanisms of CML evolution to T-cell BC remain unclear. Here, we have profiled the changes in DNA methylation patterns in human samples from BC-CML, in order to identify genes whose expression is epigenetically silenced during progression to T-cell lineage-specific BC. We have found that the CpG-island of the ENGRAILED-2 (EN2) gene becomes methylated in this progression. Afterwards, we demonstrate that En2 is expressed during T-cell development in mice and humans. Finally, we further show that genetic deletion of En2 in a CML transgenic mouse model induces a T-cell lineage BC that recapitulates human disease. These results identify En2 as a new regulator of T-cell differentiation whose disruption induces a malignant T-cell fate in CML progression, and validate the strategy used to identify new developmental regulators of hematopoiesis.

  16. Lineage-specific function of Engrailed-2 in the progression of chronic myelogenous leukemia to T-cell blast crisis

    PubMed Central

    Abollo-Jiménez, Fernando; Campos-Sánchez, Elena; Toboso-Navasa, Amparo; Vicente-Dueñas, Carolina; González-Herrero, Inés; Alonso-Escudero, Esther; González, Marcos; Segura, Víctor; Blanco, Óscar; Martínez-Climent, José Ángel; Sánchez-García, Isidro; Cobaleda, César

    2014-01-01

    In hematopoietic malignancies, oncogenic alterations interfere with cellular differentiation and lead to tumoral development. Identification of the proteins regulating differentiation is essential to understand how they are altered in malignancies. Chronic myelogenous leukemia (CML) is a biphasic disease initiated by an alteration taking place in hematopoietic stem cells. CML progresses to a blast crisis (BC) due to a secondary differentiation block in any of the hematopoietic lineages. However, the molecular mechanisms of CML evolution to T-cell BC remain unclear. Here, we have profiled the changes in DNA methylation patterns in human samples from BC-CML, in order to identify genes whose expression is epigenetically silenced during progression to T-cell lineage-specific BC. We have found that the CpG-island of the ENGRAILED-2 (EN2) gene becomes methylated in this progression. Afterwards, we demonstrate that En2 is expressed during T-cell development in mice and humans. Finally, we further show that genetic deletion of En2 in a CML transgenic mouse model induces a T-cell lineage BC that recapitulates human disease. These results identify En2 as a new regulator of T-cell differentiation whose disruption induces a malignant T-cell fate in CML progression, and validate the strategy used to identify new developmental regulators of hematopoiesis. PMID:24675889

  17. A case of cellular alchemy: lineage reprogramming and its potential in regenerative medicine.

    PubMed

    Asuelime, Grace E; Shi, Yanhong

    2012-08-01

    The field of regenerative medicine is rapidly gaining momentum as an increasing number of reports emerge concerning the induced conversions observed in cellular fate reprogramming. While in recent years, much attention has been focused on the conversion of fate-committed somatic cells to an embryonic-like or pluripotent state, there are still many limitations associated with the applications of induced pluripotent stem cell reprogramming, including relatively low reprogramming efficiency, the times required for the reprogramming event to take place, the epigenetic instability, and the tumorigenicity associated with the pluripotent state. On the other hand, lineage reprogramming involves the conversion from one mature cell type to another without undergoing conversion to an unstable intermediate. It provides an alternative approach in regenerative medicine that has a relatively lower risk of tumorigenesis and increased efficiency within specific cellular contexts. While lineage reprogramming provides exciting potential, there is still much to be assessed before this technology is ready to be applied in a clinical setting.

  18. Potential for chemolithoautotrophy among ubiquitous bacteria lineages in the dark ocean.

    PubMed

    Swan, Brandon K; Martinez-Garcia, Manuel; Preston, Christina M; Sczyrba, Alexander; Woyke, Tanja; Lamy, Dominique; Reinthaler, Thomas; Poulton, Nicole J; Masland, E Dashiell P; Gomez, Monica Lluesma; Sieracki, Michael E; DeLong, Edward F; Herndl, Gerhard J; Stepanauskas, Ramunas

    2011-09-02

    Recent studies suggest that unidentified prokaryotes fix inorganic carbon at globally significant rates in the immense dark ocean. Using single-cell sorting and whole-genome amplification of prokaryotes from two subtropical gyres, we obtained genomic DNA from 738 cells representing most cosmopolitan lineages. Multiple cells of Deltaproteobacteria cluster SAR324, Gammaproteobacteria clusters ARCTIC96BD-19 and Agg47, and some Oceanospirillales from the lower mesopelagic contained ribulose-1,5-bisphosphate carboxylase-oxygenase and sulfur oxidation genes. These results corroborated community DNA and RNA profiling from diverse geographic regions. The SAR324 genomes also suggested C(1) metabolism and a particle-associated life-style. Microautoradiography and fluorescence in situ hybridization confirmed bicarbonate uptake and particle association of SAR324 cells. Our study suggests potential chemolithoautotrophy in several uncultured Proteobacteria lineages that are ubiquitous in the dark oxygenated ocean and provides new perspective on carbon cycling in the ocean's largest habitat.

  19. Potential for Chemolithoautotrophy Among Ubiquitous Bacteria Lineages in the Dark Ocean

    NASA Astrophysics Data System (ADS)

    Swan, Brandon K.; Martinez-Garcia, Manuel; Preston, Christina M.; Sczyrba, Alexander; Woyke, Tanja; Lamy, Dominique; Reinthaler, Thomas; Poulton, Nicole J.; Masland, E. Dashiell P.; Gomez, Monica Lluesma; Sieracki, Michael E.; DeLong, Edward F.; Herndl, Gerhard J.; Stepanauskas, Ramunas

    2011-09-01

    Recent studies suggest that unidentified prokaryotes fix inorganic carbon at globally significant rates in the immense dark ocean. Using single-cell sorting and whole-genome amplification of prokaryotes from two subtropical gyres, we obtained genomic DNA from 738 cells representing most cosmopolitan lineages. Multiple cells of Deltaproteobacteria cluster SAR324, Gammaproteobacteria clusters ARCTIC96BD-19 and Agg47, and some Oceanospirillales from the lower mesopelagic contained ribulose-1,5-bisphosphate carboxylase-oxygenase and sulfur oxidation genes. These results corroborated community DNA and RNA profiling from diverse geographic regions. The SAR324 genomes also suggested C1 metabolism and a particle-associated life-style. Microautoradiography and fluorescence in situ hybridization confirmed bicarbonate uptake and particle association of SAR324 cells. Our study suggests potential chemolithoautotrophy in several uncultured Proteobacteria lineages that are ubiquitous in the dark oxygenated ocean and provides new perspective on carbon cycling in the ocean’s largest habitat.

  20. Comprehensive analysis of melanogenesis and proliferation potential of melanocyte lineage in solar lentigines.

    PubMed

    Yamada, Takaaki; Hasegawa, Seiji; Inoue, Yu; Date, Yasushi; Arima, Masaru; Yagami, Akiko; Iwata, Yohei; Abe, Masamichi; Takahashi, Masayuki; Yamamoto, Naoki; Mizutani, Hiroshi; Nakata, Satoru; Matsunaga, Kayoko; Akamatsu, Hirohiko

    2014-03-01

    Solar lentigines (SLs) are characterized by hyperpigmented macules, commonly seen on sun-exposed areas of the skin. Although it has been reported that an increase in the number of melanocytes and epidermal melanin content was observed in the lesions, the following questions remain to be answered: (1) Is acceleration of melanogenesis in the epidermis caused by an increased number of melanocytes or the high melanogenic potential of each melanocyte? (2) Why does the number of melanocytes increase? To elucidate the pathogenic mechanism of SLs by investigating the number, melanogenic potential and proliferation status of the melanocyte lineage in healthy skin and SL lesions. Immunostaining for melanocyte lineage markers (tyrosinase, MART-1, MITF, and Frizzled-4) and a proliferation marker, Ki67, was performed on skin sections, and the obtained images were analyzed by image analysis software. The expression level of tyrosinase to MART-1 of each melanocyte was significantly higher in SL lesions than healthy skin. The numbers of melanocytes in the epidermis, melanoblasts in the hair follicular infundibulum and melanocyte stem cells in the bulge region were increased in SL; however, no significant difference was observed in the Ki67-positive rate of these cells. The melanogenic potential of each melanocyte was elevated in SL lesions. It was suggested that the increased number of melanocytes in the SL epidermis might be attributed to the abnormal increase of melanocyte stem cells in the bulge. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  1. Frequency of Trypanosoma cruzi parasitemia among infected blood donors with a potential association between parasite lineage and transfusion transmission.

    PubMed

    Leiby, David A; Nguyen, Megan L; Proctor, Melanie C; Townsend, Rebecca L; Stramer, Susan L

    2017-06-01

    Trypanosoma cruzi is endemic to the Americas where it demonstrates multiple lineages over a vast geographic range (i.e., United States to Argentina). These lineages possess divergent geographic and biologic characteristics, including variations in disease manifestations. Herein, we report the frequency of parasitemia among seropositive US blood donors and the potential association between parasite lineage and transfusion transmission. Blood donors identified as T. cruzi seropositive during screening were enrolled in follow-up studies, including hemoculture testing and a risk factor questionnaire. Positive hemocultures were expanded to obtain sufficient parasites for molecular lineage determination and analysis. Country of birth, obtained from the questionnaire, was used to predict parasite lineage in the absence of demonstrable parasitemia for infected donors. Eighteen (6.8%) of 263 seropositive donors were hemoculture positive. Among the 17 hemocultures expanded for lineage determination, TcV was identified more frequently (n = 12), compared to TcI (n = 2), TcII (n = 1), and TcVI (n = 2). When presumptive parasite lineages were compared to hemoculture results, only two of 157 (1.3%) TcI versus 13 of 38 (34.2%) TcII/TcV/TcVI non-US donors were parasitemic; three of 44 (6.8%) US donors were TcV or TcVI. Based on lineage determination for donors with parasitemia; hemoculture positivity associated with presumptive parasite lineage; and implicated donors from US, Canadian, and Spanish transfusion cases, donors from Southern South America are significantly more likely to have parasitemia and transmit infection to blood recipients (TcII, TcV, or TcVI vs. TcI). Thus, parasite lineage may be associated with risk of transfusion-transmitted T. cruzi. © 2017 AABB.

  2. Septo-temporal distribution and lineage progression of hippocampal neurogenesis in a primate (Callithrix jacchus) in comparison to mice

    PubMed Central

    Amrein, Irmgard; Nosswitz, Michael; Slomianka, Lutz; van Dijk, R. Maarten; Engler, Stefanie; Klaus, Fabienne; Raineteau, Olivier; Azim, Kasum

    2015-01-01

    Adult born neurons in the hippocampus show species-specific differences in their numbers, the pace of their maturation and their spatial distribution. Here, we present quantitative data on adult hippocampal neurogenesis in a New World primate, the common marmoset (Callithrix jacchus) that demonstrate parts of the lineage progression and age-related changes. Proliferation was largely (∼70%) restricted to stem cells or early progenitor cells, whilst the remainder of the cycling pool could be assigned almost exclusively to Tbr2+ intermediate precursor cells in both neonate and adult animals (20–122 months). Proliferating DCX+ neuroblasts were virtually absent in adults, although rare MCM2+/DCX+ co-expression revealed a small, persisting proliferative potential. Co-expression of DCX with calretinin was very limited in marmosets, suggesting that these markers label distinct maturational stages. In adult marmosets, numbers of MCM2+, Ki67+, and significantly Tbr2+, DCX+, and CR+ cells declined with age. The distributions of granule cells, proliferating cells and DCX+ young neurons along the hippocampal longitudinal axis were equal in marmosets and mice. In both species, a gradient along the hippocampal septo-temporal axis was apparent for DCX+ and resident granule cells. Both cell numbers are higher septally than temporally, whilst proliferating cells were evenly distributed along this axis. Relative to resident granule cells, however, the ratio of proliferating cells and DCX+ neurons remained constant in the septal, middle, and temporal hippocampus. In marmosets, the extended phase of the maturation of young neurons that characterizes primate hippocampal neurogenesis was due to the extension in a large CR+/DCX- cell population. This clear dissociation between DCX+ and CR+ young neurons has not been reported for other species and may therefore represent a key primate-specific feature of adult hippocampal neurogenesis. PMID:26175670

  3. FOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function

    PubMed Central

    Yang, Yeqing A.; Zhao, Jonathan C.; Fong, Ka-wing; Kim, Jung; Li, Shangze; Song, Chunxiao; Song, Bing; Zheng, Bin; He, Chuan; Yu, Jindan

    2016-01-01

    Forkhead box A1 (FOXA1) is an FKHD family protein that plays pioneering roles in lineage-specific enhancer activation and gene transcription. Through genome-wide location analyses, here we show that FOXA1 expression and occupancy are, in turn, required for the maintenance of these epigenetic signatures, namely DNA hypomethylation and histone 3 lysine 4 methylation. Mechanistically, this involves TET1, a 5-methylcytosine dioxygenase. We found that FOXA1 induces TET1 expression via direct binding to its cis-regulatory elements. Further, FOXA1 physically interacts with the TET1 protein through its CXXC domain. TET1 thus co-occupies FOXA1-dependent enhancers and mediates local DNA demethylation and concomitant histone 3 lysine 4 methylation, further potentiating FOXA1 recruitment. Consequently, FOXA1 binding events are markedly reduced following TET1 depletion. Together, our results suggest that FOXA1 is not only able to recognize but also remodel the epigenetic signatures at lineage-specific enhancers, which is mediated, at least in part, by a feed-forward regulatory loop between FOXA1 and TET1. PMID:27257062

  4. A case of cellular alchemy: lineage reprogramming and its potential in regenerative medicine

    PubMed Central

    Asuelime, Grace E.; Shi, Yanhong

    2012-01-01

    The field of regenerative medicine is rapidly gaining momentum as an increasing number of reports emerge concerning the induced conversions observed in cellular fate reprogramming. While in recent years, much attention has been focused on the conversion of fate-committed somatic cells to an embryonic-like or pluripotent state, there are still many limitations associated with the applications of induced pluripotent stem cell reprogramming, including relatively low reprogramming efficiency, the times required for the reprogramming event to take place, the epigenetic instability, and the tumorigenicity associated with the pluripotent state. On the other hand, lineage reprogramming involves the conversion from one mature cell type to another without undergoing conversion to an unstable intermediate. It provides an alternative approach in regenerative medicine that has a relatively lower risk of tumorigenesis and increased efficiency within specific cellular contexts. While lineage reprogramming provides exciting potential, there is still much to be assessed before this technology is ready to be applied in a clinical setting. PMID:22371436

  5. Regulation of early T-lineage gene expression and developmental progression by the progenitor cell transcription factor PU.1

    PubMed Central

    Champhekar, Ameya; Damle, Sagar S.; Freedman, George; Carotta, Sebastian; Nutt, Stephen L.

    2015-01-01

    The ETS family transcription factor PU.1 is essential for the development of several blood lineages, including T cells, but its function in intrathymic T-cell precursors has been poorly defined. In the thymus, high PU.1 expression persists through multiple cell divisions in early stages but then falls sharply during T-cell lineage commitment. PU.1 silencing is critical for T-cell commitment, but it has remained unknown how PU.1 activities could contribute positively to T-cell development. Here we employed conditional knockout and modified antagonist PU.1 constructs to perturb PU.1 function stage-specifically in early T cells. We show that PU.1 is needed for full proliferation, restricting access to some non-T fates, and controlling the timing of T-cell developmental progression such that removal or antagonism of endogenous PU.1 allows precocious access to T-cell differentiation. Dominant-negative effects reveal that this repression by PU.1 is mediated indirectly. Genome-wide transcriptome analysis identifies novel targets of PU.1 positive and negative regulation affecting progenitor cell signaling and cell biology and indicating distinct regulatory effects on different subsets of progenitor cell transcription factors. Thus, in addition to supporting early T-cell proliferation, PU.1 regulates the timing of activation of the core T-lineage developmental program. PMID:25846797

  6. IL-4/IL-13 Signaling Inhibits the Potential of Early Thymic Progenitors To Commit to the T Cell Lineage.

    PubMed

    Barik, Subhasis; Miller, Mindy M; Cattin-Roy, Alexis N; Ukah, Tobechukwu K; Chen, Weirong; Zaghouani, Habib

    2017-09-11

    Early thymic progenitors (ETPs) are endowed with diverse potencies and can give rise to myeloid and lymphoid lineage progenitors. How the thymic environment guides ETP commitment and maturation toward a specific lineage remains obscure. We have previously shown that ETPs expressing the heteroreceptor (HR) comprising IL-4Rα and IL-13Rα1 give rise to myeloid cells but not T cells. In this article, we show that signaling through the HR inhibits ETP maturation to the T cell lineage but enacts commitment toward the myeloid cells. Indeed, HR(+) ETPs, but not HR(-) ETPs, exhibit activated STAT6 transcription factor, which parallels with downregulation of Notch1, a critical factor for T cell development. Meanwhile, the myeloid-specific transcription factor C/EBPα, usually under the control of Notch1, is upregulated. Furthermore, in vivo inhibition of STAT6 phosphorylation restores Notch1 expression in HR(+) ETPs, which regain T lineage potential. In addition, upon stimulation with IL-4 or IL-13, HR(-) ETPs expressing virally transduced HR also exhibit STAT6 phosphorylation and downregulation of Notch1, leading to inhibition of lymphoid, but not myeloid, lineage potential. These observations indicate that environmental cytokines play a role in conditioning ETP lineage choice, which would impact T cell development. Copyright © 2017 by The American Association of Immunologists, Inc.

  7. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential

    PubMed Central

    Newman, Aaron M.; Drukker, Micha; Januszyk, Michael; Krampitz, Geoffrey W.; Gurtner, Geoffrey C.; Lorenz, H. Peter; Weissman, Irving L.; Longaker, Michael T.

    2016-01-01

    Dermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined. We reveal the presence of at least two fibroblast lineages in murine dorsal skin. Lineage tracing and transplantation assays demonstrate that a single fibroblast lineage is responsible for the bulk of connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, and cancer stroma formation. Lineage-specific cell ablation leads to diminished connective tissue deposition in wounds and reduces melanoma growth. Using flow cytometry, we identify CD26/DPP4 as a surface marker that allows isolation of this lineage. Small molecule–based inhibition of CD26/DPP4 enzymatic activity during wound healing results in diminished cutaneous scarring. Identification and isolation of these lineages hold promise for translational medicine aimed at in vivo modulation of fibrogenic behavior. PMID:25883361

  8. The C. elegans NR4A nuclear receptor gene nhr-6 promotes cell cycle progression in the spermatheca lineage.

    PubMed

    Praslicka, Brandon; Gissendanner, Chris R

    2015-03-01

    NR4A nuclear receptors are a conserved, functionally diverse group of nuclear receptors that regulate multiple cellular processes including proliferation and differentiation. The gene nhr-6 encodes the sole Caenorhabditis elegans NR4A nuclear receptor homolog with an essential role in reproduction by regulating morphogenesis of the spermatheca, a somatic gonad organ involved in ovulation and fertilization. Here, we identify the spermatheca cell lineage defects that occur in nhr-6 mutants. Utilizing cell marker analysis, we find that nhr-6 is required for cell cycle progression and that the cell proliferation phenotype is not due to premature cell cycle exit. We also show that loss of the negative cell cycle regulators fzr-1 and lin-35 suppresses the cell proliferation defects. We further demonstrate that NHR-6 activity intersects with Eph receptor signaling during spermatheca cell proliferation. NHR-6 has an essential function in promoting cell cycle progression during G1 phase in a specific spermatheca cell lineage. Genetic suppression of the proliferation phenotype does not affect the differentiation phenotypes observed in nhr-6 mutants, indicating a dualistic role for nhr-6 in regulating cell proliferation and cell differentiation during spermatheca organogenesis. © 2014 Wiley Periodicals, Inc.

  9. Derivation of putative porcine embryonic germ cells and analysis of their multi-lineage differentiation potential.

    PubMed

    Cong, Yimei; Ma, Jing; Sun, Ruizhen; Wang, Jianyu; Xue, Binghua; Wang, Jiaqiang; Xie, Bingteng; Wang, Juan; Hu, Kui; Liu, Zhonghua

    2013-09-20

    Embryonic germ (EG) cells are cultured pluripotent stem cells derived from the primordial germ cells (PGCs) that migrate from the dorsal mesentery of the hindgut to the developing genital ridge. In this study, the morphology of the porcine genital ridge was assessed in embryos harvested on days 22-30 of pregnancy. PGCs from embryos at these stages were cultured to obtain porcine EG cell lines, and EG-like cells were derived from PGCs from embryos harvested on days 24-28 of pregnancy. The EG-like cells expressed Oct4, Sox2, Nanog, SSEA-3, SSEA-4 and alkaline phosphatase (AP). These cells were able to form embryoid bodies (EBs) in suspension culture and differentiate into cells representative of the three germ layers as verified by a-fetoprotein (AFP), α-smooth muscle actin (α-SMA), and Nestin expression. Spontaneous differentiation from the porcine EG-like cells of delayed passage in vitro showed that they could differentiate into epithelial-like cells, mesenchymal-like cells and neuron-like cells. In vitro directed differentiation generated osteocytes, adipocytes and a variety of neural lineage cells, as demonstrated by alizarin red staining, oil red O staining, and immunofluorescence for neuronal class Ⅲ β-tubulin (Tuj1), glial fibrillary protein (GFAP) and galactosylceramidase (GALC), respectively. These results indicate that porcine EG-like cells have the potential for multi-lineage differentiation and are useful for basic porcine stem cell research. Copyright © 2013. Published by Elsevier Ltd.

  10. Potential merger of ancient lineages in a passerine bird discovered based on evidence from host-specific ectoparasites

    PubMed Central

    Block, Nicholas L; Goodman, Steven M; Hackett, Shannon J; Bates, John M; Raherilalao, Marie J

    2015-01-01

    The merger of formerly isolated lineages is hypothesized to occur in vertebrates under certain conditions. However, despite many demonstrated instances of introgression between taxa in secondary contact, examples of lineage mergers are rare. Preliminary mtDNA sequencing of a Malagasy passerine, Xanthomixis zosterops (Passeriformes: Bernieridae), indicated a possible instance of merging lineages. We tested the hypothesis that X. zosterops lineages are merging by comparing mtDNA sequence and microsatellite data, as well as mtDNA sequence data from host-specific feather lice in the genus Myrsidea (Phthiraptera: Menoponidae). Xanthomixis zosterops comprises four deeply divergent, broadly sympatric, cryptic mtDNA clades that likely began diverging approximately 3.6 million years ago. Despite this level of divergence, the microsatellite data indicate that the X. zosterops mtDNA clades are virtually panmictic. Three major phylogroups of Myrsidea were found, supporting previous allopatry of the X. zosterops clades. In combination, the datasets from X. zosterops and its Myrsidea document a potential merger of previously allopatric lineages that likely date to the Pliocene. This represents the first report of sympatric apparent hybridization among more than two terrestrial vertebrate lineages. Further, the mtDNA phylogeographic pattern of X. zosterops, namely the syntopy of more than two deeply divergent cryptic clades, appears to be a novel scenario among vertebrates. We highlight the value of gathering multiple types of data in phylogeographic studies to contribute to the study of vertebrate speciation. PMID:26380702

  11. Potential merger of ancient lineages in a passerine bird discovered based on evidence from host-specific ectoparasites.

    PubMed

    Block, Nicholas L; Goodman, Steven M; Hackett, Shannon J; Bates, John M; Raherilalao, Marie J

    2015-09-01

    The merger of formerly isolated lineages is hypothesized to occur in vertebrates under certain conditions. However, despite many demonstrated instances of introgression between taxa in secondary contact, examples of lineage mergers are rare. Preliminary mtDNA sequencing of a Malagasy passerine, Xanthomixis zosterops (Passeriformes: Bernieridae), indicated a possible instance of merging lineages. We tested the hypothesis that X. zosterops lineages are merging by comparing mtDNA sequence and microsatellite data, as well as mtDNA sequence data from host-specific feather lice in the genus Myrsidea (Phthiraptera: Menoponidae). Xanthomixis zosterops comprises four deeply divergent, broadly sympatric, cryptic mtDNA clades that likely began diverging approximately 3.6 million years ago. Despite this level of divergence, the microsatellite data indicate that the X. zosterops mtDNA clades are virtually panmictic. Three major phylogroups of Myrsidea were found, supporting previous allopatry of the X. zosterops clades. In combination, the datasets from X. zosterops and its Myrsidea document a potential merger of previously allopatric lineages that likely date to the Pliocene. This represents the first report of sympatric apparent hybridization among more than two terrestrial vertebrate lineages. Further, the mtDNA phylogeographic pattern of X. zosterops, namely the syntopy of more than two deeply divergent cryptic clades, appears to be a novel scenario among vertebrates. We highlight the value of gathering multiple types of data in phylogeographic studies to contribute to the study of vertebrate speciation.

  12. The potential for evolutionary responses to cell-lineage selection on growth form and its plasticity in a red seaweed.

    PubMed

    Monro, Keyne; Poore, Alistair G B

    2009-02-01

    Despite much theoretical discussion on the evolutionary significance of intraclonal genetic variation, particularly for modular organisms whose lack of germ-soma segregation allows for variants arising in clonal growth to contribute to evolutionary change, the potential of this variation to fuel adaptation remains surprisingly untested. Given intraclonal variation, mitotic cell lineages, rather than sexual offspring, may frequently act as units of selection. Here, we applied artificial selection to such lineages in the branching red seaweed Asparagopsis armata, targeting aspects of clonal growth form and growth-form plasticity that enhance light acquisition on patchy subtidal reefs and predicting that a genetic basis to intraclonal variation may promote significant responses that cannot accompany phenotypic variation alone. Cell-lineage selection increased variation in branch proliferation among A. armata genets and successfully altered its plasticity to light. Correlated responses in the plasticity of branch elongation, moreover, showed that cell-lineage selection may be transmitted among the plasticities of growth-form traits in A. armata via pleiotropy. By demonstrating significant responses to cell-lineage selection on growth-form plasticity in this seaweed, our study lends support to the notion that intraclonal genetic variation may potentially help clonal organisms to evolve adaptively in the absence of sex and thereby prove surprisingly resilient to environmental change.

  13. Strains of the Propionibacterium acnes type III lineage are associated with the skin condition progressive macular hypomelanosis

    PubMed Central

    Barnard, Emma; Liu, Jared; Yankova, Eliza; Cavalcanti, Silvana M.; Magalhães, Marcelo; Li, Huiying; Patrick, Sheila; McDowell, Andrew

    2016-01-01

    Progressive macular hypomelanosis (PMH) is a common skin disorder that causes hypopigmentation in a variety of skin types. Although the underlying aetiology of this condition is unclear, there is circumstantial evidence that links the skin bacterium Propionibacterium acnes to the condition. We now describe the first detailed population genetic analysis of P. acnes isolates recovered from paired lesional and non-lesional skin of PMH patients. Our results demonstrate a strong statistical association between strains from the type III phylogenetic lineage and PMH lesions (P = 0.0019), but not those representing other phylogroups, including those associated with acne (type IA1). We also demonstrate, based on in silico 16S rDNA analysis, that PMH isolates previously recovered from patients in Europe are also consistent with the type III lineage. Using comparative genome analysis, we identified multiple genomic regions that are specific for, or absent from, type III strains compared to other phylogroups. In the former case, these include open reading frames with putative functions in metabolism, transport and transcriptional regulation, as well as predicted proteins of unknown function. Further study of these genomic elements, along with transcriptional and functional analyses, may help to explain why type III strains are associated with PMH. PMID:27555369

  14. Very Small Embryonic-Like Stem Cells: A Potential Developmental Link Between Germinal Lineage and Hematopoiesis in Humans.

    PubMed

    Virant-Klun, Irma

    2016-01-15

    It has been suggested that hematopoietic stem/progenitor cells (HSPCs) could become specified from a population of migrating primordial germ cells (PGCs), precursors of gametes, during embryogenesis. Some recent experimental data demonstrated that the cell population that is usually considered to be PGCs, moving toward the gonadal ridges of an embryo, contains a subset of cells coexpressing several germ cell and hematopoietic markers and possessing hematopoietic activity. Experimental data showed that bone morphogenetic protein 4 (BMP4) generates PGCs from mouse bone marrow-derived pluripotent stem cells. Interestingly, functional reproductive hormone receptors have been identified in HSPCs, thus indicating their potential role in reproductive function. Several reports have demonstrated fertility restoration and germ cell generation after bone marrow transplantation in both animal models and humans. A potential link between HSPCs and germinal lineage might be represented by very small embryonic-like stem cells (VSELs), which have been found in adult human bone marrow, peripheral blood, and umbilical cord blood, express a specific pattern of pluripotency, germinal lineage, and hematopoiesis, and are proposed to persist in adult tissues and organs from the embryonic period of life. Stem cell populations, similar to VSELs, expressing several genes related to pluripotency and germinal lineage, especially to PGCs, have been discovered in adult human reproductive organs, ovaries and testicles, and were related to primitive germ cell-like cell development in vitro, thus supporting the idea of VSELs as a potential link between germinal lineage and hematopoiesis.

  15. Potential susceptibility of Canadian flora to EU2 lineage of Phytophthora ramorum

    Treesearch

    S.F. Shamoun; G. Sumampong; D. Rioux; A. Schlenzig

    2017-01-01

    A total of 33 host species commonly found in eastern (8) and western (25) Canadian landscapes and forest sites were selected for this study. Detached leaves/needles were inoculated with Phytophthora ramorum EU2 lineage mycelia which was isolated from stream bait near an infected larch plantation in Scotland, UK. There was a large variation in...

  16. Biomolecular computing systems: principles, progress and potential.

    PubMed

    Benenson, Yaakov

    2012-06-12

    The task of information processing, or computation, can be performed by natural and man-made 'devices'. Man-made computers are made from silicon chips, whereas natural 'computers', such as the brain, use cells and molecules. Computation also occurs on a much smaller scale in regulatory and signalling pathways in individual cells and even within single biomolecules. Indeed, much of what we recognize as life results from the remarkable capacity of biological building blocks to compute in highly sophisticated ways. Rational design and engineering of biological computing systems can greatly enhance our ability to study and to control biological systems. Potential applications include tissue engineering and regeneration and medical treatments. This Review introduces key concepts and discusses recent progress that has been made in biomolecular computing.

  17. Genetic redundancy of GATA factors in the extraembryonic trophoblast lineage ensures the progression of preimplantation and postimplantation mammalian development

    PubMed Central

    Home, Pratik; Kumar, Ram Parikshan; Ganguly, Avishek; Saha, Biswarup; Milano-Foster, Jessica; Bhattacharya, Bhaswati; Ray, Soma; Gunewardena, Sumedha; Paul, Arindam; Camper, Sally A.; Fields, Patrick E.

    2017-01-01

    GATA transcription factors are implicated in establishing cell fate during mammalian development. In early mammalian embryos, GATA3 is selectively expressed in the extraembryonic trophoblast lineage and regulates gene expression to promote trophoblast fate. However, trophoblast-specific GATA3 function is dispensable for early mammalian development. Here, using dual conditional knockout mice, we show that genetic redundancy of Gata3 with paralog Gata2 in trophoblast progenitors ensures the successful progression of both pre- and postimplantation mammalian development. Stage-specific gene deletion in trophoblasts reveals that loss of both GATA genes, but not either alone, leads to embryonic lethality prior to the onset of their expression within the embryo proper. Using ChIP-seq and RNA-seq analyses, we define the global targets of GATA2/GATA3 and show that they directly regulate a large number of common genes to orchestrate stem versus differentiated trophoblast fate. In trophoblast progenitors, GATA factors directly regulate BMP4, Nodal and Wnt signaling components that promote embryonic-extraembryonic signaling cross-talk, which is essential for the development of the embryo proper. Our study provides genetic evidence that impairment of trophoblast-specific GATA2/GATA3 function could lead to early pregnancy failure. PMID:28232602

  18. Radiative Cooling: Principles, Progress, and Potentials

    PubMed Central

    Hossain, Md. Muntasir

    2016-01-01

    The recent progress on radiative cooling reveals its potential for applications in highly efficient passive cooling. This approach utilizes the maximized emission of infrared thermal radiation through the atmospheric window for releasing heat and minimized absorption of incoming atmospheric radiation. These simultaneous processes can lead to a device temperature substantially below the ambient temperature. Although the application of radiative cooling for nighttime cooling was demonstrated a few decades ago, significant cooling under direct sunlight has been achieved only recently, indicating its potential as a practical passive cooler during the day. In this article, the basic principles of radiative cooling and its performance characteristics for nonradiative contributions, solar radiation, and atmospheric conditions are discussed. The recent advancements over the traditional approaches and their material and structural characteristics are outlined. The key characteristics of the thermal radiators and solar reflectors of the current state‐of‐the‐art radiative coolers are evaluated and their benchmarks are remarked for the peak cooling ability. The scopes for further improvements on radiative cooling efficiency for optimized device characteristics are also theoretically estimated. PMID:27812478

  19. Radiative Cooling: Principles, Progress, and Potentials.

    PubMed

    Hossain, Md Muntasir; Gu, Min

    2016-07-01

    The recent progress on radiative cooling reveals its potential for applications in highly efficient passive cooling. This approach utilizes the maximized emission of infrared thermal radiation through the atmospheric window for releasing heat and minimized absorption of incoming atmospheric radiation. These simultaneous processes can lead to a device temperature substantially below the ambient temperature. Although the application of radiative cooling for nighttime cooling was demonstrated a few decades ago, significant cooling under direct sunlight has been achieved only recently, indicating its potential as a practical passive cooler during the day. In this article, the basic principles of radiative cooling and its performance characteristics for nonradiative contributions, solar radiation, and atmospheric conditions are discussed. The recent advancements over the traditional approaches and their material and structural characteristics are outlined. The key characteristics of the thermal radiators and solar reflectors of the current state-of-the-art radiative coolers are evaluated and their benchmarks are remarked for the peak cooling ability. The scopes for further improvements on radiative cooling efficiency for optimized device characteristics are also theoretically estimated.

  20. Ikaros sets the potential for Th17 lineage gene expression through effects on chromatin state in early T cell development.

    PubMed

    Wong, Larry Y; Hatfield, Julianne K; Brown, Melissa A

    2013-12-06

    Th17 cells are important effectors of immunity to extracellular pathogens, particularly at mucosal surfaces, but they can also contribute to pathologic tissue inflammation and autoimmunity. Defining the multitude of factors that influence their development is therefore of paramount importance. Our previous studies using Ikaros(-/-) CD4+ T cells implicated Ikaros in Th1 versus Th2 lineage decisions. Here we demonstrate that Ikaros also regulates Th17 differentiation through its ability to promote expression of multiple Th17 lineage-determining genes, including Ahr, Runx1, Rorc, Il17a, and Il22. Ikaros exerts its influence on the chromatin remodeling of these loci at two distinct stages in CD4+ T helper cell development. In naive cells, Ikaros is required to limit repressive chromatin modifications at these gene loci, thus maintaining the potential for expression of the Th17 gene program. Subsequently, Ikaros is essential for the acquisition of permissive histone marks in response to Th17 polarizing signals. Additionally, Ikaros represses the expression of genes that limit Th17 development, including Foxp3 and Tbx21. These data define new targets of the action of Ikaros and indicate that Ikaros plays a critical role in CD4+ T cell differentiation by integrating specific cytokine cues and directing epigenetic modifications that facilitate activation or repression of relevant genes that drive T cell lineage choice.

  1. The Potential of Menstrual Blood-Derived Stem Cells in Differentiation to Epidermal Lineage: A Preliminary Report

    PubMed Central

    Faramarzi, Hossein; Mehrabani, Davood; Fard, Maryam; Akhavan, Maryam; Zare, Sona; Bakhshalizadeh, Shabnam; Manafi, Amir; Kazemnejad, Somaieh; Shirazi, Reza

    2016-01-01

    BACKGROUND Menstrual blood-derived stem cells (MenSCs) are a novel source of stem cells that can be easily isolated non-invasively from female volunteered donor without ethical consideration. These mesenchymal-like stem cells have high rate of proliferation and possess multi lineage differentiation potency. This study was undertaken to isolate the MenSCs and assess their potential in differentiation into epidermal lineage. METHODS About 5-10 ml of menstrual blood (MB) was collected using sterile Diva cups inserted into vagina during menstruation from volunteered healthy fertile women aged between 22-30 years. MB was transferred into Falcon tubes containing phosphate buffered saline (PBS) without Ca2+ or Mg2+ supplemented with 2.5 µg/ml fungizone, 100 µg/mL streptomycin, 100 U/mL penicillin and 0.5 mM EDTA. Mononuclear cells were separated using Ficoll-Hypaque density gradient centrifugation and washed out in PBS. The cell pellet was suspended in DMEM-F12 medium supplemented with 10% FBS and cultured in tissue culture plates. The isolated cells were co-cultured with keratinocytes derived from the foreskin of healthy newborn male aged 2-10 months who was a candidate for circumcision for differentiation into epidermal lineage. RESULTS The isolated MenSCs were adhered to the plate and exhibited spindle-shaped morphology. Flow cytometric analysis revealed the expression of mesenchymal markers of CD10, CD29, CD73, and CD105 and lack of hematopoietic stem cells markers. An early success in derivation of epidermal lineage from MenSCs was visible. CONCLUSION The MenSCs are a real source to design differentiation to epidermal cells that can be used non-invasively in various dermatological lesions and diseases. PMID:27308237

  2. The Potential of Menstrual Blood-Derived Stem Cells in Differentiation to Epidermal Lineage: A Preliminary Report.

    PubMed

    Faramarzi, Hossein; Mehrabani, Davood; Fard, Maryam; Akhavan, Maryam; Zare, Sona; Bakhshalizadeh, Shabnam; Manafi, Amir; Kazemnejad, Somaieh; Shirazi, Reza

    2016-01-01

    Menstrual blood-derived stem cells (MenSCs) are a novel source of stem cells that can be easily isolated non-invasively from female volunteered donor without ethical consideration. These mesenchymal-like stem cells have high rate of proliferation and possess multi lineage differentiation potency. This study was undertaken to isolate the MenSCs and assess their potential in differentiation into epidermal lineage. About 5-10 ml of menstrual blood (MB) was collected using sterile Diva cups inserted into vagina during menstruation from volunteered healthy fertile women aged between 22-30 years. MB was transferred into Falcon tubes containing phosphate buffered saline (PBS) without Ca2(+) or Mg2(+) supplemented with 2.5 µg/ml fungizone, 100 µg/mL streptomycin, 100 U/mL penicillin and 0.5 mM EDTA. Mononuclear cells were separated using Ficoll-Hypaque density gradient centrifugation and washed out in PBS. The cell pellet was suspended in DMEM-F12 medium supplemented with 10% FBS and cultured in tissue culture plates. The isolated cells were co-cultured with keratinocytes derived from the foreskin of healthy newborn male aged 2-10 months who was a candidate for circumcision for differentiation into epidermal lineage. The isolated MenSCs were adhered to the plate and exhibited spindle-shaped morphology. Flow cytometric analysis revealed the expression of mesenchymal markers of CD10, CD29, CD73, and CD105 and lack of hematopoietic stem cells markers. An early success in derivation of epidermal lineage from MenSCs was visible. The MenSCs are a real source to design differentiation to epidermal cells that can be used non-invasively in various dermatological lesions and diseases.

  3. A GIS Model Predicting Potential Distributions of a Lineage: A Test Case on Hermit Spiders (Nephilidae: Nephilengys)

    PubMed Central

    Năpăruş, Magdalena; Kuntner, Matjaž

    2012-01-01

    Background Although numerous studies model species distributions, these models are almost exclusively on single species, while studies of evolutionary lineages are preferred as they by definition study closely related species with shared history and ecology. Hermit spiders, genus Nephilengys, represent an ecologically important but relatively species-poor lineage with a globally allopatric distribution. Here, we model Nephilengys global habitat suitability based on known localities and four ecological parameters. Methodology/Principal Findings We geo-referenced 751 localities for the four most studied Nephilengys species: N. cruentata (Africa, New World), N. livida (Madagascar), N. malabarensis (S-SE Asia), and N. papuana (Australasia). For each locality we overlaid four ecological parameters: elevation, annual mean temperature, annual mean precipitation, and land cover. We used linear backward regression within ArcGIS to select two best fit parameters per species model, and ModelBuilder to map areas of high, moderate and low habitat suitability for each species within its directional distribution. For Nephilengys cruentata suitable habitats are mid elevation tropics within Africa (natural range), a large part of Brazil and the Guianas (area of synanthropic spread), and even North Africa, Mediterranean, and Arabia. Nephilengys livida is confined to its known range with suitable habitats being mid-elevation natural and cultivated lands. Nephilengys malabarensis, however, ranges across the Equator throughout Asia where the model predicts many areas of high ecological suitability in the wet tropics. Its directional distribution suggests the species may potentially spread eastwards to New Guinea where the suitable areas of N. malabarensis largely surpass those of the native N. papuana, a species that prefers dry forests of Australian (sub)tropics. Conclusions Our model is a customizable GIS tool intended to predict current and future potential distributions of globally

  4. Energy in America: Progress and Potential.

    ERIC Educational Resources Information Center

    American Petroleum Inst., Washington, DC.

    An overview of America's energy situation is presented with emphasis on recent progress, the risk of depending upon foreign oil, and policy choices. Section one reviews the energy problems of the 1970s, issues of the 1980s, concerns for the future, and choices that if made today could alleviate future problems. Section two examines past problems,…

  5. Energy in America: Progress and Potential.

    ERIC Educational Resources Information Center

    American Petroleum Inst., Washington, DC.

    An overview of America's energy situation is presented with emphasis on recent progress, the risk of depending upon foreign oil, and policy choices. Section one reviews the energy problems of the 1970s, issues of the 1980s, concerns for the future, and choices that if made today could alleviate future problems. Section two examines past problems,…

  6. A developmental model of neuroblastoma: differentiating stroma-poor tumors' progress along an extra-adrenal chromaffin lineage.

    PubMed

    Hoehner, J C; Gestblom, C; Hedborg, F; Sandstedt, B; Olsen, L; Påhlman, S

    1996-11-01

    The prognosis of children with neuroblastoma (NB) is dependent upon the patient's age at diagnosis, the location of the primary tumor, and histologic tumor cell differentiation. These characteristics, as well as the presumption that NB results from clonal expansion of primitive cells involved in sympathetic nervous system (SNS) development, predict that a model of tumorigenesis based upon normal fetal SNS histogenesis might indicate tumor progenitor status and define biologic and clinical behavior. Immunohistochemistry and in situ hybridization were used to examine a panel of marker gene products predicted or shown to be expressed during SNS development in the normal human fetal SNS from 8 to 24 weeks' gestational age. A similar analysis was performed in a selection of clinical NB tumors, and the results were compared. In a subset of differentiating, often extra-adrenal NB tumors in patients who frequently had a favorable outcome; advancing morphologic tumor cell differentiation spatially paralleled an advancing fetal extra-adrenal chromaffin marker gene expression phenotype (ie, increasing TrkA, TrkC, TH, IGF-2, and neuron-specific enolase expression but a lack of phenylethanolamine N-methyltransferase expression). In these tumors, expression of gene products associated with normal fetal sympathetic ganglionic differentiation (ie, Bcl-2, HNK-1, and neuropeptide Y) was lost with morphologic tumor cell differentiation. In contrast, undifferentiated tumors, the majority of which were high stage, adrenal in origin, and prognostically unfavorable, displayed marker expression characteristics mirroring that of an early fetal ganglionic lineage. Thus, we show that morphologic differentiation in stroma-poor NB tumors, long held as an important prognostic feature in tumor grading systems, often corresponds to an extra-adrenal chromaffin rather than a ganglion cell or adrenal medullary chromaffin phenotype. Understanding the biology of extra-adrenal chromaffin tissues may

  7. Reactive astrocytes as neural stem or progenitor cells: In vivo lineage, In vitro potential, and Genome‐wide expression analysis

    PubMed Central

    Sirko, Swetlana; Beckers, Johannes; Irmler, Martin

    2015-01-01

    Here, we review the stem cell hallmarks of endogenous neural stem cells (NSCs) during development and in some niches of the adult mammalian brain to then compare these with reactive astrocytes acquiring stem cell hallmarks after traumatic and ischemic brain injury. Notably, even endogenous NSCs including the earliest NSCs, the neuroepithelial cells, generate in most cases only a single type of progeny and self‐renew only for a rather short time in vivo. In vitro, however, especially cells cultured under neurosphere conditions reveal a larger potential and long‐term self‐renewal under the influence of growth factors. This is rather well comparable to reactive astrocytes in the traumatic or ischemic brain some of which acquire neurosphere‐forming capacity including multipotency and long‐term self‐renewal in vitro, while they remain within their astrocyte lineage in vivo. Both reactive astrocytes and endogenous NSCs exhibit stem cell hallmarks largely in vitro, but their lineage differs in vivo. Both populations generate largely a single cell type in vivo, but endogenous NSCs generate neurons and reactive astrocytes remain in the astrocyte lineage. However, at some early postnatal stages or in some brain regions reactive astrocytes can be released from this fate restriction, demonstrating that they can also enact neurogenesis. Thus, reactive astrocytes and NSCs share many characteristic hallmarks, but also exhibit key differences. This conclusion is further substantiated by genome‐wide expression analysis comparing NSCs at different stages with astrocytes from the intact and injured brain parenchyma. GLIA 2015;63:1452–1468 PMID:25965557

  8. Comparative single-cell genomics reveals potential ecological niches for the freshwater acI Actinobacteria lineage.

    PubMed

    Ghylin, Trevor W; Garcia, Sarahi L; Moya, Francisco; Oyserman, Ben O; Schwientek, Patrick; Forest, Katrina T; Mutschler, James; Dwulit-Smith, Jeffrey; Chan, Leong-Keat; Martinez-Garcia, Manuel; Sczyrba, Alexander; Stepanauskas, Ramunas; Grossart, Hans-Peter; Woyke, Tanja; Warnecke, Falk; Malmstrom, Rex; Bertilsson, Stefan; McMahon, Katherine D

    2014-12-01

    Members of the acI lineage of Actinobacteria are the most abundant microorganisms in most freshwater lakes; however, our understanding of the keys to their success and their role in carbon and nutrient cycling in freshwater systems has been hampered by the lack of pure cultures and genomes. We obtained draft genome assemblies from 11 single cells representing three acI tribes (acI-A1, acI-A7, acI-B1) from four temperate lakes in the United States and Europe. Comparative analysis of acI SAGs and other available freshwater bacterial genomes showed that acI has more gene content directed toward carbohydrate acquisition as compared to Polynucleobacter and LD12 Alphaproteobacteria, which seem to specialize more on carboxylic acids. The acI genomes contain actinorhodopsin as well as some genes involved in anaplerotic carbon fixation indicating the capacity to supplement their known heterotrophic lifestyle. Genome-level differences between the acI-A and acI-B clades suggest specialization at the clade level for carbon substrate acquisition. Overall, the acI genomes appear to be highly streamlined versions of Actinobacteria that include some genes allowing it to take advantage of sunlight and N-rich organic compounds such as polyamines, di- and oligopeptides, branched-chain amino acids and cyanophycin. This work significantly expands the known metabolic potential of the cosmopolitan freshwater acI lineage and its ecological and genetic traits.

  9. Comparative single-cell genomics reveals potential ecological niches for the freshwater acI Actinobacteria lineage

    PubMed Central

    Ghylin, Trevor W; Garcia, Sarahi L; Moya, Francisco; Oyserman, Ben O; Schwientek, Patrick; Forest, Katrina T; Mutschler, James; Dwulit-Smith, Jeffrey; Chan, Leong-Keat; Martinez-Garcia, Manuel; Sczyrba, Alexander; Stepanauskas, Ramunas; Grossart, Hans-Peter; Woyke, Tanja; Warnecke, Falk; Malmstrom, Rex; Bertilsson, Stefan; McMahon, Katherine D

    2014-01-01

    Members of the acI lineage of Actinobacteria are the most abundant microorganisms in most freshwater lakes; however, our understanding of the keys to their success and their role in carbon and nutrient cycling in freshwater systems has been hampered by the lack of pure cultures and genomes. We obtained draft genome assemblies from 11 single cells representing three acI tribes (acI-A1, acI-A7, acI-B1) from four temperate lakes in the United States and Europe. Comparative analysis of acI SAGs and other available freshwater bacterial genomes showed that acI has more gene content directed toward carbohydrate acquisition as compared to Polynucleobacter and LD12 Alphaproteobacteria, which seem to specialize more on carboxylic acids. The acI genomes contain actinorhodopsin as well as some genes involved in anaplerotic carbon fixation indicating the capacity to supplement their known heterotrophic lifestyle. Genome-level differences between the acI-A and acI-B clades suggest specialization at the clade level for carbon substrate acquisition. Overall, the acI genomes appear to be highly streamlined versions of Actinobacteria that include some genes allowing it to take advantage of sunlight and N-rich organic compounds such as polyamines, di- and oligopeptides, branched-chain amino acids and cyanophycin. This work significantly expands the known metabolic potential of the cosmopolitan freshwater acI lineage and its ecological and genetic traits. PMID:25093637

  10. [Progress of Experimental Research on Differentiation of Muscle-Derived Stem Cells into Haematopoietic Lineages in Vitro -Review].

    PubMed

    Wang, Juan-Juan; Gao, Xiao-Ning; Chen, Shan-Shan; Zhang, Pan-Pan; Wang, Tao; Dou, Hao-Ying

    2016-12-01

    Muscle-derived stem cells (MDSC) are a population of multipotent stem cells in the muscular tissue. It provide an excellent prospect of hemopathy treatment due to their superiorities, such as rich sources, convenient material resource and a high survival rate after transplantation and so on. However, there are great differences in sampling, separation, purification, and proliferation when MDSC were cultured in vitro. In addition, the proliferation conditions of the MDSC in vitro are yet unclear. The related regulatory mechanisms, which MDSC transformed into haematopoietic cells, need to be investigated. In this article, the experimental researches on the differentiation of MDSC into haematopoietic lineages are reviewed, the concrete problems discussed in this review are culture of MDSC in vitro, identification of MDSC, proleferation of MDSC, differention of MDSC in to hematopoietic lineages and so on.

  11. Oceanic dispersal barriers, adaptation and larval retention: an interdisciplinary assessment of potential factors maintaining a phylogeographic break between sister lineages of an African prawn

    PubMed Central

    2008-01-01

    Background Genetic breaks separating regional lineages of marine organisms with potentially high broadcasting abilities are generally attributed either to dispersal barriers such as currents or upwelling, or to behavioural strategies promoting self-recruitment. We investigated whether such patterns could potentially also be explained by adaptations to different environmental conditions by studying two morphologically distinguishable genetic lineages of the estuarine mudprawn Upogebia africana across a biogeographic disjunction in south-eastern Africa. The study area encompasses a transition between temperate and subtropical biotas, where the warm, southward-flowing Agulhas Current is deflected away from the coast, and its inshore edge is characterised by intermittent upwelling. To determine how this phylogeographic break is maintained, we estimated gene flow among populations in the region, tested for isolation by distance as an indication of larval retention, and reared larvae of the temperate and subtropical lineages at a range of different temperatures. Results Of four populations sampled, the two northernmost exclusively included the subtropical lineage, a central population had a mixture of both lineages, and the southernmost estuary had only haplotypes of the temperate lineage. No evidence was found for isolation by distance, and gene flow was bidirectional and of similar magnitude among adjacent populations. In both lineages, the optimum temperature for larval development was at about 23°C, but a clear difference was found at lower temperatures. While larvae of the temperate lineage could complete development at temperatures as low as 12°C, those of the subtropical lineage did not complete development below 17°C. Conclusion The results indicate that both southward dispersal of the subtropical lineage inshore of the Agulhas Current, and its establishment in the temperate province, may be limited primarily by low water temperatures. There is no evidence

  12. The potential of dental stem cells differentiating into neurogenic cell lineage after cultivation in different modes in vitro.

    PubMed

    Yang, Chao; Sun, Liang; Li, Xinghan; Xie, Li; Yu, Mei; Feng, Lian; Jiang, Zongting; Guo, Weihua; Tian, Weidong

    2014-10-01

    Trauma or degenerative diseases of the central nervous system (CNS) cause the loss of neurons or glial cells. Stem cell transplantation has become a vital strategy for CNS regeneration. It is necessary to effectively induce nonneurogenic stem cells to differentiate into neurogenic cell lineages because of the limited source of neurogenic stem cells, relatively difficult cultivation, and ethical issues. Previous studies have found that dental stem cells can be used for transplantation therapy. The aim of this study was to explore a better inductive mode and time point for dental stem cells to differentiate into neural-like cells and evaluate a better candidate cell. In this study, dental follicle stem cells (DFSCs), dental papilla stem cells (DPSCs), and stem cells from apical papilla (SCAPs) were cultivated in five different modes. The proliferation ability, morphology, and expression of neural marker genes were analyzed. Results showed that DFSCs showed a higher proliferation potential. The proliferation was decreased after cultivation in chemical inductive medium as cultivation modes 3 and 5. The cells could present neural-like cell morphology after cultivation with human epidermal growth factor (EGF) and fibroblast growth factor-basic (bFGF) as cultivation modes 4 and 5. The vast majority of DFSCs gene expression levels in mode 4 on the third day was upregulated significantly. In conclusion, our data suggested that different dental stem cells exhibited different neural differentiation potentials. DFSCs might be the better candidate cell type. Furthermore, cultivation mode 4 and timing of the third day may promote differentiation into neurogenic cell lineages more effectively before transplantation to treat neurological diseases.

  13. Hepatitis B virus lineages in mammalian hosts: Potential for bidirectional cross-species transmission

    PubMed Central

    Bonvicino, Cibele R; Moreira, Miguel A; Soares, Marcelo A

    2014-01-01

    The hepatitis B virus (HBV) is a cosmopolitan infectious agent currently affecting over 350 million people worldwide, presently accounting for more than two billion infections. In addition to man, other hepatitis virus strains infect species of several mammalian families of the Primates, Rodentia and Chiroptera orders, in addition to birds. The mounting evidence of HBV infection in African, Asian and neotropical primates draws attention to the potential cross-species, zoonotic transmission of these viruses to man. Moreover, recent evidence also suggests the humans may also function as a source of viral infection to other mammals, particularly to domestic animals like poultry and swine. In this review, we list all evidence of HBV and HBV-like infection of nonhuman mammals and discuss their potential roles as donors or recipients of these viruses to humans and to other closely-related species. PMID:24976704

  14. Local parasite lineage sharing in temperate grassland birds provides clues about potential origins of Galapagos avian Plasmodium.

    PubMed

    Levin, Iris I; Colborn, Rachel E; Kim, Daniel; Perlut, Noah G; Renfrew, Rosalind B; Parker, Patricia G

    2016-02-01

    Oceanic archipelagos are vulnerable to natural introduction of parasites via migratory birds. Our aim was to characterize the geographic origins of two Plasmodium parasite lineages detected in the Galapagos Islands and in North American breeding bobolinks (Dolichonyx oryzivorus) that regularly stop in Galapagos during migration to their South American overwintering sites. We used samples from a grassland breeding bird assemblage in Nebraska, United States, and parasite DNA sequences from the Galapagos Islands, Ecuador, to compare to global data in a DNA sequence registry. Homologous DNA sequences from parasites detected in bobolinks and more sedentary birds (e.g., brown-headed cowbirds Molothrus ater, and other co-occurring bird species resident on the North American breeding grounds) were compared to those recovered in previous studies from global sites. One parasite lineage that matched between Galapagos birds and the migratory bobolink, Plasmodium lineage B, was the most common lineage detected in the global MalAvi database, matching 49 sequences from unique host/site combinations, 41 of which were of South American origin. We did not detect lineage B in brown-headed cowbirds. The other Galapagos-bobolink match, Plasmodium lineage C, was identical to two other sequences from birds sampled in California. We detected a close variant of lineage C in brown-headed cowbirds. Taken together, this pattern suggests that bobolinks became infected with lineage B on the South American end of their migratory range, and with lineage C on the North American breeding grounds. Overall, we detected more parasite lineages in bobolinks than in cowbirds. Galapagos Plasmodium had similar host breadth compared to the non-Galapagos haemosporidian lineages detected in bobolinks, brown-headed cowbirds, and other grassland species. This study highlights the utility of global haemosporidian data in the context of migratory bird-parasite connectivity. It is possible that migratory bobolinks

  15. Targeting cells of the myeloid lineage attenuates pain and disease progression in a prostate model of bone cancer.

    PubMed

    Thompson, Michelle L; Jimenez-Andrade, Juan M; Chartier, Stephane; Tsai, James; Burton, Elizabeth A; Habets, Gaston; Lin, Paul S; West, Brian L; Mantyh, Patrick W

    2015-09-01

    Tumor cells frequently metastasize to bone where they can generate cancer-induced bone pain (CIBP) that can be difficult to fully control using available therapies. Here, we explored whether PLX3397, a high-affinity small molecular antagonist that binds to and inhibits phosphorylation of colony-stimulating factor-1 receptor, the tyrosine-protein kinase c-Kit, and the FMS-like tyrosine kinase 3, can reduce CIBP. These 3 targets all regulate the proliferation and function of a subset of the myeloid cells including macrophages, osteoclasts, and mast cells. Preliminary experiments show that PLX3397 attenuated inflammatory pain after formalin injection into the hind paw of the rat. As there is an inflammatory component in CIBP, involving macrophages and osteoclasts, the effect of PLX3397 was explored in a prostate model of CIBP where skeletal pain, cancer cell proliferation, tumor metastasis, and bone remodeling could be monitored in the same animal. Administration of PLX3397 was initiated on day 14 after prostate cancer cell injection when the tumor was well established, and tumor-induced bone remodeling was first evident. Over the next 6 weeks, sustained administration of PLX3397 attenuated CIBP behaviors by approximately 50% and was equally efficacious in reducing tumor cell growth, formation of new tumor colonies in bone, and pathological tumor-induced bone remodeling. Developing a better understanding of potential effects that analgesic therapies have on the tumor itself may allow the development of therapies that not only better control the pain but also positively impact disease progression and overall survival in patients with bone cancer.

  16. Metabolic potential of a single cell belonging to one of the most abundant lineages in freshwater bacterioplankton

    PubMed Central

    Garcia, Sarahi L; McMahon, Katherine D; Martinez-Garcia, Manuel; Srivastava, Abhishek; Sczyrba, Alexander; Stepanauskas, Ramunas; Grossart, Hans-Peter; Woyke, Tanja; Warnecke, Falk

    2013-01-01

    Actinobacteria within the acI lineage are often numerically dominating in freshwater ecosystems, where they can account for >50% of total bacteria in the surface water. However, they remain uncultured to date. We thus set out to use single-cell genomics to gain insights into their genetic make-up, with the aim of learning about their physiology and ecological niche. A representative from the highly abundant acI-B1 group was selected for shotgun genomic sequencing. We obtained a draft genomic sequence in 75 larger contigs (sum=1.16 Mb), with an unusually low genomic G+C mol% (∼42%). Actinobacteria core gene analysis suggests an almost complete genome recovery. We found that the acI-B1 cell had a small genome, with a rather low percentage of genes having no predicted functions (∼15%) as compared with other cultured and genome-sequenced microbial species. Our metabolic reconstruction hints at a facultative aerobe microorganism with many transporters and enzymes for pentoses utilization (for example, xylose). We also found an actinorhodopsin gene that may contribute to energy conservation under unfavorable conditions. This project reveals the metabolic potential of a member of the global abundant freshwater Actinobacteria. PMID:22810059

  17. Statistical estimation of cell-cycle progression and lineage commitment in Plasmodium falciparum reveals a homogeneous pattern of transcription in ex vivo culture.

    PubMed

    Lemieux, Jacob E; Gomez-Escobar, Natalia; Feller, Avi; Carret, Celine; Amambua-Ngwa, Alfred; Pinches, Robert; Day, Felix; Kyes, Sue A; Conway, David J; Holmes, Chris C; Newbold, Chris I

    2009-05-05

    We have cultured Plasmodium falciparum directly from the blood of infected individuals to examine patterns of mature-stage gene expression in patient isolates. Analysis of the transcriptome of P. falciparum is complicated by the highly periodic nature of gene expression because small variations in the stage of parasite development between samples can lead to an apparent difference in gene expression values. To address this issue, we have developed statistical likelihood-based methods to estimate cell cycle progression and commitment to asexual or sexual development lineages in our samples based on microscopy and gene expression patterns. In cases subsequently matched for temporal development, we find that transcriptional patterns in ex vivo culture display little variation across patients with diverse clinical profiles and closely resemble transcriptional profiles that occur in vitro. These statistical methods, available to the research community, assist in the design and interpretation of P. falciparum expression profiling experiments where it is difficult to separate true differential expression from cell-cycle dependent expression. We reanalyze an existing dataset of in vivo patient expression profiles and conclude that previously observed discrete variation is consistent with the commitment of a varying proportion of the parasite population to the sexual development lineage.

  18. Statistical estimation of cell-cycle progression and lineage commitment in Plasmodium falciparum reveals a homogeneous pattern of transcription in ex vivo culture

    PubMed Central

    Lemieux, Jacob E.; Gomez-Escobar, Natalia; Feller, Avi; Carret, Celine; Amambua-Ngwa, Alfred; Pinches, Robert; Day, Felix; Kyes, Sue A.; Conway, David J.; Holmes, Chris C.; Newbold, Chris I.

    2009-01-01

    We have cultured Plasmodium falciparum directly from the blood of infected individuals to examine patterns of mature-stage gene expression in patient isolates. Analysis of the transcriptome of P. falciparum is complicated by the highly periodic nature of gene expression because small variations in the stage of parasite development between samples can lead to an apparent difference in gene expression values. To address this issue, we have developed statistical likelihood-based methods to estimate cell cycle progression and commitment to asexual or sexual development lineages in our samples based on microscopy and gene expression patterns. In cases subsequently matched for temporal development, we find that transcriptional patterns in ex vivo culture display little variation across patients with diverse clinical profiles and closely resemble transcriptional profiles that occur in vitro. These statistical methods, available to the research community, assist in the design and interpretation of P. falciparum expression profiling experiments where it is difficult to separate true differential expression from cell-cycle dependent expression. We reanalyze an existing dataset of in vivo patient expression profiles and conclude that previously observed discrete variation is consistent with the commitment of a varying proportion of the parasite population to the sexual development lineage. PMID:19376968

  19. Tracing the Tumor Lineage

    PubMed Central

    Navin, Nicholas E.; Hicks, James

    2010-01-01

    Defining the pathways through which tumors progress is critical to our understanding and treatment of cancer. We do not routinely sample patients at multiple time points during the progression of their disease, and thus our research is limited to inferring progression a posteriori from the examination of a single tumor sample. Despite this limitation, inferring progression is possible because the tumor genome contains a natural history of the mutations that occur during the formation of the tumor mass. There are two approaches to reconstructing a lineage of progression: (1) inter-tumor comparisons, and (2) intra-tumor comparisons. The inter-tumor approach consists of taking single samples from large collections of tumors and comparing the complexity of the genomes to identify early and late mutations. The intra-tumor approach involves taking multiple samples from individual heterogeneous tumors to compare divergent clones and reconstruct a phylogenetic lineage. Here we discuss how these approaches can be used to interpret the current models for tumor progression. We also compare data from primary and metastatic copy number profiles to shed light on the final steps of breast cancer progression. Finally, we discuss how recent technical advances in single cell genomics will herald a new era in understanding the fundamental basis of tumor heterogeneity and progression. PMID:20537601

  20. Ubiquitin: a potential cerebrospinal fluid progression marker in Huntington's disease.

    PubMed

    Vinther-Jensen, T; Simonsen, A H; Budtz-Jørgensen, E; Hjermind, L E; Nielsen, J E

    2015-10-01

    Finding early and dynamic biomarkers in Huntington's disease is a key to understanding the early pathology of Huntington's disease and potentially to tracking disease progression. This would benefit the future evaluation of potential neuroprotective and disease-modifying therapies, as well as aid in identifying an optimal time point for initiating a potential therapeutic intervention. This explorative proteomics study evaluated cerebrospinal fluid from 94 Huntington's disease gene-expansion carriers (39 premanifest and 55 manifest) and 27 Huntington's disease gene-expansion negative individuals using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry. Differences in peak intensity from SELDI-TOF spectra were evaluated. Levels of 10 peaks were statistically significantly different between manifest gene-expansion carriers and controls. One of them identified as ubiquitin was shown to be dependent on the Unified Huntington Disease Rating Scale Total Functional Capacity, a pseudo-measure of disease severity (P = 0.001), and the Symbol Digit Modalities Test (0.04) in manifest and CAG-age product score (P = 0.019) in all gene-expansion carriers. Multiple studies have shown that the ubiquitin-proteasome system is involved in Huntington's disease pathogenesis and understanding of this involvement may have therapeutic potential in humans. This is the first study on cerebrospinal fluid to confirm the involvement of the ubiquitin-proteasome system in Huntington's disease. Furthermore it is shown that ubiquitin increases with disease progression and CAG-age product score and therefore may have the potential as a Huntington's disease progression marker, also prior to motor onset. © 2015 EAN.

  1. Potential mechanisms underlying CDK5 related Osteosarcoma progression.

    PubMed

    Bao, Hang-Xing; Bi, Qing; Han, Yong; Zhao, Chen; Zou, Hai

    2017-05-01

    Identification of new prognostic biomarkers and therapeutic targets is of crucial importance for patients with osteosarcoma. Cyclin-dependent kinase 5 (CDK5) is overexpressed in several tumor types. However, the exact role CDK5 plays in osteosarcoma is still unknown. In this study, we explored the association between CDK5 expression and the prognosis of osteosarcoma patients using publicly available gene expression datasets. Potential molecular mechanisms underlying its pro-malignant role in cancer progression were also discussed. We demonstrated that tricarboxylic acid (TCA) cycle is activated while antigen presentation is repressed in patients with CDK5 overexpression and poor survival. This results indicated that sufficient energy production and tumor immune escape are important characteristics and potential therapeutic targets for this subgroup of osteosarcoma patients. Furthermore, several critical hub genes that are associated with CDK5 related osteosarcoma progression such as MELK were identified. This study discussed the pro-malignant role of CDK5 and potential mechanisms involved. Further preclinical and clinical studies to develop CDK5 based treatments are warranted.

  2. Developmental homologues: lineages and analysis.

    PubMed

    Trevarrow, B

    1998-01-01

    Developmental processes present several problems for identifying homologies and analyzing their evolution. Most evolutionary techniques approach homologies from either a taxonomic or a molecular perspective. Approaches that can accommodate many problems of developmental evolution are not well developed. Developmental process and evolutionary lineage complexity lead to a number of largely unappreciated conceptual and analytic problems. Developmental processes can evolve by duplication or diversification. Each process is in a hierarchy of super- and subprocesses. As they evolve, process components may be exchanged with or acquired by those of other processes. Because they do not fit into standard analytic procedures, these situations (including reticulate or reticulate-appearing lineages, partial homologues, iterative features, and the tracing of nontaxonomic and nonmolecular evolutionary lineages) are often ignored or considered illegitimate. Biology's disdain for the dichotomously branching phylogenetic lineages that are the basis of standard analytic approaches is ignored at the risk of making falsely negative homology evaluations. I will present an approach that can accommodate analyses of these situations. The use of nontaxonomic and nonmolecular lineages provides a way to structure comparisons between other entities, as taxonomic lineages structure comparisons among potential homologues. From an informational point of view, any entity (either a structure or process) with an evolutionary history is a potential homologue with a potential evolutionary lineage. Comparing lineages of interacting entities can reveal topological incongruences among them. Methods that identify reticulated taxonomic and molecular lineages should also apply to other lineages. Partial homologues, resulting from reticulated lineages, can be handled in several possible ways. Analytically, such an entity can be treated as a partial homologue, a novel feature, an independent sub-unit, or a

  3. Refining the phylum Chlorobi by resolving the phylogeny and metabolic potential of the representative of a deeply branching, uncultivated lineage

    DOE PAGES

    Hiras, Jennifer; Wu, Yu-Wei; Eichorst, Stephanie A.; ...

    2015-09-01

    Recent studies have expanded the phylum Chlorobi, demonstrating that the green sulfur bacteria (GSB), the original cultured representatives of the phylum, are a part of a larger lineage whose members have more diverse metabolic capabilities that overlap with members of the phylum Bacteroidetes. The 16S rRNA gene of an uncultivated clone, OPB56, distantly related to the phyla Chlorobi and Bacteroidetes, was recovered from Obsidian Pool in Yellowstone National Park; however, the detailed phylogeny and function of OPB56 and related clones have remained unknown. Culturing of thermophilic bacterial consortia from compost by adaptation to grow on ionic-liquid pretreated switchgrass provided amore » consortium in which one of the most abundant members, NICIL-2, clustered with OPB56-related clones. Phylogenetic analysis using the full-length 16S rRNA gene from NICIL-2 demonstrated that it was part of a monophyletic clade, referred to as OPB56, distinct from the Bacteroidetes and Chlorobi. A near complete draft genome ( > 95% complete) was recovered from metagenomic data from the culture adapted to grow on ionic-liquid pretreated switchgrass using an automated binning algorithm, and this genome was used for marker gene-based phylogenetic analysis and metabolic reconstruction. Six additional genomes related to NICIL-2 were reconstructed from metagenomic data sets obtained from thermal springs at Yellowstone National Park and Nevada Great Boiling Spring. In contrast to the 16S rRNA gene phylogenetic analysis, protein phylogenetic analysis was most consistent with the clustering of the Chlorobea, Ignavibacteria and OPB56 into a single phylum level clade. Metabolic reconstruction of NICIL-2 demonstrated a close linkage with the class Ignavibacteria and the family Rhodothermaceae, a deeply branching Bacteroidetes lineage. The combined phylogenetic and functional analysis of the NICIL-2 genome has refined the membership in the phylum Chlorobi and emphasized the close

  4. Dynamics of 5-carboxylcytosine during hepatic differentiation: potential general role for active demethylation by DNA repair in lineage specification.

    PubMed

    Lewis, Lara C; Lo, Peggy Cho Kiu; Foster, Jeremy M; Dai, Nan; Corrêa, Ivan R; Durczak, Paulina M; Duncan, Gary; Ramsawhook, Ashley; Aithal, Guruprasad Padur; Denning, Chris; Hannan, Nicholas R F; Ruzov, Alexey

    2017-03-07

    Patterns of DNA methylation (5-methylcytosine, 5mC) are rearranged during differentiation contributing to the regulation of cell type-specific gene expression. TET proteins oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be recognized and excised from DNA by thymine-DNA glycosylase (TDG) followed by the subsequent incorporation of unmodified cytosine into the abasic site via the base excision repair (BER) pathway. We previously demonstrated that 5caC accumulates during lineage specification of neural stem cells (NSCs) suggesting that such active demethylation pathway is operative in this system; however, it is still unknown if TDG/BER-dependent demethylation is utilized during other types of cellular differentiation. Here we analyze dynamics of the global levels of 5hmC and 5caC during differentiation of human pluripotent stem cells towards hepatic endoderm. We show that, similar to differentiating NSCs, 5caC transiently accumulates during hepatic differentiation. The levels of 5caC increase during specification of foregut, peak at the stage of hepatic endoderm commitment, and drop in differentiating cells concurrently with the onset of expression of alpha fetoprotein, a marker of committed hepatic progenitors. Moreover, we show that 5caC accumulates at promoter regions of several genes expressed during hepatic specification at differentiation stages corresponding to the beginning of their expression. Our data indicate that transient 5caC accumulation is a common feature of two different types (neural/glial and endoderm/hepatic) of cellular differentiation. This suggests that oxidation of 5mC may represent a general mechanism of rearrangement of 5mC profiles during lineage specification of somatic cells in mammals.

  5. Refining the phylum Chlorobi by resolving the phylogeny and metabolic potential of the representative of a deeply branching, uncultivated lineage.

    PubMed

    Hiras, Jennifer; Wu, Yu-Wei; Eichorst, Stephanie A; Simmons, Blake A; Singer, Steven W

    2016-04-01

    Recent studies have expanded the phylum Chlorobi, demonstrating that the green sulfur bacteria (GSB), the original cultured representatives of the phylum, are a part of a broader lineage whose members have more diverse metabolic capabilities that overlap with members of the phylum Bacteroidetes. The 16S rRNA gene of an uncultivated clone, OPB56, distantly related to the phyla Chlorobi and Bacteroidetes, was recovered from Obsidian Pool in Yellowstone National Park; however, the detailed phylogeny and function of OPB56 and related clones have remained unknown. Culturing of thermophilic bacterial consortia from compost by adaptation to grow on ionic-liquid pretreated switchgrass provided a consortium in which one of the most abundant members, NICIL-2, clustered with OPB56-related clones. Phylogenetic analysis using the full-length 16S rRNA gene from NICIL-2 demonstrated that it was part of a monophyletic clade, referred to as OPB56, distinct from the Bacteroidetes and Chlorobi. A near complete draft genome (>95% complete) was recovered from metagenomic data from the culture adapted to grow on ionic-liquid pretreated switchgrass using an automated binning algorithm, and this genome was used for marker gene-based phylogenetic analysis and metabolic reconstruction. Six additional genomes related to NICIL-2 were reconstructed from metagenomic data sets obtained from thermal springs at Yellowstone National Park and Nevada Great Boiling Spring. In contrast to the 16S rRNA gene phylogenetic analysis, protein phylogenetic analysis was most consistent with the clustering of the Chlorobea, Ignavibacteria and OPB56 into a single phylum level clade. Metabolic reconstruction of NICIL-2 demonstrated a close linkage with the class Ignavibacteria and the family Rhodothermaceae, a deeply branching Bacteroidetes lineage. The combined phylogenetic and functional analysis of the NICIL-2 genome has refined the membership in the phylum Chlorobi and emphasized the close evolutionary and

  6. Refining the phylum Chlorobi by resolving the phylogeny and metabolic potential of the representative of a deeply branching, uncultivated lineage

    SciTech Connect

    Hiras, Jennifer; Wu, Yu-Wei; Eichorst, Stephanie A.; Simmons, Blake A.; Singer, Steven W.

    2015-09-01

    Recent studies have expanded the phylum Chlorobi, demonstrating that the green sulfur bacteria (GSB), the original cultured representatives of the phylum, are a part of a larger lineage whose members have more diverse metabolic capabilities that overlap with members of the phylum Bacteroidetes. The 16S rRNA gene of an uncultivated clone, OPB56, distantly related to the phyla Chlorobi and Bacteroidetes, was recovered from Obsidian Pool in Yellowstone National Park; however, the detailed phylogeny and function of OPB56 and related clones have remained unknown. Culturing of thermophilic bacterial consortia from compost by adaptation to grow on ionic-liquid pretreated switchgrass provided a consortium in which one of the most abundant members, NICIL-2, clustered with OPB56-related clones. Phylogenetic analysis using the full-length 16S rRNA gene from NICIL-2 demonstrated that it was part of a monophyletic clade, referred to as OPB56, distinct from the Bacteroidetes and Chlorobi. A near complete draft genome ( > 95% complete) was recovered from metagenomic data from the culture adapted to grow on ionic-liquid pretreated switchgrass using an automated binning algorithm, and this genome was used for marker gene-based phylogenetic analysis and metabolic reconstruction. Six additional genomes related to NICIL-2 were reconstructed from metagenomic data sets obtained from thermal springs at Yellowstone National Park and Nevada Great Boiling Spring. In contrast to the 16S rRNA gene phylogenetic analysis, protein phylogenetic analysis was most consistent with the clustering of the Chlorobea, Ignavibacteria and OPB56 into a single phylum level clade. Metabolic reconstruction of NICIL-2 demonstrated a close linkage with the class Ignavibacteria and the family Rhodothermaceae, a deeply branching Bacteroidetes lineage. The combined phylogenetic and functional analysis of the NICIL-2 genome has refined the membership in the phylum Chlorobi and emphasized the close evolutionary and

  7. Refining the phylum Chlorobi by resolving the phylogeny and metabolic potential of the representative of a deeply branching, uncultivated lineage

    PubMed Central

    Hiras, Jennifer; Wu, Yu-Wei; Eichorst, Stephanie A; Simmons, Blake A; Singer, Steven W

    2016-01-01

    Recent studies have expanded the phylum Chlorobi, demonstrating that the green sulfur bacteria (GSB), the original cultured representatives of the phylum, are a part of a broader lineage whose members have more diverse metabolic capabilities that overlap with members of the phylum Bacteroidetes. The 16S rRNA gene of an uncultivated clone, OPB56, distantly related to the phyla Chlorobi and Bacteroidetes, was recovered from Obsidian Pool in Yellowstone National Park; however, the detailed phylogeny and function of OPB56 and related clones have remained unknown. Culturing of thermophilic bacterial consortia from compost by adaptation to grow on ionic-liquid pretreated switchgrass provided a consortium in which one of the most abundant members, NICIL-2, clustered with OPB56-related clones. Phylogenetic analysis using the full-length 16S rRNA gene from NICIL-2 demonstrated that it was part of a monophyletic clade, referred to as OPB56, distinct from the Bacteroidetes and Chlorobi. A near complete draft genome (>95% complete) was recovered from metagenomic data from the culture adapted to grow on ionic-liquid pretreated switchgrass using an automated binning algorithm, and this genome was used for marker gene-based phylogenetic analysis and metabolic reconstruction. Six additional genomes related to NICIL-2 were reconstructed from metagenomic data sets obtained from thermal springs at Yellowstone National Park and Nevada Great Boiling Spring. In contrast to the 16S rRNA gene phylogenetic analysis, protein phylogenetic analysis was most consistent with the clustering of the Chlorobea, Ignavibacteria and OPB56 into a single phylum level clade. Metabolic reconstruction of NICIL-2 demonstrated a close linkage with the class Ignavibacteria and the family Rhodothermaceae, a deeply branching Bacteroidetes lineage. The combined phylogenetic and functional analysis of the NICIL-2 genome has refined the membership in the phylum Chlorobi and emphasized the close evolutionary and

  8. Understanding stress in the healthy animal - potential paths for progress.

    PubMed

    Romero, L Michael; Platts, Steven H; Schoech, Stephan J; Wada, Haruka; Crespi, Erica; Martin, Lynn B; Buck, C Loren

    2015-01-01

    Although stress is usually associated with disease, the physiological and behavioral responses to stressors are critical mechanisms of resilience for healthy organisms. A recent workshop comprised of researchers who study healthy humans and both free-living and captive non-human animals identified a number of key roadblocks that are impeding progress in understanding how stress responses integrate into the normal physiology of an animal. These include the lack of: (1) an unambiguous definition of a stress phenotype; (2) a robust biomarker, or suite of biomarkers, to indicate that phenotype; (3) theoretical and quantitative models to predict how humans and other animals will react to stressors; (4) a comprehensive understanding of how individual variability in stress responses arise and (5) an understanding of the transitions between acute and chronic stress responses. Collectively, these deficiencies impair our ability to both assess the physiological status of individuals and develop procedures and techniques to reverse the effects elicited by chronic stress before they become pathological. Workshop participants also identified a number of potential approaches to facilitate progress on these problems. They include: (1) increased use of mathematical models to provide quantitative predictions; (2) use of network theory to expose emergent properties not predicted from traditional approaches; (3) development and deployment of improved sensor technology that will allow long-term, dynamic, non-invasive, multi-factor measurements of suites of stress mediators and (4) the recruitment of scientists with diverse skill sets, such as engineers, bioinformaticians, etc.; and (5) the training of young scientists in the multidisciplinary study of stress. Incorporating these approaches in new research should reinvigorate the study of stress and stimulate progress in understanding both how healthy humans cope with stressors and how other animals, including free-living animals, cope

  9. Metamorphic III–V Solar Cells: Recent Progress and Potential

    SciTech Connect

    Garcia, Ivan; France, Ryan M.; Geisz, John F.; McMahon, William E.; Steiner, Myles A.; Johnston, Steve; Friedman, Daniel J.

    2016-01-01

    Inverted metamorphic multijunction solar cells have been demonstrated to be a pathway to achieve the highest photovoltaic (PV) conversion efficiencies. Attaining high-quality lattice-mismatched (metamorphic) semiconductor devices is challenging. However, recent improvements to compositionally graded buffer epitaxy and junction structures have led to the achievement of high-quality metamorphic solar cells exhibiting internal luminescence efficiencies over 90%. For this high material quality, photon recycling is significant, and therefore, the optical environment of the solar cell becomes important. In this paper, we first present recent progress and performance results for 1- and 0.7-eV GaInAs solar cells grown on GaAs substrates. Then, an electrooptical model is used to assess the potential performance improvements in current metamorphic solar cells under different realizable design scenarios. The results show that the quality of 1-eV subcells is such that further improving its electronic quality does not produce significant Voc increases in the four-junction inverted metamorphic subcells, unless a back reflector is used to enhance photon recycling, which would significantly complicate the structure. Conversely, improving the electronic quality of the 0.7-eV subcell would lead to significant Voc boosts, driving the progress of four-junction inverted metamorphic solar cells.

  10. Software for analysing multifocal visual evoked potential signal latency progression.

    PubMed

    de Santiago, L; Klistorner, A; Ortiz, M; Fernández-Rodríguez, A J; Rodríguez Ascariz, J M; Barea, R; Miguel-Jiménez, J M; Boquete, L

    2015-04-01

    This paper describes a new non-commercial software application (mfVEP(2)) developed to process multifocal visual-evoked-potential (mfVEP) signals in latency (monocular and interocular) progression studies. The software performs analysis by cross-correlating signals from the same patients. The criteria applied by the software include best channels, signal window, cross-correlation limits and signal-to-noise ratio (SNR). Software features include signal display comparing different tests and groups of sectors (quadrants, rings and hemispheres). The software's performance and capabilities are demonstrated on the results obtained from a patient with acute optic neuritis who underwent 9 follow-up mfVEP tests. Numerical values and graphics are presented and discussed for this case. The authors present a software application used to study progression in mfVEP signals. It is also useful in research projects designed to improve mfVEP techniques. This software makes it easier for users to manage the signals and allows them to choose various ways of selecting signals and representing results. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Cytokines: Roles in atherosclerosis disease progression and potential therapeutic targets

    PubMed Central

    Moss, Joe W. E.; Ramji, Dipak P.

    2017-01-01

    Atherosclerosis, the primary cause of cardiovascular disease (CVD), is a chronic inflammatory disorder in the walls of medium and large arteries. CVD is currently responsible for about one in three global deaths and this is expected to rise in the future due to an increase in the prevalence of obesity and diabetes. Current therapies for atherosclerosis mainly modulate lipid homeostasis and whilst successful at reducing the risk of a CVD-related death, they are associated with considerable residual risk and various side effects. There is therefore a need for alternative therapies aimed at regulating inflammation in order to reduce atherogenesis. This review will highlight the key role cytokines play during disease progression as well as potential therapeutic strategies to target them. PMID:27357616

  12. Bacillus anthracis Diversity and Geographic Potential across Nigeria, Cameroon and Chad: Further Support of a Novel West African Lineage.

    PubMed

    Blackburn, Jason K; Odugbo, Moses Ode; Van Ert, Matthew; O'Shea, Bob; Mullins, Jocelyn; Perreten, Vincent; Perrenten, Vincent; Maho, Angaya; Hugh-Jones, Martin; Hadfield, Ted

    2015-01-01

    Zoonoses, diseases affecting both humans and animals, can exert tremendous pressures on human and veterinary health systems, particularly in resource limited countries. Anthrax is one such zoonosis of concern and is a disease requiring greater public health attention in Nigeria. Here we describe the genetic diversity of Bacillus anthracis in Nigeria and compare it to Chad, Cameroon and a broader global dataset based on the multiple locus variable number tandem repeat (MLVA-25) genetic typing system. Nigerian B. anthracis isolates had identical MLVA genotypes and could only be resolved by measuring highly mutable single nucleotide repeats (SNRs). The Nigerian MLVA genotype was identical or highly genetically similar to those in the neighboring countries, confirming the strains belong to this unique West African lineage. Interestingly, sequence data from a Nigerian isolate shares the anthrose deficient genotypes previously described for strains in this region, which may be associated with vaccine evasion. Strains in this study were isolated over six decades, indicating a high level of temporal strain stability regionally. Ecological niche models were used to predict the geographic distribution of the pathogen for all three countries. We describe a west-east habitat corridor through northern Nigeria extending into Chad and Cameroon. Ecological niche models and genetic results show B. anthracis to be ecologically established in Nigeria. These findings expand our understanding of the global B. anthracis population structure and can guide regional anthrax surveillance and control planning.

  13. Bacillus anthracis Diversity and Geographic Potential across Nigeria, Cameroon and Chad: Further Support of a Novel West African Lineage

    PubMed Central

    Blackburn, Jason K.; Odugbo, Moses Ode; Van Ert, Matthew; O’Shea, Bob; Mullins, Jocelyn; Perrenten, Vincent; Maho, Angaya; Hugh-Jones, Martin; Hadfield, Ted

    2015-01-01

    Zoonoses, diseases affecting both humans and animals, can exert tremendous pressures on human and veterinary health systems, particularly in resource limited countries. Anthrax is one such zoonosis of concern and is a disease requiring greater public health attention in Nigeria. Here we describe the genetic diversity of Bacillus anthracis in Nigeria and compare it to Chad, Cameroon and a broader global dataset based on the multiple locus variable number tandem repeat (MLVA-25) genetic typing system. Nigerian B. anthracis isolates had identical MLVA genotypes and could only be resolved by measuring highly mutable single nucleotide repeats (SNRs). The Nigerian MLVA genotype was identical or highly genetically similar to those in the neighboring countries, confirming the strains belong to this unique West African lineage. Interestingly, sequence data from a Nigerian isolate shares the anthrose deficient genotypes previously described for strains in this region, which may be associated with vaccine evasion. Strains in this study were isolated over six decades, indicating a high level of temporal strain stability regionally. Ecological niche models were used to predict the geographic distribution of the pathogen for all three countries. We describe a west-east habitat corridor through northern Nigeria extending into Chad and Cameroon. Ecological niche models and genetic results show B. anthracis to be ecologically established in Nigeria. These findings expand our understanding of the global B. anthracis population structure and can guide regional anthrax surveillance and control planning. PMID:26291625

  14. Multi-lineage differentiation and angiogenesis potentials of pigmented villonodular synovitis derived mesenchymal stem cells--pathological implication.

    PubMed

    Chiang, En-Rung; Ma, Hsiao-Li; Wang, Jung-Pan; Liu, Chien-Lin; Chen, Tain-Hsiung; Hung, Shih-Chieh

    2016-03-01

    Pigmented villonodular synovitis (PVNS) is a benign tissue proliferation characterized by its hyper-vascularity within the lesion. The true etiology and cell source of this disease entity still remain unclear. Mesenchymal stem cells (MSCs) exist in various tissues of human body. However, it has not been clarified whether MSCs could be isolated from tissue of PVNS. Here, we isolated MSCs from PVNS (PVNS-SCs), and by comparing to the MSCs from normal synovium (Syn-SCs) of the same individual, we investigated whether PVNS-SCs differed in the capacity for multi-differentiation and inducing angiogenesis. We first demonstrated that PVNS-SCs existed in the lesion of PVNS of three individuals. Moreover, we showed PVNS-SCs had better osteogenic differentiation potential than Syn-SCs, whereas Syn-SCs had better capacity for adipogenic and chondrogenic differentiation. By genome-wide analysis of gene expression profile using a complementary DNA microarray and comparing to Syn-SCs, we identified in PVNS-SCs a distinct gene expression profile characterized by up-regulation of genes involved in angiogenesis. In vitro and in vivo studies further confirmed that PVNS-SCs had better capacities for promoting angiogenesis. In summary, the identification of PVNS-SCs in PVNS tissue and their distinct angiogenic potential may help elucidate the underlying etiology of this disease. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  15. RNA in situ hybridization characterization of non-enzymatic derived bovine intervertebral disc cell lineages suggests progenitor cell potential.

    PubMed

    Kraus, Petra; Yerden, Rachel; Kocsis, Victoria; Lufkin, Thomas

    2017-03-01

    Degeneration of the intervertebral disc (IVD) is a meritorious target for therapeutic cell based regenerative medicine approaches, however, controversy over what defines the precise identity of mature IVD cells and lack of single cell based quality control measures is of concern. Bos taurus and human IVDs are histologically more similar than is Mus musculus. The mature bovine IVD is well suited as model system for technology development to be translated into therapeutic cell based regenerative medicine applications. We present a reproducible non-enzymatic protocol to isolate cell progenitor populations of three distinct areas of the mature bovine IVD. Bovine specific RNA probes were validated in situ and employed to assess fate changes, heterogeneity, stem cell characteristics and differentiation potential of the cultures. Quality control measures with single cell resolution like RNA in situ hybridization to assess culture heterogeneity (PISH) followed by optimization of culture conditions could be translated to human IVD cell culture to increase the safety of cell based regenerative medicine.

  16. [Non-empirical interatomic potentials for transition metals]. Progress report

    SciTech Connect

    Not Available

    1993-05-01

    The report is divided into the following sections: potential-energy functions for d-band metals, potential-energy functions for aluminides and quasicrystals, electronic structure of complex structures and quasicrystals, potential-energy functions in transition-metal oxides, applications to defect structure and mechanical properties, and basic theory of interatomic potentials.

  17. In vitro high-capacity assay to quantify the clonal heterogeneity in trilineage potential of mesenchymal stem cells reveals a complex hierarchy of lineage commitment.

    PubMed

    Russell, Katie C; Phinney, Donald G; Lacey, Michelle R; Barrilleaux, Bonnie L; Meyertholen, Kristin E; O'Connor, Kim C

    2010-04-01

    In regenerative medicine, bone marrow is a promising source of mesenchymal stem cells (MSCs) for a broad range of cellular therapies. This research addresses a basic prerequisite to realize the therapeutic potential of MSCs by developing a novel high-capacity assay to quantify the clonal heterogeneity in potency that is inherent to MSC preparations. The assay utilizes a 96-well format to (1) classify MSCs according to colony-forming efficiency as a measure of proliferation capacity and trilineage potential to exhibit adipo-, chondro-, and osteogenesis as a measure of multipotency and (2) preserve a frozen template of MSC clones of known potency for future use. The heterogeneity in trilineage potential of normal bone marrow MSCs is more complex than previously reported: all eight possible categories of trilineage potential were detected. In this study, the average colony-forming efficiency of MSC preparations was 55-62%, and tripotent MSCs accounted for nearly 50% of the colony-forming cells. The multiple phenotypes detected in this study infer a more convoluted hierarchy of lineage commitment than described in the literature. Greater cell amplification, colony-forming efficiency, and colony diameter for tri- versus unipotent clones suggest that MSC proliferation may be a function of potency. CD146 may be a marker of multipotency, with approximately 2-fold difference in mean fluorescence intensity between tri- and unipotent clones. The significance of these findings is discussed in the context of the efficacy of MSC therapies. The in vitro assay described herein will likely have numerous applications given the importance of heterogeneity to the therapeutic potential of MSCs.

  18. Population genetic structure of Phytophthora cinnamomi associated with avocado in California and the discovery of a potentially recent introduction of a new clonal lineage.

    PubMed

    Pagliaccia, D; Pond, E; McKee, B; Douhan, G W

    2013-01-01

    Phytophthora root rot (PRR) of avocado (Persea americana), caused by Phytophthora cinnamomi, is the most serious disease of avocado worldwide. Previous studies have determined that this pathogen exhibits a primarily clonal reproductive mode but no population level studies have been conducted in the avocado-growing regions of California. Therefore, we used amplified fragment length polymorphism based on 22 polymorphic loci and mating type to investigate pathogen diversity from 138 isolates collected in 2009 to 2010 from 15 groves from the Northern and Southern avocado-growing regions. Additional isolates collected from avocado from 1966 to 2007 as well as isolates from other countries and hosts were also used for comparative purposes. Two distinct clades of A2 mating-type isolates from avocado were found based on neighbor joining analysis; one clade contained both newer and older collections from Northern and Southern California, whereas the other clade only contained isolates collected in 2009 and 2010 from Southern California. A third clade was also found that only contained A1 isolates from various hosts. Within the California population, a total of 16 genotypes were found with only one to four genotypes identified from any one location. The results indicate significant population structure in the California avocado P. cinnamomi population, low genotypic diversity consistent with asexual reproduction, potential evidence for the movement of clonal genotypes between the two growing regions, and a potential introduction of a new clonal lineage into Southern California.

  19. Every Newborn: progress, priorities, and potential beyond survival.

    PubMed

    Lawn, Joy E; Blencowe, Hannah; Oza, Shefali; You, Danzhen; Lee, Anne C C; Waiswa, Peter; Lalli, Marek; Bhutta, Zulfiqar; Barros, Aluisio J D; Christian, Parul; Mathers, Colin; Cousens, Simon N

    2014-07-12

    In this Series paper, we review trends since the 2005 Lancet Series on Neonatal Survival to inform acceleration of progress for newborn health post-2015. On the basis of multicountry analyses and multi-stakeholder consultations, we propose national targets for 2035 of no more than 10 stillbirths per 1000 total births, and no more than 10 neonatal deaths per 1000 livebirths, compatible with the under-5 mortality targets of no more than 20 per 1000 livebirths. We also give targets for 2030. Reduction of neonatal mortality has been slower than that for maternal and child (1-59 months) mortality, slowest in the highest burden countries, especially in Africa, and reduction is even slower for stillbirth rates. Birth is the time of highest risk, when more than 40% of maternal deaths (total about 290,000) and stillbirths or neonatal deaths (5·5 million) occur every year. These deaths happen rapidly, needing a rapid response by health-care workers. The 2·9 million annual neonatal deaths worldwide are attributable to three main causes: infections (0·6 million), intrapartum conditions (0·7 million), and preterm birth complications (1·0 million). Boys have a higher biological risk of neonatal death, but girls often have a higher social risk. Small size at birth--due to preterm birth or small-for-gestational-age (SGA), or both--is the biggest risk factor for more than 80% of neonatal deaths and increases risk of post-neonatal mortality, growth failure, and adult-onset non-communicable diseases. South Asia has the highest SGA rates and sub-Saharan Africa has the highest preterm birth rates. Babies who are term SGA low birthweight (10·4 million in these regions) are at risk of stunting and adult-onset metabolic conditions. 15 million preterm births, especially of those younger than 32 weeks' gestation, are at the highest risk of neonatal death, with ongoing post-neonatal mortality risk, and important risk of long-term neurodevelopmental impairment, stunting, and non

  20. QCD at nonzero chemical potential: Recent progress on the lattice

    SciTech Connect

    Aarts, Gert; Jäger, Benjamin; Attanasio, Felipe; Seiler, Erhard; Sexty, Dénes; Stamatescu, Ion-Olimpiu

    2016-01-22

    We summarise recent progress in simulating QCD at nonzero baryon density using complex Langevin dynamics. After a brief outline of the main idea, we discuss gauge cooling as a means to control the evolution. Subsequently we present a status report for heavy dense QCD and its phase structure, full QCD with staggered quarks, and full QCD with Wilson quarks, both directly and using the hopping parameter expansion to all orders.

  1. Establishment of a GM-CSF-dependent megakaryoblastic cell line with the potential to differentiate into an eosinophilic lineage in response to retinoic acids.

    PubMed

    Ma, F; Koike, K; Higuchi, T; Kinoshita, T; Takeuchi, K; Mwamtemi, H H; Sawai, N; Kamijo, T; Shiohara, M; Horie, S; Kawa, S; Sasaki, Y; Hidaka, E; Yamagami, O; Yamashita, T; Koike, T; Ishii, E; Komiyama, A

    1998-02-01

    We recently established a human granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent cell line (HML) from colony-constituent cells grown by peripheral blood cells of a patient with acute megakaryoblastic leukaemia. The HML cells possessed megakaryocytic features, as determined by cytochemical, electron microscopic and flow cytometric analysis. In the present study we examined the effects of retinoic acid (RA) on the development of HML cells. All-trans-RA, 13-cis-RA and 9-cis-RA at 10(-8) mol/l to 10(-5) mol/l inhibited the GM-CSF-dependent cell growth. Some of the RA-treated cells contained prominent azurophilic granules and were positive for peroxidase. They also reacted with Biebrich scarlet, Luxol fast blue and a monoclonal antibody against eosinophil peroxidase. In addition, exposure to RA increased the frequency and the intensity of major basic protein-positive cells. However, eosinophil-derived neurotoxin and eosinophil cationic protein were not detected or were only detected at a low level in the lysates of the HML cells treated with RA. Although IL-5 alone could not stimulate cell growth, the addition of IL-5 to the cultures containing stem cell factor + all-trans-RA was required for the expression of the eosinophilic phenotype. These results suggest that the HML cell line is a megakaryoblastic cell line with the potential to differentiate into the eosinophilic lineage. HML cells may be a useful model for elucidating the eosinophilic differentiation programme.

  2. Rare or rarely detected? Ceraceosorus guamensis sp. nov.: a second described species of Ceraceosorales and the potential for underdetection of rare lineages with common sampling techniques.

    PubMed

    Kijpornyongpan, Teeratas; Catherine Aime, M

    2016-08-01

    Ceraceosorales is a monotypic order in Ustilaginomycotina. Its namesake, Ceraceosorus bombacis, was described as a phytopathogen of Bombax ceiba in India. In this study, we describe Ceraceosorus guamensis sp. nov., collected on the South Pacific island of Guam, which appears to represent the second isolation of any member of this order in over 40 years. Ceraceosorus species are monokaryotic and filamentous in culture, producing conidia on potato dextrose agar. However, both species behave yeast-like when cultured on corn meal agar. The internal transcribed spacer (ITS) region (spanning the ITS1-5.8S-ITS2) in both species of Ceraceosorus is highly heterogeneous containing multiple disparate copies that can vary intragenomically by up to 3.5 %. Moreover, this region could not be amplified using the fungal ITS primers most frequently used for culture-independent methods of assessing fungal biodiversity. This fact, combined with the extremely slow growth rates on commonly employed media, may indicate that members of this lineage are potentially underdetected by current sampling methods.

  3. [Progress and potential applications of induced pluripotent stem cell technology].

    PubMed

    Wu, Cui-Ling; Zhang, Yu-Ming

    2014-08-01

    Differentiated somatic cells can be reprogrammed to a pluripotent state through ectopic expression of specific transcription factors. These reprogrammed cells, which were designated as induced pluripotent stem (iPS) cells, are detected to exhibit unlimited self-renewal capacity and pluripotency. This breakthrough in stem cell research provides a powerful and novel tool for the studies on pathogenesis of diseases, reprogramming mechanism and development of new therapies. For this reason, the iPSC technology has currently become one of the hot topics in stem cells research. Recently, major progress in this field has been achieved: initially, researchers succeeded in inducing the reprogramming of mouse fibroblasts by retroviral transduction of four specific transcription factors; in succession, the accelerated development of iPSC technology by employing non-integrating viral vectors, non-viral vectors or removing the introduced foreign genes via gene knock-out has ensured the yields of much safer iPSC; meanwhile, some researches discovered the proofs that a number of micro molecular compounds were potent in accelerating the cellular reprogramming. For a prospect, iPSC are highly promising for regenerative medicine, disease modeling and drug screening. In this review, the recent progress in the generation of iPSC, prospects of their possible clinical applications and problems in the iPSC research are summarized and discussed.

  4. [Evoked potentials in multiple sclerosis: progress or stagnation?].

    PubMed

    Zakrzewska-Pniewska, Beata

    2010-01-01

    Evoked potentials (EPs): visual (VEP), short latency somatosensory (SSEP), brainstem auditory (BAEP) and motor evoked potentials (MEP) can provide objective evidence of central nervous system (CNS) abnormalities that complement the clinical and radiological findings in establishing the diagnosis of multiple sclerosis (MS). The EPs studies may also improve the sensitivity of MS diagnosis. Abnormal EPs can provide evidence for pathology to satisfy the diagnostic criteria of lesions disseminated in space in the absence of clinical findings and for a relapse in patient with new symptoms but no changes on clinical examination. Since magnetic resonance imaging (MRI) plays a critical role in the current diagnostic criteria of MS, it is important to consider the relationship between EPs and MRI. Evoked potentials provide neurophysiological information about CNS functional abnormalities, while MRI provide anatomical localisation of CNS lesions. VEPs are even more sensitive than MRI in detecting acute and old pre-chiasmatic optic nerve lesions. The revised diagnostic criteria for MS include the provision for an abnormal VEP to serve as a diagnostic factor. Rarely, patients with spinal cord pathology may have an abnormal SEP or MEP without an observed lesions on MRI. Combining multimodality evoked potentials and MRI results in the greatest diagnostic yield. More widespread use of multimodality EPs in combination with MRI might lead to better outcome measurement in clinical trials as well as in open therapeutic approach. Thought EPs have some limitations, they remain an important factor in the diagnosis and clinical management of MS patients.

  5. Adaptive coded aperture imaging: progress and potential future applications

    NASA Astrophysics Data System (ADS)

    Gottesman, Stephen R.; Isser, Abraham; Gigioli, George W., Jr.

    2011-09-01

    Interest in Adaptive Coded Aperture Imaging (ACAI) continues to grow as the optical and systems engineering community becomes increasingly aware of ACAI's potential benefits in the design and performance of both imaging and non-imaging systems , such as good angular resolution (IFOV), wide distortion-free field of view (FOV), excellent image quality, and light weight construct. In this presentation we first review the accomplishments made over the past five years, then expand on previously published work to show how replacement of conventional imaging optics with coded apertures can lead to a reduction in system size and weight. We also present a trade space analysis of key design parameters of coded apertures and review potential applications as replacement for traditional imaging optics. Results will be presented, based on last year's work of our investigation into the trade space of IFOV, resolution, effective focal length, and wavelength of incident radiation for coded aperture architectures. Finally we discuss the potential application of coded apertures for replacing objective lenses of night vision goggles (NVGs).

  6. Cell Expansion During Directed Differentiation of Stem Cells Toward the Hepatic Lineage.

    PubMed

    Raju, Ravali; Chau, David; Cho, Dong Seong; Park, Yonsil; Verfaillie, Catherine M; Hu, Wei-Shou

    2017-02-15

    The differentiation of human pluripotent stem cells toward the hepatocyte lineage can potentially provide an unlimited source of functional hepatocytes for transplantation and extracorporeal bioartificial liver applications. It is anticipated that the quantities of cells needed for these applications will be in the order of 10(9)-10(10) cells, because of the size of the liver. An ideal differentiation protocol would be to enable directed differentiation to the hepatocyte lineage with simultaneous cell expansion. We introduced a cell expansion stage after the commitment of human embryonic stem cells to the endodermal lineage, to allow for at least an eightfold increase in cell number, with continuation of cell maturation toward the hepatocyte lineage. The progressive changes in the transcriptome were measured by expression array, and the expression dynamics of certain lineage markers was measured by mass cytometry during the differentiation and expansion process. The findings revealed that while cells were expanding they were also capable of progressing in their differentiation toward the hepatocyte lineage. In addition, our transcriptome, protein and functional studies, including albumin secretion, drug-induced CYP450 expression and urea production, all indicated that the hepatocyte-like cells obtained with or without cell expansion are very similar. This method of simultaneous cell expansion and hepatocyte differentiation should facilitate obtaining large quantities of cells for liver cell applications.

  7. Residential energy efficiency: Progress since 1973 and future potential

    NASA Astrophysics Data System (ADS)

    Rosenfeld, Arthur H.

    1985-11-01

    Today's 85 million U.S. homes use 100 billion of fuel and electricity (1150/home). If their energy intensity (resource energy/ft2) were still frozen at 1973 levels, they would use 18% more. With well-insulated houses, need for space heat is vanishing. Superinsulated Saskatchewan homes spend annually only 270 for space heat, 150 for water heat, and 400 for appliances, yet they cost only 2000±1000 more than conventional new homes. The concept of Cost of Conserved Energy (CCE) is used to rank conservation technologies for existing and new homes and appliances, and to develop supply curves of conserved energy and a least cost scenario. Calculations are calibrated with the BECA and other data bases. By limiting investments in efficiency to those whose CCE is less than current fuel and electricity prices, the potential residential plus commercial energy use in 2000 AD drops to half of that estimated by DOE, and the number of power plants needed drops by 200. For the whole buildings sector, potential savings by 2000 are 8 Mbod (worth 50B/year), at an average CCE of 10/barrel.

  8. Bacteria Inside Semiconductors as Potential Sensor Elements: Biochip Progress

    PubMed Central

    Sah, Vasu R.; Baier, Robert E.

    2014-01-01

    It was discovered at the beginning of this Century that living bacteria—and specifically the extremophile Pseudomonas syzgii—could be captured inside growing crystals of pure water-corroding semiconductors—specifically germanium—and thereby initiated pursuit of truly functional “biochip-based” biosensors. This observation was first made at the inside ultraviolet-illuminated walls of ultrapure water-flowing semiconductor fabrication facilities (fabs) and has since been, not as perfectly, replicated in simpler flow cell systems for chip manufacture, described here. Recognizing the potential importance of these adducts as optical switches, for example, or probes of metabolic events, the influences of the fabs and their components on the crystal nucleation and growth phenomena now identified are reviewed and discussed with regard to further research needs. For example, optical beams of current photonic circuits can be more easily modulated by integral embedded cells into electrical signals on semiconductors. Such research responds to a recently published Grand Challenge in ceramic science, designing and synthesizing oxide electronics, surfaces, interfaces and nanoscale structures that can be tuned by biological stimuli, to reveal phenomena not otherwise possible with conventional semiconductor electronics. This short review addresses only the fabrication facilities' features at the time of first production of these potential biochips. PMID:24961215

  9. Bacteria inside semiconductors as potential sensor elements: biochip progress.

    PubMed

    Sah, Vasu R; Baier, Robert E

    2014-06-24

    It was discovered at the beginning of this Century that living bacteria-and specifically the extremophile Pseudomonas syzgii-could be captured inside growing crystals of pure water-corroding semiconductors-specifically germanium-and thereby initiated pursuit of truly functional "biochip-based" biosensors. This observation was first made at the inside ultraviolet-illuminated walls of ultrapure water-flowing semiconductor fabrication facilities (fabs) and has since been, not as perfectly, replicated in simpler flow cell systems for chip manufacture, described here. Recognizing the potential importance of these adducts as optical switches, for example, or probes of metabolic events, the influences of the fabs and their components on the crystal nucleation and growth phenomena now identified are reviewed and discussed with regard to further research needs. For example, optical beams of current photonic circuits can be more easily modulated by integral embedded cells into electrical signals on semiconductors. Such research responds to a recently published Grand Challenge in ceramic science, designing and synthesizing oxide electronics, surfaces, interfaces and nanoscale structures that can be tuned by biological stimuli, to reveal phenomena not otherwise possible with conventional semiconductor electronics. This short review addresses only the fabrication facilities' features at the time of first production of these potential biochips.

  10. Lineage sorting in apes.

    PubMed

    Mailund, Thomas; Munch, Kasper; Schierup, Mikkel Heide

    2014-01-01

    Recombination allows different parts of the genome to have different genealogical histories. When a species splits in two, allelic lineages sort into the two descendant species, and this lineage sorting varies along the genome. If speciation events are close in time, the lineage sorting process may be incomplete at the second speciation event and lead to gene genealogies that do not match the species phylogeny. We review different recent approaches to model lineage sorting along the genome and show how it is possible to learn about population sizes, natural selection, and recombination rates in ancestral species from application of these models to genome alignments of great ape species.

  11. Cytosolic phospholipase A2 (cPLA2) IVA as a potential signature molecule in cigarette smoke condensate induced pathologies in alveolar epithelial lineages.

    PubMed

    Yadav, Subodh K; Sharma, Sanjeev K; Farooque, Abdullah; Kaushik, Gaurav; Kaur, Balwinder; Pathak, Chander M; Dwarakanath, Bilikere S; Khanduja, Krishan L

    2016-08-15

    Smoking is one of the leading causes of millions of deaths worldwide. During cigarette smoking, most affected and highly exposed cells are the alveolar epithelium and generated oxidative stress in these cells leads to death and damage. Several studies suggested that oxidative stress causes membrane remodeling via Phospholipase A2s but in the case of cigarette smokers, mechanistically study is not yet fully defined. In view of present perspective, we evaluated the involvement of cytosolic phospholipase A2 (cPLA2) IVA as therapeutic target in cigarette smoke induced pathologies in transformed type I and type II alveolar epithelial cells. Transformed type I (WI26) and type II (A549) alveolar epithelial cells were used for the present study. Cigarette smoke condensate (CSC) was prepared from most commonly used cigarette (Gold Flake with filter) by the Indian population. CSC-induced molecular changes were evaluated through cell viability using MTT assay, reactive oxygen species (ROS) measurement using 2,7 dichlorodihydrofluorescin diacetate (DCFH-DA), cell membrane integrity using fluorescein diacetate (FDA) and ethidium bromide (EtBr) staining, super oxide dismutase (SOD) levels, cPLA2 activity and molecular involvement of specific cPLA2s at selected 24 h time period. CSC-induced response on both type of epithelial cells shown significantly reduction in cell viability, declined membrane integrity, with differential escalation of ROS levels in the range of 1.5-15 folds and pointedly increased cPLA2 activity (p < 0.05). Likewise, we observed distinction antioxidant potential in these two types of lineages as type I cells had considerably higher SOD levels when compared to type II cells (p < 0.05). Further molecular expression of all cPLA2s increased significantly in a dose dependent manner, specifically cytosolic phospholipase A2 IVA with maximum manifestation of 3.8 folds. Interestingly, CSC-induced ROS levels and cPLA2s expression were relatively higher in A

  12. The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis

    PubMed Central

    Storoni, Mithu; Plant, Gordon T.

    2015-01-01

    Until recently, multiple sclerosis has been viewed as an entirely inflammatory disease without acknowledgment of the significant neurodegenerative component responsible for disease progression and disability. This perspective is being challenged by observations of a dissociation between inflammation and neurodegeneration where the neurodegenerative component may play a more significant role in disease progression. In this review, we explore the relationship between mitochondrial dysfunction and neurodegeneration in multiple sclerosis. We review evidence that the ketogenic diet can improve mitochondrial function and discuss the potential of the ketogenic diet in treating progressive multiple sclerosis for which no treatment currently exists. PMID:26839705

  13. Myocardial Lineage Development

    PubMed Central

    Evans, Sylvia M.; Yelon, Deborah; Conlon, Frank L.; Kirby, Margaret L.

    2010-01-01

    The myocardium of the heart is composed of multiple highly specialized myocardial lineages, including those of the ventricular and atrial myocardium, and the specialized conduction system. Specification and maturation of each of these lineages during heart development is a highly ordered, ongoing process involving multiple signaling pathways and their intersection with transcriptional regulatory networks. Here, we attempt to summarize and compare much of what we know about specification and maturation of myocardial lineages from studies in several different vertebrate model systems. To date, most research has focused on early specification, and while there is still more to learn, less is known about factors that promote subsequent maturation of myocardial lineages required to build the functioning adult heart. PMID:21148449

  14. Phylogenetic lineages in Entomophthoromycota

    USDA-ARS?s Scientific Manuscript database

    Entomophthoromycota Humber is one of five major phylogenetic lineages among the former phylum Zygomycota. These early terrestrial fungi share evolutionarily ancestral characters such as coenocytic mycelium and gametangiogamy as a sexual process resulting in zygospore formation. Previous molecular st...

  15. Interleukin 1β—A Potential Salivary Biomarker for Cancer Progression?

    PubMed Central

    Idris, Adi; Ghazali, Nur B; Koh, David

    2015-01-01

    The relationship between cancer and inflammation is a complex but intimate one. Decades of work has shown to us that cancer progression is influenced by a multitude of factors, including genetic, environmental, and immunological factors. We often overlook that cancer progression is also a pathological consequence of a dysregulated inflammatory control in the body. A current emerging topic in cancer research is the role of inflammasomes in carcinogenesis. The inflammasome is a multicomplex protein platform that when activated results in the release of proinflammatory cytokines, such as interleukin (IL)-1β. There is increasing evidence suggesting that IL-1β plays a pivotal role in cancer progression. This short review proposes the possibility of using IL-1β as a potential cancer progression biomarker and discusses the use of saliva as a model biological fluid for measuring physiological IL-1β levels in the body. PMID:26244033

  16. Interleukin 1β-A Potential Salivary Biomarker for Cancer Progression?

    PubMed

    Idris, Adi; Ghazali, Nur B; Koh, David

    2015-01-01

    The relationship between cancer and inflammation is a complex but intimate one. Decades of work has shown to us that cancer progression is influenced by a multitude of factors, including genetic, environmental, and immunological factors. We often overlook that cancer progression is also a pathological consequence of a dysregulated inflammatory control in the body. A current emerging topic in cancer research is the role of inflammasomes in carcinogenesis. The inflammasome is a multicomplex protein platform that when activated results in the release of proinflammatory cytokines, such as interleukin (IL)-1β. There is increasing evidence suggesting that IL-1β plays a pivotal role in cancer progression. This short review proposes the possibility of using IL-1β as a potential cancer progression biomarker and discusses the use of saliva as a model biological fluid for measuring physiological IL-1β levels in the body.

  17. A novel strategy for designing specific gelatinase A inhibitors: potential use to control tumor progression.

    PubMed

    Augé, Franck; Hornebeck, William; Laronze, Jean-Yves

    2004-03-01

    Matrix metalloproteases (MMPs) are zinc endopeptidases deeply implicated in tumor progression. MMP inhibitors are attractive potential anti-cancer agent. Unfortunately, until now, clinical trials remain disappointing, that could be the result of a lack of selectivity. We propose second generation selective MMPs, directed toward gelatinase A (MMP-2), based on a non-hydroxamate Zn-ligand grafted on the galardin (ilomastat) skeleton.

  18. "Human Potential" and Progressive Pedagogy: A Long Cultural History of the Ambiguity of "Race" and "Intelligence"

    ERIC Educational Resources Information Center

    Oland, Trine

    2012-01-01

    This article examines the cultural constructs of progressive pedagogy in Danish school pedagogy and its emerging focus on the child's human potential from the 1920s to the 1950s. It draws on Foucault's notion of "dispositifs" and the "elements of history," encircling a complex transformation of continuity and discontinuity of…

  19. Preventing Progression in Men with Mild Symptoms of Benign Prostatic Hyperplasia: A Potential Role for Phytotherapy

    PubMed Central

    Fong, Yan Kit; Marihart, Sibylle; Harik, Mike; Djavan, Bob

    2004-01-01

    Prevalence of benign prostate hyperplasia (BPH) is increasing with the aging population worldwide. Throughout the 20th century, men with minimally symptomatic BPH were generally advised to defer treatment. Treatment deferral or watchful waiting has always appeared reasonable because mild lower urinary tract symptoms suggestive of bladder outlet obstruction are not bothersome and are often regarded as part of the aging process, progression is usually slow, and symptoms often regress spontaneously. This review examines the evidence of the natural history of BPH, highlighting the group of patients with mild symptoms, the risk factors for progression, and the potential role of phytotherapy in this group of men. PMID:16985600

  20. Multifocal visual evoked potential latency analysis: predicting progression to multiple sclerosis.

    PubMed

    Fraser, Clare; Klistorner, Alexander; Graham, Stuart; Garrick, Raymond; Billson, Francis; Grigg, John

    2006-06-01

    To monitor the difference in conversion rates to multiple sclerosis (MS) in 46 patients with optic neuritis between patients with multifocal visual evoked potential latency delay and those with normal latency. Prospective case series. Metropolitan neuro-ophthalmology clinic. Forty-six patients with optic neuritis who did not have a diagnosis of MS on enrollment in the study. Conversion to MS according to the McDonald criteria. Analysis revealed that only 22 subjects had multifocal visual evoked potential latency delay. Over 1 year, 36.4% of patients with optic neuritis with latency delays progressed clinically to MS compared with 0% of those with normal latencies (P = .03, chi2). This may indicate that multifocal visual evoked potential latency delay can assist in predicting progression to future MS.

  1. Lineage determinants in early endocrine development

    PubMed Central

    Rieck, Sebastian; Bankaitis, Eric D.; Wright, Christopher V.E.

    2013-01-01

    Pancreatic endocrine cells are produced from a dynamic epithelium in a process that, as in any developing organ, is driven by interacting programs of spatiotemporally regulated intercellular signals and autonomous gene regulatory networks. These algorithms work to push progenitors and their transitional intermediates through a series of railroad-station-like switching decisions to regulate flux along specific differentiation tracks. Extensive research on pancreas organogenesis over the last 20 years, greatly spurred by the potential to restore functional β-cell mass in diabetic patients by transplantation therapy, is advancing our knowledge of how endocrine lineage bias is established and allocation is promoted. The field is working towards the goal of generating a detailed blueprint of how heterogeneous cell populations interact and respond to each other, and other influences such as the extracellular matrix, to move into progressively refined and mature cell states. Here, we highlight how signaling codes and transcriptional networks might determine endocrine lineage within a complex and dynamic architecture, based largely on studies in the mouse. The process begins with the designation of multipotent progenitor cells (MPC) to pancreatic buds that subsequently move through a newly proposed period involving epithelial plexus formation-remodeling, and ends with formation of clustered endocrine islets connected to the vascular and peripheral nervous systems. Developing this knowledge base, and increasing the emphasis on direct comparisons between mouse and human, will yield a more complete and focused picture of pancreas development, and thereby inform β-cell-directed differentiation from human embryonic stem or induced pluripotent stem cells (hESC, iPSC). Additionally, a deeper understanding may provide surprising therapeutic angles by defining conditions that allow the controllable reprogramming of endodermal or pancreatic cell populations. PMID:22728667

  2. Prostate cancer progression and metastasis: potential regulatory pathways for therapeutic targeting

    PubMed Central

    Nandana, Srinivas; Chung, Leland WK

    2014-01-01

    Skeletal metastasis in advanced prostate cancer (PCa) patients remains a significant cause of morbidity and mortality. Research utilizing animal models during the past decade has reached a consensus that PCa progression and distant metastasis can be tackled at the molecular level. Although there are a good number of models that have shown to facilitate the study of PCa initiation and progression at the primary site, models that mimic the distant dissemination of cancer cells, particularly bone metastasis, are scarce. Despite this limitation, the field has gleaned valuable knowledge on the underlying molecular mechanisms and pathways of PCa progression, including local invasion and distant metastasis, and has moved forward in developing the concepts of current therapeutic modalities. The purpose of this review is to put together recent work on pathways that are currently being targeted for therapy, as well as other prospective novel therapeutic targets to be developed in the future against metastatic and potentially lethal PCa in patients. PMID:25374910

  3. Whole organism lineage tracing by combinatorial and cumulative genome editing

    PubMed Central

    McKenna, Aaron; Findlay, Gregory M.; Gagnon, James A.; Horwitz, Marshall S.; Schier, Alexander F.; Shendure, Jay

    2016-01-01

    Multicellular systems develop from single cells through distinct lineages. However, current lineage tracing approaches scale poorly to whole, complex organisms. Here we use genome editing to progressively introduce and accumulate diverse mutations in a DNA barcode over multiple rounds of cell division. The barcode, an array of CRISPR/Cas9 target sites, marks cells and enables the elucidation of lineage relationships via the patterns of mutations shared between cells. In cell culture and zebrafish, we show that rates and patterns of editing are tunable, and that thousands of lineage-informative barcode alleles can be generated. By sampling hundreds of thousands of cells from individual zebrafish, we find that most cells in adult organs derive from relatively few embryonic progenitors. In future analyses, genome editing of synthetic target arrays for lineage tracing (GESTALT) can be used to generate large-scale maps of cell lineage in multicellular systems for normal development and disease. PMID:27229144

  4. Lineage Analysis of Epidermal Stem Cells

    PubMed Central

    Alcolea, Maria P.; Jones, Philip H.

    2014-01-01

    Lineage tracing involves labeling cells to track their subsequent behavior within the normal tissue environment. The advent of genetic lineage tracing and cell proliferation assays, together with high resolution three-dimensional (3D) imaging and quantitative methods to infer cell behavior from lineage-tracing data, has transformed our understanding of murine epidermal stem and progenitor cells. Here, we review recent insights that reveal how a progenitor cell population maintains interfollicular epidermis, whereas stem cells, quiescent under homeostatic conditions, are mobilized in response to wounding. We discuss progress in understanding how the various stem cell populations of the hair follicle sustain this complex and highly dynamic structure, and recent analysis of stem cells in sweat and sebaceous glands. The extent to which insights from mouse studies can be applied to human epidermis is also considered. PMID:24384814

  5. Stanniocalcin-2 (STC2): A potential lung cancer biomarker promotes lung cancer metastasis and progression.

    PubMed

    Na, Sang-su; Aldonza, Mark Borris; Sung, Hye-Jin; Kim, Yong-In; Son, Yeon Sung; Cho, Sukki; Cho, Je-Yoel

    2015-06-01

    The homodimeric glycoprotein, stanniocalcin 2 (STC2) is previously known to be involved in the regulation of calcium and phosphate transport in the kidney and also reported to play multiple roles in several cancers. However, its function and clinical significance in lung cancer have never been reported and still remain uncertain. Here, we investigated the possibility of STC2 as a lung cancer biomarker and identified its potential role in lung cancer cell growth, metastasis and progression. Proteomic analysis of secretome of primary cultured lung cancer cells revealed higher expression of STC2 in cancers compared to that of adjacent normal cells. RT-PCR and Western blot analyses showed higher mRNA and protein expressions of STC2 in lung cancer tissues compared to the adjacent normal tissues. Knockdown of STC2 in H460 lung cancer cells slowed down cell growth progression and colony formation. Further analysis revealed suppression of migration, invasion and delayed G0/G1 cell cycle progression in the STC2 knockdown cells. STC2 knockdown also attenuated the H202-induced oxidative stress on H460 cell viability with a subsequent increase in intracellular ROS levels, which suggest a protective role of STC2 in redox regulatory system of lung cancer. These findings suggest that STC2 can be a potential lung cancer biomarker and plays a positive role in lung cancer metastasis and progression. This article is part of a Special Issue entitled: Medical Proteomics. Copyright © 2015. Published by Elsevier B.V.

  6. Genomic data reveals potential for hybridization, introgression, and incomplete lineage sorting to confound phylogenetic relationships in an adaptive radiation of narrow-mouth frogs.

    PubMed

    Alexander, Alana M; Su, Yong-Chao; Oliveros, Carl H; Olson, Karen V; Travers, Scott L; Brown, Rafe M

    2017-02-01

    The microhylid frog genus Kaloula is an adaptive radiation spanning the edge of the Asian mainland and multiple adjacent island archipelagos, with much of the clade's diversity associated with an endemic Philippine radiation. Relationships among clades from the Philippines, however, remain unresolved. With ultraconserved element (UCE) and mitogenomic data, we identified highly supported differences in topology and areas of poor resolution, for each marker set. Using the UCE data, we then identified possible instances of contemporary hybridization, past introgression, and incomplete lineage sorting (ILS) within the Philippine Kaloula. Using a simulation approach, and an estimate of the Philippine Kaloula clade origin (12.7-21.0 mya), we demonstrate that an evolutionary history including inferred instances of hybridization, introgression, and ILS leads to phylogenetic reconstructions that show concordance with results from the observed mitogenome and UCE data. In the process of validating a complex evolutionary scenario in the Philippine Kaloula, we provide the first demonstration of the efficacy of UCE data for phylogenomic studies of anuran amphibians.

  7. Potential of APDM mobility lab for the monitoring of the progression of Parkinson's disease.

    PubMed

    Mancini, Martina; Horak, Fay B

    2016-05-01

    APDM's Mobility Lab system provides portable, validated, reliable, objective measures of balance and gait that are sensitive to Parkinson's disease (PD). In this review, we describe the potential of objective measures collected with the Mobility Lab system for tracking longitudinal progression of PD. Balance and gait are among the most important motor impairments influencing quality of life for people with PD. Mobility Lab uses body-worn, Opal sensors on the legs, trunk and arms during prescribed tasks, such as the instrumented Get Up and Go test or quiet stance, to quickly quantify the quality of balance and gait in the clinical environment. The same Opal sensors can be sent home with patients to continuously monitor the quality of their daily activities. Objective measures have the potential to monitor progression of mobility impairments in PD throughout its course to improve patient care and accelerate clinical trials.

  8. Is lineage decision-making restricted during tumoral reprograming of haematopoietic stem cells?

    PubMed Central

    2015-01-01

    Within the past years there have been substantial changes to our understanding of haematopoiesis and cells that initiate and sustain leukemia. Recent studies have revealed that developing haematopoietic stem and progenitor cells are much more heterogeneous and versatile than has been previously thought. This versatility includes cells using more than one route to a fate and cells having progressed some way towards a cell type retaining other lineage options as clandestine. These notions impact substantially on our understanding of the origin and nature of leukemia. An important question is whether leukemia stem cells are as versatile as their cell of origin as an abundance of cells belonging to a lineage is often a feature of overt leukemia. In this regard, we examine the coming of age of the “leukemia stem cell” theory and the notion that leukemia, like normal haematopoiesis, is a hierarchically organized tissue. We examine evidence to support the notion that whilst cells that initiate leukemia have multi-lineage potential, leukemia stem cells are reprogrammed by further oncogenic insults to restrict their lineage decision-making. Accordingly, evolution of a sub-clone of lineage-restricted malignant cells is a key feature of overt leukemia. PMID:26498146

  9. TRPC6 regulates cell cycle progression by modulating membrane potential in bone marrow stromal cells

    PubMed Central

    Ichikawa, Jun; Inoue, Ryuji

    2014-01-01

    Background and Purpose Ca2+ influx is important for cell cycle progression, but the mechanisms involved seem to vary. We investigated the potential roles of transient receptor potential (TRP) channels and store-operated Ca2+ entry (SOCE)-related molecules STIM (stromal interaction molecule)/Orai in the cell cycle progression of rat bone marrow stromal cells (BMSCs), a reliable therapeutic resource for regenerative medicine. Experimental Approach PCR and immunoblot analyses were used to examine mRNA and protein levels, fluorescence imaging and patch clamping for Ca2+ influx and membrane potential measurements, and flow cytometry for cell cycle analysis. Key Results Cell cycle synchronization of BMSCs revealed S phase-specific enhancement of TRPC1, STIM and Orai mRNA and protein expression. In contrast, TRPC6 expression decreased in the S phase and increased in the G1 phase. Resting membrane potential (RMP) of BMSCs was most negative and positive in the S and G1 phases, respectively, and was accompanied by an enhancement and attenuation of SOCE respectively. Chemically depolarizing/hyperpolarizing the membrane erased these differences in SOCE magnitude during the cell cycle. siRNA knockdown of TRPC6 produced a negative shift in RMP, increased SOCE and caused redistribution of BMSCs with increased populations in the S and G2/M phases and accumulation of cyclins A2 and B1. A low concentration of Gd3+ (1 μM) suppressed BMSC proliferation at its concentration to inhibit SOC channels relatively specifically. Conclusions and Implications TRPC6, by changing the membrane potential, plays a pivotal role in controlling the SOCE magnitude, which is critical for cell cycle progression of BMSCs. This finding provides a new therapeutic strategy for regulating BMSC proliferation. PMID:25041367

  10. Direct somatic lineage conversion

    PubMed Central

    Tanabe, Koji; Haag, Daniel; Wernig, Marius

    2015-01-01

    The predominant view of embryonic development and cell differentiation has been that rigid and even irreversible epigenetic marks are laid down along the path of cell specialization ensuring the proper silencing of unrelated lineage programmes. This model made the prediction that specialized cell types are stable and cannot be redirected into other lineages. Accordingly, early attempts to change the identity of somatic cells had little success and was limited to conversions between closely related cell types. Nuclear transplantation experiments demonstrated, however, that specialized cells even from adult mammals can be reprogrammed into a totipotent state. The discovery that a small combination of transcription factors can reprogramme cells to pluripotency without the need of oocytes further supported the view that these epigenetic barriers can be overcome much easier than assumed, but the extent of this flexibility was still unclear. When we showed that a differentiated mesodermal cell can be directly converted to a differentiated ectodermal cell without a pluripotent intermediate, it was suggested that in principle any cell type could be converted into any other cell type. Indeed, the work of several groups in recent years has provided many more examples of direct somatic lineage conversions. Today, the question is not anymore whether a specific cell type can be generated by direct reprogramming but how it can be induced. PMID:26416679

  11. Potential biomarkers to follow the progression and treatment response of Huntington’s disease

    PubMed Central

    Disatnik, Marie-Hélène; Joshi, Amit U.; Leavitt, Blair R.

    2016-01-01

    Huntington’s disease (HD) is a rare genetic disease caused by expanded polyglutamine repeats in the huntingtin protein resulting in selective neuronal loss. Although genetic testing readily identifies those who will be affected, current pharmacological treatments do not prevent or slow down disease progression. A major challenge is the slow clinical progression and the inability to biopsy the affected tissue, the brain, making it difficult to design short and effective proof of concept clinical trials to assess treatment benefit. In this study, we focus on identifying peripheral biomarkers that correlate with the progression of the disease and treatment benefit. We recently developed an inhibitor of pathological mitochondrial fragmentation, P110, to inhibit neurotoxicity in HD. Changes in levels of mitochondrial DNA (mtDNA) and inflammation markers in plasma, a product of DNA oxidation in urine, mutant huntingtin aggregates, and 4-hydroxynonenal adducts in muscle and skin tissues were all noted in HD R6/2 mice relative to wild-type mice. Importantly, P110 treatment effectively reduced the levels of these biomarkers. Finally, abnormal levels of mtDNA were also found in plasma of HD patients relative to control subjects. Therefore, we identified several potential peripheral biomarkers as candidates to assess HD progression and the benefit of intervention for future clinical trials. PMID:27821553

  12. Potential biomarkers to follow the progression and treatment response of Huntington's disease.

    PubMed

    Disatnik, Marie-Hélène; Joshi, Amit U; Saw, Nay L; Shamloo, Mehrdad; Leavitt, Blair R; Qi, Xin; Mochly-Rosen, Daria

    2016-11-14

    Huntington's disease (HD) is a rare genetic disease caused by expanded polyglutamine repeats in the huntingtin protein resulting in selective neuronal loss. Although genetic testing readily identifies those who will be affected, current pharmacological treatments do not prevent or slow down disease progression. A major challenge is the slow clinical progression and the inability to biopsy the affected tissue, the brain, making it difficult to design short and effective proof of concept clinical trials to assess treatment benefit. In this study, we focus on identifying peripheral biomarkers that correlate with the progression of the disease and treatment benefit. We recently developed an inhibitor of pathological mitochondrial fragmentation, P110, to inhibit neurotoxicity in HD. Changes in levels of mitochondrial DNA (mtDNA) and inflammation markers in plasma, a product of DNA oxidation in urine, mutant huntingtin aggregates, and 4-hydroxynonenal adducts in muscle and skin tissues were all noted in HD R6/2 mice relative to wild-type mice. Importantly, P110 treatment effectively reduced the levels of these biomarkers. Finally, abnormal levels of mtDNA were also found in plasma of HD patients relative to control subjects. Therefore, we identified several potential peripheral biomarkers as candidates to assess HD progression and the benefit of intervention for future clinical trials. © 2016 Disatnik et al.

  13. A method to detect progression of glaucoma using the multifocal visual evoked potential technique

    PubMed Central

    Wangsupadilok, Boonchai; Kanadani, Fabio N.; Grippo, Tomas M.; Liebmann, Jeffrey M.; Ritch, Robert; Hood, Donald C.

    2010-01-01

    Purpose To describe a method for monitoring progression of glaucoma using the multifocal visual evoked potential (mfVEP) technique. Methods Eighty-seven patients diagnosed with open-angle glaucoma were divided into two groups. Group I, comprised 43 patients who had a repeat mfVEP test within 50 days (mean 0.9 ± 0.5 months), and group II, 44 patients who had a repeat test after at least 6 months (mean 20.7 ± 9.7 months). Monocular mfVEPs were obtained using a 60-sector pattern reversal dartboard display. Monocular and interocular analyses were performed. Data from the two visits were compared. The total number of abnormal test points with P < 5% within the visual field (total scores) and number of abnormal test points within a cluster (cluster size) were calculated. Data for group I provided a measure of test–retest variability independent of disease progression. Data for group II provided a possible measure of progression. Results The difference in the total scores for group II between visit 1 and visit 2 for the interocular and monocular comparison was significant (P < 0.05) as was the difference in cluster size for the interocular comparison (P < 0.05). Group I did not show a significant change in either total score or cluster size. Conclusion The change in the total score and cluster size over time provides a possible method for assessing progression of glaucoma with the mfVEP technique. PMID:18830654

  14. Oxystressed tumor microenvironment potentiates epithelial to mesenchymal transition and alters cellular bioenergetics towards cancer progression.

    PubMed

    Sridaran, Dhivya; Ramamoorthi, Ganesan; MahaboobKhan, Rasool; Kumpati, Premkumar

    2016-10-01

    During tumorigenesis, cancer cells generate complex, unresolved interactions with the surrounding oxystressed cellular milieu called tumor microenvironment (TM) that favors spread of cancer to other body parts. This dissemination of cancer cells from the primary tumor site is the main clinical challenge in cancer treatment. In addition, the significance of enhanced oxidative stress in TM during cancer progression still remains elusive. Thus, the present study was performed to investigate the molecular and cytoskeletal alterations in breast cancer cells associated with oxystressed TM that potentiates metastasis. Our results showed that depending on the extent of oxidative stress in TM, cancer cells exhibited enhanced migration and survival with reduction of chemosensitivity. Corresponding ultrastructural analysis showed radical cytoskeletal modifications that reorganize cell-cell interactions fostering transition of epithelial cells to mesenchymal morphology (EMT) marking metastasis, which was reversed upon antioxidant treatment. Decreased E-cadherin and increased vimentin, Twist1/2 expression corroborated the initiation of EMT in oxystressed TM-influenced cells. Further evaluation of cellular energetics demonstrated significant metabolic reprogramming with inclination towards glucose or external glutamine from TM as energy source depending on the breast cancer cell type. These observations prove the elemental role of oxystressed TM in cancer progression, initiating EMT and metabolic reprogramming. Further cell-type specific metabolomic analysis would unravel the alternate mechanisms in cancer progression for effective therapeutic intervention. Graphical abstract Schematic representation of the study and proposed mechanism of oxystressed TM influenced cancer progression. Cancer cells exhibit a close association with tumor microenvironment (TM), and oxystressed TM enhances cancer cell migration and survival and reduces chemosensitivity. Oxystressed TM induces dynamic

  15. Cancer imaging by optical coherence tomography: preclinical progress and clinical potential.

    PubMed

    Vakoc, Benjamin J; Fukumura, Dai; Jain, Rakesh K; Bouma, Brett E

    2012-04-05

    The past decade has seen dramatic technological advances in the field of optical coherence tomography (OCT) imaging. These advances have driven commercialization and clinical adoption in ophthalmology, cardiology and gastrointestinal cancer screening. Recently, an array of OCT-based imaging tools that have been developed for preclinical intravital cancer imaging applications has yielded exciting new capabilities to probe and to monitor cancer progression and response in vivo. Here, we review these results, forecast the future of OCT for preclinical cancer imaging and discuss its exciting potential to translate to the clinic as a tool for monitoring cancer therapy.

  16. Progress towards alkaline-earth fermions in a 1D uniform potential

    NASA Astrophysics Data System (ADS)

    Reschovsky, Benjamin J.; Barker, Daniel S.; Pisenti, Neal C.; Campbell, Gretchen K.

    2016-05-01

    We present our progress towards realizing a 1D uniform ''box trap'' potential for degenerate fermionic alkaline-earth atoms in order to study highly symmetric SU(N) spin models. Our experiment first generates a degenerate gas of 87 Sr atoms via evaporation in a crossed dipole trap. Next, we plan to load the atoms into an array of 1D box traps formed by a red-detuned 2D optical lattice and blue-detuned end-caps. The end-caps are generated by direct imaging of a digital micromirror device (DMD), which gives us dynamic control of the potential. We report initial characterization of the blue traps and heating rate measurements.

  17. Progress toward determining the potential of ODS alloys for gas turbine applications

    NASA Technical Reports Server (NTRS)

    Dreshfield, R. L.; Hoppin, G., III; Sheffler, K.

    1983-01-01

    The Materials for Advanced Turbine Engine (MATE) Program managed by the NASA Lewis Research Center is supporting two projects to evaluate the potential of oxide dispersion strengthened (ODS) alloys for aircraft gas turbine applications. One project involves the evaluation of Incoloy (TM) MA-956 for application as a combustor liner material. An assessment of advanced engine potential will be conducted by means of a test in a P&WA 2037 turbofan engine. The other project involves the evaluation of Inconel (TM) MA 6000 for application as a high pressure turbine blade material and includes a test in a Garrett TFE 731 turbofan engine. Both projects are progressing toward these engine tests in 1984.

  18. Transgenic zebrafish reporter lines reveal conserved Toll-like receptor signaling potential in embryonic myeloid leukocytes and adult immune cell lineages.

    PubMed

    Hall, Chris; Flores, Maria Vega; Chien, Annie; Davidson, Alan; Crosier, Kathryn; Crosier, Phil

    2009-05-01

    The immune response of a host to an invading pathogen is dependent on the capacity of its immune cell compartment to recognize highly conserved pathogen components using an ancient class of pattern recognition receptors known as Toll-like receptors (TLRs). Initiation of TLR-mediated signaling results in the induction of proinflammatory cytokines that help govern the scale and duration of any ensuing response. Specificity for TLR signaling is, in part, a result of the differential recruitment of intracellular adaptor molecules. Of these, MyD88 is required for the majority of TLR signaling. Zebrafish have been shown to possess TLRs and adaptor molecules throughout early development, including MyD88, strongly suggesting conservation of this ancient defense mechanism. However, information about which embryonic cells/tissues possess this conserved signaling potential is lacking. To help define which embryonic cells, in particular, those of the innate immune system, have the potential for MyD88-dependent, TLR-mediated signaling, we generated transgenic reporter lines using regulatory elements of the myd88 gene to drive the fluorescent reporters enhanced GFP and Discosoma red fluorescent protein 2 within live zebrafish. These lines possess fluorescently marked cells/tissues consistent with endogenous myd88 expression, including a subset of myeloid leukocytes. These innate immune cells were confirmed to express other TLR adaptors including Mal, trif, and Sarm. Live wound-healing and infection assays validated the potential of these myd88-expressing leukocytes to participate in immune responses. These lines will provide a valuable resource for further resolving the contribution of MyD88 to early vertebrate immunity.

  19. The Wnt11 Signaling Pathway in Potential Cellular EMT and Osteochondral Differentiation Progression in Nephrolithiasis Formation.

    PubMed

    He, Deng; Lu, Yuchao; Hu, Henglong; Zhang, Jiaqiao; Qin, Baolong; Wang, Yufeng; Xing, Shuai; Xi, Qilin; Wang, Shaogang

    2015-07-17

    The molecular events leading to nephrolithiasis are extremely complex. Previous studies demonstrated that calcium and transforming growth factor-β1 (TGF-β1) may participate in the pathogenesis of stone formation, but the explicit mechanism has not been defined. Using a self-created genetic hypercalciuric stone-forming (GHS) rat model, we observed that the increased level of serous/uric TGF-β1 and elevated intracellular calcium in primary renal tubular epithelial cells (PRECs) was associated with nephrolithiasis progression in vivo. In the setting of high calcium plus high TGF-β1 in vitro, PRECs showed great potential epithelial to mesenchymal transition (EMT) progression and osteochondral differentiation properties, representing the multifarious increased mesenchymal and osteochondral phenotypes (Zeb1, Snail1, Col2A1, OPN, Sox9, Runx2) and decreased epithelial phenotypes (E-cadherin, CK19) bythe detection of mRNAs and corresponding proteins. Moreover, TGF-β-dependent Wnt11 knockdown and L-type Ca2+ channel blocker could greatly reverse EMT progression and osteochondral differentiation in PRECs. TGF-β1 alone could effectively promote EMT, but it had no effect on osteochondral differentiation in NRK cells (Rat kidney epithelial cell line). Stimulation with Ca2+ alone did not accelerate differentiation of NRK. Co-incubation of extracellular Ca2+ and TGF-β1 synergistically promotes EMT and osteochondral differentiation in NRK control cells. Our data supplied a novel view that the pathogenesis of calcium stone development may be associated with synergic effects of TGF-β1 and Ca2+, which promote EMT and osteochondral differentiation via Wnt11 and the L-type calcium channel.

  20. Engraftment and Lineage Potential of Adult Hematopoietic Stem and Progenitor Cells Is Compromised Following Short-Term Culture in the Presence of an Aryl Hydrocarbon Receptor Antagonist

    PubMed Central

    Gu, Angel; Torres-Coronado, Monica; Tran, Chy-Anh; Vu, Hieu; Epps, Elizabeth W.; Chung, Janet; Gonzalez, Nancy; Blanchard, Suzette

    2014-01-01

    Abstract Hematopoietic stem cell gene therapy for HIV/AIDS is a promising alternative to lifelong antiretroviral therapy. One of the limitations of this approach is the number and quality of stem cells available for transplant following in vitro manipulations associated with stem cell isolation and genetic modification. The development of methods to increase the number of autologous, gene-modified stem cells available for transplantation would overcome this barrier. Hematopoietic stem and progenitor cells (HSPC) from adult growth factor-mobilized peripheral blood were cultured in the presence of an aryl hydrocarbon receptor antagonist (AhRA) previously shown to expand HSPC from umbilical cord blood. Qualitative and quantitative assessment of the hematopoietic potential of minimally cultured (MC-HSPC) or expanded HSPC (Exp-HSPC) was performed using an immunodeficient mouse model of transplantation. Our results demonstrate robust, multilineage engraftment of both MC-HSPC and Exp-HSPC although estimates of expansion based on stem cell phenotype were not supported by a corresponding increase in in vivo engrafting units. Bone marrow of animals transplanted with either MC-HSPC or Exp-HSPC contained secondary engrafting cells verifying the presence of primitive stem cells in both populations. However, the frequency of in vivo engrafting units among the more primitive CD34+/CD90+ HSPC population was significantly lower in Exp-HSPC compared with MC-HSPC. Exp-HSPC also produced fewer lymphoid progeny and more myeloid progeny than MC-HSPC. These results reveal that in vitro culture of adult HSPC in AhRA maintains but does not increase the number of in vivo engrafting cells and that HSPC expanded in vitro contain defects in lymphopoiesis as assessed in this model system. Further investigation is required before implementation of this approach in the clinical setting. PMID:25003230

  1. In utero stem cell transplantation and gene therapy: Recent progress and the potential for clinical application.

    PubMed

    McClain, Lauren E; Flake, Alan W

    2016-02-01

    Advances in prenatal diagnosis have led to the prenatal management and treatment of a variety of congenital diseases. Although surgical treatment has been successfully applied to specific anatomic defects that place the fetus at a risk of death or life-long disability, the indications for fetal surgical intervention have remained relatively limited. By contrast, prenatal stem cell and gene therapy await clinical application, but they have tremendous potential to treat a broad range of genetic disorders. If there are biological advantages unique to fetal development that favor fetal stem cell or gene therapy over postnatal treatment, prenatal therapy may become the preferred approach to the treatment of any disease that can be prenatally diagnosed and cured by stem cell or gene therapy. Here, we review the field including recent progress toward clinical application and imminent clinical trials for cellular and gene therapy.

  2. Role and therapeutic potential of G-protein coupled receptors in breast cancer progression and metastases.

    PubMed

    Singh, Anukriti; Nunes, Jessica J; Ateeq, Bushra

    2015-09-15

    G-protein-coupled receptors (GPCRs) comprise a large family of cell-surface receptors, which have recently emerged as key players in tumorigenesis, angiogenesis and metastasis. In this review, we discussed our current understanding of the many roles played by GPCRs in general, and particularly Angiotensin II type I receptor (AGTR1), a member of the seven-transmembrane-spanning G-protein coupled receptor superfamily, and its significance in breast cancer progression and metastasis. We have also discussed different strategies for targeting AGTR1, and its ligand Angiotension II (Ang II), which might unravel unique opportunities for breast cancer prevention and treatment. For example, AGTR1 blockers (ARBs) which are already in clinical use for treating hypertension, merit further investigation as a therapeutic strategy for AGTR1-positive cancer patients and may have the potential to prevent Ang II-AGTR1 signalling mediated cancer pathogenesis and metastases.

  3. Role and therapeutic potential of G-protein coupled receptors in breast cancer progression and metastases

    PubMed Central

    Singh, Anukriti; Nunes, Jessica J.; Ateeq, Bushra

    2015-01-01

    G-protein-coupled receptors (GPCRs) comprise a large family of cell-surface receptors, which have recently emerged as key players in tumorigenesis, angiogenesis and metastasis. In this review, we discussed our current understanding of the many roles played by GPCRs in general, and particularly Angiotensin II type I receptor (AGTR1), a member of the seven-transmembrane-spanning G-protein coupled receptor superfamily, and its significance in breast cancer progression and metastasis. We have also discussed different strategies for targeting AGTR1, and its ligand Angiotension II (Ang II), which might unravel unique opportunities for breast cancer prevention and treatment. For example, AGTR1 blockers (ARBs) which are already in clinical use for treating hypertension, merit further investigation as a therapeutic strategy for AGTR1-positive cancer patients and may have the potential to prevent Ang II-AGTR1 signalling mediated cancer pathogenesis and metastases. PMID:25981295

  4. An update on the pharmacogenomics of metformin: progress, problems and potential.

    PubMed

    Todd, Jennifer N; Florez, Jose C

    2014-03-01

    The increasing prevalence of Type 2 diabetes has emphasized the need to optimize treatment regimens. Metformin, the most widely used oral agent, is recommended as first-line drug therapy by multiple professional organizations. Response to metformin varies significantly at the individual level; this heterogeneity may be explained in part by genetic factors. Understanding these underlying factors may aid with tailoring treatment for individual patients as well as with designing improved Type 2 diabetes therapies. The past 10 years have seen substantial progress in the understanding of the pharmacogenetics of metformin response. The majority of this work has focused on genes involved in the pharmacokinetics of metformin. Owing to the uncertainty surrounding its mechanism of action, studies of pharmacodynamic genetics have been relatively few; genome-wide approaches have the potential to illuminate the molecular details of metformin response. In this review we summarize current knowledge about metformin pharmacogenetics and suggest directions for future investigation.

  5. Distinct Wnt-driven primitive streak-like populations reflect in vivo lineage precursors

    PubMed Central

    Tsakiridis, Anestis; Huang, Yali; Blin, Guillaume; Skylaki, Stavroula; Wymeersch, Filip; Osorno, Rodrigo; Economou, Costas; Karagianni, Eleni; Zhao, Suling; Lowell, Sally; Wilson, Valerie

    2014-01-01

    During gastrulation, epiblast cells are pluripotent and their fate is thought to be constrained principally by their position. Cell fate is progressively restricted by localised signalling cues from areas including the primitive streak. However, it is unknown whether this restriction accompanies, at the individual cell level, a reduction in potency. Investigation of these early transition events in vitro is possible via the use of epiblast stem cells (EpiSCs), self-renewing pluripotent cell lines equivalent to the postimplantation epiblast. Strikingly, mouse EpiSCs express gastrulation stage regional markers in self-renewing conditions. Here, we examined the differentiation potential of cells expressing such lineage markers. We show that undifferentiated EpiSC cultures contain a major subfraction of cells with reversible early primitive streak characteristics, which is mutually exclusive to a neural-like fraction. Using in vitro differentiation assays and embryo grafting we demonstrate that primitive streak-like EpiSCs are biased towards mesoderm and endoderm fates while retaining pluripotency. The acquisition of primitive streak characteristics by self-renewing EpiSCs is mediated by endogenous Wnt signalling. Elevation of Wnt activity promotes restriction towards primitive streak-associated lineages with mesendodermal and neuromesodermal characteristics. Collectively, our data suggest that EpiSC pluripotency encompasses a range of reversible lineage-biased states reflecting the birth of pioneer lineage precursors from a pool of uncommitted EpiSCs similar to the earliest cell fate restriction events taking place in the gastrula stage epiblast. PMID:24595287

  6. Modern Lineages of Mycobacterium tuberculosis Exhibit Lineage-Specific Patterns of Growth and Cytokine Induction in Human Monocyte-Derived Macrophages

    PubMed Central

    Sarkar, Rajesh; Lenders, Laura; Wilkinson, Katalin A.; Wilkinson, Robert J.; Nicol, Mark P.

    2012-01-01

    Background Strains of Mycobacterium tuberculosis vary in virulence. Strains that have caused outbreaks in the United States and United Kingdom have been shown to subvert the innate immune response as a potential immune evasion mechanism. There is, however, little information available as to whether these patterns of immune subversion are features of individual strains or characteristic of broad clonal lineages of M. tuberculosis. Methods Strains from two major modern lineages (lineage 2 [East-Asian] and lineage 4 [Euro-American]) circulating in the Western Cape in South Africa as well as a comparator modern lineage (lineage 3 [CAS/Delhi]) were identified. We assessed two virulence associated characteristics: mycobacterial growth (in liquid broth and monocyte derived macrophages) and early pro-inflammatory cytokine induction. Results In liquid culture, Lineage 4 strains grew more rapidly and reached higher plateau levels than other strains (lineage 4 vs. lineage 2 p = 0.0024; lineage 4 vs. lineage 3 p = 0.0005). Lineage 3 strains were characterized by low and early plateau levels, while lineage 2 strains showed an intermediate growth phenotype. In monocyte-derived macrophages, lineage 2 strains grew faster than lineage 3 strains (p<0.01) with lineage 4 strains having an intermediate phenotype. Lineage 2 strains induced the lowest levels of pro-inflammatory TNF and IL-12p40 as compared to other lineages (lineage 2: median TNF 362 pg/ml, IL-12p40 91 pg/ml; lineage 3: median TNF 1818 pg/ml, IL-12p40 123 pg/ml; lineage 4: median TNF 1207 pg/ml, IL-12p40 205 pg/ml;). In contrast, lineage 4 strains induced high levels of IL-12p40 and intermediate level of TNF. Lineage 3 strains induced high levels of TNF and intermediate levels of IL-12p40. Conclusions Strains of M. tuberculosis from the three major modern strain lineages possess distinct patterns of growth and cytokine induction. Rapid growth and immune subversion may be key characteristics to the success of

  7. Bile Acids in Polycystic Liver Diseases: Triggers of Disease Progression and Potential Solution for Treatment.

    PubMed

    Perugorria, Maria J; Labiano, Ibone; Esparza-Baquer, Aitor; Marzioni, Marco; Marin, Jose J G; Bujanda, Luis; Banales, Jesús M

    2017-01-01

    Polycystic liver diseases (PLDs) are a group of genetic hereditary cholangiopathies characterized by the development and progressive growth of cysts in the liver, which are the main cause of morbidity. Current therapies are based on surgical procedures and pharmacological strategies, which show short-term and modest beneficial effects. Therefore, the determination of the molecular mechanisms of pathogenesis appears to be crucial in order to find new potential targets for pharmacological therapy. Ductal plate malformation during embryogenesis and abnormal cystic cholangiocyte growth and secretion are some of the key mechanisms involved in the pathogenesis of PLDs. However, the discovery of the presence of bile acids in the fluid collected from human cysts and the intrahepatic accumulation of cytotoxic bile acids in an animal model of PLD (i.e. polycystic kidney (PCK) rat) suggest a potential role of impaired bile acid homeostasis in the pathogenesis of these diseases. On the other hand, ursodeoxycholic acid (UDCA) has emerged as a new potential therapeutic tool for PLDs by promoting the inhibition of cystic cholangiocyte growth in both PCK rats and highly symptomatic patients with autosomal dominant polycystic kidney disease (ADPKD: most common type of PLD), and improving symptoms. Chronic treatment with UDCA normalizes the decreased intracellular calcium levels in ADPKD human cholangiocytes in vitro, which results in the reduction of their baseline-stimulated proliferation. Moreover, UDCA decreases the liver concentration of cytotoxic bile acids in PCK rats and the bile acid-dependent enhanced proliferation of cystic cholangiocytes. Here, the role of bile acids in the pathogenesis of PLDs and the potential therapeutic value of UDCA for the treatment of these diseases are reviewed and future lines of investigation in this field are proposed.

  8. Imaging Genetics and Genomics in Psychiatry: A Critical Review of Progress and Potential.

    PubMed

    Bogdan, Ryan; Salmeron, Betty Jo; Carey, Caitlin E; Agrawal, Arpana; Calhoun, Vince D; Garavan, Hugh; Hariri, Ahmad R; Heinz, Andreas; Hill, Matthew N; Holmes, Andrew; Kalin, Ned H; Goldman, David

    2017-01-13

    Imaging genetics and genomics research has begun to provide insight into the molecular and genetic architecture of neural phenotypes and the neural mechanisms through which genetic risk for psychopathology may emerge. As it approaches its third decade, imaging genetics is confronted by many challenges, including the proliferation of studies using small sample sizes and diverse designs, limited replication, problems with harmonization of neural phenotypes for meta-analysis, unclear mechanisms, and evidence that effect sizes may be more modest than originally posited, with increasing evidence of polygenicity. These concerns have encouraged the field to grow in many new directions, including the development of consortia and large-scale data collection projects and the use of novel methods (e.g., polygenic approaches, machine learning) that enhance the quality of imaging genetic studies but also introduce new challenges. We critically review progress in imaging genetics and offer suggestions and highlight potential pitfalls of novel approaches. Ultimately, the strength of imaging genetics and genomics lies in their translational and integrative potential with other research approaches (e.g., nonhuman animal models, psychiatric genetics, pharmacologic challenge) to elucidate brain-based pathways that give rise to the vast individual differences in behavior as well as risk for psychopathology.

  9. Pluripotent reprogramming and lineage reprogramming: promises and challenges in cardiovascular regeneration.

    PubMed

    He, Wen-Jun; Hou, Qian; Han, Qing-Wang; Han, Wei-Dong; Fu, Xiao-Bing

    2014-08-01

    Cardiovascular disease is a leading cause of death in industrialized countries. Scientists are trying to generate cardiomyocytes in vitro and in vivo to repair damaged heart tissue. Pluripotent reprogramming brings an alternative source of embryonic-like stem cells, and the possibility of regenerating mammalian tissues by first reverting somatic cells to induced pluripotent stem cells, followed by redifferentiating these cells into cardiomyocytes. More recently, lineage reprogramming of fibroblasts directly into functional cardiomyocytes has been reported. The procedure does not involve reverting cells back to a pluripotent stage, and, thus, would presumably reduce tumorigenic potential. Interestingly, lineage reprogramming could be used for in situ conversion of cell fate. Moreover, zebrafish-like regenerative mechanism in mammalian heart tissue, which was observed in mice within the first week of postpartum, should be further addressed. Here, we review the landmark progresses of the two major reprogramming strategies, compare their pros and cons in cardiovascular regeneration, and forecast the future directions of cardiac repair.

  10. The potential of composite cognitive scores for tracking progression in Huntington's disease.

    PubMed

    Jones, Rebecca; Stout, Julie C; Labuschagne, Izelle; Say, Miranda; Justo, Damian; Coleman, Allison; Dumas, Eve M; Hart, Ellen; Owen, Gail; Durr, Alexandra; Leavitt, Blair R; Roos, Raymund; O'Regan, Alison; Langbehn, Doug; Tabrizi, Sarah J; Frost, Chris

    2014-01-01

    Composite scores derived from joint statistical modelling of individual risk factors are widely used to identify individuals who are at increased risk of developing disease or of faster disease progression. We investigated the ability of composite measures developed using statistical models to differentiate progressive cognitive deterioration in Huntington's disease (HD) from natural decline in healthy controls. Using longitudinal data from TRACK-HD, the optimal combinations of quantitative cognitive measures to differentiate premanifest and early stage HD individuals respectively from controls was determined using logistic regression. Composite scores were calculated from the parameters of each statistical model. Linear regression models were used to calculate effect sizes (ES) quantifying the difference in longitudinal change over 24 months between premanifest and early stage HD groups respectively and controls. ES for the composites were compared with ES for individual cognitive outcomes and other measures used in HD research. The 0.632 bootstrap was used to eliminate biases which result from developing and testing models in the same sample. In early HD, the composite score from the HD change prediction model produced an ES for difference in rate of 24-month change relative to controls of 1.14 (95% CI: 0.90 to 1.39), larger than the ES for any individual cognitive outcome and UHDRS Total Motor Score and Total Functional Capacity. In addition, this composite gave a statistically significant difference in rate of change in premanifest HD compared to controls over 24-months (ES: 0.24; 95% CI: 0.04 to 0.44), even though none of the individual cognitive outcomes produced statistically significant ES over this period. Composite scores developed using appropriate statistical modelling techniques have the potential to materially reduce required sample sizes for randomised controlled trials.

  11. Enhanced A-FABP expression in visceral fat: potential contributor to the progression of NASH

    PubMed Central

    Yoon, Min Yong; Sung, Jun Mo; Song, Chang Seok; Lee, Won Young; Rhee, Eun Jung; Shin, Jun Ho; Yoo, Chang Hak; Chae, Seoung Wan; Kim, Ja Yeon; Jin, Wook

    2012-01-01

    Background/Aims Adipose tissue is an active endocrine organ that secretes various metabolically important substances including adipokines, which represent a link between insulin resistance and nonalcoholic steatohepatitis (NASH). The factors responsible for the progression from simple steatosis to steatohepatitis remain elusive, but adipokine imbalance may play a pivotal role. We evaluated the expressions of adipokines such as visfatin, adipocyte-fatty-acid-binding protein (A-FABP), and retinol-binding protein-4 (RBP-4) in serum and tissue. The aim was to discover whether these adipokines are potential predictors of NASH. Methods Polymerase chain reaction, quantification of mRNA, and Western blots encoding A-FABP, RBP-4, and visfatin were used to study tissue samples from the liver, and visceral and subcutaneous adipose tissue. The tissue samples were from biopsy specimens obtained from patients with proven NASH who were undergoing laparoscopic cholecystectomy due to gallbladder polyps. Results Patients were classified into two groups: NASH, n=10 and non-NASH, n=20 according to their nonalcoholic fatty liver disease Activity Score. Although serum A-FABP levels did not differ between the two groups, the expressions of A-FABP mRNA and protein in the visceral adipose tissue were significantly higher in NASH group than in non-NASH group (104.34 vs. 97.05, P<0.05, and 190.01 vs. 95.15, P<0.01, respectively). Furthermore, the A-FABP protein expression ratio between visceral adipose tissue and liver was higher in NASH group than in non-NASH group (4.38 vs. 1.64, P<0.05). Conclusions NASH patients had higher levels of A-FABP expression in their visceral fat compared to non-NASH patients. This differential A-FABP expression may predispose patients to the progressive form of NASH. PMID:23091808

  12. Identification and characterization of mouse otic sensory lineage genes

    PubMed Central

    Hartman, Byron H.; Durruthy-Durruthy, Robert; Laske, Roman D.; Losorelli, Steven; Heller, Stefan

    2015-01-01

    Vertebrate embryogenesis gives rise to all cell types of an organism through the development of many unique lineages derived from the three primordial germ layers. The otic sensory lineage arises from the otic vesicle, a structure formed through invagination of placodal non-neural ectoderm. This developmental lineage possesses unique differentiation potential, giving rise to otic sensory cell populations including hair cells, supporting cells, and ganglion neurons of the auditory and vestibular organs. Here we present a systematic approach to identify transcriptional features that distinguish the otic sensory lineage (from early otic progenitors to otic sensory populations) from other major lineages of vertebrate development. We used a microarray approach to analyze otic sensory lineage populations including microdissected otic vesicles (embryonic day 10.5) as well as isolated neonatal cochlear hair cells and supporting cells at postnatal day 3. Non-otic tissue samples including periotic tissues and whole embryos with otic regions removed were used as reference populations to evaluate otic specificity. Otic populations shared transcriptome-wide correlations in expression profiles that distinguish members of this lineage from non-otic populations. We further analyzed the microarray data using comparative and dimension reduction methods to identify individual genes that are specifically expressed in the otic sensory lineage. This analysis identified and ranked top otic sensory lineage-specific transcripts including Fbxo2, Col9a2, and Oc90, and additional novel otic lineage markers. To validate these results we performed expression analysis on select genes using immunohistochemistry and in situ hybridization. Fbxo2 showed the most striking pattern of specificity to the otic sensory lineage, including robust expression in the early otic vesicle and sustained expression in prosensory progenitors and auditory and vestibular hair cells and supporting cells. PMID:25852475

  13. Identification and characterization of mouse otic sensory lineage genes.

    PubMed

    Hartman, Byron H; Durruthy-Durruthy, Robert; Laske, Roman D; Losorelli, Steven; Heller, Stefan

    2015-01-01

    Vertebrate embryogenesis gives rise to all cell types of an organism through the development of many unique lineages derived from the three primordial germ layers. The otic sensory lineage arises from the otic vesicle, a structure formed through invagination of placodal non-neural ectoderm. This developmental lineage possesses unique differentiation potential, giving rise to otic sensory cell populations including hair cells, supporting cells, and ganglion neurons of the auditory and vestibular organs. Here we present a systematic approach to identify transcriptional features that distinguish the otic sensory lineage (from early otic progenitors to otic sensory populations) from other major lineages of vertebrate development. We used a microarray approach to analyze otic sensory lineage populations including microdissected otic vesicles (embryonic day 10.5) as well as isolated neonatal cochlear hair cells and supporting cells at postnatal day 3. Non-otic tissue samples including periotic tissues and whole embryos with otic regions removed were used as reference populations to evaluate otic specificity. Otic populations shared transcriptome-wide correlations in expression profiles that distinguish members of this lineage from non-otic populations. We further analyzed the microarray data using comparative and dimension reduction methods to identify individual genes that are specifically expressed in the otic sensory lineage. This analysis identified and ranked top otic sensory lineage-specific transcripts including Fbxo2, Col9a2, and Oc90, and additional novel otic lineage markers. To validate these results we performed expression analysis on select genes using immunohistochemistry and in situ hybridization. Fbxo2 showed the most striking pattern of specificity to the otic sensory lineage, including robust expression in the early otic vesicle and sustained expression in prosensory progenitors and auditory and vestibular hair cells and supporting cells.

  14. The Status, Potential and Research Progress of CO2 Storage Worldwide

    NASA Astrophysics Data System (ADS)

    Basava-Reddi, L.; Camps, A.

    2012-04-01

    Energy demand continues to grow and is expected to have increased by 35% by 2035, and CO2 emissions continue to increase with a current pathway to 650ppm by 2050. Carbon dioxide capture and storage (CCS) is considered to be an important carbon dioxide mitigation technology. The IEA CCS Technology Roadmap 2009 based on the 'blue map' scenario predicts that to reach CO2 reduction targets 100 commercial CCS projects is desired by 20201, compared to the G8 target of 20 CCS projects by 2020. A recent analysis of current storage projects and future projections shows the G8 target is possible if adequate resourcing is provided and if CO2-EOR projects are included; however the IEA Roadmap CCS target may be unattainable2. With sufficient funding, 50 projects are achievable by 2025 and 100 projects by 2028 inclusive of CO2-EOR projects, the latter requiring 6 billion Euros of total investment. Project lead times are long, which could be up to 15 years for deep saline formation storage projects, and without sufficient funding the gap between targets and the current number of projects will widen. However, there has been progress. 74 CCS projects have been identified by the Global CCS Institute with 14 large scale integrated projects in the operate and execute phase expressing a total storage capacity of 33 Mtpa: 3 more projects in the execute phase since 2009, and 10 more have announced they will be ready for a final investment decision in the next 12 months hence ready to move to the execute phase3. Explanations of project suspension or cancellation have been predominated by non-technical issues; however there are technical challenges remaining; including injectivity and uncertainty in capacity, particularly for deep saline formations; all of which are being considered by the CCS research community. Other considerations that are currently being assessed are subsurface resource interaction, which includes potential interactions of CO2 storage with hydrocarbon production

  15. Brain stem auditory evoked potentials in patients with multiple system atrophy with progressive autonomic failure (Shy-Drager syndrome).

    PubMed Central

    Prasher, D; Bannister, R

    1986-01-01

    Brain stem potentials from three groups of patients, namely those with pure progressive autonomic failure, Parkinson's disease and multisystem atrophy with progressive autonomic failure (Shy-Drager syndrome) were compared with each other and a group of normal subjects. In virtually all the patients with multisystem atrophy with progressive autonomic failure the brain stem potentials were abnormal in contrast to normal findings with Parkinson's disease. The closely associated group of patients with progressive autonomic failure alone also revealed no abnormalities of the BAEP. This separation of the two groups, Parkinson's disease and progressive autonomic failure from multisystem atrophy with progressive autonomic failure is important clinically as multiple system atrophy of the Shy-Drager type has extra-pyramidal features closely resembling Parkinsonism or a late onset cerebellar degeneration. From the abnormalities of the brain stem response in multisystem atrophy with progressive autonomic failure, it is clear that some disruption of the auditory pathway occurs in the ponto-medullary region as in nearly all patients there is a significant delay or reduction in the amplitude of components of the response generated beyond this region. The most likely area involved is the superior olivary complex. Images PMID:3958741

  16. Satellite Remote Sensing of Particulate Matter Air Quality: Progress, Potential and Pitfalls (Invited)

    NASA Astrophysics Data System (ADS)

    Christopher, S. A.

    2009-12-01

    Satellite Remote Sensing of Particulate Matter Air Quality: Progress, Potential and Pitfalls Abstract. Fine or respirable particles with particle aerodynamic diameters less than 2.5 µm (PM2.5) affect visibility, change cloud properties, reflect and absorb incoming solar radiation, affect human health and are ubiquitous in the atmosphere. These particles are injected into the atmosphere either as primary emissions or form into the atmosphere by gas to particle conversion. There are various sources of PM2.5 including emissions from automobiles, industrial exhaust, and agricultural fires. In 2006, the United States Environmental Protection Agency (EPA) made the standards stringent by changing the 24-hr averaged PM2.5 mass values from 65µgm-3 to 35µgm-3. This was primarily based on epidemiological studies that showed the long term health benefits of making the PM2.5 standards stringent. Typically PM2.5 mass concentration is measured from surface monitors and in the United States there are nearly 1000 such filter based daily and 600 contiguous stations managed by federal, state, local, and tribal agencies. Worldwide, there are few PM2.5 ground monitors since they are expensive to purchase, maintain and operate. Satellite remote sensing therefore provides a viable method for monitoring PM2.5 from space. Although, there are several hundred satellites currently in orbit and not all of them are suited for PM2.5 air quality assessments. Typically multi-spectral reflected solar radiation measurements from space-borne sensors are converted to aerosol optical depth (AOD) which is a measure of the column (surface to top of atmosphere) integrated extinction (absorption plus scattering). This column AOD (usually at 550 nm) is often converted to PM2.5 mass near the ground using various techniques. In this presentation we discuss the progress over the last decade on assessing PM2.5 from satellites; outline the potential and discuss the various pitfalls that one encounters. We

  17. Oncogenic Fli-1 is a potential prognostic marker for the progression of epithelial ovarian cancer.

    PubMed

    Song, Wei; Hu, Lingyun; Li, Wei; Wang, Guanjun; Li, Yan; Yan, Lei; Li, Ailing; Cui, Jiuwei

    2014-06-12

    Ovarian cancer is the most lethal gynecologic malignancy, but its etiology remains poorly understood. This study investigated the role of Fli-1 in ovarian carcinogenesis and disease survival. Fli-1 protein expression was evaluated by immunohistochemistry in 104 primary epithelial ovarian cancer (EOC) patients with known follow-up data and 20 controls. Correlation between Fli-1 expression and clinical characteristics was evaluated with the logistic regression. Kaplan Meier analysis was used to assess the impact of Fli-1 expression on overall survival (OS) and disease-free survival (DFS). Cell proliferation and migration assay were used to explore the function of Fli-1 in ovarian cancer cells. Fli-1 was expressed in 74% cases and up-regulated in EOC tissues compared with normal control tissues (p< 0.05). The high expression of Fli-1 was significantly associated with advanced tumor stage, positive lymph nodal involvement, and poor OS and DFS (p< 0.05). Further analysis showed Fli-1 is an independent prognostic factor for OS and DFS. Down-regulation of Fli-1 inhibited cell proliferation but did not affect cell migration in SKOV3 cells. This study revealed that Fli-1 played an essential role in the development and progression of ovarian cancers. Its overexpression is intimately related to malignant phenotypes and poor clinical outcome, suggesting that Fli-1 is a potential prognostic marker and therapeutic molecular target in ovarian cancer.

  18. Human haematopoietic stem cell lineage commitment is a continuous process.

    PubMed

    Velten, Lars; Haas, Simon F; Raffel, Simon; Blaszkiewicz, Sandra; Islam, Saiful; Hennig, Bianca P; Hirche, Christoph; Lutz, Christoph; Buss, Eike C; Nowak, Daniel; Boch, Tobias; Hofmann, Wolf-Karsten; Ho, Anthony D; Huber, Wolfgang; Trumpp, Andreas; Essers, Marieke A G; Steinmetz, Lars M

    2017-03-20

    Blood formation is believed to occur through stepwise progression of haematopoietic stem cells (HSCs) following a tree-like hierarchy of oligo-, bi- and unipotent progenitors. However, this model is based on the analysis of predefined flow-sorted cell populations. Here we integrated flow cytometric, transcriptomic and functional data at single-cell resolution to quantitatively map early differentiation of human HSCs towards lineage commitment. During homeostasis, individual HSCs gradually acquire lineage biases along multiple directions without passing through discrete hierarchically organized progenitor populations. Instead, unilineage-restricted cells emerge directly from a 'continuum of low-primed undifferentiated haematopoietic stem and progenitor cells' (CLOUD-HSPCs). Distinct gene expression modules operate in a combinatorial manner to control stemness, early lineage priming and the subsequent progression into all major branches of haematopoiesis. These data reveal a continuous landscape of human steady-state haematopoiesis downstream of HSCs and provide a basis for the understanding of haematopoietic malignancies.

  19. Transcriptional and epigenetic regulation of T-helper lineage specification

    PubMed Central

    Tripathi, Subhash K; Lahesmaa, Riitta

    2014-01-01

    Combined with TCR stimuli, extracellular cytokine signals initiate the differentiation of naive CD4+ T cells into specialized effector T-helper (Th) and regulatory T (Treg) cell subsets. The lineage specification and commitment process occurs through the combinatorial action of multiple transcription factors (TFs) and epigenetic mechanisms that drive lineage-specific gene expression programs. In this article, we review recent studies on the transcriptional and epigenetic regulation of distinct Th cell lineages. Moreover, we review current study linking immune disease-associated single-nucleotide polymorphisms with distal regulatory elements and their potential role in the disease etiology. PMID:25123277

  20. Expanding the Entamoeba Universe: New Hosts Yield Novel Ribosomal Lineages.

    PubMed

    Jacob, Alison S; Busby, Eloise J; Levy, Abigail D; Komm, Natasha; Clark, C Graham

    2016-01-01

    Removing the requirement for cell culture has led to a substantial increase in the number of lineages of Entamoeba recognized as distinct. Surveying the range of potential host species for this parasite genus has barely been started and it is clear that additional sampling of the same host in different locations often identifies additional diversity. In this study, using small subunit ribosomal RNA gene sequencing, we identify four new lineages of Entamoeba, including the first report of Entamoeba from an elephant, and extend the host range of some previously described lineages. In addition, examination of microbiome data from a number of host animals suggests that substantial Entamoeba diversity remains to be uncovered.

  1. Potential use of coronary artery calcium progression to guide the management of patients at risk for coronary artery disease events.

    PubMed

    McEvoy, John W; Blaha, Michael J; Nasir, Khurram; Blumenthal, Roger S; Jones, Steven R

    2012-02-01

    Subclinical coronary artery disease (CAD) is widespread and under-diagnosed. Preventive efforts are required to reduce the burden of this disease and its complications. Imaging of coronary artery calcium (CAC) with cardiac computed tomography is highly specific for the diagnosis of subclinical CAD and can also facilitate treatment decisions in preventive cardiology. Indeed, CAC testing has been recommended by the American Heart Association for asymptomatic patients at intermediate risk for future cardiac events (as defined by clinical risk factors) to refine existing risk estimates. However, the optimal follow-up of those patients who have already undergone CAC testing remains unclear, particularly with regards to repeat CAC testing. The existing literature points to two major considerations for the use of CAC progression in the management of subclinical CAD. On one hand, CAC progression has been used as a surrogate marker to test the efficacy of cardiac preventive medications in halting or regressing CAD. To date, study results have been mostly disappointing and CAC progression appears resistant to medications such as statins. On the other hand, however, CAC progression has potential as a clinical indicator of underlying CAD activity. This may facilitate optimization or up-titration of preventive medications by using CAC progression as a marker of subclinical disease activity. We believe that the data, thus far, argues against the use of a CAC progression as a clinical surrogate marker of preventive therapy efficacy. Further studies with non-statin medications and with concomitant outcome data are needed. However, CAC progression has potential for monitoring subclinical CAD in some patients and may facilitate treatment decisions. In this review we will provide recommendations for repeat CAC testing and discuss when repeat CAC testing may be helpful to assess coronary artery disease progression.

  2. Complement component 7 (C7), a potential tumor suppressor, is correlated with tumor progression and prognosis

    PubMed Central

    Pan, Xiaodan; Chen, Kaiyan; Zhang, Nan; Jin, Jiaoyue; Wu, Junzhou; Feng, Jianguo; Yu, Herbert; Jin, Hongchuan; Su, Dan

    2016-01-01

    Our previous study found copy number variation of chromosome fragment 5p13.1-13.3 might involve in the progression of ovarian cancer. In the current study, the alteration was validated and complement component 7 (C7), located on 5p13.1, was identified. To further explore the clinical value of C7 in tumors, 156 malignant, 22 borderline, 33 benign and 24 normal ovarian tissues, as well as 173 non-small cell lung cancer (NSCLC) tissues along with corresponding adjacent and normal tissues from the tissue bank of Zhejiang Cancer Hospital were collected. The expression of C7 was analyzed using reverse transcriptase quantitative polymerase chain reaction. As a result, the C7 expression displayed a gradual downward trend in normal, benign, borderline and malignant ovarian tissues, and the decreased expression of C7 was correlative to poor differentiation in patients with ovarian cancer. Interestingly, a similar change of expression of C7 was found in normal, adjacent and malignant tissues in patients with NSCLC, and low expression of C7 was associated with worse grade and advanced clinical stage. Both results from this cohort and the public database indicated that NSCLC patients with low expression of C7 had a worse outcome. Furthermore, multivariate cox regression analysis showed NSCLC patients with low C7 had a 3.09 or 5.65-fold higher risk for relapse or death than those with high C7 respectively, suggesting C7 was an independent prognostic predictor for prognoses of patients with NSCLC. Additionally, overexpression of C7 inhibited colony formation of NSCLC cells, which hints C7 might be a potential tumor suppressor. PMID:27852032

  3. Mitochondrial oncobioenergetic index: A potential biomarker to predict progression from indolent to aggressive prostate cancer.

    PubMed

    Vayalil, Praveen K; Landar, Aimee

    2015-12-15

    Mitochondrial function is influenced by alterations in oncogenes and tumor suppressor genes and changes in the microenvironment occurring during tumorigenesis. Therefore, we hypothesized that mitochondrial function will be stably and dynamically altered at each stage of the prostate tumor development. We tested this hypothesis in RWPE-1 cells and its tumorigenic clones with progressive malignant characteristics (RWPE-1 < WPE-NA22 < WPE-NB14 < WPE-NB11 < WPE-NB26) using high-throughput respirometry. Our studies demonstrate that mitochondrial content do not change with increasing malignancy. In premalignant cells (WPE-NA22 and WPE-NB14), OXPHOS is elevated in presence of glucose or glutamine alone or in combination compared to RWPE-1 cells and decreases with increasing malignancy. Glutamine maintained higher OXPHOS than glucose and suggests that it may be an important substrate for the growth and proliferation of prostate epithelial cells. Glycolysis significantly increases with malignancy and follow a classical Warburg phenomenon. Fatty acid oxidation (FAO) is significantly lower in tumorigenic clones and invasive WPE-NB26 does not utilize FAO at all. In this paper, we introduce for the first time the mitochondrial oncobioenergetic index (MOBI), a mathematical representation of oncobioenergetic profile of a cancer cell, which increases significantly upon transformation into localized premalignant form and rapidly falls below the normal as they become aggressive in prostate tumorigenesis. We have validated this in five prostate cancer cell lines and MOBI appears to be not related to androgen dependence or mitochondrial content, but rather dependent on the stage of the cancer. Altogether, we propose that MOBI could be a potential biomarker to distinguish aggressive cancer from that of indolent disease.

  4. Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression.

    PubMed

    Putluri, Nagireddy; Shojaie, Ali; Vasu, Vihas T; Vareed, Shaiju K; Nalluri, Srilatha; Putluri, Vasanta; Thangjam, Gagan Singh; Panzitt, Katrin; Tallman, Christopher T; Butler, Charles; Sana, Theodore R; Fischer, Steven M; Sica, Gabriel; Brat, Daniel J; Shi, Huidong; Palapattu, Ganesh S; Lotan, Yair; Weizer, Alon Z; Terris, Martha K; Shariat, Shahrokh F; Michailidis, George; Sreekumar, Arun

    2011-12-15

    Although alterations in xenobiotic metabolism are considered causal in the development of bladder cancer, the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which exhibited significant changes in bladder cancer. This metabolic signature distinguished both normal and benign bladder from bladder cancer. Exploratory analyses of this metabolomic signature in urine showed promise in distinguishing bladder cancer from controls and also nonmuscle from muscle-invasive bladder cancer. Subsequent enrichment-based bioprocess mapping revealed alterations in phase I/II metabolism and suggested a possible role for DNA methylation in perturbing xenobiotic metabolism in bladder cancer. In particular, we validated tumor-associated hypermethylation in the cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) promoters of bladder cancer tissues by bisulfite sequence analysis and methylation-specific PCR and also by in vitro treatment of T-24 bladder cancer cell line with the DNA demethylating agent 5-aza-2'-deoxycytidine. Furthermore, we showed that expression of CYP1A1 and CYP1B1 was reduced significantly in an independent cohort of bladder cancer specimens compared with matched benign adjacent tissues. In summary, our findings identified candidate diagnostic and prognostic markers and highlighted mechanisms associated with the silencing of xenobiotic metabolism. The metabolomic signature we describe offers potential as a urinary biomarker for early detection and staging of bladder cancer, highlighting the utility of evaluating metabolomic profiles of cancer to gain insights into bioprocesses perturbed during tumor development and progression.

  5. Ancient wolf lineages in India.

    PubMed Central

    Sharma, Dinesh K; Maldonado, Jesus E; Jhala, Yadrendradev V; Fleischer, Robert C

    2004-01-01

    All previously obtained wolf (Canis lupus) and dog (Canis familiaris) mitochondrial (mt) DNA sequences fall within an intertwined and shallow clade (the 'wolf-dog' clade). We sequenced mtDNA of recent and historical samples from 45 wolves from throughout lowland peninsular India and 23 wolves from the Himalayas and Tibetan Plateau and compared these sequences with all available wolf and dog sequences. All 45 lowland Indian wolves have one of four closely related haplotypes that form a well-supported, divergent sister lineage to the wolf-dog clade. This unique lineage may have been independent for more than 400,000 years. Although seven Himalayan wolves from western and central Kashmir fall within the widespread wolf-dog clade, one from Ladakh in eastern Kashmir, nine from Himachal Pradesh, four from Nepal and two from Tibet form a very different basal clade. This lineage contains five related haplotypes that probably diverged from other canids more than 800,000 years ago, but we find no evidence of current barriers to admixture. Thus, the Indian subcontinent has three divergent, ancient and apparently parapatric mtDNA lineages within the morphologically delineated wolf. No haplotypes of either novel lineage are found within a sample of 37 Indian (or other) dogs. Thus, we find no evidence that these two taxa played a part in the domestication of canids. PMID:15101402

  6. In silico lineage tracing through single cell transcriptomics identifies a neural stem cell population in planarians.

    PubMed

    Molinaro, Alyssa M; Pearson, Bret J

    2016-04-27

    The planarian Schmidtea mediterranea is a master regenerator with a large adult stem cell compartment. The lack of transgenic labeling techniques in this animal has hindered the study of lineage progression and has made understanding the mechanisms of tissue regeneration a challenge. However, recent advances in single-cell transcriptomics and analysis methods allow for the discovery of novel cell lineages as differentiation progresses from stem cell to terminally differentiated cell. Here we apply pseudotime analysis and single-cell transcriptomics to identify adult stem cells belonging to specific cellular lineages and identify novel candidate genes for future in vivo lineage studies. We purify 168 single stem and progeny cells from the planarian head, which were subjected to single-cell RNA sequencing (scRNAseq). Pseudotime analysis with Waterfall and gene set enrichment analysis predicts a molecularly distinct neoblast sub-population with neural character (νNeoblasts) as well as a novel alternative lineage. Using the predicted νNeoblast markers, we demonstrate that a novel proliferative stem cell population exists adjacent to the brain. scRNAseq coupled with in silico lineage analysis offers a new approach for studying lineage progression in planarians. The lineages identified here are extracted from a highly heterogeneous dataset with minimal prior knowledge of planarian lineages, demonstrating that lineage purification by transgenic labeling is not a prerequisite for this approach. The identification of the νNeoblast lineage demonstrates the usefulness of the planarian system for computationally predicting cellular lineages in an adult context coupled with in vivo verification.

  7. Potential treatment mechanisms in a mindfulness-based intervention for people with progressive multiple sclerosis.

    PubMed

    Bogosian, Angeliki; Hughes, Alicia; Norton, Sam; Silber, Eli; Moss-Morris, Rona

    2016-11-01

    To explore putative mediators of a mindfulness-based intervention to decrease distress in people with multiple sclerosis (MS) and to explore the patients' perspectives on this intervention. We used an explanatory mixed methods design incorporating quantitative data from a pilot randomized control trial and a qualitative interview study with people who completed the mindfulness intervention. People with MS (n = 40) completed standardized measures of distress (outcome), and acceptance, decentring, self-compassion, and self-efficacy (potential mediators). Semi-structured interviews (n = 15) of patients' experiences of the mindfulness intervention were analysed deductively and inductively. Decentring post-intervention explained 13% of the 3-month change in distress and between 27% and 31% of concurrent changes in distress. Acceptance changed only slightly, and as a result, the indirect effect accounts for only 2% of future distress and between 3% and 11% of concurrent distress. Qualitative data showed that acceptance and self-compassion needed more time to develop, whereas decentring could be implemented readily after being introduced in the sessions. Self-efficacy also had a large mediating effect. Participants in their interviews talked about group dynamics and prior expectations as essential elements that determine their engagement with the course and their level of satisfaction. Mindfulness interventions for people with a chronic progressive condition may benefit from focusing on helping them to accept daily challenges and teach them to recognize their thoughts and feelings, allowing time for acceptance and self-compassion to develop. Group dynamics also play a fundamental role in the success of the mindfulness interventions. Statement of Contribution What is already known on this subject? Mindfulness courses improve psychological well-being for people with chronic conditions. Mindfulness courses have been successful in improving psychological well-being and

  8. Differentiation of murine embryonic stem and induced pluripotent stem cells to renal lineage in vitro

    SciTech Connect

    Morizane, Ryuji; Monkawa, Toshiaki; Itoh, Hiroshi

    2009-12-25

    Embryonic stem (ES) cells which have the unlimited proliferative capacity and extensive differentiation potency can be an attractive source for kidney regeneration therapies. Recent breakthroughs in the generation of induced pluripotent stem (iPS) cells have provided with another potential source for the artificially-generated kidney. The purpose of this study is to know how to differentiate mouse ES and iPS cells into renal lineage. We used iPS cells from mouse fibroblasts by transfection of four transcription factors, namely Oct4, Sox2, c-Myc and Klf4. Real-time PCR showed that renal lineage markers were expressed in both ES and iPS cells after the induction of differentiation. It also showed that a tubular specific marker, KSP progressively increased to day 18, although the differentiation of iPS cells was slower than ES cells. The results indicated that renal lineage cells can be differentiated from both murine ES and iPS cells. Several inducing factors were tested whether they influenced on cell differentiation. In ES cells, both of GDNF and BMP7 enhanced the differentiation to metanephric mesenchyme, and Activin enhanced the differentiation of ES cells to tubular cells. Activin also enhanced the differentiation of iPS cells to tubular cells, although the enhancement was lower than in ES cells. ES and iPS cells have a potential to differentiate to renal lineage cells, and they will be an attractive resource of kidney regeneration therapy. This differentiation is enhanced by Activin in both ES and iPS cells.

  9. Deciphering the biodiversity of Listeria monocytogenes lineage III strains by polyphasic approaches.

    PubMed

    Zhao, Hanxin; Chen, Jianshun; Fang, Chun; Xia, Ye; Cheng, Changyong; Jiang, Lingli; Fang, Weihuan

    2011-10-01

    Listeria monocytogenes is a foodborne pathogen of humans and animals. The majority of human listeriosis cases are caused by strains of lineages I and II, while lineage III strains are rare and seldom implicated in human listeriosis. We revealed by 16S rRNA sequencing the special evolutionary status of L. monocytogenes lineage III, which falls between lineages I and II strains of L. monocytogenes and the non-pathogenic species L. innocua and L. marthii in the dendrogram. Thirteen lineage III strains were then characterized by polyphasic approaches. Biochemical reactions demonstrated 8 biotypes, internalin profiling identified 10 internal-in types clustered in 4 groups, and multilocus sequence typing differentiated 12 sequence types. These typing schemes show that lineage III strains represent the most diverse population of L. monocytogenes, and comprise at least four subpopulations IIIA-1, IIIA-2, HIB, and IIIC. The in vitro and in vivo virulence assessments showed that two lineage IIIA-2 strains had reduced pathogenicity, while the other lineage III strains had comparable virulence to lineages I and II. The HIB strains are phylogenetically distinct from other sub-populations, providing additional evidence that this sublineage represents a novel lineage. The two biochemical reactions L-rhamnose and L-lactate alkalinization, and 10 internalins were identified as potential markers for lineage III subpopulations. This study provides new insights into the biodiversity and population structure of lineage III strains, which are important for understanding the evolution of the L. mono-cytogenes-L. innocua clade.

  10. The potential influence of radiation-induced microenvironments in neoplastic progression

    NASA Technical Reports Server (NTRS)

    Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

    1998-01-01

    Ionizing radiation is a complete carcinogen, able both to initiate and promote neoplastic progression and is a known carcinogen of human and murine mammary gland. Tissue response to radiation is a composite of genetic damage, cell death and induction of new gene expression patterns. Although DNA damage is believed to initiate carcinogenesis, the contribution of these other aspects of radiation response are beginning to be explored. Our studies demonstrate that radiation elicits rapid and persistent global alterations in the mammary gland microenvironment. We postulate that radiation-induced microenvironments may affect epithelial cells neoplastic transformation by altering their number or susceptibility. Alternatively, radiation induced microenvironments may exert a selective force on initiated cells and/or be conducive to progression. A key impetus for these studies is the possibility that blocking these events could be a strategy to interrupt neoplastic progression.

  11. The potential influence of radiation-induced microenvironments in neoplastic progression

    NASA Technical Reports Server (NTRS)

    Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

    1998-01-01

    Ionizing radiation is a complete carcinogen, able both to initiate and promote neoplastic progression and is a known carcinogen of human and murine mammary gland. Tissue response to radiation is a composite of genetic damage, cell death and induction of new gene expression patterns. Although DNA damage is believed to initiate carcinogenesis, the contribution of these other aspects of radiation response are beginning to be explored. Our studies demonstrate that radiation elicits rapid and persistent global alterations in the mammary gland microenvironment. We postulate that radiation-induced microenvironments may affect epithelial cells neoplastic transformation by altering their number or susceptibility. Alternatively, radiation induced microenvironments may exert a selective force on initiated cells and/or be conducive to progression. A key impetus for these studies is the possibility that blocking these events could be a strategy to interrupt neoplastic progression.

  12. Raman spectroscopy for discrimination of neural progenitor cells and their lineages (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Chen, Keren; Ong, William; Chew, Sing Yian; Liu, Quan

    2017-02-01

    Neurological diseases are one of the leading causes of adult disability and they are estimated to cause more deaths than cancer in the elderly population by 2040. Stem cell therapy has shown great potential in treating neurological diseases. However, before cell therapy can be widely adopted in the long term, a number of challenges need to be addressed, including the fundamental research about cellular development of neural progenitor cells. To facilitate the fundamental research of neural progenitor cells, many methods have been developed to identify neural progenitor cells. Although great progress has been made, there is still lack of an effective method to achieve fast, label-free and noninvasive differentiation of neural progenitor cells and their lineages. As a fast, label-free and noninvasive technique, spontaneous Raman spectroscopy has been conducted to characterize many types of stem cells including neural stem cells. However, to our best knowledge, it has not been studied for the discrimination of neural progenitor cells from specific lineages. Here we report the differentiation of neural progenitor cell from their lineages including astrocytes, oligodendrocytes and neurons using spontaneous Raman spectroscopy. Moreover, we also evaluate the influence of system parameters during spectral acquisition on the quality of measured Raman spectra and the accuracy of classification using the spectra, which yield a set of optimal system parameters facilitating future studies.

  13. Defining Developmental Potency and Cell Lineage Trajectories by Expression Profiling of Differentiating Mouse Embryonic Stem Cells

    PubMed Central

    Aiba, Kazuhiro; Nedorezov, Timur; Piao, Yulan; Nishiyama, Akira; Matoba, Ryo; Sharova, Lioudmila V.; Sharov, Alexei A.; Yamanaka, Shinya; Niwa, Hitoshi; Ko, Minoru S. H.

    2009-01-01

    Biologists rely on morphology, function and specific markers to define the differentiation status of cells. Transcript profiling has expanded the repertoire of these markers by providing the snapshot of cellular status that reflects the activity of all genes. However, such data have been used only to assess relative similarities and differences of these cells. Here we show that principal component analysis of global gene expression profiles map cells in multidimensional transcript profile space and the positions of differentiating cells progress in a stepwise manner along trajectories starting from undifferentiated embryonic stem (ES) cells located in the apex. We present three ‘cell lineage trajectories’, which represent the differentiation of ES cells into the first three lineages in mammalian development: primitive endoderm, trophoblast and primitive ectoderm/neural ectoderm. The positions of the cells along these trajectories seem to reflect the developmental potency of cells and can be used as a scale for the potential of cells. Indeed, we show that embryonic germ cells and induced pluripotent cells are mapped near the origin of the trajectories, whereas mouse embryo fibroblast and fibroblast cell lines are mapped near the far end of the trajectories. We suggest that this method can be used as the non-operational semi-quantitative definition of cell differentiation status and developmental potency. Furthermore, the global expression profiles of cell lineages provide a framework for the future study of in vitro and in vivo cell differentiation. PMID:19112179

  14. Probabilistic diffusion tractography: a potential tool to assess the rate of disease progression in amyotrophic lateral sclerosis.

    PubMed

    Ciccarelli, O; Behrens, T E; Altmann, D R; Orrell, R W; Howard, R S; Johansen-Berg, H; Miller, D H; Matthews, P M; Thompson, A J

    2006-07-01

    the connectivity measures in the left CST were found (P-values between P < 0.001 and P = 0.002, partial correlation coefficients between -0.90 and -0.82). However, there was no evidence of an association between disease progression rate and any of the FA measures in the bilateral CST. Our findings suggest that FA and connectivity provide complementary information, since FA is sensitive to the detection of all the group differences, whereas the summary connectivity measures correlate with disease progression rate. The development of such connectivity measures raises their potential as markers of disease progression in ALS, and provides guidance for their use in other neurological diseases.

  15. Smoc2 potentiates proliferation of hepatocellular carcinoma cells via promotion of cell cycle progression

    PubMed Central

    Su, Jing-Ran; Kuai, Jing-Hua; Li, Yan-Qing

    2016-01-01

    AIM To determine the influence of Smoc2 on hepatocellular carcinoma (HCC) cell proliferation and to find a possible new therapeutic target for preventing HCC progression. METHODS We detected expression of Smoc2 in HCC tissues and corresponding non-tumor liver (CNL) tissues using PCR, western blot, and immunohistochemistry methods. Subsequently, we down-regulated and up-regulated Smoc2 expression using siRNA and lentivirus transfection assay, respectively. Then, we identified the effect of Smoc2 on cell proliferation and cell cycle using CCK-8 and flow cytometry, respectively. The common cell growth signaling influenced by Smoc2 was detected by western blot assay. RESULTS The expression of Smoc2 was significantly higher in HCC tissues compared with CNL tissues. Overexpression of Smoc2 promoted HCC cell proliferation and cell cycle progression. Down-regulation of Smoc2 led to inhibition of cell proliferation and cell cycle progression. Smoc2 had positive effect on ERK and AKT signaling. CONCLUSION Smoc2 promotes the proliferation of HCC cells through accelerating cell cycle progression and might act as an anti-cancer therapeutic target in the future. PMID:28018113

  16. Progressive Muscle Relaxation and Cognitive Restructuring: Potential Problems and Proposed Solutions.

    ERIC Educational Resources Information Center

    Kiselica, Mark S.; Baker, Stanley B.

    1992-01-01

    Reviews common problems experienced by clients during progressive muscle relaxation training (PMRT) and summarizes pertinent solutions to those problems. Discusses difficulties and solutions related to cognitive restructuring training. Notes that cognitive restructuring is often used to enhance effectiveness of PMRT. Concludes with suggestions for…

  17. [Advances in lineage-specific genes].

    PubMed

    Huanping, Zhang; Tongming, Yin

    2015-06-01

    Lineage-specific genes (LSGs) are defined as genes found in one particular taxonomic group but have no significant sequence similarity with genes from other lineages, which compose about 10%?20% of the total genes in the genome of a focal organism. LSGs were first uncovered in the yeast genome in 1996. The development of the whole genome sequencing leads to the emergence of studies on LSGs as a hot topic in comparative genomics. LSGs have been extensively studied on microbial species, lower marine organisms, plant (such as Arabidopsis thaliana, Oryza sativa, Populus), insects, primate, etc; the biological functions of LSGs are important to clarify the evolution and adaptability of a species. In this review, we summarize the progress of LSGs studies, including LSGs identification, gene characterization, origin and evolution of LSGs, biological function, and expression analysis of LSGs. In addition, we discuss the existing problems and future directions for studies in this area. Our purpose is to provide some unique insights into the researches of LSGs.

  18. Cataract progression after prophylactic laser peripheral iridotomy: potential implications for the prevention of glaucoma blindness.

    PubMed

    Lim, Laurence S; Husain, Rahat; Gazzard, Gus; Seah, Steve K L; Aung, Tin

    2005-08-01

    To evaluate changes in lens opacity in the first year after prophylactic laser peripheral iridotomy (LPI) performed in fellow eyes of subjects with acute primary angle closure (APAC). Prospective observational case series. Sixty Asian subjects with unilateral APAC. All fellow eyes underwent prophylactic LPI within the first week of presentation, followed by 1 week of topical steroids. The degree of lens opacity was graded at the slit-lamp examination using the Lens Opacity Classification System III (LOCS III) with standard color photographs as the reference for grading of lens opacity. This was performed 2 weeks, 4 months, and 12 months after LPI. Progression in lens opacity was defined as an increase in LOCS III grade by 2 or more units in any lens region. Lens Opacity Classification Sytem III grades in nuclear, cortical, and posterior subcapsular (PSC) regions. Most patients were Chinese (85%) and female (63.3%), with an average age of 61.5 +/- 10.6 years. The mean baseline LOCS grades in the nuclear, cortical, and PSC regions were 3.58 +/- 0.74, 0.57 +/- 1.08, and 0.23 +/- 0.72, respectively. With 12 months of follow-up, 14 of the 60 eyes (23.3%; 95% confidence interval, 16.9-29.7%) showed significant progression in any lens region. Progression in the nuclear, cortical, and PSC regions was documented in 5%, 6.7%, and 16.7% of cases, respectively. By use of logistic regression, the following factors were not found to be significant for cataract progression in any lens region: age, race, gender, history of hypertension or diabetes, presence of peripheral anterior synechiae or angle width at baseline, and total laser energy delivered. In fellow eyes of APAC, prophylactic LPI is complicated by significant cataract progression, mainly in the posterior subcapsular region. These findings may have implications for the role of prophylactic LPI in the prevention of angle-closure blindness.

  19. A reporter mouse reveals lineage-specific and heterogeneous expression of IRF8 during lymphoid and myeloid cell differentiation1

    PubMed Central

    Wang, Hongsheng; Yan, Ming; Sun, Jiafang; Jain, Shweta; Yoshimi, Ryusuke; Abolfath, Sanaz Momben; Ozato, Keiko; Coleman, William G.; Ng, Ashley P.; Metcalf, Donald; DiRago, Ladina; Nutt, Stephen L.; Morse, Herbert C.

    2014-01-01

    The interferon regulatory factor family member 8 (IRF8) regulates differentiation of lymphoid and myeloid lineage cells by promoting or suppressing lineage-specific genes. How IRF8 promotes hematopoietic progenitors to commit to one lineage while preventing the development of alternative lineages is not known. Here we report an IRF8-EGFP fusion protein reporter mouse that revealed previously unrecognized patterns of IRF8 expression. Differentiation of hematopoietic stem cells into oligopotent progenitors is associated with progressive increases in IRF8-EGFP expression. However, significant induction of IRF8-EGFP is found in granulocyte-myeloid progenitors (GMPs) and the common lymphoid progenitors (CLPs) but not the megakaryocytic-erythroid progenitors. Surprisingly, IRF8-EGFP identifies three subsets of the seemingly homogeneous GMPs with an intermediate level of expression of EGFP defining bipotent progenitors that differentiation into either EGFPhi monocytic progenitors or EGFPlo granulocytic progenitors. Also surprisingly, IRF8-EGFP revealed a highly heterogeneous pre-pro-B population with a fluorescence intensity ranging from background to 4 orders above background. Interestingly, IRF8-EGFP readily distinguishes true B cell-committed (EGFPint) from those that are non-committed. Moreover, dendritic cell progenitors expressed extremely high levels of IRF8-EGFP. Taken together, the IRF8-EGFP reporter revealed previously unrecognized subsets with distinct developmental potentials in phenotypically well-defined oligopotent progenitors, providing new insights into the dynamic heterogeneity of developing hematopoietic progenitors. PMID:25024380

  20. Evolutionary history of the reprimo tumor suppressor gene family in vertebrates with a description of a new reprimo gene lineage.

    PubMed

    Wichmann, Ignacio A; Zavala, Kattina; Hoffmann, Federico G; Vandewege, Michael W; Corvalán, Alejandro H; Amigo, Julio D; Owen, Gareth I; Opazo, Juan C

    2016-10-10

    Genes related to human diseases should be natural targets for evolutionary studies, since they could provide clues regarding the genetic bases of pathologies and potential treatments. Here we studied the evolution of the reprimo gene family, a group of tumor-suppressor genes that are implicated in p53-mediated cell cycle arrest. These genes, especially the reprimo duplicate located on human chromosome 2, have been associated with epigenetic modifications correlated with transcriptional silencing and cancer progression. We demonstrate the presence of a third reprimo lineage that, together with the reprimo and reprimo-like genes, appears to have been differentially retained during the evolutionary history of vertebrates. We present evidence that these reprimo lineages originated early in vertebrate evolution and expanded as a result of the two rounds of whole genome duplications that occurred in the last common ancestor of vertebrates. The reprimo gene has been lost in birds, and the third reprimo gene lineage has been retained in only a few distantly related species, such as coelacanth and gar. Expression analyses revealed that the reprimo paralogs are mainly expressed in the nervous system. Different vertebrate lineages have retained different reprimo paralogs, and even in species that have retained multiple copies, only one of them is heavily expressed. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Potential for progress in carbon cycle modeling: models as tools and representations of reality (Invited)

    NASA Astrophysics Data System (ADS)

    Caldeira, K.

    2013-12-01

    attribution) Potential for progress in carbon-cycle modeling rests in being clear about the problems we seek to solve, and then developing tools to solve those problems. A global carbon cycle model that represents underlying complexity in all its detail may ultimately prove useless: 'We actually made a map of the country, on the scale of a mile to the mile!' 'Have you used it much?' I enquired. 'It has never been spread out, yet,' said Mein Herr: 'the farmers objected: they said it would cover the whole country, and shut out the sunlight! So we now use the country itself, as its own map, and I assure you it does nearly as well.' - Lewis Carroll

  2. Metabolic mechanisms of plant growth at low water potentials. Progress report

    SciTech Connect

    Boyer, J.S.

    1986-01-01

    Experiments were conducted to identify primary and secondary factors that cause cell enlargement to be inhibited in the stems of soybean seedlings exposed to low water potentials. The factors that were analyzed are wall extensibility, yield threshold of the walls, hydraulic conductance of the tissue, turgor, osmotic potential, and growth-induced water potentials.

  3. Quantitative lineage tracing strategies to resolve multipotency in tissue-specific stem cells

    PubMed Central

    Wuidart, Aline; Ousset, Marielle; Rulands, Steffen; Simons, Benjamin D.; Van Keymeulen, Alexandra; Blanpain, Cédric

    2016-01-01

    Lineage tracing has become the method of choice to study the fate and dynamics of stem cells (SCs) during development, homeostasis, and regeneration. However, transgenic and knock-in Cre drivers used to perform lineage tracing experiments are often dynamically, temporally, and heterogeneously expressed, leading to the initial labeling of different cell types and thereby complicating their interpretation. Here, we developed two methods: the first one based on statistical analysis of multicolor lineage tracing, allowing the definition of multipotency potential to be achieved with high confidence, and the second one based on lineage tracing at saturation to assess the fate of all SCs within a given lineage and the “flux” of cells between different lineages. Our analysis clearly shows that, whereas the prostate develops from multipotent SCs, only unipotent SCs mediate mammary gland (MG) development and adult tissue remodeling. These methods offer a rigorous framework to assess the lineage relationship and SC fate in different organs and tissues. PMID:27284162

  4. Feedback, Lineages and Self-Organizing Morphogenesis

    PubMed Central

    Calof, Anne L.; Lowengrub, John S.; Lander, Arthur D.

    2016-01-01

    Feedback regulation of cell lineage progression plays an important role in tissue size homeostasis, but whether such feedback also plays an important role in tissue morphogenesis has yet to be explored. Here we use mathematical modeling to show that a particular feedback architecture in which both positive and negative diffusible signals act on stem and/or progenitor cells leads to the appearance of bistable or bi-modal growth behaviors, ultrasensitivity to external growth cues, local growth-driven budding, self-sustaining elongation, and the triggering of self-organization in the form of lamellar fingers. Such behaviors arise not through regulation of cell cycle speeds, but through the control of stem or progenitor self-renewal. Even though the spatial patterns that arise in this setting are the result of interactions between diffusible factors with antagonistic effects, morphogenesis is not the consequence of Turing-type instabilities. PMID:26989903

  5. (Metabolic mechanisms of plant growth at low-water potentials): Progress report

    SciTech Connect

    Boyer, J.S.

    1988-01-01

    We used soybean seedlings grown in vermiculite in a dark, humid environment because they are convenient to grow, undergo most of the physiological changes induced by low water potentials in large plants, and have exposed growing regions. We studied how growth-induced water potentials originate; which of the parameters regulating cell enlargement are the cause of the decreased rate of stem growth observed at low water potentials; molecular changes that occur in the cell wall at low water potentials; and the mechanism of differential root and shoot growth at low water potential.

  6. The New Deal: A Potential Role for Secreted Vesicles in Innate Immunity and Tumor Progression

    PubMed Central

    Benito-Martin, Alberto; Di Giannatale, Angela; Ceder, Sophia; Peinado, Héctor

    2015-01-01

    Tumors must evade the immune system to survive and metastasize, although the mechanisms that lead to tumor immunoediting and their evasion of immune surveillance are far from clear. The first line of defense against metastatic invasion is the innate immune system that provides immediate defense through humoral immunity and cell-mediated components, mast cells, neutrophils, macrophages, and other myeloid-derived cells that protect the organism against foreign invaders. Therefore, tumors must employ different strategies to evade such immune responses or to modulate their environment, and they must do so prior metastasizing. Exosomes and other secreted vesicles can be used for cell–cell communication during tumor progression by promoting the horizontal transfer of information. In this review, we will analyze the role of such extracellular vesicles during tumor progression, summarizing the role of secreted vesicles in the crosstalk between the tumor and the innate immune system. PMID:25759690

  7. EZH2 in Cancer Progression and Potential Application in Cancer Therapy: A Friend or Foe?

    PubMed Central

    Yan, Ke-Sin; Lin, Chia-Yuan; Liao, Tan-Wei; Peng, Cheng-Ming; Lee, Shou-Chun; Liu, Yi-Jui; Chan, Wing P.; Chou, Ruey-Hwang

    2017-01-01

    Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) to regulate gene expression through epigenetic machinery. EZH2 functions as a double-facet molecule in regulation of gene expression via repression or activation mechanisms, depending on the different cellular contexts. EZH2 interacts with both histone and non-histone proteins to modulate diverse physiological functions including cancer progression and malignancy. In this review article, we focused on the updated information regarding microRNAs (miRNAs) and long non coding RNAs (lncRNAs) in regulation of EZH2, the oncogenic and tumor suppressive roles of EZH2 in cancer progression and malignancy, as well as current pre-clinical and clinical trials of EZH2 inhibitors. PMID:28561778

  8. CK2 phosphorylation of eukaryotic translation initiation factor 5 potentiates cell cycle progression

    PubMed Central

    Homma, Miwako Kato; Wada, Ikuo; Suzuki, Toshiyuki; Yamaki, Junko; Krebs, Edwin G.; Homma, Yoshimi

    2005-01-01

    Casein kinase 2 (CK2) is a ubiquitous eukaryotic Ser/Thr protein kinase that plays an important role in cell cycle progression. Although its function in this process remains unclear, it is known to be required for the G1 and G2/M phase transitions in yeast. Here, we show that CK2 activity changes notably during cell cycle progression and is increased within 3 h of serum stimulation of quiescent cells. During the time period in which it exhibits high enzymatic activity, CK2 associates with and phosphorylates a key molecule for translation initiation, eukaryotic translation initiation factor (eIF) 5. Using MS, we show that Ser-389 and -390 of eIF5 are major sites of phosphorylation by CK2. This is confirmed using eIF5 mutants that lack CK2 sites; the phosphorylation levels of mutant eIF5 proteins are significantly reduced, relative to WT eIF5, both in vitro and in vivo. Expression of these mutants reveals that they have a dominant-negative effect on phosphorylation of endogenous eIF5, and that they perturb synchronous progression of cells through S to M phase, resulting in a significant reduction in growth rate. Furthermore, the formation of mature eIF5/eIF2/eIF3 complex is reduced in these cells, and, in fact, restricted diffusional motion of WT eIF5 was almost abolished in a GFP-tagged eIF5 mutant lacking CK2 phosphorylation sites, as measured by fluorescence correlation spectroscopy. These results suggest that CK2 may be involved in the regulation of cell cycle progression by associating with and phosphorylating a key molecule for translation initiation. PMID:16227438

  9. Early and multiple origins of metastatic lineages within primary tumors

    PubMed Central

    Zhao, Zi-Ming; Zhao, Bixiao; Bai, Yalai; Iamarino, Atila; Gaffney, Stephen G.; Schlessinger, Joseph; Lifton, Richard P.; Rimm, David L.; Townsend, Jeffrey P.

    2016-01-01

    Many aspects of the evolutionary process of tumorigenesis that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages. To address these challenges, we performed tumor phylogenetics using molecular evolutionary models, reconstructed ancestral states of somatic mutations, and inferred cancer chronograms to yield three conclusions. First, in contrast to a linear model of cancer progression, metastases can originate from divergent lineages within primary tumors. Evolved genetic changes in cancer lineages likely affect only the proclivity toward metastasis. Single genetic changes are unlikely to be necessary or sufficient for metastasis. Second, metastatic lineages can arise early in tumor development, sometimes long before diagnosis. The early genetic divergence of some metastatic lineages directs attention toward research on driver genes that are mutated early in cancer evolution. Last, the temporal order of occurrence of driver mutations can be inferred from phylogenetic analysis of cancer chronograms, guiding development of targeted therapeutics effective against primary tumors and metastases. PMID:26858460

  10. The Potential Role of Nitric Oxide in Halting Cancer Progression Through Chemoprevention

    PubMed Central

    Vahora, Huzefa; Khan, Munawwar Ali; Alalami, Usama; Hussain, Arif

    2016-01-01

    Nitric oxide (NO) in general plays a beneficial physiological role as a vasorelaxant and the role of NO is decided by its concentration present in physiological environments. NO either facilitates cancer-promoting characters or act as an anti-cancer agent. The dilemma in this regard still remains unanswered. This review summarizes the recent information on NO and its role in carcinogenesis and tumor progression, as well as dietary chemopreventive agents which have NO-modulating properties with safe cytotoxic profile. Understanding the molecular mechanisms and cross-talk modulating NO effect by these chemopreventive agents can allow us to develop better therapeutic strategies for cancer treatment. PMID:27051643

  11. The role of non-coding RNAs in diabetic nephropathy: potential applications as biomarkers for disease development and progression.

    PubMed

    Alvarez, M Lucrecia; Distefano, Johanna K

    2013-01-01

    Diabetic nephropathy, a progressive kidney disease that develops secondary to diabetes, is the major cause of chronic kidney disease in developed countries, and contributes significantly to increased morbidity and mortality among individuals with diabetes. Although the causes of diabetic nephropathy are not fully understood, recent studies demonstrate a role for epigenetic factors in the development of the disease. For example, non-coding RNA (ncRNA) molecules, including microRNAs (miRNAs), have been shown to be functionally important in modulating renal response to hyperglycemia and progression of diabetic nephropathy. Characterization of miRNA expression in diabetic nephropathy from studies of animal models of diabetes, and in vitro investigations using different types of kidney cells also support this role. The goal of this review, therefore, is to summarize the current state of knowledge of specific ncRNAs involved in the development of diabetic nephropathy, with a focus on the potential role of miRNAs to serve as sensitive, non-invasive biomarkers of kidney disease and progression. Non-coding RNAs are currently recognized as potentially important regulators of genes involved in processes related to the development of diabetic nephropathy, and as such, represent viable targets for both clinical diagnostic strategies and therapeutic intervention.

  12. Confetti-like depigmentation: A potential sign of rapidly progressing vitiligo.

    PubMed

    Sosa, Juan Jesús; Currimbhoy, Sharif D; Ukoha, Uzoamaka; Sirignano, Samantha; O'Leary, Ryan; Vandergriff, Travis; Hynan, Linda S; Pandya, Amit G

    2015-08-01

    Confetti-like depigmentation was noted in patients reporting recent worsening of vitiligo. We sought to determine if confetti-like depigmentation is a marker of rapidly progressing vitiligo. Review of patient records and images of patients from a vitiligo registry resulted in 7 patients with 12 images that fit inclusion criteria and were evaluated for percent depigmentation by 3 independent reviewers. The Vitiligo Disease Activity Score and the Koebner Phenomenon in Vitiligo Score in an additional cohort of patients with confetti-like lesions were compared with patients who had vitiligo without confetti-like lesions. The mean percentage of depigmentation at baseline was 19.2%, which increased to 43.9% in images obtained at a mean of 16 weeks of follow-up. Vitiligo Disease Activity Score and Koebner Phenomenon in Vitiligo Score were significantly higher in the patients with confetti-like lesions compared with those without confetti-like lesions. A skin biopsy specimen of a confetti-like lesion in 1 patient revealed an inflammatory infiltrate in the papillary dermis with CD8(+) T cells localized to the dermoepidermal junction. Small, single-center retrospective review and lack of full-body photographs are limitations. A confetti-like pattern of depigmentation may be a negative prognostic indicator for patients with rapidly progressing vitiligo. Further, prospective studies to evaluate this physical finding should be performed. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  13. CSPG4, a potential therapeutic target, facilitates malignant progression of melanoma

    PubMed Central

    Price, Matthew A.; Wanshura, Leah E. Colvin; Yang, Jianbo; Carlson, Jennifer; Xiang, Bo; Li, Guiyuan; Ferrone, Soldano; Dudek, Arkadiusz Z.; Turley, Eva A.; McCarthy, James B.

    2012-01-01

    Summary Chondroitin sulfate proteoglycan 4 (CSPG4), a transmembrane proteoglycan originally identified as a highly immunogenic tumor antigen on the surface of melanoma cells, is associated with melanoma tumor formation and poor prognosis in certain melanomas and several other tumor types. The complex mechanisms by which CSPG4 affects melanoma progression have started to be defined, in particular the association with other cell surface proteins and receptor tyrosine kinases (RTKs) and its central role in modulating the function of these proteins. CSPG4 is essential to the growth of melanoma tumors through its modulation of integrin function and enhanced growth factor receptor-regulated pathways including sustained activation of ERK 1,2. This activation of integrin, RTK, and ERK 1,2 function by CSPG4 modulates numerous aspects of tumor progression. CSPG4 expression has further been correlated to resistance of melanoma to conventional chemotherapeutics. This review outlines recent advances in our understanding of CSPG4-associated cell signaling, describing the central role it plays in melanoma tumor cell growth, motility, and survival, and explores how modifying CSPG4 function and protein–protein interactions may provide us with novel combinatorial therapies for the treatment of advanced melanoma. PMID:22004131

  14. CSPG4, a potential therapeutic target, facilitates malignant progression of melanoma.

    PubMed

    Price, Matthew A; Colvin Wanshura, Leah E; Yang, Jianbo; Carlson, Jennifer; Xiang, Bo; Li, Guiyuan; Ferrone, Soldano; Dudek, Arkadiusz Z; Turley, Eva A; McCarthy, James B

    2011-12-01

    Chondroitin sulfate proteoglycan 4 (CSPG4), a transmembrane proteoglycan originally identified as a highly immunogenic tumor antigen on the surface of melanoma cells, is associated with melanoma tumor formation and poor prognosis in certain melanomas and several other tumor types. The complex mechanisms by which CSPG4 affects melanoma progression have started to be defined, in particular the association with other cell surface proteins and receptor tyrosine kinases (RTKs) and its central role in modulating the function of these proteins. CSPG4 is essential to the growth of melanoma tumors through its modulation of integrin function and enhanced growth factor receptor-regulated pathways including sustained activation of ERK 1,2. This activation of integrin, RTK, and ERK1,2 function by CSPG4 modulates numerous aspects of tumor progression. CSPG4 expression has further been correlated to resistance of melanoma to conventional chemotherapeutics. This review outlines recent advances in our understanding of CSPG4-associated cell signaling, describing the central role it plays in melanoma tumor cell growth, motility, and survival, and explores how modifying CSPG4 function and protein-protein interactions may provide us with novel combinatorial therapies for the treatment of advanced melanoma.

  15. Chemokines in Cancer Development and Progression and Their Potential as Targeting Molecules for Cancer Treatment

    PubMed Central

    Mukaida, Naofumi; Sasaki, So-ichiro; Baba, Tomohisa

    2014-01-01

    Chemokines were initially identified as bioactive substances, which control the trafficking of inflammatory cells including granulocytes and monocytes/macrophages. Moreover, chemokines have profound impacts on other types of cells associated with inflammatory responses, such as endothelial cells and fibroblasts. These observations would implicate chemokines as master regulators in various inflammatory responses. Subsequent studies have further revealed that chemokines can regulate the movement of a wide variety of immune cells including lymphocytes, natural killer cells, and dendritic cells in both physiological and pathological conditions. These features endow chemokines with crucial roles in immune responses. Furthermore, increasing evidence points to the vital effects of several chemokines on the proliferative and invasive properties of cancer cells. It is widely acknowledged that cancer develops and progresses to invade and metastasize in continuous interaction with noncancerous cells present in cancer tissues, such as macrophages, lymphocytes, fibroblasts, and endothelial cells. The capacity of chemokines to regulate both cancerous and noncancerous cells highlights their crucial roles in cancer development and progression. Here, we will discuss the roles of chemokines in carcinogenesis and the possibility of chemokine targeting therapy for the treatment of cancer. PMID:24966464

  16. Accelerated neuronal differentiation toward motor neuron lineage from human embryonic stem cell line (H9).

    PubMed

    Lu, David; Chen, Eric Y T; Lee, Philip; Wang, Yung-Chen; Ching, Wendy; Markey, Christopher; Gulstrom, Chase; Chen, Li-Ching; Nguyen, Thien; Chin, Wei-Chun

    2015-03-01

    Motor neurons loss plays a pivotal role in the pathoetiology of various debilitating diseases such as, but not limited to, amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy, progressive bulbar palsy, pseudobulbar palsy, and spinal muscular atrophy. However, advancement in motor neuron replacement therapy has been significantly constrained by the difficulties in large-scale production at a cost-effective manner. Current methods to derive motor neuron heavily rely on biochemical stimulation, chemical biological screening, and complex physical cues. These existing methods are seriously challenged by extensive time requirements and poor yields. An innovative approach that overcomes prior hurdles and enhances the rate of successful motor neuron transplantation in patients is of critical demand. Iron, a trace element, is indispensable for the normal development and function of the central nervous system. Whether ferric ions promote neuronal differentiation and subsequently promote motor neuron lineage has never been considered. Here, we demonstrate that elevated iron concentration can drastically accelerate the differentiation of human embryonic stem cells (hESCs) toward motor neuron lineage potentially via a transferrin mediated pathway. HB9 expression in 500 nM iron-treated hESCs is approximately twofold higher than the control. Moreover, iron treatment generated more matured and functional motor neuron-like cells that are ∼1.5 times more sensitive to depolarization when compared to the control. Our methodology renders an expedited approach to harvest motor neuron-like cells for disease, traumatic injury regeneration, and drug screening.

  17. Appearance traits in fish farming: progress from classical genetics to genomics, providing insight into current and potential genetic improvement

    PubMed Central

    Colihueque, Nelson; Araneda, Cristian

    2014-01-01

    Appearance traits in fish, those external body characteristics that influence consumer acceptance at point of sale, have come to the forefront of commercial fish farming, as culture profitability is closely linked to management of these traits. Appearance traits comprise mainly body shape and skin pigmentation. Analysis of the genetic basis of these traits in different fish reveals significant genetic variation within populations, indicating potential for their genetic improvement. Work into ascertaining the minor or major genes underlying appearance traits for commercial fish is emerging, with substantial progress in model fish in terms of identifying genes that control body shape and skin colors. In this review, we describe research progress to date, especially with regard to commercial fish, and discuss genomic findings in model fish in order to better address the genetic basis of the traits. Given that appearance traits are important in commercial fish, the genomic information related to this issue promises to accelerate the selection process in coming years. PMID:25140172

  18. Mucin (Muc) expression during pancreatic cancer progression in spontaneous mouse model: potential implications for diagnosis and therapy

    PubMed Central

    2012-01-01

    Background Pancreatic cancer (PC) is a lethal malignancy primarily driven by activated Kras mutations and characterized by the deregulation of several genes including mucins. Previous studies on mucins have identified their significant role in both benign and malignant human diseases including PC progression and metastasis. However, the initiation of MUC expression during PC remains unknown because of lack of early stage tumor tissues from PC patients. Methods In the present study, we have evaluated stage specific expression patterns of mucins during mouse PC progression in (KrasG12D;Pdx1-Cre (KC)) murine PC model from pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC) by immunohistochemistry and quantitative real-time PCR. Results In agreement with previous studies on human PC, we observed a progressive increase in the expression of mucins particularly Muc1, Muc4 and Muc5AC in the pancreas of KC (as early as PanIN I) mice with advancement of PanIN lesions and PDAC both at mRNA and protein levels. Additionally, mucin expression correlated with the increased expression of inflammatory cytokines IFN-γ (p < 0.0062), CXCL1 (p < 0.00014) and CXCL2 (p < 0.08) in the pancreas of KC mice, which are known to induce mucin expression. Further, we also observed progressive increase in inflammation in pancreas of KC mice from 10 to 50 weeks of age as indicated by the increase in the macrophage infiltration. Overall, this study corroborates with previous human studies that indicated the aberrant overexpression of MUC1, MUC4 and MUC5AC mucins during the progression of PC. Conclusions Our study reinforces the potential utility of the KC murine model for determining the functional role of mucins in PC pathogenesis by crossing KC mice with corresponding mucin knockout mice and evaluating mucin based diagnostic and therapeutic approaches for lethal PC. PMID:23102107

  19. [Application potentials and research progress of nanoparticle technologies in immune therapies].

    PubMed

    Yang, Man; Xu, Halyan

    2009-02-01

    Nanoparticles have attracted intense attention and interests in the fields of science and medical industry in recent years due to their unique chemical and physical properties that may provide new solutions to the diagnoses and therapies of some intractable diseases. It has been recognized that the nanoparticles' features including small dimensions, modifiability, diversification, and so on would play revolutionary roles in early detection and diagnosis of diseases, in tumor-specific killing, pathogen ridding and gene restoring, and would provide some new approaches in molecular imaging, targeting delivery of gene or drugs, immune regulating, etc. This review is focusing on the study progress of nanoparticle technologies in immune regulating, anti-tumor immune therapies, anti-tumor targeting therapies and new vaccine development. Also the possible mechanisms by which nanoparticles enter into cells to participate in immune therapies are discussed on the basis of references.

  20. Sequencing-based diagnostics for pediatric genetic diseases: progress and potential

    PubMed Central

    Tayoun, Ahmad Abou; Krock, Bryan; Spinner, Nancy B.

    2016-01-01

    Introduction The last two decades have witnessed revolutionary changes in clinical diagnostics, fueled by the Human Genome Project and advances in high throughput, Next Generation Sequencing (NGS). We review the current state of sequencing-based pediatric diagnostics, associated challenges, and future prospects. Areas Covered We present an overview of genetic disease in children, review the technical aspects of Next Generation Sequencing and the strategies to make molecular diagnoses for children with genetic disease. We discuss the challenges of genomic sequencing including incomplete current knowledge of variants, lack of data about certain genomic regions, mosaicism, and the presence of regions with high homology. Expert Commentary NGS has been a transformative technology and the gap between the research and clinical communities has never been so narrow. Therapeutic interventions are emerging based on genomic findings and the applications of NGS are progressing to prenatal genetics, epigenomics and transcriptomics. PMID:27388938

  1. A Program for the Potentially-Gifted Disadvantaged: A Progress Report.

    ERIC Educational Resources Information Center

    Corbin, Richard

    1968-01-01

    Schools must attempt to identify and develop those gifted young people who, because of environment and background, are faced with limited opportunities for achievement. At Hunter College High School, New York City, a program was instituted in which"disadvantaged, but potentially gifted" students made up 25% of each entering seventh-grade class.…

  2. Gaining Momentum, Losing Ground. Tapping America's Potential (TAP) Progress Report, 2008. Executive Summary

    ERIC Educational Resources Information Center

    Tapping America's Potential, 2008

    2008-01-01

    In July 2005, Business Roundtable and fifteen of America's most prominent business organizations--Tapping America's Potential, the TAP coalition--issued a report stating that "one of the pillars of American economic prosperity--U.S. scientific and technological superiority--is beginning to atrophy even as other nations are developing their own…

  3. Metabolomic profiling reveals potential biomarkers in esophageal cancer progression using liquid chromatography-mass spectrometry platform.

    PubMed

    Zhang, Haiping; Wang, Lei; Hou, Zhichao; Ma, Hong; Mamtimin, Batur; Hasim, Ayshamgul; Sheyhidin, Ilyar

    2017-09-09

    Esophageal cancer (EC) is one of the most common malignancies with poor prognosis. Metabolomics has been shown to be a powerful approach to discover the potential biomarkers for cancer diagnosis and prognosis. The goal of this study is to screen potential biomarkers for early diagnosis and prognosis. In this study, 40 tissue samples and the corresponding control samples from the same esophageal squamous cell carcinoma (ESCC) patients were analyzed by liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. 20 potential diagnostic biomarkers were selected. Moreover, 9 metabolites were found to be closely correlated with the pathological feature such as local invasion, lymphatic metastasis and postoperative survival time. Glutamate was correlated with local invasion of tumor, and oleic acid, LysoPC(15:0), uracil, inosine and choline were closely related with the lymphatic metastasis, while glutamine, kynurenine, serine and uracil were related with postoperative survival time. The results indicated that the potential biomarkers discovered by metabolomics could reflect the metabolic characterization of ESCC, and offers a novel approach for early diagnosis, assessment and prognosis of the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Conditional Lineage Ablation to Model Human Diseases

    NASA Astrophysics Data System (ADS)

    Lee, Paul; Morley, Gregory; Huang, Qian; Fischer, Avi; Seiler, Stephanie; Horner, James W.; Factor, Stephen; Vaidya, Dhananjay; Jalife, Jose; Fishman, Glenn I.

    1998-09-01

    Cell loss contributes to the pathogenesis of many inherited and acquired human diseases. We have developed a system to conditionally ablate cells of any lineage and developmental stage in the mouse by regulated expression of the diphtheria toxin A (DTA) gene by using tetracycline-responsive promoters. As an example of this approach, we targeted expression of DTA to the hearts of adult mice to model structural abnormalities commonly observed in human cardiomyopathies. Induction of DTA expression resulted in cell loss, fibrosis, and chamber dilatation. As in many human cardiomyopathies, transgenic mice developed spontaneous arrhythmias in vivo, and programmed electrical stimulation of isolated-perfused transgenic hearts demonstrated a strikingly high incidence of spontaneous and inducible ventricular tachycardia. Affected mice showed marked perturbations of cardiac gap junction channel expression and localization, including a subset with disorganized epicardial activation patterns as revealed by optical action potential mapping. These studies provide important insights into mechanisms of arrhythmogenesis and suggest that conditional lineage ablation may have wide applicability for studies of disease pathogenesis.

  5. The progressive wave pump: numerical multiphysics investigation of a novel pump concept with potential to ventricular assist device application.

    PubMed

    Perschall, Markus; Drevet, Jean Baptiste; Schenkel, Torsten; Oertel, Herbert

    2012-09-01

    This article describes the numerical fluid-structure interaction (FSI) validation of a new pumping concept and the possibility for application of a further developed type, as an implantable ventricular assist device (VAD). The novel principle of the so-called progressive wave pump is based on the interaction of an elastic membrane actuated by forced excitation with a surrounding fluid and the pump housing. By applying forced vibrations to one end of the membrane, a transversal wave builds up and progresses to the far end generating both a positive pressure gradient and flow rate. Among others, two axisymmetric geometrical configurations are possible, namely the discoidal and the tubular design. The first one has been built as a physical prototype and is experimentally investigated. In addition, a corresponding numerical FSI model is set up and validated against the experimental findings. Based on this validated numerical method, further numerical investigations are conducted focusing on the development of a tubular progressive wave pump concept with regard to its potential for application as a VAD in the future. To address VAD-relevant issues such as size, hydraulic performance, and blood trauma, corresponding numerical simulations involving macroscopic blood trauma models have been performed. Although being still in an early phase of development, the results are promising and indicate that the wave pump concept in its present state is feasible and can be further developed and investigated as a new type of blood pump.

  6. Optical coherence tomography findings in Huntington's disease: a potential biomarker of disease progression.

    PubMed

    Kersten, Hannah M; Danesh-Meyer, Helen V; Kilfoyle, Dean H; Roxburgh, Richard H

    2015-11-01

    Previous reports of ocular abnormalities in Huntington's disease (HD) have detailed eye movement disorders. The objective of this case-control study was to investigate optic nerve and macular morphology in HD using optical coherence tomography (OCT). A total of 26 HD patients and 29 controls underwent a thorough ophthalmic examination including spectral domain OCT scans of the macula and peripapillary retinal nerve fibre layer (RNFL). Genetic testing results, disease duration, HD disease burden scores and Unified HD Rating Scale motor scores were acquired for HD patients. Temporal RNFL thickness was significantly reduced in the HD group (62.3 vs. 69.8 μm, p = 0.005), and there was a significant negative correlation between temporal RNFL thickness and disease duration (R (2) = -0.51, p = 0.04). Average peripapillary RNFL thickness was not significantly different between the HD and control groups. There was a significant negative correlation between macular volume and disease duration (R (2) = -0.71, p = 0.002), and motor scores (R (2) = -0.56, p = 0.01). Colour vision was significantly poorer in the HD group. Temporal RNFL is preferentially thinned in HD patients, possibly implicating mitochondrial dysfunction as the temporal RNFL is reduced in the patients with some mitochondrial disorders, including Leber's hereditary optic neuropathy. The correlation between the decrease in macular volume and temporal RNFL, and increasing disease severity suggests that OCT may be a useful biomarker for disease progression in HD. Larger, longitudinal studies are required.

  7. Alchemy in the underworld - recent progress and future potential of organic geochemistry applied to speleothems.

    NASA Astrophysics Data System (ADS)

    Blyth, Alison

    2016-04-01

    Speleothems are well used archives for chemical records of terrestrial environmental change, and the integration of records from a range of isotopic, inorganic, and organic geochemical techniques offers significant power in reconstructing both changes in past climates and identifying the resultant response in the overlying terrestrial ecosystems. The use of organic geochemistry in this field offers the opportunity to recover new records of vegetation change (via biomarkers and compound specific isotopes), temperature change (via analysis of glycerol dialkyl glycerol tetraethers, a compound group derived from microbes and varying in structure in response to temperature and pH), and changes in soil microbial behaviour (via combined carbon isotope analysis). However, to date the use of organic geochemical techniques has been relatively limited, due to issues relating to sample size, concerns about contamination, and unanswered questions about the origins of the preserved organic matter and rates of transport. Here I will briefly review recent progress in the field, and present a framework for the future research needed to establish organic geochemical analysis in speleothems as a robust palaeo-proxy approach.

  8. Concepts of Cell Lineage in Mammalian Embryos.

    PubMed

    Papaioannou, Virginia E

    2016-01-01

    Cell lineage is the framework for understanding cellular diversity, stability of differentiation, and its relationship to pluripotency. The special condition of in utero development in mammals has presented challenges to developmental biologists in tracing cell lineages but modern imaging and cell marking techniques have allowed the gradual elucidation of lineage relationships. Early experimental embryology approaches had limited resolution and relied of suboptimal cell markers and considerable disturbance to the embryos. Transgenic technology introduced genetic markers, particularly fluorescent proteins that, combined with sophisticated imaging modalities, greatly increase resolution and allow clonal analysis within lineages. The concept of cell lineage has also undergone evolution as it became possible to trace the lineage of cells based not only on their physical location or attributes but also on their gene expression pattern, thus opening up mechanistic lines of investigation into the determinants of cell lineage. © 2016 Elsevier Inc. All rights reserved.

  9. Wood biomass: The potential of willow. Progress report, November 1987--December 1990

    SciTech Connect

    White, E.H.; Abrahamson, L.P.

    1991-10-01

    Experiments were established in central New York State in spring, 1987, to evaluate the potential of Salix for wood biomass production using ultrashort-rotation intensive-culture techniques. Five selected willow clones and one hybrid poplar clone planted at 1 {times} 1 foot spacing were tested for biomass production with annual coppicing. This report presents results of this research as of December 31, 1990. (VC)

  10. Recent progress in sustainable polymers obtained from cyclic terpenes: synthesis, properties, and application potential.

    PubMed

    Winnacker, Malte; Rieger, Bernhard

    2015-08-10

    The functionalization and polymerization of biobased monocyclic terpenes and their derivatives for the synthesis of sustainable polymers is described, especially in view of the synthetic routes and properties of the obtained macromolecular architectures. Comparison of these procedures and the obtained materials with "classical" oil-based approaches, and also with alternative biobased routes, gives interesting insights into the potential of these small terpene building-block structures for modern polymer science and technology.

  11. Clonal conversion of B lymphoid leukemia reveals cross-lineage transfer of malignant states

    PubMed Central

    Somasundaram, Rajesh; Åhsberg, Josefine; Okuyama, Kazuki; Ungerbäck, Jonas; Lilljebjörn, Henrik; Fioretos, Thoas; Strid, Tobias; Sigvardsson, Mikael

    2016-01-01

    Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either or both the Pax5 and Ebf1 genes, commonly mutated in human leukemia, can be converted into T lineage leukemia cells. Even though the conversion process involved global changes in gene expression and lineage-restricted epigenetic reconfiguration, the malignant phenotype of the cells was preserved, enabling them to expand as T lineage leukemia cells in vivo. Furthermore, while the transformed pro-B cells displayed plasticity toward myeloid lineages, the converted cells failed to cause myeloid leukemia after transplantation. These data provide evidence that a malignant phenotype can be transferred between hematopoietic lineages. This has important implications for modern cancer medicine because lineage targeted treatment of leukemia patients can be predicted to provoke the emergence of phenotypically altered subclones, causing clinical relapse. PMID:27913602

  12. Clonal conversion of B lymphoid leukemia reveals cross-lineage transfer of malignant states.

    PubMed

    Somasundaram, Rajesh; Åhsberg, Josefine; Okuyama, Kazuki; Ungerbäck, Jonas; Lilljebjörn, Henrik; Fioretos, Thoas; Strid, Tobias; Sigvardsson, Mikael

    2016-11-15

    Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either or both the Pax5 and Ebf1 genes, commonly mutated in human leukemia, can be converted into T lineage leukemia cells. Even though the conversion process involved global changes in gene expression and lineage-restricted epigenetic reconfiguration, the malignant phenotype of the cells was preserved, enabling them to expand as T lineage leukemia cells in vivo. Furthermore, while the transformed pro-B cells displayed plasticity toward myeloid lineages, the converted cells failed to cause myeloid leukemia after transplantation. These data provide evidence that a malignant phenotype can be transferred between hematopoietic lineages. This has important implications for modern cancer medicine because lineage targeted treatment of leukemia patients can be predicted to provoke the emergence of phenotypically altered subclones, causing clinical relapse. © 2016 Somasundaram et al.; Published by Cold Spring Harbor Laboratory Press.

  13. Deciphering the recent phylogenetic expansion of the originally deeply rooted Mycobacterium tuberculosis lineage 7.

    PubMed

    Yimer, Solomon A; Namouchi, Amine; Zegeye, Ephrem Debebe; Holm-Hansen, Carol; Norheim, Gunnstein; Abebe, Markos; Aseffa, Abraham; Tønjum, Tone

    2016-06-30

    A deeply rooted phylogenetic lineage of Mycobacterium tuberculosis (M. tuberculosis) termed lineage 7 was discovered in Ethiopia. Whole genome sequencing of 30 lineage 7 strains from patients in Ethiopia was performed. Intra-lineage genome variation was defined and unique characteristics identified with a focus on genes involved in DNA repair, recombination and replication (3R genes). More than 800 mutations specific to M. tuberculosis lineage 7 strains were identified. The proportion of non-synonymous single nucleotide polymorphisms (nsSNPs) in 3R genes was higher after the recent expansion of M. tuberculosis lineage 7 strain started. The proportion of nsSNPs in genes involved in inorganic ion transport and metabolism was significantly higher before the expansion began. A total of 22346 bp deletions were observed. Lineage 7 strains also exhibited a high number of mutations in genes involved in carbohydrate transport and metabolism, transcription, energy production and conversion. We have identified unique genomic signatures of the lineage 7 strains. The high frequency of nsSNP in 3R genes after the phylogenetic expansion may have contributed to recent variability and adaptation. The abundance of mutations in genes involved in inorganic ion transport and metabolism before the expansion period may indicate an adaptive response of lineage 7 strains to enable survival, potentially under environmental stress exposure. As lineage 7 strains originally were phylogenetically deeply rooted, this may indicate fundamental adaptive genomic pathways affecting the fitness of M. tuberculosis as a species.

  14. Phylogenetic lineages in the Botryosphaeriaceae

    PubMed Central

    Crous, Pedro W.; Slippers, Bernard; Wingfield, Michael J.; Rheeder, John; Marasas, Walter F.O.; Philips, Alan J.L.; Alves, Artur; Burgess, Treena; Barber, Paul; Groenewald, Johannes Z.

    2006-01-01

    Botryosphaeria is a species-rich genus with a cosmopolitan distribution, commonly associated with dieback and cankers of woody plants. As many as 18 anamorph genera have been associated with Botryosphaeria, most of which have been reduced to synonymy under Diplodia (conidia mostly ovoid, pigmented, thick-walled), or Fusicoccum (conidia mostly fusoid, hyaline, thin-walled). However, there are numerous conidial anamorphs having morphological characteristics intermediate between Diplodia and Fusicoccum, and there are several records of species outside the Botryosphaeriaceae that have anamorphs apparently typical of Botryosphaeria s.str. Recent studies have also linked Botryosphaeria to species with pigmented, septate ascospores, and Dothiorella anamorphs, or Fusicoccum anamorphs with Dichomera synanamorphs. The aim of this study was to employ DNA sequence data of the 28S rDNA to resolve apparent lineages within the Botryosphaeriaceae. From these data, 12 clades are recognised. Two of these lineages clustered outside the Botryosphaeriaceae, namely Diplodia-like anamorphs occurring on maize, which are best accommodated in Stenocarpella (Diaporthales), as well as an unresolved clade including species of Camarosporium/Microdiplodia. We recognise 10 lineages within the Botryosphaeriaceae, including an unresolved clade (Diplodia/Lasiodiplodia/Tiarosporella), Botryosphaeria s.str. (Fusicoccum anamorphs), Macrophomina, Neoscytalidium gen. nov., Dothidotthia (Dothiorella anamorphs), Neofusicoccum gen. nov. (Botryosphaeria-like teleomorphs, Dichomera-like synanamorphs), Pseudofusicoccum gen. nov., Saccharata (Fusicoccum- and Diplodia-like synanamorphs), “Botryosphaeria” quercuum (Diplodia-like anamorph), and Guignardia (Phyllosticta anamorphs). Separate teleomorph and anamorph names are not provided for newly introduced genera, even where both morphs are known. The taxonomy of some clades and isolates (e.g. B. mamane) remains unresolved due to the absence of ex

  15. Monitoring genetic and metabolic potential for in situ bioremediation: Mass spectrometry. 1997 annual progress report

    SciTech Connect

    Buchanan, M.V.; Hurst, G.B.; Britt, P.F.; McLuckey, S.A.; Doktycz, M.J.

    1997-09-01

    'A number of US Department of Energy (DOE) sites are contaminated with mixtures of dense non-aqueous phase liquids (DNAPLs) such as carbon tetrachloride, chloroform,. perchloroethylene, and trichloroethylene. At many of these sites, in situ microbial bioremediation is an attractive strategy for cleanup because it has the potential to degrade DNAPLs in situ without producing toxic byproducts. A rapid screening method to determine the broad range metabolic and genetic potential for contaminant degradation would greatly reduce the cost and time involved in assessment for in situ bioremediation as well as for monitoring ongoing bioremediation treatment. In this project, the ORNL Organic Mass Spectrometry (OMS) group is developing mass-spectrometry-based methods to screen for the genetic and metabolic potential for assessment and monitoring of in situ bioremediation of DNAPLs. In close collaboration, Professor Mary Lidstrom''s group at the University of Washington is identifying short DNA sequences related to microbial processes involved in the biodegradation of pollutants. This work will lay the foundation for development of a field-portable mass-spectrometry-based technique for rapid assessment and monitoring of bioremediation processes on site.'

  16. Serum alkaline phosphatase: a potential marker in the progression of periodontal disease in cirrhosis patients.

    PubMed

    Jaiswal, Gagan; Deo, Vikas; Bhongade, Manohar; Jaiswal, Shraddha

    2011-04-01

    As a consequence of their liver dysfunction, cirrhotic patients have elevated levels of serum alkaline phosphatase (ALP). Increased ALP activity is seen in periodontal tissues during the progression of periodontitis. The present study was carried out to compare ALP levels in cirrhosis patients with and without periodontitis and to correlate ALP levels with the severity of periodontitis. Both the test and control groups consisted of 30 liver cirrhosis patients with or without periodontitis. The parameters recorded were modified OHI-S Index, Gingival Index (GI), and clinical attachment level (CAL). All patients underwent standardized panoramic radiographs to assess alveolar bone height. The total serum ALP was determined with the kinetic method (R.A 50). Alveolar bone loss (ABL) was 1.62 ± 0.32 mm in the test group and 0.28 ± 0.04 mm in the control group. Mean clinical attachment level (CAL) for the test group was greater than the control group: 2.34 ± 0.67 mm and 0.43 ± 0.14 mm, respectively. The mean serum alkaline phosphatase level in the test group was higher (39.94 ± 3.34) than the control group (29.42 ± 6.11) and the differences was statistically significant (P > .05). When comparison was made between age group (20 to 40 years and 41 to 60 years), the older age group liver cirrhosis patients exhibited significantly higher values for bone loss, clinical attachment level, and serum ALP level. There is strong positive correlation between periodontal breakdown and serum alkaline phosphatase level in liver cirrhosis patients.

  17. DLGP: A database for lineage-conserved and lineage-specific gene pairs in animal and plant genomes.

    PubMed

    Wang, Dapeng

    2016-01-15

    The conservation of gene organization in the genome with lineage-specificity is an invaluable resource to decipher their potential functionality with diverse selective constraints, especially in higher animals and plants. Gene pairs appear to be the minimal structure for such kind of gene clusters that tend to reside in their preferred locations, representing the distinctive genomic characteristics in single species or a given lineage. Despite gene families having been investigated in a widespread manner, the definition of gene pair families in various taxa still lacks adequate attention. To address this issue, we report DLGP (http://lcgbase.big.ac.cn/DLGP/) that stores the pre-calculated lineage-based gene pairs in currently available 134 animal and plant genomes and inspect them under the same analytical framework, bringing out a set of innovational features. First, the taxonomy or lineage has been classified into four levels such as Kingdom, Phylum, Class and Order. It adopts all-to-all comparison strategy to identify the possible conserved gene pairs in all species for each gene pair in certain species and reckon those that are conserved in over a significant proportion of species in a given lineage (e.g. Primates, Diptera or Poales) as the lineage-conserved gene pairs. Furthermore, it predicts the lineage-specific gene pairs by retaining the above-mentioned lineage-conserved gene pairs that are not conserved in any other lineages. Second, it carries out pairwise comparison for the gene pairs between two compared species and creates the table including all the conserved gene pairs and the image elucidating the conservation degree of gene pairs in chromosomal level. Third, it supplies gene order browser to extend gene pairs to gene clusters, allowing users to view the evolution dynamics in the gene context in an intuitive manner. This database will be able to facilitate the particular comparison between animals and plants, between vertebrates and arthropods, and

  18. Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance.

    PubMed

    Ku, Sheng Yu; Rosario, Spencer; Wang, Yanqing; Mu, Ping; Seshadri, Mukund; Goodrich, Zachary W; Goodrich, Maxwell M; Labbé, David P; Gomez, Eduardo Cortes; Wang, Jianmin; Long, Henry W; Xu, Bo; Brown, Myles; Loda, Massimo; Sawyers, Charles L; Ellis, Leigh; Goodrich, David W

    2017-01-06

    Prostate cancer relapsing from antiandrogen therapies can exhibit variant histology with altered lineage marker expression, suggesting that lineage plasticity facilitates therapeutic resistance. The mechanisms underlying prostate cancer lineage plasticity are incompletely understood. Studying mouse models, we demonstrate that Rb1 loss facilitates lineage plasticity and metastasis of prostate adenocarcinoma initiated by Pten mutation. Additional loss of Trp53 causes resistance to antiandrogen therapy. Gene expression profiling indicates that mouse tumors resemble human prostate cancer neuroendocrine variants; both mouse and human tumors exhibit increased expression of epigenetic reprogramming factors such as Ezh2 and Sox2. Clinically relevant Ezh2 inhibitors restore androgen receptor expression and sensitivity to antiandrogen therapy. These findings uncover genetic mutations that enable prostate cancer progression; identify mouse models for studying prostate cancer lineage plasticity; and suggest an epigenetic approach for extending clinical responses to antiandrogen therapy. Copyright © 2017, American Association for the Advancement of Science.

  19. Serglycin as a potential biomarker for glioma: association of serglycin expression, extent of mast cell recruitment and glioblastoma progression

    PubMed Central

    Roy, Ananya; Attarha, Sanaz; Weishaupt, Holger; Edqvist, Per-Henrik; Swartling, Fredrik J.; Bergqvist, Michael; Siebzehnrubl, Florian A.; Smits, Anja; Pontén, Fredrik; Tchougounova, Elena

    2017-01-01

    Serglycin is an intracellular proteoglycan with a unique ability to adopt highly divergent structures by glycosylation with variable types of glycosaminoglycans (GAGs) when expressed by different cell types. Serglycin is overexpressed in aggressive cancers suggesting its protumorigenic role. In this study, we explored the expression of serglycin in human glioma and its correlation with survival and immune cell infiltration. We demonstrate that serglycin is expressed in glioma and that increased expression predicts poor survival of patients. Analysis of serglycin expression in a large cohort of low- and high-grade human glioma samples reveals that its expression is grade dependent and is positively correlated with mast cell (MC) infiltration. Moreover, serglycin expression in patient-derived glioma cells is significantly increased upon MC co-culture. This is also accompanied by increased expression of CXCL12, CXCL10, as well as markers of cancer progression, including CD44, ZEB1 and vimentin. In conclusion, these findings indicate the importance of infiltrating MCs in glioma by modulating signaling cascades involving serglycin, CD44 and ZEB1. The present investigation reveals serglycin as a potential prognostic marker for glioma and demonstrates an association with the extent of MC recruitment and glioma progression, uncovering potential future therapeutic opportunities for patients. PMID:28445977

  20. Pursuing the unlimited potential of microorganisms-progress and prospect of a fermentation company.

    PubMed

    Arisawa, Akira; Watanabe, Azuma

    2017-01-01

    Production of pharmaceuticals and chemicals using microbial functions has bestowed numerous benefits onto society. The Nobel Prize awarded to Professor Ōmura, Distinguished Emeritus Professor of Kitasato University, showed the world the importance of the discovery and practical application of microorganisms. Now, increasing attention is turned toward the future path of this field. As people involved in the microorganism industry, we will review the industrial activities thus far and consider the possible future developments in this field and its potential contribution to society.

  1. Distinguishing between storm and tsunami in the geological record; progress, perturbations and potential

    NASA Astrophysics Data System (ADS)

    Switzer, A. D.

    2010-12-01

    Palaeoestorm and palaeotsunami research now incorporates not only geologists and geomorphologists but computer and mathematical modellers, geophysicists, chronology experts, palaeontologists, hydrologists, coastal planners and ecologists. Recent studies on modern events such as the 2004 Indian Ocean tsunami and several large cyclone events (eg Hurricane Katrina) have provided new insights and now present the research community with a good opportunity to reflect on the progress made in the field, evaluate some recent criticisms and highlight knowledge gaps for future study. There is no globally applicable sedimentological criteria for differentiating between tsunami and storms in washover sandsheets. What can be compiled for the many deposits attributed to palaeo-washover is a suite of sedimentary features or commonalities, often called signatures. These signatures must be considered in terms of the local setting as they are very much site dependant. Palaeo-washover deposits can only be attributed to an event type through careful analysis of spatial features such as the elevation, lateral extent and run-up of the deposit along with sedimentary features such as grading, the presence of intraclasts, and particle size distribution of the sediments. These analyses when combined may lead to a suite of evidence that can point to storm or tsunami as the likely depositional agent. Unfortunately when considered alone many of the characteristics are equivocal. In fact most of the signatures presented in the literature for tsunami deposition, including the presence of marine diatoms or increases in particular elemental concentrations only indicate the marine origin of the sediments and inundation by ocean water. Hence storm surges, sea level change or regional subsidence may show similar sedimentological characteristics. Recent work has recognized the equivocal nature of many so called 'tsunami signatures' found in sandsheets. This stated, there remain many cases in the

  2. Recent Progress in Lab-on-a-Chip Technology and Its Potential Application to Clinical Diagnoses

    PubMed Central

    2013-01-01

    We present the construction of the lab-on-a-chip (LOC) system, a state-of-the-art technology that uses polymer materials (i.e., poly[dimethylsiloxane]) for the miniaturization of conventional laboratory apparatuses, and show the potential use of these microfluidic devices in clinical applications. In particular, we introduce the independent unit components of the LOC system and demonstrate how each component can be functionally integrated into one monolithic system for the realization of a LOC system. In specific, we demonstrate microscale polymerase chain reaction with the use of a single heater, a microscale sample injection device with a disposable plastic syringe and a strategy for device assembly under environmentally mild conditions assisted by surface modification techniques. In this way, we endeavor to construct a totally integrated, disposable microfluidic system operated by a single mode, the pressure, which can be applied on-site with enhanced device portability and disposability and with simple and rapid operation for medical and clinical diagnoses, potentially extending its application to urodynamic studies in molecular level. PMID:23610705

  3. Reticulate evolution and incomplete lineage sorting among the ponderosa pines.

    PubMed

    Willyard, Ann; Cronn, Richard; Liston, Aaron

    2009-08-01

    Interspecific gene flow via hybridization may play a major role in evolution by creating reticulate rather than hierarchical lineages in plant species. Occasional diploid pine hybrids indicate the potential for introgression, but reticulation is hard to detect because ancestral polymorphism is still shared across many groups of pine species. Nucleotide sequences for 53 accessions from 17 species in subsection Ponderosae (Pinus) provide evidence for reticulate evolution. Two discordant patterns among independent low-copy nuclear gene trees and a chloroplast haplotype are better explained by introgression than incomplete lineage sorting or other causes of incongruence. Conflicting resolution of three monophyletic Pinus coulteri accessions is best explained by ancient introgression followed by a genetic bottleneck. More recent hybridization transferred a chloroplast from P. jeffreyi to a sympatric P. washoensis individual. We conclude that incomplete lineage sorting could account for other examples of non-monophyly, and caution against any analysis based on single-accession or single-locus sampling in Pinus.

  4. Lineage of origin in rhabdomyosarcoma informs pharmacological response

    PubMed Central

    Abraham, Jinu; Nuñez-Álvarez, Yaiza; Hettmer, Simone; Carrió, Elvira; Chen, Hung-I Harry; Nishijo, Koichi; Huang, Elaine T.; Prajapati, Suresh I.; Walker, Robert L.; Davis, Sean; Rebeles, Jennifer; Wiebush, Hunter; McCleish, Amanda T.; Hampton, Sheila T.; Bjornson, Christopher R.R.; Brack, Andrew S.; Wagers, Amy J.; Rando, Thomas A.; Capecchi, Mario R.; Marini, Frank C.; Ehler, Benjamin R.; Zarzabal, Lee Ann; Goros, Martin W.; Michalek, Joel E.; Meltzer, Paul S.; Langenau, David M.; LeGallo, Robin D.; Mansoor, Atiya; Chen, Yidong; Suelves, Mònica; Rubin, Brian P.; Keller, Charles

    2014-01-01

    Lineage or cell of origin of cancers is often unknown and thus is not a consideration in therapeutic approaches. Alveolar rhabdomyosarcoma (aRMS) is an aggressive childhood cancer for which the cell of origin remains debated. We used conditional genetic mouse models of aRMS to activate the pathognomonic Pax3:Foxo1 fusion oncogene and inactivate p53 in several stages of prenatal and postnatal muscle development. We reveal that lineage of origin significantly influences tumor histomorphology and sensitivity to targeted therapeutics. Furthermore, we uncovered differential transcriptional regulation of the Pax3:Foxo1 locus by tumor lineage of origin, which led us to identify the histone deacetylase inhibitor entinostat as a pharmacological agent for the potential conversion of Pax3:Foxo1-positive aRMS to a state akin to fusion-negative RMS through direct transcriptional suppression of Pax3:Foxo1. PMID:25030697

  5. microRNAs as Potential Biomarkers in Adrenocortical Cancer: Progress and Challenges

    PubMed Central

    Cherradi, Nadia

    2016-01-01

    Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis and limited therapeutic options. Over the last decade, pan-genomic analyses of genetic and epigenetic alterations and genome-wide expression profile studies allowed major advances in the understanding of the molecular genetics of ACC. Besides the well-known dysfunctional molecular pathways in adrenocortical tumors, such as the IGF2 pathway, the Wnt pathway, and TP53, high-throughput technologies enabled a more comprehensive genomic characterization of adrenocortical cancer. Integration of expression profile data with exome sequencing, SNP array analysis, methylation, and microRNA (miRNA) profiling led to the identification of subgroups of malignant tumors with distinct molecular alterations and clinical outcomes. miRNAs post-transcriptionally silence their target gene expression either by degrading mRNA or by inhibiting translation. Although our knowledge of the contribution of deregulated miRNAs to the pathogenesis of ACC is still in its infancy, recent studies support their relevance in gene expression alterations in these tumors. Some miRNAs have been shown to carry potential diagnostic and prognostic values, while others may be good candidates for therapeutic interventions. With the emergence of disease-specific blood-borne miRNAs signatures, analyses of small cohorts of patients with ACC suggest that circulating miRNAs represent promising non-invasive biomarkers of malignancy or recurrence. However, some technical challenges still remain, and most of the miRNAs reported in the literature have not yet been validated in sufficiently powered and longitudinal studies. In this review, we discuss the current knowledge regarding the deregulation of tumor-associated and circulating miRNAs in ACC patients, while emphasizing their potential significance in pathogenic pathways in light of recent insights into the role of miRNAs in shaping the tumor microenvironment. PMID:26834703

  6. Recent Progress Toward Hydrogen Medicine: Potential of Molecular Hydrogen for Preventive and Therapeutic Applications

    PubMed Central

    Ohta, Shigeo

    2011-01-01

    Persistent oxidative stress is one of the major causes of most lifestyle-related diseases, cancer and the aging process. Acute oxidative stress directly causes serious damage to tissues. Despite the clinical importance of oxidative damage, antioxidants have been of limited therapeutic success. We have proposed that molecular hydrogen (H2) has potential as a “novel” antioxidant in preventive and therapeutic applications [Ohsawa et al., Nat Med. 2007: 13; 688-94]. H2 has a number of advantages as a potential antioxidant: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H2. There are several methods to ingest or consume H2, including inhaling hydrogen gas, drinking H2-dissolved water (hydrogen water), taking a hydrogen bath, injecting H2-dissolved saline (hydrogen saline), dropping hydrogen saline onto the eye, and increasing the production of intestinal H2 by bacteria. Since the publication of the first H2 paper in Nature Medicine in 2007, the biological effects of H2 have been confirmed by the publication of more than 38 diseases, physiological states and clinical tests in leading biological/medical journals, and several groups have started clinical examinations. Moreover, H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. H2 regulates various gene expressions and protein-phosphorylations, though the molecular mechanisms underlying the marked effects of very small amounts of H2 remain elusive. PMID:21736547

  7. Molecular mechanisms underlying lineage bias in aging hematopoiesis.

    PubMed

    Elias, Harold K; Bryder, David; Park, Christopher Y

    2017-01-01

    Although hematopoietic stem cells (HSCs) have traditionally been thought to possess the ability to give rise to all the mature cell types in the hematopoietic system, this conception of hematopoiesis was based on evaluation of hematopoietic output from large numbers of HSCs using transplantation models.  More recent studies evaluating HSCs at the clonal or near-clonal level, both in transplantation studies and during in situ hematopoiesis, have established that individual HSCs can exhibit lineage bias, giving rise to myeloid-biased, lymphoid-biased, or more balanced differentiation, with the proportion of myeloid-biased HSCs increasing with age.  This age-associated shift in lineage potential is associated with decreased cellular immunity and increased incidence of diseases with prominent inflammatory components including atherosclerosis, autoimmunity, neurodegenerative disease, and carcinogenesis. Understanding the molecular mechanisms that regulate this shift in linage bias therefore represents an important area of investigation in numerous human diseases.  In this review, we summarize our current understanding of the cell-intrinsic (autonomous) and cell-extrinsic factors that regulate HSC lineage fate bias during aging.  In addition, we have attempted to bring attention to important caveats and unanswered questions related to the issue of HSC lineage bias to encourage explorations of these important lines of inquiry. Ultimately, we expect a comprehensive understanding of HSC lineage bias during aging to have important implications for human health, since strategies to alter lineage bias in old HSCs not only has the potential to restore immune function in the elderly, but also to reduce the incidence of inflammation-associated diseases, many for which there is a current unmet need for novel and more effective treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Estimation of potential population level effects of contaminants on wildlife. 1998 annual progress report

    SciTech Connect

    Sample, B.E.; Suter, G.W. II; Rose, K.A.

    1998-06-01

    'The objective of this project is to provide DOE with improved methods to assess risks from contaminants to wildlife populations. The current approach for wildlife risk assessment consists of comparison of contaminant exposure estimates for individual animals to literature-derived toxicity test endpoints. These test endpoints are assumed to estimate thresholds for population-level effects. For several reasons, uncertainties associated with this approach are considerable. First, because toxicity data are not available for most potential wildlife endpoint species, extrapolation of toxicity data from test species to the species of interest is required. There is no consensus on the most appropriate extrapolation method. Second, toxicity data are represented as statistical measures (e.g., NOAELs or LOAELs) that provide no information on the nature or magnitude of effects. The level of effect is an artifact of the replication and dosing regime employed, and does not indicate how effects might increase with increasing exposure. Consequently, slight exceedance of a LOAEL is not distinguished from greatly exceeding it. Third, the relationship of toxic effects on individuals to effects on populations is poorly estimated by existing methods. It is assumed that if the exposure of individuals exceeds levels associated with impaired reproduction, then population level effects are likely. Uncertainty associated with this assumption is large because depending on the reproductive strategy of a given species, comparable levels of reproductive impairment may result in dramatically different population-level responses. The authors are working on several tasks to address these problems: (1) investigation of the validity of the current allometric scaling approach for interspecies extrapolation and development of new scaling models; (2) development of dose-response models for toxicity data presented in the literature; and (3) development of matrix-based population models that, coupled

  9. Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice.

    PubMed

    Singer, Alfred; Adoro, Stanley; Park, Jung-Hyun

    2008-10-01

    Following successful gene rearrangement at alphabeta T-cell receptor (TCR) loci, developing thymocytes express both CD4 and CD8 co-receptors and undergo a life-or-death selection event, which is known as positive selection, to identify cells that express TCRs with potentially useful ligand specificities. Positively selected thymocytes must then differentiate into either CD4(+) helper T cells or CD8(+) cytotoxic T cells, a crucial decision known as CD4/CD8-lineage choice. In this Review, we summarize recent advances in our understanding of the cellular and molecular events involved in lineage-fate decision and discuss them in the context of the major models of CD4/CD8-lineage choice.

  10. Mast cell diversion of T-lineage precursor cells by the essential T-lineage transcription factor GATA-3

    PubMed Central

    Taghon, Tom; Yui, Mary A.; Rothenberg, Ellen V.

    2011-01-01

    GATA-3 is essential for T cell development from the earliest stages. However, highly abundant GATA-3 can drive T-lineage precursors to a non-T fate, depending on Notch signaling and developmental stage. GATA-3 overexpression blocked pro-T cell survival when Notch-Delta signals were present, but enhanced viability in their absence. In double-negative (DN1) and DN2 but not DN3 fetal thymocytes, GATA-3 overexpression rapidly induced mast cell lineage respecification with high frequency by direct transcriptional reprogramming. Normal DN2 thymocytes also displayed mast cell potential, when interleukin 3 and stem cell factor were added in the absence of Notch signaling. Our results suggest a close relationship between the pro-T and mast cell programs and a new role for Notch in T-lineage fidelity. PMID:17603486

  11. The Characterization of Psychrophilic Microorganisms and their potentially useful Cold-Active Glycosidases Final Progress Report

    SciTech Connect

    Brenchly, Jean E.

    2008-06-30

    Our studies of novel, cold-loving microorganisms have focused on two distinct extreme environments. The first is an ice core sample from a 120,000 year old Greenland glacier. The results of this study are particularly exciting and have been highlighted with press releases and additional coverage. The first press release in 2004 was based on our presentation at the General Meeting of the American Society for Microbiology and was augmented by coverage of our publication (Appl. Environ. Microbiol. 2005. Vol. 71:7806) in the Current Topics section of the ASM news journal, “Microbe.” Of special interest for this report was the isolation of numerous, phylogenetically distinct and potentially novel ultrasmall microorganisms. The detection and isolation of members of the ultrasmall population is significant because these cells pass through 0.2 micron pore filters that are generally used to trap microorganisms from environmental samples. Thus, analyses by other investigators that examined only cells captured on the filters would have missed a significant portion of this population. Only a few ultrasmall isolates had been obtained prior to our examination of the ice core samples. Our development of a filtration enrichment and subsequent cultivation of these organisms has added extensively to the collection of, and knowledge about, this important population in the microbial world.

  12. Molecular understanding of mutagenicity using potential energy methods. Progress report, July 1, 1992--September 30, 1993

    SciTech Connect

    Broyde, S.; Shapiro, R.

    1993-09-01

    Our objective has been to elucidate on a molecular level, at atomic resolution, the structures of DNAs modified by highly mutagenic aromatic amines and hydrocarbons. The underlying hypothesis is that DNA replicates with reduced fidelity when its normal right-handed B-structure is altered, and one result is a higher mutation rate. This change in structure may occur normally at a low incidence but it may be enhanced greatly after covalent modification by a mutagenic substance. The methods that we use to elucidate structures are computational, but we keep in close contact with experimental developments, and we incorporate data from NMR studies in our calculations when they are available. X-ray and low resolution spectroscopic studies have not succeeded in producing atomic resolution views of mutagen and carcinogen-oligonucleotide adducts. Even the high resolution NMR method cannot alone yield molecular views, though it does so in combination with our computations. The specific methods that we employ are minimized potential energy calculations using the torsion angle space molecular mechanics program DUPLEX to yield static views. Molecular dynamics simulations of static structures with solvent and salt can be carried out with the program AMBER; this yields mobile views in a medium that mimics aspects of the natural aqueous environment of the cell.

  13. Progress in developing cholecystokinin (CCK)/gastrin receptor ligands which have therapeutic potential

    PubMed Central

    Berna, Marc J.; Tapia, Jose A.; Sancho, Veronica; Jensen, Robert T.

    2007-01-01

    Summary Gastrin and CCK are two of the oldest hormones and within the last 15 years there has been an exponential increase in knowledge of their pharmacology, cell biology, receptors (CCK1R, CCK2R) and roles in physiology and pathological conditions. Despite these advances there is no approved disease indication for CCK receptor antagonists and only minor use of agonists. In this review the important factors determining this slow therapeutic development are reviewed. To assess this it is necessary to briefly review what is known about the roles of CCK receptors (CCK1R, CCK2R) in normal human physiology, their role in pathologic conditions, the selectivity of available potent CCKR agonists/antagonists as well as review their use in human conditions to date and the results. Despite extensive studies in animals and some in humans, recent studies suggest that monotherapy with CCK1R agonists will not be effective in obesity, nor CCK2R antagonists in panic disorders or CCK2R antagonists to inhibit growth of pancreatic cancer. Areas that require more study include the use of CCK2R agonists for imaging tumors and radiotherapy, CCK2R antagonists in hypergastrinemic states especially with long term PPI use and for potentiation of analgesia as well as use of CCK1R antagonists for a number of gastrointestinal disorders [motility disorders (irritable bowel syndrome, dyspepsia, constipation) and pancreatitis (acute, chronic)]. PMID:17997137

  14. Numerical models of catchment scale sediment transfer: progress, problems and potential

    NASA Astrophysics Data System (ADS)

    Coulthard, T. J.

    2009-05-01

    The sediment output from a drainage basin reflects the modification and filtering of 'inputs' into the system. These 'inputs' can be internal (e.g. drainage basin configuration, sediment size and supply) or external (e.g. tectonic uplift or climatic changes). There is much interest in the relative importance of these internal and external forcings/inputs to understand past basin evolution, but also to understand and predict future development, particularly in response to human influences such as land cover modification and climate change. Numerical modelling can be a powerful tool to explore these forcings and their interactions with drainage basins. This paper reviews the state of the art for numerical simulation of sediment transfer within drainage basins over a range of time and space scales (millennia to decades, sub km to thousands of square km basins). In particular, it will examine the role of autogenic processes relative to the more classic forcings, such as climate. The paper will also examine the many limitations associated with modelling drainage basins including parameterisation and process representation looking at the widespread simplifications that are required to simulate basin processes over long time scales. Finally it concludes by discussing the potential and future direction for drainage basin modelling and how these models may benefit from close collaboration with physical modelling studies.

  15. Potential-modulated intercalation of alkali cations into metal hexacyanoferrate coated electrodes. 1998 annual progress report

    SciTech Connect

    Schwartz, D.T.

    1998-06-01

    'This program is studying potential-driven cation intercalation and deintercalation in metal hexacyanoferrate compounds, with the eventual goal of creating materials with high selectivity for cesium separations and long cycle lifetimes. The separation of radiocesium from other benign cations has important implications for the cost of processing a variety of cesium contaminated DOE wasteforms. This report summarizes results after nine months of work. Much of the initial efforts have been directed towards quantitatively characterizing the selectivity of nickel hexacyanoferrate derivatized electrodes for intercalating cesium preferentially over other alkali metal cations. Using energy dispersive xray spectroscopy (ex-situ, but non-destructive) and ICP analysis (ex-situ and destructive), the authors have demonstrated that the nickel hexacyanoferrate lattice has a strong preference for intercalated cesium over sodium. For example, when ions are reversibly loaded into a nickel hexacyanoferrate thin film from a solution containing 0.9999 M Na{sup +} and 0.0001 M Cs{sup +}, the film intercalates 40% as much Cs{sup +} as when loaded from pure 1 M Cs{sup +} containing electrolyte (all electrolytes use nitrates as the common anion). The authors have also shown that, contrary to the common assumptions found in the literature, a significant fraction of the thin film is not active initially. A new near infrared laser has been purchased and is being added to the Raman spectroscopy facilities to allow in-situ studies of the intercalation processes.'

  16. Fibroblast Growth Factor Receptor-2 Expression in Thyroid Tumor Progression: Potential Diagnostic Application

    PubMed Central

    Redler, Adriano; Di Rocco, Giorgio; Giannotti, Domenico; Frezzotti, Francesca; Bernieri, Maria Giulia; Ceccarelli, Simona; D’Amici, Sirio; Vescarelli, Enrica; Mitterhofer, Anna Paola; Angeloni, Antonio; Marchese, Cinzia

    2013-01-01

    Fibroblast growth factor receptor-2 (FGFR-2) plays an important role in tumorigenesis. In thyroid cancer it has been observed a FGFR-2 down-modulation, but the role of this receptor has not been yet clarified. Therefore, we decided to examine the expression of both FGFR-2 isoform, FGFR-2-IIIb and FGFR-2-IIIc, in different histological thyroid variants such as hyperplasia, follicular adenoma and papillary carcinoma. Immunohistochemistry and quantitative Real-Time PCR analyses were performed on samples of hyperplasia, follicular adenoma and papillary carcinoma, compared with normal thyroid tissue. Thyroid hyperplasia did not show statistically significant reduction in FGFR-2 protein and mRNA levels. Interestingly, in both follicular adenoma and papillary carcinoma samples we observed a strongly reduced expression of both FGFR-2 isoforms. We speculate that FGFR-2 down-modulation might be an early event in thyroid carcinogenesis. Furthermore, we suggest the potential use of FGFR-2 as an early marker for thyroid cancer diagnosis. PMID:23977259

  17. Progress in Nanotechnology Based Approaches to Enhance the Potential of Chemopreventive Agents

    PubMed Central

    Muqbil, Irfana; Masood, Ashiq; Sarkar, Fazlul H.; Mohammad, Ramzi M.; Azmi, Asfar S.

    2011-01-01

    Cancer chemoprevention is defined as the use of natural agents to suppress, reverse or prevent the carcinogenic process from turning into aggressive cancer. Over the last two decades, multiple natural dietary compounds with diverse chemical structures such flavonoids, tannins, curcumins and polyphenols have been proposed as chemopreventive agents. These agents have proven excellent anticancer potential in the laboratory setting, however, the observed effects in vitro do not translate in clinic where they fail to live up to their expectations. Among the various reasons for this discrepancy include inefficient systemic delivery and robust bioavailability. To overcome this barrier, researchers have focused towards coupling these agents with nano based encapsulation technology that in principle will enhance bioavailability and ultimately benefit clinical outcome. The last decade has witnessed rapid advancement in the development of nanochemopreventive technology with emergence of many nano encapsulated formulations of different dietary anticancer agents. This review summarizes the most up-to-date knowledge on the studies performed in nanochemoprevention, their proposed use in the clinic and future directions in which this field is heading. As the knowledge of the dynamics of nano encapsulation evolves, it is expected that researchers will bring forward newer and far more superior nanochemopreventive agents that may become standard drugs for different cancers. PMID:24212623

  18. Transcriptional Regulators of the Trophoblast Lineage in Mammals with Hemochorial Placentation

    PubMed Central

    Knott, Jason G.; Paul, Soumen

    2014-01-01

    Mammalian reproduction is critically dependent on the trophoblast cell lineage, which assures proper establishment of maternal-fetal interactions during pregnancy. Specification of trophoblast cell lineage begins with the development of the trophectoderm (TE) in preimplantation embryos. Subsequently, other trophoblast cell types arise with progression of pregnancy. Studies with transgenic animal models as well as trophoblast stem/progenitor cells have implicated distinct transcriptional and epigenetic regulators in trophoblast lineage development. This review focuses on our current understanding of transcriptional and epigenetic mechanisms regulating specification, determination, maintenance and differentiation of trophoblast cells. PMID:25190503

  19. Recent Progress and Future Potential for Concentrating Photovoltaic Power Systems: Preprint

    SciTech Connect

    Kurtz, S.; Lewandowski, A.; Hayden, H.

    2004-08-01

    This paper explores the potential of utility-scale PV power, and, specifically, the opportunity that may arise for concentrating photovoltaics (CPV). In the 1990s, sales of PV modules were dominated by small-size applications such as PV-powered water pumping, emergency telephones, and calculators. More recently, the dramatic growth in the PV industry has been fueled by rooftop systems, especially in Japan and Germany. Such subsidized, grid-connected PV systems are likely to drive PV markets in coming years. Distributed systems deliver power where it is needed, avoiding transmission losses; and residential and commercial systems can be financed along with the rest of a building. Japan and Germany continue to provide market incentives because of their belief in PV's long-term benefits. As successful and important as the rooftop market is for PV sales today, the PV industry will be able to penetrate a larger fraction of the electricity market if PV systems are also used in larger installations, such as utility-owned systems, PV parks, and customer-owned systems. Because retail electricity costs more than wholesale electricity, it is often assumed that PV will address, with incentives, the retail market long before the wholesale market. Here, we show data suggesting that they can grow together. CPV, which uses low-cost lenses or mirrors to focus sunlight on high-efficiency solar cells, has often been presented as a lower-cost approach to utility-scale PV power. Although CPV typically does not compete in rooftop or other current PV markets, CPV could be a major player in a utility-scale market.

  20. From regenerative dentistry to regenerative medicine: progress, challenges, and potential applications of oral stem cells.

    PubMed

    Xiao, Li; Nasu, Masanori

    2014-01-01

    Adult mesenchymal stem cells (MSCs) and epithelial stem cells play essential roles in tissue repair and self-healing. Oral MSCs and epithelial stem cells can be isolated from adult human oral tissues, for example, teeth, periodontal ligament, and gingiva. Cocultivated adult oral epithelial stem cells and MSCs could represent some developmental events, such as epithelial invagination and tubular structure formation, signifying their potentials for tissue regeneration. Oral epithelial stem cells have been used in regenerative medicine over 1 decade. They are able to form a stratified cell sheet under three-dimensional culture conditions. Both experimental and clinical data indicate that the cell sheets can not only safely and effectively reconstruct the damaged cornea in humans, but also repair esophageal ulcer in animal models. Oral MSCs include dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), periodontal ligament stem cells (PDLSCs), and mesenchymal stem cells from gingiva (GMSCs). They are widely applied in both regenerative dentistry and medicine. DPSCs, SHED, and SCAP are able to form dentin-pulp complex when being transplanted into immunodeficient animals. They have been experimentally used for the regeneration of dental pulp, neuron, bone muscle and blood vessels in animal models and have shown promising results. PDLSCs and GMSCs are demonstrated to be ideal cell sources for repairing the damaged tissues of periodontal, muscle, and tendon. Despite the abovementioned applications of oral stem cells, only a few human clinical trials are now underway to use them for the treatment of certain diseases. Since clinical use is the end goal, their true regenerative power and safety need to be further examined.

  1. Mapping the route from naive pluripotency to lineage specification

    PubMed Central

    Kalkan, Tüzer; Smith, Austin

    2014-01-01

    In the mouse blastocyst, epiblast cells are newly formed shortly before implantation. They possess a unique developmental plasticity, termed naive pluripotency. For development to proceed, this naive state must be subsumed by multi-lineage differentiation within 72 h following implantation. In vitro differentiation of naive embryonic stem cells (ESCs) cultured in controlled conditions provides a tractable system to dissect and understand the process of exit from naive pluripotency and entry into lineage specification. Exploitation of this system in recent large-scale RNAi and mutagenesis screens has uncovered multiple new factors and modules that drive or facilitate progression out of the naive state. Notably, these studies show that the transcription factor network that governs the naive state is rapidly dismantled prior to upregulation of lineage specification markers, creating an intermediate state that we term formative pluripotency. Here, we summarize these findings and propose a road map for state transitions in ESC differentiation that reflects the orderly dynamics of epiblast progression in the embryo. PMID:25349449

  2. Human haematopoietic stem cell lineage commitment is a continuous process

    PubMed Central

    Velten, Lars; Haas, Simon F.; Raffel, Simon; Blaszkiewicz, Sandra; Islam, Saiful; Hennig, Bianca P.; Hirche, Christoph; Lutz, Christoph; Buss, Eike C.; Nowak, Daniel; Boch, Tobias; Hofmann, Wolf-Karsten; Ho, Anthony D.; Huber, Wolfgang; Trumpp, Andreas; Essers, Marieke A.G.; Steinmetz, Lars M.

    2017-01-01

    Blood formation is believed to occur through step-wise progression of haematopoietic stem cells (HSCs) following a tree-like hierarchy of oligo-, bi- and unipotent progenitors. However, this model is based on the analysis of predefined flow-sorted cell populations. Here we integrated flow cytometric, transcriptomic and functional data at single-cell resolution to quantitatively map early differentiation of human HSCs towards lineage commitment. During homeostasis, individual HSCs gradually acquire lineage biases along multiple directions without passing through discrete hierarchically organized progenitor populations. Instead, unilineage-restricted cells emerge directly from a “Continuum of LOw primed UnDifferentiated hematopoietic stem- and progenitor cells” (CLOUD-HSPCs). Distinct gene expression modules operate in a combinatorial manner to control stemness, early lineage priming and the subsequent progression into all major branches of haematopoiesis. These data reveal a continuous landscape of human steady state haematopoiesis downstream of HSCs and provide a basis for the understanding of hematopoietic malignancies. PMID:28319093

  3. PROGRESSIVE VENTILATION OF THE OCEANS - POTENTIAL FOR RETURN TO ANOXIC CONDITIONS IN THE POST-PALEOZOIC

    SciTech Connect

    Wilde, Pat; Berry, William B.N.

    1980-09-01

    After the ventilation of the residual anoxic layer in the late Paleozoic (Berry and Wilde, 1978) a return to ephemeral anoxic conditions in the ocean is suggested by anoxic sediments found in the Mesozoic cores of the deep-sea drilling program (Schlanger and Jenkyns 1977, and Theide and Van Andel 1977). A preliminary physical oceanographic model is presented to explain the development of oxygen depleted layers in mid-waters below the surface wind-mixed layer during non-glacial climates. The model shows the range of temperature, salinity and density values for hypothetical water masses for two climatically related oceanographic situations: Case A where bottom waters are formed at mid-latitudes at the surface salinity maxima, and Case B where bottom waters are produced at high latitudes but not by sea-ice formation as in the modern ocean. The hypothetical water masses are characterized by examples from the modern ocean and extrapolation to non-glacial times is made by eliminating water masses produced by or influenced by sea-ice formation in modern glacial times. The state of oxidation is made by plotting the model water masses on an oxygen saturation diagram and comparing the relative oxygen capacity with modern conditions of zonal organic productivity. The model indicates for Case A (high latitude temperatures above 5°C) two oxygen, depleted layers in the equatorial regions (1) from about 200m to the depth of completed oxidation of surface material separated by an oxygenated zone to (2) a deep depleted zone along the base of the pycnocline at 2900 M. The deep depleted zone extends along the Case A pycnocline polarward toward the high latitude productivity maximum. For case B with a pycnocline at about 1500m the deep anoxic layer is not sustained. Considerations of density only, suggest that neutral stratification and the potential for overturn is enhanced for climates transitional between Case A and Case B where the density contrast between major water masses

  4. The potential for modification in cloning and vitrification technology to enhance genetic progress in beef cattle in Northern Australia.

    PubMed

    Taylor-Robinson, Andrew W; Walton, Simon; Swain, David L; Walsh, Kerry B; Vajta, Gábor

    2014-08-01

    Recent advances in embryology and related research offer considerable possibilities to accelerate genetic improvement in cattle breeding. Such progress includes optimization and standardization of laboratory embryo production (in vitro fertilization - IVF), introduction of a highly efficient method for cryopreservation (vitrification), and dramatic improvement in the efficiency of somatic cell nuclear transfer (cloning) in terms of required effort, cost, and overall outcome. Handmade cloning (HMC), a simplified version of somatic cell nuclear transfer, offers the potential for relatively easy and low-cost production of clones. A potentially modified method of vitrification used at a centrally located laboratory facility could result in cloned offspring that are economically competitive with elite animals produced by more traditional means. Apart from routine legal and intellectual property issues, the main obstacle that hampers rapid uptake of these technologies by the beef cattle industry is a lack of confidence from scientific and commercial sources. Once stakeholder support is increased, the combined application of these methods makes a rapid advance toward desirable traits (rapid growth, high-quality beef, optimized reproductive performance) a realistic goal. The potential impact of these technologies on genetic advancement in beef cattle herds in which improvement of stock is sought, such as in northern Australia, is hard to overestimate. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  5. The Theory and Practice of Lineage Tracing

    PubMed Central

    Hsu, Ya-Chieh

    2015-01-01

    Lineage tracing is a method that delineates all progeny produced by a single cell or a group of cells. The possibility of performing lineage tracing initiated the field of Developmental Biology, and continues to revolutionize Stem Cell Biology. Here, I introduce the principles behind a successful lineage-tracing experiment. In addition, I summarize and compare different methods for conducting lineage tracing and provide examples of how these strategies can be implemented to answer fundamental questions in development and regeneration. The advantages and limitations of each method are also discussed. PMID:26284340

  6. A new way to build cell lineages

    PubMed Central

    Zhang, Xiuwei

    2017-01-01

    A combination of single-cell techniques and computational analysis enables the simultaneous discovery of cell states, lineage relationships and the genes that control developmental decisions. PMID:28332977

  7. Theory and Practice of Lineage Tracing.

    PubMed

    Hsu, Ya-Chieh

    2015-11-01

    Lineage tracing is a method that delineates all progeny produced by a single cell or a group of cells. The possibility of performing lineage tracing initiated the field of Developmental Biology and continues to revolutionize Stem Cell Biology. Here, I introduce the principles behind a successful lineage-tracing experiment. In addition, I summarize and compare different methods for conducting lineage tracing and provide examples of how these strategies can be implemented to answer fundamental questions in development and regeneration. The advantages and limitations of each method are also discussed.

  8. Intermolecular potential functions from spectroscopic properties of weakly bound complexes. Third progress report, July 1, 1991--June 30, 1992

    SciTech Connect

    Muenter, J.S.

    1992-08-01

    Goal is to consolidate the information from high resolution spectroscopy of weakly bound cluster molecules through a theoretical model of intermolecular potential energy surfaces. The ability to construct analytic intermolecular potential functions that accurately predict the interaction energy between small molecules will have a major impact in chemistry, biochemistry, and biology. This document presents the evolution and capabilities of a potential function model developed here, and then describes plans for future developments and applications. This potential energy surface (PES) model was first used on (HCCH){sub 2}, (CO{sub 2}){sub 2}, HCCH - CO{sub 2}; it had to be modified to work with HX dimers and CO{sub 2}-HX complexes. Potential functions have been calculated for 15 different molecular complexes containing 7 different monomer molecules. Current questions, logical extensions and new applications of the model are discussed. The questions are those raised by changing the repulsion and dispersion terms. A major extension of the PES model will be the inclusion of induction effects. Projects in progress include PES calculations on (HCCH){sub 3}, CO{sub 2} containing complexes, (HX){sub 2}, HX - CO{sub 2}, CO{sub 2} - CO, (CO{sub 2}){sub 3}, and (OCS){sub 2}. The first PES calculation for a nonlinear molecule will be for water and ammonia complexes. Possible long-term applications for biological molecules are discussed. Differences between computer programs used for molecular mechanics and dynamics in biological systems are discussed, as is the problem of errors. 12 figs, 74 refs. (DLC)

  9. Two distinct, geographically overlapping lineages of the corallimorpharian Ricordea florida (Cnidaria: Hexacorallia: Ricordeidae)

    NASA Astrophysics Data System (ADS)

    Torres-Pratts, H.; Lado-Insua, T.; Rhyne, A. L.; Rodríguez-Matos, L.; Schizas, N. V.

    2011-06-01

    We examined the genetic variation of the corallimorpharian Ricordea florida; it is distributed throughout the Caribbean region and is heavily harvested for the marine aquarium trade. Eighty-four distinct individuals of R. florida were sequenced from four geographically distant Caribbean locations (Curaçao, Florida, Guadeloupe, and Puerto Rico). Analysis of the ribosomal nuclear region (ITS1, 5.8S, ITS2) uncovered two geographically partially overlapping genetic lineages in R. florida, probably representing two cryptic species. Lineage 1 was found in Florida and Puerto Rico, and Lineage 2 was found in Florida, Puerto Rico, Guadeloupe, and Curaçao. Because of the multi-allelic nature of the ITS region, four individuals from Lineage 1 and six from Lineage 2 were cloned to evaluate the levels of hidden intra-individual variability. Pairwise genetic comparisons indicated that the levels of intra-individual and intra-lineage variability (<1%) were approximately an order of magnitude lower than the divergence (~9%) observed between the two lineages. The fishery regulations of the aquarium trade regard R. florida as one species. More refined regulations should take into account the presence of two genetic lineages, and they should be managed separately in order to preserve the long-term evolutionary potential of this corallimorpharian. The discovery of two distinct lineages in R. florida illustrates the importance of evaluating genetic variability in harvested species prior to the implementation of management policies.

  10. Deciphering the transcriptional network of the dendritic cell lineage.

    PubMed

    Miller, Jennifer C; Brown, Brian D; Shay, Tal; Gautier, Emmanuel L; Jojic, Vladimir; Cohain, Ariella; Pandey, Gaurav; Leboeuf, Marylene; Elpek, Kutlu G; Helft, Julie; Hashimoto, Daigo; Chow, Andrew; Price, Jeremy; Greter, Melanie; Bogunovic, Milena; Bellemare-Pelletier, Angelique; Frenette, Paul S; Randolph, Gwendalyn J; Turley, Shannon J; Merad, Miriam

    2012-09-01

    Although much progress has been made in the understanding of the ontogeny and function of dendritic cells (DCs), the transcriptional regulation of the lineage commitment and functional specialization of DCs in vivo remains poorly understood. We made a comprehensive comparative analysis of CD8(+), CD103(+), CD11b(+) and plasmacytoid DC subsets, as well as macrophage DC precursors and common DC precursors, across the entire immune system. Here we characterized candidate transcriptional activators involved in the commitment of myeloid progenitor cells to the DC lineage and predicted regulators of DC functional diversity in tissues. We identified a molecular signature that distinguished tissue DCs from macrophages. We also identified a transcriptional program expressed specifically during the steady-state migration of tissue DCs to the draining lymph nodes that may control tolerance to self tissue antigens.

  11. Highly divergent mussel lineages in isolated Indonesian marine lakes

    PubMed Central

    de Leeuw, Christiaan A.; Knegt, Bram; Maas, Diede L.; de Voogd, Nicole J.; Abdunnur; Suyatna, Iwan; Peijnenburg, Katja T.C.A.

    2016-01-01

    Marine lakes, with populations in landlocked seawater and clearly delineated contours, have the potential to provide a unique model to study early stages of evolution in coastal marine taxa. Here we ask whether populations of the mussel Brachidontes from marine lakes in Berau, East Kalimantan (Indonesia) are isolated from each other and from the coastal mangrove systems. We analyzed sequence data of one mitochondrial marker (Cytochrome Oxidase I (COI)), and two nuclear markers (18S and 28S). In addition, we examined shell shape using a geometric morphometric approach. The Indonesian populations of Brachidontes spp. harbored four deeply diverged lineages (14–75% COI corrected net sequence divergence), two of which correspond to previously recorded lineages from marine lakes in Palau, 1,900 km away. These four lineages also showed significant differences in shell shape and constitute a species complex of at least four undescribed species. Each lake harbored a different lineage despite the fact that the lakes are separated from each other by only 2–6 km, while the two mangrove populations, at 20 km distance from each other, harbored the same lineage and shared haplotypes. Marine lakes thus represent isolated habitats. As each lake contained unique within lineage diversity (0.1–0.2%), we suggest that this may have resulted from in situdivergence due to isolation of founder populations after the formation of the lakes (6,000–12,000 years before present). Combined effects of stochastic processes, local adaptation and increased evolutionary rates could produce high levels of differentiation in small populations such as in marine lake environments. Such short-term isolation at small spatial scales may be an important contributing factor to the high marine biodiversity that is found in the Indo-Australian Archipelago. PMID:27761314

  12. Highly divergent mussel lineages in isolated Indonesian marine lakes.

    PubMed

    Becking, Leontine E; de Leeuw, Christiaan A; Knegt, Bram; Maas, Diede L; de Voogd, Nicole J; Abdunnur; Suyatna, Iwan; Peijnenburg, Katja T C A

    2016-01-01

    Marine lakes, with populations in landlocked seawater and clearly delineated contours, have the potential to provide a unique model to study early stages of evolution in coastal marine taxa. Here we ask whether populations of the mussel Brachidontes from marine lakes in Berau, East Kalimantan (Indonesia) are isolated from each other and from the coastal mangrove systems. We analyzed sequence data of one mitochondrial marker (Cytochrome Oxidase I (COI)), and two nuclear markers (18S and 28S). In addition, we examined shell shape using a geometric morphometric approach. The Indonesian populations of Brachidontes spp. harbored four deeply diverged lineages (14-75% COI corrected net sequence divergence), two of which correspond to previously recorded lineages from marine lakes in Palau, 1,900 km away. These four lineages also showed significant differences in shell shape and constitute a species complex of at least four undescribed species. Each lake harbored a different lineage despite the fact that the lakes are separated from each other by only 2-6 km, while the two mangrove populations, at 20 km distance from each other, harbored the same lineage and shared haplotypes. Marine lakes thus represent isolated habitats. As each lake contained unique within lineage diversity (0.1-0.2%), we suggest that this may have resulted from in situdivergence due to isolation of founder populations after the formation of the lakes (6,000-12,000 years before present). Combined effects of stochastic processes, local adaptation and increased evolutionary rates could produce high levels of differentiation in small populations such as in marine lake environments. Such short-term isolation at small spatial scales may be an important contributing factor to the high marine biodiversity that is found in the Indo-Australian Archipelago.

  13. Comparative analysis of CRISPR loci in different Listeria monocytogenes lineages.

    PubMed

    Di, Huiling; Ye, Lei; Yan, He; Meng, Hecheng; Yamasak, Shinji; Shi, Lei

    2014-11-21

    Listeria monocytogenes, an important food-borne pathogen, causes high mortality rate of listeriosis. Pan-genomic comparisons revealed the species genome of L. monocytogenes is highly stable but not completely clonal. The population structure of this species displays at least four evolutionary lineages (I-IV). Isolates of different lineages displayed distinct genetic, phenotypic and ecologic characteristics, which appear to affect their ability to be transmitted through foods and to cause human disease, as well as their ability to thrive in markedly phage-rich environments. CRISPR (clustered regularly interspaced short palindrome repeats), a recently described adaptive immunity system, not only confers defense against invading elements derived from bacteriophages or plasmids in many bacteria and archaeal, but also displays strains-level variations in almost any given endowed species. This work was aimed to investigate CRISPR diversity in L. monocytogenes strains of different lineages and estimated the potential practicability of the CRISPR-based approach to resolve this species' biodiversity. Only a third of strains contained all three CRISPR loci (here defined as LMa, LMb and LMc) at same time. Combined the strain-level variations in presence/absence of each CRISPR locus and its relative size and spacer arrangements, a total of 29 CRISPR genotypes and 11 groups were defined within a collection of 128 strains covering all serotypes. The CRISPR-based approach showed powerful ability to subtype the more commonly food-borne isolates of serotype 1/2a (lineage II) and serotypes 1/2b (lineage I), but limited by the absence of typical CRISPR structure in many lineage I isolates. Strikingly, we found a long associated cas1 gene as well as two self-targeting LMb spacers accidently homologous with endogenous genes in a fraction of serotype 1/2a isolations, demonstrated that CRISPR I B system might involve in bacterial physiology besides antiviral immunity.

  14. Stochastic dynamics of interacting haematopoietic stem cell niche lineages.

    PubMed

    Székely, Tamás; Burrage, Kevin; Mangel, Marc; Bonsall, Michael B

    2014-09-01

    Since we still know very little about stem cells in their natural environment, it is useful to explore their dynamics through modelling and simulation, as well as experimentally. Most models of stem cell systems are based on deterministic differential equations that ignore the natural heterogeneity of stem cell populations. This is not appropriate at the level of individual cells and niches, when randomness is more likely to affect dynamics. In this paper, we introduce a fast stochastic method for simulating a metapopulation of stem cell niche lineages, that is, many sub-populations that together form a heterogeneous metapopulation, over time. By selecting the common limiting timestep, our method ensures that the entire metapopulation is simulated synchronously. This is important, as it allows us to introduce interactions between separate niche lineages, which would otherwise be impossible. We expand our method to enable the coupling of many lineages into niche groups, where differentiated cells are pooled within each niche group. Using this method, we explore the dynamics of the haematopoietic system from a demand control system perspective. We find that coupling together niche lineages allows the organism to regulate blood cell numbers as closely as possible to the homeostatic optimum. Furthermore, coupled lineages respond better than uncoupled ones to random perturbations, here the loss of some myeloid cells. This could imply that it is advantageous for an organism to connect together its niche lineages into groups. Our results suggest that a potential fruitful empirical direction will be to understand how stem cell descendants communicate with the niche and how cancer may arise as a result of a failure of such communication.

  15. Creativity: Potential and Progress.

    ERIC Educational Resources Information Center

    Sisk, Dorothy A.

    This paper explores definitions of creativity, theories and models of creativity, and the classic stages of creativity. Creativity is best defined in terms of an interactive process. The creative process in adults often results in creative and useful products, and such creativity is judged in terms of their quantity and quality of patents,…

  16. Characterization of the Variability of Epstein-Barr Virus Genes in Nasopharyngeal Biopsies: Potential Predictors for Carcinoma Progression

    PubMed Central

    Banko, Ana V.; Lazarevic, Ivana B.; Folic, Miljan M.; Djukic, Vojko B.; Cirkovic, Andja M.; Karalic, Danijela Z.; Cupic, Maja D.; Jovanovic, Tanja P.

    2016-01-01

    Epstein-Barr virus (EBV) infection is a significant factor in the pathogenesis of nasopharyngeal carcinoma, especially in the undifferentiated carcinoma of nasopharyngeal type (UCNT, World Health Organization type III), which is the dominant histopathological type in high-risk areas. The major EBV oncogene is latent membrane protein 1 (LMP1). LMP1 gene shows variability with different tumorigenic and immunogenic potentials. EBV nuclear antigen 1 (EBNA1) regulates progression of EBV-related tumors; however, the influence of EBNA1 sequence variability on tumor pathogenesis is controversial. The aims of this study were to characterize polymorphisms of EBV genes in non-endemic nasopharyngeal carcinoma biopsies and to investigate potential sequence patterns that correlate with the clinical presentation of nasopharyngeal carcinoma. In total, 116 tumor biopsies of undifferentiated carcinoma of nasopharyngeal type (UCNT), collected from 2008 to 2014, were evaluated in this study. The genes EBNA2, LMP1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses. The presence of EBV DNA was significantly distributed between TNM stages. LMP1 variability showed six variants, with the detection of the first China1 and North Carolina variants in European nasopharyngeal carcinoma biopsies. Newly discovered variants Srb1 and Srb2 were UCNT-specific LMP1 polymorphisms. The B95-8 and North Carolina variants are possible predictors for favorable TNM stages. In contrast, deletions in LMP1 are possible risk factors for the most disfavorable TNM stage, independent of EBNA2 or EBNA1 variability. A newly discovered EBNA1 subvariant, P-thr-sv-5, could be a potential diagnostic marker, as it represented a UCNT-specific EBNA1 subvariant. A particular combination of EBNA2, LMP1, and EBNA1 polymorphisms, type 1/Med/P-thr was

  17. Differentiated effective connectivity patterns of the executive control network in progressive MCI: a potential biomarker for predicting AD.

    PubMed

    Cai, Suping; Peng, Yanlin; Chong, Tao; Zhang, Yun; von Deneen, Karen M; Huang, Liyu; Aibl Research Group

    2017-03-09

    Mild cognitive impairment (MCI) is often a transitional state between normal aging and Alzheimer's disease (AD). When observed longitudinally, some MCI patients convert to AD, while a considerable portion either remain MCI or revert to a normal functioning state. This divergence has provided some enlightenment on a potential biomarker be represented in the resting state brain activities of MCI patients with different post-hoc labels. Recent studies have shown impaired executive functions, other than typically explicated memory impairment with AD/MCI patients. This observation raises the question that whether or not the executive control network (ECN) was impaired, as which pivotally supports the central executive functions. Given the fact that effective connectivity is a sufficient index in detecting resting brain abnormalities in AD/MCI, the current study specifically asks a question whether the effective connectivity patterns are differentiated in MCI patients with different post-hoc labels. We divided the MCI subjects into three groups depending on their progressive state obtained longitudinally: 1) 15 MCI-R subjects: MCI reverted to the normal functioning state and stabilized to the normal state in 24 months; 2) 35 MCI-S subjects: MCI patients maintained this disease in a stable state for 24 months; 3) 22 MCI-P subjects: MCI progressed to AD and stabilized to AD in 24 months, and 4) 39 age-matched normal control subjects (NC). We conducted a Granger causality analysis after identifying the core nodes of ECN in all of the subjects using Independent Component Analysis. Our findings revealed that different MCI groups presented different effective connectivity patterns within the ECN compared to the NC group. Specifically, (1) dorsolateral prefrontal cortex (dLPFC) and medial prefrontal cortex (mPFC) were the core nodes in the ECN network that exhibited different connecting patterns; (2) an effective connection circuit "R.dLPFC right caudate Left thalamus

  18. [Progress in dedifferentiated fat cells].

    PubMed

    Cheng, Feifei; Yang, Zhi; Qian, Cheng

    2014-10-01

    When mature adipocytes are subjected to an in vitro dedifferentiation strategy referred to as ceiling culture, these mature adipocytes can revert to dedifferentiated fat (DFAT) cells. DFAT cells have many advantages compared with adipose-derived stem cells (ASCs) and bone marrow mesenchymal stem cells (BMSCs). For example, DFAT cells are homogeneous and could be obtained from donors regardless of their age. Furthermore, DFAT cells also have the same multi-lineage potentials and low immunogenicity as ASCs. As an excellent source of seed cells for tissue engineering and stem cell transplantation, DFAT cells have better prospects in the treatment of many clinical diseases, such as bone defects, neurological diseases, ischemic heart disease and kidney disease. It is necessary to make more intensive studies of DFAT cells. This article summarizes progresses in the immunological characteristics, differentiation ability and potential clinical applications of DFAT cells.

  19. Lineages with long durations are old and morphologically average: an analysis using multiple datasets.

    PubMed

    Liow, Lee Hsiang

    2007-04-01

    Lineage persistence is as central to biology as evolutionary change. Important questions regarding persistence include: why do some lineages outlive their relatives, neither becoming extinct nor evolving into separate lineages? Do these long-duration lineages have distinctive ecological or morphological traits that correlate with their geologic durations and potentially aid their survival? In this paper, I test the hypothesis that lineages (species and higher taxa) with longer geologic durations have morphologies that are more average than expected by chance alone. I evaluate this hypothesis for both individual lineages with longer durations and groups of lineages with longer durations, using more than 60 published datasets of animals with adequate fossil records. Analyses presented here show that groups of lineages with longer durations fall empirically into one of three theoretically possible scenarios, namely: (1) the morphology of groups of longer duration lineages is closer to the grand average of their inclusive group, that is, their relative morphological distance is smaller than expected by chance alone, when compared with rarified samples of their shorter duration relatives (a negative group morpho-duration distribution); (2) the relative morphological distance of groups of longer duration lineages is no different from rarified samples of their shorter duration relatives (a null group morpho-duration distribution); and (3) the relative morphological distance of groups of longer duration lineages is greater than expected when compared with rarified samples of their shorter duration relatives (a positive group morpho-duration distribution). Datasets exhibiting negative group morpho-duration distributions predominate. However, lineages with higher ranks in the Linnean hierarchy demonstrate positive morpho-duration distributions more frequently. The relative morphological distance of individual longer duration lineages is no different from that of rarified

  20. Microarray based comparison of two Escherichia coli O157:H7 lineages

    PubMed Central

    Dowd, Scot E; Ishizaki, Hiroshi

    2006-01-01

    Background Previous research has identified the potential for the existence of two separate lineages of Escherichia coli O157:H7. Clinical isolates tended to cluster primarily within one of these two lineages. To determine if there are virulence related genes differentially expressed between the two lineages we chose to utilize microarray technology to perform an initial screening. Results Using a 610 gene microarray, designed against the E. coli O157 EDL 933 transcriptome, targeting primarily virulence systems, we chose 3 representative Lineage I isolates (LI groups mostly clinical isolates) and 3 representative Lineage II isolates (LII groups mostly bovine isolates). Using standard dye swap experimental designs, statistically different expression (P < 0.05) of 73 genes between the two lineages was revealed. Result highlights indicate that under in vitro anaerobic growth conditions, there is up-regulation of stx2b, ureD, curli (csgAFEG), and stress related genes (hslJ, cspG, ibpB, ibpA) in Lineage I, which may contribute to enhanced virulence or transmission potential. Lineage II exhibits significant up-regulation of type III secretion apparatus, LPS, and flagella related transcripts. Conclusion These results give insight into comparative regulation of virulence genes as well as providing directions for future research. Ultimately, evaluating the expression of key virulence factors among different E. coli O157 isolates has inherent value and the interpretation of such expression data will continue to evolve as our understanding of virulence, pathogenesis and transmission improves. PMID:16539702

  1. The Lineage Transmission of Interpersonal Competence.

    ERIC Educational Resources Information Center

    Filsinger, Erik E.; Lamke, Leanne K.

    1983-01-01

    Suggests that interpersonal competence in intimate and general social relationships is transmitted down generational lines. Studied a sample of college students (N=105) and their parents for evidence of lineage effects. The strongest evidence of lineage transmission of characteristics was for interpersonal competence in general social situations.…

  2. Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in hematopoietic stem cells.

    PubMed

    Ng, Samuel Yao-Ming; Yoshida, Toshimi; Zhang, Jiangwen; Georgopoulos, Katia

    2009-04-17

    The mechanisms regulating lineage potential during early hematopoiesis were investigated. First, a cascade of lineage-affiliated gene expression signatures, primed in hematopoietic stem cells (HSCs) and differentially propagated in lineage-restricted progenitors, was identified. Lymphoid transcripts were primed as early as the HSC, together with myeloid and erythroid transcripts. Although this multilineage priming was resolved upon subsequent lineage restrictions, an unexpected cosegregation of lymphoid and myeloid gene expression and potential past a nominal myeloid restriction point was identified. Finally, we demonstrated that whereas the zinc finger DNA-binding factor Ikaros was required for induction of lymphoid lineage priming in the HSC, it was also necessary for repression of genetic programs compatible with self-renewal and multipotency downstream of the HSC. Taken together, our studies provide new insight into the priming and restriction of lineage potentials during early hematopoiesis and identify Ikaros as a key bivalent regulator of this process.

  3. Potential risk of TNF inhibitors on the progression of interstitial lung disease in patients with rheumatoid arthritis

    PubMed Central

    Nakashita, Tamao; Ando, Katsutoshi; Kaneko, Norihiro; Takahashi, Kazuhisa; Motojima, Shinji

    2014-01-01

    Objectives Biological therapy represents important advances in alleviating rheumatoid arthritis (RA), but the effect on interstitial lung disease (ILD) has been controversial. The objective of this study was to assess the risk of such treatment for patients with ILD. Design Case–control cohorts. Setting Single centre in Japan. Participants This study included 163 patients with RA who underwent biological therapy. Outcome measured We assessed chest CT before initiation of biological therapy and grouped 163 patients according to the presence of ILD (with (n=58) and without pre-existing ILD (n=105)). Next, we evaluated serial changes of chest CT after treatment and visually assessed the emergence of ILD or its progression, which was referred to as an ‘ILD event’. Then, we also classified the patients according to the presence of ILD events and analysed their characteristics. Results Tumour necrosis factor (TNF) inhibitors were administered to more patients with ILD events than those without ILD events (88% vs 60%, p<0.05), but recipients of tocilizumab or abatacept did not differ in this respect. Of 58 patients with pre-existing ILD, 14 had ILD events, and that proportion was greater than for those without pre-existing ILD (24% vs 3%, p<0.001). Of these 14 patients, all were treated with TNF inhibitors. Four patients developed generalised lung disease and two died from ILD progression. Baseline levels of KL-6 were similar in both groups, but increased in patients with ILD events. Conclusions TNF inhibitors have the potential risk of ILD events, particularly for patients with pre-existing ILD, and KL-6 is a valuable surrogate marker for detecting ILD events. Our data suggest that non-TNF inhibitors are a better treatment option for these patients. PMID:25125479

  4. Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets.

    PubMed

    Capurso, G; Lattimore, S; Crnogorac-Jurcevic, T; Panzuto, F; Milione, M; Bhakta, V; Campanini, N; Swift, S M; Bordi, C; Delle Fave, G; Lemoine, N R

    2006-06-01

    The intrinsic nature of tumour behaviour (stable vs progressive) and the presence of liver metastases are key factors in determining the outcome of patients with a pancreatic endocrine tumour (PET). Previous expression profile analyses of PETs were limited to non-homogeneous groups or to primary lesions only. The aim of this study was to investigate the gene expression profiles of a more uniform series of sporadic, non-functioning (NF) PETs with progressive disease and, for the first time, their liver metastases, on the Affymetrix human genome U133A and B GeneChip set. Thirteen NF PET samples (eight primaries and five liver metastases) from ten patients with progressive, metastatic disease, three cell lines (BON, QGP and CM) and four purified islet samples were analysed. The same samples were employed for confirmation of candidate gene expression by means of quantitative RT-PCR, while a further 37 PET and 15 carcinoid samples were analysed by immunohistochemistry. Analysis of genes differentially expressed between islets and primaries and metastases revealed 667 up- and 223 down-regulated genes, most of which have not previously been observed in PETs, and whose gene ontology molecular function has been detailed. Overexpression of bridging integrator 1 (BIN1) and protein Z dependent protease inhibitor (SERPINA10) which may represent useful biomarkers, and of lymphocyte specific protein tyrosine kinase (LCK) and bone marrow stromal cell antigen (BST2) which could be used as therapeutic targets, has been validated. When primary tumours were compared with metastatic lesions, no significantly differentially expressed genes were found, in accord with cluster analysis which revealed a striking similarity between primary and metastatic lesions, with the cell lines clustering separately. We have provided a comprehensive list of differentially expressed genes in a uniform set of aggressive NF PETs. A number of dysregulated genes deserve further in-depth study as potentially

  5. Concise review: chemical approaches for modulating lineage-specific stem cells and progenitors.

    PubMed

    Xu, Tao; Zhang, Mingliang; Laurent, Timothy; Xie, Min; Ding, Sheng

    2013-05-01

    Generation and manipulation of lineage-restricted stem and progenitor cells in vitro and/or in vivo are critical for the development of stem cell-based clinical therapeutics. Lineage-restricted stem and progenitor cells have many advantageous qualities, including being able to efficiently engraft and differentiate into desirable cell types in vivo after transplantation, and they are much less tumorigenic than pluripotent cells. Generation of lineage-restricted stem and progenitor cells can be achieved by directed differentiation from pluripotent stem cells or lineage conversion from easily obtained somatic cells. Small molecules can be very helpful in these processes since they offer several important benefits. For example, the risk of tumorigenesis is greatly reduced when small molecules are used to replace integrated transcription factors, which are widely used in cell fate conversion. Furthermore, small molecules are relatively easy to apply, optimize, and manufacture, and they can more readily be developed into conventional pharmaceuticals. Alternatively, small molecules can be used to expand or selectively control the differentiation of lineage-restricted stem and progenitor cells for desirable therapeutics purposes in vitro or in vivo. Here we summarize recent progress in the use of small molecules for the expansion and generation of desirable lineage-restricted stem and progenitor cells in vitro and for selectively controlling cell fate of lineage-restricted stem and progenitor cells in vivo, thereby facilitating stem cell-based clinical applications.

  6. Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos

    PubMed Central

    Petropoulos, Sophie; Edsgärd, Daniel; Reinius, Björn; Deng, Qiaolin; Panula, Sarita Pauliina; Codeluppi, Simone; Plaza Reyes, Alvaro; Linnarsson, Sten; Sandberg, Rickard; Lanner, Fredrik

    2016-01-01

    Summary Mouse studies have been instrumental in forming our current understanding of early cell-lineage decisions; however, similar insights into the early human development are severely limited. Here, we present a comprehensive transcriptional map of human embryo development, including the sequenced transcriptomes of 1,529 individual cells from 88 human preimplantation embryos. These data show that cells undergo an intermediate state of co-expression of lineage-specific genes, followed by a concurrent establishment of the trophectoderm, epiblast, and primitive endoderm lineages, which coincide with blastocyst formation. Female cells of all three lineages achieve dosage compensation of X chromosome RNA levels prior to implantation. However, in contrast to the mouse, XIST is transcribed from both alleles throughout the progression of this expression dampening, and X chromosome genes maintain biallelic expression while dosage compensation proceeds. We envision broad utility of this transcriptional atlas in future studies on human development as well as in stem cell research. PMID:27062923

  7. Single-Cell RNA-Seq Reveals Lineage and X Chromosome Dynamics in Human Preimplantation Embryos.

    PubMed

    Petropoulos, Sophie; Edsgärd, Daniel; Reinius, Björn; Deng, Qiaolin; Panula, Sarita Pauliina; Codeluppi, Simone; Plaza Reyes, Alvaro; Linnarsson, Sten; Sandberg, Rickard; Lanner, Fredrik

    2016-05-05

    Mouse studies have been instrumental in forming our current understanding of early cell-lineage decisions; however, similar insights into the early human development are severely limited. Here, we present a comprehensive transcriptional map of human embryo development, including the sequenced transcriptomes of 1,529 individual cells from 88 human preimplantation embryos. These data show that cells undergo an intermediate state of co-expression of lineage-specific genes, followed by a concurrent establishment of the trophectoderm, epiblast, and primitive endoderm lineages, which coincide with blastocyst formation. Female cells of all three lineages achieve dosage compensation of X chromosome RNA levels prior to implantation. However, in contrast to the mouse, XIST is transcribed from both alleles throughout the progression of this expression dampening, and X chromosome genes maintain biallelic expression while dosage compensation proceeds. We envision broad utility of this transcriptional atlas in future studies on human development as well as in stem cell research.

  8. Diversification of two lineages of symbiotic Photobacterium.

    PubMed

    Urbanczyk, Henryk; Urbanczyk, Yoshiko; Hayashi, Tetsuya; Ogura, Yoshitoshi

    2013-01-01

    Understanding of processes driving bacterial speciation requires examination of closely related, recently diversified lineages. To gain an insight into diversification of bacteria, we conducted comparative genomic analysis of two lineages of bioluminescent symbionts, Photobacterium leiognathi and 'P. mandapamensis'. The two lineages are evolutionary and ecologically closely related. Based on the methods used in bacterial taxonomy for classification of new species (DNA-DNA hybridization and ANI), genetic relatedness of the two lineages is at a cut-off point for species delineation. In this study, we obtained the whole genome sequence of a representative P. leiognathi strain lrivu.4.1, and compared it to the whole genome sequence of 'P. mandapamensis' svers.1.1. Results of the comparative genomic analysis suggest that P. leiognathi has a more plastic genome and acquired genes horizontally more frequently than 'P. mandapamensis'. We predict that different rates of recombination and gene acquisition contributed to diversification of the two lineages. Analysis of lineage-specific sequences in 25 strains of P. leiognathi and 'P. mandapamensis' found no evidence that bioluminescent symbioses with specific host animals have played a role in diversification of the two lineages.

  9. Diversification of Two Lineages of Symbiotic Photobacterium

    PubMed Central

    Urbanczyk, Henryk; Urbanczyk, Yoshiko; Hayashi, Tetsuya; Ogura, Yoshitoshi

    2013-01-01

    Understanding of processes driving bacterial speciation requires examination of closely related, recently diversified lineages. To gain an insight into diversification of bacteria, we conducted comparative genomic analysis of two lineages of bioluminescent symbionts, Photobacterium leiognathi and ‘P. mandapamensis’. The two lineages are evolutionary and ecologically closely related. Based on the methods used in bacterial taxonomy for classification of new species (DNA-DNA hybridization and ANI), genetic relatedness of the two lineages is at a cut-off point for species delineation. In this study, we obtained the whole genome sequence of a representative P. leiognathi strain lrivu.4.1, and compared it to the whole genome sequence of ‘P. mandapamensis’ svers.1.1. Results of the comparative genomic analysis suggest that P. leiognathi has a more plastic genome and acquired genes horizontally more frequently than ‘P. mandapamensis’. We predict that different rates of recombination and gene acquisition contributed to diversification of the two lineages. Analysis of lineage-specific sequences in 25 strains of P. leiognathi and ‘P. mandapamensis’ found no evidence that bioluminescent symbioses with specific host animals have played a role in diversification of the two lineages. PMID:24349398

  10. Coreceptor gene imprinting governs thymocyte lineage fate

    PubMed Central

    Adoro, Stanley; McCaughtry, Thomas; Erman, Batu; Alag, Amala; Van Laethem, François; Park, Jung-Hyun; Tai, Xuguang; Kimura, Motoko; Wang, Lie; Grinberg, Alex; Kubo, Masato; Bosselut, Remy; Love, Paul; Singer, Alfred

    2012-01-01

    Immature thymocytes are bipotential cells that are signalled during positive selection to become either helper- or cytotoxic-lineage T cells. By tracking expression of lineage determining transcription factors during positive selection, we now report that the Cd8 coreceptor gene locus co-opts any coreceptor protein encoded within it to induce thymocytes to express the cytotoxic-lineage factor Runx3 and to adopt the cytotoxic-lineage fate, findings we refer to as ‘coreceptor gene imprinting'. Specifically, encoding CD4 proteins in the endogenous Cd8 gene locus caused major histocompatibility complex class II-specific thymocytes to express Runx3 during positive selection and to differentiate into CD4+ cytotoxic-lineage T cells. Our findings further indicate that coreceptor gene imprinting derives from the dynamic regulation of specific cis Cd8 gene enhancer elements by positive selection signals in the thymus. Thus, for coreceptor-dependent thymocytes, lineage fate is determined by Cd4 and Cd8 coreceptor gene loci and not by the specificity of T-cell antigen receptor/coreceptor signalling. This study identifies coreceptor gene imprinting as a critical determinant of lineage fate determination in the thymus. PMID:22036949

  11. Instruction of haematopoietic lineage choices, evolution of transcriptional landscapes and cancer stem cell hierarchies derived from an AML1-ETO mouse model

    PubMed Central

    Cabezas-Wallscheid, Nina; Eichwald, Victoria; de Graaf, Jos; Löwer, Martin; Lehr, Hans-Anton; Kreft, Andreas; Eshkind, Leonid; Hildebrandt, Andreas; Abassi, Yasmin; Heck, Rosario; Dehof, Anna Katharina; Ohngemach, Svetlana; Sprengel, Rolf; Wörtge, Simone; Schmitt, Steffen; Lotz, Johannes; Meyer, Claudius; Kindler, Thomas; Zhang, Dong-Er; Kaina, Bernd; Castle, John C; Trumpp, Andreas; Sahin, Ugur; Bockamp, Ernesto

    2013-01-01

    The t(8;21) chromosomal translocation activates aberrant expression of the AML1-ETO (AE) fusion protein and is commonly associated with core binding factor acute myeloid leukaemia (CBF AML). Combining a conditional mouse model that closely resembles the slow evolution and the mosaic AE expression pattern of human t(8;21) CBF AML with global transcriptome sequencing, we find that disease progression was characterized by two principal pathogenic mechanisms. Initially, AE expression modified the lineage potential of haematopoietic stem cells (HSCs), resulting in the selective expansion of the myeloid compartment at the expense of normal erythro- and lymphopoiesis. This lineage skewing was followed by a second substantial rewiring of transcriptional networks occurring in the trajectory to manifest leukaemia. We also find that both HSC and lineage-restricted granulocyte macrophage progenitors (GMPs) acquired leukaemic stem cell (LSC) potential being capable of initiating and maintaining the disease. Finally, our data demonstrate that long-term expression of AE induces an indolent myeloproliferative disease (MPD)-like myeloid leukaemia phenotype with complete penetrance and that acute inactivation of AE function is a potential novel therapeutic option. PMID:24124051

  12. Regional assessments of the hydrocarbon generation potential of selected North American proterozoic rock sequences. Progress report, September 1989--April 1990

    SciTech Connect

    Engel, M.H.; Elmore, R.D.

    1990-04-01

    Our primary research objectives for the first year of this grant are nearing completion. This includes comprehensive sedimentologic/organic geochemical studies of two depositionally distinct, unmetamorphosed units, the Nonesuch Formation ({approximately}1.1 Ga lacustrine rift deposit) and the Dripping Spring Quartzite ({approximately}1.3 Ga marine shelf deposit). As discussed in this progress report, an attempt has been made to (1) identify source rocks by quantification and characterization of constituent organic matter, (2) recognize depositional/diagenetic/catagenetic factors that may have influenced source rock quality and (3) evaluate the possibility of previous or current hydrocarbon generation and migration. Organic petrology and geochemical analyses suggest important differences between kerogens in the Michigan (MI) and Wisconsin (WI) Nonesuch Formation study areas. When considered within a geographic/stratigraphic framework, the Nonesuch Formation in the MI study area exhibits superior source rock potential. It is suggested that sedimentary organic matter in the WI area was subject to more extensive microbial alteration during early diagenesis. It is also possible that thermal maturity levels were slightly to moderately higher in WI than MI. Petrologic evidence for migrated bitumens and the stable isotope composition of late vein carbonates suggest, furthermore, that oil generation and migration may have actually been more extensive in the WI study area.

  13. Microvesicles as a potential biomarker of neoplastic diseases and their role in development and progression of neoplasm.

    PubMed

    Kajdos, Magdalena; Janas, Łukasz; Kolasa-Zwierzchowska, Dorota; Wilczyński, Jacek R; Stetkiewicz, Tomasz

    2015-12-01

    Neoplastic diseases together with cardiovascular diseases are the most frequent causes of death in the Polish population. Cancers of reproductive organs with breast cancer are responsible for the highest morbidity and mortality in women suffering from neoplasm diseases. Asymptomatic dynamics of the development of a neoplasm and no deviations from the normal level of laboratory results contribute to the fact that malignant diseases are diagnosed too late. The aim of modern medicine is to diagnose cancer at the earliest stage, however, there is no sufficiently sensitive and specific biomarker which can be used for diagnostic, prognostic and therapeutic purposes. Cellular interactions play the main role in the development, angiogenesis and invasiveness of a tumor. Recent research suggests the possibility of microvesicles (MVs) involvement in communication between cells. The MVs ability to fuse with various cells is used in cell-to-cell contact. Microvesicles cargo may include growth factors, their receptors, protease, adhesion molecules, signaling molecules and the sequence of DNA, mRNA, and micro-RNA. Larger quantities of MVs released from neoplastic cells affect both the local environment and systematic range causing metastases and progression. The research on molecular mechanisms of MVs' release and the presence of characteristic oncogenes in blood of patients with neoplasms is being carried out. Confirmation of MVs presence in patients' serum can potentially serve as useful information for therapeutic purposes and as the biomarker of a neoplastic disease.

  14. Microvesicles as a potential biomarker of neoplastic diseases and their role in development and progression of neoplasm

    PubMed Central

    Kajdos, Magdalena; Janas, Łukasz; Kolasa-Zwierzchowska, Dorota; Wilczyński, Jacek R.

    2015-01-01

    Neoplastic diseases together with cardiovascular diseases are the most frequent causes of death in the Polish population. Cancers of reproductive organs with breast cancer are responsible for the highest morbidity and mortality in women suffering from neoplasm diseases. Asymptomatic dynamics of the development of a neoplasm and no deviations from the normal level of laboratory results contribute to the fact that malignant diseases are diagnosed too late. The aim of modern medicine is to diagnose cancer at the earliest stage, however, there is no sufficiently sensitive and specific biomarker which can be used for diagnostic, prognostic and therapeutic purposes. Cellular interactions play the main role in the development, angiogenesis and invasiveness of a tumor. Recent research suggests the possibility of microvesicles (MVs) involvement in communication between cells. The MVs ability to fuse with various cells is used in cell-to-cell contact. Microvesicles cargo may include growth factors, their receptors, protease, adhesion molecules, signaling molecules and the sequence of DNA, mRNA, and micro-RNA. Larger quantities of MVs released from neoplastic cells affect both the local environment and systematic range causing metastases and progression. The research on molecular mechanisms of MVs’ release and the presence of characteristic oncogenes in blood of patients with neoplasms is being carried out. Confirmation of MVs presence in patients’ serum can potentially serve as useful information for therapeutic purposes and as the biomarker of a neoplastic disease. PMID:26848301

  15. [Research Progress in Technology of Using Soil Micro-organisms to Generate Electricity and Its Potential Applications].

    PubMed

    Deng, Huan; Xue, Hong-jing; Jiang, Yun-bin; Zhong, Wen-hui

    2015-10-01

    Microbial fuel cells ( microbial fuel cells, MFCs) are devices in which micro-organisms convert chemical energy into electrical power. Soil has electrogenic bacteria and organic substrates, thus can generate electrical current in MFCs. Soil MFCs can be operated and applied to real-time and continuously monitor soil pollution, remove soil pollutants and to reduce methane emitted from flooded rice paddy, without energy consumption and the application of chemical reagents to the soil. Instead, the operation of soil MFCs generates small amount of electrical power. Therefore, soil MFCs are useful in the development of environment-friendly technology for monitoring and remediating soil pollution, which have potential value for applications in the domain of environmental science and engineering. However, much of advanced technology hasn't been applied into soil MFCs since the studies on soil MFCs was not started until recently. This paper summarized the research progress in related to soil MFCs combining with the frontier of MFCs technology, and brought forward the possible direction in studies on soil MFCs.

  16. Chronic stress enhances progression of periodontitis via α1-adrenergic signaling: a potential target for periodontal disease therapy.

    PubMed

    Lu, Huaixiu; Xu, Minguang; Wang, Feng; Liu, Shisen; Gu, Jing; Lin, Songshan

    2014-10-17

    This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the α1-adrenergic receptor (α1-AR) and β2-adrenergic receptor (β2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of α1-AR and β2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1β, IL-6 and IL-8 were detected after pretreatment with the α1/β2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, α1-AR and β2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of α1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of α1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1β, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an α1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.

  17. Neurophysiological and BOLD signal uncoupling of giant somatosensory evoked potentials in progressive myoclonic epilepsy: a case-series study

    PubMed Central

    Storti, Silvia F.; Del Felice, Alessandra; Canafoglia, Laura; Formaggio, Emanuela; Brigo, Francesco; Alessandrini, Franco; Bongiovanni, Luigi G.; Menegaz, Gloria; Manganotti, Paolo

    2017-01-01

    In progressive myoclonic epilepsy (PME), a rare epileptic syndrome caused by a variety of genetic disorders, the combination of peripheral stimulation and functional magnetic resonance imaging (fMRI) can shed light on the mechanisms underlying cortical dysfunction. The aim of the study is to investigate sensorimotor network modifications in PME by assessing the relationship between neurophysiological findings and blood oxygen level dependent (BOLD) activation. Somatosensory-evoked potential (SSEP) obtained briefly before fMRI and BOLD activation during median-nerve electrical stimulation were recorded in four subjects with typical PME phenotype and compared with normative data. Giant scalp SSEPs with enlarger N20-P25 complex compared to normal data (mean amplitude of 26.2 ± 8.2 μV after right stimulation and 27.9 ± 3.7 μV after left stimulation) were detected. Statistical group analysis showed a reduced BOLD activation in response to median nerve stimulation in PMEs compared to controls over the sensorimotor (SM) areas and an increased response over subcortical regions (p < 0.01, Z > 2.3, corrected). PMEs show dissociation between neurophysiological and BOLD findings of SSEPs (giant SSEP with reduced BOLD activation over SM). A direct pathway connecting a highly restricted area of the somatosensory cortex with the thalamus can be hypothesized to support the higher excitability of these areas. PMID:28294187

  18. Plasma levels of the tissue inhibitor matrix metalloproteinase-3 as a potential biomarker in oral cancer progression

    PubMed Central

    Su, Chun-Wen; Su, Bo-Feng; Chiang, Whei-Ling; Yang, Shun-Fa; Chen, Mu-Kuan; Lin, Chiao-Wen

    2017-01-01

    Oral cancer is the most common malignancy with poor prognosis and is the fourth most common cancer in men in Taiwan. The tissue inhibitor of metalloproteinase-3 (TIMP3) acts as a tumor suppressor gene by inhibiting the growth, angiogenesis, migration, and invasion of cancer cells. However, few studies have examined the association of plasma TIMP3 levels with oral squamous cell carcinoma (OSCC), and the role of plasma TIMP3 levels in OSCC progression is still unclear. We measured the plasma TIMP3 levels of 450 OSCC patients and 64 healthy controls by using a commercial enzyme-linked immunosorbent assay. We also analyzed TIMP3 mRNA levels of 328 OSCC patients and 32 normal tissues from The Cancer Genome Atlas (TCGA) dataset. Our results revealed that plasma TIMP3 levels were significantly lower in patients with OSCC than in healthy controls (p < 0.001). Moreover, plasma TIMP3 levels in patients with OSCC were significantly associated with the tumor stage and tumor status but not with the lymph node status, metastasis, and cell differentiation. To verify our findings, we also examined TCGA bioinformatics database and discovered similar results for the association with the pathological stage of OSCC. In conclusion, our results suggest that plasma TIMP3 is a potential biomarker for predicting the tumor stage and T status in patients with OSCC. PMID:28138307

  19. Effect of Temperature on Growth and Sporulation of US-22, US-23, and US-24 Clonal Lineages of Phytophthora infestans and Implications for Late Blight Epidemiology.

    PubMed

    Seidl Johnson, Anna C; Frost, Kenneth E; Rouse, Douglas I; Gevens, Amanda J

    2015-04-01

    Epidemics of late blight, caused by Phytophthora infestans (Mont.) de Bary, have been studied by plant pathologists and regarded with great concern by potato and tomato growers since the Irish potato famine in the 1840s. P. infestans populations have continued to evolve, with unique clonal lineages arising which differ in pathogen fitness and pathogenicity, potentially impacting epidemiology. In 2012 and 2013, the US-23 clonal lineage predominated late blight epidemics in most U.S. potato and tomato production regions, including Wisconsin. This lineage was unknown prior to 2009. For isolates of three recently identified clonal lineages of P. infestans (US-22, US-23, and US-24), sporulation rates were experimentally determined on potato and tomato foliage and the effect of temperature on lesion growth rate on tomato was investigated. The US-22 and US-23 isolates had greater lesion growth rates on tomato than US-24 isolates. Sporulation rates for all isolates were greater on potato than tomato, and the US-23 isolates had greater sporulation rates on both tomato and potato than the US-22 and US-24 isolates. Experimentally determined correlates of fitness were input to the LATEBLIGHT model and epidemics were simulated using archived Wisconsin weather data from four growing seasons (2009 to 2012) to investigate the effect of isolates of these new lineages on late blight epidemiology. The fast lesion growth rates of US-22 and US-23 isolates resulted in severe epidemics in all years tested, particularly in 2011. The greater sporulation rates of P. infestans on potato resulted in simulated epidemics that progressed faster than epidemics simulated for tomato; the high sporulation rates of US-23 isolates resulted in simulated epidemics more severe than simulated epidemics of isolates of the US-22 and US-24 isolates and EC-1 clonal lineages on potato and tomato. Additionally, US-23 isolates consistently caused severe simulated epidemics when lesion growth rate and sporulation

  20. Variation in asexual lineage age in Potamopyrgus antipodarum, a New Zealand snail.

    PubMed

    Neiman, M; Jokela, J; Lively, C M

    2005-09-01

    Asexual lineages are thought to be subject to rapid extinction because they cannot generate recombinant offspring. Accordingly, extant asexual lineages are expected to be of recent derivation from sexual individuals. We examined this prediction by using mitochondrial DNA sequence data to estimate asexual lineage age in populations of a freshwater snail (Potamopyrgus antipodarum) native to New Zealand and characterized by varying frequency of sexual and asexual individuals. We found considerable variation in the amount of genetic divergence of asexual lineages from sexual relatives, pointing to a wide range of asexual lineage ages. Most asexual lineages had close genetic ties (approximately 0.1% sequence divergence) to haplotypes found in sexual representatives, indicating a recent origin from sexual progenitors. There were, however, two asexual clades that were quite genetically distinct (> 1.2% sequence divergence) from sexual lineages and may have diverged from sexual progenitors more than 500,000 years ago. These two clades were found in lakes that had a significantly lower frequency of sexual individuals than lakes without the old clades, suggesting that the conditions that favor sex might select against ancient asexuality. Our results also emphasize the need for large sample sizes and spatially representative sampling when hypotheses for the age of asexual lineages are tested to adequately deal with potential biases in age estimates.

  1. Vector Competence of Culex neavei and Culex quinquefasciatus (Diptera: Culicidae) from Senegal for Lineages 1, 2, Koutango and a Putative New Lineage of West Nile virus

    PubMed Central

    Fall, Gamou; Diallo, Mawlouth; Loucoubar, Cheikh; Faye, Ousmane; Sall, Amadou Alpha

    2014-01-01

    West Nile virus (WN virus) is one of the most widespread arbovirus and exhibits a great genetic diversity with 8 lineages, at least 4 (1, 2, Koutango, and putative new) are present in Africa. In West Africa, Culex neavei and Culex quinquefasciatus are considered as potential vectors for WN virus transmission in sylvatic or urban context. We analyzed the vector competence of these Culex species from Senegal for African lineages and envelope proteins sequences of viral strains used. We showed that lineage 1 is transmitted by both Culex mosquitoes, whereas the putative new lineage 8 is transmitted only by Cx. neavei. Our findings suggest that genetic variability can affect vector competence and depend on mosquito. However, when considering the infective life rate, the mosquito population seems to be inefficient for WN virus transmission in the field and could explain the low impact of WN virus in Africa. PMID:24567319

  2. Identifying Academic Potential in Students from Under-Represented Populations: Is Using the Ravens Progressive Matrices a Good Idea?

    ERIC Educational Resources Information Center

    Mills, Carol J.; Tissot, Sherri L.

    1995-01-01

    The Raven's Progressive Matrices (RPM) and the Raven's Advanced Progressive Matrices (APM) were evaluated as possible instruments for identifying academically talented students in minority populations. A significantly higher proportion of minority children scored well on the RPM than on a traditional measure. Issues and concerns about using the…

  3. Lineage management for on-demand data

    NASA Astrophysics Data System (ADS)

    Collins, J. A.; Brodzik, M.; Billingsley, B. W.

    2009-12-01

    Most data consumers would agree that data should be easily available, and welcome the ability to subset, reformat, and reproject archived data before they retrieve the data for local use. Although these features in a data delivery system potentially enhance the interdisciplinary or collaborative use of the data, they also raise concerns for the archive providing those data. The Searchlight project at the National Snow and Ice Data Center (NSIDC) has successfully dealt with many of the technical issues surrounding the dynamic delivery of user-defined data subsets. These data manipulation accomplishments only solve part of the dynamic data delivery problem: We now need to associate accurate provenance and processing information with the customized data product. The user needs the provenance and history in order to make accurate judgements regarding the appropriate use of the data. Our User Support team may need that provenance and history in order to provide a level of service similar to that available for our documented, archived data sets. This presentation will examine the Searchlight team's response to the emerging issue of handling lineage information associated with dynamically generated data products.

  4. A new fluorogenic real-time RT-PCR assay for detection of lineage 1 and lineage 2 West Nile viruses.

    PubMed

    Jiménez-Clavero, Miguel Angel; Agüero, Montserrat; Rojo, Gema; Gómez-Tejedor, Concepción

    2006-09-01

    West Nile virus represents an emerging threat for animal and human health worldwide. This virus exhibits a marked genetic variation, with at least 2 distinct evolutionary lineages. Lineage 1 has been recognized in Africa, Asia, Europe, Oceania, and more recently in the Americas, whereas lineage 2 is restricted to Africa. Perhaps for this reason, the available real-time RT-PCR methods for detecting West Nile virus genome have mainly focused on lineage 1. However, both viruses may potentially be spread beyond their endemic areas by migratory birds. This report describes a new real-time reverse transcription-PCR (RT-PCR) method based on a 5'-Taq nuclease-3' minor groove binder DNA probe (TaqMan MGB) that allows the detection of a wide range of West Nile virus isolates, including both lineages 1 and 2. This method was able to detect West Nile viruses from different origins (North and Central Africa, Middle East, Europe, and North America), whereas other flaviviruses (Usutu, Dengue, Yellow fever) analyzed in parallel remained negative. The sensitivity achieved by this assay was 10(-2)-10(-3) pfu/tube. This method, which can be performed in 96-well format, could be suitable for the large-scale surveillance of West Nile virus in areas where both lineages can potentially spread.

  5. Saami mitochondrial DNA reveals deep maternal lineage clusters.

    PubMed

    Delghandi, M; Utsi, E; Krauss, S

    1998-01-01

    The mitochondrial DNA of 62 Saami from the north of Norway was analyzed in the D loop hypervariable region I and II and sequences were compared to other gene pools. Two major (lineage 1 and 2) and two minor (lineage 3 and 4) maternal lineage clusters were found. Lineage 1 (56.9% of all hitherto analyzed Saami samples) contains a substantial number of branching haplotypes which are unknown in European gene pools. Lineage 2 (31.5%) and lineage 4 (3.6%) have few branching points and are present at a low rate throughout European gene pools. Lineage 3 (4.7%) has polymorphisms characteristic of circumpolar lineages.

  6. Building a lineage from single cells: genetic techniques for cell lineage tracking.

    PubMed

    Woodworth, Mollie B; Girskis, Kelly M; Walsh, Christopher A

    2017-04-01

    Resolving lineage relationships between cells in an organism is a fundamental interest of developmental biology. Furthermore, investigating lineage can drive understanding of pathological states, including cancer, as well as understanding of developmental pathways that are amenable to manipulation by directed differentiation. Although lineage tracking through the injection of retroviral libraries has long been the state of the art, a recent explosion of methodological advances in exogenous labelling and single-cell sequencing have enabled lineage tracking at larger scales, in more detail, and in a wider range of species than was previously considered possible. In this Review, we discuss these techniques for cell lineage tracking, with attention both to those that trace lineage forwards from experimental labelling, and those that trace backwards across the life history of an organism.

  7. Melatonin exacerbates acute experimental autoimmune encephalomyelitis by enhancing the serum levels of lactate: A potential biomarker of multiple sclerosis progression.

    PubMed

    Ghareghani, Majid; Dokoohaki, Shima; Ghanbari, Amir; Farhadi, Naser; Zibara, Kazem; Khodadoust, Saeid; Parishani, Mohammad; Ghavamizadeh, Mehdi; Sadeghi, Heibatollah

    2017-01-01

    Melatonin has a beneficial role in adult rat models of multiple sclerosis (MS). In this study, melatonin treatment (10 mg/kg/d) was investigated in young age (5-6 weeks old) Lewis rat model of acute experimental autoimmune encephalomyelitis (EAE) followed by assessing serum levels of lactate and melatonin. Results showed that clinical outcomes were exacerbated in melatonin- (neurological score = 6) vs PBS-treated EAE rats (score = 5). Melatonin caused a significant increase in serum IFN-γ, in comparison to PBS-treated EAE rats whereas no considerable change in IL-4 levels were found, although they were significantly lower than those of controls. The ratio of IFN-γ/IL-4, an indicator of Th-1/Th-2, was significantly higher in PBS- and melatonin- treated EAE rats, in comparison to controls. Moreover, results showed increased lymphocyte infiltration, activated astrocytes (GFAP+ cells) but also higher demyelinated plaques (MBP-deficient areas) in the lumbar spinal cord of melatonin-treated EAE rats. Finally, serum levels of lactate, but not melatonin, significantly increased in the melatonin group, compared to untreated EAE and normal rats. In conclusion, our results indicated a relationship between age and the development of EAE since a negative impact was found for melatonin on EAE recovery of young rats by enhancing IFN-γ, the ratio of Th1/Th2 cells, and astrocyte activation, which seems to delay the remyelination process. While melatonin levels decline in MS patients, lactate might be a potential diagnostic biomarker for prediction of disease progression. Early administration of melatonin in the acute phase of MS might be harmful and needs further investigations. © 2016 John Wiley & Sons Australia, Ltd.

  8. Pox neuro control of cell lineages that give rise to larval poly-innervated external sensory organs in Drosophila.

    PubMed

    Jiang, Yanrui; Boll, Werner; Noll, Markus

    2015-01-15

    The Pox neuro (Poxn) gene of Drosophila plays a crucial role in the development of poly-innervated external sensory (p-es) organs. However, how Poxn exerts this role has remained elusive. In this study, we have analyzed the cell lineages of all larval p-es organs, namely of the kölbchen, papilla 6, and hair 3. Surprisingly, these lineages are distinct from any previously reported cell lineages of sensory organs. Unlike the well-established lineage of mono-innervated external sensory (m-es) organs and a previously proposed model of the p-es lineage, we demonstrate that all wild-type p-es lineages exhibit the following features: the secondary precursor, pIIa, gives rise to all three support cells-socket, shaft, and sheath, whereas the other secondary precursor, pIIb, is neuronal and gives rise to all neurons. We further show that in one of the p-es lineages, that of papilla 6, one cell undergoes apoptosis. By contrast in Poxn null mutants, all p-es lineages have a reduced number of cells and their pattern of cell divisions is changed to that of an m-es organ, with the exception of a lineage in a minority of mutant kölbchen that retains a second bipolar neuron. Indeed, the role of Poxn in p-es lineages is consistent with the specification of the developmental potential of secondary precursors and the regulation of cell division but not apoptosis.

  9. Influenza B vaccine lineage selection—An optimized trivalent vaccine

    PubMed Central

    Mosterín Höpping, Ana; Fonville, Judith M.; Russell, Colin A.; James, Sarah; Smith, Derek J.

    2016-01-01

    Epidemics of seasonal influenza viruses cause considerable morbidity and mortality each year. Various types and subtypes of influenza circulate in humans and evolve continuously such that individuals at risk of serious complications need to be vaccinated annually to keep protection up to date with circulating viruses. The influenza vaccine in most parts of the world is a trivalent vaccine, including an antigenically representative virus of recently circulating influenza A/H3N2, A/H1N1, and influenza B viruses. However, since the 1970s influenza B has split into two antigenically distinct lineages, only one of which is represented in the annual trivalent vaccine at any time. We describe a lineage selection strategy that optimizes protection against influenza B using the standard trivalent vaccine as a potentially cost effective alternative to quadrivalent vaccines. PMID:26896685

  10. Lineage-specific reprogramming as a strategy for cell therapy.

    PubMed

    Darabi, Radbod; Perlingeiro, Rita C R

    2008-06-15

    Embryonic stem (ES) cells are endowed with extensive ability for self renewal and differentiation. These features make them a promising candidate for cell therapy. However, despite the enthusiasm and hype surrounding the potential therapeutic use of human ES cells and more recently induced pluripotent stem (iPS) cells, to date few reports have documented successful therapeutic outcome with ES-derived cell populations. This is probably due to two main caveats associated with ES cells, their capacity to form teratomas and the challenge of isolating the appropriate therapeutic cell population from differentiating ES cells. We have focused our efforts on the derivation of skeletal muscle progenitors from ES cells and here we will discuss the strategy of reprogramming lineage choices by overexpression of a master regulator, which has proven successful for the generation of the skeletal myogenic lineage from mouse ES cells.

  11. Influenza B vaccine lineage selection--an optimized trivalent vaccine.

    PubMed

    Mosterín Höpping, Ana; Fonville, Judith M; Russell, Colin A; James, Sarah; Smith, Derek J

    2016-03-18

    Epidemics of seasonal influenza viruses cause considerable morbidity and mortality each year. Various types and subtypes of influenza circulate in humans and evolve continuously such that individuals at risk of serious complications need to be vaccinated annually to keep protection up to date with circulating viruses. The influenza vaccine in most parts of the world is a trivalent vaccine, including an antigenically representative virus of recently circulating influenza A/H3N2, A/H1N1, and influenza B viruses. However, since the 1970s influenza B has split into two antigenically distinct lineages, only one of which is represented in the annual trivalent vaccine at any time. We describe a lineage selection strategy that optimizes protection against influenza B using the standard trivalent vaccine as a potentially cost effective alternative to quadrivalent vaccines.

  12. Differentiation of equine induced pluripotent stem cells into a keratinocyte lineage.

    PubMed

    Aguiar, C; Therrien, J; Lemire, P; Segura, M; Smith, L C; Theoret, C L

    2016-05-01

    Skin trauma in horses often leads to the development of chronic nonhealing wounds that lack a keratinocyte cover, vital for healing. Reports in mouse and man confirm the possibility of generating functional keratinocytes from induced pluripotent stem cells (iPSC), thus presenting myriad potential applications for wound management or treatment of skin disease. Similarly, differentiation of equine iPSC (eiPSC) into a keratinocyte lineage should provide opportunities for the advancement of veterinary regenerative medicine. The purpose of this study was to develop an efficient method for the differentiation of eiPSC into a keratinocyte lineage. It was hypothesised that eiPSC can form differentiated keratinocytes (eiPSC-KC) comparable with primary equine keratinocytes (PEK) in their morphological and functional characteristics. Experimental in vitro study. Equine iPSC established using a nonviral system were treated for 30 days with retinoic acid and bone morphogenetic protein-4 to induce directed differentiation into iPSC-KC. Temporospatial gene and protein expression by eiPSC-KC was measured at weekly intervals of differentiation and in response to calcium switch. Proliferative and migratory capacities of eiPSC-KC were compared with those of PEK. Equine iPSC, upon directed differentiation, showed loss of pluripotency genes and progressive increase in pancytokeratin expression indicating ectodermal specification into keratinocytes. High differentiation efficiency was achieved, with 82.5% of eiPSC expressing keratin 14, a marker of epidermal-specific basal stem cells, after 30 days of directed differentiation. Moreover, the proliferative capacity of eiPSC-KC was superior, while the migratory capacity (measured as the ability to epithelise in vitro wounds) was comparable with that of PEK. This proof of concept study suggests that eiPSC can successfully be differentiated into equine keratinocytes (eiPSC-KC) with features that are promising to the development of a stem

  13. Myelin and oligodendrocyte lineage cells in white matter pathology and plasticity after traumatic brain injury.

    PubMed

    Armstrong, Regina C; Mierzwa, Amanda J; Sullivan, Genevieve M; Sanchez, Maria A

    2016-11-01

    Impact to the head or rapid head acceleration-deceleration can cause traumatic brain injury (TBI) with a characteristic pathology of traumatic axonal injury (TAI) and secondary damage in white matter tracts. Myelin and oligodendrocyte lineage cells have significant roles in the progression of white matter pathology after TBI and in the potential for plasticity and subsequent recovery. The myelination pattern of specific brain regions, such as frontal cortex, may also increase susceptibility to neurodegeneration and psychiatric symptoms after TBI. White matter pathology after TBI depends on the extent and distribution of axon damage, microhemorrhages and/or neuroinflammation. TAI occurs in a pattern of damaged axons dispersed among intact axons in white matter tracts. TAI accompanied by bleeding and/or inflammation produces focal regions of overt tissue destruction, resulting in loss of both axons and myelin. White matter regions with TAI may also exhibit demyelination of intact axons. Demyelinated axons that remain viable have the potential for remyelination and recovery of function. Indeed, animal models of TBI have demonstrated demyelination that is associated with evidence of remyelination, including oligodendrocyte progenitor cell proliferation, generation of new oligodendrocytes, and formation of thinner myelin. Changes in neuronal activity that accompany TBI may also involve myelin remodeling, which modifies conduction efficiency along intact myelinated fibers. Thus, effective remyelination and myelin remodeling may be neurobiological substrates of plasticity in neuronal circuits that require long-distance communication. This perspective integrates findings from multiple contexts to propose a model of myelin and oligodendrocyte lineage cell relevance in white matter injury after TBI. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'.

  14. PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target

    PubMed Central

    Li, Jiarong; Karaplis, Andrew C.; Huang, Dao C.; Siegel, Peter M.; Camirand, Anne; Yang, Xian Fang; Muller, William J.; Kremer, Richard

    2011-01-01

    Parathyroid hormone–related protein (PTHrP) is a secreted factor expressed in almost all normal fetal and adult tissues. It is involved in a wide range of developmental and physiological processes, including serum calcium regulation. PTHrP is also associated with the progression of skeletal metastases, and its dysregulated expression in advanced cancers causes malignancy-associated hypercalcemia. Although PTHrP is frequently expressed by breast tumors and other solid cancers, its effects on tumor progression are unclear. Here, we demonstrate in mice pleiotropic involvement of PTHrP in key steps of breast cancer — it influences the initiation and progression of primary tumors and metastases. Pthrp ablation in the mammary epithelium of the PyMT-MMTV breast cancer mouse model caused a delay in primary tumor initiation, inhibited tumor progression, and reduced metastasis to distal sites. Mechanistically, it reduced expression of molecular markers of cell proliferation (Ki67) and angiogenesis (factor VIII), antiapoptotic factor Bcl-2, cell-cycle progression regulator cyclin D1, and survival factor AKT1. PTHrP also influenced expression of the adhesion factor CXCR4, and coexpression of PTHrP and CXCR4 was crucial for metastatic spread. Importantly, PTHrP-specific neutralizing antibodies slowed the progression and metastasis of human breast cancer xenografts. Our data identify what we believe to be new functions for PTHrP in several key steps of breast cancer and suggest that PTHrP may constitute a novel target for therapeutic intervention. PMID:22056386

  15. Specific detection of GII-1 lineage of infectious bronchitis virus.

    PubMed

    Domanska-Blicharz, K; Lisowska, A; Pikuła, A; Sajewicz-Krukowska, J

    2017-08-01

    Infectious bronchitis virus (IBV) is a worldwide prevalent RNA virus that causes highly contagious and economically devastating disease in chicken. The virus exists in many different genetic forms which made the disease control very difficult. The present study describes the development and validation of TaqMan probe-based real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) targeting the S1 coding region of S gene characteristic for the GII-1 lineage (formerly the D1466-like variant) of IBV. These strains are quite different from other European IBV belonging to different lineages of the GI genotype. The developed method was 30-fold more sensitive than used so far for standard nested RT-PCR with detection limit of 56 RNA copies per reaction. The specificity of the assay was also evaluated with a panel of different poultry pathogens. Repeatability and reproducibility of the method was very high with coefficients of variation lower than 4%. One hundred and twenty-seven IBV-positive samples were tested by this method and GII-1 strains were detected in four of them (3·15%) which indicate a decrease in the GII-1 IBV prevalence in Poland. The assay was proven to be a valuable tool for rapid diagnosis of GII-1 lineage of IBV strains and moreover it enabled the monitoring of viral loads which can be used to assess disease progression. This study reports a TaqMan probe-based real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) for rapid and accurate identification of GII-1 lineage (formerly D1466-like variant) of infectious bronchitis virus (IBV). The assay revealed to be more sensitive than standard nested RT-PCR assay, previously used for this purpose. The developed assay has been tested on numerous field samples and revealed 3·15% prevalence of this lineage of IBV in Polish chicken population. Moreover, this new assay enables the assessment of viral load measurement which might be useful for epidemiology and pathogenesis

  16. Muscle histone deacetylase 4 upregulation in amyotrophic lateral sclerosis: potential role in reinnervation ability and disease progression.

    PubMed

    Bruneteau, Gaëlle; Simonet, Thomas; Bauché, Stéphanie; Mandjee, Nathalie; Malfatti, Edoardo; Girard, Emmanuelle; Tanguy, Marie-Laure; Behin, Anthony; Khiami, Frédéric; Sariali, Elhadi; Hell-Remy, Caroline; Salachas, François; Pradat, Pierre-François; Fournier, Emmanuel; Lacomblez, Lucette; Koenig, Jeanine; Romero, Norma Beatriz; Fontaine, Bertrand; Meininger, Vincent; Schaeffer, Laurent; Hantaï, Daniel

    2013-08-01

    Amyotrophic lateral sclerosis is a typically rapidly progressive neurodegenerative disorder affecting motor neurons leading to progressive muscle paralysis and death, usually from respiratory failure, in 3-5 years. Some patients have slow disease progression and prolonged survival, but the underlying mechanisms remain poorly understood. Riluzole, the only approved treatment, only modestly prolongs survival and has no effect on muscle function. In the early phase of the disease, motor neuron loss is initially compensated for by collateral reinnervation, but over time this compensation fails, leading to progressive muscle wasting. The crucial role of muscle histone deacetylase 4 and its regulator microRNA-206 in compensatory reinnervation and disease progression was recently suggested in a mouse model of amyotrophic lateral sclerosis (transgenic mice carrying human mutations in the superoxide dismutase gene). Here, we sought to investigate whether the microRNA-206-histone deacetylase 4 pathway plays a role in muscle compensatory reinnervation in patients with amyotrophic lateral sclerosis and thus contributes to disease outcome differences. We studied muscle reinnervation using high-resolution confocal imaging of neuromuscular junctions in muscle samples obtained from 11 patients with amyotrophic lateral sclerosis, including five long-term survivors. We showed that the proportion of reinnervated neuromuscular junctions was significantly higher in long-term survivors than in patients with rapidly progressive disease. We analysed the expression of muscle candidate genes involved in the reinnervation process and showed that histone deacetylase 4 upregulation was significantly greater in patients with rapidly progressive disease and was negatively correlated with the extent of muscle reinnervation and functional outcome. Conversely, the proposed regulator of histone deacetylase 4, microRNA-206, was upregulated in both patient groups, but did not correlate with disease

  17. Detection of Two Zoonotic Babesia microti Lineages, the Hobetsu and U.S. Lineages, in Two Sympatric Tick Species, Ixodes ovatus and Ixodes persulcatus, Respectively, in Japan

    PubMed Central

    Tsuji, Masayoshi; Qiang, Wei; Nakao, Minoru; Hirata, Haruyuki; Ishihara, Chiaki

    2012-01-01

    The species Babesia microti, commonly found in rodents, demonstrates a high degree of genetic diversity. Three lineages, U.S., Kobe, and Hobetsu, are known to have zoonotic potential, but their tick vector(s) in Japan remains to be elucidated. We conducted a field investigation at Nemuro on Hokkaido Island and at Sumoto on Awaji Island, where up to two of the three lineages occur with similar frequencies in reservoirs. By flagging vegetation at these spots and surrounding areas, 4,010 ticks, comprising six species, were collected. A nested PCR that detects the 18S rRNA gene of Babesia species revealed that Ixodes ovatus and I. persulcatus alone were positive. Lineage-specific PCR for rRNA-positive samples demonstrated that I. ovatus and I. persulcatus carried, respectively, the Hobetsu and U.S. parasites. No Kobe-specific DNA was detected. Infected I. ovatus ticks were found at multiple sites, including Nemuro and Sumoto, with minimum infection rates (MIR) of ∼12.3%. However, all I. persulcatus ticks collected within the same regions, a total of 535, were negative for the Hobetsu lineage, indicating that I. ovatus, but not I. persulcatus, was the vector for the lineage. At Nemuro, U.S. lineage was detected in 2 of 139 adult I. persulcatus ticks (MIR, 1.4%), for the first time, while 48 of I. ovatus ticks were negative for that lineage. Laboratory experiments confirmed the transmission of Hobetsu and U.S. parasites to hamsters via I. ovatus and I. persulcatus, respectively. Differences in vector capacity shown by MIRs at Nemuro, where the two species were equally likely to acquire either lineage of parasite, may explain the difference in distribution of Hobetsu throughout Japan and U.S. taxa in Nemuro. These findings are of importance in the assessment of the regional risk for babesiosis in humans. PMID:22389378

  18. Cardiac acceleration at the onset of exercise: a potential parameter for monitoring progress during physical training in sports and rehabilitation.

    PubMed

    Hettinga, Florentina J; Monden, Paul G; van Meeteren, Nico L U; Daanen, Hein A M

    2014-05-01

    There is a need for easy-to-use methods to assess training progress in sports and rehabilitation research. The present review investigated whether cardiac acceleration at the onset of physical exercise (HRonset) can be used as a monitoring variable. The digital databases of Scopus and PubMed were searched to retrieve studies investigating HRonset. In total 652 studies were retrieved. These articles were then classified as having emphasis on HRonset in a sports or rehabilitation setting, which resulted in 8 of 112 studies with a sports application and 6 of 68 studies with a rehabilitation application that met inclusion criteria. Two co-existing mechanisms underlie HRonset: feedforward (central command) and feedback (mechanoreflex, metaboreflex, baroreflex) control. A number of studies investigated HRonset during the first few seconds of exercise (HRonsetshort), in which central command and the mechanoreflex determine vagal withdrawal, the major mechanism by which heart rate (HR) increases. In subsequent sports and rehabilitation studies, interest focused on HRonset during dynamic exercise over a longer period of time (HRonsetlong). Central command, mechanoreflexes, baroreflexes, and possibly metaboreflexes contribute to HRonset during the first seconds and minutes of exercise, which in turn leads to further vagal withdrawal and an increase in sympathetic activity. HRonset has been described as the increase in HR compared with resting state (delta HR) or by exponential modeling, with measurement intervals ranging from 0-4 s up to 2 min. Delta HR was used to evaluate HRonsetshort over the first 4 s of exercise, as well as for analyzing HRonsetlong. In exponential modeling, the HR response to dynamic exercise is biphasic, consisting of fast (parasympathetic, 0-10 s) and slow (sympathetic, 1-4 min) components. Although available studies differed largely in measurement protocols, cross-sectional and longitudinal training studies showed that studies analyzing HRonset

  19. Quantitative lineage tracing strategies to resolve multipotency in tissue-specific stem cells.

    PubMed

    Wuidart, Aline; Ousset, Marielle; Rulands, Steffen; Simons, Benjamin D; Van Keymeulen, Alexandra; Blanpain, Cédric

    2016-06-01

    Lineage tracing has become the method of choice to study the fate and dynamics of stem cells (SCs) during development, homeostasis, and regeneration. However, transgenic and knock-in Cre drivers used to perform lineage tracing experiments are often dynamically, temporally, and heterogeneously expressed, leading to the initial labeling of different cell types and thereby complicating their interpretation. Here, we developed two methods: the first one based on statistical analysis of multicolor lineage tracing, allowing the definition of multipotency potential to be achieved with high confidence, and the second one based on lineage tracing at saturation to assess the fate of all SCs within a given lineage and the "flux" of cells between different lineages. Our analysis clearly shows that, whereas the prostate develops from multipotent SCs, only unipotent SCs mediate mammary gland (MG) development and adult tissue remodeling. These methods offer a rigorous framework to assess the lineage relationship and SC fate in different organs and tissues. © 2016 Wuidart et al.; Published by Cold Spring Harbor Laboratory Press.

  20. Ecological Genomics of the Uncultivated Marine Roseobacter Lineage CHAB-I-5

    PubMed Central

    Zhang, Yao; Sun, Ying; Jiao, Nianzhi; Stepanauskas, Ramunas

    2016-01-01

    Members of the marine Roseobacter clade are major participants in global carbon and sulfur cycles. While roseobacters are well represented in cultures, several abundant pelagic lineages, including SAG-O19, DC5-80-3, and NAC11-7, remain largely uncultivated and show evidence of genome streamlining. Here, we analyzed the partial genomes of three single cells affiliated with CHAB-I-5, another abundant but exclusively uncultivated Roseobacter lineage. Members of this lineage encode several metabolic potentials that are absent in streamlined genomes. Examples are quorum sensing and type VI secretion systems, which enable them to effectively interact with host and other bacteria. Further analysis of the CHAB-I-5 single-cell amplified genomes (SAGs) predicted that this lineage comprises members with relatively large genomes (4.1 to 4.4 Mbp) and a high fraction of noncoding DNA (10 to 12%), which is similar to what is observed in many cultured, nonstreamlined Roseobacter lineages. The four uncultured lineages, while exhibiting highly variable geographic distributions, together represent >60% of the global pelagic roseobacters. They are consistently enriched in genes encoding the capabilities of light harvesting, oxidation of “energy-rich” reduced sulfur compounds and methylated amines, uptake and catabolism of various carbohydrates and osmolytes, and consumption of abundant exudates from phytoplankton. These traits may define the global prevalence of the four lineages among marine bacterioplankton. PMID:26826224

  1. Adaptable individuals and innovative lineages.

    PubMed

    Sterelny, Kim

    2016-03-19

    This paper suggests (i) that while work on animal innovation has made good progress in understanding some of the proximate mechanisms and selective regimes through which innovation emerges, it has somewhat neglected the role of the social environment of innovation; a neglect manifest in the fact that innovation counts are almost always counts of resource-acquisition innovations; the invention of social tools is rarely considered. The same is true of many experimental projects, as these typically impose food acquisition tasks on their experimental subjects. (ii) That neglect is important, because innovations often pose collective action problems; the hominin species were technically innovative because they were also socially adaptable. (iii) In part for this reason, there remains a disconnect between research on hominin innovation and research on animal innovation. (iv) Finally, the paper suggests that there is something of a disconnect between the theoretical work on innovation in hominin evolution (based on theories of cultural evolution) and the experimental tradition on human innovation. That disconnect is largely due to the theoretical work retreating from strong claims about the proximate mechanisms of human cultural accumulation. © 2016 The Author(s).

  2. Adaptable individuals and innovative lineages

    PubMed Central

    Sterelny, Kim

    2016-01-01

    This paper suggests (i) that while work on animal innovation has made good progress in understanding some of the proximate mechanisms and selective regimes through which innovation emerges, it has somewhat neglected the role of the social environment of innovation; a neglect manifest in the fact that innovation counts are almost always counts of resource-acquisition innovations; the invention of social tools is rarely considered. The same is true of many experimental projects, as these typically impose food acquisition tasks on their experimental subjects. (ii) That neglect is important, because innovations often pose collective action problems; the hominin species were technically innovative because they were also socially adaptable. (iii) In part for this reason, there remains a disconnect between research on hominin innovation and research on animal innovation. (iv) Finally, the paper suggests that there is something of a disconnect between the theoretical work on innovation in hominin evolution (based on theories of cultural evolution) and the experimental tradition on human innovation. That disconnect is largely due to the theoretical work retreating from strong claims about the proximate mechanisms of human cultural accumulation. PMID:26926286

  3. Gamete Dialogs in Green Lineages.

    PubMed

    Mori, Toshiyuki; Kawai-Toyooka, Hiroko; Igawa, Tomoko; Nozaki, Hisayoshi

    2015-10-05

    Gamete fusion is a core process of sexual reproduction and, in both plants and animals, different sex gametes fuse within species. Although most of the molecular factors involved in gamete interaction are still unknown in various sex-possessing eukaryotes, reports of such factors in algae and land plants have been increasing in the past decade. In particular, knowledge of gamete interaction in flowering plants and green algae has increased since the identification of the conserved gamete fusion factor generative cell specific 1/hapless 2 (GCS1/HAP2). GCS1 was first identified as a pollen generative cell-specific transmembrane protein in the lily (Lilium longiflorum), and was then shown to function not only in flowering plant gamete fusion but also in various eukaryotes, including unicellular protists and metazoans. In addition, although initially restricted to Chlamydomonas, knowledge of gamete attachment in flowering plants was also acquired. This review focuses on recent progress in the study of gamete interaction in volvocine green algae and flowering plants and discusses conserved mechanisms of gamete recognition, attachment, and fusion leading to zygote formation. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  4. Evidence of two distinct phylogenetic lineages of dog rabies virus circulating in Cambodia.

    PubMed

    Mey, Channa; Metlin, Artem; Duong, Veasna; Ong, Sivuth; In, Sotheary; Horwood, Paul F; Reynes, Jean-Marc; Bourhy, Hervé; Tarantola, Arnaud; Buchy, Philippe

    2016-03-01

    This first extensive retrospective study of the molecular epidemiology of dog rabies in Cambodia included 149 rabies virus (RABV) entire nucleoprotein sequences obtained from 1998-2011. The sequences were analyzed in conjunction with RABVs from other Asian countries. Phylogenetic reconstruction confirmed the South-East Asian phylogenetic clade comprising viruses from Cambodia, Vietnam, Thailand, Laos and Myanmar. The present study represents the first attempt to classify the phylogenetic lineages inside this clade, resulting in the confirmation that all the Cambodian viruses belonged to the South-East Asian (SEA) clade. Three distinct phylogenetic lineages in the region were established with the majority of viruses from Cambodia closely related to viruses from Thailand, Laos and Vietnam, forming the geographically widespread phylogenetic lineage SEA1. A South-East Asian lineage SEA2 comprised two viruses from Cambodia was identified, which shared a common ancestor with RABVs originating from Laos. Viruses from Myanmar formed separate phylogenetic lineages within the major SEA clade. Bayesian molecular clock analysis suggested that the time to most recent common ancestor (TMRCA) of all Cambodian RABVs dated to around 1950. The TMRCA of the Cambodian SEA1 lineage was around 1964 and that of the SEA2 lineage was around 1953. The results identified three phylogenetically distinct and geographically separated lineages inside the earlier identified major SEA clade, covering at least five countries in the region. A greater understanding of the molecular epidemiology of rabies in South-East Asia is an important step to monitor progress on the efforts to control canine rabies in the region.

  5. Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death

    PubMed Central

    1996-01-01

    Expression of the bcl-2 gene has been shown to effectively confer resistance to programmed cell death under a variety of circumstances. However, despite a wealth of literature describing this phenomenon, very little is known about the mechanism of resistance. In the experiments described here, we show that bcl-2 gene expression can result in an inhibition of cell division cycle progression. These findings are based upon the analysis of cell cycle distribution, cell cycle kinetics, and relative phosphorylation of the retinoblastoma tumor suppressor protein, using primary tissues in vivo, ex vivo, and in vitro, as well as continuous cell lines. The effects of bcl-2 expression on cell cycle progression appear to be focused at the G1 to S phase transition, which is a critical control point in the decision between continued cell cycle progression or the induction programmed cell death. In all systems tested, bcl-2 expression resulted in a substantial 30-60% increase in the length of G1 phase; such an increase is very substantial in the context of other regulators of cell cycle progression. Based upon our findings, and the related findings of others, we propose a mechanism by which bcl-2 expression might exert its well known inhibition of programmed cell death by regulating the kinetics of cell cycle progression at a critical control point. PMID:8642331

  6. Acute Versus Progressive Onset of Diabetes in NOD Mice: Potential Implications for Therapeutic Interventions in Type 1 Diabetes.

    PubMed

    Mathews, Clayton E; Xue, Song; Posgai, Amanda; Lightfoot, Yaima L; Li, Xia; Lin, Andrea; Wasserfall, Clive; Haller, Michael J; Schatz, Desmond; Atkinson, Mark A

    2015-11-01

    Most natural history models for type 1 diabetes (T1D) propose that overt hyperglycemia results after a progressive loss of insulin-secreting β-cell mass and/or function. To experimentally address this concept, we prospectively determined morning blood glucose measurements every other day in multiple cohorts (total n = 660) of female NOD/ShiLtJ mice starting at 8 weeks of age until diabetes onset or 26 weeks of age. Consistent with this notion, a majority of mice that developed diabetes (354 of 489 [72%]) displayed a progressive increase in blood glucose with transient excursions >200 mg/dL, followed by acute and persistent hyperglycemia at diabetes onset. However, 135 of the 489 (28%) diabetic animals demonstrated normal glucose values followed by acute (i.e., sudden) hyperglycemia. Interestingly, diabetes onset occurred earlier in mice with acute versus progressive disease onset (15.37 ± 0.3207 vs. 17.44 ± 0.2073 weeks of age, P < 0.0001). Moreover, the pattern of onset (i.e., progressive vs. acute) dramatically influenced the ability to achieve reversal of T1D by immunotherapeutic intervention, with increased effectiveness observed in situations of a progressive deterioration in euglycemia. These studies highlight a novel natural history aspect in this animal model, one that may provide important guidance for the selection of subjects participating in human trials seeking disease reversal.

  7. Mitochondrial DNA polymorphism in a maternal lineage of Holstein cows.

    PubMed Central

    Hauswirth, W W; Laipis, P J

    1982-01-01

    Two mitochondrial genotypes are shown to exist within one Holstein cow maternal lineage. They were detected by the appearance of an extra Hae III recognition site in one genotype. The nucleotide sequence of this region has been determined and the genotypes are distinguished by an adenine/guanine base transition which creates the new Hae III site. This point mutation occurs within an open reading frame at the third position of a glycine codon and therefore does not alter the amino acid sequence. The present pattern of genotypes within the lineage demands that multiple shifts between genotypes must have occurred within the past 20 years with the most rapid shift taking place in no more than 4 years and indicates that mitochondrial DNA polymorphism can occur between maternally related mammals. The process that gave rise to different genotypes in one lineage is clearly of fundamental importance in understanding intraspecific mitochondrial polymorphism and evolution in mammals. Several potential mechanisms for rapid mitochondrial DNA variation are discussed in light of these results. Images PMID:6289312

  8. Inferring Gene Family Histories in Yeast Identifies Lineage Specific Expansions

    PubMed Central

    Ames, Ryan M.; Money, Daniel; Lovell, Simon C.

    2014-01-01

    The complement of genes found in the genome is a balance between gene gain and gene loss. Knowledge of the specific genes that are gained and lost over evolutionary time allows an understanding of the evolution of biological functions. Here we use new evolutionary models to infer gene family histories across complete yeast genomes; these models allow us to estimate the relative genome-wide rates of gene birth, death, innovation and extinction (loss of an entire family) for the first time. We show that the rates of gene family evolution vary both between gene families and between species. We are also able to identify those families that have experienced rapid lineage specific expansion/contraction and show that these families are enriched for specific functions. Moreover, we find that families with specific functions are repeatedly expanded in multiple species, suggesting the presence of common adaptations and that these family expansions/contractions are not random. Additionally, we identify potential specialisations, unique to specific species, in the functions of lineage specific expanded families. These results suggest that an important mechanism in the evolution of genome content is the presence of lineage-specific gene family changes. PMID:24921666

  9. Collodictyon—An Ancient Lineage in the Tree of Eukaryotes

    PubMed Central

    Zhao, Sen; Burki, Fabien; Bråte, Jon; Keeling, Patrick J.; Klaveness, Dag; Shalchian-Tabrizi, Kamran

    2012-01-01

    The current consensus for the eukaryote tree of life consists of several large assemblages (supergroups) that are hypothesized to describe the existing diversity. Phylogenomic analyses have shed light on the evolutionary relationships within and between supergroups as well as placed newly sequenced enigmatic species close to known lineages. Yet, a few eukaryote species remain of unknown origin and could represent key evolutionary forms for inferring ancient genomic and cellular characteristics of eukaryotes. Here, we investigate the evolutionary origin of the poorly studied protist Collodictyon (subphylum Diphyllatia) by sequencing a cDNA library as well as the 18S and 28S ribosomal DNA (rDNA) genes. Phylogenomic trees inferred from 124 genes placed Collodictyon close to the bifurcation of the “unikont” and “bikont” groups, either alone or as sister to the potentially contentious excavate Malawimonas. Phylogenies based on rDNA genes confirmed that Collodictyon is closely related to another genus, Diphylleia, and revealed a very low diversity in environmental DNA samples. The early and distinct origin of Collodictyon suggests that it constitutes a new lineage in the global eukaryote phylogeny. Collodictyon shares cellular characteristics with Excavata and Amoebozoa, such as ventral feeding groove supported by microtubular structures and the ability to form thin and broad pseudopods. These may therefore be ancient morphological features among eukaryotes. Overall, this shows that Collodictyon is a key lineage to understand early eukaryote evolution. PMID:22319147

  10. Collodictyon--an ancient lineage in the tree of eukaryotes.

    PubMed

    Zhao, Sen; Burki, Fabien; Bråte, Jon; Keeling, Patrick J; Klaveness, Dag; Shalchian-Tabrizi, Kamran

    2012-06-01

    The current consensus for the eukaryote tree of life consists of several large assemblages (supergroups) that are hypothesized to describe the existing diversity. Phylogenomic analyses have shed light on the evolutionary relationships within and between supergroups as well as placed newly sequenced enigmatic species close to known lineages. Yet, a few eukaryote species remain of unknown origin and could represent key evolutionary forms for inferring ancient genomic and cellular characteristics of eukaryotes. Here, we investigate the evolutionary origin of the poorly studied protist Collodictyon (subphylum Diphyllatia) by sequencing a cDNA library as well as the 18S and 28S ribosomal DNA (rDNA) genes. Phylogenomic trees inferred from 124 genes placed Collodictyon close to the bifurcation of the "unikont" and "bikont" groups, either alone or as sister to the potentially contentious excavate Malawimonas. Phylogenies based on rDNA genes confirmed that Collodictyon is closely related to another genus, Diphylleia, and revealed a very low diversity in environmental DNA samples. The early and distinct origin of Collodictyon suggests that it constitutes a new lineage in the global eukaryote phylogeny. Collodictyon shares cellular characteristics with Excavata and Amoebozoa, such as ventral feeding groove supported by microtubular structures and the ability to form thin and broad pseudopods. These may therefore be ancient morphological features among eukaryotes. Overall, this shows that Collodictyon is a key lineage to understand early eukaryote evolution.

  11. Physiological ecology and functional traits of North American native and Eurasian introduced Phragmites australis lineages

    PubMed Central

    Mozdzer, Thomas J.; Brisson, Jacques; Hazelton, Eric L. G.

    2013-01-01

    Physiological ecology and plant functional traits are often used to explain plant invasion. To gain a better understanding of how traits influence invasion, studies usually compare the invasive plant to a native congener, but there are few conspecific examples in the literature. In North America, the presence of native and introduced genetic lineages of the common reed, Phragmites australis, presents a unique example to evaluate how traits influence plant invasion. We reviewed the literature on functional traits of P. australis lineages in North America, specifically contrasting lineages present on the Atlantic Coast. We focused on differences in physiology between the lineage introduced from Eurasia and the lineage native to North America, specifically seeking to identify the causes underlying the recent expansion of the introduced lineage. Our goals were to better understand which traits may confer invasiveness, provide predictions of how these lineages may respond to interspecific competition or imminent global change, and provide guidance for future research. We reviewed published studies and articles in press, and conducted personal communications with appropriate researchers and managers to develop a comparative dataset. We compared the native and introduced lineages and focused on plant physiological ecology and functional traits. Under both stressful and favourable conditions, our review showed that introduced P. australis consistently exhibited greater ramet density, height and biomass, higher and more plastic relative growth rate, nitrogen productivity and specific leaf area, higher mass specific nitrogen uptake rates, as well as greater phenotypic plasticity compared with the native lineage. We suggest that ecophysiological and other plant functional traits elucidate potential mechanisms for the introduced lineage's invasiveness under current and predicted global change conditions. However, our review identified a disconnect between field surveys

  12. Quantifying Selective Pressures Driving Bacterial Evolution Using Lineage Analysis

    NASA Astrophysics Data System (ADS)

    Lambert, Guillaume; Kussell, Edo

    2015-01-01

    Organisms use a variety of strategies to adapt to their environments and maximize long-term growth potential, but quantitative characterization of the benefits conferred by the use of such strategies, as well as their impact on the whole population's rate of growth, remains challenging. Here, we use a path-integral framework that describes how selection acts on lineages—i.e., the life histories of individuals and their ancestors—to demonstrate that lineage-based measurements can be used to quantify the selective pressures acting on a population. We apply this analysis to Escherichia coli bacteria exposed to cyclical treatments of carbenicillin, an antibiotic that interferes with cell-wall synthesis and affects cells in an age-dependent manner. While the extensive characterization of the life history of thousands of cells is necessary to accurately extract the age-dependent selective pressures caused by carbenicillin, the same measurement can be recapitulated using lineage-based statistics of a single surviving cell. Population-wide evolutionary pressures can be extracted from the properties of the surviving lineages within a population, providing an alternative and efficient procedure to quantify the evolutionary forces acting on a population. Importantly, this approach is not limited to age-dependent selection, and the framework can be generalized to detect signatures of other trait-specific selection using lineage-based measurements. Our results establish a powerful way to study the evolutionary dynamics of life under selection and may be broadly useful in elucidating selective pressures driving the emergence of antibiotic resistance and the evolution of survival strategies in biological systems.

  13. Lineage-tracing methods and the kidney

    PubMed Central

    Humphreys, Benjamin D; DiRocco, Derek P

    2014-01-01

    The kidney is a complex organ with over 30 different cell types, and understanding the lineage relationships between these cells is challenging. During nephrogenesis, a central question is how the coordinated morphogenesis, growth, and differentiation of distinct cell types leads to development of a functional organ. In mature kidney, understanding cell division and fate during injury, regeneration and aging are critical topics for understanding disease. Genetic lineage tracing offers a powerful tool to decipher cellular hierarchies in both development and disease because it allows the progeny of a single cell, or group of cells, to be tracked unambiguously. Recent advances in this field include the use of inducible recombinases, multicolor reporters, and mosaic analysis. In this review, we discuss lineage-tracing methods focusing on the mouse model system and consider the impact of these methods on our understanding of kidney biology and prospects for future application. PMID:24088959

  14. Potential involvement of miR-375 in the premalignant progression of oral squamous cell carcinoma mediated via transcription factor KLF5.

    PubMed

    Shi, Wen; Yang, Jing; Li, Siyuan; Shan, Xiaofeng; Liu, Xiaosong; Hua, Hong; Zhao, Chuanke; Feng, Zhendong; Cai, Zhigang; Zhang, Lihe; Zhou, Demin

    2015-11-24

    To elucidate the genetic effect involved in the premalignant progression of chronic inflammation to cancer, we performed microRNA and mRNA profiling in oral lichen planus (OLP), oral squamous cell carcinoma (OSCC), and normal tissue from the same patients. We demonstrate the involvement of a suppressive microRNA, miR-375, in the regulation of this premalignant progression via KLF5, a transcription factor that modulates the expression of genes contributing to proliferation and apoptosis. We found that miR-375 abundance decreased in tissues with progression from the normal state to OLP and subsequently to OSCC. Restoration of miR-375 by transduction of a synthetic mimic into OSCC cells repressed cellular proliferation and promoted apoptosis, with concomitant down-regulation of KLF5, and vice versa. The direct binding of miR-375 to the 3'-untranslated region of KLF5 was further confirmed. Additionally, Survivin (BIRC5), a target of KLF5, was also regulated by miR-375, explaining the susceptibility of miR-375-mimic transfected cells to apoptosis. Further analysis of clinical specimens suggested that expression of KLF5 and BIRC5 is up-regulated during the progression from inflammation to cancer. Our findings provide novel insights into the involvement of microRNAs in progression of inflammation to carcinoma and suggest a potential early-stage biomarker or therapy target for oral carcinoma.

  15. The effect of dimethyl fumarate (Tecfidera™) on lymphocyte counts: A potential contributor to progressive multifocal leukoencephalopathy risk.

    PubMed

    Khatri, Bhupendra O; Garland, Jeffery; Berger, Joseph; Kramer, John; Sershon, Lisa; Olapo, Tayo; Sesing, Jean; Dukic, Mary; Rehn, Eileen

    2015-07-01

    Dimethyl fumarate (Tecfidera™) is an effective therapy for relapsing forms of multiple sclerosis (MS). Our study suggests that this drug may have immunosuppressive properties evidenced by significant sustained reduction in CD8 lymphocyte counts and, to a lesser extent, CD4 lymphocyte counts. This observation is relevant in light of the recent case of progressive multifocal leukoencephalopathy in a patient receiving this drug.

  16. Position Paper on the Potential Use of Computerized Testing Procedures for the National Assessment of Educational Progress.

    ERIC Educational Resources Information Center

    Reckase, Mark D.

    The current technology of computerized testing is discussed, and a few comments are made on how such technology might be used for assessing school-related skills as part of the National Assessment of Educational progress (NAEP). The critical feature of computerized assessment procedures is that the test items are presented in interactive fashion,…

  17. αvβ6 Expression in myoepithelial cells: a novel marker for predicting DCIS progression with therapeutic potential.

    PubMed

    Allen, Michael D; Marshall, John F; Jones, J Louise

    2014-11-01

    The tumor microenvironment dynamically regulates the progression of cancer. In the breast, a unique component of the microenvironment is the myoepithelial cell. Normal myoepithelial cells act as "natural tumor suppressors"; however, more recent evidence suggests that these cells develop phenotypic changes, which may contribute to loss of tumor suppressor activity. We have shown that myoepithelial cells in a subset of preinvasive ductal carcinoma in situ (DCIS) upregulate expression of the integrin αvβ6, switching on tumor promoter activity through activation of TGFβ and MMP9. This makes the tumor microenvironment more permissive to invasion, seen both in vitro and in vivo. In human tissue samples, increased myoepithelial αvβ6 expression correlated with increased risk of disease progression and recurrence. Current estimates suggest that as many as 50% of DCIS cases will never progress in the patient's lifetime, but there are no markers to predict the outcome of individual cases. The identification of αvβ6 in a subset of DCIS presents a unique way to stratify patients with DCIS into those who may or may not progress to more serious disease. As αvβ6 is not expressed on most normal adult tissues, this finding may also provide novel targets for therapy in this high-risk group. ©2014 American Association for Cancer Research.

  18. Phylogenetic and molecular analyses of human parainfluenza type 3 virus in Buenos Aires, Argentina, between 2009 and 2013: The emergence of new genetic lineages.

    PubMed

    Goya, Stephanie; Mistchenko, Alicia Susana; Viegas, Mariana

    2016-04-01

    Despite that human parainfluenza type 3 viruses (HPIV3) are one of the leading causes of acute lower respiratory tract infections in children under five, there is no licensed vaccine and there is limited current information on the molecular characteristics of regional and global circulating strains. The aim of this study was to describe the molecular characterization of HPIV3 circulating in Buenos Aires. We performed a genetic and phylogenetic analysis of the HN glycoprotein gene. Between 2009 and 2013, 124 HPIV3-positive samples taken from hospitalized pediatric patients were analyzed. Four new genetic lineages were described. Among them, C1c and C3d lineages showed local circulation patterns, whereas C3e and C3f comprised sequences from very distant countries. Despite the diversity of the described genotypes, C3a and C3d predominated over the others, the latter was present during the first years of the study and it was progressively replaced by C3a. Molecular analyses showed 28 non-synonymous substitutions; of these, 13 were located in potentially predicted B-cell epitopes. Taken together, the emergence of genetic lineages and the information of the molecular characteristics of HN protein may contribute to the general knowledge of HPIV3 molecular epidemiology for future vaccine development and antiviral therapies.

  19. The Role of Primary Cilia in Mesenchymal Stem Cell Differentiation: A Pivotal Switch in Guiding Lineage Commitment

    PubMed Central

    Tummala, Padmaja; Arnsdorf, Emily J.; Jacobs, Christopher R.

    2010-01-01

    Primary cilia are sensory organelles that have been shown to play a critical role in lineage commitment. It was our hypothesis that the primary cilium is necessary for chemically induced differentiation of human mesenchymal stem cells (MSC). To investigate this, polaris siRNA was used to inhibit the primary cilia and the mRNA levels of transcription factors Runx2, PPARγ were measured by RT PCR as markers of osteogenic, adipogenic and chondrogenic differentiation, respectively. MSCs with inhibited primary cilia had significantly decreased basal mRNA expression levels of all three lineages specific transcription factors indicating that primary cilia are critical in multiple differentiation pathways. Furthermore, to determine if primary cilia play a role in the differentiation potential of MSCs, progenitor cells transfected with either scrambled or polaris siRNA were cultured in osteo-inductive, chondro-inductive, or adipo-inductive media and lineage commitment was ascertained. Interestingly, within 24 h of culture, cells transfected with polaris siRNA in both osteogenic and adipogenic media lost adhesion and released from the slides; however MSCs in chondrogenic media as well as cells transfected with scrambled siRNA did not. These results suggest that the primary cilium is necessary for the normal progression of chemically induced osteogenic and adipogenic differentiation. As a control, the experiment was repeated with NIH3T3 fibroblasts and none of the effects of inhibited primary cilia were observed indicating that the loss of adhesion may be specific to MSCs. Furthermore after biochemically inducing the cells to differentiate, polaris knockdown resulted in abrogation of both Runx2 and PPARγ mRNA while SOX9 mRNA expression was significantly lower. These results suggest that primary cilia play an essential role not only in the initiation of both osteogenic and adipogenic differentiation, but also in maintaining the phenotype of differentiated cells. Interestingly

  20. Postembryonic lineages of the Drosophila brain: II. Identification of lineage projection patterns based on MARCM clones

    PubMed Central

    Wong, Darren C.; Lovick, Jennifer K.; Ngo, Kathy T.; Borisuthirattana, Wichanee; Omoto, Jaison J.; Hartenstein, Volker

    2014-01-01

    The Drosophila central brain is largely composed of lineages, units of sibling neurons derived from a single progenitor cell or neuroblast. During the early embryonic period neuroblast generate the primary neurons that constitute the larval brain. Neuroblasts reactivate in the larva, adding to their lineages a large number of secondary neurons which, according to previous studies in which selected lineages were labeled by stably expressed markers, differentiate during metamorphosis, sending terminal axonal and dendritic branches into defined volumes of the brain neuropil. We call the overall projection pattern of neurons forming a given lineage the “projection envelope” of that lineage. By inducing MARCM clones at the early larval stage, we labeled the secondary progeny of each neuroblast. For the supraesophageal ganglion excluding mushroom body (the part of the brain investigated in the present work) we obtained 81 different types of clones, Based on the trajectory of their secondary axon tracts (described in the accompanying paper), we assigned these clones to specific lineages defined in the larva. Since a labeled clone reveals all aspects (cell bodies, axon tracts, terminal arborization) of a lineage, we were able to describe projection envelopes for all secondary lineages of the supraesophageal ganglion. This work provides a framework by which the secondary neurons (forming the vast majority of adult brain neurons) can be assigned to genetically and developmentally defined groups. It also represents a step towards the goal to establish, for each lineage, the link between its mature anatomical and functional phenotype, and the genetic make-up of the neuroblast it descends from. PMID:23872236

  1. Lkb1 maintains Treg cell lineage identity

    PubMed Central

    Wu, Di; Luo, Yuechen; Guo, Wei; Niu, Qing; Xue, Ting; Yang, Fei; Sun, Xiaolei; Chen, Song; Liu, Yuanyuan; Liu, Jingru; Sun, Zhina; Zhao, Chunxiao; Huang, Huifang; Liao, Fang; Han, Zhongchao; Zhou, Dongming; Yang, Yongguang; Xu, Guogang; Cheng, Tao; Feng, Xiaoming

    2017-01-01

    Regulatory T (Treg) cells are a distinct T-cell lineage characterized by sustained Foxp3 expression and potent suppressor function, but the upstream dominant factors that preserve Treg lineage-specific features are mostly unknown. Here, we show that Lkb1 maintains Treg cell lineage identity by stabilizing Foxp3 expression and enforcing suppressor function. Upon T-cell receptor (TCR) stimulation Lkb1 protein expression is upregulated in Treg cells but not in conventional T cells. Mice with Treg cell-specific deletion of Lkb1 develop a fatal early-onset autoimmune disease, with no Foxp3 expression in most Treg cells. Lkb1 stabilizes Foxp3 expression by preventing STAT4-mediated methylation of the conserved noncoding sequence 2 (CNS2) in the Foxp3 locus. Independent of maintaining Foxp3 expression, Lkb1 programs the expression of a wide spectrum of immunosuppressive genes, through mechanisms involving the augmentation of TGF-β signalling. These findings identify a critical function of Lkb1 in maintaining Treg cell lineage identity. PMID:28621313

  2. Lineage Analysis in Pulmonary Arterial Hypertension

    DTIC Science & Technology

    2013-06-01

    SMA with some globular domains, predominantly colocalizing with GFP endothelial lineage-marked cells in the neointima (Figure 4F). Figure 4. VE...whether the neointima arises from a small population of apoptosis- resistant pulmonary artery endothelial cells that proliferate after injury to produce

  3. Two routes to senescence revealed by real-time analysis of telomerase-negative single lineages

    PubMed Central

    Xu, Zhou; Fallet, Emilie; Paoletti, Camille; Fehrmann, Steffen; Charvin, Gilles; Teixeira, Maria Teresa

    2015-01-01

    In eukaryotes, telomeres cap chromosome ends to maintain genomic stability. Failure to maintain telomeres leads to their progressive erosion and eventually triggers replicative senescence, a pathway that protects against unrestricted cell proliferation. However, the mechanisms underlying the variability and dynamics of this pathway are still elusive. Here we use a microfluidics-based live-cell imaging assay to investigate replicative senescence in individual Saccharomyces cerevisiae cell lineages following telomerase inactivation. We characterize two mechanistically distinct routes to senescence. Most lineages undergo an abrupt and irreversible switch from a replicative to an arrested state, consistent with telomeres reaching a critically short length. In contrast, other lineages experience frequent and stochastic reversible arrests, consistent with the repair of accidental telomere damage by Pol32, a subunit of polymerase δ required for break-induced replication and for post-senescence survival. Thus, at the single-cell level, replicative senescence comprises both deterministic cell fates and chaotic cell division dynamics. PMID:26158780

  4. Heterogeneous lineage marker expression in naive embryonic stem cells is mostly due to spontaneous differentiation

    PubMed Central

    Nair, Gautham; Abranches, Elsa; Guedes, Ana M. V.; Henrique, Domingos; Raj, Arjun

    2015-01-01

    Populations of cultured mouse embryonic stem cells (ESCs) exhibit a subfraction of cells expressing uncharacteristically low levels of pluripotency markers such as Nanog. Yet, the extent to which individual Nanog-negative cells are differentiated, both from ESCs and from each other, remains unclear. Here, we show the transcriptome of Nanog-negative cells exhibits expression of classes of genes associated with differentiation that are not yet active in cells exposed to differentiation conditions for one day. Long non-coding RNAs, however, exhibit more changes in expression in the one-day-differentiated cells than in Nanog-negative cells. These results are consistent with the concept that Nanog-negative cells may contain subpopulations of both lineage-primed and differentiated cells. Single cell analysis showed that Nanog-negative cells display substantial and coherent heterogeneity in lineage marker expression in progressively nested subsets of cells exhibiting low levels of Nanog, then low levels of Oct4, and then a set of lineage markers, which express intensely in a small subset of these more differentiated cells. Our results suggest that the observed enrichment of lineage-specific marker gene expression in Nanog-negative cells is associated with spontaneous differentiation of a subset of these cells rather than the more random expression that may be associated with reversible lineage priming. PMID:26292941

  5. A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages.

    PubMed

    Kimmerling, Robert J; Lee Szeto, Gregory; Li, Jennifer W; Genshaft, Alex S; Kazer, Samuel W; Payer, Kristofor R; de Riba Borrajo, Jacob; Blainey, Paul C; Irvine, Darrell J; Shalek, Alex K; Manalis, Scott R

    2016-01-06

    We introduce a microfluidic platform that enables off-chip single-cell RNA-seq after multi-generational lineage tracking under controlled culture conditions. We use this platform to generate whole-transcriptome profiles of primary, activated murine CD8+ T-cell and lymphocytic leukemia cell line lineages. Here we report that both cell types have greater intra- than inter-lineage transcriptional similarity. For CD8+ T-cells, genes with functional annotation relating to lymphocyte differentiation and function--including Granzyme B--are enriched among the genes that demonstrate greater intra-lineage expression level similarity. Analysis of gene expression covariance with matched measurements of time since division reveals cell type-specific transcriptional signatures that correspond with cell cycle progression. We believe that the ability to directly measure the effects of lineage and cell cycle-dependent transcriptional profiles of single cells will be broadly useful to fields where heterogeneous populations of cells display distinct clonal trajectories, including immunology, cancer, and developmental biology.

  6. Long-Term Live Cell Imaging and Automated 4D Analysis of Drosophila Neuroblast Lineages

    PubMed Central

    Berger, Christian; Lendl, Thomas; Knoblich, Juergen A.

    2013-01-01

    The developing Drosophila brain is a well-studied model system for neurogenesis and stem cell biology. In the Drosophila central brain, around 200 neural stem cells called neuroblasts undergo repeated rounds of asymmetric cell division. These divisions typically generate a larger self-renewing neuroblast and a smaller ganglion mother cell that undergoes one terminal division to create two differentiating neurons. Although single mitotic divisions of neuroblasts can easily be imaged in real time, the lack of long term imaging procedures has limited the use of neuroblast live imaging for lineage analysis. Here we describe a method that allows live imaging of cultured Drosophila neuroblasts over multiple cell cycles for up to 24 hours. We describe a 4D image analysis protocol that can be used to extract cell cycle times and growth rates from the resulting movies in an automated manner. We use it to perform lineage analysis in type II neuroblasts where clonal analysis has indicated the presence of a transit-amplifying population that potentiates the number of neurons. Indeed, our experiments verify type II lineages and provide quantitative parameters for all cell types in those lineages. As defects in type II neuroblast lineages can result in brain tumor formation, our lineage analysis method will allow more detailed and quantitative analysis of tumorigenesis and asymmetric cell division in the Drosophila brain. PMID:24260257

  7. Contribution of the oligodendrocyte lineage to CNS repair and neurodegenerative pathologies.

    PubMed

    Tognatta, Reshmi; Miller, Robert H

    2016-11-01

    The concept of the oligodendrocyte lineage as simply a source of myelinating cells in the vertebrate CNS is undergoing radical revision. Elucidation of the origins of oligodendrocytes in the CNS has led to identification of important signaling pathways, the timing and mechanism of lineage commitments and overlapping as well as redundant functionality among oligodendrocytes. The realization that a significant proportion of the oligodendrocyte lineage cells remain in a proliferative and immature state suggests they have roles other than as a reservoir of myelinating cells. While early studies were focused on understanding the development of oligodendrocytes, more recent work has begun to define the role of oligodendrocyte lineage cells in CNS functionality and the identification of new avenues for neural repair. A relatively unexplored aspect of the oligodendrocyte lineage is their contribution either directly or indirectly to the pathology of neurodegenerative diseases such as ALS and Alzheimer's disease. Here we briefly consider the potential role of oligodendrocyte lineage cells as mediators of neural repair and neurodegeneration in the vertebrate CNS. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. SWI/SNF-Mediated Lineage Determination in Mesenchymal Stem Cells Confers Resistance to Osteoporosis.

    PubMed

    Nguyen, Kevin Hong; Xu, Fuhua; Flowers, Stephen; Williams, Edek A J; Fritton, J Christopher; Moran, Elizabeth

    2015-10-01

    Redirecting the adipogenic potential of bone marrow-derived mesenchymal stem cells to other lineages, particularly osteoblasts, is a key goal in regenerative medicine. Controlling lineage selection through chromatin remodeling complexes such as SWI/SNF, which act coordinately to establish new patterns of gene expression, would be a desirable intervention point, but the requirement for the complex in essentially every lineage pathway has generally precluded selectivity. However, a novel approach now appears possible by targeting the subset of SWI/SNF powered by the alternative ATPase, mammalian brahma (BRM). BRM is not required for development, which has hindered understanding of its contributions, but knockdown genetics here, designed to explore the hypothesis that BRM-SWI/SNF has different regulatory roles in different mesenchymal stem cell lineages, shows that depleting BRM from mesenchymal stem cells has a dramatic effect on the balance of lineage selection between osteoblasts and adipocytes. BRM depletion enhances the proportion of cells expressing markers of osteoblast precursors at the expense of cells able to differentiate along the adipocyte lineage. This effect is evident in primary bone marrow stromal cells as well as in established cell culture models. The altered precursor balance has major physiological significance, which becomes apparent as protection against age-related osteoporosis and as reduced bone marrow adiposity in adult BRM-null mice. © 2015 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  9. Genetic divergence in elite castor bean lineages based on TRAP markers.

    PubMed

    Simões, K S; Silva, S A; Machado, E L; Silva, M S

    2017-09-27

    Castor bean (Ricinus communis L.) is a tropical plant of great commercial interest and a potential source of biodiesel. The development of genetically improved cultivars with high amounts of oil in the seeds and low ricin toxicity is crucial to increase the productivity of this crop. The use of TRAP (target region amplification polymorphism) markers to develop elite lineages and study genetic divergence is fundamental to advance the genetic improvement of this species. The goal of this study was to evaluate the genetic divergence among 40 elite lineages of R. communis, which belong to the NBIO-UFRB Genetic Improvement Program, using TRAP markers involved in the biosynthesis of oil and ricin. Total DNA was extracted and quantified from the leaf tissue of the castor bean plants, and 70 TRAP combinations (fixed and arbitrary primers) were used to genotype the 40 lineages. Of the 580 fragments amplified, 335 were polymorphic (58%). The genetic dissimilarity among the lineages was calculated by the Jaccard dissimilarity index using the UPGMA grouping method. A dendrogram was generated, and four groups formed, showing divergence among the elite lineages that favors selection. The TRAP molecular markers were efficient at characterizing the genetic variability among the lineages and, because TRAP markers are functional markers involved in the biosynthesis of oil and ricin, they are important when studying the association between a marker and a candidate gene.

  10. Comparison of Cytotoxic Activity in Leukemic Lineages Reveals Important Features of β-Hairpin Antimicrobial Peptides.

    PubMed

    Buri, Marcus V; Torquato, Heron F Vieira; Barros, Carlos Castilho; Ide, Jaime S; Miranda, Antonio; Paredes-Gamero, Edgar J

    2017-07-01

    Several reports described different modes of cell death triggered by antimicrobial peptides (AMPs) due to direct effects on membrane disruption, and more recently by apoptosis and necrosis-like patterns. Cytotoxic curves of four β-hairpin AMPs (gomesin, protegrin, tachyplesin, and polyphemusin) were obtained from several human leukemic lineages and normal monocytes and Two cell lines were then selected based on their cytotoxic sensitivity. One was sensitive to AMPs (K562) and the other resistant (KG-1) and their effect compared between these lineages. Thus, these lineages were chosen to further investigate biological features related with their cytotoxicities to AMPs. Stimulation with AMPs produced cell death, with activation of caspase-3, in K562 lineage. Increase on the fluidity of plasmatic membrane by reducing cholesterol potentiated cytotoxicity of AMPs in both lineages. Quantification of internal and external gomesin binding to the cellular membrane of both K562 and KG-1 cells showed that more peptide is accumulated inside of K562 cells. Additionally, evaluation of multi-drug resistant pumps activity showed that KG-1 has more activity than K562 lineage. A comparison of intrinsic gene patterns showed great differences between K562 and KG-1, but stimulation with gomesin promoted few changes in gene expression patterns. Differences in internalization process through the plasma membrane, multidrug resistance pumps activity, and gene expression pattern are important features to AMPs regulated cell death. J. Cell. Biochem. 118: 1764-1773, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. A novel molecular test for influenza B virus detection and lineage differentiation

    PubMed Central

    Wong, Chloe KS; Tsang, Gary CH; Chan, Kwok-Hung; Li, Olive TW; Peiris, Malik; Poon, Leo LM

    2014-01-01

    Contemporary influenza B viruses are classified into two groups known as Yamagata and Victoria lineages. The co-circulation of two viral lineages in recent years urges for a robust and simple diagnostic test for detecting influenza B viruses and for lineage differentiation. In this study, a SYBR green-based asymmetric PCR assay has been developed for influenza B virus detection. Apart from identifying influenza B virus, the assay contains sequence-specific probes for lineage differentiation. This allows identifying influenza B virus and detecting influenza B viral lineage in a single reaction. The test has been evaluated by a panel of respiratory specimens. Of 108 Influenza B virus-positive specimens, 105 (97%) were positive in this assay. None of the negative control respiratory specimens were positive in the test (N=60). Viral lineages of all samples that are positive in the assay (N=105) can also be classified correctly. These results suggest that this assay has a potential for routine influenza B virus surveillance. PMID:24760697

  12. Temporal changes in mosquito abundance (Culex pipiens), avian malaria prevalence and lineage composition

    PubMed Central

    2013-01-01

    Background Knowledge on the temporal dynamics of host/vector/parasite interactions is a pre-requisite to further address relevant questions in the fields of epidemiology and evolutionary ecology of infectious diseases. In studies of avian malaria, the natural history of Plasmodium parasites with their natural mosquito vectors, however, is mostly unknown. Methods Using artificial water containers placed in the field, we monitored the relative abundance of parous females of Culex pipiens mosquitoes during two years (2010–2011), in a population in western Switzerland. Additionally, we used molecular tools to examine changes in avian malaria prevalence and Plasmodium lineage composition in female C. pipiens caught throughout one field season (April-August) in 2011. Results C. pipiens relative abundance varied both between years and months, and was associated with temperature fluctuations. Total Plasmodium prevalence was high and increased from spring to summer months (13.1-20.3%). The Plasmodium community was composed of seven different lineages including P. relictum (SGS1, GRW11 and PADOM02 lineages), P. vaughani (lineage SYAT05) and other Plasmodium spp. (AFTRU5, PADOM1, COLL1). The most prevalent lineages, P. vaughani (lineage SYAT05) and P. relictum (lineage SGS1), were consistently found between years, although they had antagonistic dominance patterns during the season survey. Conclusions Our results suggest that the time window of analysis is critical in evaluating changes in the community of avian malaria lineages infecting mosquitoes. The potential determinants of the observed changes as well as their implications for future prospects on avian malaria are discussed. PMID:24499594

  13. Testing for intraspecific postzygotic isolation between cryptic lineages of Pseudacris crucifer

    PubMed Central

    Stewart, Kathryn A; Lougheed, Stephen C

    2013-01-01

    Phenotypically cryptic lineages appear common in nature, yet little is known about the mechanisms that initiate and/or maintain barriers to gene flow, or how secondary contact between them might influence evolutionary trajectories. The consequences of such contact between diverging lineages depend on hybrid fitness, highlighting the potential for postzygotic isolating barriers to play a role in the origins of biological species. Previous research shows that two cryptic, deeply diverged intraspecific mitochondrial lineages of a North American chorus frog, the spring peeper (Pseudacris crucifer), meet in secondary contact in Southwestern Ontario, Canada. Our study quantified hatching success, tadpole survival, size at metamorphosis, and development time for experimentally generated pure lineage and hybrid tadpoles. Results suggest that lineages differ in tadpole survival and that F1 hybrids may have equal fitness and higher than average mass at metamorphosis compared with pure parental crosses. These findings imply hybrid early life viability may not be the pivotal reproductive isolation barrier helping to maintain lineage boundaries. However, we observed instances of tadpole gigantism, failure to metamorphose, and bent tails in some tadpoles from hybrid families. We also speculate and provide some evidence that apparent advantages or similarities of hybrids compared with pure lineage tadpoles may disappear when tadpoles are raised with competitors of different genetic makeup. This pilot study implies that ecological context and consideration of extrinsic factors may be a key to revealing mechanisms causing negative hybrid fitness during early life stages, a provocative avenue for future investigations on barriers to gene flow among these intraspecific lineages. PMID:24363891

  14. Local adaptation and divergence in colour signal conspicuousness between monomorphic and polymorphic lineages in a lizard.

    PubMed

    McLean, C A; Moussalli, A; Stuart-Fox, D

    2014-12-01

    Population differences in visual environment can lead to divergence in multiple components of animal coloration including signalling traits and colour patterns important for camouflage. Divergence may reflect selection imposed by different receivers (conspecifics, predators), which depends in turn on the location of the colour patch. We tested for local adaptation of two genetically and phenotypically divergent lineages of a rock-inhabiting lizard, Ctenophorus decresii, by comparing the visual contrast of colour patches to different receivers in native and non-native environments. The lineages differ most notably in male throat coloration, which is polymorphic in the northern lineage and monomorphic in the southern lineage, but also differ in dorsal and lateral coloration, which is visible to both conspecifics and potential predators. Using models of animal colour vision, we assessed whether lineage-specific throat, dorsal and lateral coloration enhanced conspicuousness to conspecifics, increased crypsis to birds or both, respectively, when viewed against the predominant backgrounds from each lineage. Throat colours were no more conspicuous against native than non-native rock but contrasted more strongly with native lichen, which occurs patchily on rocks inhabited by C. decresii. Conversely, neck coloration (lateral) more closely matched native lichen. Furthermore, although dorsal coloration of southern males was consistently more conspicuous to birds than that of northern males, both lineages had similar absolute conspicuousness against their native backgrounds. Combined, our results are consistent with local adaptation of multiple colour traits in relation to multiple receivers, suggesting that geographic variation in background colour has influenced the evolution of lineage-specific coloration in C. decresii.

  15. Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice

    PubMed Central

    Adam, Rene C.; Yang, Hanseul; Rockowitz, Shira; Larsen, Samantha B.; Nikolova, Maria; Oristian, Daniel S.; Polak, Lisa; Kadaja, Meelis; Asare, Amma; Zheng, Deyou; Fuchs, Elaine

    2015-01-01

    Adult stem cells (SCs) reside in niches which balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, SCs outside their niche often display fate flexibility1-4. Here we show that super-enhancers5 underlie the identity, lineage commitment and plasticity of adult SCs in vivo. Using hair follicle (HF) as model, we map the global chromatin domains of HFSCs and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters (‘epicenters’) of transcription factor (TF) binding sites change upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicenters, an auto-regulatory process that abates one master regulator subset while enhancing another. We further show that when outside their niche, either in vitro or in wound-repair, HFSCs dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicenters, enabling them to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of HFSC super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense TF-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status, but also stemness, plasticity in transitional states and differentiation. PMID:25799994

  16. CRX Is a Diagnostic Marker of Retinal and Pineal Lineage Tumors

    PubMed Central

    Santagata, Sandro; Maire, Cecile L.; Idbaih, Ahmed; Geffers, Lars; Correll, Mick; Holton, Kristina; Quackenbush, John; Ligon, Keith L.

    2009-01-01

    Background CRX is a homeobox transcription factor whose expression and function is critical to maintain retinal and pineal lineage cells and their progenitors. To determine the biologic and diagnostic potential of CRX in human tumors of the retina and pineal, we examined its expression in multiple settings. Methodology/Principal Findings Using situ hybridization and immunohistochemistry we show that Crx RNA and protein expression are exquisitely lineage restricted to retinal and pineal cells during normal mouse and human development. Gene expression profiling analysis of a wide range of human cancers and cancer cell lines also supports that CRX RNA is highly lineage restricted in cancer. Immunohistochemical analysis of 22 retinoblastomas and 13 pineal parenchymal tumors demonstrated strong expression of CRX in over 95% of these tumors. Importantly, CRX was not detected in the majority of tumors considered in the differential diagnosis of pineal region tumors (n = 78). The notable exception was medulloblastoma, 40% of which exhibited CRX expression in a heterogeneous pattern readily distinguished from that seen in retino-pineal tumors. Conclusions/Significance These findings describe new potential roles for CRX in human cancers and highlight the general utility of lineage restricted transcription factors in cancer biology. They also identify CRX as a sensitive and specific clinical marker and a potential lineage dependent therapeutic target in retinoblastoma and pineoblastoma. PMID:19936203

  17. Soluble Serum αKlotho Is a Potential Predictive Marker of Disease Progression in Clear Cell Renal Cell Carcinoma

    PubMed Central

    Gigante, Margherita; Lucarelli, Giuseppe; Divella, Chiara; Netti, Giuseppe Stefano; Pontrelli, Paola; Cafiero, Cesira; Grandaliano, Giuseppe; Castellano, Giuseppe; Rutigliano, Monica; Stallone, Giovanni; Bettocchi, Carlo; Ditonno, Pasquale; Gesualdo, Loreto; Battaglia, Michele; Ranieri, Elena

    2015-01-01

    Abstract Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies, and clear cell RCC (ccRCC), that has a high metastatic index and high relapse rate, is the most common histological subtype. The identification of new biomarkers in ccRCC is fundamental for stratifying patients into prognostic risk groups and to guide therapy. The renoprotective antiaging gene, αKlotho, has recently been found to work as a tumor suppressor in different human cancers. Here, we evaluated αKlotho expression in tissue and serum of ccRCC patients and correlated it with disease progression. Tissue αKlotho expression was studied by quantitative RT-PCR and immunohistochemistry. In addition, soluble serum αKlotho levels were preoperatively measured in 160 patients who underwent nephrectomy for RCC with ELISA. Estimates of cancer-specific (CSS) and progression-free survival (PFS) were calculated according to the Kaplan–Meier method. Multivariate analysis was performed to identify the most significant variables for predicting CSS and PFS. αKlotho protein levels were significantly decreased in RCC tissues compared with normal tissues (P < 0.01) and the more advanced the disease, the more evident the down-regulation. This trend was also observed in serum samples. Statistically significant differences resulted between serum αKlotho levels and tumor size (P = 0.003), Fuhrman grade (P = 0.007), and clinical stage (P = 0.0004). CSS and PFS were significantly shorter in patients with lower levels of αKlotho (P < 0.0001 and P = 0.0004, respectively). At multivariate analysis low serum levels of αKlotho were independent adverse prognostic factors for CSS (HR = 2.11; P = 0.03) and PFS (HR = 2.18; P = 0.03). These results indicate that a decreased αKlotho expression is correlated with RCC progression, and suggest a key role of declining αKlotho in the onset of cancer metastasis. PMID:26559258

  18. Contrasting dynamics of leaf potential and gas exchange during progressive drought cycles and recovery in Amorpha fruticosa and Robinia pseudoacacia.

    PubMed

    Yan, Weiming; Zheng, Shuxia; Zhong, Yangquanwei; Shangguan, Zhouping

    2017-06-30

    Leaf gas exchange is closely associated with water relations; however, less attention has been given to this relationship over successive drought events. Dynamic changes in gas exchange and water potential in the seedlings of two woody species, Amorpha fruticosa and Robinia pseudoacacia, were monitored during recurrent drought. The pre-dawn leaf water potential declined in parallel with gas exchange in both species, and sharp declines in gas exchange occurred with decreasing water potential. A significant correlation between pre-dawn water potential and gas exchange was observed in both species and showed a right shift in R. pseudoacacia in the second drought. The results suggested that stomatal closure in early drought was mediated mainly by elevated foliar abscisic acid (ABA) in R. pseudoacacia, while a shift from ABA-regulated to leaf-water-potential-driven stomatal closure was observed in A. fruticosa. After re-watering, the pre-dawn water potential recovered quickly, whereas stomatal conductance did not fully recover from drought in R. pseudoacacia, which affected the ability to tightly control transpiration post-drought. The dynamics of recovery from drought suggest that stomatal behavior post-drought may be restricted mainly by hydraulic factors, but non-hydraulic factors may also be involved in R. pseudoacacia.

  19. Stratification of Archaea in the deep sediments of a freshwater meromictic lake: vertical shift from methanogenic to uncultured archaeal lineages.

    PubMed

    Borrel, Guillaume; Lehours, Anne-Catherine; Crouzet, Olivier; Jézéquel, Didier; Rockne, Karl; Kulczak, Amélie; Duffaud, Emilie; Joblin, Keith; Fonty, Gérard

    2012-01-01

    As for lineages of known methanogens, several lineages of uncultured archaea were recurrently retrieved in freshwater sediments. However, knowledge is missing about how these lineages might be affected and structured according to depth. In the present study, the vertical changes of archaeal communities were characterized in the deep sediment of the freshwater meromictic Lake Pavin. For that purpose, an integrated molecular approach was performed to gain information on the structure, composition, abundance and vertical stratification of archaeal communities thriving in anoxic freshwater sediments along a gradient of sediments encompassing 130 years of sedimentation. Huge changes occurred in the structure and composition of archaeal assemblages along the sediment core. Methanogenic taxa (i.e. Methanosaeta and Methanomicrobiales) were progressively replaced by uncultured archaeal lineages (i.e. Marine Benthic Group-D (MBG-D) and Miscellaneous Crenarchaeal Group (MCG)) which are suspected to be involved in the methane cycle.

  20. Stratification of Archaea in the Deep Sediments of a Freshwater Meromictic Lake: Vertical Shift from Methanogenic to Uncultured Archaeal Lineages

    PubMed Central

    Borrel, Guillaume; Lehours, Anne-Catherine; Crouzet, Olivier; Jézéquel, Didier; Rockne, Karl; Kulczak, Amélie; Duffaud, Emilie; Joblin, Keith; Fonty, Gérard

    2012-01-01

    As for lineages of known methanogens, several lineages of uncultured archaea were recurrently retrieved in freshwater sediments. However, knowledge is missing about how these lineages might be affected and structured according to depth. In the present study, the vertical changes of archaeal communities were characterized in the deep sediment of the freshwater meromictic Lake Pavin. For that purpose, an integrated molecular approach was performed to gain information on the structure, composition, abundance and vertical stratification of archaeal communities thriving in anoxic freshwater sediments along a gradient of sediments encompassing 130 years of sedimentation. Huge changes occurred in the structure and composition of archaeal assemblages along the sediment core. Methanogenic taxa (i.e. Methanosaeta and Methanomicrobiales) were progressively replaced by uncultured archaeal lineages (i.e. Marine Benthic Group-D (MBG-D) and Miscellaneous Crenarchaeal Group (MCG)) which are suspected to be involved in the methane cycle. PMID:22927959

  1. 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.

  2. Early Cretaceous lineages of monocot flowering plants

    PubMed Central

    Bremer, Kåre

    2000-01-01

    The phylogeny of flowering plants is now rapidly being disclosed by analysis of DNA sequence data, and currently, many Cretaceous fossils of flowering plants are being described. Combining molecular phylogenies with reference fossils of known minimum age makes it possible to date the nodes of the phylogenetic tree. The dating may be done by counting inferred changes in sequenced genes along the branches of the phylogeny and calculating change rates by using the reference fossils. Plastid DNA rbcL sequences and eight reference fossils indicate that ≈14 of the extant monocot lineages may have diverged from each other during the Early Cretaceous >100 million years B.P. The lineages are very different in size and geographical distribution and provide perspective on flowering plant evolution. PMID:10759567

  3. DRG1 is a potential oncogene in lung adenocarcinoma and promotes tumor progression via spindle checkpoint signaling regulation

    PubMed Central

    Lu, Li; Lv, Yanrong; Dong, Ji; Hu, Shaohua; Peng, Ruiyun

    2016-01-01

    Developmentally regulated GTP binding protein 1 (DRG1), a member of the DRG family, plays important roles in regulating cell growth. However, the molecular basis of DRG1 in cell proliferation regulation and the relationship between DRG1 and tumor progression remain poorly understood. Here, we demonstrate that DRG1 is elevated in lung adenocarcinomas while weakly expressed in adjacent lung tissues. DRG1 knockdown causes growth inhibition of tumor cells by significantly increasing the proportion of cells in M phase. Overexpression of DRG1 leads to chromosome missegregation which is an important index for tumorigenesis. Interestingly, ectopic of DRG1 reduces taxol induced apoptosis of lung adenocarcinoma cells. Mechanistic analyses confirm that DRG1 localizes at mitotic spindles in dividing cells and binds to spindle checkpoint signaling proteins in vivo. These studies highlight the expanding role of DRG1 in tumorigenesis and reveal a mechanism of DRG1 in taxol resistance. PMID:27626498

  4. Laser-induced breakdown spectroscopy (LIBS): an overview of recent progress and future potential for biomedical applications.

    PubMed

    Rehse, S J; Salimnia, H; Miziolek, A W

    2012-02-01

    The recent progress made in developing laser-induced breakdown spectroscopy (LIBS) has transformed LIBS from an elemental analysis technique to one that can be applied for the reagentless analysis of molecularly complex biological materials or clinical specimens. Rapid advances in the LIBS technology have spawned a growing number of recently published articles in peer-reviewed journals which have consistently demonstrated the capability of LIBS to rapidly detect, biochemically characterize and analyse, and/or accurately identify various biological, biomedical or clinical samples. These analyses are inherently real-time, require no sample preparation, and offer high sensitivity and specificity. This overview of the biomedical applications of LIBS is meant to summarize the research that has been performed to date, as well as to suggest to health care providers several possible specific future applications which, if successfully implemented, would be significantly beneficial to humankind.

  5. Cell Lineage Analysis of Mouse Prostate Carcinogenesis

    DTIC Science & Technology

    2015-09-01

    are derived from luminal or basal epithelial cells using genetic lineage tracing of prostate carcinogenesis in PSA-CreERT2;R26RmT/mG;EAF2-/-;PTEN...derived from luminal epithelial cells in the prostate, because a hallmark of prostate cancer is the loss of basal epithelial cells and prostate...publications [2, 3]. This project will determine whether prostate cancer cells are derived from luminal or basal epithelial cells in an EAF2-/- mouse

  6. Human papillomavirus type 16 lineage analysis based on E6 region in cervical samples of Iranian women.

    PubMed

    Vaezi, Tayebeh; Shoja, Zabihollah; Hamkar, Rasool; Shahmahmoodi, Shohreh; Nozarian, Zohreh; Marashi, Sayed Mahdi; Jalilvand, Somayeh

    2017-08-25

    It is suggested that distinct HPV 16 variants differ in oncogenic potential and geographic distribution. As such, understanding the regional variants of HPV 16 would be of great importance for evolutionary, epidemiological and biological analysis. In this regard, the sequence variations of E6 gene were investigated to characterize more common variants of HPV 16 in normal cells, premalignant and malignant lesions of the cervix. In total, 106 isolates of HPV 16 were analyzed by PCR and sequencing. Overall, two different lineages (A and D) were identified. Lineage D comprised 70.7% of samples and the remaining 29.3% belonged to lineage A. Regarding to cytology/histology, lineage D was dominant in both normal+CIN I-II and CIN III+ICC groups as it was detected in 80% and 66.2% of cases, respectively. The comparison of the lineages between different groups (35 normal+CIN I-II samples and 71 CIN III+ICC samples) revealed that lineage A is more prevalent in cervical cancer cases (7 (20%) vs. 24 (33.8%)) although the difference observed did not reach statistical significance (p=0.07). In conclusion, our findings confirm that HPV lineages A and D are more prevalent in Iran, with the lineage D as the most dominant in all studied groups. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Matrix elasticity directs stem cell lineage specification

    NASA Astrophysics Data System (ADS)

    Discher, Dennis

    2010-03-01

    Adhesion of stem cells - like most cells - is not just a membrane phenomenon. Most tissue cells need to adhere to a ``solid'' for viability, and over the last decade it has become increasingly clear that the physical ``elasticity'' of that solid is literally ``felt'' by cells. Here we show that Mesenchymal Stem Cells (MSCs) specify lineage and commit to phenotypes with extreme sensitivity to the elasticity typical of tissues [1]. In serum only media, soft matrices that mimic brain appear neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic. Inhibition of nonmuscle myosin II activity blocks all elasticity directed lineage specification, which indicates that the cytoskeleton pulls on matrix through adhesive attachments. Results have significant implications for `therapeutic' stem cells and have motivated development of a proteomic-scale method to identify mechano-responsive protein structures [2] as well as deeper physical studies of matrix physics [3] and growth factor pathways [4]. [4pt] [1] A. Engler, et al. Matrix elasticity directs stem cell lineage specification. Cell (2006).[0pt] [2] C.P. Johnson, et al. Forced unfolding of proteins within cells. Science (2007).[0pt] [3] A.E.X. Brown, et al. Multiscale mechanics of fibrin polymer: Gel stretching with protein unfolding and loss of water. Science (2009).[0pt] [4] D.E. Discher, et al. Growth factors, matrices, and forces combine and control stem cells. Science (2009).

  8. Lymphatic endothelial lineage assemblage during corneal lymphangiogenesis

    PubMed Central

    Connor, Alicia L.; Kelley, Philip M.; Tempero, Richard M.

    2015-01-01

    Post natal inflammatory lymphangiogenesis presumably requires precise regulatory processes to properly assemble proliferating lymphatic endothelial cells (LECs). The specific mechanisms that regulate the assembly of LECs during new lymphatic vessel synthesis are unclear. Dynamic endothelial shuffling and rearrangement has been proposed as a mechanism of blood vessel growth. We developed genetic lineage tracing strategies using an inductive transgenic technology to track the fate of entire tandem dimer tomato positive (tdT) lymphatic vessels or small, in some cases clonal, populations of LECs. We coupled this platform with a suture induced mouse model of corneal lymphangiogenesis and used different analytic microscopy techniques including serial live imaging to study the spatial properties of proliferating tdT+ LEC progenies. LEC precursors and their progeny expanded from the corneal limbal lymphatic vessel and were assembled contiguously to comprise a subunit within a new lymphatic vessel. VE-cadherin blockade induced morphologic abnormalities in newly synthesized lymphatic vessels, but did not disrupt the tdT+ lymphatic endothelial lineage assembly. Analysis of this static and dynamic data based largely on direct in vivo observations supports a model of lymphatic endothelial lineage assemblage during corneal inflammatory lymphangiogenesis. PMID:26658452

  9. Environmental biology of the marine Roseobacter lineage.

    PubMed

    Wagner-Döbler, Irene; Biebl, Hanno

    2006-01-01

    The Roseobacter lineage is a phylogenetically coherent, physiologically heterogeneous group of alpha-Proteobacteria comprising up to 25% of marine microbial communities, especially in coastal and polar oceans, and it is the only lineage in which cultivated bacteria are closely related to environmental clones. Currently 41 subclusters are described, covering all major marine ecological niches (seawater, algal blooms, microbial mats, sediments, sea ice, marine invertebrates). Members of the Roseobacter lineage play an important role for the global carbon and sulfur cycle and the climate, since they have the trait of aerobic anoxygenic photosynthesis, oxidize the greenhouse gas carbon monoxide, and produce the climate-relevant gas dimethylsulfide through the degradation of algal osmolytes. Production of bioactive metabolites and quorum-sensing-regulated control of gene expression mediate their success in complex communities. Studies of representative isolates in culture, whole-genome sequencing, e.g., of Silicibacter pomeroyi, and the analysis of marine metagenome libraries have started to reveal the environmental biology of this important marine group.

  10. Parallel and lineage-specific molecular adaptation to climate in boreal black spruce.

    PubMed

    Prunier, Julien; Gérardi, Sébastien; Laroche, Jérôme; Beaulieu, Jean; Bousquet, Jean

    2012-09-01

    In response to selective pressure, adaptation may follow different genetic pathways throughout the natural range of a species due to historical differentiation in standing genetic variation. Using 41 populations of black spruce (Picea mariana), the objectives of this study were to identify adaptive genetic polymorphisms related to temperature and precipitation variation across the transcontinental range of the species, and to evaluate the potential influence of historical events on their geographic distribution. Population structure was first inferred using 50 control nuclear markers. Then, 47 candidate gene SNPs identified in previous genome scans were tested for relationship with climatic factors using an F(ST) -based outlier method and regressions between allele frequencies and climatic variations. Two main intraspecific lineages related to glacial vicariance were detected at the transcontinental scale. Within-lineage analyses of allele frequencies allowed the identification of 23 candidate SNPs significantly related to precipitation and/or temperature variation, among which seven were common to both lineages, eight were specific to the eastern lineage and eight were specific to the western lineage. The implication of these candidate SNPs in adaptive processes was further supported by gene functional annotations. Multiple evidences indicated that the occurrence of lineage-specific adaptive SNPs was better explained by selection acting on historically differentiated gene pools rather than differential selection due to heterogeneity of interacting environmental factors and pleiotropic effects. Taken together, these findings suggest that standing genetic variation of potentially adaptive nature has been modified by historical events, hence affecting the outcome of recent selection and leading to different adaptive routes between intraspecific lineages. © 2012 Blackwell Publishing Ltd.

  11. Ecological opportunity and the adaptive diversification of lineages

    PubMed Central

    Wellborn, Gary A; Langerhans, R Brian

    2015-01-01

    The tenet that ecological opportunity drives adaptive diversification has been central to theories of speciation since Darwin, yet no widely accepted definition or mechanistic framework for the concept currently exists. We propose a definition for ecological opportunity that provides an explicit mechanism for its action. In our formulation, ecological opportunity refers to environmental conditions that both permit the persistence of a lineage within a community, as well as generate divergent natural selection within that lineage. Thus, ecological opportunity arises from two fundamental elements: (1) niche availability, the ability of a population with a phenotype previously absent from a community to persist within that community and (2) niche discordance, the diversifying selection generated by the adaptive mismatch between a population's niche-related traits and the newly encountered ecological conditions. Evolutionary response to ecological opportunity is primarily governed by (1) spatiotemporal structure of ecological opportunity, which influences dynamics of selection and development of reproductive isolation and (2) diversification potential, the biological properties of a lineage that determine its capacity to diversify. Diversification under ecological opportunity proceeds as an increase in niche breadth, development of intraspecific ecotypes, speciation, and additional cycles of diversification that may themselves be triggered by speciation. Extensive ecological opportunity may exist in depauperate communities, but it is unclear whether ecological opportunity abates in species-rich communities. Because ecological opportunity should generally increase during times of rapid and multifarious environmental change, human activities may currently be generating elevated ecological opportunity – but so far little work has directly addressed this topic. Our framework highlights the need for greater synthesis of community ecology and evolutionary biology, unifying

  12. Ecological opportunity and the adaptive diversification of lineages.

    PubMed

    Wellborn, Gary A; Langerhans, R Brian

    2015-01-01

    The tenet that ecological opportunity drives adaptive diversification has been central to theories of speciation since Darwin, yet no widely accepted definition or mechanistic framework for the concept currently exists. We propose a definition for ecological opportunity that provides an explicit mechanism for its action. In our formulation, ecological opportunity refers to environmental conditions that both permit the persistence of a lineage within a community, as well as generate divergent natural selection within that lineage. Thus, ecological opportunity arises from two fundamental elements: (1) niche availability, the ability of a population with a phenotype previously absent from a community to persist within that community and (2) niche discordance, the diversifying selection generated by the adaptive mismatch between a population's niche-related traits and the newly encountered ecological conditions. Evolutionary response to ecological opportunity is primarily governed by (1) spatiotemporal structure of ecological opportunity, which influences dynamics of selection and development of reproductive isolation and (2) diversification potential, the biological properties of a lineage that determine its capacity to diversify. Diversification under ecological opportunity proceeds as an increase in niche breadth, development of intraspecific ecotypes, speciation, and additional cycles of diversification that may themselves be triggered by speciation. Extensive ecological opportunity may exist in depauperate communities, but it is unclear whether ecological opportunity abates in species-rich communities. Because ecological opportunity should generally increase during times of rapid and multifarious environmental change, human activities may currently be generating elevated ecological opportunity - but so far little work has directly addressed this topic. Our framework highlights the need for greater synthesis of community ecology and evolutionary biology, unifying

  13. Phylogenomics of the Zygomycete lineages: Exploring phylogeny and genome evolution

    USDA-ARS?s Scientific Manuscript database

    The Zygomycete lineages mark the major transition from zoosporic life histories of the common ancestors of Fungi and the earliest diverging chytrid lineages (Chytridiomycota and Blastocladiomycota). Genome comparisons from these lineages may reveal gene content changes that reflect the transition to...

  14. Mycobacterium tuberculosis Lineage Distribution in Xinjiang and Gansu Provinces, China.

    PubMed

    Chen, Haixia; He, Li; Huang, Hairong; Shi, Chengmin; Ni, Xumin; Dai, Guangming; Ma, Liang; Li, Weimin

    2017-04-21

    Mycobacterium tuberculosis (M. tuberculosis) genotyping has dramatically improved the understanding of the epidemiology of tuberculosis (TB). In this study, 187 M. tuberculosis isolates from Xinjiang Uygur Autonomous Region (Xinjiang) and Gansu province in China were genotyped using large sequence polymorphisms (LSPs) and variable number tandem repeats (VNTR). Ten isolates, which represent major nodes of VNTR-based minimum spanning tree, were selected and subsequently subjected to multi-locus sequence analyses (MLSA) that include 82 genes. Based on a robust lineage assignment, we tested the association between lineages and clinical characteristics by logistic regression. There are three major lineages of M. tuberculosis prevalent in Xinjiang, viz. the East Asian Lineage 2 (42.1%; 56/133), the Euro-American Lineage 4 (33.1%; 44/133), and the Indian and East African Lineage 3 (24.8%; 33/133); two lineages prevalent in Gansu province, which are the Lineage 2 (87%; 47/54) and the Lineage 4 (13%; 7/54). The topological structures of the MLSA-based phylogeny support the LSP-based identification of M. tuberculosis lineages. The statistical results suggest an association between the Lineage 2 and the hemoptysis/bloody sputum symptom, fever in Uygur patients. The pathogenicity of the Lineage 2 remains to be further investigated.

  15. Genome sequesnce of lineage III Listeria monocytogenes strain HCC23

    USDA-ARS?s Scientific Manuscript database

    More than 98% of reported human listeriosis cases are caused by Listeria monocytogenes serotypes within lineages I and II. Serotypes within lineage III (4a and 4c) are commonly isolated from environmental and food specimens. We report the first complete genome sequence of a lineage III isolate, HCC2...

  16. Molecular characterization of a novel heavy metal uptake transporter from higher plants and its potential for use in phytoremediation. 1997 annual progress report

    SciTech Connect

    Schroeder, J.I.

    1997-01-01

    'In the following the author reports on progress on the Department of Energy Grant from the Office of Energy Research and Office of Environmental Management on the topic of Molecular characterization of a novel heavy metal uptake transporter from higher plants and its potential use in phytoremediation. In this research the authors are investigating the following hypotheses: (1) A novel metal transporter cDNA isolated in my lab functions as a plasma membrane heavy metal and uptake transporter in plants roots. (2.) Over-expression of this cDNA in plants can be used to enhance plasma membrane metal uptake into plant tissues.'

  17. Functionally convergent white adipogenic progenitors of different lineages participate in a diffused system supporting tissue regeneration.

    PubMed

    Lemos, Dario R; Paylor, Benjamin; Chang, Chihkai; Sampaio, Arthur; Underhill, T Michael; Rossi, Fabio M V

    2012-06-01

    Pathologies characterized by lipomatous infiltration of craniofacial structures as well as certain forms of lipodystrophies suggest the existence of a distinct adipogenic program in the cephalic region of mammals. Using lineage tracing, we studied the origin of craniofacial adipocytes that accumulate both in cranial fat depots and during ectopic lipomatous infiltration of craniofacial muscles. We found that unlike their counterparts in limb muscle, a significant percentage of cranial adipocytes is derived from the neural crest (NC). In addition, we identified a population of NC-derived Lin(-)/α7(-)/CD34(+)/Sca-1(+) fibro/adipogenic progenitors (NC-FAPs) that resides exclusively in the mesenchyme of cephalic fat and muscle. Comparative analysis of the adipogenic potential, impact on metabolism, and contribution to the regenerative response of NC-FAPs and mesoderm-derived FAPs (M-FAPs) suggests that these cells are functionally indistinguishable. While both NC- and M-FAPs express mesenchymal markers and promyogenic cytokines upon damage-induced activation, NC-FAPs additionally express components of the NC developmental program. Furthermore, we show that craniofacial FAP composition changes with age, with young mice containing FAPs that are almost exclusively of NC origin, while NC-FAPs are progressively replaced by M-FAPs as mice age. Based on these results, we propose that in the adult, ontogenetically distinct FAPs form a diffused system reminiscent of the endothelium, which can originate from multiple developmental intermediates to seed all anatomical locations.

  18. Pollinator-mediated selection on floral morphology: evidence for transgressive evolution in a derived hybrid lineage.

    PubMed

    Anton, K A; Ward, J R; Cruzan, M B

    2013-03-01

    Hybridization between closely related lineages is a mechanism that might promote substantive changes in phenotypic traits of descendants, resulting in transgressive evolution. Interbreeding between divergent but morphologically similar lineages can produce exceptional phenotypes, but the potential for transgressive variation to facilitate long-term trait changes in derived hybrid lineages has received little attention. We compare pollinator-mediated selection on transgressive floral traits in both early-generation and derived hybrid lineages of the Piriqueta cistoides ssp. caroliniana complex. The bowl-shaped flowers of morphotypes in this complex have similar gross morphologies and attract a common suite of small insect pollinators. However, they are defined by significant differences in characters that generate pollinator interest and visitation, including floral area and petal separation. In common garden experiments, patterns of pollen deposition in early-generation recombinant hybrids indicate that Piriqueta's pollinators favour flowers with greater area and reduced petal separation. Changes in floral morphology in derived hybrid lineages are consistent with predictions from selection gradients, but the magnitude of change is limited relative to the range of transgressive variation. These results suggest that hybridization provides variation for evolution of divergent floral traits. However, the potential for extreme transgressive variants to contribute to phenotypic shifts may be limited due to reduced heritability, evolutionary constraints or fitness trade-offs. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

  19. The Potentiality of a Healthy Self: Evaluating Progressively Empowered Internalisation and Diagnosis through the Lens of Existential Epistemology.

    PubMed

    Westin, Anna

    2016-11-01

    In this article I will examine how the language of diagnosis can engage with existential epistemology to develop a concept of Progressively Empowered Internalisation (PEI). This, I will argue, challenges conceptualisations of diagnosis as articulating and maintaining a static self-concept. It enables the individual to synthesise the language of a particular mental experience within the wider engagement of their own active process of self-becoming. I will suggest that this construction of PEI addresses the limitations of stigmatisation and static self-concepts. In seeing the language of diagnosis as a helpful tool for understanding a part of one's self-experience, it presents an alternative to the illness-based model of mental health. This conceptualisation engages with Kierkegaard's existential epistemology, as a means of using language to understand the task of becoming oneself and relating to others. Furthermore, it explores how mental health diagnosis requires communal engagement to enable the wellbeing of its members. Diagnosis is thereby seen as a process of further empowering the individual with the language to explain a particular part of their experience within the overall movement of developing an integrated self-concept.

  20. Orphan nuclear receptor Nurr1 as a potential novel marker for progression in human pancreatic ductal adenocarcinoma

    PubMed Central

    Ji, Li; Gong, Chen; Ge, Liangyu; Song, Linping; Chen, Fenfen; Jin, Chunjing; Zhu, Hongyan; Zhou, Guoxiong

    2017-01-01

    Nuclear receptor related-1 protein (Nurr1) is a novel orphan member of the nuclear receptor superfamily (the NR4A family) involved in tumorigenesis. The aim of the present study was to investigate the expression and possible function of Nurr1 in pancreatic ductal adenocarcinoma (PDAC). The expression pattern of Nurr1 protein was determined using immunohistochemical staining in 138 patients with PDAC. Elevated Nurr1 expression was more commonly observed in PDAC tissues and cell lines compared with healthy controls. Elevated expression was significantly associated with histological differentiation (P=0.041), lymph node metastasis (P=0.021), TNM classification of malignant tumors stage (P=0.031) and poor survival (P=0.001). Further experiments demonstrated that suppression of endogenous Nurr1 expression attenuated cell proliferation, migration and invasion, and induced apoptosis of PDAC cells. In conclusion, these results suggest that Nurr1 has an important role in the progression of PDAC and may be used as a novel marker for therapeutic targets. PMID:28352330

  1. Age-Specific Gene Expression Signatures for Breast Tumors and Cross-Species Conserved Potential Cancer Progression Markers in Young Women

    PubMed Central

    Colak, Dilek; Nofal, Asmaa; AlBakheet, AlBandary; Nirmal, Maimoona; Jeprel, Hatim; Eldali, Abdelmoneim; AL-Tweigeri, Taher; Tulbah, Asma; Ajarim, Dahish; Malik, Osama Al; Kaya, Namik; Park, Ben H.; Bin Amer, Suad M.

    2013-01-01

    Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross

  2. Age-specific gene expression signatures for breast tumors and cross-species conserved potential cancer progression markers in young women.

    PubMed

    Colak, Dilek; Nofal, Asmaa; Albakheet, Albandary; Nirmal, Maimoona; Jeprel, Hatim; Eldali, Abdelmoneim; Al-Tweigeri, Taher; Tulbah, Asma; Ajarim, Dahish; Malik, Osama Al; Inan, Mehmet S; Kaya, Namik; Park, Ben H; Bin Amer, Suad M

    2013-01-01

    Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross

  3. The effect of progressively increased physical efforts on visual evoked potentials in volleyball players and non-athletes.

    PubMed

    Zwierko, Teresa; Lubiński, Wojciech; Lubkowska, Anna; Niechwiej-Szwedo, Ewa; Czepita, Damian

    2011-11-01

    We assessed the effect of physical effort with increasing intensity on neural activity in the visual pathway in volleyball players (n = 10) and non-athletes (n = 10). Participants performed three 10-min tests of increasing intensity on a cycle ergometer. Each participant was assigned individual workloads below the lactate threshold (40% [Vdot]O(2max)), at the lactate threshold (65-75% [Vdot]O(2max)), and above the lactate threshold (80% [Vdot]O(2max)). Four recordings of visual evoked potentials were made: pre-exercise and immediately after each of the three subsequent tests. We assessed neural activity of the visual pathway by examining the amplitude and latency of the N75, P100, and N135 components of the visual evoked potentials waveform. Pre-exercise P100 wave latency was shorter (P < 0.05) in volleyball players than in non-athletes. In non-athletes, the latency of P100 following the first and second effort (40% and 65-75% [Vdot]O(2max)) was reduced compared with pre-exercise (P < 0.01). However, P100 latency increased and P100 amplitude decreased after the third test (80% [Vdot]O(2max)) in non-athletes. In contrast, no significant changes in the latency or amplitude of visual evoked potentials were observed in the athletes in the three tests. Neural conductivity in the visual pathway after exercise might be at least partially dependent on the individual's personal training adaptation status.

  4. MicroRNA-196a Is a Potential Marker of Progression during Barrett’s Metaplasia-Dysplasia-Invasive Adenocarcinoma Sequence in Esophagus

    PubMed Central

    Maru, Dipen M.; Singh, Rajesh R.; Hannah, Christina; Albarracin, Constance T.; Li, Yong X.; Abraham, Ronald; Romans, Angela M.; Yao, Hui; Luthra, Madan G.; Anandasabapathy, Sharmila; Swisher, Stephen G.; Hofstetter, Wayne L.; Rashid, Asif; Luthra, Rajyalakshmi

    2009-01-01

    Barrett’s esophagus (BE)/Barrett’s metaplasia (BM) is a recognized precursor of esophageal adenocarcinoma (EA) with an intermediary stage of dysplasia. The low yield and high cost of endoscopic screening of patients with BE underscores the need for novel biomarkers, such as microRNA (miRNA), which have emerged as important players in neoplastic progression for risk assessment of developing dysplasia/adenocarcinoma. Recently, we reported highly elevated levels of miRNA-196a (miR-196a) in EA and demonstrated its growth-promoting and anti-apoptotic functions. Here, we evaluated miR-196a as a marker of BE progression to low-grade dysplasia, high-grade dysplasia, and EA using microdissected paraffin-embedded tissues from 11 patients. Higher levels of miR-196a were observed in EA, BE, and dysplastic lesions compared with normal squamous mucosa, and in high-grade dysplasia compared with BE and low-grade dysplasia. Using frozen tumor tissues from 10 additional patients who had advanced EA, we evaluated the correlation of miR-196a with its in silico-predicted targets, keratin 5 (KRT5), small proline-rich protein 2C (SPRR2C), and S100 calcium-binding protein A9 (S100A9), which are down-regulated during BE progression. MiR-196a levels inversely correlated with the predicted target mRNA levels in EA. We confirmed that miR-196a specifically targets KRT5, SPRR2C, and S100A9 3′ UTRs using miR-196a-mimic and luciferase reporter-based assays. In conclusion, this study identified miR-196a as a potential marker of progression of BE and KRT5, SPRR2C, and S100A9 as its targets. PMID:19342367

  5. Reconstructing lineage hierarchies of the distal lung epithelium using single cell RNA-seq

    PubMed Central

    Treutlein, Barbara; Brownfield, Doug G.; Wu, Angela R.; Neff, Norma F.; Mantalas, Gary L.; Espinoza, F. Hernan; Desai, Tushar J.; Krasnow, Mark A.; Quake, Stephen R.

    2014-01-01

    The mammalian lung is a highly branched network, in which the distal regions of the bronchial tree transform during development into a densely packed honeycomb of alveolar air sacs that mediate gas exchange. Although this transformation has been studied by marker expression analysis and fate-mapping, the mechanisms that control the progression of lung progenitors along distinct lineages into mature alveolar cell types remain obscure, in part due to the limited number of lineage markers1-3 and the effects of ensemble averaging in conventional transcriptome analysis experiments on cell populations1–5. We used microfluidic single cell RNA sequencing (RNA-seq) on 198 individual cells at 4 different stages encompassing alveolar differentiation to measure the transcriptional states which define the developmental and cellular hierarchy of the distal mouse lung epithelium. We empirically classified cells into distinct groups using an unbiased genome-wide approach that did not require a priori knowledge of the underlying cell types or prior purification of cell populations. The results confirmed the basic outlines of the classical model of epithelial cell type diversity in the distal lung and led to the discovery of many novel cell type markers and transcriptional regulators that discriminate between the different populations. We reconstructed the molecular steps during maturation of bipotential progenitors along both alveolar lineages and elucidated the full lifecycle of the alveolar type 2 cell lineage. This single cell genomics approach is applicable to any developing or mature tissue to robustly delineate molecularly distinct cell types, define progenitors and lineage hierarchies, and identify lineage-specific regulatory factors. PMID:24739965

  6. Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq.

    PubMed

    Treutlein, Barbara; Brownfield, Doug G; Wu, Angela R; Neff, Norma F; Mantalas, Gary L; Espinoza, F Hernan; Desai, Tushar J; Krasnow, Mark A; Quake, Stephen R

    2014-05-15

    The mammalian lung is a highly branched network in which the distal regions of the bronchial tree transform during development into a densely packed honeycomb of alveolar air sacs that mediate gas exchange. Although this transformation has been studied by marker expression analysis and fate-mapping, the mechanisms that control the progression of lung progenitors along distinct lineages into mature alveolar cell types are still incompletely known, in part because of the limited number of lineage markers and the effects of ensemble averaging in conventional transcriptome analysis experiments on cell populations. Here we show that single-cell transcriptome analysis circumvents these problems and enables direct measurement of the various cell types and hierarchies in the developing lung. We used microfluidic single-cell RNA sequencing (RNA-seq) on 198 individual cells at four different stages encompassing alveolar differentiation to measure the transcriptional states which define the developmental and cellular hierarchy of the distal mouse lung epithelium. We empirically classified cells into distinct groups by using an unbiased genome-wide approach that did not require a priori knowledge of the underlying cell types or the previous purification of cell populations. The results confirmed the basic outlines of the classical model of epithelial cell-type diversity in the distal lung and led to the discovery of many previously unknown cell-type markers, including transcriptional regulators that discriminate between the different populations. We reconstructed the molecular steps during maturation of bipotential progenitors along both alveolar lineages and elucidated the full life cycle of the alveolar type 2 cell lineage. This single-cell genomics approach is applicable to any developing or mature tissue to robustly delineate molecularly distinct cell types, define progenitors and lineage hierarchies, and identify lineage-specific regulatory factors.

  7. Structural changes in the progression of atrial fibrillation: potential role of glycogen and fibrosis as perpetuating factors

    PubMed Central

    Zhang, Ling; Huang, Bing; Scherlag, Benjamin J; Ritchey, Jerry W; Embi, Abraham A; Hu, Jialu; Hou, Yuemei; Po, Sunny S

    2015-01-01

    Background: Previous studies of the goat heart subjected to prolonged atrial pacing induced sustained atrial fibrillation (AF). Structural changes included marked accumulation of glycogen in atrial myocytes. Aims: In the present study, we hypothesized that glycogen deposition in canine atrial myocytes promotes paroxysmal forms of AF and is involved in fibrosis development in the later stages of AF. Material & methods: In dogs under pentobarbital anesthesia, tissues were obtained from the right and left atrial appendages (LAA/RAA). Periodic acid Schiff (PAS) and Masson’s trichrome staining of the LAA/RAA from normal dogs, and those subjected to atrial pacing induced AF for 48 h or 8 weeks determined glycogen and collagen concentrations, respectively, using morphometric analysis. Results: At baseline, there was a significant greater concentration of glycogen in the LAA than the RAA (P ≤ 0.05). Compared to the RAA, the LAA glycogen, was dense and locked against the intercalated discs. After pacing induced AF for 48 hours and 8 weeks there was a marked increase in glycogen deposition, significantly greater than in the baseline state (P ≤ 0.05). There was a similar and progressive increase in collagen concentrations in each group (P ≤ 0.05). Conclusions: The differential in glycogen concentration, in conjunction with other factors, neural and electrophysiological, provide a basis for the greater propensity of the left atrium for paroxysmal AF, at baseline and 48 hours of pacing induced AF. The marked increase in collagen at 8 weeks of pacing provides a substrate for sustained AF. Evidence is presented linking glycogen accumulation and fibrosis as factors in the persistent forms of AF. PMID:25973058

  8. One-time intrathecal triamcinolone acetonide application alters the redox potential in cerebrospinal fluid of progressive multiple sclerosis patients: a pilot study

    PubMed Central

    Müller, Thomas; Herrling, Thomas; Lütge, Sven; Lohse, Lutz; Öhm, Gabi; Jung, Katinka

    2016-01-01

    Introduction: Cerebrospinal fluid analysis may provide insight into the interplay between chronic inflammation and response to treatment. Objectives: To demonstrate the impact of one intrathecal triamcinolone injection on the redox potential and on ascorbyl radical appearance in the cerebrospinal fluid of chronic progressive multiple sclerosis patients. Methods: A total of 16 patients received 40 mg triamcinolone. Electron-spin resonance spectroscopy measured the oxidation range after copper ion [Cu (II)] addition and ascorbyl-radical bioavailability. Results: There was an increase of Cu (II) ion absorption, which reflects an augmented content of reduced proteins. Ascorbyl radicals were present in contrast to healthy controls according to the literature. Conclusion: Intrathecal steroid application alters the redox potential in cerebrospinal fluid. Our findings support the beneficial role of steroids on oxidative stress generally demonstrated by ascorbyl radical appearance. Reactive oxygen species decline is necessary for an upregulated production of reduced proteins. PMID:27366232

  9. O-Fucose Modulates Notch-Controlled Blood Lineage Commitment

    PubMed Central

    Yan, Quanjian; Yao, David; Wei, Lebing L.; Huang, Yuanshuai; Myers, Jay; Zhang, Lihua; Xin, Wei; Shim, Jeongsup; Man, Yunfang; Petryniak, Bronislawa; Gerson, Stanton; Lowe, John B.; Zhou, Lan

    2010-01-01

    Notch receptors are cell surface molecules essential for cell fate determination. Notch signaling is subject to tight regulation at multiple levels, including the posttranslational modification of Notch receptors by O-linked fucosylation, a reaction that is catalyzed by protein O-fucosyltransferase-1 (Pofut1). Our previous studies identified a myeloproliferative phenotype in mice conditionally deficient in cellular fucosylation that is attributable to a loss of Notch-dependent suppression of myelopoiesis. Here, we report that hematopoietic stem cells deficient in cellular fucosylation display decreased frequency and defective repopulating ability as well as decreased lymphoid but increased myeloid developmental potential. This phenotype may be attributed to suppressed Notch ligand binding and reduced downstream signaling of Notch activity in hematopoietic stem cells. Consistent with this finding, we further demonstrate that mouse embryonic stem cells deficient in Notch1 (Notch1−/−) or Pofut1 (Pofut1−/−) fail to generate T lymphocytes but differentiate into myeloid cells while coculturing with Notch ligand–expressing bone marrow stromal cells in vitro. Moreover, in vivo hematopoietic reconstitution of CD34+ progenitor cells derived from either Notch1−/− or Pofut1−/− embryonic stem cells show enhanced granulopoiesis with depressed lymphoid lineage development. Together, these results indicate that Notch signaling maintains hematopoietic lineage homeostasis by promoting lymphoid development and suppressing overt myelopoiesis, in part through processes controlled by O-linked fucosylation of Notch receptors. PMID:20363915

  10. Recent Reticulate Evolution in the Ecologically Dominant Lineage of Coccolithophores

    PubMed Central

    Bendif, El Mahdi; Probert, Ian; Díaz-Rosas, Francisco; Thomas, Daniela; van den Engh, Ger; Young, Jeremy R.; von Dassow, Peter

    2016-01-01

    The coccolithophore family Noëlaerhabdaceae contains a number of taxa that are very abundant in modern oceans, including the cosmopolitan bloom-forming Emiliania huxleyi. Introgressive hybridization has been suggested to account for incongruences between nuclear, mitochondrial and plastidial phylogenies of morphospecies within this lineage, but the number of species cultured to date remains rather limited. Here, we present the characterization of 5 new Noëlaerhabdaceae culture strains isolated from samples collected in the south-east Pacific Ocean. These were analyzed morphologically using scanning electron microscopy and phylogenetically by sequencing 5 marker genes (nuclear 18S and 28S rDNA, plastidial tufA, and mitochondrial cox1 and cox3 genes). Morphologically, one of these strains corresponded to Gephyrocapsa ericsonii and the four others to Reticulofenestra parvula. Ribosomal gene sequences were near identical between these new strains, but divergent from G. oceanica, G. muellerae, and E. huxleyi. In contrast to the clear distinction in ribosomal phylogenies, sequences from other genomic compartments clustered with those of E. huxleyi strains with which they share an ecological range (i.e., warm temperate to tropical waters). These data provide strong support for the hypothesis of past (and potentially ongoing) introgressive hybridization within this ecologically important lineage and for the transfer of R. parvula to Gephyrocapsa. These results have important implications for understanding the role of hybridization in speciation in vast ocean meta-populations of phytoplankton. PMID:27252694

  11. West Nile Virus lineage-2 in Culex specimens from Iran.

    PubMed

    Shahhosseini, Nariman; Chinikar, Sadegh; Moosa-Kazemi, Seyed Hassan; Sedaghat, Mohammad Mehdi; Kayedi, Mohammad Hassan; Lühken, Renke; Schmidt-Chanasit, Jonas

    2017-10-01

    Screening of mosquitoes for viruses is an important forecasting tool for emerging and re-emerging arboviruses. Iran has been known to harbour medically important arboviruses such as West Nile virus (WNV) and dengue virus (DENV) based on seroepidemiological data. However, there are no data about the potential mosquito vectors for arboviruses in Iran. This study was performed to provide mosquito and arbovirus data from Iran. A total of 32 317 mosquitos were collected at 16 sites in five provinces of Iran in 2015 and 2016. RT-PCR for detection of flaviviruses was performed. The PCR amplicons were sequenced, and 109 WNV sequences, including one obtained in this study, were used for phylogenetic analyses. The 32 317 mosquito specimens belonging to 25 species were morphologically distinguished and distributed into 1222 pools. Culex pipiens s.l. comprised 56.429%. One mosquito pool (0.08%), containing 46 unfed Cx. pipiens pipiens form pipiens (Cpp) captured in August 2015, was positive for flavivirus RNA. Subsequent sequencing and phylogenetic analyses revealed that the detected Iranian WNV strain belongs to lineage 2 and clusters with a strain recently detected in humans. No flaviviruses other than WNV were detected in the mosquito pools. Cpp could be a vector for WNV in Iran. Our findings indicate recent circulation of WNV lineage-2 strain in Iran and provide a solid base for more targeted arbovirus surveillance programs. © 2017 John Wiley & Sons Ltd.

  12. Progress on the development of human in vitro dendritic cell based assays for assessment of the sensitizing potential of a compound

    SciTech Connect

    Galvao dos Santos, G.; Reinders, J.; Ouwehand, K.; Rustemeyer, T.; Scheper, R.J.; Gibbs, S.

    2009-05-01

    Allergic contact dermatitis is the result of an adaptive immune response of the skin to direct exposure to an allergen. Since many chemicals are also allergens, European regulations require strict screening of all ingredients in consumer products. Until recently, identifying a potential allergen has completely relied on animal testing (e.g.: Local Lymph Node Assay). In addition to the ethical problems, both the 7th Amendment to the Cosmetics Directive and REACH have stimulated the development of alternative tests for the assessment of potential sensitizers. This review is aimed at summarising the progress on cell based assays, in particular dendritic cell based assays, being developed as animal alternatives. Primary cells (CD34{sup +} derived dendritic cells, monocyte derived dendritic cells) as well as dendritic cell-like cell lines (THP-1, U-937, MUTZ-3, KG-1, HL-60, and K562) are extensively described along with biomarkers such as cell surface markers, cytokines, chemokines and kinases. From this review, it can be concluded that no single cell based assay nor single marker is yet able to distinguish all sensitizers from non-sensitizers in a test panel of chemicals, nor is it possible to rank the sensitizing potential of the test chemicals. This suggests that sensitivity and specificity may be increased by a tiered assay approach. Only a limited number of genomic and proteomic studies have been completed until now. Such studies have the potential to identify novel biomarkers for inclusion in future assay development. Although progress is promising, this review suggests that it may be difficult to meet the up and coming European regulatory deadlines.

  13. Water relations traits of C4 grasses depend on phylogenetic lineage, photosynthetic pathway, and habitat water availability

    PubMed Central

    Liu, Hui; Osborne, Colin P.

    2015-01-01

    The repeated evolution of C4 photosynthesis in independent lineages has resulted in distinct biogeographical distributions in different phylogenetic lineages and the variants of C4 photosynthesis. However, most previous studies have only considered C3/C4 differences without considering phylogeny, C4 subtype, or habitat characteristics. We hypothesized that independent lineages of C4 grasses have structural and physiological traits that adapt them to environments with differing water availability. We measured 40 traits of 33 species from two major C4 grass lineages in a common glasshouse environment. Chloridoideae species were shorter, with narrower and longer leaves, smaller but denser stomata, and faster curling leaves than Panicoideae species, but overall differences in leaf hydraulic and gas exchange traits between the two lineages were weak. Chloridoideae species had two different ways to reach higher drought resistance potential than Panicoideae; NAD-ME species used water saving, whereas PCK species used osmotic adjustment. These patterns could be explained by the interactions of lineage×C4 subtype and lineage×habitat water availability in affected traits. Specifically, phylogeny tended to have a stronger influence on structural traits, and C4 subtype had more important effects on physiological traits. Although hydraulic traits did not differ consistently between lineages, they showed strong covariation and relationships with leaf structure. Thus, phylogenetic lineage, photosynthetic pathway, and adaptation to habitat water availability act together to influence the leaf water relations traits of C4 grasses. This work expands our understanding of ecophysiology in major C4 grass lineages, with implications for explaining their regional and global distributions in relation to climate. PMID:25504656

  14. Water relations traits of C4 grasses depend on phylogenetic lineage, photosynthetic pathway, and habitat water availability.

    PubMed

    Liu, Hui; Osborne, Colin P

    2015-02-01

    The repeated evolution of C4 photosynthesis in independent lineages has resulted in distinct biogeographical distributions in different phylogenetic lineages and the variants of C4 photosynthesis. However, most previous studies have only considered C3/C4 differences without considering phylogeny, C4 subtype, or habitat characteristics. We hypothesized that independent lineages of C4 grasses have structural and physiological traits that adapt them to environments with differing water availability. We measured 40 traits of 33 species from two major C4 grass lineages in a common glasshouse environment. Chloridoideae species were shorter, with narrower and longer leaves, smaller but denser stomata, and faster curling leaves than Panicoideae species, but overall differences in leaf hydraulic and gas exchange traits between the two lineages were weak. Chloridoideae species had two different ways to reach higher drought resistance potential than Panicoideae; NAD-ME species used water saving, whereas PCK species used osmotic adjustment. These patterns could be explained by the interactions of lineage×C4 subtype and lineage×habitat water availability in affected traits. Specifically, phylogeny tended to have a stronger influence on structural traits, and C4 subtype had more important effects on physiological traits. Although hydraulic traits did not differ consistently between lineages, they showed strong covariation and relationships with leaf structure. Thus, phylogenetic lineage, photosynthetic pathway, and adaptation to habitat water availability act together to influence the leaf water relations traits of C4 grasses. This work expands our understanding of ecophysiology in major C4 grass lineages, with implications for explaining their regional and global distributions in relation to climate. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  15. [Recent progress of potential effects and mechanisms of chlorogenic acid and its intestinal metabolites on central nervous system diseases].

    PubMed

    Xing, Li-na; Zhou, Ming-mei; Li, Yun; Shi, Xiao-wen; Jia, Wei

    2015-03-01

    Chlorogenic acid displays several important roles in the therapeutic properties of many herbs, such as antioxidant activity, antibacterial, antiviral, scavenging free radicals and exciting central nervous system. Only about one-third of chlorogenic acid was absorbed in its prototype, therefore, its gut metabolites play a more important role in the therapeutic properties of chlorogenic acid. It is necessary to consider not only the bioactivities of chlorogenic acid but also its gut metabolites. This review focuses on the potential activities and mechanisms of chlorogenic acid and its gut metabolites on central nervous system diseases.

  16. Recovering mitochondrial DNA lineages of extinct Amerindian nations in extant homopatric Brazilian populations

    PubMed Central

    2010-01-01

    Background Brazilian Amerindians have experienced a drastic population decrease in the past 500 years. Indeed, many native groups from eastern Brazil have vanished. However, their mitochondrial mtDNA haplotypes, still persist in Brazilians, at least 50 million of whom carry Amerindian mitochondrial lineages. Our objective was to test whether, by analyzing extant rural populations from regions anciently occupied by specific Amerindian groups, we could identify potentially authentic mitochondrial lineages, a strategy we have named 'homopatric targeting'. Results We studied 173 individuals from Queixadinha, a small village located in a territory previously occupied by the now extinct Botocudo Amerindian nation. Pedigree analysis revealed 74 unrelated matrilineages, which were screened for Amerindian mtDNA lineages by restriction fragment length polymorphism. A cosmopolitan control group was composed of 100 individuals from surrounding cities. All Amerindian lineages identified had their hypervariable segment HVSI sequenced, yielding 13 Amerindian haplotypes in Queixadinha, nine of which were not present in available databanks or in the literature. Among these haplotypes, there was a significant excess of haplogroup C (70%) and absence of haplogroup A lineages, which were the most common in the control group. The novelty of the haplotypes and the excess of the C haplogroup suggested that we might indeed have identified Botocudo lineages. To validate our strategy, we studied teeth extracted from 14 ancient skulls of Botocudo Amerindians from the collection of the National Museum of Rio de Janeiro. We recovered mtDNA sequences from all the teeth, identifying only six different haplotypes (a low haplotypic diversity of 0.8352 ± 0.0617), one of which was present among the lineages observed in the extant individuals studied. Conclusions These findings validate the technique of homopatric targeting as a useful new strategy to study the peopling and colonization of the New

  17. Notch3 activation is sufficient but not required for inducing human T-lineage specification.

    PubMed

    Waegemans, Els; Van de Walle, Inge; De Medts, Jelle; De Smedt, Magda; Kerre, Tessa; Vandekerckhove, Bart; Leclercq, Georges; Wang, Tao; Plum, Jean; Taghon, Tom

    2014-12-15

    Although the role for the individual Notch receptors in early hematopoiesis have been thoroughly investigated in mouse, studies in human have been mostly limited to the use of pan-Notch inhibitors. However, such studies in human are important to predict potential side effects of specific Notch receptor blocking reagents because these are currently being considered as therapeutic tools to treat various Notch-dependent diseases. In this study, we studied the individual roles of Notch1 and Notch3 in early human hematopoietic lineage decisions, particularly during T-lineage specification. Although this process in mice is solely dependent on Notch1 activation, we recently reported Notch3 expression in human uncommitted thymocytes, raising the possibility that Notch3 mediates human T-lineage specification. Although expression of a constitutive activated form of Notch3 (ICN3) results in the induction of T-lineage specification in human CD34(+) hematopoietic progenitor cells, similar to ICN1 overexpression, loss-of-function studies using blocking Abs reveal that only Notch1, but not Notch3, is critical in this process. Blocking of Notch1 activation in OP9-DLL4 cocultures resulted in a complete block in T-lineage specification and induced monocytic and plasmacytoid dendritic cell differentiation instead. In fetal thymus organ cultures, impeded Notch1 activation resulted in B and dendritic cell development. In contrast, Notch3 blocking Abs only marginally affected T-lineage specification and hematopoietic differentiation with a slight increase in monocyte development. No induction of B or dendritic cell development was observed. Thus, our results unambiguously reveal a nonredundant role for Notch1 in human T-lineage specification, despite the expression of other Notch receptors. Copyright © 2014 by The American Association of Immunologists, Inc.

  18. Dynamics and Fate of Beneficial Mutations Under Lineage Contamination by Linked Deleterious Mutations.

    PubMed

    Pénisson, Sophie; Singh, Tanya; Sniegowski, Paul; Gerrish, Philip

    2017-03-01

    Beneficial mutations drive adaptive evolution, yet their selective advantage does not ensure their fixation. Haldane's application of single-type branching process theory showed that genetic drift alone could cause the extinction of newly arising beneficial mutations with high probability. With linkage, deleterious mutations will affect the dynamics of beneficial mutations and might further increase their extinction probability. Here, we model the lineage dynamics of a newly arising beneficial mutation as a multitype branching process. Our approach accounts for the combined effects of drift and the stochastic accumulation of linked deleterious mutations, which we call lineage contamination We first study the lineage-contamination phenomenon in isolation, deriving dynamics and survival probabilities (the complement of extinction probabilities) of beneficial lineages. We find that survival probability is zero when [Formula: see text] where U is deleterious mutation rate and [Formula: see text] is the selective advantage of the beneficial mutation in question, and is otherwise depressed below classical predictions by a factor bounded from below by [Formula: see text] We then put the lineage contamination phenomenon into the context of an evolving population by incorporating the effects of background selection. We find that, under the combined effects of lineage contamination and background selection, ensemble survival probability is never zero but is depressed below classical predictions by a factor bounded from below by [Formula: see text] where [Formula: see text] is mean selective advantage of beneficial mutations, and [Formula: see text] This factor, and other bounds derived from it, are independent of the fitness effects of deleterious mutations. At high enough mutation rates, lineage contamination can depress fixation probabilities to values that approach zero. This fact suggests that high mutation rates can, perhaps paradoxically, (1) alleviate competition

  19. Computational Implementation of a Thermodynamically Based Work Potential Model For Progressive Microdamage and Transverse Cracking in Fiber-Reinforced Laminates

    NASA Technical Reports Server (NTRS)

    Pineda, Evan J.; Waas, Anthony M.; Bednarcyk, Brett A.; Collier, Craig S.

    2012-01-01

    A continuum-level, dual internal state variable, thermodynamically based, work potential model, Schapery Theory, is used capture the effects of two matrix damage mechanisms in a fiber-reinforced laminated composite: microdamage and transverse cracking. Matrix microdamage accrues primarily in the form of shear microcracks between the fibers of the composite. Whereas, larger transverse matrix cracks typically span the thickness of a lamina and run parallel to the fibers. Schapery Theory uses the energy potential required to advance structural changes, associated with the damage mechanisms, to govern damage growth through a set of internal state variables. These state variables are used to quantify the stiffness degradation resulting from damage growth. The transverse and shear stiffness of the lamina are related to the internal state variables through a set of measurable damage functions. Additionally, the damage variables for a given strain state can be calculated from a set of evolution equations. These evolution equations and damage functions are implemented into the finite element method and used to govern the constitutive response of the material points in the model. Additionally, an axial failure criterion is included in the model. The response of a center-notched, buffer strip-stiffened panel subjected to uniaxial tension is investigated and results are compared to experiment.

  20. Lineage specific recombination rates and microevolution in Listeria monocytogenes

    PubMed Central

    2008-01-01

    Background The bacterium Listeria monocytogenes is a saprotroph as well as an opportunistic human foodborne pathogen, which has previously been shown to consist of at least two widespread lineages (termed lineages I and II) and an uncommon lineage (lineage III). While some L. monocytogenes strains show evidence for considerable diversification by homologous recombination, our understanding of the contribution of recombination to L. monocytogenes evolution is still limited. We therefore used STRUCTURE and ClonalFrame, two programs that model the effect of recombination, to make inferences about the population structure and different aspects of the recombination process in L. monocytogenes. Analyses were performed using sequences for seven loci (including the house-keeping genes gap, prs, purM and ribC, the stress response gene sigB, and the virulence genes actA and inlA) for 195 L. monocytogenes isolates. Results Sequence analyses with ClonalFrame and the Sawyer's test showed that recombination is more prevalent in lineage II than lineage I and is most frequent in two house-keeping genes (ribC and purM) and the two virulence genes (actA and inlA). The relative occurrence of recombination versus point mutation is about six times higher in lineage II than in lineage I, which causes a higher genetic variability in lineage II. Unlike lineage I, lineage II represents a genetically heterogeneous population with a relatively high proportion (30% average) of genetic material imported from external sources. Phylograms, constructed with correcting for recombination, as well as Tajima's D data suggest that both lineages I and II have suffered a population bottleneck. Conclusion Our study shows that evolutionary lineages within a single bacterial species can differ considerably in the relative contributions of recombination to genetic diversification. Accounting for recombination in phylogenetic studies is critical, and new evolutionary models that account for the possibility

  1. Lineage specific recombination rates and microevolution in Listeria monocytogenes.

    PubMed

    den Bakker, Henk C; Didelot, Xavier; Fortes, Esther D; Nightingale, Kendra K; Wiedmann, Martin

    2008-10-08

    The bacterium Listeria monocytogenes is a saprotroph as well as an opportunistic human foodborne pathogen, which has previously been shown to consist of at least two widespread lineages (termed lineages I and II) and an uncommon lineage (lineage III). While some L. monocytogenes strains show evidence for considerable diversification by homologous recombination, our understanding of the contribution of recombination to L. monocytogenes evolution is still limited. We therefore used STRUCTURE and ClonalFrame, two programs that model the effect of recombination, to make inferences about the population structure and different aspects of the recombination process in L. monocytogenes. Analyses were performed using sequences for seven loci (including the house-keeping genes gap, prs, purM and ribC, the stress response gene sigB, and the virulence genes actA and inlA) for 195 L. monocytogenes isolates. Sequence analyses with ClonalFrame and the Sawyer's test showed that recombination is more prevalent in lineage II than lineage I and is most frequent in two house-keeping genes (ribC and purM) and the two virulence genes (actA and inlA). The relative occurrence of recombination versus point mutation is about six times higher in lineage II than in lineage I, which causes a higher genetic variability in lineage II. Unlike lineage I, lineage II represents a genetically heterogeneous population with a relatively high proportion (30% average) of genetic material imported from external sources. Phylograms, constructed with correcting for recombination, as well as Tajima's D data suggest that both lineages I and II have suffered a population bottleneck. Our study shows that evolutionary lineages within a single bacterial species can differ considerably in the relative contributions of recombination to genetic diversification. Accounting for recombination in phylogenetic studies is critical, and new evolutionary models that account for the possibility of changes in the rate of

  2. Recent progress in OLED and flexible displays and their potential for application to aerospace and military display systems

    NASA Astrophysics Data System (ADS)

    Sarma, Kalluri

    2015-05-01

    Organic light emitting diode (OLED) display technology has advanced significantly in recent years and it is increasingly being adapted in consumer electronics products with premium performance, such as high resolution smart phones, Tablet PCs and TVs. Even flexible OLED displays are beginning to be commercialized in consumer electronic devices such as smart phones and smart watches. In addition to the advances in OLED emitters, successful development and adoption of OLED displays for premium performance applications relies on the advances in several enabling technologies including TFT backplanes, pixel drive electronics, pixel patterning technologies, encapsulation technologies and system level engineering. In this paper we will discuss the impact of the recent advances in LTPS and AOS TFTs, R, G, B and White OLED with color filter pixel architectures, and encapsulation, on the success of the OLEDs in consumer electronic devices. We will then discuss potential of these advances in addressing the requirements of OLED and flexible displays for the military and avionics applications.

  3. FY 1999 Progress Report on: Potential Groundwater Recharge from the Infiltration of Surface Runoff in Cold and Dry Creeks

    SciTech Connect

    Wigmosta, Mark S.; Guensch, Gregory R.

    2006-12-31

    The volume of water available for groundwater recharge through the infiltration of surface runoff in Cold and Dry Creeks was estimated for a 100-year storm and the Probable Maximum Precipitation (PMP) of Skaggs and Walters (1981). A 100-year, 7-day design storm was developed from 40 years of precipitation data measured at the Hanford Meteorological Station (HMS). Runoff measured in Upper Cold Creek was used with HMS precipitation data to calculate curve numbers for the Soil Conservation Service rainfall-runoff model. The estimated water available for recharge from surface runoff produced by the 100-year storm is 3-6 times the annual recharge rate from direct infiltration of precipitation over the Hanford Site. Potential recharge from the PMP is 7-11 times the annual volume of direct recharge.

  4. Progress in Evaluating Potential EM Earthquake Precursors: Comparison of Independent Ultra Low-Frequency Electro-Magnetic (ULFEM) Systems

    NASA Astrophysics Data System (ADS)

    Chen, B.; Glen, J. M. G.; Klemperer, S. L.; Christman, L.; Bleier, T.; Dunson, J. C.; DeKlotz, M.

    2014-12-01

    Ultra-low frequency anomalies in the magnetic and electric fields have been reported prior to several earthquakes. Because most prominent ULFEM anomalies have thus far only been observed on individual stations, some authors have argued that some of these anomalies have an instrumental cause, rather than being earthquake precursors. Two independent ULFEM networks are presently operating in the greater San Francisco Bay Area; one managed by the U.S. Geological Survey (USGS) and Stanford University and the other by QuakeFinder (QF).The case that these anomalies are not instrumental would be strengthened by a demonstration that identical anomalies are seen on the two networks, despite their different components (magnetometers, digitizers and telemetry). A detailed comparison of the two systems will allow data from each of the two networks to be used to confirm anomalies and to evaluate potential precursor signals. To provide this comparison, the USGS-Stanford and QF acquired data on two independent ULFEM systems at the USGS-Stanford ULFEM station located at the Jasper Ridge Biological Preserve, CA, from March 31-May 13, 2014. The two systems were set up~50m from each other and away from potential sources of noise. Both systems recorded the magnetic field with induction coils oriented along the three cardinal directions aligned with magnetic north. The results of this experiment reveal that the two systems have very similar response functions and comparable noise and drift characteristics. Both complex "noise" (a, b) and single discrete pulses (c, d) were recorded with essentially identical characteristics by the two systems. We also found, in a few instances, where the signals were observed on one system but were absent on the other, clearly indicating either internal system noise or reflecting extremely local site phenomena affecting a single system. Future efforts will involve analyses of pulses, spectral characteristics, correlation coefficients and noise.

  5. Multi-parent advanced generation inter-cross (MAGIC) populations in rice: progress and potential for genetics research and breeding.

    PubMed

    Bandillo, Nonoy; Raghavan, Chitra; Muyco, Pauline Andrea; Sevilla, Ma Anna Lynn; Lobina, Irish T; Dilla-Ermita, Christine Jade; Tung, Chih-Wei; McCouch, Susan; Thomson, Michael; Mauleon, Ramil; Singh, Rakesh Kumar; Gregorio, Glenn; Redoña, Edilberto; Leung, Hei

    2013-05-06

    This article describes the development of Multi-parent Advanced Generation Inter-Cross populations (MAGIC) in rice and discusses potential applications for mapping quantitative trait loci (QTLs) and for rice varietal development. We have developed 4 multi-parent populations: indica MAGIC (8 indica parents); MAGIC plus (8 indica parents with two additional rounds of 8-way F1 inter-crossing); japonica MAGIC (8 japonica parents); and Global MAGIC (16 parents - 8 indica and 8 japonica). The parents used in creating these populations are improved varieties with desirable traits for biotic and abiotic stress tolerance, yield, and grain quality. The purpose is to fine map QTLs for multiple traits and to directly and indirectly use the highly recombined lines in breeding programs. These MAGIC populations provide a useful germplasm resource with diverse allelic combinations to be exploited by the rice community. The indica MAGIC population is the most advanced of the MAGIC populations developed thus far and comprises 1328 lines produced by single seed descent (SSD). At the S4 stage of SSD a subset (200 lines) of this population was genotyped using a genotyping-by-sequencing (GBS) approach and was phenotyped for multiple traits, including: blast and bacterial blight resistance, salinity and submergence tolerance, and grain quality. Genome-wide association mapping identified several known major genes and QTLs including Sub1 associated with submergence tolerance and Xa4 and xa5 associated with resistance to bacterial blight. Moreover, the genome-wide association study (GWAS) results also identified potentially novel loci associated with essential traits for rice improvement. The MAGIC populations serve a dual purpose: permanent mapping populations for precise QTL mapping and for direct and indirect use in variety development. Unlike a set of naturally diverse germplasm, this population is tailor-made for breeders with a combination of useful traits derived from multiple elite

  6. Saffold Cardioviruses of 3 Lineages in Children with Respiratory Tract Infections, Beijing, China

    PubMed Central

    Ren, Lili; Gonzalez, Richard; Xie, Zhengde; Xiao, Yan; Li, Yongjun; Liu, Chunyan; Chen, Lan; Yang, Qingqing; Vernet, Guy; Paranhos-Baccalà, Gláucia; Jin, Qi; Shen, Kunling

    2010-01-01

    To clarify the potential for respiratory transmission of Saffold cardiovirus (SAFV) and characterize the pathogen, we analyzed respiratory specimens from 1,558 pediatric patients in Beijing. We detected SAFV in 7 (0.5%) patients and identified lineages 1–3. However, because 3 patients had co-infections, we could not definitively say SAFV caused disease. PMID:20587195

  7. Do asexual polyploid lineages lead short evolutionary lives? A case study from the fern genus Astrolepis.

    PubMed

    Beck, James B; Windham, Michael D; Pryer, Kathleen M

    2011-11-01

    A life-history transition to asexuality is typically viewed as leading to a heightened extinction risk, and a number of studies have evaluated this claim by examining the relative ages of asexual versus closely related sexual lineages. Surprisingly, a rigorous assessment of the age of an asexual plant lineage has never been published, although asexuality is extraordinarily common among plants. Here, we estimate the ages of sexual diploids and asexual polyploids in the fern genus Astrolepis using a well-supported plastid phylogeny and a relaxed-clock dating approach. The 50 asexual polyploid samples we included were conservatively estimated to comprise 19 distinct lineages, including a variety of auto- and allopolyploid genomic combinations. All were either the same age or younger than the crown group comprising their maternal sexual-diploid parents based simply on their phylogenetic position. Node ages estimated with the relaxed-clock approach indicated that the average maximum age of asexual lineages was 0.4 My, and individual lineages were on average 7 to 47 times younger than the crown- and total-ages of their sexual parents. Although the confounding association between asexuality and polyploidy precludes definite conclusions regarding the effect of asexuality, our results suggest that asexuality limits evolutionary potential in Astrolepis.

  8. Differential development of progenitor activity for three B-cell lineages.

    PubMed Central

    Kantor, A B; Stall, A M; Adams, S; Herzenberg, L A; Herzenberg, L A

    1992-01-01

    Cell-transfer studies presented here distinguish three murine B cell lineages: conventional B cells, which develop late and are continually replenished from progenitors in adult bone marrow; Ly-1 B cells (B-1a), which develop early and maintain their numbers by self-replenishment; and Ly-1B "sister" (B-1b) cells, which share many of the properties of Ly-1 B cells, including self-replenishment and feedback regulation of development but can also readily develop from progenitors in adult bone marrow. The sequential emergence of these lineages, the time at which their progenitors function during ontogeny, and the distinctions among their repertoires and functions suggest that evolution has created a layered immune system in which the immune response potential of each successive lineage is adapted to its particular niche. Images PMID:1565622

  9. PHF6 regulates phenotypic plasticity through chromatin organization within lineage-specific genes.

    PubMed

    Soto-Feliciano, Yadira M; Bartlebaugh, Jordan M E; Liu, Yunpeng; Sánchez-Rivera, Francisco J; Bhutkar, Arjun; Weintraub, Abraham S; Buenrostro, Jason D; Cheng, Christine S; Regev, Aviv; Jacks, Tyler E; Young, Richard A; Hemann, Michael T

    2017-05-15

    Developmental and lineage plasticity have been observed in numerous malignancies and have been correlated with tumor progression and drug resistance. However, little is known about the molecular mechanisms that enable such plasticity to occur. Here, we describe the function of the plant homeodomain finger protein 6 (PHF6) in leukemia and define its role in regulating chromatin accessibility to lineage-specific transcription factors. We show that loss of Phf6 in B-cell leukemia results in systematic changes in gene expression via alteration of the chromatin landscape at the transcriptional start sites of B-cell- and T-cell-specific factors. Additionally, Phf6(KO) cells show significant down-regulation of genes involved in the development and function of normal B cells, show up-regulation of genes involved in T-cell signaling, and give rise to mixed-lineage lymphoma in vivo. Engagement of divergent transcriptional programs results in phenotypic plasticity that leads to altered disease presentation in vivo, tolerance of aberrant oncogenic signaling, and differential sensitivity to frontline and targeted therapies. These findings suggest that active maintenance of a precise chromatin landscape is essential for sustaining proper leukemia cell identity and that loss of a single factor (PHF6) can cause focal changes in chromatin accessibility and nucleosome positioning that render cells susceptible to lineage transition. © 2017 Soto-Feliciano et al.; Published by Cold Spring Harbor Laboratory Press.

  10. Insights into the Development of the Adult Leydig Cell Lineage from Stem Leydig Cells.

    PubMed

    Ye, Leping; Li, Xiaoheng; Li, Linxi; Chen, Haolin; Ge, Ren-Shan

    2017-01-01

    Adult Leydig cells (ALCs) are the steroidogenic cells in the testes that produce testosterone. ALCs develop postnatally from a pool of stem cells, referred to as stem Leydig cells (SLCs). SLCs are spindle-shaped cells that lack steroidogenic cell markers, including luteinizing hormone (LH) receptor and 3β-hydroxysteroid dehydrogenase. The commitment of SLCs into the progenitor Leydig cells (PLCs), the first stage in the lineage, requires growth factors, including Dessert Hedgehog (DHH) and platelet-derived growth factor-AA. PLCs are still spindle-shaped, but become steroidogenic and produce mainly androsterone. The next transition in the lineage is from PLC to the immature Leydig cell (ILC). This transition requires LH, DHH, and androgen. ILCs are ovoid cells that are competent for producing a different form of androgen, androstanediol. The final stage in the developmental lineage is ALC. The transition to ALC involves the reduced expression of 5α-reductase 1, a step that is necessary to make the cells to produce testosterone as the final product. The transitions along the Leydig cell lineage are associated with the progressive down-regulation of the proliferative activity, and the up-regulation of steroidogenic capacity, with each step requiring unique regulatory signaling.

  11. Insights into the Development of the Adult Leydig Cell Lineage from Stem Leydig Cells

    PubMed Central

    Ye, Leping; Li, Xiaoheng; Li, Linxi; Chen, Haolin; Ge, Ren-Shan

    2017-01-01

    Adult Leydig cells (ALCs) are the steroidogenic cells in the testes that produce testosterone. ALCs develop postnatally from a pool of stem cells, referred to as stem Leydig cells (SLCs). SLCs are spindle-shaped cells that lack steroidogenic cell markers, including luteinizing hormone (LH) receptor and 3β-hydroxysteroid dehydrogenase. The commitment of SLCs into the progenitor Leydig cells (PLCs), the first stage in the lineage, requires growth factors, including Dessert Hedgehog (DHH) and platelet-derived growth factor-AA. PLCs are still spindle-shaped, but become steroidogenic and produce mainly androsterone. The next transition in the lineage is from PLC to the immature Leydig cell (ILC). This transition requires LH, DHH, and androgen. ILCs are ovoid cells that are competent for producing a different form of androgen, androstanediol. The final stage in the developmental lineage is ALC. The transition to ALC involves the reduced expression of 5α-reductase 1, a step that is necessary to make the cells to produce testosterone as the final product. The transitions along the Leydig cell lineage are associated with the progressive down-regulation of the proliferative activity, and the up-regulation of steroidogenic capacity, with each step requiring unique regulatory signaling. PMID:28701961

  12. Mutual antagonism between Sox10 and NFIA regulates diversification of glial lineages and glioma subtypes.

    PubMed

    Glasgow, Stacey M; Zhu, Wenyi; Stolt, C Claus; Huang, Teng-Wei; Chen, Fuyi; LoTurco, Joseph J; Neul, Jeffrey L; Wegner, Michael; Mohila, Carrie; Deneen, Benjamin

    2014-10-01

    Lineage progression and diversification is regulated by the coordinated action of unique sets of transcription factors. Oligodendrocytes (OL) and astrocytes (AS) comprise the glial sub-lineages in the CNS, and the manner in which their associated regulatory factors orchestrate lineage diversification during development and disease remains an open question. Sox10 and NFIA are key transcriptional regulators of gliogenesis associated with OL and AS. We found that NFIA inhibited Sox10 induction of OL differentiation through direct association and antagonism of its function. Conversely, we found that Sox10 antagonized NFIA function and suppressed AS differentiation in mouse and chick systems. Using this developmental paradigm as a model for glioma, we found that this relationship similarly regulated the generation of glioma subtypes. Our results describe the antagonistic relationship between Sox10 and NFIA that regulates the balance of OL and AS fate during development and demonstrate for the first time, to the best of our knowledge, that the transcriptional processes governing glial sub-lineage diversification oversee the generation of glioma subtypes.

  13. Heterochronic misexpression of Ascl1 in the Atoh7 retinal cell lineage blocks cell cycle exit.

    PubMed

    Hufnagel, Robert B; Riesenberg, Amy N; Quinn, Malgorzata; Brzezinski, Joseph A; Glaser, Tom; Brown, Nadean L

    2013-05-01

    Retinal neurons and glia arise from a common progenitor pool in a temporal order, with retinal ganglion cells (RGCs) appearing first, and Müller glia last. The transcription factors Atoh7/Math5 and Ascl1/Mash1 represent divergent bHLH clades, and exhibit distinct spatial and temporal retinal expression patterns, with little overlap during early development. Here, we tested the ability of Ascl1 to change the fate of cells in the Atoh7 lineage when misexpressed from the Atoh7 locus, using an Ascl1-IRES-DsRed2 knock-in allele. In Atoh7(Ascl1KI/+) and Atoh7(Ascl1KI/Ascl1KI) embryos, ectopic Ascl1 delayed cell cycle exit and differentiation, even in cells coexpressing Atoh7. The heterozygous retinas recovered, and eventually produced a normal complement of RGCs, while homozygous substitution of Ascl1 for Atoh7 did not promote postnatal retinal fates precociously, nor rescue Atoh7 mutant phenotypes. However, our analyses revealed two unexpected findings. First, ectopic Ascl1 disrupted cell cycle progression within the marked Atoh7 lineage, but also nonautonomously in other retinal cells. Second, the size of the Atoh7 retinal lineage was unaffected, supporting the idea of a compensatory shift of the non-proliferative cohort to maintain lineage size. Overall, we conclude that Ascl1 acts dominantly to block cell cycle exit, but is incapable of redirecting the fates of early RPCs.

  14. Recent progress in the understanding of tissue culture-induced genome level changes in plants and potential applications.

    PubMed

    Neelakandan, Anjanasree K; Wang, Kan

    2012-04-01

    In vitro cell and tissue-based systems have tremendous potential in fundamental research and for commercial applications such as clonal propagation, genetic engineering and production of valuable metabolites. Since the invention of plant cell and tissue culture techniques more than half a century ago, scientists have been trying to understand the morphological, physiological, biochemical and molecular changes associated with tissue culture responses. Establishment of de novo developmental cell fate in vitro is governed by factors such as genetic make-up, stress and plant growth regulators. In vitro culture is believed to destabilize the genetic and epigenetic program of intact plant tissue and can lead to chromosomal and DNA sequence variations, methylation changes, transposon activation, and generation of somaclonal variants. In this review, we discuss the current status of understanding the genomic and epigenomic changes that take place under in vitro conditions. It is hoped that a precise and comprehensive knowledge of the molecular basis of these variations and acquisition of developmental cell fate would help to devise strategies to improve the totipotency and embryogenic capability in recalcitrant species and genotypes, and to address bottlenecks associated with clonal propagation.

  15. Computational study involving identification of endocrine disrupting potential of herbicides: Its implication in TDS and cancer progression in CRPC patients.

    PubMed

    Ahmad, Md Irshad; Usman, Afia; Ahmad, Masood

    2017-04-01

    Several environmental pollutants, including herbicides, act as endocrine disrupting chemicals (EDCs). They can cause cancer, diabetes, obesity, metabolic diseases and developmental problems. Present study was conducted to screen 608 herbicides for evaluating their endocrine disrupting potential. The screening was carried out with the help of endocrine disruptome docking program, http://endocrinedisruptome.ki.si (Kolsek et al., 2013). This program screens the binding affinity of test ligands to 12 major nuclear receptors. As high as 252 compounds were capable of binding to at least three receptors wherein 10 of them showed affinity with at-least six receptors based on this approach. The latter were ranked as potent EDCs. Majority of the screened herbicides were acting as antagonists of human androgen receptor (hAR). A homology modeling approach was used to construct the three dimensional structure of hAR to understand their binding mechanism. Docking results reveal that the most potent antiandrogenic herbicides would bind to hydrophobic cavity of modeled hAR and may lead to testicular dysgenesis syndrome (TDS) on fetal exposure. However, on binding to T877 mutant AR they seem to act as agonists in castration-resistant prostate cancer (CRPC) patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Role of Chemokine Network in the Development and Progression of Ovarian Cancer: A Potential Novel Pharmacological Target

    PubMed Central

    Barbieri, Federica; Bajetto, Adriana; Florio, Tullio

    2010-01-01

    Ovarian cancer is the most common type of gynecologic malignancy. Despite advances in surgery and chemotherapy, the survival rate is still low since most ovarian cancers relapse and become drug-resistant. Chemokines are small chemoattractant peptides mainly involved in the immune responses. More recently, chemokines were also demonstrated to regulate extra-immunological functions. It was shown that the chemokine network plays crucial functions in the tumorigenesis in several tissues. In particular the imbalanced or aberrant expression of CXCL12 and its receptor CXCR4 strongly affects cancer cell proliferation, recruitment of immunosuppressive cells, neovascularization, and metastasization. In the last years, several molecules able to target CXCR4 or CXCL12 have been developed to interfere with tumor growth, including pharmacological inhibitors, antagonists, and specific antibodies. This chemokine ligand/receptor pair was also proposed to represent an innovative therapeutic target for the treatment of ovarian cancer. Thus, a thorough understanding of ovarian cancer biology, and how chemokines may control these different biological activities might lead to the development of more effective therapies. This paper will focus on the current biology of CXCL12/CXCR4 axis in the context of understanding their potential role in ovarian cancer development. PMID:20049170

  17. Evolution of two prototypic T cell lineages

    PubMed Central

    Das, Sabyasachi; Li, Jianxu; Hirano, Masayuki; Sutoh, Yoichi; Herrin, Brantley R.; Cooper, Max D.

    2015-01-01

    Jawless vertebrates, which occupy a unique position in chordate phylogeny, employ leucine-rich repeat (LRR)-based variable lymphocyte receptors (VLR) for antigen recognition. During the assembly of the VLR genes (VLRA, VLRB and VLRC), donor LRR-encoding sequences are copied in a step-wise manner into the incomplete germ-line genes. The assembled VLR genes are differentially expressed by discrete lymphocyte lineages: VLRA- and VLRC-producing cells are T-cell like, whereas VLRB-producing cells are B-cell like. VLRA+ and VLRC+ lymphocytes resemble the two principal T-cell lineages of jawed vertebrates that express the αβ or γδ T-cell receptors (TCR). Reminiscent of the interspersed nature of the TCRα/TCRδ locus in jawed vertebrates, the close proximity of the VLRA and VLRC loci facilitates sharing of donor LRR sequences during VLRA and VLRC assembly. Here we discuss the insight these findings provide into vertebrate T- and B-cell evolution, and the alternative types of anticipatory receptors they use for adaptive immunity. PMID:25958271

  18. Evolution of two prototypic T cell lineages.

    PubMed

    Das, Sabyasachi; Li, Jianxu; Hirano, Masayuki; Sutoh, Yoichi; Herrin, Brantley R; Cooper, Max D

    2015-07-01

    Jawless vertebrates, which occupy a unique position in chordate phylogeny, employ leucine-rich repeat (LRR)-based variable lymphocyte receptors (VLR) for antigen recognition. During the assembly of the VLR genes (VLRA, VLRB and VLRC), donor LRR-encoding sequences are copied in a step-wise manner into the incomplete germ-line genes. The assembled VLR genes are differentially expressed by discrete lymphocyte lineages: VLRA- and VLRC-producing cells are T-cell like, whereas VLRB-producing cells are B-cell like. VLRA(+) and VLRC(+) lymphocytes resemble the two principal T-cell lineages of jawed vertebrates that express the αβ or γδ T-cell receptors (TCR). Reminiscent of the interspersed nature of the TCRα/TCRδ locus in jawed vertebrates, the close proximity of the VLRA and VLRC loci facilitates sharing of donor LRR sequences during VLRA and VLRC assembly. Here we discuss the insight these findings provide into vertebrate T- and B-cell evolution, and the alternative types of anticipatory receptors they use for adaptive immunity. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Origin of strigolactones in the green lineage.

    PubMed

    Delaux, Pierre-Marc; Xie, Xiaonan; Timme, Ruth E; Puech-Pages, Virginie; Dunand, Christophe; Lecompte, Emilie; Delwiche, Charles F; Yoneyama, Koichi; Bécard, Guillaume; Séjalon-Delmas, Nathalie

    2012-09-01

    The aims of this study were to investigate the appearance of strigolactones in the green lineage and to determine the primitive function of these molecules. We measured the strigolactone content of several isolated liverworts, mosses, charophyte and chlorophyte green algae using a sensitive biological assay and LC-MS/MS analyses. In parallel, sequence comparison of strigolactone-related genes and phylogenetic analyses were performed using available genomic data and newly sequenced expressed sequence tags. The primitive function of strigolactones was determined by exogenous application of the synthetic strigolactone analog, GR24, and by mutant phenotyping. Liverworts, the most basal Embryophytes and Charales, one of the closest green algal relatives to Embryophytes, produce strigolactones, whereas several other species of green algae do not. We showed that GR24 stimulates rhizoid elongation of Charales, liverworts and mosses, and rescues the phenotype of the strigolactone-deficient Ppccd8 mutant of Physcomitrella patens. These findings demonstrate that the first function of strigolactones was not to promote arbuscular mycorrhizal symbiosis. Rather, they suggest that the strigolactones appeared earlier in the streptophyte lineage to control rhizoid elongation. They may have been conserved in basal Embryophytes for this role and then recruited for the stimulation of colonization by glomeromycotan fungi.

  20. Retinoids Accelerate B Lineage Lymphoid Differentiation

    PubMed Central

    Chen, Xinrong; Esplin, Brandt L.; Garrett, Karla P.; Welner, Robert S.; Webb, Carol F.

    2008-01-01

    Retinoids are known to have potent effects on hematopoietic stem cell integrity, and our objective was to learn if they influence cells destined to replenish the immune system. Total CD19+ B lineage cells increased substantially in marrow and spleens of ATRA treated C57BL6 mice, while lymphoid progenitors were reduced. All B lymphoid progenitors were targets of ATRA in culture and overall cell yields declined without reductions in proliferation. Remarkably, ATRA shortened the time required for primitive progenitors to generate CD19+ cells. PCR analysis and a panel of RAR/RXR agonist treatments suggested that RARα mediates these responses. The transcription factors EBF1 and Pax-5 were elevated during treatment and ATRA had similar effects on human B cell differentiation. That is, it inhibited the expansion of human progenitor cells and accelerated their differentiation to B lineage cells. There may be previously unsuspected side effects of ATRA therapy, and the new findings suggest retinoids can normally contribute to the lymphopoietic environment in bone marrow. PMID:18097013

  1. Parallel emergence of negative epistasis across experimental lineages.

    PubMed

    Zee, Peter C; Velicer, Gregory J

    2017-01-27

    Epistatic interactions can greatly impact evolutionary phenomena, particularly the process of adaptation. Here, we leverage four parallel experimentally evolved lineages to study the emergence and trajectories of epistatic interactions in the social bacterium Myxococcus xanthus. A social gene (pilA) necessary for effective group swarming on soft agar had been deleted from the common ancestor of these lineages. During selection for competitiveness at the leading edge of growing colonies, two lineages evolved qualitatively novel mechanisms for greatly increased swarming on soft agar, whereas the other two lineages evolved relatively small increases in swarming. By reintroducing pilA into different genetic backgrounds along the four lineages, we tested whether parallel lineages showed similar patterns of epistasis. In particular, we tested whether a pattern of negative epistasis between accumulating mutations and pilA previously found in the fastest lineage would be found only in the two evolved lineages with the fastest and most striking swarming phenotypes, or rather was due to common epistatic structure across all lineages arising from the generic fixation of adaptive mutations. Our analysis reveals the emergence of negative epistasis across all four independent lineages. Further, we present results showing that the observed negative epistasis is not due exclusively to evolving populations approaching a maximum phenotypic value that inherently limits positive effects of pilA reintroduction, but rather involves direct antagonistic interactions between accumulating mutations and the reintroduced social gene.

  2. Contrasting microsatellite diversity in the evolutionary lineages of Phytophthora lateralis.

    PubMed

    Vettraino, AnnaMaria; Brasier, Clive M; Webber, Joan F; Hansen, Everett M; Green, Sarah; Robin, Cecile; Tomassini, Alessia; Bruni, Natalia; Vannini, Andrea

    2017-02-01

    Following recent discovery of Phytophthora lateralis on native Chamaecyparis obtusa in Taiwan, four phenotypically distinct lineages were discriminated: the Taiwan J (TWJ) and Taiwan K (TWK) in Taiwan, the Pacific Northwest (PNW) in North America and Europe and the UK in west Scotland. Across the four lineages, we analysed 88 isolates from multiple sites for microsatellite diversity. Twenty-one multilocus genotypes (MLGs) were resolved with high levels of diversity of the TWK and PNW lineages. No alleles were shared between the PNW and the Taiwanese lineages. TWK was heterozygous at three loci, whereas TWJ isolates were homozygous apart from one isolate, which exhibited a unique allele also present in the TWK lineage. PNW lineage was heterozygous at three loci. The evidence suggests its origin may be a yet unknown Asian source. North American and European PNW isolates shared all their alleles and also a dominant MLG, consistent with a previous proposal that this lineage is a recent introduction into Europe from North America. The UK lineage was monomorphic and homozygous at all loci. It shared its alleles with the PNW and the TWJ and TWK lineages, hence a possible origin in a recent hybridisation event between a Taiwan lineage and PNW cannot be ruled out.

  3. The microRNA-205-5p is correlated to metastatic potential of 21T series: A breast cancer progression model.

    PubMed

    Stankevicins, L; Barat, A; Dessen, P; Vassetzky, Y; de Moura Gallo, C V

    2017-01-01

    MicroRNA is a class of noncoding RNAs able to base pair with complementary messenger RNA sequences, inhibiting their expression. These regulatory molecules play important roles in key cellular processes including cell proliferation, differentiation and response to DNA damage; changes in miRNA expression are a common feature of human cancers. To gain insights into the mechanisms involved in breast cancer progression we conducted a microRNA global expression analysis on a 21T series of cell lines obtained from the same patient during different stages of breast cancer progression. These stages are represented by cell lines derived from normal epithelial (H16N2), atypical ductal hyperplasia (21PT), primary in situ ductal carcinoma (21NT) and pleural effusion of a lung metastasis (21MT-1 and 21MT-2). In a global microRNA expression analysis, miR-205-5p was the only miRNA to display an important downregulation in the metastatic cell lines (21MT-1; 21MT-2) when compared to the non-invasive cells (21PT and 21NT). The lower amounts of miR-205-5p found also correlated with high histological grades biopsies and with higher invasion rates in a Boyden chamber assay. This work pinpoints miR-205-5p as a potential player in breast tumor invasiveness.

  4. Non-hematopoietic PAR-2 is essential for matriptase-driven pre-malignant progression and potentiation of ras-mediated squamous cell carcinogenesis

    PubMed Central

    Sales, Katiuchia Uzzun; Friis, Stine; Konkel, Joanne E.; Godiksen, Sine; Hatakeyama, Marcia; Hansen, Karina K.; Rogatto, Silvia Regina; Szabo, Roman; Vogel, Lotte K.; Chen, Wanjun; Gutkind, J. Silvio; Bugge, Thomas H.

    2014-01-01

    The membrane-anchored serine protease, matriptase, is consistently dysregulated in a range of human carcinomas, and high matriptase activity correlates with poor prognosis. Furthermore, matriptase is unique among tumor-associated proteases in that epithelial stem cell expression of the protease suffices to induce malignant transformation. Here, we use genetic epistasis analysis to identify proteinase-activated receptor (PAR)-2-dependent inflammatory signaling as an essential component of matriptase-mediated oncogenesis. In cell-based assays, matriptase was a potent activator of PAR-2, and PAR-2 activation by matriptase caused robust induction of NFκB through Gαi. Importantly, genetic elimination of PAR-2 from mice completely prevented matriptase-induced pre-malignant progression, including inflammatory cytokine production, inflammatory cell recruitment, epidermal hyperplasia, and dermal fibrosis. Selective ablation of PAR-2 from bone marrow-derived cells did not prevent matriptase-driven pre-malignant progression, indicating that matriptase activates keratinocyte stem cell PAR-2 to elicit its pro-inflammatory and pro-tumorigenic effects. When combined with previous studies, our data suggest that dual induction of PAR-2-NFκB inflammatory signaling and PI3K-Akt-mTor survival/proliferative signaling underlies the transforming potential of matriptase and may contribute to pro-tumorigenic signaling in human epithelial carcinogenesis. PMID:24469043

  5. The microRNA-205-5p is correlated to metastatic potential of 21T series: A breast cancer progression model

    PubMed Central

    Stankevicins, L.; Barat, A.; Dessen, P.; Vassetzky, Y.; de Moura Gallo, C. V.

    2017-01-01

    MicroRNA is a class of noncoding RNAs able to base pair with complementary messenger RNA sequences, inhibiting their expression. These regulatory molecules play important roles in key cellular processes including cell proliferation, differentiation and response to DNA damage; changes in miRNA expression are a common feature of human cancers. To gain insights into the mechanisms involved in breast cancer progression we conducted a microRNA global expression analysis on a 21T series of cell lines obtained from the same patient during different stages of breast cancer progression. These stages are represented by cell lines derived from normal epithelial (H16N2), atypical ductal hyperplasia (21PT), primary in situ ductal carcinoma (21NT) and pleural effusion of a lung metastasis (21MT-1 and 21MT-2). In a global microRNA expression analysis, miR-205-5p was the only miRNA to display an important downregulation in the metastatic cell lines (21MT-1; 21MT-2) when compared to the non-invasive cells (21PT and 21NT). The lower amounts of miR-205-5p found also correlated with high histological grades biopsies and with higher invasion rates in a Boyden chamber assay. This work pinpoints miR-205-5p as a potential player in breast tumor invasiveness. PMID:28346474

  6. Cell hierarchy and lineage commitment in the bovine mammary gland.

    PubMed

    Rauner, Gat; Barash, Itamar

    2012-01-01

    The bovine mammary gland is a favorable organ for studying mammary cell hierarchy due to its robust milk-production capabilities that reflect the adaptation of its cell populations to extensive expansion and differentiation. It also shares basic characteristics with the human breast, and identification of its cell composition may broaden our understanding of the diversity in cell hierarchy among mammals. Here, Lin⁻ epithelial cells were sorted according to expression of CD24 and CD49f into four populations: CD24(med)CD49f(pos) (putative stem cells, puStm), CD24(neg)CD49f(pos) (Basal), CD24(high)CD49f(neg) (putative progenitors, puPgt) and CD24(med)CD49f(neg) (luminal, Lum). These populations maintained differential gene expression of lineage markers and markers of stem cells and luminal progenitors. Of note was the high expression of Stat5a in the puPgt cells, and of Notch1, Delta1, Jagged1 and Hey1 in the puStm and Basal populations. Cultured puStm and Basal cells formed lineage-restricted basal or luminal clones and after re-sorting, colonies that preserved a duct-like alignment of epithelial layers. In contrast, puPgt and Lum cells generated only luminal clones and unorganized colonies. Under non-adherent culture conditions, the puPgt and puStm populations generated significantly more floating colonies. The increase in cell number during culture provides a measure of propagation potential, which was highest for the puStm cells. Taken together, these analyses position puStm cells at the top of the cell hierarchy and denote the presence of both bi-potent and luminally restricted progenitors. In addition, a population of differentiated luminal cells was marked. Finally, combining ALDH activity with cell-surface marker analyses defined a small subpopulation that is potentially stem cell-enriched.

  7. Pre-tumour clones, periodic selection and clonal interference in the origin and progression of gastrointestinal cancer: potential for biomarker development.

    PubMed

    Baker, Ann-Marie; Graham, Trevor A; Wright, Nicholas A

    2013-03-01

    Classically, the risk of cancer progression in premalignant conditions of the gastrointestinal tract is assessed by examining the degree of histological dysplasia. However, there are many putative pro-cancer genetic changes that have occurred in histologically normal tissue well before the onset of dysplasia. Here we summarize the evidence for such pre-tumour clones and the existing technology that can be used to locate these clones and characterize them at the genetic level. We also discuss the mechanisms by which pre-tumour clones may spread through large areas of normal tissue, and highlight emerging theories on how multiple clones compete and interact within the gastrointestinal mucosa. It is important to gain an understanding of these processes, as it is envisaged that certain pre-tumour changes may be powerful predictive markers, with the potential to identify patients at high risk of developing cancer at a much earlier stage.

  8. Analysis of Mycobacterium ulcerans-specific T-cell cytokines for diagnosis of Buruli ulcer disease and as potential indicator for disease progression

    PubMed Central

    Antwi-Berko, Daniel; Mubarik, Yusif; Abass, Kabiru Mohammed; Owusu, Wellington; Owusu-Dabo, Ellis; Debrah, Linda Batsa; Debrah, Alexander Yaw; Jacobsen, Marc; Phillips, Richard O.

    2017-01-01

    subset has the potential to be used as biomarker for diagnosis, severity and/or progression of disease. PMID:28241036

  9. Stem Cell Lineage Infidelity Drives Wound Repair and Cancer.

    PubMed

    Ge, Yejing; Gomez, Nicholas C; Adam, Rene C; Nikolova, Maria; Yang, Hanseul; Verma, Akanksha; Lu, Catherine Pei-Ju; Polak, Lisa; Yuan, Shaopeng; Elemento, Olivier; Fuchs, Elaine

    2017-05-04

    Tissue stem cells contribute to tissue regeneration and wound repair through cellular programs that can be hijacked by cancer cells. Here, we investigate such a phenomenon in skin, where during homeostasis, stem cells of the epidermis and hair follicle fuel their respective tissues. We find that breakdown of stem cell lineage confinement-granting privileges associated with both fates-is not only hallmark but also functional in cancer development. We show that lineage plasticity is critical in wound repair, where it operates transiently to redirect fates. Investigating mechanism, we discover that irrespective of cellular origin, lineage infidelity occurs in wounding when stress-responsive enhancers become activated and override homeostatic enhancers that govern lineage specificity. In cancer, stress-responsive transcription factor levels rise, causing lineage commanders to reach excess. When lineage and stress factors collaborate, they activate oncogenic enhancers that distinguish cancers from wounds. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Differentiation of Human Adipose-derived Stem Cells along the Keratocyte Lineage In vitro

    PubMed Central

    Zhang, Shijia; Espandar, Ladan; Imhof, Kathleen M.P.; Bunnell, Bruce A.

    2013-01-01

    Purpose To evaluate differentiation of human adipose-derived stem cells (hASCs) to the keratocyte lineage by co-culture with primary keratocytes in vitro. Materials and Methods A co-culture system using transwell inserts to grow hASCs on bottom and keratocytes on top in keratocyte differentiating medium (KDM) was developed. hASCs that were cultured in complete culture medium (CCM) and KDM were used as control. After 16 days, hASCs were examined for morphologic changes and proliferation by cell count. qRT-PCR and flow cytometry were used to detect the expression of aldehyde dehydrogenase 3 family, member A1 (ALDH3A1) and keratocan. Results hASCs became more dendritic and elongated in co-culture system relative to CCM and KDM. The doubling time of the cells was longer as differentiation progressed. qRT-PCR showed a definite trend towards increased expression of both ALDH3A1 and keratocan in co-culture system despite statistically non-significant p-values. Flow cytometry showed significantly increased protein levels of ALDH3A1 and keratocan in co-culture system relative to CCM group (p < 0.001) and even relative to KDM group (p < 0.001 for ALDH3A1 and p < 0.01 for keratocan). Conclusion The co-culture method is a promising approach to induce differentiation of stem cell populations prior to in vivo applications. This study reveals an important potential for bioengineering of corneal tissue using autologous multi-potential stem cells. PMID:23936748

  11. Prospective identification of hematopoietic lineage choice by deep learning.

    PubMed

    Buggenthin, Felix; Buettner, Florian; Hoppe, Philipp S; Endele, Max; Kroiss, Manuel; Strasser, Michael; Schwarzfischer, Michael; Loeffler, Dirk; Kokkaliaris, Konstantinos D; Hilsenbeck, Oliver; Schroeder, Timm; Theis, Fabian J; Marr, Carsten

    2017-02-20

    Differentiation alters molecular properties of stem and progenitor cells, leading to changes in their shape and movement characteristics. We present a deep neural network that prospectively predicts lineage choice in differentiating primary hematopoietic progenitors using image patches from brightfield microscopy and cellular movement. Surprisingly, lineage choice can be detected up to three generations before conventional molecular markers are observable. Our approach allows identification of cells with differentially expressed lineage-specifying genes without molecular labeling.

  12. The melanocyte lineage in development and disease

    PubMed Central

    Mort, Richard L.; Jackson, Ian J.; Patton, E. Elizabeth

    2015-01-01

    Melanocyte development provides an excellent model for studying more complex developmental processes. Melanocytes have an apparently simple aetiology, differentiating from the neural crest and migrating through the developing embryo to specific locations within the skin and hair follicles, and to other sites in the body. The study of pigmentation mutations in the mouse provided the initial key to identifying the genes and proteins involved in melanocyte development. In addition, work on chicken has provided important embryological and molecular insights, whereas studies in zebrafish have allowed live imaging as well as genetic and transgenic approaches. This cross-species approach is powerful and, as we review here, has resulted in a detailed understanding of melanocyte development and differentiation, melanocyte stem cells and the role of the melanocyte lineage in diseases such as melanoma. PMID:25670789

  13. The Drosophila cyst stem cell lineage

    PubMed Central

    Zoller, Richard; Schulz, Cordula

    2012-01-01

    In all animals, germline cells differentiate in intimate contact with somatic cells and interactions between germline and soma are particularly important for germline development and function. In the male gonad of Drosophila melanogaster, the developing germline cells are enclosed by somatic cyst cells. The cyst cells are derived from cyst stem cells (CySCs) of somatic origin and codifferentiate with the germline cells. The fast generation cycle and the genetic tractability of Drosophila has made the Drosophila testis an excellent model for studying both the roles of somatic cells in guiding germline development and the interdependence of two separate stem cell lineages. This review focuses on our current understanding of CySC specification, CySC self-renewing divisions, cyst cell differentiation, and soma-germline interactions. Many of the mechanisms guiding these processes in Drosophila testes are similarly essential for the development and function of tissues in other organisms, most importantly for gametogenesis in mammals. PMID:23087834

  14. The melanocyte lineage in development and disease.

    PubMed

    Mort, Richard L; Jackson, Ian J; Patton, E Elizabeth

    2015-02-15

    Melanocyte development provides an excellent model for studying more complex developmental processes. Melanocytes have an apparently simple aetiology, differentiating from the neural crest and migrating through the developing embryo to specific locations within the skin and hair follicles, and to other sites in the body. The study of pigmentation mutations in the mouse provided the initial key to identifying the genes and proteins involved in melanocyte development. In addition, work on chicken has provided important embryological and molecular insights, whereas studies in zebrafish have allowed live imaging as well as genetic and transgenic approaches. This cross-species approach is powerful and, as we review here, has resulted in a detailed understanding of melanocyte development and differentiation, melanocyte stem cells and the role of the melanocyte lineage in diseases such as melanoma. © 2015. Published by The Company of Biologists Ltd.

  15. Analysis of Mycobacterium tuberculosis Genotypic Lineage Distribution in Chile and Neighboring Countries

    PubMed Central

    Lagos, Jaime; Couvin, David; Arata, Loredana; Tognarelli, Javier; Aguayo, Carolina; Leiva, Tamara; Arias, Fabiola; Hormazabal, Juan Carlos; Rastogi, Nalin; Fernández, Jorge

    2016-01-01

    Tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis (MTB), remains a disease of high importance to global public health. Studies into the population structure of MTB have become vital to monitoring possible outbreaks and also to develop strategies regarding disease control. Although Chile has a low incidence of MTB, the current rates of migration have the potential to change this scenario. We collected and analyzed a total of 458 M. tuberculosis isolates (1 isolate per patient) originating from all 15 regions of Chile. The isolates were genotyped using the spoligotyping method and the data obtained were analyzed and compared with the SITVIT2 database. A total of 169 different patterns were identified, of which, 119 patterns (408 strains) corresponded to Spoligotype International Types (SITs) and 50 patterns corresponded to orphan strains. The most abundantly represented SITs/lineages were: SIT53/T1 (11.57%), SIT33/LAM3 (9.6%), SIT42/LAM9 (9.39%), SIT50/H3 (5.9%), SIT37/T3 (5%); analysis of the spoligotyping minimum spanning tree as well as spoligoforest were suggestive of a recent expansion of SIT42, SIT50 and SIT37; all of which potentially evolved from SIT53. The most abundantly represented lineages were LAM (40.6%), T (34.1%) and Haarlem (13.5%). LAM was more prevalent in the Santiago (43.6%) and Concepción (44.1%) isolates, rather than the Iquique (29.4%) strains. The proportion of X lineage was appreciably higher in Iquique and Concepción (11.7% in both) as compared to Santiago (1.6%). Global analysis of MTB lineage distribution in Chile versus neighboring countries showed that evolutionary recent lineages (LAM, T and Haarlem) accounted together for 88.2% of isolates in Chile, a pattern which mirrored MTB lineage distribution in neighboring countries (n = 7378 isolates recorded in SITVIT2 database for Peru, Brazil, Paraguay, and Argentina; and published studies), highlighting epidemiological advantage of Euro-American lineages in this region

  16. Analysis of Mycobacterium tuberculosis Genotypic Lineage Distribution in Chile and Neighboring Countries.

    PubMed

    Lagos, Jaime; Couvin, David; Arata, Loredana; Tognarelli, Javier; Aguayo, Carolina; Leiva, Tamara; Arias, Fabiola; Hormazabal, Juan Carlos; Rastogi, Nalin; Fernández, Jorge

    2016-01-01

    Tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis (MTB), remains a disease of high importance to global public health. Studies into the population structure of MTB have become vital to monitoring possible outbreaks and also to develop strategies regarding disease control. Although Chile has a low incidence of MTB, the current rates of migration have the potential to change this scenario. We collected and analyzed a total of 458 M. tuberculosis isolates (1 isolate per patient) originating from all 15 regions of Chile. The isolates were genotyped using the spoligotyping method and the data obtained were analyzed and compared with the SITVIT2 database. A total of 169 different patterns were identified, of which, 119 patterns (408 strains) corresponded to Spoligotype International Types (SITs) and 50 patterns corresponded to orphan strains. The most abundantly represented SITs/lineages were: SIT53/T1 (11.57%), SIT33/LAM3 (9.6%), SIT42/LAM9 (9.39%), SIT50/H3 (5.9%), SIT37/T3 (5%); analysis of the spoligotyping minimum spanning tree as well as spoligoforest were suggestive of a recent expansion of SIT42, SIT50 and SIT37; all of which potentially evolved from SIT53. The most abundantly represented lineages were LAM (40.6%), T (34.1%) and Haarlem (13.5%). LAM was more prevalent in the Santiago (43.6%) and Concepción (44.1%) isolates, rather than the Iquique (29.4%) strains. The proportion of X lineage was appreciably higher in Iquique and Concepción (11.7% in both) as compared to Santiago (1.6%). Global analysis of MTB lineage distribution in Chile versus neighboring countries showed that evolutionary recent lineages (LAM, T and Haarlem) accounted together for 88.2% of isolates in Chile, a pattern which mirrored MTB lineage distribution in neighboring countries (n = 7378 isolates recorded in SITVIT2 database for Peru, Brazil, Paraguay, and Argentina; and published studies), highlighting epidemiological advantage of Euro-American lineages in this region

  17. New native South American Y chromosome lineages.

    PubMed

    Jota, Marilza S; Lacerda, Daniela R; Sandoval, José R; Vieira, Pedro Paulo R; Ohasi, Dominique; Santos-Júnior, José E; Acosta, Oscar; Cuellar, Cinthia; Revollo, Susana; Paz-Y-Miño, Cesar; Fujita, Ricardo; Vallejo, Gustavo A; Schurr, Theodore G; Tarazona-Santos, Eduardo M; Pena, Sergio Dj; Ayub, Qasim; Tyler-Smith, Chris; Santos, Fabrício R

    2016-07-01

    Many single-nucleotide polymorphisms (SNPs) in the non-recombining region of the human Y chromosome have been described in the last decade. High-coverage sequencing has helped to characterize new SNPs, which has in turn increased the level of detail in paternal phylogenies. However, these paternal lineages still provide insufficient information on population history and demography, especially for Native Americans. The present study aimed to identify informative paternal sublineages derived from the main founder lineage of the Americas-haplogroup Q-L54-in a sample of 1841 native South Americans. For this purpose, we used a Y-chromosomal genotyping multiplex platform and conventional genotyping methods to validate 34 new SNPs that were identified in the present study by sequencing, together with many Y-SNPs previously described in the literature. We updated the haplogroup Q phylogeny and identified two new Q-M3 and three new Q-L54*(xM3) sublineages defined by five informative SNPs, designated SA04, SA05, SA02, SA03 and SA29. Within the Q-M3, sublineage Q-SA04 was mostly found in individuals from ethnic groups belonging to the Tukanoan linguistic family in the northwest Amazon, whereas sublineage Q-SA05 was found in Peruvian and Bolivian Amazon ethnic groups. Within Q-L54*, the derived sublineages Q-SA03 and Q-SA02 were exclusively found among Coyaima individuals (Cariban linguistic family) from Colombia, while Q-SA29 was found only in Maxacali individuals (Jean linguistic family) from southeast Brazil. Furthermore, we validated the usefulness of several published SNPs among indigenous South Americans. This new Y chromosome haplogroup Q phylogeny offers an informative paternal genealogy to investigate the pre-Columbian history of South America.Journal of Human Genetics advance online publication, 31 March 2016; doi:10.1038/jhg.2016.26.

  18. Lineage mapper: A versatile cell and particle tracker

    NASA Astrophysics Data System (ADS)

    Chalfoun, Joe; Majurski, Michael; Dima, Alden; Halter, Michael; Bhadriraju, Kiran; Brady, Mary

    2016-11-01

    The ability to accurately track cells and particles from images is critical to many biomedical problems. To address this, we developed Lineage Mapper, an open-source tracker for time-lapse images of biological cells, colonies, and particles. Lineage Mapper tracks objects independently of the segmentation method, detects mitosis in confluence, separates cell clumps mistakenly segmented as a single cell, provides accuracy and scalability even on terabyte-sized datasets, and creates division and/or fusion lineages. Lineage Mapper has been tested and validated on multiple biological and simulated problems. The software is available in ImageJ and Matlab at isg.nist.gov.

  19. Lineage mapper: A versatile cell and particle tracker

    PubMed Central

    Chalfoun, Joe; Majurski, Michael; Dima, Alden; Halter, Michael; Bhadriraju, Kiran; Brady, Mary

    2016-01-01

    The ability to accurately track cells and particles from images is critical to many biomedical problems. To address this, we developed Lineage Mapper, an open-source tracker for time-lapse images of biological cells, colonies, and particles. Lineage Mapper tracks objects independently of the segmentation method, detects mitosis in confluence, separates cell clumps mistakenly segmented as a single cell, provides accuracy and scalability even on terabyte-sized datasets, and creates division and/or fusion lineages. Lineage Mapper has been tested and validated on multiple biological and simulated problems. The software is available in ImageJ and Matlab at isg.nist.gov. PMID:27853188

  20. The C(4) plant lineages of planet Earth.

    PubMed

    Sage, Rowan F; Christin, Pascal-Antoine; Edwards, Erika J

    2011-05-01

    Using isotopic screens, phylogenetic assessments, and 45 years of physiological data, it is now possible to identify most of the evolutionary lineages expressing the C(4) photosynthetic pathway. Here, 62 recognizable lineages of C(4) photosynthesis are listed. Thirty-six lineages (60%) occur in the eudicots. Monocots account for 26 lineages, with a minimum of 18 lineages being present in the grass family and six in the sedge family. Species exhibiting the C(3)-C(4) intermediate type of photosynthesis correspond to 21 lineages. Of these, 9 are not immediately associated with any C(4) lineage, indicating that they did not share common C(3)-C(4) ancestors with C(4) species and are instead an independent line. The geographic centre of origin for 47 of the lineages could be estimated. These centres tend to cluster in areas corresponding to what are now arid to semi-arid regions of southwestern North America, south-central South America, central Asia, northeastern and southern Africa, and inland Australia. With 62 independent lineages, C(4) photosynthesis has to be considered one of the most convergent of the complex evolutionary phenomena on planet Earth, and is thus an outstanding system to study the mechanisms of evolutionary adaptation.

  1. Cardiovascular Development and the Colonizing Cardiac Neural Crest Lineage

    PubMed Central

    Snider, Paige; Olaopa, Michael; Firulli, Anthony B.

    2008-01-01

    regulate myocardial proliferation, can signal to the epicardium to subsequently secrete a growth factor/s, or may even contribute directly to the heart. Although there are species differences between mouse, chick, and Xenopus during cardiac neural crest cell morphogenesis, recent data suggest mouse and chick are more similar to each other than to the zebrafish neural crest cell lineage. Several groups have used the genetically defined Pax3 (splotch) mutant mice model to address the role of the cardiac neural crest lineage. Here we review the current literature, the neural crest-related role of the Pax3 transcription factor, and discuss potential function/s of cardiac neural crest-derived cells during cardiovascular developmental remodeling. PMID:17619792

  2. Systematic Review of Pharmacological Properties of the Oligodendrocyte Lineage

    PubMed Central

    Marinelli, Carla; Bertalot, Thomas; Zusso, Morena; Skaper, Stephen D.; Giusti, Pietro

    2016-01-01

    Oligodendrogenesis and oligodendrocyte precursor maturation are essential processes during the course of central nervous system development, and lead to the myelination of axons. Cells of the oligodendrocyte lineage are generated in the germinal zone from migratory bipolar oligodendrocyte precursor cells (OPCs), and acquire cell surface markers as they mature and respond specifically to factors which regulate proliferation, migration, differentiation, and survival. Loss of myelin underlies a wide range of neurological disorders, some of an autoimmune nature—multiple sclerosis probably being the most prominent. Current therapies are based on the use of immunomodulatory agents which are likely to promote myelin repair (remyelination) indirectly by subverting the inflammatory response, aspects of which impair the differentiation of OPCs. Cells of the oligodendrocyte lineage express and are capable of responding to a diverse array of ligand-receptor pairs, including neurotransmitters and nuclear receptors such as γ-aminobutyric acid, glutamate, adenosine triphosphate, serotonin, acetylcholine, nitric oxide, opioids, prostaglandins, prolactin, and cannabinoids. The intent of this review is to provide the reader with a synopsis of our present state of knowledge concerning the pharmacological properties of the oligodendrocyte lineage, with particular attention to these receptor-ligand (i.e., neurotransmitters and nuclear receptor) interactions that can influence oligodendrocyte migration, proliferation, differentiation, and myelination, and an appraisal of their therapeutic potential. For example, many promising mediators work through Ca2+ signaling, and the balance between Ca2+ influx and efflux can determine the temporal and spatial properties of oligodendrocytes (OLs). Moreover, Ca2+ signaling in OPCs can influence not only differentiation and myelination, but also process extension and migration, as well as cell death in mature mouse OLs. There is also evidence

  3. Unique LCR variations among lineages of HPV16, 18 and 45 isolates from women with normal cervical cytology in Ghana.

    PubMed

    Awua, Adolf K; Adanu, Richard M K; Wiredu, Edwin K; Afari, Edwin A; Zubuch, Vanessa A; Asmah, Richard H; Severini, Alberto

    2017-04-21

    In addition to being useful for classification, sequence variations of human Papillomavirus (HPV) genotypes have been implicated in differential oncogenic potential and a differential association with the different histological forms of invasive cervical cancer. These associations have also been indicated for HPV genotype lineages and sub-lineages. In order to better understand the potential implications of lineage variation in the occurrence of cervical cancers in Ghana, we studied the lineages of the three most prevalent HPV genotypes among women with normal cytology as baseline to further studies. Of previously collected self- and health personnel-collected cervical specimen, 54, which were positive for HPV16, 18 and 45, were selected and the long control region (LCR) of each HPV genotype was separately amplified by a nested PCR. DNA sequences of 41 isolates obtained with the forward and reverse primers by Sanger sequencing were analysed. Nucleotide sequence variations of the HPV16 genotypes were observed at 30 positions within the LCR (7460 - 7840). Of these, 19 were the known variations for the lineages B and C (African lineages), while the other 11 positions had variations unique to the HPV16 isolates of this study. For the HPV18 isolates, the variations were at 35 positions, 22 of which were known variations of Africa lineages and the other 13 were unique variations observed for the isolates obtained in this study (at positions 7799 and 7813). HPV45 isolates had variations at 35 positions and 2 (positions 7114 and 97) were unique to the isolates of this study. This study provides the first data on the lineages of HPV 16, 18 and 45 isolates from Ghana. Although the study did not obtain full genome sequence data for a comprehensive comparison with known lineages, these genotypes were predominately of the Africa lineages and had some unique sequence variations at positions that suggest potential oncogenic implications. These data will be useful for comparison

  4. Accuracy of Answers to Cell Lineage Questions Depends on Single-Cell Genomics Data Quality and Quantity.

    PubMed

    Spiro, Adam; Shapiro, Ehud

    2016-06-01

    Advances in single-cell (SC) genomics enable commensurate improvements in methods for uncovering lineage relations among individual cells, as determined by phylogenetic analysis of the somatic mutations harbored by each cell. Theoretically, complete and accurate knowledge of the genome of each cell of an individual can produce an extremely accurate cell lineage tree of that individual. However, the reality of SC genomics is that such complete and accurate knowledge would be wanting, in quality and in quantity, for the foreseeable future. In this paper we offer a framework for systematically exploring the feasibility of answering cell lineage questions based on SC somatic mutational analysis, as a function of SC genomics data quality and quantity. We take into consideration the current limitations of SC genomics in terms of mutation data quality, most notably amplification bias and allele dropouts (ADO), as well as cost, which puts practical limits on mutation data quantity obtained from each cell as well as on cell sample density. We do so by generating in silico cell lineage trees using a dedicated formal language, eSTG, and show how the ability to answer correctly a cell lineage question depends on the quality and quantity of the SC mutation data. The presented framework can serve as a baseline for the potential of current SC genomics to unravel cell lineage dynamics, as well as the potential contributions of future advancement, both biochemical and computational, for the task.

  5. Distinct lineages of Ebola virus in Guinea during the 2014 West African epidemic.

    PubMed

    Simon-Loriere, Etienne; Faye, Ousmane; Faye, Oumar; Koivogui, Lamine; Magassouba, Nfaly; Keita, Sakoba; Thiberge, Jean-Michel; Diancourt, Laure; Bouchier, Christiane; Vandenbogaert, Matthias; Caro, Valérie; Fall, Gamou; Buchmann, Jan P; Matranga, Christan B; Sabeti, Pardis C; Manuguerra, Jean-Claude; Holmes, Edward C; Sall, Amadou A

    2015-08-06

    An epidemic of Ebola virus disease of unprecedented scale has been ongoing for more than a year in West Africa. As of 29 April 2015, there have been 26,277 reported total cases (of which 14,895 have been laboratory confirmed) resulting in 10,899 deaths. The source of the outbreak was traced to the prefecture of Guéckédou in the forested region of southeastern Guinea. The virus later spread to the capital, Conakry, and to the neighbouring countries of Sierra Leone, Liberia, Nigeria, Senegal and Mali. In March 2014, when the first cases were detected in Conakry, the Institut Pasteur of Dakar, Senegal, deployed a mobile laboratory in Donka hospital to provide diagnostic services to the greater Conakry urban area and other regions of Guinea. Through this process we sampled 85 Ebola viruses (EBOV) from patients infected from July to November 2014, and report their full genome sequences here. Phylogenetic analysis reveals the sustained transmission of three distinct viral lineages co-circulating in Guinea, including the urban setting of Conakry and its surroundings. One lineage is unique to Guinea and closely related to the earliest sampled viruses of the epidemic. A second lineage contains viruses probably reintroduced from neighbouring Sierra Leone on multiple occasions, while a third lineage later spread from Guinea to Mali. Each lineage is defined by multiple mutations, including non-synonymous changes in the virion protein 35 (VP35), glycoprotein (GP) and RNA-dependent RNA polymerase (L) proteins. The viral GP is characterized by a glycosylation site modification and mutations in the mucin-like domain that could modify the outer shape of the virion. These data illustrate the ongoing ability of EBOV to develop lineage-specific and potentially phenotypically important variation.

  6. Sensitivity to dietary phosphorus limitation in native vs. invasive lineages of a New Zealand freshwater snail.

    PubMed

    Neiman, Maurine; Krist, Amy

    2016-10-01

    Why some species and lineages are more likely to be invasive than others is one of the most important unanswered questions in basic and applied biology. In particular, the relative contributions to the invasion process of factors like pre-adaptation to invasiveness in the native range, evolution post-colonization, and random vs. non-random sampling of colonist lineages remain unclear. We use a powerful common garden approach to address the potential for a role for sensitivity to nutrient limitation in determining the invasiveness of particular lineages of Potamopyrgus antipodarum, a New Zealand freshwater snail that has become globally invasive. We quantified specific growth rate (SGR), an important fitness-related trait in this species, under high phosphorus (P) vs. low-P conditions for a diverse set of native and invasive P. antipodarum. This experiment revealed that native-range P. antipodarum experience a more severe decline in SGR in low-P conditions relative to SGR in high-P conditions than their invasive range counterparts. Although these results suggest resilience to P limitation in invasive lineages, the absence of significant absolute differences in SGR between native and invasive lineages indicates that a straightforward connection between response to P limitation and invasiveness in P. antipodarum is unlikely. Regardless, our data demonstrate that invasive vs. native lineages of P. antipodarum exhibit consistently different responses to an important environmental variable that is rarely studied in the context of invasion success. Further studies directed at exploring and disentangling the roles of sampling effects, selection on preexisting variation, and evolution after colonization will be required to provide a comprehensive picture of the role (or lack thereof) of nutrient limitation in the global invasion of P. antipodarum, as well for as other invasive taxa.

  7. Stem cell insights into human trophoblast lineage differentiation.

    PubMed

    Gamage, Teena Kjb; Chamley, Lawrence W; James, Joanna L

    2016-12-01

    of human TSC lines, trophoblast-like cells have been induced to differentiate from hESCs and iPS. However, differentiation in these model systems is difficult to control, culture conditions employed are highly variable, and the extent to which they accurately convey the biology of 'true' human TSCs remains unclear, particularly as a consensus has not been met among the scientific community regarding which characteristics a human TSC must possess. Human TSC models have the potential to revolutionize our understanding of trophoblast differentiation, allowing us to make significant gains in understanding the underlying pathology of pregnancy disorders and to test potential therapeutic interventions on cell function in vitro. In order to do this, a collaborative effort is required to establish the criteria that define a human TSC to confirm the presence of human TSCs in both primary isolates and to determine how accurately trophoblast-like cells derived from current model systems reflect trophoblast from primary tissue. The in vitro systems currently used to model early trophoblast lineage formation have provided insights into early human placental formation but it is unclear whether these trophoblast-like cells are truly representative of primary human trophoblast. Consequently, continued refinement of current models, and standardization of culture protocols is essential to aid our ability to identify, isolate and propagate 'true' human TSCs from primary tissue. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Rotorcraft Icing - Progress and Potential.

    DTIC Science & Technology

    1986-09-01

    REQUIREMENTS ........................................................... 87 TABLE 17. SAFETY ANALYSIS - SUMMARIZED FAILURE...temperatare and altitude and e vl i, !omented. no significant difficulties have been reported in esyeting the relevant i nj -he safety recori has been...relation to safety standards. It is not within the scope of this section to discuss design and certification standards except where they are governed by

  9. Coal cleaning: progress and potential

    SciTech Connect

    Livengood, C.D.; Doctor, R.D.

    1985-01-01

    Results from a detailed analysis of sulfur dioxide (SO/sub 2/) reductions achievable through ''deep'' physical coal cleaning (PCC) at 20 coal-fired power plants in the Ohio-Indiana-Illinois region are presented here. These plants all have capacities larger than 500 MWe, are currently without any flue-gas-desulfurization (FGD) systems, and burn coal of greater than 1% sulfur content (in 1980). Their aggregate emissions of 2.4 million tons of SO/sub 2/ per year represents 55% of the SO/sub 2/ inventory for these states. The principal coal supplies for each power plant were identified and characterized as to coal seam and county of origin, so that published coal-washability data could be matched to each supplier. The SO/sub 2/ reductions that would result from deep cleaning (Level 4) and moderate cleaning (Level 3) of each coal were calculated using a PCC computer model. For deep cleaning, percentage reductions in sulfur content ranged from zero to 52%, with a mean value of 29% and costs ranged from a low of 364/ton SO/sub 2/ removed to over $2000/ton SO/sub 2/ removed. Because coal suppliers to these power plants employ some voluntary coal cleaning, the anticipated emissions reduction from current levels if deep cleaning were used should be near 20%. These emissions reductions were projected using conventional coal cleaning circuit designs. The basic elements of typical commercial PCC designs are briefly described and current research and development activities in physical, chemical, and biological desulfurization of coal are reviewed. Possible governmental actions to either encourage or mandate coal cleaning are identified and evaluated. 13 refs., 5 figs., 3 tabs.

  10. Coal cleaning: Progress and potential

    SciTech Connect

    Livengood, C.D.; Doctor, R.D.

    1985-01-01

    Results from a detailed analysis of sulfur dioxide (SO/sub 2/) reductions achievable through ''deep'' physical coal cleaning (PCC) at 20 coal-fired power plants in the Ohio-Indiana-Illinois region are presented in this paper. These plants all have capacities larger than 500 MWe are currently without any flue-gas-desulfurization (FGD) systems, and burn coal of greater than 1% sulfur content (in 1980). Their aggregate emissions of 2.4 million tons of SO/sub 2/ per year represents 55% of the SO/sub 2/ inventory for these states. The principal coal supplies for each power plant were identified and characterized as to coal seam and county of origin, so that published coal-washability data could be matched to each supplier. The SO/sub 2/ reductions that would result from deep cleaning and moderate cleaning of each coal were calculated using a PCC computer model.

  11. The elastic fibre network of the human lumbar anulus fibrosus: architecture, mechanical function and potential role in the progression of intervertebral disc degeneration

    PubMed Central

    Fazzalari, Nicola L.

    2009-01-01

    Elastic fibres are critical constituents of dynamic biological structures that functionally require elasticity and resilience. The network of elastic fibres in the anulus fibrosus of the intervertebral disc is extensive, however until recently, the majority of histological, biochemical and biomechanical studies have focussed on the roles of other extracellular matrix constituents such as collagens and proteoglycans. The resulting lack of detailed descriptions of elastic fibre network architecture and mechanical function has limited understanding of the potentially important contribution made by elastic fibres to healthy disc function and their possible roles in the progression of disc degeneration. In addition, it has made it difficult to postulate what the consequences of elastic fibre related disorders would be for intervertebral disc behaviour, and to develop treatments accordingly. In this paper, we review recent and historical studies which have examined both the structure and the function of the human lumbar anulus fibrosus elastic fibre network, provide a synergistic discussion in an attempt to clarify its potentially critical contribution both to normal intervertebral disc behaviour and the processes relating to its degeneration, and recommend critical areas for future research. PMID:19263091

  12. Genetic structure of the paternal lineage of the Roma people.

    PubMed

    Pamjav, Horolma; Zalán, Andrea; Béres, Judit; Nagy, Melinda; Chang, Yuet Meng

    2011-05-01

    According to written sources, Roma (Romanies, Gypsies) arrived in the Balkans around 1,000 years ago from India and have subsequently spread through several parts of Europe. Genetic data, particularly from the Y chromosome, have supported this model, and can potentially refine it. We now provide an analysis of Y-chromosomal markers from five Roma and two non-Roma populations (N = 787) in order to investigate the genetic relatedness of the Roma population groups to one another, and to gain further understanding of their likely Indian origins, the genetic contribution of non-Roma males to the Roma populations, and the early history of their splits and migrations in Europe. The two main sources of the Roma paternal gene pool were identified as South Asian and European. The reduced diversity and expansion of H1a-M82 lineages in all Roma groups imply shared descent from a single paternal ancestor in the Indian subcontinent. The Roma paternal gene pool also contains a specific subset of E1b1b1a-M78 and J2a2-M67 lineages, implying admixture during early settlement in the Balkans and the subsequent influx into the Carpathian Basin. Additional admixture, evident in the low and moderate frequencies of typical European haplogroups I1-M253, I2a-P37.2, I2b-M223, R1b1-P25, and R1a1-M198, has occurred in a more population-specific manner. Copyright © 2011 Wiley-Liss, Inc.

  13. Evidence for a lineage of virulent bacteriophages that target Campylobacter.

    PubMed

    Timms, Andrew R; Cambray-Young, Joanna; Scott, Andrew E; Petty, Nicola K; Connerton, Phillippa L; Clarke, Louise; Seeger, Kathy; Quail, Mike; Cummings, Nicola; Maskell, Duncan J; Thomson, Nicholas R; Connerton, Ian F

    2010-03-30

    Our understanding of the dynamics of genome stability versus gene flux within bacteriophage lineages is limited. Recently, there has been a renewed interest in the use of bacteriophages as 'therapeutic' agents; a prerequisite for their use in such therapies is a thorough understanding of their genetic complement, genome stability and their ecology to avoid the dissemination or mobilisation of phage or bacterial virulence and toxin genes. Campylobacter, a food-borne pathogen, is one of the organisms for which the use of bacteriophage is being considered to reduce human exposure to this organism. Sequencing and genome analysis was performed for two Campylobacter bacteriophages. The genomes were extremely similar at the nucleotide level (> or = 96%) with most differences accounted for by novel insertion sequences, DNA methylases and an approximately 10 kb contiguous region of metabolic genes that were dissimilar at the sequence level but similar in gene function between the two phages. Both bacteriophages contained a large number of radical S-adenosylmethionine (SAM) genes, presumably involved in boosting host metabolism during infection, as well as evidence that many genes had been acquired from a wide range of bacterial species. Further bacteriophages, from the UK Campylobacter typing set, were screened for the presence of bacteriophage structural genes, DNA methylases, mobile genetic elements and regulatory genes identified from the genome sequences. The results indicate that many of these bacteriophages are related, with 10 out of 15 showing some relationship to the sequenced genomes. Two large virulent Campylobacter bacteriophages were found to show very high levels of sequence conservation despite separation in time and place of isolation. The bacteriophages show adaptations to their host and possess genes that may enhance Campylobacter metabolism, potentially advantaging both the bacteriophage and its host. Genetic conservation has been shown to extend to other

  14. Phylogenetic ecology of the freshwater Actinobacteria acI lineage.

    PubMed

    Newton, Ryan J; Jones, Stuart E; Helmus, Matthew R; McMahon, Katherine D

    2007-11-01

    The acI lineage of freshwater Actinobacteria is a cosmopolitan and often numerically dominant member of lake bacterial communities. We conducted a survey of acI 16S rRNA genes and 16S-23S rRNA internal transcribed spacer regions from 18 Wisconsin lakes and used standard nonphylogenetic and phylogenetic statistical approaches to investigate the factors that determine acI community composition at the local scale (within lakes) and at the regional scale (across lakes). Phylogenetic reconstruction of 434 acI 16S rRNA genes revealed a well-defined and highly resolved phylogeny. Eleven previously unrecognized monophyletic clades, each with > or =97.9% within-clade 16S rRNA gene sequence identity, were identified. Clade community similarity positively correlated with lake environmental similarity but not with geographic distance, implying that the lakes represent a single biotic region containing environmental filters for communities that have similar compositions. Phylogenetically disparate clades within the acI lineage were most abundant at the regional scale, and local communities were comprised of more closely related clades. Lake pH was a strong predictor of the community composition, but only when lakes with a pH below 6 were included in the data set. In the remaining lakes (pH above 6) biogeographic patterns in the landscape were instead a predictor of the observed acI community structure. The nonrandom distribution of the newly defined acI clades suggests potential ecophysiological differences between the clades, with acI clades AI, BII, and BIII preferring acidic lakes and acI clades AII, AVI, and BI preferring more alkaline lakes.

  15. FUT11 as a potential biomarker of clear cell renal cell carcinoma progression based on meta-analysis of gene expression data.

    PubMed

    Zodro, Elżbieta; Jaroszewski, Marcin; Ida, Agnieszka; Wrzesiński, Tomasz; Kwias, Zbigniew; Bluyssen, Hans; Wesoly, Joanna

    2014-03-01

    In this paper, we provide a comprehensive summary of available clear cell renal cell carcinoma (ccRCC) microarray data in the form of meta-analysis of genes differentially regulated in tumors as compared to healthy tissue, using effect size to measure the strength of a relationship between the disease and gene expression. We identified 725 differentially regulated genes, with a number of interesting targets, such as TMEM213, SMIM5, or ATPases: ATP6V0A4 and ATP6V1G3, of which limited or no information is available in terms of their function in ccRCC pathology. Downregulated genes tended to represent pathways related to tissue remodeling, blood clotting, vasodilation, and energy metabolism, while upregulated genes were classified into pathways generally deregulated in cancers: immune system response, inflammatory response, angiogenesis, and apoptosis. One hundred fifteen deregulated genes were included in network analysis, with EGLN3, AP-2, NR3C1, HIF1A, and EPAS1 (gene encoding HIF2-α) as points of functional convergence, but, interestingly, 610 genes failed to join previously identified molecular networks. Furthermore, we validated the expression of 14 top deregulated genes in independent sample set of 32 ccRCC tumors by qPCR and tested if it could serve as a marker of disease progression. We found a correlation of high fucosyltransferase 11 (FUT11) expression with non-symptomatic course of the disease, which suggests that FUT11's expression might be potentially used as a biomarker of disease progression.

  16. Differentiation in Stem Cell Lineages and in Life: Explorations in the Male Germ Line Stem Cell Lineage.

    PubMed

    Fuller, Margaret T

    2016-01-01

    I have been privileged to work on cellular differentiation during a great surge of discovery that has revealed the molecular mechanisms and genetic regulatory circuitry that control embryonic development and adult tissue maintenance and repair. Studying the regulation of proliferation and differentiation in the male germ line stem cell lineage has allowed us investigate how the developmental program imposes layers of additional controls on fundamental cellular processes like cell cycle progression and gene expression to give rise to the huge variety of specialized cell types in our bodies. We are beginning to understand how local signals from somatic support cells specify self-renewal versus differentiation in the stem cell niche at the apical tip of the testis. We are discovering the molecular events that block cell proliferation and initiate terminal differentiation at the switch from mitosis to meiosis-a signature event of the germ cell program. Our work is beginning to reveal how the developmental program that sets up the dramatic new cell type-specific transcription program that prepares germ cells for meiotic division and spermatid differentiation is turned on when cells become spermatocytes. I have had the privilege of working with incredible students, postdocs, and colleagues who have discovered, brainstormed, challenged, and refined our science and our ideas of how developmental pathways and cellular mechanisms work together to drive differentiation. © 2016 Elsevier Inc. All rights reserved.

  17. On the roles of Notch, Delta, kuzbanian, and inscuteable during the development of Drosophila embryonic neuroblast lineages.

    PubMed

    Udolph, Gerald; Rath, Priyadarshini; Tio, Murni; Toh, Joanne; Fang, Wanru; Pandey, Rahul; Technau, Gerhard M; Chia, William

    2009-12-15

    The generation of cellular diversity in the nervous system involves the mechanism of asymmetric cell division. Besides an array of molecules, including the Par protein cassette, a heterotrimeric G protein signalling complex, Inscuteable plays a major role in controlling asymmetric cell division, which ultimately leads to differential activation of the Notch signalling pathway and correct specification of the two daughter cells. In this context, Notch is required to be active in one sibling and inactive in the other. Here, we investigated the requirement of genes previously known to play key roles in sibling cell fate specification such as members of the Notch signalling pathway, e.g., Notch (N), Delta (Dl), and kuzbanian (kuz) and a crucial regulator of asymmetric cell division, inscuteable (insc) throughout lineage progression of 4 neuroblasts (NB1-1, MP2, NB4-2, and NB7-1). Notch-mediated cell fate specification defects were cell-autonomous and were observed in all neuroblast lineages even in cells born from late ganglion mother cells (GMC) within the lineages. We also show that Dl functions non-autonomously during NB lineage progression and clonal cells do not require Dl from within the clone. This suggests that within a NB lineage Dl is dispensable for sibling cell fate specification. Furthermore, we provide evidence that kuz is involved in sibling cell fate specification in the central nervous system. It is cell-autonomously required in the same postmitotic cells which also depend on Notch function. This indicates that KUZ is required to facilitate a functional Notch signal in the Notch-dependent cell for correct cell fate specification. Finally, we show that three neuroblast lineages (NB1-1, NB4-2, and NB7-1) require insc function for sibling cell fate specification in cells born from early GMCs whereas insc is not required in cells born from later GMCs of the same lineages. Thus, there is differential requirement for insc for cell fate specification

  18. Denial of lineage: clinical investigation of 50 cases.

    PubMed

    Tsai, N; Kao, Z X; Lenz, H

    1987-01-01

    Fifty randomly selected Chinese schizophrenic patients with denial of lineage were investigated. This delusion concerns the generation of parents, sisters, but not the offspring. Twenty-four of them manifested delusion of high-ranking lineage or of distinguished leadership lineage. Denial of lineage, involving the delusion of high-ranking lineage and the delusion of leadership lineage, may occur at the onset or during the course of schizophrenia. The clinical characteristics of this delusion are described and its concept, diagnosis, differential diagnosis, course and also possible mechanism are discussed. One possible mechanism is of psychodynamical origin. Emotional conflicts resulting from dissatisfaction of the primary need of being loved from birth may contribute to the onset of the denial of lineage. The second possible mechanism is a sociocultural fact. Far Eastern culture is based on the clan whereas occidental culture is based on the self. Thus can observe the denial of lineage in the Far East, but in the occident we can experience instead the idea of surmounting our self so as to be god or now to experience the omnipotence in form of technical ideas, e.g. the rays.

  19. Gender, Lineage, and Fertility-Related Outcomes in Ghana

    ERIC Educational Resources Information Center

    Takyi, Baffour K.; Nii-Amoo Dodoo, F.

    2005-01-01

    A growing literature examines the empirical relationship between the joint reproductive preferences of marital partners and reproductive outcomes in Africa. Less explored is how spousal power in decision making may be influenced by lineage type. Using pooled data from Ghana, we investigate how lineage affects gendered reproductive decision…

  20. Genomic Variability within an Organism Exposes Its Cell Lineage Tree

    PubMed Central

    Kaplan, Shai; Feige, Uriel; Shapiro, Ehud

    2005-01-01

    What is the lineage relation among the cells of an organism? The answer is sought by developmental biology, immunology, stem cell research, brain research, and cancer research, yet complete cell lineage trees have been reconstructed only for simple organisms such as Caenorhabditis elegans. We discovered that somatic mutations accumulated during normal development of a higher organism implicitly encode its entire cell lineage tree with very high precision. Our mathematical analysis of known mutation rates in microsatellites (MSs) shows that the entire cell lineage tree of a human embryo, or a mouse, in which no cell is a descendent of more than 40 divisions, can be reconstructed from information on somatic MS mutations alone with no errors, with probability greater than 99.95%. Analyzing all ~1.5 million MSs of each cell of an organism may not be practical at present, but we also show that in a genetically unstable organism, analyzing only a few hundred MSs may suffice to reconstruct portions of its cell lineage tree. We demonstrate the utility of the approach by reconstructing cell lineage trees from DNA samples of a human cell line displaying MS instability. Our discovery and its associated procedure, which we have automated, may point the way to a future “Human Cell Lineage Project” that would aim to resolve fundamental open questions in biology and medicine by reconstructing ever larger portions of the human cell lineage tree. PMID:16261192

  1. Phenotypic differences among three clonal lineages of Phytophthora ramorum

    USDA-ARS?s Scientific Manuscript database

    There are three major clonal lineages of Phytophthora ramorum present in North America and Europe named NA1, NA2, and EU1. Twenty-three isolates representing all three lineages were evaluated for phenotype including (i) aggressiveness on detached Rhododendron leaves and (ii) growth rate at minimum, ...

  2. The use of pyrosequencer-generated sequence-signatures to identify the influenza B-lineage and the subclade of the B/Yamataga-lineage viruses from currently circulating human influenza B viruses.

    PubMed

    Deng, Yi-Mo; Iannello, Pina; Caldwell, Natalie; Jelley, Lauren; Komadina, Naomi; Baas, Chantal; Kelso, Anne; Barr, Ian G

    2013-09-01

    Influenza B viruses belong to two antigenically and genetically distinct lineages which co-circulate in varying proportions in many countries. To develop simple, rapid, accurate and robust methods to detect and differentiate currently circulating B-lineage viruses in respiratory samples and virus isolates. Haemagglutinin (HA) gene sequences from more than 6300 influenza B strains were analysed to identify signature sequences that could be used to distinguish between B-lineages and sublineages. Pyrosequencing and a real time PCR assays were developed to detect the major B-lineages (B/Victoria/2/87 or B/Yamagata/16/88) and pyrosequencing for a unique mutation was used to further differentiate the B/Yamagata viruses into two currently co-circulating subgroups. More than 300 influenza virus-containing samples, including original specimens, cell and egg grown viruses, were tested with a 100% accuracy. Furthermore, when the same PCR primers were used in an rRT-PCR assay, the two lineages could be differentiated by their distinct ranges of melting temperature with an overall accuracy of 99% for 158 samples tested. These new pyrosequencing and rRT-PCR methods have the potential to aid the rapid identification of influenza B-lineages for surveillance purposes and to increase the available data for bi-annual selection of viruses for updating influenza vaccines. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Visual Evoked Potential and Magnetic Resonance Imaging are More Effective Markers of Multiple Sclerosis Progression than Laser Polarimetry with Variable Corneal Compensation.

    PubMed

    Kantorová, Ema; Ziak, Peter; Kurča, Egon; Koyšová, Mária; Hladká, Mária; Zeleňák, Kamil; Michalik, Jozef

    2014-01-01

    The aim of our study was to assess the role of laser polarimetry and visual evoked potentials (VEP) as potential biomarkers of disease progression in multiple sclerosis (MS). A total of 41 patients with MS (82 eyes) and 22 age-related healthy volunteers (44 eyes) completed the study. MS patients were divided into two groups, one (ON) with a history of optic neuritis (17 patients, 34 eyes) and another group (NON) without it (24 patients, 48 eyes). The MS patients and controls underwent laser polarimetry (GDx) examination of the retinal nerve fiber layer (RNFL). In the MS group, we also examined: Kurtzke "expanded disability status scale" (EDSS), the duration of the disorder, VEP - latency and amplitude, and conventional brain magnetic resonance imaging (MRI). Our results were statistically analyzed using ANOVA, Mann-Whitney, and Spearman correlation analyses. In the MS group, brain atrophy and new T2 brain lesions in MRI correlated with both VEP latencies and amplitudes. Separate comparisons revealed VEP latency testing to be less sensitive in ON than in NON-patients. In ON patients, VEP amplitudes correlated mildly with brain atrophy (r = -0.15) and strongly with brain new MRI lesions (r = -0.8). In NON-patients, highly significant correlation of new MRI brain lesions with VEP latencies (r = 0.63, r = 0.6) and amplitudes (r = -0.3, r = -4.2) was found. EDSS also correlated with brain atrophy in this group (r = 0.5). Our study did not find a correlation of GDx measures with MRI tests. The GDx method was not able to detect whole brain demyelinization and the degeneration process, but was only able to reveal the involvement of optic nerves in ON and NON-patients. In our study, we found that both methods (VEP and GDx) can be used for the detection of optic nerve damage, but VEP was found to be superior in evaluating whole brain demyelinization and axonal degeneration. Both VEP and MRI, but not GDx, have an important role in monitoring

  4. Visual Evoked Potential and Magnetic Resonance Imaging are More Effective Markers of Multiple Sclerosis Progression than Laser Polarimetry with Variable Corneal Compensation

    PubMed Central

    Kantorová, Ema; Žiak, Peter; Kurča, Egon; Koyšová, Mária; Hladká, Mária; Zeleňák, Kamil; Michalik, Jozef

    2014-01-01

    Background: The aim of our study was to assess the role of laser polarimetry and visual evoked potentials (VEP) as potential biomarkers of disease progression in multiple sclerosis (MS). Participants: A total of 41 patients with MS (82 eyes) and 22 age-related healthy volunteers (44 eyes) completed the study. MS patients were divided into two groups, one (ON) with a history of optic neuritis (17 patients, 34 eyes) and another group (NON) without it (24 patients, 48 eyes). The MS patients and controls underwent laser polarimetry (GDx) examination of the retinal nerve fiber layer (RNFL). In the MS group, we also examined: Kurtzke “expanded disability status scale” (EDSS), the duration of the disorder, VEP – latency and amplitude, and conventional brain magnetic resonance imaging (MRI). Our results were statistically analyzed using ANOVA, Mann–Whitney, and Spearman correlation analyses. Results: In the MS group, brain atrophy and new T2 brain lesions in MRI correlated with both VEP latencies and amplitudes. Separate comparisons revealed VEP latency testing to be less sensitive in ON than in NON-patients. In ON patients, VEP amplitudes correlated mildly with brain atrophy (r = −0.15) and strongly with brain new MRI lesions (r = −0.8). In NON-patients, highly significant correlation of new MRI brain lesions with VEP latencies (r = 0.63, r = 0.6) and amplitudes (r = −0.3, r = −4.2) was found. EDSS also correlated with brain atrophy in this group (r = 0.5). Our study did not find a correlation of GDx measures with MRI tests. The GDx method was not able to detect whole brain demyelinization and the degeneration process, but was only able to reveal the involvement of optic nerves in ON and NON-patients. Conclusion: In our study, we found that both methods (VEP and GDx) can be used for the detection of optic nerve damage, but VEP was found to be superior in evaluating whole brain demyelinization and axonal degeneration. Both VEP

  5. Quantitative Analysis of Synthetic Cell Lineage Tracing Using Nuclease Barcoding.

    PubMed

    Schmidt, Stephanie Tzouanas; Zimmerman, Stephanie M; Wang, Jianbin; Kim, Stuart K; Quake, Stephen R

    2017-06-16

    Lineage tracing by the determination and mapping of progeny arising from single cells is an important approach enabling the elucidation of mechanisms underlying diverse biological processes ranging from development to disease. We developed a dynamic sequence-based barcode system for synthetic lineage tracing and have demonstrated its performance in C. elegans, a model organism whose lineage tree is well established. The strategy we use creates lineage trees based upon the introduction of synthetically controlled mutations into cells and the propagation of these mutations to daughter cells at each cell division. We analyzed this experimental proof of concept along with a corresponding simulation and analytical model to gain a deeper understanding of the coding capacity of the system. Our results provide specific bounds on the fidelity of lineage tracing using such approaches.

  6. Stereotypical physiological properties emerge during early neuronal and glial lineage development in the embryonic rat neocortex.

    PubMed

    Maric, D; Maric, I; Chang, Y H; Barker, J L

    2000-08-01

    Surface immunolabeling was used together with membrane potential and/or Ca(2+) indicator dyes to characterize physiological properties emerging among precursors, neuroglial progenitors and differentiating neurons during neurogenesis of embryonic rat neocortex. Cells were immunoidentified with tetanus toxin (TnTx), which binds to gangliosides expressed by neurons, and anti-A2B5, which reacts with gangliosides expressed by neuroglial progenitors. Microdissection of the neocortex into ventricular/subventricular zone (VZ/SVZ) and cortical plate/subplate (CP/SP) regions further resolved the TnTx/A2B5-immunoidentified cells into pre- and post-migratory subpopulations. Quantitative immunocytochemistry revealed mainly proliferative (BrdU(+)) and immature (nestin(+)) elements among TnTx(-)A2B5(-) precursors and TnTx(-)A2B5(+) progenitors in the VZ/SVZ, and the appearance of neuron-specific antigens among post-mitotic TnTx(+) subpopulations of the CP/SP. Flow cytometry of acutely prepared cells in suspension and dual-imaging of cells in culture revealed that ionotropic amino acid receptors and metabotropic acetylcholine receptors closely paralleled the emergence of voltage-dependent Na(+) and Ca(2+) channels and Na(+)-Ca(2+) exchange activity among TnTx(+) neuronal progenitors migrating from VZ/SVZ to CP/SP. During this period, TnTx(-)A2B5(-) precursors and TnTx(-)A2B5(+) neuroglial progenitors from VZ/SVZ predominantly exhibited Ca(2+) responses to ATP. Thus, stereotypical and contrasting physiologies emerge among embryonic cortical cells in vivo as they initially progress from proliferating precursors and progenitors along neuronal and glial cell lineages.

  7. The tumor microenvironment shapes lineage, transcriptional, and functional diversity of infiltrating myeloid cells.

    PubMed

    Elpek, Kutlu G; Cremasco, Viviana; Shen, Hua; Harvey, Christopher J; Wucherpfennig, Kai W; Goldstein, Daniel R; Monach, Paul A; Turley, Shannon J

    2014-07-01

    Myeloid cells play important regulatory roles within the tumor environment by directly promoting tumor progression and modulating the function of tumor-infiltrating lymphocytes, and as such, they represent a potential therapeutic target for the treatment of cancer. Although distinct subsets of tumor-associated myeloid cells have been identified, a broader analysis of the complete myeloid cell landscape within individual tumors and also across different tumor types has been lacking. By establishing the developmental and transcriptomic signatures of infiltrating myeloid cells from multiple primary tumors, we found that tumor-associated macrophages (TAM) and tumor-associated neutrophils (TAN), while present within all tumors analyzed, exhibited strikingly different frequencies, gene expression profiles, and functions across cancer types. We also evaluated the impact of anatomic location and circulating factors on the myeloid cell composition of tumors. The makeup of the myeloid compartment was determined by the tumor microenvironment rather than the anatomic location of tumor development or tumor-derived circulating factors. Protumorigenic and hypoxia-associated genes were enriched in TAMs and TANs compared with splenic myeloid-derived suppressor cells. Although all TANs had an altered expression pattern of secretory effector molecules, in each tumor type they exhibited a unique cytokine, chemokine, and associated receptor expression profile. One such molecule, haptoglobin, was uniquely expressed by 4T1 TANs and identified as a possible diagnostic biomarker for tumors characterized by the accumulation of myeloid cells. Thus, we have identified considerable cancer-specific diversity in the lineage, gene expression, and function of tumor-infiltrating myeloid cells.

  8. Triple Staining Including FOXA2 Identifies Stem Cell Lineages Undergoing Hepatic and Biliary Differentiation in Cirrhotic Human Liver.

    PubMed

    Rogler, Charles E; Bebawee, Remon; Matarlo, Joe; Locker, Joseph; Pattamanuch, Nicole; Gupta, Sanjeev; Rogler, Leslie E

    2017-01-01

    Recent investigations have reported many markers associated with human liver stem/progenitor cells, "oval cells," and identified "niches" in diseased livers where stem cells occur. However, there has remained a need to identify entire lineages of stem cells as they differentiate into bile ducts or hepatocytes. We have used combined immunohistochemical staining for a marker of hepatic commitment and specification (FOXA2 [Forkhead box A2]), hepatocyte maturation (Albumin and HepPar1), and features of bile ducts (CK19 [cytokeratin 19]) to identify lineages of stem cells differentiating toward the hepatocytic or bile ductular compartments of end-stage cirrhotic human liver. We identified large clusters of disorganized, FOXA2 expressing, oval cells in localized liver regions surrounded by fibrotic matrix, designated as "micro-niches." Specific FOXA2-positive cells within the micro-niches organize into primitive duct structures that support both hepatocytic and bile ductular differentiation enabling identification of entire lineages of cells forming the two types of structures. We also detected expression of hsa-miR-122 in primitive ductular reactions expected for hepatocytic differentiation and hsa-miR-23b cluster expression that drives liver cell fate decisions in cells undergoing lineage commitment. Our data establish the foundation for a mechanistic hypothesis on how stem cell lineages progress in specialized micro-niches in cirrhotic end-stage liver disease.

  9. Micromere lineages in the glossiphoniid leech Helobdella

    NASA Technical Reports Server (NTRS)

    Huang, Francoise Z.; Kang, Dongmin; Ramirez-Weber, Felipe-Andres; Bissen, Shirley T.; Weisblat, David A.

    2002-01-01

    In leech embryos, segmental mesoderm and ectoderm arise from teloblasts by lineages that are already relatively well characterized. Here, we present data concerning the early divisions and the definitive fate maps of the micromeres, a group of 25 small cells that arise during the modified spiral cleavage in leech (Helobdella robusta) and contribute to most of the nonsegmental tissues of the adult. Three noteworthy results of this work are as follows. (1) The c"' and dm' clones (3d and 3c in traditional nomenclature) give rise to a hitherto undescribed network of fibers that run from one end of the embryo to the other. (2) The clones of micromeres b" and b"' (2b and 3b in traditional nomenclature) die in normal development; the b" clone can be rescued to assume the normal c" fate if micromere c" or its clone are ablated in early development. (3) Two qualitative differences in micromere fates are seen between H. robusta (Sacramento) and another Helobdella sp. (Galt). First, in Helobdella sp. (Galt), the clone of micromere b" does not normally die, and contributes a subset of the cells arising exclusively from c" in H. robusta (Sacramento). Second, in Helobdella sp. (Galt), micromere c"' makes no definitive contribution, whereas micromere dm' gives rise to cells equivalent to those arising from c"' and dm' in H. robusta (Sacramento).

  10. Lineage-dependent ecological coherence in bacteria.

    PubMed

    Koeppel, Alexander F; Wu, Martin

    2012-09-01

    Bacteria comprise an essential element of all ecosystems, including those present on and within the human body. Understanding bacterial diversity therefore offers enormous scientific and medical benefit, but significant questions remain regarding how best to characterize that diversity and organize it into biologically meaningful units. Bacterial communities are routinely characterized based on the relative abundances of taxa at the genus or even the phylum level, but the ecological coherence of these high-level taxonomic units is uncertain. Using human microbiota from the skin and gut as our model systems, we tested the ecological coherence of bacteria by investigating the habitat associations of bacteria at all levels of the taxonomic hierarchy. We observed four distinct taxonomic patterns of habitat association, reflecting different levels of ecological coherence among taxa. Our results support the hypothesis that deep-branch bacterial clades could be ecologically coherent and suggest that the phylogenetic depth of ecological coherence varies among the bacterial lineages and is an important factor to consider in studies of human microbiome associations.

  11. Burnet Oration: living in the Burnet lineage.

    PubMed

    Doherty, P C

    1999-04-01

    Scientific discoveries are not made in isolation. Innovation depends on resources, both intellectual and physical. A primary requirement is the development and maintenance of appropriate institutions. Such structures do not emerge by chance, but arise from opportunity, political will and the continued efforts and commitment of many people over long periods. Suitable buildings, laboratories and state-of-the-art equipment are obviously necessary, but hardware alone is of little value in the absence of a vibrant research culture. The key characteristics of the latter are intellectual foment, open debate and a body of wisdom and knowledge about the particular subject area. Rolf Zinkernagel and 1 played a part in triggering a paradigm shift in the understanding of T cell recognition, a contribution recognized by the 1996 Nobel Prize for Physiology or Medicine. In our Nobel lectures, we both discussed briefly why it was that the John Curtin School of Medical Research (JCSMR) of 1973-75 provided a milieu that facilitated the emergence of the underlying experiments and ideas. My intention here is to discuss in more detail the scientific lineages that put this physical and intellectual environment in place, focusing particularly on the influence of Sir Frank Macfarlane (Sir Mac) Burnet as we celebrate his centenary year.

  12. Micromere lineages in the glossiphoniid leech Helobdella

    NASA Technical Reports Server (NTRS)

    Huang, Francoise Z.; Kang, Dongmin; Ramirez-Weber, Felipe-Andres; Bissen, Shirley T.; Weisblat, David A.

    2002-01-01

    In leech embryos, segmental mesoderm and ectoderm arise from teloblasts by lineages that are already relatively well characterized. Here, we present data concerning the early divisions and the definitive fate maps of the micromeres, a group of 25 small cells that arise during the modified spiral cleavage in leech (Helobdella robusta) and contribute to most of the nonsegmental tissues of the adult. Three noteworthy results of this work are as follows. (1) The c"' and dm' clones (3d and 3c in traditional nomenclature) give rise to a hitherto undescribed network of fibers that run from one end of the embryo to the other. (2) The clones of micromeres b" and b"' (2b and 3b in traditional nomenclature) die in normal development; the b" clone can be rescued to assume the normal c" fate if micromere c" or its clone are ablated in early development. (3) Two qualitative differences in micromere fates are seen between H. robusta (Sacramento) and another Helobdella sp. (Galt). First, in Helobdella sp. (Galt), the clone of micromere b" does not normally die, and contributes a subset of the cells arising exclusively from c" in H. robusta (Sacramento). Second, in Helobdella sp. (Galt), micromere c"' makes no definitive contribution, whereas micromere dm' gives rise to cells equivalent to those arising from c"' and dm' in H. robusta (Sacramento).

  13. CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity

    PubMed Central

    Jacoby, Elad; Nguyen, Sang M.; Fountaine, Thomas J.; Welp, Kathryn; Gryder, Berkley; Qin, Haiying; Yang, Yinmeng; Chien, Christopher D.; Seif, Alix E.; Lei, Haiyan; Song, Young K.; Khan, Javed; Lee, Daniel W.; Mackall, Crystal L.; Gardner, Rebecca A.; Jensen, Michael C.; Shern, Jack F.; Fry, Terry J.

    2016-01-01

    Adoptive immunotherapy using chimeric antigen receptor (CAR) expressing T cells targeting the CD19 B lineage receptor has demonstrated marked success in relapsed pre-B-cell acute lymphoblastic leukaemia (ALL). Persisting CAR-T cells generate sustained pressure against CD19 that may drive unique mechanisms of resistance. Pre-B ALL originates from a committed pre-B cell or an earlier progenitor, with potential to reprogram into other hematopoietic lineages. Here we report changes in lineage markers including myeloid conversion in patients following CD19 CAR therapy. Using murine ALL models we study the long-term effects of CD19 CAR-T cells and demonstrate partial or complete lineage switch as a consistent mechanism of CAR resistance depending on the underlying genetic oncogenic driver. Deletion of Pax5 or Ebf1 recapitulates lineage reprogramming occurring during CD19 CAR pressure. Our findings establish lineage switch as a mechanism of CAR resistance exposing inherent plasticity in genetic subtypes of pre-B-cell ALL. PMID:27460500

  14. Staphylococcus aureus Nasal Colonization Differs among Pig Lineages and Is Associated with the Presence of Other Staphylococcal Species.

    PubMed

    Verstappen, Koen M; Willems, Eveline; Fluit, Ad C; Duim, Birgitta; Martens, Marc; Wagenaar, Jaap A

    2017-01-01

    Staphylococcus aureus is a common colonizer in pigs, with methicillin-resistant S. aureus (MRSA) in particular being a potential health risk to humans. To reduce the exposure to humans, the colonization in pigs should be reduced. The aim of this study was to quantitatively compare the susceptibility of pig lineages for S. aureus colonization, and if the absence of S. aureus could be associated with the presence or absence of other staphylococcal species. Nasal samples (n = 129) were obtained from seven different pig lineages in the Netherlands, France, and Germany. S. aureus and other staphylococci were enumerated from these samples by real-time (RT)-PCR and culture. Associations were explored between the presence of S. aureus and other staphylococci. S. aureus was detected by RT-PCR on all farms and in samples from pigs of all lineages. Twenty-five percent of the pigs from lineage F (from two farms) were colonized with S. aureus, while in all other lineages it was more than 50% (p < 0.01). Moreover, in S. aureus-positive samples from pigs of lineage F smaller amounts of S. aureus were found than in other lineages. Staphylococcus sciuri, Staphylococcus cohnii, and Staphylococcus saprophyticus were usually not found in combination with S. aureus in these samples. (i) pigs from different genetic lineages have different susceptibilities for colonization with S. aureus. These pigs might contain a genetic factor influencing nasal colonization. (ii) Colonization of S. aureus is also associated with the absence of S. sciuri, S. cohnii, or S. saprophyticus. (iii) The farm environment seems to influence the presence of S. aureus in pigs.

  15. Tracing European founder lineages in the Near Eastern mtDNA pool.

    PubMed

    Richards, M; Macaulay, V; Hickey, E; Vega, E; Sykes, B; Guida, V; Rengo, C; Sellitto, D; Cruciani, F; Kivisild, T; Villems, R; Thomas, M; Rychkov, S; Rychkov, O; Rychkov, Y; Gölge, M; Dimitrov, D; Hill, E; Bradley, D; Romano, V; Calì, F; Vona, G; Demaine, A; Papiha, S; Triantaphyllidis, C; Stefanescu, G; Hatina, J; Belledi, M; Di Rienzo, A; Novelletto, A; Oppenheim, A; Nørby, S; Al-Zaheri, N; Santachiara-Benerecetti, S; Scozari, R; Torroni, A; Bandelt, H J

    2000-11-01

    Founder analysis is a method for analysis of nonrecombining DNA sequence data, with the aim of identification and dating of migrations into new territory. The method picks out founder sequence types in potential source populations and dates lineage clusters deriving from them in the settlement zone of interest. Here, using mtDNA, we apply the approach to the colonization of Europe, to estimate the proportion of modern lineages whose ancestors arrived during each major phase of settlement. To estimate the Palaeolithic and Neolithic contributions to European mtDNA diversity more accurately than was previously achievable, we have now extended the Near Eastern, European, and northern-Caucasus databases to 1,234, 2, 804, and 208 samples, respectively. Both back-migration into the source population and recurrent mutation in the source and derived populations represent major obstacles to this approach. We have developed phylogenetic criteria to take account of both these factors, and we suggest a way to account for multiple dispersals of common sequence types. We conclude that (i) there has been substantial back-migration into the Near East, (ii) the majority of extant mtDNA lineages entered Europe in several waves during the Upper Palaeolithic, (iii) there was a founder effect or bottleneck associated with the Last Glacial Maximum, 20,000 years ago, from which derives the largest fraction of surviving lineages, and (iv) the immigrant Neolithic component is likely to comprise less than one-quarter of the mtDNA pool of modern Europeans.

  16. Natural epigenetic variation contributes to heritable flowering divergence in a widespread asexual dandelion lineage.

    PubMed

    Wilschut, Rutger A; Oplaat, Carla; Snoek, L Basten; Kirschner, Jan; Verhoeven, Koen J F

    2016-04-01

    Epigenetic variation has been proposed to contribute to the success of asexual plants, either as a contributor to phenotypic plasticity or by enabling transient adaptation via selection on transgenerationally stable, but reversible, epialleles. While recent studies in experimental plant populations have shown the potential for epigenetic mechanisms to contribute to adaptive phenotypes, it remains unknown whether heritable variation in ecologically relevant traits is at least partially epigenetically determined in natural populations. Here, we tested the hypothesis that DNA methylation variation contributes to heritable differences in flowering time within a single widespread apomictic clonal lineage of the common dandelion (Taraxacum officinale s. lat.). Apomictic clone members of the same apomictic lineage collected from different field sites showed heritable differences in flowering time, which was correlated with inherited differences in methylation-sensitive AFLP marker profiles. Differences in flowering between apomictic clone members were significantly reduced after in vivo demethylation using the DNA methyltransferase inhibitor zebularine. This synchronization of flowering times suggests that flowering time divergence within an apomictic lineage was mediated by differences in DNA methylation. While the underlying basis of the methylation polymorphism at functional flowering time-affecting loci remains to be demonstrated, our study shows that epigenetic variation contributes to heritable phenotypic divergence in ecologically relevant traits in natural plant populations. This result also suggests that epigenetic mechanisms can facilitate adaptive divergence within genetically uniform asexual lineages. © 2015 John Wiley & Sons Ltd.

  17. Lineage-tracking of stem cell differentiation: a neutral model of hematopoiesis in rhesus macaque

    NASA Astrophysics Data System (ADS)

    Chou, Tom

    How a potentially diverse population of hematopoietic stem cells (HSCs) differentiates and proliferates to supply more than 1011 mature blood cells every day in humans remains a key biological question. We investigated this process by quantitatively analyzing the clonal structure of peripheral blood that is generated by a population of transplanted lentivirus-marked HSCs in myeloablated rhesus macaques. Each transplanted HSC generates a clonal lineage of cells in the peripheral blood that is then detected and quantified through deep sequencing of the viral vector integration sites (VIS) common within each lineage. This approach allowed us to observe, over a period of 4-12 years, hundreds of distinct clonal lineages. Surprisingly, while the distinct clone sizes varied by three orders of magnitude, we found that collectively, they form a steady-state clone size-distribution with a distinctive shape. Our concise model shows that slow HSC differentiation followed by fast progenitor growth is responsible for the observed broad clone size-distribution. Although all cells are assumed to be statistically identical, analogous to a neutral theory for the different clone lineages, our mathematical approach captures the intrinsic variability in the times to HSC differentiation after transplantation. Steady-state solutions of our model show that the predicted clone size-distribution is sensitive to only two combinations of parameters. By fitting the measured clone size-distributions to our mechanistic model, we estimate both the effective HSC differentiation rate and the number of active HSCs. NSF and NIH.

  18. 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

  19. Diverse origin of mitochondrial lineages in Iron Age Black Sea Scythians

    PubMed Central

    Juras, Anna; Krzewińska, Maja; Nikitin, Alexey G.; Ehler, Edvard; Chyleński, Maciej; Łukasik, Sylwia; Krenz-Niedbała, Marta; Sinika, Vitaly; Piontek, Janusz; Ivanova, Svetlana; Dabert, Miroslawa; Götherström, Anders

    2017-01-01

    Scythians were nomadic and semi-nomadic people that ruled the Eurasian steppe during much of the first millennium BCE. While having been extensively studied by archaeology, very little is known about their genetic identity. To fill this gap, we analyzed ancient mitochondrial DNA (mtDNA) from Scythians of the North Pontic Region (NPR) and successfully retrieved 19 whole mtDNA genomes. We have identified three potential mtDNA lineage ancestries of the NPR Scythians tracing back to hunter-gatherer and nomadic populations of east and west Eurasia as well as the Neolithic farming expansion into Europe. One third of all mt lineages in our dataset belonged to subdivisions of mt haplogroup U5. A comparison of NPR Scythian mtDNA linages with other contemporaneous Scythian groups, the Saka and the Pazyryks, reveals a common mtDNA package comprised of haplogroups H/H5, U5a, A, D/D4, and F1/F2. Of these, west Eurasian lineages show a downward cline in the west-east direction while east Eurasian haplogroups display the opposite trajectory. An overall similarity in mtDNA lineages of the NPR Scythians was found with the late Bronze Age Srubnaya population of the Northern Black Sea region which supports the archaeological hypothesis suggesting Srubnaya people as ancestors of the NPR Scythians. PMID:28266657

  20. Equine encephalomyelitis outbreak caused by a genetic lineage 2 West Nile virus in Hungary.

    PubMed

    Kutasi, O; Bakonyi, T; Lecollinet, S; Biksi, I; Ferenczi, E; Bahuon, C; Sardi, S; Zientara, S; Szenci, O

    2011-01-01

    The spread of lineage 2 West Nile virus (WNV) from sub-Saharan regions to Europe and the unpredictable change in pathogenicity indicate a potential public and veterinary health threat and requires scientific awareness. To describe the results of clinical and virological investigations of the 1st outbreak of a genetic lineage 2 WNV encephalomyelitis in horses. Seventeen horses with neurologic signs. Information regarding signalment, clinical signs, and outcome was obtained for each animal. Serology was performed in 15 cases, clinicopathological examination in 7 cases, and cerebrospinal fluid was collected from 2 horses. Histopathology was carried out in 4 horses, 2 of which were assessed for the presence of WNV in their nervous system. WNV neutralizing antibody titers were between 10 and 270 (median, 90) and the results of other serological assays were in agreement with those of the plaque reduction neutralization test. Common signs included ataxia, weakness, asymmetric gait, muscle tremors, hypersensitivity, cranial nerve deficits, and recumbency. Twelve animals survived. Amplicons derived from the infection-positive specimens allowed molecular characterization of the viral strain. From our results, we conclude that this outbreak was caused by a lineage 2 WNV strain, even though such strains often are considered nonpathogenic. Neurological signs and survival rates were similar to those reported for lineage 1 virus infections. The disease occurrence was not geographically limited as had been the typical case during European outbreaks; this report describes a substantial northwestern spread of the pathogen. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  1. Study of the carapace shape and growth in two Galápagos tortoise lineages.

    PubMed

    Chiari, Ylenia; Claude, Julien

    2011-03-01

    Galápagos tortoises possess two main shell forms, domed and saddleback, that correlate with the biogeographic history of this species group. However, the lack of description of morphological shell variation within and among populations has prevented the understanding of the contribution of evolutionary forces and the potential role of ontogeny in shaping morphological shell differences. Here, we analyze two lineages of Galápagos tortoises inhabiting Santa Cruz Island by applying geometric morphometrics in combination with a photogrammetry 3D reconstruction method on a set of tortoises of different ages (from juvenile to adult). The aim of this study is to describe morphological features on the carapace that could be used for taxonomic recognition by taking into account confounding factors, such as the morphological changes occurring during growth. Our results indicate that despite the shared similarities of growth patterns and of morphological changes observed during growth, the two lineages and the different sexes can be distinguished on the basis of distinct carapace features. Lineages differ by the shape of the vertebral (especially concerning their width) and pleural scutes, with one lineage having a more compressed carapace shape, whereas the other possesses a carapace that is more elongated and expanded toward the sides as well as an higher positioning of the first vertebral scute. Furthermore, females have a more elongated and wider carapace shape than males. Finally, carapace shape changes with growth, with vertebral scutes becoming narrower and pleural scutes becoming larger during late ontogeny.

  2. Overwintering of Uranotaenia Unguiculata Adult Females in Central Europe: A Possible Way of Persistence of the Putative New Lineage of West Nile Virus?

    PubMed

    Rudolf, Ivo; Šebesta, Oldřich; Straková, Petra; Betášová, Lenka; Blažejová, Hana; VEnclíková, Kristýna; Seidel, Bernhard; Tóth, Sandor; Hubálek, Zdeněk; Schaffner, Francis

    2015-12-01

    We report the overwintering of Uranotaenia unguiculata adult females in Central Europe (Czech Republic, Hungary, Austria). This finding suggests a potential mode of winter persistence of putative novel lineage of West Nile virus in the temperate regions of Europe.

  3. Numerical Implementation of a Multiple-ISV Thermodynamically-Based Work Potential Theory for Modeling Progressive Damage and Failure in Fiber-Reinforced Laminates

    NASA Technical Reports Server (NTRS)

    Pineda, Evan J.; Waas, Anthony M.

    2011-01-01

    A thermodynamically-based work potential theory for modeling progressive damage and failure in fiber-reinforced laminates is presented. The current, multiple-internal state variable (ISV) formulation, enhanced Schapery theory (EST), utilizes separate ISVs for modeling the effects of damage and failure. Damage is considered to be the effect of any structural changes in a material that manifest as pre-peak non-linearity in the stress versus strain response. Conversely, failure is taken to be the effect of the evolution of any mechanisms that results in post-peak strain softening. It is assumed that matrix microdamage is the dominant damage mechanism in continuous fiber-reinforced polymer matrix laminates, and its evolution is controlled with a single ISV. Three additional ISVs are introduced to account for failure due to mode I transverse cracking, mode II transverse cracking, and mode I axial failure. Typically, failure evolution (i.e., post-peak strain softening) results in pathologically mesh dependent solutions within a finite element method (FEM) setting. Therefore, consistent character element lengths are introduced into the formulation of the evolution of the three failure ISVs. Using the stationarity of the total work potential with respect to each ISV, a set of thermodynamically consistent evolution equations for the ISVs is derived. The theory is implemented into commercial FEM software. Objectivity of total energy dissipated during the failure process, with regards to refinements in the FEM mesh, is demonstrated. The model is also verified against experimental results from two laminated, T800/3900-2 panels containing a central notch and different fiber-orientation stacking sequences. Global load versus displacement, global load versus local strain gage data, and macroscopic failure paths obtained from the models are compared to the experiments.

  4. A Thermodynamically-Based Mesh Objective Work Potential Theory for Predicting Intralaminar Progressive Damage and Failure in Fiber-Reinforced Laminates

    NASA Technical Reports Server (NTRS)

    Pineda, Evan J.; Waas, Anthony M.

    2012-01-01

    A thermodynamically-based work potential theory for modeling progressive damage and failure in fiber-reinforced laminates is presented. The current, multiple-internal state variable (ISV) formulation, enhanced Schapery theory (EST), utilizes separate ISVs for modeling the effects of damage and failure. Damage is considered to be the effect of any structural changes in a material that manifest as pre-peak non-linearity in the stress versus strain response. Conversely, failure is taken to be the effect of the evolution of any mechanisms that results in post-peak strain softening. It is assumed that matrix microdamage is the dominant damage mechanism in continuous fiber-reinforced polymer matrix laminates, and its evolution is controlled with a single ISV. Three additional ISVs are introduced to account for failure due to mode I transverse cracking, mode II transverse cracking, and mode I axial failure. Typically, failure evolution (i.e., post-peak strain softening) results in pathologically mesh dependent solutions within a finite element method (FEM) setting. Therefore, consistent character element lengths are introduced into the formulation of the evolution of the three failure ISVs. Using the stationarity of the total work potential with respect to each ISV, a set of thermodynamically consistent evolution equations for the ISVs is derived. The theory is implemented into commercial FEM software. Objectivity of total energy dissipated during the failure process, with regards to refinements in the FEM mesh, is demonstrated. The model is also verified against experimental results from two laminated, T800/3900-2 panels containing a central notch and different fiber-orientation stacking sequences. Global load versus displacement, global load versus local strain gage data, and macroscopic failure paths obtained from the models are compared to the experiments.

  5. Aspects of marine geoscience: a review and thoughts on potential for observing active processes and progress through collaboration between the ocean sciences.

    PubMed

    Mitchell, Neil C

    2012-12-13

    Much progress has been made in the UK in characterizing the internal structures of major physiographic features in the oceans and in developing understanding of the geological processes that have created or shaped them. UK researchers have authored articles of high impact in all areas described here. In contrast to terrestrial geoscience, however, there have been few instrumented observations made of active processes by UK scientists. This is an area that could be developed over the next decades in the UK. Research on active processes has the potential ability to engage the wider public: Some active processes present significant geo-hazards to populations and offshore infrastructure that require monitoring and there could be commercial applications of technological developments needed for science. Some of the suggestions could involve studies in shallow coastal waters where ship costs are much reduced, addressing tighter funding constraints over the near term. The possibilities of measuring aspects of volcanic eruptions, flowing lava, turbidity currents and mass movements (landslides) are discussed. A further area of potential development is in greater collaboration between the ocean sciences. For example, it is well known in terrestrial geomorphology that biological agents are important in modulating erosion and the transport of sediments, ultimately affecting the shape of the Earth's surface in various ways. The analogous effect of biology on large-scale geomorphology in the oceans is also known but remains poorly quantified. Physical oceanographic models are becoming increasingly accurate and could be used to study further the patterns of erosion, particle transport and deposition in the oceans. Marine geological and geophysical data could in turn be useful for further verification of such models. Adapting them to conditions of past oceans could address the shorter-period movements, such as due to internal waves and tides, which have been barely addressed in

  6. Diverse pathways of epithelial mesenchymal transition related with cancer progression and metastasis and potential effects of endocrine disrupting chemicals on epithelial mesenchymal transition process.

    PubMed

    Lee, Hae-Miru; Hwang, Kyung-A; Choi, Kyung-Chul

    2017-12-05

    Endocrine disrupting chemicals (EDCs) are natural or synthetic compounds that interfere with normal functions of natural hormones in the body, leading to a disruption of the endocrine system. Specifically, EDCs have the potential to cause formation of several hormone-dependent cancers, including breast, ovarian, and prostate cancers. Epithelial mesenchymal transition (EMT) process by which epithelial cells lose their cell polarity and cell-cell adhesion and acquire mesenchymal phenotype is closely associated with malignant transformation and the initiation of cancer metastasis. As a key epithelial marker responsible for adherens junction, E-cadherin enables the cells to maintain epithelial phenotypes. EMT event is induced by E-cadherin loss which can be carried out by many transcription factors (TFs), including Snail, Slug, ZEB1, ZEB2, Kruppel-like factor 8 (KLF8), and Twist. N-cadherin, fibronectin, and vimentin are mesenchymal markers needed for cellular migration. The EMT process is regulated by several signaling pathways mediated by transforming growth factor β (TGF-β), Wnt-β-catenin, Notch, Hedgehog, and receptor tyrosine kinases. In the present article, we reviewed the current understanding of cancer progression effects of synthetic chemical EDCs such as bisphenol A (BPA), phthalates, tetrachlorodibenzo-p-dioxin (TCDD), and triclosan by focusing their roles in the EMT process. Collectively, the majority of previous studies revealed that BPA, phthalates, TCDD, and triclosan have the potential to induce cancer metastasis through regulating EMT markers and migration via several signaling pathways associated with the EMT program. Therefore, it is considered that the exposure to these EDCs can increase the risk aggravating the disease for the patients suffering cancer and that more regulations about the use of these EDCs are needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Decreased zinc in the development and progression of malignancy: an important common relationship and potential for prevention and treatment of carcinomas.

    PubMed

    Costello, Leslie C; Franklin, Renty B

    2017-01-01

    Efficacious chemotherapy does not exist for treatment or prevention of prostate, liver, and pancreatic carcinomas, and some other cancers that exhibit decreased zinc in malignancy. Zinc treatment offers a potential solution; but its support has been deterred by adverse bias. Areas covered: 1. The clinical and experimental evidence for the common ZIP transporter/Zn down regulation in these cancers. 2. The evidence for a zinc approach to prevent and/or treat these carcinomas. 3. The issues that introduce bias against support for the zinc approach. Expert opinion: ZIP/Zn downregulation is a clinically established common event in prostate, hepatocellular and pancreatic cancers. 2. Compelling evidence supports the plausibility that a zinc treatment regimen will prevent development of malignancy and termination of progressing malignancy in these cancers; and likely other carcinomas that exhibit decreased zinc. 3. Scientifically-unfounded issues that oppose this ZIP/Zn relationship have introduced bias against support for research and funding of a zinc treatment approach. 4. The clinically-established and supporting experimental evidence provide the scientific credibility that should dictate the support for research and funding of a zinc approach for the treatment and possible prevention of these cancers. 5. This is in the best interest of the medical community and the public-at-large.

  8. Decreased zinc in the development and progression of malignancy: an important common relationship and potential for prevention and treatment of carcinomas

    PubMed Central

    Costello, Leslie C.; Franklin, Renty B.

    2016-01-01

    Introduction Efficacious chemotherapy does not exist for treatment or prevention of prostate, liver, and pancreatic carcinomas, and some other cancers that exhibit decreased zinc in malignancy. Zinc treatment offers a potential solution; but its support has been deterred by adverse bias. Areas covered 1. The clinical and experimental evidence for the common ZIP transporter/Zn down regulation in these cancers. 2. The evidence for a zinc approach to prevent and/or treat these carcinomas. 3. The issues that introduce bias against support for the zinc approach. Expert opinion ZIP/Zn downregulation is a clinically established common event in prostate, hepatocellular and pancreatic cancers. 2. Compelling evidence supports the plausibility that a zinc treatment regimen will prevent development of malignancy and termination of progressing malignancy in these cancers; and likely other carcinomas that exhibit decreased zinc. 3. Scientifically-unfounded issues that oppose this ZIP/Zn relationship have introduced bias against support for research and funding of a zinc treatment approach. 4. The clinically-established and supporting experimental evidence provide the scientific credibility that should dictate the support for research and funding of a zinc approach for the treatment and possible prevention of these cancers. 5. This is in the best interest of the medical community and the public-at-large. PMID:27885880

  9. Evidence of Natural Hybridization in Brazilian Wild Lineages of Saccharomyces cerevisiae.

    PubMed

    Barbosa, Raquel; Almeida, Pedro; Safar, Silvana V B; Santos, Renata Oliveira; Morais, Paula B; Nielly-Thibault, Lou; Leducq, Jean-Baptiste; Landry, Christian R; Gonçalves, Paula; Rosa, Carlos A; Sampaio, José Paulo

    2016-01-18

    The natural biology of Saccharomyces cerevisiae, the best known unicellular model eukaryote, remains poorly documented and understood although recent progress has started to change this situation. Studies carried out recently in the Northern Hemisphere revealed the existence of wild populations associated with oak trees in North America, Asia, and in the Mediterranean region. However, in spite of these advances, the global distribution of natural populations of S. cerevisiae, especially in regions were oaks and other members of the Fagaceae are absent, is not well understood. Here we investigate the occurrence of S. cerevisiae in Brazil, a tropical region where oaks and other Fagaceae are absent. We report a candidate natural habitat of S. cerevisiae in South America and, using whole-genome data, we uncover new lineages that appear to have as closest relatives the wild populations found in North America and Japan. A population structure analysis revealed the penetration of the wine genotype into the wild Brazilian population, a first observation of the impact of domesticated microbe lineages on the genetic structure of wild populations. Unexpectedly, the Brazilian population shows conspicuous evidence of hybridization with an American population of Saccharomyces paradoxus. Introgressions from S. paradoxus were significantly enriched in genes encoding secondary active transmembrane transporters. We hypothesize that hybridization in tropical wild lineages may have facilitated the habitat transition accompanying the colonization of the tropical ecosystem.

  10. Targeted Deletion of Capn4 in Cells of the Chondrocyte Lineage Impairs Chondrocyte Proliferation and Differentiation▿

    PubMed Central

    Kashiwagi, Aki; Schipani, Ernestina; Fein, Mikaela J.; Greer, Peter A.; Shimada, Masako

    2010-01-01

    Calpains are calcium-dependent intracellular cysteine proteases, which include ubiquitously expressed μ- and m-calpains. Both calpains are heterodimers consisting of a large catalytic subunit and a small regulatory subunit. The calpain small subunit encoded by the gene Capn4 directly binds to the intracellular C-terminal tail of the receptor for the parathyroid hormone (PTH) and PTH-related peptide and modulates cellular functions in cells of the osteoblast lineage in vitro and in vivo. To investigate a physiological role of the calpain small subunit in cells of the chondrocyte lineage, we generated chondrocyte-specific Capn4 knockout mice. Mutant embryos had reduced chondrocyte proliferation and differentiation in embryonic growth plates compared with control littermates. In vitro analysis further revealed that deletion of Capn4 in cells of the chondrocyte lineage correlated with impaired cell cycle progression at the G1/S transition, reduced cyclin D gene transcription, and accumulated cell cycle proteins known as calpain substrates. Moreover, silencing of p27Kip1 rescued an impaired cell growth phenotype in Capn4 knockdown cells, and reintroducing the calpain small subunit partially normalized cell growth and accumulated cyclin D protein levels in a dose-dependent manner. Collectively, our findings suggest that the calpain small subunit is essential for proper chondrocyte functions in embryonic growth plates. PMID:20368361

  11. Evidence of Natural Hybridization in Brazilian Wild Lineages of Saccharomyces cerevisiae

    PubMed Central

    Barbosa, Raquel; Almeida, Pedro; Safar, Silvana V.B.; Santos, Renata Oliveira; Morais, Paula B.; Nielly-Thibault, Lou; Leducq, Jean-Baptiste; Landry, Christian R.; Gonçalves, Paula; Rosa, Carlos A.; Sampaio, José Paulo

    2016-01-01

    The natural biology of Saccharomyces cerevisiae, the best known unicellular model eukaryote, remains poorly documented and understood although recent progress has started to change this situation. Studies carried out recently in the Northern Hemisphere revealed the existence of wild populations associated with oak trees in North America, Asia, and in the Mediterranean region. However, in spite of these advances, the global distribution of natural populations of S. cerevisiae, especially in regions were oaks and other members of the Fagaceae are absent, is not well understood. Here we investigate the occurrence of S. cerevisiae in Brazil, a tropical region where oaks and other Fagaceae are absent. We report a candidate natural habitat of S. cerevisiae in South America and, using whole-genome data, we uncover new lineages that appear to have as closest relatives the wild populations found in North America and Japan. A population structure analysis revealed the penetration of the wine genotype into the wild Brazilian population, a first observation of the impact of domesticated microbe lineages on the genetic structure of wild populations. Unexpectedly, the Brazilian population shows conspicuous evidence of hybridization with an American population of Saccharomyces paradoxus. Introgressions from S. paradoxus were significantly enriched in genes encoding secondary active transmembrane transporters. We hypothesize that hybridization in tropical wild lineages may have facilitated the habitat transition accompanying the colonization of the tropical ecosystem. PMID:26782936

  12. Histone demethylase KDM2B regulates lineage commitment in normal and malignant hematopoiesis

    PubMed Central

    Andricovich, Jaclyn; Kai, Yan; Peng, Weiqun; Foudi, Adlen; Tzatsos, Alexandros

    2016-01-01

    The development of the hematopoietic system is a dynamic process that is controlled by the interplay between transcriptional and epigenetic networks to determine cellular identity. These networks are critical for lineage specification and are frequently dysregulated in leukemias. Here, we identified histone demethylase KDM2B as a critical regulator of definitive hematopoiesis and lineage commitment of murine hematopoietic stem and progenitor cells (HSPCs). RNA sequencing of Kdm2b-null HSPCs and genome-wide ChIP studies in human leukemias revealed that KDM2B cooperates with polycomb and trithorax complexes to regulate differentiation, lineage choice, cytokine signaling, and cell cycle. Furthermore, we demonstrated that KDM2B exhibits a dichotomous role in hematopoietic malignancies. Specifically, we determined that KDM2B maintains lymphoid leukemias, but restrains RAS-driven myeloid transformation. Our study reveals that KDM2B is an important mediator of hematopoietic cell development and has opposing roles in tumor progression that are dependent on cellular context. PMID:26808549

  13. Contemporaneous and recent radiations of the world's major succulent plant lineages

    PubMed Central

    Arakaki, Mónica; Christin, Pascal-A