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Sample records for integrated sox trap

  1. SO2 sorption on fresh and aged SOx traps

    International Nuclear Information System (INIS)

    Limousy, L.; Mahzoul, H.; Brilhac, J.F.; Gilot, P.; Garin, F.; Maire, G.

    2003-01-01

    This study has an important impact on gasoline engine-pollution control working under lean conditions. While NO x trap systems can remove NO x under an oxidative atmosphere, they are poisoned by SO x present in the exhaust gases. In order to protect NO x traps, an upstream SO x trap has to be used. SO 2 adsorption was studied in the presence of water and oxygen. Model and commercial catalysts were tested between 300 and 700C. In order to assign the TPD peaks, the decomposition of commercial sulphates was studied versus the temperature. Adsorption capacity is not sensitive to oxygen and SO 2 concentrations but is strongly related to barium content. Cerium content is not a key parameter for SO 2 adsorption capacity in the presence of oxygen. XPS analysis allowed us to differentiate between all the species formed during the adsorption process. When the catalysts are aged, specific surface area decreases as well as adsorption capacity

  2. Microfabricated Microwave-Integrated Surface Ion Trap

    Science.gov (United States)

    Revelle, Melissa C.; Blain, Matthew G.; Haltli, Raymond A.; Hollowell, Andrew E.; Nordquist, Christopher D.; Maunz, Peter

    2017-04-01

    Quantum information processing holds the key to solving computational problems that are intractable with classical computers. Trapped ions are a physical realization of a quantum information system in which qubits are encoded in hyperfine energy states. Coupling the qubit states to ion motion, as needed for two-qubit gates, is typically accomplished using Raman laser beams. Alternatively, this coupling can be achieved with strong microwave gradient fields. While microwave radiation is easier to control than a laser, it is challenging to precisely engineer the radiated microwave field. Taking advantage of Sandia's microfabrication techniques, we created a surface ion trap with integrated microwave electrodes with sub-wavelength dimensions. This multi-layered device permits co-location of the microwave antennae and the ion trap electrodes to create localized microwave gradient fields and necessary trapping fields. Here, we characterize the trap design and present simulated microwave performance with progress towards experimental results. This research was funded, in part, by the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA).

  3. Sox9

    DEFF Research Database (Denmark)

    Seymour, Philip A

    2014-01-01

    Over the last decade, it has been discovered that the transcription factor Sox9 plays several critical roles in governing the development of the embryonic pancreas and the homeostasis of the mature organ. While analysis of pancreata from patients affected by the Sox9 haploinsufficiency syndrome...... endocrine differentiation and maintaining pancreatic ductal identity, and it has recently been unveiled as a key player in the initiation of pancreatic cancer. These functions of Sox9 are discussed in this article, with special emphasis on the knowledge gained from various loss-of-function and lineage...

  4. Integrated Visible Photonics for Trapped-Ion Quantum Computing

    Science.gov (United States)

    2017-06-10

    etch to provide a smooth oxide facet, and clearance for fiber positioning for edge input coupling. Integrated Visible Photonics for Trapped-Ion...capability to optically address individual ions at several wavelengths. We demonstrate a dual-layered silicon nitride photonic platform for integration...coherence times, strong coulomb interactions, and optical addressability, hold great promise for implementation of practical quantum information

  5. Integrated microfluidic device for single-cell trapping and spectroscopy

    KAUST Repository

    Liberale, Carlo

    2013-02-13

    Optofluidic microsystems are key components towards lab-on-a-chip devices for manipulation and analysis of biological specimens. In particular, the integration of optical tweezers (OT) in these devices allows stable sample trapping, while making available mechanical, chemical and spectroscopic analyses.

  6. Integrated microfluidic device for single-cell trapping and spectroscopy

    KAUST Repository

    Liberale, Carlo; Cojoc, G.; Bragheri, F.; Minzioni, P.; Perozziello, G.; La Rocca, R.; Ferrara, L.; Rajamanickam, V.; Di Fabrizio, Enzo M.; Cristiani, I.

    2013-01-01

    Optofluidic microsystems are key components towards lab-on-a-chip devices for manipulation and analysis of biological specimens. In particular, the integration of optical tweezers (OT) in these devices allows stable sample trapping, while making available mechanical, chemical and spectroscopic analyses.

  7. Integrated System Technologies for Modular Trapped Ion Quantum Information Processing

    Science.gov (United States)

    Crain, Stephen G.

    Although trapped ion technology is well-suited for quantum information science, scalability of the system remains one of the main challenges. One of the challenges associated with scaling the ion trap quantum computer is the ability to individually manipulate the increasing number of qubits. Using micro-mirrors fabricated with micro-electromechanical systems (MEMS) technology, laser beams are focused on individual ions in a linear chain and steer the focal point in two dimensions. Multiple single qubit gates are demonstrated on trapped 171Yb+ qubits and the gate performance is characterized using quantum state tomography. The system features negligible crosstalk to neighboring ions (technologies demonstrated in this thesis can be integrated to form a single quantum register with all of the necessary resources to perform local gates as well as high fidelity readout and provide a photon link to other systems.

  8. Advanced ion trap structures with integrated tools for qubit manipulation

    Science.gov (United States)

    Sterk, J. D.; Benito, F.; Clark, C. R.; Haltli, R.; Highstrete, C.; Nordquist, C. D.; Scott, S.; Stevens, J. E.; Tabakov, B. P.; Tigges, C. P.; Moehring, D. L.; Stick, D.; Blain, M. G.

    2012-06-01

    We survey the ion trap fabrication technologies available at Sandia National Laboratories. These include four metal layers, precision backside etching, and low profile wirebonds. We demonstrate loading of ions in a variety of ion traps that utilize these technologies. Additionally, we present progress towards integration of on-board filtering with trench capacitors, photon collection via an optical cavity, and integrated microwave electrodes for localized hyperfine qubit control and magnetic field gradient quantum gates. [4pt] This work was supported by Sandia's Laboratory Directed Research and Development (LDRD) Program and the Intelligence Advanced Research Projects Activity (IARPA). Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the US Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  9. Cellular Reprogramming Employing Recombinant Sox2 Protein

    Directory of Open Access Journals (Sweden)

    Marc Thier

    2012-01-01

    Full Text Available Induced pluripotent stem (iPS cells represent an attractive option for the derivation of patient-specific pluripotent cells for cell replacement therapies as well as disease modeling. To become clinically meaningful, safe iPS cells need to be generated exhibiting no permanent genetic modifications that are caused by viral integrations of the reprogramming transgenes. Recently, various experimental strategies have been applied to accomplish transgene-free derivation of iPS cells, including the use of nonintegrating viruses, episomal expression, or excision of transgenes after reprogramming by site-specific recombinases or transposases. A straightforward approach to induce reprogramming factors is the direct delivery of either synthetic mRNA or biologically active proteins. We previously reported the generation of cell-permeant versions of Oct4 (Oct4-TAT and Sox2 (Sox2-TAT proteins and showed that Oct4-TAT is reprogramming-competent, that is, it can substitute for Oct4-encoding virus. Here, we explore conditions for enhanced Sox2-TAT protein stabilization and functional delivery into somatic cells. We show that cell-permeant Sox2 protein can be stabilized by lipid-rich albumin supplements in serum replacement or low-serum-supplemented media. Employing optimized conditions for protein delivery, we demonstrate that Sox2-TAT protein is able to substitute for viral Sox2. Sox2-piPS cells express pluripotency-associated markers and differentiate into all three germ layers.

  10. Molecular basis for the genome engagement by Sox proteins.

    Science.gov (United States)

    Hou, Linlin; Srivastava, Yogesh; Jauch, Ralf

    2017-03-01

    The Sox transcription factor family consists of 20 members in the human genome. Many of them are key determinants of cellular identities and possess the capacity to reprogram cell fates by pioneering the epigenetic remodeling of the genome. This activity is intimately tied to their ability to specifically bind and bend DNA alone or with other proteins. Here we discuss our current knowledge on how Sox transcription factors such as Sox2, Sox17, Sox18 and Sox9 'read' the genome to find and regulate their target genes and highlight the roles of partner factors including Pax6, Nanog, Oct4 and Brn2. We integrate insights from structural and biochemical studies as well as high-throughput assays to probe DNA specificity in vitro as well as in cells and tissues. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  11. Remarkable evolutionary conservation of SOX14 orthologues

    Indian Academy of Sciences (India)

    similar amino acid residues are shaded grey. N: N- terminus of SOX14, specific for B2 group of SOX proteins; HMG domain: High Mobility Group binding domain; GBHR: Group B Homology Region; B, C, E, F and G, SOX14 specific regions; A, h1, h2 and h3, SOX14/SOX21 homology regions. 1. SOX14 Homo sapiens, 2.

  12. SOX9 regulates ERBB signalling in pancreatic cancer development.

    Science.gov (United States)

    Grimont, Adrien; Pinho, Andreia V; Cowley, Mark J; Augereau, Cécile; Mawson, Amanda; Giry-Laterrière, Marc; Van den Steen, Géraldine; Waddell, Nicola; Pajic, Marina; Sempoux, Christine; Wu, Jianmin; Grimmond, Sean M; Biankin, Andrew V; Lemaigre, Frédéric P; Rooman, Ilse; Jacquemin, Patrick

    2015-11-01

    The transcription factor SOX9 was recently shown to stimulate ductal gene expression in pancreatic acinar-to-ductal metaplasia and to accelerate development of premalignant lesions preceding pancreatic ductal adenocarcinoma (PDAC). Here, we investigate how SOX9 operates in pancreatic tumourigenesis. We analysed genomic and transcriptomic data from surgically resected PDAC and extended the expression analysis to xenografts from PDAC samples and to PDAC cell lines. SOX9 expression was manipulated in human cell lines and mouse models developing PDAC. We found genetic aberrations in the SOX9 gene in about 15% of patient tumours. Most PDAC samples strongly express SOX9 protein, and SOX9 levels are higher in classical PDAC. This tumour subtype is associated with better patient outcome, and cell lines of this subtype respond to therapy targeting epidermal growth factor receptor (EGFR/ERBB1) signalling, a pathway essential for pancreatic tumourigenesis. In human PDAC, high expression of SOX9 correlates with expression of genes belonging to the ERBB pathway. In particular, ERBB2 expression in PDAC cell lines is stimulated by SOX9. Inactivating Sox9 expression in mice confirmed its role in PDAC initiation; it demonstrated that Sox9 stimulates expression of several members of the ERBB pathway and is required for ERBB signalling activity. By integrating data from patient samples and mouse models, we found that SOX9 regulates the ERBB pathway throughout pancreatic tumourigenesis. Our work opens perspectives for therapy targeting tumourigenic mechanisms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Optical stretching of giant unilamellar vesicles with an integrated dual-beam optical trap.

    Science.gov (United States)

    Solmaz, Mehmet E; Biswas, Roshni; Sankhagowit, Shalene; Thompson, James R; Mejia, Camilo A; Malmstadt, Noah; Povinelli, Michelle L

    2012-10-01

    We have integrated a dual-beam optical trap into a microfluidic platform and used it to study membrane mechanics in giant unilamellar vesicles (GUVs). We demonstrate the trapping and stretching of GUVs and characterize the membrane response to a step stress. We then measure area strain as a function of applied stress to extract the bending modulus of the lipid bilayer in the low-tension regime.

  14. SOX sensitivity study

    Energy Technology Data Exchange (ETDEWEB)

    Martyn, Johann [Johannes Gutenberg-Universitaet, Mainz (Germany); Collaboration: BOREXINO-Collaboration

    2016-07-01

    To this day most experimental results on neutrino oscillations can be explained in the standard three neutrino model. There are however a few experiments that show anomalous behaviour at a very short baselines. These anomalies can hypothetically be explained with the existence of one or additional more light neutrino states that do not take part in weak interactions and are thus called sterile. Although the anomalies only give a hint that such sterile neutrinos could exist the prospect for physics beyond the standard model is a major motivation to investigate the neutrino oscillations in new very short baseline experiments. The SOX (Short distance Oscillations in BoreXino) experiment will use the Borexino detector and a {sup 144}Ce source to search for sterile neutrinos via the occurance of an oscillation pattern at a baseline of several meters. This talk examines the impact of the Borexino detector systematics on the experimental sensitivity of SOX.

  15. Experimental system design for the integration of trapped-ion and superconducting qubit systems

    Science.gov (United States)

    De Motte, D.; Grounds, A. R.; Rehák, M.; Rodriguez Blanco, A.; Lekitsch, B.; Giri, G. S.; Neilinger, P.; Oelsner, G.; Il'ichev, E.; Grajcar, M.; Hensinger, W. K.

    2016-12-01

    We present a design for the experimental integration of ion trapping and superconducting qubit systems as a step towards the realization of a quantum hybrid system. The scheme addresses two key difficulties in realizing such a system: a combined microfabricated ion trap and superconducting qubit architecture, and the experimental infrastructure to facilitate both technologies. Developing upon work by Kielpinski et al. (Phys Rev Lett 108(13):130504, 2012. doi: 10.1103/PhysRevLett.108.130504), we describe the design, simulation and fabrication process for a microfabricated ion trap capable of coupling an ion to a superconducting microwave LC circuit with a coupling strength in the tens of kHz. We also describe existing difficulties in combining the experimental infrastructure of an ion trapping set-up into a dilution refrigerator with superconducting qubits and present solutions that can be immediately implemented using current technology.

  16. Genetics Home Reference: SOX2 anophthalmia syndrome

    Science.gov (United States)

    ... Twitter Home Health Conditions SOX2 anophthalmia syndrome SOX2 anophthalmia syndrome Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description SOX2 anophthalmia syndrome is a rare disorder characterized by abnormal ...

  17. Integrated Metabolomics and Morphogenesis Reveal Volatile Signaling of the Nematode-Trapping Fungus Arthrobotrys oligospora.

    Science.gov (United States)

    Wang, Bai-Le; Chen, Yong-Hong; He, Jia-Ning; Xue, Hua-Xi; Yan, Ni; Zeng, Zhi-Jun; Bennett, Joan W; Zhang, Ke-Qin; Niu, Xue-Mei

    2018-05-01

    The adjustment of metabolic patterns is fundamental to fungal biology and plays vital roles in adaptation to diverse ecological challenges. Nematode-trapping fungi can switch their lifestyle from saprophytic to pathogenic by developing specific trapping devices induced by nematodes to infect their prey as a response to nutrient depletion in nature. However, the chemical identity of the specific fungal metabolites used during the switch remains poorly understood. We hypothesized that these important signal molecules might be volatile in nature. Gas chromatography-mass spectrometry was used to carry out comparative analysis of fungal metabolomics during the saprophytic and pathogenic lifestyles of the model species Arthrobotrys oligospora Two media commonly used in research on this species, cornmeal agar (CMA) and potato dextrose agar (PDA), were chosen for use in this study. The fungus produced a small group of volatile furanone and pyrone metabolites that were associated with the switch from the saprophytic to the pathogenic stage. A. oligospora fungi grown on CMA tended to produce more traps and employ attractive furanones to improve the utilization of traps, while fungi grown on PDA developed fewer traps and used nematode-toxic furanone metabolites to compensate for insufficient traps. Another volatile pyrone metabolite, maltol, was identified as a morphological regulator for enhancing trap formation. Deletion of the gene AOL_s00079g496 in A. oligospora led to increased amounts of the furanone attractant (2-fold) in mutants and enhanced the attractive activity (1.5-fold) of the fungus, while it resulted in decreased trap formation. This investigation provides new insights regarding the comprehensive tactics of fungal adaptation to environmental stress, integrating both morphological and metabolomic mechanisms. IMPORTANCE Nematode-trapping fungi are a unique group of soil-living fungi that can switch from the saprophytic to the pathogenic lifestyle once they come

  18. Integrated fiber-mirror ion trap for strong ion-cavity coupling

    International Nuclear Information System (INIS)

    Brandstätter, B.; Schüppert, K.; Casabone, B.; Friebe, K.; Stute, A.; Northup, T. E.; McClung, A.; Schmidt, P. O.; Deutsch, C.; Reichel, J.; Blatt, R.

    2013-01-01

    We present and characterize fiber mirrors and a miniaturized ion-trap design developed to integrate a fiber-based Fabry-Perot cavity (FFPC) with a linear Paul trap for use in cavity-QED experiments with trapped ions. Our fiber-mirror fabrication process not only enables the construction of FFPCs with small mode volumes, but also allows us to minimize the influence of the dielectric fiber mirrors on the trapped-ion pseudopotential. We discuss the effect of clipping losses for long FFPCs and the effect of angular and lateral displacements on the coupling efficiencies between cavity and fiber. Optical profilometry allows us to determine the radii of curvature and ellipticities of the fiber mirrors. From finesse measurements, we infer a single-atom cooperativity of up to 12 for FFPCs longer than 200 μm in length; comparison to cavities constructed with reference substrate mirrors produced in the same coating run indicates that our FFPCs have similar scattering losses. We characterize the birefringence of our fiber mirrors, finding that careful fiber-mirror selection enables us to construct FFPCs with degenerate polarization modes. As FFPCs are novel devices, we describe procedures developed for handling, aligning, and cleaning them. We discuss experiments to anneal fiber mirrors and explore the influence of the atmosphere under which annealing occurs on coating losses, finding that annealing under vacuum increases the losses for our reference substrate mirrors. X-ray photoelectron spectroscopy measurements indicate that these losses may be attributable to oxygen depletion in the mirror coating. Special design considerations enable us to introduce a FFPC into a trapped ion setup. Our unique linear Paul trap design provides clearance for such a cavity and is miniaturized to shield trapped ions from the dielectric fiber mirrors. We numerically calculate the trap potential in the absence of fibers. In the experiment additional electrodes can be used to compensate

  19. Expression of Sox genes in tooth development.

    Science.gov (United States)

    Kawasaki, Katsushige; Kawasaki, Maiko; Watanabe, Momoko; Idrus, Erik; Nagai, Takahiro; Oommen, Shelly; Maeda, Takeyasu; Hagiwara, Nobuko; Que, Jianwen; Sharpe, Paul T; Ohazama, Atsushi

    2015-01-01

    Members of the Sox gene family play roles in many biological processes including organogenesis. We carried out comparative in situ hybridization analysis of seventeen sox genes (Sox1-14, 17, 18, 21) during murine odontogenesis from the epithelial thickening to the cytodifferentiation stages. Localized expression of five Sox genes (Sox6, 9, 13, 14 and 21) was observed in tooth bud epithelium. Sox13 showed restricted expression in the primary enamel knots. At the early bell stage, three Sox genes (Sox8, 11, 17 and 21) were expressed in pre-ameloblasts, whereas two others (Sox5 and 18) showed expression in odontoblasts. Sox genes thus showed a dynamic spatio-temporal expression during tooth development.

  20. A microfluidic device integrating plasmonic nanodevices for Raman spectroscopy analysis on trapped single living cells

    KAUST Repository

    Perozziello, Gerardo

    2013-11-01

    In this work we developed a microfluidic device integrating nanoplasmonic devices combined with fluidic trapping regions. The microfuidic traps allow to capture single cells in areas where plasmonic sensors are placed. In this way it is possible to perform Enhanced Raman analysis on the cell membranes. Moreover, by changing direction of the flux it is possible to change the orientation of the cell in the trap, so that it is possible to analyze different points of the membrane of the same cell. We shows an innovative procedure to fabricate and assembly the microfluidic device which combine photolithography, focused ion beam machining, and hybrid bonding between a polymer substrate and lid of Calcium fluoride. This procedure is compatible with the fabrication of the plasmonic sensors in close proximity of the microfluidic traps. Moreover, the use of Calcium fluoride as lid allows full compatibility with Raman measurements producing negligible Raman background signal and avoids Raman artifacts. Finally, we performed Raman analysis on cells to monitor their oxidative stress under particular non physiological conditions. © 2013 Elsevier B.V. All rights reserved.

  1. A microfluidic device integrating plasmonic nanodevices for Raman spectroscopy analysis on trapped single living cells

    KAUST Repository

    Perozziello, Gerardo; Catalano, Rossella; Francardi, Marco; Rondanina, Eliana; Pardeo, Francesca; De Angelis, Francesco De; Malara, Natalia Maria; Candeloro, Patrizio; Morrone, Giovanni; Di Fabrizio, Enzo M.

    2013-01-01

    In this work we developed a microfluidic device integrating nanoplasmonic devices combined with fluidic trapping regions. The microfuidic traps allow to capture single cells in areas where plasmonic sensors are placed. In this way it is possible to perform Enhanced Raman analysis on the cell membranes. Moreover, by changing direction of the flux it is possible to change the orientation of the cell in the trap, so that it is possible to analyze different points of the membrane of the same cell. We shows an innovative procedure to fabricate and assembly the microfluidic device which combine photolithography, focused ion beam machining, and hybrid bonding between a polymer substrate and lid of Calcium fluoride. This procedure is compatible with the fabrication of the plasmonic sensors in close proximity of the microfluidic traps. Moreover, the use of Calcium fluoride as lid allows full compatibility with Raman measurements producing negligible Raman background signal and avoids Raman artifacts. Finally, we performed Raman analysis on cells to monitor their oxidative stress under particular non physiological conditions. © 2013 Elsevier B.V. All rights reserved.

  2. An integrated ion trap and time-of-flight mass spectrometer for chemical and photo- reaction dynamics studies.

    Science.gov (United States)

    Schowalter, Steven J; Chen, Kuang; Rellergert, Wade G; Sullivan, Scott T; Hudson, Eric R

    2012-04-01

    We demonstrate the integration of a linear quadrupole trap with a simple time-of-flight mass spectrometer with medium-mass resolution (m/Δm ∼ 50) geared towards the demands of atomic, molecular, and chemical physics experiments. By utilizing a novel radial ion extraction scheme from the linear quadrupole trap into the mass analyzer, a device with large trap capacity and high optical access is realized without sacrificing mass resolution. This provides the ability to address trapped ions with laser light and facilitates interactions with neutral background gases prior to analyzing the trapped ions. Here, we describe the construction and implementation of the device as well as present representative ToF spectra. We conclude by demonstrating the flexibility of the device with proof-of-principle experiments that include the observation of molecular-ion photodissociation and the measurement of trapped-ion chemical reaction rates. © 2012 American Institute of Physics

  3. An integrated ion trap and time-of-flight mass spectrometer for chemical and photo- reaction dynamics studies

    International Nuclear Information System (INIS)

    Schowalter, Steven J.; Chen Kuang; Rellergert, Wade G.; Sullivan, Scott T.; Hudson, Eric R.

    2012-01-01

    We demonstrate the integration of a linear quadrupole trap with a simple time-of-flight mass spectrometer with medium-mass resolution (m/Δm∼ 50) geared towards the demands of atomic, molecular, and chemical physics experiments. By utilizing a novel radial ion extraction scheme from the linear quadrupole trap into the mass analyzer, a device with large trap capacity and high optical access is realized without sacrificing mass resolution. This provides the ability to address trapped ions with laser light and facilitates interactions with neutral background gases prior to analyzing the trapped ions. Here, we describe the construction and implementation of the device as well as present representative ToF spectra. We conclude by demonstrating the flexibility of the device with proof-of-principle experiments that include the observation of molecular-ion photodissociation and the measurement of trapped-ion chemical reaction rates.

  4. Precise positioning of an ion in an integrated Paul trap-cavity system using radiofrequency signals

    Science.gov (United States)

    Kassa, Ezra; Takahashi, Hiroki; Christoforou, Costas; Keller, Matthias

    2018-03-01

    We report a novel miniature Paul ion trap design with an integrated optical fibre cavity which can serve as a building block for a fibre-linked quantum network. In such cavity quantum electrodynamic set-ups, the optimal coupling of the ions to the cavity mode is of vital importance and this is achieved by moving the ion relative to the cavity mode. The trap presented herein features an endcap-style design complemented with extra electrodes on which additional radiofrequency voltages are applied to fully control the pseudopotential minimum in three dimensions. This method lifts the need to use three-dimensional translation stages for moving the fibre cavity with respect to the ion and achieves high integrability, mechanical rigidity and scalability. Not based on modifying the capacitive load of the trap, this method leads to precise control of the pseudopotential minimum allowing the ion to be moved with precisions limited only by the ion's position spread. We demonstrate this by coupling the ion to the fibre cavity and probing the cavity mode profile.

  5. Development of a flexible microfluidic system integrating magnetic micro-actuators for trapping biological species

    International Nuclear Information System (INIS)

    Fulcrand, R; Jugieu, D; Escriba, C; Bancaud, A; Bourrier, D; Boukabache, A; Gué, A M

    2009-01-01

    A flexible microfluidic system embedding microelectromagnets has been designed, modeled and fabricated by using a photosensitive resin as structural material. The fabrication process involves the integration of micro-coils in a multilayer SU-8 microfluidic system by combining standard electroplating and dry films lamination. This technique offers numerous advantages in terms of integration, biocompatibility and chemical resistance. Various designs of micro-coils, including spiral, square or serpentine wires, have been simulated and experimentally tested. It has been established that thermal dissipation in micro-coils depends strongly on the number of turns and current density but remains compatible with biological applications. Real-time experimentations show that these micro-actuators are efficient in trapping magnetic micro-beads without any external field source or a permanent magnet and highlight that the size of microfluidic channels has been adequately designed for optimal trapping. Moreover, we trap magnetic beads in less than 2 s and release them instantaneously into the micro-channel. The actuation solely relies on electric fields, which are easier to control than standard magneto-fluidic modules

  6. Development of a flexible microfluidic system integrating magnetic micro-actuators for trapping biological species

    Science.gov (United States)

    Fulcrand, R.; Jugieu, D.; Escriba, C.; Bancaud, A.; Bourrier, D.; Boukabache, A.; Gué, A. M.

    2009-10-01

    A flexible microfluidic system embedding microelectromagnets has been designed, modeled and fabricated by using a photosensitive resin as structural material. The fabrication process involves the integration of micro-coils in a multilayer SU-8 microfluidic system by combining standard electroplating and dry films lamination. This technique offers numerous advantages in terms of integration, biocompatibility and chemical resistance. Various designs of micro-coils, including spiral, square or serpentine wires, have been simulated and experimentally tested. It has been established that thermal dissipation in micro-coils depends strongly on the number of turns and current density but remains compatible with biological applications. Real-time experimentations show that these micro-actuators are efficient in trapping magnetic micro-beads without any external field source or a permanent magnet and highlight that the size of microfluidic channels has been adequately designed for optimal trapping. Moreover, we trap magnetic beads in less than 2 s and release them instantaneously into the micro-channel. The actuation solely relies on electric fields, which are easier to control than standard magneto-fluidic modules.

  7. Integrated Status and Effectiveness Monitoring Program - Entiat River Snorkel Surveys and Rotary Screw Trap, 2007.

    Energy Technology Data Exchange (ETDEWEB)

    Nelle, R.D.

    2008-01-01

    The USFWS Mid-Columbia River Fishery Resource Office conducted snorkel surveys at 24 sites during the summer and fall periods of 2006 survey periods as part of the Integrated Status and Effectiveness Monitoring Program in the Entiat River. A total of 37,938 fish from 15 species/genera and an unknown category were enumerated. Chinook salmon were the overall most common fish observed and comprised 15% of fish enumerated followed by rainbow trout (10%) and mountain whitefish (7%). Day surveys were conducted during the summer period 2007 (August), while night surveys were conducted during the fall 2007 (October) surveys. The USFWS Mid-Columbia River Fishery Resource Office (MCFRO) operated two rotary screw traps on the Entiat River as part of the Integrated Status and Effectiveness Monitoring Program (ISEMP) program from August through November of 2007. Along with the smolt traps, juvenile emigrants were also captured at remote locations throughout the Entiat watershed and its major tributary, the Mad River. A total of 999 wild Oncorhynchus mykiss and 5,107 wild run O. tshawytscha were PIT tagged during the study period. Rotary screw trap efficiencies averaged 22.3% for juvenile O. tshawytscha and 9.0% for juvenile O. mykiss. Rotary screw traps operated 7 days a week and remote capture operations were conducted when flow and temperature regimes permitted. This is third annual progress report to Bonneville Power Administration for the snorkel surveys conducted in the Entiat River as related to long-term effectiveness monitoring of restoration programs in this watershed. The objective of this study is to monitor the fish habitat utilization of planned in-stream restoration efforts in the Entiat River by conducting pre- and post-construction snorkel surveys at selected treatment and control sites.

  8. Integrated transport code system for a multicomponent plasma in a gas dynamic trap

    International Nuclear Information System (INIS)

    Anikeev, A.V.; Karpushov, A.N.; Noak, K.; Strogalova, S.L.

    2000-01-01

    This report is focused on the development of the theoretical and numerical models of multicomponent high-β plasma confinement and transport in the gas-dynamic trap (GDT). In order to simulate the plasma behavior in the GDT as well as that in the GDT-based neutron source the Integrated Transport Code System is developed from existing stand-alone codes calculating the target plasma, the fast ions and the neutral gas in the GDT. The code system considers the full dependence of the transport phenomena on space, time, energy and angle variables as well as the interactions between the particle fields [ru

  9. Integration of laser trapping for continuous and selective monitoring of photothermal response of a single microparticle.

    Science.gov (United States)

    Vasudevan, Srivathsan; Chen, George C K; Ahluwalia, Balpreet Singh

    2008-12-01

    Photothermal response (PTR) is an established pump and probe technique for real-time sensing of biological assays. Continuous and selective PTR monitoring is difficult owing to the Brownian motion changing the relative position of the target with respect to the beams. Integration of laser trapping with PTR is proposed as a solution. The proposed method is verified on red polystyrene microparticles. PTR is continuously monitored for 30 min. Results show that the mean relaxation time variation of the acquired signals is less than 5%. The proposed method is then applied to human red blood cells for continuous and selective PTR.

  10. A charged-particle manipulator utilizing a co-axial tube electrodynamic trap with an integrated camera

    International Nuclear Information System (INIS)

    Jiang, L; Pau, S; Whitten, W B

    2011-01-01

    A charged-particle manipulator was designed and fabricated with an integrated imaging camera allowing real-time in-situ monitoring of trapped particle motion even when the trap device is under motion or rotation. The trap device was made of two co-axial electrically conductive tubes with diameters of 5.5 mm and 7 mm for the inner tube and outer tube, respectively; the imaging camera with its optical fiber bundle was integrated within the tubular trap device to realize a single instrument functioning as a manipulator. Motion of suspended microparticles of 3 μm to 50 μm in diameter can be monitored using the integrated camera regardless of the trap device orientations. This manipulator provides capability of controlled manipulation of trapped particles by tuning the operating conditions while monitoring the feedback of real-time particle motion. Imaging of suspended particles was not interrupted while the manipulator was translated and/or rotated. This integrated manipulator can be used for charged particle transport and repositioning.

  11. SOX2 anophthalmia syndrome and dental anomalies.

    Science.gov (United States)

    Chacon-Camacho, Oscar Francisco; Fuerte-Flores, Bertha Irene; Ricardez-Marcial, Edgar F; Zenteno, Juan Carlos

    2015-11-01

    SOX2 anophthalmia syndrome is an uncommon autosomal dominant syndrome caused by mutations in the SOX2 gene and clinically characterized by severe eye malformations (anophthalmia/microphthalmia) and extraocular anomalies mainly involving brain, esophagus, and genitalia. In this work, a patient with the SOX2 anophthalmia syndrome and exhibiting a novel dental anomaly is described. SOX2 genotyping in this patient revealed an apparently de novo c.70del20 deletion, a commonly reported SOX2 mutation. A review of the phenotypic variation observed in patients carrying the recurrent SOX2 c.70del20 mutation is presented. Although dental anomalies are uncommonly reported in the SOX2 anophthalmia syndrome, we suggest that a dental examination should be performed in patients with SOX2 mutations. © 2015 Wiley Periodicals, Inc.

  12. Incomplete Thermalization from Trap-Induced Integrability Breaking: Lessons from Classical Hard Rods

    Science.gov (United States)

    Cao, Xiangyu; Bulchandani, Vir B.; Moore, Joel E.

    2018-04-01

    We study a one-dimensional gas of hard rods trapped in a harmonic potential, which breaks integrability of the hard-rod interaction in a nonuniform way. We explore the consequences of such broken integrability for the dynamics of a large number of particles and find three distinct regimes: initial, chaotic, and stationary. The initial regime is captured by an evolution equation for the phase-space distribution function. For any finite number of particles, this hydrodynamics breaks down and the dynamics becomes chaotic after a characteristic timescale determined by the interparticle distance and scattering length. The system fails to thermalize over the timescale studied (1 04 natural units), but the time-averaged ensemble is a stationary state of the hydrodynamic evolution. We close by discussing logical extensions of the results to similar systems of quantum particles.

  13. Electroporation-mediated transfer of SOX trio genes (SOX-5, SOX-6, and SOX-9) to enhance the chondrogenesis of mesenchymal stem cells.

    Science.gov (United States)

    Kim, Hye-Joung; Im, Gun-Il

    2011-12-01

    The purpose of this study was to test the hypothesis that the SOX trio genes (SOX-5, SOX-6, and SOX-9) have a lower level of expression during the chondrogenic differentiation of mesenchymal stem cells (MSCs) compared with chondrocytes and that the electroporation-mediated gene transfer of SOX trio promotes chondrogenesis from human MSCs. An in vitro pellet culture was carried out using MSCs or chondrocytes at passage 3 and analyzed after 7 and 21 days. Then, MSCs were transfected with SOX trio genes and analyzed for the expression of chondrogenic markers after 21 days of in vitro culture. Without transforming growth factor-β1, the untransfected MSCs had a lower level of SOX trio gene and protein expression than chondrocytes. However, the level of SOX-9 gene expression increased in MSCs when treated with transforming growth factor-β1. GAG level significantly increased 7-fold in MSCs co-transfected with SOX trio, which was corroborated by Safranin-O staining. SOX trio co-transfection significantly increased COL2A1 gene and protein and decreased COL10A1 protein in MSCs. It is concluded that the SOX trio have a significantly lower expression in human MSCs than in chondrocytes and that the electroporation-mediated co-transfection of SOX trio enhances chondrogenesis and suppresses hypertrophy of human MSCs.

  14. SOX4 expression in bladder carcinoma

    DEFF Research Database (Denmark)

    Aaboe, Mads; Birkenkamp-Demtroder, Karin; Wiuf, Carsten

    2006-01-01

    The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4-specific antibody, we found that the cancer cells expressed...... in the clinical bladder material and a small subset of the genes showed a high correlation to SOX4 expression. The present data suggest a role of SOX4 in the bladder cancer disease....... the SOX4 protein and, thus, did an evaluation of SOX4 protein expression in 2,360 bladder tumors using a tissue microarray with clinical annotation. We found a correlation (P bladder cell line HU609, SOX4...

  15. Redundant roles of Sox17 and Sox18 in early cardiovascular development of mouse embryos

    International Nuclear Information System (INIS)

    Sakamoto, Youhei; Hara, Kenshiro; Kanai-Azuma, Masami; Matsui, Toshiyasu; Miura, Yutaroh; Tsunekawa, Naoki; Kurohmaru, Masamichi; Saijoh, Yukio; Koopman, Peter; Kanai, Yoshiakira

    2007-01-01

    Sox7, -17 and -18 constitute the Sox subgroup F (SoxF) of HMG box transcription factor genes, which all are co-expressed in developing vascular endothelial cells in mice. Here we characterized cardiovascular phenotypes of Sox17/Sox18-double and Sox17-single null embryos during early-somite stages. Whole-mount PECAM staining demonstrated the aberrant heart looping, enlarged cardinal vein and mild defects in anterior dorsal aorta formation in Sox17 single-null embryos. The Sox17/Sox18 double-null embryos showed more severe defects in formation of anterior dorsal aorta and head/cervical microvasculature, and in some cases, aberrant differentiation of endocardial cells and defective fusion of the endocardial tube. However, the posterior dorsal aorta and allantoic microvasculature was properly formed in all of the Sox17/Sox18 double-null embryos. The anomalies in both anterior dorsal aorta and head/cervical vasculature corresponded with the weak Sox7 expression sites. This suggests the region-specific redundant activities of three SoxF members along the anteroposterior axis of embryonic vascular network

  16. Integrated Status and Effectiveness Monitoring Program - Entiat River Rotary Screw Traps,Snorkel Surveys, and Steelhead Redd Surveys, 2008.

    Energy Technology Data Exchange (ETDEWEB)

    Nelle, R.D.; Desgroseiller, Tom; Cotter, Michael (U.S. Fish and Wildlife Service)

    2009-02-17

    The USFWS Mid-Columbia River Fishery Resource Office (MCRFRO) operated two rotary screw traps on the Entiat River as part of the Integrated Status and Effectiveness Monitoring Program from March through November of 2008. Along with the smolt traps, juvenile emigrants were also captured at remote locations throughout the Entiat watershed and its major tributary, the Mad River. A total of 16,782 wild salmonids were PIT tagged during the study period. Of this, 3,961(23.6%) were wild Oncorhynchus mykiss, 6,987 (41.6%) were wild spring run O. tshawytscha, and 5,591 (33.3%) were identified as wild O. tshawytscha of unknown run. Rotary screw trap efficiencies averaged 40.3% at the upper (Rkm 11.0) trap and 7.8% for the lower (Rkm 2.0) trap. These efficiencies were pooled for emigrant O. tshawytscha and O. mykiss. The MCRFRO conducted effectiveness monitoring snorkel surveys at 24 sites during the winter period and 30 sites during the summer and fall periods of 2008 as part of the Integrated Status and Effectiveness Monitoring Program in the Entiat River. The 2008 steelhead spawning grounds surveys were conducted weekly in the main Entiat River from rkm 1.1 to 44.2. A total of 222 steelhead redds were identified over the period from February 28 to June 16 2008 with April being the peak spawning month. Approximately 80% of the steelhead redds were located downstream of the rkm 26.

  17. Integrated Status and Effectiveness Monitoring Program - Entiat River Rotary Screw Traps, Snorkel Surveys, and Steelhead Redd Surveys, 2008-2009.

    Energy Technology Data Exchange (ETDEWEB)

    Nelle, R.D.; Desgroseillier, Tom; Cotter, Michael [U.S. Fish and Wildlife Service

    2009-04-14

    The USFWS Mid-Columbia River Fishery Resource Office (MCRFRO) operated two rotary screw traps on the Entiat River as part of the Integrated Status and Effectiveness Monitoring Program from March through November of 2008. Along with the smolt traps, juvenile emigrants were also captured at remote locations throughout the Entiat watershed and its major tributary, the Mad River. A total of 16,782 wild salmonids were PIT tagged during the study period. Of this, 3,961(23.6%) were wild Oncorhynchus mykiss, 6,987 (41.6%) were wild spring run O. tshawytscha, and 5,591 (33.3%) were identified as wild O. tshawytscha of unknown run. Rotary screw trap efficiencies averaged 40.3% at the upper (Rkm 11.0) trap and 7.8% for the lower (Rkm 2.0) trap. These efficiencies were pooled for emigrant O. tshawytscha and O. mykiss. The MCRFRO conducted effectiveness monitoring snorkel surveys at 24 sites during the winter period and 30 sites during the summer and fall periods of 2008 as part of the Integrated Status and Effectiveness Monitoring Program in the Entiat River. The 2008 steelhead spawning grounds surveys were conducted weekly in the main Entiat River from rkm 1.1 to 44.2. A total of 222 steelhead redds were identified over the period from February 28 to June 16 2008 with April being the peak spawning month. Approximately 80% of the steelhead redds were located downstream of the rkm 26.

  18. [SOX2 defect and anophthalmia and microphthalmia].

    Science.gov (United States)

    Ye, Fu-xiang; Fan, Xian-qun

    2012-11-01

    As a severe congenital developmental disorder, anophthalmia and microphthalmia are usually accompanied with vision impairment and hypoevolutism of the orbit in the affected side. Many genes are involved in anophthalmia and microphthalmia, in which, SOX2 is an important one. The defect of SOX2 causes multiple system disorders, including anophthalmia and microphthalmia. We describe the relationship between the SOX2 defect and anophthalmia/microphthalmia, in order to offer some proposals for the differential diagnosis, treatment and research of anophthalmia and microphthalmia.

  19. Sox17 drives functional engraftment of endothelium converted from non-vascular cells.

    Science.gov (United States)

    Schachterle, William; Badwe, Chaitanya R; Palikuqi, Brisa; Kunar, Balvir; Ginsberg, Michael; Lis, Raphael; Yokoyama, Masataka; Elemento, Olivier; Scandura, Joseph M; Rafii, Shahin

    2017-01-16

    Transplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy to treat vasculopathies and to promote tissue regeneration. However, transplantation strategies have been challenging to develop, because ECs are difficult to culture and little is known about how to direct them to stably integrate into vasculature. Here we show that only amniotic cells could convert to cells that maintain EC gene expression. Even so, these converted cells perform sub-optimally in transplantation studies. Constitutive Akt signalling increases expression of EC morphogenesis genes, including Sox17, shifts the genomic targeting of Fli1 to favour nearby Sox consensus sites and enhances the vascular function of converted cells. Enforced expression of Sox17 increases expression of morphogenesis genes and promotes integration of transplanted converted cells into injured vessels. Thus, Ets transcription factors specify non-vascular, amniotic cells to EC-like cells, whereas Sox17 expression is required to confer EC function.

  20. Sox2 Suppresses Gastric Tumorigenesis in Mice

    Directory of Open Access Journals (Sweden)

    Abby Sarkar

    2016-08-01

    Full Text Available Sox2 expression marks gastric stem and progenitor cells, raising important questions regarding the genes regulated by Sox2 and the role of Sox2 itself during stomach homeostasis and disease. By using ChIP-seq analysis, we have found that the majority of Sox2 targets in gastric epithelial cells are tissue specific and related to functions such as endoderm development, Wnt signaling, and gastric cancer. Unexpectedly, we found that Sox2 itself is dispensable for gastric stem cell and epithelial self-renewal, yet Sox2+ cells are highly susceptible to tumorigenesis in an Apc/Wnt-driven mouse model. Moreover, Sox2 loss enhances, rather than impairs, tumor formation in Apc-deficient gastric cells in vivo and in vitro by inducing Tcf/Lef-dependent transcription and upregulating intestinal metaplasia-associated genes, providing a mechanistic basis for the observed phenotype. Together, these data identify Sox2 as a context-dependent tumor suppressor protein that is dispensable for normal tissue regeneration but restrains stomach adenoma formation through modulation of Wnt-responsive and intestinal genes.

  1. Verification of geomechanical integrity and prediction of long-term mineral trapping for the Ketzin CO2 storage pilot site

    Science.gov (United States)

    Kempka, Thomas; De Lucia, Marco; Kühn, Michael

    2014-05-01

    Static and dynamic numerical modelling generally accompany the entire CO2 storage site life cycle. Thereto, it is required to match the employed models with field observations on a regular basis in order to predict future site behaviour. We investigated the coupled processes at the Ketzin CO2 storage pilot site [1] using a model coupling concept focusing on the temporal relevance of processes involved (hydraulic, chemical and mechanical) at given time-scales (site operation, abandonment and long-term stabilization). For that purpose, long-term dynamic multi-phase flow simulations [2], [3] established the basis for all simulations discussed in the following. Hereby, pressure changes resulting in geomechanical effects are largest during site operation, whereas geochemical reactions are governed by slow kinetics resulting in a long-term stabilization. To account for mechanical integrity, which may be mainly affected during site operation, we incorporated a regional-scale coupled hydro-mechanical model. Our simulation results show maximum ground surface displacements of about 4 mm, whereas shear and tensile failure are not observed. Consequently, the CO2 storage operation at the Ketzin pilot site does not compromise reservoir, caprock and fault integrity. Chemical processes responsible for mineral trapping are expected to mainly occur during long-term stabilization at the Ketzin pilot site [4]. Hence, our previous assessment [3] was extended by integrating two long-term mineral trapping scenarios. Thereby, mineral trapping contributes to the trapping mechanisms with 11.7 % after 16,000 years of simulation in our conservative and with 30.9 % in our maximum reactivity scenarios. Dynamic flow simulations indicate that only 0.2 % of the CO2 injected (about 67,270 t CO2 in total) is in gaseous state, but structurally trapped after 16,000 years. Depending on the studied long-term scenario, CO2 dissolution is the dominating trapping mechanism with 68.9 % and 88

  2. Sox10 expressing cells in the lateral wall of the aged mouse and human cochlea.

    Directory of Open Access Journals (Sweden)

    Xinping Hao

    Full Text Available Age-related hearing loss (presbycusis is a common human disorder, affecting one in three Americans aged 60 and over. Previous studies have shown that presbyacusis is associated with a loss of non-sensory cells in the cochlear lateral wall. Sox10 is a transcription factor crucial to the development and maintenance of neural crest-derived cells including some non-sensory cell types in the cochlea. Mutations of the Sox10 gene are known to cause various combinations of hearing loss and pigmentation defects in humans. This study investigated the potential relationship between Sox10 gene expression and pathological changes in the cochlear lateral wall of aged CBA/CaJ mice and human temporal bones from older donors. Cochlear tissues prepared from young adult (1-3 month-old and aged (2-2.5 year-old mice, and human temporal bone donors were examined using quantitative immunohistochemical analysis and transmission electron microscopy. Cells expressing Sox10 were present in the stria vascularis, outer sulcus and spiral prominence in mouse and human cochleas. The Sox10(+ cell types included marginal and intermediate cells and outer sulcus cells, including those that border the scala media and those extending into root processes (root cells in the spiral ligament. Quantitative analysis of immunostaining revealed a significant decrease in the number of Sox10(+ marginal cells and outer sulcus cells in aged mice. Electron microscopic evaluation revealed degenerative alterations in the surviving Sox10(+ cells in aged mice. Strial marginal cells in human cochleas from donors aged 87 and older showed only weak immunostaining for Sox10. Decreases in Sox10 expression levels and a loss of Sox10(+ cells in both mouse and human aged ears suggests an important role of Sox10 in the maintenance of structural and functional integrity of the lateral wall. A loss of Sox10(+ cells may also be associated with a decline in the repair capabilities of non-sensory cells in the

  3. Tunable superconducting resonators with integrated trap structures for coupling with ultracold atomic gases

    Energy Technology Data Exchange (ETDEWEB)

    Ferdinand, Benedikt; Wiedmaier, Dominik; Koelle, Dieter; Kleiner, Reinhold [Physikalisches Institut and Center for Quantum Science in LISA+, Universitaet Tuebingen (Germany); Bothner, Daniel [Physikalisches Institut and Center for Quantum Science in LISA+, Universitaet Tuebingen (Germany); Kavli Institute of Nanoscience, Delft University of Technology, Delft (Netherlands)

    2016-07-01

    We intend to investigate a hybrid quantum system where ultracold atomic gases play the role of a long-living quantum memory, coupled to a superconducting qubit via a coplanar waveguide transmission line resonator. As a first step we developed a resonator chip containing a Z-shaped trapping wire for the atom trap. In order to suppress parasitic resonances due to stray capacitances, and to achieve good ground connection we use hybrid superconductor - normal conductor chips. As an additional degree of freedom we add a ferroelectric capacitor making the resonators voltage-tunable. We furthermore show theoretical results on the expected coupling strength between resonator and atomic cloud.

  4. Quantitative analysis of trapping probability for quasi-integrable two degree of freedom maps

    CERN Document Server

    Bazzani, A; Hernalsteens, C; Williams, J

    2014-01-01

    A key ingredient for the Multi-Turn Extraction (MTE) at the CERN Proton Synchrotron is the beam trapping in stable islands of transverse phase space. In a previous paper a method allowing analytical estimation of the fraction of beam trapped into resonance islands as a function of the Hamiltonian parameters has been presented. Such amethod applies to one-degree of freedom models of betatronic motion. In this paper, the analysis is extended to the more realistic and challenging case of two-degree of freedom systems, in which the interplay between the horizontal and vertical motion is fully included. Numerical simulations are presented and the results are discussed in detail.

  5. Long-range activation of Sox9 in Odd Sex (Ods) mice.

    Science.gov (United States)

    Qin, Yangjun; Kong, Ling-kun; Poirier, Christophe; Truong, Cavatina; Overbeek, Paul A; Bishop, Colin E

    2004-06-15

    The Odd Sex mouse mutation arose in a transgenic line of mice carrying a tyrosinase minigene driven by the dopachrome tautomerase (Dct) promoter region. The minigene integrated 0.98 Mb upstream of Sox9 and was accompanied by a deletion of 134 kb. This mutation causes female to male sex reversal in XX Ods/+ mice, and a characteristic eye phenotype of microphthalmia with cataracts in all mice carrying the transgene. Ods causes sex reversal in the absence of Sry by upregulating Sox9 expression and maintaining a male pattern of Sox9 expression in XX Ods/+ embryonic gonads. This expression, which begins at E11.5, triggers downstream events leading to the formation of a testis. We report here that the 134 kb deletion, in itself, is insufficient to cause sex reversal. We demonstrate that in Ods, the Dct promoter is capable of acting over a distance of 1 Mb to induce inappropriate expression of Sox9 in the retinal pigmented epithelium of the eye, causing the observed microphthalmia. In addition, it induces Sox9 expression in the melanocytes where it causes pigmentation defects. We propose that Ods sex reversal is due to the Dct promoter element interacting with gonad-specific enhancer elements to produce the observed male pattern expression of Sox9 in the embryonic gonads.

  6. Cloning and analysis of the HMG domains of ten Sox genes from ...

    African Journals Online (AJOL)

    Sox is a large gene family which encodes Sry-related transcription factors and contains a HMG box that is responsible for the sequence-specific DNA binding. In this paper, we obtained ten clones representing HMG box-containing Sox genes (BmSox1a, BmSox1b, BmSox3a, BmSox3b, BmSox3c, BmSox11a, BmSox11b, ...

  7. 76 FR 4724 - Catawba Sox, LLC Formerly Known as Catawba Sox, Inc. Including Workers Whose Unemployment...

    Science.gov (United States)

    2011-01-26

    ... Known as Catawba Sox, Inc. Including Workers Whose Unemployment Insurance UI) Wages Are Paid Through...., had their wages reported under a separated unemployment insurance (UI) tax account under the name..., LLC, formerly known as Catawba Sox, Inc., including workers whose unemployment insurance (UI) wages...

  8. SOX15 regulates proliferation and migration of endometrial cancer cells.

    Science.gov (United States)

    Rui, Xiaohui; Xu, Yun; Jiang, Xiping; Guo, Caixia; Jiang, Jingting

    2017-10-31

    The study aimed to investigate the effects of Sry-like high mobility group box 15 ( SOX15 ) on proliferation and migration of endometrial cancer (EC) cells. Immunohistochemistry (IHC) was applied to determine the expression of SOX15 in EC tissues and adjacent tissues. We used cell transfection method to construct the HEC-1-A and Ishikawa cell lines with stable overexpression and low expression SOX15 Reverse-transcription quantitative real-time PCR (RT-qPCR) and Western blot were performed to examine expression of SOX15 mRNA and SOX15 protein, respectively. By conducting a series of cell proliferation assay and migration assay, we analyzed the influence of SOX15 overexpression or low expression on EC cell proliferation and migration. The expression of SOX15 mRNA and protein in EC tissues was significantly lower than that in adjacent tissues. After lentivirus-transfecting SOX15 , the expression level of SOX15 mRNA and protein was significantly increased in cells of SOX15 group, and decreased in sh- SOX15 group. Overexpression of SOX15 could suppress cell proliferation, while down-regulation of SOX15 increased cell proliferation. Flow cytometry results indicated that overexpression of SOX15 induced the ratio of cell-cycle arrest in G 1 stage. In addition, Transwell migration assay results showed that SOX15 overexpression significantly inhibited cell migration, and also down-regulation of SOX15 promoted the migration. As a whole, SOX15 could regulate the proliferation and migration of EC cells and up- regulation of SOX15 could be valuable for EC treatment. © 2017 The Author(s).

  9. Integrating reaction and analysis: investigation of higher-order reactions by cryogenic trapping

    Directory of Open Access Journals (Sweden)

    Skrollan Stockinger

    2013-09-01

    Full Text Available A new approach for the investigation of a higher-order reaction by on-column reaction gas chromatography is presented. The reaction and the analytical separation are combined in a single experiment to investigate the Diels–Alder reaction of benzenediazonium-2-carboxylate as a benzyne precursor with various anthracene derivatives, i.e. anthracene, 9-bromoanthracene, 9-anthracenecarboxaldehyde and 9-anthracenemethanol. To overcome limitations of short reaction contact times at elevated temperatures a novel experimental setup was developed involving a cooling trap to achieve focusing and mixing of the reactants at a defined spot in a fused-silica capillary. This trap functions as a reactor within the separation column in the oven of a gas chromatograph. The reactants are sequentially injected to avoid undefined mixing in the injection port. An experimental protocol was developed with optimized injection intervals and cooling times to achieve sufficient conversions at short reaction times. Reaction products were rapidly identified by mass spectrometric detection. This new approach represents a practical procedure to investigate higher-order reactions at an analytical level and it simultaneously provides valuable information for the optimization of the reaction conditions.

  10. Integration of ammonia-plasma-functionalized graphene nanodiscs as charge trapping centers for nonvolatile memory applications

    KAUST Repository

    Wang, Jer-Chyi

    2016-11-23

    Graphene nanodiscs (GNDs), functionalized using NH3 plasma, as charge trapping sites (CTSs) for non-volatile memory applications have been investigated in this study. The fabrication process relies on the patterning of Au nanoparticles (Au-NPs), whose thicknesses are tuned to adjust the GND density and size upon etching. A GND density as high as 8 × 1011 cm−2 and a diameter of approximately 20 nm are achieved. The functionalization of GNDs by NH3 plasma creates Nsingle bondH+ functional groups that act as CTSs, as observed by Raman and Fourier transform infrared spectroscopy. This inherently enhances the density of CTSs in the GNDs, as a result, the memory window becomes more than 2.4 V and remains stable after 104 operating cycles. The charge loss is less than 10% for a 10-year data retention testing, making this low-temperature process suitable for low-cost non-volatile memory applications on flexible substrates.

  11. Study of a Microfluidic Chip Integrating Single Cell Trap and 3D Stable Rotation Manipulation

    Directory of Open Access Journals (Sweden)

    Liang Huang

    2016-08-01

    Full Text Available Single cell manipulation technology has been widely applied in biological fields, such as cell injection/enucleation, cell physiological measurement, and cell imaging. Recently, a biochip platform with a novel configuration of electrodes for cell 3D rotation has been successfully developed by generating rotating electric fields. However, the rotation platform still has two major shortcomings that need to be improved. The primary problem is that there is no on-chip module to facilitate the placement of a single cell into the rotation chamber, which causes very low efficiency in experiment to manually pipette single 10-micron-scale cells into rotation position. Secondly, the cell in the chamber may suffer from unstable rotation, which includes gravity-induced sinking down to the chamber bottom or electric-force-induced on-plane movement. To solve the two problems, in this paper we propose a new microfluidic chip with manipulation capabilities of single cell trap and single cell 3D stable rotation, both on one chip. The new microfluidic chip consists of two parts. The top capture part is based on the least flow resistance principle and is used to capture a single cell and to transport it to the rotation chamber. The bottom rotation part is based on dielectrophoresis (DEP and is used to 3D rotate the single cell in the rotation chamber with enhanced stability. The two parts are aligned and bonded together to form closed channels for microfluidic handling. Using COMSOL simulation and preliminary experiments, we have verified, in principle, the concept of on-chip single cell traps and 3D stable rotation, and identified key parameters for chip structures, microfluidic handling, and electrode configurations. The work has laid a solid foundation for on-going chip fabrication and experiment validation.

  12. SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

    Science.gov (United States)

    Oosterveen, Tony; Kurdija, Sanja; Ensterö, Mats; Uhde, Christopher W; Bergsland, Maria; Sandberg, Magnus; Sandberg, Rickard; Muhr, Jonas; Ericson, Johan

    2013-04-30

    The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.

  13. Integration of single oocyte trapping, in vitro fertilization and embryo culture in a microwell-structured microfluidic device.

    Science.gov (United States)

    Han, Chao; Zhang, Qiufang; Ma, Rui; Xie, Lan; Qiu, Tian; Wang, Lei; Mitchelson, Keith; Wang, Jundong; Huang, Guoliang; Qiao, Jie; Cheng, Jing

    2010-11-07

    In vitro fertilization (IVF) therapy is an important treatment for human infertility. However, the methods for clinical IVF have only changed slightly over decades: culture medium is held in oil-covered drops in Petri dishes and manipulation occurs by manual pipetting. Here we report a novel microwell-structured microfluidic device that integrates single oocyte trapping, fertilization and subsequent embryo culture. A microwell array was used to capture and hold individual oocytes during the flow-through process of oocyte and sperm loading, medium substitution and debris cleaning. Different microwell depths were compared by computational modeling and flow washing experiments for their effectiveness in oocyte trapping and debris removal. Fertilization was achieved in the microfluidic devices with similar fertilization rates to standard oil-covered drops in Petri dishes. Embryos could be cultured to blastocyst stages in our devices with developmental status individually monitored and tracked. The results suggest that the microfluidic device may bring several advantages to IVF practices by simplifying oocyte handling and manipulation, allowing rapid and convenient medium changing, and enabling automated tracking of any single embryo development.

  14. Sox9 induces testis development in XX transgenic mice

    NARCIS (Netherlands)

    Vidal, V. P.; Chaboissier, M. C.; de rooij, D. G.; Schedl, A.

    2001-01-01

    Mutations in SOX9 are associated with male-to-female sex reversal in humans. To analyze Sox9 function during sex determination, we ectopically expressed this gene in XX gonads. Here, we show that Sox9 is sufficient to induce testis formation in mice, indicating that it can substitute for the

  15. Process and device integration for silicon tunnel FETs utilizing isoelectronic trap technology to enhance the ON current

    Science.gov (United States)

    Mori, Takahiro; Asai, Hidehiro; Fukuda, Koichi; Matsukawa, Takashi

    2018-04-01

    A tunnel FET (TFET) is a candidate replacement for conventional MOSFETs to realize low-power LSI. The most significant issue with the practical application of TFETs concerns their low tunneling current. Si is an indirect-gap material with a low band-to-band tunneling probability and is not favored for the channel. However, a new technology has recently been proposed to enhance the tunneling current in Si-TFETs by utilizing isoelectronic trap (IET) technology. IET technology provides an innovative approach to realizing low-power LSI with TFETs. In this paper, state-of-the-art research on Si-TFETs with IET technology from the viewpoint of process and device integration is reviewed.

  16. Systems and methods for integrating ion mobility and ion trap mass spectrometers

    Science.gov (United States)

    Ibrahim, Yehia M.; Garimella, Sandilya; Prost, Spencer A.

    2018-04-10

    Described herein are examples of systems and methods for integrating IMS and MS systems. In certain examples, systems and methods for decoding double multiplexed data are described. The systems and methods can also perform multiple refining procedures in order to minimize the demultiplexing artifacts. The systems and methods can be used, for example, for the analysis of proteomic and petroleum samples, where the integration of IMS and high mass resolution are used for accurate assignment of molecular formulae.

  17. Numerical studies of the integration of a trapped vortex combustor into traditional combustion chambers

    Energy Technology Data Exchange (ETDEWEB)

    Patrignani, L.; Losurdo, M.; Bruno, C. [Sapienza Univ. de Roma, Rome (Italy)

    2010-09-15

    Exhaust emissions from furnace burners can be reduced by premixing reactants with combustion products. This paper discussed the use of a trapped vortex combustor (TVC) as a very promising technology for gas turbines. The TVC can reduce emissions and ensure that the temperature is uniform in the exhaust products, which is a key aspect for certain types of heat treatments, such as in steel rolling mills. The TVC for gas turbines is configured to mix air, fuel and hot products at turbulent scales fine enough to render the combustion mode flameless, or close to flameless. The vortex ensures a high recirculation factor between hot combustion products and reactants, and ultimately flame stability. In this study, the TVC configuration for an existing gas turbine was numerically investigated by means of RANS and LES. According to preliminary results of the fast-flameless combustion (FFC) strategy, the proposed TVC is a suitable candidate to reduce nitrogen oxide (NOx) emissions while keeping the pressure drop below 1 per cent. Both RANS and LES show that too much fuel burns along the main duct. Better fuel splitting or a different position for the injectors may enhance combustion inside the recirculation zone. Behaviour of the main vortices showed that a more accurate design of the internal shape of the combustor is needed to prevent excessive velocity fluctuation or vortex instabilities and therefore emissions. 13 refs., 9 figs.

  18. (SOXS) Mission Amish B. Shah , NM

    Indian Academy of Sciences (India)

    to estimate correct thresholds for flare detection. Memory check-out and read out modes are usable for on-board diagnosis. 2.4 Data communication. This package provides a common interface to all SOXS packages with spacecraft bus. It minimizes the chance of damage of mainframe bus because of anomaly in packages.

  19. Sox6 directly silences epsilon globin expression in definitive erythropoiesis.

    Directory of Open Access Journals (Sweden)

    2006-02-01

    Full Text Available Sox6 is a member of the Sox transcription factor family that is defined by the conserved high mobility group (HMG DNA binding domain, first described in the testis determining gene, Sry. Previous studies have suggested that Sox6 plays a role in the development of the central nervous system, cartilage, and muscle. In the Sox6-deficient mouse, p100H, epsilony globin is persistently expressed, and increased numbers of nucleated red cells are present in the fetal circulation. Transfection assays in GM979 (erythroleukemic cells define a 36-base pair region of the epsilony proximal promoter that is critical for Sox6 mediated repression. Electrophoretic mobility shift assay (EMSA and chromatin immunoprecipitation (ChIP assays demonstrate that Sox6 acts as a repressor by directly binding to the epsilony promoter. The normal expression of Sox6 in wild-type fetal liver and the ectopic expression of epsilony in p100H homozygous fetal liver demonstrate that Sox6 functions in definitive erythropoiesis. The present study shows that Sox6 is required for silencing of epsilony globin in definitive erythropoiesis and suggests a role for Sox6 in erythroid cell maturation. Thus, Sox6 regulation of epsilony globin might provide a novel therapeutical target in the treatment of hemoglobinopathies such as sickle cell anemia and thalassemia.

  20. POLAR ORGANIC CHEMICAL INTEGRATIVE SAMPLING AND LIQUID CHROMATOGRAPHY-ELECTROSPRAY/ION-TRAP MASS SPECTROMETRY FOR ASSESSING SELECTED PRESCRIPTION AND ILLICIT DRUGS IN TREATED SEWAGE EFFLUENTS

    Science.gov (United States)

    The purpose of the research presented in this paper is two-fold: (1) to demonstrate the 4 coupling of two state-of-the-art techniques: a time-weighted polar organic integrative sampler (POCIS) and micro-liquid chromatography-electrospray/ion trap mass spectrometry (u-LC-6 ES/ITMS...

  1. A novel luciferase knock-in reporter system for studying transcriptional regulation of the human Sox2 gene.

    Science.gov (United States)

    Xiao, Dan; Zhang, Weifeng; Li, Yan; Liu, Kuan; Zhao, Junli; Sun, Xiaohong; Shan, Linlin; Mao, Qinwen; Xia, Haibin

    2016-02-10

    Sox2 is an important transcriptional factor that has multiple functions in stem cell maintenance and tumorigenesis. To investigate the transcriptional regulation of the Sox2 gene, a luciferase knock-in reporter system was established in HEK293 cells by placing the luciferase gene in the genome under the control of the Sox2 gene promoter using a transcription activator-like effector nuclease (TALEN)-mediated genome editing technique. PCR and Southern blot results confirmed the site-specific integration of a single copy of the exogenous luciferase gene into the genome. To prove the reliability and sensitivity of this novel luciferase knock-in system, a CRISPR/Cas transcription activation system for the Sox2 gene was constructed and applied to the knock-in system. The results indicated that luciferase activity was directly correlated with the activity of the Sox2 endogenous promoter. This novel system will be a useful tool to study the transcriptional regulation of Sox2, and has great potential in medical and industrial applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. ompW is cooperatively upregulated by MarA and SoxS in response to menadione.

    Science.gov (United States)

    Collao, B; Morales, E H; Gil, F; Calderón, I L; Saavedra, C P

    2013-04-01

    OmpW is a minor porin whose biological function has not been clearly defined. Evidence obtained in our laboratory indicates that in Salmonella enterica serovar Typhimurium the expression of OmpW is activated by SoxS upon exposure to paraquat and it is required for resistance. SoxS belongs to the AraC family of transcriptional regulators, like MarA and Rob. Due to their high structural similarity, the genes under their control have been grouped in the mar/sox/rob regulon, which presents a DNA-binding consensus sequence denominated the marsox box. In this work, we evaluated the role of the transcription factors MarA, SoxS and Rob of S. enterica serovar Typhimurium in regulating ompW expression in response to menadione. We determined the transcript and protein levels of OmpW in different genetic backgrounds; in the wild-type and Δrob strains ompW was upregulated in response to menadione, while in the ΔmarA and ΔsoxS strains the induction was abolished. In a double marA soxS mutant, ompW transcript levels were lowered after exposure to menadione, and only complementation in trans with both genes restored the positive regulation. Using transcriptional fusions and electrophoretic mobility shift assays with mutant versions of the promoter region we demonstrated that two of the predicted sites were functional. Additionally, we demonstrated that MarA increases the affinity of SoxS for the ompW promoter region. In conclusion, our study shows that ompW is upregulated in response to menadione in a cooperative manner by MarA and SoxS through a direct interaction with the promoter region.

  3. The dark side of SOX2: cancer - a comprehensive overview.

    Science.gov (United States)

    Wuebben, Erin L; Rizzino, Angie

    2017-07-04

    The pluripotency-associated transcription factor SOX2 is essential during mammalian embryogenesis and later in life, but SOX2 expression can also be highly detrimental. Over the past 10 years, SOX2 has been shown to be expressed in at least 25 different cancers. This review provides a comprehensive overview of the roles of SOX2 in cancer and focuses on two broad topics. The first delves into the expression and function of SOX2 in cancer focusing on the connection between SOX2 levels and tumor grade as well as patient survival. As part of this discussion, we address the developing connection between SOX2 expression and tumor drug resistance. We also call attention to an under-appreciated property of SOX2, its levels in actively proliferating tumor cells appear to be optimized to maximize tumor growth - too little or too much SOX2 dramatically alters tumor growth. The second topic of this review focuses on the exquisite array of molecular mechanisms that control the expression and transcriptional activity of SOX2. In addition to its complex regulation at the transcriptional level, SOX2 expression and activity are controlled carefully by microRNAs, long non-coding RNAs, and post-translational modifications. In the Conclusion and Future Perspectives section, we point out that there are still important unanswered questions. Addressing these questions is expected to lead to new insights into the functions of SOX2 in cancer, which will help design novels strategies for more effectively treating some of the most deadly cancers.

  4. Time for a second look at SOX compliance.

    Science.gov (United States)

    Bigalke, John T; Burrill, Stephen J

    2007-08-01

    Incentives for tax-exempt healthcare organizations to comply with the Sarbanes-Oxley Act (SOX) abound from many quarters, including government, various associations, and the capital markets. New proposals from the Securities and Exchange Commission and the Public Company Accountability Oversight Board will streamline the processes of SOX compliance, even as the cost of compliance is dropping. Voluntary SOX compliance can best be achieved by adopting a four-phased control rationalization approach to implementation and maintenance.

  5. SOX1 links the function of neural patterning and Notch signalling in the ventral spinal cord during the neuron-glial fate switch

    Energy Technology Data Exchange (ETDEWEB)

    Genethliou, Nicholas; Panayiotou, Elena [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus); Panayi, Helen; Orford, Michael; Mean, Richard; Lapathitis, George; Gill, Herman; Raoof, Sahir [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Gasperi, Rita De; Elder, Gregory [James J. Peters VA Medical Center, Research and Development (3F22), 130 West Kingsbridge Road, Bronx, NY 10468 (United States); Kessaris, Nicoletta; Richardson, William D. [Wolfson Institute for Biomedical Research and Research Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT (United Kingdom); Malas, Stavros, E-mail: smalas@cing.ac.cy [The Cyprus Institute of Neurology and Genetics, Airport Avenue, No. 6, Agios Dometios, 2370 Nicosia (Cyprus); Department of Biological Sciences, University of Cyprus, P.O. Box 20537, 1678 Nicosia (Cyprus)

    2009-12-25

    During neural development the transition from neurogenesis to gliogenesis, known as the neuron-glial ({Nu}/G) fate switch, requires the coordinated function of patterning factors, pro-glial factors and Notch signalling. How this process is coordinated in the embryonic spinal cord is poorly understood. Here, we demonstrate that during the N/G fate switch in the ventral spinal cord (vSC) SOX1 links the function of neural patterning and Notch signalling. We show that, SOX1 expression in the vSC is regulated by PAX6, NKX2.2 and Notch signalling in a domain-specific manner. We further show that SOX1 regulates the expression of Hes1 and that loss of Sox1 leads to enhanced production of oligodendrocyte precursors from the pMN. Finally, we show that Notch signalling functions upstream of SOX1 during this fate switch and is independently required for the acquisition of the glial fate perse by regulating Nuclear Factor I A expression in a PAX6/SOX1/HES1/HES5-independent manner. These data integrate functional roles of neural patterning factors, Notch signalling and SOX1 during gliogenesis.

  6. Evaluation of a peridomestic mosquito trap for integration into an Aedes aegypti (Diptera: Culicidae) push-pull control strategy.

    Science.gov (United States)

    Salazar, Ferdinand V; Achee, Nicole L; Grieco, John P; Prabaripai, Atchariya; Eisen, Lars; Shah, Pankhil; Chareonviriyaphap, Theeraphap

    2012-06-01

    We determined the feasibility of using the BG-Sentinel™ mosquito trap (BGS) as the pull component in a push-pull strategy to reduce indoor biting by Aedes aegypti. This included evaluating varying numbers of traps (1-4) and mosquito release numbers (10, 25, 50, 100, 150, 200, and 250) on recapture rates under screen house conditions. Based on these variations in trap and mosquito numbers, release intervals were rotated through a completely randomized design with environmental factors (temperature, relative humidity, and light intensity) and monitored throughout each experiment. Data from four sampling time points (05:30, 09:30, 13:30, and 17:30) indicate a recapture range among treatments of 66-98%. Furthermore, 2-3 traps were as effective in recapturing mosquitoes as 4 traps for all mosquito release numbers. Time trends indicate Day 1 (the day the mosquitoes were released) as the "impact period" for recapture with peak numbers of marked mosquitoes collected at 09:30 or 4 h post-release. Information from this study will be used to guide the configuration of the BGS trap component of a push-pull vector control strategy currently in the proof-of-concept stage of development in Thailand and Peru. © 2012 The Society for Vector Ecology.

  7. Deciphering the Sox-Oct partner code by quantitative cooperativity measurements.

    Science.gov (United States)

    Ng, Calista K L; Li, Noel X; Chee, Sheena; Prabhakar, Shyam; Kolatkar, Prasanna R; Jauch, Ralf

    2012-06-01

    Several Sox-Oct transcription factor (TF) combinations have been shown to cooperate on diverse enhancers to determine cell fates. Here, we developed a method to quantify biochemically the Sox-Oct cooperation and assessed the pairing of the high-mobility group (HMG) domains of 11 Sox TFs with Oct4 on a series of composite DNA elements. This way, we clustered Sox proteins according to their dimerization preferences illustrating that Sox HMG domains evolved different propensities to cooperate with Oct4. Sox2, Sox14, Sox21 and Sox15 strongly cooperate on the canonical element but compete with Oct4 on a recently discovered compressed element. Sry also cooperates on the canonical element but binds additively to the compressed element. In contrast, Sox17 and Sox4 cooperate more strongly on the compressed than on the canonical element. Sox5 and Sox18 show some cooperation on both elements, whereas Sox8 and Sox9 compete on both elements. Testing rationally mutated Sox proteins combined with structural modeling highlights critical amino acids for differential Sox-Oct4 partnerships and demonstrates that the cooperativity correlates with the efficiency in producing induced pluripotent stem cells. Our results suggest selective Sox-Oct partnerships in genome regulation and provide a toolset to study protein cooperation on DNA.

  8. Conserved genomic organisation of Group B Sox genes in insects.

    Directory of Open Access Journals (Sweden)

    Woerfel Gertrud

    2005-05-01

    Full Text Available Abstract Background Sox domain containing genes are important metazoan transcriptional regulators implicated in a wide rage of developmental processes. The vertebrate B subgroup contains the Sox1, Sox2 and Sox3 genes that have early functions in neural development. Previous studies show that Drosophila Group B genes have been functionally conserved since they play essential roles in early neural specification and mutations in the Drosophila Dichaete and SoxN genes can be rescued with mammalian Sox genes. Despite their importance, the extent and organisation of the Group B family in Drosophila has not been fully characterised, an important step in using Drosophila to examine conserved aspects of Group B Sox gene function. Results We have used the directed cDNA sequencing along with the output from the publicly-available genome sequencing projects to examine the structure of Group B Sox domain genes in Drosophila melanogaster, Drosophila pseudoobscura, Anopheles gambiae and Apis mellifora. All of the insect genomes contain four genes encoding Group B proteins, two of which are intronless, as is the case with vertebrate group B genes. As has been previously reported and unusually for Group B genes, two of the insect group B genes, Sox21a and Sox21b, contain introns within their DNA-binding domains. We find that the highly unusual multi-exon structure of the Sox21b gene is common to the insects. In addition, we find that three of the group B Sox genes are organised in a linked cluster in the insect genomes. By in situ hybridisation we show that the pattern of expression of each of the four group B genes during embryogenesis is conserved between D. melanogaster and D. pseudoobscura. Conclusion The DNA-binding domain sequences and genomic organisation of the group B genes have been conserved over 300 My of evolution since the last common ancestor of the Hymenoptera and the Diptera. Our analysis suggests insects have two Group B1 genes, SoxN and

  9. XPC Promotes Pluripotency of Human Dental Pulp Cells through Regulation of Oct-4/Sox2/c-Myc

    Directory of Open Access Journals (Sweden)

    Lu Liu

    2016-01-01

    Full Text Available Introduction. Xeroderma pigmentosum group C (XPC, essential component of multisubunit stem cell coactivator complex (SCC, functions as the critical factor modulating pluripotency and genome integrity through interaction with Oct-4/Sox2. However, its specific role in regulating pluripotency and multilineage differentiation of human dental pulp cells (DPCs remains unknown. Methods. To elucidate the functional role XPC played in pluripotency and multilineage differentiation of DPCs, expressions of XPC in DPCs with long-term culture were examined by real-time PCR and western blot. DPCs were transfected with lentiviral-mediated human XPC gene; then transfection rate was investigated by real-time PCR and western blot. Cell cycle, apoptosis, proliferation, senescence, multilineage differentiation, and expression of Oct-4/Sox2/c-Myc in transfected DPCs were examined. Results. XPC, Oct-4, Sox2, and c-Myc were downregulated at P7 compared with P3 in DPCs with long-term culture. XPC genes were upregulated in DPCs at P2 after transfection and maintained high expression level at P3 and P7. Cell proliferation, PI value, and telomerase activity were enhanced, whereas apoptosis was suppressed in transfected DPCs. Oct-4/Sox2/c-Myc were significantly upregulated, and multilineage differentiation in DPCs with XPC overexpression was enhanced after transfection. Conclusions. XPC plays an essential role in the modulation of pluripotency and multilineage differentiation of DPCs through regulation of Oct-4/Sox2/c-Myc.

  10. XPC Promotes Pluripotency of Human Dental Pulp Cells through Regulation of Oct-4/Sox2/c-Myc.

    Science.gov (United States)

    Liu, Lu; Peng, Zhengjun; Xu, Zhezhen; Wei, Xi

    2016-01-01

    Introduction. Xeroderma pigmentosum group C (XPC), essential component of multisubunit stem cell coactivator complex (SCC), functions as the critical factor modulating pluripotency and genome integrity through interaction with Oct-4/Sox2. However, its specific role in regulating pluripotency and multilineage differentiation of human dental pulp cells (DPCs) remains unknown. Methods. To elucidate the functional role XPC played in pluripotency and multilineage differentiation of DPCs, expressions of XPC in DPCs with long-term culture were examined by real-time PCR and western blot. DPCs were transfected with lentiviral-mediated human XPC gene; then transfection rate was investigated by real-time PCR and western blot. Cell cycle, apoptosis, proliferation, senescence, multilineage differentiation, and expression of Oct-4/Sox2/c-Myc in transfected DPCs were examined. Results. XPC, Oct-4, Sox2, and c-Myc were downregulated at P7 compared with P3 in DPCs with long-term culture. XPC genes were upregulated in DPCs at P2 after transfection and maintained high expression level at P3 and P7. Cell proliferation, PI value, and telomerase activity were enhanced, whereas apoptosis was suppressed in transfected DPCs. Oct-4/Sox2/c-Myc were significantly upregulated, and multilineage differentiation in DPCs with XPC overexpression was enhanced after transfection. Conclusions. XPC plays an essential role in the modulation of pluripotency and multilineage differentiation of DPCs through regulation of Oct-4/Sox2/c-Myc.

  11. Profiling spermatogenic failure in adult testes bearing Sox9-deficient Sertoli cells identifies genes involved in feminization, inflammation and stress

    Directory of Open Access Journals (Sweden)

    Barrionuevo Francisco

    2010-12-01

    Full Text Available Abstract Background Sox9 (Sry box containing gene 9 is a DNA-binding transcription factor involved in chondrocyte development and sex determination. The protein's absence in testicular Sertoli nurse cells has been shown to disrupt testicular function in adults but little is known at the genome-wide level about molecular events concomitant with testicular break-down. Methods To determine the genome-wide effect on mRNA concentrations triggered by the absence of Sox9 in Sertoli cells we analysed adult testicular tissue from wild-type versus mutant mice with high-density oligonucleotide microarrays and integrated the output of this experiment with regulatory motif predictions and protein-protein network data. Results We report the genome-wide mRNA signature of adult testes lacking Sox9 in Sertoli cells before and after the onset of late spermatogenic failure as compared to fertile controls. The GeneChip data integrated with evolutionarily conserved Sox9 DNA binding motifs and regulatory network data identified genes involved in feminization, stress response and inflammation. Conclusions Our results extend previous observations that genes required for female gonadogenesis are up-regulated in the absence of Sox9 in fetal Sertoli cells to the adult stage. Importantly, we identify gene networks involved in immunological processes and stress response which is reminiscent of a phenomenon occurring in a sub-group of infertile men. This suggests mice lacking Sox9 in their Sertoli cells to be a potentially useful model for adult human testicular failure.

  12. The Trapping Index: How to integrate the Eulerian and the Lagrangian approach for the computation of the transport time scales of semi-enclosed basins.

    Science.gov (United States)

    Cucco, Andrea; Umgiesser, Georg

    2015-09-15

    In this work, we investigated if the Eulerian and the Lagrangian approaches for the computation of the Transport Time Scales (TTS) of semi-enclosed water bodies can be used univocally to define the spatial variability of basin flushing features. The Eulerian and Lagrangian TTS were computed for both simplified test cases and a realistic domain: the Venice Lagoon. The results confirmed the two approaches cannot be adopted univocally and that the spatial variability of the water renewal capacity can be investigated only through the computation of both the TTS. A specific analysis, based on the computation of a so-called Trapping Index, was then suggested to integrate the information provided by the two different approaches. The obtained results proved the Trapping Index to be useful to avoid any misleading interpretation due to the evaluation of the basin renewal features just from an Eulerian only or from a Lagrangian only perspective. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. SoxC transcription factors in retinal development and regeneration

    Directory of Open Access Journals (Sweden)

    Kun-Che Chang

    2017-01-01

    Full Text Available Glaucoma and other optic neuropathies result in optic nerve degeneration and the loss of retinal ganglion cells (RGCs through complex signaling pathways. Although the mechanisms that regulate RGC development remain unclear, uncovering novel developmental pathways may support new strategies to regenerate the optic nerve or replace RGCs. Here we review recent studies that provide strong evidence that the Sry-related high-mobility-group C (SoxC subfamily of transcription factors (TFs are necessary and sufficient for axon guidance and RGC fate specification. These findings also uncover novel SoxC-dependent mechanisms that serve as master regulators during important steps of RGC development. For example, we review work showing that SoxC TFs regulate RGC axon guidance and direction through the optic chiasm towards their appropriate targets in the brain. We also review work demonstrating that Sox11 subcellular localization is, in part, controlled through small ubiquitin-like post-translational modifier (SUMO and suggest compensatory cross-talk between Sox4 and Sox11. Furthermore, Sox4 overexpression is shown to positively drive RGC differentiation in human induced pluripotent stem cells (hiPSCs. Finally, we discuss how these findings may contribute to the advancement of regenerative and cell-based therapies to treat glaucoma and other optic nerve neuropathies.

  14. Sox11 Reduces Caspase-6 Cleavage and Activity.

    Directory of Open Access Journals (Sweden)

    Elaine Waldron-Roby

    Full Text Available The apoptotic cascade is an orchestrated event, whose final stages are mediated by effector caspases. Regulatory binding proteins have been identified for caspases such as caspase-3, -7, -8, and -9. Many of these proteins belong to the inhibitor of apoptosis (IAP family. By contrast, caspase-6 is not believed to be influenced by IAPs, and little is known about its regulation. We therefore performed a yeast-two-hybrid screen using a constitutively inactive form of caspase-6 for bait in order to identify novel regulators of caspase-6 activity. Sox11 was identified as a potential caspase-6 interacting protein. Sox11 was capable of dramatically reducing caspase-6 activity, as well as preventing caspase-6 self- cleavage. Several regions, including amino acids 117-214 and 362-395 within sox11 as well as a nuclear localization signal (NLS all contributed to the reduction in caspase-6 activity. Furthermore, sox11 was also capable of decreasing other effector caspase activity but not initiator caspases -8 and -9. The ability of sox11 to reduce effector caspase activity was also reflected in its capacity to reduce cell death following toxic insult. Interestingly, other sox proteins also had the ability to reduce caspase-6 activity but to a lesser extent than sox11.

  15. Dual lineage-specific expression of Sox17 during mouse embryogenesis

    DEFF Research Database (Denmark)

    Choi, Eunyoung; Kraus, Marine R C; Lemaire, Laurence A

    2012-01-01

    Sox17 is essential for both endoderm development and fetal hematopoietic stem cell (HSC) maintenance. While endoderm-derived organs are well known to originate from Sox17-expressing cells, it is less certain whether fetal HSCs also originate from Sox17-expressing cells. By generating a Sox17(GFPC...

  16. Improved concentration and separation of particles in a 3D dielectrophoretic chip integrating focusing, aligning and trapping

    KAUST Repository

    Li, Ming

    2012-10-18

    This article presents a dielectrophoresis (DEP)-based microfluidic device with the three-dimensional (3D) microelectrode configuration for concentrating and separating particles in a continuous throughflow. The 3D electrode structure, where microelectrode array are patterned on both the top and bottom surfaces of the microchannel, is composed of three units: focusing, aligning and trapping. As particles flowing through the microfluidic channel, they are firstly focused and aligned by the funnel-shaped and parallel electrode array, respectively, before being captured at the trapping unit due to negative DEP force. For a mixture of two particle populations of different sizes or dielectric properties, with a careful selection of suspending medium and applied field, the population exhibits stronger negative DEP manipulated by the microelectrode array and, therefore, separated from the other population which is easily carried away toward the outlet due to hydrodynamic force. The functionality of the proposed microdevice was verified by concentrating different-sized polystyrene (PS) microparticles and yeast cells dynamically flowing in the microchannel. Moreover, separation based on size and dielectric properties was achieved by sorting PS microparticles, and isolating 5 μm PS particles from yeast cells, respectively. The performance of the proposed micro-concentrator and separator was also studied, including the threshold voltage at which particles begin to be trapped, variation of cell-trapping efficiency with respect to the applied voltage and flow rate, and the efficiency of separation experiments. The proposed microdevice has various advantages, including multi-functionality, improved manipulation efficiency and throughput, easy fabrication and operation, etc., which shows a great potential for biological, chemical and medical applications. © 2012 Springer-Verlag Berlin Heidelberg.

  17. Genome-wide Reconstruction of OxyR and SoxRS Transcriptional Regulatory Networks under Oxidative Stress in Escherichia coli K-12 MG1655

    Directory of Open Access Journals (Sweden)

    Sang Woo Seo

    2015-08-01

    Full Text Available Three transcription factors (TFs, OxyR, SoxR, and SoxS, play a critical role in transcriptional regulation of the defense system for oxidative stress in bacteria. However, their full genome-wide regulatory potential is unknown. Here, we perform a genome-scale reconstruction of the OxyR, SoxR, and SoxS regulons in Escherichia coli K-12 MG1655. Integrative data analysis reveals that a total of 68 genes in 51 transcription units (TUs belong to these regulons. Among them, 48 genes showed more than 2-fold changes in expression level under single-TF-knockout conditions. This reconstruction expands the genome-wide roles of these factors to include direct activation of genes related to amino acid biosynthesis (methionine and aromatic amino acids, cell wall synthesis (lipid A biosynthesis and peptidoglycan growth, and divalent metal ion transport (Mn2+, Zn2+, and Mg2+. Investigating the co-regulation of these genes with other stress-response TFs reveals that they are independently regulated by stress-specific TFs.

  18. De novo SOX11 mutations cause Coffin-Siris syndrome.

    Science.gov (United States)

    Tsurusaki, Yoshinori; Koshimizu, Eriko; Ohashi, Hirofumi; Phadke, Shubha; Kou, Ikuyo; Shiina, Masaaki; Suzuki, Toshifumi; Okamoto, Nobuhiko; Imamura, Shintaro; Yamashita, Michiaki; Watanabe, Satoshi; Yoshiura, Koh-ichiro; Kodera, Hirofumi; Miyatake, Satoko; Nakashima, Mitsuko; Saitsu, Hirotomo; Ogata, Kazuhiro; Ikegawa, Shiro; Miyake, Noriko; Matsumoto, Naomichi

    2014-06-02

    Coffin-Siris syndrome (CSS) is a congenital disorder characterized by growth deficiency, intellectual disability, microcephaly, characteristic facial features and hypoplastic nails of the fifth fingers and/or toes. We previously identified mutations in five genes encoding subunits of the BAF complex, in 55% of CSS patients. Here we perform whole-exome sequencing in additional CSS patients, identifying de novo SOX11 mutations in two patients with a mild CSS phenotype. sox11a/b knockdown in zebrafish causes brain abnormalities, potentially explaining the brain phenotype of CSS. SOX11 is the downstream transcriptional factor of the PAX6-BAF complex, highlighting the importance of the BAF complex and SOX11 transcriptional network in brain development.

  19. SOX2 regulates acinar cell development in the salivary gland

    Science.gov (United States)

    Emmerson, Elaine; May, Alison J; Nathan, Sara; Cruz-Pacheco, Noel; Lizama, Carlos O; Maliskova, Lenka; Zovein, Ann C; Shen, Yin; Muench, Marcus O; Knox, Sarah M

    2017-01-01

    Acinar cells play an essential role in the secretory function of exocrine organs. Despite this requirement, how acinar cells are generated during organogenesis is unclear. Using the acini-ductal network of the developing human and murine salivary gland, we demonstrate an unexpected role for SOX2 and parasympathetic nerves in generating the acinar lineage that has broad implications for epithelial morphogenesis. Despite SOX2 being expressed by progenitors that give rise to both acinar and duct cells, genetic ablation of SOX2 results in a failure to establish acini but not ducts. Furthermore, we show that SOX2 targets acinar-specific genes and is essential for the survival of acinar but not ductal cells. Finally, we illustrate an unexpected and novel role for peripheral nerves in the creation of acini throughout development via regulation of SOX2. Thus, SOX2 is a master regulator of the acinar cell lineage essential to the establishment of a functional organ. DOI: http://dx.doi.org/10.7554/eLife.26620.001 PMID:28623666

  20. Artificial induction of Sox21 regulates sensory cell formation in the embryonic chicken inner ear.

    Directory of Open Access Journals (Sweden)

    Stephen D Freeman

    Full Text Available During embryonic development, hair cells and support cells in the sensory epithelia of the inner ear derive from progenitors that express Sox2, a member of the SoxB1 family of transcription factors. Sox2 is essential for sensory specification, but high levels of Sox2 expression appear to inhibit hair cell differentiation, suggesting that factors regulating Sox2 activity could be critical for both processes. Antagonistic interactions between SoxB1 and SoxB2 factors are known to regulate cell differentiation in neural tissue, which led us to investigate the potential roles of the SoxB2 member Sox21 during chicken inner ear development. Sox21 is normally expressed by sensory progenitors within vestibular and auditory regions of the early embryonic chicken inner ear. At later stages, Sox21 is differentially expressed in the vestibular and auditory organs. Sox21 is restricted to the support cell layer of the auditory epithelium, while it is enriched in the hair cell layer of the vestibular organs. To test Sox21 function, we used two temporally distinct gain-of-function approaches. Sustained over-expression of Sox21 from early developmental stages prevented prosensory specification, and abolished the formation of both hair cells and support cells. However, later induction of Sox21 expression at the time of hair cell formation in organotypic cultures of vestibular epithelia inhibited endogenous Sox2 expression and Notch activity, and biased progenitor cells towards a hair cell fate. Interestingly, Sox21 did not promote hair cell differentiation in the immature auditory epithelium, which fits with the expression of endogenous Sox21 within mature support cells in this tissue. These results suggest that interactions among endogenous SoxB family transcription factors may regulate sensory cell formation in the inner ear, but in a context-dependent manner.

  1. Trapped antihydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Butler, E., E-mail: eoin.butler@cern.ch [CERN, Physics Department (Switzerland); Andresen, G. B. [Aarhus University, Department of Physics and Astronomy (Denmark); Ashkezari, M. D. [Simon Fraser University, Department of Physics (Canada); Baquero-Ruiz, M. [University of California, Department of Physics (United States); Bertsche, W. [Swansea University, Department of Physics (United Kingdom); Bowe, P. D. [Aarhus University, Department of Physics and Astronomy (Denmark); Cesar, C. L. [Universidade Federal do Rio de Janeiro, Instituto de Fisica (Brazil); Chapman, S. [University of California, Department of Physics (United States); Charlton, M.; Deller, A.; Eriksson, S. [Swansea University, Department of Physics (United Kingdom); Fajans, J. [University of California, Department of Physics (United States); Friesen, T.; Fujiwara, M. C. [University of Calgary, Department of Physics and Astronomy (Canada); Gill, D. R. [TRIUMF (Canada); Gutierrez, A. [University of British Columbia, Department of Physics and Astronomy (Canada); Hangst, J. S. [Aarhus University, Department of Physics and Astronomy (Denmark); Hardy, W. N. [University of British Columbia, Department of Physics and Astronomy (Canada); Hayden, M. E. [Simon Fraser University, Department of Physics (Canada); Humphries, A. J. [Swansea University, Department of Physics (United Kingdom); Collaboration: ALPHA Collaboration; and others

    2012-12-15

    Precision spectroscopic comparison of hydrogen and antihydrogen holds the promise of a sensitive test of the Charge-Parity-Time theorem and matter-antimatter equivalence. The clearest path towards realising this goal is to hold a sample of antihydrogen in an atomic trap for interrogation by electromagnetic radiation. Achieving this poses a huge experimental challenge, as state-of-the-art magnetic-minimum atom traps have well depths of only {approx}1 T ({approx}0.5 K for ground state antihydrogen atoms). The atoms annihilate on contact with matter and must be 'born' inside the magnetic trap with low kinetic energies. At the ALPHA experiment, antihydrogen atoms are produced from antiprotons and positrons stored in the form of non-neutral plasmas, where the typical electrostatic potential energy per particle is on the order of electronvolts, more than 10{sup 4} times the maximum trappable kinetic energy. In November 2010, ALPHA published the observation of 38 antiproton annihilations due to antihydrogen atoms that had been trapped for at least 172 ms and then released-the first instance of a purely antimatter atomic system confined for any length of time (Andresen et al., Nature 468:673, 2010). We present a description of the main components of the ALPHA traps and detectors that were key to realising this result. We discuss how the antihydrogen atoms were identified and how they were discriminated from the background processes. Since the results published in Andresen et al. (Nature 468:673, 2010), refinements in the antihydrogen production technique have allowed many more antihydrogen atoms to be trapped, and held for much longer times. We have identified antihydrogen atoms that have been trapped for at least 1,000 s in the apparatus (Andresen et al., Nature Physics 7:558, 2011). This is more than sufficient time to interrogate the atoms spectroscopically, as well as to ensure that they have relaxed to their ground state.

  2. Structural basis for the SOX-dependent genomic redistribution of OCT4 in stem cell differentiation.

    Science.gov (United States)

    Merino, Felipe; Ng, Calista Keow Leng; Veerapandian, Veeramohan; Schöler, Hans Robert; Jauch, Ralf; Cojocaru, Vlad

    2014-09-02

    In pluripotent cells, OCT4 associates with SOX2 to maintain pluripotency or with SOX17 to induce primitive endoderm commitment. The OCT4-SOX2 and OCT4-SOX17 combinations bind mutually exclusive to two distinct composite DNA elements, known as the "canonical" and "compressed" motifs, respectively. The structural basis for the OCT4-SOX17 cooperativity is unknown. Whereas SOX17 has been engineered to replace SOX2 in the pluripotency circuitry, all generated SOX2 mutants have failed to act like SOX17. From molecular simulations, we revealed the OCT4-SOX17 interaction interface and elucidated the SOX-dependent motif preference of OCT4. Moreover, we designed a SOX2 mutant that we predicted and confirmed experimentally to bind cooperatively with OCT4 to the compressed motif. Ultimately, we found a strong correlation between the experimental and calculated relative cooperative-binding free energies of 12 OCT4-SOX-DNA complexes. Therefore, we validated the OCT4-SOX interfaces and demonstrated that in silico design of DNA-binding cooperativity is suitable for altering transcriptional circuitries. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Sox genes in grass carp (Ctenopharyngodon idella) with their implications for genome duplication and evolution

    OpenAIRE

    Zhong , Lei; Yu , Xiaomu; Tong , Jingou

    2006-01-01

    Abstract The Sox gene family is found in a broad range of animal taxa and encodes important gene regulatory proteins involved in a variety of developmental processes. We have obtained clones representing the HMG boxes of twelve Sox genes from grass carp (Ctenopharyngodon idella), one of the four major domestic carps in China. The cloned Sox genes belong to group B1, B2 and C. Our analyses show that whereas the human genome contains a single copy of Sox4, Sox11 and Sox14, each of these genes h...

  4. Selenium analysis by an integrated microwave digestion-needle trap device with hydride sorption on carbon nanotubes and electrothermal atomic absorption spectrometry determination

    Science.gov (United States)

    Maratta Martínez, Ariel; Vázquez, Sandra; Lara, Rodolfo; Martínez, Luis Dante; Pacheco, Pablo

    2018-02-01

    An integrated microwave assisted digestion (MW-AD) - needle trap device (NTD) for selenium determination in grape pomace samples is presented. The NTD was filled with oxidized multiwall carbon nanotubes (oxMWCNTS) where Se hydrides were preconcentrated. Determination was carried out by flow injection-electrothermal atomic absorption spectrometry (FI-ETAAS). The variables affecting the system were established by a multivariate design (Plackett Burman), indicating that the following variables significantly affect the system: sample amount, HNO3 digestion solution concentration, NaBH4 volume and elution volume. A Box-Behnken design was implemented to determine the optimized values of these variables. The system improved Se atomization in the graphite furnace, since only trapped hydrides reached the graphite furnace, and the pyrolysis stage was eliminated according to the aqueous matrix of the eluate. Under optimized conditions the system reached a limit of quantification of 0.11 μg kg- 1, a detection limit of 0.032 μg kg- 1, a relative standard deviation of 4% and a preconcentration factor (PF) of 100, reaching a throughput sample of 5 samples per hour. Sample analysis show Se concentrations between 0.34 ± 0.03 μg kg- 1 to 0.48 ± 0.03 μg kg- 1 in grape pomace. This system provides minimal reagents and sample consumption, eliminates discontinuous stages between samples processing reaching a simpler and faster Se analysis.

  5. Identification and characterization of the human SOX6 promoter

    International Nuclear Information System (INIS)

    Ikeda, Toshiyuki; Saito, Taku; Ushita, Masahiro; Yano, Fumiko; Kan, Akinori; Itaka, Keiji; Moro, Toru; Nakamura, Kozo; Kawaguchi, Hiroshi; Chung, Ung-il

    2007-01-01

    The present study attempted to identify and characterize the embryonic promoter of Sox6, a determinant regulator of chondrogenic differentiation. A common transcription start region for human and mouse Sox6 was initially identified, which contained a highly conserved sequence, A-box. Tandem repeats of A-box had a strong transcriptional activity both at the basal level and in response to Sox9. Cells carrying the 4xA-box-DsRed2 reporter fluoresced only upon chondrogenic differentiation. The 46-bp core enhancer region (CES6) was then identified in the 3' half of A-box, within which a C/EBP-binding motif was identified. Overexpressed C/EBPβ activated the Sox6 promoter, and mutant 4xCES6 constructs lacking the C/EBP motif lost their basal activity. CES6 and nuclear extracts formed a specific complex, which was supershifted by anti-C/EBPβ antibody, and in vitro translated C/EBPβ specifically bound to CES6. Thus, we successfully identified the Sox6 promoter and its core enhancer and characterized the interactions with regulatory transcription factors

  6. Evolutionarily Conserved, Growth Plate Zone-Specific Regulation of the Matrilin-1 Promoter: L-Sox5/Sox6 and Nfi Factors Bound near TATA Finely Tune Activation by Sox9 ▿

    Science.gov (United States)

    Nagy, Andrea; Kénesi, Erzsébet; Rentsendorj, Otgonchimeg; Molnár, Annamária; Szénási, Tibor; Sinkó, Ildikó; Zvara, Ágnes; Thottathil Oommen, Sajit; Barta, Endre; Puskás, László G.; Lefebvre, Veronique; Kiss, Ibolya

    2011-01-01

    To help uncover the mechanisms underlying the staggered expression of cartilage-specific genes in the growth plate, we dissected the transcriptional mechanisms driving expression of the matrilin-1 gene (Matn1). We show that a unique assembly of evolutionarily conserved cis-acting elements in the Matn1 proximal promoter restricts expression to the proliferative and prehypertrophic zones of the growth plate. These elements functionally interact with distal elements and likewise are capable of restricting the domain of activity of a pancartilaginous Col2a1 enhancer. The proximal elements include a Pe1 element binding the chondrogenic L-Sox5, Sox6, and Sox9 proteins, a SI element binding Nfi proteins, and an initiator Ine element binding the Sox trio and other factors. Sox9 binding to Pe1 is indispensable for functional interaction with the distal promoter. Binding of L-Sox5/Sox6 to Ine and Nfib to SI modulates Sox9 transactivation in a protein dose-dependent manner, possibly to enhance Sox9 activity in early stages of chondrogenesis and repress it at later stages. Hence, our data suggest a novel model whereby Sox and Nfi proteins bind to conserved Matn1 proximal elements and functionally interact with each other to finely tune gene expression in specific zones of the cartilage growth plate. PMID:21173167

  7. SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas.

    Science.gov (United States)

    Watanabe, Hideo; Ma, Qiuping; Peng, Shouyong; Adelmant, Guillaume; Swain, Danielle; Song, Wenyu; Fox, Cameron; Francis, Joshua M; Pedamallu, Chandra Sekhar; DeLuca, David S; Brooks, Angela N; Wang, Su; Que, Jianwen; Rustgi, Anil K; Wong, Kwok-kin; Ligon, Keith L; Liu, X Shirley; Marto, Jarrod A; Meyerson, Matthew; Bass, Adam J

    2014-04-01

    The transcription factor SOX2 is an essential regulator of pluripotent stem cells and promotes development and maintenance of squamous epithelia. We previously reported that SOX2 is an oncogene and subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs). Here, we have further characterized the function of SOX2 in SCC. Using ChIP-seq analysis, we compared SOX2-regulated gene profiles in multiple SCC cell lines to ES cell profiles and determined that SOX2 binds to distinct genomic loci in SCCs. In SCCs, SOX2 preferentially interacts with the transcription factor p63, as opposed to the transcription factor OCT4, which is the preferred SOX2 binding partner in ES cells. SOX2 and p63 exhibited overlapping genomic occupancy at a large number of loci in SCCs; however, coordinate binding of SOX2 and p63 was absent in ES cells. We further demonstrated that SOX2 and p63 jointly regulate gene expression, including the oncogene ETV4, which was essential for SOX2-amplified SCC cell survival. Together, these findings demonstrate that the action of SOX2 in SCC differs substantially from its role in pluripotency. The identification of the SCC-associated interaction between SOX2 and p63 will enable deeper characterization the downstream targets of this interaction in SCC and normal squamous epithelial physiology.

  8. SOXE neofunctionalization and elaboration of the neural crest during chordate evolution

    Science.gov (United States)

    Tai, Andrew; Cheung, Martin; Huang, Yong-Heng; Jauch, Ralf; Bronner, Marianne E.; Cheah, Kathryn S. E.

    2016-01-01

    During chordate evolution, two genome-wide duplications facilitated acquisition of vertebrate traits, including emergence of neural crest cells (NCCs), in which neofunctionalization of the duplicated genes are thought to have facilitated development of craniofacial structures and the peripheral nervous system. How these duplicated genes evolve and acquire the ability to specify NC and their derivatives are largely unknown. Vertebrate SoxE paralogues, most notably Sox9/10, are essential for NC induction, delamination and lineage specification. In contrast, the basal chordate, amphioxus, has a single SoxE gene and lacks NC-like cells. Here, we test the hypothesis that duplication and divergence of an ancestral SoxE gene may have facilitated elaboration of NC lineages. By using an in vivo expression assay to compare effects of AmphiSoxE and vertebrate Sox9 on NC development, we demonstrate that all SOXE proteins possess similar DNA binding and homodimerization properties and can induce NCCs. However, AmphiSOXE is less efficient than SOX9 in transactivation activity and in the ability to preferentially promote glial over neuronal fate, a difference that lies within the combined properties of amino terminal and transactivation domains. We propose that acquisition of AmphiSoxE expression in the neural plate border led to NCC emergence while duplication and divergence produced advantageous mutations in vertebrate homologues, promoting elaboration of NC traits. PMID:27734831

  9. Action spectroscopy of SrCl{sup +} using an integrated ion trap time-of-flight mass spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Puri, Prateek, E-mail: teek24@ucla.edu; Schowalter, Steven J.; Hudson, Eric R. [Department of Physics and Astronomy, University of California, Los Angeles, California 90095 (United States); Kotochigova, Svetlana; Petrov, Alexander [Department of Physics, Temple University, Philadelphia, Pennsylvania 19122 (United States)

    2014-07-07

    The photodissociation cross-section of SrCl{sup +} is measured in the spectral range of 36 000–46 000 cm{sup −1} using a modular time-of-flight mass spectrometer (TOF-MS). By irradiating a sample of trapped SrCl{sup +} molecular ions with a pulsed dye laser, X{sup 1}Σ{sup +} state molecular ions are electronically excited to the repulsive wall of the A{sup 1}Π state, resulting in dissociation. Using the TOF-MS, the product fragments are detected and the photodissociation cross-section is determined for a broad range of photon energies. Detailed ab initio calculations of the SrCl{sup +} molecular potentials and spectroscopic constants are also performed and are found to be in good agreement with experiment. The spectroscopic constants for SrCl{sup +} are also compared to those of another alkaline earth halogen, BaCl{sup +}, in order to highlight structural differences between the two molecular ions. This work represents the first spectroscopy and ab initio calculations of SrCl{sup +}.

  10. Genome-wide mapping of Sox6 binding sites in skeletal muscle reveals both direct and indirect regulation of muscle terminal differentiation by Sox6

    Directory of Open Access Journals (Sweden)

    An Chung-Il

    2011-10-01

    Full Text Available Abstract Background Sox6 is a multi-faceted transcription factor involved in the terminal differentiation of many different cell types in vertebrates. It has been suggested that in mice as well as in zebrafish Sox6 plays a role in the terminal differentiation of skeletal muscle by suppressing transcription of slow fiber specific genes. In order to understand how Sox6 coordinately regulates the transcription of multiple fiber type specific genes during muscle development, we have performed ChIP-seq analyses to identify Sox6 target genes in mouse fetal myotubes and generated muscle-specific Sox6 knockout (KO mice to determine the Sox6 null muscle phenotype in adult mice. Results We have identified 1,066 Sox6 binding sites using mouse fetal myotubes. The Sox6 binding sites were found to be associated with slow fiber-specific, cardiac, and embryonic isoform genes that are expressed in the sarcomere as well as transcription factor genes known to play roles in muscle development. The concurrently performed RNA polymerase II (Pol II ChIP-seq analysis revealed that 84% of the Sox6 peak-associated genes exhibited little to no binding of Pol II, suggesting that the majority of the Sox6 target genes are transcriptionally inactive. These results indicate that Sox6 directly regulates terminal differentiation of muscle by affecting the expression of sarcomere protein genes as well as indirectly through influencing the expression of transcription factors relevant to muscle development. Gene expression profiling of Sox6 KO skeletal and cardiac muscle revealed a significant increase in the expression of the genes associated with Sox6 binding. In the absence of the Sox6 gene, there was dramatic upregulation of slow fiber-specific, cardiac, and embryonic isoform gene expression in Sox6 KO skeletal muscle and fetal isoform gene expression in Sox6 KO cardiac muscle, thus confirming the role Sox6 plays as a transcriptional suppressor in muscle development

  11. SOXs in human prostate cancer: implication as progression and prognosis factors

    International Nuclear Information System (INIS)

    Zhong, Wei-de; Chen, Xi-bin; Lin, Zhuo-yuan; Deng, Ye-han; Wu, Shu-lin; He, Hui-chan; Wu, Chin-lee; Qin, Guo-qiang; Dai, Qi-shan; Han, Zhao-dong; Chen, Shan-ming; Ling, Xiao-hui; Fu, Xin; Cai, Chao; Chen, Jia-hong

    2012-01-01

    SOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa). The gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa. The microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance. Our data offer the convince

  12. Ripple Trap

    Science.gov (United States)

    2006-01-01

    3 April 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows the margin of a lava flow on a cratered plain in the Athabasca Vallis region of Mars. Remarkably, the cratered plain in this scene is essentially free of bright, windblown ripples. Conversely, the lava flow apparently acted as a trap for windblown materials, illustrated by the presence of the light-toned, wave-like texture over much of the flow. That the lava flow surface trapped windblown sand and granules better than the cratered plain indicates that the flow surface has a rougher texture at a scale too small to resolve in this image. Location near: 10.7oN, 204.5oW Image width: 3 km (1.9 mi) Illumination from: lower left Season: Northern Winter

  13. Sox genes in grass carp (Ctenopharyngodon idella with their implications for genome duplication and evolution

    Directory of Open Access Journals (Sweden)

    Tong Jingou

    2006-11-01

    Full Text Available Abstract The Sox gene family is found in a broad range of animal taxa and encodes important gene regulatory proteins involved in a variety of developmental processes. We have obtained clones representing the HMG boxes of twelve Sox genes from grass carp (Ctenopharyngodon idella, one of the four major domestic carps in China. The cloned Sox genes belong to group B1, B2 and C. Our analyses show that whereas the human genome contains a single copy of Sox4, Sox11 and Sox14, each of these genes has two co-orthologs in grass carp, and the duplication of Sox4 and Sox11 occurred before the divergence of grass carp and zebrafish, which support the "fish-specific whole-genome duplication" theory. An estimation for the origin of grass carp based on the molecular clock using Sox1, Sox3 and Sox11 genes as markers indicates that grass carp (subfamily Leuciscinae and zebrafish (subfamily Danioninae diverged approximately 60 million years ago. The potential uses of Sox genes as markers in revealing the evolutionary history of grass carp are discussed.

  14. Structure and decoy-mediated inhibition of the SOX18/Prox1-DNA interaction.

    Science.gov (United States)

    Klaus, Miriam; Prokoph, Nina; Girbig, Mathias; Wang, Xuecong; Huang, Yong-Heng; Srivastava, Yogesh; Hou, Linlin; Narasimhan, Kamesh; Kolatkar, Prasanna R; Francois, Mathias; Jauch, Ralf

    2016-05-05

    The transcription factor (TF) SOX18 drives lymphatic vessel development in both embryogenesis and tumour-induced neo-lymphangiogenesis. Genetic disruption of Sox18 in a mouse model protects from tumour metastasis and established the SOX18 protein as a molecular target. Here, we report the crystal structure of the SOX18 DNA binding high-mobility group (HMG) box bound to a DNA element regulating Prox1 transcription. The crystals diffracted to 1.75Å presenting the highest resolution structure of a SOX/DNA complex presently available revealing water structure, structural adjustments at the DNA contact interface and non-canonical conformations of the DNA backbone. To explore alternatives to challenging small molecule approaches for targeting the DNA-binding activity of SOX18, we designed a set of five decoys based on modified Prox1-DNA. Four decoys potently inhibited DNA binding of SOX18 in vitro and did not interact with non-SOX TFs. Serum stability, nuclease resistance and thermal denaturation assays demonstrated that a decoy circularized with a hexaethylene glycol linker and terminal phosphorothioate modifications is most stable. This SOX decoy also interfered with the expression of a luciferase reporter under control of a SOX18-dependent VCAM1 promoter in COS7 cells. Collectively, we propose SOX decoys as potential strategy for inhibiting SOX18 activity to disrupt tumour-induced neo-lymphangiogenesis. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. THRAP3 interacts with and inhibits the transcriptional activity of SOX9 during chondrogenesis.

    Science.gov (United States)

    Sono, Takashi; Akiyama, Haruhiko; Miura, Shigenori; Deng, Jian Min; Shukunami, Chisa; Hiraki, Yuji; Tsushima, Yu; Azuma, Yoshiaki; Behringer, Richard R; Matsuda, Shuichi

    2018-07-01

    Sex-determining region Y (Sry)-box (Sox)9 is required for chondrogenesis as a transcriptional activator of genes related to chondrocyte proliferation, differentiation, and cartilage-specific extracellular matrix. Although there have been studies investigating the Sox9-dependent transcriptional complexes, not all their components have been identified. In the present study, we demonstrated that thyroid hormone receptor-associated protein (THRAP)3 is a component of a SOX9 transcriptional complex by liquid chromatography mass spectrometric analysis of FLAG-tagged Sox9-binding proteins purified from FLAG-HA-tagged Sox9 knock-in mice. Thrap3 knockdown in ATDC5 chondrogenic cells increased the expression of Collagen type II alpha 1 chain (Col2a1) without affecting Sox9 expression. THRAP3 and SOX9 overexpression reduced Col2a1 levels to a greater degree than overexpression of SOX9 alone. The negative regulation of SOX9 transcriptional activity by THRAP3 was mediated by interaction between the proline-, glutamine-, and serine-rich domain of SOX9 and the innominate domain of THRAP3. These results indicate that THRAP3 negatively regulates SOX9 transcriptional activity as a cofactor of a SOX9 transcriptional complex during chondrogenesis.

  16. Trapped antihydrogen

    CERN Document Server

    Butler, E; Ashkezari, M D; Baquero-Ruiz, M; Bertsche, W; Bowe, P D; Cesar, C L; Chapman, S; Charlton, M; Deller, A; Eriksson, S; Fajans, J; Friesen, T; Fujiwara, M C; Gill, D R; Gutierrez, A; Hangst, J S; Hardy, W N; Hayden, M E; Humphries, A J; Hydomako, R; Jenkins, M J; Jonsell, S; Jørgensen, L V; Kemp, S L; Kurchaninov, L; Madsen, N; Menary, S; Nolan, P; Olchanski, K; Olin, A; Povilus, A; Pusa, P; Rasmussen, C Ø; Robicheaux, F; Sarid, E; Seif el Nasr, S; Silveira, D M; So, C; Storey, J W; Thompson, R I; van der Werf, D P; Wurtele, J S; Yamazaki,Y

    2012-01-01

    Precision spectroscopic comparison of hydrogen and antihydrogen holds the promise of a sensitive test of the Charge-Parity-Time theorem and matter-antimatter equivalence. The clearest path towards realising this goal is to hold a sample of antihydrogen in an atomic trap for interrogation by electromagnetic radiation. Achieving this poses a huge experimental challenge, as state-of-the-art magnetic-minimum atom traps have well depths of only ∼1 T (∼0.5 K for ground state antihydrogen atoms). The atoms annihilate on contact with matter and must be ‘born’ inside the magnetic trap with low kinetic energies. At the ALPHA experiment, antihydrogen atoms are produced from antiprotons and positrons stored in the form of non-neutral plasmas, where the typical electrostatic potential energy per particle is on the order of electronvolts, more than 104 times the maximum trappable kinetic energy. In November 2010, ALPHA published the observation of 38 antiproton annihilations due to antihydrogen atoms that had been ...

  17. SXT/R391 Integrative and Conjugative Elements (ICEs) Encode a Novel 'Trap-Door' Strategy for Mobile Element Escape.

    Science.gov (United States)

    Ryan, Michael P; Armshaw, Patricia; Pembroke, J Tony

    2016-01-01

    Integrative conjugative elements (ICEs) are a class of bacterial mobile elements that have the ability to mediate their own integration, excision, and transfer from one host genome to another by a mechanism of site-specific recombination, self-circularisation, and conjugative transfer. Members of the SXT/R391 ICE family of enterobacterial mobile genetic elements display an unusual UV-inducible sensitization function which results in stress induced killing of bacterial cells harboring the ICE. This sensitization has been shown to be associated with a stress induced overexpression of a mobile element encoded conjugative transfer gene, orf43, a traV homolog. This results in cell lysis and release of a circular form of the ICE. Induction of this novel system may allow transfer of an ICE, enhancing its survival potential under conditions not conducive to conjugative transfer.

  18. Small-Molecule Inhibitors of the SOX18 Transcription Factor.

    Science.gov (United States)

    Fontaine, Frank; Overman, Jeroen; Moustaqil, Mehdi; Mamidyala, Sreeman; Salim, Angela; Narasimhan, Kamesh; Prokoph, Nina; Robertson, Avril A B; Lua, Linda; Alexandrov, Kirill; Koopman, Peter; Capon, Robert J; Sierecki, Emma; Gambin, Yann; Jauch, Ralf; Cooper, Matthew A; Zuegg, Johannes; Francois, Mathias

    2017-03-16

    Pharmacological modulation of transcription factors (TFs) has only met little success over the past four decades. This is mostly due to standard drug discovery approaches centered on blocking protein/DNA binding or interfering with post-translational modifications. Recent advances in the field of TF biology have revealed a central role of protein-protein interaction in their mode of action. In an attempt to modulate the activity of SOX18 TF, a known regulator of vascular growth in development and disease, we screened a marine extract library for potential small-molecule inhibitors. We identified two compounds, which inspired a series of synthetic SOX18 inhibitors, able to interfere with the SOX18 HMG DNA-binding domain, and to disrupt HMG-dependent protein-protein interaction with RBPJ. These compounds also perturbed SOX18 transcriptional activity in a cell-based reporter gene system. This approach may prove useful in developing a new class of anti-angiogenic compounds based on the inhibition of TF activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Study of Microflares through SOXS Mission Rajmal Jain , Vishal ...

    Indian Academy of Sciences (India)

    Abstract. We present a study of 10 microflares observed in 4–30 keV by SOXS mission simultaneously with Hα observations made at NAOJ,. Japan during the interval between February and August 2004. The X-ray and Hα light curves showed that the lifetime of microflares varies between. 4 and 25 min. We found that the ...

  20. Performance of a high-precision calorimeter for the measurement of the antineutrino-source strength in the SOX experiment

    Energy Technology Data Exchange (ETDEWEB)

    Altenmueller, Konrad [Technische Universitaet Muenchen (Germany); Collaboration: BOREXINO-Collaboration

    2016-07-01

    A calorimeter was developed to measure the thermal power and thus the antineutrino-generation rate of a {sup 144}Ce - {sup 144}Pr antineutrino-source with < 1% overall accuracy for the SOX experiment. SOX is searching for neutrino oscillations at short baselines with the Borexino detector to investigate the existence of eV-scale sterile neutrinos. The calorimeter design is based on a copper heat exchanger with integrated water lines for the heat extraction, mounted around the source. A high precision measurement is possible thanks to an elaborate thermal insulation. In this talk, the design of the calorimeter is reviewed and results of calibration measurements are presented. The thermal insulation of the system was examined and heat losses were quantified. The methods to reconstruct the source power and the decay rate from measurements are described.

  1. Genome wide binding (ChIP-Seq of murine Bapx1 and Sox9 proteins in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Sumantra Chatterjee

    2016-12-01

    Full Text Available This work pertains to GEO submission GSE36672, in vivo and in vitro genome wide binding (ChIP-Seq of Bapx1/Nkx3.2 and Sox9 proteins. We have previously shown that data from a genome wide binding assay combined with transcriptional profiling is an insightful means to divulge the mechanisms directing cell type specification and the generation of tissues and subsequent organs [1]. Our earlier work identified the role of the DNA-binding homeodomain containing protein Bapx1/Nkx3.2 in midgestation murine embryos. Microarray analysis of EGFP-tagged cells (both wildtype and null was integrated using ChIP-Seq analysis of Bapx1/Nkx3.2 and Sox9 DNA-binding proteins in living tissue.

  2. Observation of Cleft Palate in an Individual with SOX11 Mutation: Indication of a Role for SOX11 in Human Palatogenesis.

    Science.gov (United States)

    Khan, Umair; Study, Ddd; Baker, Eleanor; Clayton-Smith, Jill

    2018-03-01

    Point mutations and deletions within the SOX11 gene have recently been described in individuals with a rare variant of Coffin-Siris syndrome, OMIM 615866, an intellectual disability syndrome with associated features of nail hypoplasia, microcephaly, and characteristic facial features including a wide mouth and prominent lips. We describe a further patient with a mutation in SOX11 and phenotype resembling mild Coffin-Siris syndrome. This boy had a cleft palate, a feature not previously seen in other patients with SOX11 mutations. We discuss This adds to the current evidence that SOX11 is a gene involved in palatogenesis.

  3. Unravelling pathways downstream Sox6 induction in K562 erythroid cells by proteomic analysis

    KAUST Repository

    Barbarani, Gloria

    2017-10-20

    The Sox6 transcription factor is crucial for terminal maturation of definitive red blood cells. Sox6-null mouse fetuses present misshapen and nucleated erythrocytes, due to impaired actin assembly and cytoskeleton stability. These defects are accompanied with a reduced survival of Sox6-/- red blood cells, resulting in a compensated anemia. Sox6-overexpression in K562 cells and in human primary ex vivo erythroid cultures enhances erythroid differentiation and leads to hemoglobinization, the hallmark of erythroid maturation. To obtain an overview on processes downstream to Sox6 expression, we performed a differential proteomic analysis on human erythroid K562 cells overexpressing Sox6. Sox6-overexpression induces dysregulation of 64 proteins, involved in cytoskeleton remodeling and in protein synthesis, folding and trafficking, key processes for erythroid maturation. Moreover, 43 out of 64 genes encoding for differentially expressed proteins contain within their proximal regulatory regions sites that are bound by SOX6 according to ENCODE ChIP-seq datasets and are possible direct SOX6 targets. SAR1B, one of the most induced proteins upon Sox6 overexpression, shares a conserved regulatory module, composed by a double SOX6 binding site and a GATA1 consensus, with the adjacent SEC24 A gene. Since both genes encode for COPII components, this element could concur to the coordinated expression of these proteins during erythropoiesis.

  4. Patients with Multiple Myeloma Develop SOX2-Specific Autoantibodies after Allogeneic Stem Cell Transplantation

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    Sebastian Kobold

    2011-01-01

    Full Text Available The occurrence of SOX2-specific autoantibodies seems to be associated with an improved prognosis in patients with monoclonal gammopathy of undetermined significance (MGUS. However, it is unclear if SOX2-specific antibodies also develop in established multiple myeloma (MM. Screening 1094 peripheral blood (PB sera from 196 MM patients and 100 PB sera from healthy donors, we detected SOX2-specific autoantibodies in 7.7% and 2.0% of patients and donors, respectively. We identified SOX2211–230 as an immunodominant antibody-epitope within the full protein sequence. SOX2 antigen was expressed in most healthy tissues and its expression did not correlate with the number of BM-resident plasma cells. Accordingly, anti-SOX2 immunity was not related to SOX2 expression levels or tumor burden in the patients’ BM. The only clinical factor predicting the development of anti-SOX2 immunity was application of allogeneic stem cell transplantation (alloSCT. Anti-SOX2 antibodies occurred more frequently in patients who had received alloSCT (n=74. Moreover, most SOX2-seropositive patients had only developed antibodies after alloSCT. This finding indicates that alloSCT is able to break tolerance towards this commonly expressed antigen. The questions whether SOX2-specific autoantibodies merely represent an epiphenomenon, are related to graft-versus-host effects or participate in the immune control of myeloma needs to be answered in prospective studies.

  5. Identification of SOX3 as an XX male sex reversal gene in mice and humans.

    Science.gov (United States)

    Sutton, Edwina; Hughes, James; White, Stefan; Sekido, Ryohei; Tan, Jacqueline; Arboleda, Valerie; Rogers, Nicholas; Knower, Kevin; Rowley, Lynn; Eyre, Helen; Rizzoti, Karine; McAninch, Dale; Goncalves, Joao; Slee, Jennie; Turbitt, Erin; Bruno, Damien; Bengtsson, Henrik; Harley, Vincent; Vilain, Eric; Sinclair, Andrew; Lovell-Badge, Robin; Thomas, Paul

    2011-01-01

    Sex in mammals is genetically determined and is defined at the cellular level by sex chromosome complement (XY males and XX females). The Y chromosome-linked gene sex-determining region Y (SRY) is believed to be the master initiator of male sex determination in almost all eutherian and metatherian mammals, functioning to upregulate expression of its direct target gene Sry-related HMG box-containing gene 9 (SOX9). Data suggest that SRY evolved from SOX3, although there is no direct functional evidence to support this hypothesis. Indeed, loss-of-function mutations in SOX3 do not affect sex determination in mice or humans. To further investigate Sox3 function in vivo, we generated transgenic mice overexpressing Sox3. Here, we report that in one of these transgenic lines, Sox3 was ectopically expressed in the bipotential gonad and that this led to frequent complete XX male sex reversal. Further analysis indicated that Sox3 induced testis differentiation in this particular line of mice by upregulating expression of Sox9 via a similar mechanism to Sry. Importantly, we also identified genomic rearrangements within the SOX3 regulatory region in three patients with XX male sex reversal. Together, these data suggest that SOX3 and SRY are functionally interchangeable in sex determination and support the notion that SRY evolved from SOX3 via a regulatory mutation that led to its de novo expression in the early gonad.

  6. Identification of SOX3 as an XX male sex reversal gene in mice and humans

    Science.gov (United States)

    Sutton, Edwina; Hughes, James; White, Stefan; Sekido, Ryohei; Tan, Jacqueline; Arboleda, Valerie; Rogers, Nicholas; Knower, Kevin; Rowley, Lynn; Eyre, Helen; Rizzoti, Karine; McAninch, Dale; Goncalves, Joao; Slee, Jennie; Turbitt, Erin; Bruno, Damien; Bengtsson, Henrik; Harley, Vincent; Vilain, Eric; Sinclair, Andrew; Lovell-Badge, Robin; Thomas, Paul

    2010-01-01

    Sex in mammals is genetically determined and is defined at the cellular level by sex chromosome complement (XY males and XX females). The Y chromosome–linked gene sex-determining region Y (SRY) is believed to be the master initiator of male sex determination in almost all eutherian and metatherian mammals, functioning to upregulate expression of its direct target gene Sry-related HMG box–containing gene 9 (SOX9). Data suggest that SRY evolved from SOX3, although there is no direct functional evidence to support this hypothesis. Indeed, loss-of-function mutations in SOX3 do not affect sex determination in mice or humans. To further investigate Sox3 function in vivo, we generated transgenic mice overexpressing Sox3. Here, we report that in one of these transgenic lines, Sox3 was ectopically expressed in the bipotential gonad and that this led to frequent complete XX male sex reversal. Further analysis indicated that Sox3 induced testis differentiation in this particular line of mice by upregulating expression of Sox9 via a similar mechanism to Sry. Importantly, we also identified genomic rearrangements within the SOX3 regulatory region in three patients with XX male sex reversal. Together, these data suggest that SOX3 and SRY are functionally interchangeable in sex determination and support the notion that SRY evolved from SOX3 via a regulatory mutation that led to its de novo expression in the early gonad. PMID:21183788

  7. SOX17 Regulates Cholangiocyte Differentiation and Acts as a Tumor Suppressor in Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Merino-Azpitarte, M; Lozano, E; Perugorria, M J

    2017-01-01

    /function was evaluated along the differentiation of human induced pluripotent stem cells (iPSC) into cholangiocytes, in the dedifferentiation process of normal human cholangiocytes (NHC) in culture and in cholangiocarcinogenesis. Lentiviruses for SOX17 overexpression or knock-down were used. Gene expression and DNA......BACKGROUND & AIMS: Cholangiocarcinoma (CCA) is a biliary malignancy linked to genetic and epigenetic abnormalities, such as hypermethylation of SOX17 promoter. Here, the role of SOX17 in cholangiocyte differentiation and cholangiocarcinogenesis was studied. METHODS: SOX17 expression...... methylation profiling were performed. RESULTS: SOX17 expression is induced in the last stage of cholangiocyte differentiation from iPSC and regulates the acquisition of biliary markers. SOX17 becomes downregulated in NHC undergoing dedifferentiation; experimental SOX17 knock-down in differentiated NHC...

  8. Inhibition of DNA binding of Sox2 by the SUMO conjugation

    International Nuclear Information System (INIS)

    Tsuruzoe, Shu; Ishihara, Ko; Uchimura, Yasuhiro; Watanabe, Sugiko; Sekita, Yoko; Aoto, Takahiro; Saitoh, Hisato; Yuasa, Yasuhito; Niwa, Hitoshi; Kawasuji, Michio; Baba, Hideo; Nakao, Mitsuyoshi

    2006-01-01

    Sox2 is a member of the high mobility group (HMG) domain DNA-binding proteins for transcriptional control and chromatin architecture. The HMG domain of Sox2 binds the DNA to facilitate transactivation by the cooperative transcription factors such as Oct3/4. We report that mouse Sox2 is modified by SUMO at lysine 247. Substitution of the target lysine to arginine lost the sumoylation but little affected transcriptional potential or nuclear localization of Sox2. By contrast with the unmodified form, Sox2 fused to SUMO-1 did not augment transcription via the Fgf4 enhancer in the presence of Oct3/4. Further, SUMO-1-conjugated Sox2 at the lysine 247 or at the carboxyl terminus reduced the binding to the Fgf4 enhancer. These indicate that Sox2 sumoylation negatively regulates its transcriptional role through impairing the DNA binding

  9. Conversion of Sox17 into a pluripotency reprogramming factor by reengineering its association with Oct4 on DNA.

    Science.gov (United States)

    Jauch, Ralf; Aksoy, Irene; Hutchins, Andrew Paul; Ng, Calista Keow Leng; Tian, Xian Feng; Chen, Jiaxuan; Palasingam, Paaventhan; Robson, Paul; Stanton, Lawrence W; Kolatkar, Prasanna R

    2011-06-01

    Very few proteins are capable to induce pluripotent stem (iPS) cells and their biochemical uniqueness remains unexplained. For example, Sox2 cooperates with other transcription factors to generate iPS cells, but Sox17, despite binding to similar DNA sequences, cannot. Here, we show that Sox2 and Sox17 exhibit inverse heterodimerization preferences with Oct4 on the canonical versus a newly identified compressed sox/oct motif. We can swap the cooperativity profiles of Sox2 and Sox17 by exchanging single amino acids at the Oct4 interaction interface resulting in Sox2KE and Sox17EK proteins. The reengineered Sox17EK now promotes reprogramming of somatic cells to iPS, whereas Sox2KE has lost this potential. Consistently, when Sox2KE is overexpressed in embryonic stem cells it forces endoderm differentiation similar to wild-type Sox17. Together, we demonstrate that strategic point mutations that facilitate Sox/Oct4 dimer formation on variant DNA motifs lead to a dramatic swap of the bioactivities of Sox2 and Sox17. Copyright © 2011 AlphaMed Press.

  10. Effects of SOX2 on Proliferation, Migration and Adhesion of Human Dental Pulp Stem Cells.

    Directory of Open Access Journals (Sweden)

    Pengfei Liu

    Full Text Available As a key factor for cell pluripotent and self-renewing phenotypes, SOX2 has attracted scientists' attention gradually in recent years. However, its exact effects in dental pulp stem cells (DPSCs are still unclear. In this study, we mainly investigated whether SOX2 could affect some biological functions of DPSCs. DPSCs were isolated from the dental pulp of human impacted third molar. SOX2 overexpressing DPSCs (DPSCs-SOX2 were established through retroviral infection. The effect of SOX2 on cell proliferation, migration and adhesion ability was evaluated with CCK-8, trans-well system and fibronectin-induced cell attachment experiment respectively. Whole genome expression of DPSCs-SOX2 was analyzed with RNA microarray. Furthermore, a rescue experiment was performed with SOX2-siRNA in DPSC-SOX2 to confirm the effect of SOX2 overexpression in DPSCs. We found that SOX2 overexpression could result in the enhancement of cell proliferation, migration, and adhesion in DPSCs obviously. RNA microarray analysis indicated that some key genes in the signal pathways associated with cell cycle, migration and adhesion were upregulated in different degree, and the results were further confirmed with qPCR and western-blot. Finally, DPSC-SOX2 transfected with SOX2-siRNA showed a decrease of cell proliferation, migration and adhesion ability, which further confirmed the biological effect of SOX2 in human DPSCs. This study indicated that SOX2 could improve the cell proliferation, migration and adhesion ability of DPSCs through regulating gene expression about cell cycle, migration and adhesion, and provided a novel strategy to develop seed cells with strong proliferation, migration and adhesion ability for tissue engineering.

  11. Effects of SOX2 on Proliferation, Migration and Adhesion of Human Dental Pulp Stem Cells.

    Science.gov (United States)

    Liu, Pengfei; Cai, Jinglei; Dong, Delu; Chen, Yaoyu; Liu, Xiaobo; Wang, Yi; Zhou, Yulai

    2015-01-01

    As a key factor for cell pluripotent and self-renewing phenotypes, SOX2 has attracted scientists' attention gradually in recent years. However, its exact effects in dental pulp stem cells (DPSCs) are still unclear. In this study, we mainly investigated whether SOX2 could affect some biological functions of DPSCs. DPSCs were isolated from the dental pulp of human impacted third molar. SOX2 overexpressing DPSCs (DPSCs-SOX2) were established through retroviral infection. The effect of SOX2 on cell proliferation, migration and adhesion ability was evaluated with CCK-8, trans-well system and fibronectin-induced cell attachment experiment respectively. Whole genome expression of DPSCs-SOX2 was analyzed with RNA microarray. Furthermore, a rescue experiment was performed with SOX2-siRNA in DPSC-SOX2 to confirm the effect of SOX2 overexpression in DPSCs. We found that SOX2 overexpression could result in the enhancement of cell proliferation, migration, and adhesion in DPSCs obviously. RNA microarray analysis indicated that some key genes in the signal pathways associated with cell cycle, migration and adhesion were upregulated in different degree, and the results were further confirmed with qPCR and western-blot. Finally, DPSC-SOX2 transfected with SOX2-siRNA showed a decrease of cell proliferation, migration and adhesion ability, which further confirmed the biological effect of SOX2 in human DPSCs. This study indicated that SOX2 could improve the cell proliferation, migration and adhesion ability of DPSCs through regulating gene expression about cell cycle, migration and adhesion, and provided a novel strategy to develop seed cells with strong proliferation, migration and adhesion ability for tissue engineering.

  12. Genetic and epigenetic modifications of Sox2 contribute to the invasive phenotype of malignant gliomas.

    Directory of Open Access Journals (Sweden)

    Marta M Alonso

    Full Text Available We undertook this study to understand how the transcription factor Sox2 contributes to the malignant phenotype of glioblastoma multiforme (GBM, the most aggressive primary brain tumor. We initially looked for unbalanced genomic rearrangements in the Sox2 locus in 42 GBM samples and found that Sox2 was amplified in 11.5% and overexpressed in all the samples. These results prompted us to further investigate the mechanisms involved in Sox2 overexpression in GBM. We analyzed the methylation status of the Sox2 promoter because high CpG density promoters are associated with key developmental genes. The Sox2 promoter presented a CpG island that was hypomethylated in all the patient samples when compared to normal cell lines. Treatment of Sox2-negative glioma cell lines with 5-azacitidine resulted in the re-expression of Sox2 and in a change in the methylation status of the Sox2 promoter. We further confirmed these results by analyzing data from GBM cases generated by The Cancer Genome Atlas project. We observed Sox2 overexpression (86%; N = 414, Sox2 gene amplification (8.5%; N = 492, and Sox 2 promoter hypomethylation (100%; N = 258, suggesting the relevance of this factor in the malignant phenotype of GBMs. To further explore the role of Sox2, we performed in vitro analysis with brain tumor stem cells (BTSCs and established glioma cell lines. Downmodulation of Sox2 in BTSCs resulted in the loss of their self-renewal properties. Surprisingly, ectopic expression of Sox2 in established glioma cells was not sufficient to support self-renewal, suggesting that additional factors are required. Furthermore, we observed that ectopic Sox2 expression was sufficient to induce invasion and migration of glioma cells, and knockdown experiments demonstrated that Sox2 was essential for maintaining these properties. Altogether, our data underscore the importance of a pleiotropic role of Sox2 and suggest that it could be used as a therapeutic target in GBM.

  13. Massively parallel signature sequencing and bioinformatics analysis identifies up-regulation of TGFBI and SOX4 in human glioblastoma.

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    Biaoyang Lin

    Full Text Available BACKGROUND: A comprehensive network-based understanding of molecular pathways abnormally altered in glioblastoma multiforme (GBM is essential for developing effective therapeutic approaches for this deadly disease. METHODOLOGY/PRINCIPAL FINDINGS: Applying a next generation sequencing technology, massively parallel signature sequencing (MPSS, we identified a total of 4535 genes that are differentially expressed between normal brain and GBM tissue. The expression changes of three up-regulated genes, CHI3L1, CHI3L2, and FOXM1, and two down-regulated genes, neurogranin and L1CAM, were confirmed by quantitative PCR. Pathway analysis revealed that TGF- beta pathway related genes were significantly up-regulated in GBM tumor samples. An integrative pathway analysis of the TGF beta signaling network identified two alternative TGF-beta signaling pathways mediated by SOX4 (sex determining region Y-box 4 and TGFBI (Transforming growth factor beta induced. Quantitative RT-PCR and immunohistochemistry staining demonstrated that SOX4 and TGFBI expression is elevated in GBM tissues compared with normal brain tissues at both the RNA and protein levels. In vitro functional studies confirmed that TGFBI and SOX4 expression is increased by TGF-beta stimulation and decreased by a specific inhibitor of TGF-beta receptor 1 kinase. CONCLUSIONS/SIGNIFICANCE: Our MPSS database for GBM and normal brain tissues provides a useful resource for the scientific community. The identification of non-SMAD mediated TGF-beta signaling pathways acting through SOX4 and TGFBI (GENE ID:7045 in GBM indicates that these alternative pathways should be considered, in addition to the canonical SMAD mediated pathway, in the development of new therapeutic strategies targeting TGF-beta signaling in GBM. Finally, the construction of an extended TGF-beta signaling network with overlaid gene expression changes between GBM and normal brain extends our understanding of the biology of GBM.

  14. Sox5 induces epithelial to mesenchymal transition by transactivation of Twist1

    International Nuclear Information System (INIS)

    Pei, Xin-Hong; Lv, Xin-Quan; Li, Hui-Xiang

    2014-01-01

    Highlights: • Depletion of Sox5 inhibits breast cancer proliferation, migration, and invasion. • Sox5 transactivates Twist1 expression. • Sox5 induces epithelial to mesenchymal transition through transactivation of Twist1 expression. - Abstract: The epithelial to mesenchymal transition (EMT), a highly conserved cellular program, plays an important role in normal embryogenesis and cancer metastasis. Twist1, a master regulator of embryonic morphogenesis, is overexpressed in breast cancer and contributes to metastasis by promoting EMT. In exploring the mechanism underlying the increased Twist1 in breast cancer cells, we found that the transcription factor SRY (sex-determining region Y)-box 5(Sox5) is up-regulation in breast cancer cells and depletion of Sox5 inhibits breast cancer cell proliferation, migration, and invasion. Furthermore, depletion of Sox5 in breast cancer cells caused a dramatic decrease in Twist1 and chromosome immunoprecipitation assay showed that Sox5 can bind directly to the Twist1 promoter, suggesting that Sox5 transactivates Twist1 expression. We further demonstrated that knockdown of Sox5 up-regulated epithelial phenotype cell biomarker (E-cadherin) and down-regulated mesenchymal phenotype cell biomarkers (N-cadherin, Vimentin, and Fibronectin 1), resulting in suppression of EMT. Our study suggests that Sox5 transactivates Twist1 expression and plays an important role in the regulation of breast cancer progression

  15. Sox4 Links Tumor Suppression to Accelerated Aging in Mice by Modulating Stem Cell Activation

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    Miguel Foronda

    2014-07-01

    Full Text Available Sox4 expression is restricted in mammals to embryonic structures and some adult tissues, such as lymphoid organs, pancreas, intestine, and skin. During embryogenesis, Sox4 regulates mesenchymal and neural progenitor survival, as well as lymphocyte and myeloid differentiation, and contributes to pancreas, bone, and heart development. Aberrant Sox4 expression is linked to malignant transformation and metastasis in several types of cancer. To understand the role of Sox4 in the adult organism, we first generated mice with reduced whole-body Sox4 expression. These mice display accelerated aging and reduced cancer incidence. To specifically address a role for Sox4 in adult stem cells, we conditionally deleted Sox4 (Sox4cKO in stratified epithelia. Sox4cKO mice show increased skin stem cell quiescence and resistance to chemical carcinogenesis concomitantly with downregulation of cell cycle, DNA repair, and activated hair follicle stem cell pathways. Altogether, these findings highlight the importance of Sox4 in regulating adult tissue homeostasis and cancer.

  16. Parent-of-origin effects in SOX2 anophthalmia syndrome.

    Science.gov (United States)

    Osborne, Robert J; Kurinczuk, Jennifer J; Ragge, Nicola K

    2011-01-01

    Sex determining region Y (SRY)-box 2 (SOX2) anophthalmia syndrome is an autosomal dominant disorder manifesting as severe developmental eye malformations associated with brain, esophageal, genital, and kidney abnormalities. The syndrome is usually caused by de novo mutations or deletions in the transcription factor SOX2. To investigate any potential parental susceptibility factors, we set out to determine the parent of origin of the mutations or deletions, and following this, to determine if birth order or parental age were significant factors, as well as whether mutation susceptibility was related to any sequence variants in cis with the mutant allele. We analyzed 23 cases of de novo disease to determine the parental origin of SOX2 mutations and deletions using informative single nucleotide polymorphisms and a molecular haplotyping approach. We examined parental ages for SOX2 mutation and deletion cases, compared these with the general population, and adjusted for birth order. Although the majority of subjects had mutations or deletions that arose in the paternal germline (5/7 mutation and 5/8 deletion cases), there was no significant paternal bias for new mutations (binomial test, p=0.16) or deletions (binomial test, p=0.22). For both mutation and deletion cases, there was no significant association between any single nucleotide polymorphism allele and the mutant chromosome (p>0.05). Parents of the subjects with mutations were on average older at the birth of the affected child than the general population by 3.8 years (p=0.05) for mothers and 3.3 years (p=0.66) for fathers. Parents of the subjects with deletions were on average younger than the general population by 3.0 years (p=0.17) for mothers and 2.1 years (p=0.19) for fathers. Combining these data, the difference in pattern of parental age between the subjects with deletions and mutations was evident, with a difference of 6.5 years for mothers (p=0.05) and 5.0 years for fathers (p=0.22), with the mothers and

  17. [Molecular pathogenesis of Waardenburg syndrome type II resulting from SOX10 gene mutation].

    Science.gov (United States)

    Zhang, Hua; Chen, Hongsheng; Feng, Yong; Qian, Minfei; Li, Jiping; Liu, Jun; Zhang, Chun

    2016-08-01

    To explore the molecular mechanism of Waardenburg syndrome type II (WS2) resulting from SOX10 gene mutation E248fs through in vitro experiment. 293T cells were transiently transfected with wild type (WT) SOX10 and mutant type (MT) E248fs plasmids. The regulatory effect of WT/MT SOX10 on the transcriptional activity of MITF gene and influence of E248fs on WT SOX10 function were determined with a luciferase activity assay. The DNA binding capacity of the WT/MT SOX10 with the promoter of the MITF gene was determined with a biotinylated double-stranded oligonucleotide probe containing the SOX10 binding sequence cattgtc to precipitate MITF and E248fs, respectively. The stability of SOX10 and E248fs were also analyzed. As a loss-of-function mutation, the E248fs mutant failed to transactivate the MITF promoter as compared with the WT SOX10 (P<0.01), which also showed a dominant-negative effect on WT SOX10. The WT SOX10 and E248fs mutant were also able to bind specifically to the cattgtc motif in the MITF promoter, whereas E248fs had degraded faster than WT SOX10. Despite the fact that the E248fs has a dominant-negative effect on SOX10, its reduced stability may down-regulate the transcription of MITF and decrease the synthesis of melanin, which may result in haploinsufficiency of SOX10 protein and cause the milder WS2 phenotype.

  18. Sox2 promotes survival of satellite glial cells in vitro

    International Nuclear Information System (INIS)

    Koike, Taro; Wakabayashi, Taketoshi; Mori, Tetsuji; Hirahara, Yukie; Yamada, Hisao

    2015-01-01

    Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors. - Highlights: • We established satellite glial cell culture system. • Function of Sox2 in satellite glial cell was examined using siRNA. • Sox2 knockdown downregulated expression level of ErbB2 and ErbB3 mRNA. • Sox2 knockdown increased apoptotic satellite glial cell. • Sox2 promotes satellite glial cell survival through ErbB signaling

  19. Sox2 Is an Androgen Receptor-Repressed Gene That Promotes Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Kregel, Steven; Kiriluk, Kyle J.; Rosen, Alex M.; Cai, Yi; Reyes, Edwin E.; Otto, Kristen B.; Tom, Westin; Paner, Gladell P.; Szmulewitz, Russell Z.; Vander Griend, Donald J.

    2013-01-01

    Despite advances in detection and therapy, castration-resistant prostate cancer continues to be a major clinical problem. The aberrant activity of stem cell pathways, and their regulation by the Androgen Receptor (AR), has the potential to provide insight into novel mechanisms and pathways to prevent and treat advanced, castrate-resistant prostate cancers. To this end, we investigated the role of the embryonic stem cell regulator Sox2 [SRY (sex determining region Y)-box 2] in normal and malignant prostate epithelial cells. In the normal prostate, Sox2 is expressed in a portion of basal epithelial cells. Prostate tumors were either Sox2-positive or Sox2-negative, with the percentage of Sox2-positive tumors increasing with Gleason Score and metastases. In the castration-resistant prostate cancer cell line CWR-R1, endogenous expression of Sox2 was repressed by AR signaling, and AR chromatin-IP shows that AR binds the enhancer element within the Sox2 promoter. Likewise, in normal prostate epithelial cells and human embryonic stem cells, increased AR signaling also decreases Sox2 expression. Resistance to the anti-androgen MDV3100 results in a marked increase in Sox2 expression within three prostate cancer cell lines, and in the castration-sensitive LAPC-4 prostate cancer cell line ectopic expression of Sox2 was sufficient to promote castration-resistant tumor formation. Loss of Sox2 expression in the castration-resistant CWR-R1 prostate cancer cell line inhibited cell growth. Up-regulation of Sox2 was not associated with increased CD133 expression but was associated with increased FGF5 (Fibroblast Growth Factor 5) expression. These data propose a model of elevated Sox2 expression due to loss of AR-mediated repression during castration, and consequent castration-resistance via mechanisms not involving induction of canonical embryonic stem cell pathways. PMID:23326489

  20. Sox2 promotes survival of satellite glial cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Koike, Taro, E-mail: koiket@hirakata.kmu.ac.jp; Wakabayashi, Taketoshi; Mori, Tetsuji; Hirahara, Yukie; Yamada, Hisao

    2015-08-14

    Sox2 is a transcriptional factor expressed in neural stem cells. It is known that Sox2 regulates cell differentiation, proliferation and survival of the neural stem cells. Our previous study showed that Sox2 is expressed in all satellite glial cells of the adult rat dorsal root ganglion. In this study, to examine the role of Sox2 in satellite glial cells, we establish a satellite glial cell-enriched culture system. Our culture method succeeded in harvesting satellite glial cells with the somata of neurons in the dorsal root ganglion. Using this culture system, Sox2 was downregulated by siRNA against Sox2. The knockdown of Sox2 downregulated ErbB2 and ErbB3 mRNA at 2 and 4 days after siRNA treatment. MAPK phosphorylation, downstream of ErbB, was also inhibited by Sox2 knockdown. Because ErbB2 and ErbB3 are receptors that support the survival of glial cells in the peripheral nervous system, apoptotic cells were also counted. TUNEL-positive cells increased at 5 days after siRNA treatment. These results suggest that Sox2 promotes satellite glial cell survival through the MAPK pathway via ErbB receptors. - Highlights: • We established satellite glial cell culture system. • Function of Sox2 in satellite glial cell was examined using siRNA. • Sox2 knockdown downregulated expression level of ErbB2 and ErbB3 mRNA. • Sox2 knockdown increased apoptotic satellite glial cell. • Sox2 promotes satellite glial cell survival through ErbB signaling.

  1. Differential expression of ID4 and its association with TP53 mutation, SOX2, SOX4 and OCT-4 expression levels.

    Directory of Open Access Journals (Sweden)

    Thais Fernanda de Almeida Galatro

    Full Text Available Inhibitor of DNA Binding 4 (ID4 is a member of the helix-loop-helix ID family of transcription factors, mostly present in the central nervous system during embryonic development, that has been associated with TP53 mutation and activation of SOX2. Along with other transcription factors, ID4 has been implicated in the tumorigenic process of astrocytomas, contributing to cell dedifferentiation, proliferation and chemoresistance. In this study, we aimed to characterize the ID4 expression pattern in human diffusely infiltrative astrocytomas of World Health Organization (WHO grades II to IV of malignancy (AGII-AGIV; to correlate its expression level to that of SOX2, SOX4, OCT-4 and NANOG, along with TP53 mutational status; and to correlate the results with the clinical end-point of overall survival among glioblastoma patients. Quantitative real time PCR (qRT-PCR was performed in 130 samples of astrocytomas for relative expression, showing up-regulation of all transcription factors in tumor cases. Positive correlation was found when comparing ID4 relative expression of infiltrative astrocytomas with SOX2 (r = 0.50; p<0.005, SOX4 (r = 0.43; p<0.005 and OCT-4 (r = 0.39; p<0.05. The results from TP53 coding exon analysis allowed comparisons between wild-type and mutated status only in AGII cases, demonstrating significantly higher levels of ID4, SOX2 and SOX4 in mutated cases (p<0.05. This pattern was maintained in secondary GBM and further confirmed by immunohistochemistry, suggesting a role for ID4, SOX2 and SOX4 in early astrocytoma tumorigenesis. Combined hyperexpression of ID4, SOX4 and OCT-4 conferred a much lower (6 months median survival than did hypoexpression (18 months. Because both ID4 alone and a complex of SOX4 and OCT-4 activate SOX2 transcription, it is possible that multiple activation of SOX2 impair the prognosis of GBM patients. These observational results of associated expression of ID4 with SOX4 and OCT-4 may be used as a

  2. Na2SO4-based solid electrolytes for SOx sensors

    DEFF Research Database (Denmark)

    Rao, N.; Schoonman, J.; Toft Sørensen, O.

    1992-01-01

    on the phases present and the structure of the specimens. From a point of view of practical application as SOx sensor material, the Na2SO4 + 5 mol% Y2(SO4)3 + Na2WO4 and Na2SO4+ 4 mol% La2(SO4)3 + Na2WO4 materials are better than undoped Na2SO4 because of their higher conductivity, and absence of a phase...

  3. Ion traps fabricated in a CMOS foundry

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, K. K.; Ram, R. J. [Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States); Eltony, A. M.; Chuang, I. L. [Center for Ultracold Atoms, Research Laboratory of Electronics and Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States); Bruzewicz, C. D.; Sage, J. M., E-mail: jsage@ll.mit.edu; Chiaverini, J., E-mail: john.chiaverini@ll.mit.edu [Lincoln Laboratory, Massachusetts Institute of Technology, Lexington, Massachusetts 02420 (United States)

    2014-07-28

    We demonstrate trapping in a surface-electrode ion trap fabricated in a 90-nm CMOS (complementary metal-oxide-semiconductor) foundry process utilizing the top metal layer of the process for the trap electrodes. The process includes doped active regions and metal interconnect layers, allowing for co-fabrication of standard CMOS circuitry as well as devices for optical control and measurement. With one of the interconnect layers defining a ground plane between the trap electrode layer and the p-type doped silicon substrate, ion loading is robust and trapping is stable. We measure a motional heating rate comparable to those seen in surface-electrode traps of similar size. This demonstration of scalable quantum computing hardware utilizing a commercial CMOS process opens the door to integration and co-fabrication of electronics and photonics for large-scale quantum processing in trapped-ion arrays.

  4. Sox17 regulates liver lipid metabolism and adaptation to fasting.

    Directory of Open Access Journals (Sweden)

    Samuel Rommelaere

    Full Text Available Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting.

  5. Embryonic transcription factor SOX9 drives breast cancer endocrine resistance.

    Science.gov (United States)

    Jeselsohn, Rinath; Cornwell, MacIntosh; Pun, Matthew; Buchwalter, Gilles; Nguyen, Mai; Bango, Clyde; Huang, Ying; Kuang, Yanan; Paweletz, Cloud; Fu, Xiaoyong; Nardone, Agostina; De Angelis, Carmine; Detre, Simone; Dodson, Andrew; Mohammed, Hisham; Carroll, Jason S; Bowden, Michaela; Rao, Prakash; Long, Henry W; Li, Fugen; Dowsett, Mitchell; Schiff, Rachel; Brown, Myles

    2017-05-30

    The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases. Through the analysis of the ER cistrome in tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2-ER complex that stimulates the transcription of a set of genes, including most notably the stem cell factor SOX9, that promote proliferation and a metastatic phenotype. We show that up-regulation of SOX9 is sufficient to cause relative endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with tamoxifen resistance was validated in a unique set of clinical samples supporting the need for the development of improved ER antagonists.

  6. Sediment Trapping in Estuaries

    Science.gov (United States)

    Burchard, Hans; Schuttelaars, Henk M.; Ralston, David K.

    2018-01-01

    Estuarine turbidity maxima (ETMs) are generated by a large suite of hydrodynamic and sediment dynamic processes, leading to longitudinal convergence of cross-sectionally integrated and tidally averaged transport of cohesive and noncohesive suspended particulate matter (SPM). The relative importance of these processes for SPM trapping varies substantially among estuaries depending on topography, fluvial and tidal forcing, and SPM composition. The high-frequency dynamics of ETMs are constrained by interactions with the low-frequency dynamics of the bottom pool of easily erodible sediments. Here, we use a transport decomposition to present processes that lead to convergent SPM transport, and review trapping mechanisms that lead to ETMs at the landward limit of the salt intrusion, in the freshwater zone, at topographic transitions, and by lateral processes within the cross section. We use model simulations of example estuaries to demonstrate the complex concurrence of ETM formation mechanisms. We also discuss how changes in SPM trapping mechanisms, often caused by direct human interference, can lead to the generation of hyperturbid estuaries.

  7. Globalisation Trapped

    Directory of Open Access Journals (Sweden)

    João Caraça

    2017-05-01

    Full Text Available The promise of making society progress through the direct applications of science was finally fulfilled in the mid-20th century. Science progressed immensely, propelled by the effects of the two world wars. The first science-based technologies saw the daylight during the 1940s and their transformative power was such that neither the military, nor subsequently the markets, allowed science to return intact to its curiosity-driven nest. Technoscience was born then and (being progressively pulled away from curiosity-driven science was able to grow enormously, erecting a formidable structure of networks of institutions that impacted decisively on the economy. It is a paradox, or maybe a trap, that the fulfillment of science’s solemn promise of ‘transforming nature’ means seeing ourselves and our Western societies entangled in crises after crises with no clear outcome in view. A redistribution of geopolitical power is under way, along with the deployment of information and communication technologies, forcing dominant structures to oscillate, as knowledge about organization and methods, marketing, design, and software begins to challenge the role of technoscience as the main vector of economic growth and wealth accumulation. What ought to be done?

  8. Long noncoding RNA lnc-sox5 modulates CRC tumorigenesis by unbalancing tumor microenvironment.

    Science.gov (United States)

    Wu, Kaiming; Zhao, Zhenxian; Liu, Kuanzhi; Zhang, Jian; Li, Guanghua; Wang, Liang

    2017-07-03

    Long non-coding RNAs (LncRNAs) have been recently regarded as systemic regulators in multiple biologic processes including tumorigenesis. In this study, we observed the expression of lncRNA lnc-sox5 was significantly increased in colorectal cancer (CRC). Despite the CRC cell growth, cell cycle and cell apoptosis was not affected by lnc-sox5 knock-down, lnc-sox5 knock-down suppressed CRC cell migration and invasion. In addition, xenograft animal model suggested that lnc-sox5 knock-down significantly suppressed the CRC tumorigenesis. Our results also showed that the expression of indoleamine 2,3-dioxygenase 1 (IDO1) was significantly reduced by lnc-sox5 knock-down and therefore modulated the infiltration and cytotoxicity of CD3 + CD8 + T cells. Taken together, these results suggested that lnc-sox5 unbalances tumor microenvironment to regulate colorectal cancer progression.

  9. An evolutionarily conserved intronic region controls the spatiotemporal expression of the transcription factor Sox10

    Directory of Open Access Journals (Sweden)

    Pavan William J

    2008-10-01

    Full Text Available Abstract Background A major challenge lies in understanding the complexities of gene regulation. Mutation of the transcription factor SOX10 is associated with several human diseases. The disease phenotypes reflect the function of SOX10 in diverse tissues including the neural crest, central nervous system and otic vesicle. As expected, the SOX10 expression pattern is complex and highly dynamic, but little is known of the underlying mechanisms regulating its spatiotemporal pattern. SOX10 expression is highly conserved between all vertebrates characterised. Results We have combined in vivo testing of DNA fragments in zebrafish and computational comparative genomics to identify the first regulatory regions of the zebrafish sox10 gene. Both approaches converged on the 3' end of the conserved 1st intron as being critical for spatial patterning of sox10 in the embryo. Importantly, we have defined a minimal region crucial for this function. We show that this region contains numerous binding sites for transcription factors known to be essential in early neural crest induction, including Tcf/Lef, Sox and FoxD3. We show that the identity and relative position of these binding sites are conserved between zebrafish and mammals. A further region, partially required for oligodendrocyte expression, lies in the 5' region of the same intron and contains a putative CSL binding site, consistent with a role for Notch signalling in sox10 regulation. Furthermore, we show that β-catenin, Notch signalling and Sox9 can induce ectopic sox10 expression in early embryos, consistent with regulatory roles predicted from our transgenic and computational results. Conclusion We have thus identified two major sites of sox10 regulation in vertebrates and provided evidence supporting a role for at least three factors in driving sox10 expression in neural crest, otic epithelium and oligodendrocyte domains.

  10. Silencing of the Drosophila ortholog of SOX5 leads to abnormal neuronal development and behavioral impairment.

    Science.gov (United States)

    Li, Airong; Hooli, Basavaraj; Mullin, Kristina; Tate, Rebecca E; Bubnys, Adele; Kirchner, Rory; Chapman, Brad; Hofmann, Oliver; Hide, Winston; Tanzi, Rudolph E

    2017-04-15

    SOX5 encodes a transcription factor that is expressed in multiple tissues including heart, lung and brain. Mutations in SOX5 have been previously found in patients with amyotrophic lateral sclerosis (ALS) and developmental delay, intellectual disability and dysmorphic features. To characterize the neuronal role of SOX5, we silenced the Drosophila ortholog of SOX5, Sox102F, by RNAi in various neuronal subtypes in Drosophila. Silencing of Sox102F led to misorientated and disorganized michrochaetes, neurons with shorter dendritic arborization (DA) and reduced complexity, diminished larval peristaltic contractions, loss of neuromuscular junction bouton structures, impaired olfactory perception, and severe neurodegeneration in brain. Silencing of SOX5 in human SH-SY5Y neuroblastoma cells resulted in a significant repression of WNT signaling activity and altered expression of WNT-related genes. Genetic association and meta-analyses of the results in several large family-based and case-control late-onset familial Alzheimer's disease (LOAD) samples of SOX5 variants revealed several variants that show significant association with AD disease status. In addition, analysis for rare and highly penetrate functional variants revealed four novel variants/mutations in SOX5, which taken together with functional prediction analysis, suggests a strong role of SOX5 causing AD in the carrier families. Collectively, these findings indicate that SOX5 is a novel candidate gene for LOAD with an important role in neuronal function. The genetic findings warrant further studies to identify and characterize SOX5 variants that confer risk for AD, ALS and intellectual disability. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Cryogenic surface ion traps

    International Nuclear Information System (INIS)

    Niedermayr, M.

    2015-01-01

    Microfabricated surface traps are a promising architecture to realize a scalable quantum computer based on trapped ions. In principle, hundreds or thousands of surface traps can be located on a single substrate in order to provide large arrays of interacting ions. To this end, trap designs and fabrication methods are required that provide scalable, stable and reproducible ion traps. This work presents a novel surface-trap design developed for cryogenic applications. Intrinsic silicon is used as the substrate material of the traps. The well-developed microfabrication and structuring methods of silicon are utilized to create simple and reproducible traps. The traps were tested and characterized in a cryogenic setup. Ions could be trapped and their life time and motional heating were investigated. Long ion lifetimes of several hours were observed and the measured heating rates were reproducibly low at around 1 phonon per second at a trap frequency of 1 MHz. (author) [de

  12. XX male sex reversal with genital abnormalities associated with a de novo SOX3 gene duplication.

    Science.gov (United States)

    Moalem, Sharon; Babul-Hirji, Riyana; Stavropolous, Dmitri J; Wherrett, Diane; Bägli, Darius J; Thomas, Paul; Chitayat, David

    2012-07-01

    Differentiation of the bipotential gonad into testis is initiated by the Y chromosome-linked gene SRY (Sex-determining Region Y) through upregulation of its autosomal direct target gene SOX9 (Sry-related HMG box-containing gene 9). Sequence and chromosome homology studies have shown that SRY most probably evolved from SOX3, which in humans is located at Xq27.1. Mutations causing SOX3 loss-of-function do not affect the sex determination in mice or humans. However, transgenic mouse studies have shown that ectopic expression of Sox3 in the bipotential gonad results in upregulation of Sox9, resulting in testicular induction and XX male sex reversal. However, the mechanism by which these rearrangements cause sex reversal and the frequency with which they are associated with disorders of sex development remains unclear. Rearrangements of the SOX3 locus were identified recently in three cases of human XX male sex reversal. We report on a case of XX male sex reversal associated with a novel de novo duplication of the SOX3 gene. These data provide additional evidence that SOX3 gain-of-function in the XX bipotential gonad causes XX male sex reversal and further support the hypothesis that SOX3 is the evolutionary antecedent of SRY. Copyright © 2012 Wiley Periodicals, Inc.

  13. Sox2 marks epithelial competence to generate teeth in mammals and reptiles

    Science.gov (United States)

    Juuri, Emma; Jussila, Maria; Seidel, Kerstin; Holmes, Scott; Wu, Ping; Richman, Joy; Heikinheimo, Kristiina; Chuong, Cheng-Ming; Arnold, Katrin; Hochedlinger, Konrad; Klein, Ophir; Michon, Frederic; Thesleff, Irma

    2013-01-01

    Tooth renewal is initiated from epithelium associated with existing teeth. The development of new teeth requires dental epithelial cells that have competence for tooth formation, but specific marker genes for these cells have not been identified. Here, we analyzed expression patterns of the transcription factor Sox2 in two different modes of successional tooth formation: tooth replacement and serial addition of primary teeth. We observed specific Sox2 expression in the dental lamina that gives rise to successional teeth in mammals with one round of tooth replacement as well as in reptiles with continuous tooth replacement. Sox2 was also expressed in the dental lamina during serial addition of mammalian molars, and genetic lineage tracing indicated that Sox2+ cells of the first molar give rise to the epithelial cell lineages of the second and third molars. Moreover, conditional deletion of Sox2 resulted in hyperplastic epithelium in the forming posterior molars. Our results indicate that the Sox2+ dental epithelium has competence for successional tooth formation and that Sox2 regulates the progenitor state of dental epithelial cells. The findings imply that the function of Sox2 has been conserved during evolution and that tooth replacement and serial addition of primary teeth represent variations of the same developmental process. The expression patterns of Sox2 support the hypothesis that dormant capacity for continuous tooth renewal exists in mammals. PMID:23462476

  14. SOX4 regulates gonad morphogenesis and promotes male germ cell differentiation in mice.

    Science.gov (United States)

    Zhao, Liang; Arsenault, Michel; Ng, Ee Ting; Longmuss, Enya; Chau, Tevin Chui-Ying; Hartwig, Sunny; Koopman, Peter

    2017-03-01

    The group C SOX transcription factors SOX4, -11 and -12 play important and mutually overlapping roles in development of a number of organs. Here, we examined the role of SoxC genes during gonadal development in mice. All three genes were expressed in developing gonads of both sexes, predominantly in somatic cells, with Sox4 being most strongly expressed. Sox4 deficiency resulted in elongation of both ovaries and testes, and an increased number of testis cords. While female germ cells entered meiosis normally, male germ cells showed reduced levels of differentiation markers Nanos2 and Dnmt3l and increased levels of pluripotency genes Cripto and Nanog, suggesting that SOX4 may normally act to restrict the pluripotency period of male germ cells and ensure their proper differentiation. Finally, our data reveal that SOX4 (and, to a lesser extent, SOX11 and -12) repressed transcription of the sex-determining gene Sox9 via an upstream testis-specific enhancer core (TESCO) element in fetal gonads, raising the possibility that SOXC proteins may function as transcriptional repressors in a context-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Sox1 marks an activated neural stem/progenitor cell in the hippocampus

    OpenAIRE

    Venere, Monica; Han, Young-Goo; Bell, Robert; Song, Jun S.; Alvarez-Buylla, Arturo; Blelloch, Robert

    2012-01-01

    The dentate gyrus of the hippocampus continues generating new neurons throughout life. These neurons originate from radial astrocytes within the subgranular zone (SGZ). Here, we find that Sox1, a member of the SoxB1 family of transcription factors, is expressed in a subset of radial astrocytes. Lineage tracing using Sox1-tTA;tetO-Cre;Rosa26 reporter mice shows that the Sox1-expressing cells represent an activated neural stem/progenitor population that gives rise to most if not all newly born ...

  16. Coffin-Siris syndrome and cardiac anomaly with a novel SOX11 mutation.

    Science.gov (United States)

    Okamoto, Nobuhiko; Ehara, Eiji; Tsurusaki, Yoshinori; Miyake, Noriko; Matsumoto, Naomichi

    2017-08-08

    Coffin-Siris syndrome (CSS) is characterized by growth deficiency, intellectual disability, microcephaly, dysmorphic features, and hypoplastic nails of the fifth fingers and/or toes. Variants in the genes encoding subunits of the BAF complex as well as in SOX11 encoding the transcriptional factor under the control of BAF complex are associated with CSS. We report a new patient with a novel SOX11 mutation. He showed the CSS phenotype and coarctation of the aorta. Sox11 is known to be associated with cardiac outflow development in mouse studies. Therefore, cardiac anomalies might be an important complication in patients with SOX11 mutations. © 2017 Japanese Teratology Society.

  17. Sox9b is a key regulator of pancreaticobiliary ductal system development.

    Directory of Open Access Journals (Sweden)

    Marion Delous

    Full Text Available The pancreaticobiliary ductal system connects the liver and pancreas to the intestine. It is composed of the hepatopancreatic ductal (HPD system as well as the intrahepatic biliary ducts and the intrapancreatic ducts. Despite its physiological importance, the development of the pancreaticobiliary ductal system remains poorly understood. The SRY-related transcription factor SOX9 is expressed in the mammalian pancreaticobiliary ductal system, but the perinatal lethality of Sox9 heterozygous mice makes loss-of-function analyses challenging. We turned to the zebrafish to assess the role of SOX9 in pancreaticobiliary ductal system development. We first show that zebrafish sox9b recapitulates the expression pattern of mouse Sox9 in the pancreaticobiliary ductal system and use a nonsense allele of sox9b, sox9b(fh313, to dissect its function in the morphogenesis of this structure. Strikingly, sox9b(fh313 homozygous mutants survive to adulthood and exhibit cholestasis associated with hepatic and pancreatic duct proliferation, cyst formation, and fibrosis. Analysis of sox9b(fh313 mutant embryos and larvae reveals that the HPD cells appear to mis-differentiate towards hepatic and/or pancreatic fates, resulting in a dysmorphic structure. The intrahepatic biliary cells are specified but fail to assemble into a functional network. Similarly, intrapancreatic duct formation is severely impaired in sox9b(fh313 mutants, while the embryonic endocrine and acinar compartments appear unaffected. The defects in the intrahepatic and intrapancreatic ducts of sox9b(fh313 mutants worsen during larval and juvenile stages, prompting the adult phenotype. We further show that Sox9b interacts with Notch signaling to regulate intrahepatic biliary network formation: sox9b expression is positively regulated by Notch signaling, while Sox9b function is required to maintain Notch signaling in the intrahepatic biliary cells. Together, these data reveal key roles for SOX9 in the

  18. Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells

    Science.gov (United States)

    2012-01-01

    Background In contrast to mammals, amphibians, such as adult urodeles (for example, newts) and anuran larvae (for example, Xenopus) can regenerate their spinal cord after injury. However, the cellular and molecular mechanisms involved in this process are still poorly understood. Results Here, we report that tail amputation results in a global increase of Sox2 levels and proliferation of Sox2+ cells. Overexpression of a dominant negative form of Sox2 diminished proliferation of spinal cord resident cells affecting tail regeneration after amputation, suggesting that spinal cord regeneration is crucial for the whole process. After spinal cord transection, Sox2+ cells are found in the ablation gap forming aggregates. Furthermore, Sox2 levels correlated with regenerative capabilities during metamorphosis, observing a decrease in Sox2 levels at non-regenerative stages. Conclusions Sox2+ cells contribute to the regeneration of spinal cord after tail amputation and transection. Sox2 levels decreases during metamorphosis concomitantly with the lost of regenerative capabilities. Our results lead to a working hypothesis in which spinal cord damage activates proliferation and/or migration of Sox2+ cells, thus allowing regeneration of the spinal cord after tail amputation or reconstitution of the ependymal epithelium after spinal cord transection. PMID:22537391

  19. Functional analysis of Waardenburg syndrome-associated PAX3 and SOX10 mutations: report of a dominant-negative SOX10 mutation in Waardenburg syndrome type II.

    Science.gov (United States)

    Zhang, Hua; Chen, Hongsheng; Luo, Hunjin; An, Jing; Sun, Lin; Mei, Lingyun; He, Chufeng; Jiang, Lu; Jiang, Wen; Xia, Kun; Li, Jia-Da; Feng, Yong

    2012-03-01

    Waardenburg syndrome (WS) is an auditory-pigmentary disorder resulting from melanocyte defects, with varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four subtypes (WS1-WS4) based on additional symptoms. PAX3 and SOX10 are two transcription factors that can activate the expression of microphthalmia-associated transcription factor (MITF), a critical transcription factor for melanocyte development. Mutations of PAX3 are associated with WS1 and WS3, while mutations of SOX10 cause WS2 and WS4. Recently, we identified some novel WS-associated mutations in PAX3 and SOX10 in a cohort of Chinese WS patients. Here, we further identified an E248fsX30 SOX10 mutation in a family of WS2. We analyzed the subcellular distribution, expression and in vitro activity of two PAX3 mutations (p.H80D, p.H186fsX5) and four SOX10 mutations (p.E248fsX30, p.G37fsX58, p.G38fsX69 and p.R43X). Except H80D PAX3, which retained partial activity, the other mutants were unable to activate MITF promoter. The H80D PAX3 and E248fsX30 SOX10 were localized in the nucleus as wild type (WT) proteins, whereas the other mutant proteins were distributed in both cytoplasm and nucleus. Furthermore, E248fsX30 SOX10 protein retained the DNA-binding activity and showed dominant-negative effect on WT SOX10. However, E248fsX30 SOX10 protein seems to decay faster than the WT one, which may underlie the mild WS2 phenotype caused by this mutation.

  20. Trapped Inflation

    Energy Technology Data Exchange (ETDEWEB)

    Green, Daniel; Horn, Bart; /SLAC /Stanford U., Phys. Dept.; Senatore, Leonardo; /Princeton, Inst. Advanced Study /Harvard U., Phys. Dept. /Harvard-Smithsonian Ctr. Astrophys.; Silverstein, Eva; /SLAC /Stanford U., Phys. Dept.

    2009-06-19

    We analyze a distinctive mechanism for inflation in which particle production slows down a scalar field on a steep potential, and show how it descends from angular moduli in string compactifications. The analysis of density perturbations - taking into account the integrated effect of the produced particles and their quantum fluctuations - requires somewhat new techniques that we develop. We then determine the conditions for this effect to produce sixty e-foldings of inflation with the correct amplitude of density perturbations at the Gaussian level, and show that these requirements can be straightforwardly satisfied. Finally, we estimate the amplitude of the non-Gaussianity in the power spectrum and find a significant equilateral contribution.

  1. cDNA cloning and expression analysis of two distinct Sox8 genes in Paramisgurnus dabryanus (Cypriniformes).

    Science.gov (United States)

    Xia, Xiaohua; Zhao, Jie; Du, Qiyan; Chang, Zhongjie

    2010-08-01

    The Sox9 gene attracts a lot of attention because of its connection with gonadal development and differentiation. However, Sox8, belonging to the same subgroup SoxE, has rarely been studied. To investigate the function as well as the evolutionary origin of SOXE subgroup, we amplified the genomic DNA of Paramisgurnus dabryanu using a pair of degenerate primers. Using rapid amplification of the cDNA ends (RACE), it was discovered that P. dabryanu has two duplicates: Sox8a and Sox8b. Each has an intron of different length in the conserved HMG-box region. The overall sequence similarity of the deduced amino acid of PdSox8a and PdSox8b was 46.26%, and only two amino acids changed in the HMG-box. This is the first evidence showing that there are two distinct duplications of Sox8 genes in Cypriniformes. Southern blot analysis showed only one hybrid band, with lengths 7.4 or 9.2 kb. Both semi-quantitative RT-PCR and real-time quantitative PCR assay displayed that both PdSox8a and PdSox8b are downregulated during early embryonic development. In adult tissues, the two Sox8 genes expressed ubiquitously, and expression levels are particularly high in the gonads and brain. In gonads, both PdSox8a and PdSox8b are expressed at a higher level in the tesis than in the ovary. PdSox8a and PdSox8b may have functional overlaps and are essential for the neuronal development and differentiation of gonads.

  2. Sox11 is required to maintain proper levels of Hedgehog signaling during vertebrate ocular morphogenesis.

    Directory of Open Access Journals (Sweden)

    Lakshmi Pillai-Kastoori

    2014-07-01

    Full Text Available Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the Hedgehog pathway inhibitor cyclopamine. We further demonstrate that the elevated Hedgehog signaling in Sox11-deficient zebrafish was caused by a large increase in shha transcription; indeed, suppressing Shha expression rescued the ocular phenotypes of sox11 morphants. Conversely, over-expression of sox11 induced cyclopia, a phenotype consistent with reduced levels of Sonic hedgehog. We screened DNA samples from 79 patients with microphthalmia, anophthalmia, or coloboma (MAC and identified two novel heterozygous SOX11 variants in individuals with coloboma. In contrast to wild type human SOX11 mRNA, mRNA containing either variant failed to rescue the lens and coloboma phenotypes of Sox11-deficient zebrafish, and both exhibited significantly reduced transactivation ability in a luciferase reporter assay. Moreover, decreased gene dosage from a segmental deletion encompassing the SOX11 locus resulted in microphthalmia and related ocular phenotypes. Therefore, our study reveals a novel role for Sox11 in controlling Hedgehog signaling, and suggests that SOX11 variants contribute to pediatric eye disorders.

  3. [SOX10 mutation is relevant to inner ear malformation in patients with Waardenburg syndrome].

    Science.gov (United States)

    Xu, G Y; Hao, Q Q; Zhong, L L; Ren, W; Yan, Y; Liu, R Y; Li, J N; Guo, W W; Zhao, H; Yang, S M

    2016-11-07

    Objective: To determine the relevance between the SOX 10 mutation and Waardenburg syndrome (WS) accompanied with inner ear abnormality by analyzing the inner ear imaging results and molecular and genetic results of the WS patients with the SOX 10 mutation. Methods: This study included 36 WS in patients during 2001 and 2015 in the department of otorhinolaryngology head and neck surgery, Chinese Peoples's Liberation Army General Hospital. The condition of the inner ear of each patient was assessed by analyzing HRCT scans of the temporal bone and MRI scans of the brain and internal auditory canal. Meanwhile, the possible pathogenic genes of WS, including SOX10, MITF , and PAX 3, were also screened. Patients were divided into two groups according to SOX 10 mutation.The Fisher accuracy test was used to determine statistical difference of inner ear deformation incidence between the two groups. Results: Among all 36 patients, 12 were found to have inner ear abnormality. Most abnormalities were posterior semicircular canal deformations, some accompanied with cochlear deformation and an enlarged vestibule. Among all patients, 9 patients were SOX 10 heterozygous mutation carriers, among which six showed bilateral inner ear abnormality. Fisher accuracy test results suggested a significant correlation between the SOX 10 mutation and inner ear abnormality in WS patients ( P =0.036). Conclusion: This study found that WS patients with the SOX 10 mutation are more likely to have deformed inner ears when compared to WS patients without the SOX 10 mutation.

  4. Spontaneous evolution of an unusual cortical malformation in SOX2 anophthalmia syndrome

    Directory of Open Access Journals (Sweden)

    Jay Desai

    2013-01-01

    Full Text Available Brain malformations such as agenesis and dysgenesis of corpus callosum, pituitary hypoplasia, hypothalamic hamartoma, mesial temporal periventricular heterotopia, and abnormally oriented and misshapen hippocampi have been described with SOX2 gene mutations. A neocortical malformation is presented here in association with SOX2 deletion that over time underwent spontaneous evolution and decrease in size.

  5. A Model for Dimerization of the SOX Group E Transcription Factor Family.

    Directory of Open Access Journals (Sweden)

    Sarah N Ramsook

    Full Text Available Group E members of the SOX transcription factor family include SOX8, SOX9, and SOX10. Preceding the high mobility group (HMG domain in each of these proteins is a thirty-eight amino acid region that supports the formation of dimers on promoters containing tandemly inverted sites. The purpose of this study was to obtain new structural insights into how the dimerization region functions with the HMG domain. From a mutagenic scan of the dimerization region, the most essential amino acids of the dimerization region were clustered on the hydrophobic face of a single, predicted amphipathic helix. Consistent with our hypothesis that the dimerization region directly contacts the HMG domain, a peptide corresponding to the dimerization region bound a preassembled HMG-DNA complex. Sequence conservation among Group E members served as a basis to identify two surface exposed amino acids in the HMG domain of SOX9 that were necessary for dimerization. These data were combined to make a molecular model that places the dimerization region of one SOX9 protein onto the HMG domain of another SOX9 protein situated at the opposing site of a tandem promoter. The model provides a detailed foundation for assessing the impact of mutations on SOX Group E transcription factors.

  6. Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43

    NARCIS (Netherlands)

    Boogerd, C.J.; Wong, L.Y.; van den Boogaard, M.; Bakker, M.A.J.; Tessadori, F.; Bakkers, J.; 't Hoen, P.A.C.; Moorman, A.F.; Christoffels, V.M.; Barnett, P.

    2011-01-01

    Tbx3, a T-box transcription factor, regulates key steps in development of the heart and other organ systems. Here, we identify Sox4 as an interacting partner of Tbx3. Pull-down and nuclear retention assays verify this interaction and in situ hybridization reveals Tbx3 and Sox4 to co-localize

  7. Unravelling pathways downstream Sox6 induction in K562 erythroid cells by proteomic analysis

    KAUST Repository

    Barbarani, Gloria; Ronchi, Antonella; Ruoppolo, Margherita; Santorelli, Lucia; Steinfelder, Robert; Elangovan, Sudharshan; Fugazza, Cristina; Caterino, Marianna

    2017-01-01

    are accompanied with a reduced survival of Sox6-/- red blood cells, resulting in a compensated anemia. Sox6-overexpression in K562 cells and in human primary ex vivo erythroid cultures enhances erythroid differentiation and leads to hemoglobinization, the hallmark

  8. Solar X-ray Spectrometer (SOXS) Mission – Low Energy Payload ...

    Indian Academy of Sciences (India)

    Solar X-ray Spectrometer (SOXS)' mission, which was launched onboard GSAT-2 Indian spacecraft on 08 May 2003 by GSLV-D2 rocket to study the solar flares. The SOXS Low Energy Detector (SLD) payload was designed, developed and ...

  9. Solar X-ray Spectrometer (SOXS) Mission – Low Energy Payload

    Indian Academy of Sciences (India)

    2016-01-27

    Jan 27, 2016 ... We present the first results from the 'Low Energy Detector' payload of 'Solar X-ray Spectrometer (SOXS)' mission, which was launched onboard GSAT-2 Indian spacecraft on 08 May 2003 by GSLV-D2 rocket to study the solar flares. The SOXS Low Energy Detector (SLD) payload was designed, developed ...

  10. SOX9-mediated upregulation of LGR5 is important for glioblastoma tumorigenicity

    International Nuclear Information System (INIS)

    Hiraoka, Koji; Hayashi, Tomoatsu; Kaneko, Ryusuke; Nasu-Nishimura, Yukiko; Koyama-Nasu, Ryo; Kawasaki, Yoshihiro; Akiyama, Tetsu

    2015-01-01

    LGR5 plays an important role in the self-renewal of stem cells and is used as a marker identifying self-renewing stem cells in small intestine and hair follicles. Moreover, LGR5 has been reported to be overexpressed in several cancers. SOX9 is a transcription factor that plays a key role in development, differentiation and lineage commitment in various tissues. It has also been reported that SOX9 is overexpressed in a variety of cancers and contributes to their malignant phenotype. Here we show that LGR5 is required for the tumorigenicity of glioblastoma cells. We further show that SOX9 is upregulated in glioblastoma cells and directly enhances the expression of LGR5. We also demonstrate that knockdown of SOX9 suppresses the proliferation and tumorigenicity of glioblastoma cells. These results suggest that SOX9-mediated transcriptional regulation of LGR5 is critical for the tumorigenicity of glioblastoma cells. We speculate that the SOX9-LGR5 pathway could be a potentially promising target for the therapy of glioblastoma. - Highlights: • LGR5 is required for the tumorigenicity of glioblastoma cells. • SOX9 directly enhances the expression of LGR5. • SOX9 is required for the tumorigenicity of glioblastoma cells

  11. SOX9-mediated upregulation of LGR5 is important for glioblastoma tumorigenicity

    Energy Technology Data Exchange (ETDEWEB)

    Hiraoka, Koji; Hayashi, Tomoatsu; Kaneko, Ryusuke; Nasu-Nishimura, Yukiko; Koyama-Nasu, Ryo; Kawasaki, Yoshihiro; Akiyama, Tetsu, E-mail: akiyama@iam.u-tokyo.ac.jp

    2015-05-01

    LGR5 plays an important role in the self-renewal of stem cells and is used as a marker identifying self-renewing stem cells in small intestine and hair follicles. Moreover, LGR5 has been reported to be overexpressed in several cancers. SOX9 is a transcription factor that plays a key role in development, differentiation and lineage commitment in various tissues. It has also been reported that SOX9 is overexpressed in a variety of cancers and contributes to their malignant phenotype. Here we show that LGR5 is required for the tumorigenicity of glioblastoma cells. We further show that SOX9 is upregulated in glioblastoma cells and directly enhances the expression of LGR5. We also demonstrate that knockdown of SOX9 suppresses the proliferation and tumorigenicity of glioblastoma cells. These results suggest that SOX9-mediated transcriptional regulation of LGR5 is critical for the tumorigenicity of glioblastoma cells. We speculate that the SOX9-LGR5 pathway could be a potentially promising target for the therapy of glioblastoma. - Highlights: • LGR5 is required for the tumorigenicity of glioblastoma cells. • SOX9 directly enhances the expression of LGR5. • SOX9 is required for the tumorigenicity of glioblastoma cells.

  12. SOX9 Expression Predicts Relapse of Stage II Colon Cancer Patients

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Linnemann, Dorte; Christensen, Ib Jarle

    2016-01-01

    The aim of this study was to investigate if the protein expression of Sex-determining region y-box 9 (SOX9) in primary tumors could predict relapse of stage II colon cancer patients.144 patients with stage II primary colon cancer were retrospectively enrolledin the study. SOX9 expression...

  13. Trapped atoms along nanophotonic resonators

    Science.gov (United States)

    Fields, Brian; Kim, May; Chang, Tzu-Han; Hung, Chen-Lung

    2017-04-01

    Many-body systems subject to long-range interactions have remained a very challenging topic experimentally. Ultracold atoms trapped in extreme proximity to the surface of nanophotonic structures provides a dynamic system combining the strong atom-atom interactions mediated by guided mode photons with the exquisite control implemented with trapped atom systems. The hybrid system promises pair-wise tunability of long-range interactions between atomic pseudo spins, allowing studies of quantum magnetism extending far beyond nearest neighbor interactions. In this talk, we will discuss our current status developing high quality nanophotonic ring resonators, engineered on CMOS compatible optical chips with integrated nanostructures that, in combination with a side illuminating beam, can realize stable atom traps approximately 100nm above the surface. We will report on our progress towards loading arrays of cold atoms near the surface of these structures and studying atom-atom interaction mediated by photons with high cooperativity.

  14. Conserved regulatory modules in the Sox9 testis-specific enhancer predict roles for SOX, TCF/LEF, Forkhead, DMRT, and GATA proteins in vertebrate sex determination.

    Science.gov (United States)

    Bagheri-Fam, Stefan; Sinclair, Andrew H; Koopman, Peter; Harley, Vincent R

    2010-03-01

    While the primary sex determining switch varies between vertebrate species, a key downstream event in testicular development, namely the male-specific up-regulation of Sox9, is conserved. To date, only two sex determining switch genes have been identified, Sry in mammals and the Dmrt1-related gene Dmy (Dmrt1bY) in the medaka fish Oryzias latipes. In mice, Sox9 expression is evidently up-regulated by SRY and maintained by SOX9 both of which directly activate the core 1.3 kb testis-specific enhancer of Sox9 (TESCO). How Sox9 expression is up-regulated and maintained in species without Sry (i.e. non-mammalian species) is not understood. In this study, we have undertaken an in-depth comparative genomics approach and show that TESCO contains an evolutionarily conserved region (ECR) of 180 bp which is present in marsupials, monotremes, birds, reptiles and amphibians. The ECR contains highly conserved modules that predict regulatory roles for SOX, TCF/LEF, Forkhead, DMRT, and GATA proteins in vertebrate sex determination/differentiation. Our data suggest that tetrapods share common aspects of Sox9 regulation in the testis, despite having different sex determining switch mechanisms. They also suggest that Sox9 autoregulation is an ancient mechanism shared by all tetrapods, raising the possibility that in mammals, SRY evolved by mimicking this regulation. The validation of ECR regulatory sequences conserved from human to frogs will provide new insights into vertebrate sex determination. Copyright 2009 Elsevier Ltd. All rights reserved.

  15. Supernumerary impacted teeth in a patient with SOX2 anophthalmia syndrome.

    Science.gov (United States)

    Numakura, Chikahiko; Kitanaka, Sachiko; Kato, Mitsuhiro; Ishikawa, Shigeo; Hamamoto, Yoshioki; Katsushima, Yuriko; Kimura, Toshiyuki; Hayasaka, Kiyoshi

    2010-09-01

    SOX2 anophthalmia syndrome characteristically presents as anophthalmia or microphthalmia, with various extraocular symptoms, such as hypogonadotropic hypogonadism, brain anomaly, and esophageal abnormalities. In this report, we describe a patient with SOX2 anophthalmia syndrome complicated with a dental anomaly, multiple supernumerary impacted teeth, and persistence of deciduous teeth. Multiple supernumerary teeth are usually not solitary symptoms, but indicate systemic syndrome such as cleidocranial dysplasia. In odontogenesis, many transcriptional factors, such as BMPs, FGFs, and Wnts, play significant roles and SOX2 is known to interact with some of them. The role of SOX2 in dental development remains unknown, however, multiple supernumerary teeth can be considered as extraocular symptoms of SOX2 anophthalmia syndrome, rather than the coincidence of two rare diseases.

  16. [A Case of Rhabdomyolysis Related to SOX Therapy for Liver Metastasis of Gastric Cancer].

    Science.gov (United States)

    Sato, Kei; Akiyama, Hirotoshi; Kogure, Yuu; Suwa, Yusuke; Momiyama, Masashi; Ishibe, Atsushi; Endo, Itaru

    2017-04-01

    We report a case of rhabdomyolysis related to S-1 plus oxaliplatin(SOX)therapy for liver metastasis of gastric cancer. A 76- year-old man who had received SOX therapy for metastatic gastric cancer was admitted to our hospital for a chief complaint of fatigue and weakness. He diagnosed with rhabdomyolysis related to SOX therapy because of his symptoms and because his laboratory studies showed significant elevation of his serum creatine kinase(CK)level. The symptoms disappeared and the CK level normalized following large-volume transfusions. Rhabdomyolysis following SOX therapy is a very rare, but severe adverse event. This is the first detailed case report of rhabdomyolysis related to SOX therapy.

  17. Shrew trap efficiency

    DEFF Research Database (Denmark)

    Gambalemoke, Mbalitini; Mukinzi, Itoka; Amundala, Drazo

    2008-01-01

    We investigated the efficiency of four trap types (pitfall, Sherman LFA, Victor snap and Museum Special snap traps) to capture shrews. This experiment was conducted in five inter-riverine forest blocks in the region of Kisangani. The total trapping effort was 6,300, 9,240, 5,280 and 5,460 trap......, our results indicate that pitfall traps are the most efficient for capturing shrews: not only do they have a higher efficiency (yield), but the taxonomic diversity of shrews is also higher when pitfall traps are used....

  18. Parallel Expansions of Sox Transcription Factor Group B Predating the Diversifications of the Arthropods and Jawed Vertebrates

    Science.gov (United States)

    Zhong, Lei; Wang, Dengqiang; Gan, Xiaoni; Yang, Tong; He, Shunping

    2011-01-01

    Group B of the Sox transcription factor family is crucial in embryo development in the insects and vertebrates. Sox group B, unlike the other Sox groups, has an unusually enlarged functional repertoire in insects, but the timing and mechanism of the expansion of this group were unclear. We collected and analyzed data for Sox group B from 36 species of 12 phyla representing the major metazoan clades, with an emphasis on arthropods, to reconstruct the evolutionary history of SoxB in bilaterians and to date the expansion of Sox group B in insects. We found that the genome of the bilaterian last common ancestor probably contained one SoxB1 and one SoxB2 gene only and that tandem duplications of SoxB2 occurred before the arthropod diversification but after the arthropod-nematode divergence, resulting in the basal repertoire of Sox group B in diverse arthropod lineages. The arthropod Sox group B repertoire expanded differently from the vertebrate repertoire, which resulted from genome duplications. The parallel increases in the Sox group B repertoires of the arthropods and vertebrates are consistent with the parallel increases in the complexity and diversification of these two important organismal groups. PMID:21305035

  19. SOXE transcription factors form selective dimers on non-compact DNA motifs through multifaceted interactions between dimerization and high-mobility group domains.

    Science.gov (United States)

    Huang, Yong-Heng; Jankowski, Aleksander; Cheah, Kathryn S E; Prabhakar, Shyam; Jauch, Ralf

    2015-05-27

    The SOXE transcription factors SOX8, SOX9 and SOX10 are master regulators of mammalian development directing sex determination, gliogenesis, pancreas specification and neural crest development. We identified a set of palindromic SOX binding sites specifically enriched in regulatory regions of melanoma cells. SOXE proteins homodimerize on these sequences with high cooperativity. In contrast to other transcription factor dimers, which are typically rigidly spaced, SOXE group proteins can bind cooperatively at a wide range of dimer spacings. Using truncated forms of SOXE proteins, we show that a single dimerization (DIM) domain, that precedes the DNA binding high mobility group (HMG) domain, is sufficient for dimer formation, suggesting that DIM : HMG rather than DIM:DIM interactions mediate the dimerization. All SOXE members can also heterodimerize in this fashion, whereas SOXE heterodimers with SOX2, SOX4, SOX6 and SOX18 are not supported. We propose a structural model where SOXE-specific intramolecular DIM:HMG interactions are allosterically communicated to the HMG of juxtaposed molecules. Collectively, SOXE factors evolved a unique mode to combinatorially regulate their target genes that relies on a multifaceted interplay between the HMG and DIM domains. This property potentially extends further the diversity of target genes and cell-specific functions that are regulated by SOXE proteins.

  20. SOXE transcription factors form selective dimers on non-compact DNA motifs through multifaceted interactions between dimerization and high-mobility group domains

    Science.gov (United States)

    Huang, Yong-Heng; Jankowski, Aleksander; Cheah, Kathryn S. E.; Prabhakar, Shyam; Jauch, Ralf

    2015-01-01

    The SOXE transcription factors SOX8, SOX9 and SOX10 are master regulators of mammalian development directing sex determination, gliogenesis, pancreas specification and neural crest development. We identified a set of palindromic SOX binding sites specifically enriched in regulatory regions of melanoma cells. SOXE proteins homodimerize on these sequences with high cooperativity. In contrast to other transcription factor dimers, which are typically rigidly spaced, SOXE group proteins can bind cooperatively at a wide range of dimer spacings. Using truncated forms of SOXE proteins, we show that a single dimerization (DIM) domain, that precedes the DNA binding high mobility group (HMG) domain, is sufficient for dimer formation, suggesting that DIM : HMG rather than DIM:DIM interactions mediate the dimerization. All SOXE members can also heterodimerize in this fashion, whereas SOXE heterodimers with SOX2, SOX4, SOX6 and SOX18 are not supported. We propose a structural model where SOXE-specific intramolecular DIM:HMG interactions are allosterically communicated to the HMG of juxtaposed molecules. Collectively, SOXE factors evolved a unique mode to combinatorially regulate their target genes that relies on a multifaceted interplay between the HMG and DIM domains. This property potentially extends further the diversity of target genes and cell-specific functions that are regulated by SOXE proteins. PMID:26013289

  1. St. Croix trap study

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The data set contains detailed information about the catch from 600 trap stations around St. Croix. Data fields include species caught, size data, trap location...

  2. SOX2 regulates self-renewal and tumorigenicity of human melanoma-initiating cells.

    Science.gov (United States)

    Santini, R; Pietrobono, S; Pandolfi, S; Montagnani, V; D'Amico, M; Penachioni, J Y; Vinci, M C; Borgognoni, L; Stecca, B

    2014-09-18

    Melanoma is one of the most aggressive types of human cancer, characterized by enhanced heterogeneity and resistance to conventional therapy at advanced stages. We and others have previously shown that HEDGEHOG-GLI (HH-GLI) signaling is required for melanoma growth and for survival and expansion of melanoma-initiating cells (MICs). Recent reports indicate that HH-GLI signaling regulates a set of genes typically expressed in embryonic stem cells, including SOX2 (sex-determining region Y (SRY)-Box2). Here we address the function of SOX2 in human melanomas and MICs and its interaction with HH-GLI signaling. We find that SOX2 is highly expressed in melanoma stem cells. Knockdown of SOX2 sharply decreases self-renewal in melanoma spheres and in putative melanoma stem cells with high aldehyde dehydrogenase activity (ALDH(high)). Conversely, ectopic expression of SOX2 in melanoma cells enhances their self-renewal in vitro. SOX2 silencing also inhibits cell growth and induces apoptosis in melanoma cells. In addition, depletion of SOX2 progressively abrogates tumor growth and leads to a significant decrease in tumor-initiating capability of ALDH(high) MICs upon xenotransplantation, suggesting that SOX2 is required for tumor initiation and for continuous tumor growth. We show that SOX2 is regulated by HH signaling and that the transcription factors GLI1 and GLI2, the downstream effectors of HH-GLI signaling, bind to the proximal promoter region of SOX2 in primary melanoma cells. In functional studies, we find that SOX2 function is required for HH-induced melanoma cell growth and MIC self-renewal in vitro. Thus SOX2 is a critical factor for self-renewal and tumorigenicity of MICs and an important mediator of HH-GLI signaling in melanoma. These findings could provide the basis for novel therapeutic strategies based on the inhibition of SOX2 for the treatment of a subset of human melanomas.

  3. Angular trap for macroparticles

    International Nuclear Information System (INIS)

    Aksyonov, D.S.

    2013-01-01

    Properties of angular macroparticle traps were investigated in this work. These properties are required to design vacuum arc plasma filters. The correlation between trap geometry parameters and its ability to absorb macroparticles were found. Calculations allow one to predict the behaviour of filtering abilities of separators which contain such traps in their design. Recommendations regarding the use of angular traps in filters of different builds are given.

  4. Genome-wide analysis of the sox family in the calcareous sponge Sycon ciliatum: multiple genes with unique expression patterns

    Directory of Open Access Journals (Sweden)

    Fortunato Sofia

    2012-07-01

    Full Text Available Abstract Background Sox genes are HMG-domain containing transcription factors with important roles in developmental processes in animals; many of them appear to have conserved functions among eumetazoans. Demosponges have fewer Sox genes than eumetazoans, but their roles remain unclear. The aim of this study is to gain insight into the early evolutionary history of the Sox gene family by identification and expression analysis of Sox genes in the calcareous sponge Sycon ciliatum. Methods Calcaronean Sox related sequences were retrieved by searching recently generated genomic and transcriptome sequence resources and analyzed using variety of phylogenetic methods and identification of conserved motifs. Expression was studied by whole mount in situ hybridization. Results We have identified seven Sox genes and four Sox-related genes in the complete genome of Sycon ciliatum. Phylogenetic and conserved motif analyses showed that five of Sycon Sox genes represent groups B, C, E, and F present in cnidarians and bilaterians. Two additional genes are classified as Sox genes but cannot be assigned to specific subfamilies, and four genes are more similar to Sox genes than to other HMG-containing genes. Thus, the repertoire of Sox genes is larger in this representative of calcareous sponges than in the demosponge Amphimedon queenslandica. It remains unclear whether this is due to the expansion of the gene family in Sycon or a secondary reduction in the Amphimedon genome. In situ hybridization of Sycon Sox genes revealed a variety of expression patterns during embryogenesis and in specific cell types of adult sponges. Conclusions In this study, we describe a large family of Sox genes in Sycon ciliatum with dynamic expression patterns, indicating that Sox genes are regulators in development and cell type determination in sponges, as observed in higher animals. The revealed differences between demosponge and calcisponge Sox genes repertoire highlight the need to

  5. A zebrafish model for Waardenburg syndrome type IV reveals diverse roles for Sox10 in the otic vesicle.

    Science.gov (United States)

    Dutton, Kirsten; Abbas, Leila; Spencer, Joanne; Brannon, Claire; Mowbray, Catriona; Nikaido, Masataka; Kelsh, Robert N; Whitfield, Tanya T

    2009-01-01

    In humans, mutations in the SOX10 gene are a cause of the auditory-pigmentary disorder Waardenburg syndrome type IV (WS4) and related variants. SOX10 encodes an Sry-related HMG box protein essential for the development of the neural crest; deafness in WS4 and other Waardenburg syndromes is usually attributed to loss of neural-crest-derived melanocytes in the stria vascularis of the cochlea. However, SOX10 is strongly expressed in the developing otic vesicle and so direct roles for SOX10 in the otic epithelium might also be important. Here, we examine the otic phenotype of zebrafish sox10 mutants, a model for WS4. As a cochlea is not present in the fish ear, the severe otic phenotype in these mutants cannot be attributed to effects on this tissue. In zebrafish sox10 mutants, we see abnormalities in all otic placodal derivatives. Gene expression studies indicate deregulated expression of several otic genes, including fgf8, in sox10 mutants. Using a combination of mutant and morphant data, we show that the three sox genes belonging to group E (sox9a, sox9b and sox10) provide a link between otic induction pathways and subsequent otic patterning: they act redundantly to maintain sox10 expression throughout otic tissue and to restrict fgf8 expression to anterior macula regions. Single-cell labelling experiments indicate a small and transient neural crest contribution to the zebrafish ear during normal development, but this is unlikely to account for the strong defects seen in the sox10 mutant. We discuss the implication that the deafness in WS4 patients with SOX10 mutations might reflect a haploinsufficiency for SOX10 in the otic epithelium, resulting in patterning and functional abnormalities in the inner ear.

  6. Familial recurrence of SOX2 anophthalmia syndrome: phenotypically normal mother with two affected daughters.

    Science.gov (United States)

    Schneider, Adele; Bardakjian, Tanya M; Zhou, Jie; Hughes, Nkecha; Keep, Rosanne; Dorsainville, Darnelle; Kherani, Femida; Katowitz, James; Schimmenti, Lisa A; Hummel, Marybeth; Fitzpatrick, David R; Young, Terri L

    2008-11-01

    The SOX2 anophthalmia syndrome is emerging as a clinically recognizable disorder that has been identified in 10-15% of individuals with bilateral anophthalmia. Extra-ocular anomalies are common. The majority of SOX2 mutations identified appear to arise de novo in probands ascertained through the presence of anophthalmia or microphthalmia. In this report, we describe two sisters with bilateral anophthalmia/microphthalmia, brain anomalies and a novel heterozygous SOX2 gene single-base pair nucleotide deletion, c.551delC, which predicts p.Pro184ArgfsX19. The hypothetical protein product is predicted to lead to haploinsufficient SOX2 function. Mosaicism for this mutation in the SOX2 gene was also identified in their clinically unaffected mother in peripheral blood DNA. Thus it cannot be assumed that all SOX2 mutations in individuals with anophthalmia/microphthalmia are de novo. Testing of parents is indicated when a SOX2 mutation is identified in a proband. Copyright 2008 Wiley-Liss, Inc.

  7. Novel SOX2 mutations and genotype-phenotype correlation in anophthalmia and microphthalmia.

    Science.gov (United States)

    Schneider, Adele; Bardakjian, Tanya; Reis, Linda M; Tyler, Rebecca C; Semina, Elena V

    2009-12-01

    SOX2 represents a High Mobility Group domain containing transcription factor that is essential for normal development in vertebrates. Mutations in SOX2 are known to result in a spectrum of severe ocular phenotypes in humans, also typically associated with other systemic defects. Ocular phenotypes include anophthalmia/microphthalmia (A/M), optic nerve hypoplasia, ocular coloboma and other eye anomalies. We screened 51 unrelated individuals with A/M and identified SOX2 mutations in the coding region of the gene in 10 individuals. Seven of the identified mutations are novel alterations, while the remaining three individuals carry the previously reported recurrent 20-nucleotide deletion in SOX2, c.70del20. Among the SOX2-positive cases, seven patients had bilateral A/M and mutations resulting in premature termination of the normal protein sequence (7/38; 18% of all bilateral cases), one patient had bilateral A/M associated with a single amino acid insertion (1/38; 3% of bilateral cases), and the final two patients demonstrated unilateral A/M associated with missense mutations (2/13; 15% of all unilateral cases). These findings and review of previously reported cases suggest a potential genotype/phenotype correlation for SOX2 mutations with missense changes generally leading to less severe ocular defects. In addition, we report a new familial case of affected siblings with maternal mosaicism for the identified SOX2 mutation, which further underscores the importance of parental testing to provide accurate genetic counseling to families.

  8. Dissecting the role of distinct OCT4-SOX2 heterodimer configurations in pluripotency

    Science.gov (United States)

    Tapia, Natalia; MacCarthy, Caitlin; Esch, Daniel; Gabriele Marthaler, Adele; Tiemann, Ulf; Araúzo-Bravo, Marcos J.; Jauch, Ralf; Cojocaru, Vlad; Schöler, Hans R.

    2015-01-01

    The transcription factors OCT4 and SOX2 are required for generating induced pluripotent stem cells (iPSCs) and for maintaining embryonic stem cells (ESCs). OCT4 and SOX2 associate and bind to DNA in different configurations depending on the arrangement of their individual DNA binding elements. Here we have investigated the role of the different OCT4-SOX2-DNA assemblies in regulating and inducing pluripotency. To this end, we have generated SOX2 mutants that interfere with specific OCT4-SOX2 heterodimer configurations and assessed their ability to generate iPSCs and to rescue ESC self-renewal. Our results demonstrate that the OCT4-SOX2 configuration that dimerizes on a Hoxb1-like composite, a canonical element with juxtaposed individual binding sites, plays a more critical role in the induction and maintenance of pluripotency than any other OCT4-SOX2 configuration. Overall, the results of this study provide new insight into the protein interactions required to establish a de novo pluripotent network and to maintain a true pluripotent cell fate. PMID:26314899

  9. Prolonged Sox4 expression in oligodendrocytes interferes with normal myelination in the central nervous system.

    Science.gov (United States)

    Potzner, Michaela R; Griffel, Carola; Lütjen-Drecoll, Elke; Bösl, Michael R; Wegner, Michael; Sock, Elisabeth

    2007-08-01

    The highly related transcription factors Sox4 and Sox11 are both expressed in oligodendrocyte precursors. Yet whether they have a function in oligodendrocyte development is unknown. By overexpressing Sox4 under the control of 3.1 kb of 5' flanking sequences of the myelin basic protein gene in transgenic mice, we extended Sox4 expression in the oligodendrocyte lineage from oligodendrocyte precursors to cells undergoing terminal differentiation. As a consequence of transgene expression, mice develop the full spectrum of phenotypic traits associated with a severe hypomyelination during the first postnatal weeks. Myelin gene expression was severely reduced, and myelin dramatically thinned in several central nervous system (CNS) regions. Despite these disturbances in CNS myelination, the number of oligodendrocytic cells remained unaltered. Considering that apoptosis rates were normal and proliferation only slightly increased, oligodendrocytes likely persist in a premyelinating to early myelinating state. This shows that prolonged Sox4 expression in cells of the oligodendrocyte lineage is incompatible with the acquisition of a fully mature phenotype and argues that the presence of Sox4, and possibly Sox11, in oligodendrocyte precursors may normally prevent premature differentiation.

  10. Prolonged Sox4 Expression in Oligodendrocytes Interferes with Normal Myelination in the Central Nervous System▿ †

    Science.gov (United States)

    Potzner, Michaela R.; Griffel, Carola; Lütjen-Drecoll, Elke; Bösl, Michael R.; Wegner, Michael; Sock, Elisabeth

    2007-01-01

    The highly related transcription factors Sox4 and Sox11 are both expressed in oligodendrocyte precursors. Yet whether they have a function in oligodendrocyte development is unknown. By overexpressing Sox4 under the control of 3.1 kb of 5′ flanking sequences of the myelin basic protein gene in transgenic mice, we extended Sox4 expression in the oligodendrocyte lineage from oligodendrocyte precursors to cells undergoing terminal differentiation. As a consequence of transgene expression, mice develop the full spectrum of phenotypic traits associated with a severe hypomyelination during the first postnatal weeks. Myelin gene expression was severely reduced, and myelin dramatically thinned in several central nervous system (CNS) regions. Despite these disturbances in CNS myelination, the number of oligodendrocytic cells remained unaltered. Considering that apoptosis rates were normal and proliferation only slightly increased, oligodendrocytes likely persist in a premyelinating to early myelinating state. This shows that prolonged Sox4 expression in cells of the oligodendrocyte lineage is incompatible with the acquisition of a fully mature phenotype and argues that the presence of Sox4, and possibly Sox11, in oligodendrocyte precursors may normally prevent premature differentiation. PMID:17515609

  11. The Sox2 high mobility group transcription factor inhibits mature osteoblast function in transgenic mice

    Science.gov (United States)

    Holmes, Greg; Bromage, Timothy G.; Basilico, Claudio

    2011-01-01

    We have previously shown that in osteoblasts Sox2 expression can be induced by Fgfs, and can inhibit Wnt signaling and differentiation. Furthermore, in mice in which Sox2 is conditionally deleted in the osteoblastic lineage, bones are osteopenic, and Sox2 inactivation in cultured osteoblasts leads to a loss of proliferative ability with a senescent phenotype. To help understand the role of Sox2 in osteoblast development we have specifically expressed Sox2 in bone from a Col1α1 promoter, which extended Sox2 expression into more mature osteoblasts. In long bones, trabecular cartilage remodeling was delayed and the transition from endochondral to cortical bone was disrupted, resulting in porous and undermineralized cortical bone. Collagen deposition was disorganized, and patterns of osteoclast activity were altered. Calvarial bones were thinner and parietal bones failed to develop the diploic space. Microarray analysis showed significant up- or downregulation of a variety of genes coding for non-collagenous extracellular matrix proteins, with a number of genes typical of mature osteoblasts being downregulated. Our results position Sox2 as a negative regulator of osteoblast maturation in vivo. PMID:21703370

  12. Wnt signaling in ovarian development inhibits Sf1 activation of Sox9 via the Tesco enhancer.

    Science.gov (United States)

    Bernard, Pascal; Ryan, Janelle; Sim, Helena; Czech, Daniel P; Sinclair, Andrew H; Koopman, Peter; Harley, Vincent R

    2012-02-01

    Genome analysis of patients with disorders of sex development, and gain- and loss-of-function studies in mice indicate that gonadal development is regulated by opposing signals. In females, the Wnt/β-catenin canonical pathway blocks testicular differentiation by repressing the expression of the Sertoli cell-specific gene Sox9 by an unknown mechanism. Using cell and embryonic gonad culture models, we show that activation of the Wnt/β-catenin pathway inhibits the expression of Sox9 and Amh, whereas mRNA and protein levels of Sry and steroidogenic factor 1 (Sf1), two key transcriptional regulators of Sox9, are not altered. Ectopic activation of Wnt/β-catenin signaling in male gonads led to a loss of Sf1 binding to the Tesco enhancer and absent Sox9 expression that we also observed in wild-type ovaries. Moreover, ectopic Wnt/β-catenin signaling induced the expression of the female somatic cell markers, Bmp2 and Rspo1, as a likely consequence of Sox9 loss. Wnt/β-catenin signaling in XY gonads did not, however, affect gene expression of the steroidogenic Leydig cell Sf1 target gene, Cyp11a1, or Sf1 binding to the Cyp11a1 promoter. Our data support a model in ovary development whereby activation of β-catenin prevents Sf1 binding to the Sox9 enhancer, thereby inhibiting Sox9 expression and Sertoli cell differentiation.

  13. The Aarhus Ion Micro-Trap Project

    DEFF Research Database (Denmark)

    Miroshnychenko, Yevhen; Nielsen, Otto; Poulsen, Gregers

    As part of our involvement in the EU MICROTRAP project, we have designed, manufactured and assembled a micro-scale ion trap with integrated optical fibers. These prealigned fibers will allow delivering cooling laser light to single ions. Therefore, such a trap will not require any direct optical...... and installed in an ultra high vacuum chamber, which includes an ablation oven for all-optical loading of the trap [2]. The next steps on the project are to demonstrate the operation of the micro-trap and the cooling of ions using fiber delivered light. [1] D. Grant, Development of Micro-Scale Ion traps, Master...... Thesis (2008). [2] R.J. Hendricks, D.M. Grant, P.F. Herskind, A. Dantan and M. Drewsen, An all-optical ion-loading technique for scalable microtrap architectures, Applied Physics B, 88, 507 (2007)....

  14. Characterisation and expression of Sox9 in the Leopard gecko, Eublepharis macularius.

    Science.gov (United States)

    Valleley, E M; Cartwright, E J; Croft, N J; Markham, A F; Coletta, P L

    2001-04-15

    Since the discovery of the sex-determining gene, Sry, a number of genes have been identified which are involved in sex determination and gonadogenesis in mammals. Although Sry is known to be the testis-determining factor in mammals, this is not the case in non-mammalian vertebrates. Sox9 is another gene that has been shown to have a male-specific role in sex determination, but, unlike Sry, Sox9 has been shown to be involved in sex determination in mammals, birds, and reptiles. This is the first gene to be described that has a conserved role in sex determination in species with either chromosomal or environmental sex-determining mechanisms. Many reptiles do not have sex chromosomes but exhibit temperature-dependent sex determination (TSD). Sox9 has been shown to be expressed in both turtle and alligator during gonadogenesis. To determine if Sox9 also has a role in a gecko species with TSD, we studied gonadal expression of Sox9 during embryonic development of the Leopard gecko (Eublepharis macularius). Gecko Sox9 was found to be highly conserved at the nucleotide level when compared to other vertebrate species including human, chick, alligator, and turtle. Sox9 was found to be expressed in embryos incubated at the male-producing temperature (32.5 degrees C) as well as in embryos incubated at the female-producing temperatures (26 and 34 degrees C), Northern blot analysis showed that Sox9 was expressed at both temperatures from morphological stages 31 to 37. mRNA in situ hybridisation on isolated urogenital systems showed expression at both female- and male-producing temperatures up to stage 36. After this stage, no expression was seen in the female gonads but expression remained in the male. These data provide further evidence that Sox9 is an essential component of a testis-determining pathway that is conserved in species with differing sex-determining mechanisms.

  15. Sox2 Promotes Malignancy in Glioblastoma by Regulating Plasticity and Astrocytic Differentiation

    Directory of Open Access Journals (Sweden)

    Artem D. Berezovsky

    2014-03-01

    Full Text Available The high-mobility group–box transcription factor sex-determining region Y–box 2 (Sox2 is essential for the maintenance of stem cells from early development to adult tissues. Sox2 can reprogram differentiated cells into pluripotent cells in concert with other factors and is overexpressed in various cancers. In glioblastoma (GBM, Sox2 is a marker of cancer stemlike cells (CSCs in neurosphere cultures and is associated with the proneural molecular subtype. Here, we report that Sox2 expression pattern in GBM tumors and patient-derived mouse xenografts is not restricted to a small percentage of cells and is coexpressed with various lineage markers, suggesting that its expression extends beyond CSCs to encompass more differentiated neoplastic cells across molecular subtypes. Employing a CSC derived from a patient with GBM and isogenic differentiated cell model, we show that Sox2 knockdown in the differentiated state abolished dedifferentiation and acquisition of CSC phenotype. Furthermore, Sox2 deficiency specifically impaired the astrocytic component of a biphasic gliosarcoma xenograft model while allowing the formation of tumors with sarcomatous phenotype. The expression of genes associated with stem cells and malignancy were commonly downregulated in both CSCs and serum-differentiated cells on Sox2 knockdown. Genes previously shown to be associated with pluripontency and CSCs were only affected in the CSC state, whereas embryonic stem cell self-renewal genes and cytokine signaling were downregulated, and the Wnt pathway activated in differentiated Sox2-deficient cells. Our results indicate that Sox2 regulates the expression of key genes and pathways involved in GBM malignancy, in both cancer stemlike and differentiated cells, and maintains plasticity for bidirectional conversion between the two states, with significant clinical implications.

  16. SOX4 expression is associated with treatment failure and chemoradioresistance in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Yoon, Tae Mi; Kim, Sun-Ae; Cho, Wan Seok; Lee, Dong Hoon; Lee, Joon Kyoo; Park, Young-Lan; Lee, Kyung-Hwa; Lee, Jae Hyuk; Kweon, Sun-Seog; Chung, Ik-Joo; Lim, Sang Chul; Joo, Young-Eun

    2015-01-01

    In humans, sex-determining region-Y (SRY) related high-mobility-group box 4 (SOX4) is linked to development and tumorigenesis. SOX4 is over-expressed in several cancers and has prognostic significance. This study evaluated whether SOX4 affects oncogenic behavior and chemoradiotherapy response in head and neck squamous cell carcinoma (HNSCC) cells, and documented the relationship between its expression and prognosis in oral squamous cell carcinoma (OSCC). We used small interfering RNA in HNSCC cells to evaluate the effect of SOX4 on cell proliferation, apoptosis, chemoradiation-induced apoptosis, invasion, and migration. SOX4 expression in OSCC tissues was investigated by immunohistochemistry. SOX4 knockdown (KO) decreased cell proliferation and induced apoptosis by activating caspases-3 and −7, and poly-ADP ribose polymerase and suppressing X-linked inhibitor of apoptosis protein in HNSCC cells; it also enhanced radiation/cisplatin-induced apoptosis; and suppressed tumor cell invasion and migration. Immunostaining showed SOX4 protein was significantly increased in OSCC tissues compared with adjacent normal mucosa. SOX4 expression was observed in 51.8 % of 85 OSCC tissues, and was significantly correlated with treatment failure (P = 0.032) and shorter overall survival (P = 0.036) in patients with OSCC. SOX4 may contribute to oncogenic phenotypes of HNSCC cells by promoting cell survival and causing chemoradioresistance. It could be a potential prognostic marker for OSCC. The online version of this article (doi:10.1186/s12885-015-1875-8) contains supplementary material, which is available to authorized users

  17. Suppression of SOX18 by siRNA inhibits cell growth and invasion of breast cancer cells.

    Science.gov (United States)

    Zhang, Jianxiang; Ma, Yanmei; Wang, Shoujun; Chen, Fu; Gu, Yuanting

    2016-06-01

    Breast cancer is the most common malignancy in women around the world, and its incidence and mortality rates are still rising. An increasing number of studies have reported that SOX18 plays an important role in various cancers. However, the role of SOX18 in breast cancer remains poorly understood. In this study, we aimed to investigate the biological role and potential molecular mechanism of SOX18 in breast cancer. We found that the mRNA and protein expression levels of SOX18 were prevalently and significantly overexpressed in human breast cancer cell lines. Next, we performed loss-of-function experiments by transfection of two breast cancer cell lines, BT-474 and MCF-7, with SOX18 small interfering RNAs (siRNA). Results showed that SOX18 siRNA transfection significantly suppressed mRNA and protein expression of SOX18 in breast cancer cells. Furthermore, knockdown of SOX18 significantly inhibited cell proliferation and invasion, but promoted apoptosis in breast cancer cells. Importantly, several oncogenic proteins, including the Ras homolog gene family member A (RhoA), platelet-derived growth factor B (PDGFB), Insulin-like growth factor 1 receptor (IGF-1R), and matrix metalloproteinase-7 (MMP-7), were markedly decreased by SOX18 siRNA. Taken together, the results of our study suggest that knockdown of SOX18 inhibits breast cancer cell growth and invasion, possibly by downregulating downstream oncogenic proteins, providing novel insights into the development of breast cancer therapy through targeting of SOX18.

  18. The role of Sox6 in zebrafish muscle fiber type specification.

    Science.gov (United States)

    Jackson, Harriet E; Ono, Yosuke; Wang, Xingang; Elworthy, Stone; Cunliffe, Vincent T; Ingham, Philip W

    2015-01-01

    The transcription factor Sox6 has been implicated in regulating muscle fiber type-specific gene expression in mammals. In zebrafish, loss of function of the transcription factor Prdm1a results in a slow to fast-twitch fiber type transformation presaged by ectopic expression of sox6 in slow-twitch progenitors. Morpholino-mediated Sox6 knockdown can suppress this transformation but causes ectopic expression of only one of three slow-twitch specific genes assayed. Here, we use gain and loss of function analysis to analyse further the role of Sox6 in zebrafish muscle fiber type specification. The GAL4 binary misexpression system was used to express Sox6 ectopically in zebrafish embryos. Cis-regulatory elements were characterized using transgenic fish. Zinc finger nuclease mediated targeted mutagenesis was used to analyse the effects of loss of Sox6 function in embryonic, larval and adult zebrafish. Zebrafish transgenic for the GCaMP3 Calcium reporter were used to assay Ca2+ transients in wild-type and mutant muscle fibres. Ectopic Sox6 expression is sufficient to downregulate slow-twitch specific gene expression in zebrafish embryos. Cis-regulatory elements upstream of the slow myosin heavy chain 1 (smyhc1) and slow troponin c (tnnc1b) genes contain putative Sox6 binding sites required for repression of the former but not the latter. Embryos homozygous for sox6 null alleles expressed tnnc1b throughout the fast-twitch muscle whereas other slow-specific muscle genes, including smyhc1, were expressed ectopically in only a subset of fast-twitch fibers. Ca2+ transients in sox6 mutant fast-twitch fibers were intermediate in their speed and amplitude between those of wild-type slow- and fast-twitch fibers. sox6 homozygotes survived to adulthood and exhibited continued misexpression of tnnc1b as well as smaller slow-twitch fibers. They also exhibited a striking curvature of the spine. The Sox6 transcription factor is a key regulator of fast-twitch muscle fiber differentiation

  19. Overexpression of SOX18 correlates with accelerated cell growth and poor prognosis in human pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Wang, Yazhou; Guo, Huahu; Zhang, Dafang; Yu, Xin; Leng, Xisheng; Li, Shu; Zhu, Weihua

    2016-01-01

    Transcription factor SOX18 has been proved to play a significant role in carcinogenesis. However, no investigation was performed about the expression of SOX18 in pancreatic ductal adenocarcinoma (PDAC). In our work, we found that the PDAC tissues had higher level of SOX18 mRNA and protein expression than matched non-tumor pancreatic tissues and high level of SOX18 protein indicated poor prognosis for PDAC patients. After knockdown of SOX18 gene in PANC-1 and SW1990 cell lines, which showed higher expression level of SOX18 among five PDAC cell lines, the abilities of proliferation, migration and invasion were inhibited and the tumor growth was suppressed in vivo. In addition, the flow cytometry results indicated that down-regulation of SOX18 induced G1/S phase arrest. Furthermore, we found that the expression of cyclin D1, c-myc and MMP-7, three tumorigenesis promoters, was inhabited with downregulation of SOX18. In conclusion, our study reveals that SOX18 plays a significant role in promoting the growth of PDAC, and might serve as a promising target for PDAC therapy. - Highlights: • Overexpression of SOX18 correlates with poor prognosis for pancreatic cancer. • SOX18 promotes pancreatic cancer cell growth in vitro and in vivo. • SOX18 promotes pancreatic cancer cell migration and invasion. • Knockdown of SOX18 induces G1/S phase arrest. • Knockdown of SOX18 induces decrease of cyclin D1, c-myc and MMP-7.

  20. The Impact of an Integrated Program of Return-to-Field and Targeted Trap-Neuter-Return on Feline Intake and Euthanasia at a Municipal Animal Shelter.

    Science.gov (United States)

    Spehar, Daniel D; Wolf, Peter J

    2018-04-13

    Available evidence indicates that overall levels of feline intake and euthanasia at U.S. shelters have significantly declined in recent decades. Nevertheless, millions of cats, many of them free-roaming, continue to be admitted to shelters each year. In some locations, as many as 70% of cats, perhaps up to one million or more per year nationally, are euthanized. New approaches, including return-to-field (RTF) and targeted trap-neuter-return (TNR) appear to have transformative potential. The purpose of the present study was to examine changes in feline intake and euthanasia, as well as additional associated metrics, at a municipal animal shelter in Albuquerque, New Mexico, after institutionalized RTF and targeted TNR protocols, together referred to as a community cat program (CCP), were added to ongoing community-based TNR efforts and a pilot RTF initiative. Over the course of the CCP, which ran from April 2012 to March 2015, 11,746 cats were trapped, sterilized, vaccinated, and returned or adopted. Feline euthanasia at the Albuquerque Animal Welfare Department (AAWD) declined by 84.1% and feline intake dropped by 37.6% over three years; the live release rate (LRR) increased by 47.7% due primarily to these reductions in both intake and euthanasia. Modest increases in the percentage of cats returned to owner (RTO) and the adoption rate were also observed, although both metrics decreased on an absolute basis, while the number of calls to the city about dead cats declined.

  1. The Impact of an Integrated Program of Return-to-Field and Targeted Trap-Neuter-Return on Feline Intake and Euthanasia at a Municipal Animal Shelter

    Directory of Open Access Journals (Sweden)

    Daniel D. Spehar

    2018-04-01

    Full Text Available Available evidence indicates that overall levels of feline intake and euthanasia at U.S. shelters have significantly declined in recent decades. Nevertheless, millions of cats, many of them free-roaming, continue to be admitted to shelters each year. In some locations, as many as 70% of cats, perhaps up to one million or more per year nationally, are euthanized. New approaches, including return-to-field (RTF and targeted trap-neuter-return (TNR appear to have transformative potential. The purpose of the present study was to examine changes in feline intake and euthanasia, as well as additional associated metrics, at a municipal animal shelter in Albuquerque, New Mexico, after institutionalized RTF and targeted TNR protocols, together referred to as a community cat program (CCP, were added to ongoing community-based TNR efforts and a pilot RTF initiative. Over the course of the CCP, which ran from April 2012 to March 2015, 11,746 cats were trapped, sterilized, vaccinated, and returned or adopted. Feline euthanasia at the Albuquerque Animal Welfare Department (AAWD declined by 84.1% and feline intake dropped by 37.6% over three years; the live release rate (LRR increased by 47.7% due primarily to these reductions in both intake and euthanasia. Modest increases in the percentage of cats returned to owner (RTO and the adoption rate were also observed, although both metrics decreased on an absolute basis, while the number of calls to the city about dead cats declined.

  2. [Analysis of SOX10 gene mutation in a family affected with Waardenburg syndrome type II].

    Science.gov (United States)

    Zheng, Lei; Yan, Yousheng; Chen, Xue; Zhang, Chuan; Zhang, Qinghua; Feng, Xuan; Hao, Shen

    2018-02-10

    OBJECTIVE To detect potential mutation of SOX10 gene in a pedigree affected with Warrdenburg syndrome type II. METHODS Genomic DNA was extracted from peripheral blood samples of the proband and his family members. Exons and flanking sequences of MITF, PAX3, SOX10, SNAI2, END3 and ENDRB genes were analyzed by chip capturing and high throughput sequencing. Suspected mutations were verified with Sanger sequencing. RESULTS A c.127C>T (p.R43X) mutation of the SOX10 gene was detected in the proband, for which both parents showed a wild-type genotype. CONCLUSION The c.127C>T (p.R43X) mutation of SOX10 gene probably underlies the ocular symptoms and hearing loss of the proband.

  3. A novel heterozygous SOX2 mutation causing congenital bilateral anophthalmia, hypogonadotropic hypogonadism and growth hormone deficiency.

    Science.gov (United States)

    Macchiaroli, Annamaria; Kelberman, Daniel; Auriemma, Renata Simona; Drury, Suzanne; Islam, Lily; Giangiobbe, Sara; Ironi, Gabriele; Lench, Nicholas; Sowden, Jane C; Colao, Annamaria; Pivonello, Rosario; Cavallo, Luciano; Gasperi, Maurizio; Faienza, Maria Felicia

    2014-01-25

    Heterozygous de novo mutations in SOX2 have been reported in approximately 10-20% of patients with unilateral or bilateral anophthalmia or microphthalmia. An additional phenotype of hypopituitarism, with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, has been reported in patients carrying SOX2 alterations. We report a novel heterozygous mutation in the SOX2 gene in a male affected with congenital bilateral anophthalmia, hypogonadotrophic hypogonadism and growth hormone deficiency. The mutation we describe is a cytosine deletion in position 905 (c905delC) which causes frameshift and an aberrant C-terminal domain. Our report highlights the fact that subjects affected with eye anomalies and harboring SOX2 mutations are at high risk for gonadotropin deficiency, which has important implications for their clinical management. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. SoxB2 in sea urchin development: implications in neurogenesis, ciliogenesis and skeletal patterning.

    Science.gov (United States)

    Anishchenko, Evgeniya; Arnone, Maria Ina; D'Aniello, Salvatore

    2018-01-01

    Current studies in evolutionary developmental biology are focused on the reconstruction of gene regulatory networks in target animal species. From decades, the scientific interest on genetic mechanisms orchestrating embryos development has been increasing in consequence to the fact that common features shared by evolutionarily distant phyla are being clarified. In 2011, a study across eumetazoan species showed for the first time the existence of a highly conserved non-coding element controlling the SoxB2 gene, which is involved in the early specification of the nervous system. This discovery raised several questions about SoxB2 function and regulation in deuterostomes from an evolutionary point of view. Due to the relevant phylogenetic position within deuterostomes, the sea urchin Strongylocentrotus purpuratus represents an advantageous animal model in the field of evolutionary developmental biology. Herein, we show a comprehensive study of SoxB2 functions in sea urchins, in particular its expression pattern in a wide range of developmental stages, and its co-localization with other neurogenic markers, as SoxB1 , SoxC and Elav . Moreover, this work provides a detailed description of the phenotype of sea urchin SoxB2 knocked-down embryos, confirming its key function in neurogenesis and revealing, for the first time, its additional roles in oral and aboral ectoderm cilia and skeletal rod morphology. We concluded that SoxB2 in sea urchins has a neurogenic function; however, this gene could have multiple roles in sea urchin embryogenesis, expanding its expression in non-neurogenic cells. We showed that SoxB2 is functionally conserved among deuterostomes and suggested that in S. purpuratus this gene acquired additional functions, being involved in ciliogenesis and skeletal patterning.

  5. Mutations in SOX17 are Associated with Congenital Anomalies of the Kidney and the Urinary Tract

    Science.gov (United States)

    Gimelli, Stefania; Caridi, Gianluca; Beri, Silvana; McCracken, Kyle; Bocciardi, Renata; Zordan, Paola; Dagnino, Monica; Fiorio, Patrizia; Murer, Luisa; Benetti, Elisa; Zuffardi, Orsetta; Giorda, Roberto; Wells, James M; Gimelli, Giorgio; Ghiggeri, Gian Marco

    2010-01-01

    Congenital anomalies of the kidney and the urinary tract (CAKUT) represent a major source of morbidity and mortality in children. Several factors (PAX, SOX,WNT, RET, GDFN, and others) play critical roles during the differentiation process that leads to the formation of nephron epithelia. We have identified mutations in SOX17, an HMG-box transcription factor and Wnt signaling antagonist, in eight patients with CAKUT (seven vesico-ureteric reflux, one pelvic obstruction). One mutation, c.775T>A (p.Y259N), recurred in six patients. Four cases derived from two small families; renal scars with urinary infection represented the main symptom at presentation in all but two patients. Transfection studies indicated a 5–10-fold increase in the levels of the mutant protein relative to wild-type SOX17 in transfected kidney cells. Moreover we observed a corresponding increase in the ability of SOX17 p.Y259N to inhibit Wnt/β-catenin transcriptional activity, which is known to regulate multiple stages of kidney and urinary tract development. In conclusion, SOX17 p.Y259N mutation is recurrent in patients with CAKUT. Our data shows that this mutation correlates with an inappropriate accumulation of SOX17-p.Y259N protein and inhibition of the β-catenin/Wnt signaling pathway. These data indicate a role of SOX17 in human kidney and urinary tract development and implicate the SOX17–p.Y259N mutation as a causative factor in CAKUT. Hum Mutat 31:1352–1359, 2010. © 2010 Wiley-Liss, Inc. PMID:20960469

  6. Ion Trap Quantum Computing

    Science.gov (United States)

    2011-12-01

    variations of ion traps, including (1) the cylindrically symmetric 3D ring trap; (2) the linear trap with a combination of cavity QED; (#) the symmetric...concepts of quantum information. The major demonstration has been the test of a Bell inequality as demonstrated by Rowe et al. [50] and a decoherence...famous physics experiment [62]. Wolfgang Paul demonstrated a similar apparatus during his Nobel Prize speech [63]. This device is hyperbolic- parabolic

  7. Towards trapped antihydrogen

    CERN Document Server

    Jorgensen, L V; Bertsche, W; Boston, A; Bowe, P D; Cesar, C L; Chapman, S; Charlton, M; Fajans, J; Fujiwara, M C; Funakoshi, R; Gill, D R; Hangst, J S; Hayano, R S; Hydomako, R; Jenkins, M J; Kurchaninov, L; Madsen, N; Nolan, P; Olchanski, K; Olin, A; Page, R D; Povilus, A; Robicheaux, F; Sarid, E; Silveira, D M; Storey, J W; Thompson, R I; van der Werf, D P; Wurtele, J S; Yamazaki, Y

    2008-01-01

    Substantial progress has been made in the last few years in the nascent field of antihydrogen physics. The next big step forward is expected to be the trapping of the formed antihydrogen atoms using a magnetic multipole trap. ALPHA is a new international project that started to take data in 2006 at CERN’s Antiproton Decelerator facility. The primary goal of ALPHA is stable trapping of cold antihydrogen atoms to facilitate measurements of its properties. We discuss the status of the ALPHA project and the prospects for antihydrogen trapping.

  8. The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner

    International Nuclear Information System (INIS)

    Yano, Fumiko; Kugimiya, Fumitaka; Ohba, Shinsuke; Ikeda, Toshiyuki; Chikuda, Hirotaka; Ogasawara, Toru; Ogata, Naoshi; Takato, Tsuyoshi; Nakamura, Kozo; Kawaguchi, Hiroshi; Chung, Ung-il

    2005-01-01

    To better understand the role of the canonical Wnt signaling pathway in cartilage development, we adenovirally expressed a constitutively active (Canada) or a dominant negative (dn) form of lymphoid enhancer factor-1 (LEF-1), the main nuclear effector of the pathway, in undifferentiated mesenchymal cells, chondrogenic cells, and primary chondrocytes, and examined the expression of markers for chondrogenic differentiation and hypertrophy. caLEF-1 and LiCl, an activator of the canonical pathway, promoted both chondrogenic differentiation and hypertrophy, whereas dnLEF-1 and the gene silencing of β-catenin suppressed LiCl-promoted effects. To investigate whether these effects were dependent on Sox9, a master regulator of cartilage development, we stimulated Sox9-deficient ES cells with the pathway. caLEF-1 and LiCl promoted both chondrogenic differentiation and hypertrophy in wild-type, but not in Sox9-deficient, cells. The response of Sox9-deficient cells was restored by the adenoviral expression of Sox9. Thus, the canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner

  9. A Korean boy with 46,XX testicular disorder of sex development caused by SOX9 duplication.

    Science.gov (United States)

    Lee, Gyung Min; Ko, Jung Min; Shin, Choong Ho; Yang, Sei Won

    2014-06-01

    The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male syndrome, is a rare form of DSD and clinical phenotype shows complete sex reversal from female to male. The sex-determining region Y (SRY) gene can be identified in most 46,XX testicular DSD patients; however, approximately 20% of patients with 46,XX testicular DSD are SRY-negative. The SRY-box 9 (SOX9) gene has several important functions during testis development and differentiation in males, and overexpression of SOX9 leads to the male development of 46,XX gonads in the absence of SRY. In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans. Here, we report a 4.2-year-old SRY-negative 46,XX boy with complete sex reversal caused by SOX9 duplication for the first time in Korea. He showed normal external and internal male genitalia except for small testes. Fluorescence in situ hybridization and polymerase chain reaction (PCR) analyses failed to detect the presence of SRY, and SOX9 intragenic mutation was not identified by direct sequencing analysis. Therefore, we performed real-time PCR analyses with specific primer pairs, and duplication of the SOX9 gene was revealed. Although SRY-negative 46,XX testicular DSD is a rare condition, an effort to make an accurate diagnosis is important for the provision of proper genetic counseling and for guiding patients in their long-term management.

  10. Sox5 Functions as a Fate Switch in Medaka Pigment Cell Development

    Science.gov (United States)

    Nagao, Yusuke; Suzuki, Takao; Shimizu, Atsushi; Kimura, Tetsuaki; Seki, Ryoko; Adachi, Tomoko; Inoue, Chikako; Omae, Yoshihiro; Kamei, Yasuhiro; Hara, Ikuyo; Taniguchi, Yoshihito; Naruse, Kiyoshi; Wakamatsu, Yuko; Kelsh, Robert N.; Hibi, Masahiko; Hashimoto, Hisashi

    2014-01-01

    Mechanisms generating diverse cell types from multipotent progenitors are crucial for normal development. Neural crest cells (NCCs) are multipotent stem cells that give rise to numerous cell-types, including pigment cells. Medaka has four types of NCC-derived pigment cells (xanthophores, leucophores, melanophores and iridophores), making medaka pigment cell development an excellent model for studying the mechanisms controlling specification of distinct cell types from a multipotent progenitor. Medaka many leucophores-3 (ml-3) mutant embryos exhibit a unique phenotype characterized by excessive formation of leucophores and absence of xanthophores. We show that ml-3 encodes sox5, which is expressed in premigratory NCCs and differentiating xanthophores. Cell transplantation studies reveal a cell-autonomous role of sox5 in the xanthophore lineage. pax7a is expressed in NCCs and required for both xanthophore and leucophore lineages; we demonstrate that Sox5 functions downstream of Pax7a. We propose a model in which multipotent NCCs first give rise to pax7a-positive partially fate-restricted intermediate progenitors for xanthophores and leucophores; some of these progenitors then express sox5, and as a result of Sox5 action develop into xanthophores. Our results provide the first demonstration that Sox5 can function as a molecular switch driving specification of a specific cell-fate (xanthophore) from a partially-restricted, but still multipotent, progenitor (the shared xanthophore-leucophore progenitor). PMID:24699463

  11. Sox5 functions as a fate switch in medaka pigment cell development.

    Directory of Open Access Journals (Sweden)

    Yusuke Nagao

    2014-04-01

    Full Text Available Mechanisms generating diverse cell types from multipotent progenitors are crucial for normal development. Neural crest cells (NCCs are multipotent stem cells that give rise to numerous cell-types, including pigment cells. Medaka has four types of NCC-derived pigment cells (xanthophores, leucophores, melanophores and iridophores, making medaka pigment cell development an excellent model for studying the mechanisms controlling specification of distinct cell types from a multipotent progenitor. Medaka many leucophores-3 (ml-3 mutant embryos exhibit a unique phenotype characterized by excessive formation of leucophores and absence of xanthophores. We show that ml-3 encodes sox5, which is expressed in premigratory NCCs and differentiating xanthophores. Cell transplantation studies reveal a cell-autonomous role of sox5 in the xanthophore lineage. pax7a is expressed in NCCs and required for both xanthophore and leucophore lineages; we demonstrate that Sox5 functions downstream of Pax7a. We propose a model in which multipotent NCCs first give rise to pax7a-positive partially fate-restricted intermediate progenitors for xanthophores and leucophores; some of these progenitors then express sox5, and as a result of Sox5 action develop into xanthophores. Our results provide the first demonstration that Sox5 can function as a molecular switch driving specification of a specific cell-fate (xanthophore from a partially-restricted, but still multipotent, progenitor (the shared xanthophore-leucophore progenitor.

  12. Disrupted SOX10 function causes spongiform neurodegeneration in gray tremor mice

    Science.gov (United States)

    Anderson, Sarah R.; Lee, Inyoul; Ebeling, Christine; Stephenson, Dennis A.; Schweitzer, Kelsey M.; Baxter, David; Moon, Tara M.; LaPierre, Sarah; Jaques, Benjamin; Silvius, Derek; Wegner, Michael; Hood, Leroy E.; Carlson, George; Gunn, Teresa M.

    2014-01-01

    Mice homozygous for the gray tremor (gt) mutation have a pleiotropic phenotype that includes pigmentation defects, megacolon, whole body tremors, sporadic seizures, hypo- and dysmyelination of the CNS and PNS, vacuolation of the CNS, and early death. Vacuolation similar to that caused by prions was originally reported to be transmissible, but subsequent studies showed the inherited disease was not infectious. The gt mutation mapped to distal mouse chromosome 15, to the same region as Sox10, which encodes a transcription factor with essential roles in neural crest survival and differentiation. As dominant mutations in mouse or human SOX10 cause white spotting and intestinal aganglionosis, we screened the Sox10 coding region for mutations in gt/gt DNA. An adenosine to guanine transversion was identified in exon 2 that changes a highly conserved glutamic acid residue in the SOX10 DNA binding domain to glycine. This mutant allele was not seen in wildtype mice, including the related GT/Le strain, and failed to complement a Sox10 null allele. Gene expression analysis revealed significant down-regulation of genes involved in myelin lipid biosynthesis pathways in gt/gt brains. Knockout mice for some of these genes develop CNS vacuolation and/or myelination defects, suggesting that their down-regulation may contribute to these phenotypes in gt mutants and could underlie the neurological phenotypes associated with Peripheral demyelinating neuropathy-Central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung (PCWH) disease, caused by mutations in human SOX10. PMID:25399070

  13. Deletions at the SOX10 gene locus cause Waardenburg syndrome types 2 and 4.

    Science.gov (United States)

    Bondurand, Nadege; Dastot-Le Moal, Florence; Stanchina, Laure; Collot, Nathalie; Baral, Viviane; Marlin, Sandrine; Attie-Bitach, Tania; Giurgea, Irina; Skopinski, Laurent; Reardon, William; Toutain, Annick; Sarda, Pierre; Echaieb, Anis; Lackmy-Port-Lis, Marilyn; Touraine, Renaud; Amiel, Jeanne; Goossens, Michel; Pingault, Veronique

    2007-12-01

    Waardenburg syndrome (WS) is an auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair and skin. Depending on additional symptoms, WS is classified into four subtypes, WS1-WS4. Absence of additional features characterizes WS2. The association of facial dysmorphic features defines WS1 and WS3, whereas the association with Hirschsprung disease (aganglionic megacolon) characterizes WS4, also called "Waardenburg-Hirschsprung disease." Mutations within the genes MITF and SNAI2 have been identified in WS2, whereas mutations of EDN3, EDNRB, and SOX10 have been observed in patients with WS4. However, not all cases are explained at the molecular level, which raises the possibility that other genes are involved or that some mutations within the known genes are not detected by commonly used genotyping methods. We used a combination of semiquantitative fluorescent multiplex polymerase chain reaction and fluorescent in situ hybridization to search for SOX10 heterozygous deletions. We describe the first characterization of SOX10 deletions in patients presenting with WS4. We also found SOX10 deletions in WS2 cases, making SOX10 a new gene of WS2. Interestingly, neurological phenotypes reminiscent of that observed in WS4 (PCWH syndrome [peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, WS, and Hirschsprung disease]) were observed in some WS2-affected patients with SOX10 deletions. This study further characterizes the molecular complexity and the close relationship that links the different subtypes of WS.

  14. Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

    Directory of Open Access Journals (Sweden)

    Irene Forno

    Full Text Available Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the "stemness" marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.

  15. Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

    Science.gov (United States)

    Forno, Irene; Ferrero, Stefano; Russo, Maria Veronica; Gazzano, Giacomo; Giangiobbe, Sara; Montanari, Emanuele; Del Nero, Alberto; Rocco, Bernardo; Albo, Giancarlo; Languino, Lucia R; Altieri, Dario C; Vaira, Valentina; Bosari, Silvano

    2015-01-01

    Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the "stemness" marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.

  16. Adsorption of SOX and NOX in activated viscose fibers

    Directory of Open Access Journals (Sweden)

    Ana Carolina O. Plens

    2015-06-01

    Full Text Available SOx and NOx are emissions resulting from combustion processes and are the main agents that contribute to the formation of acid rain, which causes harm to humans and the environment. Several techniques for removing these pollutants are applied in i.e. oil refineries, thermoelectric that use petroleum oils and vehicular pollution. Among these, highlight the adsorption of contaminants by the usage of activated carbon fibers and activated carbon, which are characterized by high surface area and uniform distribution of pores, providing appropriate conditions for application in processes of removing environmental contaminants. In the present work, activated viscose fibers (AVF were prepared and applied in adsorption experiments of NO and SO2. The materials produced showed high values of surface area, with a predominance of micro pores with diameters in the range of 1.0 nm. The AVF had satisfactory performance in the removal of contaminants and are compatible with other synthetic fibers. Thus, the formation of active sites of carbon provides contaminants adsorption, demonstrating that carbon fibers cloth can be applied for the removal of pollutants.

  17. SOX2 and SOX2-MYC Reprogramming Process of Fibroblasts to the Neural Stem Cells Compromised by Senescence.

    Directory of Open Access Journals (Sweden)

    Marta Winiecka-Klimek

    Full Text Available Tumorigenic potential of induced pluripotent stem cells (iPSCs infiltrating population of induced neural stem cells (iNSCs generated from iPSCs may limit their medical applications. To overcome such a difficulty, direct reprogramming of adult somatic cells into iNSCs was proposed. The aim of this study was the systematic comparison of induced neural cells (iNc obtained with different methods-direct reprogramming of human adult fibroblasts with either SOX2 (SiNSc-like or SOX2 and c-MYC (SMiNSc-like and induced pluripotent stem cells differentiation to ebiNSc-in terms of gene expression profile, differentiation potential as well as proliferation properties. Immunocytochemistry and real-time PCR analyses were used to evaluate gene expression profile and differentiation potential of various iNc types. Bromodeoxyuridine (BrdU incorporation and senescence-associated beta-galactosidase (SA-β-gal assays were used to estimate proliferation potential. All three types of iNc were capable of neuronal differentiation; however, astrocytic differentiation was possible only in case of ebiNSc. Contrary to ebiNSc generation, the direct reprogramming was rarely a propitious process, despite 100% transduction efficiency. The potency of direct iNSCs-like cells generation was lower as compared to iNSCs obtained by iPSCs differentiation, and only slightly improved when c-MYC was added. Directly reprogrammed iNSCs-like cells were lacking the ability to differentiate into astrocytic cells and characterized by poor efficiency of neuronal cells formation. Such features indicated that these cells could not be fully reprogrammed, as confirmed mainly with senescence detection. Importantly, SiNSc-like and SMiNSc-like cells were unable to achieve the long-term survival and became senescent, which limits their possible therapeutic applicability. Our results suggest that iNSCs-like cells, generated in the direct reprogramming attempts, were either not fully reprogrammed or

  18. Versatile electrostatic trap

    NARCIS (Netherlands)

    van Veldhoven, J.; Bethlem, H.L.; Schnell, M.; Meijer, G.

    2006-01-01

    A four electrode electrostatic trap geometry is demonstrated that can be used to combine a dipole, quadrupole, and hexapole field. A cold packet of ND315 molecules is confined in both a purely quadrupolar and hexapolar trapping field and additionally, a dipole field is added to a hexapole field to

  19. Liquid metal cold trap

    International Nuclear Information System (INIS)

    Hundal, R.

    1976-01-01

    A cold trap assembly for removing impurities from a liquid metal is described. A hole between the incoming impure liquid metal and purified outgoing liquid metal acts as a continuous bleed means and thus prevents the accumulation of cover gases within the cold trap assembly

  20. The early human germ cell lineage does not express SOX2 during in vivo development or upon in vitro culture

    DEFF Research Database (Denmark)

    Perrett, Rebecca M; Turnpenny, Lee; Eckert, Judith J

    2008-01-01

    NANOG, POU5F1, and SOX2 are required by the inner cell mass of the blastocyst and act cooperatively to maintain pluripotency in both mouse and human embryonic stem cells. Inadequacy of any one of them causes loss of the undifferentiated state. Mouse primordial germ cells (PGCs), from which...... pluripotent embryonic germ cells (EGCs) are derived, also express POU5F1, NANOG, and SOX2. Thus, a similar expression profile has been predicted for human PGCs. Here we show by RT-PCR, immunoblotting, and immunohistochemistry that human PGCs express POU5F1 and NANOG but not SOX2, with no evidence...... of redundancy within the group B family of human SOX genes. Although lacking SOX2, proliferative human germ cells can still be identified in situ during early development and are capable of culture in vitro. Surprisingly, with the exception of FGF4, many stem cell-restricted SOX2 target genes remained detected...

  1. Deuterium trapping in tungsten

    Science.gov (United States)

    Poon, Michael

    Tungsten is one of the primary material candidates being investigated for use in the first-wall of a magnetic confinement fusion reactor. An ion accelerator was used to simulate the type of ion interaction that may occur at a plasma-facing material. Thermal desorption spectroscopy (TDS) was the primary tool used to analyze the effects of the irradiation. Secondary ion mass spectroscopy (SIMS) was used to determine the distribution of trapped D in the tungsten specimen. The tritium migration analysis program (TMAP) was used to simulate thermal desorption profiles from the D depth distributions. Fitting of the simulated thermal desorption profiles with the measured TDS results provided values of the D trap energies. Deuterium trapping in single crystal tungsten was studied as a function of the incident ion fluence, ion flux, irradiation temperature, irradiation history, and surface impurity levels during irradiation. The results show that deuterium was trapped at vacancies and voids. Two deuterium atoms could be trapped at a tungsten vacancy, with trapping energies of 1.4 eV and 1.2 eV for the first and second D atoms, respectively. In a tungsten void, D is trapped as atoms adsorbed on the inner walls of the void with a trap energy of 2.1 eV, or as D2 molecules inside the void with a trap energy of 1.2 eV. Deuterium trapping in polycrystalline tungsten was also studied as a function of the incident fluence, irradiation temperature, and irradiation history. Deuterium trapping in polycrystalline tungsten also occurs primarily at vacancies and voids with the same trap energies as in single crystal tungsten; however, the presence of grain boundaries promotes the formation of large surface blisters with high fluence irradiations at 500 K. In general, D trapping is greater in polycrystalline tungsten than in single crystal tungsten. To simulate mixed materials comprising of carbon (C) and tungsten, tungsten specimens were pre-irradiated with carbon ions prior to D

  2. Deuterium trapping in tungsten

    International Nuclear Information System (INIS)

    Poon, M.

    2004-01-01

    Tungsten is one of the primary material candidates being investigated for use in the first-wall of a magnetic confinement fusion reactor. An ion accelerator was used to simulate the type of ion interaction that may occur at a plasma-facing material. Thermal desorption spectroscopy (TDS) was the primary tool used to analyze the effects of the irradiation Secondary ion mass spectroscopy (SIMS) was used to determine the distribution of trapped D in the tungsten specimen. The tritium migration analysis program (TMAP) was used to simulate thermal desorption profiles from the D depth distributions. Fitting of the simulated thermal desorption profiles with the measured TDS results provided values of the D trap energies. . Deuterium trapping in single crystal tungsten was studied as a function of the incident ion fluence, ion flux, irradiation temperature, irradiation history, and surface impurity levels during irradiation The results show that deuterium was trapped at vacancies and voids. Two deuterium atoms could be trapped at a tungsten vacancy, with trapping energies of 1.4 eV and 1.2 eV for the first and second D atoms, respectively. In a tungsten void, D is trapped as atoms adsorbed on the inner walls of the void with a trap energy of 2.1 eV, or as D 2 molecules inside the void with a trap energy of 1.2 eV. . Deuterium trapping in polycrystalline tungsten was also studied as a function of the incident fluence, irradiation temperature, and irradiation history. Deuterium trapping in polycrystalline tungsten also occurs primarily at vacancies and voids with the same trap energies as in single crystal tungsten; however, the presence of grain boundaries promotes the formation of large surface blisters with high fluence irradiations at 500 K. In general, D trapping is greater in polycrystalline tungsten than in single crystal tungsten. To simulate mixed materials comprising of carbon (C) and tungsten, tungsten specimens were pre-irradiated with carbon ions prior to D

  3. Deuterium trapping in tungsten

    Energy Technology Data Exchange (ETDEWEB)

    Poon, M

    2004-07-01

    Tungsten is one of the primary material candidates being investigated for use in the first-wall of a magnetic confinement fusion reactor. An ion accelerator was used to simulate the type of ion interaction that may occur at a plasma-facing material. Thermal desorption spectroscopy (TDS) was the primary tool used to analyze the effects of the irradiation Secondary ion mass spectroscopy (SIMS) was used to determine the distribution of trapped D in the tungsten specimen. The tritium migration analysis program (TMAP) was used to simulate thermal desorption profiles from the D depth distributions. Fitting of the simulated thermal desorption profiles with the measured TDS results provided values of the D trap energies. . Deuterium trapping in single crystal tungsten was studied as a function of the incident ion fluence, ion flux, irradiation temperature, irradiation history, and surface impurity levels during irradiation The results show that deuterium was trapped at vacancies and voids. Two deuterium atoms could be trapped at a tungsten vacancy, with trapping energies of 1.4 eV and 1.2 eV for the first and second D atoms, respectively. In a tungsten void, D is trapped as atoms adsorbed on the inner walls of the void with a trap energy of 2.1 eV, or as D{sub 2} molecules inside the void with a trap energy of 1.2 eV. . Deuterium trapping in polycrystalline tungsten was also studied as a function of the incident fluence, irradiation temperature, and irradiation history. Deuterium trapping in polycrystalline tungsten also occurs primarily at vacancies and voids with the same trap energies as in single crystal tungsten; however, the presence of grain boundaries promotes the formation of large surface blisters with high fluence irradiations at 500 K. In general, D trapping is greater in polycrystalline tungsten than in single crystal tungsten. To simulate mixed materials comprising of carbon (C) and tungsten, tungsten specimens were pre-irradiated with carbon ions prior to D

  4. Trapping radioactive ions

    CERN Document Server

    Kluge, Heinz-Jürgen

    2004-01-01

    Trapping devices for atomic and nuclear physics experiments with radioactive ions are becoming more and more important at accelerator facilities. While about ten years ago only one online Penning trap experiment existed, namely ISOLTRAP at ISOLDE/CERN, meanwhile almost every radioactive beam facility has installed or plans an ion trap setup. This article gives an overview on ion traps in the operation, construction or planing phase which will be used for fundamental studies with short-lived radioactive nuclides such as mass spectrometry, laser spectroscopy and nuclear decay spectroscopy. In addition, this article summarizes the use of gas cells and radiofrequency quadrupole (Paul) traps at different facilities as a versatile tool for ion beam manipulation like retardation, cooling, bunching, and cleaning.

  5. Trapping radioactive ions

    International Nuclear Information System (INIS)

    Kluge, H.-J.; Blaum, K.

    2004-01-01

    Trapping devices for atomic and nuclear physics experiments with radioactive ions are becoming more and more important at accelerator facilities. While about ten years ago only one online Penning trap experiment existed, namely ISOLTRAP at ISOLDE/CERN, meanwhile almost every radioactive beam facility has installed or plans an ion trap setup. This article gives an overview on ion traps in the operation, construction or planing phase which will be used for fundamental studies with short-lived radioactive nuclides such as mass spectrometry, laser spectroscopy and nuclear decay spectroscopy. In addition, this article summarizes the use of gas cells and radiofrequency quadrupole (Paul) traps at different facilities as a versatile tool for ion beam manipulation like retardation, cooling, bunching, and cleaning

  6. Novel Ion Trap Design for Strong Ion-Cavity Coupling

    Directory of Open Access Journals (Sweden)

    Alejandro Márquez Seco

    2016-04-01

    Full Text Available We present a novel ion trap design which facilitates the integration of an optical fiber cavity into the trap structure. The optical fibers are confined inside hollow electrodes in such a way that tight shielding and free movement of the fibers are simultaneously achievable. The latter enables in situ optimization of the overlap between the trapped ions and the cavity field. Through numerical simulations, we systematically analyze the effects of the electrode geometry on the trapping characteristics such as trap depths, secular frequencies and the optical access angle. Additionally, we simulate the effects of the presence of the fibers and confirm the robustness of the trapping potential. Based on these simulations and other technical considerations, we devise a practical trap configuration that isviable to achieve strong coupling of a single ion.

  7. SOX9 as a Predictor for Neurogenesis Potentiality of Amniotic Fluid Stem Cells

    Science.gov (United States)

    Wei, Pei-Cih; Chao, Angel; Peng, Hsiu-Huei; Chao, An-Shine; Chang, Yao-Lung; Chang, Shuenn-Dyh; Wang, Hsin-Shih; Chang, Yu-Jen; Tsai, Ming-Song; Sieber, Martin; Chen, Hua-Chien; Chen, Shu-Jen; Lee, Yun-Shien

    2014-01-01

    Preclinical studies of amniotic fluid-derived cell therapy have been successful in the research of neurodegenerative diseases, peripheral nerve injury, spinal cord injury, and brain ischemia. Transplantation of human amniotic fluid stem cells (AFSCs) into rat brain ventricles has shown improvement in symptoms of Parkinson's disease and also highlighted the minimal immune rejection risk of AFSCs, even between species. Although AFSCs appeared to be a promising resource for cell-based regenerative therapy, AFSCs contain a heterogeneous pool of distinct cell types, rendering each preparation of AFSCs unique. Identification of predictive markers for neuron-prone AFSCs is necessary before such stem cell-based therapeutics can become a reality. In an attempt to identify markers of AFSCs to predict their ability for neurogenesis, we performed a two-phase study. In the discovery phase of 23 AFSCs, we tested ZNF521/Zfp521, OCT6, SOX1, SOX2, SOX3, and SOX9 as predictive markers of AFSCs for neural differentiation. In the validation phase, the efficacy of these predictive markers was tested in independent sets of 18 AFSCs and 14 dental pulp stem cells (DPSCs). We found that high expression of SOX9 in AFSCs is associated with good neurogenetic ability, and these positive correlations were confirmed in independent sets of AFSCs and DPSCs. Furthermore, knockdown of SOX9 in AFSCs inhibited their neuronal differentiation. In conclusion, the discovery of SOX9 as a predictive marker for neuron-prone AFSCs could expedite the selection of useful clones for regenerative medicine, in particular, in neurological diseases and injuries. PMID:25154783

  8. Identification of direct regulatory targets of the transcription factor Sox10 based on function and conservation

    Directory of Open Access Journals (Sweden)

    Lee Sanghyuk

    2008-09-01

    Full Text Available Abstract Background Sox10, a member of the Sry-related HMG-Box gene family, is a critical transcription factor for several important cell lineages, most notably the neural crest stem cells and the derivative peripheral glial cells and melanocytes. Thus far, only a handful of direct target genes are known for this transcription factor limiting our understanding of the biological network it governs. Results We describe identification of multiple direct regulatory target genes of Sox10 through a procedure based on function and conservation. By combining RNA interference technique and DNA microarray technology, we have identified a set of genes that show significant down-regulation upon introduction of Sox10 specific siRNA into Schwannoma cells. Subsequent comparative genomics analyses led to potential binding sites for Sox10 protein conserved across several mammalian species within the genomic region proximal to these genes. Multiple sites belonging to 4 different genes (proteolipid protein, Sox10, extracellular superoxide dismutase, and pleiotrophin were shown to directly interact with Sox10 by chromatin immunoprecipitation assay. We further confirmed the direct regulation through the identified cis-element for one of the genes, extracellular superoxide dismutase, using electrophoretic mobility shift assay and reporter assay. Conclusion In sum, the process of combining differential expression profiling and comparative genomics successfully led to further defining the role of Sox10, a critical transcription factor for the development of peripheral glia. Our strategy utilizing relatively accessible techniques and tools should be applicable to studying the function of other transcription factors.

  9. Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Li, Qiuping [Zhongshan Hospital of Fudan University, Shanghai 200032 (China); Yang, Zhiyuan; Wu, Guoqiang [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Sun, Shuhui [Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Gu, Jianxin [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Institutes of Biomedical Sciences of Fudan University, Shanghai 200032 (China); Wei, Yuanyan, E-mail: yywei@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Jiang, Jianhai, E-mail: jianhaijiang@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China)

    2010-07-09

    Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.

  10. Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

    International Nuclear Information System (INIS)

    Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan; Li, Qiuping; Yang, Zhiyuan; Wu, Guoqiang; Sun, Shuhui; Gu, Jianxin; Wei, Yuanyan; Jiang, Jianhai

    2010-01-01

    Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.

  11. Sox9 is required for precursor cell expansion and extracellular matrix organization during mouse heart valve development.

    Science.gov (United States)

    Lincoln, Joy; Kist, Ralf; Scherer, Gerd; Yutzey, Katherine E

    2007-05-01

    Heart valve structures derived from mesenchymal cells of the endocardial cushions (ECs) are composed of highly organized cell lineages and extracellular matrix. Sox9 is a transcription factor required for both early and late stages of cartilage formation that is also expressed in the developing valves of the heart. The requirements for Sox9 function during valvulogenesis and adult valve homeostasis in mice were examined by conditional inactivation of Sox9 using Tie2-cre and Col2a1-cre transgenes. Sox9(flox/flox);Tie2-cre mice die before E14.5 with hypoplastic ECs, reduced cell proliferation and altered extracellular matrix protein (ECM) deposition. Sox9(flox/flox);Col2a1-cre mice die at birth with thickened heart valve leaflets, reduced expression of cartilage-associated proteins and abnormal ECM patterning. Thickened valve leaflets and calcium deposits, characteristic of valve disease, are observed in heterozygous adult Sox9(flox/+);Col2a1-cre mice. Therefore, Sox9 is required early in valve development for expansion of the precursor cell population and later is required for normal expression and distribution of valvular ECM proteins. These data indicate that Sox9 is required for early and late stages of valvulogenesis and identify a potential role for Sox9 in valve disease mechanisms.

  12. Nematode-Trapping Fungi.

    Science.gov (United States)

    Jiang, Xiangzhi; Xiang, Meichun; Liu, Xingzhong

    2017-01-01

    Nematode-trapping fungi are a unique and intriguing group of carnivorous microorganisms that can trap and digest nematodes by means of specialized trapping structures. They can develop diverse trapping devices, such as adhesive hyphae, adhesive knobs, adhesive networks, constricting rings, and nonconstricting rings. Nematode-trapping fungi have been found in all regions of the world, from the tropics to Antarctica, from terrestrial to aquatic ecosystems. They play an important ecological role in regulating nematode dynamics in soil. Molecular phylogenetic studies have shown that the majority of nematode-trapping fungi belong to a monophyletic group in the order Orbiliales (Ascomycota). Nematode-trapping fungi serve as an excellent model system for understanding fungal evolution and interaction between fungi and nematodes. With the development of molecular techniques and genome sequencing, their evolutionary origins and divergence, and the mechanisms underlying fungus-nematode interactions have been well studied. In recent decades, an increasing concern about the environmental hazards of using chemical nematicides has led to the application of these biological control agents as a rapidly developing component of crop protection.

  13. Identification and functional analysis of SOX10 missense mutations in different subtypes of Waardenburg syndrome.

    Science.gov (United States)

    Chaoui, Asma; Watanabe, Yuli; Touraine, Renaud; Baral, Viviane; Goossens, Michel; Pingault, Veronique; Bondurand, Nadege

    2011-12-01

    Waardenburg syndrome (WS) is a rare disorder characterized by pigmentation defects and sensorineural deafness, classified into four clinical subtypes, WS1-S4. Whereas the absence of additional features characterizes WS2, association with Hirschsprung disease defines WS4. WS is genetically heterogeneous, with six genes already identified, including SOX10. About 50 heterozygous SOX10 mutations have been described in patients presenting with WS2 or WS4, with or without myelination defects of the peripheral and central nervous system (PCWH, Peripheral demyelinating neuropathy-Central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung disease, or PCW, PCWH without HD). The majority are truncating mutations that most often remove the main functional domains of the protein. Only three missense mutations have been thus far reported. In the present study, novel SOX10 missense mutations were found in 11 patients and were examined for effects on SOX10 characteristics and functions. The mutations were associated with various phenotypes, ranging from WS2 to PCWH. All tested mutations were found to be deleterious. Some mutants presented with partial cytoplasmic redistribution, some lost their DNA-binding and/or transactivation capabilities on various tissue-specific target genes. Intriguingly, several mutants were redistributed in nuclear foci. Whether this phenomenon is a cause or a consequence of mutation-associated pathogenicity remains to be determined, but this observation could help to identify new SOX10 modes of action. © 2011 Wiley-Liss, Inc.

  14. Long-Term Expandable SOX9+ Chondrogenic Ectomesenchymal Cells from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Katsutsugu Umeda

    2015-04-01

    Full Text Available Here we report the successful generation and long-term expansion of SOX9-expressing CD271+PDGFRα+CD73+ chondrogenic ectomesenchymal cells from the PAX3/SOX10/FOXD3-expressing MIXL1−CD271hiPDGFRαloCD73− neural crest-like progeny of human pluripotent stem cells in a chemically defined medium supplemented with Nodal/Activin/transforming growth factorβ (TGFβ inhibitor and fibroblast growth factor (FGF. When “primed” with TGFβ, such cells efficiently formed translucent cartilage particles, which were completely mineralized in 12 weeks in immunocompromized mice. The ectomesenchymal cells were expandable without loss of chondrogenic potential for at least 16 passages. They maintained normal karyotype for at least 10 passages and expressed genes representing embryonic progenitors (SOX4/12, LIN28A/B, cranial mesenchyme (ALX1/3/4, and chondroprogenitors (SOX9, COL2A1 of neural crest origin (SOX8/9, NGFR, NES. Ectomesenchyme is a source of many craniofacial bone and cartilage structures. The method we describe for obtaining a large quantity of human ectomesenchymal cells will help to model craniofacial disorders in vitro and potentially provide cells for the repair of craniofacial damage.

  15. Duplication of SOX9 associated with 46,XX ovotesticular disorder of sex development.

    Science.gov (United States)

    López-Hernández, Berenice; Méndez, Juan Pablo; Coral-Vázquez, Ramón Mauricio; Benítez-Granados, Jesús; Zenteno, Juan Carlos; Villegas-Ruiz, Vanessa; Calzada-León, Raúl; Soderlund, Daniela; Canto, Patricia

    2018-04-04

    The purpose of the present study was to investigate whether ten unrelated SRY-negative individuals with this sex differentiation disorder presented a double dose of SOX9 as the cause of their disease. Ten unrelated SRY-negative 46,XX ovotesticular disorder of sexual development (DSD) subjects were molecularly studied. Multiplex-ligation dependent probe amplification (MLPA) and quantitative real-time PCR analysis (qRT-PCR) for SOX9 were performed. The MLPA analysis demonstrated that one patient presented a heterozygous duplication of the entire SOX9 coding region (above 1.3 value of peak ratio), as well as at least a ~ 483 kb upstream duplication. Moreover, no duplication of other SOX9 probes was observed corresponding to the region between -1007 and -1500 kb upstream. A qRT-PCR analysis showed a duplication of at least -581 kb upstream and ~1.63 kb of the coding region that encompasses exon 3. The limits of the duplication were mapped approximately from ~71539762 to 72122741 of Chr17. No molecular abnormalities were found in the remaining nine patients. This study is thought to be the first report regarding a duplication of SOX9 that is associated with the presence of 46,XX ovotesticular DSD, encompassing at least -581 kb upstream, and the almost entire coding region of the gene. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  16. Identification of a polyoxometalate inhibitor of the DNA binding activity of Sox2.

    Science.gov (United States)

    Narasimhan, Kamesh; Pillay, Shubhadra; Bin Ahmad, Nor Rizal; Bikadi, Zsolt; Hazai, Eszter; Yan, Li; Kolatkar, Prasanna R; Pervushin, Konstantin; Jauch, Ralf

    2011-06-17

    Aberrant expression of transcription factors is a frequent cause of disease, yet drugs that modulate transcription factor protein-DNA interactions are presently unavailable. To this end, the chemical tractability of the DNA binding domain of the stem cell inducer and oncogene Sox2 was explored in a high-throughput fluorescence anisotropy screen. The screening revealed a Dawson polyoxometalate (K(6)[P(2)Mo(18)O(62)]) as a direct and nanomolar inhibitor of the DNA binding activity of Sox2. The Dawson polyoxometalate (Dawson-POM) was found to be selective for Sox2 and related Sox-HMG family members when compared to unrelated paired and zinc finger DNA binding domains. [(15)N,(1)H]-Transverse relaxation optimized spectroscopy (TROSY) experiments coupled with docking studies suggest an interaction site of the POM on the Sox2 surface that enabled the rationalization of its inhibitory activity. The unconventional molecular scaffold of the Dawson-POM and its inhibitory mode provides strategies for the development of drugs that modulate transcription factors.

  17. Analysis of SOX10 mutations identified in Waardenburg-Hirschsprung patients: Differential effects on target gene regulation.

    Science.gov (United States)

    Chan, Kwok Keung; Wong, Corinne Kung Yen; Lui, Vincent Chi Hang; Tam, Paul Kwong Hang; Sham, Mai Har

    2003-10-15

    SOX10 is a member of the SOX gene family related by homology to the high-mobility group (HMG) box region of the testis-determining gene SRY. Mutations of the transcription factor gene SOX10 lead to Waardenburg-Hirschsprung syndrome (Waardenburg-Shah syndrome, WS4) in humans. A number of SOX10 mutations have been identified in WS4 patients who suffer from different extents of intestinal aganglionosis, pigmentation, and hearing abnormalities. Some patients also exhibit signs of myelination deficiency in the central and peripheral nervous systems. Although the molecular bases for the wide range of symptoms displayed by the patients are still not clearly understood, a few target genes for SOX10 have been identified. We have analyzed the impact of six different SOX10 mutations on the activation of SOX10 target genes by yeast one-hybrid and mammalian cell transfection assays. To investigate the transactivation activities of the mutant proteins, three different SOX target binding sites were introduced into luciferase reporter gene constructs and examined in our series of transfection assays: consensus HMG domain protein binding sites; SOX10 binding sites identified in the RET promoter; and Sox10 binding sites identified in the P0 promoter. We found that the same mutation could have different transactivation activities when tested with different target binding sites and in different cell lines. The differential transactivation activities of the SOX10 mutants appeared to correlate with the intestinal and/or neurological symptoms presented in the patients. Among the six mutant SOX10 proteins tested, much reduced transactivation activities were observed when tested on the SOX10 binding sites from the RET promoter. Of the two similar mutations X467K and 1400del12, only the 1400del12 mutant protein exhibited an increase of transactivation through the P0 promoter. While the lack of normal SOX10 mediated activation of RET transcription may lead to intestinal aganglionosis

  18. Trapping and Probing Antihydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Wurtele, Jonathan [UC Berkeley and LBNL

    2013-03-27

    Precision spectroscopy of antihydrogen is a promising path to sensitive tests of CPT symmetry. The most direct route to achieve this goal is to create and probe antihydrogen in a magnetic minimum trap. Antihydrogen has been synthesized and trapped for 1000s at CERN by the ALPHA Collaboration. Some of the challenges associated with achieving these milestones will be discussed, including mixing cryogenic positron and antiproton plasmas to synthesize antihydrogen with kinetic energy less than the trap potential of .5K. Recent experiments in which hyperfine transitions were resonantly induced with microwaves will be presented. The opportunity for gravitational measurements in traps based on detailed studies of antihydrogen dynamics will be described. The talk will conclude with a discussion future antihydrogen research that will use a new experimental apparatus, ALPHA-I.

  19. EBIT trapping program

    International Nuclear Information System (INIS)

    Elliott, S.R.; Beck, B.; Beiersdorfer, P.; Church, D.; DeWitt, D.; Knapp, D.K.; Marrs, R.E.; Schneider, D.; Schweikhard, L.

    1993-01-01

    The LLNL electron beam ion trap provides the world's only source of stationary highly charged ions up to bare U. This unique capability makes many new atomic and nuclear physics experiments possible. (orig.)

  20. Microfabricated Waveguide Atom Traps.

    Energy Technology Data Exchange (ETDEWEB)

    Jau, Yuan-Yu [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-09-01

    A nanoscale , microfabricated waveguide structure can in - principle be used to trap atoms in well - defined locations and enable strong photon-atom interactions . A neutral - atom platform based on this microfabrication technology will be prealigned , which is especially important for quantum - control applications. At present, there is still no reported demonstration of evanescent - field atom trapping using a microfabricated waveguide structure. We described the capabilities established by our team for future development of the waveguide atom - trapping technology at SNL and report our studies to overcome the technical challenges of loading cold atoms into the waveguide atom traps, efficient and broadband optical coupling to a waveguide, and the waveguide material for high - power optical transmission. From the atomic - physics and the waveguide modeling, w e have shown that a square nano-waveguide can be utilized t o achieve better atomic spin squeezing than using a nanofiber for first time.

  1. Search For Trapped Antihydrogen

    CERN Document Server

    Andresen, Gorm B.; Baquero-Ruiz, Marcelo; Bertsche, William; Bowe, Paul D.; Bray, Crystal C.; Butler, Eoin; Cesar, Claudio L.; Chapman, Steven; Charlton, Michael; Fajans, Joel; Friesen, Tim; Fujiwara, Makoto C.; Gill, David R.; Hangst, Jeffrey S.; Hardy, Walter N.; Hayano, Ryugo S.; Hayden, Michael E.; Humphries, Andrew J.; Hydomako, Richard; Jonsell, Svante; Jorgensen, Lars V.; Kurchaninov, Lenoid; Lambo, Ricardo; Madsen, Niels; Menary, Scott; Nolan, Paul; Olchanski, Konstantin; Olin, Art; Povilus, Alexander; Pusa, Petteri; Robicheaux, Francis; Sarid, Eli; Nasr, Sarah Seif El; Silveira, Daniel M.; So, Chukman; Storey, James W.; Thompson, Robert I.; van der Werf, Dirk P.; Wilding, Dean; Wurtele, Jonathan S.; Yamazaki, Yasunori

    2011-01-01

    We present the results of an experiment to search for trapped antihydrogen atoms with the ALPHA antihydrogen trap at the CERN Antiproton Decelerator. Sensitive diagnostics of the temperatures, sizes, and densities of the trapped antiproton and positron plasmas have been developed, which in turn permitted development of techniques to precisely and reproducibly control the initial experimental parameters. The use of a position-sensitive annihilation vertex detector, together with the capability of controllably quenching the superconducting magnetic minimum trap, enabled us to carry out a high-sensitivity and low-background search for trapped synthesised antihydrogen atoms. We aim to identify the annihilations of antihydrogen atoms held for at least 130 ms in the trap before being released over ~30 ms. After a three-week experimental run in 2009 involving mixing of 10^7 antiprotons with 1.3 10^9 positrons to produce 6 10^5 antihydrogen atoms, we have identified six antiproton annihilation events that are consist...

  2. Craniopharyngiomas express embryonic stem cell markers (SOX2, OCT4, KLF4, and SOX9) as pituitary stem cells but do not coexpress RET/GFRA3 receptors.

    Science.gov (United States)

    Garcia-Lavandeira, Montserrat; Saez, Carmen; Diaz-Rodriguez, Esther; Perez-Romero, Sihara; Senra, Ana; Dieguez, Carlos; Japon, Miguel A; Alvarez, Clara V

    2012-01-01

    Adult stem cells maintain some markers expressed by embryonic stem cells and express other specific markers depending on the organ where they reside. Recently, stem/progenitor cells in the rodent and human pituitary have been characterized as expressing GFRA2/RET, PROP1, and stem cell markers such as SOX2 and OCT4 (GPS cells). Our objective was to detect other specific markers of the pituitary stem cells and to investigate whether craniopharyngiomas (CRF), a tumor potentially derived from Rathke's pouch remnants, express similar markers as normal pituitary stem cells. We conducted mRNA and Western blot studies in pituitary extracts, and immunohistochemistry and immunofluorescence on sections from normal rat and human pituitaries and 20 CRF (18 adamantinomatous and two papillary). Normal pituitary GPS stem cells localized in the marginal zone (MZ) express three key embryonic stem cell markers, SOX2, OCT4, and KLF4, in addition to SOX9 and PROP1 and β-catenin overexpression. They express the RET receptor and its GFRA2 coreceptor but also express the coreceptor GFRA3 that could be detected in the MZ of paraffin pituitary sections. CRF maintain the expression of SOX2, OCT4, KLF4, SOX9, and β-catenin. However, RET and GFRA3 expression was altered in CRF. In 25% (five of 20), both RET and GFRA3 were detected but not colocalized in the same cells. The other 75% (15 of 20) lose the expression of RET, GFRA3, or both proteins simultaneously. Human pituitary adult stem/progenitor cells (GPS) located in the MZ are characterized by expression of embryonic stem cell markers SOX2, OCT4, and KLF4 plus the specific pituitary embryonic factor PROP1 and the RET system. Redundancy in RET coreceptor expression (GFRA2 and GFRA3) suggest an important systematic function in their physiological behavior. CRF share the stem cell markers suggesting a common origin with GPS. However, the lack of expression of the RET/GFRA system could be related to the cell mislocation and deregulated

  3. A novel heterozygous SOX2 mutation causing anophthalmia/microphthalmia with genital anomalies.

    Science.gov (United States)

    Pedace, Lucia; Castori, Marco; Binni, Francesco; Pingi, Alberto; Grammatico, Barbara; Scommegna, Salvatore; Majore, Silvia; Grammatico, Paola

    2009-01-01

    Anophthalmia/microphthalmia is a rare developmental craniofacial defect, which recognizes a wide range of causes, including chromosomal abnormalities, single-gene mutations as well as environmental factors. Heterozygous mutations in the SOX2 gene are the most common monogenic form of anophthalmia/microphthalmia, as they are reported in up to 10-15% cases. Here, we describe a sporadic patient showing bilateral anophthalmia/microphthalmia and micropenis caused by a novel mutation (c.59_60insGG) in the SOX2 gene. Morphological and endocrinological evaluations excluded any anomaly of the hypothalamus-pituitary axis. Our finding supports the hypothesis that SOX2 is particularly prone to slipped-strand mispairing, which results in a high frequency of point deletions/insertions.

  4. Recurrent SOX9 deletion campomelic dysplasia due to somatic mosaicism in the father.

    Science.gov (United States)

    Smyk, M; Obersztyn, E; Nowakowska, B; Bocian, E; Cheung, S W; Mazurczak, T; Stankiewicz, P

    2007-04-15

    Haploinsufficiency of SOX9, a master gene in chondrogenesis and testis development, leads to the semi-lethal skeletal malformation syndrome campomelic dysplasia (CD), with or without XY sex reversal. We report on two children with CD and a phenotypically normal father, a carrier of a somatic mosaic SOX9 deletion. This is the first report of a mosaic deletion of SOX9; few familial CD cases with germline and somatic mutation mosaicism have been described. Our findings confirm the utility of aCGH and indicate that for a more accurate estimate of the recurrence risk for a completely penetrant autosomal dominant disorder, parental somatic mosaicism should be considered in healthy parents. Copyright 2007 Wiley-Liss, Inc.

  5. A family with X-linked anophthalmia: exclusion of SOX3 as a candidate gene.

    Science.gov (United States)

    Slavotinek, Anne; Lee, Stephen S; Hamilton, Steven P

    2005-10-01

    We report on a four-generation family with X-linked anophthalmia in four affected males and show that this family has LOD scores consistent with linkage to Xq27, the third family reported to be linked to the ANOP1 locus. We sequenced the SOX3 gene at Xq27 as a candidate gene for the X-linked anophthalmia based on the high homology of this gene to SOX2, a gene previously mutated in bilateral anophthlamia. However, no amino acid sequence alterations were identified in SOX3. We have improved the definition of the phenotype in males with anophthalmia linked to the ANOP1 locus, as microcephaly, ocular colobomas, and severe renal malformations have not been described in families linked to ANOP1. (c) 2005 Wiley-Liss, Inc.

  6. A de novo SOX10 mutation causing severe type 4 Waardenburg syndrome without Hirschsprung disease.

    Science.gov (United States)

    Sznajer, Yves; Coldéa, Cristina; Meire, Françoise; Delpierre, Isabelle; Sekhara, Tayeb; Touraine, Renaud L

    2008-04-15

    Type 4 Waardenburg syndrome represents a well define entity caused by neural crest derivatives anomalies (melanocytes, intrinsic ganglion cells, central, autonomous and peripheral nervous systems) leading, with variable expressivity, to pigmentary anomalies, deafness, mental retardation, peripheral neuropathy, and Hirschsprung disease. Autosomal dominant mode of inheritance is prevalent when Sox10 gene mutation is identified. We report the natural history of a child who presented with synophrys, vivid blue eye, deafness, bilateral complete semicircular canals agenesis with mental retardation, subtle signs for peripheral neuropathy and lack of Hirschsprung disease. SOX10 gene sequencing identified "de novo" splice site mutation (c.698-2A > C). The present phenotype and the genotype findings underline the wide spectrum of SOX10 gene implication in unusual type 4 Waardenburg syndrome patient. Copyright 2008 Wiley-Liss, Inc.

  7. The epigenetic regulation of SOX9 by miR-145 in human chondrosarcoma.

    Science.gov (United States)

    Mak, Isabella W Y; Singh, Shalini; Turcotte, Robert; Ghert, Michelle

    2015-01-01

    Chondrosarcoma is the most common primary bone malignancy in the adult population with a high rate of pulmonary metastasis. Chondrosarcoma is managed with surgical excision as the tumors do not respond well to conventional chemotherapy or radiation therapy. Thus, there exists a dire need to develop systemic treatment options to target chondrosarcoma cells for metastatic spread. We hypothesized that the expression of miR-145 is low in chondrosarcoma, leading to decreased transcriptional control of SOX9 (the master regulator of chondrogenesis), and downstream activation of the transcription factor ETV5. We have previously shown that ETV5 activates MMP-2 expression in chondrosarcoma, which in turn increases local bone matrix resorption. In this study, we confirm high expression of SOX9 in human chondrosarcoma using real-time PCR, Western blotting, and immunofluorescence. An ETV5 promoter-reporter plasmid was transfected into chondrosarcoma cells to determine if SOX9 directly regulates the expression of ETV5. Co-transfection of the ETV5 promoter-plasmid with SOX9 lentivirus significantly increased the luciferase activity derived from the ETV5 promoter, from which the regulatory relationship between SOX9 and ETV5 is established. MiR-145 was found to be down-regulated in chondrosarcoma cell lines, patient samples, and further confirmed with a public sarcoma database. After stable miR-145 lentiviral transfection, the subsequent mRNA expression levels of SOX9, ETV5, and MMP-2 were significantly decreased in chondrosarcoma cells. The results generated by this study may have important clinical significance in the treatment of patients with chondrosarcoma in that targeted miRNA may have the potential to downregulate the upstream activators of proteases such as MMP-2. © 2014 Wiley Periodicals, Inc.

  8. Podoplanin and SOX2 Expression in CIN 3-like Squamous Cell Carcinoma of the Cervix.

    Science.gov (United States)

    Stewart, Colin J R; Crook, Maxine L

    2018-01-01

    Squamous cell carcinoma (SCC) of the uterine cervix occasionally demonstrates a deceptive growth pattern that mimics endocervical crypt involvement by cervical intraepithelial neoplasia, grade 3 (CIN 3). Such CIN 3-like SCCs may be misinterpreted as noninvasive or minimally invasive leading to delays in diagnosis. Little is known of the factors that influence the growth patterns of cervical SCC but we suggested recently that CIN 3-like tumors might demonstrate "collective cellular invasion," which is characterized by a retained epithelial phenotype. This contrasts with the more overtly infiltrative growth of conventional SCC, which exhibits features suggestive of epithelial-mesenchymal transition. In the current study we investigated podoplanin (PP) and SOX2 expression in normal squamous epithelium, in CIN 3 and in 16 CIN 3-like SCCs 11 of which also showed a conventional invasive component. Compared with normal epithelium, CIN 3 often showed a focal loss of basal PP staining and most cases showed increased, typically diffuse, SOX2 expression. Although the immunohistochemical findings were not uniform, they generally supported collective cellular invasion in CIN 3-like tumor areas as these were often PP positive and showed diffuse SOX2 expression. In contrast, most conventional SCCs showed only focal SOX2 staining and they were typically negative, or only focally positive, for PP. The staining patterns did not reliably distinguish CIN 3 from CIN 3-like SCC. Small infiltrative tumor nests around the margins of CIN 3 or deeply invasive CIN 3-like SCC often showed a localized reduction in SOX2 expression suggesting SOX2 downregulation during the transition to invasive growth.

  9. Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness.

    Science.gov (United States)

    Pingault, Veronique; Bodereau, Virginie; Baral, Viviane; Marcos, Severine; Watanabe, Yuli; Chaoui, Asma; Fouveaut, Corinne; Leroy, Chrystel; Vérier-Mine, Odile; Francannet, Christine; Dupin-Deguine, Delphine; Archambeaud, Françoise; Kurtz, François-Joseph; Young, Jacques; Bertherat, Jérôme; Marlin, Sandrine; Goossens, Michel; Hardelin, Jean-Pierre; Dodé, Catherine; Bondurand, Nadege

    2013-05-02

    Transcription factor SOX10 plays a role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation and is a major actor in the development of the neural crest. It has been implicated in Waardenburg syndrome (WS), a rare disorder characterized by the association between pigmentation abnormalities and deafness, but SOX10 mutations cause a variable phenotype that spreads over the initial limits of the syndrome definition. On the basis of recent findings of olfactory-bulb agenesis in WS individuals, we suspected SOX10 was also involved in Kallmann syndrome (KS). KS is defined by the association between anosmia and hypogonadotropic hypogonadism due to incomplete migration of neuroendocrine gonadotropin-releasing hormone (GnRH) cells along the olfactory, vomeronasal, and terminal nerves. Mutations in any of the nine genes identified to date account for only 30% of the KS cases. KS can be either isolated or associated with a variety of other symptoms, including deafness. This study reports SOX10 loss-of-function mutations in approximately one-third of KS individuals with deafness, indicating a substantial involvement in this clinical condition. Study of SOX10-null mutant mice revealed a developmental role of SOX10 in a subpopulation of glial cells called olfactory ensheathing cells. These mice indeed showed an almost complete absence of these cells along the olfactory nerve pathway, as well as defasciculation and misrouting of the nerve fibers, impaired migration of GnRH cells, and disorganization of the olfactory nerve layer of the olfactory bulbs. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  10. The transcription factor SOX18 regulates the expression of matrix metalloproteinase 7 and guidance molecules in human endothelial cells.

    Directory of Open Access Journals (Sweden)

    Martina Hoeth

    Full Text Available Mutations in the transcription factor SOX18 are responsible for specific cardiovascular defects in humans and mice. In order to gain insight into the molecular basis of its action, we identified target genes of SOX18 and analyzed one, MMP7, in detail.SOX18 was expressed in HUVEC using a recombinant adenoviral vector and the altered gene expression profile was analyzed using microarrays. Expression of several regulated candidate SOX18 target genes was verified by real-time PCR. Knock-down of SOX18 using RNA interference was then used to confirm the effect of the transcription factor on selected genes that included the guidance molecules ephrin B2 and semaphorin 3G. One gene, MMP7, was chosen for further analysis, including detailed promoter studies using reporter gene assays, electrophoretic mobility shift analysis and chromatin-immunoprecipitation, revealing that it responds directly to SOX18. Immunohistochemical analysis demonstrated the co-expression of SOX18 and MMP7 in blood vessels of human skin.The identification of MMP7 as a direct SOX18 target gene as well as other potential candidates including guidance molecules provides a molecular basis for the proposed function of this transcription factor in the regulation of vessel formation.

  11. Expression of SRY-related HMG Box Transcription Factors (Sox) 2 and 9 in Craniopharyngioma Subtypes and Surrounding Brain Tissue.

    Science.gov (United States)

    Thimsen, Vivian; John, Nora; Buchfelder, Michael; Flitsch, Jörg; Fahlbusch, Rudolf; Stefanits, Harald; Knosp, Engelbert; Losa, Marco; Buslei, Rolf; Hölsken, Annett

    2017-11-20

    Stem cells have been discovered as key players in the genesis of different neoplasms including craniopharyngioma (CP), a rare tumour entity in the sellar region. Sox2 and Sox9 are well-known stem cell markers involved in pituitary development. In this study we analysed the expression of both transcription factors using immunohistochemistry in a large cohort of 64 adamantinomatous (aCP) and 9 papillary CP (pCP) and quantitative PCR in 26 aCP and 7 pCP. Whereas immunohistochemically Sox2+ cells were verifiable in only five aCP (7.8%) and in 39.1% of the respective surrounding cerebral tissue, pCP specimens appeared always negative. In contrast, Sox9 was detectable in all tumours with a significantly higher expression in aCP compared to pCP (protein, p < 0.0001; mRNA p = 0.0484) This was also true for the respective tumour adjacent CNS where 63 aCP (98.4%) and six pCP (66.7%) showed Sox9+ cells. We further confirmed absence of Sox9 expression in nuclear β-catenin accumulating cells of aCP. Our results point to the conclusion that Sox2 and Sox9, seem to play essential roles not only in the specific formation of aCP, but also in processes involving the cerebral tumour environment, which needs to be illuminated in the future.

  12. The promotion of cartilage defect repair using adenovirus mediated Sox9 gene transfer of rabbit bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Cao, Lei; Yang, Fei; Liu, Guangwang; Yu, Degang; Li, Huiwu; Fan, Qiming; Gan, Yaokai; Tang, Tingting; Dai, Kerong

    2011-06-01

    Although Sox9 is essential for chondrogenic differentiation and matrix production, its application in cartilage tissue engineering has been rarely reported. In this study, the chondrogenic effect of Sox9 on bone marrow mesenchymal stem cells (BMSCs) in vitro and its application in articular cartilage repair in vivo were evaluated. Rabbit BMSCs were transduced with adenoviral vector containing Sox9. Toluidine blue, safranin O staining and real-time PCR were performed to check chondrogenic differentiation. The results showed that Sox9 could induce chondrogenesis of BMSCs both in monolayer and on PGA scaffold effectively. The rabbit model with full-thickness cartilage defects was established and then repaired by PGA scaffold and rabbit BMSCs with or without Sox9 transduction. HE, safranin O staining and immunohistochemistry were used to assess the repair of defects by the complex. Better repair, including more newly-formed cartilage tissue and hyaline cartilage-specific extracellular matrix and greater expression of several chondrogenesis marker genes were observed in PGA scaffold and BMSCs with Sox9 transduction, compared to that without transduction. Our findings defined the important role of Sox9 in the repair of cartilage defects in vivo and provided evidence that Sox9 had the potential and advantage in the application of tissue engineering. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Xiaowei Zhang

    Full Text Available Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9 is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrating recombinant SOX9 protein in regeneration of hyaline cartilage in situ at the site of cartilage injury. We generated a recombinant SOX9 protein which was fused with super positively charged green fluorescence protein (GFP (scSOX9 to facilitate cell penetration. scSOX9 was able to induce chondrogenesis of bone marrow derived MSC in vitro. In a rabbit cartilage injury model, scSOX9 in combination with microfracture significantly improved quality of repaired cartilage as shown by macroscopic appearance. Histological analysis revealed that the reparative tissue induced by microfracture with scSOX9 had features of hyaline cartilage; and collagen type II to type I ratio was similar to that in normal cartilage. This short term in vivo study demonstrated that when administered at the site of microfracture, scSOX9 was able to induce reparative tissue with features of hyaline cartilage.

  14. Elevated Levels of SOX10 in Serum from Vitiligo and Melanoma Patients, Analyzed by Proximity Ligation Assay.

    Directory of Open Access Journals (Sweden)

    Andries Blokzijl

    Full Text Available The diagnosis of malignant melanoma currently relies on clinical inspection of the skin surface and on the histopathological status of the excised tumor. The serum marker S100B is used for prognostic estimates at later stages of the disease, but analyses are marred by false positives and inadequate sensitivity in predicting relapsing disorder.To investigate SOX10 as a potential biomarker for melanoma and vitiligo.In this study we have applied proximity ligation assay (PLA to detect the transcription factor SOX10 as a possible serum marker for melanoma. We studied a cohort of 110 melanoma patients. We further investigated a second cohort of 85 patients with vitiligo, which is a disease that also affects melanocytes.The specificity of the SOX10 assay in serum was high, with only 1% of healthy blood donors being positive. In contrast, elevated serum SOX10 was found with high frequency among vitiligo and melanoma patients. In patients with metastases, lack of SOX10 detection was associated with treatment benefit. In two responding patients, a change from SOX10 positivity to undetectable levels was seen before the response was evident clinically.We show for the first time that SOX10 represents a promising new serum melanoma marker for detection of early stage disease, complementing the established S100B marker. Our findings imply that SOX10 can be used to monitor responses to treatment and to assess if the treatment is of benefit at stages earlier than what is possible radiologically.

  15. Continuous hydrostatic pressure induces differentiation phenomena in chondrocytes mediated by changes in polycystins, SOX9, and RUNX2.

    Science.gov (United States)

    Karamesinis, Konstantinos; Spyropoulou, Anastasia; Dalagiorgou, Georgia; Katsianou, Maria A; Nokhbehsaim, Marjan; Memmert, Svenja; Deschner, James; Vastardis, Heleni; Piperi, Christina

    2017-01-01

    The present study aimed to investigate the long-term effects of hydrostatic pressure on chondrocyte differentiation, as indicated by protein levels of transcription factors SOX9 and RUNX2, on transcriptional activity of SOX9, as determined by pSOX9 levels, and on the expression of polycystin-encoding genes Pkd1 and Pkd2. ATDC5 cells were cultured in insulin-supplemented differentiation medium (ITS) and/or exposed to 14.7 kPa of hydrostatic pressure for 12, 24, 48, and 96 h. Cell extracts were assessed for SOX9, pSOX9, and RUNX2 using western immunoblotting. The Pkd1 and Pkd2 mRNA levels were detected by real-time PCR. Hydrostatic pressure resulted in an early drop in SOX9 and pSOX9 protein levels at 12 h followed by an increase from 24 h onwards. A reverse pattern was followed by RUNX2, which reached peak levels at 24 h of hydrostatic pressure-treated chondrocytes in ITS culture. Pkd1 and Pkd2 mRNA levels increased at 24 h of combined hydrostatic pressure and ITS treatment, with the latter remaining elevated up to 96 h. Our data indicate that long periods of continuous hydrostatic pressure stimulate chondrocyte differentiation through a series of molecular events involving SOX9, RUNX2, and polycystins-1, 2, providing a theoretical background for functional orthopedic mechanotherapies.

  16. Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Zhang, Xiaowei; Wu, Shili; Naccarato, Ty; Prakash-Damani, Manan; Chou, Yuan; Chu, Cong-Qiu; Zhu, Yong

    2017-01-01

    Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC) to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9) is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrating recombinant SOX9 protein in regeneration of hyaline cartilage in situ at the site of cartilage injury. We generated a recombinant SOX9 protein which was fused with super positively charged green fluorescence protein (GFP) (scSOX9) to facilitate cell penetration. scSOX9 was able to induce chondrogenesis of bone marrow derived MSC in vitro. In a rabbit cartilage injury model, scSOX9 in combination with microfracture significantly improved quality of repaired cartilage as shown by macroscopic appearance. Histological analysis revealed that the reparative tissue induced by microfracture with scSOX9 had features of hyaline cartilage; and collagen type II to type I ratio was similar to that in normal cartilage. This short term in vivo study demonstrated that when administered at the site of microfracture, scSOX9 was able to induce reparative tissue with features of hyaline cartilage.

  17. MicroRNA-320 suppresses colorectal cancer by targeting SOX4, FOXM1, and FOXQ1

    DEFF Research Database (Denmark)

    Vishnubalaji, Radhakrishnan; Hamam, Rimi; Yue, Shijun

    2016-01-01

    gene targets for the miR-320 family. Inverse correlation between the expression of miR-320 members with SOX4, FOXM1, and FOXQ1 was observed in primary CRC patients' specimens, suggesting that these genes are likely bona fide targets for the miR-320 family. Interestingly, interrogation of the expression...... for the miR-320/SOX4/FOXM1/FOXQ1 axes in promoting CRC development and progression and suggest targeting those networks as potential therapeutic strategy for CRC....

  18. Mutations of the SRY-responsive enhancer of SOX9 are uncommon in XY gonadal dysgenesis.

    Science.gov (United States)

    Georg, I; Bagheri-Fam, S; Knower, K C; Wieacker, P; Scherer, Gerd; Harley, V R

    2010-01-01

    During mouse sex determination, SRY upregulates the core testis-specific enhancer of Sox9, TESCO. Mutations in human SRY are found in one third of cases with XY pure gonadal dysgenesis (XY GD; Swyer syndrome), while two thirds remain unexplained. Heterozygous SOX9 mutations can cause XY GD in association with the skeletal malformation syndrome campomelic dysplasia. We hypothesized that human TESCO mutations could cause isolated XY GD. Sixty-six XY GD cases with an intact SRY were analyzed for TESCO point mutations or deletions. No mutations were identified. We conclude that TESCO mutations are not a common cause of XY GD. Copyright © 2010 S. Karger AG, Basel.

  19. Regulation by SoxR of mfsA, Which Encodes a Major Facilitator Protein Involved in Paraquat Resistance in Stenotrophomonas maltophilia.

    Directory of Open Access Journals (Sweden)

    Kriangsuk Srijaruskul

    Full Text Available Stenotrophomonas maltophilia MfsA (Smlt1083 is an efflux pump in the major facilitator superfamily (MFS. Deletion of mfsA renders the strain more susceptible to paraquat, but no alteration in the susceptibility levels of other oxidants is observed. The expression of mfsA is inducible upon challenge with redox cycling/superoxide-generating drug (paraquat, menadione and plumbagin treatments and is directly regulated by SoxR, which is a transcription regulator and sensor of superoxide-generating agents. Analysis of mfsA expression patterns in wild-type and a soxR mutant suggests that oxidized SoxR functions as a transcription activator of the gene. soxR (smlt1084 is located in a head-to-head fashion with mfsA, and these genes share the -10 motif of their promoter sequences. Purified SoxR specifically binds to the putative mfsA promoter motifs that contain a region that is highly homologous to the consensus SoxR binding site, and mutation of the SoxR binding site abolishes binding of purified SoxR protein. The SoxR box is located between the putative -35 and -10 promoter motifs of mfsA; and this position is typical for a promoter in which SoxR acts as a transcriptional activator. At the soxR promoter, the SoxR binding site covers the transcription start site of the soxR transcript; thus, binding of SoxR auto-represses its own transcription. Taken together, our results reveal for the first time that mfsA is a novel member of the SoxR regulon and that SoxR binds and directly regulates its expression.

  20. Duplication of SOX9 is not a common cause of 46,XX testicular or 46,XX ovotesticular DSD.

    Science.gov (United States)

    Seeherunvong, Tossaporn; Ukarapong, Supamit; McElreavey, Kenneth; Berkovitz, Gary D; Perera, Erasmo M

    2012-01-01

    Translocation of the SRY gene to the paternal X chromosome is the explanation for testis development in the majority of subjects with 46,XX testicular disorder of sexual development (DSD). However, nearly all subjects with 46,XX ovotesticular DSD and up to one third of subjects with 46,XX testicular DSD lack SRY. SRY-independent expression of SOX9 has been implicated in the etiology of testis development in some individuals. We amplified microsatellite markers in the region of SOX9 from a cohort of 30 subjects with either 46,XX testicular or 46,XX ovotesticular DSD to detect SOX9 duplications. Duplication of the SOX9 region in 17q was not detected in any subject. Duplication in the region of 17q that contains SOX9 is not a common cause of testis development in subjects with SRY-negative 46,XX testicular or ovotesticular DSD.

  1. Sox17-Mediated XEN Cell Conversion Identifies Dynamic Networks Controlling Cell-Fate Decisions in Embryo-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Angela C.H. McDonald

    2014-10-01

    Full Text Available Little is known about the gene regulatory networks (GRNs distinguishing extraembryonic endoderm (ExEn stem (XEN cells from those that maintain the extensively characterized embryonic stem cell (ESC. An intriguing network candidate is Sox17, an essential transcription factor for XEN derivation and self-renewal. Here, we show that forced Sox17 expression drives ESCs toward ExEn, generating XEN cells that contribute to ExEn when placed back into early mouse embryos. Transient Sox17 expression is sufficient to drive this fate change during which time cells transit through distinct intermediate states prior to the generation of functional XEN-like cells. To orchestrate this conversion process, Sox17 acts in autoregulatory and feedforward network motifs, regulating dynamic GRNs directing cell fate. Sox17-mediated XEN conversion helps to explain the regulation of cell-fate changes and reveals GRNs regulating lineage decisions in the mouse embryo.

  2. "I Feel Trapped": The Tension Between Personal and Structural Factors of Social Isolation and the Desire for Social Integration Among Older Residents of a High-Crime Neighborhood.

    Science.gov (United States)

    Portacolone, Elena; Perissinotto, Carla; Yeh, Jarmin Christine; Greysen, S Ryan

    2018-01-18

    The aim of this study was to examine the factors contributing to the social isolation of older residents of a high-crime neighborhood through the in-depth examination of their lived experiences. A deeper understanding of factors contributing to social isolation can allow policymakers and health care providers to create policies and programs to alleviate the social isolation of these vulnerable and understudied individuals. Participants were recruited through the support of the Housing Authority and Police and Fire Departments of Richmond, California, a town with a high-crime rate. Fifty-nine ethnographic interviews were conducted with 20 individuals of 58-95 years of age. Transcripts and fieldnotes were analyzed with a focus on the specific factors contributing the social isolation of participants. An overarching theme of tension between personal and structural factors of social isolation and desire for social integration emerged from qualitative content analysis. A tension emerged between a longing to participate in society and the immersion in a reality so dense with obstacles that made participation in society difficult to attain. Four specific themes also emerged. Three themes demonstrated underlying factors of social isolation stemming from the personal sphere and the physical and social environment. The fourth theme illustrated participants' desire for social integration. Findings demonstrate the salience of interventions and programs to make neighborhoods safe and accessible to older residents. Findings also suggest a need to reframe the conceptual framework for social isolation to better measure and alleviate this public health problem. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin–Siris syndrome

    Science.gov (United States)

    Hempel, Annmarie; Pagnamenta, Alistair T; Blyth, Moira; Mansour, Sahar; McConnell, Vivienne; Kou, Ikuyo; Ikegawa, Shiro; Tsurusaki, Yoshinori; Matsumoto, Naomichi; Lo-Castro, Adriana; Plessis, Ghislaine; Albrecht, Beate; Battaglia, Agatino; Taylor, Jenny C; Howard, Malcolm F; Keays, David; Sohal, Aman Singh; Kühl, Susanne J; Kini, Usha; McNeill, Alisdair

    2016-01-01

    Background SOX11 is a transcription factor proposed to play a role in brain development. The relevance of SOX11 to human developmental disorders was suggested by a recent report of SOX11 mutations in two patients with Coffin–Siris syndrome. Here we further investigate the role of SOX11 variants in neurodevelopmental disorders. Methods We used array based comparative genomic hybridisation and trio exome sequencing to identify children with intellectual disability who have deletions or de novo point mutations disrupting SOX11. The pathogenicity of the SOX11 mutations was assessed using an in vitro gene expression reporter system. Loss-of-function experiments were performed in xenopus by knockdown of Sox11 expression. Results We identified seven individuals with chromosome 2p25 deletions involving SOX11. Trio exome sequencing identified three de novo SOX11 variants, two missense (p.K50N; p.P120H) and one nonsense (p.C29*). The biological consequences of the missense mutations were assessed using an in vitro gene expression system. These individuals had microcephaly, developmental delay and shared dysmorphic features compatible with mild Coffin–Siris syndrome. To further investigate the function of SOX11, we knocked down the orthologous gene in xenopus. Morphants had significant reduction in head size compared with controls. This suggests that SOX11 loss of function can be associated with microcephaly. Conclusions We thus propose that SOX11 deletion or mutation can present with a Coffin–Siris phenotype. PMID:26543203

  4. Silencing of the Drosophila ortholog of SOX5 in heart leads to cardiac dysfunction as detected by optical coherence tomography.

    Science.gov (United States)

    Li, Airong; Ahsen, Osman O; Liu, Jonathan J; Du, Chuang; McKee, Mary L; Yang, Yan; Wasco, Wilma; Newton-Cheh, Christopher H; O'Donnell, Christopher J; Fujimoto, James G; Zhou, Chao; Tanzi, Rudolph E

    2013-09-15

    The SRY-related HMG-box 5 (SOX5) gene encodes a member of the SOX family of transcription factors. Recently, genome-wide association studies have implicated SOX5 as a candidate gene for susceptibility to four cardiac-related endophenotypes: higher resting heart rate (HR), the electrocardiographic PR interval, atrial fibrillation and left ventricular mass. We have determined that human SOX5 has a highly conserved Drosophila ortholog, Sox102F, and have employed transgenic Drosophila models to quantitatively measure cardiac function in adult flies. For this purpose, we have developed a high-speed and ultrahigh-resolution optical coherence tomography imaging system, which enables rapid cross-sectional imaging of the heart tube over various cardiac cycles for the measurement of cardiac structural and dynamical parameters such as HR, dimensions and areas of heart chambers, cardiac wall thickness and wall velocities. We have found that the silencing of Sox102F resulted in a significant decrease in HR, heart chamber size and cardiac wall velocities, and a significant increase in cardiac wall thickness that was accompanied by disrupted myofibril structure in adult flies. In addition, the silencing of Sox102F in the wing led to increased L2, L3 and wing marginal veins and increased and disorganized expression of wingless, the central component of the Wnt signaling pathway. Collectively, the silencing of Sox102F resulted in severe cardiac dysfunction and structural defects with disrupted Wnt signaling transduction in flies. This implicates an important functional role for SOX5 in heart and suggests that the alterations in SOX5 levels may contribute to the pathogenesis of multiple cardiac diseases or traits.

  5. During development intense Sox2 expression marks not only Prox1-expressing taste bud cell but also perigemmal cell lineages.

    Science.gov (United States)

    Nakayama, Ayumi; Miura, Hirohito; Ooki, Makoto; Harada, Shuitsu

    2015-03-01

    Sox2 is proposed to regulate the differentiation of bipotential progenitor cells into taste bud cells. However, detailed expression of Sox2 remains unclear. In this report, Sox2 expression during taste bud development in the fungiform (FF), circumvallate (CV) and soft palate (SP) areas is examined together with Prox1. First, we immunohistochemically checked Prox1 expression in adults and found that almost all taste bud cells are Prox1-positive. During FF development, intense Sox2 expression was restricted to taste bud primordia expressing Prox1 at E12.5. However, at E14.5, Sox2 was intensely expressed outside the developing taste buds resolving to perigemmal Sox2 expression in adults. In the SP, at E14.5, taste bud primordia emerged as Prox1-expressing cell clusters. However, intense Sox2 expression was not restricted to taste bud primordia but was detected widely in the epithelium. During development, Sox2 expression outside developing taste buds was generally down-regulated but was retained in the perigemmal region similarly to that in the FF. In the CV, the initial stage of taste bud development remained unclear because of the lack of taste bud primordia comparable to that in the FF and SP. Here, we show that Prox1-expressing cells appear in the apical epithelium at E12.5, in the inner trench wall at E17.5 and in the outer trench wall at E18.5. Sox2 was again not restricted to developing taste bud cells expressing Prox1 during CV development. The expression patterns support that Sox2 does not serve as a cell fate selector between taste bud cells and surrounding keratinocytes but rather may contribute to them both.

  6. The NSSDC trapped radiation model facility

    International Nuclear Information System (INIS)

    Gaffey, J.D. Jr.; Bilitza, D.

    1990-01-01

    The National Space Science Data Center (NSSDC) trapped radiation models calculate the integral and differential electron and proton flux for given values of the particle energy E, drift shell parameter L, and magnetic field strength B for either solar maximum or solar minimum. The most recent versions of the series of models, which have been developed and continuously improved over several decades by Dr. James Vette and coworkers at NSSDC, are AE-8 for electrons and AP-8 for protons. The present status of the NSSDC trapped particle models is discussed. The limits of validity of the models are described. 17 refs

  7. Physics with Trapped Antihydrogen

    Science.gov (United States)

    Charlton, Michael

    2017-04-01

    For more than a decade antihydrogen atoms have been formed by mixing antiprotons and positrons held in arrangements of charged particle (Penning) traps. More recently, magnetic minimum neutral atom traps have been superimposed upon the anti-atom production region, promoting the trapping of a small quantity of the antihydrogen yield. We will review these advances, and describe some of the first physics experiments performed on anrtihydrogen including the observation of the two-photon 1S-2S transition, invesigation of the charge neutrailty of the anti-atom and studies of the ground state hyperfine splitting. We will discuss the physics motivations for undertaking these experiments and describe some near-future initiatives.

  8. Ion trap device

    Science.gov (United States)

    Ibrahim, Yehia M.; Smith, Richard D.

    2016-01-26

    An ion trap device is disclosed. The device includes a series of electrodes that define an ion flow path. A radio frequency (RF) field is applied to the series of electrodes such that each electrode is phase shifted approximately 180 degrees from an adjacent electrode. A DC voltage is superimposed with the RF field to create a DC gradient to drive ions in the direction of the gradient. A second RF field or DC voltage is applied to selectively trap and release the ions from the device. Further, the device may be gridless and utilized at high pressure.

  9. Asymmetric ion trap

    Science.gov (United States)

    Barlow, Stephan E.; Alexander, Michael L.; Follansbee, James C.

    1997-01-01

    An ion trap having two end cap electrodes disposed asymmetrically about a center of a ring electrode. The inner surface of the end cap electrodes are conformed to an asymmetric pair of equipotential lines of the harmonic formed by the application of voltages to the electrodes. The asymmetry of the end cap electrodes allows ejection of charged species through the closer of the two electrodes which in turn allows for simultaneously detecting anions and cations expelled from the ion trap through the use of two detectors charged with opposite polarity.

  10. Technologies for Trapped-Ion Quantum Information Systems

    Science.gov (United States)

    2016-03-21

    we discuss work aiming to leverage a commer- cial CMOS (complementary metal-oxide- semiconductor ) process to develop an integrated ion trap architecture...this integration: alignment of optical elements with tiny modes to point emitters, and trap- ping charged particles close to dielectric surfaces. Inte...far by heating in several ways. The deep optical potentials required to confine a charged particle against stray fields impart significant recoil

  11. Optical trapping of carbon nanotubes and graphene

    Directory of Open Access Journals (Sweden)

    S. Vasi

    2011-09-01

    Full Text Available We study optical trapping of nanotubes and graphene. We extract the distribution of both centre-of-mass and angular fluctuations from three-dimensional tracking of these optically trapped carbon nanostructures. The optical force and torque constants are measured from auto and cross-correlation of the tracking signals. We demonstrate that nanotubes enable nanometer spatial, and femto-Newton force resolution in photonic force microscopy by accurately measuring the radiation pressure in a double frequency optical tweezers. Finally, we integrate optical trapping with Raman and photoluminescence spectroscopy demonstrating the use of a Raman and photoluminescence tweezers by investigating the spectroscopy of nanotubes and graphene flakes in solution. Experimental results are compared with calculations based on electromagnetic scattering theory.

  12. Sox4 is a key oncogenic target in C/EBP alpha mutant acute myeloid leukemia

    Czech Academy of Sciences Publication Activity Database

    Zhang, H.; Alberich-Jorda, Meritxell; Amabile, G.; Yang, H.; Staber, P.B.; DiRuscio, A.; Welner, R.S.; Ebralidze, A.; Zhang, J.; Levantini, E.; Lefebvre, V.; Valk, P.J.; Delwel, R.; Hoogenkamp, M.; Nerlov, C.; Cammenga, J.; Saez, B.; Scadden, D.T.; Bonifer, C.; Ye, M.; Tenen, D.G.

    2013-01-01

    Roč. 24, č. 5 (2013), s. 575-588 ISSN 1535-6108 R&D Projects: GA MŠk LK21307 Institutional support: RVO:68378050 Keywords : Sox4 * C/EBP alpha * acute myeloid leukemia Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 23.893, year: 2013

  13. Screening of MITF and SOX10 regulatory regions in Waardenburg syndrome type 2.

    Directory of Open Access Journals (Sweden)

    Viviane Baral

    Full Text Available Waardenburg syndrome (WS is a rare auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and pigmentation defects. Four subtypes are clinically defined based on the presence or absence of additional symptoms. WS type 2 (WS2 can result from mutations within the MITF or SOX10 genes; however, 70% of WS2 cases remain unexplained at the molecular level, suggesting that other genes might be involved and/or that mutations within the known genes escaped previous screenings. The recent identification of a deletion encompassing three of the SOX10 regulatory elements in a patient presenting with another WS subtype, WS4, defined by its association with Hirschsprung disease, led us to search for deletions and point mutations within the MITF and SOX10 regulatory elements in 28 yet unexplained WS2 cases. Two nucleotide variations were identified: one in close proximity to the MITF distal enhancer (MDE and one within the U1 SOX10 enhancer. Functional analyses argued against a pathogenic effect of these variations, suggesting that mutations within regulatory elements of WS genes are not a major cause of this neurocristopathy.

  14. Screening of MITF and SOX10 Regulatory Regions in Waardenburg Syndrome Type 2

    Science.gov (United States)

    Baral, Viviane; Chaoui, Asma; Watanabe, Yuli; Goossens, Michel; Attie-Bitach, Tania; Marlin, Sandrine; Pingault, Veronique; Bondurand, Nadege

    2012-01-01

    Waardenburg syndrome (WS) is a rare auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and pigmentation defects. Four subtypes are clinically defined based on the presence or absence of additional symptoms. WS type 2 (WS2) can result from mutations within the MITF or SOX10 genes; however, 70% of WS2 cases remain unexplained at the molecular level, suggesting that other genes might be involved and/or that mutations within the known genes escaped previous screenings. The recent identification of a deletion encompassing three of the SOX10 regulatory elements in a patient presenting with another WS subtype, WS4, defined by its association with Hirschsprung disease, led us to search for deletions and point mutations within the MITF and SOX10 regulatory elements in 28 yet unexplained WS2 cases. Two nucleotide variations were identified: one in close proximity to the MITF distal enhancer (MDE) and one within the U1 SOX10 enhancer. Functional analyses argued against a pathogenic effect of these variations, suggesting that mutations within regulatory elements of WS genes are not a major cause of this neurocristopathy. PMID:22848661

  15. Sorting live stem cells based on Sox2 mRNA expression.

    Directory of Open Access Journals (Sweden)

    Hans M Larsson

    Full Text Available While cell sorting usually relies on cell-surface protein markers, molecular beacons (MBs offer the potential to sort cells based on the presence of any expressed mRNA and in principle could be extremely useful to sort rare cell populations from primary isolates. We show here how stem cells can be purified from mixed cell populations by sorting based on MBs. Specifically, we designed molecular beacons targeting Sox2, a well-known stem cell marker for murine embryonic (mES and neural stem cells (NSC. One of our designed molecular beacons displayed an increase in fluorescence compared to a nonspecific molecular beacon both in vitro and in vivo when tested in mES and NSCs. We sorted Sox2-MB(+SSEA1(+ cells from a mixed population of 4-day retinoic acid-treated mES cells and effectively isolated live undifferentiated stem cells. Additionally, Sox2-MB(+ cells isolated from primary mouse brains were sorted and generated neurospheres with higher efficiency than Sox2-MB(- cells. These results demonstrate the utility of MBs for stem cell sorting in an mRNA-specific manner.

  16. Cloning and analysis of the HMG domains of ten Sox genes from ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-04-20

    Apr 20, 2009 ... Sox is a large gene family which encodes Sry-related transcription factors and ..... Gene orthology are boxed drawing by straight line and dotted line. .... HMG Box Functions as a Kinetic Clamp to Augment DNA Bending. J. Mol.

  17. Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice.

    Directory of Open Access Journals (Sweden)

    Kristie Lee

    Full Text Available Congenital hydrocephalus (CH is a life-threatening medical condition in which excessive accumulation of CSF leads to ventricular expansion and increased intracranial pressure. Stenosis (blockage of the Sylvian aqueduct (Aq; the narrow passageway that connects the third and fourth ventricles is a common form of CH in humans, although the genetic basis of this condition is unknown. Mouse models of CH indicate that Aq stenosis is associated with abnormal development of the subcommmissural organ (SCO a small secretory organ located at the dorsal midline of the caudal diencephalon. Glycoproteins secreted by the SCO generate Reissner's fibre (RF, a thread-like structure that descends into the Aq and is thought to maintain its patency. However, despite the importance of SCO function in CSF homeostasis, the genetic program that controls SCO development is poorly understood. Here, we show that the X-linked transcription factor SOX3 is expressed in the murine SCO throughout its development and in the mature organ. Importantly, overexpression of Sox3 in the dorsal diencephalic midline of transgenic mice induces CH via a dose-dependent mechanism. Histological, gene expression and cellular proliferation studies indicate that Sox3 overexpression disrupts the development of the SCO primordium through inhibition of diencephalic roof plate identity without inducing programmed cell death. This study provides further evidence that SCO function is essential for the prevention of hydrocephalus and indicates that overexpression of Sox3 in the dorsal midline alters progenitor cell differentiation in a dose-dependent manner.

  18. Screening of MITF and SOX10 regulatory regions in Waardenburg syndrome type 2.

    Science.gov (United States)

    Baral, Viviane; Chaoui, Asma; Watanabe, Yuli; Goossens, Michel; Attie-Bitach, Tania; Marlin, Sandrine; Pingault, Veronique; Bondurand, Nadege

    2012-01-01

    Waardenburg syndrome (WS) is a rare auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and pigmentation defects. Four subtypes are clinically defined based on the presence or absence of additional symptoms. WS type 2 (WS2) can result from mutations within the MITF or SOX10 genes; however, 70% of WS2 cases remain unexplained at the molecular level, suggesting that other genes might be involved and/or that mutations within the known genes escaped previous screenings. The recent identification of a deletion encompassing three of the SOX10 regulatory elements in a patient presenting with another WS subtype, WS4, defined by its association with Hirschsprung disease, led us to search for deletions and point mutations within the MITF and SOX10 regulatory elements in 28 yet unexplained WS2 cases. Two nucleotide variations were identified: one in close proximity to the MITF distal enhancer (MDE) and one within the U1 SOX10 enhancer. Functional analyses argued against a pathogenic effect of these variations, suggesting that mutations within regulatory elements of WS genes are not a major cause of this neurocristopathy.

  19. On-chip particle trapping and manipulation

    Science.gov (United States)

    Leake, Kaelyn Danielle

    The ability to control and manipulate the world around us is human nature. Humans and our ancestors have used tools for millions of years. Only in recent years have we been able to control objects at such small levels. In order to understand the world around us it is frequently necessary to interact with the biological world. Optical trapping and manipulation offer a non-invasive way to move, sort and interact with particles and cells to see how they react to the world around them. Optical tweezers are ideal in their abilities but they require large, non-portable, and expensive setups limiting how and where we can use them. A cheap portable platform is required in order to have optical manipulation reach its full potential. On-chip technology offers a great solution to this challenge. We focused on the Liquid-Core Anti-Resonant Reflecting Optical Waveguide (liquid-core ARROW) for our work. The ARROW is an ideal platform, which has anti-resonant layers which allow light to be guided in liquids, allowing for particles to easily be manipulated. It is manufactured using standard silicon manufacturing techniques making it easy to produce. The planner design makes it easy to integrate with other technologies. Initially I worked to improve the ARROW chip by reducing the intersection losses and by reducing the fluorescence and background on the ARROW chip. The ARROW chip has already been used to trap and push particles along its channel but here I introduce several new methods of particle trapping and manipulation on the ARROW chip. Traditional two beam traps use two counter propagating beams. A trapping scheme that uses two orthogonal beams which counter to first instinct allow for trapping at their intersection is introduced. This scheme is thoroughly predicted and analyzed using realistic conditions. Simulations of this method were done using a program which looks at both the fluidics and optical sources to model complex situations. These simulations were also used to

  20. The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation

    International Nuclear Information System (INIS)

    Sernbo, Sandra; Gustavsson, Elin; Brennan, Donal J; Gallagher, William M; Rexhepaj, Elton; Rydnert, Frida; Jirström, Karin; Borrebaeck, Carl AK; Ek, Sara

    2011-01-01

    The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking. SOX11 expression and clinicopathological data was compared using χ 2 test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation. SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5'-Aza-2'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11. SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours

  1. The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation

    LENUS (Irish Health Repository)

    Sernbo, Sandra

    2011-09-24

    Abstract Background The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking. Methods SOX11 expression and clinicopathological data was compared using χ2 test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation. Results SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5\\'-Aza-2\\'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11. Conclusions SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours.

  2. The Integrated Status and Effectiveness Monitoring Program : Expansion of Existing Smolt Trapping Program and Steelhead Spawner Surveys : March 1st, 2008 - February 28th, 2009.

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Todd; Tonseth, Michael

    2009-01-01

    The Integrated Status and Effectiveness Monitoring Program (ISEMP - BPA project No.2003-0017) has been created as a cost effective means of developing protocols and new technologies, novel indicators, sample designs, analytical, data management and communication tools and skills, and restoration experiments that support the development of a region-wide Research, Monitoring and Evaluation (RME) program to assess the status of anadromous salmonid populations, their tributary habitat and restoration and management actions. The most straightforward approach to developing a regional-scale monitoring and evaluation program would be to increase standardization among status and trend monitoring programs. However, the diversity of species and their habitat, as well as the overwhelming uncertainty surrounding indicators, metrics, and data interpretation methods, requires the testing of multiple approaches. Thus, the approach ISEMP has adopted is to develop a broad template that may differ in the details among subbasins, but one that will ultimately lead to the formation of a unified RME process for the management of anadromous salmonid populations and habitat across the Columbia River Basin. ISEMP has been initiated in three pilot subbasins, the Wenatchee/Entiat, John Day, and Salmon. To balance replicating experimental approaches with the goal of developing monitoring and evaluation tools that apply as broadly as possible across the Pacific Northwest, these subbasins were chosen as representative of a wide range of potential challenges and conditions, e.g., differing fish species composition and life histories, ecoregions, institutional settings, and existing data. ISEMP has constructed a framework that builds on current status and trend monitoring infrastructures in these pilot subbasins, but challenges current programs by testing alternative monitoring approaches. In addition, the ISEMP is: (1) Collecting information over a hierarchy of spatial scales, allowing for a

  3. Integrated Status and Effectiveness Monitoring Program, Entiat River Status and Trend Snorkel Surveys and Rotary Smolt Trap Operations in Nason Creek, March 2007 through March 2008.

    Energy Technology Data Exchange (ETDEWEB)

    Collins, Matthew; Jorgensen, John; Murdock, Keely

    2008-03-10

    The Integrated Status and Effectiveness Monitoring Program (ISEMP-BPA project No.2003-0017) has been created as a cost effective means of developing protocols and new technologies, novel indicators, sample designs, analytical, data management and communication tools and skills, and restoration experiments that support the development of a region-wide Research, Monitoring and Evaluation (RME) program to assess the status of anadromous salmonid populations, their tributary habitat and restoration and management actions. The most straightforward approach to developing a regional-scale monitoring and evaluation program would be to increase standardization among status and trend monitoring programs. However, the diversity of species and their habitat, as well as the overwhelming uncertainty surrounding indicators, metrics, and data interpretation methods, requires the testing of multiple approaches. Thus, the approach ISEMP has adopted is to develop a broad template that may differ in the details among subbasins, but one that will ultimately lead to the formation of a unified RME process for the management of anadromous salmonid populations and habitat across the Columbia River Basin. ISEMP has been initiated in three pilot subbasins, the Wenatchee/Entiat, John Day, and Salmon. To balance replicating experimental approaches with the goal of developing monitoring and evaluation tools that apply as broadly as possible across the Pacific Northwest, these subbasins were chosen as representative of a wide range of potential challenges and conditions, e.g., differing fish species composition and life histories, ecoregions, institutional settings, and existing data. ISEMP has constructed a framework that builds on current status and trend monitoring infrastructures in these pilot subbasins, but challenges current programs by testing alternative monitoring approaches. In addition, the ISEMP is: (1) Collecting information over a hierarchy of spatial scales, allowing for a

  4. WATER-TRAPPED WORLDS

    International Nuclear Information System (INIS)

    Menou, Kristen

    2013-01-01

    Although tidally locked habitable planets orbiting nearby M-dwarf stars are among the best astronomical targets to search for extrasolar life, they may also be deficient in volatiles and water. Climate models for this class of planets show atmospheric transport of water from the dayside to the nightside, where it is precipitated as snow and trapped as ice. Since ice only slowly flows back to the dayside upon accumulation, the resulting hydrological cycle can trap a large amount of water in the form of nightside ice. Using ice sheet dynamical and thermodynamical constraints, I illustrate how planets with less than about a quarter the Earth's oceans could trap most of their surface water on the nightside. This would leave their dayside, where habitable conditions are met, potentially dry. The amount and distribution of residual liquid water on the dayside depend on a variety of geophysical factors, including the efficiency of rock weathering at regulating atmospheric CO 2 as dayside ocean basins dry up. Water-trapped worlds with dry daysides may offer similar advantages as land planets for habitability, by contrast with worlds where more abundant water freely flows around the globe

  5. Redesigning octopus traps

    Directory of Open Access Journals (Sweden)

    Eduarda Gomes

    2014-06-01

    In order to minimise the identified problems in the actual traps, the present work proposes a new design with the aim of reducing the volume and weight during transport, and also during onshore storage. Alternative materials to avoid corrosion and formation of encrustations were also proposed.

  6. WATER-TRAPPED WORLDS

    Energy Technology Data Exchange (ETDEWEB)

    Menou, Kristen [Department of Astronomy, Columbia University, 550 West 120th Street, New York, NY 10027 (United States)

    2013-09-01

    Although tidally locked habitable planets orbiting nearby M-dwarf stars are among the best astronomical targets to search for extrasolar life, they may also be deficient in volatiles and water. Climate models for this class of planets show atmospheric transport of water from the dayside to the nightside, where it is precipitated as snow and trapped as ice. Since ice only slowly flows back to the dayside upon accumulation, the resulting hydrological cycle can trap a large amount of water in the form of nightside ice. Using ice sheet dynamical and thermodynamical constraints, I illustrate how planets with less than about a quarter the Earth's oceans could trap most of their surface water on the nightside. This would leave their dayside, where habitable conditions are met, potentially dry. The amount and distribution of residual liquid water on the dayside depend on a variety of geophysical factors, including the efficiency of rock weathering at regulating atmospheric CO{sub 2} as dayside ocean basins dry up. Water-trapped worlds with dry daysides may offer similar advantages as land planets for habitability, by contrast with worlds where more abundant water freely flows around the globe.

  7. Waardenburg syndrome type 4: report of two new cases caused by SOX10 mutations in Spain.

    Science.gov (United States)

    Fernández, Raquel M; Núñez-Ramos, Raquel; Enguix-Riego, M Valle; Román-Rodríguez, Francisco José; Galán-Gómez, Enrique; Blesa-Sánchez, Emilio; Antiñolo, Guillermo; Núñez-Núñez, Ramón; Borrego, Salud

    2014-02-01

    Shah-Waardenburg syndrome or Waardenburg syndrome type 4 (WS4) is a neurocristopathy characterized by the association of deafness, depigmentation and Hirschsprung disease. Three disease-causing genes have been identified so far for WS4: EDNRB, EDN3, and SOX10. SOX10 mutations, found in 45-55% of WS4 patients, are inherited in autosomal dominant way. In addition, mutations in SOX10 are also responsible for an extended syndrome involving peripheral and central neurological phenotypes, referred to as PCWH (peripheral demyelinating neuropathy, central dysmyelinating leucodystrophy, Waardenburg syndrome, Hirschsprung disease). Such mutations are mostly private, and a high intra- and inter-familial variability exists. In this report, we present a patient with WS4 and a second with PCWH due to SOX10 mutations supporting again the genetic and phenotypic heterogeneity of these syndromes. Interestingly, the WS4 family carries an insertion of 19 nucleotides in exon 5 of SOX10, which results in distinct phenotypes along three different generations: hypopigmentation in the maternal grandmother, hearing loss in the mother, and WS4 in the proband. Since mosaicism cannot explain the three different related-WS features observed in this family, we propose as the most plausible explanation the existence of additional molecular events, acting in an additive or multiplicative fashion, in genes or regulatory regions unidentified so far. On the other hand, the PCWH case was due to a de novo deletion in exon 5 of the gene. Efforts should be devoted to unravel the mechanisms underlying the intrafamilial phenotypic variability observed in the families affected, and to identify new genes responsible for the still unsolved WS4 cases. © 2013 Wiley Periodicals, Inc.

  8. Andrographolide Induces Cell Cycle Arrest and Apoptosis of Chondrosarcoma by Targeting TCF-1/SOX9 Axis.

    Science.gov (United States)

    Zhang, Huan-Tian; Yang, Jie; Liang, Gui-Hong; Gao, Xue-Juan; Sang, Yuan; Gui, Tao; Liang, Zu-Jian; Tam, Man-Seng; Zha, Zhen-Gang

    2017-12-01

    Chondrosarcoma is the second most malignant bone tumor with poor prognosis and limited treatment options. Thus, development of more effective treatments has become urgent. Recently, natural compounds derived from medicinal plants have emerged as promising therapeutic options via targeting multiple key cellular molecules. Andrographolide (Andro) is such a compound, which has previously been shown to induce cell cycle arrest and apoptosis in several human cancers. However, the molecular mechanism through which Andro exerts its anti-cancer effect on chondrosarcoma remains to be elucidated. In the present study, we showed that Andro-induced G2/M cell cycle arrest of chondrosarcoma by fine-tuning the expressions of several cell cycle regulators such as p21, p27, and Cyclins, and that prolonged treatment of cells with Andro caused pronounced cell apoptosis. Remarkably, we found that SOX9 was highly expressed in poor-differentiated chondrosarcoma, and that knockdown of SOX9 suppressed chondrosarcoma cell growth. Further, our results showed that Andro dose-dependently down-regulated SOX9 expression in chondrosarcoma cells. Concomitantly, an inhibition of T cell factor 1 (TCF-1) mRNA expression and an enhancement of TCF-1 protein degradation by Andro were observed. In contrast, the expression and subcellular localization of β-catenin were not altered upon the treatment of Andro, suggesting that β-catenin might not function as the primary target of Andro. Additionally, we provided evidence that there was a mutual regulation between TCF-1 and SOX9 in chondrosarcoma cells. In conclusion, these results highlight the potential therapeutic effects of Andro in treatment of chondrosarcoma via targeting the TCF-1/SOX9 axis. J. Cell. Biochem. 118: 4575-4586, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. SOX10-Nano-Lantern Reporter Human iPS Cells; A Versatile Tool for Neural Crest Research.

    Directory of Open Access Journals (Sweden)

    Tomoko Horikiri

    Full Text Available The neural crest is a source to produce multipotent neural crest stem cells that have a potential to differentiate into diverse cell types. The transcription factor SOX10 is expressed through early neural crest progenitors and stem cells in vertebrates. Here we report the generation of SOX10-Nano-lantern (NL reporter human induced pluripotent stem cells (hiPS by using CRISPR/Cas9 systems, that are beneficial to investigate the generation and maintenance of neural crest progenitor cells. SOX10-NL positive cells are produced transiently from hiPS cells by treatment with TGFβ inhibitor SB431542 and GSK3 inhibitor CHIR99021. We found that all SOX10-NL-positive cells expressed an early neural crest marker NGFR, however SOX10-NL-positive cells purified from differentiated hiPS cells progressively attenuate their NL-expression under proliferation. We therefore attempted to maintain SOX10-NL-positive cells with additional signaling on the plane and sphere culture conditions. These SOX10-NL cells provide us to investigate mass culture with neural crest cells for stem cell research.

  10. Heterozygous deletion at the SOX10 gene locus in two patients from a Chinese family with Waardenburg syndrome type II.

    Science.gov (United States)

    Wenzhi, He; Ruijin, Wen; Jieliang, Li; Xiaoyan, Ma; Haibo, Liu; Xiaoman, Wang; Jiajia, Xian; Shaoying, Li; Shuanglin, Li; Qing, Li

    2015-10-01

    Waardenburg syndrome (WS) is a rare disease characterized by sensorineural deafness and pigment disturbance. To date, almost 100 mutations have been reported, but few reports on cases with SOX10 gene deletion. The inheritance pattern of SOX10 gene deletion is still unclear. Our objective was to identify the genetic causes of Waardenburg syndrome type II in a two-generation Chinese family. Clinical evaluations were conducted in both of the patients. Microarray analysis and multiplex ligation-dependent probe amplification (MLPA) were performed to identify disease-related copy number variants (CNVs). DNA sequencing of the SOX10, MITF and SNAI2 genes was performed to identify the pathogenic mutation responsible for WS2. A 280kb heterozygous deletion at the 22q13.1 chromosome region (including SOX10) was detected in both of the patients. No mutation was found in the patients, unaffected family members and 30 unrelated healthy controls. This report is the first to describe SOX10 heterozygous deletions in Chinese WS2 patients. Our result conform the thesis that heterozygous deletions at SOX10 is an important pathogenicity for WS, and present as autosomal dominant inheritance. Nevertheless, heterozygous deletion of the SOX10 gene would be worth investigating to understand their functions and contributions to neurologic phenotypes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. De novo dominant mutation of SOX10 gene in a Chinese family with Waardenburg syndrome type II.

    Science.gov (United States)

    Chen, Kaitian; Zong, Ling; Liu, Min; Zhan, Yuan; Wu, Xuan; Zou, Wenting; Jiang, Hongyan

    2014-06-01

    Waardenburg syndrome is a rare genetic disorder, inherited as an autosomal dominant trait. The condition is characterized by sensorineural hearing loss and pigment disturbances of the hair, skin, and iris. The de novo mutation in the SOX10 gene, responsible for Waardenburg syndrome type II, is rarely seen. The present study aimed to identify the genetic causes of Waardenburg syndrome type II in a Chinese family. Clinical and molecular evaluations were conducted in a Chinese family with Waardenburg syndrome type II. A novel SOX10 heterozygous c.259-260delCT mutation was identified. Heterozygosity was not observed in the parents and sister of the proband, indicating that the mutation has arisen de novo. The novel frameshift mutation, located in exon 3 of the SOX10 gene, disrupted normal amino acid coding from Leu87, leading to premature termination at nucleotide 396 (TGA). The high mobility group domain of SOX10 was inferred to be partially impaired. The novel heterozygous c.259-260delCT mutation in the SOX10 gene was considered to be the cause of Waardenburg syndrome in the proband. The clinical and genetic characterization of this family would help elucidate the genetic heterogeneity of SOX10 in Waardenburg syndrome type II. Moreover, the de novo pattern expanded the mutation data of SOX10. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes

    Science.gov (United States)

    Hata, Kenji; Takashima, Rikako; Amano, Katsuhiko; Ono, Koichiro; Nakanishi, Masako; Yoshida, Michiko; Wakabayashi, Makoto; Matsuda, Akio; Maeda, Yoshinobu; Suzuki, Yutaka; Sugano, Sumio; Whitson, Robert H.; Nishimura, Riko; Yoneda, Toshiyuki

    2013-11-01

    Histone modification, a critical step for epigenetic regulation, is an important modulator of biological events. Sox9 is a transcription factor critical for endochondral ossification; however, proof of its epigenetic regulation remains elusive. Here we identify AT-rich interactive domain 5b (Arid5b) as a transcriptional co-regulator of Sox9. Arid5b physically associates with Sox9 and synergistically induces chondrogenesis. Growth of Arid5b-/- mice is retarded with delayed endochondral ossification. Sox9-dependent chondrogenesis is attenuated in Arid5b-deficient cells. Arid5b recruits Phf2, a histone lysine demethylase, to the promoter region of Sox9 target genes and stimulates H3K9me2 demethylation of these genes. In the promoters of chondrogenic marker genes, H3K9me2 levels are increased in Arid5b-/- chondrocytes. Finally, we show that Phf2 knockdown inhibits Sox9-induced chondrocyte differentiation. Our findings establish an epigenomic mechanism of skeletal development, whereby Arid5b promotes chondrogenesis by facilitating Phf2-mediated histone demethylation of Sox9-regulated chondrogenic gene promoters.

  13. CRISPR reveals a distal super-enhancer required for Sox2 expression in mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Yan Li

    Full Text Available The pluripotency of embryonic stem cells (ESCs is maintained by a small group of master transcription factors including Oct4, Sox2 and Nanog. These core factors form a regulatory circuit controlling the transcription of a number of pluripotency factors including themselves. Although previous studies have identified transcriptional regulators of this core network, the cis-regulatory DNA sequences required for the transcription of these key pluripotency factors remain to be defined. We analyzed epigenomic data within the 1.5 Mb gene-desert regions around the Sox2 gene and identified a 13kb-long super-enhancer (SE located 100kb downstream of Sox2 in mouse ESCs. This SE is occupied by Oct4, Sox2, Nanog, and the mediator complex, and physically interacts with the Sox2 locus via DNA looping. Using a simple and highly efficient double-CRISPR genome editing strategy we deleted the entire 13-kb SE and characterized transcriptional defects in the resulting monoallelic and biallelic deletion clones with RNA-seq. We showed that the SE is responsible for over 90% of Sox2 expression, and Sox2 is the only target gene along the chromosome. Our results support the functional significance of a SE in maintaining the pluripotency transcription program in mouse ESCs.

  14. Hyperphagia, mild developmental delay but apparently no structural brain anomalies in a boy without SOX3 expression.

    Science.gov (United States)

    Helle, Johan Robert; Barøy, Tuva; Misceo, Doriana; Braaten, Øivind; Fannemel, Madeleine; Frengen, Eirik

    2013-05-01

    The transcription factor SOX3 is widely expressed in early vertebrate brain development. In humans, duplication of SOX3 and polyalanine expansions at its C-terminus may cause intellectual disability and hypopituitarism. Sox3 knock-out mice show a variable phenotype including structural and functional anomalies affecting the branchial arches and midline cerebral structures such as the optic chiasm and the hypothalamo-pituitary axis. SOX3 is claimed to be required in normal brain development and function in mice and humans, as well as in pituitary and craniofacial development. We report on an 8-year-old boy with a 2.1 Mb deletion in Xq27.1q27.2, which was found to be inherited from his healthy mother. To our knowledge, this is the smallest deletion including the entire SOX3 gene in a male reported to date. He is mildly intellectually disabled with language delay, dysarthria, behavior problems, minor facial anomalies, and hyperphagia. Hormone levels including growth, adrenocorticotropic and thyroid stimulating hormones are normal. Magnetic resonance imaging (MRI) at age 6 years showed no obvious brain anomalies. Genetic redundancy between the three members of the B1 subfamily of SOX proteins during early human brain development likely explains the apparently normal development of brain structures in our patient who is nullisomic for SOX3. Copyright © 2012 Wiley Periodicals, Inc.

  15. SOX2 co-occupies distal enhancer elements with distinct POU factors in ESCs and NPCs to specify cell state.

    Directory of Open Access Journals (Sweden)

    Michael A Lodato

    Full Text Available SOX2 is a master regulator of both pluripotent embryonic stem cells (ESCs and multipotent neural progenitor cells (NPCs; however, we currently lack a detailed understanding of how SOX2 controls these distinct stem cell populations. Here we show by genome-wide analysis that, while SOX2 bound to a distinct set of gene promoters in ESCs and NPCs, the majority of regions coincided with unique distal enhancer elements, important cis-acting regulators of tissue-specific gene expression programs. Notably, SOX2 bound the same consensus DNA motif in both cell types, suggesting that additional factors contribute to target specificity. We found that, similar to its association with OCT4 (Pou5f1 in ESCs, the related POU family member BRN2 (Pou3f2 co-occupied a large set of putative distal enhancers with SOX2 in NPCs. Forced expression of BRN2 in ESCs led to functional recruitment of SOX2 to a subset of NPC-specific targets and to precocious differentiation toward a neural-like state. Further analysis of the bound sequences revealed differences in the distances of SOX and POU peaks in the two cell types and identified motifs for additional transcription factors. Together, these data suggest that SOX2 controls a larger network of genes than previously anticipated through binding of distal enhancers and that transitions in POU partner factors may control tissue-specific transcriptional programs. Our findings have important implications for understanding lineage specification and somatic cell reprogramming, where SOX2, OCT4, and BRN2 have been shown to be key factors.

  16. Enteric Neuron Imbalance and Proximal Dysmotility in Ganglionated Intestine of the Sox10Dom/+ Hirschsprung Mouse ModelSummary

    Directory of Open Access Journals (Sweden)

    Melissa A. Musser

    2015-01-01

    Full Text Available Background & Aims: In Hirschsprung disease (HSCR, neural crest-derived progenitors (NCPs fail to completely colonize the intestine so that the enteric nervous system is absent from distal bowel. Despite removal of the aganglionic region, many HSCR patients suffer from residual intestinal dysmotility. To test the hypothesis that inappropriate lineage segregation of NCPs in proximal ganglionated regions of the bowel could contribute to such postoperative disease, we investigated neural crest (NC-derived lineages and motility in ganglionated, postnatal intestine of the Sox10Dom/+ HSCR mouse model. Methods: Cre-mediated fate-mapping was applied to evaluate relative proportions of NC-derived cell types. Motility assays were performed to assess gastric emptying and small intestine motility while colonic inflammation was assessed by histopathology for Sox10Dom/+ mutants relative to wild-type controls. Results: Sox10Dom/+ mice showed regional alterations in neuron and glia proportions as well as calretinin+ and neuronal nitric oxide synthase (nNOS+ neuronal subtypes. In the colon, imbalance of enteric NC derivatives correlated with the extent of aganglionosis. All Sox10Dom/+ mice exhibited reduced small intestinal transit at 4 weeks of age; at 6 weeks of age, Sox10Dom/+ males had increased gastric emptying rates. Sox10Dom/+ mice surviving to 6 weeks of age had little or no colonic inflammation when compared with wild-type littermates, suggesting that these changes in gastrointestinal motility are neurally mediated. Conclusions: The Sox10Dom mutation disrupts the balance of NC-derived lineages and affects gastrointestinal motility in the proximal, ganglionated intestine of adult animals. This is the first report identifying alterations in enteric neuronal classes in Sox10Dom/+ mutants, which suggests a previously unrecognized role for Sox10 in neuronal subtype specification. Keywords: Aganglionosis, Enteric Nervous System, Neural Crest

  17. Cross-species functional analyses reveal shared and separate roles for Sox11 in frog primary neurogenesis and mouse cortical neuronal differentiation

    Directory of Open Access Journals (Sweden)

    Chao Chen

    2016-04-01

    Full Text Available A well-functioning brain requires production of the correct number and types of cells during development; cascades of transcription factors are essential for cellular coordination. Sox proteins are transcription factors that affect various processes in the development of the nervous system. Sox11, a member of the SoxC family, is expressed in differentiated neurons and supports neuronal differentiation in several systems. To understand how generalizable the actions of Sox11 are across phylogeny, its function in the development of the frog nervous system and the mouse cerebral cortex were compared. Expression of Sox11 is largely conserved between these species; in the developing frog, Sox11 is expressed in the neural plate, neural tube and throughout the segmented brain, while in the mouse cerebral cortex, Sox11 is expressed in differentiated zones, including the preplate, subplate, marginal zone and cortical plate. In both frog and mouse, data demonstrate that Sox11 supports a role in promoting neuronal differentiation, with Sox11-positive cells expressing pan-neural markers and becoming morphologically complex. However, frog and mouse Sox11 cannot substitute for one another; a functional difference likely reflected in sequence divergence. Thus, Sox11 appears to act similarly in subserving neuronal differentiation but is species-specific in frog neural development and mouse corticogenesis.

  18. SOX2 plays a critical role in EGFR-mediated self-renewal of human prostate cancer stem-like cells.

    Science.gov (United States)

    Rybak, Adrian P; Tang, Damu

    2013-12-01

    SOX2 is an essential transcription factor for stem cells and plays a role in tumorigenesis, however its role in prostate cancer stem cells (PCSCs) remains unclear. We report here a significant upregulation of SOX2 at both mRNA and protein levels in DU145 PCSCs propagated as suspension spheres in vitro. The expression of SOX2 in DU145 PCSCs is positively regulated by epidermal growth factor receptor (EGFR) signaling. Activation of EGFR signaling, following the addition of epidermal growth factor (EGF) or ectopic expression of a constitutively-active EGFR mutant (EGFRvIII), increased SOX2 expression and the self-renewal of DU145 PCSCs. Conversely, a small molecule EGFR inhibitor (AG1478) blocked EGFR activation, reduced SOX2 expression and inhibited PCSC self-renewal activity, implicating SOX2 in mediating EGFR-dependent self-renewal of PCSCs. In line with this notion, ectopic SOX2 expression enhanced EGF-induced self-renewal of DU145 PCSCs, while SOX2 knockdown reduced PCSC self-renewal with EGF treatment no longer capable of enhancing their propagation. Furthermore, SOX2 knockdown reduced the capacity of DU145 PCSCs to grow under anchorage-independent conditions. Finally, DU145 PCSCs generated xenograft tumors more aggressively with elevated levels of SOX2 expression compared to xenograft tumors derived from non-PCSCs. Collectively, we provide evidence that SOX2 plays a critical role in EGFR-mediated self-renewal of DU145 PCSCs. © 2013.

  19. Genome-wide Reconstruction of OxyR and SoxRS Transcriptional Regulatory Networks under Oxidative Stress in Escherichia coli K-12 MG1655

    DEFF Research Database (Denmark)

    Seo, Sang Woo; Kim, Donghyuk; Szubin, Richard

    2015-01-01

    Three transcription factors (TFs), OxyR, SoxR, and SoxS, play a critical role in transcriptional regulation of the defense system for oxidative stress in bacteria. However, their full genome-wide regulatory potential is unknown. Here, we perform a genome-scale reconstruction of the OxyR, SoxR, an...

  20. Microwave quantum logic gates for trapped ions.

    Science.gov (United States)

    Ospelkaus, C; Warring, U; Colombe, Y; Brown, K R; Amini, J M; Leibfried, D; Wineland, D J

    2011-08-10

    Control over physical systems at the quantum level is important in fields as diverse as metrology, information processing, simulation and chemistry. For trapped atomic ions, the quantized motional and internal degrees of freedom can be coherently manipulated with laser light. Similar control is difficult to achieve with radio-frequency or microwave radiation: the essential coupling between internal degrees of freedom and motion requires significant field changes over the extent of the atoms' motion, but such changes are negligible at these frequencies for freely propagating fields. An exception is in the near field of microwave currents in structures smaller than the free-space wavelength, where stronger gradients can be generated. Here we first manipulate coherently (on timescales of 20 nanoseconds) the internal quantum states of ions held in a microfabricated trap. The controlling magnetic fields are generated by microwave currents in electrodes that are integrated into the trap structure. We also generate entanglement between the internal degrees of freedom of two atoms with a gate operation suitable for general quantum computation; the entangled state has a fidelity of 0.76(3), where the uncertainty denotes standard error of the mean. Our approach, which involves integrating the quantum control mechanism into the trapping device in a scalable manner, could be applied to quantum information processing, simulation and spectroscopy.

  1. [Trapping techniques for Solenopsis invicta].

    Science.gov (United States)

    Liang, Xiao-song; Zhang, Qiang; Zhuang, Yiong-lin; Li, Gui-wen; Ji, Lin-peng; Wang, Jian-guo; Dai, Hua-guo

    2007-06-01

    A field study was made to investigate the trapping effects of different attractants, traps, and wind directions on Solenopsis invicta. The results showed that among the test attractants, TB1 (50 g fishmeal, 40 g peptone, 10 ml 10% sucrose water solution and 20 ml soybean oil) had the best effect, followed by TB2 (ham), TB6 (100 g cornmeal and 20 ml soybean oil) and TB4 (10 ml 10% sucrose water solution, 100 g sugarcane powder and 20 ml soybean oil), with a mean capture efficiency being 77.6, 58.7, 29 and 7.7 individuals per trap, respectively. No S. invicta was trapped with TB3 (10 ml 10% sucrose water solution, 100 g cornmeal and 20 ml soybean oil) and TB5 (honey). Tube trap was superior to dish trap, with a trapping efficiency of 75.2 and 35 individuals per trap, respectively. The attractants had better effects in leeward than in windward.

  2. Optical trapping of gold aerosols

    DEFF Research Database (Denmark)

    Schmitt, Regina K.; Pedersen, Liselotte Jauffred; Taheri, S. M.

    2015-01-01

    Aerosol trapping has proven challenging and was only recently demonstrated.1 This was accomplished by utilizing an air chamber designed to have a minimum of turbulence and a laser beam with a minimum of aberration. Individual gold nano-particles with diameters between 80 nm and 200 nm were trapped...... in air using a 1064 nm laser. The positions visited by the trapped gold nano-particle were quantified using a quadrant photo diode placed in the back focal plane. The time traces were analyzed and the trapping stiffness characterizing gold aerosol trapping determined and compared to aerosol trapping...... of nanometer sized silica and polystyrene particles. Based on our analysis, we concluded that gold nano-particles trap more strongly in air than similarly sized polystyrene and silica particles. We found that, in a certain power range, the trapping strength of polystyrene particles is linearly decreasing...

  3. Escaping the tolerance trap

    International Nuclear Information System (INIS)

    Hammoudeh, S.; Madan, V.

    1994-01-01

    In order to examine the implications of the weakening of OPEC's responsiveness in adjusting its production levels, this paper explicitly incorporates rigidity in the quantity adjustment mechanism, thereby extending previous research which assumed smooth quantity adjustments. The rigidity is manifested in a tolerance range for the discrepancy between the declared target price and that of the market. This environment gives rise to a 'tolerance trap' which impedes the convergence process and inevitably brings the market to a standstill before its reaches the targeted price and revenue objectives. OPEC's reaction to the standstill has important implications for the achievement of the target-based equilibrium and for the potential collapse of the market price. This paper examines OPEC's policy options in the tolerance trap and reveals that the optional policy in order to break this impasse and move closer to the equilibrium point is gradually to reduce output and not to flood the market. (Author)

  4. Trapped Ion Qubits

    Energy Technology Data Exchange (ETDEWEB)

    Maunz, Peter Lukas Wilhelm

    2017-04-01

    Qubits can be encoded in clock states of trapped ions. These states are well isolated from the environment resulting in long coherence times [1] while enabling efficient high-fidelity qubit interactions mediated by the Coulomb coupled motion of the ions in the trap. Quantum states can be prepared with high fidelity and measured efficiently using fluorescence detection. State preparation and detection with 99.93% fidelity have been realized in multiple systems [1,2]. Single qubit gates have been demonstrated below rigorous fault-tolerance thresholds [1,3]. Two qubit gates have been realized with more than 99.9% fidelity [4,5]. Quantum algorithms have been demonstrated on systems of 5 to 15 qubits [6–8].

  5. Integration

    DEFF Research Database (Denmark)

    Emerek, Ruth

    2004-01-01

    Bidraget diskuterer de forskellige intergrationsopfattelse i Danmark - og hvad der kan forstås ved vellykket integration......Bidraget diskuterer de forskellige intergrationsopfattelse i Danmark - og hvad der kan forstås ved vellykket integration...

  6. Single florescent nanodiamond in a three dimensional ABEL trap

    Science.gov (United States)

    Kayci, Metin; Radenovic, Aleksandra

    2015-01-01

    Three dimensional single particle trapping and manipulation is an outstanding challenge in various fields ranging from basic physics to life sciences. By monitoring the response of a trapped particle to a designed environment one can extract its characteristics. In addition, quantum dynamics of a spatially scanned well-known particle can provide environmental information. Precise tracking and positioning of such a particle in aqueous environment is crucial task for achieving nano-scale resolution. Here we experimentally demonstrate three dimensional ABEL trap operating at high frequency by employing a hybrid approach in particle tracking. The particle location in the transverse plane is detected via a scanning laser beam while the axial position is determined by defocused imaging. The scanning of the trapped particle is accomplished through a nano positioning stage integrated to the trap platform. PMID:26559890

  7. SOX10-positive cells emerge in the rat pituitary gland during late embryogenesis and start to express S100β.

    Science.gov (United States)

    Ueharu, Hiroki; Yoshida, Saishu; Kanno, Naoko; Horiguchi, Kotaro; Nishimura, Naoto; Kato, Takako; Kato, Yukio

    2018-04-01

    In the pituitary gland, S100β-positive cells localize in the neurohypophysis and adenohypophysis but the lineage of the two groups remains obscure. S100β is often observed in many neural crest-derived cell types. Therefore, in this study, we investigate the origin of pituitary S100β-positive cells by immunohistochemistry for SOX10, a potent neural crest cell marker, using S100β-green fluorescence protein-transgenic rats. On embryonic day 21.5, a SOX10-positive cell population, which was also positive for the stem/progenitor cell marker SOX2, emerged in the pituitary stalk and posterior lobe and subsequently expanded to create a rostral-caudal gradient on postnatal day 3 (P3). Thereafter, SOX10-positive cells appeared in the intermediate lobe by P15, localizing to the boundary facing the posterior lobe, the gap between the lobule structures and the marginal cell layer, a pituitary stem/progenitor cell niche. Subsequently, there was an increase in SOX10/S100β double-positive cells; some of these cells in the gap between the lobule structures showed extended cytoplasm containing F-actin, indicating a feature of migration activity. The proportion of SOX10-positive cells in the postnatal anterior lobe was lower than 0.025% but about half of them co-localized with the pituitary-specific progenitor cell marker PROP1. Collectively, the present study identified that one of the lineages of S100β-positive cells is a SOX10-positive one and that SOX10-positive cells express pituitary stem/progenitor cell marker genes.

  8. SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions.

    Science.gov (United States)

    Bakrania, P; Robinson, D O; Bunyan, D J; Salt, A; Martin, A; Crolla, J A; Wyatt, A; Fielder, A; Ainsworth, J; Moore, A; Read, S; Uddin, J; Laws, D; Pascuel-Salcedo, D; Ayuso, C; Allen, L; Collin, J R O; Ragge, N K

    2007-11-01

    Developmental eye anomalies, which include anophthalmia (absent eye) or microphthalmia (small eye) are an important cause of severe visual impairment in infants and young children. Heterozygous mutations in SOX2, a SOX1B-HMG box transcription factor, have been found in up to 10% of individuals with severe microphthalmia or anophthalmia and such mutations could also be associated with a range of non-ocular abnormalities. We performed mutation analysis on a new cohort of 120 patients with congenital eye abnormalities, mainly anophthalmia, microphthalmia and coloboma. Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridisation (FISH) were used to detect whole gene deletion. We identified four novel intragenic SOX2 mutations (one single base deletion, one single base duplication and two point mutations generating premature translational termination codons) and two further cases with the previously reported c.70del20 mutation. Of 52 patients with severe microphthalmia or anophthalmia analysed by MLPA, 5 were found to be deleted for the whole SOX2 gene and 1 had a partial deletion. In two of these, FISH studies identified sub-microscopic deletions involving a minimum of 328 Kb and 550 Kb. The SOX2 phenotypes include a patient with anophthalmia, oesophageal abnormalities and horseshoe kidney, and a patient with a retinal dystrophy implicating SOX2 in retinal development. Our results provide further evidence that SOX2 haploinsufficiency is a common cause of severe developmental ocular malformations and that background genetic variation determines the varying phenotypes. Given the high incidence of whole gene deletion we recommend that all patients with severe microphthalmia or anophthalmia, including unilateral cases be screened by MLPA and FISH for SOX2 deletions.

  9. Efficacy and safety of SOX chemotherapy with or without surgery in AFP-producing advanced gastric cancer

    OpenAIRE

    Li, Zhu; Hou, Xu; Chen, Juan; Sun, Huidong; Mi, Yuetang; Sui, Yongling; Li, Yuhong; Xie, Jiaping; Qiao, Yingli; Lei, Xiaofeng; Che, Xiaoshuang; Liu, Jun

    2017-01-01

    The present study investigated the clinical efficacy of S-1 plus oxaliplatin (SOX) regimen, with or without surgery in ?-fetoprotein-producing gastric cancer (APGC) with liver metastasis. A total of 24 patients with APGC treated at the Liaocheng People's Hospital between January 2011 and December 2013 were retrospectively reviewed. Clinical efficacy and patient safety were compared between the two groups. The median progression-free survival (PFS) and overall survival (OS) in the SOX group we...

  10. Interchromosomal insertional translocation at Xq26.3 alters SOX3 expression in an individual with XX male sex reversal.

    Science.gov (United States)

    Haines, Bryan; Hughes, James; Corbett, Mark; Shaw, Marie; Innes, Josie; Patel, Leena; Gecz, Jozef; Clayton-Smith, Jill; Thomas, Paul

    2015-05-01

    46,XX male sex reversal occurs in approximately 1: 20 000 live births and is most commonly caused by interchromosomal translocations of the Y-linked sex-determining gene, SRY. Rearrangements of the closely related SOX3 gene on the X chromosome are also associated with 46,XX male sex reversal. It has been hypothesized that sex reversal in the latter is caused by ectopic expression of SOX3 in the developing urogenital ridge where it triggers male development by acting as an analog of SRY. However, altered regulation of SOX3 in individuals with XX male sex reversal has not been demonstrated. Here we report a boy with SRY-negative XX male sex reversal who was diagnosed at birth with a small phallus, mixed gonads, and borderline-normal T. Molecular characterization of the affected individual was performed using array comparative genomic hybridization, fluorescent in situ hybridization of metaphase chromosomes, whole-genome sequencing, and RT-PCR expression analysis of lymphoblast cell lines. The affected male carries ∼774-kb insertion translocation from chromosome 1 into a human-specific palindromic sequence 82 kb distal to SOX3. Importantly, robust SOX3 expression was identified in cells derived from the affected individual but not from control XX or XY cells, indicating that the translocation has a direct effect on SOX3 regulation. This is the first demonstration of altered SOX3 expression in an individual with XX male sex reversal and suggests that SOX3 can substitute for SRY to initiate male development in humans.

  11. SOX4 inhibits GBM cell growth and induces G0/G1 cell cycle arrest through Akt-p53 axis.

    Science.gov (United States)

    Zhang, Jing; Jiang, Huawei; Shao, Jiaofang; Mao, Ruifang; Liu, Jie; Ma, Yingying; Fang, Xuefeng; Zhao, Na; Zheng, Shu; Lin, Biaoyang

    2014-11-01

    SOX4 is a transcription factor required for tissue development and differentiation in vertebrates. Overexpression of SOX4 has been reported in many cancers including glioblastoma multiforme (GBM), however, the underlying mechanism of actions has not been studied. In this study, we investigated the role of SOX4 in GBM. Kaplan-Meier analysis was performed to assess the association between SOX4 expression levels and survival times in primary GBM samples. Cre/lox P system was used to generate gain or loss of SOX4 in GBM cells, and microarray analysis uncovered the regulation network of SOX4 in GBM cells. High SOX4 expression was significantly associated with good prognosis of primary GBMs. SOX4 inhibited the growth of GBM cell line LN229, A172G and U87MG, partly via the activation of p53-p21 signaling and down-regulation of phosphorylated AKT1. Gene expression profiling and subsequent gene ontology analysis showed that SOX4 influenced several key pathways including the Wnt/ beta-catenin and TGF-beta signaling pathways. Our study found that SOX4 acts as a tumor suppressor in GBM cells by induce cell cycle arrest and inhibiting cell growth.

  12. Global regulator SoxR is a negative regulator of efflux pump gene expression and affects antibiotic resistance and fitness in Acinetobacter baumannii.

    Science.gov (United States)

    Li, Henan; Wang, Qi; Wang, Ruobing; Zhang, Yawei; Wang, Xiaojuan; Wang, Hui

    2017-06-01

    SoxR is a global regulator contributing to multidrug resistance in Enterobacteriaceae. However, the contribution of SoxR to antibiotic resistance and fitness in Acinetobacter baumannii has not yet been studied. Comparisons of molecular characteristics were performed between 32 multidrug-resistant A. baumannii isolates and 11 susceptible isolates. A soxR overexpression mutant was constructed, and its resistance phenotype was analyzed. The impact of SoxR on efflux pump gene expression was measured at the transcription level. The effect of SoxR on the growth and fitness of A. baumannii was analyzed using a growth rate assay and an in vitro competition assay. The frequency of the Gly39Ser mutation in soxR was higher in multidrug-resistant A. baumannii, whereas the soxS gene was absent in all strains analyzed. SoxR overexpression led to increased susceptibility to chloramphenicol (4-fold), tetracycline (2-fold), tigecycline (2-fold), ciprofloxacin (2-fold), amikacin (2-fold), and trimethoprim (2-fold), but it did not influence imipenem susceptibility. Decreased expression of abeS (3.8-fold), abeM (1.3-fold), adeJ (2.4-fold), and adeG (2.5-fold) were correlated with soxR overexpression (P baumannii.

  13. Waardenburg syndrome: a rare cause of inherited neuropathy due to SOX10 mutation.

    Science.gov (United States)

    Bogdanova-Mihaylova, Petya; Alexander, Michael D; Murphy, Raymond P J; Murphy, Sinéad M

    2017-09-01

    Waardenburg syndrome (WS) is a rare disorder comprising sensorineural deafness and pigmentation abnormalities. Four distinct subtypes are defined based on the presence or absence of additional symptoms. Mutations in six genes have been described in WS. SOX10 mutations are usually associated with a more severe phenotype of WS with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, and Hirschsprung disease. Here we report a 32-year-old man with a novel heterozygous missense variant in SOX10 gene, who presented with congenital deafness, Hirschsprung disease, iris heterochromia, foot deformity, and intermediate conduction velocity length-dependent sensorimotor neuropathy. This case highlights that the presence of other non-neuropathic features in a patient with presumed hereditary neuropathy should alert the clinician to possible atypical rare causes. © 2017 Peripheral Nerve Society.

  14. Isolated hypogonadotropic hypogonadism with SOX2 mutation and anophthalmia/microphthalmia in offspring.

    Science.gov (United States)

    Stark, Zornitza; Storen, Rebecca; Bennetts, Bruce; Savarirayan, Ravi; Jamieson, Robyn V

    2011-07-01

    Isolated hypogonadotropic hypogonadism (IHH) is a genetically heterogeneous condition in which patients frequently require assisted reproduction to achieve fertility. In patients with IHH who are otherwise well, no particular increased risk of congenital anomalies in the resultant offspring has been highlighted. Heterozygous mutations in SOX2 are the commonest single-gene cause of anophthalmia/microphthalmia (A/M) and sometimes result in pituitary abnormalities. We report a family with a novel frameshift mutation in the SOX2 transactivation domain, p.Gly280AlafsX91, resulting in bilateral anophthalmia and subtle endocrinological abnormalities in a male sibling, and unilateral microphthalmia in a female sibling. The mutation is present in their mother who has IHH, but has no eye disorders or other anomalies. She underwent assisted reproduction to achieve fertility. This report has important implications for the evaluation of patients with IHH, particularly in the setting of planned infertility treatment.

  15. Argumentative SOX Compliant and Quality Decision Support Intelligent Expert System over the Suppliers Selection Process

    Directory of Open Access Journals (Sweden)

    Jesus Angel Fernandez Canelas

    2013-01-01

    Full Text Available The objective of this paper is to define a decision support system over SOX (Sarbanes-Oxley Act compatibility and quality of the Suppliers Selection Process based on Artificial Intelligence and Argumentation Theory knowledge and techniques. The present SOX Law, in effect nowadays, was created to improve financial government control over US companies. This law is a factor standard out United States due to several factors like present globalization, expansion of US companies, or key influence of US stock exchange markets worldwide. This paper constitutes a novel approach to this kind of problems due to following elements: (1 it has an optimized structure to look for the solution, (2 it has a dynamic learning method to handle court and control gonvernment bodies decisions, (3 it uses fuzzy knowledge to improve its performance, and (4 it uses its past accumulated experience to let the system evolve far beyond its initial state.

  16. Transcription Factor SOX5 Promotes the Migration and Invasion of Fibroblast-Like Synoviocytes in Part by Regulating MMP-9 Expression in Collagen-Induced Arthritis

    Directory of Open Access Journals (Sweden)

    Yumeng Shi

    2018-04-01

    Full Text Available ObjectivesFibroblast-like synoviocytes (FLS exhibit a unique aggressive phenotype in rheumatoid arthritis (RA. Increased FLS migration and subsequent invasion of the extracellular matrix are essential to joint destruction in RA. Our previous research reported that transcription factor SOX5 was highly expressed in RA-FLS. Here, the effects of SOX5 in RA-FLS migration and invasion will be investigated.MethodsThe migration and invasion of RA-FLS were evaluated using a transwell chamber assay. The expression of several potential SOX5-targeted genes, including matrix metalloproteinases (MMP-1, 2, 3 and 9, chemokines (CCL4, CCL2, CCR5 and CCR2, and pro-inflammatory cytokines (TNF-α and IL-6, were examined in RA-FLS using SOX5 gain- and loss-of-function study. The molecular mechanisms of SOX5-mediated MMP-9 expressions were assayed by luciferase reporter gene and chromatin immunoprecipitation (ChIP studies. The in vivo effect of SOX5 on FLS migration and invasion was examined using collagen-induced arthritis (CIA in DBA/1J mice.ResultsKnockdown SOX5 decreased lamellipodium formation, migration, and invasion of RA-FLS. The expression of MMP-9 was the only gene tested to be concomitantly affected by silencing or overexpressing SOX5. ChIP assay revealed that SOX5 was bound to the MMP-9 promoter in RA-FLS. The overexpression of SOX5 markedly enhanced the MMP-9 promoter activity, and specific deletion of a putative SOX5-binding site in MMP-9 promoter diminished this promoter-driven transcription in FLS. Locally knocked down SOX5 inhibited MMP-9 expression in the joint tissue and reduced pannus migration and invasion into the cartilage in CIA mice.ConclusionSOX5 plays a novel role in mediating migration and invasion of FLS in part by regulating MMP-9 expression in RA.

  17. Transcription Factor SOX5 Promotes the Migration and Invasion of Fibroblast-Like Synoviocytes in Part by Regulating MMP-9 Expression in Collagen-Induced Arthritis.

    Science.gov (United States)

    Shi, Yumeng; Wu, Qin; Xuan, Wenhua; Feng, Xiaoke; Wang, Fang; Tsao, Betty P; Zhang, Miaojia; Tan, Wenfeng

    2018-01-01

    Fibroblast-like synoviocytes (FLS) exhibit a unique aggressive phenotype in rheumatoid arthritis (RA). Increased FLS migration and subsequent invasion of the extracellular matrix are essential to joint destruction in RA. Our previous research reported that transcription factor SOX5 was highly expressed in RA-FLS. Here, the effects of SOX5 in RA-FLS migration and invasion will be investigated. The migration and invasion of RA-FLS were evaluated using a transwell chamber assay. The expression of several potential SOX5-targeted genes, including matrix metalloproteinases (MMP-1, 2, 3 and 9), chemokines (CCL4, CCL2, CCR5 and CCR2), and pro-inflammatory cytokines (TNF-α and IL-6), were examined in RA-FLS using SOX5 gain- and loss-of-function study. The molecular mechanisms of SOX5-mediated MMP-9 expressions were assayed by luciferase reporter gene and chromatin immunoprecipitation (ChIP) studies. The in vivo effect of SOX5 on FLS migration and invasion was examined using collagen-induced arthritis (CIA) in DBA/1J mice. Knockdown SOX5 decreased lamellipodium formation, migration, and invasion of RA-FLS. The expression of MMP-9 was the only gene tested to be concomitantly affected by silencing or overexpressing SOX5. ChIP assay revealed that SOX5 was bound to the MMP-9 promoter in RA-FLS. The overexpression of SOX5 markedly enhanced the MMP-9 promoter activity, and specific deletion of a putative SOX5-binding site in MMP-9 promoter diminished this promoter-driven transcription in FLS. Locally knocked down SOX5 inhibited MMP-9 expression in the joint tissue and reduced pannus migration and invasion into the cartilage in CIA mice. SOX5 plays a novel role in mediating migration and invasion of FLS in part by regulating MMP-9 expression in RA.

  18. LSD1 demethylase and the methyl-binding protein PHF20L1 prevent SET7 methyltransferase-dependent proteolysis of the stem-cell protein SOX2.

    Science.gov (United States)

    Zhang, Chunxiao; Hoang, Nam; Leng, Feng; Saxena, Lovely; Lee, Logan; Alejo, Salvador; Qi, Dandan; Khal, Anthony; Sun, Hong; Lu, Fei; Zhang, Hui

    2018-03-09

    The pluripotency-controlling stem-cell protein SRY-box 2 (SOX2) plays a pivotal role in maintaining the self-renewal and pluripotency of embryonic stem cells and also of teratocarcinoma or embryonic carcinoma cells. SOX2 is monomethylated at lysine 119 (Lys-119) in mouse embryonic stem cells by the SET7 methyltransferase, and this methylation triggers ubiquitin-dependent SOX2 proteolysis. However, the molecular regulators and mechanisms controlling SET7-induced SOX2 proteolysis are unknown. Here, we report that in human ovarian teratocarcinoma PA-1 cells, methylation-dependent SOX2 proteolysis is dynamically regulated by the LSD1 lysine demethylase and a methyl-binding protein, PHD finger protein 20-like 1 (PHF20L1). We found that LSD1 not only removes the methyl group from monomethylated Lys-117 (equivalent to Lys-119 in mouse SOX2), but it also demethylates monomethylated Lys-42 in SOX2, a reaction that SET7 also regulated and that also triggered SOX2 proteolysis. Our studies further revealed that PHF20L1 binds both monomethylated Lys-42 and Lys-117 in SOX2 and thereby prevents SOX2 proteolysis. Down-regulation of either LSD1 or PHF20L1 promoted SOX2 proteolysis, which was prevented by SET7 inactivation in both PA-1 and mouse embryonic stem cells. Our studies also disclosed that LSD1 and PHF20L1 normally regulate the growth of pluripotent mouse embryonic stem cells and PA-1 cells by preventing methylation-dependent SOX2 proteolysis. In conclusion, our findings reveal an important mechanism by which the stability of the pluripotency-controlling stem-cell protein SOX2 is dynamically regulated by the activities of SET7, LSD1, and PHF20L1 in pluripotent stem cells. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Two-stage gene regulation of the superoxide stress response soxRS system in Escherichia coli.

    Science.gov (United States)

    Nunoshiba, T

    1996-01-01

    All organisms have adapted to environmental changes by acquiring various functions controlled by gene regulation. In bacteria, a number of specific responses have been found to confer cell survival in various nutrient-limited conditions, and under physiological stresses such as high or low temperature, extreme pH, radiation, and oxidation (for review, see Neidhardt et al., 1987). In this article, I introduce an Escherichia coli (E. coli) global response induced by superoxide stress, the soxRS regulon. The functions controlled by this system consist of a wide variety of enzymes such as manganese-containing SOD (Mn-SOD); glucose 6-phosphate dehydrogenase (G6PD), the DNA repair enzyme endonuclease IV, fumarase C, NADPH:ferredoxin oxidoreductase, and aconitase. This response is positively regulated by a two-stage control system in which SoxR iron-sulfur protein senses exposure to superoxide and nitric oxide, and then activates transcription of the soxS gene, whose product stimulates the expression of the regulon genes. Our recent finding indicates that soxS transcription is initiated in a manner dependent on the rpoS gene encoding RNA polymerase sigma factor, theta s, in response to entering the stationary phase of growth. With this information, mechanisms for prokaryotic coordinating gene expression in response to superoxide stress and in stationary phase are discussed.

  20. Purification, crystallization and preliminary X-ray diffraction analysis of the HMG domain of Sox17 in complex with DNA

    International Nuclear Information System (INIS)

    Ng, Calista Keow Leng; Palasingam, Paaventhan; Venkatachalam, Rajakannan; Baburajendran, Nithya; Cheng, Jason; Jauch, Ralf; Kolatkar, Prasanna R.

    2008-01-01

    Crystals of the Sox17 HMG domain bound to LAMA1 enhancer DNA-element crystals that diffracted to 2.75 Å resolution were obtained. Sox17 is a member of the SRY-related high-mobility group (HMG) of transcription factors that have been shown to direct endodermal differentiation in early mammalian development. The LAMA1 gene encoding the α-chain of laminin-1 has been reported to be directly bound and regulated by Sox17. This paper describes the details of initial crystallization attempts with the HMG domain of mouse Sox17 (mSox17-HMG) with a 16-mer DNA element derived from the LAMA1 enhancer and optimization strategies to obtain a better diffracting crystal. The best diffracting crystal was obtained in a condition containing 0.1 M Tris–HCl pH 7.4, 0.2 M MgCl 2 , 30% PEG 3350 using the hanging-drop vapour-diffusion method. A highly redundant in-house data set was collected to 2.75 Å resolution with 99% completeness. The presence of the mSox17-HMG–DNA complex within the crystals was confirmed and Matthews analysis indicated the presence of one complex per asymmetric unit

  1. De novo SOX10 Nonsense Mutation in a Patient with Kallmann Syndrome, Deafness, Iris Hypopigmentation, and Hyperthyroidism.

    Science.gov (United States)

    Wang, Fang; Zhao, Shaoli; Xie, Yanhong; Yang, Wenjun; Mo, Zhaohui

    2018-03-01

    Kallmann syndrome (KS) is a clinically and genetically heterogeneous disorder characterized by hypogonadotropic hypogonadism and olfactory dysfunction. Recently, mutations in SOX10, a well-known causative gene of Waardenburg syndrome (WS), have been identified in a few KS patients with additional developmental defects including hearing loss. However, the understanding of SOX10 mutation associates with KS and other clinical consequences remains fragmentary. A 30-year-old Chinese male patient presented with no pubertal sex development when he was at the age of twelve years. Additionally, he showed anosmia, sensory deafness, and blue irises. Last year, he developed clinical symptoms of hyperthyroidism with a fast heartbeat, heat intolerance and weight loss. Blood examinations revealed low levels of FSH, LH, and testosterone. Thyroid function showed high levels of FT3, FT4 and extremely low level of TSH. Molecular analysis detected a de novo (c.565G>T/p.E189X) mutation in SOX10, which has previously been reported in a patient with WS4 (WS with Hirschsprung). The mutation was predicted to be probably damaging. These results highlight the significance of SOX10 haploinsufficiency as a genetic cause of KS. Importantly, our result implies that the same SOX10 mutation can underlie both typical KS and WS, while the correlation between SOX10 and hyperthyroidism still needs to be clarified in the future. © 2018 by the Association of Clinical Scientists, Inc.

  2. Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects.

    Science.gov (United States)

    Bauters, Marijke; Frints, Suzanna G; Van Esch, Hilde; Spruijt, Liesbeth; Baldewijns, Marcella M; de Die-Smulders, Christine E M; Fryns, Jean-Pierre; Marynen, Peter; Froyen, Guy

    2014-08-01

    Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from 138.7 to 139.8 Mb, harboring only two annotated genes, SOX3 and ATP11C, and was shown to be a direct tandem copy number gain. Unexpectedly, the microduplication did not fully segregate with the disease in this family suggesting that SOX3 duplications have variable penetrance for X-linked hypopituitarism. In the same family, a female fetus presenting with a neural tube defect was also shown to carry the SOX3 copy number gain. Since we also demonstrated increased SOX3 mRNA levels in amnion cells derived from an unrelated t(X;22)(q27;q11) female fetus with spina bifida, we propose that increased levels of SOX3 could be a risk factor for neural tube defects. © 2014 Wiley Periodicals, Inc.

  3. Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients: Discovery and validation studies

    Directory of Open Access Journals (Sweden)

    Karin Hellner

    2016-08-01

    Full Text Available Current screening methods for ovarian cancer can only detect advanced disease. Earlier detection has proved difficult because the molecular precursors involved in the natural history of the disease are unknown. To identify early driver mutations in ovarian cancer cells, we used dense whole genome sequencing of micrometastases and microscopic residual disease collected at three time points over three years from a single patient during treatment for high-grade serous ovarian cancer (HGSOC. The functional and clinical significance of the identified mutations was examined using a combination of population-based whole genome sequencing, targeted deep sequencing, multi-center analysis of protein expression, loss of function experiments in an in-vivo reporter assay and mammalian models, and gain of function experiments in primary cultured fallopian tube epithelial (FTE cells. We identified frequent mutations involving a 40 kb distal repressor region for the key stem cell differentiation gene SOX2. In the apparently normal FTE, the region was also mutated. This was associated with a profound increase in SOX2 expression (p < 2−16, which was not found in patients without cancer (n = 108. Importantly, we show that SOX2 overexpression in FTE is nearly ubiquitous in patients with HGSOCs (n = 100, and common in BRCA1-BRCA2 mutation carriers (n = 71 who underwent prophylactic salpingo-oophorectomy. We propose that the finding of SOX2 overexpression in FTE could be exploited to develop biomarkers for detecting disease at a premalignant stage, which would reduce mortality from this devastating disease.

  4. SOx-NOx-Rox Box{trademark} flue gas clean-up demonstration. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    Babcock and Wilcox`s (B and W) SOx-NOx-Rox Box{trademark} process effectively removes SOx, NOx and particulate (Rox) from flue gas generated from coal-fired boilers in a single unit operation, a high temperature baghouse. The SNRB technology utilizes dry sorbent injection upstream of the baghouse for removal of SOx and ammonia injection upstream of a zeolitic selective catalytic reduction (SCR) catalyst incorporated in the baghouse to reduce NOx emissions. Because the SOx and NOx removal processes require operation at elevated gas temperatures (800--900 F) for high removal efficiency, high-temperature fabric filter bags are used in the baghouse. The SNRB technology evolved from the bench and laboratory pilot scale to be successfully demonstrated at the 5-MWe field scale. This report represents the completion of Milestone M14 as specified in the Work Plan. B and W tested the SNRB pollution control system at a 5-MWe demonstration facility at Ohio Edison`s R.E. Burger Plant located near Shadyside, Ohio. The design and operation were influenced by the results from laboratory pilot testing at B and W`s Alliance Research Center. The intent was to demonstrate the commercial feasibility of the SNRB process. The SNRB facility treated a 30,000 ACFM flue gas slipstream from Boiler No. 8. Operation of the facility began in May 1992 and was completed in May 1993. About 2,300 hours of high-temperature operation were achieved. The main emissions control performance goals of: greater than 70% SO{sub 2} removal using a calcium-based sorbent; greater than 90% NOx removal with minimal ammonia slip; and particulate emissions in compliance with the New Source Performance Standards (NSPS) of 0.03 lb/million Btu were exceeded simultaneously in the demonstration program when the facility was operated at optimal conditions. Testing also showed significant reductions in emissions of some hazardous air pollutants.

  5. OCT4 and SOX2 are reliable markers in detecting stem cells in odontogenic lesions

    Directory of Open Access Journals (Sweden)

    Abhishek Banerjee

    2016-01-01

    Full Text Available Context (Background: Stem cells are a unique subpopulation of cells in the human body with a capacity to initiate differentiation into various cell lines. Tumor stem cells (TSCs are a unique subpopulation of cells that possess the ability to initiate a neoplasm and sustain self-renewal. Epithelial stem cell (ESC markers such as octamer-binding transcription factor 4 (OCT4 and sex-determining region Y (SRY-box 2 (SOX2 are capable of identifying these stem cells expressed during the early stages of tooth development. Aims: To detect the expression of the stem cell markers OCT4 and SOX2 in the normal odontogenic tissues and the odontogenic cysts and tumors. Materials and Methods: Paraffin sections of follicular tissue, radicular cyst, dentigerous cyst, odontogenic keratocyst, ameloblastoma, adenomatoid odontogenic tumor, and ameloblastic carcinoma were obtained from the archives. The sections were subjected to immunohistochemical assay by the use of mouse monoclonal antibodies to OCT4 and SOX2. Statistical Analysis: The results were evaluated by descriptive analysis. Results: The results show the presence of stem cells in the normal and lesional tissues with these stem cell identifying markers. SOX2 was found to be more consistent and reliable in the detection of stem cells. Conclusion: The stem cell expressions are maintained in the tumor transformation of tissue and probably suggest that there is no phenotypic change of stem cells in progression from normal embryonic state to its tumor component. The quantification and localization reveals interesting trends that indicate the probable role of the cells in the pathogenesis of the lesions.

  6. Exploring the utility of organo-polyoxometalate hybrids to inhibit SOX transcription factors.

    Science.gov (United States)

    Narasimhan, Kamesh; Micoine, Kevin; Lacôte, Emmanuel; Thorimbert, Serge; Cheung, Edwin; Hasenknopf, Bernold; Jauch, Ralf

    2014-01-01

    SOX transcription factors constitute an attractive target class for intervention with small molecules as they play a prominent role in the field of regenerative biomedicine and cancer biology. However, rationally engineering specific inhibitors that interfere with transcription factor DNA interfaces continues to be a monumental challenge in the field of transcription factor chemical biology. Polyoxometalates (POMs) are inorganic compounds that were previously shown to target the high-mobility group (HMG) of SOX proteins at nanomolar concentrations. In continuation of this work, we carried out an assessment of the selectivity of a panel of newly synthesized organo-polyoxometalate hybrids in targeting different transcription factor families to enable the usage of polyoxometalates as specific SOX transcription factor drugs. The residual DNA-binding activities of 15 different transcription factors were measured after treatment with a panel of diverse polyoxometalates. Polyoxometalates belonging to the Dawson structural class were found to be more potent inhibitors than the Keggin class. Further, organically modified Dawson polyoxometalates were found to be the most potent in inhibiting transcription factor DNA binding activity. The size of the polyoxometalates and its derivitization were found to be the key determinants of their potency. Polyoxometalates are highly potent, nanomolar range inhibitors of the DNA binding activity of the Sox-HMG family. However, binding assays involving a limited subset of structurally diverse polyoxometalates revealed a low selectivity profile against different transcription factor families. Further progress in achieving selectivity and deciphering structure-activity relationship of POMs require the identification of POM binding sites on transcription factors using elaborate approaches like X-ray crystallography and multidimensional NMR. In summary, our report reaffirms that transcription factors are challenging molecular architectures

  7. miR-126 Functions as a Tumor Suppressor in Osteosarcoma by Targeting Sox2

    Directory of Open Access Journals (Sweden)

    Chenglin Yang

    2013-12-01

    Full Text Available Osteosarcoma (OS is the most common malignant bone tumor in children and young adults, the early symptoms and signs of which are non-specific. The discovery of microRNAs (miRNAs provides a new avenue for the early diagnosis and treatment of OS. miR-126 has been reported to be highly expressed in vascularized tissues, and is recently widely studied in cancers. Herein, we explored the expression and significance of miR-126 in OS. Using TaqMan RT-PCR analysis, we analyzed the expression of miR-126 in 32 paired OS tumor tissues and 4 OS cell lines and found that miR-126 was consistently under-expressed in OS tissues and cell lines compared with normal bone tissues and normal osteoblast cells (NHOst, respectively. As miR-126 is significantly decreased in OS tissues and cell lines, we sought to compensate for its loss through exogenous transfection into MG-63 cells with a miR-126 mimic. Ectopic expression of miR-126 inhibited cell proliferation, migration and invasion, and induced apoptosis of MG-63 cells. Moreover, bioinformatic prediction suggested that the sex-determining region Y-box 2 (Sox2 is a target gene of miR-126. Using mRNA and protein expression analysis, luciferase assays and rescue assays, we demonstrate that restored expression of Sox2 dampened miR-126-mediated suppression of tumor progression, which suggests the important role of miR-126/Sox2 interaction in tumor progression. Taken together, our data indicate that miR-126 functions as a tumor suppressor in OS, which exerts its activity by suppressing the expression of Sox2.

  8. [Integrity].

    Science.gov (United States)

    Gómez Rodríguez, Rafael Ángel

    2014-01-01

    To say that someone possesses integrity is to claim that that person is almost predictable about responses to specific situations, that he or she can prudentially judge and to act correctly. There is a closed interrelationship between integrity and autonomy, and the autonomy rests on the deeper moral claim of all humans to integrity of the person. Integrity has two senses of significance for medical ethic: one sense refers to the integrity of the person in the bodily, psychosocial and intellectual elements; and in the second sense, the integrity is the virtue. Another facet of integrity of the person is la integrity of values we cherish and espouse. The physician must be a person of integrity if the integrity of the patient is to be safeguarded. The autonomy has reduced the violations in the past, but the character and virtues of the physician are the ultimate safeguard of autonomy of patient. A field very important in medicine is the scientific research. It is the character of the investigator that determines the moral quality of research. The problem arises when legitimate self-interests are replaced by selfish, particularly when human subjects are involved. The final safeguard of moral quality of research is the character and conscience of the investigator. Teaching must be relevant in the scientific field, but the most effective way to teach virtue ethics is through the example of the a respected scientist.

  9. Quantum Information Experiments with Trapped Ions at NIST

    Science.gov (United States)

    Wilson, Andrew

    2015-03-01

    We present an overview of recent trapped-ion quantum information experiments at NIST. Advancing beyond few-qubit ``proof-of-principle'' experiments to the many-qubit systems needed for practical quantum simulation and information processing, without compromising on the performance demonstrated with small systems, remains a major challenge. One approach to scalable hardware development is surface-electrode traps. Micro-fabricated planar traps can have a number of useful features, including flexible electrode geometries, integrated microwave delivery, and spatio-temporal tuning of potentials for ion transport and spin-spin interactions. In this talk we report on a number of on-going investigations with surface traps. Experiments feature a multi-zone trap with closely spaced ions in a triangular arrangement (a first step towards 2D arrays of ions with tunable spin-spin interactions), a scheme for smooth transport through a junction in a 2D structure based on switchable RF potentials, and a micro-fabricated photo-detector integrated into a trap. We also give a progress report on our latest efforts to improve the fidelity of both optical and microwave 2-qubit gates. This work was supported by IARPA, ONR and the NIST Quantum Information Program. The 3-ion and switchable-RF-junction traps were developed in collaboration with Sandia National Laboratory.

  10. Spectrum of temporal bone abnormalities in patients with Waardenburg syndrome and SOX10 mutations.

    Science.gov (United States)

    Elmaleh-Bergès, M; Baumann, C; Noël-Pétroff, N; Sekkal, A; Couloigner, V; Devriendt, K; Wilson, M; Marlin, S; Sebag, G; Pingault, V

    2013-01-01

    Waardenburg syndrome, characterized by deafness and pigmentation abnormalities, is clinically and genetically heterogeneous, consisting of 4 distinct subtypes and involving several genes. SOX10 mutations have been found both in types 2 and 4 Waardenburg syndrome and neurologic variants. The purpose of this study was to evaluate both the full spectrum and relative frequencies of inner ear malformations in these patients. Fifteen patients with Waardenburg syndrome and different SOX10 mutations were studied retrospectively. Imaging was performed between February 2000 and March 2010 for cochlear implant work-up, diagnosis of hearing loss, and/or evaluation of neurologic impairment. Eleven patients had both CT and MR imaging examinations, 3 had MR imaging only, and 1 had CT only. Temporal bone abnormalities were bilateral. The most frequent pattern associated agenesis or hypoplasia of ≥1 semicircular canal, an enlarged vestibule, and a cochlea with a reduced size and occasionally an abnormal shape, but with normal partition in the 13/15 cases that could be analyzed. Three patients lacked a cochlear nerve, bilaterally in 2 patients. In addition, associated abnormalities were found when adequate MR imaging sequences were available: agenesis of the olfactory bulbs (7/8), hypoplastic or absent lacrimal glands (11/14), hypoplastic parotid glands (12/14), and white matter signal anomalies (7/13). In the appropriate clinical context, bilateral agenesis or hypoplasia of the semicircular canals or both, associated with an enlarged vestibule and a cochlear deformity, strongly suggests a diagnosis of Waardenburg syndrome linked to a SOX10 mutation.

  11. SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia.

    Science.gov (United States)

    Mauri, Lucia; Franzoni, Alessandra; Scarcello, Manuela; Sala, Stefano; Garavelli, Livia; Modugno, Alessandra; Grammatico, Paola; Patrosso, Maria Cristina; Piozzi, Elena; Del Longo, Alessandra; Gesu, Giovanni P; Manfredini, Emanuela; Primignani, Paola; Damante, Giuseppe; Penco, Silvana

    2015-02-01

    Anophthalmia (A) and microphthalmia (M) are rare developmental anomalies that have significant effects on visual activity. In fraction of A/M subjects, single genetic defects have been identified as causative. In this study we analysed 65 Italian A/M patients, 21 of whom are syndromic, for mutations in SOX2, OTX2 and PAX6 genes. In syndromic patients the presence of genome imbalances through array CGH was also investigated. No mutations were found for OTX2 and PAX6 genes. Three causative SOX2 mutations were found in subjects with syndromic A. In a subject with syndromic signs and monolateral M, two de novo 6.26 Mb and 1.37 Mb deletions in 4q13.2q13.3 have been identified. A SOX2 missense (p.Ala161Ser) mutation was found in 1 out of 39 a subject with non-syndromic monolateral M. Alanine at position 161 is conserved along phylogeny and the p.Ala161Ser mutation is estimated pathogenic by in silico analysis. However, this mutation was also present in the unaffected patient's daughter. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. MicroRNA-320 suppresses colorectal cancer by targeting SOX4, FOXM1, and FOXQ1

    DEFF Research Database (Denmark)

    Vishnubalaji, Radhakrishnan; Hamam, Rimi; Shijun, Yue

    2016-01-01

    Colorectal cancer (CRC) is the third most common cancer causing high mortality rates world-wide. Delineating the molecular mechanisms leading to CRC development and progression, including the role of microRNAs (miRNAs), are currently being unravelled at a rapid rate. Here, we report frequent down...... for the miR-320/SOX4/FOXM1/FOXQ1 axes in promoting CRC development and progression and suggest targeting those networks as potential therapeutic strategy for CRC....... mice. Global gene expression analysis in CRC cells over-expressing miR-320c, combined with in silico prediction identified 84 clinically-relevant potential gene targets for miR-320 in CRC. Using a series of biochemical assays and functional validation, SOX4, FOXM1, and FOXQ1 were validated as novel...... gene targets for the miR-320 family. Inverse correlation between the expression of miR-320 members with SOX4, FOXM1, and FOXQ1 was observed in primary CRC patients' specimens, suggesting that these genes are likely bona fide targets for the miR-320 family. Interestingly, interrogation of the expression...

  13. Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice

    Science.gov (United States)

    Overman, Jeroen; Fontaine, Frank; Moustaqil, Mehdi; Mittal, Deepak; Sierecki, Emma; Sacilotto, Natalia; Zuegg, Johannes; Robertson, Avril AB; Holmes, Kelly; Salim, Angela A; Mamidyala, Sreeman; Butler, Mark S; Robinson, Ashley S; Lesieur, Emmanuelle; Johnston, Wayne; Alexandrov, Kirill; Black, Brian L; Hogan, Benjamin M; De Val, Sarah; Capon, Robert J; Carroll, Jason S; Bailey, Timothy L; Koopman, Peter; Jauch, Ralf; Smyth, Mark J; Cooper, Matthew A; Gambin, Yann; Francois, Mathias

    2017-01-01

    Pharmacological targeting of transcription factors holds great promise for the development of new therapeutics, but strategies based on blockade of DNA binding, nuclear shuttling, or individual protein partner recruitment have yielded limited success to date. Transcription factors typically engage in complex interaction networks, likely masking the effects of specifically inhibiting single protein-protein interactions. Here, we used a combination of genomic, proteomic and biophysical methods to discover a suite of protein-protein interactions involving the SOX18 transcription factor, a known regulator of vascular development and disease. We describe a small-molecule that is able to disrupt a discrete subset of SOX18-dependent interactions. This compound selectively suppressed SOX18 transcriptional outputs in vitro and interfered with vascular development in zebrafish larvae. In a mouse pre-clinical model of breast cancer, treatment with this inhibitor significantly improved survival by reducing tumour vascular density and metastatic spread. Our studies validate an interactome-based molecular strategy to interfere with transcription factor activity, for the development of novel disease therapeutics. DOI: http://dx.doi.org/10.7554/eLife.21221.001 PMID:28137359

  14. NFATc4 Regulates Sox9 Gene Expression in Acinar Cell Plasticity and Pancreatic Cancer Initiation

    Directory of Open Access Journals (Sweden)

    Elisabeth Hessmann

    2016-01-01

    Full Text Available Acinar transdifferentiation toward a duct-like phenotype constitutes the defining response of acinar cells to external stress signals and is considered to be the initial step in pancreatic carcinogenesis. Despite the requirement for oncogenic Kras in pancreatic cancer (PDAC development, oncogenic Kras is not sufficient to drive pancreatic carcinogenesis beyond the level of premalignancy. Instead, secondary events, such as inflammation-induced signaling activation of the epidermal growth factor (EGFR or induction of Sox9 expression, are required for tumor formation. Herein, we aimed to dissect the mechanism that links EGFR signaling to Sox9 gene expression during acinar-to-ductal metaplasia in pancreatic tissue adaptation and PDAC initiation. We show that the inflammatory transcription factor NFATc4 is highly induced and localizes in the nucleus in response to inflammation-induced EGFR signaling. Moreover, we demonstrate that NFATc4 drives acinar-to-ductal conversion and PDAC initiation through direct transcriptional induction of Sox9. Therefore, strategies designed to disrupt NFATc4 induction might be beneficial in the prevention or therapy of PDAC.

  15. Stable Trapping of Multielectron Helium Bubbles in a Paul Trap

    Science.gov (United States)

    Joseph, E. M.; Vadakkumbatt, V.; Pal, A.; Ghosh, A.

    2017-06-01

    In a recent experiment, we have used a linear Paul trap to store and study multielectron bubbles (MEBs) in liquid helium. MEBs have a charge-to-mass ratio (between 10^{-4} and 10^{-2} C/kg) which is several orders of magnitude smaller than ions (between 10^6 and 10^8 C/kg) studied in traditional ion traps. In addition, MEBs experience significant drag force while moving through the liquid. As a result, the experimental parameters for stable trapping of MEBs, such as magnitude and frequency of the applied electric fields, are very different from those used in typical ion trap experiments. The purpose of this paper is to model the motion of MEBs inside a linear Paul trap in liquid helium, determine the range of working parameters of the trap, and compare the results with experiments.

  16. Scalable error correction in distributed ion trap computers

    International Nuclear Information System (INIS)

    Oi, Daniel K. L.; Devitt, Simon J.; Hollenberg, Lloyd C. L.

    2006-01-01

    A major challenge for quantum computation in ion trap systems is scalable integration of error correction and fault tolerance. We analyze a distributed architecture with rapid high-fidelity local control within nodes and entangled links between nodes alleviating long-distance transport. We demonstrate fault-tolerant operator measurements which are used for error correction and nonlocal gates. This scheme is readily applied to linear ion traps which cannot be scaled up beyond a few ions per individual trap but which have access to a probabilistic entanglement mechanism. A proof-of-concept system is presented which is within the reach of current experiment

  17. Atom trap trace analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Z.-T.; Bailey, K.; Chen, C.-Y.; Du, X.; Li, Y.-M.; O' Connor, T. P.; Young, L.

    2000-05-25

    A new method of ultrasensitive trace-isotope analysis has been developed based upon the technique of laser manipulation of neutral atoms. It has been used to count individual {sup 85}Kr and {sup 81}Kr atoms present in a natural krypton sample with isotopic abundances in the range of 10{sup {minus}11} and 10{sup {minus}13}, respectively. The atom counts are free of contamination from other isotopes, elements,or molecules. The method is applicable to other trace-isotopes that can be efficiently captured with a magneto-optical trap, and has a broad range of potential applications.

  18. Atom trap trace analysis

    International Nuclear Information System (INIS)

    Lu, Z.-T.; Bailey, K.; Chen, C.-Y.; Du, X.; Li, Y.-M.; O'Connor, T. P.; Young, L.

    2000-01-01

    A new method of ultrasensitive trace-isotope analysis has been developed based upon the technique of laser manipulation of neutral atoms. It has been used to count individual 85 Kr and 81 Kr atoms present in a natural krypton sample with isotopic abundances in the range of 10 -11 and 10 -13 , respectively. The atom counts are free of contamination from other isotopes, elements,or molecules. The method is applicable to other trace-isotopes that can be efficiently captured with a magneto-optical trap, and has a broad range of potential applications

  19. Magnetic traps with a sperical separatrix: Tornado traps

    International Nuclear Information System (INIS)

    Peregood, B.P.; Lehnert, B.

    1979-11-01

    A review is given on the features of magnetic traps with a spherical separatrix, with special emphesis on Tornado spiral coil configurations. The confinement and heating of static plasmas in Tornado traps is treated, including the topology of the magnetic field structure, the magneto-mechanical properties of the magnetic coil system, as well as the particle orbits and plasma behaviour in these traps. In additio, the mode of rotating plasma operation by crossed electric and magnetic fields is being described. The results of experiments on static and rotating plasmas are summarized, and conclusions are drawn about future possibilities of Tornado traps for the creation and containment of hot plasmas. (author)

  20. Magnetic traps with a spherical separatrix: Tornado traps

    International Nuclear Information System (INIS)

    Peregood, B.P.; Lehnert, B.

    1981-01-01

    A review is given on the features of magnetic traps with a spherical separatrix, with special emphasis on Tornado spiral coil configurations. The confinement and heating of static plasms in Tornado traps is treated, including the topology of the magnetic field structure, the magneto-mechanical properties of the magnetic coil system, as well as the particle orbits and plasma behaviour in these traps. In addition, the mode of rotating plasma operation by crossed electric and magnetic fields is described. The results of experiments on static and rotating plasmas are summarized, and conclusions are drawn about future possibilities of Tornado traps in the creation and containment of hot plasmas. (orig.)

  1. Characteristics of trapped electrons and electron traps in single crystals

    International Nuclear Information System (INIS)

    Budzinski, E.E.; Potter, W.R.; Potienko, G.; Box, H.C.

    1979-01-01

    Two additional carbohydrates are reported whose crystal structures trap electrons intermolecularly in single crystals x irradiated at low temperature, namely sucrose and rhamnose. Five carbohydrate and polyhydroxy compounds are now known which exhibit this phenomenon. The following characteristics of the phenomenon were investigated: (1) the hyperfine couplings of the electron with protons of the polarized hydroxy groups forming the trap; (2) the distances between these protons and the trapped electron; (3) the spin density of the electron at the protons and (4) the relative stabilities of the electron trapped in various crystal structures

  2. SOX9 governs differentiation stage-specific gene expression in growth plate chondrocytes via direct concomitant transactivation and repression.

    Directory of Open Access Journals (Sweden)

    Victor Y L Leung

    2011-11-01

    Full Text Available Cartilage and endochondral bone development require SOX9 activity to regulate chondrogenesis, chondrocyte proliferation, and transition to a non-mitotic hypertrophic state. The restricted and reciprocal expression of the collagen X gene, Col10a1, in hypertrophic chondrocytes and Sox9 in immature chondrocytes epitomise the precise spatiotemporal control of gene expression as chondrocytes progress through phases of differentiation, but how this is achieved is not clear. Here, we have identified a regulatory element upstream of Col10a1 that enhances its expression in hypertrophic chondrocytes in vivo. In immature chondrocytes, where Col10a1 is not expressed, SOX9 interacts with a conserved sequence within this element that is analogous to that within the intronic enhancer of the collagen II gene Col2a1, the known transactivation target of SOX9. By analysing a series of Col10a1 reporter genes in transgenic mice, we show that the SOX9 binding consensus in this element is required to repress expression of the transgene in non-hypertrophic chondrocytes. Forced ectopic Sox9 expression in hypertrophic chondrocytes in vitro and in mice resulted in down-regulation of Col10a1. Mutation of a binding consensus motif for GLI transcription factors, which are the effectors of Indian hedgehog signaling, close to the SOX9 site in the Col10a1 regulatory element, also derepressed transgene expression in non-hypertrophic chondrocytes. GLI2 and GLI3 bound to the Col10a1 regulatory element but not to the enhancer of Col2a1. In addition to Col10a1, paired SOX9-GLI binding motifs are present in the conserved non-coding regions of several genes that are preferentially expressed in hypertrophic chondrocytes and the occurrence of pairing is unlikely to be by chance. We propose a regulatory paradigm whereby direct concomitant positive and negative transcriptional control by SOX9 ensures differentiation phase-specific gene expression in chondrocytes. Discrimination between

  3. Prdm1a and miR-499 act sequentially to restrict Sox6 activity to the fast-twitch muscle lineage in the zebrafish embryo.

    Science.gov (United States)

    Wang, XinGang; Ono, Yosuke; Tan, Swee Chuan; Chai, Ruth JinFen; Parkin, Caroline; Ingham, Philip W

    2011-10-01

    Sox6 has been proposed to play a conserved role in vertebrate skeletal muscle fibre type specification. In zebrafish, sox6 transcription is repressed in slow-twitch progenitors by the Prdm1a transcription factor. Here we identify sox6 cis-regulatory sequences that drive fast-twitch-specific expression in a Prdm1a-dependent manner. We show that sox6 transcription subsequently becomes derepressed in slow-twitch fibres, whereas Sox6 protein remains restricted to fast-twitch fibres. We find that translational repression of sox6 is mediated by miR-499, the slow-twitch-specific expression of which is in turn controlled by Prdm1a, forming a regulatory loop that initiates and maintains the slow-twitch muscle lineage.

  4. ATRAP - Progress Towards Trapped Antihydrogen

    International Nuclear Information System (INIS)

    Grzonka, D.; Goldenbaum, F.; Oelert, W.; Sefzick, T.; Zhang, Z.; Comeau, D.; Hessels, E.A.; Storry, C.H.; Gabrielse, G.; Larochelle, P.; Lesage, D.; Levitt, B.; Speck, A.; Haensch, T.W.; Pittner, H.; Walz, J.

    2005-01-01

    The ATRAP experiment at the CERN antiproton decelerator AD aims for a test of the CPT invariance by a high precision comparison of the 1s-2s transition in the hydrogen and the antihydrogen atom.Antihydrogen production is routinely operated at ATRAP and detailed studies have been performed in order to optimize the production efficiency of useful antihydrogen.For high precision measurements of atomic transitions cold antihydrogen in the ground state is required which must be trapped due to the low number of available antihydrogen atoms compared to the cold hydrogen beam used for hydrogen spectroscopy. To ensure a reasonable antihydrogen trapping efficiency a magnetic trap has to be superposed the nested Penning trap. First trapping tests of charged particles within a combined magnetic/Penning trap have started at ATRAP

  5. ATRAP Progress Towards Trapped Antihydrogen

    CERN Document Server

    Grzonka, D; Gabrielse, G; Goldenbaum, F; Hänsch, T W; Hessels, E A; Larochelle, P; Le Sage, D; Levitt, B; Oelert, W; Pittner, H; Sefzick, T; Speck, A; Storry, C H; Walz, J; Zhang, Z

    2005-01-01

    The ATRAP experiment at the CERN antiproton decelerator AD aims for a test of the CPT invariance by a high precision comparison of the 1s‐2s transition in the hydrogen and the antihydrogen atom. Antihydrogen production is routinely operated at ATRAP and detailed studies have been performed in order to optimize the production efficiency of useful antihydrogen. For high precision measurements of atomic transitions cold antihydrogen in the ground state is required which must be trapped due to the low number of available antihydrogen atoms compared to the cold hydrogen beam used for hydrogen spectroscopy. To ensure a reasonable antihydrogen trapping efficiency a magnetic trap has to be superposed the nested Penning trap. First trapping tests of charged particles within a combined magnetic/Penning trap have started at ATRAP.

  6. Calibration of optically trapped nanotools

    Energy Technology Data Exchange (ETDEWEB)

    Carberry, D M; Simpson, S H; Grieve, J A; Hanna, S; Miles, M J [H H Wills Physics Laboratory, University of Bristol, Tyndall Avenue, Bristol BS8 1TL (United Kingdom); Wang, Y; Schaefer, H; Steinhart, M [Institute for Chemistry, University of Osnabrueck, Osnabrueck (Germany); Bowman, R; Gibson, G M; Padgett, M J, E-mail: m.j.miles@bristol.ac.uk [SUPA, Department of Physics and Astronomy, University of Glasgow, Science Road, Glasgow G12 8QQ (United Kingdom)

    2010-04-30

    Holographically trapped nanotools can be used in a novel form of force microscopy. By measuring the displacement of the tool in the optical traps, the contact force experienced by the probe can be inferred. In the following paper we experimentally demonstrate the calibration of such a device and show that its behaviour is independent of small changes in the relative position of the optical traps. Furthermore, we explore more general aspects of the thermal motion of the tool.

  7. Deletions and de novo mutations of SOX11 are associated with a neurodevelopmental disorder with features of Coffin-Siris syndrome.

    Science.gov (United States)

    Hempel, Annmarie; Pagnamenta, Alistair T; Blyth, Moira; Mansour, Sahar; McConnell, Vivienne; Kou, Ikuyo; Ikegawa, Shiro; Tsurusaki, Yoshinori; Matsumoto, Naomichi; Lo-Castro, Adriana; Plessis, Ghislaine; Albrecht, Beate; Battaglia, Agatino; Taylor, Jenny C; Howard, Malcolm F; Keays, David; Sohal, Aman Singh; Kühl, Susanne J; Kini, Usha; McNeill, Alisdair

    2016-03-01

    SOX11 is a transcription factor proposed to play a role in brain development. The relevance of SOX11 to human developmental disorders was suggested by a recent report of SOX11 mutations in two patients with Coffin-Siris syndrome. Here we further investigate the role of SOX11 variants in neurodevelopmental disorders. We used array based comparative genomic hybridisation and trio exome sequencing to identify children with intellectual disability who have deletions or de novo point mutations disrupting SOX11. The pathogenicity of the SOX11 mutations was assessed using an in vitro gene expression reporter system. Loss-of-function experiments were performed in xenopus by knockdown of Sox11 expression. We identified seven individuals with chromosome 2p25 deletions involving SOX11. Trio exome sequencing identified three de novo SOX11 variants, two missense (p.K50N; p.P120H) and one nonsense (p.C29*). The biological consequences of the missense mutations were assessed using an in vitro gene expression system. These individuals had microcephaly, developmental delay and shared dysmorphic features compatible with mild Coffin-Siris syndrome. To further investigate the function of SOX11, we knocked down the orthologous gene in xenopus. Morphants had significant reduction in head size compared with controls. This suggests that SOX11 loss of function can be associated with microcephaly. We thus propose that SOX11 deletion or mutation can present with a Coffin-Siris phenotype. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. Optical traps with geometric aberrations

    International Nuclear Information System (INIS)

    Roichman, Yael; Waldron, Alex; Gardel, Emily; Grier, David G.

    2006-01-01

    We assess the influence of geometric aberrations on the in-plane performance of optical traps by studying the dynamics of trapped colloidal spheres in deliberately distorted holographic optical tweezers. The lateral stiffness of the traps turns out to be insensitive to moderate amounts of coma, astigmatism, and spherical aberration. Moreover holographic aberration correction enables us to compensate inherent shortcomings in the optical train, thereby adaptively improving its performance. We also demonstrate the effects of geometric aberrations on the intensity profiles of optical vortices, whose readily measured deformations suggest a method for rapidly estimating and correcting geometric aberrations in holographic trapping systems

  9. Effectiveness of compression stockings to prevent the post-thrombotic syndrome (The SOX Trial and Bio-SOX biomarker substudy: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Rodger Marc A

    2007-07-01

    Full Text Available Abstract Background Post thrombotic syndrome (PTS is a burdensome and costly complication of deep venous thrombosis (DVT that develops in 20–40% of patients within 1–2 years after symptomatic DVT. Affected patients have chronic leg pain and swelling and may develop ulcers. Venous valve disruption from the thrombus itself or thrombus-associated mediators of inflammation is considered to be a key initiating event for the development of venous hypertension that often underlies PTS. As existing treatments for PTS are extremely limited, strategies that focus on preventing the development of PTS in patients with DVT are more likely to be effective and cost-effective in reducing its burden. Elastic compression stockings (ECS could be helpful in preventing PTS; however, data on their effectiveness are scarce and conflicting. Methods/Design The SOX Trial is a randomized, allocation concealed, double-blind multicenter clinical trial. The objective of the study is to evaluate ECS to prevent PTS. A total of 800 patients with proximal DVT will be randomized to one of 2 treatment groups: ECS or placebo (inactive stockings worn on the DVT-affected leg daily for 2 years. The primary outcome is the incidence of PTS during follow-up. Secondary outcomes are severity of PTS, venous thromboembolism (VTE recurrence, death from VTE, quality of life and cost-effectiveness. Outcomes will be evaluated during 6 clinic visits and 2 telephone follow ups. At baseline, 1 and 6 months, blood samples will be obtained to evaluate the role of inflammatory mediators and genetic markers of thrombophilia in the development of PTS (Bio-SOX substudy. Discussion The SOX Trial will be the largest study and the first with a placebo control to evaluate the effectiveness of ECS to prevent PTS. It is designed to provide definitive data on the effects of ECS on the occurrence and severity of PTS, as well as DVT recurrence, cost-effectiveness and quality of life. This study will also

  10. Coop-Seq Analysis Demonstrates that Sox2 Evokes Latent Specificities in the DNA Recognition by Pax6.

    Science.gov (United States)

    Hu, Caizhen; Malik, Vikas; Chang, Yiming Kenny; Veerapandian, Veeramohan; Srivastava, Yogesh; Huang, Yong-Heng; Hou, Linlin; Cojocaru, Vlad; Stormo, Gary D; Jauch, Ralf

    2017-11-24

    Sox2 and Pax6 co-regulate genes in neural lineages and the lens by forming a ternary complex likely facilitated allosterically through DNA. We used the quantitative and scalable cooperativity-by-sequencing (Coop-seq) approach to interrogate Sox2/Pax6 dimerization on a DNA library where five positions of the Pax6 half-site were randomized yielding 1024 cooperativity factors. Consensus positions normally required for the high-affinity DNA binding by Pax6 need to be mutated for effective dimerization with Sox2. Out of the five randomized bases, a 5' thymidine is present in most of the top ranking elements. However, this thymidine maps to a region outside of the Pax half site and is not expected to directly interact with Pax6 in known binding modes suggesting structural reconfigurations. Re-analysis of ChIP-seq data identified several genomic regions where the cooperativity promoting sequence pattern is co-bound by Sox2 and Pax6. A highly conserved Sox2/Pax6 bound site near the Sprouty2 locus was verified to promote cooperative dimerization designating Sprouty2 as a potential target reliant on Sox2/Pax6 cooperativity in several neural cell types. Collectively, the functional interplay of Sox2 and Pax6 demands the relaxation of high-affinity binding sites and is enabled by alternative DNA sequences. We conclude that this binding mode evolved to warrant that a subset of target genes is only regulated in the presence of suitable partner factors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. A live-trap and trapping technique for fossorial mammals

    African Journals Online (AJOL)

    mammals. G.C. Hickman. An effective live-trap was designed for Cryptomys hottentotus .... that there is an animal in the burrow system, and to lessen the likelihood of the .... the further testing and modification of existing trap types. Not only is it ...

  12. Electron traps in semiconducting polymers : Exponential versus Gaussian trap distribution

    NARCIS (Netherlands)

    Nicolai, H. T.; Mandoc, M. M.; Blom, P. W. M.

    2011-01-01

    The low electron currents in poly(dialkoxy-p-phenylene vinylene) (PPV) derivatives and their steep voltage dependence are generally explained by trap-limited conduction in the presence of an exponential trap distribution. Here we demonstrate that the electron transport of several PPV derivatives can

  13. Electron traps in semiconducting polymers: exponential versus Gaussian trap distribution

    NARCIS (Netherlands)

    Nicolai, H.T.; Mandoc, M.M.; Blom, P.W.M.

    2011-01-01

    The low electron currents in poly(dialkoxy-p-phenylene vinylene) (PPV) derivatives and their steep voltage dependence are generally explained by trap-limited conduction in the presence of an exponential trap distribution. Here we demonstrate that the electron transport of several PPV derivatives can

  14. In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus

    Science.gov (United States)

    Suh, Hoonkyo; Consiglio, Antonella; Ray, Jasodhara; Sawai, Toru; D'Amour, Kevin A.; Gage, Fred H.

    2007-01-01

    Summary To characterize the properties of adult neural stem cells (NSCs), we generated and analyzed Sox2-GFP transgenic mice. Sox2-GFP cells in the subgranular zone (SGZ) express markers specific for progenitors, but they represent two morphologically distinct populations that differ in proliferation levels. Lentivirus- and retrovirus-mediated fate tracing studies showed that Sox2+ cells in the SGZ have potential to give rise to neurons and astrocytes, revealing their multipotency at the population as well as a single cell level. More interestingly, a subpopulation of Sox2+ cells gives rise to cells that retain Sox2, highlighting Sox2+ cells as a primary source for adult NSCs. In response to mitotic signals, increased proliferation of Sox2+ cells is coupled with the generation of Sox2+ NSCs as well as neuronal precursors. An asymmetric contribution of Sox2+ NSCs may play an important role in maintaining the constant size of the NSC pool and producing newly born neurons during adult neurogenesis. PMID:18371391

  15. Segmented trapped vortex cavity

    Science.gov (United States)

    Grammel, Jr., Leonard Paul (Inventor); Pennekamp, David Lance (Inventor); Winslow, Jr., Ralph Henry (Inventor)

    2010-01-01

    An annular trapped vortex cavity assembly segment comprising includes a cavity forward wall, a cavity aft wall, and a cavity radially outer wall there between defining a cavity segment therein. A cavity opening extends between the forward and aft walls at a radially inner end of the assembly segment. Radially spaced apart pluralities of air injection first and second holes extend through the forward and aft walls respectively. The segment may include first and second expansion joint features at distal first and second ends respectively of the segment. The segment may include a forward subcomponent including the cavity forward wall attached to an aft subcomponent including the cavity aft wall. The forward and aft subcomponents include forward and aft portions of the cavity radially outer wall respectively. A ring of the segments may be circumferentially disposed about an axis to form an annular segmented vortex cavity assembly.

  16. Detection of trapped antihydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Hydomako, Richard [Calgary Univ., AB (Canada). Dept. of Physics and Astronomy

    2013-02-01

    A landmark thesis describing the first ever trapping of antihydrogen atoms in CERN's ALPHA apparatus. Opens the way to crucial tests of fundamental theories. Nominated as an outstanding contribution by the University of Calgary. In 2010, the ALPHA collaboration achieved a first for mankind: the stable, long-term storage of atomic antimatter, a project carried out a the Antiproton Decelerator facility at CERN. A crucial element of this observation was a dedicated silicon vertexing detector used to identify and analyze antihydrogen annihilations. This thesis reports the methods used to reconstruct the annihilation location. Specifically, the methods used to identify and extrapolate charged particle tracks and estimate the originating annihilation location are outlined. Finally, the experimental results demonstrating the first-ever magnetic confinement of antihydrogen atoms are presented. These results rely heavily on the silicon detector, and as such, the role of the annihilation vertex reconstruction is emphasized.

  17. Porcine SOX9 Gene Expression Is Influenced by an 18 bp Indel in the 5'-Untranslated Region.

    Directory of Open Access Journals (Sweden)

    Bertram Brenig

    Full Text Available Sex determining region Y-box 9 (SOX9 is an important regulator of sex and skeletal development and is expressed in a variety of embryonal and adult tissues. Loss or gain of function resulting from mutations within the coding region or chromosomal aberrations of the SOX9 locus lead to a plethora of detrimental phenotypes in humans and animals. One of these phenotypes is the so-called male-to-female or female-to-male sex-reversal which has been observed in several mammals including pig, dog, cat, goat, horse, and deer. In 38,XX sex-reversal French Large White pigs, a genome-wide association study suggested SOX9 as the causal gene, although no functional mutations were identified in affected animals. However, besides others an 18 bp indel had been detected in the 5'-untranslated region of the SOX9 gene by comparing affected animals and controls. We have identified the same indel (Δ18 between position +247 bp and +266 bp downstream the transcription start site of the porcine SOX9 gene in four other pig breeds; i.e., German Large White, Laiwu Black, Bamei, and Erhualian. These animals have been genotyped in an attempt to identify candidate genes for porcine inguinal and/or scrotal hernia. Because the 18 bp segment in the wild type 5'-UTR harbours a highly conserved cAMP-response element (CRE half-site, we analysed its role in SOX9 expression in vitro. Competition and immunodepletion electromobility shift assays demonstrate that the CRE half-site is specifically recognized by CREB. Both binding of CREB to the wild type as well as the absence of the CRE half-site in Δ18 reduced expression efficiency in HEK293T, PK-15, and ATDC5 cells significantly. Transfection experiments of wild type and Δ18 SOX9 promoter luciferase constructs show a significant reduction of RNA and protein levels depending on the presence or absence of the 18 bp segment. Hence, the data presented here demonstrate that the 18 bp indel in the porcine SOX9 5'-UTR is of functional

  18. ROCK inhibition stimulates SOX9/Smad3-dependent COL2A1 expression in inner meniscus cells.

    Science.gov (United States)

    Furumatsu, Takayuki; Maehara, Ami; Ozaki, Toshifumi

    2016-07-01

    Proper functioning of the meniscus depends on the composition and organization of its fibrocartilaginous extracellular matrix. We previously demonstrated that the avascular inner meniscus has a more chondrocytic phenotype compared with the outer meniscus. Inhibition of the Rho family GTPase ROCK, the major regulator of the actin cytoskeleton, stimulates the chondrogenic transcription factor Sry-type HMG box (SOX) 9-dependent α1(II) collagen (COL2A1) expression in inner meniscus cells. However, the crosstalk between ROCK inhibition, SOX9, and other transcription modulators on COL2A1 upregulation remains unclear in meniscus cells. The aim of this study was to investigate the role of SOX9-related transcriptional complex on COL2A1 expression under the inhibition of ROCK in human meniscus cells. Human inner and outer meniscus cells were prepared from macroscopically intact lateral menisci. Cells were cultured in the presence or absence of ROCK inhibitor (ROCKi, Y27632). Gene expression, collagen synthesis, and nuclear translocation of SOX9 and Smad2/3 were analyzed. Treatment of ROCKi increased the ratio of type I/II collagen double positive cells derived from the inner meniscus. In real-time PCR analyses, expression of SOX9 and COL2A1 genes was stimulated by ROCKi treatment in inner meniscus cells. ROCKi treatment also induced nuclear translocation of SOX9 and phosphorylated Smad2/3 in immunohistological analyses. Complex formation between SOX9 and Smad3 was increased by ROCKi treatment in inner meniscus cells. Chromatin immunoprecipitation analyses revealed that association between SOX9/Smad3 transcriptional complex with the COL2A1 enhancer region was increased by ROCKi treatment. This study demonstrated that ROCK inhibition stimulated SOX9/Smad3-dependent COL2A1 expression through the immediate nuclear translocation of Smad3 in inner meniscus cells. Our results suggest that ROCK inhibition can stimulates type II collagen synthesis through the cooperative activation

  19. Flux trapping in superconducting cavities

    International Nuclear Information System (INIS)

    Vallet, C.; Bolore, M.; Bonin, B.; Charrier, J.P.; Daillant, B.; Gratadour, J.; Koechlin, F.; Safa, H.

    1992-01-01

    The flux trapped in various field cooled Nb and Pb samples has been measured. For ambient fields smaller than 3 Gauss, 100% of the flux is trapped. The consequences of this result on the behavior of superconducting RF cavities are discussed. (author) 12 refs.; 2 figs

  20. Injection into electron plasma traps

    International Nuclear Information System (INIS)

    Gorgadze, Vladimir; Pasquini, Thomas A.; Fajans, Joel; Wurtele, Jonathan S.

    2003-01-01

    Computational studies and experimental measurements of plasma injection into a Malmberg-Penning trap reveal that the number of trapped particles can be an order of magnitude higher than predicted by a simple estimates based on a ballistic trapping model. Enhanced trapping is associated with a rich nonlinear dynamics generated by the space-charge forces of the evolving trapped electron density. A particle-in-cell simulation is used to identify the physical mechanisms that lead to the increase in trapped electrons. The simulations initially show strong two-stream interactions between the electrons emitted from the cathode and those reflected off the end plug of the trap. This is followed by virtual cathode oscillations near the injection region. As electrons are trapped, the initially hollow longitudinal phase-space is filled, and the transverse radial density profile evolves so that the plasma potential matches that of the cathode. Simple theoretical arguments are given that describe the different dynamical regimes. Good agreement is found between simulation and theory

  1. The ALPHA antihydrogen trapping apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Amole, C. [Department of Physics and Astronomy, York University, Toronto ON Canada, M3J 1P3 (Canada); Andresen, G.B. [Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C (Denmark); Ashkezari, M.D. [Department of Physics, Simon Fraser University, Burnaby, BC Canada, V5A 1S6 (Canada); Baquero-Ruiz, M. [Department of Physics, University of California at Berkeley, Berkeley, CA 94720-7300 (United States); Bertsche, W. [Department of Physics, College of Science, Swansea University, Swansea SA2 8PP (United Kingdom); School of Physics and Astronomy, University of Manchester, Manchester M13 9PL (United Kingdom); The Cockcroft Institute, Warrington WA4 4AD (United Kingdom); Bowe, P.D. [Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C (Denmark); Butler, E. [Physics Department, CERN, CH-1211 Geneva 23 (Switzerland); Capra, A. [Department of Physics and Astronomy, York University, Toronto ON Canada, M3J 1P3 (Canada); Carpenter, P.T. [Department of Physics, Auburn University, Auburn, AL 36849-5311 (United States); Cesar, C.L. [Instituto de Física, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-972 (Brazil); Chapman, S. [Department of Physics, University of California at Berkeley, Berkeley, CA 94720-7300 (United States); Charlton, M.; Deller, A.; Eriksson, S. [Department of Physics, College of Science, Swansea University, Swansea SA2 8PP (United Kingdom); Escallier, J. [Brookhaven National Laboratory, Upton, NY 11973 (United States); Fajans, J. [Department of Physics, University of California at Berkeley, Berkeley, CA 94720-7300 (United States); Friesen, T. [Department of Physics and Astronomy, University of Calgary, Calgary AB, Canada, T2N 1N4 (Canada); Fujiwara, M.C.; Gill, D.R. [TRIUMF, 4004 Wesbrook Mall, Vancouver BC, Canada V6T 2A3 (Canada); Gutierrez, A. [Department of Physics and Astronomy, University of British Columbia, Vancouver BC, Canada V6T 1Z4 (Canada); and others

    2014-01-21

    The ALPHA collaboration, based at CERN, has recently succeeded in confining cold antihydrogen atoms in a magnetic minimum neutral atom trap and has performed the first study of a resonant transition of the anti-atoms. The ALPHA apparatus will be described herein, with emphasis on the structural aspects, diagnostic methods and techniques that have enabled antihydrogen trapping and experimentation to be achieved.

  2. Electromagnetic trapping of neutral atoms

    International Nuclear Information System (INIS)

    Metcalf, H.J.

    1986-01-01

    Cooling and trapping of neutral atoms is a new branch of applied physics that has potential for application in many areas. The authors present an introduction to laser cooling and magnetic trapping. Some basic ideas and fundamental limitations are discussed, and the first successful experiments are reviewed. Trapping a neutral object depends on the interaction between an inhomogeneous electromagnetic field and a multiple moment that results in the exchange of kinetic for potential energy. In neutral atom traps, the potential energy must be stored as internal atomic energy, resulting in two immediate and extremely important consequences. First, the atomic energy levels will necessarily shift as the atoms move in the trap, and, second, practical traps for ground state neutral atoms atr necessarily very shallow compared to thermal energy. This small depth also dictates stringent vacuum requirements because a trapped atom cannot survive a single collision with a thermal energy background gas molecule. Neutral trapping, therefore, depends on substantial cooling of a thermal atomic sample and is inextricably connected with the cooling process

  3. Quantum computing with trapped ions

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, R.J.

    1998-01-01

    The significance of quantum computation for cryptography is discussed. Following a brief survey of the requirements for quantum computational hardware, an overview of the ion trap quantum computation project at Los Alamos is presented. The physical limitations to quantum computation with trapped ions are analyzed and an assessment of the computational potential of the technology is made.

  4. Trapped surfaces in spherical stars

    International Nuclear Information System (INIS)

    Bizon, P.; Malec, E.; O'Murchadha, N.

    1988-01-01

    We give necessary and sufficient conditions for the existence of trapped surfaces in spherically symmetric spacetimes. These conditions show that the formation of trapped surfaces depends on both the degree of concentration and the average flow of the matter. The result can be considered as a partial validation of the cosmic-censorship hypothesis

  5. Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature.

    Science.gov (United States)

    Verheij, Johanna B G M; Sival, Deborah A; van der Hoeven, Johannes H; Vos, Yvonne J; Meiners, Linda C; Brouwer, Oebele F; van Essen, Anthonie J

    2006-01-01

    Shah-Waardenburg syndrome is a rare congenital disorder with variable clinical expression, characterised by aganglionosis of the rectosigmoïd (Hirschsprung disease), and abnormal melanocyte migration, resulting in pigmentary abnormalities and sensorineural deafness (Waardenburg syndrome). Mutations in the EDN, EDNRB and SOX10 genes can be found in patients with this syndrome. SOX10 mutations are specifically associated with a more severe phenotype called PCWH: peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease. Neuronal expression of SOX10 occurs in neural crest cells during early embryonic development and in glial cells of the peripheral and central nervous systems during late embryonic development and in adults. We present a 4-year-old girl with the PCWH phenotype associated with a de novo nonsense mutation (S384X) in SOX10. Main clinical features were mental retardation, peripheral neuropathy, deafness, Hirschsprung disease, distal arthrogryposis, white hairlock, and growth retardation. She presented with hypotonia, developmental delay, reduced peripheral nerve conduction velocities, and radiologically assessed central hypomyelination. Subsequently, the formation of abnormal myelin within the central and peripheral nervous system was functionally and radiologically assessed. Children presenting with features of Waardenburg syndrome and neurological dysfunction should be tested for mutations in the SOX10 gene to enable diagnosis and counselling.

  6. Transcriptional role of androgen receptor in the expression of long non-coding RNA Sox2OT in neurogenesis.

    Directory of Open Access Journals (Sweden)

    Valentina Tosetti

    Full Text Available The complex architecture of adult brain derives from tightly regulated migration and differentiation of precursor cells generated during embryonic neurogenesis. Changes at transcriptional level of genes that regulate migration and differentiation may lead to neurodevelopmental disorders. Androgen receptor (AR is a transcription factor that is already expressed during early embryonic days. However, AR role in the regulation of gene expression at early embryonic stage is yet to be determinate. Long non-coding RNA (lncRNA Sox2 overlapping transcript (Sox2OT plays a crucial role in gene expression control during development but its transcriptional regulation is still to be clearly defined. Here, using Bicalutamide in order to pharmacologically inactivated AR, we investigated whether AR participates in the regulation of the transcription of the lncRNASox2OTat early embryonic stage. We identified a new DNA binding region upstream of Sox2 locus containing three androgen response elements (ARE, and found that AR binds such a sequence in embryonic neural stem cells and in mouse embryonic brain. Our data suggest that through this binding, AR can promote the RNA polymerase II dependent transcription of Sox2OT. Our findings also suggest that AR participates in embryonic neurogenesis through transcriptional control of the long non-coding RNA Sox2OT.

  7. Growth factors and medium hyperglycemia induce Sox9+ ductal cell differentiation into β cells in mice with reversal of diabetes

    Science.gov (United States)

    Zhang, Mingfeng; Lin, Qing; Qi, Tong; Wang, Tiankun; Chen, Ching-Cheng; Riggs, Arthur D.; Zeng, Defu

    2016-01-01

    We previously reported that long-term administration of a low dose of gastrin and epidermal growth factor (GE) augments β-cell neogenesis in late-stage diabetic autoimmune mice after eliminating insulitis by induction of mixed chimerism. However, the source of β-cell neogenesis is still unknown. SRY (sex-determining region Y)-box 9+ (Sox9+) ductal cells in the adult pancreas are clonogenic and can give rise to insulin-producing β cells in an in vitro culture. Whether Sox9+ ductal cells in the adult pancreas can give rise to β cells in vivo remains controversial. Here, using lineage-tracing with genetic labeling of Insulin- or Sox9-expressing cells, we show that hyperglycemia (>300 mg/dL) is required for inducing Sox9+ ductal cell differentiation into insulin-producing β cells, and medium hyperglycemia (300–450 mg/dL) in combination with long-term administration of low-dose GE synergistically augments differentiation and is associated with normalization of blood glucose in nonautoimmune diabetic C57BL/6 mice. Short-term administration of high-dose GE cannot augment differentiation, although it can augment preexisting β-cell replication. These results indicate that medium hyperglycemia combined with long-term administration of low-dose GE represents one way to induce Sox9+ ductal cell differentiation into β cells in adult mice. PMID:26733677

  8. The Impact of SOX Adoption on the Compensation of Non-US Companies’ Boards: The Case of Canadian Companies

    Directory of Open Access Journals (Sweden)

    Nadejda SERDIUC

    2015-11-01

    Full Text Available The purpose of this article is to study the relationship between the adoption of the Sarbanes-Oxley Act (SOX and the compensation of the board of directors of Canadian companies listed on US stock markets. The SOX act, promulgated on 30 July 2002 and the rules adopted by the Securities and Exchange Commission (SEC require, among furthermore, a majority of independent directors on boards. The literature focuses on two main differences between US companies and Canadian companies: more concentrated ownership and the smaller market capitalization of Canadian companies. Therefore, a consistent application of SOX on all the companies that differ at the base, in their size and structure, may have a different impact on the costs of compliance. Using a sample of 17 Canadian companies listed on US stock exchanges from 2001 to 2004, our analysis show that there is a link between the adoption of SOX and the increased in the cash compensation of the board of directors. The results also show that the effect of SOX is different depending on the company’s size.

  9. Direct Reprogramming of Adult Human Somatic Stem Cells Into Functional Neurons Using Sox2, Ascl1, and Neurog2

    Directory of Open Access Journals (Sweden)

    Jessica Alves de Medeiros Araújo

    2018-06-01

    Full Text Available Reprogramming of somatic cells into induced pluripotent stem cells (iPS or directly into cells from a different lineage, including neurons, has revolutionized research in regenerative medicine in recent years. Mesenchymal stem cells are good candidates for lineage reprogramming and autologous transplantation, since they can be easily isolated from accessible sources in adult humans, such as bone marrow and dental tissues. Here, we demonstrate that expression of the transcription factors (TFs SRY (sex determining region Y-box 2 (Sox2, Mammalian achaete-scute homolog 1 (Ascl1, or Neurogenin 2 (Neurog2 is sufficient for reprogramming human umbilical cord mesenchymal stem cells (hUCMSC into induced neurons (iNs. Furthermore, the combination of Sox2/Ascl1 or Sox2/Neurog2 is sufficient to reprogram up to 50% of transfected hUCMSCs into iNs showing electrical properties of mature neurons and establishing synaptic contacts with co-culture primary neurons. Finally, we show evidence supporting the notion that different combinations of TFs (Sox2/Ascl1 and Sox2/Neurog2 may induce multiple and overlapping neuronal phenotypes in lineage-reprogrammed iNs, suggesting that neuronal fate is determined by a combination of signals involving the TFs used for reprogramming but also the internal state of the converted cell. Altogether, the data presented here contribute to the advancement of techniques aiming at obtaining specific neuronal phenotypes from lineage-converted human somatic cells to treat neurological disorders.

  10. Transcription factor Sox4 is required for PUMA-mediated apoptosis induced by histone deacetylase inhibitor, TSA.

    Science.gov (United States)

    Jang, Sang-Min; Kang, Eun-Jin; Kim, Jung-Woong; Kim, Chul-Hong; An, Joo-Hee; Choi, Kyung-Hee

    2013-08-23

    PUMA is a crucial regulator of apoptotic cell death mediated by p53-dependent and p53-independent mechanisms. In many cancer cells, PUMA expression is induced in response to DNA-damaging reagent in a p53-dependent manner. However, few studies have investigated transcription factors that lead to the induction of PUMA expression via p53-independent apoptotic signaling. In this study, we found that the transcription factor Sox4 increased PUMA expression in response to trichostatin A (TSA), a histone deacetylase inhibitor in the p53-null human lung cancer cell line H1299. Ectopic expression of Sox4 led to the induction of PUMA expression at the mRNA and protein levels, and TSA-mediated up-regulation of PUMA transcription was repressed by the knockdown of Sox4. Using luciferase assays and chromatin immunoprecipitation, we also determined that Sox4 recruits p300 on the PUMA promoter region and increases PUMA gene expression in response to TSA treatment. Taken together, these results suggest that Sox4 is required for p53-independent apoptotic cell death mediated by PUMA induction via TSA treatment. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  11. In depth analysis of the Sox4 gene locus that consists of sense and natural antisense transcripts

    Science.gov (United States)

    Ling, King-Hwa; Brautigan, Peter J.; Moore, Sarah; Fraser, Rachel; Leong, Melody Pui-Yee; Leong, Jia-Wen; Zainal Abidin, Shahidee; Lee, Han-Chung; Cheah, Pike-See; Raison, Joy M.; Babic, Milena; Lee, Young Kyung; Daish, Tasman; Mattiske, Deidre M.; Mann, Jeffrey R.; Adelson, David L.; Thomas, Paul Q.; Hahn, Christopher N.; Scott, Hamish S.

    2016-01-01

    SRY (Sex Determining Region Y)-Box 4 or Sox4 is an important regulator of the pan-neuronal gene expression during post-mitotic cell differentiation within the mammalian brain. Sox4 gene locus has been previously characterized with multiple sense and overlapping natural antisense transcripts [1], [2]. Here we provide accompanying data on various analyses performed and described in Ling et al. [2]. The data include a detail description of various features found at Sox4 gene locus, additional experimental data derived from RNA-Fluorescence in situ Hybridization (RNA-FISH), Western blotting, strand-specific reverse-transcription quantitative polymerase chain reaction (RT-qPCR), gain-of-function and in situ hybridization (ISH) experiments. All the additional data provided here support the existence of an endogenous small interfering- or PIWI interacting-like small RNA known as Sox4_sir3, which origin was found within the overlapping region consisting of a sense and a natural antisense transcript known as Sox4ot1. PMID:26958646

  12. Quantitative profiling of selective Sox/POU pairing on hundreds of sequences in parallel by Coop-seq.

    Science.gov (United States)

    Chang, Yiming K; Srivastava, Yogesh; Hu, Caizhen; Joyce, Adam; Yang, Xiaoxiao; Zuo, Zheng; Havranek, James J; Stormo, Gary D; Jauch, Ralf

    2017-01-25

    Cooperative binding of transcription factors is known to be important in the regulation of gene expression programs conferring cellular identities. However, current methods to measure cooperativity parameters have been laborious and therefore limited to studying only a few sequence variants at a time. We developed Coop-seq (cooperativity by sequencing) that is capable of efficiently and accurately determining the cooperativity parameters for hundreds of different DNA sequences in a single experiment. We apply Coop-seq to 12 dimer pairs from the Sox and POU families of transcription factors using 324 unique sequences with changed half-site orientation, altered spacing and discrete randomization within the binding elements. The study reveals specific dimerization profiles of different Sox factors with Oct4. By contrast, Oct4 and the three neural class III POU factors Brn2, Brn4 and Oct6 assemble with Sox2 in a surprisingly indistinguishable manner. Two novel half-site configurations can support functional Sox/Oct dimerization in addition to known composite motifs. Moreover, Coop-seq uncovers a nucleotide switch within the POU half-site when spacing is altered, which is mirrored in genomic loci bound by Sox2/Oct4 complexes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. In depth analysis of the Sox4 gene locus that consists of sense and natural antisense transcripts

    Directory of Open Access Journals (Sweden)

    King-Hwa Ling

    2016-06-01

    Full Text Available SRY (Sex Determining Region Y-Box 4 or Sox4 is an important regulator of the pan-neuronal gene expression during post-mitotic cell differentiation within the mammalian brain. Sox4 gene locus has been previously characterized with multiple sense and overlapping natural antisense transcripts [1,2]. Here we provide accompanying data on various analyses performed and described in Ling et al. [2]. The data include a detail description of various features found at Sox4 gene locus, additional experimental data derived from RNA-Fluorescence in situ Hybridization (RNA-FISH, Western blotting, strand-specific reverse-transcription quantitative polymerase chain reaction (RT-qPCR, gain-of-function and in situ hybridization (ISH experiments. All the additional data provided here support the existence of an endogenous small interfering- or PIWI interacting-like small RNA known as Sox4_sir3, which origin was found within the overlapping region consisting of a sense and a natural antisense transcript known as Sox4ot1.

  14. Differential Expression of Sox11 and Bdnf mRNA Isoforms in the Injured and Regenerating Nervous Systems

    Directory of Open Access Journals (Sweden)

    Felix L. Struebing

    2017-11-01

    Full Text Available In both the central nervous system (CNS and the peripheral nervous system (PNS, axonal injury induces changes in neuronal gene expression. In the PNS, a relatively well-characterized alteration in transcriptional activation is known to promote axonal regeneration. This transcriptional cascade includes the neurotrophin Bdnf and the transcription factor Sox11. Although both molecules act to facilitate successful axon regeneration in the PNS, this process does not occur in the CNS. The present study examines the differential expression of Sox11 and Bdnf mRNA isoforms in the PNS and CNS using three experimental paradigms at different time points: (i the acutely injured CNS (retina after optic nerve crush and PNS (dorsal root ganglion after sciatic nerve crush, (ii a CNS regeneration model (retina after optic nerve crush and induced regeneration; and (iii the retina during a chronic form of central neurodegeneration (the DBA/2J glaucoma model. We find an initial increase of Sox11 in both PNS and CNS after injury; however, the expression of Bdnf isoforms is higher in the PNS relative to the CNS. Sustained upregulation of Sox11 is seen in the injured retina following regeneration treatment, while the expression of two Bdnf mRNA isoforms is suppressed. Furthermore, two isoforms of Sox11 with different 3′UTR lengths are present in the retina, and the long isoform is specifically upregulated in later stages of glaucoma. These results provide insight into the molecular cascades active during axonal injury and regeneration in mammalian neurons.

  15. Toxic responses of Sox2 gene in the regeneration of the earthworm Eisenia foetida exposed to Retnoic acid.

    Science.gov (United States)

    Tao, Jing; Rong, Wei; Diao, Xiaoping; Zhou, Hailong

    2018-01-01

    Exogenous retinoic acid delays and disturbs the regeneration of Eisenia foetida. The stem cell pluripotency factor, Sox2, can play a crucial role in cell reprogramming and dedifferentiation. In this study, we compared the regeneration of Eisenia foetida in different segments after amputation and the effects of retinoic acid on the regeneration of different segments. The results showed that the regeneration speed of the head and tail was slightly faster than the middle part, and retinoic acid disrupted and delayed the regeneration of the earthworm. The qRT-PCR and Western blot analysis showed that the expression of the Sox2 gene and Sox2 protein was highest on the seventh day in different segments (pregeneration of earthworms and the formation of blastema are related to the expression of the Sox2 gene and protein. Retinoic acid delays and interferes with the regeneration of the earthworm by affecting the expression levels of the Sox2 gene and protein. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Activation of Sox3 Gene by Thyroid Hormone in the Developing Adult Intestinal Stem Cell During Xenopus Metamorphosis

    Science.gov (United States)

    Sun, Guihong; Fu, Liezhen; Wen, Luan

    2014-01-01

    The maturation of the intestine into the adult form involves the formation of adult stem cells in a thyroid hormone (T3)-dependent process in vertebrates. In mammals, this takes place during postembryonic development, a period around birth when the T3 level peaks. Due to the difficulty of manipulating late-stage, uterus-enclosed embryos, very little is known about the development of the adult intestinal stem cells. Interestingly, the remodeling of the intestine during the T3-dependent amphibian metamorphosis mimics the maturation of mammalian intestine. Our earlier microarray studies in Xenopus laevis revealed that the transcription factor SRY (sex-determining region Y)-box 3 (Sox3), well known for its involvement in neural development, was upregulated in the intestinal epithelium during metamorphosis. Here, we show that Sox3 is highly and specifically expressed in the developing adult intestinal progenitor/stem cells. We further show that its induction by T3 is independent of new protein synthesis, suggesting that Sox3 is directly activated by liganded T3 receptor. Thus, T3 activates Sox3 as one of the earliest changes in the epithelium, and Sox3 in turn may facilitate the dedifferentiation of the larval epithelial cells into adult stem cells. PMID:25211587

  17. Spin resonance with trapped ions

    Energy Technology Data Exchange (ETDEWEB)

    Wunderlich, Ch; Balzer, Ch; Hannemann, T; Mintert, F; Neuhauser, W; Reiss, D; Toschek, P E [Institut fuer Laser-Physik, Universitaet Hamburg, Jungiusstrasse 9, 20355 Hamburg (Germany)

    2003-03-14

    A modified ion trap is described where experiments (in particular related to quantum information processing) that usually require optical radiation can be carried out using microwave or radio frequency electromagnetic fields. Instead of applying the usual methods for coherent manipulation of trapped ions, a string of ions in such a modified trap can be treated like a molecule in nuclear magnetic resonance experiments taking advantage of spin-spin coupling. The collection of trapped ions can be viewed as an N-qubit molecule with adjustable spin-spin coupling constants. Given N identically prepared quantum mechanical two-level systems (qubits), the optimal strategy to estimate their quantum state requires collective measurements. Using the ground state hyperfine levels of electrodynamically trapped {sup 171}Yb{sup +}, we have implemented an adaptive algorithm for state estimation involving sequential measurements on arbitrary qubit states.

  18. Spin resonance with trapped ions

    International Nuclear Information System (INIS)

    Wunderlich, Ch; Balzer, Ch; Hannemann, T; Mintert, F; Neuhauser, W; Reiss, D; Toschek, P E

    2003-01-01

    A modified ion trap is described where experiments (in particular related to quantum information processing) that usually require optical radiation can be carried out using microwave or radio frequency electromagnetic fields. Instead of applying the usual methods for coherent manipulation of trapped ions, a string of ions in such a modified trap can be treated like a molecule in nuclear magnetic resonance experiments taking advantage of spin-spin coupling. The collection of trapped ions can be viewed as an N-qubit molecule with adjustable spin-spin coupling constants. Given N identically prepared quantum mechanical two-level systems (qubits), the optimal strategy to estimate their quantum state requires collective measurements. Using the ground state hyperfine levels of electrodynamically trapped 171 Yb + , we have implemented an adaptive algorithm for state estimation involving sequential measurements on arbitrary qubit states

  19. Raman Spectroscopy of Optically Trapped Single Biological Micro-Particles

    Science.gov (United States)

    Redding, Brandon; Schwab, Mark J.; Pan, Yong-le

    2015-01-01

    The combination of optical trapping with Raman spectroscopy provides a powerful method for the study, characterization, and identification of biological micro-particles. In essence, optical trapping helps to overcome the limitation imposed by the relative inefficiency of the Raman scattering process. This allows Raman spectroscopy to be applied to individual biological particles in air and in liquid, providing the potential for particle identification with high specificity, longitudinal studies of changes in particle composition, and characterization of the heterogeneity of individual particles in a population. In this review, we introduce the techniques used to integrate Raman spectroscopy with optical trapping in order to study individual biological particles in liquid and air. We then provide an overview of some of the most promising applications of this technique, highlighting the unique types of measurements enabled by the combination of Raman spectroscopy with optical trapping. Finally, we present a brief discussion of future research directions in the field. PMID:26247952

  20. Deep superconducting magnetic traps for neutral atoms and molecules

    International Nuclear Information System (INIS)

    Harris, J.G.E.; Michniak, R.A.; Nguyen, S.V.; Campbell, W.C.; Egorov, D.; Maxwell, S.E.; Buuren, L.D. van; Doyle, J.M.

    2004-01-01

    We describe the design, construction and performance of three realizations of a high-field superconducting magnetic trap for neutral atoms and molecules. Each of these traps utilizes a pair of coaxial coils in the anti-Helmholtz geometry and achieves depths greater than 4 T, allowing it to capture magnetic atoms and molecules cooled in a cryogenic buffer gas. Achieving this depth requires that the repulsive force between the coils (which can exceed 30 metric tons) be contained. We also describe additional features of the traps, including the elimination of trapped fluxes from the coils and the integration of the coils into a cryogenic vacuum environment suitable for producing cold atoms and molecules

  1. Formation of the embryonic organizer is restricted by the competitive influences of Fgf signaling and the SoxB1 transcription factors.

    Directory of Open Access Journals (Sweden)

    Cheng-Liang Kuo

    Full Text Available The organizer is one of the earliest structures to be established during vertebrate development and is crucial to subsequent patterning of the embryo. We have previously shown that the SoxB1 transcription factor, Sox3, plays a central role as a transcriptional repressor of zebrafish organizer gene expression. Recent data suggest that Fgf signaling has a positive influence on organizer formation, but its role remains to be fully elucidated. In order to better understand how Fgf signaling fits into the complex regulatory network that determines when and where the organizer forms, the relationship between the positive effects of Fgf signaling and the repressive effects of the SoxB1 factors must be resolved. This study demonstrates that both fgf3 and fgf8 are required for expression of the organizer genes, gsc and chd, and that SoxB1 factors (Sox3, and the zebrafish specific factors, Sox19a and Sox19b can repress the expression of both fgf3 and fgf8. However, we also find that these SoxB1 factors inhibit the expression of gsc and chd independently of their repression of fgf expression. We show that ectopic expression of organizer genes induced solely by the inhibition of SoxB1 function is dependent upon the activation of fgf expression. These data allow us to describe a comprehensive signaling network in which the SoxB1 factors restrict organizer formation by inhibiting Fgf, Nodal and Wnt signaling, as well as independently repressing the targets of that signaling. The organizer therefore forms only where Nodal-induced Fgf signaling overlaps with Wnt signaling and the SoxB1 proteins are absent.

  2. P53-miR-191-SOX4 regulatory loop affects apoptosis in breast cancer.

    Science.gov (United States)

    Sharma, Shivani; Nagpal, Neha; Ghosh, Prahlad C; Kulshreshtha, Ritu

    2017-08-01

    miRNAs have emerged as key participants of p53 signaling pathways because they regulate or are regulated by p53. Here, we provide the first study demonstrating direct regulation of an oncogenic miRNA, miR-191-5p, by p53 and existence of a regulatory feedback loop. Using a combination of qRT-PCR, promoter-luciferase, and chromatin-immunoprecipitation assays, we show that p53 brings about down-regulation of miR-191-5p in breast cancer. miR-191-5p overexpression brought about inhibition of apoptosis in breast cancer cell lines (MCF7 and ZR-75) as demonstrated by reduction in annexin-V stained cells and caspase 3/7 activity, whereas miR-191-5p down-regulation showed the opposite. We further unveiled that SOX4 was a direct target of miR-191-5p. SOX4 overexpression was shown to increase p53 protein levels in MCF7 cells. miR-191-5p overexpression brought about down-regulation of SOX4 and thus p53 levels, suggesting the existence of a regulatory feedback loop. Breast cancer treatment by doxorubicin, an anti-cancer drug, involves induction of apoptosis by p53; we thus wanted to check whether miR-191-5p affects doxorubicin sensitivity. Interestingly, Anti-miR-191 treatment significantly decreased the IC50 of the doxorubicin drug and thus sensitized breast cancer cells to doxorubicin treatment by promoting apoptosis. Overall, this work highlights the importance of the p53-miR-191- SOX4 axis in the regulation of apoptosis and drug resistance in breast cancer and offers a preclinical proof-of-concept for use of an Anti-miR-191 and doxorubicin combination as a rational approach to pursue for better breast cancer treatment. © 2017 Sharma et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  3. Exploring the utility of organo-polyoxometalate hybrids to inhibit SOX transcription factors

    Directory of Open Access Journals (Sweden)

    Kamesh Narasimhan

    2014-01-01

    Conclusion: Polyoxometalates are highly potent, nanomolar range inhibitors of the DNA binding activity of the Sox-HMG family. However, binding assays involving a limited subset of structurally diverse polyoxometalates revealed a low selectivity profile against different transcription factor families. Further progress in achieving selectivity and deciphering structure-activity relationship of POMs require the identification of POM binding sites on transcription factors using elaborate approaches like X-ray crystallography and multidimensional NMR. In summary, our report reaffirms that transcription factors are challenging molecular architectures and that future polyoxometalate chemistry must consider further modification strategies, to address the substantial challenges involved in achieving target selectivity.

  4. Lamb–Shaffer syndrome, deferred outside not described by SOX5 mutation

    Directory of Open Access Journals (Sweden)

    I. V. Sharkova

    2018-01-01

    Full Text Available Clinical and genetic characteristics of a patient with Lamb–Shaffer syndrome due to the newly discovered heterozygous missense mutation p.1868A>C in the 14 exon of the SOX5 gene are presented in the next generation sequencing of exom. It is shown that, in contrast to the previously described patients due to the presence of a deletion in the region of the gene or segment of chromosome 12p12.1, in the presence of missense mutation, the intellectual deficit and the dysmorphic features of the structure are not pronounced sharply and there is no anomaly in the development of other organs and systems.

  5. Enhancer Analysis Unveils Genetic Interactions between TLX and SOX2 in Neural Stem Cells and In Vivo Reprogramming.

    Science.gov (United States)

    Islam, Mohammed M; Smith, Derek K; Niu, Wenze; Fang, Sanhua; Iqbal, Nida; Sun, Guoqiang; Shi, Yanhong; Zhang, Chun-Li

    2015-11-10

    The orphan nuclear receptor TLX is a master regulator of postnatal neural stem cell (NSC) self-renewal and neurogenesis; however, it remains unclear how TLX expression is precisely regulated in these tissue-specific stem cells. Here, we show that a highly conserved cis-element within the Tlx locus functions to drive gene expression in NSCs. We demonstrate that the transcription factors SOX2 and MYT1 specifically interact with this genomic element to directly regulate Tlx enhancer activity in vivo. Knockdown experiments further reveal that SOX2 dominantly controls endogenous expression of TLX, whereas MYT1 only plays a modulatory role. Importantly, TLX is essential for SOX2-mediated in vivo reprogramming of astrocytes and itself is also sufficient to induce neurogenesis in the adult striatum. Together, these findings unveil functional genetic interactions among transcription factors that are critical to NSCs and in vivo cell reprogramming.

  6. Enhancer Analysis Unveils Genetic Interactions between TLX and SOX2 in Neural Stem Cells and In Vivo Reprogramming

    Science.gov (United States)

    Islam, Mohammed M.; Smith, Derek K.; Niu, Wenze; Fang, Sanhua; Iqbal, Nida; Sun, Guoqiang; Shi, Yanhong; Zhang, Chun-Li

    2015-01-01

    Summary The orphan nuclear receptor TLX is a master regulator of postnatal neural stem cell (NSC) self-renewal and neurogenesis; however, it remains unclear how TLX expression is precisely regulated in these tissue-specific stem cells. Here, we show that a highly conserved cis-element within the Tlx locus functions to drive gene expression in NSCs. We demonstrate that the transcription factors SOX2 and MYT1 specifically interact with this genomic element to directly regulate Tlx enhancer activity in vivo. Knockdown experiments further reveal that SOX2 dominantly controls endogenous expression of TLX, whereas MYT1 only plays a modulatory role. Importantly, TLX is essential for SOX2-mediated in vivo reprogramming of astrocytes and itself is also sufficient to induce neurogenesis in the adult striatum. Together, these findings unveil functional genetic interactions among transcription factors that are critical to NSCs and in vivo cell reprogramming. PMID:26607952

  7. Enhancer Analysis Unveils Genetic Interactions between TLX and SOX2 in Neural Stem Cells and In Vivo Reprogramming

    Directory of Open Access Journals (Sweden)

    Mohammed M. Islam

    2015-11-01

    Full Text Available The orphan nuclear receptor TLX is a master regulator of postnatal neural stem cell (NSC self-renewal and neurogenesis; however, it remains unclear how TLX expression is precisely regulated in these tissue-specific stem cells. Here, we show that a highly conserved cis-element within the Tlx locus functions to drive gene expression in NSCs. We demonstrate that the transcription factors SOX2 and MYT1 specifically interact with this genomic element to directly regulate Tlx enhancer activity in vivo. Knockdown experiments further reveal that SOX2 dominantly controls endogenous expression of TLX, whereas MYT1 only plays a modulatory role. Importantly, TLX is essential for SOX2-mediated in vivo reprogramming of astrocytes and itself is also sufficient to induce neurogenesis in the adult striatum. Together, these findings unveil functional genetic interactions among transcription factors that are critical to NSCs and in vivo cell reprogramming.

  8. RepSox improves viability and regulates gene expression in rhesus monkey-pig interspecies cloned embryos.

    Science.gov (United States)

    Zhu, Hai-Ying; Jin, Long; Guo, Qing; Luo, Zhao-Bo; Li, Xiao-Chen; Zhang, Yu-Chen; Xing, Xiao-Xu; Xuan, Mei-Fu; Zhang, Guang-Lei; Luo, Qi-Rong; Wang, Jun-Xia; Cui, Cheng-Du; Li, Wen-Xue; Cui, Zheng-Yun; Yin, Xi-Jun; Kang, Jin-Dan

    2017-05-01

    To investigate the effect of the small molecule, RepSox, on the expression of developmentally important genes and the pre-implantation development of rhesus monkey-pig interspecies somatic cell nuclear transfer (iSCNT) embryos. Rhesus monkey cells expressing the monomeric red fluorescent protein 1 which have a normal (42) chromosome complement, were used as donor cells to generate iSCNT embryos. RepSox increased the expression levels of the pluripotency-related genes, Oct4 and Nanog (p  0.05), this was not significant. RepSox can improve the developmental potential of rhesus monkey-pig iSCNT embryos by regulating the expression of pluripotency-related genes.

  9. FGF signalling controls the specification of hair placode-derived SOX9 positive progenitors to Merkel cells.

    Science.gov (United States)

    Nguyen, Minh Binh; Cohen, Idan; Kumar, Vinod; Xu, Zijian; Bar, Carmit; Dauber-Decker, Katherine L; Tsai, Pai-Chi; Marangoni, Pauline; Klein, Ophir D; Hsu, Ya-Chieh; Chen, Ting; Mikkola, Marja L; Ezhkova, Elena

    2018-06-13

    Merkel cells are innervated mechanosensory cells responsible for light-touch sensations. In murine dorsal skin, Merkel cells are located in touch domes and found in the epidermis around primary hairs. While it has been shown that Merkel cells are skin epithelial cells, the progenitor cell population that gives rise to these cells is unknown. Here, we show that during embryogenesis, SOX9-positive (+) cells inside hair follicles, which were previously known to give rise to hair follicle stem cells (HFSCs) and cells of the hair follicle lineage, can also give rise to Merkel Cells. Interestingly, while SOX9 is critical for HFSC specification, it is dispensable for Merkel cell formation. Conversely, FGFR2 is required for Merkel cell formation but is dispensable for HFSCs. Together, our studies uncover SOX9(+) cells as precursors of Merkel cells and show the requirement for FGFR2-mediated epithelial signalling in Merkel cell specification.

  10. Novel mutations in the SOX10 gene in the first two Chinese cases of type IV Waardenburg syndrome.

    Science.gov (United States)

    Jiang, Lu; Chen, Hongsheng; Jiang, Wen; Hu, Zhengmao; Mei, Lingyun; Xue, Jingjie; He, Chufeng; Liu, Yalan; Xia, Kun; Feng, Yong

    2011-05-20

    We analyzed the clinical features and family-related gene mutations for the first two Chinese cases of type IV Waardenburg syndrome (WS4). Two families were analyzed in this study. The analysis included a medical history, clinical analysis, a hearing test and a physical examination. In addition, the EDNRB, EDN3 and SOX10 genes were sequenced in order to identify the pathogenic mutation responsible for the WS4 observed in these patients. The two WS4 cases presented with high phenotypic variability. Two novel heterozygous mutations (c.254G>A and c.698-2A>T) in the SOX10 gene were detected. The mutations identified in the patients were not found in unaffected family members or in 200 unrelated control subjects. This is the first report of WS4 in Chinese patients. In addition, two novel mutations in SOX10 gene have been identified. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  11. Trapping tsetse flies on water

    Directory of Open Access Journals (Sweden)

    Laveissière C.

    2011-05-01

    Full Text Available Riverine tsetse flies such as Glossina palpalis gambiensis and G. tachinoides are the vectors of human and animal trypanosomoses in West Africa. Despite intimate links between tsetse and water, to our knowledge there has never been any attempt to design trapping devices that would catch tsetse on water. In mangrove (Guinea one challenging issue is the tide, because height above the ground for a trap is a key factor affecting tsetse catches. The trap was mounted on the remains of an old wooden dugout, and attached with rope to nearby branches, thereby allowing it to rise and fall with the tide. Catches showed a very high density of 93.9 flies/”water-trap”/day, which was significantly higher (p < 0.05 than all the catches from other habitats where the classical trap had been used. In savannah, on the Comoe river of South Burkina Faso, the biconical trap was mounted on a small wooden raft anchored to a stone, and catches were compared with the classical biconical trap put on the shores. G. p. gambiensis and G. tachinoides densities were not significantly different from those from the classical biconical one. The adaptations described here have allowed to efficiently catch tsetse on the water, which to our knowledge is reported here for the first time. This represents a great progress and opens new opportunities to undertake studies on the vectors of trypanosomoses in mangrove areas of Guinea, which are currently the areas showing the highest prevalences of sleeping sickness in West Africa. It also has huge potential for tsetse control using insecticide impregnated traps in savannah areas where traps become less efficient in rainy season. The Guinean National control programme has already expressed its willingness to use such modified traps in its control campaigns in Guinea, as has the national PATTEC programme in Burkina Faso during rainy season.

  12. Status of THe-Trap

    Energy Technology Data Exchange (ETDEWEB)

    Streubel, Sebastian; Eronen, Tommi; Hoecker, Martin; Ketter, Jochen; Blaum, Klaus [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany); Van Dyck, Robert S. Jr. [Department of Physics, University of Washington, Seattle, WA (United States)

    2013-07-01

    THe-Trap (short for Tritium-{sup 3}He Trap) is a Penning-trap setup dedicated to measure the {sup 3}H to {sup 3}He mass-ratio with a relative uncertainty of better than 10{sup -11}. The ratio is of relevance for the KArlsruhe TRItium Neutrino experiment (KATRIN), which aims to measure the electron anti-neutrino mass, by measuring the shape of the β-decay energy spectrum close to its endpoint. An independent measurement of the {sup 3}H to {sup 3}He mass-ratio pins down this endpoint, and thus will help to determine the systematics of KATRIN. The trap setup consists of two Penning-traps: One trap for precision measurements, the other trap for ion storage. Ideally, the trap content will be periodically switched, which reduces the time between the measurements of the two ions' motional frequencies. In 2012, a mass ratio measurement of {sup 12}C{sup 4+} to {sup 14}N{sup 5+} was performed to characterize systematic effects of the traps. This measurement yielded a accuracy of 10{sup -9}. Further investigations revealed that a major reason for the modest accuracy is the large axial amplitude of ∼100 μm, compared to a ideal case of 3 μm at 4 K. In addition, relative magnetic fluctuations at a 3 x 10{sup -10} level on a 10 h timescale need to be significantly improved. In this contribution, the aforementioned findings and further systematic studies will be presented.

  13. β-Catenin/POU5F1/SOX2 transcription factor complex mediates IGF-I receptor signaling and predicts poor prognosis in lung adenocarcinoma.

    Science.gov (United States)

    Xu, Chuan; Xie, Dan; Yu, Shi-Cang; Yang, Xiao-Jun; He, Li-Ru; Yang, Jing; Ping, Yi-Fang; Wang, Bin; Yang, Lang; Xu, Sen-Lin; Cui, Wei; Wang, Qing-Liang; Fu, Wen-Juan; Liu, Qing; Qian, Cheng; Cui, You-Hong; Rich, Jeremy N; Kung, Hsiang-Fu; Zhang, Xia; Bian, Xiu-Wu

    2013-05-15

    Cancer stem-like cells (CSLC) are crucial in tumor initiation and progression; however, the underlying mechanism for the self-renewal of cancer cells remains undefined. In the study, immunohistochemical analysis of specimens freshly excised from patients with lung adenocarcinoma showed that high expression of insulin-like growth factor I receptor (IGF-IR) in lung adenocarcinoma cells was positively correlated with the expressions of cancer stem cell markers CD133 and aldehyde dehydrogenase 1 family member A1 (ALDH1A1). IGF-IR activation enhanced POU class 5 homeobox 1 (POU5F1) expression on human lung adenocarcinoma stem-like cells (LACSLC) through PI3K/AKT/GSK3β/β-catenin cascade. POU5F1 could form a novel complex with β-catenin and SOX2 to bind Nanog promoter for transcription to maintain self-renewal of LACSLCs, which was dependent on the functional IGF-IR. Genetic and pharmacologic inhibition of IGF-IR abrogated LACSLC capabilities for self-renewal and tumorigenicity in vitro. In an in vivo xenograft tumor model, knockdown of either IGF-IR or POU5F1 impeded tumorigenic potentials of LACSLCs. By analyzing pathologic specimens excised from 200 patients with lung adenocarcinoma, we found that colocalization of highly expressed IGF-IR with β-catenin and POU5F1 predicted poor prognosis. Taken together, we show that IGF-IR-mediated POU5F1 expression to form a complex with β-catenin and SOX2 is crucial for the self-renewal and oncogenic potentials of LACSLCs, and the integrative clinical detection of the expressions of IGF-IR, β-catenin, and POU5F1 is indicatory for predicting prognosis in the patients of lung adenocarcinoma. ©2013 AACR.

  14. Use of methanol as cryoprotectant and its effect on sox genes and proteins in chilled zebrafish embryos.

    Science.gov (United States)

    Desai, Kunjan; Spikings, Emma; Zhang, Tiantian

    2015-08-01

    Methanol is a widely used cryoprotectant (CPA) in cryopreservation of fish embryos, however little is known about its effect at the molecular level. This study investigated the effect of methanol on sox gene and protein expression in zebrafish embryos (50% epiboly) when they were chilled for 3 h and subsequently warmed and cultured to the hatching stages. Initial experiments were carried out to evaluate the chilling tolerance of 50% epiboly embryos which showed no significant differences in hatching rates for up to 6 h chilling in methanol (0.2-, 0.5- and 1 M). Subsequent experiments in embryos that had been chilled for 3 h in 1 M methanol and warmed and cultured up to the hatching stages found that sox2 and sox3 gene expression were increased significantly in hatched embryos that had been chilled compared to non-chilled controls. Sox19a gene expression also remained above control levels in the chilled embryos at all developmental stages tested. Whilst stable sox2 protein expression was observed between non-chilled controls and embryos chilled for 3 h with or without MeOH, a surge in sox19a protein expression was observed in embryos chilled for 3 h in the presence of 1 M MeOH compared to non-chilled controls and then returned to control levels by the hatching stage. The protective effect of MeOH was increased with increasing concentrations. Effect of methanol at molecular level during chilling was reported here first time which could add new parameter in selection of cryoprotectant while designing cryopreservation protocol. Copyright © 2015. Published by Elsevier Inc.

  15. A reservoir trap for antiprotons

    CERN Document Server

    Smorra, Christian; Franke, Kurt; Nagahama, Hiroki; Schneider, Georg; Higuchi, Takashi; Van Gorp, Simon; Blaum, Klaus; Matsuda, Yasuyuki; Quint, Wolfgang; Walz, Jochen; Yamazaki, Yasunori; Ulmer, Stefan

    2015-01-01

    We have developed techniques to extract arbitrary fractions of antiprotons from an accumulated reservoir, and to inject them into a Penning-trap system for high-precision measurements. In our trap-system antiproton storage times > 1.08 years are estimated. The device is fail-safe against power-cuts of up to 10 hours. This makes our planned comparisons of the fundamental properties of protons and antiprotons independent from accelerator cycles, and will enable us to perform experiments during long accelerator shutdown periods when background magnetic noise is low. The demonstrated scheme has the potential to be applied in many other precision Penning trap experiments dealing with exotic particles.

  16. Phenotypic variability in Waardenburg syndrome resulting from a 22q12.3-q13.1 microdeletion involving SOX10.

    Science.gov (United States)

    Jelena, Brezo; Christina, Lam; Eric, Vilain; Fabiola, Quintero-Rivera

    2014-06-01

    Waardenburg syndrome (WS) is a neurocristopathy characterized by pigmentation abnormalities of the skin, hair, and iris, as well as sensorineural hearing loss. Contiguous gene deletions encompassing SOX10 are rare, which limits conclusions about genotype-phenotype correlation regarding patient prognosis and management. This study adds to the existing body of knowledge by characterizing a 2.4 Mb deletion [arr[hg19] 22q12.3-q13.1 (36467502-38878207)x1] encompassing SOX10 and 53 additional RefSeq genes in a 15-year-old female with atypical WS. The patient presented with developmental delay, profound bilateral sensorineural hearing loss, heterochromia iridis, hypotonia, and bilateral finger contractures. Published genomic and phenotypic profiles of patients with SOX10-encompassing deletions point toward several plausible candidate gene that could account for the considerable clinical heterogeneity. These studies suggest the existence of modifiers among the co-deleted, dosage-sensitive genes (e.g., MYH9) and among genes whose effect may depend on the unmasking of recessive mutations (e.g., PLA2G6). Finally, we highlight evidence illustrating extensive interconnectivity of SOX10-hypothesizing that haploinsufficiency of SOX10 may "unmask" subtler effects on expression or epistasis associated with variants in SOX10 targets (e.g., DHH), in its partners (e.g., PAX3, EGR2), and in genes with functional overlap (e.g., SOX8, SOX9). © 2014 Wiley Periodicals, Inc.

  17. Sox2, a stemness gene, regulates tumor-initiating and drug-resistant properties in CD133-positive glioblastoma stem cells

    Directory of Open Access Journals (Sweden)

    Wen-Shin Song

    2016-10-01

    Conclusion: SOX2 plays a crucial role in regulating tumorigenicity in CD133+ GBM cells. Our results not only revealed the genetic plasticity contributing to drug resistance and stemness but also demonstrated the dominant role of SOX2 in maintenance of GBM CSCs, which may provide a novel therapeutic target to overcome the conundrum of poor survival of brain cancers.

  18. Genome-Wide Identification and Transcriptome-Based Expression Profiling of the Sox Gene Family in the Nile Tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Wei, Ling; Yang, Chao; Tao, Wenjing; Wang, Deshou

    2016-02-23

    The Sox transcription factor family is characterized with the presence of a Sry-related high-mobility group (HMG) box and plays important roles in various biological processes in animals, including sex determination and differentiation, and the development of multiple organs. In this study, 27 Sox genes were identified in the genome of the Nile tilapia (Oreochromis niloticus), and were classified into seven groups. The members of each group of the tilapia Sox genes exhibited a relatively conserved exon-intron structure. Comparative analysis showed that the Sox gene family has undergone an expansion in tilapia and other teleost fishes following their whole genome duplication, and group K only exists in teleosts. Transcriptome-based analysis demonstrated that most of the tilapia Sox genes presented stage-specific and/or sex-dimorphic expressions during gonadal development, and six of the group B Sox genes were specifically expressed in the adult brain. Our results provide a better understanding of gene structure and spatio-temporal expression of the Sox gene family in tilapia, and will be useful for further deciphering the roles of the Sox genes during sex determination and gonadal development in teleosts.

  19. Genome-Wide Identification and Transcriptome-Based Expression Profiling of the Sox Gene Family in the Nile Tilapia (Oreochromis niloticus

    Directory of Open Access Journals (Sweden)

    Ling Wei

    2016-02-01

    Full Text Available The Sox transcription factor family is characterized with the presence of a Sry-related high-mobility group (HMG box and plays important roles in various biological processes in animals, including sex determination and differentiation, and the development of multiple organs. In this study, 27 Sox genes were identified in the genome of the Nile tilapia (Oreochromis niloticus, and were classified into seven groups. The members of each group of the tilapia Sox genes exhibited a relatively conserved exon-intron structure. Comparative analysis showed that the Sox gene family has undergone an expansion in tilapia and other teleost fishes following their whole genome duplication, and group K only exists in teleosts. Transcriptome-based analysis demonstrated that most of the tilapia Sox genes presented stage-specific and/or sex-dimorphic expressions during gonadal development, and six of the group B Sox genes were specifically expressed in the adult brain. Our results provide a better understanding of gene structure and spatio-temporal expression of the Sox gene family in tilapia, and will be useful for further deciphering the roles of the Sox genes during sex determination and gonadal development in teleosts.

  20. Political economy of low sulfurization and air pollution control policy in Japan : SOx emission reduction by fuel conversion

    OpenAIRE

    Terao, Tadayoshi

    2013-01-01

    In the early stages of the development of Japan’s environmental policy, sulfur oxide (SOx) emissions, which seriously damage health, was the most important air pollution problem. In the second half of the 1960s and the first half of the 1970s, the measures against SOx emissions progressed quickly, and these emissions were reduced drastically. The most important factor of the reduction was the conversion to a low-sulfur fuel for large-scale fuel users, such as the electric power industry. Howe...

  1. Alu-mediated deletion of SOX10 regulatory elements in Waardenburg syndrome type 4.

    Science.gov (United States)

    Bondurand, Nadége; Fouquet, Virginie; Baral, Viviane; Lecerf, Laure; Loundon, Natalie; Goossens, Michel; Duriez, Benedicte; Labrune, Philippe; Pingault, Veronique

    2012-09-01

    Waardenburg syndrome type 4 (WS4) is a rare neural crest disorder defined by the combination of Waardenburg syndrome (sensorineural hearing loss and pigmentation defects) and Hirschsprung disease (intestinal aganglionosis). Three genes are known to be involved in this syndrome, that is, EDN3 (endothelin-3), EDNRB (endothelin receptor type B), and SOX10. However, 15-35% of WS4 remains unexplained at the molecular level, suggesting that other genes could be involved and/or that mutations within known genes may have escaped previous screenings. Here, we searched for deletions within recently identified SOX10 regulatory sequences and describe the first characterization of a WS4 patient presenting with a large deletion encompassing three of these enhancers. Analysis of the breakpoint region suggests a complex rearrangement involving three Alu sequences that could be mediated by a FosTes/MMBIR replication mechanism. Taken together with recent reports, our results demonstrate that the disruption of highly conserved non-coding elements located within or at a long distance from the coding sequences of key genes can result in several neurocristopathies. This opens up new routes to the molecular dissection of neural crest disorders.

  2. Sox9 duplications are a relevant cause of Sry-negative XX sex reversal dogs.

    Science.gov (United States)

    Rossi, Elena; Radi, Orietta; De Lorenzi, Lisa; Vetro, Annalisa; Groppetti, Debora; Bigliardi, Enrico; Luvoni, Gaia Cecilia; Rota, Ada; Camerino, Giovanna; Zuffardi, Orsetta; Parma, Pietro

    2014-01-01

    Sexual development in mammals is based on a complicated and delicate network of genes and hormones that have to collaborate in a precise manner. The dark side of this pathway is represented by pathological conditions, wherein sexual development does not occur properly either in the XX and the XY background. Among them a conundrum is represented by the XX individuals with at least a partial testis differentiation even in absence of SRY. This particular condition is present in various mammals including the dog. Seven dogs characterized by XX karyotype, absence of SRY gene, and testicular tissue development were analysed by Array-CGH. In two cases the array-CGH analysis detected an interstitial heterozygous duplication of chromosome 9. The duplication contained the SOX9 coding region. In this work we provide for the first time a causative mutation for the XXSR condition in the dog. Moreover this report supports the idea that the dog represents a good animal model for the study of XXSR condition caused by abnormalities in the SOX9 locus.

  3. SOX2 Reprograms Resident Astrocytes into Neural Progenitors in the Adult Brain

    Directory of Open Access Journals (Sweden)

    Wenze Niu

    2015-05-01

    Full Text Available Glial cells can be in vivo reprogrammed into functional neurons in the adult CNS; however, the process by which this reprogramming occurs is unclear. Here, we show that a distinct cellular sequence is involved in SOX2-driven in situ conversion of adult astrocytes to neurons. This includes ASCL1+ neural progenitors and DCX+ adult neuroblasts (iANBs as intermediates. Importantly, ASCL1 is required, but not sufficient, for the robust generation of iANBs in the adult striatum. These progenitor-derived iANBs predominantly give rise to calretinin+ interneurons when supplied with neurotrophic factors or the small-molecule valproic acid. Patch-clamp recordings from the induced neurons reveal subtype heterogeneity, though all are functionally mature, fire repetitive action potentials, and receive synaptic inputs. Together, these results show that SOX2-mediated in vivo reprogramming of astrocytes to neurons passes through proliferative intermediate progenitors, which may be exploited for regenerative medicine.

  4. Sox9 duplications are a relevant cause of Sry-negative XX sex reversal dogs.

    Directory of Open Access Journals (Sweden)

    Elena Rossi

    Full Text Available Sexual development in mammals is based on a complicated and delicate network of genes and hormones that have to collaborate in a precise manner. The dark side of this pathway is represented by pathological conditions, wherein sexual development does not occur properly either in the XX and the XY background. Among them a conundrum is represented by the XX individuals with at least a partial testis differentiation even in absence of SRY. This particular condition is present in various mammals including the dog. Seven dogs characterized by XX karyotype, absence of SRY gene, and testicular tissue development were analysed by Array-CGH. In two cases the array-CGH analysis detected an interstitial heterozygous duplication of chromosome 9. The duplication contained the SOX9 coding region. In this work we provide for the first time a causative mutation for the XXSR condition in the dog. Moreover this report supports the idea that the dog represents a good animal model for the study of XXSR condition caused by abnormalities in the SOX9 locus.

  5. Reducing NOx and SOx pollutants in an industrial units using electron accelerator

    Directory of Open Access Journals (Sweden)

    H Nouri

    2017-08-01

    Full Text Available Electron beam accelerators technology has made significant progress in environmental applications in recent years. Including some environmental applications of industrial accelerators, is clearing the air from oxides of nitrogen and sulfur(NOx , SOx produced by industrial facilities. Combustion  of coal, oil, natural gas and other gases that are produced in power plant, refineries and industrial factories, produce high extent of these oxides wshich exceed the limit in most cases. Clearing by irradiation involves adding amounts of ammonia to output gases and irradiation by Electron beam accelerators. Irradiation produces radicals that interact again with  NOx , SOx  and produced the related gases. Due to the ammonia, these acids transform into ammonium sulfate ((NH42SO4 and ammonium nitrate (NH4NO3 are precipitated by electrostatic precipitators, and are used as chemical fertilizer. Cosidering purification process of pollutant  gases by electron beam and the importance of electron accelerator in industrial plants that are polluting the environment in Iran, can be a suitable sollution for this environmental problem

  6. The clinical impact of chromosomal rearrangements with breakpoints upstream of the SOX9 gene: two novel de novo balanced translocations associated with acampomelic campomelic dysplasia.

    Science.gov (United States)

    Fonseca, Ana Carolina S; Bonaldi, Adriano; Bertola, Débora R; Kim, Chong A; Otto, Paulo A; Vianna-Morgante, Angela M

    2013-05-07

    The association of balanced rearrangements with breakpoints near SOX9 [SRY (sex determining region Y)-box 9] with skeletal abnormalities has been ascribed to the presumptive altering of SOX9 expression by the direct disruption of regulatory elements, their separation from SOX9 or the effect of juxtaposed sequences. We report on two sporadic apparently balanced translocations, t(7;17)(p13;q24) and t(17;20)(q24.3;q11.2), whose carriers have skeletal abnormalities that led to the diagnosis of acampomelic campomelic dysplasia (ACD; MIM 114290). No pathogenic chromosomal imbalances were detected by a-CGH. The chromosome 17 breakpoints were mapped, respectively, 917-855 kb and 601-585 kb upstream of the SOX9 gene. A distal cluster of balanced rearrangements breakpoints on chromosome 17 associated with SOX9-related skeletal disorders has been mapped to a segment 932-789 kb upstream of SOX9. In this cluster, the breakpoint of the herein described t(17;20) is the most telomeric to SOX9, thus allowing the redefining of the telomeric boundary of the distal breakpoint cluster region related to skeletal disorders to 601-585 kb upstream of SOX9. Although both patients have skeletal abnormalities, the t(7;17) carrier presents with relatively mild clinical features, whereas the t(17;20) was detected in a boy with severe broncheomalacia, depending on mechanical ventilation. Balanced and unbalanced rearrangements associated with disorders of sex determination led to the mapping of a regulatory region of SOX9 function on testicular differentiation to a 517-595 kb interval upstream of SOX9, in addition to TESCO (Testis-specific enhancer of SOX9 core). As the carrier of t(17;20) has an XY sex-chromosome constitution and normal male development for his age, the segment of chromosome 17 distal to the translocation breakpoint should contain the regulatory elements for normal testis development. These two novel translocations illustrate the clinical variability in carriers of balanced

  7. Urban fall traps

    Directory of Open Access Journals (Sweden)

    Vera Lucia de Almeida Valsecchi

    2007-06-01

    Full Text Available Objectives: To evaluate the repercussion of falls in the elderly peoplewho live in the city of São Paulo and address - though synthetically- some questions regarding the city and its relation to aging and thequality of life of the elderly. Methods: This is a qualitative study. As fordata collection, “in-depth individual interviews” were applied. Selectionof subjects was guided by a procedure named as “network”. Results:Ten interviews were performed, nine with elderly individuals who werevictims of falls and one with a public authority representative. Dataresulting from interviews confirmed that significant changes occurin live of the elderly, who are victims of what has been called “urbantraps”, and that, by extrapolating mobility and dependence contexts,invade feelings, emotions and desires. The inappropriate environmentprovided by the city of São Paulo is confirmed by absence of adequateurban planning and lack of commitment of public authorities. It alsorevealed that the particular way of being old and living an elderlylife, in addition to right to citizenship, is reflected by major or lesserdifficulties imposed to the elderly to fight for their rights and have theirpublic space respected. Conclusion: The city of São Paulo is not anideal locus for an older person to live in. To the traps that are found inpublic places one can add those that are found in private places andthat contribute to the hard experience of falls among the elderly, anexperience that is sometimes fatal. In Brazil, the attention is basicallyfocused on the consequences of falls and not on prevention, by meansof urban planning that should meet the needs of the most vulnerablegroups - the physically disabled and the elderly.

  8. Innovation: the classic traps.

    Science.gov (United States)

    Kanter, Rosabeth Moss

    2006-11-01

    these traps.

  9. Zinc finger protein 219-like (ZNF219L) and Sox9a regulate synuclein-γ2 (sncgb) expression in the developing notochord of zebrafish.

    Science.gov (United States)

    Lien, Huang-Wei; Yang, Chung-Hsiang; Cheng, Chia-Hsiung; Liao, Yung-Feng; Han, Yu-San; Huang, Chang-Jen

    2013-12-13

    Zebrafish synuclein-γ2 (sncgb) has been reported to be expressed specifically in the notochord. However, the mechanism by which the sncgb gene promoter is regulated has not been described. In this paper, we demonstrate that Zinc finger protein 219-like (ZNF219L) and sox9a are involved in the regulation of sncgb gene expression. Furthermore, we observed that over-expression of both ZNF219L and Sox9a resulted in increased sncgb expression. In addition, ZNF219L is physically associated with Sox9a, and simultaneous morpholino knockdown of znf219L and sox9a caused a synergistic decrease of sncgb expression in the notochord. Taken together, our results reveal that coordination of ZNF219L with Sox9a is involved in the regulation of notochord-specific expression of sncgb. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  10. The Waardenburg Syndrome Type 4 Gene, SOX10, Is a Novel Tumor-associated Antigen Identified in a Patient with a Dramatic Response to Immunotherapy

    Science.gov (United States)

    Khong, Hung T.; Rosenberg, Steven A.

    2008-01-01

    In this study, we have identified, for the first time, the presence of de novo cellular immune reactivity against the transcription factor SOX10, using tumor-infiltrating lymphocytes obtained from a patient who experienced a dramatic clinical response to immunotherapy. SOX10 acts as a critical transactivator of tyrosinase-related protein-2 during melanoblast development and a potent transactivator of micropthalmia-associated transcription factor, which is considered to be a master gene that controls the development and postnatal survival of melanocytes. Mutations in SOX10 result in Waardenburg syndrome type 4. The overlapping epitopes AWISKPPGV and SAWISKPPGV, designated SOX10: 332–340 and SOX10: 331–340, respectively, were recognized by tumor-infiltrating lymphocyte clone M37 in an HLA-A2-restricted fashion. PMID:12036907

  11. Mini ion trap mass spectrometer

    Science.gov (United States)

    Dietrich, D.D.; Keville, R.F.

    1995-09-19

    An ion trap is described which operates in the regime between research ion traps which can detect ions with a mass resolution of better than 1:10{sup 9} and commercial mass spectrometers requiring 10{sup 4} ions with resolutions of a few hundred. The power consumption is kept to a minimum by the use of permanent magnets and a novel electron gun design. By Fourier analyzing the ion cyclotron resonance signals induced in the trap electrodes, a complete mass spectra in a single combined structure can be detected. An attribute of the ion trap mass spectrometer is that overall system size is drastically reduced due to combining a unique electron source and mass analyzer/detector in a single device. This enables portable low power mass spectrometers for the detection of environmental pollutants or illicit substances, as well as sensors for on board diagnostics to monitor engine performance or for active feedback in any process involving exhausting waste products. 10 figs.

  12. Charged particle traps II applications

    CERN Document Server

    Werth, Günther; Major, Fouad G

    2009-01-01

    This, the second volume of Charged Particle Traps, is devoted to applications, complementing the first volume’s comprehensive treatment of the theory and practice of charged particle traps, their many variants and refinements. In recent years, applications of far reaching importance have emerged ranging from the ultra-precise mass determinations of elementary particles and their antiparticles and short-lived isotopes, to high-resolution Zeeman spectroscopy on multiply-charged ions, to microwave and optical spectroscopy, some involving "forbidden" transitions from metastable states of such high resolution that optical frequency standards are realized by locking lasers to them. Further the potential application of trapped ions to quantum computing is explored, based on the extraordinary quantum state coherence made possible by the particle isolation. Consideration is given to the Paul and Penning traps as potential quantum information processors.

  13. Holes in magneto electrostatic traps

    International Nuclear Information System (INIS)

    Jones, R.

    1996-01-01

    We observe that in magneto electrostatic confinement (MEC) devices the magnetic surfaces are not always equipotentials. The lack of symmetry in the equipotential surfaces can result in holes in MEC plasma traps. (author)

  14. Trapping Triatominae in Silvatic Habitats

    Directory of Open Access Journals (Sweden)

    Noireau François

    2002-01-01

    Full Text Available Large-scale trials of a trapping system designed to collect silvatic Triatominae are reported. Live-baited adhesive traps were tested in various ecosystems and different triatomine habitats (arboreal and terrestrial. The trials were always successful, with a rate of positive habitats generally over 20% and reaching 48.4% for palm trees of the Amazon basin. Eleven species of Triatominae belonging to the three genera of public health importance (Triatoma, Rhodnius and Panstrongylus were captured. This trapping system provides an effective way to detect the presence of triatomines in terrestrial and arboreal silvatic habitats and represents a promising tool for ecological studies. Various lines of research are contemplated to improve the performance of this trapping system.

  15. 'Integration'

    DEFF Research Database (Denmark)

    Olwig, Karen Fog

    2011-01-01

    , while the countries have adopted disparate policies and ideologies, differences in the actual treatment and attitudes towards immigrants and refugees in everyday life are less clear, due to parallel integration programmes based on strong similarities in the welfare systems and in cultural notions...... of equality in the three societies. Finally, it shows that family relations play a central role in immigrants’ and refugees’ establishment of a new life in the receiving societies, even though the welfare society takes on many of the social and economic functions of the family....

  16. Overexpression of microRNA-194 suppresses the epithelial-mesenchymal transition in targeting stem cell transcription factor Sox3 in endometrial carcinoma stem cells.

    Science.gov (United States)

    Gong, Baolan; Yue, Yan; Wang, Renxiao; Zhang, Yi; Jin, Quanfang; Zhou, Xi

    2017-06-01

    The epithelial-mesenchymal transition is the key process driving cancer metastasis. MicroRNA-194 inhibits epithelial-mesenchymal transition in several cancers and its downregulation indicates a poor prognosis in human endometrial carcinoma. Self-renewal factor Sox3 induces epithelial-mesenchymal transition at gastrulation and is also involved epithelial-mesenchymal transition in several cancers. We intended to determine the roles of Sox3 in inducing epithelial-mesenchymal transition in endometrial cancer stem cells and the possible role of microRNA-194 in controlling Sox3 expression. Firstly, we found that Sox3 and microRNA-194 expressions were associated with the status of endometrial cancer stem cells in a panel of endometrial carcinoma tissue, the CD133+ cell was higher in tumorsphere than in differentiated cells, and overexpression of microRNA-194 would decrease CD133+ cell expression. Silencing of Sox3 in endometrial cancer stem cell upregulated the epithelial marker E-cadherin, downregulated the mesenchymal marker vimentin, and significantly reduced cell invasion in vitro; overexpression of Sox3 reversed these phenotypes. Furthermore, we discovered that the expression of Sox3 was suppressed by microRNA-194 through direct binding to the Sox3 3'-untranslated region. Ectopic expression of microRNA-194 in endometrial cancer stem cells induced a mesenchymal-epithelial transition by restoring E-cadherin expression, decreasing vimentin expression, and inhibiting cell invasion in vitro. Moreover, overexpression of microRNA-194 inhibited endometrial cancer stem cell invasion or metastasis in vivo by injection of adenovirus microRNA-194. These findings demonstrate the novel mechanism by which Sox3 contributes to endometrial cancer stem cell invasion and suggest that repression of Sox3 by microRNA-194 may have therapeutic potential to suppress endometrial carcinoma metastasis. The cancer stem cell marker, CD133, might be the surface marker of endometrial cancer stem

  17. Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone.

    Science.gov (United States)

    Gonen, Nitzan; Quinn, Alexander; O'Neill, Helen C; Koopman, Peter; Lovell-Badge, Robin

    2017-01-01

    During mouse sex determination, transient expression of the Y-linked gene Sry up-regulates its direct target gene Sox9, via a 3.2 kb testis specific enhancer of Sox9 (TES), which includes a core 1.4 kb element, TESCO. SOX9 activity leads to differentiation of Sertoli cells, rather than granulosa cells from the bipotential supporting cell precursor lineage. Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh. Although human patients heterozygous for null mutations in SOX9, which are assumed to have 50% of normal expression, often show XY female sex reversal, mice deleted for one copy of Sox9 do not. Consistent with this, we did not observe sex reversal in either TESCO-/- or TES-/- XY embryos or adult mice. However, embryos carrying both a conditional Sox9 null allele and the TES deletion developed ovotestes. Quantitative analysis of these revealed levels of 23% expression of Sox9 compared to wild type, and a significant increase in the expression of the granulosa cell marker Foxl2. This indicates that the threshold in mice where sex reversal begins to be seen is about half that of the ~50% levels predicted in humans. Our results demonstrate that TES/TESCO is a crucial enhancer regulating Sox9 expression in the gonad, but point to the existence of additional enhancers that act redundantly.

  18. Normal Levels of Sox9 Expression in the Developing Mouse Testis Depend on the TES/TESCO Enhancer, but This Does Not Act Alone.

    Directory of Open Access Journals (Sweden)

    Nitzan Gonen

    2017-01-01

    Full Text Available During mouse sex determination, transient expression of the Y-linked gene Sry up-regulates its direct target gene Sox9, via a 3.2 kb testis specific enhancer of Sox9 (TES, which includes a core 1.4 kb element, TESCO. SOX9 activity leads to differentiation of Sertoli cells, rather than granulosa cells from the bipotential supporting cell precursor lineage. Here, we present functional analysis of TES/TESCO, using CRISPR/Cas9 genome editing in mice. Deletion of TESCO or TES reduced Sox9 expression levels in XY fetal gonads to 60 or 45% respectively relative to wild type gonads, and reduced expression of the SOX9 target Amh. Although human patients heterozygous for null mutations in SOX9, which are assumed to have 50% of normal expression, often show XY female sex reversal, mice deleted for one copy of Sox9 do not. Consistent with this, we did not observe sex reversal in either TESCO-/- or TES-/- XY embryos or adult mice. However, embryos carrying both a conditional Sox9 null allele and the TES deletion developed ovotestes. Quantitative analysis of these revealed levels of 23% expression of Sox9 compared to wild type, and a significant increase in the expression of the granulosa cell marker Foxl2. This indicates that the threshold in mice where sex reversal begins to be seen is about half that of the ~50% levels predicted in humans. Our results demonstrate that TES/TESCO is a crucial enhancer regulating Sox9 expression in the gonad, but point to the existence of additional enhancers that act redundantly.

  19. Science, conservation, and camera traps

    Science.gov (United States)

    Nichols, James D.; Karanth, K. Ullas; O'Connel, Allan F.; O'Connell, Allan F.; Nichols, James D.; Karanth, K. Ullas

    2011-01-01

    Biologists commonly perceive camera traps as a new tool that enables them to enter the hitherto secret world of wild animals. Camera traps are being used in a wide range of studies dealing with animal ecology, behavior, and conservation. Our intention in this volume is not to simply present the various uses of camera traps, but to focus on their use in the conduct of science and conservation. In this chapter, we provide an overview of these two broad classes of endeavor and sketch the manner in which camera traps are likely to be able to contribute to them. Our main point here is that neither photographs of individual animals, nor detection history data, nor parameter estimates generated from detection histories are the ultimate objective of a camera trap study directed at either science or management. Instead, the ultimate objectives are best viewed as either gaining an understanding of how ecological systems work (science) or trying to make wise decisions that move systems from less desirable to more desirable states (conservation, management). Therefore, we briefly describe here basic approaches to science and management, emphasizing the role of field data and associated analyses in these processes. We provide examples of ways in which camera trap data can inform science and management.

  20. Status of THe-trap

    Energy Technology Data Exchange (ETDEWEB)

    Ketter, Jochen; Eronen, Tommi; Hoecker, Martin; Streubel, Sebastian; Blaum, Klaus [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany); Van Dyck, Robert S. Jr. [Department of Physics, University of Washington, Seattle, WA (United States)

    2012-07-01

    Originally developed at the University of Washington and relocated to the Max-Planck-Institut fuer Kernphysik in 2008, the Penning-trap spectrometer THe-Trap is specially tailored for a {sup 3}H/{sup 3}He mass-ratio measurement, from which the Q-value of the beta-decay of {sup 3}H to {sup 3}He can be derived. Improving the current best value by at least an order of magnitude will provide an important independent test parameter for the determination of the electron-antineutrino's mass by the Karlsruhe Tritium Neutrino Experiment (KATRIN). However, Penning-trap mass spectrometry has to be pushed to its limits in a dedicated experiment for a sufficiently accurate mass-ratio measurement with a relative uncertainty of 10{sup -11}. Unlike the closed-envelope, single-trap predecessor, the new spectrometer features an external ion source, owing to the radioactive nature of tritium, and two traps in order to speed up the measurement cycle. While the double-trap technique holds great promise, it also calls for more intricate procedures, such as ion transfer. Details about the recent progress of the experiment are given.

  1. Evaluation of monitoring traps with novel bait for navel orangeworm (Lepidoptera: Pyralidae) in California almond and pistachio orchards.

    Science.gov (United States)

    Nay, Justin E; Peterson, Elonce M; Boyd, Elizabeth A

    2012-08-01

    Experiments conducted in three almond, Prunus dulcis (Rosales: Rosaceae), orchards and three pistachio, Pistacia vera (Sapindales: Anicardiaceae), orchards in 2009 and 2010, and determined that sticky bottom wing traps baited with ground pistachio mummies, or a combination of ground pistachio plus ground almond mummies, trapped more adult female navel orangeworm, Amyelois transitella (Walker) (Lepidoptera: Pyralidae), than did traps baited with ground almond mummies alone. During both years of this study, 2.9 and 1.8 more moths were caught in traps baited with pistachio mummies compared with traps baited with almond mummies in almond orchards and pistachio orchards, respectively. Also, traps located in pistachio orchards caught 5.9 and 8.3 times more navel orangeworm than were trapped from almond orchards in 2009 and 2010, respectively. Implications for use of this novel baited trap in almond and pistachio orchard integrated pest management programs are discussed.

  2. Effects of oxide traps, interface traps, and ''border traps'' on metal-oxide-semiconductor devices

    International Nuclear Information System (INIS)

    Fleetwood, D.M.; Winokur, P.S.; Reber, R.A. Jr.; Meisenheimer, T.L.; Schwank, J.R.; Shaneyfelt, M.R.; Riewe, L.C.

    1993-01-01

    We have identified several features of the 1/f noise and radiation response of metal-oxide-semiconductor (MOS) devices that are difficult to explain with standard defect models. To address this issue, and in response to ambiguities in the literature, we have developed a revised nomenclature for defects in MOS devices that clearly distinguishes the language used to describe the physical location of defects from that used to describe their electrical response. In this nomenclature, ''oxide traps'' are simply defects in the SiO 2 layer of the MOS structure, and ''interface traps'' are defects at the Si/SiO 2 interface. Nothing is presumed about how either type of defect communicates with the underlying Si. Electrically, ''fixed states'' are defined as trap levels that do not communicate with the Si on the time scale of the measurements, but ''switching states'' can exchange charge with the Si. Fixed states presumably are oxide traps in most types of measurements, but switching states can either be interface traps or near-interfacial oxide traps that can communicate with the Si, i.e., ''border traps'' [D. M. Fleetwood, IEEE Trans. Nucl. Sci. NS-39, 269 (1992)]. The effective density of border traps depends on the time scale and bias conditions of the measurements. We show the revised nomenclature can provide focus to discussions of the buildup and annealing of radiation-induced charge in non-radiation-hardened MOS transistors, and to changes in the 1/f noise of MOS devices through irradiation and elevated-temperature annealing

  3. Trapping, self-trapping and the polaron family

    International Nuclear Information System (INIS)

    Stoneham, A M; Gavartin, J; Shluger, A L; Kimmel, A V; Ramo, D Munoz; Roennow, H M; Aeppli, G; Renner, C

    2007-01-01

    The earliest ideas of the polaron recognized that the coupling of an electron to ionic vibrations would affect its apparent mass and could effectively immobilize the carrier (self-trapping). We discuss how these basic ideas have been generalized to recognize new materials and new phenomena. First, there is an interplay between self-trapping and trapping associated with defects or with fluctuations in an amorphous solid. In high dielectric constant oxides, like HfO 2 , this leads to oxygen vacancies having as many as five charge states. In colossal magnetoresistance manganites, this interplay makes possible the scanning tunnelling microscopy (STM) observation of polarons. Second, excitons can self-trap and, by doing so, localize energy in ways that can modify the material properties. Third, new materials introduce new features, with polaron-related ideas emerging for uranium dioxide, gate dielectric oxides, Jahn-Teller systems, semiconducting polymers and biological systems. The phonon modes that initiate self-trapping can be quite different from the longitudinal optic modes usually assumed to dominate. Fourth, there are new phenomena, like possible magnetism in simple oxides, or with the evolution of short-lived polarons, like muons or excitons. The central idea remains that of a particle whose properties are modified by polarizing or deforming its host solid, sometimes profoundly. However, some of the simpler standard assumptions can give a limited, indeed misleading, description of real systems, with qualitative inconsistencies. We discuss representative cases for which theory and experiment can be compared in detail

  4. Defects in cardiac outflow tract formation and pro-B-lymphocyte expansion in mice lacking Sox-4

    NARCIS (Netherlands)

    Schilham, M. W.; Oosterwegel, M. A.; Moerer, P.; Ya, J.; de Boer, P. A.; van de Wetering, M.; Verbeek, S.; Lamers, W. H.; Kruisbeek, A. M.; Cumano, A.; Clevers, H.

    1996-01-01

    A striking example of the relationship between regulation of transcription and phenotype is the central role of the Y-chromosomal gene Sry in mammalian sex determination. Sry is the founding member of a large family of so-called Sox genes. During murine embryogenesis, the transcriptional activator

  5. Chronic constipation recognized as a sign of a SOX10 mutation in a patient with Waardenburg syndrome.

    Science.gov (United States)

    Arimoto, Yukiko; Namba, Kazunori; Nakano, Atsuko; Matsunaga, Tatsuo

    2014-05-01

    Waardenburg syndrome is characterized by hearing loss, pigmentation abnormalities, dysmorphologic features, and neurological phenotypes. Waardenburg syndrome consists of four distinct subtypes, and SOX10 mutations have been identified in type II and type IV. Type IV differs from type II owing to the presence of Hirschsprung disease. We identified a de novo nonsense mutation in SOX10 (p.G39X) in a female pediatric patient with Waardenburg syndrome with heterochromia iridis, profound bilateral sensorineural hearing loss, inner ear malformations, and overall hypopigmentation of the hair without dystopia canthorum. This patient has experienced chronic constipation since she was a neonate, but anorectal manometry showed a normal anorectal reflex. Chronic constipation in this patient was likely to be a consequence of a mild intestinal disorder owing to the SOX10 mutation, and this patient was considered to have a clinical phenotype intermediate between type II and type IV of the syndrome. Chronic constipation may be recognized as indicative of a SOX10 mutation in patients with Waardenburg syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Identification and functional analysis of a novel mutation in the SOX10 gene associated with Waardenburg syndrome type IV.

    Science.gov (United States)

    Wang, Hong-Han; Chen, Hong-Sheng; Li, Hai-Bo; Zhang, Hua; Mei, Ling-Yun; He, Chu-Feng; Wang, Xing-Wei; Men, Mei-Chao; Jiang, Lu; Liao, Xin-Bin; Wu, Hong; Feng, Yong

    2014-03-15

    Waardenburg syndrome type IV (WS4) is a rare genetic disorder, characterized by auditory-pigmentary abnormalities and Hirschsprung disease. Mutations of the EDNRB gene, EDN3 gene, or SOX10 gene are responsible for WS4. In the present study, we reported a case of a Chinese patient with clinical features of WS4. In addition, the three genes mentioned above were sequenced in order to identify whether mutations are responsible for the case. We revealed a novel nonsense mutation, c.1063C>T (p.Q355*), in the last coding exon of SOX10. The same mutation was not found in three unaffected family members or 100 unrelated controls. Then, the function and mechanism of the mutation were investigated in vitro. We found both wild-type (WT) and mutant SOX10 p.Q355* were detected at the expected size and their expression levels are equivalent. The mutant protein also localized in the nucleus and retained the DNA-binding activity as WT counterpart; however, it lost its transactivation capability on the MITF promoter and acted as a dominant-negative repressor impairing function of the WT SOX10. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Sox21 deletion in mice causes postnatal growth deficiency without physiological disruption of hypothalamic-pituitary endocrine axes.

    Science.gov (United States)

    Cheung, Leonard Y M; Okano, Hideyuki; Camper, Sally A

    2017-01-05

    The hypothalamic-pituitary axes are the coordinating centers for multiple endocrine gland functions and physiological processes. Defects in the hypothalamus or pituitary gland can cause reduced growth and severe short stature, affecting approximately 1 in 4000 children, and a large percentage of cases of pituitary hormone deficiencies do not have an identified genetic cause. SOX21 is a protein that regulates hair, neural, and trophoblast stem cell differentiation. Mice lacking Sox21 have reduced growth, but the etiology of this growth defect has not been described. We studied the expression of Sox21 in hypothalamic-pituitary development and examined multiple endocrine axes in these mice. We find no evidence of reduced intrauterine growth, food intake, or physical activity, but there is evidence for increased energy expenditure in mutants. In addition, despite changes in pituitary hormone expression, hypothalamic-pituitary axes appear to be functional. Therefore, SOX21 variants may be a cause of non-endocrine short stature in humans. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. A Sox Transcription Factor Is a Critical Regulator of Adult Stem Cell Proliferation in the Drosophila Intestine

    Directory of Open Access Journals (Sweden)

    Fanju W. Meng

    2015-11-01

    Full Text Available Adult organs and their resident stem cells are constantly facing the challenge of adapting cell proliferation to tissue demand, particularly in response to environmental stresses. Whereas most stress-signaling pathways are conserved between progenitors and differentiated cells, stem cells have the specific ability to respond by increasing their proliferative rate, using largely unknown mechanisms. Here, we show that a member of the Sox family of transcription factors in Drosophila, Sox21a, is expressed in intestinal stem cells (ISCs in the adult gut. Sox21a is essential for the proliferation of these cells during both normal epithelium turnover and repair. Its expression is induced in response to tissue damage, downstream of the Jun N-terminal kinase (JNK and extracellular signal-regulated kinase (ERK pathways, to promote ISC proliferation. Although short-lived, Sox21a mutant flies show no developmental defects, supporting the notion that this factor is a specific regulator of adult stem cell proliferation.

  9. SOX6 and PDCD4 enhance cardiomyocyte apoptosis through LPS-induced miR-499 inhibition.

    Science.gov (United States)

    Jia, Zhuqing; Wang, Jiaji; Shi, Qiong; Liu, Siyu; Wang, Weiping; Tian, Yuyao; Lu, Qin; Chen, Ping; Ma, Kangtao; Zhou, Chunyan

    2016-02-01

    Sepsis-induced cardiac apoptosis is one of the major pathogenic factors in myocardial dysfunction. As it enhances numerous proinflammatory factors, lipopolysaccharide (LPS) is considered the principal mediator in this pathological process. However, the detailed mechanisms involved are unclear. In this study, we attempted to explore the mechanisms involved in LPS-induced cardiomyocyte apoptosis. We found that LPS stimulation inhibited microRNA (miR)-499 expression and thereby upregulated the expression of SOX6 and PDCD4 in neonatal rat cardiomyocytes. We demonstrate that SOX6 and PDCD4 are target genes of miR-499, and they enhance LPS-induced cardiomyocyte apoptosis by activating the BCL-2 family pathway. The apoptosis process enhanced by overexpression of SOX6 or PDCD4, was rescued by the cardiac-abundant miR-499. Overexpression of miR-499 protected the cardiomyocytes against LPS-induced apoptosis. In brief, our results demonstrate the existence of a miR-499-SOX6/PDCD4-BCL-2 family pathway in cardiomyocytes in response to LPS stimulation.

  10. SOX9/miR-130a/CTR1 axis modulates DDP-resistance of cervical cancer cell.

    Science.gov (United States)

    Feng, Chenzhe; Ma, Fang; Hu, Chunhong; Ma, Jin-An; Wang, Jingjing; Zhang, Yang; Wu, Fang; Hou, Tao; Jiang, Shun; Wang, Yapeng; Feng, Yeqian

    2018-01-01

    Cisplatin (DDP) -based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a huge challenge. Copper transporter protein 1 (CTR1), a copper influx transporter required for high affinity copper (probably reduced Cu I) transport into the cell, reportedly promotes a significant fraction of DDP internalization in tumor cells. In the present study, we evaluated the function of CTR1 in the cell proliferation of cervical cancer upon DDP treatment. MicroRNAs (miRNAs) have been regarded as essential regulators of cell proliferation, apoptosis, migration, as well as chemoresistance. By using online tools, we screened for candidate miRNAs potentially regulate CTR1, among which miR-130a has been proved to promote cervical cancer cell proliferation through targeting PTEN in our previous study. In the present study, we investigated the role of miR-130a in cervical cancer chemoresistance to DDP, and confirmed the binding of miR-130a to CTR1. SOX9 also reportedly act on cancer chemoresistance. In the present study, we revealed that SOX9 inversely regulated miR-130a through direct targeting the promoter of miR-130a. Consistent with previous studies, SOX9 could affect cervical cancer chemoresistance to DDP. Taken together, we demonstrated a SOX9/miR-130a/CTR1 axis which modulated the chemoresistance of cervical cancer cell to DDP, and provided promising targets for dealing with the chemoresistance of cervical cancer.

  11. Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence.

    Science.gov (United States)

    Benko, Sabina; Fantes, Judy A; Amiel, Jeanne; Kleinjan, Dirk-Jan; Thomas, Sophie; Ramsay, Jacqueline; Jamshidi, Negar; Essafi, Abdelkader; Heaney, Simon; Gordon, Christopher T; McBride, David; Golzio, Christelle; Fisher, Malcolm; Perry, Paul; Abadie, Véronique; Ayuso, Carmen; Holder-Espinasse, Muriel; Kilpatrick, Nicky; Lees, Melissa M; Picard, Arnaud; Temple, I Karen; Thomas, Paul; Vazquez, Marie-Paule; Vekemans, Michel; Roest Crollius, Hugues; Hastie, Nicholas D; Munnich, Arnold; Etchevers, Heather C; Pelet, Anna; Farlie, Peter G; Fitzpatrick, David R; Lyonnet, Stanislas

    2009-03-01

    Pierre Robin sequence (PRS) is an important subgroup of cleft palate. We report several lines of evidence for the existence of a 17q24 locus underlying PRS, including linkage analysis results, a clustering of translocation breakpoints 1.06-1.23 Mb upstream of SOX9, and microdeletions both approximately 1.5 Mb centromeric and approximately 1.5 Mb telomeric of SOX9. We have also identified a heterozygous point mutation in an evolutionarily conserved region of DNA with in vitro and in vivo features of a developmental enhancer. This enhancer is centromeric to the breakpoint cluster and maps within one of the microdeletion regions. The mutation abrogates the in vitro enhancer function and alters binding of the transcription factor MSX1 as compared to the wild-type sequence. In the developing mouse mandible, the 3-Mb region bounded by the microdeletions shows a regionally specific chromatin decompaction in cells expressing Sox9. Some cases of PRS may thus result from developmental misexpression of SOX9 due to disruption of very-long-range cis-regulatory elements.

  12. Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10.

    Science.gov (United States)

    Pingault, Veronique; Pierre-Louis, Laurence; Chaoui, Asma; Verloes, Alain; Sarrazin, Elisabeth; Brandberg, Goran; Bondurand, Nadege; Uldall, Peter; Manouvrier-Hanu, Sylvie

    2014-09-01

    Waardenburg syndrome (WS) is characterized by an association of pigmentation abnormalities and sensorineural hearing loss. Four types, defined on clinical grounds, have been delineated, but this phenotypic classification correlates imperfectly with known molecular anomalies. SOX10 mutations have been found in patients with type II and type IV WS (i.e., with Hirschsprung disease), more complex syndromes, and partial forms of the disease. The phenotype induced by SOX10 mutations is highly variable and, except for the neurological forms of the disease, no genotype-phenotype correlation has been characterized to date. There is no mutation hotspot in SOX10 and most cases are sporadic, making it particularly difficult to correlate the phenotypic and genetic variability. This study reports on three independent families with SOX10 mutations predicted to result in the same missense mutation at the protein level (p.Met112Ile), offering a rare opportunity to improve our understanding of the mechanisms underlying phenotypic variability. The pigmentation defects of these patients are very similar, and the neurological symptoms showed a somewhat similar evolution over time, indicating a potential partial genotype-phenotype correlation. However, variability in gastrointestinal symptoms suggests that other genetic factors contribute to the expression of these phenotypes. No correlation between the rs2435357 polymorphism of RET and the expression of Hirschsprung disease was found. In addition, one of the patients has esophageal achalasia, which has rarely been described in WS. © 2014 Wiley Periodicals, Inc.

  13. Sox2-Mediated Conversion of NG2 Glia into Induced Neurons in the Injured Adult Cerebral Cortex

    Directory of Open Access Journals (Sweden)

    Christophe Heinrich

    2014-12-01

    Full Text Available The adult cerebral cortex lacks the capacity to replace degenerated neurons following traumatic injury. Conversion of nonneuronal cells into induced neurons has been proposed as an innovative strategy toward brain repair. Here, we show that retrovirus-mediated expression of the transcription factors Sox2 and Ascl1, but strikingly also Sox2 alone, can induce the conversion of genetically fate-mapped NG2 glia into induced doublecortin (DCX+ neurons in the adult mouse cerebral cortex following stab wound injury in vivo. In contrast, lentiviral expression of Sox2 in the unlesioned cortex failed to convert oligodendroglial and astroglial cells into DCX+ cells. Neurons induced following injury mature morphologically and some acquire NeuN while losing DCX. Patch-clamp recording of slices containing Sox2- and/or Ascl1-transduced cells revealed that a substantial fraction of these cells receive synaptic inputs from neurons neighboring the injury site. Thus, NG2 glia represent a potential target for reprogramming strategies toward cortical repair.

  14. Evidence for increased SOX3 dosage as a risk factor for X-linked hypopituitarism and neural tube defects

    NARCIS (Netherlands)

    Bauters, M.; Frints, S.G.; Esch, H. van; Spruijt, L.; Baldewijns, M.M.; Die-Smulders, C.E.M. de; Fryns, J.P.; Marynen, P.; Froyen, G.

    2014-01-01

    Genomic duplications of varying lengths at Xq26-q27 involving SOX3 have been described in families with X-linked hypopituitarism. Using array-CGH we detected a 1.1 Mb microduplication at Xq27 in a large family with three males suffering from X-linked hypopituitarism. The duplication was mapped from

  15. Neuronal cell fate decisions:  O2 and CO2 sensing neurons require egl-13/Sox5

    DEFF Research Database (Denmark)

    Gramstrup Petersen, Jakob; Pocock, Roger David John

    2013-01-01

    We recently conducted a study that aimed to describe the differentiation mechanisms used to generate O2 and CO2 sensing neurons in C. elegans. We identified egl-13/Sox5 to be required for the differentiation of both O2 and CO2 sensing neurons. We found that egl-13 functions cell autonomously...

  16. Microwave regenerated particulate trap

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, A.C. Jr.; Yonushonis, T.M. [Cummins Engine Co., Inc., Columbus, IN (United States); Haberkamp, W.C.; Mako, F.; Len, L.K,; Silberglitt, R.; Ahmed, I. [FM Technologies, Inc., Fairfax, VA (United States)

    1997-12-31

    It has been demonstrated that a fibrous particulate filter can extract particulate matter from the diesel exhaust. However, additional engineering efforts remains to achieve the design target of 90%. It has also be shown that with minor modifications magnetrons produced for home ovens can endure a simulated diesel operating environment. Much work remains to develop a robust product ready to complete extensive engine testing and evaluation. These efforts include: (1) additional environmental testing of magnetrons; (2) vibration testing of the filter in the housing; (3) evaluating alternative methods/designs to seal the center bore; and (4) determining the optimum coating thickness that provides sufficient structural integrity while maintaining rapid heating rates.

  17. A magnetic particle micro-trap for large trapping surfaces

    KAUST Repository

    Gooneratne, Chinthaka P.

    2012-01-08

    Manipulation of micron-size magnetic particles of the superparamagnetic type contributes significantly in many applications like controlling the antibody/antigen binding process in immunoassays. Specifically, more target biomolecules can be attached/tagged and analyzed since the three dimensional structure of the magnetic particles increases the surface to volume ratio. Additionally, such biomolecular-tagged magnetic particles can be easily manipulated by an external magnetic field due to their superparamagnetic behavior. Therefore, magnetic particle- based immunoassays are extensively applied in micro-flow cytometry. The design of a square-loop micro-trap as a magnetic particle manipulator as well as numerical and experimental analysis is presented. Experimental results showed that the micro-trap could successfully trap and concentrate magnetic particles from a large to a small area with a high spatial range.

  18. A magnetic particle micro-trap for large trapping surfaces

    KAUST Repository

    Gooneratne, Chinthaka P.; Liang, Cai; Giouroudi, Ioanna; Kosel, Jü rgen

    2012-01-01

    Manipulation of micron-size magnetic particles of the superparamagnetic type contributes significantly in many applications like controlling the antibody/antigen binding process in immunoassays. Specifically, more target biomolecules can be attached/tagged and analyzed since the three dimensional structure of the magnetic particles increases the surface to volume ratio. Additionally, such biomolecular-tagged magnetic particles can be easily manipulated by an external magnetic field due to their superparamagnetic behavior. Therefore, magnetic particle- based immunoassays are extensively applied in micro-flow cytometry. The design of a square-loop micro-trap as a magnetic particle manipulator as well as numerical and experimental analysis is presented. Experimental results showed that the micro-trap could successfully trap and concentrate magnetic particles from a large to a small area with a high spatial range.

  19. Particle trapping in stimulated scattering processes

    International Nuclear Information System (INIS)

    Karttunen, S.J.; Heikkinen, J.A.

    1981-01-01

    Particle trapping effects on stimulated Brillouin and Raman scattering are investigated. A time and space dependent model assumes a Maxwellian plasma which is taken to be homogeneous in the interaction region. Ion trapping has a rather weak effect on stimulated Brillouin scattering and large reflectivities are obtained even in strong trapping regime. Stimulated Raman scattering is considerably reduced by electron trapping. Typically 15-20 times larger laser intensities are required to obtain same reflectivity levels than without trapping. (author)

  20. Calcium Atom Trap for Atom Trap Mass Spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Kwang Hoon; Park, Hyun Min; Han, Jae Min; Kim, Taek Soo; Cha, Yong Ho; Lim, Gwon; Jeong, Do Young [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2012-05-15

    Trace isotope analysis has been an important role in science, archaeological dating, geology, biology and nuclear industry. Artificially produced fission products such as Sr-90, Cs-135 and Kr-85 can be released to the environment when nuclear accident occurs and the reprocessing factory operates. Thus, the analysis of them has been of interest in nuclear industry. But it is difficult to detect them due to low natural abundance less then 10-10. The ultra-trace radio isotopes have been analyzed by the radio-chemical method, accelerator mass spectrometer, and laser based method. The radiochemical method has been used in the nuclear industry. But this method has disadvantages of long measurement time for long lived radioisotopes and toxic chemical process for the purification. The accelerator mass spectrometer has high isotope selectivity, but the system is huge and it has the isobar effects. The laser based method, such as RIMS (Resonance Ionization Mass Spectrometry) is a basically isobar-effect free method. Recently, ATTA (Atom Trap Trace Analysis), one of the laser based method, has been successfully demonstrated sufficient isotope selectivity with small system size. It has been applied for the detection of Kr-81 and Kr-85. However, it is not suitable for real sample detection, because it requires steady atomic beam generation during detection and is not allowed simultaneous detection of other isotopes. Therefore, we proposed the coupled method of Atom Trap and Mass Spectrometer. It consists of three parts, neutral atom trap, ionization and mass spectrometer. In this paper, we present the demonstration of the magneto-optical trap of neutral calcium. We discuss the isotope selective characteristics of the MOT (Magneto Optical Trap) of calcium by the fluorescence measurement. In addition, the frequency stabilization of the trap beam will be presented

  1. Wnt/β-catenin signalling regulates Sox17 expression and is essential for organizer and endoderm formation in the mouse.

    Science.gov (United States)

    Engert, Silvia; Burtscher, Ingo; Liao, W Perry; Dulev, Stanimir; Schotta, Gunnar; Lickert, Heiko

    2013-08-01

    Several signalling cascades are implicated in the formation and patterning of the three principal germ layers, but their precise temporal-spatial mode of action in progenitor populations remains undefined. We have used conditional gene deletion of mouse β-catenin in Sox17-positive embryonic and extra-embryonic endoderm as well as vascular endothelial progenitors to address the function of canonical Wnt signalling in cell lineage formation and patterning. Conditional mutants fail to form anterior brain structures and exhibit posterior body axis truncations, whereas initial blood vessel formation appears normal. Tetraploid rescue experiments reveal that lack of β-catenin in the anterior visceral endoderm results in defects in head organizer formation. Sox17 lineage tracing in the definitive endoderm (DE) shows a cell-autonomous requirement for β-catenin in midgut and hindgut formation. Surprisingly, wild-type posterior visceral endoderm (PVE) in midgut- and hindgut-deficient tetraploid chimera rescues the posterior body axis truncation, indicating that the PVE is important for tail organizer formation. Upon loss of β-catenin in the visceral endoderm and DE lineages, but not in the vascular endothelial lineage, Sox17 expression is not maintained, suggesting downstream regulation by canonical Wnt signalling. Strikingly, Tcf4/β-catenin transactivation complexes accumulated on Sox17 cis-regulatory elements specifically upon endoderm induction in an embryonic stem cell differentiation system. Together, these results indicate that the Wnt/β-catenin signalling pathway regulates Sox17 expression for visceral endoderm pattering and DE formation and provide the first functional evidence that the PVE is necessary for gastrula organizer gene induction and posterior axis development.

  2. Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Z.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Li, X.L. [Department of Dermatology, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); He, X.J. [Department of Orthopedics, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Wu, B.J.; Xu, M. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Chang, H.M. [Department of Otolaryngology - Head and Neck Surgery, Affiliated Hospital of Xi' an Medical University, Xi' an (China); Zhang, X.H. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China); Xing, Z. [Department of Clinical Dentistry, Faculty of Dentistry, Center for Clinical Dental Research, University of Bergen, Bergen (Norway); Jing, X.H.; Kong, D.M.; Kou, X.H.; Yang, Y.Y. [Department of Otolaryngology - Head and Neck Surgery, The Second Hospital, Xi' an Jiaotong University, Xi' an (China)

    2014-03-18

    SRY-related high-mobility-group box 9 (Sox9) gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs). After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering.

  3. Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

    Directory of Open Access Journals (Sweden)

    Z.H. Wang

    2014-04-01

    Full Text Available SRY-related high-mobility-group box 9 (Sox9 gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs. After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering.

  4. Copy number variation in the region harboring SOX9 gene in dogs with testicular/ovotesticular disorder of sex development (78,XX; SRY-negative).

    Science.gov (United States)

    Marcinkowska-Swojak, Malgorzata; Szczerbal, Izabela; Pausch, Hubert; Nowacka-Woszuk, Joanna; Flisikowski, Krzysztof; Dzimira, Stanislaw; Nizanski, Wojciech; Payan-Carreira, Rita; Fries, Ruedi; Kozlowski, Piotr; Switonski, Marek

    2015-10-01

    Although the disorder of sex development in dogs with female karyotype (XX DSD) is quite common, its molecular basis is still unclear. Among mutations underlying XX DSD in mammals are duplication of a long sequence upstream of the SOX9 gene (RevSex) and duplication of the SOX9 gene (also observed in dogs). We performed a comparative analysis of 16 XX DSD and 30 control female dogs, using FISH and MLPA approaches. Our study was focused on a region harboring SOX9 and a region orthologous to the human RevSex (CanRevSex), which was located by in silico analysis downstream of SOX9. Two highly polymorphic copy number variable regions (CNVRs): CNVR1 upstream of SOX9 and CNVR2 encompassing CanRevSex were identified. Although none of the detected copy number variants were specific to either affected or control animals, we observed that the average number of copies in CNVR1 was higher in XX DSD. No copy variation of SOX9 was observed. Our extensive studies have excluded duplication of SOX9 as the common cause of XX DSD in analyzed samples. However, it remains possible that the causative mutation is hidden in highly polymorphic CNVR1.

  5. Delivery of the Sox9 gene promotes chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells in an in vitro model

    International Nuclear Information System (INIS)

    Wang, Z.H.; Li, X.L.; He, X.J.; Wu, B.J.; Xu, M.; Chang, H.M.; Zhang, X.H.; Xing, Z.; Jing, X.H.; Kong, D.M.; Kou, X.H.; Yang, Y.Y.

    2014-01-01

    SRY-related high-mobility-group box 9 (Sox9) gene is a cartilage-specific transcription factor that plays essential roles in chondrocyte differentiation and cartilage formation. The aim of this study was to investigate the feasibility of genetic delivery of Sox9 to enhance chondrogenic differentiation of human umbilical cord blood-derived mesenchymal stem cells (hUC-MSCs). After they were isolated from human umbilical cord blood within 24 h after delivery of neonates, hUC-MSCs were untreated or transfected with a human Sox9-expressing plasmid or an empty vector. The cells were assessed for morphology and chondrogenic differentiation. The isolated cells with a fibroblast-like morphology in monolayer culture were positive for the MSC markers CD44, CD105, CD73, and CD90, but negative for the differentiation markers CD34, CD45, CD19, CD14, or major histocompatibility complex class II. Sox9 overexpression induced accumulation of sulfated proteoglycans, without altering the cellular morphology. Immunocytochemistry demonstrated that genetic delivery of Sox9 markedly enhanced the expression of aggrecan and type II collagen in hUC-MSCs compared with empty vector-transfected counterparts. Reverse transcription-polymerase chain reaction analysis further confirmed the elevation of aggrecan and type II collagen at the mRNA level in Sox9-transfected cells. Taken together, short-term Sox9 overexpression facilitates chondrogenesis of hUC-MSCs and may thus have potential implications in cartilage tissue engineering

  6. Functional analysis of a SOX10 gene mutation associated with Waardenburg syndrome II.

    Science.gov (United States)

    Wang, Xue-Ping; Hao, Zi-Qi; Liu, Ya-Lan; Mei, Ling-Yun; He, Chu-Feng; Niu, Zhi-Jie; Sun, Jie; Zhao, Yu-Lin; Feng, Yong

    2017-11-04

    Waardenburg syndrome (WS) is an autosomal dominant inherited non-syndromic type of hereditary hearing loss characterized by varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four subtypes (WS1-WS4) based on additional symptoms. WS2 is characterized by the absence of additional symptoms. Recently, we identified a SOX10 missense mutation c.422T > C (p.L141P) associated with WS2. We performed functional assays and found the mutant loses DNA-binding capacity, shows aberrant cytoplasmic and nuclear localization, and fails to interact with PAX3. Therefore, the mutant cannot transactivate the MITF promoter effectively, inhibiting melanin synthesis and leading to WS2. Our study confirmed haploinsufficiency as the underlying pathogenesis for WS2. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. C. elegans HIM-8 functions outside of meiosis to antagonize EGL-13 Sox protein function.

    Science.gov (United States)

    Nelms, Brian L; Hanna-Rose, Wendy

    2006-05-15

    egl-13 encodes a Sox domain protein that is required for proper uterine seam cell development in Caenorhabditis elegans. We demonstrate that mutations of the C2H2 zinc fingers encoded by the him-8 (high incidence of males) gene partially suppress the egg-laying and connection-of-gonad morphology defects caused by incompletely penetrant alleles of egl-13. him-8 alleles have previously characterized recessive effects on recombination and segregation of the X chromosome during meiosis due to failure of X chromosome homolog pairing and subsequent synapsis. However, we show that him-8 alleles are semi-dominant suppressors of egl-13, and the semi-dominant effect is due to haplo-insufficiency of the him-8 locus. Thus, we conclude that the wild-type him-8 gene product acts antagonistically to EGL-13. Null alleles of egl-13 cannot be suppressed, suggesting that this antagonistic interaction most likely occurs either upstream of or in parallel with EGL-13. Moreover, we conclude that suppression of egl-13 is due to a meiosis-independent function of him-8 because suppression is observed in mutants that have severely reduced meiotic germ cell populations and suppression does not depend on the function of him-8 in the maternal germ line. We also show that the chromosomal context of egl-13 seems important in the him-8 suppression mechanism. Interactions between these genes can give insight into function of Sox family members, which are important in many aspects of metazoan development, and into functions of him-8 outside of meiosis.

  8. Copy number variation of two separate regulatory regions upstream of SOX9 causes isolated 46,XY or 46,XX disorder of sex development.

    Science.gov (United States)

    Kim, Gwang-Jin; Sock, Elisabeth; Buchberger, Astrid; Just, Walter; Denzer, Friederike; Hoepffner, Wolfgang; German, James; Cole, Trevor; Mann, Jillian; Seguin, John H; Zipf, William; Costigan, Colm; Schmiady, Hardi; Rostásy, Moritz; Kramer, Mildred; Kaltenbach, Simon; Rösler, Bernd; Georg, Ina; Troppmann, Elke; Teichmann, Anne-Christin; Salfelder, Anika; Widholz, Sebastian A; Wieacker, Peter; Hiort, Olaf; Camerino, Giovanna; Radi, Orietta; Wegner, Michael; Arnold, Hans-Henning; Scherer, Gerd

    2015-04-01

    SOX9 mutations cause the skeletal malformation syndrome campomelic dysplasia in combination with XY sex reversal. Studies in mice indicate that SOX9 acts as a testis-inducing transcription factor downstream of SRY, triggering Sertoli cell and testis differentiation. An SRY-dependent testis-specific enhancer for Sox9 has been identified only in mice. A previous study has implicated copy number variations (CNVs) of a 78 kb region 517-595 kb upstream of SOX9 in the aetiology of both 46,XY and 46,XX disorders of sex development (DSD). We wanted to better define this region for both disorders. By CNV analysis, we identified SOX9 upstream duplications in three cases of SRY-negative 46,XX DSD, which together with previously reported duplications define a 68 kb region, 516-584 kb upstream of SOX9, designated XXSR (XX sex reversal region). More importantly, we identified heterozygous deletions in four families with SRY-positive 46,XY DSD without skeletal phenotype, which define a 32.5 kb interval 607.1-639.6 kb upstream of SOX9, designated XY sex reversal region (XYSR). To localise the suspected testis-specific enhancer, XYSR subfragments were tested in cell transfection and transgenic experiments. While transgenic experiments remained inconclusive, a 1.9 kb SRY-responsive subfragment drove expression specifically in Sertoli-like cells. Our results indicate that isolated 46,XY and 46,XX DSD can be assigned to two separate regulatory regions, XYSR and XXSR, far upstream of SOX9. The 1.9 kb SRY-responsive subfragment from the XYSR might constitute the core of the Sertoli-cell enhancer of human SOX9, representing the so far missing link in the genetic cascade of male sex determination. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. Neutral atom traps of radioactives

    International Nuclear Information System (INIS)

    Behr, J.A.

    2003-01-01

    Neutral atoms trapped with modern laser cooling techniques offer the promise of improving several broad classes of experiments with radioactive isotopes. In nuclear β decay, neutrino spectroscopy from beta-recoil coincidences, along with highly polarized samples, enable experiments to search for non-Standard Model interactions, test whether parity symmetry is maximally violated, and search for new sources of time reversal violation. Ongoing efforts at TRIUMF, Los Alamos and Berkeley will be highlighted. The traps also offer bright sources for Doppler-free spectroscopy, particularly in high-Z atoms where precision measurements could measure the strength of weak neutral nucleon-nucleon and electron-nucleon interactions. Physics with francium atoms has been vigorously pursued at Stony Brook. Several facilities plan work with radioactive atom traps; concrete plans and efforts at KVI Groningen and Legnaro will be among those summarized. Contributions to the multidisciplinary field of trace analysis will be left up to other presenters

  10. Neutral atom traps of radioactives

    CERN Document Server

    Behr, J A

    2003-01-01

    Neutral atoms trapped with modern laser cooling techniques offer the promise of improving several broad classes of experiments with radioactive isotopes. In nuclear beta decay, neutrino spectroscopy from beta-recoil coincidences, along with highly polarized samples, enable experiments to search for non-Standard Model interactions, test whether parity symmetry is maximally violated, and search for new sources of time reversal violation. Ongoing efforts at TRIUMF, Los Alamos and Berkeley will be highlighted. The traps also offer bright sources for Doppler-free spectroscopy, particularly in high-Z atoms where precision measurements could measure the strength of weak neutral nucleon-nucleon and electron-nucleon interactions. Physics with francium atoms has been vigorously pursued at Stony Brook. Several facilities plan work with radioactive atom traps; concrete plans and efforts at KVI Groningen and Legnaro will be among those summarized. Contributions to the multidisciplinary field of trace analysis will be left...

  11. Quantized motion of trapped ions

    International Nuclear Information System (INIS)

    Steinbach, J.

    1999-01-01

    This thesis is concerned with a theoretical and numerical study of the preparation and coherent manipulation of quantum states in the external and internal degrees of freedom of trapped ions. In its first part, this thesis proposes and investigates schemes for generating several nonclassical states for the quantized vibrational motion of a trapped ion. Based on dark state preparation specific laser excitation configurations are presented which, given appropriately chosen initial states, realize the desired motional states in the steady-state, indicated by the cessation of the fluorescence emitted by the ion. The focus is on the SU(1,1) intelligent states in both their single- and two-mode realization, corresponding to one- and two-dimensional motion of the ion. The presented schemes are also studied numerically using a Monte-Carlo state-vector method. The second part of the thesis describes how two vibrational degrees of freedom of a single trapped ion can be coupled through the action of suitably chosen laser excitation. Concentrating on a two-dimensional ion trap with dissimilar vibrational frequencies a variety of quantized two-mode couplings are derived. The focus is on a linear coupling that takes excitations from one mode to another. It is demonstrated how this can result in a state rotation, in which it is possible to coherently transfer the motional state of the ion between orthogonal directions without prior knowledge of that motional state. The third part of this thesis presents a new efficient method for generating maximally entangled internal states of a collection of trapped ions. The method is deterministic and independent of the number of ions in the trap. As the essential element of the scheme a mechanism for the realization of a controlled NOT operation that can operate on multiple ions is proposed. The potential application of the scheme for high-precision frequency standards is explored. (author)

  12. Open trap with ambipolar mirrors

    International Nuclear Information System (INIS)

    Dimov, G.I.; Zakajdakov, V.V.; Kishinevskij, M.E.

    1977-01-01

    Results of numerical calculations on the behaviour of a thermonuclear plasma, allowing for α-particles in a trap with longitudinal confinement of the main ions by ambipolar electric fields are presented. This trap is formed by connecting two small-volume ''mirrortrons'' to an ordinary open trap. Into the extreme mirrortrons, approximately 1-MeV ions are introduced continuously by ionization of atomic beams on the plasma, and approximately 10-keV ions are similarly introduced into the main central region of the trap. By a suitable choice of injection currents, the plasma density established in the extreme mirrortrons is higher than in the central region. As a result of the quasi-neutrality condition, a longitudinal ambipolar field forming a potential well not only for electrons but also for the central ions is formed in the plasma. When the depth of the well for the central ions is much greater than their temperature, their life-time considerably exceeds the time of confinement by the magnetic mirrors. As a result, the plasma density is constant over the entire length of the central mirrortron, including the regions near the mirrors, and an ambipolar field is formed only in the extreme mirrortrons. The distribution of central ions and ambipolar potential in the extreme mirrortrons is uniquely determined by the density distribution of fast extreme ions. It is shown in the present study that an amplification coefficient Q as high as desired can, in principle, be reached in the trap under consideration, allowing for α-particles. However, this requires high magnetic fields in the mirrors and a sufficient length of the central mirrotron. It is shown that for moderate values of Q=3-8, it is desirable not to confine the central fast α-particles. To achieve a coefficient of Q=5, it is necessary to create fields of 250 kG in the mirrors, and the length of the trap must not be greater than 100 m. (author)

  13. Inhibition of SOX2 induces cell apoptosis and G1/S arrest in Ewing's sarcoma through the PI3K/Akt pathway.

    Science.gov (United States)

    Ren, Chongmin; Ren, Tingting; Yang, Kang; Wang, Shidong; Bao, Xing; Zhang, Fan; Guo, Wei

    2016-03-11

    Ewing's sarcoma is an aggressive bone and soft tissue tumor with a high incidence in children and adolescents. Due to its high malignancy and poor prognosis, identification of novel biomarkers for intervention therapies is necessary to improve outcome. The EWS/FLI1 fusion gene is a characteristic of Ewing's sarcoma in most cases. Sex determining region Y-box 2 (SOX2) is a primary target of EWS/FLI1. It has been identified as an oncogene and linked to apoptotic resistance in several types of cancer. However, its role and regulatory mechanisms in Ewing's sarcoma are largely unknown. We systematically investigated the role of SOX2 in Ewing's sarcoma cell lines, human tissue samples and xenograft models. The expression of SOX2 was detected in Ewing's sarcoma samples by WB and IHC. siRNAs were used to knockdown EWS/FLI1 and SOX2 in A673 and RD-ES cell lines with the efficiencies tested by qRT-PCR and WB. The effect of SOX2 on cell cycle and apoptosis was determined by Flow cytometric and TUNEL assays. Akt overexpression was performed with plasmid. The protein expression of the corresponding factors was examined by WB analysis. Inhibition of SOX2 in vivo was performed by siRNA against SOX2 in xenograft models, and the protein expression of the regulators testified in vitro was examined in xenograft tumors by IHC and WB. The results confirmed that SOX2 was highly expressed in Ewing's sarcoma and was the target of EWS/FLI1. SOX2 advanced Ewing's sarcoma cell survival and proliferation by regulating p21, p27 and cyclin-E to facilitate G1/S phase transition and mediating caspase-3, PARP via both extrinsic (Fas and caspase-8) and intrinsic (caspase-9, Bad, Bcl-2 and XIAP) apoptotic pathways to restrain cell apoptosis. Additionally, SOX2 regulated the cell-cycle progression and apoptosis via activation of the PI3K/Akt signaling pathway. The mechanisms were proved both in vitro and in vivo. The results demonstrate that SOX2 played a central role in promoting Ewing's sarcoma

  14. Efficacy of female attractant trapping systems for medfly for use in suppression programmes

    International Nuclear Information System (INIS)

    Seewooruthun, S.I.; Permalloo, S.; Sookar, P.

    1999-01-01

    Several species of fruit flies cause serious losses to fleshy fruits in Mauritius. Due to fruit production being confined mainly to backyard gardens, traditional methods of control do not give satisfactory results. Full cover sprays with chemicals also pose potential environmental and health risks. Alternative control methods were developed and an area-wide control programme was conceived, using bait application to bring down fruit fly population, followed by intensive trapping of males, using pheromones, to keep the population at low levels. An effective attractant system for mass trapping of females integrated into the wide area programme would greatly enhance control. The use of synthetic food-based attractants for trapping Ceratitis capitata and other fruit fly species was investigated in two phases and compared with different trapping systems. In the Phase III experiments, a two component lure, ammonium acetate + putrescine (FA-2) and a three component lure, ammonium acetate + putrescine + trimethylamine (FA-3) were tested in different traps and compared with standard liquid protein-baited International Pheromone's McPhail Trap (IPMT). Frutect trap, Tephri-trap and Jackson trap with Trimedlure were also used. The medfly female catch with the FA-3 lure used in the Open Bottom Dry Trap outnumbered the catches in other traps. In Phase IV, the final year of the trial, the FA-3 lure was tested in wet and dry IPMT and Tephri traps. These were compared with IPMT containing NuLure + borax (NU+B) as standard and with locally developed traps. The FA-3 lure gave the highest catches of female medflies in the IPMT with water as retaining device followed by IPMT with DDVP, although catches were not significantly different from IPMT with NU+B. (author)

  15. Ion trap architectures and new directions

    Science.gov (United States)

    Siverns, James D.; Quraishi, Qudsia

    2017-12-01

    Trapped ion technology has seen advances in performance, robustness and versatility over the last decade. With increasing numbers of trapped ion groups worldwide, a myriad of trap architectures are currently in use. Applications of trapped ions include: quantum simulation, computing and networking, time standards and fundamental studies in quantum dynamics. Design of such traps is driven by these various research aims, but some universally desirable properties have lead to the development of ion trap foundries. Additionally, the excellent control achievable with trapped ions and the ability to do photonic readout has allowed progress on quantum networking using entanglement between remotely situated ion-based nodes. Here, we present a selection of trap architectures currently in use by the community and present their most salient characteristics, identifying features particularly suited for quantum networking. We also discuss our own in-house research efforts aimed at long-distance trapped ion networking.

  16. Artificial covering on trap nests improves the colonization of trap-nesting wasps

    OpenAIRE

    Taki, Hisatomo; Kevan, Peter G.; Viana, Blandina Felipe; Silva, Fabiana O.; Buck, Matthias

    2008-01-01

    Acesso restrito: Texto completo. p. 225-229 To evaluate the role that a trap-nest cover might have on sampling methodologies, the abundance of each species of trap-nesting Hymenoptera and the parasitism rate in a Canadian forest were compared between artificially covered and uncovered traps. Of trap tubes exposed at eight forest sites in six trap-nest boxes, 531 trap tubes were occupied and 1216 individuals of 12 wasp species of four predatory families, Vespidae (Eumeninae), Crabronidae...

  17. Microfabricated linear Paul-Straubel ion trap

    Science.gov (United States)

    Mangan, Michael A [Albuquerque, NM; Blain, Matthew G [Albuquerque, NM; Tigges, Chris P [Albuquerque, NM; Linker, Kevin L [Albuquerque, NM

    2011-04-19

    An array of microfabricated linear Paul-Straubel ion traps can be used for mass spectrometric applications. Each ion trap comprises two parallel inner RF electrodes and two parallel outer DC control electrodes symmetric about a central trap axis and suspended over an opening in a substrate. Neighboring ion traps in the array can share a common outer DC control electrode. The ions confined transversely by an RF quadrupole electric field potential well on the ion trap axis. The array can trap a wide array of ions.

  18. Asymmetric Penning trap coherent states

    International Nuclear Information System (INIS)

    Contreras-Astorga, Alonso; Fernandez, David J.

    2010-01-01

    By using a matrix technique, which allows to identify directly the ladder operators, the coherent states of the asymmetric Penning trap are derived as eigenstates of the appropriate annihilation operators. They are compared with those obtained through the displacement operator method.

  19. Indeterminacy, sunspots, and development traps

    Czech Academy of Sciences Publication Activity Database

    Slobodyan, Sergey

    2005-01-01

    Roč. 29, 1-2 (2005), s. 159-185 ISSN 0165-1889 Institutional research plan: CEZ:AV0Z70850503 Keywords : indeterminacy * development trap * stochastic stability Subject RIV: AH - Economics Impact factor: 0.691, year: 2005 http://dx.doi.org/10.1016/j.jedc.2003.04.011

  20. Efficiency of subaquatic light traps

    Czech Academy of Sciences Publication Activity Database

    Ditrich, Tomáš; Čihák, P.

    2017-01-01

    Roč. 38, č. 3 (2017), s. 171-184 ISSN 0165-0424 R&D Projects: GA ČR(CZ) GA14-29857S Institutional support: RVO:60077344 Keywords : Heteroptera * Diptera * light trap Subject RIV: EH - Ecology, Behaviour OBOR OECD: Ecology Impact factor: 0.524, year: 2016

  1. The rise of trapped populations

    Directory of Open Access Journals (Sweden)

    April T Humble

    2014-02-01

    Full Text Available As border security increases and borders become less permeable, cross-border migration is becoming increasingly difficult, selective and dangerous. Growing numbers of people are becoming trapped in their own countries or in transit countries, or being forced to roam border areas, unable to access legal protection or basic social necessities.

  2. Magnetic trapping of Rydberg atoms

    NARCIS (Netherlands)

    Niestadt, D.; Naber, J.; Kokkelmans, S.J.J.M.F.; Spreeuw, R.J.C.

    2016-01-01

    Magnetic trapping is a well-established technique for ground state atoms. We seek to extend this concept to Rydberg atoms. Rydberg atoms are important for current visions of quantum simulators that will be used in the near future to simulate and analyse quantum problems. Current efforts in Amsterdam

  3. Quantum computing with trapped ions

    International Nuclear Information System (INIS)

    Haeffner, H.; Roos, C.F.; Blatt, R.

    2008-01-01

    Quantum computers hold the promise of solving certain computational tasks much more efficiently than classical computers. We review recent experimental advances towards a quantum computer with trapped ions. In particular, various implementations of qubits, quantum gates and some key experiments are discussed. Furthermore, we review some implementations of quantum algorithms such as a deterministic teleportation of quantum information and an error correction scheme

  4. 22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.

    Science.gov (United States)

    Falah, Nadia; Posey, Jennifer E; Thorson, Willa; Benke, Paul; Tekin, Mustafa; Tarshish, Brocha; Lupski, James R; Harel, Tamar

    2017-04-01

    Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather than dominant negative activity underlies PCWH. © 2017 Wiley Periodicals, Inc.

  5. 50 CFR 697.19 - Trap limits and trap tag requirements for vessels fishing with lobster traps.

    Science.gov (United States)

    2010-10-01

    ... vessels fishing with lobster traps. 697.19 Section 697.19 Wildlife and Fisheries FISHERY CONSERVATION AND... requirements for vessels fishing with lobster traps. (a) Trap limits for vessels fishing or authorized to fish... management area designation certificate or valid limited access American lobster permit specifying one or...

  6. SOX2 expression is associated with a cancer stem cell state and down-regulation of CDX2 in colorectal cancer

    International Nuclear Information System (INIS)

    Lundberg, Ida V.; Edin, Sofia; Eklöf, Vincy; Öberg, Åke; Palmqvist, Richard; Wikberg, Maria L.

    2016-01-01

    To improve current treatment strategies for patients with aggressive colorectal cancer (CRC), the molecular understanding of subgroups of CRC with poor prognosis is of vast importance. SOX2 positive tumors have been associated with a poor patient outcome, but the functional role of SOX2 in CRC patient prognosis is still unclear. An in vitro cell culture model expressing SOX2 was used to investigate the functional role of SOX2 in CRC. In vitro findings were verified using RNA from fresh frozen tumor tissue or immunohistochemistry on formalin fixed paraffin embedded (FFPE) tumor tissue from a cohort of 445 CRC patients. Using our in vitro model, we found that SOX2 expressing cells displayed several characteristics of cancer stem cells; such as a decreased proliferative rate, a spheroid growth pattern, and increased expression of stem cell markers CD24 and CD44. Cells expressing SOX2 also showed down-regulated expression of the intestinal epithelial marker CDX2. We next evaluated CDX2 expression in our patient cohort. CDX2 down-regulation was more often found in right sided tumors of high grade and high stage. Furthermore, a decreased expression of CDX2 was closely linked to MSI, CIMP-high as well as BRAF mutated tumors. A decreased expression of CDX2 was also, in a stepwise manner, strongly correlated to a poor patient prognosis. When looking at SOX2 expression in relation to CDX2, we found that SOX2 expressing tumors more often displayed a down-regulated expression of CDX2. In addition, SOX2 expressing tumors with a down-regulated CDX2 expression had a worse patient prognosis compared to those with retained CDX2 expression. Our results indicate that SOX2 expression induces a cellular stem cell state in human CRC with a decreased expression of CDX2. Furthermore, a down-regulated expression of CDX2 results in a poor patient prognosis in CRC and at least part of the prognostic importance of SOX2 is mediated through CDX2 down-regulation. The online version of this

  7. Scaling ion traps for quantum computing

    CSIR Research Space (South Africa)

    Uys, H

    2010-09-01

    Full Text Available The design, fabrication and preliminary testing of a chipscale, multi-zone, surface electrode ion trap is reported. The modular design and fabrication techniques used are anticipated to advance scalability of ion trap quantum computing architectures...

  8. Servo control of an optical trap.

    Science.gov (United States)

    Wulff, Kurt D; Cole, Daniel G; Clark, Robert L

    2007-08-01

    A versatile optical trap has been constructed to control the position of trapped objects and ultimately to apply specified forces using feedback control. While the design, development, and use of optical traps has been extensive and feedback control has played a critical role in pushing the state of the art, few comprehensive examinations of feedback control of optical traps have been undertaken. Furthermore, as the requirements are pushed to ever smaller distances and forces, the performance of optical traps reaches limits. It is well understood that feedback control can result in both positive and negative effects in controlled systems. We give an analysis of the trapping limits as well as introducing an optical trap with a feedback control scheme that dramatically improves an optical trap's sensitivity at low frequencies.

  9. MiR-129-5p Inhibits Proliferation and Invasion of Chondrosarcoma Cells by Regulating SOX4/Wnt/β-Catenin Signaling Pathway.

    Science.gov (United States)

    Zhang, Peng; Li, Jifeng; Song, Yuze; Wang, Xiao

    2017-01-01

    Recently, microRNAs (miRNA) have been identified as novel regulators in Chondrosarcoma (CHS). This study was aimed to identify the roles of miR-129-5p-5p in regulation of SOX4 and Wnt/β-catenin signaling pathway, as well as cell proliferation and apoptosis in chondrosarcomas. Tissue samples were obtained from chondrosarcoma patients. Immunohistochemistry, real-time quantitative RT-PCR (RT-qPCR) and western blot analysis were performed to detect the expressions of miR-129-5p and SOX4. Luciferase assay was conducted to confirm that miR-129-5p directly targeted SOX4 mRNA. Manipulations of miR-129-5p and SOX4 expression were achieved through cell transfection. Cell proliferation, migration and apoptosis were evaluated by CCK-8 assay, colony forming assay, wound healing assay and flow cytometry in vitro. For in vivo experiment, the tumor xenograft model was established to evaluate the effects of miR-129-5p and SOX4 on chondrosarcomas. The expression of miR-129-5p was significantly down-regulated in chondrosarcoma tissues as well as cells in comparison with normal ones, while SOX4 was over-activated. Further studies suggested that miR-129-5p suppressed cell proliferation, migration and promoted apoptosis by inhibiting SOX4 and Wnt/β-catenin pathway. MiR-129-5p inhibits the Wnt/β-catenin signaling pathway by targeting SOX4 and further suppresses cell proliferation, migration and promotes apoptosis in chondrosarcomas. © 2017 The Author(s). Published by S. Karger AG, Basel.

  10. SOX9 regulates microRNA miR-202-5p/3p expression during mouse testis differentiation

    DEFF Research Database (Denmark)

    Wainwright, Elanor N; Jorgensen, Joan S; Kim, Youngha

    2013-01-01

    MicroRNAs are important regulators of developmental gene expression, but their contribution to fetal gonad development is not well understood. We have identified the evolutionarily conserved gonadal microRNAs miR-202-5p and miR-202-3p as having a potential role in regulating mouse embryonic gonad....... Expression of the primary transcript of miR-202-5p/3p remained low in XY gonads in a conditional Sox9-null mouse model, suggesting that pri-miR-202 transcription is downstream of SOX9, a transcription factor that is both necessary and sufficient for male sex determination. We identified the pri-miR-202...

  11. Two-baffle trap for macroparticles

    International Nuclear Information System (INIS)

    Aksyonov, D.S.

    2014-01-01

    In this work, properties of two-baffle macroparticle traps were investigated. These properties are needed for designing and optimization of vacuum arc plasma filters. The dependencies between trap geometry parameters and its ability to absorb macroparticles were found. Calculations made allow one to predict the behaviour of filtering abilities of separators containing such traps in their design. Recommendations regarding the use of two-baffle traps in filters of different builds are given

  12. A rare case of 46, XX SRY-negative male with approximately 74-kb duplication in a region upstream of SOX9.

    Science.gov (United States)

    Xiao, Bing; Ji, Xing; Xing, Ya; Chen, Ying-Wei; Tao, Jiong

    2013-12-01

    The 46, XX male disorder of sex development (DSD) is a rare genetic condition. Here, we report the case of a 46, XX SRY-negative male with complete masculinization. The coding region and exon/intron boundaries of the DAX1, SOX9 and RSPO1 genes were sequenced, and no mutations were detected. Using whole genome array analysis and real-time PCR, we identified a approximately 74-kb duplication in a region approximately 510-584 kb upstream of SOX9 (chr17:69,533,305-69,606,825, hg19). Combined with the results of previous studies, the minimum critical region associated with gonadal development is a 67-kb region located 584-517 kb upstream of SOX9. The amplification of this region might lead to SOX9 overexpression, causing female-to-male sex reversal. Gonadal-specific enhancers in the region upstream of SOX9 may activate the SOX9 expression through long-range regulation, thus triggering testicular differentiation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  13. DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors.

    Science.gov (United States)

    Narasimhan, Kamesh; Pillay, Shubhadra; Huang, Yong-Heng; Jayabal, Sriram; Udayasuryan, Barath; Veerapandian, Veeramohan; Kolatkar, Prasanna; Cojocaru, Vlad; Pervushin, Konstantin; Jauch, Ralf

    2015-02-18

    Sox2 and Pax6 are transcription factors that direct cell fate decision during neurogenesis, yet the mechanism behind how they cooperate on enhancer DNA elements and regulate gene expression is unclear. By systematically interrogating Sox2 and Pax6 interaction on minimal enhancer elements, we found that cooperative DNA recognition relies on combinatorial nucleotide switches and precisely spaced, but cryptic composite DNA motifs. Surprisingly, all tested Sox and Pax paralogs have the capacity to cooperate on such enhancer elements. NMR and molecular modeling reveal very few direct protein-protein interactions between Sox2 and Pax6, suggesting that cooperative binding is mediated by allosteric interactions propagating through DNA structure. Furthermore, we detected and validated several novel sites in the human genome targeted cooperatively by Sox2 and Pax6. Collectively, we demonstrate that Sox-Pax partnerships have the potential to substantially alter DNA target specificities and likely enable the pleiotropic and context-specific action of these cell-lineage specifiers. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. The crystal structure of the Sox4 HMG domain-DNA complex suggests a mechanism for positional interdependence in DNA recognition.

    Science.gov (United States)

    Jauch, Ralf; Ng, Calista K L; Narasimhan, Kamesh; Kolatkar, Prasanna R

    2012-04-01

    It has recently been proposed that the sequence preferences of DNA-binding TFs (transcription factors) can be well described by models that include the positional interdependence of the nucleotides of the target sites. Such binding models allow for multiple motifs to be invoked, such as principal and secondary motifs differing at two or more nucleotide positions. However, the structural mechanisms underlying the accommodation of such variant motifs by TFs remain elusive. In the present study we examine the crystal structure of the HMG (high-mobility group) domain of Sox4 [Sry (sex-determining region on the Y chromosome)-related HMG box 4] bound to DNA. By comparing this structure with previously solved structures of Sox17 and Sox2, we observed subtle conformational differences at the DNA-binding interface. Furthermore, using quantitative electrophoretic mobility-shift assays we validated the positional interdependence of two nucleotides and the presence of a secondary Sox motif in the affinity landscape of Sox4. These results suggest that a concerted rearrangement of two interface amino acids enables Sox4 to accommodate primary and secondary motifs. The structural adaptations lead to altered dinucleotide preferences that mutually reinforce each other. These analyses underline the complexity of the DNA recognition by TFs and provide an experimental validation for the conceptual framework of positional interdependence and secondary binding motifs.

  15. SOX2 and OCT4 mRNA-expressing cells, detected by molecular beacons, localize to the center of neurospheres during differentiation.

    Directory of Open Access Journals (Sweden)

    Mirolyuba Ilieva

    Full Text Available Neurospheres are used as in vitro assay to measure the properties of neural stem cells. To investigate the molecular and phenotypic heterogeneity of neurospheres, molecular beacons (MBs targeted against the stem cell markers OCT4 and SOX2 were designed, and synthesized with a 2'-O-methyl RNA backbone. OCT4 and SOX2 MBs were transfected into human embryonic mesencephalon derived cells, which spontaneously form neurospheres when grown on poly-L-ornitine/fibronectin matrix and medium complemented with bFGF. OCT4 and SOX2 gene expression were tracked in individual cell using the MBs. Quantitative image analysis every day for seven days showed that the OCT4 and SOX2 mRNA-expressing cells clustered in the centre of the neurospheres cultured in differentiation medium. By contrast, cells at the periphery of the differentiating spheres developed neurite outgrowths and expressed the tyrosine hydroxylase protein, indicating terminal differentiation. Neurospheres cultured in growth medium contained OCT4 and SOX2-positive cells distributed throughout the entire sphere, and no differentiating neurones. Gene expression of SOX2 and OCT4 mRNA detected by MBs correlated well with gene and protein expression measured by qRT-PCR and immunostaining, respectively. These experimental data support the theoretical model that stem cells cluster in the centre of neurospheres, and demonstrate the use of MBs for the spatial localization of specific gene-expressing cells within heterogeneous cell populations.

  16. Importance of Sox2 in maintenance of cell proliferation and multipotency of mesenchymal stem cells in low-density culture.

    Science.gov (United States)

    Yoon, D S; Kim, Y H; Jung, H S; Paik, S; Lee, J W

    2011-10-01

    This study has aimed to repopulate 'primitive' cells from late-passage mesenchymal stem cells (MSCs) of poor multipotentiality and low cell proliferation rate, by simply altering plating density. Effects of low density culture compared t high density culture on late-passage bone marrow (BM)-derived MSCs and pluripotency markers of multipotentiality were investigated. Cell proliferation, gene expression, RNA interference and differentiation potential were assayed. We repopulated 'primitive' cells by replating late-passage MSCs at low density (17 cells/cm(2) ) regardless of donor age. Repopulated MSCs from low-density culture were smaller cells with spindle shaped morphology compared to MSCs from high-density culture. The latter had enhanced colony-forming ability, proliferation rate, and adipogenic and chondrogenic potential. Strong expression of osteogenic-related genes (Cbfa1, Dlx5, alkaline phosphatase and type Ι collagen) in late-passage MSCs was reduced by replating at low density, whereas expression of three pluripotency markers (Sox2, Nanog and Oct-4), Osterix and Msx2 reverted to levels of early-passage MSCs. Knockdown of Sox2 and Msx2 but not Nanog, using RNA interference, showed significant decrease in colony-forming ability. Specifically, knockdown of Sox2 significantly inhibited multipotentiality and cell proliferation. Our data suggest that plating density should be considered to be a critical factor for enrichment of 'primitive' cells from heterogeneous BM and that replicative senescence and multipotentiality of MSCs during in vitro expansion may be predominantly regulated through Sox2. © 2011 Blackwell Publishing Ltd.

  17. Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells

    OpenAIRE

    Zhang, Xiaowei; Wu, Shili; Naccarato, Ty; Prakash-Damani, Manan; Chou, Yuan; Chu, Cong-Qiu; Zhu, Yong

    2017-01-01

    Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC) to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9) is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrat...

  18. Cavity sideband cooling of trapped molecules

    NARCIS (Netherlands)

    Kowalewski, Markus; Morigi, Giovanna; Pinkse, Pepijn Willemszoon Harry; de Vivie-Riedle, Regina

    2011-01-01

    The efficiency of cavity sideband cooling of trapped molecules is theoretically investigated for the case in which the infrared transition between two rovibrational states is used as a cycling transition. The molecules are assumed to be trapped either by a radiofrequency or optical trapping

  19. An Open Standard for Camera Trap Data

    NARCIS (Netherlands)

    Forrester, Tavis; O'Brien, Tim; Fegraus, Eric; Jansen, P.A.; Palmer, Jonathan; Kays, Roland; Ahumada, Jorge; Stern, Beth; McShea, William

    2016-01-01

    Camera traps that capture photos of animals are a valuable tool for monitoring biodiversity. The use of camera traps is rapidly increasing and there is an urgent need for standardization to facilitate data management, reporting and data sharing. Here we offer the Camera Trap Metadata Standard as an

  20. Keep your Sox on: Community genomics-directed isolation and microscopic characterization of the dominant subsurface sulfur-oxidizing bacterium in a sediment aquifer

    Science.gov (United States)

    Mullin, S. W.; Wrighton, K. C.; Luef, B.; Wilkins, M. J.; Handley, K. M.; Williams, K. H.; Banfield, J. F.

    2012-12-01

    Community genomics and proteomics (proteogenomics) can be used to predict the metabolic potential of complex microbial communities and provide insight into microbial activity and nutrient cycling in situ. Inferences regarding the physiology of specific organisms then can guide isolation efforts, which, if successful, can yield strains that can be metabolically and structurally characterized to further test metagenomic predictions. Here we used proteogenomic data from an acetate-stimulated, sulfidic sediment column deployed in a groundwater well in Rifle, CO to direct laboratory amendment experiments to isolate a bacterial strain potentially involved in sulfur oxidation for physiological and microscopic characterization (Handley et al, submitted 2012). Field strains of Sulfurovum (genome r9c2) were predicted to be capable of CO2 fixation via the reverse TCA cycle and sulfur oxidation (Sox and SQR) coupled to either nitrate reduction (Nap, Nir, Nos) in anaerobic environments or oxygen reduction in microaerobic (cbb3 and bd oxidases) environments; however, key genes for sulfur oxidation (soxXAB) were not identified. Sulfidic groundwater and sediment from the Rifle site were used to inoculate cultures that contained various sulfur species, with and without nitrate and oxygen. We isolated a bacterium, Sulfurovum sp. OBA, whose 16S rRNA gene shares 99.8 % identity to the gene of the dominant genomically characterized strain (genome r9c2) in the Rifle sediment column. The 16S rRNA gene of the isolate most closely matches (95 % sequence identity) the gene of Sulfurovum sp. NBC37-1, a genome-sequenced deep-sea sulfur oxidizer. Strain OBA grew via polysulfide, colloidal sulfur, and tetrathionate oxidation coupled to nitrate reduction under autotrophic and mixotrophic conditions. Strain OBA also grew heterotrophically, oxidizing glucose, fructose, mannose, and maltose with nitrate as an electron acceptor. Over the range of oxygen concentrations tested, strain OBA was not

  1. Influence of trap location on the efficiency of trapping in dendrimers and regular hyperbranched polymers.

    Science.gov (United States)

    Lin, Yuan; Zhang, Zhongzhi

    2013-03-07

    The trapping process in polymer systems constitutes a fundamental mechanism for various other dynamical processes taking place in these systems. In this paper, we study the trapping problem in two representative polymer networks, Cayley trees and Vicsek fractals, which separately model dendrimers and regular hyperbranched polymers. Our goal is to explore the impact of trap location on the efficiency of trapping in these two important polymer systems, with the efficiency being measured by the average trapping time (ATT) that is the average of source-to-trap mean first-passage time over every staring point in the whole networks. For Cayley trees, we derive an exact analytic formula for the ATT to an arbitrary trap node, based on which we further obtain the explicit expression of ATT for the case that the trap is uniformly distributed. For Vicsek fractals, we provide the closed-form solution for ATT to a peripheral node farthest from the central node, as well as the numerical solutions for the case when the trap is placed on other nodes. Moreover, we derive the exact formula for the ATT corresponding to the trapping problem when the trap has a uniform distribution over all nodes. Our results show that the influence of trap location on the trapping efficiency is completely different for the two polymer networks. In Cayley trees, the leading scaling of ATT increases with the shortest distance between the trap and the central node, implying that trap's position has an essential impact on the trapping efficiency; while in Vicsek fractals, the effect of location of the trap is negligible, since the dominant behavior of ATT is identical, respective of the location where the trap is placed. We also present that for all cases of trapping problems being studied, the trapping process is more efficient in Cayley trees than in Vicsek fractals. We demonstrate that all differences related to trapping in the two polymer systems are rooted in their underlying topological structures.

  2. Identification of a de novo mutation of SOX10 in a Chinese patient with Waardenburg syndrome type IV.

    Science.gov (United States)

    Liang, Fenghe; Zhao, Min; Fan, Lynn; Zhang, Hongyan; Shi, Yang; Han, Rui; Qu, Chunyan

    2016-12-01

    Waardenburg syndrome is a rare genetic disorder, characterized by the association of sensorineural hearing loss and pigmentation abnormalities. Four subtypes have been classified. The present study aimed to analyze the clinical feature and investigate the genetic cause for a Chinese case of Waardenburg type IV (WS4). The patient and his family members were subjected to mutation detection in the candidate gene SOX10 by Sanger sequencing. The patient has the clinical features of WS4, including sensorineural hearing loss, bright blue irides, premature graying of the hair and Hirschsprung disease. A novel heterozygous frameshift mutation, c.752_753ins7 (p.Gly252Alafs*31) in the exon 5 of SOX10 was detected in the patient, but not found in the unaffected family members and 100 normal controls. This mutation results in a premature stop codon 31 amino acid downstream. The novel mutation c.752_753ins7 (p.Gly252Alafs*31) arose de novo and was considered as the cause of WS4 in the proband. This study further characterized the molecular complexity of WS4 and provided a clinical case for genotype-phenotype correlation studies of different phenotypes caused by SOX10 mutations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Waardenburg syndrome type II in a Chinese patient caused by a novel nonsense mutation in the SOX10 gene.

    Science.gov (United States)

    Ma, Jing; Zhang, Tie-Song; Lin, Ken; Sun, Hao; Jiang, Hong-Chao; Yang, Yan-Li; Low, Fan; Gao, Ying-Qin; Ruan, Biao

    2016-06-01

    Waardenburg syndrome is a congenital genetic disorder. It is the most common type of syndromic hearing impairment with highly genetic heterogeneity and proved to be related by 6 genes as follows: PAX3, MITF, SNAI2, EDN3, EDNRB and SOX10. This article aims to identify the genetic causes of a Chinese WS child patient. A Chinese WS child was collected for clinical data collection by questionnaire survey. DNA samples of proband and his parents were extracted from peripheral blood samples. Six candidate genes were sequenced by the Trusight One sequencing panel on the illumina NextSeq 500 platform. A novel nonsense heterozygous mutation was found in the coding region of exon 2 in the SOX10 gene of proband. The novel nonsense heterozygous mutation could cause the replacement of the 55th lysine codon by stop codon (484T > C, C142R) and further more possibly cause terminating the protein translation in advance. However, both proband's parents had no mutation of genes above mentioned. The gene mutation of SOX10 [NM_006941.3 c.163A > T] is a novel nonsense mutation. No record of this mutation has been found in dbSNP, HGMD, 1000 Genomes Project, ClinVar and ESP6500 databases. It meets the condition of PS2 of strong evidence in 2015 ACMG Standards and Guidelines. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. A de novo deletion mutation in SOX10 in a Chinese family with Waardenburg syndrome type 4.

    Science.gov (United States)

    Wang, Xiong; Zhu, Yaowu; Shen, Na; Peng, Jing; Wang, Chunyu; Liu, Haiyi; Lu, Yanjun

    2017-01-27

    Waardenburg syndrome type 4 (WS4) or Waardenburg-Shah syndrome is a rare genetic disorder with a prevalence of <1/1,000,000 and characterized by the association of congenital sensorineural hearing loss, pigmentary abnormalities, and intestinal aganglionosis. There are three types of WS4 (WS4A-C) caused by mutations in endothelin receptor type B, endothelin 3, and SRY-box 10 (SOX10), respectively. This study investigated a genetic mutation in a Chinese family with one WS4 patient in order to improve genetic counselling. Genomic DNA was extracted, and mutation analysis of the three WS4 related genes was performed using Sanger sequencing. We detected a de novo heterozygous deletion mutation [c.1333delT (p.Ser445Glnfs*57)] in SOX10 in the patient; however, this mutation was absent in the unaffected parents and 40 ethnicity matched healthy controls. Subsequent phylogenetic analysis and three-dimensional modelling of the SOX10 protein confirmed that the c.1333delT heterozygous mutation was pathogenic, indicating that this mutation might constitute a candidate disease-causing mutation.

  5. ER stress inducer tunicamycin suppresses the self-renewal of glioma-initiating cell partly through inhibiting Sox2 translation.

    Science.gov (United States)

    Xing, Yang; Ge, Yuqing; Liu, Chanjuan; Zhang, Xiaobiao; Jiang, Jianhai; Wei, Yuanyan

    2016-06-14

    Glioma-initiating cells possess tumor-initiating potential and are relatively resistant to conventional chemotherapy and irradiation. Therefore, their elimination is an essential factor for the development of efficient therapy. Here, we report that endoplasmic reticulum (ER) stress inducer tunicamycin inhibits glioma-initiating cell self-renewal as determined by neurosphere formation assay. Moreover, tunicamycin decreases the efficiency of glioma-initiating cell to initiate tumor formation. Although tunicamycin induces glioma-initiating cell apoptosis, apoptosis inhibitor z-VAD-fmk only partly abrogates the reduction in glioma-initiating cell self-renewal induced by tunicamycin. Indeed, tunicamycin reduces the expression of self-renewal regulator Sox2 at translation level. Overexpression of Sox2 obviously abrogates the reduction in glioma-initiating cell self-renewal induced by tunicamycin. Taken together, tunicamycin suppresses the self-renewal and tumorigenic potential of glioma-initiating cell partly through reducing Sox2 translation. This finding provides a cue to potential effective treatment of glioblastoma through controlling stem cells.

  6. Clinical and molecular characterization of a Brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations

    Directory of Open Access Journals (Sweden)

    Eduardo P. Mattos

    2015-03-01

    Full Text Available Campomelic dysplasia (CD is an autosomal, dominantly inherited, skeletal abnormality belonging to the subgroup of bent bone dysplasias. In addition to bowed lower limbs, CD typically includes the following: disproportionate short stature, flat face, micrognathia, cleft palate, bell-shaped thorax, and club feet. Up to three quarters of 46, XY individuals may be sex-reversed. Radiological signs include scapular and pubic hypoplasia, narrow iliac wings, spaced ischia, and bowed femora and tibiae. Lethal CD is usually due to heterozygous mutations in SOX9, a major regulator of chondrocytic development. We present a detailed clinical and molecular characterization of nine Brazilian CD patients. Infants were either stillborn (n = 2 or died shortly after birth and presented similar phenotypes. Sex-reversal was observed in one of three chromosomally male patients. Sequencing of SOX9 revealed new heterozygous mutations in seven individuals. Six patients had mutations that resulted in premature transcriptional termination, while one infant had a single-nucleotide substitution at the conserved splice-site acceptor of intron 1. No clear genotype-phenotype correlations were observed. This study highlights the diversity of SOX9 mutations leading to lethal CD, and expands the group of known genetic alterations associated with this skeletal dysplasia.

  7. Fundamental physics in particle traps

    International Nuclear Information System (INIS)

    Quint, Wolfgang; Vogel, Manuel

    2014-01-01

    The individual topics are covered by leading experts in the respective fields of research. Provides readers with present theory and experiments in this field. A useful reference for researchers. This volume provides detailed insight into the field of precision spectroscopy and fundamental physics with particles confined in traps. It comprises experiments with electrons and positrons, protons and antiprotons, antimatter and highly charged ions, together with corresponding theoretical background. Such investigations represent stringent tests of quantum electrodynamics and the Standard model, antiparticle and antimatter research, test of fundamental symmetries, constants, and their possible variations with time and space. They are key to various aspects within metrology such as mass measurements and time standards, as well as promising to further developments in quantum information processing. The reader obtains a valuable source of information suited for beginners and experts with an interest in fundamental studies using particle traps.

  8. Trapping and spectroscopy of hydrogen

    International Nuclear Information System (INIS)

    Cesar, Claudio Lenz

    1997-01-01

    I review the results and techniques used by the MIT H↑ group to achieve a fractional resolution of 2 parts in 10 12 in the 1S-2S transition in hydrogen [Cesar, D. Fried, T. Killian, A. Polcyn, J. Sandberg, I.A. Yu, T. Greytak, D. Kleppner and J. Doyle, Two-photon spectroscopy of trapped atomic hydrogen, Phys. Rev. Lett. 77 (1996) 255.] With some improvements, this system should deliver 100 times higher resolution with an improved signal count rate getting us closer to an old advertised goal of a precision of 1 part in 10 18 . While these developments are very important for the proposed test of the CPT theorem through the comparison with anti-hydrogen, some of the techniques used with hydrogen are not applicable to anti-hydrogen and I discuss some difficulties and alternatives for the trapping and spectroscopy of anti-hydrogen

  9. Centrifugal trapping in the magnetotail

    Directory of Open Access Journals (Sweden)

    D. C. Delcourt

    Full Text Available Particles leaving the neutral sheet in the distant magnetotail at times display adiabatic trajectory sequences characterized by an inflection toward the equator and subsequent mirroring in its vicinity. We demonstrate that this low-latitude mirroring results primarily from a centrifugal deceleration due to the fast direction-changing E×B drift. This effect which we refer to as "centrifugal trapping" appears both in guiding centre and full particle treatments. It thus does not directly relate to nonadiabatic motion. However, pitch angle scattering due to nonadiabatic neutral sheet interaction does play a role in reducing the parallel speed of the particles. We show that centrifugal trapping is an important mechanism for the confinement of the slowest (typically below the equatorial E×B drift speed plasma sheet populations to the midplane vicinity.

  10. Centrifugal trapping in the magnetotail

    Directory of Open Access Journals (Sweden)

    D. C. Delcourt

    1995-03-01

    Full Text Available Particles leaving the neutral sheet in the distant magnetotail at times display adiabatic trajectory sequences characterized by an inflection toward the equator and subsequent mirroring in its vicinity. We demonstrate that this low-latitude mirroring results primarily from a centrifugal deceleration due to the fast direction-changing E×B drift. This effect which we refer to as "centrifugal trapping" appears both in guiding centre and full particle treatments. It thus does not directly relate to nonadiabatic motion. However, pitch angle scattering due to nonadiabatic neutral sheet interaction does play a role in reducing the parallel speed of the particles. We show that centrifugal trapping is an important mechanism for the confinement of the slowest (typically below the equatorial E×B drift speed plasma sheet populations to the midplane vicinity.

  11. Vapor trap for liquid metal

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, T

    1968-05-22

    In a pipe system which transfers liquid metal, inert gas (cover gas) is packed above the surface of the liquid metal to prevent oxidization of the liquid. If the metal vapor is contained in such cover gas, the circulating system of the cover gas is blocked due to condensation of liquid metal inside the system. The present invention relates to an improvement in vapor trap to remove the metal vapor from the cover gas. The trap consists of a cylindrical outer body, an inlet nozzle which is deeply inserted inside the outer body and has a number of holes to inject the cove gas into the body, metal mesh or steel wool which covers the exterior of the nozzle and on which the condensation of the metal gas takes place, and a heater wire hich is wound around the nozzle to prevent condensation of the metal vapor at the inner peripheral side of the mesh.

  12. Optical trapping for analytical biotechnology.

    Science.gov (United States)

    Ashok, Praveen C; Dholakia, Kishan

    2012-02-01

    We describe the exciting advances of using optical trapping in the field of analytical biotechnology. This technique has opened up opportunities to manipulate biological particles at the single cell or even at subcellular levels which has allowed an insight into the physical and chemical mechanisms of many biological processes. The ability of this technique to manipulate microparticles and measure pico-Newton forces has found several applications such as understanding the dynamics of biological macromolecules, cell-cell interactions and the micro-rheology of both cells and fluids. Furthermore we may probe and analyse the biological world when combining trapping with analytical techniques such as Raman spectroscopy and imaging. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Lift enhancement by trapped vortex

    Science.gov (United States)

    Rossow, Vernon J.

    1992-01-01

    The viewgraphs and discussion of lift enhancement by trapped vortex are provided. Efforts are continuously being made to find simple ways to convert wings of aircraft from an efficient cruise configuration to one that develops the high lift needed during landing and takeoff. The high-lift configurations studied here consist of conventional airfoils with a trapped vortex over the upper surface. The vortex is trapped by one or two vertical fences that serve as barriers to the oncoming stream and as reflection planes for the vortex and the sink that form a separation bubble on top of the airfoil. Since the full three-dimensional unsteady flow problem over the wing of an aircraft is so complicated that it is hard to get an understanding of the principles that govern the vortex trapping process, the analysis is restricted here to the flow field illustrated in the first slide. It is assumed that the flow field between the two end plates approximates a streamwise strip of the flow over a wing. The flow between the endplates and about the airfoil consists of a spanwise vortex located between the suction orifices in the endplates. The spanwise fence or spoiler located near the nose of the airfoil serves to form a separated flow region and a shear layer. The vorticity in the shear layer is concentrated into the vortex by withdrawal of fluid at the suction orifices. As the strength of the vortex increases with time, it eventually dominates the flow in the separated region so that a shear or vertical layer is no longer shed from the tip of the fence. At that point, the vortex strength is fixed and its location is such that all of the velocity contributions at its center sum to zero thereby making it an equilibrium point for the vortex. The results of a theoretical analysis of such an idealized flow field are described.

  14. C60 as an Atom Trap to Capture Co Adatoms

    DEFF Research Database (Denmark)

    Yang, Peng; Li, Dongzhe; Repain, Vincent

    2015-01-01

    C60 molecules were used to trap Co adatoms and clusters on a Au(111) surface using atomic/molecular manipulation with a scanning tunneling microscope. Two manipulation pathways (successive integration of single Co atoms in one molecule or direct integration of a Co cluster) were found...... to efficiently allow the formation of complexes mixing a C60 molecule with Co atoms. Scanning tunneling spectroscopy reveals the robustness of the pi states of C60 that are preserved after Co trapping. Scanning tunneling microscopy images and density functional theory calculations reveal that dissociated Co...... clusters of up to nine atoms can be formed at the molecule-substrate interface. These results open new perspectives in the interactions between metal adatoms and molecules, for applications in metal-organic devices...

  15. Antihydrogen Formation, Dynamics and Trapping

    CERN Document Server

    Butler, Eoin; Charlton, Michael

    2011-01-01

    Antihydrogen, the simplest pure-antimatter atomic system, holds the promise of direct tests of matter-antimatter equivalence and CPT invariance, two of the outstanding unanswered questions in modern physics. Antihydrogen is now routinely produced in charged-particle traps through the combination of plasmas of antiprotons and positrons, but the atoms escape and are destroyed in a minuscule fraction of a second. The focus of this work is the production of a sample of cold antihydrogen atoms in a magnetic atom trap. This poses an extreme challenge, because the state-of-the-art atom traps are only approximately 0.5 K deep for ground-state antihydrogen atoms, much shallower than the energies of particles stored in the plasmas. This thesis will outline the main parts of the ALPHA experiment, with an overview of the important physical processes at work. Antihydrogen production techniques will be described, and an analysis of the spatial annihilation distribution to give indications of the temperature and binding ene...

  16. Ion trapping within the dust grain plasma sheath

    International Nuclear Information System (INIS)

    Jovanovic, D.; Shukla, P.K.

    2002-01-01

    One of the most important and still unresolved problems in the physics of dusty plasmas is the determination of the dust charge. The grains are not directly accessible to measurements and it is necessary to have a reliable theoretical model of the electron and ion dynamics inside the Debye sphere for the interpretation of the relevant experimental data, which include also the effects of the surrounding electron and ion clouds. Recent computer simulations [6] and laboratory experiments [9] indicate that the plasma sheath is dominated by trapped ions, orbiting the grain on closed trajectories at distances smaller than the Debye radius, that cannot be accounted for by the classical theories. We present the first analytical, fully self-consistent, calculations of the electrostatic shielding of a charged dust grain in a collisional plasma. In the regime when the mean free path for the ion-dust collisions is larger than that for the ion-neutral collisions, we solve the kinetic equation for the ions, coupled with Boltzmann distributed electrons and Poisson's equation. The ion velocity distribution function, in the form of a spherically symmetric ion hole, is found to be anisotropic in the presence of charge-exchange collisions. The number of trapped ions and their spatial distribution are determined from the interplay between the collective plasma interaction and the collisional trapping/de-trapping. The stationary state results from the self-tuning of the trapped ion density by the feedback based on the nonlocality of the collisional integral, and on the ion mixing in the radial direction along elongated orbits. Our results confirm the existence of a strong Debye shielding of the dust charge, allowing also the over-population of the trapped ion distribution (ion hump)

  17. Synergistic effect of SRY and its direct target, WDR5, on Sox9 expression.

    Directory of Open Access Journals (Sweden)

    Zhen Xu

    Full Text Available SRY is a sex-determining gene that encodes a transcription factor, which triggers male development in most mammals. The molecular mechanism of SRY action in testis determination is, however, poorly understood. In this study, we demonstrate that WDR5, which encodes a WD-40 repeat protein, is a direct target of SRY. EMSA experiments and ChIP assays showed that SRY could bind to the WDR5 gene promoter directly. Overexpression of SRY in LNCaP cells significantly increased WDR5 expression concurrent with histone H3K4 methylation on the WDR5 promoter. To specifically address whether SRY contributes to WDR5 regulation, we introduced a 4-hydroxy-tamoxifen-inducible SRY allele into LNCaP cells. Conditional SRY expression triggered enrichment of SRY on the WDR5 promoter resulting in induction of WDR5 transcription. We found that WDR5 was self regulating through a positive feedback loop. WDR5 and SRY interacted and were colocalized in cells. In addition, the interaction of WDR5 with SRY resulted in activation of Sox9 while repressing the expression of β-catenin. These results suggest that, in conjunction with SRY, WDR5 plays an important role in sex determination.

  18. Sox9-dependent expression of Gstm6 in Sertoli cells during testis development in mice.

    Science.gov (United States)

    Beverdam, Annemiek; Svingen, Terje; Bagheri-Fam, Stefan; Bernard, Pascal; McClive, Peter; Robson, Mathew; Khojasteh, Mahdi Banan; Salehi, Mahboubeh; Sinclair, Andrew H; Harley, Vincent R; Koopman, Peter

    2009-03-01

    Glutathione S-transferases (GSTs) are an important family of multifunctional enzymes that play a role in the protection of tissues by the detoxification of hazardous and carcinogenic compounds. We found previously that Gstm6 is upregulated in the somatic cells of male mouse fetal gonads relative to female gonads. In this study, we describe the spatial and temporal expression pattern of Gstm6 during mouse development. We show that Gstm6 is predominantly expressed in the reproductive system, at significantly higher levels in XY gonads compared with XX gonads from 11.5 dpc onwards, and remains expressed in the testes in adult mice. Its expression is associated with the Sertoli cell lineage, and is dependent on the expression of the male sex-determining gene Sox9. Our data suggest that Gstm6 plays a male-specific role in gonad development or function, possibly by modulating the exposure of somatic tissue and/or germ cells to endogenous or exogenous toxicants.

  19. Nonadiabatic transitions in electrostatically trapped ammonia molecules

    International Nuclear Information System (INIS)

    Kirste, Moritz; Schnell, Melanie; Meijer, Gerard; Sartakov, Boris G.

    2009-01-01

    Nonadiabatic transitions are known to be major loss channels for atoms in magnetic traps but have thus far not been experimentally reported upon for trapped molecules. We have observed and quantified losses due to nonadiabatic transitions for three isotopologues of ammonia in electrostatic traps by comparing the trapping times in traps with a zero and a nonzero electric field at the center. Nonadiabatic transitions are seen to dominate the overall loss rate even for the present samples that are at relatively high temperatures of 30 mK. It is anticipated that losses due to nonadiabatic transitions in electric fields are omnipresent in ongoing experiments on cold molecules.

  20. Penning traps with unitary architecture for storage of highly charged ions

    International Nuclear Information System (INIS)

    Tan, Joseph N.; Guise, Nicholas D.; Brewer, Samuel M.

    2012-01-01

    Penning traps are made extremely compact by embedding rare-earth permanent magnets in the electrode structure. Axially-oriented NdFeB magnets are used in unitary architectures that couple the electric and magnetic components into an integrated structure. We have constructed a two-magnet Penning trap with radial access to enable the use of laser or atomic beams, as well as the collection of light. An experimental apparatus equipped with ion optics is installed at the NIST electron beam ion trap (EBIT) facility, constrained to fit within 1 meter at the end of a horizontal beamline for transporting highly charged ions. Highly charged ions of neon and argon, extracted with initial energies up to 4000 eV per unit charge, are captured and stored to study the confinement properties of a one-magnet trap and a two-magnet trap. Design considerations and some test results are discussed.

  1. Penning traps with unitary architecture for storage of highly charged ions.

    Science.gov (United States)

    Tan, Joseph N; Brewer, Samuel M; Guise, Nicholas D

    2012-02-01

    Penning traps are made extremely compact by embedding rare-earth permanent magnets in the electrode structure. Axially-oriented NdFeB magnets are used in unitary architectures that couple the electric and magnetic components into an integrated structure. We have constructed a two-magnet Penning trap with radial access to enable the use of laser or atomic beams, as well as the collection of light. An experimental apparatus equipped with ion optics is installed at the NIST electron beam ion trap (EBIT) facility, constrained to fit within 1 meter at the end of a horizontal beamline for transporting highly charged ions. Highly charged ions of neon and argon, extracted with initial energies up to 4000 eV per unit charge, are captured and stored to study the confinement properties of a one-magnet trap and a two-magnet trap. Design considerations and some test results are discussed.

  2. Fabrication and optical characterization of light trapping silicon nanopore and nanoscrew devices

    International Nuclear Information System (INIS)

    Jin, Hyunjong; Logan Liu, G

    2012-01-01

    We have fabricated nanotextured Si substrates that exhibit controllable optical reflection intensities and colors. Si nanopore has a photon trapping nanostructure but has abrupt changes in the index of refraction displaying a darkened specular reflection. Nanoscrew Si shows graded refractive-index photon trapping structures that enable diffuse reflection to be as low as 2.2% over the visible wavelengths. By tuning the 3D nanoscale silicon structure, the optical reflection peak wavelength and intensity are changed in the wavelength range of 300–800 nm, making the surface have different reflectivity and apparent colors. The relation between the surface optical properties with the spatial features of the photon trapping nanostructures is examined. Integration of photon trapping structures with planar Si structure on the same substrate is also demonstrated. The tunable photon trapping silicon structures have potential applications in enhancing the performance of semiconductor photoelectric devices. (paper)

  3. Sognenavne, Albertslund Kommune (3 artikler). trap.dk

    DEFF Research Database (Denmark)

    Kællerød, Lars-Jakob Harding

    2019-01-01

    Artikler til Trap Danmarks netpublikation trap.dk Sognenavnene Herstedvester, Herstedøster og Opstandelseskirkens Sogn......Artikler til Trap Danmarks netpublikation trap.dk Sognenavnene Herstedvester, Herstedøster og Opstandelseskirkens Sogn...

  4. Generation of highly purified neural stem cells from human adipose-derived mesenchymal stem cells by Sox1 activation.

    Science.gov (United States)

    Feng, Nianhua; Han, Qin; Li, Jing; Wang, Shihua; Li, Hongling; Yao, Xinglei; Zhao, Robert Chunhua

    2014-03-01

    Neural stem cells (NSCs) are ideal candidates in stem cell-based therapy for neurodegenerative diseases. However, it is unfeasible to get enough quantity of NSCs for clinical application. Generation of NSCs from human adipose-derived mesenchymal stem cells (hAD-MSCs) will provide a solution to this problem. Currently, the differentiation of hAD-MSCs into highly purified NSCs with biological functions is rarely reported. In our study, we established a three-step NSC-inducing protocol, in which hAD-MSCs were induced to generate NSCs with high purity after sequentially cultured in the pre-inducing medium (Step1), the N2B27 medium (Step2), and the N2B27 medium supplement with basic fibroblast growth factor and epidermal growth factor (Step3). These hAD-MSC-derived NSCs (adNSCs) can form neurospheres and highly express Sox1, Pax6, Nestin, and Vimentin; the proportion was 96.1% ± 1.3%, 96.8% ± 1.7%, 96.2% ± 1.3%, and 97.2% ± 2.5%, respectively, as detected by flow cytometry. These adNSCs can further differentiate into astrocytes, oligodendrocytes, and functional neurons, which were able to generate tetrodotoxin-sensitive sodium current. Additionally, we found that the neural differentiation of hAD-MSCs were significantly suppressed by Sox1 interference, and what's more, Step1 was a key step for the following induction, probably because it was associated with the initiation and nuclear translocation of Sox1, an important transcriptional factor for neural development. Finally, we observed that bone morphogenetic protein signal was inhibited, and Wnt/β-catenin signal was activated during inducing process, and both signals were related with Sox1 expression. In conclusion, we successfully established a three-step inducing protocol to derive NSCs from hAD-MSCs with high purity by Sox1 activation. These findings might enable to acquire enough autologous transplantable NSCs for the therapy of neurodegenerative diseases in clinic.

  5. miRNA-21 is developmentally regulated in mouse brain and is co-expressed with SOX2 in glioma

    International Nuclear Information System (INIS)

    Põlajeva, Jelena; Swartling, Fredrik J; Jiang, Yiwen; Singh, Umashankar; Pietras, Kristian; Uhrbom, Lene; Westermark, Bengt; Roswall, Pernilla

    2012-01-01

    MicroRNAs (miRNAs) and their role during tumor development have been studied in great detail during the last decade, albeit their expression pattern and regulation during normal development are however not so well established. Previous studies have shown that miRNAs are differentially expressed in solid human tumors. Platelet-derived growth factor (PDGF) signaling is known to be involved in normal development of the brain as well as in malignant primary brain tumors, gliomas, but the complete mechanism is still lacking. We decided to investigate the expression of the oncogenic miR-21 during normal mouse development and glioma, focusing on PDGF signaling as a potential regulator of miR-21. We generated mouse glioma using the RCAS/tv-a system for driving PDGF-BB expression in a cell-specific manner. Expression of miR-21 in mouse cell cultures and mouse brain were assessed using Northern blot analysis and in situ hybridization. Immunohistochemistry and Western blot analysis were used to investigate SOX2 expression. LNA-modified siRNA was used for irreversible depletion of miR-21. For inhibition of PDGF signaling Gleevec (imatinib mesylate), Rapamycin and U0126, as well as siRNA were used. Statistical significance was calculated using double-sided unpaired Student´s t-test. We identified miR-21 to be highly expressed during embryonic and newborn brain development followed by a gradual decrease until undetectable at postnatal day 7 (P7), this pattern correlated with SOX2 expression. Furthermore, miR-21 and SOX2 showed up-regulation and overlapping expression pattern in RCAS/tv-a generated mouse brain tumor specimens. Upon irreversible depletion of miR-21 the expression of SOX2 was strongly diminished in both mouse primary glioma cultures and human glioma cell lines. Interestingly, in normal fibroblasts the expression of miR-21 was induced by PDGF-BB, and inhibition of PDGF signaling in mouse glioma primary cultures resulted in suppression of miR-21 suggesting that mi

  6. Algae commensal community in Genlisea traps

    Directory of Open Access Journals (Sweden)

    Konrad Wołowski

    2011-01-01

    Full Text Available The community of algae occurring in Genlisea traps and on the external traps surface in laboratory conditions were studied. A total of 29 taxa were found inside the traps, with abundant diatoms, green algae (Chlamydophyceae and four morphotypes of chrysophytes stomatocysts. One morphotype is described as new for science. There are two ways of algae getting into Genlisea traps. The majority of those recorded inside the traps, are mobile; swimming freely by flagella or moving exuding mucilage like diatoms being ablate to colonize the traps themselves. Another possibility is transport of algae by invertebrates such as mites and crustaceans. In any case algae in the Genlisea traps come from the surrounding environment. Two dominant groups of algae (Chladymonas div. and diatoms in the trap environment, show ability to hydrolyze phosphomonoseters. We suggest that algae in carnivorous plant traps can compete with plant (host for organic phosphate (phosphomonoseters. From the spectrum and ecological requirements of algal species found in the traps, environment inside the traps seems to be acidic. However, further studies are needed to test the relations between algae and carnivorous plants both in laboratory conditions and in the natural environment. All the reported taxa are described briefly and documented with 74 LM and SEM micrographs.

  7. Trapping Dust to Form Planets

    Science.gov (United States)

    Kohler, Susanna

    2017-10-01

    Growing a planet from a dust grain is hard work! A new study explores how vortices in protoplanetary disks can assist this process.When Dust Growth FailsTop: ALMA image of the protoplanetary disk of V1247 Orionis, with different emission components labeled. Bottom: Synthetic image constructed from the best-fit model. [Kraus et al. 2017]Gradual accretion onto a seed particle seems like a reasonable way to grow a planet from a grain of dust; after all, planetary embryos orbit within dusty protoplanetary disks, which provides them with plenty of fuel to accrete so they can grow. Theres a challenge to this picture, though: the radial drift problem.The radial drift problem acknowledges that, as growing dust grains orbit within the disk, the drag force on them continues to grow as well. For large enough dust grains perhaps around 1 millimeter the drag force will cause the grains orbits to decay, and the particles drift into the star before they are able to grow into planetesimals and planets.A Close-Up Look with ALMASo how do we overcome the radial drift problem in order to form planets? A commonly proposed mechanism is dust trapping, in which long-lived vortices in the disk trap the dust particles, preventing them from falling inwards. This allows the particles to persist for millions of years long enough to grow beyond the radial drift barrier.Observationally, these dust-trapping vortices should have signatures: we would expect to see, at millimeter wavelengths, specific bright, asymmetric structures where the trapping occurs in protoplanetary disks. Such disk structures have been difficult to spot with past instrumentation, but the Atacama Large Millimeter/submillimeter Array (ALMA) has made some new observations of the disk V1247 Orionis that might be just what were looking for.Schematic of the authors model for the disk of V1247 Orionis. [Kraus et al. 2017]Trapped in a Vortex?ALMAs observations of V1247 Orionis are reported by a team of scientists led by Stefan

  8. Trapped

    OpenAIRE

    Storvik, Pamela

    2012-01-01

    This study explores how the Muslim Sunni Women in the city of Tripoli- Lebanon perceive the the inequity in the rights of women in terms of those of men within the Personal Status codes practiced today in the Sunni Muslim Sharīʻa Courts in the country. Lebanese women and men in general are subject to an imbalanced patronage as a result of the patriarchal conditions dominating the Lebanese society and its various communities. This project further explores the factors that have led to the failu...

  9. Ultralow-Power Electronic Trapping of Nanoparticles with Sub-10 nm Gold Nanogap Electrodes.

    Science.gov (United States)

    Barik, Avijit; Chen, Xiaoshu; Oh, Sang-Hyun

    2016-10-12

    We demonstrate nanogap electrodes for rapid, parallel, and ultralow-power trapping of nanoparticles. Our device pushes the limit of dielectrophoresis by shrinking the separation between gold electrodes to sub-10 nm, thereby creating strong trapping forces at biases as low as the 100 mV ranges. Using high-throughput atomic layer lithography, we manufacture sub-10 nm gaps between 0.8 mm long gold electrodes and pattern them into individually addressable parallel electronic traps. Unlike pointlike junctions made by electron-beam lithography or larger micron-gap electrodes that are used for conventional dielectrophoresis, our sub-10 nm gold nanogap electrodes provide strong trapping forces over a mm-scale trapping zone. Importantly, our technology solves the key challenges associated with traditional dielectrophoresis experiments, such as high voltages that cause heat generation, bubble formation, and unwanted electrochemical reactions. The strongly enhanced fields around the nanogap induce particle-transport speed exceeding 10 μm/s and enable the trapping of 30 nm polystyrene nanoparticles using an ultralow bias of 200 mV. We also demonstrate rapid electronic trapping of quantum dots and nanodiamond particles on arrays of parallel traps. Our sub-10 nm gold nanogap electrodes can be combined with plasmonic sensors or nanophotonic circuitry, and their low-power electronic operation can potentially enable high-density integration on a chip as well as portable biosensing.

  10. A microfluidic chip for direct and rapid trapping of white blood cells from whole blood

    Science.gov (United States)

    Chen, Jingdong; Chen, Di; Yuan, Tao; Xie, Yao; Chen, Xiang

    2013-01-01

    Blood analysis plays a major role in medical and science applications and white blood cells (WBCs) are an important target of analysis. We proposed an integrated microfluidic chip for direct and rapid trapping WBCs from whole blood. The microfluidic chip consists of two basic functional units: a winding channel to mix and arrays of two-layer trapping structures to trap WBCs. Red blood cells (RBCs) were eliminated through moving the winding channel and then WBCs were trapped by the arrays of trapping structures. We fabricated the PDMS (polydimethylsiloxane) chip using soft lithography and determined the critical flow velocities of tartrazine and brilliant blue water mixing and whole blood and red blood cell lysis buffer mixing in the winding channel. They are 0.25 μl/min and 0.05 μl/min, respectively. The critical flow velocity of the whole blood and red blood cell lysis buffer is lower due to larger volume of the RBCs and higher kinematic viscosity of the whole blood. The time taken for complete lysis of whole blood was about 85 s under the flow velocity 0.05 μl/min. The RBCs were lysed completely by mixing and the WBCs were trapped by the trapping structures. The chip trapped about 2.0 × 103 from 3.3 × 103 WBCs. PMID:24404026

  11. The effect of steroid hormones on the mRNA expression of oct4 and sox2 in uterine tissue of the ovariectomized mice model of menopause

    Directory of Open Access Journals (Sweden)

    Marzieh Davoudi

    2016-07-01

    Full Text Available Background: The uterus is a dynamic tissue responding to hormonal changes during reproductive cycles. As such, uterine stem cells have been studied in recent years. Transcription factors oct4 and sox2 are critical for effective maintenance of pluripotent cell identity. Objective: The present research evaluated the mRNA expression of oct4 and sox2 in the uterine tissues of ovariectomized mice treated with steroid hormones. Materials and Methods: In this experimental study, adult virgin female mice were ovariectomized and treated with estradiol 17β (E2, progesterone (P4, and a combination of E2 and P4 (E2 & P4 for 5 days. Uterine tissues were removed, and immunofluorescent (IF staining and quantitative real-time PCR of oct4 and sox2 markers were performed. Results: IF showed oct4 and sox2 expression in the uterine endometrium and myometrium among all groups. The mRNA expression of oct4 (p=0.022 and sox2 (p=0.042 in the E2-treated group significantly were decreased compared to that in the control group. By contrast, the mRNA expression of oct4 and sox2 in the P4 (p=0.641 and 0.489 respectively and E2 & P4-treated groups (p=0.267 and 0.264 respectively did not show significant differences compared to the control group. Conclusion: The results indicate ovarian steroid hormones change the expression of oct4 and sox2 in the mice uterine tissues, which suggest the involvement of steroid hormonal regulation in uterine stem cells.

  12. Graphene-edge dielectrophoretic tweezers for trapping of biomolecules.

    Science.gov (United States)

    Barik, Avijit; Zhang, Yao; Grassi, Roberto; Nadappuram, Binoy Paulose; Edel, Joshua B; Low, Tony; Koester, Steven J; Oh, Sang-Hyun

    2017-11-30

    The many unique properties of graphene, such as the tunable optical, electrical, and plasmonic response make it ideally suited for applications such as biosensing. As with other surface-based biosensors, however, the performance is limited by the diffusive transport of target molecules to the surface. Here we show that atomically sharp edges of monolayer graphene can generate singular electrical field gradients for trapping biomolecules via dielectrophoresis. Graphene-edge dielectrophoresis pushes the physical limit of gradient-force-based trapping by creating atomically sharp tweezers. We have fabricated locally backgated devices with an 8-nm-thick HfO 2 dielectric layer and chemical-vapor-deposited graphene to generate 10× higher gradient forces as compared to metal electrodes. We further demonstrate near-100% position-controlled particle trapping at voltages as low as 0.45 V with nanodiamonds, nanobeads, and DNA from bulk solution within seconds. This trapping scheme can be seamlessly integrated with sensors utilizing graphene as well as other two-dimensional materials.

  13. Status and outlook of CHIP-TRAP: The Central Michigan University high precision Penning trap

    Science.gov (United States)

    Redshaw, M.; Bryce, R. A.; Hawks, P.; Gamage, N. D.; Hunt, C.; Kandegedara, R. M. E. B.; Ratnayake, I. S.; Sharp, L.

    2016-06-01

    At Central Michigan University we are developing a high-precision Penning trap mass spectrometer (CHIP-TRAP) that will focus on measurements with long-lived radioactive isotopes. CHIP-TRAP will consist of a pair of hyperbolic precision-measurement Penning traps, and a cylindrical capture/filter trap in a 12 T magnetic field. Ions will be produced by external ion sources, including a laser ablation source, and transported to the capture trap at low energies enabling ions of a given m / q ratio to be selected via their time-of-flight. In the capture trap, contaminant ions will be removed with a mass-selective rf dipole excitation and the ion of interest will be transported to the measurement traps. A phase-sensitive image charge detection technique will be used for simultaneous cyclotron frequency measurements on single ions in the two precision traps, resulting in a reduction in statistical uncertainty due to magnetic field fluctuations.

  14. Discriminating between antihydrogen and mirror-trapped antiprotons in a minimum-B trap

    CERN Document Server

    Amole, C; Ashkezari, M D; Baquero-Ruiz, M; Bertsche, W; Butler, E; Cesar, C L; Chapman, S; Charlton, M; Deller, A; Eriksson, S; Fajans, J; Friesen, T; Fujiwara, M C; Gill, D R; Gutierrez, A; Hangst, J S; Hardy, W N; Hayden, M E; Humphries, A J; Hydomako, R; Kurchaninov, L; Jonsell, S; Madsen, N; Menary, S; Nolan, P; Olchanski, K; Olin, A; Povilus, A; Pusa, P; Robicheaux, F; Sarid, E; Silveira, D M; So, C; Storey, J W; Thompson, R I; van der Werf, D P; Wurtele, J S

    2012-01-01

    Recently, antihydrogen atoms were trapped at CERN in a magnetic minimum (minimum-B) trap formed by superconducting octupole and mirror magnet coils. The trapped antiatoms were detected by rapidly turning off these magnets, thereby eliminating the magnetic minimum and releasing any antiatoms contained in the trap. Once released, these antiatoms quickly hit the trap wall, whereupon the positrons and antiprotons in the antiatoms annihilated. The antiproton annihilations produce easily detected signals; we used these signals to prove that we trapped antihydrogen. However, our technique could be confounded by mirror-trapped antiprotons, which would produce seemingly-identical annihilation signals upon hitting the trap wall. In this paper, we discuss possible sources of mirror-trapped antiprotons and show that antihydrogen and antiprotons can be readily distinguished, often with the aid of applied electric fields, by analyzing the annihilation locations and times. We further discuss the general properties of antipr...

  15. Portable Pbars, traps that travel

    International Nuclear Information System (INIS)

    Howe, S.D.; Hynes, M.V.; Picklesimer, A.

    1987-10-01

    The advent of antiproton research utilizing relatively small scale storage devices for very large numbers of these particles opens the possibility of transporting these devices to a research site removed from the accelerator center that produced the antiprotons. Such a portable source of antiprotons could open many new areas of research and make antiprotons available to a new research community. At present antiprotons are available at energies down to 1 MeV. From a portable source these particles can be made available at energies ranging from several tens of kilovolts down to a few millielectron volts. These low energies are in the domain of interest to the atomic and condensed matter physicist. In addition such a source can be used as an injector for an accelerator which could increase the energy domain even further. Moreover, the availability of such a source at a university will open research with antiprotons to a broader range of students than possible at a centralized research facility. This report focuses on the use of ion traps, in particular cylindrical traps, for the antiproton storage device. These devices store the charged antiprotons in a combination of electric and magnet fields. At high enough density and low enough temperature the charged cloud will be susceptible to plasma instabilities. Present day ion trap work is just starting to explore this domain. Our assessment of feasibility is based on what could be done with present day technology and what future technology could achieve. We conclude our report with a radiation safety study that shows that about 10 11 antiprotons can be transported safely, however the federal guidelines for this transport must be reviewed in detail. More antiprotons than this will require special transportation arrangements. 28 refs., 8 figs