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Sample records for mapping alteration caused

  1. Mapping Alteration Caused by Hydrocarbon Microseepages in Patrick Draw area Southwest Wyoming Using Image Spectroscopy and Hyperspectral Remote Sensing

    SciTech Connect

    Shuhab D. Khan

    2008-06-21

    Detection of underlying reservoir accumulations using remote sensing techniques had its inception with the identification of macroseeps. However, today we find ourselves relying on the detection of more subtle characteristics associated with petroleum reservoirs, such as microseeps. Microseepages are the result of vertical movement of light hydrocarbons from the reservoir to the surface through networks of fractures, faults, and bedding planes that provide permeable routes within the overlying rock. Microseepages express themselves at the surface in an array of alterations and anomalies, such as chemical or mineralogical changes in overlying soils and sediments. Using NASA's Hyperion hyperspectral imaging sensors, this project has developed spectral and geochemical ground truthing techniques to identify and map alterations caused by hydrocarbon microseepages and to determine their relationships to the underlying geology in the Patrick Draw area of Southwest Wyoming. Training the classification of satellite imagery with spectral inputs of samples collected over previously defined areas of hydrocarbon microseepage resulted in the successful identification of an anomalous zone. Geochemical characteristics of samples that defined this anomalous zone were then compared to the remaining non-anomalous samples using XRD, ICP, spectroscopy and carbon isotope techniques.

  2. Mutations in MAP3K7 that Alter the Activity of the TAK1 Signaling Complex Cause Frontometaphyseal Dysplasia.

    PubMed

    Wade, Emma M; Daniel, Philip B; Jenkins, Zandra A; McInerney-Leo, Aideen; Leo, Paul; Morgan, Tim; Addor, Marie Claude; Adès, Lesley C; Bertola, Debora; Bohring, Axel; Carter, Erin; Cho, Tae-Joon; Duba, Hans-Christoph; Fletcher, Elaine; Kim, Chong A; Krakow, Deborah; Morava, Eva; Neuhann, Teresa; Superti-Furga, Andrea; Veenstra-Knol, Irma; Wieczorek, Dagmar; Wilson, Louise C; Hennekam, Raoul C M; Sutherland-Smith, Andrew J; Strom, Tim M; Wilkie, Andrew O M; Brown, Matthew A; Duncan, Emma L; Markie, David M; Robertson, Stephen P

    2016-08-01

    Frontometaphyseal dysplasia (FMD) is a progressive sclerosing skeletal dysplasia affecting the long bones and skull. The cause of FMD in some individuals is gain-of-function mutations in FLNA, although how these mutations result in a hyperostotic phenotype remains unknown. Approximately one half of individuals with FMD have no identified mutation in FLNA and are phenotypically very similar to individuals with FLNA mutations, except for an increased tendency to form keloid scars. Using whole-exome sequencing and targeted Sanger sequencing in 19 FMD-affected individuals with no identifiable FLNA mutation, we identified mutations in two genes-MAP3K7, encoding transforming growth factor β (TGF-β)-activated kinase (TAK1), and TAB2, encoding TAK1-associated binding protein 2 (TAB2). Four mutations were found in MAP3K7, including one highly recurrent (n = 15) de novo mutation (c.1454C>T [ p.Pro485Leu]) proximal to the coiled-coil domain of TAK1 and three missense mutations affecting the kinase domain (c.208G>C [p.Glu70Gln], c.299T>A [p.Val100Glu], and c.502G>C [p.Gly168Arg]). Notably, the subjects with the latter three mutations had a milder FMD phenotype. An additional de novo mutation was found in TAB2 (c.1705G>A, p.Glu569Lys). The recurrent mutation does not destabilize TAK1, or impair its ability to homodimerize or bind TAB2, but it does increase TAK1 autophosphorylation and alter the activity of more than one signaling pathway regulated by the TAK1 kinase complex. These findings show that dysregulation of the TAK1 complex produces a close phenocopy of FMD caused by FLNA mutations. Furthermore, they suggest that the pathogenesis of some of the filaminopathies caused by FLNA mutations might be mediated by misregulation of signaling coordinated through the TAK1 signaling complex. PMID:27426733

  3. Noncirrhotic hyperammonemia causing relapsing altered mental status

    PubMed Central

    Khatiwada, Binod; Holbrook, Christopher; Ekeh, Ifeoma Sylvia; Uzoka, Chukwuemeka; Ikwu, Isaac; Upadhyay, Bishwas

    2015-01-01

    Hyperammonemia is a recognized cause of encephalopathy. However, it is commonly seen in patients with liver disease. The clinical entity of noncirrhotic hyperammonemia is now being increasingly recognized. We report a man who presented to our hospital with relapsing altered mental status later diagnosed as noncirrhotic hyperammonemia. PMID:26424945

  4. Tularosa Basin Play Fairway Analysis: Hydrothermal Alteration Map

    DOE Data Explorer

    Adam Brandt

    2015-11-15

    This is a hydrothermal alteration map of the Tularosa Basin area, New Mexico and Texas that was created using Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) multispectral data band ratios based upon diagnostic features of clay, calcite, silica, gypsum, ferric iron, and ferrous iron. Mesoproterozoic granite in the San Andreas Range often appeared altered, but this may be from clays produced by weathering or, locally, by hydrothermal alteration. However, no field checking was done. This work was done under U.S. D.O.E. Contract #DE-EE0006730

  5. Alteration mapping at Goldfield, Nevada, by cluster and discriminant analysis of Landsat digital data. [mapping of hydrothermally altered volcanic rocks

    NASA Technical Reports Server (NTRS)

    Ballew, G.

    1977-01-01

    The ability of Landsat multispectral digital data to differentiate among 62 combinations of rock and alteration types at the Goldfield mining district of Western Nevada was investigated by using statistical techniques of cluster and discriminant analysis. Multivariate discriminant analysis was not effective in classifying each of the 62 groups, with classification results essentially the same whether data of four channels alone or combined with six ratios of channels were used. Bivariate plots of group means revealed a cluster of three groups including mill tailings, basalt and all other rock and alteration types. Automatic hierarchical clustering based on the fourth dimensional Mahalanobis distance between group means of 30 groups having five or more samples was performed using Johnson's HICLUS program. The results of the cluster analysis revealed hierarchies of mill tailings vs. natural materials, basalt vs. non-basalt, highly reflectant rocks vs. other rocks and exclusively unaltered rocks vs. predominantly altered rocks. The hierarchies were used to determine the order in which sets of multiple discriminant analyses were to be performed and the resulting discriminant functions were used to produce a map of geology and alteration which has an overall accuracy of 70 percent for discriminating exclusively altered rocks from predominantly altered rocks.

  6. Ultrastructural alterations during embryonic rats' lung development caused by ozone.

    PubMed

    López, Irma; Sánchez, Ivonne; Bizarro, Patricia; Acevedo, Sandra; Ustarroz, Martha; Fortoul, Teresa

    2008-01-01

    Ozone (O3) is an oxidizing agent that acts on phospholipids, proteins and sugars of cellular membranes producing free radicals, which cause oxidative damages. The O3 exposure has been used as a model to study oxidative stress, in which the respiratory airways represent the entrance to the organism. In this study, ultrastructural alterations were identified at the bronchiolar level during the intra-uterine lung development, using an O3 exposure model in pregnant rats during 18, 20 and 21 days of gestation. Twelve pregnant Wistar rats, six controls and six exposed to 1 ppm O3 inhalation during 12 h per day, were used. The rats were sacrificed at gestational days 18, 20 and 21; the fetuses were obtained and their lungs dissected. The ultrastructural analysis evidenced swollen mitochondria, cytoplasmic vacuolization of the epithelial cells and structural disorder caused by the oxidative stress. At gestation day 20, flake-off epithelial cells and laminar bodies in the bronchiolar lumen were observed. In the 21-gestation-day group, the mitochondria were edematous and their cristae were disrupted by the damage caused in mitochondrial membranes. PMID:18083976

  7. Hydrothermal Alteration Mapping Studies for Geothermal Energy Exploration

    NASA Astrophysics Data System (ADS)

    Calvin, W. M.; Kratt, C.; Littlefield, E. F.; Lamb, A. K.

    2011-12-01

    We use a combination of satellite and aerial surveys at varying spatial resolutions to obtain regional information on hydrothermal alteration patterns and to target more expensive, but also more detailed, airborne spectral data collects. In the past decade we have performed numerous site assessments to characterize mineral, vegetation, and thermal properties as surface identifiers of geothermal resources. Our work has included the satellite sensors Landsat, ASTER, and ALI and airborne sensors MASTER, HyMap, ProSpecTIR, AVIRIS and SEBASS. As part of our validation process we collect data in the field to confirm remote identifications and we also collect samples for later laboratory analysis. These field and lab measurements corroborate our detections and help to define confidence limits in refining regions where alteration minerals are found. Validation work includes the use of an ASD field spectrometer for measurement from 0.4 to 2.5 μm in both field and lab configurations. We have a Thermo/Nicolet Nexus 6700 FTIR spectrometer and shared use of a Designs and Prototypes FTIR field instrument for validation in the thermal infrared spectral range. We usually follow remote sensing work with shallow (2m) ground probe temperature measurements. Past work has identified sinter, tufa, various argillic and propyllitic alteration zones, vegetation concentration near small surface seeps or springs, and thermal anomalies as indicative of resource potential and structural controls on fluid pathways. Playa evaporites have also been used as diagnostic indicators of geothermal systems, where thermal springs discharge into closed basins. Mapped imagery is geo-rectified to standard projections and integrated into GIS databases so that mineral maps can be readily included in regional and site specific assessments. The presentation will describe common and unique features in our surveys of geothermal fields in Nevada as outlined in the table.
    Surveyed Geothermal Sites in Nevada

  8. Multicenter mapping of structural network alterations in autism.

    PubMed

    Valk, Sofie L; Di Martino, Adriana; Milham, Michael P; Bernhardt, Boris C

    2015-06-01

    Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions primarily characterized by abnormalities in social cognition. Abundant previous functional MRI studies have shown atypical activity in networks encompassing medial prefrontal cortex (mPFC) and medial parietal regions corresponding to posterior cingulate cortex and precuneus (PCC/PCU). Conversely, studies assessing structural brain anomalies in ASD have been rather inconsistent. The current work evaluated whether structural changes in ASD can be reliability detected in a large multicenter dataset. Our comprehensive structural MRI framework encompassed cortical thickness mapping and structural covariance analysis based on three independent samples comprising individuals with ASD and controls (n = 220), selected from the Autism Brain Imaging Data Exchange open-access database. Surface-based analysis revealed increased cortical thickness in ASD relative to controls in mPFC and lateral prefrontal cortex. Clusters encompassing mPFC were embedded in altered inter-regional covariance networks, showing decreased covariance in ASD relative to controls primarily to PCC/PCU and inferior parietal regions. Cortical thickness increases and covariance reductions in ASD were consistent, yet of variable effect size, across the different sites evaluated and measurable both in children and adults. Our multisite study shows regional and network-level structural alterations in mPFC in ASD that, possibly, relate to atypical socio-cognitive functions in this condition. PMID:25727858

  9. Altered PLP1 splicing causes hypomyelination of early myelinating structures

    PubMed Central

    Kevelam, Sietske H; Taube, Jennifer R; van Spaendonk, Rosalina M L; Bertini, Enrico; Sperle, Karen; Tarnopolsky, Mark; Tonduti, Davide; Valente, Enza Maria; Travaglini, Lorena; Sistermans, Erik A; Bernard, Geneviève; Catsman-Berrevoets, Coriene E; van Karnebeek, Clara D M; Østergaard, John R; Friederich, Richard L; Fawzi Elsaid, Mahmoud; Schieving, Jolanda H; Tarailo-Graovac, Maja; Orcesi, Simona; Steenweg, Marjan E; van Berkel, Carola G M; Waisfisz, Quinten; Abbink, Truus E M; van der Knaap, Marjo S; Hobson, Grace M; Wolf, Nicole I

    2015-01-01

    Objective The objective of this study was to investigate the genetic etiology of the X-linked disorder “Hypomyelination of Early Myelinating Structures” (HEMS). Methods We included 16 patients from 10 families diagnosed with HEMS by brain MRI criteria. Exome sequencing was used to search for causal mutations. In silico analysis of effects of the mutations on splicing and RNA folding was performed. In vitro gene splicing was examined in RNA from patients’ fibroblasts and an immortalized immature oligodendrocyte cell line after transfection with mutant minigene splicing constructs. Results All patients had unusual hemizygous mutations of PLP1 located in exon 3B (one deletion, one missense and two silent), which is spliced out in isoform DM20, or in intron 3 (five mutations). The deletion led to truncation of PLP1, but not DM20. Four mutations were predicted to affect PLP1/DM20 alternative splicing by creating exonic splicing silencer motifs or new splice donor sites or by affecting the local RNA structure of the PLP1 splice donor site. Four deep intronic mutations were predicted to destabilize a long-distance interaction structure in the secondary PLP1 RNA fragment involved in regulating PLP1/DM20 alternative splicing. Splicing studies in fibroblasts and transfected cells confirmed a decreased PLP1/DM20 ratio. Interpretation Brain structures that normally myelinate early are poorly myelinated in HEMS, while they are the best myelinated structures in Pelizaeus–Merzbacher disease, also caused by PLP1 alterations. Our data extend the phenotypic spectrum of PLP1-related disorders indicating that normal PLP1/DM20 alternative splicing is essential for early myelination and support the need to include intron 3 in diagnostic sequencing. PMID:26125040

  10. Acetaldehyde alters MAP kinase signalling and epigenetic histone modifications in hepatocytes.

    PubMed

    Shukla, Shivendra D; Lee, Youn Ju; Park, Pil-hoon; Aroor, Annayya R

    2007-01-01

    Although both oxidative and non-oxidative metabolites of ethanol are involved in generating ethanol matabolic stress (Emess), the oxidative metabolite acetaldehyde plays a critical role in the cellular actions of ethanol. We have investigated the effects of acetaldehyde on p42/44 MAP kinase, p46/p54 c-jun N-terminal kinase (JNK1/JNK2) and p38 MAP kinase in hepatocytes. Acetaldehyde caused temporal activation of p42/44 MAPK followed by JNK, but the activation of the p42/44 MAPK was not a prerequisite for the JNK activation. Activation ofJNK1 by acetaldehyde was greater than JNK2. Ethanol and acetaldehyde activatedJNK have opposing roles; ethanol-induced JNK activation increased apoptosis whereas that by acetaldehyde decreased apoptosis. Acetaldehyde also caused histone H3 acetylation at Lys9 and phosphorylation of histone H3 at Serl0 and 28, the latter being dependent on p38 MAP kinase. Phosphorylation at Ser28 was higher than at Serl0. Thus acetaldehyde distinctively alters MAP kinase signalling and histone modifications, processes involved in transcriptional activation. PMID:17590997

  11. Ocean acidification causes ecosystem shifts via altered competitive interactions

    NASA Astrophysics Data System (ADS)

    Kroeker, Kristy J.; Micheli, Fiorenza; Gambi, Maria Cristina

    2013-02-01

    Ocean acidification represents a pervasive environmental change that is predicted to affect a wide range of species, yet our understanding of the emergent ecosystem impacts is very limited. Many studies report detrimental effects of acidification on single species in lab studies, especially those with calcareous shells or skeletons. Observational studies using naturally acidified ecosystems have shown profound shifts away from such calcareous species, and there has been an assumption that direct impacts of acidification on sensitive species drive most ecosystem responses. We tested an alternative hypothesis that species interactions attenuate or amplify the direct effects of acidification on individual species. Here, we show that altered competitive dynamics between calcareous species and fleshy seaweeds drive significant ecosystem shifts in acidified conditions. Although calcareous species recruited and grew at similar rates in ambient and low pH conditions during early successional stages, they were rapidly overgrown by fleshy seaweeds later in succession in low pH conditions. The altered competitive dynamics between calcareous species and fleshy seaweeds is probably the combined result of decreased growth rates of calcareous species, increased growth rates of fleshy seaweeds, and/or altered grazing rates. Phase shifts towards ecosystems dominated by fleshy seaweed are common in many marine ecosystems, and our results suggest that changes in the competitive balance between these groups represent a key leverage point through which the physiological responses of individual species to acidification could indirectly lead to profound ecosystem changes in an acidified ocean.

  12. ALTERATIONS IN LUNG STRUCTURE CAUSED BY INHALATION OF OXIDANTS

    EPA Science Inventory

    Morphometric and morphologic methods have been used to evaluate changes in rat lungs caused by the inhalation of a variety of oxidants. Exposure to 100% oxygen causes diffuse pulmonary injury and leads to death after 66-72 h of exposure. The primary insult leading to death in rat...

  13. Preferential Radionuclide Transport in a Tuff with Altered Zones: Micro-scale Mapping

    NASA Astrophysics Data System (ADS)

    Hu, Q.; Liu, X.; Zuo, R.

    2009-12-01

    Understanding radionuclide transport in fractured rock is important for performance assessment of proposed radioactive waste disposal sites. We performed laboratory tests to study water imbibition and radionuclide transport into initially dry tuff by contacting one end of a sample with water containing a mixture of tracers (Re, 99Tc, Sr, Cs, 235U, 237Np, and 242Pu). The tuff sample, collected from Yucca Mountain, Nevada, is a cube 1-cm on each side and has a 1-mm thick altered gray zone embedded within the tuff matrix. Such gray zones are observed to be adjacent to lithophysae and fractures, are primarily quartz and tridymite, and have different hydraulic and chemical properties from the rock matrix. Capillary-driven imbibition transports tracer chemicals away from the imbibing face, causing separation of non-sorbing and sorbing tracers in tuff. Using a micro-scale profiling technique of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), we directly mapped the distribution of radionuclides along the altered zone (as well as transverse to the unaltered matrix). We found that the altered zone shows higher permeability, and less retardation of sorbing radionuclides, than the unaltered matrix, leading to preferential transport along the altered zone. Transverse profiling of the unaltered matrix indicated only limited penetration of strongly sorbing radionuclides, such as Pu.

  14. Immature cortex lesions alter retinotopic maps and interhemispheric connections.

    PubMed

    Restrepo, C Ernesto; Manger, Paul R; Spenger, Christian; Innocenti, Giorgio M

    2003-07-01

    Unilateral lesions of the occipital visual areas performed on postnatal day 5 (P5) in the ferret are not compensated by the appearance, in the lesioned hemisphere, of visual responses at ectopic locations. Instead, when parts of the visual areas are spared, they show abnormal retinotopic organizations; furthermore, callosal connections are abnormally distributed in relation to the retinotopic maps. Lesions that completely eliminate the visual areas including the posterior parietal cortex cause the appearance of abnormal callosal connections from the primary somatosensory cortex on the lesion side to the contralateral, intact, posterior parietal cortex. The occipital visual areas (17, 18, 19, and 21) of the intact hemisphere show a normal retinotopy but lose callosal connections in territories homotopic to the lesions. These findings clarify the nature and limits of structural developmental plasticity in the visual cortex. Early in life, certain regions of cortex have been irreversibly allocated to the visual areas, but two properties defining the areas, that is, retinotopy and connections, remain modifiable. The findings might be relevant for understanding the consequences of early-onset visual cortical lesions in humans. PMID:12838520

  15. Intracellular clusterin causes juxtanuclear aggregate formation and mitochondrial alteration.

    PubMed

    Debure, Laure; Vayssiere, Jean-Luc; Rincheval, Vincent; Loison, Fabien; Le Drean, Yves; Michel, Denis

    2003-08-01

    Clusterin is a puzzling protein upregulated in many diseased tissues, presented as either a survival or a death protein. The role of clusterin might depend on the final maturation and localization of the protein, which can be secreted or reside inside cells, either after in situ synthesis or uptake of extracellular clusterin. We studied the biological effects of intracellular clusterin and observed that clusterin forms containing the alpha-chain region strongly accumulated in an ubiquitinated form in juxtanuclear aggregates meeting the main criterions of aggresomes and leading to profound alterations of the mitochondrial network. The viability of cells transfected by intracellular forms of clusterin was improved by overexpression of Bcl-2, and caspase inhibition was capable of rescuing cells expressing clusterin, which presented an altered mitochondrial permeability. We propose that, although it might be an inherently pro-survival and anti-apoptotic protein expressed by cells under stress in an attempt to protect themselves, clusterin can become highly cytotoxic when accumulated in the intracellular compartment. This activity might reconcile the opposite purported influences of clusterin on cell survival and explain how clusterin can be causally involved in neurodegeneration. PMID:12799419

  16. Spectral properties and ASTER-based alteration mapping of Masahim volcano facies, SE Iran

    NASA Astrophysics Data System (ADS)

    Tayebi, Mohammad H.; Tangestani, Majid H.; Vincent, Robert K.; Neal, Devin

    2014-10-01

    This study applies Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data and the Mixture Tuned Matched Filtering (MTMF) algorithm to map the sub-pixel distribution of alteration minerals associated with the Masahim volcano, SE Iran for understanding the spatial relationship between alteration minerals and volcano facies. Investigations of the alteration mineralogy were conducted using field-spectroscopy, X-ray diffraction (XRD) analysis and ASTER Short Wave Infrared (SWIR) spectral data. In order to spectrally characterize the stratovolcano deposits, lithological units and alteration minerals, the volcano was divided into three facies: the Central, Proximal, and Medial-distal facies. The reflectance spectra of rock samples show absorption features of a number of minerals including white mica, kaolinite, montmorillonite, illite, goethite, hematite, jarosite, opal, and chlorite. The end-members of key alteration minerals including sericite (phyllic zone), kaolinite (argillic zone) and chlorite (propylitic zone) were extracted from imagery using the Pixel Purity Index (PPI) method and were used to map alteration minerals. Accuracy assessment through field observations was used to verify the fraction maps. The results showed that most prominent altered rocks situated at the central facies of volcano. The alteration minerals were discriminated with the coefficient of determination (R2) of 0.74, 0.81, and 0.68 for kaolinite, sericite, and chlorite, respectively. The results of this study have the potential to refine the map of alteration zones in the Masahim volcano.

  17. Interleukin-11 alters placentation and causes preeclampsia features in mice

    PubMed Central

    Winship, Amy L.; Koga, Kaori; Menkhorst, Ellen; Van Sinderen, Michelle; Rainczuk, Katarzyna; Nagai, Miwako; Cuman, Carly; Yap, Joanne; Zhang, Jian-Guo; Simmons, David; Young, Morag J.; Dimitriadis, Evdokia

    2015-01-01

    Preeclampsia (PE) is a pregnancy-specific disorder characterized by hypertension and proteinuria after 20 wk gestation. Abnormal extravillous trophoblast (EVT) invasion and remodeling of uterine spiral arterioles is thought to contribute to PE development. Interleukin-11 (IL11) impedes human EVT invasion in vitro and is elevated in PE decidua in women. We demonstrate that IL11 administered to mice causes development of PE features. Immunohistochemistry shows IL11 compromises trophoblast invasion, spiral artery remodeling, and placentation, leading to increased systolic blood pressure (SBP), proteinuria, and intrauterine growth restriction, although nonpregnant mice were unaffected. Real-time PCR array analysis identified pregnancy-associated plasma protein A2 (PAPPA2), associated with PE in women, as an IL11 regulated target. IL11 increased PAPPA2 serum and placental tissue levels in mice. In vitro, IL11 compromised primary human EVT invasion, whereas siRNA knockdown of PAPPA2 alleviated the effect. Genes regulating uterine natural killer (uNK) recruitment and differentiation were down-regulated and uNK cells were reduced after IL11 treatment in mice. IL11 withdrawal in mice at onset of PE features reduced SBP and proteinuria to control levels and alleviated placental labyrinth defects. In women, placental IL11 immunostaining levels increased in PE pregnancies and in serum collected from women before development of early-onset PE, shown by ELISA. These results indicate that elevated IL11 levels result in physiological changes at the maternal–fetal interface, contribute to abnormal placentation, and lead to the development of PE. Targeting placental IL11 may provide a new treatment option for PE. PMID:26655736

  18. Interleukin-11 alters placentation and causes preeclampsia features in mice.

    PubMed

    Winship, Amy L; Koga, Kaori; Menkhorst, Ellen; Van Sinderen, Michelle; Rainczuk, Katarzyna; Nagai, Miwako; Cuman, Carly; Yap, Joanne; Zhang, Jian-Guo; Simmons, David; Young, Morag J; Dimitriadis, Evdokia

    2015-12-29

    Preeclampsia (PE) is a pregnancy-specific disorder characterized by hypertension and proteinuria after 20 wk gestation. Abnormal extravillous trophoblast (EVT) invasion and remodeling of uterine spiral arterioles is thought to contribute to PE development. Interleukin-11 (IL11) impedes human EVT invasion in vitro and is elevated in PE decidua in women. We demonstrate that IL11 administered to mice causes development of PE features. Immunohistochemistry shows IL11 compromises trophoblast invasion, spiral artery remodeling, and placentation, leading to increased systolic blood pressure (SBP), proteinuria, and intrauterine growth restriction, although nonpregnant mice were unaffected. Real-time PCR array analysis identified pregnancy-associated plasma protein A2 (PAPPA2), associated with PE in women, as an IL11 regulated target. IL11 increased PAPPA2 serum and placental tissue levels in mice. In vitro, IL11 compromised primary human EVT invasion, whereas siRNA knockdown of PAPPA2 alleviated the effect. Genes regulating uterine natural killer (uNK) recruitment and differentiation were down-regulated and uNK cells were reduced after IL11 treatment in mice. IL11 withdrawal in mice at onset of PE features reduced SBP and proteinuria to control levels and alleviated placental labyrinth defects. In women, placental IL11 immunostaining levels increased in PE pregnancies and in serum collected from women before development of early-onset PE, shown by ELISA. These results indicate that elevated IL11 levels result in physiological changes at the maternal-fetal interface, contribute to abnormal placentation, and lead to the development of PE. Targeting placental IL11 may provide a new treatment option for PE. PMID:26655736

  19. Mapping Acid Sulfate Alteration of Basaltic Andesite with Thermal Infrared Data

    NASA Technical Reports Server (NTRS)

    Vaughan, R. G.; Calvin, W. M.; Hook, S. J.; Taranik, J. V.

    2002-01-01

    Airborne thermal infrared multi- and hyperspectral data sets are used to map sulfate alteration of basaltic andesites near Reno, NV. Alteration includes quartz-alunite, jarosite and a number of clay minerals such as kaolinite and montmorillonite. Additional information is contained in the original extended abstract.

  20. Cause-and-effect mapping of critical events.

    PubMed

    Graves, Krisanne; Simmons, Debora; Galley, Mark D

    2010-06-01

    Health care errors are routinely reported in the scientific and public press and have become a major concern for most Americans. In learning to identify and analyze errors health care can develop some of the skills of a learning organization, including the concept of systems thinking. Modern experts in improving quality have been working in other high-risk industries since the 1920s making structured organizational changes through various frameworks for quality methods including continuous quality improvement and total quality management. When using these tools, it is important to understand systems thinking and the concept of processes within organization. Within these frameworks of improvement, several tools can be used in the analysis of errors. This article introduces a robust tool with a broad analytical view consistent with systems thinking, called CauseMapping (ThinkReliability, Houston, TX, USA), which can be used to systematically analyze the process and the problem at the same time. PMID:20541073

  1. Hydrothermal Alteration Mineral Mapping Using Hyperspectral Imagery in Dixie Valley, Nevada

    SciTech Connect

    Kennedy-Bowdoin, T; Martini, B A; Silver, E A; Pickles, W L

    2004-04-02

    Hyperspectral (HyMap) data was used to map the location of outcrops of high temperature, hydrothermally alterated minerals (including alunite, pyrophyllite, and hematite) along a 15 km swath of the eastern front of the Stillwater Mountain Range in Dixie Valley, Nevada. Analysis of this data set reveals that several outcrops of these altered minerals exist in the area, and that one outcrop, roughly 1 square kilometer in area, shows abundant high temperature alteration. Structural analysis of the altered region using a Digital Elevation Model (DEM) suggests that this outcrop is bounded on all sides by a set of cross-cutting faults. This fault set lies within the Dixie Valley Fault system (Caskey et al. 1996). Both the intense alteration in this area and the presence of cross-cutting faults indicate a high probability of recent hot fluid escape.

  2. Altered splicing of ATP6AP2 causes X-linked parkinsonism with spasticity (XPDS)

    PubMed Central

    Korvatska, Olena; Strand, Nicholas S.; Berndt, Jason D.; Strovas, Tim; Chen, Dong-Hui; Leverenz, James B.; Kiianitsa, Konstantin; Mata, Ignacio F.; Karakoc, Emre; Greenup, J. Lynne; Bonkowski, Emily; Chuang, Joseph; Moon, Randall T.; Eichler, Evan E.; Nickerson, Deborah A.; Zabetian, Cyrus P.; Kraemer, Brian C.; Bird, Thomas D.; Raskind, Wendy H.

    2013-01-01

    We report a novel gene for a parkinsonian disorder. X-linked parkinsonism with spasticity (XPDS) presents either as typical adult onset Parkinson's disease or earlier onset spasticity followed by parkinsonism. We previously mapped the XPDS gene to a 28 Mb region on Xp11.2–X13.3. Exome sequencing of one affected individual identified five rare variants in this region, of which none was missense, nonsense or frame shift. Using patient-derived cells, we tested the effect of these variants on expression/splicing of the relevant genes. A synonymous variant in ATP6AP2, c.345C>T (p.S115S), markedly increased exon 4 skipping, resulting in the overexpression of a minor splice isoform that produces a protein with internal deletion of 32 amino acids in up to 50% of the total pool, with concomitant reduction of isoforms containing exon 4. ATP6AP2 is an essential accessory component of the vacuolar ATPase required for lysosomal degradative functions and autophagy, a pathway frequently affected in Parkinson's disease. Reduction of the full-size ATP6AP2 transcript in XPDS cells and decreased level of ATP6AP2 protein in XPDS brain may compromise V-ATPase function, as seen with siRNA knockdown in HEK293 cells, and may ultimately be responsible for the pathology. Another synonymous mutation in the same exon, c.321C>T (p.D107D), has a similar molecular defect of exon inclusion and causes X-linked mental retardation Hedera type (MRXSH). Mutations in XPDS and MRXSH alter binding sites for different splicing factors, which may explain the marked differences in age of onset and manifestations. PMID:23595882

  3. Altered splicing of ATP6AP2 causes X-linked parkinsonism with spasticity (XPDS).

    PubMed

    Korvatska, Olena; Strand, Nicholas S; Berndt, Jason D; Strovas, Tim; Chen, Dong-Hui; Leverenz, James B; Kiianitsa, Konstantin; Mata, Ignacio F; Karakoc, Emre; Greenup, J Lynne; Bonkowski, Emily; Chuang, Joseph; Moon, Randall T; Eichler, Evan E; Nickerson, Deborah A; Zabetian, Cyrus P; Kraemer, Brian C; Bird, Thomas D; Raskind, Wendy H

    2013-08-15

    We report a novel gene for a parkinsonian disorder. X-linked parkinsonism with spasticity (XPDS) presents either as typical adult onset Parkinson's disease or earlier onset spasticity followed by parkinsonism. We previously mapped the XPDS gene to a 28 Mb region on Xp11.2-X13.3. Exome sequencing of one affected individual identified five rare variants in this region, of which none was missense, nonsense or frame shift. Using patient-derived cells, we tested the effect of these variants on expression/splicing of the relevant genes. A synonymous variant in ATP6AP2, c.345C>T (p.S115S), markedly increased exon 4 skipping, resulting in the overexpression of a minor splice isoform that produces a protein with internal deletion of 32 amino acids in up to 50% of the total pool, with concomitant reduction of isoforms containing exon 4. ATP6AP2 is an essential accessory component of the vacuolar ATPase required for lysosomal degradative functions and autophagy, a pathway frequently affected in Parkinson's disease. Reduction of the full-size ATP6AP2 transcript in XPDS cells and decreased level of ATP6AP2 protein in XPDS brain may compromise V-ATPase function, as seen with siRNA knockdown in HEK293 cells, and may ultimately be responsible for the pathology. Another synonymous mutation in the same exon, c.321C>T (p.D107D), has a similar molecular defect of exon inclusion and causes X-linked mental retardation Hedera type (MRXSH). Mutations in XPDS and MRXSH alter binding sites for different splicing factors, which may explain the marked differences in age of onset and manifestations. PMID:23595882

  4. Auditory map plasticity: Diversity in causes and consequences

    PubMed Central

    Schreiner, Christoph E.; Polley, Daniel B.

    2014-01-01

    Auditory cortical maps have been a long-standing focus of studies that assess the expression, mechanisms, and consequences of sensory plasticity. Here we discuss recent progress in understanding how auditory experience transforms spatially organized sound representations at higher levels of the central auditory pathways. New insights into the mechanisms underlying map changes have been achieved and more refined interpretations of various map plasticity effects and their consequences in terms of behavioral corollaries and learning as well as other cognitive aspects have been offered. The systematic organizational principles of cortical sound processing remains a key-aspect in studying and interpreting the role of plasticity in hearing. PMID:24492090

  5. Auditory map plasticity: diversity in causes and consequences.

    PubMed

    Schreiner, Christoph E; Polley, Daniel B

    2014-02-01

    Auditory cortical maps have been a long-standing focus of studies that assess the expression, mechanisms, and consequences of sensory plasticity. Here we discuss recent progress in understanding how auditory experience transforms spatially organized sound representations at higher levels of the central auditory pathways. New insights into the mechanisms underlying map changes have been achieved and more refined interpretations of various map plasticity effects and their consequences in terms of behavioral corollaries and learning as well as other cognitive aspects have been offered. The systematic organizational principles of cortical sound processing remain a key aspect in studying and interpreting the role of plasticity in hearing. PMID:24492090

  6. Satellite detection of vegetative damage and alteration caused by pollutants emitted by a zinc smelter

    NASA Technical Reports Server (NTRS)

    Mcmurtry, G. J.; Petersen, G. W. (Principal Investigator); Fritz, E. L.; Pennypacker, S. P.

    1974-01-01

    The author has identified the following significant results. Field observations and data collected by low flying aircraft were used to verify the accuracy of maps produced from the satellite data. Although areas of vegetation as small as six acres can accurately be detected, a white pine stand that was severely damaged by sulfur dioxide could not be differentiated from a healthy white pine stand because spectral differences were not large enough. When winter data were used to eliminate interference from herbaceous and deciduous vegetation, the damage was still undetectable. The analysis was able to produce a character map that accurately delineated areas of vegetative alteration due to high zinc levels accumulating in the soil. The map depicted a distinct gradient of less damage and alteration as the distance from the smelter increased. Although the satellite data will probably not be useful for detecting small acreages of damaged vegetation, it is concluded that the data may be very useful as an inventory tool to detect and delineate large vegetative areas possessing differing spectral signatures.

  7. Mapping advanced argillic alteration zones with ASTER and Hyperion data in the Andes Mountains of Peru

    NASA Astrophysics Data System (ADS)

    Ramos, Yuddy; Goïta, Kalifa; Péloquin, Stéphane

    2016-04-01

    This study evaluates Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and Hyperion hyperspectral sensor datasets to detect advanced argillic minerals. The spectral signatures of some alteration clay minerals, such as dickite and alunite, have similar absorption features; thus separating them using multispectral satellite images is a complex challenge. However, Hyperion with its fine spectral bands has potential for good separability of features. The Spectral Angle Mapper algorithm was used in this study to map three advanced argillic alteration minerals (alunite, kaolinite, and dickite) in a known alteration zone in the Peruvian Andes. The results from ASTER and Hyperion were analyzed, compared, and validated using a Portable Infrared Mineral Analyzer field spectrometer. The alterations corresponding to kaolinite and alunite were detected with both ASTER and Hyperion (80% to 84% accuracy). However, the dickite mineral was identified only with Hyperion (82% accuracy).

  8. Evaluation of LANDSAT multispectral scanner images for mapping altered rocks in the east Tintic Mountains, Utah

    NASA Technical Reports Server (NTRS)

    Rowan, L. C.; Abrams, M. J. (Principal Investigator)

    1979-01-01

    The author has identified the following significant results. Positive findings of earlier evaluations of the color-ratio compositing technique for mapping limonitic altered rocks in south-central Nevada are confirmed, but important limitations in the approach used are pointed out. These limitations arise from environmental, geologic, and image processing factors. The greater vegetation density in the East Tintic Mountains required several modifications in procedures to improve the overall mapping accuracy of the CRC approach. Large format ratio images provide better internal registration of the diazo films and avoids the problems associated with magnifications required in the original procedure. Use of the Linoscan 204 color recognition scanner permits accurate consistent extraction of the green pixels representing limonitic bedrock maps that can be used for mapping at large scales as well as for small scale reconnaissance.

  9. Alteration mineral mapping for iron prospecting using ETM+ data, Tonkolili iron field, northern Sierra Leone

    NASA Astrophysics Data System (ADS)

    Mansaray, Lamin R.; Liu, Lei; Zhou, Jun; Ma, Zhimin

    2013-10-01

    The Tonkolili iron field in northern Sierra Leone has the largest known iron ore deposit in Africa. It occurs in a greenstone belt in an Achaean granitic basement. This study focused mainly on mapping areas with iron-oxide and hydroxyl bearing minerals, and identifying potential areas for haematite mineralization and banded iron formations (BIFs) in Tonkolili. The predominant mineral assemblage at the surface (laterite duricrust) of this iron field is haematitegoethite- limonite ±magnetite. The mineralization occurs in quartzitic banded ironstones, layered amphibolites, granites, schists and hornblendites. In this study, Crosta techniques were applied on Enhanced Thematic Mapper (ETM+) data to enhance areas with alteration minerals and target potential areas of haematite and BIF units in the Tonkolili iron field. Synthetic analysis shows that alteration zones mapped herein are consistent with the already discovered magnetite BIFs in Tonkolili. Based on the overlaps of the simplified geological map and the remote sensing-based alteration mineral maps obtained in this study, three new haematite prospects were inferred within, and one new haematite prospect was inferred outside the tenement boundary of the Tonkolili exploration license. As the primary iron mineral in Tonkolili is magnetite, the study concludes that, these haematite prospects could also be underlain by magnetite BIFs. This study also concludes that, the application of Crosta techniques on ETM+ data is effective not only in mapping iron-oxide and hydroxyl alterations but can also provide a basis for inferring areas of potential iron resources in Algoma-type banded iron formations (BIFs), such as those in the Tonkolili field.

  10. DNA demethylation caused by 5-Aza-2′-deoxycytidine induces mitotic alterations and aneuploidy

    PubMed Central

    Lentini, Laura; Cilluffo, Danilo; Di Leonardo, Aldo

    2016-01-01

    Aneuploidy, the unbalanced number of chromosomes in a cell, is considered a prevalent form of genetic instability and is largely acknowledged as a condition implicated in tumorigenesis. Epigenetic alterations like DNA hypomethylation have been correlated with cancer initiation/progression. Furthermore, a growing body of evidence suggests the involvement of epigenome-wide disruption as a cause of global DNA hypomethylation in aneuploidy generation. Here, we report that the DNA hypomethylating drug 5-aza-2′-deoxycytidine (DAC), affects the correct ploidy of nearly diploid HCT-116 human cells by altering the methylation pattern of the chromosomes. Specifically, we show that a DAC-induced reduction of 5-Methyl Cytosine at the pericentromeric region of chromosomes correlates with aneuploidy and mitotic defects. Our results suggest that DNA hypomethylation leads to aneuploidy by altering the DNA methylation landscape at the centromere that is necessary to ensure proper chromosomes segregation by recruiting the proteins necessary to build up a functional kinetochore. PMID:26771138

  11. Genetic defect causing familial Alzheimer's disease maps on chromosome 21

    SciTech Connect

    St. George-Hyslop, P.H.; Tanzi, R.E.; Polinsky, R.J.; Haines, J.L.; Nee, L.; Watkins, P.C.; Myers, R.H.; Feldman, R.G.; Pollen, D.; Drachman, D.; Growdon, J.

    1987-02-20

    Alzheimer's disease is a leading cause of morbidity and mortality among the elderly. Several families have been described in which Alzheimer's disease is caused by an autosomal dominant gene defect. The chromosomal location of this defective gene has been discovered by using genetic linkage to DNA markers on chromosome 21. The localization on chromosome 21 provides an explanation for the occurrence of Alzheimer's disease-like pathology in Down syndrome. Isolation and characterization of the gene at this locus may yield new insights into the nature of the defect causing familial Alzheimer's disease and possibly, into the etiology of all forms of Alzheimer's disease.

  12. Inter-Species Grafting Caused Extensive and Heritable Alterations of DNA Methylation in Solanaceae Plants

    PubMed Central

    Lin, Yan; Ma, Yiqiao; Liu, Gang; Yu, Xiaoming; Zhong, Silin; Liu, Bao

    2013-01-01

    Background Grafting has been extensively used to enhance the performance of horticultural crops. Since Charles Darwin coined the term “graft hybrid” meaning that asexual combination of different plant species may generate products that are genetically distinct, highly discrepant opinions exist supporting or against the concept. Recent studies have documented that grafting enables exchanges of both RNA and DNA molecules between the grafting partners, thus providing a molecular basis for grafting-induced genetic variation. DNA methylation is known as prone to alterations as a result of perturbation of internal and external conditions. Given characteristics of grafting, it is interesting to test whether the process may cause an alteration of this epigenetic marker in the grafted organismal products. Methodology/Principal Findings We analyzed relative global DNA methylation levels and locus-specific methylation patterns by the MSAP marker and locus-specific bisulfite-sequencing in the seed plants (wild-type controls), self- and hetero-grafted scions/rootstocks, selfed progenies of scions and their seed-plant controls, involving three Solanaceae species. We quantified expression of putative genes involved in establishing and/or maintaining DNA methylation by q-(RT)-PCR. We found that (1) hetero-grafting caused extensive alteration of DNA methylation patterns in a locus-specific manner, especially in scions, although relative methylation levels remain largely unaltered; (2) the altered methylation patterns in the hetero-grafting-derived scions could be inherited to sexual progenies with some sites showing further alterations or revisions; (3) hetero-grafting caused dynamic changes in steady-state transcript abundance of genes encoding for a set of enzymes functionally relevant to DNA methylation. Conclusions/Significance Our results demonstrate that inter-species grafting in plants could produce extensive and heritable alterations in DNA methylation. We suggest that

  13. Alteration mapping at Goldfield, Nevada, by cluster and discriminant analysis of LANDSAT digital data

    NASA Technical Reports Server (NTRS)

    Ballew, G.

    1977-01-01

    The ability of Landsat multispectral digital data to differentiate among 62 combinations of rock and alteration types at the Goldfield mining district of Western Nevada was investigated by using statistical techniques of cluster and discriminant analysis. Multivariate discriminant analysis was not effective in classifying each of the 62 groups, with classification results essentially the same whether data of four channels alone or combined with six ratios of channels were used. Bivariate plots of group means revealed a cluster of three groups including mill tailings, basalt and all other rock and alteration types. Automatic hierarchical clustering based on the fourth dimensional Mahalanobis distance between group means of 30 groups having five or more samples was performed. The results of the cluster analysis revealed hierarchies of mill tailings vs. natural materials, basalt vs. non-basalt, highly reflectant rocks vs. other rocks and exclusively unaltered rocks vs. predominantly altered rocks. The hierarchies were used to determine the order in which sets of multiple discriminant analyses were to be performed and the resulting discriminant functions were used to produce a map of geology and alteration which has an overall accuracy of 70 percent for discriminating exclusively altered rocks from predominantly altered rocks.

  14. Iron Overload Causes Alterations of E-Cadherin in the Liver.

    PubMed

    Fujikura, Y; Krijt, J; Povýšil, C; Mělková, Z; Přikryl, P; Vokurka, M; Nečas, E

    2016-01-01

    Iron overload causes tissue damage in the liver, but its initial effects at the molecular and cellular level are not well understood. Epithelial cadherin (E-cad) is a major adhesion protein in adherens junctions and is associated with several signal transduction pathways. Dysfunction of E-cad causes instability of adherens junctions, which leads to cell invasion, cell migration, and carcinogenesis. We found in liver samples from iron-overloaded mice that the apparent molecular mass of E-cad was reduced from 125 to 115 kDa in sodium dodecyl sulphate polyacrylamide gel electrophoresis under reducing conditions and immunoblotting, and that the cellular expression of E-cad was decreased in immunohistochemistry. The mRNA level of E-cad, however, did not change significantly, suggesting that the alterations are posttranslational. Interestingly, incubation of control liver extracts with Fe2+ alone also produced the same mobility shift. Neither an oxidant nor an antioxidant influenced this shift in vitro, suggesting that reactive oxygen species, which are generated by iron and known to cause damage to macromolecules, are not involved. Treatment of the 115 kDa E-cad with deferoxamine, an iron chelator, thus removing Fe2+, shifted the molecular mass back to 125 kDa, demonstrating that the shift is reversible. The observation also implies that the alteration that causes the mobility shift is not due to transcriptional control, deglycosylation, and proteolysis. This reversible mobility shift of E-cad has not been previously known. The alteration of E-cad that causes the mobility shift might be an initial step to liver diseases by iron overload. PMID:27516188

  15. An assessment of AVIRIS data for hydrothermal alteration mapping in the Goldfield Mining District, Nevada

    NASA Technical Reports Server (NTRS)

    Carrere, Veronique; Abrams, Michael J.

    1988-01-01

    Airborne Visible and Infrared Imaging Spectrometer (AVIRIS) data were acquired over the Goldfield Mining District, Nevada, in September 1987. Goldfield is one of the group of large epithermal precious metal deposits in Tertiary volcanic rocks, associated with silicic volcanism and caldera formation. Hydrothermal alteration consists of silicification along fractures, advanced agrillic and argillic zones further away from veins and more widespread propylitic zones. An evaluation of AVIRIS data quality was performed. Faults in the data, related to engineering problems and a different behavior of the instrument while on-board the U2, were encountered. Consequently, a decision was made to use raw data and correct them only for dark current variations and detector read-out-delays. New software was written to that effect. Atmospheric correction was performed using the flat field correction technique. Analysis of the data was then performed to extract spectral information, mainly concentrating on the 2 to 2.45 micron window, as the alteration minerals of interest have their distinctive spectral reflectance features in this region. Principally kaolinite and alunite spectra were clearly obtained. Mapping of the different minerals and alteration zones was attempted using ratios and clustering techniques. Poor signal-to-noise performance of the instrument and the lack of appropriate software prevented the production of an alteration map of the area. Spectra extracted locally from the AVIRIS data were checked in the field by collecting representative samples of the outcrops.

  16. Use of airborne imaging spectrometer data to map minerals associated with hydrothermally altered rocks in the northern grapevine mountains, Nevada, and California

    USGS Publications Warehouse

    Kruse, F.A.

    1988-01-01

    Three flightlines of Airborne Imaging Spectrometer (AIS) data, acquired over the northern Grapevine Mountains, Nevada, and California, were used to map minerals associated with hydrothermally altered rocks. The data were processed to remove vertical striping, normalized using an equal area normalization, and reduced to reflectance relative to an average spectrum derived from the data. An algorithm was developed to automatically calculate the absorption band parameters band position, band depth, and band width for the strongest absorption feature in each pixel. These parameters were mapped into an intensity, hue, saturation (IHS) color system to produce a single color image that summarized the absorption band information, This image was used to map areas of potential alteration based upon the predicted relationships between the color image and mineral absorption band. Individual AIS spectra for these areas were then examined to identify specific minerals. Two types of alteration were mapped with the AIS data. Areas of quartz-sericite-pyrite alteration were identified based upon a strong absorption feature near 2.21 ??m, a weak shoulder near 2.25 ??m, and a weak absorption band near 2.35 ??m caused by sericite (fine-grained muscovite). Areas of argillic alteration were defined based on the presence of montmorillonite, identified by a weak to moderate absorption feature near 2.21 ??m and the absence of the 2.35 ??m band. Montmorillonite could not be identified in mineral mixtures. Calcite and dolomite were identified based on sharp absorption features near 2.34 and 2.32 ??m, respectively. Areas of alteration identified using the AIS data corresponded well with areas mapped using field mapping, field reflectance spectra, and laboratory spectral measurements. ?? 1988.

  17. Mapping out a search for environmental causes of breast cancer.

    PubMed Central

    Brody, J G; Rudel, R; Maxwell, N I; Swedis, S R

    1996-01-01

    Geographic patterns and time trends for breast cancer suggest there are preventable causes that may include environmental factors. This article describes the development of new methods used in the Cape Cod Breast Cancer and Environment Study to investigate whether synthetic chemicals in the environment contribute to breast cancer risk. Images p[495]-a p499-a PMID:8955694

  18. Defects in MAP1S-mediated autophagy turnover of fibronectin cause renal fibrosis

    PubMed Central

    He, Yongzhong; Li, Xun; Zhao, Haibo; Su, Zhengming; Jiang, Xianhan; Li, Wenjiao; Zou, Jing; Chen, Qi; Liu, Leyuan

    2016-01-01

    Excessive deposition of extracellular matrix proteins in renal tissues causes renal fibrosis and renal function failure. Mammalian cells primarily use the autophagy-lysosome system to degrade misfolded/aggregated proteins and dysfunctional organelles. MAP1S is an autophagy activator and promotes the biogenesis and degradation of autophagosomes. Previously, we reported that MAP1S suppresses hepatocellular carcinogenesis in a mouse model and predicts a better prognosis in patients suffering from clear cell renal cell carcinomas. Furthermore, we have characterized that MAP1S enhances the turnover of fibronectin, and mice overexpressing LC3 but with MAP1S deleted accumulate fibronectin and develop liver fibrosis because of the synergistic impact of LC3-induced over-synthesis of fibronectin and MAP1S depletion-caused impairment of fibronectin degradation. Here we show that a suppression of MAP1S in renal cells caused an impairment of autophagy clearance of fibronectin and an activation of pyroptosis. Depletion of MAP1S in mice leads to an accumulation of fibrosis-related proteins and the development of renal fibrosis in aged mice. The levels of MAP1S were dramatically reduced and levels of fibronectin were greatly elevated in renal fibrotic tissues from patients diagnosed as renal atrophy and renal failure. Therefore, MAP1S deficiency may cause the accumulation of fibronectin and the development of renal fibrosis. PMID:27236336

  19. Alteration, slope-classified alteration, and potential lahar inundation maps of volcanoes for the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Volcano Archive

    USGS Publications Warehouse

    Mars, John C.; Hubbard, Bernard E.; Pieri, David; Linick, Justin

    2015-01-01

    This study was undertaken during 2012–2013 in cooperation with the National Aeronautics and Space Administration (NASA). Since completion of this study, a new lahar modeling program (LAHAR_pz) has been released, which may produce slightly different modeling results from the LAHARZ model used in this study. The maps and data from this study should not be used in place of existing volcano hazard maps published by local authorities. For volcanoes without hazard maps and (or) published lahar-related hazard studies, this work will provide a starting point from which more accurate hazard maps can be produced. This is the first dataset to provide digital maps of altered volcanoes and adjacent watersheds that can be used for assessing volcanic hazards, hydrothermal alteration, and other volcanic processes in future studies.

  20. Mapping hydrothermally altered rocks on Mount Rainier, Washington, with Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) data

    USGS Publications Warehouse

    Crowley, J.K.; Zimbelman, D.R.

    1997-01-01

    Mount Rainier has produced numerous Holocene debris flows, the largest of which contain clays and other minerals derived from hydrothermally altered rocks on the volcano's edifice. Imagery from an advanced airborne sensor was used to map altered rocks at Mount Rainier and demonstrates their distinctly nonuniform distribution. The mapping of altered rocks helps to identify edifice failure surfaces and to recognize the source areas for the largest debris flow events. Remote sensing methods like those used at Mount Rainier can enhance ground-based mapping efforts and should prove useful for rapidly identifying hazardous sectors at other volcanoes.

  1. Mapping of hydrothermally altered rocks using airborne multispectral scanner data, Marysvale, Utah, mining district

    USGS Publications Warehouse

    Podwysocki, M.H.; Segal, D.B.; Jones, O.D.

    1983-01-01

    Multispectral data covering an area near Marysvale, Utah, collected with the airborne National Aeronautics and Space Administration (NASA) 24-channel Bendix multispectral scanner, were analyzed to detect areas of hydrothermally altered, potentially mineralized rocks. Spectral bands were selected for analysis that approximate those of the Landsat 4 Thematic Mapper and which are diagnostic of the presence of hydrothermally derived products. Hydrothermally altered rocks, particularly volcanic rocks affected by solutions rich in sulfuric acid, are commonly characterized by concentrations of argillic minerals such as alunite and kaolinite. These minerals are important for identifying hydrothermally altered rocks in multispectral images because they have intense absorption bands centered near a wavelength of 2.2 ??m. Unaltered volcanic rocks commonly do not contain these minerals and hence do not have the absorption bands. A color-composite image was constructed using the following spectral band ratios: 1.6??m/2.2??m, 1.6??m/0.48??m, and 0.67??m/1.0??m. The particular bands were chosen to emphasize the spectral contrasts that exist for argillic versus non-argillic rocks, limonitic versus nonlimonitic rocks, and rocks versus vegetation, respectively. The color-ratio composite successfully distinguished most types of altered rocks from unaltered rocks. Some previously unrecognized areas of hydrothermal alteration were mapped. The altered rocks included those having high alunite and/or kaolinite content, siliceous rocks containing some kaolinite, and ash-fall tuffs containing zeolitic minerals. The color-ratio-composite image allowed further division of these rocks into limonitic and nonlimonitic phases. The image did not allow separation of highly siliceous or hematitically altered rocks containing no clays or alunite from unaltered rocks. A color-coded density slice image of the 1.6??m/2.2??m band ratio allowed further discrimination among the altered units. Areas

  2. Surface materials map of Afghanistan: carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Dudek, Kathleen B.; Livo, Keith E.

    2012-01-01

    This map shows the distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of HyMap imaging spectrometer data of Afghanistan. Using a NASA (National Aeronautics and Space Administration) WB-57 aircraft flown at an altitude of ~15,240 meters or ~50,000 feet, 218 flight lines of data were collected over Afghanistan between August 22 and October 2, 2007. The HyMap data were converted to apparent surface reflectance, then further empirically adjusted using ground-based reflectance measurements. The reflectance spectrum of each pixel of HyMap data was compared to the spectral features of reference entries in a spectral library of minerals, vegetation, water, ice, and snow. This map shows the spatial distribution of minerals that have diagnostic absorption features in the shortwave infrared wavelengths. These absorption features result primarily from characteristic chemical bonds and mineralogical vibrations. Several criteria, including (1) the reliability of detection and discrimination of minerals using the HyMap spectrometer data, (2) the relative abundance of minerals, and (3) the importance of particular minerals to studies of Afghanistan's natural resources, guided the selection of entries in the reference spectral library and, therefore, guided the selection of mineral classes shown on this map. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated. Minerals having similar spectral features were less easily discriminated, especially where the minerals were not particularly abundant and (or) where vegetation cover reduced the absorption strength of mineral features. Complications in reflectance calibration also affected the detection and identification of minerals.

  3. Nucleosome alterations caused by mutations at modifiable histone residues in Saccharomyces cerevisiae

    PubMed Central

    Liu, Hongde; Wang, Pingyan; Liu, Lingjie; Min, Zhu; Luo, Kun; Wan, Yakun

    2015-01-01

    Nucleosome organization exhibits dynamic properties depending on the cell state and environment. Histone proteins, fundamental components of nucleosomes, are subject to chemical modifications on particular residues. We examined the effect of substituting modifiable residues of four core histones with the non-modifiable residue alanine on nucleosome dynamics. We mapped the genome-wide nucleosomes in 22 histone mutants of Saccharomyces cerevisiae and compared the nucleosome alterations relative to the wild-type strain. Our results indicated that different types of histone mutation resulted in different phenotypes and a distinct reorganization of nucleosomes. Nucleosome occupancy was altered at telomeres, but not at centromeres. The first nucleosomes upstream (−1) and downstream (+1) of the transcription start site (TSS) were more dynamic than other nucleosomes. Mutations in histones affected the nucleosome array downstream of the TSS. Highly expressed genes, such as ribosome genes and genes involved in glycolysis, showed increased nucleosome occupancy in many types of histone mutant. In particular, the H3K56A mutant exhibited a high percentage of dynamic genomic regions, decreased nucleosome occupancy at telomeres, increased occupancy at the +1 and −1 nucleosomes, and a slow growth phenotype under stress conditions. Our findings provide insight into the influence of histone mutations on nucleosome dynamics. PMID:26498326

  4. Methamphetamine Self-Administration Causes Persistent Striatal Dopaminergic Alterations and Mitigates the Deficits Caused by a Subsequent Methamphetamine Exposure

    PubMed Central

    McFadden, Lisa M.; Hadlock, Greg C.; Allen, Scott C.; Vieira-Brock, Paula L.; Stout, Kristen A.; Ellis, Jonathan D.; Hoonakker, Amanda J.; Andrenyak, David M.; Nielsen, Shannon M.; Wilkins, Diana G.; Hanson, Glen R.

    2012-01-01

    Preclinical studies have demonstrated that repeated methamphetamine (METH) injections (referred to herein as a “binge” treatment) cause persistent dopaminergic deficits. A few studies have also examined the persistent neurochemical impact of METH self-administration in rats, but with variable results. These latter studies are important because: 1) they have relevance to the study of METH abuse; and 2) the effects of noncontingent METH treatment do not necessarily predict effects of contingent exposure. Accordingly, the present study investigated the impact of METH self-administration on dopaminergic neuronal function. Results revealed that self-administration of METH, given according to a regimen that produces brain METH levels comparable with those reported postmortem in human METH abusers (0.06 mg/infusion; 8-h sessions for 7 days), decreased striatal dopamine transporter (DAT) uptake and/or immunoreactivity as assessed 8 or 30 days after the last self-administration session. Increasing the METH dose per infusion did not exacerbate these deficits. These deficits were similar in magnitude to decreases in DAT densities reported in imaging studies of abstinent METH abusers. It is noteworthy that METH self-administration mitigated the persistent deficits in dopaminergic neuronal function, as well as the increases in glial fibrillary acidic protein immunoreactivity, caused by a subsequent binge METH exposure. This protection was independent of alterations in METH pharmacokinetics, but may have been attributable (at least in part) to a pretreatment-induced attenuation of binge-induced hyperthermia. Taken together, these results may provide insight into the neurochemical deficits reported in human METH abusers. PMID:22034657

  5. Mapping Phyllic and Argillic-Altered Rocks in Southeastern Afghanistan using Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Data

    USGS Publications Warehouse

    Mars, John L.; Rowan, Lawrence C.

    2007-01-01

    Introduction: ASTER data and logical operators were successfully used to map phyllic and argillic-altered rocks in the southeastern part of Afghanistan. Hyperion data were used to correct ASTER band 5 and ASTER data were georegistered to orthorectified Landsat TM data. Logical operator algorithms produced argillic and phyllic byte ASTER images that were converted to vector data and overlain on ASTER and Landsat TM images. Alteration and fault patterns indicated that two areas, the Argandab igneous complex, and the Katawaz basin may contain potential polymetallic vein and porphyry copper deposits. ASTER alteration mapping in the Chagai Hills indicates less extensive phyllic and argillic-altered rocks than mapped in the Argandab igneous complex and the Katawaz basin and patterns of alteration are inconclusive to predict potential deposit types.

  6. Alterations of retinal pigment epithelium cause AMD-like retinopathy in senescence-accelerated OXYS rats

    PubMed Central

    Markovets, Anton M.; Saprunova, Valeriya B.; Zhdankina, Anna A.; Fursova, Anzhella Zh.; Bakeeva, Lora E.; Kolosova, Natalia G.

    2011-01-01

    Pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the world, remains poorly understood. This makes it necessary to create animal models for studying AMD pathogenesis and to design new therapeutic approaches. Here we showed that retinopathy in OXYS rats is similar to human AMD according to clinical signs, morphology, and vascular endothelium growth factor (VEGF) and pigment epithelium-derived factor (PEDF) genes expression. Clinical signs of retinopathy OXYS rats manifest by the age 3 months against the background of significantly reduced expression level of VEGF and PEDF genes due to the decline of the amount of retinal pigment epithelium (RPE) cells and alteration of choroidal microcirculation. The disruption in OXYS rats' retina starts at the age of 20 days and appears as reduce the area of RPE cells but does not affect their ultrastructure. Ultrastructural pathological alterations of RPE as well as develop forms of retinopathy are observed in OXYS rats from age 12 months and manifested as excessive accumulation of lipofuscin in RPE regions adjacent to the rod cells, whirling extentions of the basement membrane into the cytoplasm. These data suggest that primary cellular degenerative alterations in the RPE cells secondarily lead to choriocapillaris atrophy and results in complete loss of photoreceptor cells in the OXYS rats' retina by the age of 24 months. PMID:21191149

  7. Di-(2-Ethylhexyl)-Phthalate (DEHP) Causes Impaired Adipocyte Function and Alters Serum Metabolites

    PubMed Central

    Klöting, Nora; Hesselbarth, Nico; Gericke, Martin; Kunath, Anne; Biemann, Ronald; Chakaroun, Rima; Kosacka, Joanna; Kovacs, Peter; Kern, Matthias; Stumvoll, Michael; Fischer, Bernd; Rolle-Kampczyk, Ulrike; Feltens, Ralph; Otto, Wolfgang; Wissenbach, Dirk K.; von Bergen, Martin; Blüher, Matthias

    2015-01-01

    Di-(2-ethylhexyl)-phthalate (DEHP), an ubiquitous environmental contaminant, has been shown to cause adverse effects on glucose homeostasis and insulin sensitivity in epidemiological studies, but the underlying mechanisms are still unknown. We therefore tested the hypothesis that chronic DEHP exposure causes impaired insulin sensitivity, affects body weight, adipose tissue (AT) function and circulating metabolic parameters of obesity resistant 129S6 mice in vivo. An obesity-resistant mouse model was chosen to reduce a potential obesity bias of DEHP effects on metabolic parameters and AT function. The metabolic effects of 10-weeks exposure to DEHP were tested by insulin tolerance tests and quantitative assessment of 183 metabolites in mice. Furthermore, 3T3-L1 cells were cultured with DEHP for two days, differentiated into mature adipocytes in which the effects on insulin stimulated glucose and palmitate uptake, lipid content as well as on mRNA/protein expression of key adipocyte genes were investigated. We observed in female mice that DEHP treatment causes enhanced weight gain, fat mass, impaired insulin tolerance, changes in circulating adiponectin and adipose tissue Pparg, adiponectin and estrogen expression. Serum metabolomics indicated a general increase in phospholipid and carnitine concentrations. In vitro, DEHP treatment increases the proliferation rate and alters glucose uptake in adipocytes. Taken together, DEHP has significant effects on adipose tissue (AT) function and alters specific serum metabolites. Although, DEHP treatment led to significantly impaired insulin tolerance, it did not affect glucose tolerance, HOMA-IR, fasting glucose, insulin or triglyceride serum concentrations. This may suggest that DEHP treatment does not cause impaired glucose metabolism at the whole body level. PMID:26630026

  8. Lithologic discrimination and alteration mapping from AVIRIS Data, Socorro, New Mexico

    NASA Technical Reports Server (NTRS)

    Beratan, K. K.; Delillo, N.; Jacobson, A.; Blom, R.; Chapin, C. E.

    1993-01-01

    Geologic maps are, by their very nature, interpretive documents. In contrasts, images prepared from AVIRIS data can be used as uninterpreted, and thus unbiased, geologic maps. We are having significant success applying AVIRIS data in this non-quantitative manner to geologic problems. Much of our success has come from the power of the Linked Windows Interactive Data System. LinkWinds is a visual data analysis and exploration system under development at JPL which is designed to rapidly and interactively investigate large multivariate data sets. In this paper, we present information on the analysis technique, and preliminary results from research on potassium metasomatism, a distinctive and structurally significant type of alteration associated with crustal extension.

  9. Hydrothermal alteration mapping of Siberian gold-ore fields based on satellite spectroscopy data

    NASA Astrophysics Data System (ADS)

    Ananyev, Yu S.; Maskov, A. A.; Abramova, R. N.

    2015-11-01

    The mapping of the hydrothermal alterations in Urjahskoe and Fedorov-Kedrov gold-ore fields was conducted by applying channel relationship method (band ratio) based on ASTER spectral-zonal satellite image data. It was determined that the calculated mineral indices in ore-bearing structures are zonal. Outer ore-bearing structures revealed increased ferric mineral index values, while inner - high epidote- chlorite- calcite and muscovite- siderite mineral index values. Detected regularities could be used in identifying potential gold-ore bearing areas within identical fields based on remote sensing survey data.

  10. Mapping alteration minerals at prospect, outcrop and drill core scales using imaging spectrometry

    PubMed Central

    Kruse, Fred A.; L. Bedell, Richard; Taranik, James V.; Peppin, William A.; Weatherbee, Oliver; Calvin, Wendy M.

    2011-01-01

    Imaging spectrometer data (also known as ‘hyperspectral imagery’ or HSI) are well established for detailed mineral mapping from airborne and satellite systems. Overhead data, however, have substantial additional potential when used together with ground-based measurements. An imaging spectrometer system was used to acquire airborne measurements and to image in-place outcrops (mine walls) and boxed drill core and rock chips using modified sensor-mounting configurations. Data were acquired at 5 nm nominal spectral resolution in 360 channels from 0.4 to 2.45 μm. Analysis results using standardized hyperspectral methodologies demonstrate rapid extraction of representative mineral spectra and mapping of mineral distributions and abundances in map-plan, with core depth, and on the mine walls. The examples shown highlight the capabilities of these data for mineral mapping. Integration of these approaches promotes improved understanding of relations between geology, alteration and spectral signatures in three dimensions and should lead to improved efficiency of mine development, operations and ultimately effective mine closure. PMID:25937681

  11. Mapping Hydrothermal Alterations in the Muteh Gold Mining Area in Iran by using ASTER satellite Imagery data

    NASA Astrophysics Data System (ADS)

    Asadi Haroni, Hooshang; Hassan Tabatabaei, Seyed

    2016-04-01

    Muteh gold mining area is located in 160 km NW of Isfahan town. Gold mineralization is meso-thermal type and associated with silisic, seresitic and carbonate alterations as well as with hematite and goethite. Image processing and interpretation were applied on the ASTER satellite imagery data of about 400 km2 at the Muteh gold mining area to identify hydrothermal alterations and iron oxides associated with gold mineralization. After applying preprocessing methods such as radiometric and geometric corrections, image processing methods of Principal Components Analysis (PCA), Least Square Fit (Ls-Fit) and Spectral Angle Mapper (SAM) were applied on the ASTER data to identify hydrothermal alterations and iron oxides. In this research reference spectra of minerals such as chlorite, hematite, clay minerals and phengite identified from laboratory spectral analysis of collected samples were used to map the hydrothermal alterations. Finally, identified hydrothermal alteration and iron oxides were validated by visiting and sampling some of the mapped hydrothermal alterations.

  12. The enteropathogenic Escherichia coli (EPEC) Map effector is imported into the mitochondrial matrix by the TOM/Hsp70 system and alters organelle morphology.

    PubMed

    Papatheodorou, Panagiotis; Domańska, Grazyna; Oxle, Marius; Mathieu, Johannes; Selchow, Olaf; Kenny, Brendan; Rassow, Joachim

    2006-04-01

    Enteropathogenic Escherichia coli (EPEC) is a human intestinal pathogen and a major cause of diarrhoea, particularly among infants in developing countries. EPEC target the Map and EspF multifunctional effector proteins to host mitochondria - organelles that play crucial roles in regulating cellular processes such as programmed cell death (apoptosis). While both molecules interfere with the organelles ability to maintain a membrane potential, EspF plays the predominant role and is responsible for triggering cell death. To learn more about the Map-mitochondria interaction, we studied Map localization to mitochondria with purified mitochondria (from mammalian and yeast cells) and within intact yeast. This revealed that (i) Map targeting is dependent on the predicted N-terminal mitochondrial targeting sequence, (ii) the N-terminal 44 residues are sufficient to target proteins to mitochondria and (iii) Map import involves the mitochondrial outer membrane translocase (Tom22 and Tom40), the mitochondrial membrane potential, and the matrix chaperone, mtHsp70. These results are consistent with Map import into the mitochondria matrix via the classical import mechanism. As all known, Map-associated phenotypes in mammalian cells are independent of mitochondrial targeting, this may indicate that import serves as a mechanism to remove Map from the cytoplasm thereby regulating cytoplasmic function. Intriguingly, Map, but not EspF, alters mitochondrial morphology with deletion analysis revealing important roles for residues 101-152. Changes in mitochondrial morphology have been linked to alterations in the ability of these organelles to regulate cellular processes providing a possible additional role for Map import into mitochondria. PMID:16548893

  13. BRF1 mutations alter RNA polymerase III-dependent transcription and cause neurodevelopmental anomalies.

    PubMed

    Borck, Guntram; Hög, Friederike; Dentici, Maria Lisa; Tan, Perciliz L; Sowada, Nadine; Medeira, Ana; Gueneau, Lucie; Thiele, Holger; Kousi, Maria; Lepri, Francesca; Wenzeck, Larissa; Blumenthal, Ian; Radicioni, Antonio; Schwarzenberg, Tito Livio; Mandriani, Barbara; Fischetto, Rita; Morris-Rosendahl, Deborah J; Altmüller, Janine; Reymond, Alexandre; Nürnberg, Peter; Merla, Giuseppe; Dallapiccola, Bruno; Katsanis, Nicholas; Cramer, Patrick; Kubisch, Christian

    2015-02-01

    RNA polymerase III (Pol III) synthesizes tRNAs and other small noncoding RNAs to regulate protein synthesis. Dysregulation of Pol III transcription has been linked to cancer, and germline mutations in genes encoding Pol III subunits or tRNA processing factors cause neurogenetic disorders in humans, such as hypomyelinating leukodystrophies and pontocerebellar hypoplasia. Here we describe an autosomal recessive disorder characterized by cerebellar hypoplasia and intellectual disability, as well as facial dysmorphic features, short stature, microcephaly, and dental anomalies. Whole-exome sequencing revealed biallelic missense alterations of BRF1 in three families. In support of the pathogenic potential of the discovered alleles, suppression or CRISPR-mediated deletion of brf1 in zebrafish embryos recapitulated key neurodevelopmental phenotypes; in vivo complementation showed all four candidate mutations to be pathogenic in an apparent isoform-specific context. BRF1 associates with BDP1 and TBP to form the transcription factor IIIB (TFIIIB), which recruits Pol III to target genes. We show that disease-causing mutations reduce Brf1 occupancy at tRNA target genes in Saccharomyces cerevisiae and impair cell growth. Moreover, BRF1 mutations reduce Pol III-related transcription activity in vitro. Taken together, our data show that BRF1 mutations that reduce protein activity cause neurodevelopmental anomalies, suggesting that BRF1-mediated Pol III transcription is required for normal cerebellar and cognitive development. PMID:25561519

  14. BRF1 mutations alter RNA polymerase III–dependent transcription and cause neurodevelopmental anomalies

    PubMed Central

    Hög, Friederike; Dentici, Maria Lisa; Tan, Perciliz L.; Sowada, Nadine; Medeira, Ana; Gueneau, Lucie; Thiele, Holger; Kousi, Maria; Lepri, Francesca; Wenzeck, Larissa; Blumenthal, Ian; Radicioni, Antonio; Schwarzenberg, Tito Livio; Mandriani, Barbara; Fischetto, Rita; Morris-Rosendahl, Deborah J.; Altmüller, Janine; Reymond, Alexandre; Nürnberg, Peter; Merla, Giuseppe; Dallapiccola, Bruno; Katsanis, Nicholas; Cramer, Patrick; Kubisch, Christian

    2015-01-01

    RNA polymerase III (Pol III) synthesizes tRNAs and other small noncoding RNAs to regulate protein synthesis. Dysregulation of Pol III transcription has been linked to cancer, and germline mutations in genes encoding Pol III subunits or tRNA processing factors cause neurogenetic disorders in humans, such as hypomyelinating leukodystrophies and pontocerebellar hypoplasia. Here we describe an autosomal recessive disorder characterized by cerebellar hypoplasia and intellectual disability, as well as facial dysmorphic features, short stature, microcephaly, and dental anomalies. Whole-exome sequencing revealed biallelic missense alterations of BRF1 in three families. In support of the pathogenic potential of the discovered alleles, suppression or CRISPR-mediated deletion of brf1 in zebrafish embryos recapitulated key neurodevelopmental phenotypes; in vivo complementation showed all four candidate mutations to be pathogenic in an apparent isoform-specific context. BRF1 associates with BDP1 and TBP to form the transcription factor IIIB (TFIIIB), which recruits Pol III to target genes. We show that disease-causing mutations reduce Brf1 occupancy at tRNA target genes in Saccharomyces cerevisiae and impair cell growth. Moreover, BRF1 mutations reduce Pol III–related transcription activity in vitro. Taken together, our data show that BRF1 mutations that reduce protein activity cause neurodevelopmental anomalies, suggesting that BRF1-mediated Pol III transcription is required for normal cerebellar and cognitive development. PMID:25561519

  15. Hydrothermal alteration mapping using ASTER data in Baogutu porphyry deposit, China

    NASA Astrophysics Data System (ADS)

    Li, Q.; Zhang, B.; Lu, L.; Lin, Q.

    2014-03-01

    Remote sensing plays an important role in mineral exploration. One of its proven applications is extracting host-rock lithology and alteration zones that are related to porphyry copper deposits. An Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) was used to map the Baogutu porphyry deposit alteration area. A circular alteration mineral zoning pattern was clearly observed in the classification result of potassic, phyllic, argillic, propylitic zones. The potassic is characterized by biotite and anhydrite with an absorption feature centered at 1.94 and 2.1um. The phyllic zone is characterized by illite and sericite that indicates an intense Al-OH absorption feature centered at 2.20um. The narrower argillic zone including kaolinite and alunite displays a secondary Al-OH absorption feature at 2.17 um. The mineral assemblages of the outer propylitic zone are epidote, chlorite and calcite that exhibit absorption features at 2.335um.The performance of Principal Component Analysis(PCA), Minimum Noise Fraction (MNF), band ratio(BR) and Constrained Energy Minimization(CEM) has been evaluated. These techniques identified new prospects of porphyry copper mineralization in the study areas. These results indicate that ASTER is a powerful tool in the initial steps of mineral exploration.

  16. Proteome Alterations of Hippocampal Cells Caused by Clostridium botulinum C3 Exoenzyme.

    PubMed

    Schröder, Anke; Rohrbeck, Astrid; Just, Ingo; Pich, Andreas

    2015-11-01

    C3bot from Clostridium botulinum is a bacterial mono-ADP-ribosylating enzyme, which transfers an ADP-ribose moiety onto the small GTPases Rho A/B/C. C3bot and the catalytic inactive mutant (C3E174Q) cause axonal and dendritic growth as well as branching in primary hippocampal neurons. In cultured murine hippocampal HT22 cells, protein abundances were analyzed in response to C3bot or C3E174Q treatment using a shotgun proteomics approach. Proteome analyses were performed at four time points over 6 days. More than 4000 protein groups were identified at each time point and quantified in triplicate analyses. On day one, 46 proteins showed an altered abundance, and after 6 days, more than 700 proteins responded to C3bot with an up- or down-regulation. In contrast, C3E174Q had no provable impact on protein abundance. Protein quantification was verified for several proteins by multiple reaction monitoring. Data analysis of altered proteins revealed different cellular processes that were affected by C3bot. They are particularly involved in mitochondrial and lysosomal processes, adhesion, carbohydrate and glucose metabolism, signal transduction, and nuclear proteins of translation and ribosome biogenesis. The results of this study gain novel insights into the function of C3bot in hippocampal cells. PMID:26393427

  17. Emergent Ecohydrologic Thresholds as a Cause of Loss of Forested Wetlands in Hydrologically Altered Environments

    NASA Astrophysics Data System (ADS)

    Allen, S. T.; Keim, R. F.

    2012-12-01

    Forested wetlands in the southeastern United States are critical not only for timber products and wildlife habitat, but also because they benefit society by moderating hydrological, biogeochemical, and geomorphological processes. However, extensive modification of the landscape in the lower Mississippi River deltaic plain has resulted in a radically altered hydrologic environment. In this new hydrologic environment, many forested wetlands remain flooded for the majority of the year, causing shifts in dominant tree species, increased tree mortality, and widespread loss of forested wetlands. Evapotranspiration is a key component of the water budget in swamp-forests with evapotranspiration rates that often exceed open-water evaporation rates. In disconnected and impounded swamps, the transpiration flux may be crucial for lowering the water table and creating conditions that are necessary for the reproduction and survival of trees. However, even the most flood tolerant species are inhibited by extended, deep flooding; one effect is stomatal closure and decreased transpiration. Therefore when flooding is greatest, the evapotranspiration flux, which reduces flooding, is lowest. This potential positive feedback cycle between flooding and reduced transpiration invites the question of whether there are threshold conditions that result in mortality and loss of swamp forests. In this proposed project, we will investigate whether the human-altered hydrology of the Lower Mississippi River region has introduced a new vulnerability to this system due to this ecohydrologic feedback. An understanding of ecohydrologic feedback cycles and thresholds are necessary to improve the current inadequate management practices for these vital ecosystems.

  18. Prevention of metabolic alterations caused by suspension hypokinesia in leg muscles of rats

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.; Jaspers, S. R.; Fagan, J. M.

    1983-01-01

    Rats were subjected to tail-cast suspension hypokinesia for 6 days with one leg immobilized in dorsal flexion by casting. Control animals were also tail-casted. The soleus, gastrocnemius and plantaris muscles of uncasted hypokinetic legs were smaller than control muscles. Dorsal flexion prevented atrophy of these muscles and caused the soleus to hypertrophy. The anterior muscles were unaffected by hypokinesia. The smaller size of the soleus of the uncasted leg relative to the dorsal flexed and weight bearing limbs correlated with slower protein synthesis and faster proteolysis. The capacity of this muscle to synthesize glutamine (gln), which carries nitrogenous waste from muscle was also measured. Although tissue homogenates showed higher activities of gln synthetase, the rate of de novo synthesis was not altered in intact muscle but the tissue ratio of gln/glutamate was decreased. Glutamate and ATP were not limiting for gln synthesis, but availability of ammonia may be a limiting factor for this process in hypokinesia.

  19. An unusual cause of altered mental status: the importance of monitoring a patient's blood pressure

    PubMed Central

    Mathew, Jacob; Koo, Matthew; Crook, Irina R; Jahanmir, Jay

    2014-01-01

    A 73-year-old man presented to the emergency room for acute onset altered mental status. The initial work-up yielded no definitive cause. An MRI demonstrated lesions in the bilateral posterior occipital lobes (not noted on an earlier MRI obtained from an outside institution) that were suggestive of posterior reversible encephalopathy syndrome (PRES). He had a history of Parkinson's disease complicated by autonomic instability (wide blood pressure fluctuations) that was medically controlled in the outpatient setting. During the early course of his hospitalisation, he again displayed wide blood pressure fluctuations. After his blood pressure stabilised, his mental status eventually improved to baseline. A repeat MRI obtained demonstrated near-complete resolution of the previously noted lesions and confirmed the diagnosis of PRES. PMID:25096651

  20. Altered map of visual space in the superior colliculus of mice lacking early retinal waves.

    PubMed

    Mrsic-Flogel, Thomas D; Hofer, Sonja B; Creutzfeldt, Claire; Cloëz-Tayarani, Isabelle; Changeux, Jean-Pierre; Bonhoeffer, Tobias; Hübener, Mark

    2005-07-20

    During the development of the mammalian retinocollicular projection, a coarse retinotopic map is set up by the graded distribution of axon guidance molecules. Subsequent refinement of the initially diffuse projection has been shown to depend on the spatially correlated firing of retinal ganglion cells. In this scheme, the abolition of patterned retinal activity is not expected to influence overall retinotopic organization, but this has not been investigated. We used optical imaging of intrinsic signals to visualize the complete retinotopic map in the superior colliculus (SC) of mice lacking early retinal waves, caused by the deletion of the beta2 subunit of the nicotinic acetylcholine receptor. As expected from previous anatomical studies in the SC of beta2(-/-) mice, regions activated by individual visual stimuli were much larger and had less sharp borders than those in wild-type mice. Importantly, however, we also found systematic distortions of the entire retinotopic map: the map of visual space was expanded anteriorly and compressed posteriorly. Thus, patterned neuronal activity in the early retina has a substantial influence on the coarse retinotopic organization of the SC. PMID:16033902

  1. Reduced secretion and altered proteolytic processing caused by missense mutations in progranulin.

    PubMed

    Kleinberger, Gernot; Capell, Anja; Brouwers, Nathalie; Fellerer, Katrin; Sleegers, Kristel; Cruts, Marc; Van Broeckhoven, Christine; Haass, Christian

    2016-03-01

    Progranulin (GRN) is a secreted growth factor involved in various cellular functions, and loss-of-function mutations are a major cause of frontotemporal lobar degeneration (FTLD) with TDP-43 positive pathology. Most FTLD-related GRN mutations are nonsense mutations resulting in reduced GRN expression. Nonsynonymous GRN missense mutations have been described as risk factor for neurodegenerative brain diseases, but their pathogenic nature remains largely elusive. We identified a double missense mutation in GRN leading to amino acid changes p.D33E and p.G35R in an FTLD patient from Turkish origin. Biochemical and cell biological analysis of the double-mutation together with 2 so-far uncharacterized GRN missense mutations (p.C105R and p.V514M) revealed a reduced secretion efficiency of the GRN p.D33E/p.G35R and p.C105R proteins. Furthermore, loss of the conserved cysteine residue affects protein folding and altered proteolytic processing by neutrophil elastase and proteinase 3. Our data indicate that the described variants may cause a loss-of-function, albeit to a lesser extent than GRN null mutations, and hence could be considered as low-penetrant risk factors for neurodegenerative diseases. PMID:26811050

  2. Altered expression of neuropeptide Y receptors caused by focal cortical dysplasia in human intractable epilepsy

    PubMed Central

    Luo, Hanjiang; Guan, Yuguang; Zhou, Jian; Qi, Xueling; Li, Tianfu; Xu, Zhiqing David; Luan, Guo-Ming

    2016-01-01

    Focal cortical dysplasia (FCD) is a common cause of pharmacologically-intractable epilepsy, however, the precise mechanisms underlying the epileptogenicity of FCD remains to be determined. Neuropeptide Y (NPY), an endogenous anticonvulsant in the central nervous system, plays an important role in the regulation of neuronal excitability. Increased expression of NPY and its receptors has been identified in the hippocampus of patients with mesial temporal lobe epilepsy, presumed to act as an endogenous anticonvulsant mechanism. Therefore, we investigated whether expression changes in NPY receptors occurs in patients with FCD. We specifically investigated the expression of seizure-related NPY receptor subtypes Y1, Y2, and Y5 in patients with FCD versus autopsy controls. We found that Y1R and Y2R were up-regulated at the mRNA and protein levels in the temporal and frontal lobes in FCD lesions. By contrast, there was no significant change in either receptor detected in parietal lesions. Notably, overexpression of Y5R was consistently observed in all FCD lesions. Our results demonstrate the altered expression of Y1R, Y2R and Y5R occurs in FCD lesions within the temporal, frontal and parietal lobe. Abnormal NPY receptor subtype expression may be associated with the onset and progression of epileptic activity and may act as a therapeutic candidate for the treatment of refractory epilepsy caused by FCD. PMID:26943580

  3. Removing noises caused by motion artefacts in microcirculation maps of human skin in vivo.

    PubMed

    Chen, C; Shi, W; Gao, W

    2015-12-01

    This paper presents a zero-padding and cross-correlation technique-based correlation mapping optical coherence tomography (ZPCC-cmOCT) to reconstruct microcirculation maps of human skin in vivo, which can remove the background decorrelation noise caused by motion artefacts. In conventional correlation mapping optical coherence tomography method, the correlation degree of static tissue may be lowered by the motion artefacts due to cardiac and respiratory motion, resulting in background decorrelation noise in microcirculation maps. In zero-padding and cross-correlation technique-based correlation mapping optical coherence tomography method, structural images are first obtained by performing Fourier transform on zero-padded interference fringes, and then cross-correlation-based image registration is utilized to align local areas in two adjacent structural images. Finally, correlation mapping optical coherence tomography method is performed to generate microcirculation maps. Both phantom experiments and in vivo experiments were implemented and the results demonstrate that the proposed method is capable of providing microcirculation maps with the background decorrelation noise removed. PMID:26356237

  4. Ultrastructural alterations of Erwinia carotovora subsp. atroseptica caused by treatment with aluminum chloride and sodium metabisulfite.

    PubMed

    Yaganza, Elian-Simplice; Rioux, Danny; Simard, Marie; Arul, Joseph; Tweddell, Russell J

    2004-11-01

    Aluminum and bisulfite salts inhibit the growth of several fungi and bacteria, and their application effectively controls potato soft rot caused by Erwinia carotovora. In an effort to understand their inhibitory action, ultrastructural changes in Erwinia carotovora subsp. atroseptica after exposure (0 to 20 min) to different concentrations (0.05, 0.1, and 0.2 M) of these salts were examined by using transmission electron microscopy. Plasma membrane integrity was evaluated by using the SYTOX Green fluorochrome that penetrates only cells with altered membranes. Bacteria exposed to all aluminum chloride concentrations, especially 0.2 M, exhibited loosening of the cell walls, cell wall rupture, cytoplasmic aggregation, and an absence of extracellular vesicles. Sodium metabisulfite caused mainly a retraction of plasma membrane and cellular voids which were more pronounced with increasing concentration. Bacterial mortality was closely associated with SYTOX stain absorption when bacteria were exposed to either a high concentration (0.2 M) of aluminum chloride or prolonged exposure (20 min) to 0.05 M aluminum chloride or to a pH of 2.5. Bacteria exposed to lower concentrations of aluminum chloride (0.05 and 0.1 M) for 10 min or less, or to metabisulfite at all concentrations, did not exhibit significant stain absorption, suggesting that no membrane damage occurred or it was too weak to allow the penetration of the stain into the cell. While mortality caused by aluminum chloride involves membrane damage and subsequent cytoplasmic aggregation, sulfite exerts its effect intracellularly; it is transported across the membrane by free diffusion of molecular SO2 with little damage to the cellular membrane. PMID:15528547

  5. Missense mutation T485S alters NBCe1-A electrogenicity causing proximal renal tubular acidosis.

    PubMed

    Zhu, Quansheng; Shao, Xuesi M; Kao, Liyo; Azimov, Rustam; Weinstein, Alan M; Newman, Debra; Liu, Weixin; Kurtz, Ira

    2013-08-15

    Mutations in SLC4A4, the gene encoding the electrogenic Na(+)-HCO3(-) cotransporter NBCe1, cause severe proximal renal tubular acidosis (pRTA), growth retardation, decreased IQ, and eye and teeth abnormalities. Among the known NBCe1 mutations, the disease-causing mechanism of the T485S (NBCe1-A numbering) mutation is intriguing because the substituted amino acid, serine, is structurally and chemically similar to threonine. In this study, we performed intracellular pH and whole cell patch-clamp measurements to investigate the base transport and electrogenic properties of NBCe1-A-T485S in mammalian HEK 293 cells. Our results demonstrated that Ser substitution of Thr485 decreased base transport by ~50%, and importantly, converted NBCe1-A from an electrogenic to an electroneutral transporter. Aqueous accessibility analysis using sulfhydryl reactive reagents indicated that Thr485 likely resides in an NBCe1-A ion interaction site. This critical location is also supported by the finding that G486R (a pRTA causing mutation) alters the position of Thr485 in NBCe1-A thereby impairing its transport function. By using NO3(-) as a surrogate ion for CO3(2-), our result indicated that NBCe1-A mediates electrogenic Na(+)-CO3(2-) cotransport when functioning with a 1:2 charge transport stoichiometry. In contrast, electroneutral NBCe1-T485S is unable to transport NO3(-), compatible with the hypothesis that it mediates Na(+)-HCO3(-) cotransport. In patients, NBCe1-A-T485S is predicted to transport Na(+)-HCO3(-) in the reverse direction from blood into proximal tubule cells thereby impairing transepithelial HCO3(-) absorption, possibly representing a new pathogenic mechanism for generating human pRTA. PMID:23636456

  6. 44 CFR 65.12 - Revision of flood insurance rate maps to reflect base flood elevations caused by proposed...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... INSURANCE AND HAZARD MITIGATION National Flood Insurance Program IDENTIFICATION AND MAPPING OF SPECIAL HAZARD AREAS § 65.12 Revision of flood insurance rate maps to reflect base flood elevations caused by... rate maps to reflect base flood elevations caused by proposed encroachments. 65.12 Section...

  7. 44 CFR 65.12 - Revision of flood insurance rate maps to reflect base flood elevations caused by proposed...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... INSURANCE AND HAZARD MITIGATION National Flood Insurance Program IDENTIFICATION AND MAPPING OF SPECIAL HAZARD AREAS § 65.12 Revision of flood insurance rate maps to reflect base flood elevations caused by... rate maps to reflect base flood elevations caused by proposed encroachments. 65.12 Section...

  8. 44 CFR 65.12 - Revision of flood insurance rate maps to reflect base flood elevations caused by proposed...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... INSURANCE AND HAZARD MITIGATION National Flood Insurance Program IDENTIFICATION AND MAPPING OF SPECIAL HAZARD AREAS § 65.12 Revision of flood insurance rate maps to reflect base flood elevations caused by... rate maps to reflect base flood elevations caused by proposed encroachments. 65.12 Section...

  9. Alteration of protein synthesis in Saccharomyces cerevisiae caused by transition metals

    SciTech Connect

    Chang, E.C.; Willsky, G.R.; Kosman, D.J.

    1986-05-01

    The effects of transition metals and metal oxides (Co/sup 2 +/, Cu/sup 2 +/, Ni/sup 2 +/, Zn/sup 2 +/, arsenite (AsO/sub 2//sup -/), arsenate (AsO/sub 4//sup 3 -/) and vanadate (VO/sub 4//sup 3 -/)) on protein synthesis and cellular thermotolerance in Saccharomyces cerevisiae have been examined. Arsenate and vanadate differ in that they are known to be physiologic phosphate analogues, e.g. in yeast, arsenate is a competitive inhibitor of phosphate transport and is incorporated into phosphoinositide, while vanadate inhibits the formation of various phosphoproteins and phosphoprotein intermediates. Arsenite and arsenate at concentrations above 0.5 mM and 5 mM, respectively, in minimal glucose media inhibited growth. These two oxides at 1 mM induced 4 of the 6 major heat shock proteins (Hsps): 105, 78, 74 and 36 Kd. The 36 Kd protein as not induced by arsenite at 0.1 mM. Vanadate induced no known Hsp but did induce one polypeptide of 155 Kd. These metal-induced proteins did not confer cellular thermotolerance. No protein induction was observed after 45 min preincubation with 0.5 mM divalent Co, Cu, Ni or Zn despite the fact that as with the metal oxides a significant inhibition of growth and over-all protein synthesis was caused by Co/sup 2 +/, Cu/sup 2 +/ and Ni/sup 2 +/ at that concentration. Thus, among this group of metals the induction of specific proteins appears to be unique to those species which mimic the phosphate group. Stress which alters the growth to cells does not always trigger a specific alteration of protein synthesis.

  10. Toxic doses of paraoxon alter the respiratory pattern without causing respiratory failure in rats.

    PubMed

    Villa, Antoine F; Houze, Pascal; Monier, Claire; Risède, Patricia; Sarhan, Hala; Borron, Stephen W; Mégarbane, Bruno; Garnier, Robert; Baud, Frederic J

    2007-03-22

    Respiratory failure, through a combination of muscarinic, nicotinic, and central effects, is the primary cause of death in acute organophosphate poisoning. However, the mechanisms inducing respiratory failure remain unclear. In rats poisoned subcutaneously with paraoxon at doses near the LD(50), we studied the pattern of respiration using whole body plethysmography and the occurrence of respiratory failure using arterial blood gases. Subsequently, we studied the effects of atropine on paraoxon-induced modification of ventilation and arterial blood gases. Fifty and 75%, but not 10% of the subcutaneous LD(50) of paraoxon induced marked and sustained signs and symptoms. At 30min post-injection and throughout the study, there was a significant decrease in the respiratory frequency (34% (50% versus solvent), and 29% (75% versus solvent)) and a significant increase in the expiratory time (72% (50% versus solvent) and 60% (75% versus solvent)) with no modifications of the inspiratory time. The tidal volume was significantly increased for the 75% but not for the 50% dose. Apnea was never detected. Even at the 75% dose, paraoxon had no effects on PaO(2), PaCO(2) or HCO(3)(-); however, a significant decrease in arterial pH was observed at 30min (7.34+/-0.07 versus 7.51+/-0.01, p=0.03). Atropine completely reversed the paraoxon-induced respiratory alterations. We conclude that paraoxon, at doses equal to 50 and 75% of the LD(50), alters ventilation at rest without inducing respiratory failure during the study period. PMID:17250945

  11. Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight

    SciTech Connect

    Kawakami, Takashige Yoshimi, Masaki; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

    2014-03-01

    The role of endoplasmic reticulum (ER) stress in pregnancy remains largely unknown. Pregnant mice were subcutaneously administered tunicamycin (Tun), an ER stressor, as a single dose [0, 50, and 100 μg Tun/kg/body weight (BW)] on gestation days (GDs) 8.5, 12.5, and 15.5. A high incidence (75%) of preterm delivery was observed only in the group treated with Tun 100 μg/kg BW at GD 15.5, indicating that pregnant mice during late gestation are more susceptible to ER stress on preterm delivery. We further examined whether prolonged in utero exposure to ER stress affects fetal development. Pregnant mice were subcutaneously administered a dose of 0, 20, 40, and 60 μg Tun/kg from GD 12.5 to 16.5. Tun treatment decreased the placental and fetal weights in a dose-dependent manner. Histological evaluation showed the formation of a cluster of spongiotrophoblast cells in the labyrinth zone of the placenta of Tun-treated mice. The glycogen content of the fetal liver and placenta from Tun-treated mice was lower than that from control mice. Tun treatment decreased mRNA expression of Slc2a1/glucose transporter 1 (GLUT1), which is a major transporter for glucose, but increased placental mRNA levels of Slc2a3/GLUT3. Moreover, maternal exposure to Tun resulted in a decrease in vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, and placental growth factor. These results suggest that excessive and exogenous ER stress may induce functional abnormalities in the placenta, at least in part, with altered GLUT and vascular-related gene expression, resulting in low infant birth weight. - Highlights: • Maternal exposure to excessive ER stress induced preterm birth and IUGR. • Prolonged excessive ER stress altered the formation of the placental labyrinth. • ER stress decreased GLUT1 mRNA expression in the placenta, but increased GLUT3. • ER stress-induced IUGR causes decreased glycogen and altered glucose transport.

  12. In Vivo Tumour Mapping Using Electrocorticography Alterations During Awake Brain Surgery: A Pilot Study.

    PubMed

    Boussen, Salah; Velly, Lionel; Benar, Christian; Metellus, Philippe; Bruder, Nicolas; Trébuchon, Agnès

    2016-09-01

    During awake brain surgery for tumour resection, in situ EEG recording (ECoG) is used to identify eloquent areas surrounding the tumour. We used the ECoG setup to record the electrical activity of cortical and subcortical tumours and then performed frequency and connectivity analyses in order to identify ECoG impairments and map tumours. We selected 16 patients with cortical (8) and subcortical (8) tumours undergoing awake brain surgery. For each patient, we computed the spectral content of tumoural and healthy areas in each frequency band. We computed connectivity of each electrode using connectivity markers (linear and non-linear correlations, phase-locking and coherence). We performed comparisons between healthy and tumour electrodes. The ECoG alterations were used to implement automated classification of the electrodes using clustering or neural network algorithms. ECoG alterations were used to image cortical tumours.Cortical tumours were found to profoundly alter all frequency contents (normalized and absolute power), with an increase in the δ activity and a decreases for the other bands (P < 0.05). Cortical tumour electrodes showed high level of connectivity compared to surrounding electrodes (all markers, P < 0.05). For subcortical tumours, a relative decrease in the γ1 band and in the alpha band in absolute amplitude (P < 0.05) were the only abnormalities. The neural network algorithm classification had a good performance: 93.6 % of the electrodes were classified adequately on a test subject. We found significant spectral and connectivity ECoG changes for cortical tumours, which allowed tumour recognition. Artificial neural algorithm pattern recognition seems promising for electrode classification in awake tumour surgery. PMID:27324381

  13. Correction of Proton Resonance Frequency Shift Temperature Maps for Magnetic Field Disturbances Caused by Breathing

    NASA Astrophysics Data System (ADS)

    Shmatukha, Andriy V.; Bakker, Chris J. G.

    2006-05-01

    Respiratory Induced Resonance Offset (RIRO) is a periodic disturbance of the magnetic field due to breathing. Such disturbances handicap the accuracy of the Proton Resonance Frequency Shift (PRFS) method of MRI temperature mapping in anatomies situated nearby the lungs and chest wall. In this work, we propose a method capable of minimizing errors caused by RIRO in PRFS temperature maps. In this method, a set of baseline images characterizing RIRO at a variety of respiratory cycle instants is acquired before the thermal treatment starts. During the treatment, the temperature evolution is found from two successive images. Then, the calculated temperature changes are corrected for the additional contribution caused by RIRO using the pre-treatment baseline images acquired at the identical instances of the respiratory cycle. Our method is shown to improve the accuracy and stability of PRFS temperature maps in the presence of RIRO and motion in phantom and volunteer experiments.

  14. Altered cholesterol biosynthesis causes precocious neurogenesis in the developing mouse forebrain.

    PubMed

    Driver, Ashley M; Kratz, Lisa E; Kelley, Richard I; Stottmann, Rolf W

    2016-07-01

    We previously reported a mutation in the cholesterol biosynthesis gene, hydroxysteroid (17-beta) dehydrogenase 7 (Hsd17b7(rudolph)), that results in striking embryonic forebrain dysgenesis. Here we describe abnormal patterns of neuroprogenitor proliferation in the mutant forebrain, namely, a decrease in mitotic cells within the ventricular zone (VZ) and an increase through the remainder of the cortex by E11.5. Further evidence suggests mutant cells undergo abnormal interkinetic nuclear migration (IKNM). Furthermore, intermediate progenitors are increased at the expense of apical progenitors by E12.5, and post-mitotic neurons are expanded by E14.5. In vitro primary neuron culture further supports our model of accelerated cortical differentiation in the mutant. Combined administration of a statin and dietary cholesterol in utero achieved partial reversal of multiple developmental abnormalities in the Hsd17b7(rudolph) embryo, including the forebrain. These results suggest that abnormally increased levels of specific cholesterol precursors in the Hsd17b7(rudolph) embryo cause cortical dysgenesis by altering patterns of neurogenesis. PMID:26921468

  15. EVALUATION OF LOW-SUN ILLUMINATED LANDSAT-4 THEMATIC MAPPER DATA FOR MAPPING HYDROTHERMALLY ALTERED ROCKS IN SOUTHERN NEVADA.

    USGS Publications Warehouse

    Podwysocki, Melvin H.; Power, Marty S.; Salisbury, Jack; Jones, O.D.

    1984-01-01

    Landsat-4 Thematic Mapper (TM) data of southern Nevada collected under conditions of low-angle solar illumination were digitally processed to identify hydroxyl-bearing minerals commonly associated with hydrothermal alteration in volcanic terrains. Digital masking procedures were used to exclude shadow areas and vegetation and thus to produce a CRC image suitable for testing the new TM bands as a means to map hydrothermally altered rocks. Field examination of a masked CRC image revealed that several different types of altered rocks displayed hues associated with spectral characteristics common to hydroxyl-bearing minerals. Several types of unaltered rocks also displayed similar hues.

  16. Three-dimensional geophysical mapping of rock alteration and water content at Mount Adams, Washington: Implications for lahar hazards

    USGS Publications Warehouse

    Finn, C.A.; Deszcz-Pan, M.; Anderson, E.D.; John, D.A.

    2007-01-01

    Hydrothermally altered rocks, particularly if water saturated, can weaken stratovolcanoes, thereby increasing the potential for catastrophic sector collapses that can lead to far-traveled, destructive debris flows. Evaluating the hazards associated with such alteration is difficult because alteration has been mapped on few active volcanoes and the distribution and intensity of subsurface alteration are largely unknown on any active volcano. At Mount Adams, some Holocene debris flows contain abundant hydrothermal minerals derived from collapse of the altered, edifice. Intense hydrothermal alteration significantly reduces the resistivity and magnetization of volcanic rock, and therefore hydrothermally altered rocks can be identified with helicopter electromagnetic and magnetic measurements. Electromagnetic and magnetic data, combined with geological mapping and rock property measurements, indicate the presence of appreciable thicknesses of hydrothermally altered rock in the central core of Mount Adams north of the summit. We identify steep cliffs at the western edge of this zone as the likely source for future large debris flows. In addition, the electromagnetic data identified water in the brecciated core of the upper 100-200 m of the volcano. Water helps alter the rocks, reduces the effective stress, thereby increasing the potential for slope failure, and acts, with entrained melting ice, as a lubricant to transform debris avalanches into lahars. Therefore knowing the distribution of water is also important for hazard assessments. Our results demonstrate that high-resolution geophysical and geological observations can yield unprecedented views of the three-dimensional distribution of altered rock and shallow pore water aiding evaluation of the debris avalanche hazard.

  17. Mapping Transient Hyperventilation Induced Alterations with Estimates of the Multi-Scale Dynamics of BOLD Signal

    PubMed Central

    Kiviniemi, Vesa; Remes, Jukka; Starck, Tuomo; Nikkinen, Juha; Haapea, Marianne; Silven, Olli; Tervonen, Osmo

    2009-01-01

    Temporal blood oxygen level dependent (BOLD) contrast signals in functional MRI during rest may be characterized by power spectral distribution (PSD) trends of the form 1/fα. Trends with 1/f characteristics comprise fractal properties with repeating oscillation patterns in multiple time scales. Estimates of the fractal properties enable the quantification of phenomena that may otherwise be difficult to measure, such as transient, non-linear changes. In this study it was hypothesized that the fractal metrics of 1/f BOLD signal trends can map changes related to dynamic, multi-scale alterations in cerebral blood flow (CBF) after a transient hyperventilation challenge. Twenty-three normal adults were imaged in a resting-state before and after hyperventilation. Different variables (1/f trend constant α, fractal dimension Df, and, Hurst exponent H) characterizing the trends were measured from BOLD signals. The results show that fractal metrics of the BOLD signal follow the fractional Gaussian noise model, even during the dynamic CBF change that follows hyperventilation. The most dominant effect on the fractal metrics was detected in grey matter, in line with previous hyperventilation vaso-reactivity studies. The α was able to differentiate also blood vessels from grey matter changes. Df was most sensitive to grey matter. H correlated with default mode network areas before hyperventilation but this pattern vanished after hyperventilation due to a global increase in H. In the future, resting-state fMRI combined with fractal metrics of the BOLD signal may be used for analyzing multi-scale alterations of cerebral blood flow. PMID:19636388

  18. Altered host behaviour and brain serotonergic activity caused by acanthocephalans: evidence for specificity

    PubMed Central

    Tain, Luke; Perrot-Minnot, Marie-Jeanne; Cézilly, Frank

    2006-01-01

    Manipulative parasites can alter the phenotype of intermediate hosts in various ways. However, it is unclear whether such changes are just by-products of infection or adaptive and enhance transmission to the final host. Here, we show that the alteration of serotonergic activity is functionally linked to the alteration of specific behaviour in the amphipod Gammarus pulex infected with acanthocephalan parasites. Pomphorhynchus laevis and, to a lesser extent, Pomphorhynchus tereticollis altered phototactism, but not geotactism, in G. pulex, whereas the reverse was true for Polymorphus minutus. Serotonin (5-hydroxytryptamine, 5-HT) injected to uninfected G. pulex mimicked the altered phototactism, but had no effect on geotactism. Photophilic G. pulex infected with P. laevis or P. tereticollis showed a 40% increase in brain 5-HT immunoreactivity compared to photophobic, uninfected individuals. In contrast, brain 5-HT immunoreactivity did not differ between P. minutus-infected and uninfected G. pulex. Finally, brain 5-HT immunoreactivity differed significantly among P. tereticollis-infected individuals in accordance with their degree of manipulation. Our results demonstrate that altered 5-HT activity is not the mere consequence of infection by acanthocephalans but is specifically linked to the disruption of host photophobic behaviour, whereas the alteration of other behaviours such as geotactism may rely on distinct physiological routes. PMID:17015346

  19. Toxoplasma gondii causes death and plastic alteration in the jejunal myenteric plexus

    PubMed Central

    Araújo, Eduardo José de Almeida; Zaniolo, Larissa Marchi; Vicentino, Suellen Laís; Góis, Marcelo Biondaro; Zanoni, Jacqueline Nelisis; da Silva, Aristeu Vieira; Sant’Ana, Débora de Mello Gonçales

    2015-01-01

    AIM: To assess the effects of ME-49 Toxoplasma gondii (T. gondii) strain infection on the myenteric plexus and external muscle of the jejunum in rats. METHODS: Thirty rats were distributed into two groups: the control group (CG) (n = 15) received 1 mL of saline solution orally, and the infected group (IG) (n = 15) inoculated with 1 mL of saline solution containing 500 oocysts of M-49 T. gondii strain orally. After 36 d of infection, the rats were euthanized. Infection with T. gondii was confirmed by blood samples collected from all rats at the beginning and end of the experiment. The jejunum of five animals was removed and submitted to routine histological processing (paraffin) for analysis of external muscle thickness. The remaining jejunum from the others animals was used to analyze the general population and the NADH-diaphorase, VIPergic and nitrergic subpopulations of myenteric neurons; and the enteric glial cells (S100-IR). RESULTS: Serological analysis showed that animals from the IG were infected with the parasite. Hypertrophy affecting jejunal muscle thickness was observed in the IG rats (77.02 ± 42.71) in relation to the CG (51.40 ± 12.34), P < 0.05. In addition, 31.2% of the total number of myenteric neurons died (CG: 39839.3 ± 5362.3; IG: 26766.6 ± 2177.6; P < 0.05); hyperplasia of nitrergic myenteric neurons was observed (CG: 7959.0 ± 1290.4; IG: 10893.0 ± 1156.3; P < 0.05); general hypertrophy of the cell body in the remaining myenteric neurons was noted [CG: 232.5 (187.2-286.0); IG: 248.2 (204.4-293.0); P < 0.05]; hypertrophy of the smallest varicosities containing VIP neurotransmitter was seen (CG: 0.46 ± 0.10; IG: 0.80 ± 0.16; P < 0.05) and a reduction of 25.3% in enteric glia cells (CG: 12.64 ± 1.27; IG: 10.09 ± 2.10; P < 0.05) was observed in the infected rats. CONCLUSION: It was concluded that infection with oocysts of ME-49 T. gondii strain caused quantitative and plastic alterations in the myenteric plexus of the jejunum in rats. PMID

  20. Microemboli alter the acute stress response and cause prolonged expression of MCP-1 in the hippocampus.

    PubMed

    Nemeth, Christina L; Neigh, Gretchen N

    2015-04-01

    Microvascular ischemia is linked to cardiovascular disease pathology, as well as alterations in mood and cognition. Ischemia activates the hypothalamic-pituitary-adrenal (HPA) axis and through chronic activation, alters HPA axis function. Dysregulation of the HPA axis can lead to the chronic release of glucocorticoids, a hyper-inflammatory cerebral response, cell damage, and changes in behavior. Although the interactions between injury and HPA axis activity have been established in global ischemia, HPA-related repercussions of diffuse ischemic damage and subsequent inflammation have not been assessed. The current study used a rat model of microsphere embolism (ME) ischemia to test the hypothesis that microvascular ischemia would lead to long term alterations in HPA axis function and inflammatory activity. Furthermore, given the pro-inflammatory nature of chronic stress, we assessed the implications of chronic stress for gene expression of inflammatory factors and key components of the glucocorticoid receptor response, following microvascular ischemia. Results indicated that ME altered the response to an acute stress fourteen days following ME injury and increased hippocampal expression of monocyte chemoattractant protein 1 (Mcp-1) as long as 4 weeks following ME injury, without concomitant effects on gene expression of the glucocorticoid receptor or its co-chaperones. Furthermore, no exacerbative effects of chronic stress exposure were observed following ME injury beyond the effects of ME injury alone. Together, these results indicate that ME injury is sufficient to alter both HPA axis activity and cerebral inflammation for a prolonged period of time following injury. PMID:25697594

  1. Fuzzy cognitive map in differential diagnosis of alterations in urinary elimination: A nursing approach

    PubMed Central

    de Moraes Lopes, Maria Helena Baena; Ortega, Neli Regina Siqueira; Silveira, Paulo Sérgio Panse; Massad, Eduardo; Higa, Rosângela; de Fátima Marin, Heimar

    2013-01-01

    Purpose To develop a decision support system to discriminate the diagnoses of alterations in urinary elimination, according to the nursing terminology of NANDA International (NANDA-I). Methods A fuzzy cognitive map (FCM) was structured considering six possible diagnoses: stress urinary incontinence, reflex urinary incontinence, urge urinary incontinence, functional urinary incontinence, total urinary incontinence and urinary retention; and 39 signals associated with them. The model was implemented in Microsoft Visual C++® Edition 2005 and applied in 195 real cases. Its performance was evaluated through the agreement test, comparing its results with the diagnoses determined by three experts (nurses). The sensitivity and specificity of the model were calculated considering the expert’s opinion as a gold standard. In order to compute the Kappa’s values we considered two situations, since more than one diagnosis was possible: the overestimation of the accordance in which the case was considered as concordant when at least one diagnoses was equal; and the underestimation of the accordance, in which the case was considered as discordant when at least one diagnosis was different. Results The overestimation of the accordance showed an excellent agreement (kappa = 0.92, p < 0.0001); and the underestimation provided a moderate agreement (kappa = 0.42, p < 0.0001). In general the FCM model showed high sensitivity and specificity, of 0.95 and 0.92, respectively, but provided a low specificity value in determining the diagnosis of urge urinary incontinence (0.43) and a low sensitivity value to total urinary incontinence (0.42). Conclusions The decision support system developed presented a good performance compared to other types of expert systems for differential diagnosis of alterations in urinary elimination. Since there are few similar studies in the literature, we are convinced of the importance of investing in this kind of modeling, both from the theoretical and from

  2. Interneuron Transcriptional Dysregulation Causes Frequency-Dependent Alterations in the Balance of Inhibition and Excitation in Hippocampus

    PubMed Central

    Bartley, Aundrea F.; Lucas, Elizabeth K.; Brady, Lillian J.; Li, Qin; Hablitz, John J.; Cowell, Rita M.

    2015-01-01

    Circuit dysfunction in complex brain disorders such as schizophrenia and autism is caused by imbalances between inhibitory and excitatory synaptic transmission (I/E). Short-term plasticity differentially alters responses from excitatory and inhibitory synapses, causing the I/E ratio to change as a function of frequency. However, little is known about I/E ratio dynamics in complex brain disorders. Transcriptional dysregulation in interneurons, particularly parvalbumin interneurons, is a consistent pathophysiological feature of schizophrenia. Peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) is a transcriptional coactivator that in hippocampus is highly concentrated in inhibitory interneurons and regulates parvalbumin transcription. Here, we used PGC-1α−/− mice to investigate effects of interneuron transcriptional dysregulation on the dynamics of the I/E ratio at the synaptic and circuit level in hippocampus. We find that loss of PGC-1α increases the I/E ratio onto CA1 pyramidal cells in response to Schaffer collateral stimulation in slices from young adult mice. The underlying mechanism is enhanced basal inhibition, including increased inhibition from parvalbumin interneurons. This decreases the spread of activation in CA1 and dramatically limits pyramidal cell spiking, reducing hippocampal output. The I/E ratio and CA1 output are partially restored by paired-pulse stimulation at short intervals, indicating frequency-dependent effects. However, circuit dysfunction persists, indicated by alterations in kainate-induced gamma oscillations and impaired nest building. Together, these results show that transcriptional dysregulation in hippocampal interneurons causes frequency-dependent alterations in I/E ratio and circuit function, suggesting that PGC-1α deficiency in psychiatric and neurological disorders contributes to disease by causing functionally relevant alterations in I/E balance. SIGNIFICANCE STATEMENT Alteration in the inhibitory and

  3. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export

    PubMed Central

    Legati, Andrea; Giovannini, Donatella; Nicolas, Gaël; López-Sánchez, Uriel; Quintáns, Beatriz; Oliveira, João; Sears, Renee L.; Marisa Ramos, Eliana; Spiteri, Elizabeth; Sobrido, María-Jesús; Carracedo, Ángel; Castro-Fernández, Cristina; Cubizolle, Stéphanie; Fogel, Brent L.; Goizet, Cyril; Jen, Joanna C.; Kirdlarp, Suppachok; Lang, Anthony E.; Miedzybrodzka, Zosia; Mitarnun, Witoon; Paucar, Martin; Paulson, Henry; Pariente, Jérémie; Richard, Anne-Claire; Salins, Naomi S.; Simpson, Sheila A.; Striano, Pasquale; Svenningsson, Per; Tison, François; Unni, Vivek K.; Vanakker, Olivier; Wessels, Marja W.; Wetchaphanphesat, Suppachok; Yang, Michele; Boller, Francois; Campion, Dominique; Hannequin, Didier; Sitbon, Marc; Geschwind, Daniel H.; Battini, Jean-Luc; Coppola, Giovanni

    2015-01-01

    Primary familial brain calcification (PFBC) is a neurological disease characterized by calcium phosphate deposits in the basal ganglia and other brain regions, thus far associated with SLC20A2, PDGFB, or PDGFRB mutations. We identified in multiple PFBC families mutations in XPR1, a gene encoding a retroviral receptor with phosphate export function. These mutations alter phosphate export, providing a direct evidence of an impact of XPR1 and phosphate homeostasis in PFBC. PMID:25938945

  4. Mapping hydrothermally altered rocks in the Northern Grapevine Mountains, Nevada and California with the airborne imaging spectrometer

    NASA Technical Reports Server (NTRS)

    Kruse, Fred A.

    1987-01-01

    Seven flightlines of Airborne Imaging Spectrometer (AIS) data were analyzed for an area of hydrothermally altered rocks. The data were reduced to reflectance relative to an average spectrum, and an automated procedure was used to produce a color coded image displaying absorption band information. Individual spectra were extracted from the AIS images to determine the detailed mineralogy. Two alteration types were mapped based upon mineralogy identified using the AIS data. The primary alteration type is quartz sericite pyrite alteration which occurs in northwest-trending zones in quartz monzonite porphyry. The AIS data allow identification of sericite (muscovite) based upon a strong absorption feature near 2.21 micron and weaker absorption features near 2.35 and 2.45 micron. The second alteration type occurs as a zone of argillic alteration associated with a granitic intrusion. Montmorillonite was identified based on a weak to moderate absorption feature near 2.2 micron and the absence of the two absorption features at longer wavelengths characteristic of sericite. Montmorillonite could be identified only where concentrations of sericite did not mask the montmorillonite spectrum.

  5. Repeated episodes of heroin cause enduring alterations of circadian activity in protracted abstinence.

    PubMed

    Stinus, Luis; Cador, Martine; Caille, Stephanie

    2012-01-01

    Opiate withdrawal is followed by a protracted abstinence syndrome consisting of craving and physiological changes. However, few studies have been dedicated to both the characterization and understanding of these long-term alterations in post-dependent subjects. The aim of the present study was to develop an opiate dependence model, which induces long-lasting behavioral changes in abstinent rats. Here, we first compared the effects of several protocols for the induction of opiate dependence (morphine pellets, repeated morphine or heroin injections) on the subsequent response to heroin challenges (0.25 mg/kg) at different time points during abstinence (3, 6, 9 and 18 weeks). In a second set of experiments, rats were exposed to increasing doses of heroin and subsequently monitored for general circadian activity up to 20 weeks of abstinence. Results show that heroin injections rather than the other methods of opiate administration have long-term consequences on rats' sensitivity to heroin with its psychostimulant effects persisting up to 18 weeks of abstinence. Moreover, intermittent episodes of heroin dependence rather than a single exposure produce enduring alteration of the basal circadian activity both upon heroin cessation and protracted abstinence. Altogether, these findings suggest that the induction of heroin dependence through intermittent increasing heroin injections is the optimal method to model long-term behavioral alterations during protracted abstinence in rats. This animal model would be useful in further characterizing long-lasting changes in post-dependent subjects to help understand the prolonged vulnerability to relapse. PMID:24961201

  6. Repeated Episodes of Heroin Cause Enduring Alterations of Circadian Activity in Protracted Abstinence

    PubMed Central

    Stinus, Luis; Cador, Martine; Caille, Stephanie

    2012-01-01

    Opiate withdrawal is followed by a protracted abstinence syndrome consisting of craving and physiological changes. However, few studies have been dedicated to both the characterization and understanding of these long-term alterations in post-dependent subjects. The aim of the present study was to develop an opiate dependence model, which induces long-lasting behavioral changes in abstinent rats. Here, we first compared the effects of several protocols for the induction of opiate dependence (morphine pellets, repeated morphine or heroin injections) on the subsequent response to heroin challenges (0.25 mg/kg) at different time points during abstinence (3, 6, 9 and 18 weeks). In a second set of experiments, rats were exposed to increasing doses of heroin and subsequently monitored for general circadian activity up to 20 weeks of abstinence. Results show that heroin injections rather than the other methods of opiate administration have long-term consequences on rats’ sensitivity to heroin with its psychostimulant effects persisting up to 18 weeks of abstinence. Moreover, intermittent episodes of heroin dependence rather than a single exposure produce enduring alteration of the basal circadian activity both upon heroin cessation and protracted abstinence. Altogether, these findings suggest that the induction of heroin dependence through intermittent increasing heroin injections is the optimal method to model long-term behavioral alterations during protracted abstinence in rats. This animal model would be useful in further characterizing long-lasting changes in post-dependent subjects to help understand the prolonged vulnerability to relapse. PMID:24961201

  7. Mapping Weak, Altered Zones and Perched Water With Aerogeophysical Measurements at Mount Adams, Washington: Implications for Volcanic Instability

    NASA Astrophysics Data System (ADS)

    Finn, C. A.; Deszcz-Pan, M.; Anderson, E. D.; Horton, R.

    2006-12-01

    Hydrothermally altered rocks, particularly if water saturated, can weaken stratovolcanoes. This increases the potential for catastrophic sector collapses that can lead to destructive debris flows. Evaluating the hazards associated with such alteration is difficult, because alteration has been mapped on few active volcanoes and the distribution and intensity of subsurface alteration and location of perched water tables are largely unknown on any active volcano. At Mount Adams, some Holocene debris flows contain abundant hydrothermal minerals derived from collapse of an altered edifice. Intense hydrothermal alteration can significantly reduce the resistivity (from hundreds to tens ohm-m) and magnetization of volcanic rocks. These changes can be identified with helicopter electromagnetic and magnetic measurements and visualized in 3D. 100 m is the greatest depth that the lowest frequency electromagnetic data could penetrate into the low resistivity, altered zones; outside the altered zones, the depth of penetration was up to 300 m. Total-field magnetic data can detect magnetization variations to several thousand meters depth. Electromagnetic and magnetic data, combined with geological mapping and rock property measurements, indicate the presence of appreciable thicknesses of hydrothermally altered rock in the central core of Mount Adams north of the summit. We identify steep cliffs at the western edge of this zone as the likely source for future large debris flows. Water, and perhaps melted ice, is needed as a lubricant to transform debris avalanches into lahars. Therefore, knowing the distribution of both is important for hazard assessments. Over the low resistivity summit, the electromagnetic data detected ice with a thickness of 0 to about 80 m and an estimated volume of up to 0.1 km3. Over resistive ridges ice thicknesses could not be determined. The electromagnetic data also identified perched water tables in the brecciated core of the upper 300 m of the volcano

  8. Alteration of Bile Canalicular Enzymes in Cholestasis. A POSSIBLE CAUSE OF BILE SECRETORY FAILURE

    PubMed Central

    Simon, Francis R.; Arias, Irwin M.

    1973-01-01

    Bile secretory failure (cholestasis) may result from several possible mechanisms involved in bile secretion. We have examined the possibility that abnormalities in enzyme content, composition, and turnover of liver plasma membrane constituents are altered in cholestasis. Severe and mild cholestasis were produced by 5 days of bile duct ligation and ethinyl estradiol administration, respectively. Bile duct ligation but not ethinyl estradiol treatments was associated with elevations of the serum bilirubin level and 5′-nucleotidase activity. However, basal bile flow and bilirubin transport maximum (Tm) were significantly reduced after ethinyl estradiol treatment. Liver plasma membrane fractions rich in canalicular membranes were prepared from groups of rats in each of three categories; normal, after bile duct ligation, or ethinyl estradiol administration, and their respective controls. Electron microscopy and enzyme marker studies demonstrated plasma membrane fractions free of significant contamination. Plasma membrane fractions prepared from mild as well as severe cholestasis had increased alkaline phosphatase activity, and reduced 5′-nucleotidase and Mg2+-ATPase activities. Co2+-CMPase activity was unchanged. Kinetic analysis of 5′-nucleotidase and Mg2+-ATPase activities in plasma membrane fractions demonstrated reduced Vmaz (but unaltered Km). Reducted Vmaz was unrelated to addition in vitro of di-or trihydroxy bile salts or ethinyl estradiol and, therefore, suggests that reduced activities in cholestasis are due to decreased enzyme content. Cholestasis was not associated with changes in the synthesis or degradation rate of pulse-labeled plasma membrane proteins or alterations in the major protein bands separated on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Plasma membrane cholesterol, phospholipid, and neutral sugar content was unaltered, but sialic acid content was significantly increased in both forms of cholestasis. Alterations in

  9. CauseMap: fast inference of causality from complex time series.

    PubMed

    Maher, M Cyrus; Hernandez, Ryan D

    2015-01-01

    Background. Establishing health-related causal relationships is a central pursuit in biomedical research. Yet, the interdependent non-linearity of biological systems renders causal dynamics laborious and at times impractical to disentangle. This pursuit is further impeded by the dearth of time series that are sufficiently long to observe and understand recurrent patterns of flux. However, as data generation costs plummet and technologies like wearable devices democratize data collection, we anticipate a coming surge in the availability of biomedically-relevant time series data. Given the life-saving potential of these burgeoning resources, it is critical to invest in the development of open source software tools that are capable of drawing meaningful insight from vast amounts of time series data. Results. Here we present CauseMap, the first open source implementation of convergent cross mapping (CCM), a method for establishing causality from long time series data (≳25 observations). Compared to existing time series methods, CCM has the advantage of being model-free and robust to unmeasured confounding that could otherwise induce spurious associations. CCM builds on Takens' Theorem, a well-established result from dynamical systems theory that requires only mild assumptions. This theorem allows us to reconstruct high dimensional system dynamics using a time series of only a single variable. These reconstructions can be thought of as shadows of the true causal system. If reconstructed shadows can predict points from opposing time series, we can infer that the corresponding variables are providing views of the same causal system, and so are causally related. Unlike traditional metrics, this test can establish the directionality of causation, even in the presence of feedback loops. Furthermore, since CCM can extract causal relationships from times series of, e.g., a single individual, it may be a valuable tool to personalized medicine. We implement CCM in Julia, a

  10. Chronic hepcidin induction causes hyposideremia and alters the pattern of cellular iron accumulation in hemochromatotic mice.

    PubMed

    Viatte, Lydie; Nicolas, Gaël; Lou, Dan-Qing; Bennoun, Myriam; Lesbordes-Brion, Jeanne-Claire; Canonne-Hergaux, François; Schönig, Kai; Bujard, Hermann; Kahn, Axel; Andrews, Nancy C; Vaulont, Sophie

    2006-04-01

    We report the generation of a tetracycline-regulated (Tet ON) transgenic mouse model for acute and chronic expression of the iron regulatory peptide hepcidin in the liver. We demonstrate that short-term and long-term tetracycline-dependent activation of hepcidin in adult mice leads to hypoferremia and iron-limited erythropoiesis, respectively. This clearly establishes the key role of hepcidin in regulating the extracellular iron concentration. We previously demonstrated that, when expressed early in fetal development, constitutive transgenic hepcidin expression prevented iron accumulation in an Hfe-/- mouse model of hemochromatosis. We now explore the effect of chronic hepcidin expression in adult Hfe-/- mice that have already developed liver iron overload. We demonstrate that induction of chronic hepcidin expression in 2-month-old Hfe-/- mice alters their pattern of cellular iron accumulation, leading to increased iron in tissue macrophages and duodenal cells but less iron in hepatocytes. These hepcidin-induced changes in the pattern of cellular iron accumulation are associated with decreased expression of the iron exporter ferroportin in macrophages but no detectable alteration of ferroportin expression in the hepatocytes. We speculate that this change in iron homeostasis could offer a therapeutic advantage by protecting against damage to parenchymal cells. PMID:16339398

  11. An Unusual Cause of Altered Mental Status in Multiple Myeloma: An Extraosseous Manifestation.

    PubMed

    Jaruvongvanich, Veeravich; Spanuchart, Ittikorn; O-Charoen, Pichaya; Kitamura, Christian; Sumida, Lauren; Roytman, Marina

    2016-04-01

    Multiple myeloma typically presents as lytic bony lesions, hypercalcemia, anemia, and renal failure. Extraosseous manifestations are rare. We report on a patient who was recently diagnosed with multiple myeloma and completed the first cycle of bortezomib, dexamethasone, and palliative radiation therapy with good response. Two weeks after discharge, she became confused and was re-admitted. Despite treatment with lactulose and rifaximin, altered mental status worsened. Computer tomographic scan of abdomen showed hepatomegaly and numerous ill-defined small hyperdense nodules scattered throughout the liver. Liver biopsy demonstrated aggregation of plasma cell myeloma. Magnetic resonance imaging of brain revealed dural thickening. Patient's altered mental status was likely from leptomeningeal myelomatosis and hyperammonemic encephalopathy. Although extraosseous manifestations in multiple myeloma including liver and leptomeningeal involvement are rare, its incidence has increased. This condition portends a poor prognosis. The non-specific manifestations of extraosseous myeloma can be confused with complications of multiple sclerosis and lead to incorrect management, thus clinicians should be aware of these pathologies and perform proper diagnostic tests including imaging and tissue pathology. The most effective treatment is unknown, however bortezomib and thalidomide show promise. PMID:27099806

  12. An Unusual Cause of Altered Mental Status in Multiple Myeloma: An Extraosseous Manifestation

    PubMed Central

    Spanuchart, Ittikorn; O-charoen, Pichaya; Kitamura, Christian; Sumida, Lauren; Roytman, Marina

    2016-01-01

    Multiple myeloma typically presents as lytic bony lesions, hypercalcemia, anemia, and renal failure. Extraosseous manifestations are rare. We report on a patient who was recently diagnosed with multiple myeloma and completed the first cycle of bortezomib, dexamethasone, and palliative radiation therapy with good response. Two weeks after discharge, she became confused and was re-admitted. Despite treatment with lactulose and rifaximin, altered mental status worsened. Computer tomographic scan of abdomen showed hepatomegaly and numerous ill-defined small hyperdense nodules scattered throughout the liver. Liver biopsy demonstrated aggregation of plasma cell myeloma. Magnetic resonance imaging of brain revealed dural thickening. Patient's altered mental status was likely from leptomeningeal myelomatosis and hyperammonemic encephalopathy. Although extraosseous manifestations in multiple myeloma including liver and leptomeningeal involvement are rare, its incidence has increased. This condition portends a poor prognosis. The non-specific manifestations of extraosseous myeloma can be confused with complications of multiple sclerosis and lead to incorrect management, thus clinicians should be aware of these pathologies and perform proper diagnostic tests including imaging and tissue pathology. The most effective treatment is unknown, however bortezomib and thalidomide show promise. PMID:27099806

  13. Human papillomavirus causes an angiogenic switch in keratinocytes which is sufficient to alter endothelial cell behavior

    SciTech Connect

    Chen, W.; Li, F.; Mead, L.; White, H.; Walker, J.; Ingram, D.A.; Roman, A.

    2007-10-10

    One of the requirements for tumor growth is the ability to recruit a blood supply, a process known as angiogenesis. Angiogenesis begins early in the progression of cervical disease from mild to severe dysplasia and on to invasive cancer. We have previously reported that expression of human papillomavirus type 16 E6 and E7 (HPV16 E6E7) proteins in primary foreskin keratinocytes (HFKs) decreases expression of two inhibitors and increases expression of two angiogenic inducers [Toussaint-Smith, E., Donner, D.B., Roman, A., 2004. Expression of human papillomavirus type 16 E6 and E7 oncoproteins in primary foreskin keratinocytes is sufficient to alter the expression of angiogenic factors. Oncogene 23, 2988-2995]. Here we report that HPV-induced early changes in the keratinocyte phenotype are sufficient to alter endothelial cell behavior both in vitro and in vivo. Conditioned media from HPV16 E6E7 expressing HFKs as well as from human cervical keratinocytes containing the intact HPV16 were able to stimulate proliferation and migration of human microvascular endothelial cells. In addition, introduction of the conditioned media into immunocompetent mice using a Matrigel plug model resulted in a clear angiogenic response. These novel data support the hypothesis that HPV proteins contribute not only to the uncontrolled keratinocyte growth seen following HPV infection but also to the angiogenic response needed for tumor formation.

  14. Microscale mapping of alteration conditions and potential biosignatures in basaltic-ultramafic rocks on early Earth and beyond.

    PubMed

    Grosch, Eugene G; McLoughlin, Nicola; Lanari, Pierre; Erambert, Muriel; Vidal, Olivier

    2014-03-01

    Subseafloor environments preserved in Archean greenstone belts provide an analogue for investigating potential subsurface habitats on Mars. The c. 3.5-3.4 Ga pillow lava metabasalts of the mid-Archean Barberton greenstone belt, South Africa, have been argued to contain the earliest evidence for microbial subseafloor life. This includes candidate trace fossils in the form of titanite microtextures, and sulfur isotopic signatures of pyrite preserved in metabasaltic glass of the c. 3.472 Ga Hooggenoeg Formation. It has been contended that similar microtextures in altered martian basalts may represent potential extraterrestrial biosignatures of microbe-fluid-rock interaction. But despite numerous studies describing these putative early traces of life, a detailed metamorphic characterization of the microtextures and their host alteration conditions in the ancient pillow lava metabasites is lacking. Here, we present a new nondestructive technique with which to study the in situ metamorphic alteration conditions associated with potential biosignatures in mafic-ultramafic rocks of the Hooggenoeg Formation. Our approach combines quantitative microscale compositional mapping by electron microprobe with inverse thermodynamic modeling to derive low-temperature chlorite crystallization conditions. We found that the titanite microtextures formed under subgreenschist to greenschist facies conditions. Two chlorite temperature groups were identified in the maps surrounding the titanite microtextures and record peak metamorphic conditions at 315 ± 40°C (XFe3+(chlorite) = 25-34%) and lower-temperature chlorite veins/microdomains at T = 210 ± 40°C (lower XFe3+(chlorite) = 40-45%). These results provide the first metamorphic constraints in textural context on the Barberton titanite microtextures and thereby improve our understanding of the local preservation conditions of these potential biosignatures. We suggest that this approach may prove to be an important tool in future

  15. Lasting Effects of Instruction Guided by the Conflict Map: Experimental Study of Learning about the Causes of the Seasons

    ERIC Educational Resources Information Center

    Tsai, Chin-Chung; Chang, Chun-Yen

    2005-01-01

    This study was based on the framework of the "conflict map" to facilitate student conceptual learning about causes of the seasons. Instruction guided by the conflict map emphasizes not only the use of discrepant events, but also the resolution of conflict between students' alternative conceptions and scientific conceptions, using critical events…

  16. 44 CFR 65.12 - Revision of flood insurance rate maps to reflect base flood elevations caused by proposed...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Revision of flood insurance rate maps to reflect base flood elevations caused by proposed encroachments. 65.12 Section 65.12... INSURANCE AND HAZARD MITIGATION National Flood Insurance Program IDENTIFICATION AND MAPPING OF...

  17. 44 CFR 65.12 - Revision of flood insurance rate maps to reflect base flood elevations caused by proposed...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Revision of flood insurance rate maps to reflect base flood elevations caused by proposed encroachments. 65.12 Section 65.12... INSURANCE AND HAZARD MITIGATION National Flood Insurance Program IDENTIFICATION AND MAPPING OF...

  18. Mapping hydrothermal alteration using aircraft VNIR scanners at the Rosemont porphyry copper deposit. [Visible-Near Infrared

    NASA Technical Reports Server (NTRS)

    Sadowski, R. M.; Abrams, M. J.

    1983-01-01

    Two Visible-Near Infrared (VNIR) scanners, the NS-001 and the M2S, were flown over the Rosemont porphyry copper deposit as part of the NASA/JPL/GEOSAT test site program. This program was established to determine the feasibility and limitations of mapping hydrothermal alteration with multispectral scanners. Data from the NS-001 at 0.83 and 2.2 microns were used to identify Fe(3+) and OH enriched outcrops. These areas were then correlated with three alteration assemblages. The first correlation, hematite-epidote, was the most obvious and appeared as a strong ferric iron signature associated with hematite stained Cretaceous arkoses and andesites. The second correlation, qtz-sericite, showed a combined ferric-hydroxyl signature for a phyllicly altered quartz monzonite. The third correlation, skarn, was identified only after a review of calc-silicate mineral VNIR spectra. Altered limestones that outcrop west of the deposit have a similar ferric iron-hydroxyl signature as the quartz-sericite altered quartz monzonite. This skarn signature has been interpreted to indicate the presence of andradite, hydro-grossularite and idocrase. Data from the second scanner, M2S, was used to search for variation in ferric iron mineral type. Resulting imagery data indicated that hematite was the dominant ferric iron mineral present in the Rosemont area.

  19. Prenatal Cigarette Smoke Exposure Causes Hyperactivity and Agressive Behavior: Role of Altered Catcholamines and BDNF

    PubMed Central

    Yochum, Carrie; Doherty-Lyon, Shannon; Hoffman, Carol; Hossain, Muhammad M.; Zellikoff, Judith T.; Richardson, Jason R.

    2014-01-01

    Smoking during pregnancy is associated with a variety of untoward effects on the offspring. However, recent epidemiological studies have brought into question whether the association between neurobehavioral deficits and maternal smoking is causal. We utilized an animal model of maternal smoking to determine the effects of prenatal cigarette smoke (CS) exposure on neurobehavioral development. Pregnant mice were exposed to either filtered air or mainstream CS from gestation day (GD) 4 to parturition for 4 hr/d and 5 d/wk, with each exposure producing maternal plasma concentration of cotinine equivalent to smoking <1 pack of cigarettes per day (25 ng/ml plasma cotinine level). Pups were weaned at postnatal day (PND) 21 and behavior assessed on at 4 weeks of age and again at 4–6 months of age. Male, but not female, offspring of CS-exposed dams demonstrated a significant increase in locomotor activity during adolescence and adulthood that was ameliorated by methylphenidate treatment. Additionally, male offspring exhibited increased aggression, as evidenced by decreased latency to attack and number of attacks in a resident intruder task. These behavioral abnormalities were accompanied by a significant decrease in striatal and cortical dopamine and serotonin and a significant reduction in brain-derived neurotrophic factor (BDNF) mRNA and protein. Taken in concert, these data demonstrate that prenatal exposure to CS produces behavioral alterations in mice that are similar to those observed in epidemiological studies linking maternal smoking to neurodevelopmental disorders and suggest a role for monoaminergic and BDNF alterations in these effects. PMID:24486851

  20. MCP-1 deficiency causes altered inflammation with impaired skeletal muscle regeneration.

    PubMed

    Shireman, Paula K; Contreras-Shannon, Verónica; Ochoa, Oscar; Karia, Bijal P; Michalek, Joel E; McManus, Linda M

    2007-03-01

    We examined the role of MCP-1, a potent chemotactic and activating factor for macrophages, in perfusion, inflammation, and skeletal muscle regeneration post-ischemic injury. MCP-1-/- or C57Bl/6J control mice [wild-type (WT)] underwent femoral artery excision (FAE). Muscles were collected for histology, assessment of tissue chemokines, and activity measurements of lactate dehydrogenase (LDH) and myeloperoxidase. In MCP-1-/- mice, restoration of perfusion was delayed, and LDH and fiber size, indicators of muscle regeneration, were decreased. Altered inflammation was observed with increased neutrophil accumulation in MCP-1-/- versus WT mice at Days 1 and 3 (P< or =0.003), whereas fewer macrophages were present in MCP-1-/- mice at Day 3. As necrotic tissue was removed in WT mice, macrophages decreased (Day 7). In contrast, macrophage accumulation in MCP-1-/- was increased in association with residual necrotic tissue and impaired muscle regeneration. Consistent with altered inflammation, neutrophil chemotactic factors (keratinocyte-derived chemokine and macrophage inflammatory protein-2) were increased at Day 1 post-FAE. The macrophage chemotactic factor MCP-5 was increased significantly in WT mice at Day 3 compared with MCP-1-/- mice. However, at post-FAE Day 7, MCP-5 was significantly elevated in MCP-1-/- mice versus WT mice. Addition of exogenous MCP-1 did not induce proliferation in murine myoblasts (C2C12 cells) in vitro. MCP-1 is essential for reperfusion and the successful completion of normal skeletal muscle regeneration after ischemic tissue injury. Impaired muscle regeneration in MCP-1-/- mice suggests an important role for macrophages and MCP-1 in tissue reparative processes. PMID:17135576

  1. Prenatal cigarette smoke exposure causes hyperactivity and aggressive behavior: role of altered catecholamines and BDNF.

    PubMed

    Yochum, Carrie; Doherty-Lyon, Shannon; Hoffman, Carol; Hossain, Muhammad M; Zelikoff, Judith T; Richardson, Jason R

    2014-04-01

    Smoking during pregnancy is associated with a variety of untoward effects on the offspring. However, recent epidemiological studies have brought into question whether the association between neurobehavioral deficits and maternal smoking is causal. We utilized an animal model of maternal smoking to determine the effects of prenatal cigarette smoke (CS) exposure on neurobehavioral development. Pregnant mice were exposed to either filtered air or mainstream CS from gestation day (GD) 4 to parturition for 4h/d and 5d/wk, with each exposure producing maternal plasma concentration of cotinine equivalent to smoking <1 pack of cigarettes per day (25ng/ml plasma cotinine level). Pups were weaned at postnatal day (PND) 21 and behavior was assessed at 4weeks of age and again at 4-6months of age. Male, but not female, offspring of CS-exposed dams demonstrated a significant increase in locomotor activity during adolescence and adulthood that was ameliorated by methylphenidate treatment. Additionally, male offspring exhibited increased aggression, as evidenced by decreased latency to attack and number of attacks in a resident-intruder task. These behavioral abnormalities were accompanied by a significant decrease in striatal and cortical dopamine and serotonin and a significant reduction in brain-derived neurotrophic factor (BDNF) mRNA and protein. Taken in concert, these data demonstrate that prenatal exposure to CS produces behavioral alterations in mice that are similar to those observed in epidemiological studies linking maternal smoking to neurodevelopmental disorders. Further, these data also suggest a role for monaminergic and BDNF alterations in these effects. PMID:24486851

  2. Extensive alterations in DNA methylation and transcription in rice caused by introgression from Zizania latifolia.

    PubMed

    Liu, Zhenlan; Wang, Yongming; Shen, Ye; Guo, Wanli; Hao, Shui; Liu, Bao

    2004-03-01

    It has been demonstrated that insertion of foreign DNA into mammalian genome can profoundly alter the patterns of DNA methylation and transcription of the host genome. Introgression of alien DNA into plant genomes through sexual crossing and genetic engineering are commonly used in breeding, but it is not known if plant genomes have similar responses to alien DNA introgression as those of animals. Two stable rice lines with introgression from wild rice, Zizania latifolia, were analyzed for patterns of cytosine DNA methylation and transcription of a set of selected sequences, including cellular genes and transposable element (TE)-related DNA segments. In 21 of the 30 studied sequences, marked changes in DNA methylation and/or transcription were observed compared with those of the rice parent. In all analyzed sequences, the absence of Zizania homologues in the introgression lines was confirmed. No change in DNA methylation and expression patterns was detected in randomly selected individuals of the rice parent nor in two sibling lines without introgressed Zizania DNA. The changed methylation patterns in both introgression lines were stably maintained in all five randomly sampled individuals of a given line, as well as in selfed progenies of the lines. Changed patterns in methylation and expression were also found in an independently produced asymmetric somatic nuclear hybrid (SH6) of rice and Z. latifolia that involves a different rice genotype but also contains a small amount of Z. latifolia DNA integrated into the rice genome. Thus, we have demonstrated that alien DNA introgression into a plant genome can induce extensive alterations in DNA methylation and transcription of both cellular genes and TE-related DNA segments in a genotype-independent manner. PMID:15316290

  3. Brain studies may alter long-held concepts about likely causes of some voice disorders

    SciTech Connect

    Not Available

    1989-02-17

    Two voice disorders long considered to be psychological problems, stuttering and spasmodic dysphonia, have been shown in many persons to have a neurophysiological basis. Investigators at the 155th national meeting of the American Association for the Advancement of Science, in San Francisco, described their findings, which are based on new analytic techniques. The research is being done at the Dallas Center for Vocal Motor Control, Callier Center for Communication Disorders, University of Texas at Dallas Health Science Center. The technology employed to learn what's wrong with the brains, rather than the psyches, of persons with certain speech disorders includes magnetic resonance imaging (MRI), brain electrical activity mapping (BEAM), and single photon emission computerized tomography (SPECT). The results of applying these techniques are combined with quantitative behavioral measures of vocal and nonvocal motor control, language performance, and cognition to arrive at a better understanding of the problem.

  4. Induction of oxidative stress causes functional alterations in mouse urothelium via a TRPM8-mediated mechanism: implications for aging

    PubMed Central

    Nocchi, Linda; Daly, Donna M; Chapple, Christopher; Grundy, David

    2014-01-01

    The incidence of bladder conditions such as overactive bladder syndrome and its associated urinary incontinence is highly prevalent in the elderly. However, the mechanisms underlying these disorders are unclear. Studies suggest that the urothelium forms a ‘sensory network’ with the underlying innervation, alterations in which, could compromise bladder function. As the accumulation of reactive oxygen species can cause functional alterations with age, the aim of this study was to investigate whether oxidative stress alters urothelial sensory signalling and whether the mechanism underlying the effect of oxidative stress on the urothelium plays a role in aging. Five-month-old(young) and 24-month-old (aged) mice were used. H2O2, used to induce oxidative stress, resulted in an increase in bladder afferent nerve activity and urothelial intracellular calcium in preparations from young mice. These functional changes were concurrent with upregulation of TRPM8 in the urothelium. Moreover, application of a TRPM8 antagonist significantly attenuated the H2O2-induced calcium responses. Interestingly, an upregulation of TRPM8 was also found in the urothelium from aged mice, where high oxidative stress levels were observed, together with a greater calcium response to the TRPM8 agonist WS12. Furthermore, these calcium responses were attenuated by pretreatment with the antioxidant N-acetyl-cysteine. This study shows that oxidative stress affects urothelial function involving a TRPM8-mediated mechanism and these effects may have important implications for aging. These data provide an insight into the possible mechanisms by which oxidative stress causes physiological alterations in the bladder, which may also occur in other organs susceptible to aging. PMID:24593692

  5. Slow to fast alterations in skeletal muscle fibers caused by clenbuterol, a beta(2)-receptor agonist

    NASA Technical Reports Server (NTRS)

    Zeman, Richard J.; Ludemann, Robert; Easton, Thomas G.; Etlinger, Joseph D.

    1988-01-01

    The effects of a beta(2)-receptor agonist, clenbuterol, and a beta(2) antagonist, butoxamine, on the skeletal muscle fibers of rats were investigated. It was found that chronic treatment of rats with clenbuterol caused hypertrophy of histochemically identified fast-twitch, but not slow-twitch, fibers within the soleus, while in the extensor digitorum longus the mean areas of both fiber types were increased; in both muscles, the ratio of the number of fast-twitch to slow-twitch fibers was increased. In contrast, a treatment with butoxamine caused a reduction of the fast-twitch fiber size in both muscles, and the ratio of the fast-twitch to slow-twitch fibers was decreased.

  6. Mutations in the Microtubule-Associated Protein 1A (Map1a) Gene Cause Purkinje Cell Degeneration

    PubMed Central

    Liu, Ye; Lee, Jeong Woong

    2015-01-01

    The structural microtubule-associated proteins (MAPs) are critical for the organization of neuronal microtubules (MTs). Microtubule-associated protein 1A (MAP1A) is one of the most abundantly expressed MAPs in the mammalian brain. However, its in vivo function remains largely unknown. Here we describe a spontaneous mouse mutation, nm2719, which causes tremors, ataxia, and loss of cerebellar Purkinje neurons in aged homozygous mice. The nm2719 mutation disrupts the Map1a gene. We show that targeted deletion of mouse Map1a gene leads to similar neurodegenerative defects. Before neuron death, Map1a mutant Purkinje cells exhibited abnormal focal swellings of dendritic shafts and disruptions in axon initial segment (AIS) morphology. Furthermore, the MT network was reduced in the somatodendritic and AIS compartments, and both the heavy and light chains of MAP1B, another brain-enriched MAP, was aberrantly distributed in the soma and dendrites of mutant Purkinje cells. MAP1A has been reported to bind to the membrane-associated guanylate kinase (MAGUK) scaffolding proteins, as well as to MTs. Indeed, PSD-93, the MAGUK specifically enriched in Purkinje cells, was reduced in Map1a−/− Purkinje cells. These results demonstrate that MAP1A functions to maintain both the neuronal MT network and the level of PSD-93 in neurons of the mammalian brain. PMID:25788676

  7. Alteration Map Showing Major Faults and Veins and Associated Water-Quality Signatures of the Animas River Watershed Headwaters Near Silverton, Southwest Colorado

    USGS Publications Warehouse

    Bove, Dana J.; Yager, Douglas B.; Mast, M. Alisa; Dalton, J. Brad

    2007-01-01

    This map was produced to provide hard-copy and digital data for alteration assemblages in the historical mining area centered on the Tertiary San Juan and Silverton calderas. The data have direct application to geoenvironmental and mineral exploration objectives. This dataset represents alteration mapping for the upper Animas River watershed near Silverton, Colorado. The map is based on detailed 1:12,000-scale field mapping, X-ray diffraction (XRD) analysis, mineral mapping by remote sensing (AVIRIS) data, and 1:24,000-scale aerial photographic interpretation. Geologic structures were compiled and generalized from multiple published and unpublished sources (Burbank and Luedke, 1964; Steven and others, 1974; Luedke and Burbank 1975a, b; Lipman, 1976; Luedke and Burbank, 1987; Luedke, 1996) (see Index Map). Unpublished mapping of the Ironton quadrangle by D.J. Bove and J.P. Kurtz in 1997-1999 was included.

  8. Progressive alterations of central nervous system structure and function are caused by charged particle radiation

    NASA Astrophysics Data System (ADS)

    Nelson, G. A.; Cns Nscor Team

    A new NASA-sponsored program project (NSCOR) has been organized to conduct the first comprehensive investigation of the response of a mammalian brain structure (mouse hippocampus) to charged-particle radiation. The NSCOR collaboration has three main goals. The first goal is to quantify the time- and dose-dependent changes in cellular composition and architecture. By using stereology on preserved brains, subsets of cells (neurons, glia, endothelia and stem cells) will be quantified out to 2 years after irradiation with accelerated protons and iron ions. To further characterize changes in vasculature architecture a polymer infusion technique will be used to produce a three-dimensional vasculature cast that then will be mapped by x-ray tomography to determine topological changes, and microscopic infarcts associated with amyloid protein deposits. The 2nd goal is to quantify hippocampal function(s). The primary measurement of function will be extracellular electrical recordings from hippocampal ``brain slices'' that reflect underlying functions such as connectivity, action potential generation & conduction, and neurotransmitter formation, secretion, and uptake. Individual nerve membrane properties will be assessed by ``patch clamp'' recordings. Two non-invasive methods will evaluate brain function and the evolution of changes with time. Electroencephalograms will map macroscopic spontaneous electrical activity while two state-of-the-art MRI magnetization sequences will visualize and quantify local oxygen utilization and white matter fiber tracts structural integrity. To quantify the brains' overall performance under stress, animals will receive a systemic shock mediated by the immune system in the form of a reaction to lipopolysaccharide. A second strategy will employ the APP23 transgenic mouse that develops the pathological changes associated with Alzheimer's disease. Measurements of irradiated mice will determine whether radiation exposure affects the latency and

  9. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders

    PubMed Central

    Kleinridders, Andre; Cai, Weikang; Cappellucci, Laura; Ghazarian, Armen; Collins, William R.; Vienberg, Sara G.; Pothos, Emmanuel N.; Kahn, C. Ronald

    2015-01-01

    Diabetes and insulin resistance are associated with altered brain imaging, depression, and increased rates of age-related cognitive impairment. Here we demonstrate that mice with a brain-specific knockout of the insulin receptor (NIRKO mice) exhibit brain mitochondrial dysfunction with reduced mitochondrial oxidative activity, increased levels of reactive oxygen species, and increased levels of lipid and protein oxidation in the striatum and nucleus accumbens. NIRKO mice also exhibit increased levels of monoamine oxidase A and B (MAO A and B) leading to increased dopamine turnover in these areas. Studies in cultured neurons and glia cells indicate that these changes in MAO A and B are a direct consequence of loss of insulin signaling. As a result, NIRKO mice develop age-related anxiety and depressive-like behaviors that can be reversed by treatment with MAO inhibitors, as well as the tricyclic antidepressant imipramine, which inhibits MAO activity and reduces oxidative stress. Thus, insulin resistance in brain induces mitochondrial and dopaminergic dysfunction leading to anxiety and depressive-like behaviors, demonstrating a potential molecular link between central insulin resistance and behavioral disorders. PMID:25733901

  10. Cytotoxicity and alterations at transcriptional level caused by metals on fish erythrocytes in vitro.

    PubMed

    Morcillo, Patricia; Romero, Diego; Meseguer, José; Esteban, M Ángeles; Cuesta, Alberto

    2016-06-01

    The in vitro use of fish erythrocytes to test the toxicity of aquatic pollutants could be a valuable alternative to fish bioassays but has received little attention. In this study, erythrocytes from marine gilthead sea bream (Sparus aurata L.) and European sea bass (Dicentrarchus labrax L.) specimens were exposed for 24 h to Cd, Hg, Pb and As and the resulting cytotoxicity was evaluated. Exposure to metals produced a dose-dependent reduction in the viability, and mercury showed the highest toxicity followed by MeHg, Cd, As and Pb. Moreover, fish erythrocytes incubated with each one of the metals exhibited alteration in gene expression profile of metallothionein, superoxide dismutase, catalase, peroxiredoxin, glutathione reductase, heat shock proteins 70 and 90, Bcl2-associated X protein and calpain1 indicating cellular protection, stress and apoptosis death as well as oxidative stress. This study points to the benefits for evaluating the toxicological mechanisms of marine pollution using fish erythrocytes in vitro. PMID:26976014

  11. Microstructure alterations in beef intramuscular connective tissue caused by hydrodynamic pressure processing.

    PubMed

    Zuckerman, H; Bowker, B C; Eastridge, J S; Solomon, M B

    2013-11-01

    Scanning electron microscopy (SEM) was utilized to evaluate microstructural changes in intramuscular connective tissue of beef semimembranosus muscle subjected to hydrodynamic pressure processing (HDP). Samples were HDP treated in a plastic container (HDP-PC) or a steel commercial unit (HDP-CU). Control and HDP samples were obtained immediately post-treatment and after 14days of aging for SEM and Warner-Bratzler shear force (WBSF) analysis. Immediately post-treatment, HDP treated samples exhibited lower (P<0.01) WBSF than did controls. After aging, HDP-PC samples had lower (P<0.01) WBSF than that of aged controls. SEM analysis indicated that HDP-PC treatment disrupted the integrity of the collagen fibril network of the endomysium in both the non-aged and aged samples. Aging effects on the intramuscular connective tissue were observed in the HDP-PC and control samples. Both WBSF and connective tissue changes were greater in the HDP-PC than in the HDP-CU treated samples. Data suggest that shockwave alterations to connective tissue contribute to the meat tenderization of HDP. PMID:23803280

  12. Removal of GABAA Receptor γ2 Subunits from Parvalbumin Neurons Causes Wide-Ranging Behavioral Alterations

    PubMed Central

    Leppä, Elli; Linden, Anni-Maija; Vekovischeva, Olga Y.; Swinny, Jerome D.; Rantanen, Ville; Toppila, Esko; Höger, Harald; Sieghart, Werner; Wulff, Peer; Wisden, William; Korpi, Esa R.

    2011-01-01

    We investigated the behavioral significance of fast synaptic inhibition by αβγ2-type GABAA receptors on parvalbumin (Pv) cells. The GABAA receptor γ2 subunit gene was selectively inactivated in Pv-positive neurons by Cre/loxP recombination. The resulting Pv-Δγ2 mice were relatively healthy in the first postnatal weeks; but then as Cre started to be expressed, the mice progressively developed wide-ranging phenotypic alterations including low body weight, motor deficits and tremor, decreased anxiety levels, decreased pain sensitivity and deficient prepulse inhibition of the acoustic startle reflex and impaired spatial learning. Nevertheless, the deletion was not lethal, and mice did not show increased mortality even after one year. Autoradiography with t-butylbicyclophosphoro[35S]thionate suggested an increased amount of GABAA receptors with only α and β subunits in central nervous system regions that contained high levels of parvalbumin neurons. Using BAC-transgenesis, we reduced some of the Pv-Δγ2 phenotype by selectively re-expressing the wild-type γ2 subunit back into some Pv cells (reticular thalamic neurons and cerebellar Pv-positive neurons). This produced less severe impairments of motor skills and spatial learning compared with Pv-Δγ2 mice, but all other deficits remained. Our results reveal the widespread significance of fast GABAergic inhibition onto Pv-positive neurons for diverse behavioral modalities, such as motor coordination, sensorimotor integration, emotional behavior and nociception. PMID:21912668

  13. Hematological alterations in Astyanax altiparanae (Characidade) caused by Lernaea cyprinacea (Copepoda: Lernaeidae).

    PubMed

    Corrêa, Lincoln L; Tavares-Dias, Marcos; Ceccarelli, Paulo S; Adriano, Edson A

    2016-06-15

    This study describes the hematological alterations in Astyanax altiparanae associated with infestation with Lernaea cyprinacea. The study was carried out in a lagoon of the Mogi-Guaçu River, in the municipality of Pirassununga, in the state of São Paulo, Brazil. Of 46 fish examined, 45.6% had their integument infested by L. cyprinacea, with a mean intensity of 4.9 parasites per fish and a mean abundance of 2.2, giving a total of 139 recovered crustaceans. The abundance of L. cyprinacea correlated positively with the length and weight of the hosts, and the intensity of infestation was higher in female hosts. Macroscopic observation of lesions associated with the parasite showed a severe inflammatory reaction around the site of attachment of L. cyprinacea, associated with a lower relative condition factor and blood parameters. The hematocrit, number of red blood cells and thrombocytes were higher in non-parasitized than in parasitized fish. However, the hemoglobin concentration, hematimetric indices and the number of white blood cells were not influenced by infestation. PMID:27304872

  14. Subclinical mastitis causes alterations in nitric oxide, total oxidant and antioxidant capacity in cow milk.

    PubMed

    Atakisi, Onur; Oral, Hasan; Atakisi, Emine; Merhan, Oguz; Metin Pancarci, S; Ozcan, Ayla; Marasli, Saban; Polat, Bulent; Colak, Armagan; Kaya, Semra

    2010-08-01

    The aim of this study was to investigate total antioxidant (TAC), and oxidant capacity (TOC) and nitric oxide (NO) levels in milk of cows with subclinical mastitis. Brown Swiss and Holstein breed cows were screened with California Mastitis Test (CMT) to determine mammary glands with subclinical mastitis. Moreover, somatic cell counts (SCC) were determined electronically in all milk samples. Mammary quarters were classified as healthy (n=25) or subclinical mastitis (n=35) based on CMT scores and somatic cell count (SCC: < or =200,000/ml or >200,000/ml) in milk. Nitric oxide, TOC and SCC levels were significantly higher (p<0.001, p<0.005 and p<0.001, respectively) in milk from mammary quarters with subclinical mastitis compared to those from healthy mammary quarters. In conclusion, subclinical mastitis results in higher NO concentrations, TOC and SCC, and NO and TOC were positively correlated with SCC. Moreover, alterations in NO levels and TOC in milk could be used as an alternative diagnostic tool to screen for subclinical mastitis. PMID:20132956

  15. Hydrothermal alteration maps of the central and southern Basin and Range province of the United States compiled from Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data

    USGS Publications Warehouse

    Mars, John L.

    2013-01-01

    Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data and Interactive Data Language (IDL) logical operator algorithms were used to map hydrothermally altered rocks in the central and southern parts of the Basin and Range province of the United States. The hydrothermally altered rocks mapped in this study include (1) hydrothermal silica-rich rocks (hydrous quartz, chalcedony, opal, and amorphous silica), (2) propylitic rocks (calcite-dolomite and epidote-chlorite mapped as separate mineral groups), (3) argillic rocks (alunite-pyrophyllite-kaolinite), and (4) phyllic rocks (sericite-muscovite). A series of hydrothermal alteration maps, which identify the potential locations of hydrothermal silica-rich, propylitic, argillic, and phyllic rocks on Landsat Thematic Mapper (TM) band 7 orthorectified images, and geographic information systems shape files of hydrothermal alteration units are provided in this study.

  16. PORPHOBILINOGEN DEAMINASE Deficiency Alters Vegetative and Reproductive Development and Causes Lesions in Arabidopsis

    PubMed Central

    Quesada, Víctor; Hricová, Andrea; Ponce, María Rosa; Micol, José Luis

    2013-01-01

    The Arabidopsis rugosa1 (rug1) mutant has irregularly shaped leaves and reduced growth. In the absence of pathogens, leaves of rug1 plants have spontaneous lesions reminiscent of those seen in lesion-mimic mutants; rug1 plants also express cytological and molecular markers associated with defence against pathogens. These rug1 phenotypes are made stronger by dark/light transitions. The rug1 mutant also has delayed flowering time, upregulation of the floral repressor FLOWERING LOCUS C (FLC) and downregulation of the flowering promoters FT and SOC1/AGL20. Vernalization suppresses the late flowering phenotype of rug1 by repressing FLC. Microarray analysis revealed that 280 nuclear genes are differentially expressed between rug1 and wild type; almost a quarter of these genes are involved in plant defence. In rug1, the auxin response is also affected and several auxin-responsive genes are downregulated. We identified the RUG1 gene by map-based cloning and found that it encodes porphobilinogen deaminase (PBGD), also known as hydroxymethylbilane synthase, an enzyme of the tetrapyrrole biosynthesis pathway, which produces chlorophyll, heme, siroheme and phytochromobilin in plants. PBGD activity is reduced in rug1 plants, which accumulate porphobilinogen. Our results indicate that Arabidopsis PBGD deficiency impairs the porphyrin pathway and triggers constitutive activation of plant defence mechanisms leading to leaf lesions and affecting vegetative and reproductive development. PMID:23308205

  17. Tyrosinemia type I and not treatment with NTBC causes slower learning and altered behavior in mice.

    PubMed

    Hillgartner, Megan A; Coker, Sarah B; Koenig, Ashton E; Moore, Marissa E; Barnby, Elizabeth; MacGregor, Gordon G

    2016-09-01

    Tyrosinemia type I is a recessive inborn error of metabolism caused by mutations in the fumarylacetoacetate hydrolase (FAH) gene, coding for the final enzyme in the metabolism of tyrosine. This renders FAH nonfunctional and without treatment, toxic metabolites accumulate causing liver and kidney damage. Introduction of the drug NTBC in 2002 offered a treatment which inhibits an upstream enzyme, preventing the production of the toxic metabolites. There is now a long-term survival rate of greater than 90 % in children, but there are reports of lower cognitive function and IQ as well as schooling and behavioral problems in these children. We studied a mouse model of tyrosinemia type I to gain insight into the effects of tyrosinemia type I and treatment with NTBC on mouse learning, memory, and behavior. In the Barnes maze, visual and spatial cues can be used by mice to remember the location of a dark escape box. The primary time, distance, and strategy taken by the mice to locate the escape box is a measure of learning and memory. Our findings show that mice with tyrosinemia type I were slower to learn than wild-type mice treated with NTBC and made more mistakes, but were capable of learning and storing long-term memory. After learning the location of the target hole, mice with tyrosinemia type I respond differently to a change in location and were less flexible in learning the new target hole location. Our findings suggest that this slower learning and cognitive difference is caused by tyrosinemia type I and not by the treatment with NTBC. PMID:27271696

  18. Organ-specific alterations in tobacco transcriptome caused by the PVX-derived P25 silencing suppressor transgene

    PubMed Central

    2013-01-01

    Background RNA silencing affects a broad range of regulatory processes in all eukaryotes ranging from chromatin structure maintenance to transcriptional and translational regulation and longevity of the mRNAs. Particularly in plants, it functions as the major defense mechanism against viruses. To counter-act this defense, plant viruses produce suppressors of RNA silencing (Viral suppressors of RNA silencing, VSRSs), which are essential for viruses to invade their specific host plants. Interactions of these VSRSs with the hosts’ silencing pathways, and their direct and indirect interference with different cellular regulatory networks constitute one of the main lines of the molecular virus-host interactions. Here we have used a microarray approach to study the effects of the Potato virus X Potexvirus (PVX)-specific P25 VSRS protein on the transcript profile of tobacco plants, when expressed as a transgene in these plants. Results The expression of the PVX-specific P25 silencing suppressor in transgenic tobacco plants caused significant up-regulation of 1350 transcripts, but down-regulation of only five transcripts in the leaves, and up- and down-regulation of 51 and 13 transcripts, respectively, in the flowers of these plants, as compared to the wild type control plants. Most of the changes occurred in the transcripts related to biotic and abiotic stresses, transcription regulation, signaling, metabolic pathways and cell wall modifications, and many of them appeared to be induced through up-regulation of the signaling pathways regulated by ethylene, jasmonic acid and salicylic acid. Correlations of these alterations with the protein profile and related biological functions were analyzed. Surprisingly, they did not cause significant alterations in the protein profile, and caused only very mild alteration in the phenotype of the P25-expressing transgenic plants. Conclusion Expression of the PVX-specific P25 VSRS protein causes major alterations in the transcriptome

  19. Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence?

    PubMed

    Lean, M E J; Malkova, D

    2016-04-01

    The aim of this article is to review the research into the main peripheral appetite signals altered in human obesity, together with their modifications after body weight loss with diet and exercise and after bariatric surgery, which may be relevant to strategies for obesity treatment. Body weight homeostasis involves the gut-brain axis, a complex and highly coordinated system of peripheral appetite hormones and centrally mediated neuronal regulation. The list of peripheral anorexigenic and orexigenic physiological factors in both animals and humans is intimidating and expanding, but anorexigenic glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY) and orexigenic ghrelin from the gastrointestinal tract, pancreatic polypeptide (PP) from the pancreas and anorexigenic leptin from adiposites remain the most widely studied hormones. Homeostatic control of food intake occurs in humans, although its relative importance for eating behaviour is uncertain, compared with social and environmental influences. There are perturbations in the gut-brain axis in obese compared with lean individuals, as well as in weight-reduced obese individuals. Fasting and postprandial levels of gut hormones change when obese individuals lose weight, either with surgical or with dietary and/or exercise interventions. Diet-induced weight loss results in long-term changes in appetite gut hormones, postulated to favour increased appetite and weight regain while exercise programmes modify responses in a direction expected to enhance satiety and permit weight loss and/or maintenance. Sustained weight loss achieved by bariatric surgery may in part be mediated via favourable changes to gut hormones. Future work will be necessary to fully elucidate the role of each element of the axis, and whether modifying these signals can reduce the risk of obesity. PMID:26499438

  20. Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence?

    PubMed Central

    Lean, M E J; Malkova, D

    2016-01-01

    The aim of this article is to review the research into the main peripheral appetite signals altered in human obesity, together with their modifications after body weight loss with diet and exercise and after bariatric surgery, which may be relevant to strategies for obesity treatment. Body weight homeostasis involves the gut–brain axis, a complex and highly coordinated system of peripheral appetite hormones and centrally mediated neuronal regulation. The list of peripheral anorexigenic and orexigenic physiological factors in both animals and humans is intimidating and expanding, but anorexigenic glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY) and orexigenic ghrelin from the gastrointestinal tract, pancreatic polypeptide (PP) from the pancreas and anorexigenic leptin from adiposites remain the most widely studied hormones. Homeostatic control of food intake occurs in humans, although its relative importance for eating behaviour is uncertain, compared with social and environmental influences. There are perturbations in the gut–brain axis in obese compared with lean individuals, as well as in weight-reduced obese individuals. Fasting and postprandial levels of gut hormones change when obese individuals lose weight, either with surgical or with dietary and/or exercise interventions. Diet-induced weight loss results in long-term changes in appetite gut hormones, postulated to favour increased appetite and weight regain while exercise programmes modify responses in a direction expected to enhance satiety and permit weight loss and/or maintenance. Sustained weight loss achieved by bariatric surgery may in part be mediated via favourable changes to gut hormones. Future work will be necessary to fully elucidate the role of each element of the axis, and whether modifying these signals can reduce the risk of obesity. PMID:26499438

  1. Household Air Pollution Causes Dose-Dependent Inflammation and Altered Phagocytosis in Human Macrophages

    PubMed Central

    Fullerton, Duncan G.; Scriven, James; Aljurayyan, Abdullah N.; Mzinza, David; Barrett, Steve; Wright, Adam K. A.; Wootton, Daniel G.; Glennie, Sarah J.; Baple, Katy; Knott, Amy; Mortimer, Kevin; Russell, David G.; Heyderman, Robert S.; Gordon, Stephen B.

    2015-01-01

    Three billion people are exposed to household air pollution from biomass fuel use. Exposure is associated with higher incidence of pneumonia, and possibly tuberculosis. Understanding mechanisms underlying these defects would improve preventive strategies. We used human alveolar macrophages obtained from healthy Malawian adults exposed naturally to household air pollution and compared them with human monocyte-derived macrophages exposed in vitro to respirable-sized particulates. Cellular inflammatory response was assessed by IL-6 and IL-8 production in response to particulate challenge; phagosomal function was tested by uptake and oxidation of fluorescence-labeled beads; ingestion and killing of Streptococcus pneumoniae and Mycobacterium tuberculosis were measured by microscopy and quantitative culture. Particulate ingestion was quantified by digital image analysis. We were able to reproduce the carbon loading of naturally exposed alveolar macrophages by in vitro exposure of monocyte-derived macrophages. Fine carbon black induced IL-8 release from monocyte-derived and alveolar macrophages (P < 0.05) with similar magnitude responses (log10 increases of 0.93 [SEM = 0.2] versus 0.74 [SEM = 0.19], respectively). Phagocytosis of pneumococci and mycobacteria was impaired with higher particulate loading. High particulate loading corresponded with a lower oxidative burst capacity (P = 0.0015). There was no overall effect on killing of M. tuberculosis. Alveolar macrophage function is altered by particulate loading. Our macrophage model is comparable morphologically to the in vivo uptake of particulates. Wood smoke–exposed cells demonstrate reduced phagocytosis, but unaffected mycobacterial killing, suggesting defects related to chronic wood smoke inhalation limited to specific innate immune functions. PMID:25254931

  2. Household air pollution causes dose-dependent inflammation and altered phagocytosis in human macrophages.

    PubMed

    Rylance, Jamie; Fullerton, Duncan G; Scriven, James; Aljurayyan, Abdullah N; Mzinza, David; Barrett, Steve; Wright, Adam K A; Wootton, Daniel G; Glennie, Sarah J; Baple, Katy; Knott, Amy; Mortimer, Kevin; Russell, David G; Heyderman, Robert S; Gordon, Stephen B

    2015-05-01

    Three billion people are exposed to household air pollution from biomass fuel use. Exposure is associated with higher incidence of pneumonia, and possibly tuberculosis. Understanding mechanisms underlying these defects would improve preventive strategies. We used human alveolar macrophages obtained from healthy Malawian adults exposed naturally to household air pollution and compared them with human monocyte-derived macrophages exposed in vitro to respirable-sized particulates. Cellular inflammatory response was assessed by IL-6 and IL-8 production in response to particulate challenge; phagosomal function was tested by uptake and oxidation of fluorescence-labeled beads; ingestion and killing of Streptococcus pneumoniae and Mycobacterium tuberculosis were measured by microscopy and quantitative culture. Particulate ingestion was quantified by digital image analysis. We were able to reproduce the carbon loading of naturally exposed alveolar macrophages by in vitro exposure of monocyte-derived macrophages. Fine carbon black induced IL-8 release from monocyte-derived and alveolar macrophages (P < 0.05) with similar magnitude responses (log10 increases of 0.93 [SEM = 0.2] versus 0.74 [SEM = 0.19], respectively). Phagocytosis of pneumococci and mycobacteria was impaired with higher particulate loading. High particulate loading corresponded with a lower oxidative burst capacity (P = 0.0015). There was no overall effect on killing of M. tuberculosis. Alveolar macrophage function is altered by particulate loading. Our macrophage model is comparable morphologically to the in vivo uptake of particulates. Wood smoke-exposed cells demonstrate reduced phagocytosis, but unaffected mycobacterial killing, suggesting defects related to chronic wood smoke inhalation limited to specific innate immune functions. PMID:25254931

  3. Cancer causes increased mortality and is associated with altered apoptosis in murine sepsis

    PubMed Central

    Fox, Amy C.; Robertson, Charles M.; Belt, Brian; Clark, Andrew T.; Chang, Katherine C.; Leathersich, Ann M.; Dominguez, Jessica A.; Perrone, Erin E.; Dunne, W. Michael; Hotchkiss, Richard S.; Buchman, Timothy G.; Linehan, David C.; Coopersmith, Craig M.

    2009-01-01

    alterations in both intestinal epithelial and lymphocyte apoptosis may help explain this differential response. PMID:20009755

  4. Hypertension Does Not Alter the Increase in Cardiac Baroreflex Sensitivity Caused by Moderate Cold Exposure.

    PubMed

    Hintsala, Heidi E; Kiviniemi, Antti M; Tulppo, Mikko P; Helakari, Heta; Rintamäki, Hannu; Mäntysaari, Matti; Herzig, Karl-Heinz; Keinänen-Kiukaanniemi, Sirkka; Jaakkola, Jouni J K; Ikäheimo, Tiina M

    2016-01-01

    Exposure to cold increases blood pressure and may contribute to higher wintertime cardiovascular morbidity and mortality in hypertensive people, but the mechanisms are not well-established. While hypertension does not alter responses of vagally-mediated heart rate variability to cold, it is not known how hypertension modifies baroreflex sensitivity (BRS) and blood pressure variability during cold exposure. Our study assessed this among untreated hypertensive men during short-term exposure comparable to habitual winter time circumstances in subarctic areas. We conducted a population-based recruitment of 24 untreated hypertensive and 17 men without hypertension (age 55-65 years) who underwent a whole-body cold exposure (-10°C, wind 3 m/s, winter clothes, 15 min, standing). Electrocardiogram and continuous blood pressure were measured to compute spectral powers of systolic blood pressure and heart rate variability at low (0.04-0.15 Hz) and high frequency (0.15-0.4 Hz) and spontaneous BRS at low frequency (LF). Comparable increases in BRS were detected in hypertensive men, from 2.6 (2.0, 4.2) to 3.8 (2.5, 5.1) ms/mmHg [median (interquartile range)], and in control group, from 4.3 (2.7, 5.0) to 4.4 (3.1, 7.1) ms/mmHg. Instead, larger increase (p < 0.05) in LF blood pressure variability was observed in control group; response as median (interquartile range): 8 (2, 14) mmHg(2), compared with hypertensive group [0 (-13, 20) mmHg(2)]. Untreated hypertension does not disturb cardiovascular protective mechanisms during moderate cold exposure commonly occurring in everyday life. Blunted response of the estimate of peripheral sympathetic modulation may indicate higher tonic sympathetic activity and decreased sympathetic responsiveness to cold in hypertension. PMID:27313543

  5. Hypertension Does Not Alter the Increase in Cardiac Baroreflex Sensitivity Caused by Moderate Cold Exposure

    PubMed Central

    Hintsala, Heidi E.; Kiviniemi, Antti M.; Tulppo, Mikko P.; Helakari, Heta; Rintamäki, Hannu; Mäntysaari, Matti; Herzig, Karl-Heinz; Keinänen-Kiukaanniemi, Sirkka; Jaakkola, Jouni J. K.; Ikäheimo, Tiina M.

    2016-01-01

    Exposure to cold increases blood pressure and may contribute to higher wintertime cardiovascular morbidity and mortality in hypertensive people, but the mechanisms are not well-established. While hypertension does not alter responses of vagally-mediated heart rate variability to cold, it is not known how hypertension modifies baroreflex sensitivity (BRS) and blood pressure variability during cold exposure. Our study assessed this among untreated hypertensive men during short-term exposure comparable to habitual winter time circumstances in subarctic areas. We conducted a population-based recruitment of 24 untreated hypertensive and 17 men without hypertension (age 55–65 years) who underwent a whole-body cold exposure (−10°C, wind 3 m/s, winter clothes, 15 min, standing). Electrocardiogram and continuous blood pressure were measured to compute spectral powers of systolic blood pressure and heart rate variability at low (0.04–0.15 Hz) and high frequency (0.15–0.4 Hz) and spontaneous BRS at low frequency (LF). Comparable increases in BRS were detected in hypertensive men, from 2.6 (2.0, 4.2) to 3.8 (2.5, 5.1) ms/mmHg [median (interquartile range)], and in control group, from 4.3 (2.7, 5.0) to 4.4 (3.1, 7.1) ms/mmHg. Instead, larger increase (p < 0.05) in LF blood pressure variability was observed in control group; response as median (interquartile range): 8 (2, 14) mmHg2, compared with hypertensive group [0 (−13, 20) mmHg2]. Untreated hypertension does not disturb cardiovascular protective mechanisms during moderate cold exposure commonly occurring in everyday life. Blunted response of the estimate of peripheral sympathetic modulation may indicate higher tonic sympathetic activity and decreased sympathetic responsiveness to cold in hypertension. PMID:27313543

  6. Haematologic alterations caused by Ipomoea carnea in experimental poisoning of guinea pig.

    PubMed

    García, Enrique N; Aguirre, María V; Gimeno, Eduardo J; Rios, Elvio E; Acosta, Ofelia C; Cholich, Luciana A

    2015-10-01

    Ipomoea carnea subsp. fistulosa (Convolvulaceae) causes poisoning of goats, sheep and cattle in many tropical and subtropical countries. The pathophysiology of this poisoning mainly involves an abnormal glycoprotein metabolism. The aim of this study was to describe the potential toxicity of I. carnea in a guinea pig model through its effect on hematopoiesis in a time course study of 40 days. Experimental poisoning was achieved by feeding animals with "small balls" prepared with milled leaves of I. carnea mixed with commercial crushed pellets for rodents. Hematologic and biochemical parameters, bone marrow and spleencellularities, histopathologic evaluations and lectin-histochemistrywere performed during the scheduled time of the study.The treatment with "small balls" caused significant changes in the weight of spleen, a notable decrease in peripheral red blood cells, and concomitantwith morphological and histopathologicalalterationsin hematopoietic tissues. Overall, the present study suggested that 20 days ofthis treatmentcouldbe enough to develop bone marrow hypoplasia and vacuolation of white cells of spleen, blood and lymph nodes with a transient erythropoietic contribution of the splenic niche.Moreover, this work provides a cheap and simple method for detecting preclinical cases of intoxication by I. carnea in livestock. PMID:26208869

  7. Phosphatidylinositol 4,5-bisphosphate alters pharmacological selectivity for epilepsy-causing KCNQ potassium channels

    PubMed Central

    Zhou, Pingzheng; Yu, Haibo; Gu, Min; Nan, Fa-jun; Gao, Zhaobing; Li, Min

    2013-01-01

    Pharmacological augmentation of neuronal KCNQ muscarinic (M) currents by drugs such as retigabine (RTG) represents a first-in-class therapeutic to treat certain hyperexcitatory diseases by dampening neuronal firing. Whereas all five potassium channel subtypes (KCNQ1–KCNQ5) are found in the nervous system, KCNQ2 and KCNQ3 are the primary players that mediate M currents. We investigated the plasticity of subtype selectivity by two M current effective drugs, retigabine and zinc pyrithione (ZnPy). Retigabine is more effective on KCNQ3 than KCNQ2, whereas ZnPy is more effective on KCNQ2 with no detectable effect on KCNQ3. In neurons, activation of muscarinic receptor signaling desensitizes effects by retigabine but not ZnPy. Importantly, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) causes KCNQ3 to become sensitive to ZnPy but lose sensitivity to retigabine. The dynamic shift of pharmacological selectivity caused by PIP2 may be induced orthogonally by voltage-sensitive phosphatase, or conversely, abolished by mutating a PIP2 site within the S4–S5 linker of KCNQ3. Therefore, whereas drug-channel binding is a prerequisite, the drug selectivity on M current is dynamic and may be regulated by receptor signaling pathways via PIP2. PMID:23650395

  8. Phosphatidylinositol 4,5-bisphosphate alters pharmacological selectivity for epilepsy-causing KCNQ potassium channels.

    PubMed

    Zhou, Pingzheng; Yu, Haibo; Gu, Min; Nan, Fa-jun; Gao, Zhaobing; Li, Min

    2013-05-21

    Pharmacological augmentation of neuronal KCNQ muscarinic (M) currents by drugs such as retigabine (RTG) represents a first-in-class therapeutic to treat certain hyperexcitatory diseases by dampening neuronal firing. Whereas all five potassium channel subtypes (KCNQ1-KCNQ5) are found in the nervous system, KCNQ2 and KCNQ3 are the primary players that mediate M currents. We investigated the plasticity of subtype selectivity by two M current effective drugs, retigabine and zinc pyrithione (ZnPy). Retigabine is more effective on KCNQ3 than KCNQ2, whereas ZnPy is more effective on KCNQ2 with no detectable effect on KCNQ3. In neurons, activation of muscarinic receptor signaling desensitizes effects by retigabine but not ZnPy. Importantly, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) causes KCNQ3 to become sensitive to ZnPy but lose sensitivity to retigabine. The dynamic shift of pharmacological selectivity caused by PIP2 may be induced orthogonally by voltage-sensitive phosphatase, or conversely, abolished by mutating a PIP2 site within the S4-S5 linker of KCNQ3. Therefore, whereas drug-channel binding is a prerequisite, the drug selectivity on M current is dynamic and may be regulated by receptor signaling pathways via PIP2. PMID:23650395

  9. Altering context speech rate can cause words to appear or disappear.

    PubMed

    Dilley, Laura C; Pitt, Mark A

    2010-11-01

    Speech is produced over time, and this makes sensitivity to timing between speech events crucial for understanding language. Two experiments investigated whether perception of function words (e.g., or, are) is rate dependent in casual speech, which often contains phonetic segments that are spectrally quite reduced. In Experiment 1, talkers spoke sentences containing a target function word; slowing talkers' speech rate around this word caused listeners to perceive sentences as lacking the word (e.g., leisure or time was perceived as leisure time). In Experiment 2, talkers spoke matched sentences lacking a function word; speeding talkers' speech rate around the region in which the function word had been embedded in Experiment 1 caused listeners to perceive a function word that was never spoken (e.g., leisure time was perceived as leisure or time). The results suggest that listeners formed expectancies based on speech rate, and these expectancies influenced the number of words and word boundaries perceived. These findings may help explain the robustness of speech recognition when speech signals are distorted (e.g., because of a casual speaking style). PMID:20876883

  10. Mapping QTL conferring resistance in maize to gray leaf spot disease caused by Cercospora zeina

    PubMed Central

    2014-01-01

    Background Gray leaf spot (GLS) is a globally important foliar disease of maize. Cercospora zeina, one of the two fungal species that cause the disease, is prevalent in southern Africa, China, Brazil and the eastern corn belt of the USA. Identification of QTL for GLS resistance in subtropical germplasm is important to support breeding programmes in developing countries where C. zeina limits production of this staple food crop. Results A maize RIL population (F7:S6) from a cross between CML444 and SC Malawi was field-tested under GLS disease pressure at five field sites over three seasons in KwaZulu-Natal, South Africa. Thirty QTL identified from eleven field trials (environments) were consolidated to seven QTL for GLS resistance based on their expression in at least two environments and location in the same core maize bins. Four GLS resistance alleles were derived from the more resistant parent CML444 (bin 1.10, 4.08, 9.04/9.05, 10.06/10.07), whereas the remainder were from SC Malawi (bin 6.06/6.07, 7.02/7.03, 9.06). QTLs in bin 4.08 and bin 6.06/6.07 were also detected as joint QTLs, each explained more than 11% of the phenotypic variation, and were identified in four and seven environments, respectively. Common markers were used to allocate GLS QTL from eleven previous studies to bins on the IBM2005 map, and GLS QTL “hotspots” were noted. Bin 4.08 and 7.02/7.03 GLS QTL from this study overlapped with hotspots, whereas the bin 6.06/6.07 and bin 9.06 QTLs appeared to be unique. QTL for flowering time (bin 1.07, 4.09) in this population did not correspond to QTL for GLS resistance. Conclusions QTL mapping of a RIL population from the subtropical maize parents CML444 and SC Malawi identified seven QTL for resistance to gray leaf spot disease caused by C. zeina. These QTL together with QTL from eleven studies were allocated to bins on the IBM2005 map to provide a basis for comparison. Hotspots of GLS QTL were identified on chromosomes one, two, four, five and

  11. Exposure to the BPA-Substitute Bisphenol S Causes Unique Alterations of Germline Function

    PubMed Central

    Chen, Yichang; Qiu, Zhiqun; Lee, Dong Yeon; Telesca, Donatello; Yang, Xia; Allard, Patrick

    2016-01-01

    Concerns about the safety of Bisphenol A, a chemical found in plastics, receipts, food packaging and more, have led to its replacement with substitutes now found in a multitude of consumer products. However, several popular BPA-free alternatives, such as Bisphenol S, share a high degree of structural similarity with BPA, suggesting that these substitutes may disrupt similar developmental and reproductive pathways. We compared the effects of BPA and BPS on germline and reproductive functions using the genetic model system Caenorhabditis elegans. We found that, similarly to BPA, BPS caused severe reproductive defects including germline apoptosis and embryonic lethality. However, meiotic recombination, targeted gene expression, whole transcriptome and ontology analyses as well as ToxCast data mining all indicate that these effects are partly achieved via mechanisms distinct from BPAs. These findings therefore raise new concerns about the safety of BPA alternatives and the risk associated with human exposure to mixtures. PMID:27472198

  12. Alterations to the remote control of Shh gene expression cause congenital abnormalities.

    PubMed

    Hill, Robert E; Lettice, Laura A

    2013-01-01

    Multi-species conserved non-coding elements occur in the vertebrate genome and are clustered in the vicinity of developmentally regulated genes. Many are known to act as cis-regulators of transcription and may reside at long distances from the genes they regulate. However, the relationship of conserved sequence to encoded regulatory information and indeed, the mechanism by which these contribute to long-range transcriptional regulation is not well understood. The ZRS, a highly conserved cis-regulator, is a paradigm for such long-range gene regulation. The ZRS acts over approximately 1 Mb to control spatio-temporal expression of Shh in the limb bud and mutations within it result in a number of limb abnormalities, including polydactyly, tibial hypoplasia and syndactyly. We describe the activity of this developmental regulator and discuss a number of mechanisms by which regulatory mutations in this enhancer function to cause congenital abnormalities. PMID:23650631

  13. Methods to evaluate alterations in polyamine metabolism caused by Helicobacter pylori infection.

    PubMed

    Gobert, Alain P; Chaturvedi, Rupesh; Wilson, Keith T

    2011-01-01

    Helicobacter pylori is a Gram-negative bacteria that infects the human stomach of half of the world's -population. Colonization is followed by infiltration of the gastric mucosa by lymphocytes and myeloid cells. These cells are activated by various bacterial factors, causing them to produce immune/inflammatory mediators, including reactive nitrogen species and polyamines that contribute to cellular damage and the pathogenesis of H. pylori-associated gastric cancer. In vitro experiments have revealed that H. pylori induces macrophage polyamine production by upregulation of the arginase 2/ornithine decarboxylase (ODC) metabolic pathway and enhances hydrogen peroxide synthesis through the activity of spermidine oxidase (SMO). In this chapter, we present a survey of the methods used to analyze the induction and the role of the enzymes related to polyamine metabolism, i.e., arginase, ODC, and SMO in H. pylori-infected macrophages. PMID:21318889

  14. Alterations to the remote control of Shh gene expression cause congenital abnormalities

    PubMed Central

    Hill, Robert E.; Lettice, Laura A.

    2013-01-01

    Multi-species conserved non-coding elements occur in the vertebrate genome and are clustered in the vicinity of developmentally regulated genes. Many are known to act as cis-regulators of transcription and may reside at long distances from the genes they regulate. However, the relationship of conserved sequence to encoded regulatory information and indeed, the mechanism by which these contribute to long-range transcriptional regulation is not well understood. The ZRS, a highly conserved cis-regulator, is a paradigm for such long-range gene regulation. The ZRS acts over approximately 1 Mb to control spatio-temporal expression of Shh in the limb bud and mutations within it result in a number of limb abnormalities, including polydactyly, tibial hypoplasia and syndactyly. We describe the activity of this developmental regulator and discuss a number of mechanisms by which regulatory mutations in this enhancer function to cause congenital abnormalities. PMID:23650631

  15. Exposure to the BPA-Substitute Bisphenol S Causes Unique Alterations of Germline Function.

    PubMed

    Chen, Yichang; Shu, Le; Qiu, Zhiqun; Lee, Dong Yeon; Settle, Sara J; Que Hee, Shane; Telesca, Donatello; Yang, Xia; Allard, Patrick

    2016-07-01

    Concerns about the safety of Bisphenol A, a chemical found in plastics, receipts, food packaging and more, have led to its replacement with substitutes now found in a multitude of consumer products. However, several popular BPA-free alternatives, such as Bisphenol S, share a high degree of structural similarity with BPA, suggesting that these substitutes may disrupt similar developmental and reproductive pathways. We compared the effects of BPA and BPS on germline and reproductive functions using the genetic model system Caenorhabditis elegans. We found that, similarly to BPA, BPS caused severe reproductive defects including germline apoptosis and embryonic lethality. However, meiotic recombination, targeted gene expression, whole transcriptome and ontology analyses as well as ToxCast data mining all indicate that these effects are partly achieved via mechanisms distinct from BPAs. These findings therefore raise new concerns about the safety of BPA alternatives and the risk associated with human exposure to mixtures. PMID:27472198

  16. Permeability Evolution of Fractured Anhydrite Caused by Chemical and Mechanical Alteration

    NASA Astrophysics Data System (ADS)

    Detwiler, R. L.; Elkhoury, J. E.; Ameli, P.

    2011-12-01

    Geologic carbon sequestration requires competent structural seals (caprock) to prevent leakage over decadal time scales. Injection of large volumes of CO2 perturbs the target formation from chemical and mechanical equilibrium leading to the possible creation or enhancement of leakage pathways. We investigate the potential for leakage pathways (fractures) to grow over time under reservoir conditions in a series of anhydrite (Ca2SO4) cores. To simulate a potential leakage event in the laboratory, we fractured and jacketed the cores, and placed them in a flow-through reactor vessel. A high-pressure syringe pump applied confining stresses ranging from 7 to 17 MPa and another syringe pump pushed water through the sample at a constant flow rate with pressure control at the outlet. Effluent was sampled periodically and analyzed for Ca2+ and SO42- using an ion chromatograph. Before and after each experiment, we characterized the surfaces of the fractures using a high-resolution optical profilometer and a scanning electron microscope. Careful alignment of the surfaces during optical profiling allowed reproduction of the fracture aperture before and after each experiment. We present results from several experiments each carried out under different conditions in similar fractured anhydrite cores. One involved a well-mated pre-existing fracture and results showed that the permeability of the fractured core was similar to the intact rock matrix (O(10-18 m2); chemical alteration of the core was largely limited to the inflow face of the core and the fracture surfaces remained largely unaltered. To enhance permeability during subsequent experiments, we imposed a small (380 μm) shear displacement between the fracture surfaces resulting in a four-order-of-magnitude increase in initial permeability. The first of these was run at a constant flow rate of 0.6 ml/min for a period of 7 days. The measured pressure gradient within the core increased slowly for a period of 4 days followed

  17. Applied DC magnetic fields cause alterations in the time of cell divisions and developmental abnormalities in early sea urchin embryos

    SciTech Connect

    Levin, M.; Ernst, S.G.

    1997-05-01

    Most work on magnetic field effects focuses on AC fields. The present study demonstrates that exposure to medium-strength (10 mT--0.1 T) static magnetic fields can alter the early embryonic development of two species of sea urchin embryos. Batches of fertilized eggs from two species of urchin were exposed to fields produced by permanent magnets. Samples of the continuous cultures were scored for the timing of the first two cell divisions, time of hatching, and incidence of exogastrulation. It was found that static fields delay the onset of mitosis in both species by an amount dependent on the exposure timing relative to fertilization. The exposure time that caused the maximum effect differed between the two species. Thirty millitesla fields, but not 15 mT fields, caused an eightfold increase in the incidence of exogastrulation in Lytechinus pictus, whereas neither of these fields produced exogastrulation in Strongylocentrotus purpuratus.

  18. Alteration of the retinotectal map in Xenopus by antibodies to neural cell adhesion molecules.

    PubMed Central

    Fraser, S E; Murray, B A; Chuong, C M; Edelman, G M

    1984-01-01

    The neural cell adhesion molecule (N-CAM) mediates neuron-neuron adhesion, is ubiquitous in the nervous system of developing and mature vertebrates, and undergoes major alterations in both amount and distribution during development. Perturbation of homophilic (N-CAM to N-CAM) binding by univalent fragments of specific anti-N-CAM antibodies has previously been found to alter neural tissue patterns in vitro. To show that significant alterations can also occur in vivo, antibodies to Xenopus N-CAM were embedded in agarose microcylinders and implanted in the tecta of juvenile Xenopus laevis frogs that were undergoing regeneration of their retinotectal projections; 1 week later, the effects of implantation on the projection pattern from the optic nerve were determined. Both polyclonal and monoclonal antibodies to N-CAM distorted the retinotectal projection pattern and greatly decreased the precision of the projection; these alterations recovered to near normal after an additional 3 weeks. Similar but smaller effects were obtained when normally developing froglets received tectal implants. In control animals, implants of immunoglobulins from preimmune serum and monoclonal antibodies not directed against N-CAM had little or no effect on the pattern. The results suggest that neuronal adhesion mediated by N-CAM is important in establishing and maintaining the precision and topography of neural patterns. Images PMID:6588385

  19. The A31P missense mutation in cardiac myosin binding protein C alters protein structure but does not cause haploinsufficiency.

    PubMed

    van Dijk, Sabine J; Bezold Kooiker, Kristina; Mazzalupo, Stacy; Yang, Yuanzhang; Kostyukova, Alla S; Mustacich, Debbie J; Hoye, Elaine R; Stern, Joshua A; Kittleson, Mark D; Harris, Samantha P

    2016-07-01

    Mutations in MYBPC3, the gene encoding cardiac myosin binding protein C (cMyBP-C), are a major cause of hypertrophic cardiomyopathy (HCM). While most mutations encode premature stop codons, missense mutations causing single amino acid substitutions are also common. Here we investigated effects of a single proline for alanine substitution at amino acid 31 (A31P) in the C0 domain of cMyBP-C, which was identified as a natural cause of HCM in cats. Results using recombinant proteins showed that the mutation disrupted C0 structure, altered sensitivity to trypsin digestion, and reduced recognition by an antibody that preferentially recognizes N-terminal domains of cMyBP-C. Western blots detecting A31P cMyBP-C in myocardium of cats heterozygous for the mutation showed a reduced amount of A31P mutant protein relative to wild-type cMyBP-C, but the total amount of cMyBP-C was not different in myocardium from cats with or without the A31P mutation indicating altered rates of synthesis/degradation of A31P cMyBP-C. Also, the mutant A31P cMyBP-C was properly localized in cardiac sarcomeres. These results indicate that reduced protein expression (haploinsufficiency) cannot account for effects of the A31P cMyBP-C mutation and instead suggest that the A31P mutation causes HCM through a poison polypeptide mechanism that disrupts cMyBP-C or myocyte function. PMID:26777460

  20. Application of geoelectric methods for man-caused gas deposit mapping and monitoring

    NASA Astrophysics Data System (ADS)

    Yakymchuk, M. A.; Levashov, S. P.; Korchagin, I. N.; Syniuk, B. B.

    2009-04-01

    The rather new application of original geoelectric methods of forming of short-pulsed electromagnetic field (FSPEF) and vertical electric-resonance sounding (VERS) (FSPEF-VERS technology) (Levashov et al., 2003; 2004) is discussed. In 2008 the FSPEF-VERS methods were used for ascertaining the reasons of serious man-caused accident on gas field. The emission of water with gas has occurred near an operational well on one gas field. The assumption was discussed, that some part of gas from producing horizons has got into the upper horizons, in aquiferous stratum layers. It promoted creation of superfluous pressure in aquiferous stratums which has led to accident on the field. Operative geophysical investigations within an accident site were carried out by FSPEF and VERS geoelectric methods on 07.10.08 and 13.10.08 on the first stage. The primary goal of executed works was detection and mapping of gas penetration zones in aquiferous stratums of cross-section upper part, and also the determination of bedding depths and a total area of distribution of gas in upper aquiferous stratums. The anomalous zone were revealed and mapped by FSPEF survey. It is caused by raised migration of water in upper horizons of a cross-section. The depths of anomalous polarized layers (APL) of "gas" and „aquiferous stratum" type were defined by VERS method. The VERS data are presented by sounding diagram's and columns, by vertical cross-sections lengthways and transversely of gas penetration zones, by map of thicknesses of man-caused gas "deposit". The perforation on depths of 450 and 310 m was spent in a producing borehole on the first day investigation data. Gas discharges were received from 450 and 310 m depths. Three degassing boreholes have been drilled on 08.11.08 working day. Depths of wells are about 340 m. Gas inflows were received from 330 m depth. Drilling of fourth well was conducted. The anomalous zone area has decreased twice in comparison with two previous surveys. So, the

  1. Inflammatory cytokines cause coronary arteriosclerosis-like changes and alterations in the smooth-muscle phenotypes in pigs.

    PubMed

    Fukumoto, Y; Shimokawa, H; Ito, A; Kadokami, T; Yonemitsu, Y; Aikawa, M; Owada, M K; Egashira, K; Sueishi, K; Nagai, R; Yazaki, Y; Takeshita, A

    1997-02-01

    We recently developed a porcine model in which chronic, local treatment with interleukin-1 beta (IL-1 beta) causes coronary arteriosclerosis-like changes and hyperconstrictive responses. This study was designed to examine whether or not other major inflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) might also cause similar coronary responses and whether those responses are associated with alterations in the smooth-muscle phenotypes. A segment of the porcine coronary artery was aseptically wrapped with cotton mesh, absorbing IL-1 beta, TNF-alpha, and IL-1 alpha. Two weeks after the operation, coronary arteriography showed the development of mild stenotic lesions at the cytokine-treated sites, where hyperconstrictive responses were repeatedly induced by intracoronary serotonin or histamine. Histologically mild intimal thickening was noted at those cytokine-treated sites. Immunostaining and immunoblotting demonstrated that all three myosin heavy chain isoforms, SM1, SM2 (smooth-muscle type), and SMemb (nonmuscle type), were noted in the normal coronary segments, whereas in the segments treated with inflammatory cytokines, SM1 and SM2 were markedly reduced, and only SMemb was noted. These results indicate that inflammatory cytokines all have a similar ability to induce coronary arteriosclerosis-like changes and hyperconstrictive responses, which are associated with alterations in smooth-muscle phenotypes toward dedifferentiation. PMID:9057072

  2. Altered longevity-assurance activity of p53:p44 in the mouse causes memory loss, neurodegeneration and premature death.

    PubMed

    Pehar, Mariana; O'Riordan, Kenneth J; Burns-Cusato, Melissa; Andrzejewski, Matthew E; del Alcazar, Carlos Gil; Burger, Corinna; Scrable, Heidi; Puglielli, Luigi

    2010-04-01

    The longevity-assurance activity of the tumor suppressor p53 depends on the levels of Delta40p53 (p44), a short and naturally occurring isoform of the p53 gene. As such, increased dosage of p44 in the mouse leads to accelerated aging and short lifespan. Here we show that mice homozygous for a transgene encoding p44 (p44(+/+)) display cognitive decline and synaptic impairment early in life. The synaptic deficits are attributed to hyperactivation of insulin-like growth factor 1 receptor (IGF-1R) signaling and altered metabolism of the microtubule-binding protein tau. In fact, they were rescued by either Igf1r or Mapt haploinsufficiency. When expressing a human or a 'humanized' form of the amyloid precursor protein (APP), p44(+/+) animals developed a selective degeneration of memory-forming and -retrieving areas of the brain, and died prematurely. Mechanistically, the neurodegeneration was caused by both paraptosis- and autophagy-like cell deaths. These results indicate that altered longevity-assurance activity of p53:p44 causes memory loss and neurodegeneration by affecting IGF-1R signaling. Importantly, Igf1r haploinsufficiency was also able to correct the synaptic deficits of APP(695/swe) mice, a model of Alzheimer's disease. PMID:20409077

  3. Histopathological alterations in the striatum caused by Karwinskia humboldtiana (Buckthorn) fruit in an experimental model of peripheral neuropathy.

    PubMed

    Díaz-Pérez, Rosa Nelly; Castillo-González, Juan Antonio; Carcaño-Díaz, Katya; García-Juárez, Jaime; Salazar-Leal, Martha E; Muñoz-Maldonado, Gerardo E; Montes-de-Oca-Luna, Roberto; Saucedo-Cárdenas, Odila; Soto-Domínguez, Adolfo

    2016-04-01

    The accidental ingestion of Karwinskia humboldtiana (Kh) fruit in humans and animals causes chronic or acute intoxication. Acute poisoning induces respiratory failure that progresses rapidly to death. Studies in animals intoxicated with Kh describe lesions in cerebral cortex, cerebellum, spinal cord, hippocampus and caudate nucleus. Kh intoxication in Wistar rats models the sub-lethal clinical phase observed in humans. Considering these reports, the present study analyzed the histopathological alterations within the striatum following experimental Kh intoxication. Twenty Wistar rats were divided into three groups (n =5) and were intoxicated with Kh fruit. A control group (n =5) was included. Animals were euthanized at several time points (48, 58 and 170 days post-intoxication). The brain was collected, divided and processed for conventional histology or electron microscopy. Sections were stained with hematoxylin and eosin, cresyl violet, Klüver-Barrera, and toluidine blue. Immunolabeling was performed for glial cells in the striatum, and the samples were analyzed with light microscopy. Morphometric and statistical analyses were performed. In control group, neurons, axon bundles and neuropil had a normal appearance. At 48 days, hyperchromic neurons with apparent decreased size were observed interspersed among the normal neurons. At 58 days, we observed an increased number of hyperchromic neurons and disorganization of the myelin sheath and neuropil. At 170 days, these alterations persisted in the paralysis group. In treated groups, we observed signs of gliosis and increased axonal diameters. This study is the first report that describes the histopathological alterations within the striatum caused by chronic intoxication with Kh fruit in the Wistar rat. PMID:26544757

  4. Altered cell shapes, hyperplasia, and secondary growth in Arabidopsis caused by beet curly top geminivirus infection.

    PubMed

    Park, Jongbum; Hwang, Hyunsik; Shim, Haekyung; Im, Kyunghoan; Auh, Chung-Kyoon; Lee, Sukchan; Davis, Keith R

    2004-02-29

    Arabidopsis Sei-O ecotype was found to be hypersusceptible to the BCTV-Logan strain in that it developed very severe symptoms, including severely deformed inflorescences with the callus-like structure, and accumulated high level of viral DNA. Microscopic studies of the BCTV-induced cell divisions demonstrated that the activation of cell divisions was preceded by the phloem disruption and the callus-like structure seemed to be originated from the cortex nearby disrupted phloem. We have further defined the callus-like structure formed by BCTV infection using molecular and histochemical analyses. Results indicate that BCTV infection causes the phloem disruption, following by cell enlargement and elongation in cortex and even epidermis. Finally, BCTV induced symptomatic secondary growth in cortex by de novo anticlinal and periclinal cell divisions. Expression of cdc2 and saur from BCTV-infected Arabidopsis correlates with symptom development. These results suggest a critical role of auxin in symptom development in the interactions between Arabidopsis and BCTV. PMID:15055537

  5. Chronic treatment with anti-bipolar drugs causes intracellular alkalinization in astrocytes, altering their functions.

    PubMed

    Song, Dan; Li, Baoman; Yan, Enzhi; Man, Yi; Wolfson, Marina; Chen, Ye; Peng, Liang

    2012-11-01

    Bipolar disorder I and II are affective disorders with mood changes between depressive and manic (bipolar I) or hypomanic (bipolar II) periods. Current therapy of these conditions is chronic treatment with one or more of the anti-bipolar drugs, Li(+) ('lithium'), carbamazepine and valproic acid. The pathophysiology of bipolar disorder is multifactorial and far from clear. Recent data on the dependence of normal brain function on neuronal-astrocytic interactions raise the possibility of astrocytic involvement. We will discuss our previously published and new results on effects of chronic treatment of primary cultures of normal mouse astrocytes with any of three conventional anti-bipolar drugs. The focus will be on several drug-induced events in relation to therapeutic effects of the drugs, such as myo-inositol uptake, intracellular pH and alkalinization, drug-induced modulation of glutamatergic activity in astrocytes and release of astrocytic 'gliotransmitters'. Finally, we will discuss the importance of phospholipase A2 (PLA(2)) and arachidonic acid cascade in drug-treated astrocytes, partly based on Dr. Barneda Cuirana's published thesis. All three drugs cause gradual intracellular alkalinization through different mechanisms. Alkalinization inhibit myo-inositol uptake, resulting in reduced inositolphosphate/phospholipid signaling. Accordingly, transmitter-induced increase in free intracellular Ca(2+) ([Ca(2+)](i)) becomes inhibited, aborting release of astrocytic 'gliotransmitters'. The reduction of "gliotransmitter" effects on neurons may have therapeutic effects in mania. Alkalinization also up-regulates expression of cPLA(2), an enzyme releasing arachidonic acid, and triggered arachidonic acid cascade and production, but perhaps not release, of prostaglandins. Whenever tested, identical effects were observed in freshly isolated astrocytes, but not neurons, from carbamazepine-treated healthy animals. PMID:22965852

  6. Systemic pathological alterations caused by Philodryas patagoniensis colubrid snake venom in rats.

    PubMed

    Peichoto, María Elisa; Teibler, Pamela; Ruíz, Raquel; Leiva, Laura; Acosta, Ofelia

    2006-10-01

    Very little is known about the systemic effects caused by Philodryas patagoniensis colubrid snake venom. In this work, this venom was tested for its ability to induce histopathological changes in rats after its intramuscular, subcutaneous or intravenous administration, by light microscopic examination of some organs (cerebellum, cerebrum, lung, liver, kidney and heart). Four rats were used for each dose of 0.23, 0.45 and 0.90 mg of venom in 0.3 ml of phosphate-buffered saline solution (pH 7.4). Aliquots of blood were withdrawn at different time intervals for enzymatic determination of alanine aminotransferase, aspartate aminotransferase and creatine kinase levels. After 2h the animals were killed by an overdose of anesthetic, and samples of kidney, heart, liver, lung, cerebrum and cerebellum were taken to microscopic examination (hematoxylin and eosin stain). Histologically, no abnormality was observed in heart tissue, in none of the administration routes of the venom used. However, histological observations showed multifocal hemorrhage in cerebellum, cerebrum and lung sections, severe peritubular capillary congestion in kidney sections and hydropic degeneration in liver sections, when venom was administrated intravenously. The subcutaneous route showed similar results to the previous one, with the exception of cerebellar hemorrhage. Intramuscularly, neither cerebral nor cerebellar hemorrhage was observed. Plasma alanine aminotransferase and aspartate aminotransferase increased levels were demonstrated, mainly when venom was administered intravenously or subcutaneously. Our results suggest that P. patagoniensis venom induces moderate histopathological changes in vital organs of rats. These changes are initiated at early stages of the envenomation and may be associated with a behavioral or functional abnormality of those organs during envenoming. PMID:16911815

  7. Albinism-Causing Mutations in Recombinant Human Tyrosinase Alter Intrinsic Enzymatic Activity

    PubMed Central

    Dolinska, Monika B.; Kovaleva, Elena; Backlund, Peter; Wingfield, Paul T.; Brooks, Brian P.; Sergeev, Yuri V.

    2014-01-01

    Background Tyrosinase (TYR) catalyzes the rate-limiting, first step in melanin production and its gene (TYR) is mutated in many cases of oculocutaneous albinism (OCA1), an autosomal recessive cause of childhood blindness. Patients with reduced TYR activity are classified as OCA1B; some OCA1B mutations are temperature-sensitive. Therapeutic research for OCA1 has been hampered, in part, by the absence of purified, active, recombinant wild-type and mutant human enzymes. Methodology/Principal Findings The intra-melanosomal domain of human tyrosinase (residues 19–469) and two OCA1B related temperature-sensitive mutants, R422Q and R422W were expressed in insect cells and produced in T. ni larvae. The short trans-membrane fragment was deleted to avoid potential protein insolubility, while preserving all other functional features of the enzymes. Purified tyrosinase was obtained with a yield of >1 mg per 10 g of larval biomass. The protein was a monomeric glycoenzyme with maximum enzyme activity at 37°C and neutral pH. The two purified mutants when compared to the wild-type protein were less active and temperature sensitive. These differences are associated with conformational perturbations in secondary structure. Conclusions/Significance The intramelanosomal domains of recombinant wild-type and mutant human tyrosinases are soluble monomeric glycoproteins with activities which mirror their in vivo function. This advance allows for the structure – function analyses of different mutant TYR proteins and correlation with their corresponding human phenotypes; it also provides an important tool to discover drugs that may improve tyrosinase activity and treat OCA1. PMID:24392141

  8. Evaluation of 0.46- to 2.36-micrometre multispectral scanner images of the East Tintic mining district, Utah, for mapping hydrothermally altered rocks.

    USGS Publications Warehouse

    Rowan, L.C.; Kahle, A.B.

    1982-01-01

    Airborne multispectral scanner images recorded in the 0.46 to 2.36 micrometre region for the E Tintic mining district, Utah, were evaluated to determine their usefulness for distinguishing six types of hydrothermally altered rocks from a wide range of sedimentary and igneous rock types. The laboratory and field evaluation of a color ratio composite image, supported by in situ spectral reflectance measurements and an alteration map compiled from a published map, shows that silicified, argillized, and pyritized rocks can be mapped in detail utilizing an intense OH absorption band centered near 2.2 micrometre. This absorption band is absent or weak in most of the unaltered rocks. -from Authors

  9. Does degree of alteration in effort sense caused by eccentric exercise significantly affect initial exercise hyperpnea in humans?

    PubMed

    Hotta, Norio; Yamamoto, Kaoru; Ogata, Hisayoshi; Maher, Patrick; Okumura, Naoya; Ishida, Koji

    2016-01-01

    Previous research has shown an exaggeration in exercise hyperpnea 2 days after eccentric exercise (ECC). Enhancement in central command has been suggested as one candidate to account for this effect given that ECC-induced neuromuscular dysfunction increases relative exercise intensity, thus resulting in reinforcement of effort sense. The purpose of this study was, therefore, to elucidate whether the degree of alteration in effort sense caused by ECC affects exercise hyperpnea. Ten subjects performed 20-s single-arm extension-flexion exercises with weight strapped to the wrist, and ventilatory response was measured before (Pre) and 2 days after ECC (D2). Relative exercise intensity at Pre was 5 % of maximal voluntary contraction (MVC) of Pre, whereas that at D2 was 9 % MVC of D2 because of decline in muscle strength. Ventilatory responses were significantly exaggerated at D2 with a significant increase in effort sense. Although effort sense was significantly reduced during exercise at D2 when wrist weight was subtracted to match relative exercise intensity at Pre (5 % MVC of D2), ventilatory responses were still significantly higher than those of Pre. After the disappearance of post-ECC muscle damage, subjects performed the same exercise with weight added (9 % MVC of Pre) so that effort was equalized to match that of D2; however, no significant increase in ventilatory response was detected. The fact that the extent of change in effort sense caused by ECC-induced neuromuscular dysfunction did not affect ventilatory response at the onset of exercise after ECC may suggest that the exaggeration of ventilatory response after ECC is caused by mechanisms other than alteration of the central command. PMID:27558395

  10. Quantitative Chemical-Genetic Interaction Map Connects Gene Alterations to Drug Responses | Office of Cancer Genomics

    Cancer.gov

    In a recent Cancer Discovery report, CTD2 researchers at the University of California in San Francisco developed a new quantitative chemical-genetic interaction mapping approach to evaluate drug sensitivity or resistance in isogenic cell lines. Performing a high-throughput screen with isogenic cell lines allowed the researchers to explore the impact of a panel of emerging and established drugs on cells overexpressing a single cancer-associated gene in isolation.

  11. Mineral identification and mapping of hydrothermal alteration zones using high-spectral resolution images (AVIRIS)

    NASA Technical Reports Server (NTRS)

    Van Der Meer, Freek D.

    1994-01-01

    High-spectral resolution images (AVIRIS) of the cuprite mining area were used to evaluate atmospheric calibration algorithms and test several mineral mapping techniques. Four scene normalization techniques were used: (1) the flat-field method, (2) the internal average reflectance method, (3) the empirical line method, and (4) the atmospheric absorption removal method (ATREM). The algorithms were evaluated in terms of their spectral interpret- ability and their ability to remove both solar irradiance and atmospheric absorption features, noise, and artifacts. Noise was quantified by calculating the coefficient of variation of the spectra, and spectral interpretability was quantified by calcu- lating a difference spectrum (eg, laboratory spectrum minus pixel spectrum) for areas with known occurrences of clay minerals. These difference spectra were useful in evaluating the degree of removal of atmospheric features. The empirical line method produced the best calibration results. Mineral mapping as done using (1) color-composites of bands on the shoulders and centers of expected absorption features, (2) color-coded spectra, and (3) spectral angle mapping.

  12. Description and validation of an automated methodology for mapping mineralogy, vegetation, and hydrothermal alteration type from ASTER satellite imagery with examples from the San Juan Mountains, Colorado

    USGS Publications Warehouse

    Rockwell, Barnaby W.

    2012-01-01

    The efficacy of airborne spectroscopic, or "hyperspectral," remote sensing for geoenvironmental watershed evaluations and deposit-scale mapping of exposed mineral deposits has been demonstrated. However, the acquisition, processing, and analysis of such airborne data at regional and national scales can be time and cost prohibitive. The Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) sensor carried by the NASA Earth Observing System Terra satellite was designed for mineral mapping and the acquired data can be efficiently used to generate uniform mineral maps over very large areas. Multispectral remote sensing data acquired by the ASTER sensor were analyzed to identify and map minerals, mineral groups, hydrothermal alteration types, and vegetation groups in the western San Juan Mountains, Colorado, including the Silverton and Lake City calderas. This mapping was performed in support of multidisciplinary studies involving the predictive modeling of surface water geochemistry at watershed and regional scales. Detailed maps of minerals, vegetation groups, and water were produced from an ASTER scene using spectroscopic, expert system-based analysis techniques which have been previously described. New methodologies are presented for the modeling of hydrothermal alteration type based on the Boolean combination of the detailed mineral maps, and for the entirely automated mapping of alteration types, mineral groups, and green vegetation. Results of these methodologies are compared with the more detailed maps and with previously published mineral mapping results derived from analysis of high-resolution spectroscopic data acquired by the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) sensor. Such comparisons are also presented for other mineralized and (or) altered areas including the Goldfield and Cuprite mining districts, Nevada and the central Marysvale volcanic field, Wah Wah Mountains, and San Francisco Mountains, Utah. The automated

  13. The Rose-comb Mutation in Chickens Constitutes a Structural Rearrangement Causing Both Altered Comb Morphology and Defective Sperm Motility

    PubMed Central

    Boije, Henrik; Bed'hom, Bertrand; Fillon, Valérie; Dorshorst, Ben; Rubin, Carl-Johan; Liu, Ranran; Gao, Yu; Gu, Xiaorong; Wang, Yanqiang; Gourichon, David; Zody, Michael C.; Zecchin, William; Vieaud, Agathe; Tixier-Boichard, Michèle; Hu, Xiaoxiang; Hallböök, Finn; Li, Ning; Andersson, Leif

    2012-01-01

    Rose-comb, a classical monogenic trait of chickens, is characterized by a drastically altered comb morphology compared to the single-combed wild-type. Here we show that Rose-comb is caused by a 7.4 Mb inversion on chromosome 7 and that a second Rose-comb allele arose by unequal crossing over between a Rose-comb and wild-type chromosome. The comb phenotype is caused by the relocalization of the MNR2 homeodomain protein gene leading to transient ectopic expression of MNR2 during comb development. We also provide a molecular explanation for the first example of epistatic interaction reported by Bateson and Punnett 104 years ago, namely that walnut-comb is caused by the combined effects of the Rose-comb and Pea-comb alleles. Transient ectopic expression of MNR2 and SOX5 (causing the Pea-comb phenotype) occurs in the same population of mesenchymal cells and with at least partially overlapping expression in individual cells in the comb primordium. Rose-comb has pleiotropic effects, as homozygosity in males has been associated with poor sperm motility. We postulate that this is caused by the disruption of the CCDC108 gene located at one of the inversion breakpoints. CCDC108 is a poorly characterized protein, but it contains a MSP (major sperm protein) domain and is expressed in testis. The study illustrates several characteristic features of the genetic diversity present in domestic animals, including the evolution of alleles by two or more consecutive mutations and the fact that structural changes have contributed to fast phenotypic evolution. PMID:22761584

  14. Refined mapping of the gene causing familial mediterranean fever, by linkage and homozygosity studies

    PubMed Central

    Aksentijevich, Ivona; Pras, Elon; Gruberg, Luis; Shen, Yang; Holman, Katherine; Helling, Sharon; Prosen, Leandrea; Sutherland, Grant R.; Richards, Robert I.; Ramsburg, Mark; Dean, Michael; Pras, Mordechai; Amos, Christopher I.; Kastner, Daniel L.

    1993-01-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by attacks of fever and serosal inflammation; the biochemical basis is unknown. We recently reported linkage of the gene causing FMF (designated “MEF”) to two markers on chromosome 16p. To map MEF more precisely, we have now tested nine 16p markers. Two-point and multipoint linkage analysis, as well as a study of recombinant haplotypes, placed MEF between D16S94 and D16S80, a genetic interval of about 9 cM. We also examined rates of homozygosity for markers in this region, among offspring of consanguineous marriages. For eight of nine markers, the rate of homozygosity among 26 affected inbred individuals was higher than that among their 20 unaffected sibs. Localizing MEF more precisely on the basis of homozygosity rates alone would be difficult, for two reasons: First, the high FMF carrier frequency increases the chance that inbred offspring could have the disease without being homozygous by descent at MEF. Second, several of the markers in this region are relatively nonpolymorphic, with a high rate of homozygosity, regardless of their chromosomal location. PMID:8328461

  15. Longitudinal assessment of fractional anisotropy alterations caused by simian immunodeficiency virus infection: a preliminary diffusion tensor imaging study.

    PubMed

    Tang, Zhenchao; Dong, Enqing; Liu, Jiaojiao; Liu, Zhenyu; Wei, Wenjuan; Wang, Bo; Li, Hongjun; Tian, Jie

    2016-04-01

    Previous diffusion tensor imaging (DTI) studies found that human immunodeficiency virus (HIV) infection led to white matter (WM) microstructure degeneration. Most of the DTI studies were cross-sectional and thus merely investigated only one specific point in the disease. In order to systematically study the WM impairments caused by HIV infection, more longitudinal studies are needed. However, longitudinal studies on HIV patients are very difficult to conduct. To address this question, we employed the simian immunodeficiency virus (SIV)-infected rhesus monkeys model to carry out a longitudinal DTI study. We aimed to longitudinally access the WM abnormalities of SIV-infected rhesus monkeys by studying the fractional anisotropy (FA) alterations with Tract Based Spatial Statistic (TBSS) analysis. Four rhesus monkeys inoculated intravenously with SIVmac239 were utilized in the study. DTI scans and peripheral blood CD4(+) and CD8(+) T cell counts were acquired prior to virus inoculation (as the baseline) and in the 12th and 24th week postvirus inoculation. Significant FA alterations were found in the two areas of the inferotemporal regions (iTE), respectively located in the ventral subregion of posterior iTE (iTEpv) and the dorsal subregion of iTE (iTEpd). The decreased FA values in iTEpd were found significantly negatively correlated with the elevated peripheral blood CD4(+)/CD8(+) ratios. It might suggest that WM in iTEpd was still impaired even though the immune dysfunction alleviated temporally. PMID:26438160

  16. Interpretation of aircraft multispectral scanner images for mapping of alteration with uranium mineralization, Copper Mountain, Wyoming

    NASA Technical Reports Server (NTRS)

    Conel, J. E.

    1983-01-01

    NS-001 multispectral scanner data (0.45-2.35 micron) combined as principal components were utilized to map distributions of surface oxidation/weathering in Precambrian granitic rocks at Copper Mountain, Wyoming. Intense oxidation is found over granitic outcrops in partly exhumed pediments along the southern margin of the Owl Creek uplift, and along paleodrainages higher in the range. Supergene(?) uranium mineralization in the granites is localized beneath remnant Tertiary sediments covering portions of the pediments. The patterns of mineralization and oxidation are in agreement, but the genetic connections between the two remain in doubt.

  17. Alteration of the intestinal microbiota as a cause of and a potential therapeutic option in irritable bowel syndrome.

    PubMed

    König, J; Brummer, R J

    2014-09-01

    The intestinal microbiota forms a complex ecosystem that is in close contact with its host and has an important impact on health. An increasing number of disorders are associated with disturbances in this ecosystem. Also patients suffering from irritable bowel syndrome (IBS) show an altered composition of their gut microbiota. IBS is a multifactorial chronic disorder characterised by various abdominal complaints and a worldwide prevalence of 10-20%. Even though its aetiology and pathophysiology are complex and not well understood, it is widely accepted that aberrations along the microbe-gut-brain axis are involved. In this review, it will be discussed how exogenous factors, e.g. antibiotics, can cause disbalance in the intestinal microbiota and thereby contribute to the development of IBS. In addition, several new IBS treatment options that aim at re-establishing a healthy, beneficial ecosystem will be described. These include antibiotics, probiotics, prebiotics and faecal transplantation. PMID:24583610

  18. Microtubule-associated protein 1B (MAP1B)-deficient neurons show structural presynaptic deficiencies in vitro and altered presynaptic physiology.

    PubMed

    Bodaleo, Felipe J; Montenegro-Venegas, Carolina; Henríquez, Daniel R; Court, Felipe A; Gonzalez-Billault, Christian

    2016-01-01

    Microtubule-associated protein 1B (MAP1B) is expressed predominantly during the early stages of development of the nervous system, where it regulates processes such as axonal guidance and elongation. Nevertheless, MAP1B expression in the brain persists in adult stages, where it participates in the regulation of the structure and physiology of dendritic spines in glutamatergic synapses. Moreover, MAP1B expression is also found in presynaptic synaptosomal preparations. In this work, we describe a presynaptic phenotype in mature neurons derived from MAP1B knockout (MAP1B KO) mice. Mature neurons express MAP1B, and its deficiency does not alter the expression levels of a subgroup of other synaptic proteins. MAP1B KO neurons display a decrease in the density of presynaptic and postsynaptic terminals, which involves a reduction in the density of synaptic contacts, and an increased proportion of orphan presynaptic terminals. Accordingly, MAP1B KO neurons present altered synaptic vesicle fusion events, as shown by FM4-64 release assay, and a decrease in the density of both synaptic vesicles and dense core vesicles at presynaptic terminals. Finally, an increased proportion of excitatory immature symmetrical synaptic contacts in MAP1B KO neurons was detected. Altogether these results suggest a novel role for MAP1B in presynaptic structure and physiology regulation in vitro. PMID:27425640

  19. Microtubule-associated protein 1B (MAP1B)-deficient neurons show structural presynaptic deficiencies in vitro and altered presynaptic physiology

    PubMed Central

    Bodaleo, Felipe J.; Montenegro-Venegas, Carolina; Henríquez, Daniel R.; Court, Felipe A.; Gonzalez-Billault, Christian

    2016-01-01

    Microtubule-associated protein 1B (MAP1B) is expressed predominantly during the early stages of development of the nervous system, where it regulates processes such as axonal guidance and elongation. Nevertheless, MAP1B expression in the brain persists in adult stages, where it participates in the regulation of the structure and physiology of dendritic spines in glutamatergic synapses. Moreover, MAP1B expression is also found in presynaptic synaptosomal preparations. In this work, we describe a presynaptic phenotype in mature neurons derived from MAP1B knockout (MAP1B KO) mice. Mature neurons express MAP1B, and its deficiency does not alter the expression levels of a subgroup of other synaptic proteins. MAP1B KO neurons display a decrease in the density of presynaptic and postsynaptic terminals, which involves a reduction in the density of synaptic contacts, and an increased proportion of orphan presynaptic terminals. Accordingly, MAP1B KO neurons present altered synaptic vesicle fusion events, as shown by FM4-64 release assay, and a decrease in the density of both synaptic vesicles and dense core vesicles at presynaptic terminals. Finally, an increased proportion of excitatory immature symmetrical synaptic contacts in MAP1B KO neurons was detected. Altogether these results suggest a novel role for MAP1B in presynaptic structure and physiology regulation in vitro. PMID:27425640

  20. Mapping Weathering and Alteration Minerals in the Comstock and Geiger Grade Areas using Visible to Thermal Infrared Airborne Remote Sensing Data

    NASA Technical Reports Server (NTRS)

    Vaughan, Greg R.; Calvin, Wendy M.

    2005-01-01

    To support research into both precious metal exploration and environmental site characterization a combination of high spatial/spectral resolution airborne visible, near infrared, short wave infrared (VNIR/SWIR) and thermal infrared (TIR) image data were acquired to remotely map hydrothermal alteration minerals around the Geiger Grade and Comstock alteration regions, and map the mineral by-products of weathered mine dumps in Virginia City. Remote sensing data from the Airborne Visible Infrared Imaging Spectrometer (AVIRIS), SpecTIR Corporation's airborne hyperspectral imager (HyperSpecTIR), the MODIS-ASTER airborne simulator (MASTER), and the Spatially Enhanced Broadband Array Spectrograph System (SEBASS) were acquired and processed into mineral maps based on the unique spectral signatures of image pixels. VNIR/SWIR and TIR field spectrometer data were collected for both calibration and validation of the remote data sets, and field sampling, laboratory spectral analyses and XRD analyses were made to corroborate the surface mineralogy identified by spectroscopy. The resulting mineral maps show the spatial distribution of several important alteration minerals around each study area including alunite, quartz, pyrophyllite, kaolinite, montmorillonite/muscovite, and chlorite. In the Comstock region the mineral maps show acid-sulfate alteration, widespread propylitic alteration and extensive faulting that offsets the acid-sulfate areas, in contrast to the larger, dominantly acid-sulfate alteration exposed along Geiger Grade. Also, different mineral zones within the intense acid-sulfate areas were mapped. In the Virginia City historic mining district the important weathering minerals mapped include hematite, goethite, jarosite and hydrous sulfate minerals (hexahydrite, alunogen and gypsum) located on mine dumps. Sulfate minerals indicate acidic water forming in the mine dump environment. While there is not an immediate threat to the community, there are clearly sources of

  1. A synonymous mutation in SPINK5 exon 11 causes Netherton syndrome by altering exonic splicing regulatory elements.

    PubMed

    Fortugno, Paola; Grosso, Fabiana; Zambruno, Giovanna; Pastore, Serena; Faletra, Flavio; Castiglia, Daniele

    2012-05-01

    Netherton syndrome (NS) is a rare, life-threatening ichthyosiform syndrome caused by recessive loss-of-function mutations in SPINK5 gene encoding lymphoepithelial Kazal-type-related inhibitor (LEKTI), a serine protease inhibitor expressed in the most differentiated epidermal layers and crucial for skin barrier function. We report the functional characterization of a previously unrecognized synonymous variant, c.891C>T (p.Cys297Cys), identified in the SPINK5 exon 11 of an NS patient. We demonstrated that the c.891C>T mutation is associated with abnormal pre-mRNA splicing and residual LEKTI expression in the patient's keratinocytes. Subsequent minigene splicing assays and in silico predictions confirmed the direct role of the synonymous mutation in inhibiting exon 11 inclusion by a mechanism that involves the activity of exonic regulatory sequences, namely splicing enhancer and silencer. However, this deleterious effect was not complete and a residual amount of normal mRNA and LEKTI protein could be detected, correlating with the relatively mild patient's phenotype. Our study represents the first identification of a disease-causing SPINK5 mutation that alters splicing without affecting canonical splice sites. PMID:22377713

  2. Absence of BRINP1 in mice causes increase of hippocampal neurogenesis and behavioral alterations relevant to human psychiatric disorders

    PubMed Central

    2014-01-01

    Background We have previously identified BRINP (BMP/RA-inducible neural-specific protein-1, 2, 3) family genes that possess the ability to suppress cell cycle progression in neural stem cells. Of the three family members, BRINP1 is the most highly expressed in various brain regions, including the hippocampus, in adult mice and its expression in dentate gyrus (DG) is markedly induced by neural activity. In the present study, we generated BRINP1-deficient (KO) mice to clarify the physiological functions of BRINP1 in the nervous system. Results Neurogenesis in the subgranular zone of dentate gyrus was increased in BRINP1-KO mice creating a more immature neuronal population in granule cell layer. The number of parvalbumin expressing interneuron in hippocampal CA1 subregion was also increased in BRINP1-KO mice. Furthermore, BRINP1-KO mice showed abnormal behaviors with increase in locomotor activity, reduced anxiety-like behavior, poor social interaction, and slight impairment of working memory, all of which resemble symptoms of human psychiatric disorders such as schizophrenia and attention–deficit/hyperactivity disorder (ADHD). Conclusions Absence of BRINP1 causes deregulation of neurogenesis and impairments of neuronal differentiation in adult hippocampal circuitry. Abnormal behaviors comparable to those of human psychiatric disorders such as hyperactivity and poor social behavior were observed in BRINP1-KO mice. These abnormal behaviors could be caused by alteration of hippocampal circuitry as a consequence of the lack of BRINP1. PMID:24528488

  3. Alteration of intracellular protein expressions as a key mechanism of the deterioration of bacterial denitrification caused by copper oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Su, Yinglong; Zheng, Xiong; Chen, Yinguang; Li, Mu; Liu, Kun

    2015-10-01

    The increasing production and utilization of copper oxide nanoparticles (CuO NPs) result in the releases into the environment. However, the influence of CuO NPs on bacterial denitrification, one of the most important pathways to transform nitrate to dinitrogen in environment, has seldom been studied. Here we reported that CuO NPs caused a significant alteration of key protein expressions of a model denitrifier, Paracoccus denitrificans, leading to severe inhibition to denitrification. Total nitrogen removal efficiency was decreased from 98.3% to 62.1% with the increase of CuO NPs from 0.05 to 0.25 mg/L. Cellular morphology and integrity studies indicated that nanoparticles entered the cells. The proteomic bioinformatics analysis showed that CuO NPs caused regulation of proteins involved in nitrogen metabolism, electron transfer and substance transport. The down-regulation of GtsB protein (responsible for glucose transport) decreased the production of NADH (electron donor for denitrification). Also, the expressions of key electron-transfer proteins (including NADH dehydrogenase and cytochrome) were suppressed by CuO NPs, which adversely affected electrons transfer for denitrification. Further investigation revealed that CuO NPs significantly inhibited the expressions and catalytic activities of nitrate reductase and nitrite reductase. These results provided a fundamental understanding of the negative influences of CuO NPs on bacterial denitrification.

  4. Metabonomic Analysis Reveals Efficient Ameliorating Effects of Acupoint Stimulations on the Menopause-caused Alterations in Mammalian Metabolism

    NASA Astrophysics Data System (ADS)

    Zhang, Limin; Wang, Yulan; Xu, Yunxiang; Lei, Hehua; Zhao, Ying; Li, Huihui; Lin, Xiaosheng; Chen, Guizhen; Tang, Huiru

    2014-01-01

    Acupoint stimulations are effective in ameliorating symptoms of menopause which is an unavoidable ageing consequence for women. To understand the mechanistic aspects of such treatments, we systematically analyzed the effects of acupoint laser-irradiation and catgut-embedding on the ovariectomy-induced rat metabolic changes using NMR and GC-FID/MS methods. Results showed that ovariectomization (OVX) caused comprehensive metabolic changes in lipid peroxidation, glycolysis, TCA cycle, choline and amino acid metabolisms. Both acupoint laser-irradiation and catgut-embedding ameliorated the OVX-caused metabonomic changes more effectively than hormone replacement therapy (HRT) with nilestriol. Such effects of acupoint stimulations were highlighted in alleviating lipid peroxidation, restoring glucose homeostasis and partial reversion of the OVX-altered amino acid metabolism. These findings provided new insights into the menopause effects on mammalian biochemistry and beneficial effects of acupoint stimulations in comparison with HRT, demonstrating metabonomics as a powerful approach for potential applications in disease prognosis and developments of effective therapies.

  5. Alteration of intracellular protein expressions as a key mechanism of the deterioration of bacterial denitrification caused by copper oxide nanoparticles.

    PubMed

    Su, Yinglong; Zheng, Xiong; Chen, Yinguang; Li, Mu; Liu, Kun

    2015-01-01

    The increasing production and utilization of copper oxide nanoparticles (CuO NPs) result in the releases into the environment. However, the influence of CuO NPs on bacterial denitrification, one of the most important pathways to transform nitrate to dinitrogen in environment, has seldom been studied. Here we reported that CuO NPs caused a significant alteration of key protein expressions of a model denitrifier, Paracoccus denitrificans, leading to severe inhibition to denitrification. Total nitrogen removal efficiency was decreased from 98.3% to 62.1% with the increase of CuO NPs from 0.05 to 0.25 mg/L. Cellular morphology and integrity studies indicated that nanoparticles entered the cells. The proteomic bioinformatics analysis showed that CuO NPs caused regulation of proteins involved in nitrogen metabolism, electron transfer and substance transport. The down-regulation of GtsB protein (responsible for glucose transport) decreased the production of NADH (electron donor for denitrification). Also, the expressions of key electron-transfer proteins (including NADH dehydrogenase and cytochrome) were suppressed by CuO NPs, which adversely affected electrons transfer for denitrification. Further investigation revealed that CuO NPs significantly inhibited the expressions and catalytic activities of nitrate reductase and nitrite reductase. These results provided a fundamental understanding of the negative influences of CuO NPs on bacterial denitrification. PMID:26508362

  6. Alteration of intracellular protein expressions as a key mechanism of the deterioration of bacterial denitrification caused by copper oxide nanoparticles

    PubMed Central

    Su, Yinglong; Zheng, Xiong; Chen, Yinguang; Li, Mu; Liu, Kun

    2015-01-01

    The increasing production and utilization of copper oxide nanoparticles (CuO NPs) result in the releases into the environment. However, the influence of CuO NPs on bacterial denitrification, one of the most important pathways to transform nitrate to dinitrogen in environment, has seldom been studied. Here we reported that CuO NPs caused a significant alteration of key protein expressions of a model denitrifier, Paracoccus denitrificans, leading to severe inhibition to denitrification. Total nitrogen removal efficiency was decreased from 98.3% to 62.1% with the increase of CuO NPs from 0.05 to 0.25 mg/L. Cellular morphology and integrity studies indicated that nanoparticles entered the cells. The proteomic bioinformatics analysis showed that CuO NPs caused regulation of proteins involved in nitrogen metabolism, electron transfer and substance transport. The down-regulation of GtsB protein (responsible for glucose transport) decreased the production of NADH (electron donor for denitrification). Also, the expressions of key electron-transfer proteins (including NADH dehydrogenase and cytochrome) were suppressed by CuO NPs, which adversely affected electrons transfer for denitrification. Further investigation revealed that CuO NPs significantly inhibited the expressions and catalytic activities of nitrate reductase and nitrite reductase. These results provided a fundamental understanding of the negative influences of CuO NPs on bacterial denitrification. PMID:26508362

  7. A transcription map of a yeast centromere plasmid: unexpected transcripts and altered gene expression.

    PubMed Central

    Marczynski, G T; Jaehning, J A

    1985-01-01

    YCp19 is a yeast centromere plasmid capable of autonomous replication in both yeast and E. coli (J. Mol. Biol., 158: 157-179, 1982). It is stably maintained as a single copy in the yeast cell and is therefore a model yeast "minichromosome" and cloning vector. We have located the positions and measured the abundance of the in vivo yeast transcripts from YCp19. Transcripts from the selectable marker genes TRP1 and URA3 were present at increased levels relative to chromosomal copies of the genes. Unanticipated transcripts from the yeast CEN4 and E. coli pBR322 sequences were also found. Although much of the plasmid vector is actively transcribed in vivo, the regions around the most useful cloning sites (BamHI, EcoRI, SalI) are free of transcripts. We have analyzed transcription of BamHI inserts containing promoter variants of the HIS3 gene and determined that although initiation events are accurate, plasmid context may alter levels of gene expression. Images PMID:3909105

  8. Mapping surface alteration effects associated with hydrocarbon reservoirs at Gypsum Plain, Texas, and Cement, Oklahoma, using multispectral information

    SciTech Connect

    Carrerre, V.; Lang, H.R. ); Crawford, M.F. )

    1991-08-01

    Two test sites, Gypsum Plain, Texas, and Cement, Oklahoma, were selected to evaluate combined use of airborne visible/infrared imaging spectrometer (AVIRIS) and thermal infrared multispectral scanner (TIMS) for detection of alteration effects associated with hydrocarbon microseepage. Bleaching of redbuds, variations in carbonate cement, replacement of gypsum, exidation of iron, and changes in clay mineralogy may correlate spatially with oil and gas production and subsurface structures. Spectral features due to iron oxides, calcite, gypsum, smectite, and kaolinite can be mapped using AVIRIS image data, using various techniques such as ratios, scene-dependent log residuals, and scene-independent radioactive transfer approach using LOWTRAN7, and with TIMSA data using DSTRETCH. Poor signal-to-noise in the 2.0-2.4 {mu}m region limited the ability to map clay, gypsum, and carbonates both at Cement and Gypsum Plain, carbonate and quartz-rich sediments at Gypsum Plain, and differentiated soils developed on the Rush Spring Sandstone from soil derived from the Cloud Chief Formation at Cement. Combined spectral and photogeologic interpretation of coregistered AVIRIS, TIMS, and Landsat TM, and digital elevation data demonstrate the practical approaches for surface oil and gas exploration using presently operational commercial aircraft and future satellite systems.

  9. Na+ Influx Induced by New Antimalarials Causes Rapid Alterations in the Cholesterol Content and Morphology of Plasmodium falciparum

    PubMed Central

    Das, Sudipta; Bhatanagar, Suyash; Morrisey, Joanne M.; Daly, Thomas M.; Burns, James M.; Coppens, Isabelle; Vaidya, Akhil B.

    2016-01-01

    Among the several new antimalarials discovered over the past decade are at least three clinical candidate drugs, each with a distinct chemical structure, that disrupt Na+ homeostasis resulting in a rapid increase in intracellular Na+ concentration ([Na+]i) within the erythrocytic stages of Plasmodium falciparum. At present, events triggered by Na+ influx that result in parasite demise are not well-understood. Here we report effects of two such drugs, a pyrazoleamide and a spiroindolone, on intraerythrocytic P. falciparum. Within minutes following the exposure to these drugs, the trophozoite stage parasite, which normally contains little cholesterol, was made permeant by cholesterol-dependent detergents, suggesting it acquired a substantial amount of the lipid. Consistently, the merozoite surface protein 1 and 2 (MSP1 and MSP2), glycosylphosphotidylinositol (GPI)-anchored proteins normally uniformly distributed in the parasite plasma membrane, coalesced into clusters. These alterations were not observed following drug treatment of P. falciparum parasites adapted to grow in a low [Na+] growth medium. Both cholesterol acquisition and MSP1 coalescence were reversible upon the removal of the drugs, implicating an active process of cholesterol exclusion from trophozoites that we hypothesize is inhibited by high [Na+]i. Electron microscopy of drug-treated trophozoites revealed substantial morphological changes normally seen at the later schizont stage including the appearance of partial inner membrane complexes, dense organelles that resemble “rhoptries” and apparent nuclear division. Together these results suggest that [Na+]i disruptor drugs by altering levels of cholesterol in the parasite, dysregulate trophozoite to schizont development and cause parasite demise. PMID:27227970

  10. Na+ Influx Induced by New Antimalarials Causes Rapid Alterations in the Cholesterol Content and Morphology of Plasmodium falciparum.

    PubMed

    Das, Sudipta; Bhatanagar, Suyash; Morrisey, Joanne M; Daly, Thomas M; Burns, James M; Coppens, Isabelle; Vaidya, Akhil B

    2016-05-01

    Among the several new antimalarials discovered over the past decade are at least three clinical candidate drugs, each with a distinct chemical structure, that disrupt Na+ homeostasis resulting in a rapid increase in intracellular Na+ concentration ([Na+]i) within the erythrocytic stages of Plasmodium falciparum. At present, events triggered by Na+ influx that result in parasite demise are not well-understood. Here we report effects of two such drugs, a pyrazoleamide and a spiroindolone, on intraerythrocytic P. falciparum. Within minutes following the exposure to these drugs, the trophozoite stage parasite, which normally contains little cholesterol, was made permeant by cholesterol-dependent detergents, suggesting it acquired a substantial amount of the lipid. Consistently, the merozoite surface protein 1 and 2 (MSP1 and MSP2), glycosylphosphotidylinositol (GPI)-anchored proteins normally uniformly distributed in the parasite plasma membrane, coalesced into clusters. These alterations were not observed following drug treatment of P. falciparum parasites adapted to grow in a low [Na+] growth medium. Both cholesterol acquisition and MSP1 coalescence were reversible upon the removal of the drugs, implicating an active process of cholesterol exclusion from trophozoites that we hypothesize is inhibited by high [Na+]i. Electron microscopy of drug-treated trophozoites revealed substantial morphological changes normally seen at the later schizont stage including the appearance of partial inner membrane complexes, dense organelles that resemble "rhoptries" and apparent nuclear division. Together these results suggest that [Na+]i disruptor drugs by altering levels of cholesterol in the parasite, dysregulate trophozoite to schizont development and cause parasite demise. PMID:27227970

  11. Structure-Guided Mutations in the Terminal Organelle Protein MG491 Cause Major Motility and Morphologic Alterations on Mycoplasma genitalium.

    PubMed

    Martinelli, Luca; García-Morales, Luis; Querol, Enrique; Piñol, Jaume; Fita, Ignacio; Calisto, Bárbara M

    2016-04-01

    The emergent human pathogen Mycoplasma genitalium, with one of the smallest genomes among cells capable of growing in axenic cultures, presents a flask-shaped morphology due to a protrusion of the cell membrane, known as the terminal organelle, that is involved in cell adhesion and motility and is an important virulence factor of this microorganism. The terminal organelle is supported by a cytoskeleton complex of about 300 nm in length that includes three substructures: the terminal button, the rod and the wheel complex. The crystal structure of the MG491 protein, a proposed component of the wheel complex, has been determined at ~3 Å resolution. MG491 subunits are composed of a 60-residue N-terminus, a central three-helix-bundle spanning about 150 residues and a C-terminal region that appears to be quite flexible and contains the region that interacts with MG200, another key protein of the terminal organelle. The MG491 molecule is a tetramer presenting a unique organization as a dimer of asymmetric pairs of subunits. The asymmetric arrangement results in two very different intersubunit interfaces between the central three-helix-bundle domains, which correlates with the formation of only ~50% of the intersubunit disulfide bridges of the single cysteine residue found in MG491 (Cys87). Moreover, M. genitalium cells with a point mutation in the MG491 gene causing the change of Cys87 to Ser present a drastic reduction in motility (as determined by microcinematography) and important alterations in morphology (as determined by electron microscopy), while preserving normal levels of the terminal organelle proteins. Other variants of MG491, designed also according to the structural information, altered significantly the motility and/or the cell morphology. Together, these results indicate that MG491 plays a key role in the functioning, organization and stabilization of the terminal organelle. PMID:27082435

  12. Structure-Guided Mutations in the Terminal Organelle Protein MG491 Cause Major Motility and Morphologic Alterations on Mycoplasma genitalium

    PubMed Central

    Querol, Enrique; Piñol, Jaume; Fita, Ignacio; Calisto, Bárbara M.

    2016-01-01

    The emergent human pathogen Mycoplasma genitalium, with one of the smallest genomes among cells capable of growing in axenic cultures, presents a flask-shaped morphology due to a protrusion of the cell membrane, known as the terminal organelle, that is involved in cell adhesion and motility and is an important virulence factor of this microorganism. The terminal organelle is supported by a cytoskeleton complex of about 300 nm in length that includes three substructures: the terminal button, the rod and the wheel complex. The crystal structure of the MG491 protein, a proposed component of the wheel complex, has been determined at ~3 Å resolution. MG491 subunits are composed of a 60-residue N-terminus, a central three-helix-bundle spanning about 150 residues and a C-terminal region that appears to be quite flexible and contains the region that interacts with MG200, another key protein of the terminal organelle. The MG491 molecule is a tetramer presenting a unique organization as a dimer of asymmetric pairs of subunits. The asymmetric arrangement results in two very different intersubunit interfaces between the central three-helix-bundle domains, which correlates with the formation of only ~50% of the intersubunit disulfide bridges of the single cysteine residue found in MG491 (Cys87). Moreover, M. genitalium cells with a point mutation in the MG491 gene causing the change of Cys87 to Ser present a drastic reduction in motility (as determined by microcinematography) and important alterations in morphology (as determined by electron microscopy), while preserving normal levels of the terminal organelle proteins. Other variants of MG491, designed also according to the structural information, altered significantly the motility and/or the cell morphology. Together, these results indicate that MG491 plays a key role in the functioning, organization and stabilization of the terminal organelle. PMID:27082435

  13. In vivo knockdown of intersectin-1s alters endothelial cell phenotype and causes microvascular remodeling in the mouse lungs.

    PubMed

    Bardita, Cristina; Predescu, Dan; Justice, Matthew J; Petrache, Irina; Predescu, Sanda

    2013-01-01

    Intersectin-1s (ITSN-1s) is a general endocytic protein involved in regulating lung vascular permeability and endothelial cells (ECs) survival, via MEK/Erk1/2(MAPK) signaling. To investigate the in vivo effects of ITSN-1s deficiency and the resulting ECs apoptosis on pulmonary vasculature and lung homeostasis, we used an ITSN-1s knocked-down (KD(ITSN)) mouse generated by repeated delivery of a specific siRNA targeting ITSN-1 gene (siRNA(ITSN)). Biochemical and histological analyses as well as electron microscopy (EM) revealed that acute KD(ITSN) [3-days (3d) post-siRNA(ITSN) treatment] inhibited Erk1/2(MAPK) pro-survival signaling, causing significant ECs apoptosis and lung injury; at 10d of KD(ITSN), caspase-3 activation was at peak, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive ECs showed 3.4-fold increase, the mean linear intercept (MLI) showed 48 % augment and pulmonary microvessel density as revealed by aquaporin-1 staining (AQP-1) decreased by 30 %, all compared to controls; pulmonary function was altered. Concomitantly, expression of several growth factors known to activate Erk1/2(MAPK) and suppress Bad pro-apoptotic activity increased. KD(ITSN) altered Smads activity, downstream of the transforming growth factor beta-receptor-1 (TβR1), as shown by subcellular fractionation and immunoblot analyses. Moreover, 24d post-siRNA(ITSN), surviving ECs became hyper-proliferative and apoptotic-resistant against ITSN-1s deficiency, as demonstrated by EM imaging, 5-bromo-deoxyuridine (BrdU) incorporation and Bad-Ser(112/155) phosphorylation, respectively, leading to increased microvessel density and repair of the injured lungs, as well as matrix deposition. In sum, ECs endocytic dysfunction and apoptotic death caused by KD(ITSN) contribute to the initial lung injury and microvascular loss, followed by endothelial phenotypic changes and microvascular remodeling in the remaining murine pulmonary microvascular bed. PMID:23054079

  14. Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism

    PubMed Central

    Yang, Wanchun; Jiang, Wanxiang; Luo, Liping; Bu, Jicheng; Pang, Dejiang; Wei, Jing; Du, Chongyangzi; Xia, Xiaoqiang; Cui, Yiyuan; Liu, Shuang; Mao, Qing; Chen, Mina

    2014-01-01

    Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral metabolism need to be better understood for developing pharmacological interventions to manage eating behavior and obesity. Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a master regulator of cellular metabolism in different cell types. Pharmacological manipulations of mTOR complex 1 (mTORC1) activity in hypothalamic neurons alter food intake and body weight. Our previous study identified Rheb1 (Ras homolog enriched in brain 1) as an essential activator of mTORC1 activity in the brain. Here we examine whether central Rheb1 regulates food intake and peripheral metabolism through mTORC1 signaling. We find that genetic deletion of Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid mobilization in adipose tissue and ketogenesis in the liver. Our work highlights the importance of central Rheb1 signaling in euglycemia and energy homeostasis in animals. PMID:24451134

  15. Interstitial chromatin alteration causes persistent p53 activation involved in the radiation-induced senescence-like growth arrest

    SciTech Connect

    Suzuki, Masatoshi; Suzuki, Keiji; Kodama, Seiji; Watanabe, Masami . E-mail: nabe@rri.kyoto-u.ac.jp

    2006-02-03

    Various stresses including ionizing radiation give normal human fibroblasts a phenotype of senescence-like growth arrest (SLGA), manifested by p53-dependent irreversible G1 arrest. To determine the mechanism of persistent activation of p53, we examined phosphorylated Ataxia telangiectasia mutated (ATM) and phosphorylated histone H2AX foci formation after X-irradiation. Although the multiple tiny foci, detected soon after (<30 min) irradiation, gradually disappeared, some of these foci changed to large foci and persisted for 5 days. Large foci containing phosphorylated ATM and {gamma}-H2AX co-localized and foci with p53 phosphorylated at serine 15 also showed the same distribution. Interestingly, the signals obtained by telomere fluorescence in situ hybridization (FISH) assay did not co-localize with 90% of the large foci. Our results indicate that chromatin alteration in interstitial chromosomal regions is the most likely cause of continuous activation of p53, which results in the induction of SLGA by ionizing radiation.

  16. Alterations in protein expression caused by the hha mutation in Escherichia coli: influence of growth medium osmolarity.

    PubMed

    Balsalobre, C; Johansson, J; Uhlin, B E; Juárez, A; Muñoa, F J

    1999-05-01

    The Hha protein belongs to a new family of regulators involved in the environmental regulation of virulence factors. The aim of this work was to study the effect of the hha mutation on the overall protein pattern of Escherichia coli cells by two-dimensional polyacrylamide gel electrophoresis. The growth medium osmolarity clearly influenced the effect of the hha mutation. The number of proteins whose expression was altered in hha cells, compared with wild-type cells, was three times larger at a high osmolarity than at a low osmolarity. Among the proteins whose expression was modified by the hha allele, both OmpA and protein IIAGlc of the phosphotransferase system could be identified. As this latter enzyme participates in the regulation of the synthesis of cyclic AMP and hence influences the catabolite repression system, we tested whether the expression of the lacZ gene was also modified in hha mutants. This was the case, suggesting that at least some of the pleiotropic effects of the hha mutation could be caused by its effect on the catabolite repression system. PMID:10322001

  17. Altered GPM6A/M6 dosage impairs cognition and causes phenotypes responsive to cholesterol in human and Drosophila.

    PubMed

    Gregor, Anne; Kramer, Jamie M; van der Voet, Monique; Schanze, Ina; Uebe, Steffen; Donders, Rogier; Reis, André; Schenck, Annette; Zweier, Christiane

    2014-12-01

    Glycoprotein M6A (GPM6A) is a neuronal transmembrane protein of the PLP/DM20 (proteolipid protein) family that associates with cholesterol-rich lipid rafts and promotes filopodia formation. We identified a de novo duplication of the GPM6A gene in a patient with learning disability and behavioral anomalies. Expression analysis in blood lymphocytes showed increased GPM6A levels. An increase of patient-derived lymphoblastoid cells carrying membrane protrusions supports a functional effect of this duplication. To study the consequences of GPM6A dosage alterations in an intact nervous system, we employed Drosophila melanogaster as a model organism. We found that knockdown of Drosophila M6, the sole member of the PLP family in flies, in the wing, and whole organism causes malformation and lethality, respectively. These phenotypes as well as the protrusions of patient-derived lymphoblastoid cells with increased GPM6A levels can be alleviated by cholesterol supplementation. Notably, overexpression as well as loss of M6 in neurons specifically compromises long-term memory in the courtship conditioning paradigm. Our findings thus indicate a critical role of correct GPM6A/M6 levels for cognitive function and support a role of the GPM6A duplication for the patient's phenotype. Together with other recent findings, this study highlights compromised cholesterol homeostasis as a recurrent feature in cognitive phenotypes. PMID:25224183

  18. Interstitial chromatin alteration causes persistent p53 activation involved in the radiation-induced senescence-like growth arrest.

    PubMed

    Suzuki, Masatoshi; Suzuki, Keiji; Kodama, Seiji; Watanabe, Masami

    2006-02-01

    Various stresses including ionizing radiation give normal human fibroblasts a phenotype of senescence-like growth arrest (SLGA), manifested by p53-dependent irreversible G1 arrest. To determine the mechanism of persistent activation of p53, we examined phosphorylated Ataxia telangiectasia mutated (ATM) and phosphorylated histone H2AX foci formation after X-irradiation. Although the multiple tiny foci, detected soon after (<30 min) irradiation, gradually disappeared, some of these foci changed to large foci and persisted for 5 days. Large foci containing phosphorylated ATM and gamma-H2AX co-localized and foci with p53 phosphorylated at serine 15 also showed the same distribution. Interestingly, the signals obtained by telomere fluorescence in situ hybridization (FISH) assay did not co-localize with 90% of the large foci. Our results indicate that chromatin alteration in interstitial chromosomal regions is the most likely cause of continuous activation of p53, which results in the induction of SLGA by ionizing radiation. PMID:16360120

  19. [Incidence and causes of early end in awake surgery for language mapping not directly related to eloquence].

    PubMed

    Villalba, Gloria; Pacreu, Susana; Fernández-Candil, Juan Luis; León, Alba; Serrano, Laura; Conesa, Gerardo

    2016-01-01

    The incidence and causes that may lead to an early end (unfinished cortical/subcortical mapping) of awake surgery for language mapping are little known. A study was conducted on 41 patients with brain glioma located in the language area that had awake surgery under conscious sedation. Surgery was ended early in 6 patients. The causes were: tonic-clonic seizure (1), lack of cooperation due to fatigue/sleep (4), whether or not word articulation was involved, a decreased level of consciousness for ammonia encephalopathy that required endotracheal intubation (1). There are causes that could be expected and in some cases avoided. Tumour size, preoperative aphasia, valproate treatment, and type of anaesthesia used are variables to consider to avoid failure in awake surgery for language mapping. With these results, the following measures are proposed: l) If the tumour is large, perform surgery in two times to avoid fatigue, 2) if patient has a preoperative aphasia, do not use sedation during surgery to ensure that sleepiness does not cause worse word articulation, 3) if the patient is on valproate treatment, it is necessary to rule out the pre-operative symptoms that are not due to ammonia encephalopathy. PMID:26260205

  20. Mapping.

    ERIC Educational Resources Information Center

    Kinney, Douglas M.; McIntosh, Willard L.

    1979-01-01

    The area of geological mapping in the United States in 1978 increased greatly over that reported in 1977; state geological maps were added for California, Idaho, Nevada, and Alaska last year. (Author/BB)

  1. Mapping of the Land Cover Spatiotemporal Characteristics in Northern Russia Caused by Climate Change

    NASA Astrophysics Data System (ADS)

    Panidi, E.; Tsepelev, V.; Torlopova, N.; Bobkov, A.

    2016-06-01

    The study is devoted to the investigation of regional climate change in Northern Russia. Due to sparseness of the meteorological observation network in northern regions, we investigate the application capabilities of remotely sensed vegetation cover as indicator of climate change at the regional scale. In previous studies, we identified statistically significant relationship between the increase of surface air temperature and increase of the shrub vegetation productivity. We verified this relationship using ground observation data collected at the meteorological stations and Normalised Difference Vegetation Index (NDVI) data produced from Terra/MODIS satellite imagery. Additionally, we designed the technique of growing seasons separation for detailed investigation of the land cover (shrub cover) dynamics. Growing seasons are the periods when the temperature exceeds +5°C and +10°C. These periods determine the vegetation productivity conditions (i.e., conditions that allow growth of the phytomass). We have discovered that the trend signs for the surface air temperature and NDVI coincide on planes and river floodplains. On the current stage of the study, we are working on the automated mapping technique, which allows to estimate the direction and magnitude of the climate change in Northern Russia. This technique will make it possible to extrapolate identified relationship between land cover and climate onto territories with sparse network of meteorological stations. We have produced the gridded maps of NDVI and NDWI for the test area in European part of Northern Russia covered with the shrub vegetation. Basing on these maps, we may determine the frames of growing seasons for each grid cell. It will help us to obtain gridded maps of the NDVI linear trend for growing seasons on cell-by-cell basis. The trend maps can be used as indicative maps for estimation of the climate change on the studied areas.

  2. Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms

    PubMed Central

    2014-01-01

    Background Despite strong evidence that the pathophysiology of Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia and cortical frontal areas, findings from in vivo imaging studies have provided conflicting results. In this study we used whole brain diffusion tensor imaging (DTI) to investigate the microstructural integrity of white matter pathways and brain tissue in 19 unmedicated, adult, male patients with TS “only” (without comorbid psychiatric disorders) and 20 age- and sex-matched control subjects. Results Compared to normal controls, TS patients showed a decrease in the fractional anisotropy index (FA) bilaterally in the medial frontal gyrus, the pars opercularis of the left inferior frontal gyrus, the middle occipital gyrus, the right cingulate gyrus, and the medial premotor cortex. Increased apparent diffusion coefficient (ADC) maps were detected in the left cingulate gyrus, prefrontal areas, left precentral gyrus, and left putamen. There was a negative correlation between tic severity and FA values in the left superior frontal gyrus, medial frontal gyrus bilaterally, cingulate gyrus bilaterally, and ventral posterior lateral nucleus of the right thalamus, and a positive correlation in the body of the corpus callosum, left thalamus, right superior temporal gyrus, and left parahippocampal gyrus. There was also a positive correlation between regional ADC values and tic severity in the left cingulate gyrus, putamen bilaterally, medial frontal gyrus bilaterally, left precentral gyrus, and ventral anterior nucleus of the left thalamus. Conclusions Our results confirm prior studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus seem to reflect secondary compensatory mechanisms. Due to the study design, influences from comorbidities, gender, medication and age can be excluded. PMID:24397347

  3. Streptococcus iniae cpsG alters capsular carbohydrate composition and is a cause of serotype switching in vaccinated fish.

    PubMed

    Heath, Candice; Gillen, Christine M; Chrysanthopoulos, Panagiotis; Walker, Mark J; Barnes, Andrew C

    2016-09-25

    Streptococcus iniae causes septicaemia and meningitis in marine and freshwater fish wherever they are farmed in warm-temperate and tropical regions. Although serotype specific, vaccination with bacterins (killed bacterial cultures) is largely successful and vaccine failure occurs only occasionally through emergence of new capsular serotypes. Previously we showed that mutations in vaccine escapes are restricted to a limited repertoire of genes within the 20-gene capsular polysaccharide (cps) operon. cpsG, a putative UDP-galactose 4-epimerase, has three sequence types based on the insertion or deletion of the three amino acids leucine, serine and lysine in the substrate binding site of the protein. To elucidate the role of cpsG in capsular polysaccharide (CPS) biosynthesis and capsular composition, we first prepared isogenic knockout and complemented mutants of cpsG by allelic exchange mutagenesis. Deletion of cpsG resulted in changes to colony morphology and cell buoyant density, and also significantly decreased galactose content relative to glucose in the capsular polysaccharide as determined by GC-MS, consistent with epimerase activity of CpsG. There was also a metabolic penalty of cpsG knockout revealed by slower growth in complex media, and reduced proliferation in whole fish blood. Moreover, whilst antibodies raised in fish against the wild type cross-reacted in whole cell and cps ELISA, they did not cross-opsonise the mutant in a peripheral blood neutrophil opsonisation assay, consistent with reported vaccine escape. We have shown here that mutation in cpsG results in altered CPS composition and this in turn results in poor cross-opsonisation that explains some of the historic vaccination failure on fish farms in Australia. PMID:27599938

  4. Analysis of protein gene products in cells with altered chromosome sets for the purpose of genetic mapping

    SciTech Connect

    Shishkin, S.S.; Zakharov, S.F.; Gromov, P.S.; Shcheglova, M.V.; Kukharenko, V.I.; Shilov, A.G.; Matveeva, N.M.; Zhdanova, N.S.; Efimochkin, A.S.; Krokhina, T.B. |

    1994-12-01

    Two-dimensional electrophoresis was used for analyzing proteins in hybrid cells that contained single human chromosomes (chromosome 5, chromosome 21, or chromosomes 5 and 21) against the background of the mouse genome. By comparing the protein patterns of hybrid and parent cells (about 1000 protein fractions for each kind of cell), five fractions among proteins of hybrid cells were supposedly identified as human proteins. The genes of two of them are probably located on chromosome 5, and those of the other three on chromosome 21. Moreover, analysis of proteins in fibroblasts of patients with the cri-du-chat syndrome (5p-) revealed a decrease in the content of two proteins as compared with those in preparations of diploid fibroblasts. This fact was regarded as evidence that two corresponding genes are located on the short arm of chromosome 5. Methodological problems associated with the use of protein pattern analysis in cells with altered chromosome sets for the purposes of genetic mapping are discussed.

  5. Heterozygous Mutations in MAP3K7, Encoding TGF-β-Activated Kinase 1, Cause Cardiospondylocarpofacial Syndrome.

    PubMed

    Le Goff, Carine; Rogers, Curtis; Le Goff, Wilfried; Pinto, Graziella; Bonnet, Damien; Chrabieh, Maya; Alibeu, Olivier; Nistchke, Patrick; Munnich, Arnold; Picard, Capucine; Cormier-Daire, Valérie

    2016-08-01

    Cardiospondylocarpofacial (CSCF) syndrome is characterized by growth retardation, dysmorphic facial features, brachydactyly with carpal-tarsal fusion and extensive posterior cervical vertebral synostosis, cardiac septal defects with valve dysplasia, and deafness with inner ear malformations. Whole-exome sequencing identified heterozygous MAP3K7 mutations in six distinct CSCF-affected individuals from four families and ranging in age from 5 to 37 years. MAP3K7 encodes transforming growth factor β (TGF-β)-activated kinase 1 (TAK1), which is involved in the mitogen-activated protein kinase (MAPK)-p38 signaling pathway. MAPK-p38 signaling was markedly altered when expression of non-canonical TGF-β-driven target genes was impaired. These findings support the loss of transcriptional control of the TGF-β-MAPK-p38 pathway in fibroblasts obtained from affected individuals. Surprisingly, although TAK1 is located at the crossroad of inflammation, immunity, and cancer, this study reports MAP3K7 mutations in a developmental disorder affecting mainly cartilage, bone, and heart. PMID:27426734

  6. Mapping global potential risk of mango sudden decline disease caused by fungus Ceratocystis fimbriata

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mango Sudden Decline (MSD), sometimes referred to as mango wilt, is an important disease of mango caused by one of the most significant fungal species causing disease in woody plants, Ceratocystis fimbriata. This species is mainly disseminated by the mango bark beetle, Hypocryphalus mangiferae (Steb...

  7. Alteration zone Mapping in the Meiduk and Sar Cheshmeh Porphyry Copper Mining Districts of Iran using Advanced Land Imager (ALI) Satellite Data

    NASA Astrophysics Data System (ADS)

    Beiranvand Pour, A.; Hashim, M.

    2015-10-01

    This study evaluates the capability of Earth Observing-1 (EO1) Advanced Land Imager (ALI) data for hydrothermal alteration mapping in the Meiduk and Sar Cheshmeh porphyry copper mining districts, SE Iran. Feature-oriented principal components selection, 4/2, 8/9, 5/4 band ratioing were applied to ALI data for enhancing the hydrothermally altered rocks associated with porphyry copper mineralization, lithological units and vegetation. Mixture-tuned matched-filtering (MTMF) was tested to discriminate the hydrothermal alteration areas of porphyry copper mineralization from surrounding environment using the shortwave infrared bands of ALI. Results indicate that the tested methods are able to yield spectral information for identifying vegetation, iron oxide/hydroxide and clay minerals, lithological units and the discrimination of hydrothermally altered rocks from unaltered rocks using ALI data.

  8. Lasting effects of instruction guided by the conflict map: Experimental study of learning about the causes of the seasons

    NASA Astrophysics Data System (ADS)

    Tsai, Chin-Chung; Chang, Chun-Yen

    2005-12-01

    This study was based on the framework of the conflict map to facilitate student conceptual learning about causes of the seasons. Instruction guided by the conflict map emphasizes not only the use of discrepant events, but also the resolution of conflict between students' alternative conceptions and scientific conceptions, using critical events or explanations and relevant perceptions and conceptions that explicate the scientific conceptions. Two ninth grade science classes in Taiwan participated in this quasi-experimental study in which one class was assigned to a traditional teaching group and the other class was assigned to a conflict map instruction treatment. Students' ideas were gathered through three interviews: the first was conducted 1 week after the instruction; the second 2 months afterward; and the third at 8 months after the treatment. Through an analysis of students' interview responses, it was revealed that many students, even after instruction, had a common alternative conception that seasons were determined by the earth's distance to the sun. However, the instruction guided by the framework of the conflict map was shown to be a potential way of changing the alternative conception and acquiring scientific understandings, especially in light of long-term observations. A detailed analysis of students' ideas across the interviews also strongly suggests that researchers as well as practicing teachers need to pay particular attention to those students who can simply recall the scientific fact without deep thinking, as these students may learn science through rote memorization and soon regress to alternative conceptions after science instruction.

  9. Use of imaging in the 0.46-2.36 [micrometers] spectral region for alteration mapping in the Cuprite mining district, Nevada

    USGS Publications Warehouse

    Abrams, Michael J.; Ashley, R.P.; Rowan, L.C.; Goetz, A.F.H.; Kahle, A.B.

    1977-01-01

    Color composites of Landsat MSS ratio images that display variations in the intensity of ferric-iron absorption bands are highly effective for mapping limonitic altered rocks, but ineffective for mapping nonlimonitic altered rocks. Analysis of 0.45-2.5 ?m field and laboratory spectra shows that iron-deficient opalites in the Cuprite mining district, Nevada, have an intense OH-absorption band near 2.2 ?m owing to their clay mineral and alunite contents and that this spectral feature is absent or weak in adjacent unaltered tuff and basalt. To evaluate the usefulness of this spectral feature for discriminating between altered and unaltered rocks, we generated color-ratio composite images from multispectral (0.46-2.36 ?m) aircraft data. The altered rocks in the district can be discriminated from unaltered rocks with few ambiguities; in addition, some effects of mineralogical zoning can be discriminated within the altered area. Only variations in amounts of limonite can be discerned in shorter wavelength aircraft data, Landsat MSS bands, and color aerial photographs.

  10. Ammonia encephalopathy and awake craniotomy for brain language mapping: cause of failed awake craniotomy.

    PubMed

    Villalba Martínez, G; Fernández-Candil, J L; Vivanco-Hidalgo, R M; Pacreu Terradas, S; León Jorba, A; Arroyo Pérez, R

    2015-05-01

    We report the case of an aborted awake craniotomy for a left frontotemporoinsular glioma due to ammonia encephalopathy on a patient taking Levetiracetam, valproic acid and clobazam. This awake mapping surgery was scheduled as a second-stage procedure following partial resection eight days earlier under general anesthesia. We planned to perform the surgery with local anesthesia and sedation with remifentanil and propofol. After removal of the bone flap all sedation was stopped and we noticed slow mentation and excessive drowsiness prompting us to stop and control the airway and proceed with general anesthesia. There were no post-operative complications but the patient continued to exhibit bradypsychia and hand tremor. His ammonia level was found to be elevated and was treated with an infusion of l-carnitine after discontinuation of the valproic acid with vast improvement. Ammonia encephalopathy should be considered in patients treated with valproic acid and mental status changes who require an awake craniotomy with patient collaboration. PMID:25475698

  11. Mapping a gene causing cerebral cavernous malformation to 7q11.2-q21.

    PubMed Central

    Günel, M; Awad, I A; Anson, J; Lifton, R P

    1995-01-01

    Cerebral cavernous malformation is a common disease of the brain vasculature of unknown cause characterized by dilated thin-walled sinusoidal vessels (caverns); these lesions cause varying clinical presentations which include headache, seizure, and hemorrhagic stroke. This disorder is frequently familial, with autosomal dominant inheritance. Using a general linkage approach in two extended cavernous malformation kindreds, we have identified linkage of this trait to chromosome 7q11.2-q21. Multipoint linkage analysis yields a peak logarithm of odds (lod) score of 6.88 with zero recombination with locus D7S669 and localizes the gene to a 7-cM region in the interval between loci ELN and D7S802. Images Fig. 1 Fig. 2 PMID:7604043

  12. Alterations of choline phospholipid metabolism in endometrial cancer are caused by choline kinase alpha overexpression and a hyperactivated deacylation pathway.

    PubMed

    Trousil, Sebastian; Lee, Patrizia; Pinato, David J; Ellis, James K; Dina, Roberto; Aboagye, Eric O; Keun, Hector C; Sharma, Rohini

    2014-12-01

    Metabolic rearrangements subsequent to malignant transformation are not well characterized in endometrial cancer. Identification of altered metabolites could facilitate imaging-guided diagnosis, treatment surveillance, and help to identify new therapeutic options. Here, we used high-resolution magic angle spinning magnetic resonance mass spectroscopy on endometrial cancer surgical specimens and normal endometrial tissue to investigate the key modulators that might explain metabolic changes, incorporating additional investigations using qRT-PCR, Western blotting, tissue microarrays (TMA), and uptake assays of [(3)H]-labeled choline. Lipid metabolism was severely dysregulated in endometrial cancer with various amino acids, inositols, nucleobases, and glutathione also altered. Among the most important lipid-related alterations were increased phosphocholine levels (increased 70% in endometrial cancer). Mechanistic investigations revealed that changes were not due to altered choline transporter expression, but rather due to increased expression of choline kinase α (CHKA) and an activated deacylation pathway, as indicated by upregulated expression of the catabolic enzymes LYPLA1, LYPLA2, and GPCPD1. We confirmed the significance of CHKA overexpression on a TMA, including a large series of endometrial hyperplasia, atypical hyperplasia, and adenocarcinoma tissues, supporting a role for CHKA in malignant transformation. Finally, we documented several-fold increases in the uptake of [(3)H]choline in endometrial cancer cell lines compared with normal endometrial stromal cells. Our results validate deregulated choline biochemistry as an important source of noninvasive imaging biomarkers for endometrial cancer. PMID:25267063

  13. Molecular cause and functional impact of altered synaptic lipid signaling due to a prg-1 gene SNP.

    PubMed

    Vogt, Johannes; Yang, Jenq-Wei; Mobascher, Arian; Cheng, Jin; Li, Yunbo; Liu, Xingfeng; Baumgart, Jan; Thalman, Carine; Kirischuk, Sergei; Unichenko, Petr; Horta, Guilherme; Radyushkin, Konstantin; Stroh, Albrecht; Richers, Sebastian; Sahragard, Nassim; Distler, Ute; Tenzer, Stefan; Qiao, Lianyong; Lieb, Klaus; Tüscher, Oliver; Binder, Harald; Ferreiros, Nerea; Tegeder, Irmgard; Morris, Andrew J; Gropa, Sergiu; Nürnberg, Peter; Toliat, Mohammad R; Winterer, Georg; Luhmann, Heiko J; Huai, Jisen; Nitsch, Robert

    2016-01-01

    Loss of plasticity-related gene 1 (PRG-1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg-1 (R345T/mutPRG-1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss-of-PRG-1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG-1(+/-) mice, which are animal correlates of human PRG-1(+/mut) carriers, showed an altered cortical network function and stress-related behavioral changes indicating altered resilience against psychiatric disorders. These could be reversed by modulation of phospholipid signaling via pharmacological inhibition of the LPA-synthesizing molecule autotaxin. In line, EEG recordings in a human population-based cohort revealed an E/I balance shift in monoallelic mutPRG-1 carriers and an impaired sensory gating, which is regarded as an endophenotype of stress-related mental disorders. Intervention into bioactive lipid signaling is thus a promising strategy to interfere with glutamate-dependent symptoms in psychiatric diseases. PMID:26671989

  14. DMSP dosimetry data: a space measurement and mapping of upset-causing phenomena

    SciTech Connect

    Mullen, E.G.; Gussenhoven, M.S.; Lynch, K.A.; Brautigam, D.H.

    1987-12-01

    Data from the DMSP/F7 satellite-dosimeter star-event counters are presented. The DMSP dosimeter star-event counters measure the number of pulses that exceed set energy deposition levels (40 MeV for three detectors and 75 MeV for the fourth detector) behind four different thicknesses of aluminum shielding. The term star event is used because linear-energy-transfer depositions above 40 MeV can be produced by high-energy proton or heavy-ion interactions with nuclei in the detector creating a star-type release of energetic secondaries. The energy deposition that creates the high-energy pulses in the detectors can come either directly from incident cosmic rays, directly from high-energy protons that traverse long path lengths in the detector volume, indirectly from nuclear reactions in the detector created by incident high-energy protons, or indirectly from nuclear reactions in the vicinity of the detector which create recoiling nuclei that deposit energy in the detector. These nuclear stars and direct energy pulses create single event upsets (SEUs) in microelectronic components in the near-Earth space environment. Properties of the star channel of the dosimeter on DMSP/F7, the star-count maps of the 840-km region of space, and their relation to upset phenomena are described.

  15. DMSP dosimetry data: A space measurement and mapping of upset causing phenomena

    SciTech Connect

    Mullen, E.G.; Gussenhoven, M.S.; Lynch, K.A.; Brautigam, D.H.

    1987-12-01

    Data from the DMSP/F7 satellite dosimeter star event counters are presented. The DMSP dosimeter star event counters measure the number of pulses that exceed set energy deposition levels (40 MeV for three detectors and 75 MeV for the fourth detector) behind four different thicknesses of aluminum shielding. The term ''star event'' is used because linear energy transfer depositions above 40 MeV can be produced by high energy proton or heavy ion interactions with nuclei in the detector creating a star type release of energetic secondaries. The energy deposition that creates the high energy pulses in the detectors can come either directly from incident cosmic rays, directly from high energy protons that traverse long path lengths in the detector volume, indirectly from nuclear reactions in the detector created by incident high energy protons, or indirectly from nuclear reactions in the vicinity of the detector which create recoiling nuclei that deposit energy in the detector. These nuclear stars and direct energy pulses create single event upsets (SEUs) in microelectronic components in the near-Earth space environment. Here the authors first describe the properties of the star channel of the dosimeter on DMSP/F7; then present the star count maps of the 840 km region of space; and finally discuss their relation to upset phenomena.

  16. Mapping Global Potential Risk of Mango Sudden Decline Disease Caused by Ceratocystis fimbriata

    PubMed Central

    Oliveira, Leonardo S. S.; Alfenas, Acelino C.; Neven, Lisa G.; Al-Sadi, Abdullah M.

    2016-01-01

    The Mango Sudden Decline (MSD), also referred to as Mango Wilt, is an important disease of mango in Brazil, Oman and Pakistan. This fungus is mainly disseminated by the mango bark beetle, Hypocryphalus mangiferae (Stebbing), by infected plant material, and the infested soils where it is able to survive for long periods. The best way to avoid losses due to MSD is to prevent its establishment in mango production areas. Our objectives in this study were to: (1) predict the global potential distribution of MSD, (2) identify the mango growing areas that are under potential risk of MSD establishment, and (3) identify climatic factors associated with MSD distribution. Occurrence records were collected from Brazil, Oman and Pakistan where the disease is currently known to occur in mango. We used the correlative maximum entropy based model (MaxEnt) algorithm to assess the global potential distribution of MSD. The MaxEnt model predicted suitable areas in countries where the disease does not already occur in mango, but where mango is grown. Among these areas are the largest mango producers in the world including India, China, Thailand, Indonesia, and Mexico. The mean annual temperature, precipitation of coldest quarter, precipitation seasonality, and precipitation of driest month variables contributed most to the potential distribution of MSD disease. The mango bark beetle vector is known to occur beyond the locations where MSD currently exists and where the model predicted suitable areas, thus showing a high likelihood for disease establishment in areas predicted by our model. Our study is the first to map the potential risk of MSD establishment on a global scale. This information can be used in designing strategies to prevent introduction and establishment of MSD disease, and in preparation of efficient pest risk assessments and monitoring programs. PMID:27415625

  17. Mapping Global Potential Risk of Mango Sudden Decline Disease Caused by Ceratocystis fimbriata.

    PubMed

    Galdino, Tarcísio Visintin da Silva; Kumar, Sunil; Oliveira, Leonardo S S; Alfenas, Acelino C; Neven, Lisa G; Al-Sadi, Abdullah M; Picanço, Marcelo C

    2016-01-01

    The Mango Sudden Decline (MSD), also referred to as Mango Wilt, is an important disease of mango in Brazil, Oman and Pakistan. This fungus is mainly disseminated by the mango bark beetle, Hypocryphalus mangiferae (Stebbing), by infected plant material, and the infested soils where it is able to survive for long periods. The best way to avoid losses due to MSD is to prevent its establishment in mango production areas. Our objectives in this study were to: (1) predict the global potential distribution of MSD, (2) identify the mango growing areas that are under potential risk of MSD establishment, and (3) identify climatic factors associated with MSD distribution. Occurrence records were collected from Brazil, Oman and Pakistan where the disease is currently known to occur in mango. We used the correlative maximum entropy based model (MaxEnt) algorithm to assess the global potential distribution of MSD. The MaxEnt model predicted suitable areas in countries where the disease does not already occur in mango, but where mango is grown. Among these areas are the largest mango producers in the world including India, China, Thailand, Indonesia, and Mexico. The mean annual temperature, precipitation of coldest quarter, precipitation seasonality, and precipitation of driest month variables contributed most to the potential distribution of MSD disease. The mango bark beetle vector is known to occur beyond the locations where MSD currently exists and where the model predicted suitable areas, thus showing a high likelihood for disease establishment in areas predicted by our model. Our study is the first to map the potential risk of MSD establishment on a global scale. This information can be used in designing strategies to prevent introduction and establishment of MSD disease, and in preparation of efficient pest risk assessments and monitoring programs. PMID:27415625

  18. Coagulation Factor Concentrates Fail to Restore Alterations in Fibrin Formation Caused by Rivaroxaban or Dabigatran in Studies With Flowing Blood From Treated Healthy Volunteers.

    PubMed

    Arellano-Rodrigo, Eduardo; Lopez-Vilchez, Irene; Galan, Ana M; Molina, Patricia; Reverter, Joan Carles; Carné, Xavier; Villalta, Jaume; Tassies, Dolors; Lozano, Miguel; Díaz-Ricart, Maribel; Escolar, Gines

    2015-10-01

    We evaluated the hemostatic alterations in blood from healthy individuals treated for 5 days with direct oral anticoagulants (DOACs) rivaroxaban (20 mg/d) or dabigatran (150 mg/12 h) in a single-blind clinical trial with crossover assignment (NCT01478282). We assessed the potential of prothrombin complex concentrates, activated prothrombin complex concentrates, or recombinant activated factor VII, when added ex vivo, to reverse the alterations caused by these DOACs. Blood was drawn at maximum plasma concentration after the last dose of each DOAC, and modifications in coagulation biomarkers were evaluated using a series of tests performed under steady conditions including routine coagulation, thrombin generation, and thromboelastometry assays. Additional studies in standardized flow devices were applied to evaluate alterations on platelet deposition and fibrin formation on damaged vascular surfaces exposed to flowing blood. Both DOACs caused important modifications of all coagulation biomarkers and significantly reduced fibrin formation in flow studies. Alterations in biomarkers observed in steady laboratory tests were normalized and occasionally overcompensated by procoagulant strategies. In contrast, reductions in fibrin formation observed in studies with flowing blood were improved, although never completely restored to baseline levels. Effects of dabigatran in flow studies appeared more resistant to reversal strategies than those of rivaroxaban. Inconsistencies between results of coagulation studies in steady or flowing assays not only raise concerns about the adequacy of the earlier tests to predict the restoration of the coagulopathy induced by DOACs but also suggest limitations of nonspecific procoagulant strategies to control severe coagulopathy in patients inadvertently overexposed these agents. PMID:26364029

  19. Ground-based Hyperspectral Remote Sensing for Mapping Rock Alterations and Lithologies: Case Studies from Semail Ophiolite, Oman and Rush Springs Sandstone, Oklahoma

    NASA Astrophysics Data System (ADS)

    Sun, L.; Khan, S.; Hauser, D. L.; Glennie, C. L.; Snyder, C.; Okyay, U.

    2014-12-01

    This study used ground-based hyperspectral remote sensing data to map rock alterations and lithologies at Semail Ophiolite, Oman, as well as hydrocarbon-induced rock alterations at Cement, Oklahoma. The Samail Ophiolite exposed the largest, least-deformed, and the most-studied ophiolite in the world. Hydrocarbon seepages at Cement, Oklahoma brought hydrocarbons to the Rush Springs sandstones at surface, and generated rock alterations including bleaching of red beds, and carbonate cementation. Surficial expressions of rock alterations and different lithofacies are distinct from adjacent rocks, and can be detected by remote sensing techniques. Hyperspectral remote sensing acquires light intensity for hundreds of bands in a continuous electromagnetic spectrum from visible light to short-wave infrared radiation, and holds potential to characterize rocks with great precision. Ground-based hyperspectral study could scan the objects at close ranges thus provide very fine spatial resolutions (millimeters to centimeters). This study mapped all the major iconic outcrops of Semail ophiolite including pillow lava, sheeted dykes, layered gabbros, and peridotites. This study also identified surficial rock alterations induced by hydrocarbons at Cement, Oklahoma. Reddish-brown Rush Spring sandstones are bleached to pink, yellow, and gray colors; pore spaces in the sandstones have been filled with carbonate cementation. Laboratory spectroscopy was used to assist with mineral identification and classification in hyperspectral data. Terrestrial laser scanning (TLS) was used to provide high-accuracy spatial references. Principal component analysis, minimum noise fraction, spectral angle mapper, and band ratios are used in image processing. Combining lithological, remote sensing and geochemical data, this study built a model for petroleum seepage and related rock alterations, and provided a workflow for employing ground-based hyperspectral remote sensing techniques in petrological

  20. Sub-lethal glyphosate exposure alters flowering phenology and causes transient male-sterility in Brassica spp

    PubMed Central

    2014-01-01

    Background Herbicide resistance in weedy plant populations can develop through different mechanisms such as gene flow of herbicide resistance transgenes from crop species into compatible weedy species or by natural evolution of herbicide resistance or tolerance following selection pressure. Results from our previous studies suggest that sub-lethal levels of the herbicide glyphosate can alter the pattern of gene flow between glyphosate resistant Canola®, Brassica napus, and glyphosate sensitive varieties of B. napus and B. rapa. The objectives of this study were to examine the phenological and developmental changes that occur in Brassica crop and weed species following sub-lethal doses of the herbicides glyphosate and glufosinate. We examined several vegetative and reproductive traits of potted plants under greenhouse conditions, treated with sub-lethal herbicide sprays. Results Our results indicate that exposure of Brassica spp. to a sub-lethal dose of glyphosate results in altering flowering phenology and reproductive function. Flowering of all sensitive species was significantly delayed and reproductive function, specifically male fertility, was suppressed. Higher dosage levels typically contributed to an increase in the magnitude of phenotypic changes. Conclusions These results demonstrate that Brassica spp. plants that are exposed to sub-lethal doses of glyphosate could be subject to very different pollination patterns and an altered pattern of gene flow that would result from changes in the overlap of flowering phenology between species. Implications include the potential for increased glyphosate resistance evolution and spread in weedy communities exposed to sub-lethal glyphosate. PMID:24655547

  1. Improving palm oil quality through identification and mapping of the lipase gene causing oil deterioration.

    PubMed

    Morcillo, F; Cros, D; Billotte, N; Ngando-Ebongue, G-F; Domonhédo, H; Pizot, M; Cuéllar, T; Espéout, S; Dhouib, R; Bourgis, F; Claverol, S; Tranbarger, T J; Nouy, B; Arondel, V

    2013-01-01

    The oil palm fruit mesocarp contains high lipase activity that increases free fatty acids and necessitates post-harvest inactivation by heat treatment of fruit bunches. Even before heat treatment the mesocarp lipase activity causes consequential oil losses and requires costly measures to limit free fatty acids quantities. Here we demonstrate that elite low-lipase lines yield oil with substantially less free fatty acids than standard genotypes, allowing more flexibility for post-harvest fruit processing and extended ripening for increased yields. We identify the lipase and its gene cosegregates with the low-/high-lipase trait, providing breeders a marker to rapidly identify potent elite genitors and introgress the trait into major cultivars. Overall, economic gains brought by wide adoption of this material could represent up to one billion dollars per year. Expected benefits concern all planters but are likely to be highest for African smallholders who would be more able to produce oil that meets international quality standards. PMID:23857501

  2. Alterations in sociability and functional brain connectivity caused by early-life seizures are prevented by bumetanide.

    PubMed

    Holmes, Gregory L; Tian, Chengju; Hernan, Amanda E; Flynn, Sean; Camp, Devon; Barry, Jeremy

    2015-05-01

    There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P)days 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-P25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of ECl toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure

  3. Alterations in Sociability and Functional Brain Connectivity Caused by Early-Life Seizures is Reversed by Bumetanide

    PubMed Central

    Holmes, Gregory L.; Tian, Chengju; Hernan, Amanda E.; Flynn, Sean; Camp, Devon; Barry, Jeremy

    2015-01-01

    There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P) day 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of ECl toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure

  4. Metabolic alterations caused by HNF1β expression in ovarian clear cell carcinoma contribute to cell survival

    PubMed Central

    Amano, Yasuaki; Mandai, Masaki; Yamaguchi, Ken; Matsumura, Noriomi; Kharma, Budiman; Baba, Tsukasa; Abiko, Kaoru; Hamanishi, Junzo; Yoshioka, Yumiko; Konishi, Ikuo

    2015-01-01

    HNF1β is expressed exclusively in ovarian clear cell carcinoma (OCCC) and not in other ovarian cancers, regarded as a hallmark of this tumor. This implies its central role in the unique character of OCCC, including resistance to chemotherapy, but its exact role and influence in cancer biology or the molecular bases of its function are largely unknown. Using comprehensive metabolome analysis of HNF1β_shRNA-stable cell lines, we show here that HNF1β drastically alters intracellular metabolism, especially in direction to enhance aerobic glycolysis, so called the “Warburg effect”. The consequence of the metabolic change contributed cell survival under stresses such as hypoxia and chemo-reagent, only when sufficient glucose supply was available. Augmented cell survival was based on the reduced ROS activity derived from metabolic alteration such as shift from oxidative phosphorylation to glycolysis and increased intracellular anti-oxidant, glutathione (GSH). One of the cystine transporters, rBAT is likely to play a major role in this GSH increase. These data suggest that HNF1β, possibly induced by stressful microenvironment in the endometriotic cyst, confers survival advantage to the epithelial cells, which leads to the occurrence of OCCC, a chemo-resistant phenotype of ovarian cancer. PMID:26318292

  5. Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats.

    PubMed

    Shortall, Sinead E; Green, A Richard; Fone, Kevin Cf; King, Madeleine V

    2016-07-01

    Administration of caffeine with 3,4-methylenedioxymethamphetamine (MDMA) alters the pharmacological properties of MDMA in rats. The current study examined whether caffeine alters the behavioural and neurochemical effects of mephedrone, which has similar psychoactive effects to MDMA. Rats received either saline, mephedrone (10 mg/kg), caffeine (10 mg/kg) or combined caffeine and mephedrone intraperitoneally twice weekly on consecutive days for three weeks. Locomotor activity (days 1 and 16), novel object discrimination (NOD, day 2), elevated plus maze (EPM) exploration (day 8), rectal temperature changes (day 9) and pre-pulse inhibition (PPI) of acoustic startle response (day 15) were assessed. Seven days after the final injection, brain regions were collected for the measurement of 5-hydroxytryptamine (5-HT), dopamine and their metabolites. Combined caffeine and mephedrone further enhanced the locomotor response observed following either drug administered alone, and converted mephedrone-induced hypothermia to hyperthermia. Co-administration also abolished mephedrone-induced anxiogenic response on the EPM, but had no effect on NOD or PPI. Importantly, no long-term neurotoxicity was detected following repeated mephedrone alone or when co-administered with caffeine. In conclusion, the study suggests a potentially dangerous effect of concomitant caffeine and mephedrone, and highlights the importance of taking polydrug use into consideration when investigating the acute adverse effect profile of popular recreational drugs. PMID:27257032

  6. Applied AC and DC magnetic fields cause alterations in the mitotic cycle of early sea urchin embryos

    SciTech Connect

    Levin, M.; Ernst, S.G.

    1995-09-01

    This study demonstrates that exposure to 60 Hz magnetic fields (3.4--8.8 mt) and magnetic fields over the range DC-600 kHz (2.5--6.5 mT) can alter the early embryonic development of sea urchin embryos by inducing alterations in the timing of the cell cycle. Batches of fertilized eggs were exposed to the fields produced by a coil system. Samples of the continuous cultures were taken and scored for cell division. The times of both the first and second cell divisions were advanced by ELF AC fields and by static fields. The magnitude of the 60 Hz effect appears proportional to the field strength over the range tested. the relationship to field frequency was nonlinear and complex. For certain frequencies above the ELF range, the exposure resulted in a delay of the onset of mitosis. The advance of mitosis was also dependent on the duration of exposure and on the timing of exposure relative to fertilization.

  7. Disturbed Neuronal ER-Golgi Sorting of Unassembled Glycine Receptors Suggests Altered Subcellular Processing Is a Cause of Human Hyperekplexia

    PubMed Central

    Schaefer, Natascha; Kluck, Christoph J.; Price, Kerry L.; Meiselbach, Heike; Vornberger, Nadine; Schwarzinger, Stephan; Hartmann, Stephanie; Langlhofer, Georg; Schulz, Solveig; Schlegel, Nadja; Brockmann, Knut; Lynch, Bryan; Becker, Cord-Michael; Lummis, Sarah C.R.

    2015-01-01

    Recent studies on the pathogenic mechanisms of recessive hyperekplexia indicate disturbances in glycine receptor (GlyR) α1 biogenesis. Here, we examine the properties of a range of novel glycine receptor mutants identified in human hyperekplexia patients using expression in transfected cell lines and primary neurons. All of the novel mutants localized in the large extracellular domain of the GlyR α1 have reduced cell surface expression with a high proportion of receptors being retained in the ER, although there is forward trafficking of glycosylated subpopulations into the ER-Golgi intermediate compartment and cis-Golgi compartment. CD spectroscopy revealed that the mutant receptors have proportions of secondary structural elements similar to wild-type receptors. Two mutants in loop B (G160R, T162M) were functional, but none of those in loop D/β2–3 were. One nonfunctional truncated mutant (R316X) could be rescued by coexpression with the lacking C-terminal domain. We conclude that a proportion of GlyR α1 mutants can be transported to the plasma membrane but do not necessarily form functional ion channels. We suggest that loop D/β2–3 is an important determinant for GlyR trafficking and functionality, whereas alterations to loop B alter agonist potencies, indicating that residues here are critical elements in ligand binding. PMID:25568133

  8. EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia

    PubMed Central

    Boczonadi, Veronika; Müller, Juliane S.; Pyle, Angela; Munkley, Jennifer; Dor, Talya; Quartararo, Jade; Ferrero, Ileana; Karcagi, Veronika; Giunta, Michele; Polvikoski, Tuomo; Birchall, Daniel; Princzinger, Agota; Cinnamon, Yuval; Lützkendorf, Susanne; Piko, Henriett; Reza, Mojgan; Florez, Laura; Santibanez-Koref, Mauro; Griffin, Helen; Schuelke, Markus; Elpeleg, Orly; Kalaydjieva, Luba; Lochmüller, Hanns; Elliott, David J.; Chinnery, Patrick F.; Edvardson, Shimon; Horvath, Rita

    2014-01-01

    The exosome is a multi-protein complex, required for the degradation of AU-rich element (ARE) containing messenger RNAs (mRNAs). EXOSC8 is an essential protein of the exosome core, as its depletion causes a severe growth defect in yeast. Here we show that homozygous missense mutations in EXOSC8 cause progressive and lethal neurological disease in 22 infants from three independent pedigrees. Affected individuals have cerebellar and corpus callosum hypoplasia, abnormal myelination of the central nervous system or spinal motor neuron disease. Experimental downregulation of EXOSC8 in human oligodendroglia cells and in zebrafish induce a specific increase in ARE mRNAs encoding myelin proteins, showing that the imbalanced supply of myelin proteins causes the disruption of myelin, and explaining the clinical presentation. These findings show the central role of the exosomal pathway in neurodegenerative disease. PMID:24989451

  9. A rare cause of altered mental status and fever in a young military recruit in Puerto Rico.

    PubMed

    Boodosingh, Dev Richard; Robles-Arias, Carlos; Alemán-Ortiz, Jesse R; Rodríguez-Cintrón, William

    2014-12-01

    Heat stroke (HS) is a medical emergency characterized by increased core body temperature with associated systemic inflammatory response leading to a syndrome of multi-organ damage in which encephalopathy predominates. We describe a case of a 29 year old male recruit presenting with altered mental status during military training in Puerto Rico. Associated symptoms included high grade fever, dizziness, nausea, vomiting, blurred vision and profuse sweating followed by loss of consciousness. Upon arrival to medical evaluation the patient was found with dry skin and depressed Glasgow Coma Score. Initial laboratories, clinical evolution of symptoms and imaging studies were consistent with the diagnosis of HS. Patient was managed with mechanical ventilatory support, intravenous fluids and external cooling measures. He was later discharged home without any neurological sequelae. To our knowledge this is the first documented case of HS in Puerto Rico. PMID:25563039

  10. Specific inflammatory response of Anemonia sulcata (Cnidaria) after bacterial injection causes tissue reaction and enzymatic activity alteration.

    PubMed

    Trapani, M R; Parisi, M G; Parrinello, D; Sanfratello, M A; Benenati, G; Palla, F; Cammarata, M

    2016-03-01

    The evolution of multicellular organisms was marked by adaptations to protect against pathogens. The mechanisms for discriminating the ''self'' from ''non-self" have evolved into a long history of cellular and molecular strategies, from damage repair to the co-evolution of host-pathogen interactions. We investigated the inflammatory response in Anemonia sulcata (Cnidaria: Anthozoa) following injection of substances that varied in type and dimension, and observed clear, strong and specific reactions, especially after injection of Escherichia coli and Vibrio alginolyticus. Moreover, we analyzed enzymatic activity of protease, phosphatase and esterase, showing how the injection of different bacterial strains alters the expression of these enzymes and suggesting a correlation between the appearance of the inflammatory reaction and the modification of enzymatic activities. Our study shows for the first time, a specific reaction and enzymatic responses following injection of bacteria in a cnidarian. PMID:26836977

  11. Developmental treatment with ethinyl estradiol, but not bisphenol A, causes alterations in sexually dimorphic behaviors in male and female Sprague Dawley rats.

    PubMed

    Ferguson, Sherry A; Law, Charles Delbert; Kissling, Grace E

    2014-08-01

    The developing central nervous system may be particularly sensitive to bisphenol A (BPA)-induced alterations. Here, pregnant Sprague Dawley rats (n = 11-12/group) were gavaged daily with vehicle, 2.5 or 25.0 μg/kg BPA, or 5.0 or 10.0 μg/kg ethinyl estradiol (EE2) on gestational days 6-21. The BPA doses were selected to be below the no-observed-adverse-effect level (NOAEL) of 5 mg/kg/day. On postnatal days 1-21, all offspring/litter were orally treated with the same dose. A naïve control group was not gavaged. Body weight, pubertal age, estrous cyclicity, and adult serum hormone levels were measured. Adolescent play, running wheel activity, flavored solution intake, female sex behavior, and manually elicited lordosis were assessed. No significant differences existed between the vehicle and naïve control groups. Vehicle controls exhibited significant sexual dimorphism for most behaviors, indicating these evaluations were sensitive to sex differences. However, only EE2 treatment caused significant effects. Relative to female controls, EE2-treated females were heavier, exhibited delayed vaginal opening, aberrant estrous cyclicity, increased play behavior, decreased running wheel activity, and increased aggression toward the stimulus male during sexual behavior assessments. Relative to male controls, EE2-treated males were older at testes descent and preputial separation and had lower testosterone levels. These results suggest EE2-induced masculinization/defeminization of females and are consistent with increased volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) at weaning in female siblings of these subjects (He, Z., Paule, M. G. and Ferguson, S. A. (2012) Low oral doses of bisphenol A increase volume of the sexually dimorphic nucleus of the preoptic area in male, but not female, rats at postnatal day 21. Neurotoxicol. Teratol. 34, 331-337). Although EE2 treatment caused pubertal delays and decreased testosterone levels in males, their

  12. Developmental Treatment with Ethinyl Estradiol, but Not Bisphenol A, Causes Alterations in Sexually Dimorphic Behaviors in Male and Female Sprague Dawley Rats

    PubMed Central

    Ferguson, Sherry A.; Law, Charles Delbert; Kissling, Grace E.

    2014-01-01

    The developing central nervous system may be particularly sensitive to bisphenol A (BPA)-induced alterations. Here, pregnant Sprague Dawley rats (n = 11–12/group) were gavaged daily with vehicle, 2.5 or 25.0 μg/kg BPA, or 5.0 or 10.0 μg/kg ethinyl estradiol (EE2) on gestational days 6–21. The BPA doses were selected to be below the no-observed-adverse-effect level (NOAEL) of 5 mg/kg/day. On postnatal days 1–21, all offspring/litter were orally treated with the same dose. A naïve control group was not gavaged. Body weight, pubertal age, estrous cyclicity, and adult serum hormone levels were measured. Adolescent play, running wheel activity, flavored solution intake, female sex behavior, and manually elicited lordosis were assessed. No significant differences existed between the vehicle and naïve control groups. Vehicle controls exhibited significant sexual dimorphism for most behaviors, indicating these evaluations were sensitive to sex differences. However, only EE2 treatment caused significant effects. Relative to female controls, EE2-treated females were heavier, exhibited delayed vaginal opening, aberrant estrous cyclicity, increased play behavior, decreased running wheel activity, and increased aggression toward the stimulus male during sexual behavior assessments. Relative to male controls, EE2-treated males were older at testes descent and preputial separation and had lower testosterone levels. These results suggest EE2-induced masculinization/defeminization of females and are consistent with increased volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) at weaning in female siblings of these subjects (He, Z., Paule, M. G. and Ferguson, S. A. (2012) Low oral doses of bisphenol A increase volume of the sexually dimorphic nucleus of the preoptic area in male, but not female, rats at postnatal day 21. Neurotoxicol. Teratol. 34, 331–337). Although EE2 treatment caused pubertal delays and decreased testosterone levels in males, their

  13. Heat stress causes alterations in the cell-wall polymers and anatomy of coffee leaves (Coffea arabica L.).

    PubMed

    Lima, Rogério Barbosa; dos Santos, Tiago Benedito; Vieira, Luiz Gonzaga Esteves; Ferrarese, Maria de Lourdes Lúcio; Ferrarese-Filho, Osvaldo; Donatti, Lucélia; Boeger, Maria Regina Torres; Petkowicz, Carmen Lúcia de Oliveira

    2013-03-01

    Coffee plants were subjected to heat stress (37 °C) and compared with control plants (24 °C). Cell wall polysaccharides were extracted using water (W), EDTA (E) and 4M NaOH (H30 and H70). In addition, monolignols were analyzed, and the leaves were observed by microscopy. Plants under heat stress accumulated higher contents of arabinose and galactose in fraction W. Xylose contents were observed to decrease in H30 fractions after the heat stress, whereas galactose and uronic acid increased. H70 fractions from plants exposed to heat stress showed increased xylose contents, whereas the contents of arabinose and glucose decreased. Differences in the molar-mass profiles of polysaccharides were also observed. The primary monolignol contents increased after the heat stress. Structural alterations in palisade cells and ultrastructural damage in chloroplasts were also observed. Our results demonstrate that the chemical profile of coffee cell-wall polymers and structural cell anatomy change under heat stress. PMID:23465912

  14. A High-Fat Diet Causes Impairment in Hippocampal Memory and Sex-Dependent Alterations in Peripheral Metabolism

    PubMed Central

    Underwood, Erica L.; Thompson, Lucien T.

    2016-01-01

    While high-fat diets are associated with rising incidence of obesity/type-2 diabetes and can induce metabolic and cognitive deficits, sex-dependent comparisons are rarely systematically made. Effects of exclusive consumption of a high-fat diet (HFD) on systemic metabolism and on behavioral measures of hippocampal-dependent memory were compared in young male and female LE rats. Littermates were fed from weaning either a HFD or a control diet (CD) for 12 wk prior to testing. Sex-different effects of the HFD were observed in classic metabolic signs associated with type-2 diabetes. Males fed the HFD became obese, and had elevated fasted blood glucose levels, elevated corticosterone, and impaired glucose-tolerance, while females on the HFD exhibited only elevated corticosterone. Regardless of peripheral metabolism alteration, rats of both sexes fed the HFD were equally impaired in a spatial object recognition memory task associated with impaired hippocampal function. While the metabolic changes reported here have been characterized previously in males, the set of diet-induced effects observed here in females are novel. Impaired memory can have significant cognitive consequences, over the short-term and over the lifespan. A significant need exists for comparative research into sex-dependent differences underlying obesity and metabolic syndromes relating systemic, cognitive, and neural plasticity mechanisms. PMID:26819773

  15. Long-Term Increased Carnitine Palmitoyltransferase 1A Expression in Ventromedial Hypotalamus Causes Hyperphagia and Alters the Hypothalamic Lipidomic Profile

    PubMed Central

    Fabriàs, Gemma; Casas, Josefina; Costa, Ana S. H.; Malandrino, Maria Ida; Fernández-López, José-Antonio; Remesar, Xavier; Gao, Su; Chohnan, Shigeru; Rodríguez-Peña, Maria Sol; Petry, Harald; Asins, Guillermina; Hegardt, Fausto G.; Herrero, Laura; Serra, Dolors

    2014-01-01

    Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT) 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH), long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT) and reduced vesicular glutamate transporter 2 (VGLUT2) expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH. PMID:24819600

  16. Visible foliar injury caused by ozone alters the relationship between SPAD meter readings and chlorophyll concentrations in cutleaf coneflower.

    PubMed

    Neufeld, Howard S; Chappelka, Arthur H; Somers, Greg L; Burkey, Kent O; Davison, Alan W; Finkelstein, Peter L

    2006-03-01

    The ability of the SPAD-502 chlorophyll meter to quantify chlorophyll amounts in ozone-affected leaves of cutleaf coneflower (Rudbeckia laciniata var. digitata) was assessed in this study. When relatively uninjured leaves were measured (percent leaf area affected by stipple less than 6%), SPAD meter readings were linearly related to total chlorophyll with an adjusted R (2) of 0.84. However, when leaves with foliar injury (characterized as a purple to brownish stipple on the upper leaf surface affecting more than 6% of the leaf area) were added, likelihood ratio tests showed that it was no longer possible to use the same equation to obtain chlorophyll estimations for both classes of leaves. Either an equation with a common slope or a common intercept was necessary. We suspect several factors are involved in altering the calibration of the SPAD meter for measuring chlorophyll amounts in visibly ozone-injured leaves, with the most likely being changes in either light absorption or scattering resulting from tissue necrosis. PMID:16699918

  17. Alteration of chromophoric dissolved organic matter by solar UV radiation causes rapid changes in bacterial community composition†

    PubMed Central

    Piccini, Claudia; Conde, Daniel; Pernthaler, Jakob; Sommaruga, Ruben

    2010-01-01

    We evaluated the effect of photochemical alterations of chromophoric dissolved organic matter (CDOM) on bacterial abundance, activity and community composition in a coastal lagoon of the Atlantic Ocean with high dissolved organic carbon concentration. On two occasions during the austral summer, bacteria-free water of the lagoon was exposed to different regions of the solar spectrum (full solar radiation, UV-A + PAR, PAR) or kept in the dark. Subsequently, dilution cultures were established with bacterioplankton from the lagoon that were incubated in the pre-exposed water for 5 h in the dark. Cell abundance, activity, and community composition of bacterioplankton were assessed before and after incubation in the different treatments. Changes in absorption, fluorescence, and DOC concentration were used as proxies for CDOM photoalteration. We found a significant CDOM photobleaching signal, DOC loss, as well as a stimulation of bacterial activity in the treatments pre-exposed to UV radiation, suggesting increased bioavailability of DOM. Bacterial community analysis by fluorescence in situ hybridization revealed that this stimulation was mainly accompanied by the specific enrichment of Alpha- and Betaproteobacteria. Thus, our results suggest that CDOM photoalteration not only stimulates bacterioplankton growth, but also induces rapid changes in bacterioplankton composition, which can be of relevance for ecosystem functioning, particularly considering present and future changes in the input of terrestrial CDOM to aquatic systems. PMID:19707620

  18. Long-term increased carnitine palmitoyltransferase 1A expression in ventromedial hypotalamus causes hyperphagia and alters the hypothalamic lipidomic profile.

    PubMed

    Mera, Paula; Mir, Joan Francesc; Fabriàs, Gemma; Casas, Josefina; Costa, Ana S H; Malandrino, Maria Ida; Fernández-López, José-Antonio; Remesar, Xavier; Gao, Su; Chohnan, Shigeru; Rodríguez-Peña, Maria Sol; Petry, Harald; Asins, Guillermina; Hegardt, Fausto G; Herrero, Laura; Serra, Dolors

    2014-01-01

    Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. Carnitine palmitoyltransferase (CPT) 1A is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation and it has been proposed as a crucial mediator of fasting and ghrelin orexigenic signalling. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood. To this end, we examined the effect of long-term expression of a permanently activated CPT1A isoform by using an adeno-associated viral vector injected into the VMH of rats. Peripherally, this procedure provoked hyperghrelinemia and hyperphagia, which led to overweight, hyperglycemia and insulin resistance. In the mediobasal hypothalamus (MBH), long-term CPT1AM expression in the VMH did not modify acyl-CoA or malonyl-CoA levels. However, it altered the MBH lipidomic profile since ceramides and sphingolipids increased and phospholipids decreased. Furthermore, we detected increased vesicular γ-aminobutyric acid transporter (VGAT) and reduced vesicular glutamate transporter 2 (VGLUT2) expressions, both transporters involved in this orexigenic signal. Taken together, these observations indicate that CPT1A contributes to the regulation of feeding by modulating the expression of neurotransmitter transporters and lipid components that influence the orexigenic pathways in VMH. PMID:24819600

  19. Small Molecule Disruption of Quorum Sensing Cross-Regulation in Pseudomonas aeruginosa Causes Major and Unexpected Alterations to Virulence Phenotypes

    PubMed Central

    Welsh, Michael A.; Eibergen, Nora R.; Moore, Joseph D.; Blackwell, Helen E.

    2015-01-01

    The opportunistic pathogen Pseudomonas aeruginosa uses three interwoven quorum-sensing (QS) circuits—Las, Rhl, and Pqs—to regulate the global expression of myriad virulence-associated genes. Interception of these signaling networks with small molecules represents an emerging strategy for the development of anti-infective agents against this bacterium. In the current study, we applied a chemical approach to investigate how the Las-Rhl-Pqs QS hierarchy coordinates key virulence phenotypes in wild-type P. aeruginosa. We screened a focused library of synthetic, non-native N-acyl l-homoserine lactones and identified compounds that can drastically alter production of two important virulence factors: pyocyanin and rhamnolipid. We demonstrate that these molecules act by targeting RhlR in P. aeruginosa, a QS receptor that has seen far less scrutiny to date relative to other circuitry. Unexpectedly, modulation of RhlR activity by a single compound induces inverse regulation of pyocyanin and rhamnolipid, a result that was not predicted using genetic approaches to interrogate QS in P. aeruginosa. Further, we show that certain RhlR agonists strongly repress Pqs signaling, revealing disruption of Rhl-Pqs cross-regulation as a novel mechanism for QS inhibition. These compounds significantly expand the known repertoire of chemical probes available to study RhlR in P. aeruginosa. Moreover, our results suggest that designing chemical agents to disrupt Rhl-Pqs crosstalk could be an effective antivirulence strategy to fight this common pathogen. PMID:25574853

  20. Dominant mutations causing alterations in acetyl-coenzyme A carboxylase confer tolerance to cyclohexanedione and aryloxyphenoxypropionate herbicides in maize.

    PubMed Central

    Parker, W B; Marshall, L C; Burton, J D; Somers, D A; Wyse, D L; Gronwald, J W; Gengenbach, B G

    1990-01-01

    A partially dominant mutation exhibiting increased tolerance to cyclohexanedione and aryloxyphenoxypropionate herbicides was isolated by exposing susceptible maize (Zea mays) tissue cultures to increasingly inhibitory concentrations of sethoxydim (a cyclohexanedione). The selected tissue culture (S2) was greater than 40-fold more tolerant to sethoxydim and 20-fold more tolerant to haloxyfop (an aryloxyphenoxypropionate) than the nonselected wild-type tissue culture. Regenerated S2 plants were heterozygous for the mutant allele and exhibited a high-level, but not complete, tolerance to both herbicides. Homozygous mutant families derived by self-pollinating the regenerated S2 plants exhibited no injury after treatment with 0.8 kg of sethoxydim per ha, which was greater than 16-fold the rate lethal to wild-type plants. Acetyl-coenzyme A carboxylase (ACCase; EC 6.4.1.2) is the target enzyme of cyclohexanedione and aryloxyphenoxypropionate herbicides. ACCase activities of the nonselected wild-type and homozygous mutant seedlings were similar in the absence of herbicide. ACCase activity from homozygous tolerant plants required greater than 100-fold more sethoxydim and 16-fold more haloxyfop for 50% inhibition than ACCase from wild-type plants. These results indicate that tolerance to sethoxydim and haloxyfop is controlled by a partially dominant nuclear mutation encoding a herbicide-insensitive alteration in maize ACCase. Images PMID:1976254

  1. A High-Fat Diet Causes Impairment in Hippocampal Memory and Sex-Dependent Alterations in Peripheral Metabolism.

    PubMed

    Underwood, Erica L; Thompson, Lucien T

    2016-01-01

    While high-fat diets are associated with rising incidence of obesity/type-2 diabetes and can induce metabolic and cognitive deficits, sex-dependent comparisons are rarely systematically made. Effects of exclusive consumption of a high-fat diet (HFD) on systemic metabolism and on behavioral measures of hippocampal-dependent memory were compared in young male and female LE rats. Littermates were fed from weaning either a HFD or a control diet (CD) for 12 wk prior to testing. Sex-different effects of the HFD were observed in classic metabolic signs associated with type-2 diabetes. Males fed the HFD became obese, and had elevated fasted blood glucose levels, elevated corticosterone, and impaired glucose-tolerance, while females on the HFD exhibited only elevated corticosterone. Regardless of peripheral metabolism alteration, rats of both sexes fed the HFD were equally impaired in a spatial object recognition memory task associated with impaired hippocampal function. While the metabolic changes reported here have been characterized previously in males, the set of diet-induced effects observed here in females are novel. Impaired memory can have significant cognitive consequences, over the short-term and over the lifespan. A significant need exists for comparative research into sex-dependent differences underlying obesity and metabolic syndromes relating systemic, cognitive, and neural plasticity mechanisms. PMID:26819773

  2. Ultrastructural alterations in the mouse lung caused by real-life ambient PM10 at urban traffic sites.

    PubMed

    Samara, Constantini; Kouras, Athanasios; Kaidoglou, Katerina; Emmanouil-Nikoloussi, Elpida-Niki; Simou, Chrysanthi; Bousnaki, Maria; Kelessis, Apostolos

    2015-11-01

    Current levels of ambient air particulate matter (PM) are associated with mortality and morbidity in urban populations worldwide. Nevertheless, current knowledge does not allow precise quantification or definitive ranking of the health effects of individual PM components and indeed, associations may be the result of multiple components acting on different physiological mechanisms. In this paper, healthy Balb/c mice were exposed to ambient PM10 at a traffic site of a large city (Thessaloniki, northern Greece), in parallel to control mice that were exposed to filtered air. Structural damages were examined in ultrafine sections of lung tissues by Transmission Electronic Microscopy (TEM). Ambient PM10 samples were also collected during the exposure experiment and characterized with respect to chemical composition and oxidative potential. Severe ultrastructural alterations in the lung tissue after a 10-week exposure of mice at PM10 levels often exceeding the daily limit of Directive 2008/50/EC were revealed mainly implying PM-induced oxidative stress. The DTT-based redox activity of PM10 was found within the range of values reported for traffic sites being correlated with traffic-related constituents. Although linkage of the observed lung damage with specific chemical components or sources need further elucidation, the magnitude of biological responses highlight the necessity for national and local strategies for mitigation of particle emissions from combustion sources. PMID:26081735

  3. Homozygosity Mapping and Whole Exome Sequencing Reveal a Novel Homozygous COL18A1 Mutation Causing Knobloch Syndrome

    PubMed Central

    Piri, Niloofar; Nürnberg, Gudrun; Saleh-Gohari, Nasrollah; Haghighi, Amirreza; Neidhardt, John; Nürnberg, Peter; Berger, Wolfgang

    2014-01-01

    The aim of this study was to identify the genetic basis of a chorioretinal dystrophy with high myopia of unknown origin in a child of a consanguineous marriage. The proband and ten family members of Iranian ancestry participated in this study. Linkage analysis was carried out with DNA samples of the proband and her parents by using the Human SNP Array 6.0. Whole exome sequencing (WES) was performed with the patients’ DNA. Specific sequence alterations within the homozygous regions identified by whole exome sequencing were verified by Sanger sequencing. Upon genetic analysis, a novel homozygous frameshift mutation was found in exon 42 of the COL18A1 gene in the patient. Both parents were heterozygous for this sequence variation. Mutations in COL18A1 are known to cause Knobloch syndrome (KS). Retrospective analysis of clinical records of the patient revealed surgical removal of a meningocele present at birth. The clinical features shown by our patient were typical of KS with the exception of chorioretinal degeneration which is a rare manifestation. This is the first case of KS reported in a family of Iranian ancestry. We identified a novel disease-causing (deletion) mutation in the COL18A1 gene leading to a frameshift and premature stop codon in the last exon. The mutation was not present in SNP databases and was also not found in 192 control individuals. Its localization within the endostatin domain implicates a functional relevance of endostatin in KS. A combined approach of linkage analysis and WES led to a rapid identification of the disease-causing mutation even though the clinical description was not completely clear at the beginning. PMID:25392994

  4. Hyperspectral surface materials map of quadrangle 3770, Faizabad (217) and Parkhaw (218) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Giles, Stuart A.; Johnson, Michaela R.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  5. Hyperspectral surface materials map of quadrangle 3468, Chak-e Wardak-Siyahgird (509) and Kabul (510) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Giles, Stuart A.; Johnson, Michaela R.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  6. Hyperspectral surface materials map of quadrangle 3262, Farah (421) and Hokumat-e-pur-Chaman (422) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  7. Hyperspectral surface materials map of quadrangle 3466, La`l wa Sar Jangal (507) and Bamyan (508) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Giles, Stuart A.; Johnson, Michaela R.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  8. Hyperspectral Surface Materials Map of Quadrangle 3566, Sangcharak (501) and Sayghan-o-Kamard (502) Quadrangles, Afghanistan, Showing Carbonates, Phyllosilicates, Sulfates, Altered Minerals, and Other Materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Giles, Stuart A.; Johnson, Michaela R.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  9. Hyperspectral surface materials map of quadrangle 3568, Pul-e Khumri (503) and Charikar (504) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  10. Hyperspectral surface materials map of quadrangle 3166, Jaldak (701) and Maruf-Nawa (702) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Giles, Stuart A.; Johnson, Michaela R.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  11. Hyperspectral surface materials map of quadrangle 3268, Khayr Kot (521) and Urgun (522) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Giles, Stuart A.; Johnson, Michaela R.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  12. Hyperspectral surface materials map of quadrangle 3162, Chakhansur (603) and Kotalak (604) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  13. Hyperspectral surface materials map of quadrangle 3564, Jowand (405) and Gurziwan (406) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  14. Hyperspectral surface materials map of quadrangle 3362, Shindand (415) and Tulak (416) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Giles, Stuart A.; Johnson, Michaela R.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  15. Hyperspectral surface materials map of quadrangle 3368, Ghazni (515) and Gardez (516) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Giles, Stuart A.; Johnson, Michaela R.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  16. Hyperspectral surface materials map of quadrangle 3464, Shahrak (411) and Kasi (412) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  17. Hyperspectral surface materials map of quadrangle 3266, Uruzgan (519) and Moqur (520) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Giles, Stuart A.; Johnson, Michaela R.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  18. Hyperspectral surface materials map of quadrangle 3570, Tagab-e-Munjan (505) and Asmar-Kamdesh (506) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  19. Hyperspectral surface materials map of quadrangle 3264, Naw Zad-Musa Qala (423) and Dihrawud (424) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  20. Hyperspectral surface materials map of quadrangle 3164, Lashkar Gah (605) and Kandahar (606) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  1. Hyperspectral surface materials map of quadrangle 3562, Khawja-Jir (403) and Murghab (404) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  2. Hyperspectral surface materials map of quadrangle 3462, Herat (409) and Chishti Sharif (410) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  3. Hyperspectral surface materials map of quadrangle 3670, Jurm-Kishim (223) and Zebak (224) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  4. Hyperspectral surface materials map of quadrangle 3364, Pasaband (417) and Markaz-e Kajiran (418) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  5. Hyperspectral surface materials map of quadrangle 3366, Gizab (513) and Nawer (514) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  6. Hyperspectral surface materials map of quadrangle 3470, Jalalabad (511) and Chaghasaray (512) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Giles, Stuart A.; Johnson, Michaela R.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  7. Defective ceramide synthases in mice cause reduced amplitudes in electroretinograms and altered sphingolipid composition in retina and cornea.

    PubMed

    Brüggen, Bianca; Kremser, Christiane; Bickert, Andreas; Ebel, Philipp; Vom Dorp, Katharina; Schultz, Konrad; Dörmann, Peter; Willecke, Klaus; Dedek, Karin

    2016-07-01

    Complex sphingolipids are strongly expressed in neuronal tissue and contain ceramides in their backbone. Ceramides are synthesized by six ceramide synthases (CerS1-6). Although it is known that each tissue has a unique profile of ceramide synthase expression and ceramide synthases are implicated in several neurodegenerative disorders, the expression of ceramide synthase isoforms has not been investigated in the retina. Here we demonstrate CerS1, CerS2 and CerS4 expression in mouse retina and cornea, with CerS4 ubiquitously expressed in all retinal neurons and Müller cells. To test whether ceramide synthase deficiency affects retinal function, we compared electroretinograms and retina morphology between wild-type and CerS1-, CerS2- and CerS4-deficient mice. Electroretinograms were strongly reduced in amplitude in ceramide synthase-deficient mice, suggesting that signalling in the outer retina is affected. However, the number of photoreceptors and cone outer segment length were unaltered and no changes in retinal layer thickness or synaptic structures were found. Mass spectrometric analyses of ceramides, hexosyl-ceramides and sphingomyelins showed that C20 to C24 acyl-containing species were decreased whereas C16-containing species were increased in the retina of ceramide synthase-deficient mice. Similar but smaller changes were also found in the cornea. Thus, we hypothesize that the replacement of very long-chain fatty acyl residues by shorter C16 residues may affect the electrical properties of retina and cornea, and alter receptor-mediated signal transduction, vesicle-mediated synaptic transmission or corneal light transmission. Future studies need to identify the molecular targets of ceramides or derived sphingolipids in light signal transduction and transmission in the eye. PMID:27086873

  8. Sublethal exposure to azamethiphos causes neurotoxicity, altered energy allocation and high mortality during simulated live transport in American lobster.

    PubMed

    Couillard, C M; Burridge, L E

    2015-05-01

    In the Bay of Fundy, New Brunswick, sea lice outbreaks in caged salmon are treated with pesticides including Salmosan(®), applied as bath treatments and then released into the surrounding seawater. The effect of chronic exposure to low concentrations of this pesticide on neighboring lobster populations is a concern. Adult male lobsters were exposed to 61 ngL(-1) of azamethiphos (a.i. in Salmosan(®) formulation) continuously for 10 days. In addition to the direct effects of pesticide exposure, effects on the ability to cope with shipping conditions and the persistence of the effects after a 24h depuration period in clean seawater were assessed. Indicators of stress and hypoxia (serum total proteins, hemocyanin and lactate), oxidative damage (protein carbonyls in gills and serum) and altered energy allocation (hepatosomatic and gonadosomatic indices, hepatopancreas lipids) were assessed in addition to neurotoxicity (chlolinesterase activity in muscle). Directly after exposure, azamethiphos-treated lobsters had inhibition of muscle cholinesterase, reduced gonadosomatic index and enhanced hepatosomatic index and hepatopancreas lipid content. All these responses persisted after 24-h depuration, increasing the risk of cumulative impacts with further exposure to chemical or non-chemical stressors. In both control and treated lobsters exposed to simulated shipment conditions, concentrations of protein and lactate in serum, and protein carbonyls in gills increased. However, mortality rate was higher in azamethiphos-treated lobsters (33 ± 14%) than in controls (2.6 ± 4%). Shipment and azamethiphos had cumulative impacts on serum proteins. Both direct effects on neurological function and energy allocation and indirect effect on ability to cope with shipping stress could have significant impacts on lobster population and/or fisheries. PMID:25499691

  9. Single housing during early adolescence causes time-, area- and peptide-specific alterations in endogenous opioids of rat brain

    PubMed Central

    Granholm, L; Roman, E; Nylander, I

    2015-01-01

    BACKGROUND AND PURPOSE A number of experimental procedures require single housing to assess individual behaviour and physiological responses to pharmacological treatments. The endogenous opioids are closely linked to social interaction, especially early in life, and disturbance in the social environment may affect opioid peptides and thereby confound experimental outcome. The aim of the present study was to examine time-dependent effects of single housing on opioid peptides in rats. EXPERIMENTAL APPROACH Early adolescent Sprague Dawley rats (post-natal day 22) were subjected to either prolonged (7 days) or short (30 min) single housing. Several brain regions were dissected and immunoreactive levels of Met-enkephalin-Arg6Phe7 (MEAP), dynorphin B and nociception/orphanin FQ, as well as serum corticosterone were measured using RIA. KEY RESULTS Prolonged single housing reduced immunoreactive MEAP in hypothalamus, cortical regions, amygdala, substantia nigra and periaqueductal grey. Short single housing resulted in an acute stress response as indicated by high levels of corticosterone, accompanied by elevated immunoreactive nociceptin/orphanin FQ in medial prefrontal cortex, nucleus accumbens and amygdala. Neither short nor prolonged single housing affected dynorphin B. CONCLUSIONS AND IMPLICATIONS Disruption in social environmental conditions of rats, through single housing during early adolescence, resulted in time-, area- and peptide-specific alterations in endogenous opioids in the brain. These results provide further evidence for an association between early life social environment and opioids. Furthermore, the results have implications for experimental design; in any pharmacological study involving opioid peptides, it is important to distinguish between effects induced by housing and treatment. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http

  10. Alterations in mitosis and cell cycle progression caused by a mutant lamin A known to accelerate human aging.

    PubMed

    Dechat, Thomas; Shimi, Takeshi; Adam, Stephen A; Rusinol, Antonio E; Andres, Douglas A; Spielmann, H Peter; Sinensky, Michael S; Goldman, Robert D

    2007-03-20

    Mutations in the gene encoding nuclear lamin A (LA) cause the premature aging disease Hutchinson-Gilford Progeria Syndrome. The most common of these mutations results in the expression of a mutant LA, with a 50-aa deletion within its C terminus. In this study, we demonstrate that this deletion leads to a stable farnesylation and carboxymethylation of the mutant LA (LADelta50/progerin). These modifications cause an abnormal association of LADelta50/progerin with membranes during mitosis, which delays the onset and progression of cytokinesis. Furthermore, we demonstrate that the targeting of nuclear envelope/lamina components into daughter cell nuclei in early G(1) is impaired in cells expressing LADelta50/progerin. The mutant LA also appears to be responsible for defects in the retinoblastoma protein-mediated transition into S-phase, most likely by inhibiting the hyperphosphorylation of retinoblastoma protein by cyclin D1/cdk4. These results provide insights into the mechanisms responsible for premature aging and also shed light on the role of lamins in the normal process of human aging. PMID:17360326

  11. Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID

    PubMed Central

    Sauer, Aisha V.; Brigida, Immacolata; Carriglio, Nicola; Jofra Hernandez, Raisa; Scaramuzza, Samantha; Clavenna, Daniela; Sanvito, Francesca; Poliani, Pietro L.; Gagliani, Nicola; Carlucci, Filippo; Tabucchi, Antonella; Roncarolo, Maria Grazia; Traggiai, Elisabetta; Villa, Anna

    2012-01-01

    Adenosine acts as anti-inflammatory mediator on the immune system and has been described in regulatory T cell (Treg)–mediated suppression. In the absence of adenosine deaminase (ADA), adenosine and other purine metabolites accumulate, leading to severe immunodeficiency with recurrent infections (ADA-SCID). Particularly ADA-deficient patients with late-onset forms and after enzyme replacement therapy (PEG-ADA) are known to manifest immune dysregulation. Herein we provide evidence that alterations in the purine metabolism interfere with Treg function, thereby contributing to autoimmune manifestations in ADA deficiency. Tregs isolated from PEG-ADA–treated patients are reduced in number and show decreased suppressive activity, whereas they are corrected after gene therapy. Untreated murine ADA−/− Tregs show alterations in the plasma membrane CD39/CD73 ectonucleotidase machinery and limited suppressive activity via extracellular adenosine. PEG-ADA–treated mice developed multiple autoantibodies and hypothyroidism in contrast to mice treated with bone marrow transplantation or gene therapy. Tregs isolated from PEG-ADA–treated mice lacked suppressive activity, suggesting that this treatment interferes with Treg functionality. The alterations in the CD39/CD73 adenosinergic machinery and loss of function in ADA-deficient Tregs provide new insights into a predisposition to autoimmunity and the underlying mechanisms causing defective peripheral tolerance in ADA-SCID. Trials were registered at www.clinicaltrials.gov as NCT00598481/NCT00599781. PMID:22184407

  12. Necator americanus Infection: A Possible Cause of Altered Dendritic Cell Differentiation and Eosinophil Profile in Chronically Infected Individuals

    PubMed Central

    Fujiwara, Ricardo T.; Cançado, Guilherme G. L.; Freitas, Paula A.; Santiago, Helton C.; Massara, Cristiano Lara; dos Santos Carvalho, Omar; Corrêa-Oliveira, Rodrigo; Geiger, Stefan M.; Bethony, Jeffrey

    2009-01-01

    Background Hookworms survive for several years (5 to 7 years) in the host lumen, inducing a robust but largely ineffective immune response. Among the most striking aspects of the immune response to hookworm (as with many other helminths) is the ablation of parasite-specific T cell proliferative response (hyporesponsiveness). While the role of the adaptive immune response in human helminth infection has been well investigated, the role of the innate immune responses (e.g., dendritic cells and eosinophils) has received less attention and remains to be clearly elucidated. Methodology/Principal Findings We report on the differentiation/maturation of host dendritic cells in vitro and the eosinophil activation/function associated with human hookworm infection. Mature DCs (mDCs) from Necator americanus (Necator)–infected individuals showed an impaired differentiation process compared to the mDCs of non-infected individuals, as evidenced by the differential expression of CD11c and CD14. These same hookworm-infected individuals also presented significantly down-regulated expression of CD86, CD1a, HLA-ABC, and HLA-DR. The lower expression of co-stimulatory and antigen presentation molecules by hookworm-infected–derived mDCs was further evidenced by their reduced ability to induce cell proliferation. We also showed that this alternative DC differentiation is partially induced by excreted-secreted hookworm products. Conversely, eosinophils from the same individuals showed a highly activated status, with an upregulation of major cell surface markers. Antigen-pulsed eosinophils from N. americanus–infected individuals induced significant cell proliferation of autologous PBMCs, when compared to non-infected individuals. Conclusion Chronic N. americanus infection alters the host's innate immune response, resulting in a possible modulation of the maturation process of DCs, a functional change that may diminish their ability for antigen presentation and thus contribute to the

  13. Detection and mapping of hydrothermally altered rocks in the vicinity of the Comstock Lode, Virginia Range, Nevada, using enhanced Landsat images

    USGS Publications Warehouse

    Ashley, Roger P.; Goetz, A.F.H.; Rowan, L.C.; Abrams, M.J.

    1979-01-01

    The Virginia Range, immediately southeast of Reno, Nev., consists mainly of flows, breccias, and turfs of Miocene age. Most of these volcanic rocks are of intermediate composition; rhyodacite is the most common rock type. Basalt, rhyolite and rhyolite tuff, and tuffaceous sedimentary rocks of Miocene and Pliocene age also cover substantial areas in the range. Pre-Tertiary metasedimentary, metavolcanic, and granitic rocks are exposed in scattered inliers, mostly along the southern and eastern margins of the range. Several large areas and many small areas within the volcanic pile were subjected to hydrothermal alteration during and after the period of intermediate volcanic activity. Economic precious metal mineralization is spatially and temporally associated with the hydrothermal alteration in several areas. The most important deposit is the Comstock Lode, which produced 192 million troy ounces of silver and 8.3 million troy ounces of gold from epithermal veins (Bonham, 1969). The hydrothermally altered rocks include silicified, advanced argillic, montmorillonite-bearing argillic, and propylitic types. The first three types typically contain pyrite, and some propylitic rocks contain pyrite as well. Supergene oxidation of these pyritic rocks produces limonitic bleached rocks. The term 'limonite,' as used here, refers to any combination of the minerals hematite, goethite, and Jarosite. Where vegetation cover is sparse to moderate, these limonitic rocks are readily identified on Landsat images enhanced by the color-ratio composite technique developed by Rowan and others (1974), so the altered areas can be mapped. About 30 percent tree cover (here mainly pinyon pine) is sufficient to change the spectral signature of individual picture elements (pixels) enough so that limonitic materials can no longer be uniquely identified. As in all other areas where this technique has been applied, limonitic unaltered rocks with intermediate to high albedos have the same appearance on

  14. A new mutation in the CFTR gene, composed of two adjacent DNA alterations, is a common cause of cystic fibrosis among Georgian Jews

    SciTech Connect

    Shoshani, T.; Berkun, Y.; Yahav, Y.; Augarten, A.; Bashan, N.; Rivlin, Y.; Gazit, E.; Sereth, H.; Kerem, E.; Kerem, B.S. )

    1993-01-01

    Five Jewish cystic fibrosis (CF) patients from four unrelated families, all of whom emigrated from what was Soviet Georgia were studied. The parents in two of the families are first-degree relatives. The clinical phenotype of the patients seems to be associated with a severe disease, as reflected by early age of diagnosis (before the age of 1 year), high sweat chloride level (105-140 meq/liter), and pancreatic insufficiency. The pulmonary function and nutritional status of these patients are normal. These patients were tested for [Delta]F508 by analysis of heteroduplex DNA (4). None of the CF chromosomes was found to carry the [Delta]F508 mutation. Subsequently, PCR-amplified genomic DNA samples from two of these patients were subjected to direct sequencing (5) of regions containing exons 7, 9-12, an 19-21 of the CF gene using the oligonucleotides previously described (3, 6). In exon 7, two DNA alterations 3 bp apart were identified in both patients. The first alteration in a C [yields] A transversion at nucleotide position 1207, changing the glutamine codon to lysine (Q359K). The second DNA alteration is a C [yields] A transversion at nucleotide position 1211 changing the threonine codon to lysine (T360K). The two DNA alterations cause nonconservative amino acid substitutions, changing each of the two uncharged polar amino acids (glutamine and threonine) to a basic amino acid, lysine. The Q359K substitution destroys an Rsal recognition site and can be detected by PCR amplification of exon 7 using 7i-5 and 7i-3 oligonucleotides (6), followed by Rsal digestion and electrophoresis on 10% polyacrylamide gels. Two Rsal sites are found in a normal amplified DNA fragment, resulting in three restriction fragments of 292, 68, and 50 bp. Digestion of the PCR fragment of an individual homozygous for this substitution resulted in only two fragments of 342 and 68 bp. 6 refs., 3 figs.

  15. Comparative alteration mineral mapping using visible to shortwave infrared (0.4-2.4 μm) Hyperion, ALI, and ASTER imagery

    USGS Publications Warehouse

    Hubbard, B.E.; Crowley, J.K.; Zimbelman, D.R.

    2003-01-01

    Advanced Land Imager (ALI), Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER), and Hyperion imaging spectrometer data covering an area in the Central Andes between Volcan Socompa and Salar de Llullaillaco were used to map hydrothermally altered rocks associated with several young volcanic systems. Six ALI channels in the visible and near-infrared wavelength range (0.4-1.0 ??m) were useful for discriminating between ferric-iron alteration minerals based on the spectral shapes of electronic absorption features seen in continuum-removed spectra. Six ASTER channels in the short wavelength infrared (1.0-2.5 ??m) enabled distinctions between clay and sulfate mineral types based on the positions of band minima related to Al-OH vibrational absorption features. Hyperion imagery embedded in the broader image coverage of ALI and ASTER provided essential leverage for calibrating and improving the mapping accuracy of the multispectral data. This capability is especially valuable in remote areas of the earth where available geologic and other ground truth information is limited.

  16. Caenorhabditis elegans par2.1/mtssb-1 is essential for mitochondrial DNA replication and its defect causes comprehensive transcriptional alterations including a hypoxia response

    SciTech Connect

    Sugimoto, Tomoko; Mori, Chihiro; Takanami, Takako; Sasagawa, Yohei; Saito, Rumiko; Ichiishi, Eiichiro; Higashitani, Atsushi

    2008-01-01

    DNA polymerase {gamma} and mtSSB are key components of the mtDNA replication machinery. To study the biological influences of defects in mtDNA replication, we used RNAi to deplete the gene for a putative mtSSB, par2.1, in Caenorhabditis elegans. In previous systematic RNAi screens, downregulation of this gene has not caused any clearly defective phenotypes. Here, we continuously fed a dsRNA targeting par2.1 to C. elegans over generations. Seventy-nine percent of F1 progeny produced 60-72 h after feeding grew to adulthood but were completely sterile, with an arrest of germline cell proliferation. Analyses of mtDNA copy number and cell cytology indicated that the sterile hermaphrodites had fewer mitochondria. These results indicated that par2.1 essentially functions for germline cell proliferation through mtDNA replication; we therefore termed it mtssb-1. Comprehensive transcriptional alterations including hypoxia response induction dependent on and independent of hif-1 function, occurred by RNAi depletion of mtssb-1. Treatment with ethidium bromide, which impairs mtDNA replication and transcription, caused similar transcriptional alterations. In addition, the frequency of apoptosis in the germline cells was reduced in fertile progeny with a partial RNAi effect. These suggest that RNAi depletion of C. elegans mtssb-1 is useful as a model system of mitochondrial dysfunction.

  17. A single-nucleotide deletion in the POMP 5' UTR causes a transcriptional switch and altered epidermal proteasome distribution in KLICK genodermatosis.

    PubMed

    Dahlqvist, Johanna; Klar, Joakim; Tiwari, Neha; Schuster, Jens; Törmä, Hans; Badhai, Jitendra; Pujol, Ramon; van Steensel, Maurice A M; Brinkhuizen, Tjinta; Brinkhuijzen, Tjinta; Gijezen, Lieke; Chaves, Antonio; Tadini, Gianluca; Vahlquist, Anders; Dahl, Niklas

    2010-04-01

    KLICK syndrome is a rare autosomal-recessive skin disorder characterized by palmoplantar keratoderma, linear hyperkeratotic papules, and ichthyosiform scaling. In order to establish the genetic cause of this disorder, we collected DNA samples from eight European probands. Using high-density genome-wide SNP analysis, we identified a 1.5 Mb homozygous candidate region on chromosome 13q. Sequence analysis of the ten annotated genes in the candidate region revealed homozygosity for a single-nucleotide deletion at position c.-95 in the proteasome maturation protein (POMP) gene, in all probands. The deletion is included in POMP transcript variants with long 5' untranslated regions (UTRs) and was associated with a marked increase of these transcript variants in keratinocytes from KLICK patients. POMP is a ubiquitously expressed protein and functions as a chaperone for proteasome maturation. Immunohistochemical analysis of skin biopsies from KLICK patients revealed an altered epidermal distribution of POMP, the proteasome subunit proteins alpha 7 and beta 5, and the ER stress marker CHOP. Our results suggest that KLICK syndrome is caused by a single-nucleotide deletion in the 5' UTR of POMP resulting in altered distribution of POMP in epidermis and a perturbed formation of the outermost layers of the skin. These findings imply that the proteasome has a prominent role in the terminal differentiation of human epidermis. PMID:20226437

  18. Single-cell genetic expression of mutant GABAA receptors causing Human genetic epilepsy alters dendritic spine and GABAergic bouton formation in a mutation-specific manner

    PubMed Central

    Lachance-Touchette, Pamela; Choudhury, Mayukh; Stoica, Ana; Di Cristo, Graziella; Cossette, Patrick

    2014-01-01

    Mutations in genes encoding for GABAA receptor subunits is a well-established cause of genetic generalized epilepsy. GABA neurotransmission is implicated in several developmental processes including neurite outgrowth and synapse formation. Alteration in excitatory/inhibitory synaptic activities plays a critical role in epilepsy, thus here we investigated whether mutations in α1 subunit of GABAA receptor may affect dendritic spine and GABAergic bouton formation. In particular, we examined the effects of three mutations of the GABRA1 gene (D219N, A322D and K353delins18X) that were found in a cohort of French Canadian families with genetic generalized epilepsy. We used a novel single-cell genetic approach, by preparing cortical organotypic cultures from GABRA1flox/flox mice and simultaneously inactivating endogenous GABRA1 and transfecting mutant α1 subunits in single glutamatergic pyramidal cells and basket GABAergic interneurons by biolistic transfection. We found that GABRA1−/− GABAergic cells showed reduced innervation field, which was rescued by co-expressing α1-A322D and α1-WT but not α1-D219N. We further found that the expression of the most severe GABRA1 missense mutation (α1-A322D) induced a striking increase of spine density in pyramidal cells along with an increase in the number of mushroom-like spines. In addition, α1-A322D expression in GABAergic cells slightly increased perisomatic bouton density, whereas other mutations did not alter bouton formation. All together, these results suggest that the effects of different GABAAR mutations on GABAergic bouton and dendritic spine formation are specific to the mutation and cannot be always explained by a simple loss-of-function gene model. The use of single cell genetic manipulation in organotypic cultures may provide a better understanding of the specific and distinct neural circuit alterations caused by different GABAA receptor subunit mutations and will help define the pathophysiology of genetic

  19. Single-cell genetic expression of mutant GABAA receptors causing Human genetic epilepsy alters dendritic spine and GABAergic bouton formation in a mutation-specific manner.

    PubMed

    Lachance-Touchette, Pamela; Choudhury, Mayukh; Stoica, Ana; Di Cristo, Graziella; Cossette, Patrick

    2014-01-01

    Mutations in genes encoding for GABAA receptor subunits is a well-established cause of genetic generalized epilepsy. GABA neurotransmission is implicated in several developmental processes including neurite outgrowth and synapse formation. Alteration in excitatory/inhibitory synaptic activities plays a critical role in epilepsy, thus here we investigated whether mutations in α1 subunit of GABAA receptor may affect dendritic spine and GABAergic bouton formation. In particular, we examined the effects of three mutations of the GABRA1 gene (D219N, A322D and K353delins18X) that were found in a cohort of French Canadian families with genetic generalized epilepsy. We used a novel single-cell genetic approach, by preparing cortical organotypic cultures from GABRA1 (flox/flox) mice and simultaneously inactivating endogenous GABRA1 and transfecting mutant α1 subunits in single glutamatergic pyramidal cells and basket GABAergic interneurons by biolistic transfection. We found that GABRA1 (-/-) GABAergic cells showed reduced innervation field, which was rescued by co-expressing α1-A322D and α1-WT but not α1-D219N. We further found that the expression of the most severe GABRA1 missense mutation (α1-A322D) induced a striking increase of spine density in pyramidal cells along with an increase in the number of mushroom-like spines. In addition, α1-A322D expression in GABAergic cells slightly increased perisomatic bouton density, whereas other mutations did not alter bouton formation. All together, these results suggest that the effects of different GABAAR mutations on GABAergic bouton and dendritic spine formation are specific to the mutation and cannot be always explained by a simple loss-of-function gene model. The use of single cell genetic manipulation in organotypic cultures may provide a better understanding of the specific and distinct neural circuit alterations caused by different GABAA receptor subunit mutations and will help define the pathophysiology of genetic

  20. Sepsis in preterm infants causes alterations in mucosal gene expression and microbiota profiles compared to non-septic twins.

    PubMed

    Cernada, María; Bäuerl, Christine; Serna, Eva; Collado, Maria Carmen; Martínez, Gaspar Pérez; Vento, Máximo

    2016-01-01

    Sepsis is a life-threatening condition in preterm infants. Neonatal microbiota plays a pivotal role in the immune system maturation. Changes in gut microbiota have been associated to inflammatory disorders; however, a link with sepsis in the neonatal period has not yet been established. We aimed to analyze gut microbiota and mucosal gene expression using non-invasively obtained samples to provide with an integrative perspective of host-microbe interactions in neonatal sepsis. For this purpose, a prospective observational case-control study was conducted in septic preterm dizygotic twins and their non-septic twin controls. Fecal samples were used for both microbiota analysis and host genome-wide expression using exfoliated intestinal cells. Gene expression of exfoliated intestinal cells in septic preterm showed an induction of inflammatory and oxidative stress pathways in the gut and pro-oxidant profile that caused dysbiosis in the gut microbiota with predominance of Enterobacteria and reduction of Bacteroides and Bifidobacterium spp.in fecal samples, leading to a global reduction of beneficial anaerobic bacteria. Sepsis in preterm infants induced low-grade inflammation and oxidative stress in the gut mucosa, and also changes in the gut microbiota. This study highlights the role of inflammation and oxidative stress in neonatal sepsis on gut microbial profiles. PMID:27180802

  1. Morphological alterations in the freshwater rotifer Brachionus calyciflorus Pallas 1766 (Rotifera: Monogononta) caused by vinclozolin chronic exposure.

    PubMed

    Alvarado-Flores, Jesús; Rico-Martínez, Roberto; Adabache-Ortíz, Araceli; Silva-Briano, Marcelo

    2015-05-01

    Vinclozolin (VZ) is a dicarboximide fungicide widely used on fruits, vegetables and wines, effective against fungi plagues. In this study we characterized the effects of VZ using a 4-day reproductive chronic assay with the freshwater rotifer Brachionus calyciflorus. The assay included observations of several features of asexual and sexual reproduction. Our results indicate that VZ: (a) increased asexual and sexual reproduction, (b) caused severe abnormality in females and (c) these abnormalities were inherited by sexual and asexual reproduction. At 1.2 mg/L three abnormal females were found out of 457 total females (0.66 %). This low percentage is consistent and reproducible according to further analysis, where we increased the number of replicates and total females exposed to 1.2 mg/L of VZ, and found 18 abnormal females out of 2868 total females (0.63 % abnormality). Interestingly, abnormal females found at 5.6 mg/L VZ exposure, were able to show mating behavior. Our results suggest that VZ behaves as a strong endocrine disruptor whose effects show the characteristic inverted-U-shape exposure concentration response curve regarding the intrinsic population increase and the percentage of abnormalities as endpoints. PMID:25725815

  2. Sepsis in preterm infants causes alterations in mucosal gene expression and microbiota profiles compared to non-septic twins

    PubMed Central

    Cernada, María; Bäuerl, Christine; Serna, Eva; Collado, Maria Carmen; Martínez, Gaspar Pérez; Vento, Máximo

    2016-01-01

    Sepsis is a life-threatening condition in preterm infants. Neonatal microbiota plays a pivotal role in the immune system maturation. Changes in gut microbiota have been associated to inflammatory disorders; however, a link with sepsis in the neonatal period has not yet been established. We aimed to analyze gut microbiota and mucosal gene expression using non-invasively obtained samples to provide with an integrative perspective of host-microbe interactions in neonatal sepsis. For this purpose, a prospective observational case-control study was conducted in septic preterm dizygotic twins and their non-septic twin controls. Fecal samples were used for both microbiota analysis and host genome-wide expression using exfoliated intestinal cells. Gene expression of exfoliated intestinal cells in septic preterm showed an induction of inflammatory and oxidative stress pathways in the gut and pro-oxidant profile that caused dysbiosis in the gut microbiota with predominance of Enterobacteria and reduction of Bacteroides and Bifidobacterium spp.in fecal samples, leading to a global reduction of beneficial anaerobic bacteria. Sepsis in preterm infants induced low-grade inflammation and oxidative stress in the gut mucosa, and also changes in the gut microbiota. This study highlights the role of inflammation and oxidative stress in neonatal sepsis on gut microbial profiles. PMID:27180802

  3. Deficiency of nicotinamide mononucleotide adenylyltransferase 3 (nmnat3) causes hemolytic anemia by altering the glycolytic flow in mature erythrocytes.

    PubMed

    Hikosaka, Keisuke; Ikutani, Masashi; Shito, Masayuki; Kazuma, Kohei; Gulshan, Maryam; Nagai, Yoshinori; Takatsu, Kiyoshi; Konno, Katsuhiro; Tobe, Kazuyuki; Kanno, Hitoshi; Nakagawa, Takashi

    2014-05-23

    NAD biosynthesis is of substantial interest because of its important roles in regulating various biological processes. Nicotinamide mononucleotide adenylyltransferase 3 (Nmnat3) is considered a mitochondria-localized NAD synthesis enzyme involved in de novo and salvage pathways. Although the biochemical properties of Nmnat3 are well documented, its physiological function in vivo remains unclear. In this study, we demonstrated that Nmnat3 was localized in the cytoplasm of mature erythrocytes and critically regulated their NAD pool. Deficiency of Nmnat3 in mice caused splenomegaly and hemolytic anemia, which was associated with the findings that Nmnat3-deficient erythrocytes had markedly lower ATP levels and shortened lifespans. However, the NAD level in other tissues were not apparently affected by the deficiency of Nmnat3. LC-MS/MS-based metabolomics revealed that the glycolysis pathway in Nmnat3-deficient erythrocytes was blocked at a glyceraldehyde 3-phosphate dehydrogenase (GAPDH) step because of the shortage of the coenzyme NAD. Stable isotope tracer analysis further demonstrated that deficiency of Nmnat3 resulted in glycolysis stall and a shift to the pentose phosphate pathway. Our findings indicate the critical roles of Nmnat3 in maintenance of the NAD pool in mature erythrocytes and the physiological impacts at its absence in mice. PMID:24739386

  4. Hypothyroidism minimizes the effects of acute hepatic failure caused by endoplasmic reticulum stress and redox environment alterations in rats.

    PubMed

    Blas-Valdivia, Vanessa; Cano-Europa, Edgar; Martinez-Perez, Yoalli; Lezama-Palacios, Ruth; Franco-Colin, Margarita; Ortiz-Butron, Rocio

    2015-10-01

    The aim of this study was to investigate if a protective effect from hypothyroidism in acute liver failure resulted from reduced endoplasmic reticulum stress and changes to the redox environment. Twenty male Sprague-Dawley rats were divided in four groups: (1) euthyroid (sham surgery), (2) hypothyroid, (3) euthyroid (sham surgery)+thioacetamide and (4) hypothyroid+thioacetamide. Hypothyroidism was confirmed two weeks after thyroidectomy, and thioacetamide (TAA) (400mg/kg, ip) was administrated to the appropriate groups for three days with supportive therapy. Grades of encephalopathy in all animals were determined using behavioral tests. Animals were decapitated and their blood was obtained to assess liver function. The liver was dissected: the left lobe was used for histology and the right lobe was frozen for biochemical assays. Body weight, rectal temperature and T4 concentration were lower in hypothyroid groups. When measurements of oxidative stress markers, redox environment, γ-glutamylcysteine synthetase and glutathione-S-transferase were determined, we observed that hypothyroid animals with TAA compensated better with oxidative damage than euthyroid animals treated with TAA. Furthermore, we measured reduced expressions of GADD34, caspase-12 and GRP78 and subsequently less hypothyroidism-induced cellular damage in hypothyroid animals. We conclude that hypothyroidism protects against hepatic damage caused by TAA because it reduces endoplasmic reticulum stress and changes to the redox environment. PMID:26238033

  5. Deficiency of Nicotinamide Mononucleotide Adenylyltransferase 3 (Nmnat3) Causes Hemolytic Anemia by Altering the Glycolytic Flow in Mature Erythrocytes*

    PubMed Central

    Hikosaka, Keisuke; Ikutani, Masashi; Shito, Masayuki; Kazuma, Kohei; Gulshan, Maryam; Nagai, Yoshinori; Takatsu, Kiyoshi; Konno, Katsuhiro; Tobe, Kazuyuki; Kanno, Hitoshi; Nakagawa, Takashi

    2014-01-01

    NAD biosynthesis is of substantial interest because of its important roles in regulating various biological processes. Nicotinamide mononucleotide adenylyltransferase 3 (Nmnat3) is considered a mitochondria-localized NAD synthesis enzyme involved in de novo and salvage pathways. Although the biochemical properties of Nmnat3 are well documented, its physiological function in vivo remains unclear. In this study, we demonstrated that Nmnat3 was localized in the cytoplasm of mature erythrocytes and critically regulated their NAD pool. Deficiency of Nmnat3 in mice caused splenomegaly and hemolytic anemia, which was associated with the findings that Nmnat3-deficient erythrocytes had markedly lower ATP levels and shortened lifespans. However, the NAD level in other tissues were not apparently affected by the deficiency of Nmnat3. LC-MS/MS-based metabolomics revealed that the glycolysis pathway in Nmnat3-deficient erythrocytes was blocked at a glyceraldehyde 3-phosphate dehydrogenase (GAPDH) step because of the shortage of the coenzyme NAD. Stable isotope tracer analysis further demonstrated that deficiency of Nmnat3 resulted in glycolysis stall and a shift to the pentose phosphate pathway. Our findings indicate the critical roles of Nmnat3 in maintenance of the NAD pool in mature erythrocytes and the physiological impacts at its absence in mice. PMID:24739386

  6. Mapping and Exome Sequencing Identifies a Mutation in the IARS Gene as the Cause of Hereditary Perinatal Weak Calf Syndrome

    PubMed Central

    Hirano, Takashi; Kobayashi, Naohiko; Matsuhashi, Tamako; Watanabe, Daisaku; Watanabe, Toshio; Takasuga, Akiko; Sugimoto, Mayumi; Sugimoto, Yoshikazu

    2013-01-01

    We identified an IARS (isoleucyl-tRNA synthetase) c.235G>C (p.Val79Leu) substitution as the causative mutation for neonatal weakness with intrauterine growth retardation (perinatal weak calf syndrome). In Japanese Black cattle, the syndrome was frequently found in calves sired by Bull A. Hence, we employed homozygosity mapping and linkage analysis. In order to identify the perinatal weak calf syndrome locus in a 4.04-Mb region of BTA 8, we analysed a paternal half-sibling family with a BovineSNP50 BeadChip and microsatellites. In this critical region, we performed exome sequencing to identify a causative mutation. Three variants were detected as possible candidates for causative mutations that were predicted to disrupt the protein function, including a G>C (p.Val79Leu) mutation in IARS c.235. The IARS c.235G>C mutation was not a homozygous risk allele in the 36 healthy offspring of Bull A. Moreover, the IARS Val79 residue and its flanking regions were evolutionarily and highly conserved. The IARS mutant (Leu79) had decreased aminoacylation activity. Additionally, the homozygous mutation was not found in any of 1526 healthy cattle. Therefore, we concluded that the IARS c.235G>C mutation was the cause of hereditary perinatal weak calf syndrome. PMID:23700453

  7. Altered heme catabolism by heme oxygenase-1 caused by mutations in human NADPH cytochrome P450 reductase

    SciTech Connect

    Pandey, Amit V.; Flueck, Christa E.; Mullis, Primus E.

    2010-09-24

    Research highlights: {yields} Mutations in POR identified from patients lead to reduced HO-1 activities. {yields} POR mutation Y181D affecting FMN binding results in total loss of HO-1 activity. {yields} POR mutations A287P, C569Y and V608F, lost 50-70% activity. {yields} Mutations in FAD binding domain, R457H, Y459H and V492E lost all HO-1 activity. {yields} POR polymorphisms P228L, R316W, G413S, A503V and G504R have normal activity. -- Abstract: Human heme oxygenase-1 (HO-1) carries out heme catabolism supported by electrons supplied from the NADPH through NADPH P450 reductase (POR, CPR). Previously we have shown that mutations in human POR cause a rare form of congenital adrenal hyperplasia. In this study, we have evaluated the effects of mutations in POR on HO-1 activity. We used purified preparations of wild type and mutant human POR and in vitro reconstitution with purified HO-1 to measure heme degradation in a coupled assay using biliverdin reductase. Here we show that mutations in POR found in patients may reduce HO-1 activity, potentially influencing heme catabolism in individuals carrying mutant POR alleles. POR mutants Y181D, A457H, Y459H, V492E and R616X had total loss of HO-1 activity, while POR mutations A287P, C569Y and V608F lost 50-70% activity. The POR variants P228L, R316W and G413S, A503V and G504R identified as polymorphs had close to WT activity. Loss of HO-1 activity may result in increased oxidative neurotoxicity, anemia, growth retardation and iron deposition. Further examination of patients affected with POR deficiency will be required to assess the metabolic effects of reduced HO-1 activity in affected individuals.

  8. Alterations in midline cortical thickness and gyrification patterns mapped in children with 22q11.2 deletions.

    PubMed

    Bearden, Carrie E; van Erp, Theo G M; Dutton, Rebecca A; Lee, Agatha D; Simon, Tony J; Cannon, Tyrone D; Emanuel, Beverly S; McDonald-McGinn, Donna; Zackai, Elaine H; Thompson, Paul M

    2009-01-01

    The 22q11.2 deletion syndrome (velocardiofacial/DiGeorge syndrome) is a neurogenetic condition associated with visuospatial deficits, as well as elevated rates of attentional disturbance, mood disorder, and psychosis. Previously, we detected pronounced cortical thinning in superior parietal and right parieto-occipital cortices in patients with this syndrome, regions critical for visuospatial processing. Here we applied cortical pattern-matching algorithms to structural magnetic resonance images obtained from 21 children with confirmed 22q11.2 deletions (ages 8-17) and 13 demographically matched comparison subjects, in order to map cortical thickness across the medial hemispheric surfaces. In addition, cortical models were remeshed in frequency space to compute their surface complexity. Cortical maps revealed a pattern of localized thinning in the ventromedial occipital-temporal cortex, critical for visuospatial representation, and the anterior cingulate, a key area for attentional control. However, children with 22q11.2DS showed significantly increased gyral complexity bilaterally in occipital cortex. Regional gray matter volumes, particularly in medial frontal cortex, were strongly correlated with both verbal and nonverbal cognitive functions. These findings suggest that aberrant parieto-occipital brain development, as evidenced by both increased complexity and cortical thinning in these regions, may be a neural substrate for the deficits in visuospatial and numerical understanding characteristic of this syndrome. PMID:18483006

  9. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    SciTech Connect

    Miki, Takanori; Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo; Kusaka, Takashi; Warita, Katsuhiko; Yokoyama, Toshifumi; Jamal, Mostofa; Ueki, Masaaki; Yakura, Tomiko; Tamai, Motoki; Sumitani, Kazunori; Hosomi, Naohisa; Takeuchi, Yoshiki

    2013-12-06

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

  10. Excessive disgust caused by brain lesions or temporary inactivations: Mapping hotspots of nucleus accumbens and ventral pallidum

    PubMed Central

    Ho, Chao-Yi; Berridge, Kent C.

    2014-01-01

    Disgust is a prototypical type of negative affect. In animal models of excessive disgust, only a few brain sites are known in which localized dysfunction (lesions or neural inactivations) can induce intense ‘disgust reactions’ (e.g., gapes) to a normally pleasant sensation such as sweetness. Here we aimed to map forebrain candidates more precisely to identify where either local neuronal damage (excitotoxin lesions) or local pharmacological inactivation (muscimol-baclofen microinjections) caused rats to emit excessive sensory disgust reactions to sucrose. Our study compared subregions of nucleus accumbens shell, ventral pallidum, lateral hypothalamus and adjacent extended amygdala. Results indicated the posterior half of ventral pallidum to be the only forebrain site where intense sensory disgust gapes to sucrose were induced by both lesions and temporary inactivations (this site was previously identified as a hedonic hotspot for enhancements of sweetness ‘liking’). By comparison, for the nucleus accumbens, temporary GABA inactivations in the caudal half of the medial shell also generated sensory disgust but lesions never did at any site. Further, even inactivations failed to induce disgust in the rostral half of accumbens shell (which also contains a hedonic hotspot). In other structures, neither lesions nor inactivations induced disgust as long as the posterior ventral pallidum remained spared. We conclude that the posterior ventral pallidum is an especially crucial hotspot for producing excessive sensory disgust by local pharmacological/lesion dysfunction. By comparison, the nucleus accumbens appears to segregate sites for pharmacological disgust induction and hedonic enhancement into separate posterior versus rostral halves of medial shell. PMID:25229197

  11. The connexin46 mutant, Cx46T19M, causes loss of gap junction function and alters hemi-channel gating.

    PubMed

    Tong, Jun-Jie; Minogue, Peter J; Kobeszko, Matthew; Beyer, Eric C; Berthoud, Viviana M; Ebihara, Lisa

    2015-02-01

    An N-terminal mutant of connexin46 (T19M) alters a highly conserved threonine and has been linked to autosomal dominant cataracts. To study the cellular and functional consequences of substitution of this amino acid, T19M was expressed in Xenopus oocytes and in HeLa cells. Unlike wild-type Cx46, T19M did not induce intercellular conductances in Xenopus oocytes. In transfected HeLa cells, T19M was largely localized within the cytoplasm, with drastically reduced formation of gap junction plaques. Expression of rat T19M was cytotoxic, as evidenced by an almost complete loss of viable cells expressing the mutant protein by 48-72 h following transfection. When incubated in medium containing physiological concentrations of divalent cations, T19M-expressing cells showed increased uptake of DAPI as compared with cells expressing wild-type Cx46, suggesting aberrant connexin hemi-channel activity. Time-lapse and dye uptake studies suggested that T19M hemi-channels had reduced sensitivity to Ca(2+). Whole cell patch clamp studies of single transfected HeLa cells demonstrated that rat T19M formed functional hemi-channels with altered voltage-dependent gating. These data suggest that T19M causes cataracts by loss of gap junctional channel function and abnormally increased hemi-channel activity. Furthermore, they implicate this conserved threonine in both gap junction plaque formation and channel/hemi-channel gating in Cx46. PMID:25404239

  12. Identifying Senior High School Students' Misconceptions about Statistical Correlation, and Their Possible Causes: An Exploratory Study Using Concept Mapping with Interviews

    ERIC Educational Resources Information Center

    Liu, Tzu-Chien; Lin, Yi-Chun; Tsai, Chin-Chung

    2009-01-01

    Correlation is an essential concept in statistics; however, students may hold misconceptions about correlation, even after receiving instruction. This study aimed to elucidate (1) the misconceptions held by senior high school students about correlation, using the tool of concept mapping along with interviewing, (2) the possible causes of these…

  13. A stochastic approach to estimate the uncertainty of dose mapping caused by uncertainties in b-spline registration

    SciTech Connect

    Hub, Martina; Thieke, Christian; Kessler, Marc L.; Karger, Christian P.

    2012-04-15

    Purpose: In fractionated radiation therapy, image guidance with daily tomographic imaging becomes more and more clinical routine. In principle, this allows for daily computation of the delivered dose and for accumulation of these daily dose distributions to determine the actually delivered total dose to the patient. However, uncertainties in the mapping of the images can translate into errors of the accumulated total dose, depending on the dose gradient. In this work, an approach to estimate the uncertainty of mapping between medical images is proposed that identifies areas bearing a significant risk of inaccurate dose accumulation. Methods: This method accounts for the geometric uncertainty of image registration and the heterogeneity of the dose distribution, which is to be mapped. Its performance is demonstrated in context of dose mapping based on b-spline registration. It is based on evaluation of the sensitivity of dose mapping to variations of the b-spline coefficients combined with evaluation of the sensitivity of the registration metric with respect to the variations of the coefficients. It was evaluated based on patient data that was deformed based on a breathing model, where the ground truth of the deformation, and hence the actual true dose mapping error, is known. Results: The proposed approach has the potential to distinguish areas of the image where dose mapping is likely to be accurate from other areas of the same image, where a larger uncertainty must be expected. Conclusions: An approach to identify areas where dose mapping is likely to be inaccurate was developed and implemented. This method was tested for dose mapping, but it may be applied in context of other mapping tasks as well.

  14. Pathologic and phenotypic alterations in a mouse expressing a connexin47 missense mutation that causes Pelizaeus-Merzbacher-like disease in humans.

    PubMed

    Tress, Oliver; Maglione, Marta; Zlomuzica, Armin; May, Dennis; Dicke, Nikolai; Degen, Joachim; Dere, Ekrem; Kettenmann, Helmut; Hartmann, Dieter; Willecke, Klaus

    2011-07-01

    Gap junction channels are intercellular conduits that allow diffusional exchange of ions, second messengers, and metabolites. Human oligodendrocytes express the gap junction protein connexin47 (Cx47), which is encoded by the GJC2 gene. The autosomal recessive mutation hCx47M283T causes Pelizaeus-Merzbacher-like disease 1 (PMLD1), a progressive leukodystrophy characterized by hypomyelination, retarded motor development, nystagmus, and spasticity. We introduced the human missense mutation into the orthologous position of the mouse Gjc2 gene and inserted the mCx47M282T coding sequence into the mouse genome via homologous recombination in embryonic stem cells. Three-week-old homozygous Cx47M282T mice displayed impaired rotarod performance but unchanged open-field behavior. 10-15-day-old homozygous Cx47M282T and Cx47 null mice revealed a more than 80% reduction in the number of cells participating in glial networks after biocytin injections into oligodendrocytes in sections of corpus callosum. Homozygous expression of mCx47M282T resulted in reduced MBP expression and astrogliosis in the cerebellum of ten-day-old mice which could also be detected in Cx47 null mice of the same age. Three-month-old homozygous Cx47M282T mice exhibited neither altered open-field behavior nor impaired rotarod performance anymore. Adult mCx47M282T expressing mice did not show substantial myelin alterations, but homozygous Cx47M282T mice, additionally deprived of connexin32, which is also expressed in oligodendrocytes, died within six weeks after birth and displayed severe myelin defects accompanied by astrogliosis and activated microglia. These results strongly suggest that PMLD1 is caused by the loss of Cx47 channel function that results in impaired panglial coupling in white matter tissue. PMID:21750683

  15. Detection and mapping of hydrothermally altered rocks in the vicinity of the comstock lode, Virginia Range, Nevada, using enhanced LANDSAT images

    NASA Technical Reports Server (NTRS)

    Ashley, R. P. (Principal Investigator); Goetz, A. F. H.; Rowan, L. C.; Abrams, M. J.

    1979-01-01

    The author has identified the following significant results. LANDSAT images enhanced by the band-ratioing method can be used for reconnaissance alteration mapping in moderately heavily vegetated semiarid terrain as well as in sparsely vegetated to semiarid terrain where the technique was originally developed. Significant vegetation cover in a scene, however, requires the use of MSS ratios 4/5, 4/6, and 6/7 rather than 4/5, 5/6, and 6/7, and requires careful interpretation of the results. Supplemental information suitable to vegetation identification and cover estimates, such as standard LANDSAT false-color composites and low altitude aerial photographs of selected areas is desirable.

  16. Genome Wide Association Mapping in Arabidopsis thaliana Identifies Novel Genes Involved in Linking Allyl Glucosinolate to Altered Biomass and Defense

    PubMed Central

    Francisco, Marta; Joseph, Bindu; Caligagan, Hart; Li, Baohua; Corwin, Jason A.; Lin, Catherine; Kerwin, Rachel E.; Burow, Meike; Kliebenstein, Daniel J.

    2016-01-01

    A key limitation in modern biology is the ability to rapidly identify genes underlying newly identified complex phenotypes. Genome wide association studies (GWAS) have become an increasingly important approach for dissecting natural variation by associating phenotypes with genotypes at a genome wide level. Recent work is showing that the Arabidopsis thaliana defense metabolite, allyl glucosinolate (GSL), may provide direct feedback regulation, linking defense metabolism outputs to the growth, and defense responses of the plant. However, there is still a need to identify genes that underlie this process. To start developing a deeper understanding of the mechanism(s) that modulate the ability of exogenous allyl GSL to alter growth and defense, we measured changes in plant biomass and defense metabolites in a collection of natural 96 A. thaliana accessions fed with 50 μM of allyl GSL. Exogenous allyl GSL was introduced exclusively to the roots and the compound transported to the leaf leading to a wide range of heritable effects upon plant biomass and endogenous GSL accumulation. Using natural variation we conducted GWAS to identify a number of new genes which potentially control allyl responses in various plant processes. This is one of the first instances in which this approach has been successfully utilized to begin dissecting a novel phenotype to the underlying molecular/polygenic basis. PMID:27462337

  17. Functional near-infrared spectroscopy maps cortical plasticity underlying altered motor performance induced by transcranial direct current stimulation

    PubMed Central

    Hodics, Timea; Hervey, Nathan; Kondraske, George; Stowe, Ann M.; Alexandrakis, George

    2013-01-01

    Abstract. Transcranial direct current stimulation (tDCS) of the human sensorimotor cortex during physical rehabilitation induces plasticity in the injured brain that improves motor performance. Bi-hemispheric tDCS is a noninvasive technique that modulates cortical activation by delivering weak current through a pair of anodal–cathodal (excitation–suppression) electrodes, placed on the scalp and centered over the primary motor cortex of each hemisphere. To quantify tDCS-induced plasticity during motor performance, sensorimotor cortical activity was mapped during an event-related, wrist flexion task by functional near-infrared spectroscopy (fNIRS) before, during, and after applying both possible bi-hemispheric tDCS montages in eight healthy adults. Additionally, torque applied to a lever device during isometric wrist flexion and surface electromyography measurements of major muscle group activity in both arms were acquired concurrently with fNIRS. This multiparameter approach found that hemispheric suppression contralateral to wrist flexion changed resting-state connectivity from intra-hemispheric to inter-hemispheric and increased flexion speed (p<0.05). Conversely, exciting this hemisphere increased opposing muscle output resulting in a decrease in speed but an increase in accuracy (p<0.05 for both). The findings of this work suggest that tDCS with fNIRS and concurrent multimotor measurements can provide insights into how neuroplasticity changes muscle output, which could find future use in guiding motor rehabilitation. PMID:24193947

  18. Telomeric repeat-containing RNA/G-quadruplex-forming sequences cause genome-wide alteration of gene expression in human cancer cells in vivo

    PubMed Central

    Hirashima, Kyotaro; Seimiya, Hiroyuki

    2015-01-01

    Telomere erosion causes cell mortality, suggesting that longer telomeres enable more cell divisions. In telomerase-positive human cancer cells, however, telomeres are often kept shorter than those of surrounding normal tissues. Recently, we showed that cancer cell telomere elongation represses innate immune genes and promotes their differentiation in vivo. This implies that short telomeres contribute to cancer malignancy, but it is unclear how such genetic repression is caused by elongated telomeres. Here, we report that telomeric repeat-containing RNA (TERRA) induces a genome-wide alteration of gene expression in telomere-elongated cancer cells. Using three different cell lines, we found that telomere elongation up-regulates TERRA signal and down-regulates innate immune genes such as STAT1, ISG15 and OAS3 in vivo. Ectopic TERRA oligonucleotides repressed these genes even in cells with short telomeres under three-dimensional culture conditions. This appeared to occur from the action of G-quadruplexes (G4) in TERRA, because control oligonucleotides had no effect and a nontelomeric G4-forming oligonucleotide phenocopied the TERRA oligonucleotide. Telomere elongation and G4-forming oligonucleotides showed similar gene expression signatures. Most of the commonly suppressed genes were involved in the innate immune system and were up-regulated in various cancers. We propose that TERRA G4 counteracts cancer malignancy by suppressing innate immune genes. PMID:25653161

  19. Map of debris flows caused by rainfall during 1996 in parts of the Reedsport and Deer Head Point quadrangles, Douglas County, southern Coast Range, Oregon

    USGS Publications Warehouse

    Coe, Jeffrey A.; Michael, John A.; Burgos, Marianela Mercado

    2011-01-01

    This 1:12,000-scale map shows an inventory of debris flows caused by rainfall during 1996 in a 94.4 km2 area in the southern Coast Range of Oregon. This map and associated digital data are part of a larger U.S. Geological Survey study of debris flows in the southern Coast Range. Available evidence indicates that the flows were triggered by a rain storm that occurred between November 17 and 19. The closest rain gage in the Coast Range (Goodwin Peak) recorded 245 mm during the storm. Maximum rainfall intensity during the storm was 13.2 mm/hr on November 18. Debris flows were photogrammetrically mapped from 1:12,000-scale aerial photographs flown in May, 1997. The inventory is presented on imagery derived from LiDAR data acquired in 2008. We classified mapped debris flows into four categories based on the type of debris-flow activity: (1) discrete slide source areas, (2) predominantly erosion, (3) predominantly transport or mixed erosion and deposition, and (4) predominantly deposition. Locations of woody-debris jams are also shown on the map. The area encompassed by debris flows is 2.1 percent of the 94.4 km2 map area.

  20. Alteration mineral mapping and metallogenic prediction using CASI/SASI airborne hyperspectral data in Mingshujing area of Gansu Province, NW China

    NASA Astrophysics Data System (ADS)

    Sun, Yu; Zhao, Yingjun; Qin, Kai; Tian, Feng

    2016-04-01

    Hyperspectral remote sensing is a frontier of remote sensing. Due to its advantage of integrated image with spectrum, it can realize objects identification, superior to objects classification of multispectral remote sensing. Taken the Mingshujing area in Gansu Province of China as an example, this study extracted the alteration minerals and thus to do metallogenic prediction using CASI/SASI airborne hyperspectral data. The Mingshujing area, located in Liuyuan region of Gansu Province, is dominated by middle Variscan granites and Indosinian granites, with well developed EW- and NE-trending faults. In July 2012, our project team obtained the CASI/SASI hyperspectral data of Liuyuan region by aerial flight. The CASI hyperspectral data have 32 bands and the SASI hyperspectral data have 88 bands, with spectral resolution of 15nm for both. The hyperspectral raw data were first preprocessed, including radiometric correction and geometric correction. We then conducted atmospheric correction using empirical line method based on synchronously measured ground spectra to obtain hyperspectral reflectance data. Spectral dimension of hyperspectral data was reduced by the minimum noise fraction transformation method, and then purity pixels were selected. After these steps, image endmember spectra were obtained. We used the endmember spectrum election method based on expert knowledge to analyze the image endmember spectra. Then, the mixture tuned matched filter (MTMF) mapping method was used to extract mineral information, including limonite, Al-rich sericite, Al-poor sericite and chlorite. Finally, the distribution of minerals in the Mingshujing area was mapped. According to the distribution of limonite and Al-rich sericite mapped by CASI/SASI hyperspectral data, we delineated five gold prospecting areas, and further conducted field verification in these areas. It is shown that there are significant gold mineralized anomalies in surface in the Baixianishan and Xitan prospecting

  1. N-cadherin mediated distribution of beta-catenin alters MAP kinase and BMP-2 signaling on chondrogenesis-related gene expression.

    PubMed

    Modarresi, Rozbeh; Lafond, Toulouse; Roman-Blas, Jorge A; Danielson, Keith G; Tuan, Rocky S; Seghatoleslami, M Reza

    2005-05-01

    We have examined the effect of calcium-dependent adhesion, mediated by N-cadherin, on cell signaling during chondrogenesis of multipotential embryonic mouse C3H10T1/2 cells. The activity of chondrogenic genes, type II collagen, aggrecan, and Sox9 were examined in monolayer (non-chondrogenic), and micromass (chondrogenic) cultures of parental C3H10T1/2 cells and altered C3H10T1/2 cell lines that express a dominant negative form of N-cadherin (delta390-T1/2) or overexpress normal N-cadherin (MNCD2-T1/2). Our findings show that missexpression or inhibition of N-cadherin in C3H10T1/2 cells results in temporal and spatial changes in expression of the chondrogenic genes Sox9, aggrecan, and collagen type II. We have also analyzed activity of the serum response factor (SRF), a nuclear target of MAP kinase signaling implicated in chondrogenesis. In semi-confluent monolayer cultures (minimum cell-cell contact) of C3H10T1/2, MNCD2-T1/2, or delta390-T1/2 cells, there was no significant change in the pattern of MAP kinase or bone morphogenetic protein-2 (BMP-2) regulation of SRF. However, in micromass cultures, the effect of MAP kinase and BMP-2 on SRF activity was proportional to the nuclear localization of beta-catenin, a Wnt stabilized cytoplasmic factor that can associate with lymphoid enhancer-binding factor (LEF) to serve as a transcription factor. Our findings suggest that the extent of adherens junction formation mediated by N-cadherin can modulate the potential Wnt-induced nuclear activity of beta-catenin. PMID:15723280

  2. Mapping hydrothermally altered rocks at Cuprite, Nevada, using the advanced spaceborne thermal emission and reflection radiometer (Aster), a new satellite-imaging system

    USGS Publications Warehouse

    Rowan, L.C.; Hook, S.J.; Abrams, M.J.; Mars, J.C.

    2003-01-01

    The Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) is a 14-band multispectral instrument on board the Earth Observing System (EOS), TERRA. The three bands between 0.52 and 0.86 ??m and the six bands from 1.60 and 2.43 ??m, which have 15- and 30-m spatial resolution, respectively, were selected primarily for making remote mineralogical determinations. The Cuprite, Nevada, mining district comprises two hydrothermal alteration centers where Tertiary volcanic rocks have been hydrothermally altered mainly to bleached silicified rocks and opalized rocks, with a marginal zone of limonitic argilized rocks. Country rocks are mainly Cambrian phyllitic siltstone and limestone. Evaluation of an ASTER image of the Cuprite district shows that spectral reflectance differences in the nine bands in the 0.52 to 2.43 ??m region provide a basis for identifying and mapping mineralogical components which characterize the main hydrothermal alteration zones: opal is the spectrally dominant mineral in the silicified zone; whereas, alunite and kaolinite are dominant in the opalized zone. In addition, the distribution of unaltered country rocks was mapped because of the presence of spectrally dominant muscovite in the siltstone and calcite in limestone, and the tuffaceous rocks and playa deposits were distinguishable due to their relatively flat spectra and weak absorption features at 2.33 and 2.20 ??m, respectively. An Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) image of the study area was processed using a similar methodology used with the ASTER data. Comparison of the ASTER and AVIRIS results shows that the results are generally similar, but the higher spectral resolution of AVIRIS (224 bands) permits identification of more individual minerals, including certain polymorphs. However, ASTER has recorded images of more than 90 percent of the Earth's land surface with less than 20 percent cloud cover, and these data are available at nominal or no cost

  3. Suspensor-derived polyembryony caused by altered expression of valyl-tRNA synthetase in the twn2 mutant of Arabidopsis

    PubMed Central

    Zhang, James Z.; Somerville, Chris R.

    1997-01-01

    The twn2 mutant of Arabidopsis exhibits a defect in early embryogenesis where, following one or two divisions of the zygote, the decendents of the apical cell arrest. The basal cells that normally give rise to the suspensor proliferate abnormally, giving rise to multiple embryos. A high proportion of the seeds fail to develop viable embryos, and those that do, contain a high proportion of partially or completely duplicated embryos. The adult plants are smaller and less vigorous than the wild type and have a severely stunted root. The twn2-1 mutation, which is the only known allele, was caused by a T-DNA insertion in the 5′ untranslated region of a putative valyl-tRNA synthetase gene, valRS. The insertion causes reduced transcription of the valRS gene in reproductive tissues and developing seeds but increased expression in leaves. Analysis of transcript initiation sites and the expression of promoter–reporter fusions in transgenic plants indicated that enhancer elements inside the first two introns interact with the border of the T-DNA to cause the altered pattern of expression of the valRS gene in the twn2 mutant. The phenotypic consequences of this unique mutation are interpreted in the context of a model, suggested by Vernon and Meinke [Vernon, D. M. & Meinke, D. W. (1994) Dev. Biol. 165, 566–573], in which the apical cell and its decendents normally suppress the embryogenic potential of the basal cell and its decendents during early embryo development. PMID:9207094

  4. Maternal separation and early stress cause long-lasting effects on dopaminergic and endocannabinergic systems and alters dendritic morphology in the nucleus accumbens and frontal cortex in rats.

    PubMed

    Romano-López, Antonio; Méndez-Díaz, Mónica; García, Fabio García; Regalado-Santiago, Citlalli; Ruiz-Contreras, Alejandra E; Prospéro-García, Oscar

    2016-08-01

    A considerable amount experimental studies have shown that maternal separation (MS) is associated with adult offspring abnormal behavior and cognition disorder. Accordingly, this experimental procedure has been proposed as a predictor for alcohol and drug dependence based on the neurodevelopmental soon after birth. Endocannabinoid system (eCBs) has been implicated in reward processes, including drug abuse and dependence. MS and associated stress causes changes in the eCBs that seem to facilitate alcohol consumption. In this study, we seek to evaluate potential morphological changes in neurons of the frontal cortex (FCx) and nucleus accumbens (NAcc), in the expression of receptors and enzymes of the endocannabinoid and dopamine systems and in second messengers, such as Akt, in adult rats subjected to MS and early stress (MS + ES; 2 × 180 min daily) vs. nonseparated rats (NMS). Results showed that MS + ES induces higher D2R expression and lower D3R, FAAH, and MAGL expression compared with NMS rats. Alterations in total dendritic length were also detected and were characterized by increases in the NAcc while there were decreases in the FCx. We believe MS + ES-induced changes in the dopaminergic and endocannabinergic systems and in the neuronal microstructure might be contributing to alcohol seeking behavior and, potential vulnerability to other drugs in rats. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 819-831, 2016. PMID:26539755

  5. Mutation of a family 8 glycosyltransferase gene alters cell wall carbohydrate composition and causes a humidity-sensitive semi-sterile dwarf phenotype in Arabidopsis.

    PubMed

    Lao, Nga T; Long, Debbie; Kiang, Sophie; Coupland, George; Shoue, Douglas A; Carpita, Nicholas C; Kavanagh, Tony A

    2003-11-01

    The genome of Arabidopsis thaliana contains about 400 genes coding for glycosyltransferases, many of which are predicted to be involved in the synthesis and remodelling of cell wall components. We describe the isolation of a transposon-tagged mutant, parvus, which under low humidity conditions exhibits a severely dwarfed growth phenotype and failure of anther dehiscence resulting in semi-sterility. All aspects of the mutant phenotype were partially rescued by growth under high-humidity conditions, but not by the application of growth hormones or jasmonic acid. The mutation is caused by insertion of a maize Dissociation (Ds) element in a gene coding for a putative Golgi-localized glycosyltransferase belonging to family 8. Members of this family, originally identified on the basis of similarity to bacterial lipooligosaccharide glycosyltransferases, include enzymes known to be involved in the synthesis of bacterial and plant cell walls. Cell-wall carbohydrate analyses of the parvus mutant indicated reduced levels of rhamnogalacturonan I branching and alterations in the abundance of some xyloglucan linkages that may, however, be indirect consequences of the mutation. PMID:15010604

  6. Removal of immunoglobulin-like domains from titin’s spring segment alters titin splicing in mouse skeletal muscle and causes myopathy

    PubMed Central

    Buck, Danielle; Smith, John E.; Chung, Charles S.; Ono, Yasuko; Sorimachi, Hiroyuki; Labeit, Siegfried

    2014-01-01

    Titin is a molecular spring that determines the passive stiffness of muscle cells. Changes in titin’s stiffness occur in various myopathies, but whether these are a cause or an effect of the disease is unknown. We studied a novel mouse model in which titin’s stiffness was slightly increased by deleting nine immunoglobulin (Ig)-like domains from titin’s constitutively expressed proximal tandem Ig segment (IG KO). KO mice displayed mild kyphosis, a phenotype commonly associated with skeletal muscle myopathy. Slow muscles were atrophic with alterations in myosin isoform expression; functional studies in soleus muscle revealed a reduced specific twitch force. Exon expression analysis showed that KO mice underwent additional changes in titin splicing to yield smaller than expected titin isoforms that were much stiffer than expected. Additionally, splicing occurred in the PEVK region of titin, a finding confirmed at the protein level. The titin-binding protein Ankrd1 was highly increased in the IG KO, but this did not play a role in generating small titin isoforms because titin expression was unaltered in IG KO mice crossed with Ankrd1-deficient mice. In contrast, the splicing factor RBM20 (RNA-binding motif 20) was also significantly increased in IG KO mice, and additional differential splicing was reversed in IG KO mice crossed with a mouse with reduced RBM20 activity. Thus, increasing titin’s stiffness triggers pathological changes in skeletal muscle, with an important role played by RBM20. PMID:24470489

  7. Regional mapping of hydrothermally altered igneous rocks along the Urumieh-Dokhtar, Chagai, and Alborz Belts of western Asia using Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data and Interactive Data Language (IDL) logical operators: a tool for porphyry copper exploration and assessment: Chapter O in Global mineral resource assessment

    USGS Publications Warehouse

    Mars, John L.

    2014-01-01

    The ASTER alteration map and corresponding geologic maps were used to select circular to elliptical patterns of argillic- and phyllic-altered volcanic and intrusive rocks as potential porphyry copper sites. One hundred and seventy eight potential porphyry copper sites were mapped along the UDVB, and 23 sites were mapped along the CVB. The potential sites were selected to assist in further exploration and assessments of undiscovered porphyry copper deposits.

  8. Resting-state functional connectivity density mapping of etiology confirmed unilateral pulsatile tinnitus patients: Altered functional hubs in the early stage of disease.

    PubMed

    Han, L; Pengfei, Z; Zhaohui, L; Fei, Y; Ting, L; Cheng, D; Zhenchang, W

    2015-12-01

    Functional magnetic resonance imaging (fMRI) has been widely used to identify altered intrinsic local neural activities and global networks of tinnitus patients. In this study, functional connectivity density (FCD) mapping, a newly developed voxelwise data-driven method based on fMRI, was applied for the first time to measure the functional reorganization pattern in thirty-two unilateral pulsatile tinnitus (PT) patients in the early stage of disease (less than 48 months). FCD analysis was employed to compute short-range and long-range FCD values. A correlation analysis with clinical variables was also performed. Compared with normal controls, PT patients showed significantly increased short-range FCD, mainly in the precuneus (PCu), bilateral inferior frontal gyrus (IFG) and middle occipital gyrus (MOG), and increased long-range FCD in the PCu, posterior cingulate cortex (PCC), and bilateral middle frontal gyrus (MFG). In addition, correlation analysis showed positive correlations between PT duration and short-range FCD values in the right MOG. Positive correlations were also found between the disease duration and the long-range FCD value in the PCC. The increased short-/long-range FCD in bilateral dorsal visual areas indicated that the enhanced pathway between the auditory cortex and bilateral dorsal visual areas may have activated the "auditory occipital activations" (AOAs) pathway. The bilaterally altered FCD values in the dorsal visual areas reflected the cooperation of different brain areas. This study is a foundation of the connectivity research in PT patients. Our work may advance the understanding of the disrupted neural network of patients with PT. PMID:26384961

  9. Histamine activates p38 MAP kinase and alters local lamellipodia dynamics, reducing endothelial barrier integrity and eliciting central movement of actin fibers.

    PubMed

    Adderley, Shaquria P; Lawrence, Curtis; Madonia, Eyong; Olubadewo, Joseph O; Breslin, Jerome W

    2015-07-01

    The role of the actin cytoskeleton in endothelial barrier function has been debated for nearly four decades. Our previous investigation revealed spontaneous local lamellipodia in confluent endothelial monolayers that appear to increase overlap at intercellular junctions. We tested the hypothesis that the barrier-disrupting agent histamine would reduce local lamellipodia protrusions and investigated the potential involvement of p38 mitogen-activated protein (MAP) kinase activation and actin stress fiber formation. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) expressing green fluorescent protein-actin were studied using time-lapse fluorescence microscopy. The protrusion and withdrawal characteristics of local lamellipodia were assessed before and after addition of histamine. Changes in barrier function were determined using electrical cell-substrate impedance sensing. Histamine initially decreased barrier function, lamellipodia protrusion frequency, and lamellipodia protrusion distance. A longer time for lamellipodia withdrawal and reduced withdrawal distance and velocity accompanied barrier recovery. After barrier recovery, a significant number of cortical fibers migrated centrally, eventually resembling actin stress fibers. The p38 MAP kinase inhibitor SB203580 attenuated the histamine-induced decreases in barrier function and lamellipodia protrusion frequency. SB203580 also inhibited the histamine-induced decreases in withdrawal distance and velocity, and the subsequent actin fiber migration. These data suggest that histamine can reduce local lamellipodia protrusion activity through activation of p38 MAP kinase. The findings also suggest that local lamellipodia have a role in maintaining endothelial barrier integrity. Furthermore, we provide evidence that actin stress fiber formation may be a reaction to, rather than a cause of, reduced endothelial barrier integrity. PMID:25948734

  10. Histamine activates p38 MAP kinase and alters local lamellipodia dynamics, reducing endothelial barrier integrity and eliciting central movement of actin fibers

    PubMed Central

    Adderley, Shaquria P.; Lawrence, Curtis; Madonia, Eyong; Olubadewo, Joseph O.

    2015-01-01

    The role of the actin cytoskeleton in endothelial barrier function has been debated for nearly four decades. Our previous investigation revealed spontaneous local lamellipodia in confluent endothelial monolayers that appear to increase overlap at intercellular junctions. We tested the hypothesis that the barrier-disrupting agent histamine would reduce local lamellipodia protrusions and investigated the potential involvement of p38 mitogen-activated protein (MAP) kinase activation and actin stress fiber formation. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) expressing green fluorescent protein-actin were studied using time-lapse fluorescence microscopy. The protrusion and withdrawal characteristics of local lamellipodia were assessed before and after addition of histamine. Changes in barrier function were determined using electrical cell-substrate impedance sensing. Histamine initially decreased barrier function, lamellipodia protrusion frequency, and lamellipodia protrusion distance. A longer time for lamellipodia withdrawal and reduced withdrawal distance and velocity accompanied barrier recovery. After barrier recovery, a significant number of cortical fibers migrated centrally, eventually resembling actin stress fibers. The p38 MAP kinase inhibitor SB203580 attenuated the histamine-induced decreases in barrier function and lamellipodia protrusion frequency. SB203580 also inhibited the histamine-induced decreases in withdrawal distance and velocity, and the subsequent actin fiber migration. These data suggest that histamine can reduce local lamellipodia protrusion activity through activation of p38 MAP kinase. The findings also suggest that local lamellipodia have a role in maintaining endothelial barrier integrity. Furthermore, we provide evidence that actin stress fiber formation may be a reaction to, rather than a cause of, reduced endothelial barrier integrity. PMID:25948734

  11. Luteinizing hormone causes MAP kinase-dependent phosphorylation and closure of connexin 43 gap junctions in mouse ovarian follicles: one of two paths to meiotic resumption

    PubMed Central

    Norris, Rachael P.; Freudzon, Marina; Mehlmann, Lisa M.; Cowan, Ann E.; Simon, Alexander M.; Paul, David L.; Lampe, Paul D.; Jaffe, Laurinda A.

    2008-01-01

    SUMMARY Luteinizing hormone (LH) acts on ovarian follicles to reinitiate meiosis in prophase-arrested mammalian oocytes, and this has been proposed to occur by interruption of a meioisis-inhibitory signal that is transmitted through gap junctions into the oocyte from the somatic cells that surround it. To investigate this idea, we microinjected fluorescent tracers into live antral follicle-enclosed mouse oocytes, and demonstrate for the first time that LH causes a decrease in the gap junction permeability between the somatic cells, prior to nuclear envelope breakdown (NEBD). The decreased permeability results from MAP kinase-dependent phosphorylation of connexin 43 on serines 255, 262, and 279/282. We then tested whether inhibition of gap junction communication is sufficient and necessary for the reinitiation of meiosis. Inhibitors that reduced gap junction permeability caused NEBD, but an inhibitor of MAP kinase activation that blocked gap junction closure in response to LH did not prevent NEBD. Thus both MAP kinase-dependent gap junction closure and another redundant pathway function in parallel to ensure that meiosis resumes in response to LH. PMID:18776144

  12. Early postnatal nicotine exposure causes hippocampus-dependent memory impairments in adolescent mice: association with altered nicotinic cholinergic modulation of LTP, but not impaired LTP

    PubMed Central

    Nakauchi, Sakura; Malvaez, Melissa; Su, Hailing; Kleeman, Elise; Dang, Richard; Wood, Marcelo A.; Sumikawa, Katumi

    2014-01-01

    Fetal nicotine exposure from smoking during pregnancy causes long-lasting cognitive impairments in offspring, yet little is known about the mechanisms that underlie this effect. Here we demonstrate that early postnatal exposure of mouse pups to nicotine via maternal milk impairs long-term, but not short-term, hippocampus-dependent memory during adolescence. At the Schaffer collateral (SC) pathway, the most widely studied synapses for a cellular correlate of hippocampus-dependent memory, the induction of N-methyl-d-aspartate receptor-dependent transient long-term potentiation (LTP) and protein synthesis-dependent long-lasting LTP are not diminished by nicotine exposure, but rather unexpectedly the threshold for LTP induction becomes lower after nicotine treatment. Using voltage sensitive dye to visualize hippocampal activity, we found that early postnatal nicotine exposure also results in enhanced CA1 depolarization and hyperpolarization after SC stimulation. Furthermore, we show that postnatal nicotine exposure induces pervasive changes to the nicotinic modulation of CA1 activity: activation of nicotinic receptors no longer increases CA1 network depolarization, acute nicotine inhibits rather than facilitates the induction of LTP at the SC pathway by recruiting an additional nicotinic receptor subtype, and acute nicotine no longer blocks LTP induction at the temporoammonic pathway. These findings reflect the pervasive impact of nicotine exposure during hippocampal development, and demonstrate an association of hippocampal memory impairments with altered nicotinic cholinergic modulation of LTP, but not impaired LTP. The implication of our results is that nicotinic cholinergic-dependent plasticity is required for long-term memory formation and that postnatal nicotine exposure disrupts this form of plasticity. PMID:25545599

  13. Altered Pre-mRNA Splicing Caused by a Novel Intronic Mutation c.1443+5G>A in the Dihydropyrimidinase (DPYS) Gene.

    PubMed

    Nakajima, Yoko; Meijer, Judith; Zhang, Chunhua; Wang, Xu; Kondo, Tomomi; Ito, Tetsuya; Dobritzsch, Doreen; Van Kuilenburg, André B P

    2016-01-01

    Dihydropyrimidinase (DHP) deficiency is an autosomal recessive disease caused by mutations in the DPYS gene. Patients present with highly elevated levels of dihydrouracil and dihydrothymine in their urine, blood and cerebrospinal fluid. The analysis of the effect of mutations in DPYS on pre-mRNA splicing is hampered by the fact that DHP is primarily expressed in liver and kidney cells. The minigene approach can detect mRNA splicing aberrations using cells that do not express the endogenous mRNA. We have used a minigene-based approach to analyze the effects of a presumptive pre-mRNA splicing mutation in two newly identified Chinese pediatric patients with DHP deficiency. Mutation analysis of DPYS showed that both patients were compound heterozygous for a novel intronic mutation c.1443+5G>A in intron 8 and a previously described missense mutation c.1001A>G (p.Q334R) in exon 6. Wild-type and the mutated minigene constructs, containing exons 7, 8 and 9 of DPYS, yielded different splicing products after expression in HEK293 cells. The c.1443+5G>A mutation resulted in altered pre-mRNA splicing of the DPYS minigene construct with full skipping of exon 8. Analysis of the DHP crystal structure showed that the deletion of exon 8 severely affects folding, stability and homooligomerization of the enzyme as well as disruption of the catalytic site. Thus, the analysis suggests that the c.1443+5G>A mutation results in aberrant splicing of the pre-mRNA encoding DHP, underlying the DHP deficiency in two unrelated Chinese patients. PMID:26771602

  14. Alterations in the glycoform of cisplatin-resistant human carcinoma cells are caused by defects in the endoplasmic reticulum-associated degradation system.

    PubMed

    Nakagawa, Hiroaki; Ohira, Miki; Hayashi, Shunji; Abe, Shigeaki; Saito, Shin; Nagahori, Noriko; Monde, Kenji; Shinohara, Yasuro; Fujitani, Naoki; Kondo, Hirosato; Akiyama, Shin-Ichi; Nakagawara, Akira; Nishimura, Shin-Ichiro

    2008-11-01

    Cisplatin, cis-diamineplatinum-(II) dichloride (CDDP), is one of the most common and valuable chemotherapeutic reagents for various cancers. However, it is well known that tumor cells gain acquired or intrinsic resistance to treatment by this anti-cancer reagent. In spite of extensive efforts using genetic and proteomic approaches, the mechanism underlying CDDP resistance remains unclear. In the present study, we report drastic structural changes in the N-glycans of glycoproteins in CDDP-resistant tumor cells (the KCP-4 cell line obtained from KB-3-1 human carcinoma cells). It was suggested that the CDDP-resistant cells exhibited an increase in one of the high-mannose-type glycans, particularly M8.1. This N-glycan is well known as a tag for the transport of unfolded protein from the endoplasmic reticulum to the lysosome, a process known as endoplasmic reticulum-associated degradation (ERAD) system. The revertant cells (KCP-4R) obtained from the KCP-4 cell line showed almost the same glycoform profile as that of the parental cells, suggesting that N-glycan biosynthesis in tumor cells clearly corresponds to the alteration in the sensitivity against CDDP. Gene expression analysis using a cDNA microarray showed a decrease in the expression of major histocompatibility complex (MHC) proteins in the resistant cells. MHC proteins form a complex with lysosome-degradated proteins and are presented on the cell surface. These results suggest that CDDP tolerance in KCP-4 cells is caused by a defect in the ERAD system. PMID:18573595

  15. Chronic exposure to low levels of inorganic arsenic causes alterations in locomotor activity and in the expression of dopaminergic and antioxidant systems in the albino rat.

    PubMed

    Rodríguez, Verónica Mireya; Limón-Pacheco, Jorge Humberto; Carrizales, Leticia; Mendoza-Trejo, María Soledad; Giordano, Magda

    2010-01-01

    Several studies have associated chronic arsenicism with decreases in IQ and sensory and motor alterations in humans. Likewise, studies of rodents exposed to inorganic arsenic ((i)As) have found changes in locomotor activity, brain neurochemistry, behavioral tasks, oxidative stress, and in sensory and motor nerves. In the current study, male Sprague-Dawley rats were exposed to environmentally relevant doses of (i)As (0.05, 0.5 mg (i)As/L) and to a high dose (50 mg (i)As/L) in drinking water for one year. Hypoactivity and increases in the striatal dopamine content were found in the group treated with 50 mg (i)As/L. Exposure to 0.5 and 50 mg (i)As/L increased the total brain content of As. Furthermore, (i)As exposure produced a dose-dependent up-regulation of mRNA for Mn-SOD and Trx-1 and a down-regulation of DAR-D₂ mRNA levels in the nucleus accumbens. DAR-D₁ and Nrf2 mRNA expression were down-regulated in nucleus accumbens in the group exposed to 50 mg (i)As/L. Trx-1 mRNA levels were up-regulated in the cortex in an (i)As dose-dependent manner, while DAR-D₁ mRNA expression was increased in striatum in the 0.5 mg (i)As/L group. These results show that chronic exposure to low levels of arsenic causes subtle but region-specific changes in the nervous system, especially in antioxidant systems and dopaminergic elements. These changes became behaviorally evident only in the group exposed to 50 mg (i)As/L. PMID:20699118

  16. Altered Pre-mRNA Splicing Caused by a Novel Intronic Mutation c.1443+5G>A in the Dihydropyrimidinase (DPYS) Gene

    PubMed Central

    Nakajima, Yoko; Meijer, Judith; Zhang, Chunhua; Wang, Xu; Kondo, Tomomi; Ito, Tetsuya; Dobritzsch, Doreen; Van Kuilenburg, André B. P.

    2016-01-01

    Dihydropyrimidinase (DHP) deficiency is an autosomal recessive disease caused by mutations in the DPYS gene. Patients present with highly elevated levels of dihydrouracil and dihydrothymine in their urine, blood and cerebrospinal fluid. The analysis of the effect of mutations in DPYS on pre-mRNA splicing is hampered by the fact that DHP is primarily expressed in liver and kidney cells. The minigene approach can detect mRNA splicing aberrations using cells that do not express the endogenous mRNA. We have used a minigene-based approach to analyze the effects of a presumptive pre-mRNA splicing mutation in two newly identified Chinese pediatric patients with DHP deficiency. Mutation analysis of DPYS showed that both patients were compound heterozygous for a novel intronic mutation c.1443+5G>A in intron 8 and a previously described missense mutation c.1001A>G (p.Q334R) in exon 6. Wild-type and the mutated minigene constructs, containing exons 7, 8 and 9 of DPYS, yielded different splicing products after expression in HEK293 cells. The c.1443+5G>A mutation resulted in altered pre-mRNA splicing of the DPYS minigene construct with full skipping of exon 8. Analysis of the DHP crystal structure showed that the deletion of exon 8 severely affects folding, stability and homooligomerization of the enzyme as well as disruption of the catalytic site. Thus, the analysis suggests that the c.1443+5G>A mutation results in aberrant splicing of the pre-mRNA encoding DHP, underlying the DHP deficiency in two unrelated Chinese patients. PMID:26771602

  17. Knock-down of methyl CpG-binding protein 2 (MeCP2) causes alterations in cell proliferation and nuclear lamins expression in mammalian cells

    PubMed Central

    2012-01-01

    Background MeCP2 (CpG-binding protein 2) is a nuclear multifunctional protein involved in several cellular processes, like large-scale chromatin reorganization and architecture, and transcriptional regulation. In recent years, a non-neuronal role for MeCP2 has emerged in cell growth and proliferation. Mutations in the MeCP2 gene have been reported to determine growth disadvantages in cultured lymphocyte cells, and its functional ablation suppresses cell growth in glial cells and proliferation in mesenchymal stem cells and prostate cancer cells. MeCP2 interacts with lamin B receptor (LBR) and with Heterochromatin Protein 1 (HP1) at the nuclear envelope (NE), suggesting that it could be part of complexes involved in attracting heterochromatin at the nuclear periphery and in mediating gene silencing. The nuclear lamins, major components of the lamina, have a role in maintaining NE integrity, in orchestrating mitosis, in DNA replication and transcription, in regulation of mitosis and apoptosis and in providing anchoring sites for chromatin domains. In this work, we inferred that MeCP2 might have a role in nuclear envelope stability, thereby affecting the proliferation pattern of highly proliferating systems. Results By performing knock-down (KD) of MeCP2 in normal murine (NIH-3 T3) and in human prostate transformed cells (PC-3 and LNCaP), we observed a strong proliferation decrease and a defect in the cell cycle progression, with accumulation of cells in S/G2M, without triggering a strong apoptotic and senescent phenotype. In these cells, KD of MeCP2 evidenced a considerable decrease of the levels of lamin A, lamin C, lamin B1 and LBR proteins. Moreover, by confocal analysis we confirmed the reduction of lamin A levels, but we also observed an alteration in the shape of the nuclear lamina and an irregular nuclear rim. Conclusions Our results that indicate reduced levels of NE components, are consistent with a hypothesis that the deficiency of MeCP2 might cause the

  18. Deletion of individual Ku subunits in mice causes an NHEJ-independent phenotype potentially by altering apurinic/apyrimidinic site repair.

    PubMed

    Choi, Yong Jun; Li, Han; Son, Mi Young; Wang, Xiao-Hong; Fornsaglio, Jamie L; Sobol, Robert W; Lee, Moonsook; Vijg, Jan; Imholz, Sandra; Dollé, Martijn E T; van Steeg, Harry; Reiling, Erwin; Hasty, Paul

    2014-01-01

    Ku70 and Ku80 form a heterodimer called Ku that forms a holoenzyme with DNA dependent-protein kinase catalytic subunit (DNA-PKCS) to repair DNA double strand breaks (DSBs) through the nonhomologous end joining (NHEJ) pathway. As expected mutating these genes in mice caused a similar DSB repair-defective phenotype. However, ku70(-/-) cells and ku80(-/-) cells also appeared to have a defect in base excision repair (BER). BER corrects base lesions, apurinic/apyrimidinic (AP) sites and single stand breaks (SSBs) utilizing a variety of proteins including glycosylases, AP endonuclease 1 (APE1) and DNA Polymerase β (Pol β). In addition, deleting Ku70 was not equivalent to deleting Ku80 in cells and mice. Therefore, we hypothesized that free Ku70 (not bound to Ku80) and/or free Ku80 (not bound to Ku70) possessed activity that influenced BER. To further test this hypothesis we performed two general sets of experiments. The first set showed that deleting either Ku70 or Ku80 caused an NHEJ-independent defect. We found ku80(-/-) mice had a shorter life span than dna-pkcs(-/-) mice demonstrating a phenotype that was greater than deleting the holoenzyme. We also found Ku70-deletion induced a p53 response that reduced the level of small mutations in the brain suggesting defective BER. We further confirmed that Ku80-deletion impaired BER via a mechanism that was not epistatic to Pol β. The second set of experiments showed that free Ku70 and free Ku80 could influence BER. We observed that deletion of either Ku70 or Ku80, but not both, increased sensitivity of cells to CRT0044876 (CRT), an agent that interferes with APE1. In addition, free Ku70 and free Ku80 bound to AP sites and in the case of Ku70 inhibited APE1 activity. These observations support a novel role for free Ku70 and free Ku80 in altering BER. PMID:24466051

  19. Alterations caused to soil organic matter by post-fire rehabilitation actions in a pine forest from doñana national park (southwest Spain)

    NASA Astrophysics Data System (ADS)

    González-Pérez, José A.; Jiménez-Morillo, Nicasio T.; Jordán, Antonio; Zavala, Lorena M.; Granged, Arturo J. P.; González-Vila, Francisco J.

    2016-04-01

    Post-fire rehabilitation actions and recovery attempts of burned soils include a range of management practices (tillage, tree logging, reforestation …), in some cases producing an additional damage to that directly caused by fire. Among negative impacts derived from unappropriated rehab practices are the increase soil erosion, loss of soil fertility and alterations in the hydrological cycle. Analytical pyrolysis (Py-GC/MS) is an appropriate technique to study organic matter characteristics within complex matrices. Here this technique is used to study the alterations caused by burning and post-fire rehab plans to soil organic matter (SOM). Fire and post-fire rehab actions impact on SOM is studied in a sandy soil under pine (Pinus pinea) forest that was affected by a severe fire in August 2012 in Doñana National Park (SW Spain). Bulk samples as well as its sieved soil fractions (coarse, 1-2 mm, and fine, <0.05 mm) collected from an undisturbed burned area (B) and in an adjacent burned area after rehab practices (BR) (logging and extraction of burned trees) were studied. An additional adjacent unburned (UB) area was used as a control. Conspicuous differences among bulk samples from the B, BR and UB control areas were found in the relative proportions of the main molecular families obtained by analytical pyrolysis, including alkane/alkene pairs, unspecific aromatic compounds (UAC), peptides, methoxyphenols, fatty acids, carbohydrates, N-compounds and polycyclic aromatic hydrocarbons (PAH). The B site SOM showed lower proportion of lignin methoxyphenols and higher of UAC and PAH than the SOM from the UB site. This indicates that fire produced methoxyphenol de-functionalization, increasing the proportion of recalcitrant compounds. With respect to soil size fractions, in all cases, the coarse fraction showed a high content of carbohydrate-derived compounds and methoxyphenols followed by fatty acids, in line with inputs of new litter from stressed post-fire vegetation

  20. Mapping the gene causing hereditary primary hyperparathyroidism in a Portuguese kindred to chromosome 1q22-q31.

    PubMed

    Williamson, C; Cavaco, B M; Jauch, A; Dixon, P H; Forbes, S; Harding, B; Holtgreve-Grez, H; Schoell, B; Pereira, M C; Font, A P; Loureiro, M M; Sobrinho, L G; Santos, M A; Thakker, R V; Jausch, A

    1999-02-01

    A Portuguese kindred with autosomal dominant isolated primary hyperparathyroidism (HPT) that was associated with parathyroid adenomas and carcinomas was investigated with the aim of determining the chromosomal location of this gene, designated HPTPort. Leukocyte DNA from 9 affected and 16 unaffected members and 7 parathyroid tumors from 4 patients was used in comparative genomic hybridization (CGH), tumor loss of heterozygosity (LOH), and family linkage studies. The CGH studies revealed abnormalities of chromosomes 1 and 13, and the results of LOH studies were consistent with the involvements of tumor suppressor genes from these regions. Family segregation studies mapped HPTPort to chromosome 1q22-q31 by establishing linkage with eight loci (D1S254, D1S222, D1S202, D1S238, D1S428, D1S2877, D1S422, and D1S412) (peak two-point LOD scores = 3. 46-5.14 at 0% recombination), and defined the location of HPT Port to a 21 cM region flanked centromerically by D1S215 and telomerically by D1S306. Thus, HPTPort has been mapped to chromosome 1q22-q31, and a characterization of this gene will help to elucidate further the mechanisms that are involved in the development of parathyroid tumors. PMID:9933477

  1. Map showing areas of visible land disturbances caused by two military training operations in the Mojave Desert, California

    USGS Publications Warehouse

    Prose, D.V.

    1986-01-01

    Land disturbances caused by these training exercises are still evident today throughout the designated training areas (Lathrop, 1983; Prose, 1985; Prose and Metzger, 1985). The World War II base-camp locations are easily identified because the networks of dirt roads are still used by campers, hunters, artifact seekers, and other visitors. Vehicle trails and single tracks remain on many relatively stable surfaces and are most conspicuous on surfaces composed of a veneer of stones (desert pavement).

  2. A gene defect causing a novel progressive epilepsy with mental retardation, EPMR, maps to chromosome 8p

    SciTech Connect

    Ranta, S.; Tahvanainen, E.; Karila, E.

    1994-09-01

    EPMR (progressive epilepsy with mental retardation) is a newly discovered autosomal recessively inherited disorder which occurs with high frequency in an isolated rural population in Finland. So far 25 patients have been identified, 21 of whom are alive. Twenty-three patients share a common ancestor from the 18th century. The main features of EPMR are: normal early development, tonic-clonic seizures with onset between ages 5 and 10, and mental retardation which begins approximately 2 years after the onset of epilepsy and soon leads to deepening mental retardation. Adult patients do not manage their daily life without help. The EEG is normal at the onset of epilepsy but later progressive slowing of the background activity occurs. The etiology and pathogenesis of EPMR remain known. As this is a novel disease entity without any definitive diagnostic marker we wished to begin its elucidation by first defining its gene locus. A random search for linkage in four multiplex families (only 20 individuals tested) resulted in the finding of linkage to marker D8S264 with a lod score of 4.45 at zero recombination. The EPMR gene resides in a 7 centimorgan interval between marker loci AFM185xb2 and D8S262 with a maximum multipoint lod score of 7.03 at 1.8 centimorgans proximal to D8S264. Physically this region is very distal on 8p. Of the sixteen EPMR chromosomes haplotyped 15 were identical or almost identical. One chromosome, however, had a distinctly different haplotype raising the possibility of there being two different mutations or one very old mutation. These findings are a starting point toward isolating and characterizing the gene and its protein product. Physical mapping has been initiated by isolating nine YACs from the region.

  3. Ecdysone and insulin signaling play essential roles in readjusting the altered body size caused by the dGPAT4 mutation in Drosophila.

    PubMed

    Yan, Yan; Wang, Hao; Chen, Hanqing; Lindström-Battle, Anya; Jiao, Renjie

    2015-09-20

    Body size is one of the features that distinguish one species from another in the biological world. Animals have developed mechanisms to control their body size during normal development. However, how animals cope with genetic alterations and/or environmental stresses to develop into normal-sized adults remain poorly understood. The ability of the animals to develop into a normal-sized adult after the challenges of genetic alterations and/or environmental stresses reveals a robustness of body size control. Here we show that the mutation of dGPAT4, a de novo synthase of lysophosphatidic acid, is a genetic alteration that triggers such a robust response of the animals to body size challenges in Drosophila. Loss of dGPAT4 leads to a severe delay of development, slow growth and resultant small-sized animals during the larval stages, but results in normal-sized adult flies. The robust body size adjustment of the dGPAT4 mutant is likely achieved by corresponding changes in ecdysone and insulin signaling, which is also manifested by compromised food intake. Thus, we propose that a strategy has been evolved by the animals to reach final body size when challenged by genetic alterations, which requires the coordinated ecdysone and insulin signaling. PMID:26408093

  4. A deficit in zinc availability can cause alterations in tubulin thiol redox status in cultured neurons and in the developing fetal rat brain

    PubMed Central

    Mackenzie, Gerardo G.; Salvador, Gabriela A.; Romero, Carolina; Keen, Carl L.; Oteiza, Patricia I.

    2012-01-01

    Zinc (Zn) deficiency during early development can result in multiple brain abnormalities and altered neuronal functions. In rats, a gestational deficit of Zn can affect the fetal brain cytoskeleton, and signaling cascades involved in cellular processes that are central to brain development. In the current paper, we tested the hypothesis that oxidative stress is involved in Zn deficiency-induced altered tubulin dynamics and the associated dysregulation of transcription factor NF-κB. For this purpose, we used two cell culture models (rat cortical neurons, human IMR-32 neuroblastoma cells) and an animal model of Zn deficiency. A low rate of in vitro tubulin polymerization, an increase in tubulin oligomers and a higher protein cysteine oxidation were observed in the Zn deficient neuronal cells, and in gestation day 19 fetal brains obtained from dams fed marginal Zn diets throughout pregnancy. These alterations could be prevented by treating the Zn deficient cells with the reducing agent tris(2-carboxyethyl)phosphine, or the presence of N-acetyl cysteine (NAC) and α-lipoic acid (LA). Consistent with the above, Zn deficiency-induced tubulin-mediated alterations in transcription factor NF-κB nuclear translocation were prevented by treating IMR-32 cells with LA and NAC. Binding of the NF-κB protein p50, dynein and karyopherin alpha (components of the NF-κB transport complex) to β-tubulin as well as the expression of NF-κB dependent genes (bcl-2, cyclin D1 and c-myc) were also restored by the addition of LA and NAC to Zn deficient cells. In conclusion, a deficit in Zn viability could affect early brain development through: 1) an induction of oxidative stress; 2) tubulin oxidation; 3) altered tubulin dynamics, and 4) deregulation of signals (e.q. NF-κB) involved in critical developmental events. PMID:21600978

  5. A gene causing Hermansky-Pudlak syndrome in a Puerto Rican population maps to chromosome 10q2

    SciTech Connect

    Wildenberg, S.C.; Oetting, W.S.; King, R.A.

    1995-10-01

    Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that affects pigment production and platelet function and causes the deposition of a ceroid like material in various tissues. Variability in the phenotype and the presence of several potential mouse models suggest that HPS may be a heterogeneous disorder. In order to identify a gene responsible for HPS, we collected blood samples from a relatively homogeneous population in Puerto Rico where the HPS carrier frequency is estimated to be 1 in 21. Analysis of pooled DNA samples allowed us to rapidly screen the genome for candidate loci, and significant evidence for linkage was detected for a marker on chromosome 10q. This region of the human genome is conserved syntenically with the region on mouse chromosome 19 where two possible mouse models for HPS, pale ear and ruby eye, are located. This linkage result was verified with additional markers, and a maximum LOD score of 5.07 at {theta} = .001 was calculated for marker D10S198. Haplotype analysis places the HPS gene in a region of {approximately} 14 cM that contains the markers D10S198 and D10S1239. 41 refs., 3 figs., 4 tabs.

  6. Homozygosity mapping reveals mutations of GRXCR1 as a cause of autosomal-recessive nonsyndromic hearing impairment.

    PubMed

    Schraders, Margit; Lee, Kwanghyuk; Oostrik, Jaap; Huygen, Patrick L M; Ali, Ghazanfar; Hoefsloot, Lies H; Veltman, Joris A; Cremers, Frans P M; Basit, Sulman; Ansar, Muhammad; Cremers, Cor W R J; Kunst, Henricus P M; Ahmad, Wasim; Admiraal, Ronald J C; Leal, Suzanne M; Kremer, Hannie

    2010-02-12

    We identified overlapping homozygous regions within the DFNB25 locus in two Dutch and ten Pakistani families with sensorineural autosomal-recessive nonsyndromic hearing impairment (arNSHI). Only one of the families, W98-053, was not consanguineous, and its sibship pointed toward a reduced critical region of 0.9 Mb. This region contained the GRXCR1 gene, and the orthologous mouse gene was described to be mutated in the pirouette (pi) mutant with resulting hearing loss and circling behavior. Sequence analysis of the GRXCR1 gene in hearing-impaired family members revealed splice-site mutations in two Dutch families and a missense and nonsense mutation, respectively, in two Pakistani families. The splice-site mutations are predicted to cause frameshifts and premature stop codons. In family W98-053, this could be confirmed by cDNA analysis. GRXCR1 is predicted to contain a GRX-like domain. GRX domains are involved in reversible S-glutathionylation of proteins and thereby in the modulation of activity and/or localization of these proteins. The missense mutation is located in this domain, whereas the nonsense and splice-site mutations may result in complete or partial absence of the GRX-like domain or of the complete protein. Hearing loss in patients with GRXCR1 mutations is congenital and is moderate to profound. Progression of the hearing loss was observed in family W98-053. Vestibular dysfunction was observed in some but not all affected individuals. Quantitative analysis of GRXCR1 transcripts in fetal and adult human tissues revealed a preferential expression of the gene in fetal cochlea, which may explain the nonsyndromic nature of the hearing impairment. PMID:20137778

  7. Fine Mapping of the 1p36 Deletion Syndrome Identifies Mutation of PRDM16 as a Cause of Cardiomyopathy

    PubMed Central

    Arndt, Anne-Karin; Schafer, Sebastian; Drenckhahn, Jorg-Detlef; Sabeh, M. Khaled; Plovie, Eva R.; Caliebe, Almuth; Klopocki, Eva; Musso, Gabriel; Werdich, Andreas A.; Kalwa, Hermann; Heinig, Matthias; Padera, Robert F.; Wassilew, Katharina; Bluhm, Julia; Harnack, Christine; Martitz, Janine; Barton, Paul J.; Greutmann, Matthias; Berger, Felix; Hubner, Norbert; Siebert, Reiner; Kramer, Hans-Heiner; Cook, Stuart A.; MacRae, Calum A.; Klaassen, Sabine

    2013-01-01

    Deletion 1p36 syndrome is recognized as the most common terminal deletion syndrome. Here, we describe the loss of a gene within the deletion that is responsible for the cardiomyopathy associated with monosomy 1p36, and we confirm its role in nonsyndromic left ventricular noncompaction cardiomyopathy (LVNC) and dilated cardiomyopathy (DCM). With our own data and publically available data from array comparative genomic hybridization (aCGH), we identified a minimal deletion for the cardiomyopathy associated with 1p36del syndrome that included only the terminal 14 exons of the transcription factor PRDM16 (PR domain containing 16), a gene that had previously been shown to direct brown fat determination and differentiation. Resequencing of PRDM16 in a cohort of 75 nonsyndromic individuals with LVNC detected three mutations, including one truncation mutant, one frameshift null mutation, and a single missense mutant. In addition, in a series of cardiac biopsies from 131 individuals with DCM, we found 5 individuals with 4 previously unreported nonsynonymous variants in the coding region of PRDM16. None of the PRDM16 mutations identified were observed in more than 6,400 controls. PRDM16 has not previously been associated with cardiac disease but is localized in the nuclei of cardiomyocytes throughout murine and human development and in the adult heart. Modeling of PRDM16 haploinsufficiency and a human truncation mutant in zebrafish resulted in both contractile dysfunction and partial uncoupling of cardiomyocytes and also revealed evidence of impaired cardiomyocyte proliferative capacity. In conclusion, mutation of PRDM16 causes the cardiomyopathy in 1p36 deletion syndrome as well as a proportion of nonsyndromic LVNC and DCM. PMID:23768516

  8. Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy.

    PubMed

    Arndt, Anne-Karin; Schafer, Sebastian; Drenckhahn, Jorg-Detlef; Sabeh, M Khaled; Plovie, Eva R; Caliebe, Almuth; Klopocki, Eva; Musso, Gabriel; Werdich, Andreas A; Kalwa, Hermann; Heinig, Matthias; Padera, Robert F; Wassilew, Katharina; Bluhm, Julia; Harnack, Christine; Martitz, Janine; Barton, Paul J; Greutmann, Matthias; Berger, Felix; Hubner, Norbert; Siebert, Reiner; Kramer, Hans-Heiner; Cook, Stuart A; MacRae, Calum A; Klaassen, Sabine

    2013-07-11

    Deletion 1p36 syndrome is recognized as the most common terminal deletion syndrome. Here, we describe the loss of a gene within the deletion that is responsible for the cardiomyopathy associated with monosomy 1p36, and we confirm its role in nonsyndromic left ventricular noncompaction cardiomyopathy (LVNC) and dilated cardiomyopathy (DCM). With our own data and publically available data from array comparative genomic hybridization (aCGH), we identified a minimal deletion for the cardiomyopathy associated with 1p36del syndrome that included only the terminal 14 exons of the transcription factor PRDM16 (PR domain containing 16), a gene that had previously been shown to direct brown fat determination and differentiation. Resequencing of PRDM16 in a cohort of 75 nonsyndromic individuals with LVNC detected three mutations, including one truncation mutant, one frameshift null mutation, and a single missense mutant. In addition, in a series of cardiac biopsies from 131 individuals with DCM, we found 5 individuals with 4 previously unreported nonsynonymous variants in the coding region of PRDM16. None of the PRDM16 mutations identified were observed in more than 6,400 controls. PRDM16 has not previously been associated with cardiac disease but is localized in the nuclei of cardiomyocytes throughout murine and human development and in the adult heart. Modeling of PRDM16 haploinsufficiency and a human truncation mutant in zebrafish resulted in both contractile dysfunction and partial uncoupling of cardiomyocytes and also revealed evidence of impaired cardiomyocyte proliferative capacity. In conclusion, mutation of PRDM16 causes the cardiomyopathy in 1p36 deletion syndrome as well as a proportion of nonsyndromic LVNC and DCM. PMID:23768516

  9. Maps Showing Locations of Damaging Landslides Caused by El Nino Rainstorms, Winter Season 1997-98, San Francisco Bay Region, California

    USGS Publications Warehouse

    Godt, Jonathan W.

    1999-01-01

    Heavy rainfall associated with a strong El Nino caused over $150 million in landslide damage in the 10-county San Francisco Bay region during the winter and spring of 1998. Reports of landsliding began in early January 1998 and continued throughout the winter and spring. On February 9, President Clinton declared all 10 counties eligible for Federal Emergency Management Agency (FEMA) disaster assistance. In April and May of 1998, personnel from the U.S. Geological Survey (USGS) conducted a field reconnaissance in the area to provide a general overview of landslide damage resulting from the 1997-98 sequence of El Nino-related storms. Seven scientists from the USGS Landslide Hazards Program based in Reston, Virginia; Golden, Colorado; and Menlo Park, California; and five scientists from the USGS Geologic Mapping Program?s San Francisco Bay Mapping Team based in Menlo Park, California, cooperated in the landslide-damage assessments. The assessments were done for 10 counties in the Bay area: Alameda, Contra Costa, Marin, Napa, San Francisco, Santa Clara, Santa Cruz, San Mateo, Solano, and Sonoma. USGS Maps in this series include: MF-2325-A (Napa County), MF-2325-B (Alameda County), MF-2325-C (Marin County), MF-2325-D (Santa Cruz County), MF-2325-E (Contra Costa County), MF-2325-F (Sonoma County), MF-2325-G (San Francisco City and County), MF-2325-H (San Mateo County), MF-2325-I (Solano County), MF-2325-J (Santa Clara County). In addition to USGS scientists providing data from the field evaluation, each of the counties, many consultants, and others cooperated fully in providing the landslide-damage information compiled here.

  10. Aggregation of the 35-kDa fragment of TDP-43 causes formation of cytoplasmic inclusions and alteration of RNA processing.

    PubMed

    Che, Mei-Xia; Jiang, Ya-Jun; Xie, Yuan-Yuan; Jiang, Lei-Lei; Hu, Hong-Yu

    2011-07-01

    TAR DNA binding protein of 43 kDa (TDP-43) is a nuclear factor functioning in RNA processing. It is also a major deposited protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin (FTLD-U). To understand the mechanism underlying the inclusion body formation and possible functional alteration, we studied some TDP-43 fragments and their effects on RNA processing in cell models. The results show that the 35-kDa fragment of TDP-43 (namely TDP-35, residues 90-414), but not TDP-25A (184-414), is capable of forming cytoplasmic inclusion bodies and altering pre-mRNA splicing. The inclusions formed by TDP-35 can also recruit full-length TDP-43 to cytoplasmic deposition from functionally nuclear localization. The in vitro studies demonstrate that TDP-35, rather than TDP-43 and TDP-25A, is prone to aggregation, and it further serves as a seed to facilitate aggregation of full-length TDP-43. This suggests that fragmentation of TDP-43 leads to cellular redistribution, inclusion body formation, and altered RNA processing, which are implicated in the molecular pathogenesis of ALS and FTLD. PMID:21450909

  11. Genomic and Phenotypic Alterations of the Neuronal-Like Cells Derived from Human Embryonal Carcinoma Stem Cells (NT2) Caused by Exposure to Organophosphorus Compounds Paraoxon and Mipafox

    PubMed Central

    Pamies, David; Sogorb, Miguel A.; Fabbri, Marco; Gribaldo, Laura; Collotta, Angelo; Scelfo, Bibiana; Vilanova, Eugenio; Harris, Georgina; Bal-Price, Anna

    2014-01-01

    Historically, only few chemicals have been identified as neurodevelopmental toxicants, however, concern remains, and has recently increased, based upon the association between chemical exposures and increased developmental disorders. Diminution in motor speed and latency has been reported in preschool children from agricultural communities. Organophosphorus compounds (OPs) are pesticides due to their acute insecticidal effects mediated by the inhibition of acetylcholinesterase, although other esterases as neuropathy target esterase (NTE) can also be inhibited. Other neurological and neurodevelopmental toxic effects with unknown targets have been reported after chronic exposure to OPs in vivo. We studied the initial stages of retinoic acid acid-triggered differentiation of pluripotent cells towards neural progenitors derived from human embryonal carcinoma stem cells to determine if neuropathic OP, mipafox, and non-neuropathic OP, paraoxon, are able to alter differentiation of neural precursor cells in vitro. Exposure to 1 μM paraoxon (non-cytotoxic concentrations) altered the expression of different genes involved in signaling pathways related to chromatin assembly and nucleosome integrity. Conversely, exposure to 5 μM mipafox, a known inhibitor of NTE activity, showed no significant changes on gene expression. We conclude that 1 μM paraoxon could affect the initial stage of in vitro neurodifferentiation possibly due to a teratogenic effect, while the absence of transcriptional alterations by mipafox exposure did not allow us to conclude a possible effect on neurodifferentiation pathways at the tested concentration. PMID:24413757

  12. Neonatal exposure to benzo[a]pyrene induces oxidative stress causing altered hippocampal cytomorphometry and behavior during early adolescence period of male Wistar rats.

    PubMed

    Patel, Bhupesh; Das, Saroj Kumar; Das, Swagatika; Das, Lipsa; Patri, Manorama

    2016-05-01

    Environmental neurotoxicants like benzo[a]pyrene (B[a]P) have been well documented regarding their potential to induce oxidative stress. However, neonatal exposure to B[a]P and its subsequent effect on anti-oxidant defence system and hippocampal cytomorphometry leading to behavioral changes have not been fully elucidated. We investigated the effect of acute exposure of B[a]P on five days old male Wistar pups administered with single dose of B[a]P (0.2 μg/kg BW) through intracisternal mode. Control group was administered with vehicle i.e., DMSO and a separate group of rats without any treatment was taken as naive group. Behavioral analysis showed anxiolytic-like behavior with significant increase in time spent in open arm in elevated plus maze. Further, significant reduction in fall off time during rotarod test showing B[a]P induced locomotor hyperactivity and impaired motor co-ordination in adolescent rats. B[a]P induced behavioral changes were further associated with altered anti-oxidant defence system involving significant reduction in the total ATPase, Na(+) K(+) ATPase, Mg(2+) ATPase, GR and GPx activity with a significant elevation in the activity of catalase and GST as compared to naive and control groups. Cytomorphometry of hippocampus showed that the number of neurons and glia in B[a]P treated group were significantly reduced as compared to naive and control. Subsequent observation showed that the area and perimeter of hippocampus, hippocampal neurons and neuronal nucleus were significantly reduced in B[a]P treated group as compared to naive and control. The findings of the present study suggest that the alteration in hippocampal cytomorphometry and neuronal population associated with impaired antioxidant signaling and mood in B[a]P treated group could be an outcome of neuromorphological alteration leading to pyknotic cell death or impaired differential migration of neurons during early postnatal brain development. PMID:26946409

  13. Chronic low-level arsenic exposure causes gender-specific alterations in locomotor activity, dopaminergic systems, and thioredoxin expression in mice

    SciTech Connect

    Bardullas, U.; Limon-Pacheco, J.H.; Giordano, M.; Carrizales, L.; Mendoza-Trejo, M.S.; Rodriguez, V.M.

    2009-09-01

    Arsenic (As) is a toxic metalloid widely present in the environment. Human exposure to As has been associated with the development of skin and internal organ cancers and cardiovascular disorders, among other diseases. A few studies report decreases in intelligence quotient (IQ), and sensory and motor alterations after chronic As exposure in humans. On the other hand, studies of rodents exposed to high doses of As have found alterations in locomotor activity, brain neurochemistry, behavioral tasks, and oxidative stress. In the present study both male and female C57Bl/6J mice were exposed to environmentally relevant doses of As such as 0.05, 0.5, 5.0, or 50 mg As/L of drinking water for 4 months, and locomotor activity was assessed every month. Male mice presented hyperactivity in the group exposed to 0.5 mg As/L and hypoactivity in the group exposed to 50 mg As/L after 4 months of As exposure, whereas female mice exposed to 0.05, 0.5, and 5.0 mg As/L exhibited hyperactivity in every monthly test during As exposure. Furthermore, striatal and hypothalamic dopamine content was decreased only in female mice. Also decreases in tyrosine hydroxylase (TH) and cytosolic thioredoxin (Trx-1) mRNA expression in striatum and nucleus accumbens were observed in male and female mice, respectively. These results indicate that chronic As exposure leads to gender-dependent alterations in dopaminergic markers and spontaneous locomotor activity, and down-regulation of the antioxidant capacity of the brain.

  14. Maternal influenza viral infection causes schizophrenia-like alterations of 5-HT₂A and mGlu₂ receptors in the adult offspring.

    PubMed

    Moreno, José L; Kurita, Mitsumasa; Holloway, Terrell; López, Javier; Cadagan, Richard; Martínez-Sobrido, Luis; García-Sastre, Adolfo; González-Maeso, Javier

    2011-02-01

    Epidemiological studies indicate that maternal influenza viral infection increases the risk for schizophrenia in the adult offspring. The serotonin and glutamate systems are suspected in the etiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. The effects of hallucinogens, such as psilocybin and mescaline, require the serotonin 5-HT(2A) receptor, and induce schizophrenia-like psychosis in humans. In addition, metabotropic glutamate receptor mGlu(2/3) agonists show promise as a new treatment for schizophrenia. Here, we investigated the level of expression and behavioral function of 5-HT(2A) and mGlu(2) receptors in a mouse model of maternal influenza viral infection. We show that spontaneous locomotor activity is diminished by maternal infection with the mouse-adapted influenza A/WSN/33 (H1N1) virus. The behavioral responses to hallucinogens and glutamate antipsychotics are both affected by maternal exposure to influenza virus, with increased head-twitch response to hallucinogens and diminished antipsychotic-like effect of the glutamate agonist. In frontal cortex of mice born to influenza virus-infected mothers, the 5-HT(2A) receptor is upregulated and the mGlu(2) receptor is downregulated, an alteration that may be involved in the behavioral changes observed. Additionally, we find that the cortical 5-HT(2A) receptor-dependent signaling pathways are significantly altered in the offspring of infected mothers, showing higher c-fos, egr-1, and egr-2 expression in response to the hallucinogenic drug DOI. Identifying a biochemical alteration that parallels the behavioral changes observed in a mouse model of prenatal viral infection may facilitate targeting therapies for treatment and prevention of schizophrenia. PMID:21289196

  15. Chronic low-level arsenic exposure causes gender-specific alterations in locomotor activity, dopaminergic systems, and thioredoxin expression in mice.

    PubMed

    Bardullas, U; Limón-Pacheco, J H; Giordano, M; Carrizales, L; Mendoza-Trejo, M S; Rodríguez, V M

    2009-09-01

    Arsenic (As) is a toxic metalloid widely present in the environment. Human exposure to As has been associated with the development of skin and internal organ cancers and cardiovascular disorders, among other diseases. A few studies report decreases in intelligence quotient (IQ), and sensory and motor alterations after chronic As exposure in humans. On the other hand, studies of rodents exposed to high doses of As have found alterations in locomotor activity, brain neurochemistry, behavioral tasks, and oxidative stress. In the present study both male and female C57Bl/6J mice were exposed to environmentally relevant doses of As such as 0.05, 0.5, 5.0, or 50 mg As/L of drinking water for 4 months, and locomotor activity was assessed every month. Male mice presented hyperactivity in the group exposed to 0.5 mg As/L and hypoactivity in the group exposed to 50 mg As/L after 4 months of As exposure, whereas female mice exposed to 0.05, 0.5, and 5.0 mg As/L exhibited hyperactivity in every monthly test during As exposure. Furthermore, striatal and hypothalamic dopamine content was decreased only in female mice. Also decreases in tyrosine hydroxylase (TH) and cytosolic thioredoxin (Trx-1) mRNA expression in striatum and nucleus accumbens were observed in male and female mice, respectively. These results indicate that chronic As exposure leads to gender-dependent alterations in dopaminergic markers and spontaneous locomotor activity, and down-regulation of the antioxidant capacity of the brain. PMID:19121333

  16. Mutation of the RDR1 gene caused genome-wide changes in gene expression, regional variation in small RNA clusters and localized alteration in DNA methylation in rice

    PubMed Central

    2014-01-01

    Background Endogenous small (sm) RNAs (primarily si- and miRNAs) are important trans/cis-acting regulators involved in diverse cellular functions. In plants, the RNA-dependent RNA polymerases (RDRs) are essential for smRNA biogenesis. It has been established that RDR2 is involved in the 24 nt siRNA-dependent RNA-directed DNA methylation (RdDM) pathway. Recent studies have suggested that RDR1 is involved in a second RdDM pathway that relies mostly on 21 nt smRNAs and functions to silence a subset of genomic loci that are usually refractory to the normal RdDM pathway in Arabidopsis. Whether and to what extent the homologs of RDR1 may have similar functions in other plants remained unknown. Results We characterized a loss-of-function mutant (Osrdr1) of the OsRDR1 gene in rice (Oryza sativa L.) derived from a retrotransposon Tos17 insertion. Microarray analysis identified 1,175 differentially expressed genes (5.2% of all expressed genes in the shoot-tip tissue of rice) between Osrdr1 and WT, of which 896 and 279 genes were up- and down-regulated, respectively, in Osrdr1. smRNA sequencing revealed regional alterations in smRNA clusters across the rice genome. Some of the regions with altered smRNA clusters were associated with changes in DNA methylation. In addition, altered expression of several miRNAs was detected in Osrdr1, and at least some of which were associated with altered expression of predicted miRNA target genes. Despite these changes, no phenotypic difference was identified in Osrdr1 relative to WT under normal condition; however, ephemeral phenotypic fluctuations occurred under some abiotic stress conditions. Conclusions Our results showed that OsRDR1 plays a role in regulating a substantial number of endogenous genes with diverse functions in rice through smRNA-mediated pathways involving DNA methylation, and which participates in abiotic stress response. PMID:24980094

  17. Lysosomal storage of heparan sulfate causes mitochondrial defects, altered autophagy, and neuronal death in the mouse model of mucopolysaccharidosis III type C.

    PubMed

    Pshezhetsky, Alexey V

    2016-06-01

    The genetic metabolic disease mucopolysaccharidosis III type C (MPS IIIC, Sanfilippo disease type C) causes progressive neurodegeneration in infants and children, leading to dementia and death before adulthood. MPS IIIC stands out among lysosomal diseases because it is the only one caused by a deficiency not of a hydrolase but of HGSNAT (heparan--glucosaminide N-acetyltransferase), which catalyzes acetylation of glycosaminoglycan heparan sulfate (HS) prior to its hydrolysis. PMID:25998837

  18. Altered Ion Channel/Receptor Expression and Function in Extrinsic Sensory Neurons: The Cause of and Solution to Chronic Visceral Pain?

    PubMed

    Brierley, Stuart

    2016-01-01

    The gastrointestinal tract is unique in that it is innervated by several distinct populations of neurons, whose cell bodies are either intrinsic (enteric, viscerofugal) or extrinsic (sympathetic, sensory afferents) to the wall of the gut. We are usually completely unaware of the continuous, complicated orchestra of functions that these neurons conduct. However, for patients with Inflammatory Bowel Disease (IBD) or functional gastrointestinal disorders, such as Functional Dyspepsia (FD) and Irritable Bowel Syndrome (IBS) altered gastrointestinal motility, discomfort and pain are common, debilitating symptoms. Whilst bouts of inflammation underlie the symptoms associated with IBD, over the past few years there is increased pre-clinical and clinical evidence that infection and inflammation are key risk factors for the development of several functional gastrointestinal disorders, in particular IBS. There is a strong correlation between prior exposure to gut infection and symptom occurrence; with the duration and severity of the initial illness the strongest associated risk factors. This review discusses the current body of evidence for neuroplasticity during inflammation and how in many cases fails to reset back to normal, long after healing of the damaged tissues. Recent evidence suggests that the altered expression and function of key ion channels and receptors within extrinsic sensory neurons play fundamental roles in the aberrant pain sensation associated with these gastrointestinal diseases and disorders. PMID:27379637

  19. Infection by a black spot-causing species of Uvulifer and associated opercular alterations in fishes from a high-desert stream in Wyoming

    USGS Publications Warehouse

    Quist, M.C.; Bower, M.R.; Hubert, W.A.

    2007-01-01

    Black spot is a common disease syndrome of freshwater fishes. This study provides information on the rank of density of the black spot agent and opercular bone alterations associated with at least one digenean, Uvulifer sp., infecting native and non-native catostomids and cyprinids of the Upper Colorado River Basin. We evaluated the density rank of pigmented metacercariae and associated alterations in the operculum of the bluehead sucker Catostomus discobolus, flannelmouth sucker C. latipinnis, white sucker C. commersoni, catostomid hybrids, roundtail chub Gila robusta, and creek chub Semotilus atromaculatus, sampled from Muddy Creek, Wyoming, USA in 2003 or 2004. All fish species contained individuals that exhibited gross signs of the black spot agent. Bluehead and flannelmouth suckers had 100% prevalence of infection. Although the other suckers and chubs contained encysted metacercariae in at least one individual, the presence of pigmented metacercariae was not apparent (i.e. based on gross observations) in many individuals. Catostomids had higher densities of metacercariae than cyprinids, as shown by frequency distributions of density ranks. Opercular holes (i.e. holes that completely penetrated the opercle and were in direct association with the pigment associated metacercariae) and pockets (depressions on the external surface of the opercle associated with metacercariae) were abundant among catostomids but rare among cyprinids. ?? Inter-Research 2007.

  20. FGF-2 deficiency causes dysregulation of Arhgef6 and downstream targets in the cerebral cortex accompanied by altered neurite outgrowth and dendritic spine morphology.

    PubMed

    Baum, Philip; Vogt, Miriam A; Gass, Peter; Unsicker, Klaus; von Bohlen Und Halbach, Oliver

    2016-05-01

    Fibroblast growth factor 2 (FGF-2) is an abundant growth factor in the brain and exerts multiple functions on neural cells ranging from cell division, cell fate determination to differentiation. However, many details of the molecular mechanisms underlying the diverse functions of FGF-2 are poorly understood. In a comparative microarray analysis of motor sensory cortex (MSC) tissue of adult knockout (FGF-2(-/-)) and control (FGF-2(+/+)) mice, we found a substantial number of regulated genes, which are implicated in cytoskeletal machinery dynamics. Specifically, we found a prominent downregulation of Arhgef6. Arhgef6 mRNA was significantly reduced in the FGF-2(-/-) cortex, and Arhgef6 protein virtually absent, while RhoA protein levels were massively increased and Cdc42 protein levels were reduced. Since Arhgef6 is localized to dendritic spines, we next analyzed dendritic spines of adult FGF2(-/-) and control mouse cortices. Spine densities were significantly increased, whereas mean length of spines on dendrites of layer V of MSC neurons in adult FGF-2(-/-) mice was significantly decreased as compared to respective controls. Furthermore, neurite length in dissociated cortical cultures from E18 FGF-2(-/-) mice was significantly reduced at DIV7 as compared to wildtype neurons. Despite the fact that altered neuronal morphology and alterations in dendritic spines were observed, FGF-2(-/-) mice behave relatively unsuspicious in several behavioral tasks. However, FGF-2(-/-) mice exhibited decreased thermal pain sensitivity in the hotplate-test. PMID:26970009

  1. Osbpl8 Deficiency in Mouse Causes an Elevation of High-Density Lipoproteins and Gender-Specific Alterations of Lipid Metabolism

    PubMed Central

    Béaslas, Olivier; Metso, Jari; Nissilä, Eija; Laurila, Pirkka-Pekka; Kaiharju, Essi; Batchu, Krishna Chaithanya; Kaipiainen, Leena; Mäyränpää, Mikko I.; Yan, Daoguang; Gylling, Helena; Jauhiainen, Matti; Olkkonen, Vesa M.

    2013-01-01

    OSBP-related protein 8 (ORP8) encoded by Osbpl8 is an endoplasmic reticulum sterol sensor implicated in cellular lipid metabolism. We generated an Osbpl8−/− (KO) C57Bl/6 mouse strain. Wild-type and Osbpl8KO animals at the age of 13-weeks were fed for 5 weeks either chow or high-fat diet, and their plasma lipids/lipoproteins and hepatic lipids were analyzed. The chow-fed Osbpl8KO male mice showed a marked elevation of high-density lipoprotein (HDL) cholesterol (+79%) and phospholipids (+35%), while only minor increase of apolipoprotein A-I (apoA-I) was detected. In chow-fed female KO mice a less prominent increase of HDL cholesterol (+27%) was observed, while on western diet the HDL increment was prominent in both genders. The HDL increase was accompanied by an elevated level of HDL-associated apolipoprotein E in male, but not female KO animals. No differences between genotypes were observed in lecithin:cholesterol acyltransferase (LCAT) or hepatic lipase (HL) activity, or in the fractional catabolic rate of fluorescently labeled mouse HDL injected in chow-diet fed animals. The Osbpl8KO mice of both genders displayed reduced phospholipid transfer protein (PLTP) activity, but only on chow diet. These findings are consistent with a model in which Osbpl8 deficiency results in altered biosynthesis of HDL. Consistent with this hypothesis, ORP8 depleted mouse hepatocytes secreted an increased amount of nascent HDL into the culture medium. In addition to the HDL phenotype, distinct gender-specific alterations in lipid metabolism were detected: Female KO animals on chow diet showed reduced lipoprotein lipase (LPL) activity and increased plasma triglycerides, while the male KO mice displayed elevated plasma cholesterol biosynthetic markers cholestenol, desmosterol, and lathosterol. Moreover, modest gender-specific alterations in the hepatic expression of lipid homeostatic genes were observed. In conclusion, we report the first viable OsbplKO mouse model, demonstrating a

  2. Vru (Sub0144) controls expression of proven and putative virulence determinants and alters the ability of Streptococcus uberis to cause disease in dairy cattle.

    PubMed

    Egan, Sharon A; Ward, Philip N; Watson, Michael; Field, Terence R; Leigh, James A

    2012-06-01

    The regulation and control of gene expression in response to differing environmental stimuli is crucial for successful pathogen adaptation and persistence. The regulatory gene vru of Streptococcus uberis encodes a stand-alone response regulator with similarity to the Mga of group A Streptococcus. Mga controls expression of a number of important virulence determinants. Experimental intramammary challenge of dairy cattle with a mutant of S. uberis carrying an inactivating lesion in vru showed reduced ability to colonize the mammary gland and an inability to induce clinical signs of mastitis compared with the wild-type strain. Analysis of transcriptional differences of gene expression in the mutant, determined by microarray analysis, identified a number of coding sequences with altered expression in the absence of Vru. These consisted of known and putative virulence determinants, including Lbp (Sub0145), SclB (Sub1095), PauA (Sub1785) and hasA (Sub1696). PMID:22383474

  3. Neurochemical and electrophysiological deficits in the ventral hippocampus and selective behavioral alterations caused by high-fat diet in female C57BL/6 mice.

    PubMed

    Krishna, S; Keralapurath, M M; Lin, Z; Wagner, J J; de La Serre, C B; Harn, D A; Filipov, N M

    2015-06-25

    Mounting experimental evidence, predominantly from male rodents, demonstrates that high-fat diet (HFD) consumption and ensuing obesity are detrimental to the brain. To shed additional light on the neurological consequences of HFD consumption in female rodents and to determine the relatively early impact of HFD in the likely continuum of neurological dysfunction in the context of chronic HFD intake, this study investigated effects of HFD feeding for up to 12weeks on selected behavioral, neurochemical, and electrophysiological parameters in adult female C57BL/6 mice; particular focus was placed on the ventral hippocampus (vHIP). Selected locomotor, emotional and cognitive functions were evaluated using behavioral tests after 5weeks on HFD or control (low-fat diet) diets. One week later, mice were sacrificed and brain regional neurochemical (monoamine) analysis was performed. Behaviorally naïve mice were maintained on their respective diets for an additional 5-6weeks at which time synaptic plasticity was determined in ex vivo slices from the vHIP. HFD-fed female mice exhibited increased: (i) locomotor activity in the open field testing, (ii) mean turn time on the pole test, (iii) swimming time in the forced swim test, and (iv) number of marbles buried in the marble burying test. In contrast, the novel object recognition memory was unaffected. Mice on HFD also had decreased norepinephrine and dopamine turnover, respectively, in the prefrontal cortex and the vHIP. HFD consumption for a total of 11-12weeks altered vHIP synaptic plasticity, evidenced by significant reductions in the paired-pulse ratio and long-term potentiation (LTP) magnitude. In summary, in female mice, HFD intake for several weeks induced multiple behavioral alterations of mainly anxiety-like nature and impaired monoamine pathways in a brain region-specific manner, suggesting that in the female, certain behavioral domains (anxiety) and associated brain regions, i.e., the vHIP, are preferentially

  4. A MIXTURE OF AMMONIUM PERCHLORATE AND SODIUM CHLORATE ENHANCES ALTERATIONS OF THE PITUITARY-THYROID AXIS CAUSED BY THE INDIVIDUAL CHEMICALS IN ADULT MALE F344 RATS

    EPA Science Inventory

    Ammonium perchlorate (AP) and sodium chlorate (SC) have been detected in public drinking water supplies in many parts of the U.S. These chemicals cause perturbations in pituitary-thyroid homeostasis in animals by competitively inhibiting the iodide uptake, thus hindering the synt...

  5. MAPK signaling pathway alters expression of midgut ALP and ABCC genes and causes resistance to Bacillus thuringiensis Cry1Ac toxin in diamondback moth.

    PubMed

    Guo, Zhaojiang; Kang, Shi; Chen, Defeng; Wu, Qingjun; Wang, Shaoli; Xie, Wen; Zhu, Xun; Baxter, Simon W; Zhou, Xuguo; Jurat-Fuentes, Juan Luis; Zhang, Youjun

    2015-04-01

    Insecticidal crystal toxins derived from the soil bacterium Bacillus thuringiensis (Bt) are widely used as biopesticide sprays or expressed in transgenic crops to control insect pests. However, large-scale use of Bt has led to field-evolved resistance in several lepidopteran pests. Resistance to Bt Cry1Ac toxin in the diamondback moth, Plutella xylostella (L.), was previously mapped to a multigenic resistance locus (BtR-1). Here, we assembled the 3.15 Mb BtR-1 locus and found high-level resistance to Cry1Ac and Bt biopesticide in four independent P. xylostella strains were all associated with differential expression of a midgut membrane-bound alkaline phosphatase (ALP) outside this locus and a suite of ATP-binding cassette transporter subfamily C (ABCC) genes inside this locus. The interplay between these resistance genes is controlled by a previously uncharacterized trans-regulatory mechanism via the mitogen-activated protein kinase (MAPK) signaling pathway. Molecular, biochemical, and functional analyses have established ALP as a functional Cry1Ac receptor. Phenotypic association experiments revealed that the recessive Cry1Ac resistance was tightly linked to down-regulation of ALP, ABCC2 and ABCC3, whereas it was not linked to up-regulation of ABCC1. Silencing of ABCC2 and ABCC3 in susceptible larvae reduced their susceptibility to Cry1Ac but did not affect the expression of ALP, whereas suppression of MAP4K4, a constitutively transcriptionally-activated MAPK upstream gene within the BtR-1 locus, led to a transient recovery of gene expression thereby restoring the susceptibility in resistant larvae. These results highlight a crucial role for ALP and ABCC genes in field-evolved resistance to Cry1Ac and reveal a novel trans-regulatory signaling mechanism responsible for modulating the expression of these pivotal genes in P. xylostella. PMID:25875245

  6. MAPK Signaling Pathway Alters Expression of Midgut ALP and ABCC Genes and Causes Resistance to Bacillus thuringiensis Cry1Ac Toxin in Diamondback Moth

    PubMed Central

    Wu, Qingjun; Wang, Shaoli; Xie, Wen; Zhu, Xun; Baxter, Simon W.; Zhou, Xuguo; Jurat-Fuentes, Juan Luis; Zhang, Youjun

    2015-01-01

    Insecticidal crystal toxins derived from the soil bacterium Bacillus thuringiensis (Bt) are widely used as biopesticide sprays or expressed in transgenic crops to control insect pests. However, large-scale use of Bt has led to field-evolved resistance in several lepidopteran pests. Resistance to Bt Cry1Ac toxin in the diamondback moth, Plutella xylostella (L.), was previously mapped to a multigenic resistance locus (BtR-1). Here, we assembled the 3.15 Mb BtR-1 locus and found high-level resistance to Cry1Ac and Bt biopesticide in four independent P. xylostella strains were all associated with differential expression of a midgut membrane-bound alkaline phosphatase (ALP) outside this locus and a suite of ATP-binding cassette transporter subfamily C (ABCC) genes inside this locus. The interplay between these resistance genes is controlled by a previously uncharacterized trans-regulatory mechanism via the mitogen-activated protein kinase (MAPK) signaling pathway. Molecular, biochemical, and functional analyses have established ALP as a functional Cry1Ac receptor. Phenotypic association experiments revealed that the recessive Cry1Ac resistance was tightly linked to down-regulation of ALP, ABCC2 and ABCC3, whereas it was not linked to up-regulation of ABCC1. Silencing of ABCC2 and ABCC3 in susceptible larvae reduced their susceptibility to Cry1Ac but did not affect the expression of ALP, whereas suppression of MAP4K4, a constitutively transcriptionally-activated MAPK upstream gene within the BtR-1 locus, led to a transient recovery of gene expression thereby restoring the susceptibility in resistant larvae. These results highlight a crucial role for ALP and ABCC genes in field-evolved resistance to Cry1Ac and reveal a novel trans-regulatory signaling mechanism responsible for modulating the expression of these pivotal genes in P. xylostella. PMID:25875245

  7. Hyperspectral surface materials map of quadrangles 3666 and 3766, Balkh (219), Mazar-e Sharif (220), Qarqin (213), and Hazara Toghai (214) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  8. Hyperspectral surface materials map of quadrangles 2962 and 3062, Gawdezereh (615), Galachah (616), Chahar Burjak (609), and Khan Neshin (610) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Hoefen, Todd M.; Kokaly, Raymond F.; King, Trude V.V.; Livo, Keith E.; Giles, Stuart A.; Johnson, Michaela R.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  9. Hyperspectral surface materials map of quadrangles 3668 and 3768, Baghlan (221), Taluqan (222), Imam Sahib (215), and Rustaq (216) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  10. Hyperspectral surface materials map of quadrangles 3360 and 3460, Kawir-e Naizar (413), Kohe-Mahmudo-Esmailjan (414), Kol-e Namaksar (407), and Ghoriyan (408) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  11. Hyperspectral surface materials map of quadrangles 3664 and 3764, Char Shengo (123), Shibirghan (124), Jalajin (117), and Kham-Ab (118) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  12. Hyperspectral surface materials map of quadrangle 3260, Dasht-e-Chah-e-Mazar (419) and Anar Darah (420) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Kokaly, Raymond F.; King, Trude V.V.; Hoefen, Todd M.; Livo, Keith E.; Johnson, Michaela R.; Giles, Stuart A.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  13. Identification of altered microRNAs and mRNAs in the cumulus cells of PCOS patients: miRNA-509-3p promotes oestradiol secretion by targeting MAP3K8.

    PubMed

    Huang, Xin; Liu, Chang; Hao, Cuifang; Tang, Qianqing; Liu, Riming; Lin, Shaoxia; Zhang, Luping; Yan, Wei

    2016-06-01

    Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women and is characterised by polycystic ovaries, hyperandrogenism and chronic anovulation. Although the clinical and biochemical signs of PCOS are typically heterogeneous, abnormal folliculogenesis is considered a common characteristic of PCOS. Our aim is to identify the altered miRNA and mRNA expression profiles in the cumulus cells of PCOS patients to investigate their molecular function in the aetiology and pathophysiology of PCOS. In this study, the miRNA expression profiles of the cumulus cell samples isolated from five PCOS and five control patients were determined by an miRNA microarray. At the same time, the altered mRNA profiles of the same cumulus cell samples were also identified by a cDNA microarray. From the microarray data, 17 miRNAs and 1263 mRNAs showed significantly different expression in the PCOS cumulus cells. The differentially expressed miRNA-509-3p and its potential target gene (MAP3K8) were identified from the miRNA and mRNA microarrays respectively. The expression of miRNA-509-3p was up-regulated and MAP3K8 was down-regulated in the PCOS cumulus cells. The direct interaction between miRNA-509-3p and MAP3K8 was confirmed by a luciferase activity assay in KGN cells. In addition, miRNA-509-3p mimics or inhibitor transfection tests in KGN cells further confirmed that miRNA-509-3p improved oestradiol (E2) secretion by inhibiting the expression of MAP3K8 These results help to characterise the pathogenesis of anovulation in PCOS, especially the regulation of E2 production. PMID:27001999

  14. Exposure to the synthetic FXR agonist GW4064 causes alterations in gene expression and sublethal hepatotoxicity in eleutheroembryo medaka (Oryzias latipes)

    SciTech Connect

    Howarth, Deanna L.; Law, Sheran H.W.; Law, J. McHugh; Mondon, J.A.; Kullman, Seth W.; Hinton, David E.

    2010-02-15

    The small freshwater teleost, medaka (Oryzias latipes), has a history of usage in studies of chronic toxicity of liver and biliary system. Recent progress with this model has focused on defining the medaka hepatobiliary system. Here we investigate critical liver function and toxicity by examining the in vivo role and function of the farnesoid X receptor alpha (FXRalpha, NR1H4), a member of the nuclear receptor superfamily that plays an essential role in the regulation of bile acid homeostasis. Quantitative mRNA analysis of medaka FXRalpha demonstrates differential expression of two FXRalpha isoforms designated Fxralpha1 and Fxralpha2, in both free swimming medaka embryos with remaining yolk (eleutheroembryos, EEs) and adults. Activation of medaka Fxralpha in vivo with GW4064 (a strong FXRalpha agonist) resulted in modification of gene expression for defined FXRalpha gene targets including the bile salt export protein, small heterodimer partner, and cytochrome P450 7A1. Histological examination of medaka liver subsequent to GW4064 exposure demonstrated significant lipid accumulation, cellular and organelle alterations in both hepatocytes and biliary epithelial cells of the liver. This report of hepatobiliary injury following GW4064 exposure extends previous investigations of the intrahepatic biliary system in medaka, reveals sensitivity to toxicant exposure, and illustrates the need for added resolution in detection and interpretation of toxic responses in this vertebrate.

  15. Mapping argillic and advanced argillic alteration in volcanic rocks, quartzites, and quartz arenites in the western Richfield 1° x 2 ° quadrangle, southwestern Utah, using ASTER satellite data

    USGS Publications Warehouse

    Rockwell, Barnaby W.; Hofstra, Albert H.

    2012-01-01

    The Richfield quadrangle in southwestern Utah is known to contain a variety of porphyry Mo, skarn, polymetallic replacement and vein, alunite, and kaolin resources associated with 27-32 Ma calc-alkaline or 12-23 Ma bimodal volcano-plutonic centers in Neoproterozoic to Mesozoic carbonate and siliciclastic rocks. Four scenes of visible to shortwave-infrared image data acquired by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) sensor were analyzed to generate maps of exposed clay, sulfate, mica, and carbonate minerals, and ASTER thermal infrared data were analyzed to identify quartz and carbonate minerals. Argillic and advanced argillic alteration minerals including alunite, pyrophyllite, dickite, and kaolinite were identified in both undocumented (U) and known (K) areas, including in the southern Paradise Mtns. (U); in calc-alkaline volcanic rocks in the Wah Wah Mtns. between Broken Ridge and the NG area (U/K); at Wah Wah Summit in a small zone adjacent to 33.1 Ma diorite and marble (U); in fractures cutting quartzites surrounding the 20-22 Ma Pine Grove Mo deposit (U); in volcanic rocks in the Shauntie Hills (U/K); in quartzites in the west-central San Francisco Mtns. (U); in volcanic rocks in the Black Mtns. (K); and in mainly 12-13 Ma rhyolitic rocks along a 20 km E-W belt that includes the Bible Spring fault zone west of Broken Ridge, with several small centers in the Escalante Desert to the south (U/K). Argillized Navajo Sandstone with kaolinite and (or) dickite ± alunite was mapped adjacent to calc-alkaline intrusions in the Star Range (U). Intense quartz-sericite alteration (K) with local kaolinite was identified in andesite adjacent to calc-alkaline intrusions in the Beaver Lake Mountains. Mo-bearing phyllic alteration was identified in 22.2 Ma rhyolite plugs at the center of the NG alunite area. Limestones, dolomites, and marbles were differentiated, and quartz and sericite were identified in most unaltered quartzites. Halos of

  16. Comparison of the duration and power spectral changes of monopolar and bipolar M waves caused by alterations in muscle fibre conduction velocity.

    PubMed

    Rodriguez-Falces, Javier; Navallas, Javier; Malanda, Armando; Rodriguez-Martin, Olivia

    2014-08-01

    The muscle compound action potential (M wave) recorded under monopolar configuration reflects both the propagation of the action potentials along the muscle fibres and their extinction at the tendon. M waves recorded under a bipolar configuration contain less cross talk and noise than monopolar M waves, but they do not contain the entire informative content of the propagating potential. The objective of this study was to compare the effect of changes in muscle fibre conduction velocity (MFCV) on monopolar and bipolar M waves and how this effect depends on the distance between the recording electrodes and tendon. The study was based on a simulation approach and on an experimental investigation of the characteristics of surface M waves evoked in the vastus lateralis during 4-s step-wise isometric contractions in knee extension at 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% MVC. The peak-to-peak duration (Durpp) and median frequency (Fmedian) of the M waves were calculated. For monopolar M waves, changes in Durpp and Fmedian produced by MFCV depended on the distance from the electrode to the tendon, whereas, for bipolar M waves, changes in Durpp and Fmedian were largely independent of the electrode-to-tendon distance. When the distance between the detection point and tendon lay between approximately 15 and 40mm, changes in Durpp of bipolar M waves were more pronounced than those of distal monopolar M waves but less marked than those of proximal monopolar M waves, and the opposite occurred for Fmedian. Since, for bipolar M waves, changes in duration and power spectral features produced by alterations in MFCV are not influenced by the electrode-to-tendon distance, the bipolar electrode configuration is a preferable choice over monopolar arrangements to estimate changes in conduction velocity. PMID:24774228

  17. Clofibrate causes an upregulation of PPAR-{alpha} target genes but does not alter expression of SREBP target genes in liver and adipose tissue of pigs.

    PubMed

    Luci, Sebastian; Giemsa, Beatrice; Kluge, Holger; Eder, Klaus

    2007-07-01

    This study investigated the effect of clofibrate treatment on expression of target genes of peroxisome proliferator-activated receptor (PPAR)-alpha and various genes of the lipid metabolism in liver and adipose tissue of pigs. An experiment with 18 pigs was performed in which pigs were fed either a control diet or the same diet supplemented with 5 g clofibrate/kg for 28 days. Pigs treated with clofibrate had heavier livers, moderately increased mRNA concentrations of various PPAR-alpha target genes in liver and adipose tissue, a higher concentration of 3-hydroxybutyrate, and markedly lower concentrations of triglycerides and cholesterol in plasma and lipoproteins than control pigs (P < 0.05). mRNA concentrations of sterol regulatory element-binding proteins (SREBP)-1 and -2, insulin-induced genes (Insig)-1 and Insig-2, and the SREBP target genes acetyl-CoA carboxylase, 3-methyl-3-hydroxyglutaryl-CoA reductase, and low-density lipoprotein receptor in liver and adipose tissue and mRNA concentrations of apolipoproteins A-I, A-II, and C-III in the liver were not different between both groups of pigs. In conclusion, this study shows that clofibrate treatment activates PPAR-alpha in liver and adipose tissue and has a strong hypotriglyceridemic and hypocholesterolemic effect in pigs. The finding that mRNA concentrations of some proteins responsible for the hypolipidemic action of fibrates in humans were not altered suggests that there were certain differences in the mode of action compared with humans. It is also shown that PPAR-alpha activation by clofibrate does not affect hepatic expression of SREBP target genes involved in synthesis of triglycerides and cholesterol homeostasis in liver and adipose tissue of pigs. PMID:17363680

  18. Electrical Stimuli Are Anti-Apoptotic in Skeletal Muscle via Extracellular ATP. Alteration of This Signal in Mdx Mice Is a Likely Cause of Dystrophy

    PubMed Central

    Valladares, Denisse; Almarza, Gonzalo; Contreras, Ariel; Pavez, Mario; Buvinic, Sonja; Jaimovich, Enrique; Casas, Mariana

    2013-01-01

    ATP signaling has been shown to regulate gene expression in skeletal muscle and to be altered in models of muscular dystrophy. We have previously shown that in normal muscle fibers, ATP released through Pannexin1 (Panx1) channels after electrical stimulation plays a role in activating some signaling pathways related to gene expression. We searched for a possible role of ATP signaling in the dystrophy phenotype. We used muscle fibers from flexor digitorum brevis isolated from normal and mdx mice. We demonstrated that low frequency electrical stimulation has an anti-apoptotic effect in normal muscle fibers repressing the expression of Bax, Bim and PUMA. Addition of exogenous ATP to the medium has a similar effect. In dystrophic fibers, the basal levels of extracellular ATP were higher compared to normal fibers, but unlike control fibers, they do not present any ATP release after low frequency electrical stimulation, suggesting an uncoupling between electrical stimulation and ATP release in this condition. Elevated levels of Panx1 and decreased levels of Cav1.1 (dihydropyridine receptors) were found in triads fractions prepared from mdx muscles. Moreover, decreased immunoprecipitation of Cav1.1 and Panx1, suggest uncoupling of the signaling machinery. Importantly, in dystrophic fibers, exogenous ATP was pro-apoptotic, inducing the transcription of Bax, Bim and PUMA and increasing the levels of activated Bax and cytosolic cytochrome c. These evidence points to an involvement of the ATP pathway in the activation of mechanisms related with cell death in muscular dystrophy, opening new perspectives towards possible targets for pharmacological therapies. PMID:24282497

  19. Electrical stimuli are anti-apoptotic in skeletal muscle via extracellular ATP. Alteration of this signal in Mdx mice is a likely cause of dystrophy.

    PubMed

    Valladares, Denisse; Almarza, Gonzalo; Contreras, Ariel; Pavez, Mario; Buvinic, Sonja; Jaimovich, Enrique; Casas, Mariana

    2013-01-01

    ATP signaling has been shown to regulate gene expression in skeletal muscle and to be altered in models of muscular dystrophy. We have previously shown that in normal muscle fibers, ATP released through Pannexin1 (Panx1) channels after electrical stimulation plays a role in activating some signaling pathways related to gene expression. We searched for a possible role of ATP signaling in the dystrophy phenotype. We used muscle fibers from flexor digitorum brevis isolated from normal and mdx mice. We demonstrated that low frequency electrical stimulation has an anti-apoptotic effect in normal muscle fibers repressing the expression of Bax, Bim and PUMA. Addition of exogenous ATP to the medium has a similar effect. In dystrophic fibers, the basal levels of extracellular ATP were higher compared to normal fibers, but unlike control fibers, they do not present any ATP release after low frequency electrical stimulation, suggesting an uncoupling between electrical stimulation and ATP release in this condition. Elevated levels of Panx1 and decreased levels of Cav1.1 (dihydropyridine receptors) were found in triads fractions prepared from mdx muscles. Moreover, decreased immunoprecipitation of Cav1.1 and Panx1, suggest uncoupling of the signaling machinery. Importantly, in dystrophic fibers, exogenous ATP was pro-apoptotic, inducing the transcription of Bax, Bim and PUMA and increasing the levels of activated Bax and cytosolic cytochrome c. These evidence points to an involvement of the ATP pathway in the activation of mechanisms related with cell death in muscular dystrophy, opening new perspectives towards possible targets for pharmacological therapies. PMID:24282497

  20. A spatial assessment of hydrologic alteration caused by dams in the Northeastern United States using a Neural Network based daily reservoir operation scheme

    NASA Astrophysics Data System (ADS)

    Ehsani, N.; Vorosmarty, C. J.; Fekete, B. M.; Rosenzweig, B.; Tessler, Z. D.

    2014-12-01

    Considering the impacts of dams on natural hydrology and ecosystems, it is important to be able to simulate their behavior and effects in hydrological and ecological models. Overlooking human engineering of river systems may significantly affect modelling results and impact decisions addressing water management issues. Simulating reservoir operation at the regional and global scale remains a challenge in water resource and environmental science. There are numerous studies that model the operating rules of a single or small cluster of dams based on available observed data or that try to find an optimized set of rules for their operation based on their characteristics and intended purpose. On the other hand, there are few works that consider the operation of dams for regional and global hydrological models. One major problem in modeling dams operation in such large-scale systems is the lack of efficient algorithms for modelling reservoir operation. Depending on site-specific characteristics of the dam, its watershed and its intended purpose, each dam has a specific and optimum operating rule; as a result, effective simulation of their operation is not a trivial task when hundreds and thousands of dams exist in the area of study. As part of the development of the Northeast Regional Earth System Model (NE-RESM), we are developing an integrated hydrological modeling framework that incorporates various aspects of the coupled human-hydrologic system, from supply to demand, into a single framework. We use an Artificial Neural Network to develop an accurate yet generalized daily operating rule with minimal input requirements that is suitable for use in large scale hydrological models. We implement this reservoir operating scheme into WBMplus and study how dams alter natural hydrology of the Northeastern United States. We also show how climate change impacts the operation of reservoirs and hence availability of water in the region by the end of the 21st century.

  1. Deregulation of the OsmiR160 Target Gene OsARF18 Causes Growth and Developmental Defects with an Alteration of Auxin Signaling in Rice.

    PubMed

    Huang, Jian; Li, Zhiyong; Zhao, Dazhong

    2016-01-01

    MicroRNAs (miRNAs) control gene expression as key negative regulators at the post-transcriptional level. MiR160 plays a pivotal role in Arabidopsis growth and development through repressing expression of its target AUXIN RESPONSE FACTOR (ARF) genes; however, the function of miR160 in monocots remains elusive. In this study, we found that the mature rice miR160 (OsmiR160) was mainly derived from OsMIR160a and OsMIR160b genes. Among four potential OsmiR160 target OsARF genes, the OsARF18 transcript was cleaved at the OsmiR160 target site. Rice transgenic plants (named mOsARF18) expressing an OsmiR160-resistant version of OsARF18 exhibited pleiotropic defects in growth and development, including dwarf stature, rolled leaves, and small seeds. mOsARF18 leaves were abnormal in bulliform cell differentiation and epidermal cell division. Starch accumulation in mOsARF18 seeds was also reduced. Moreover, auxin induced expression of OsMIR160a, OsMIR160b, and OsARF18, whereas expression of OsMIR160a and OsMIR160b as well as genes involved in auxin signaling was altered in mOsARF18 plants. Our results show that negative regulation of OsARF18 expression by OsmiR160 is critical for rice growth and development via affecting auxin signaling, which will advance future studies on the molecular mechanism by which miR160 fine-tunes auxin signaling in plants. PMID:27444058

  2. Deregulation of the OsmiR160 Target Gene OsARF18 Causes Growth and Developmental Defects with an Alteration of Auxin Signaling in Rice

    PubMed Central

    Huang, Jian; Li, Zhiyong; Zhao, Dazhong

    2016-01-01

    MicroRNAs (miRNAs) control gene expression as key negative regulators at the post-transcriptional level. MiR160 plays a pivotal role in Arabidopsis growth and development through repressing expression of its target AUXIN RESPONSE FACTOR (ARF) genes; however, the function of miR160 in monocots remains elusive. In this study, we found that the mature rice miR160 (OsmiR160) was mainly derived from OsMIR160a and OsMIR160b genes. Among four potential OsmiR160 target OsARF genes, the OsARF18 transcript was cleaved at the OsmiR160 target site. Rice transgenic plants (named mOsARF18) expressing an OsmiR160-resistant version of OsARF18 exhibited pleiotropic defects in growth and development, including dwarf stature, rolled leaves, and small seeds. mOsARF18 leaves were abnormal in bulliform cell differentiation and epidermal cell division. Starch accumulation in mOsARF18 seeds was also reduced. Moreover, auxin induced expression of OsMIR160a, OsMIR160b, and OsARF18, whereas expression of OsMIR160a and OsMIR160b as well as genes involved in auxin signaling was altered in mOsARF18 plants. Our results show that negative regulation of OsARF18 expression by OsmiR160 is critical for rice growth and development via affecting auxin signaling, which will advance future studies on the molecular mechanism by which miR160 fine-tunes auxin signaling in plants. PMID:27444058

  3. Lack of Protein 4.1G Causes Altered Expression and Localization of the Cell Adhesion Molecule Nectin-Like 4 in Testis and Can Cause Male Infertility ▿

    PubMed Central

    Yang, Shaomin; Weng, Haibo; Chen, Lixiang; Guo, Xinhua; Parra, Marilyn; Conboy, John; Debnath, Gargi; Lambert, Amy J.; Peters, Luanne L.; Baines, Anthony J.; Mohandas, Narla; An, Xiuli

    2011-01-01

    Protein 4.1G is a member of the protein 4.1 family, which in general serves as adaptors linking transmembrane proteins to the cytoskeleton. 4.1G is thought to be widely expressed in many cells and tissues, but its function remains largely unknown. To explore the function of 4.1G in vivo, we generated 4.1G−/− mice and bred the mice in two backgrounds: C57BL/6 (B6) and 129/Sv (129) hybrids (B6-129) and inbred B6. Although the B6 4.1G−/− mice showed no obvious abnormalities, deficiency of 4.1G in B6-129 hybrids was associated with male infertility. Histological examinations of these 4.1G−/− mice revealed atrophy, impaired cell-cell contact and sloughing off of spermatogenic cells in seminiferous epithelium, and lack of mature spermatids in the epididymis. Ultrastructural examination revealed enlarged intercellular spaces between spermatogenic and Sertoli cells as well as the spermatid deformities. At the molecular level, 4.1G is associated with the nectin-like 4 (NECL4) adhesion molecule. Importantly, the expression of NECL4 was decreased, and the localization of NECL4 was altered in 4.1G−/− testis. Thus, our findings imply that 4.1G plays a role in spermatogenesis by mediating cell-cell adhesion between spermatogenic and Sertoli cells through its interaction with NECL4 on Sertoli cells. Additionally, the finding that infertility is present in B6-129 but not on the B6 background suggests the presence of a major modifier gene(s) that influences 4.1G function and is associated with male infertility. PMID:21482674

  4. Altered Wnt Signaling Pathway in Cognitive Impairment Caused by Chronic Intermittent Hypoxia: Focus on Glycogen Synthase Kinase-3β and β-catenin

    PubMed Central

    Pan, Yue-Ying; Deng, Yan; Xie, Sheng; Wang, Zhi-Hua; Wang, Yu; Ren, Jie; Liu, Hui-Guo

    2016-01-01

    Background: Cognitive impairment is a severe complication caused by obstructive sleep apnea (OSA). The mechanisms of causation are still unclear. The Wnt/β-catenin signaling pathway is involved in cognition, and abnormalities in it are implicated in neurological disorders. Here, we explored the Wnt/β-catenin signaling pathway abnormalities caused by chronic intermittent hypoxia (CIH), the most characteristic pathophysiological component of OSA. Methods: We divided 32 4-week-old male C57/BL mice into four groups of eight each: a CIH + normal saline (NS) group, CIH + LiCl group, sham CIH + NS group, and a sham CIH + LiCl group. The spatial learning performance of each group was assessed by using the Morris water maze (MWM). Protein expressions of glycogen synthase kinase-3β (GSK-3β) and β-catenin in the hippocampus were examined using the Western blotting test. EdU labeling and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining methods were used, respectively, to determine the proliferation and apoptosis of neurons in the hippocampal dentate gyrus region. Results: Mice exposed to CIH showed impaired spatial learning performance in the MWM, including increased mean escape latencies to reach the target platform, decreased mean times passing through the target platform and mean duration in the target quadrant. The GSK-3β activity increased, and expression of β-catenin decreased significantly in the hippocampus of the CIH-exposed mice. Besides, CIH significantly increased hippocampal neuronal apoptosis, with an elevated apoptosis index. Meanwhile, LiCl decreased the activity of GSK-3β and increased the expression of β-catenin and partially reversed the spatial memory deficits in MWM and the apoptosis caused by CIH. Conclusions: Wnt/β-catenin signaling pathway abnormalities possibly play an important role in the development of cognitive deficits among mice exposed to CIH and that LiCl might attenuate CIH-induced cognitive

  5. OVER-EXPRESSION OF INSULIN RECEPTOR SUBSTRATE-1 AND HEPATITIS B X GENES CAUSES PRE-MALIGNANT ALTERATIONS IN THE LIVER

    PubMed Central

    Longato, Lisa; de la Monte, Suzanne; Kuzushita, Noriyoshi; Horimoto, Masayoshi; Rogers, Arlin B.; Slagle, Betty L.; Wands, Jack R.

    2009-01-01

    Background Activation of the insulin (IN)/IRS-1/MAPK and the Wnt/β-catenin signaling cascades occurs frequently in hepatocellular carcinoma (HCC) associated with persistent viral infection. The aims of this study were to provide a chronic proliferative stimulus via IRS-1 in the context of hepatitis Bx (HBx) protein expression in transgenic mice and determine if constitutive expression of these genes is sufficient to cause hepatocyte dysplasia and cellular transformation. Methods We generated transgenic mice in which the HBx (ATX), IRS-1 or both (ATX+/IRS-1) genes were expressed under a liver specific promoter. We also assessed histology and oxidative damage as well as upregulation of molecules related to these signal transduction cascades in the liver by qRT-PCR. Results Whereas mice with a single transgene (ATX or IRS-1) did not develop tumors, ATX+/IRS-1+ double transgenic livers had increased frequency of hepatocellular dysplasia and developed HCC. All three transgenic lines had significantly increased IGF-1, Wnt 1 and Wnt 3 mRNA levels, and evidence of DNA damage and oxidative stress. The ATX+/IRS+ double transgenic mice were distinguished by having the highest level of activation of Wnt 3 and Frizzled 7 and selectively increased expression of IGF-II, PCNA, and aspartyl (-asparaginyl)-β-hydroxylase (AAH) a gene associated with increased cell migration. Conclusions These results suggest that continued expression of the ATX or IRS-1 transgenes can contribute to hepatocyte transformation but are not sufficient to trigger neoplastic changes in the liver. However, dual expression that activates both the IN/IRS-1/MAPK and Wnt/β-catenin cascades is sufficient to cause dysplasia and HCC in a previously normal liver. PMID:19475691

  6. A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia.

    PubMed

    Coutelier, Marie; Blesneac, Iulia; Monteil, Arnaud; Monin, Marie-Lorraine; Ando, Kunie; Mundwiller, Emeline; Brusco, Alfredo; Le Ber, Isabelle; Anheim, Mathieu; Castrioto, Anna; Duyckaerts, Charles; Brice, Alexis; Durr, Alexandra; Lory, Philippe; Stevanin, Giovanni

    2015-11-01

    Hereditary cerebellar ataxias (CAs) are neurodegenerative disorders clinically characterized by a cerebellar syndrome, often accompanied by other neurological or non-neurological signs. All transmission modes have been described. In autosomal-dominant CA (ADCA), mutations in more than 30 genes are implicated, but the molecular diagnosis remains unknown in about 40% of cases. Implication of ion channels has long been an ongoing topic in the genetics of CA, and mutations in several channel genes have been recently connected to ADCA. In a large family affected by ADCA and mild pyramidal signs, we searched for the causative variant by combining linkage analysis and whole-exome sequencing. In CACNA1G, we identified a c.5144G>A mutation, causing an arginine-to-histidine (p.Arg1715His) change in the voltage sensor S4 segment of the T-type channel protein Cav3.1. Two out of 479 index subjects screened subsequently harbored the same mutation. We performed electrophysiological experiments in HEK293T cells to compare the properties of the p.Arg1715His and wild-type Cav3.1 channels. The current-voltage and the steady-state activation curves of the p.Arg1715His channel were shifted positively, whereas the inactivation curve had a higher slope factor. Computer modeling in deep cerebellar nuclei (DCN) neurons suggested that the mutation results in decreased neuronal excitability. Taken together, these data establish CACNA1G, which is highly expressed in the cerebellum, as a gene whose mutations can cause ADCA. This is consistent with the neuropathological examination, which showed severe Purkinje cell loss. Our study further extends our knowledge of the link between calcium channelopathies and CAs. PMID:26456284

  7. A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia

    PubMed Central

    Coutelier, Marie; Blesneac, Iulia; Monteil, Arnaud; Monin, Marie-Lorraine; Ando, Kunie; Mundwiller, Emeline; Brusco, Alfredo; Le Ber, Isabelle; Anheim, Mathieu; Castrioto, Anna; Duyckaerts, Charles; Brice, Alexis; Durr, Alexandra; Lory, Philippe; Stevanin, Giovanni

    2015-01-01

    Hereditary cerebellar ataxias (CAs) are neurodegenerative disorders clinically characterized by a cerebellar syndrome, often accompanied by other neurological or non-neurological signs. All transmission modes have been described. In autosomal-dominant CA (ADCA), mutations in more than 30 genes are implicated, but the molecular diagnosis remains unknown in about 40% of cases. Implication of ion channels has long been an ongoing topic in the genetics of CA, and mutations in several channel genes have been recently connected to ADCA. In a large family affected by ADCA and mild pyramidal signs, we searched for the causative variant by combining linkage analysis and whole-exome sequencing. In CACNA1G, we identified a c.5144G>A mutation, causing an arginine-to-histidine (p.Arg1715His) change in the voltage sensor S4 segment of the T-type channel protein Cav3.1. Two out of 479 index subjects screened subsequently harbored the same mutation. We performed electrophysiological experiments in HEK293T cells to compare the properties of the p.Arg1715His and wild-type Cav3.1 channels. The current-voltage and the steady-state activation curves of the p.Arg1715His channel were shifted positively, whereas the inactivation curve had a higher slope factor. Computer modeling in deep cerebellar nuclei (DCN) neurons suggested that the mutation results in decreased neuronal excitability. Taken together, these data establish CACNA1G, which is highly expressed in the cerebellum, as a gene whose mutations can cause ADCA. This is consistent with the neuropathological examination, which showed severe Purkinje cell loss. Our study further extends our knowledge of the link between calcium channelopathies and CAs. PMID:26456284

  8. Using an extended 2D hydrodynamic model for evaluating damage risk caused by extreme rain events: Flash-Flood-Risk-Map (FFRM) Upper Austria

    NASA Astrophysics Data System (ADS)

    Humer, Günter; Reithofer, Andreas

    2016-04-01

    Using an extended 2D hydrodynamic model for evaluating damage risk caused by extreme rain events: Flash-Flood-Risk-Map (FFRM) Upper Austria Considering the increase in flash flood events causing massive damage during the last years in urban but also rural areas [1-4], the requirement for hydrodynamic calculation of flash flood prone areas and possible countermeasures has arisen to many municipalities and local governments. Besides the German based URBAS project [1], also the EU-funded FP7 research project "SWITCH-ON" [5] addresses the damage risk caused by flash floods in the sub-project "FFRM" (Flash Flood Risk Map Upper Austria) by calculating damage risk for buildings and vulnerable infrastructure like schools and hospitals caused by flash-flood driven inundation. While danger zones in riverine flooding are established as an integral part of spatial planning, flash floods caused by overland runoff from extreme rain events have been for long an underrated safety hazard not only for buildings and infrastructure, but man and animals as well. Based on the widespread 2D-model "hydro_as-2D", an extension was developed, which calculates the runoff formation from a spatially and temporally variable precipitation and determines two dimensionally the land surface area runoff and its concentration. The conception of the model is to preprocess the precipitation data and calculate the effective runoff-volume for a short time step of e.g. five minutes. This volume is applied to the nodes of the 2D-model and the calculation of the hydrodynamic model is started. At the end of each time step, the model run is stopped, the preprocessing step is repeated and the hydraulic model calculation is continued. In view of the later use for the whole of Upper Austria (12.000 km²) a model grid of 25x25 m² was established using digital elevation data. Model parameters could be estimated for the small catchment of river Ach, which was hit by an intense rain event with up to 109 mm per hour

  9. Using an extended 2D hydrodynamic model for evaluating damage risk caused by extreme rain events: Flash-Flood-Risk-Map (FFRM) Upper Austria

    NASA Astrophysics Data System (ADS)

    Humer, Günter; Reithofer, Andreas

    2016-04-01

    Using an extended 2D hydrodynamic model for evaluating damage risk caused by extreme rain events: Flash-Flood-Risk-Map (FFRM) Upper Austria Considering the increase in flash flood events causing massive damage during the last years in urban but also rural areas [1-4], the requirement for hydrodynamic calculation of flash flood prone areas and possible countermeasures has arisen to many municipalities and local governments. Besides the German based URBAS project [1], also the EU-funded FP7 research project "SWITCH-ON" [5] addresses the damage risk caused by flash floods in the sub-project "FFRM" (Flash Flood Risk Map Upper Austria) by calculating damage risk for buildings and vulnerable infrastructure like schools and hospitals caused by flash-flood driven inundation. While danger zones in riverine flooding are established as an integral part of spatial planning, flash floods caused by overland runoff from extreme rain events have been for long an underrated safety hazard not only for buildings and infrastructure, but man and animals as well. Based on the widespread 2D-model "hydro_as-2D", an extension was developed, which calculates the runoff formation from a spatially and temporally variable precipitation and determines two dimensionally the land surface area runoff and its concentration. The conception of the model is to preprocess the precipitation data and calculate the effective runoff-volume for a short time step of e.g. five minutes. This volume is applied to the nodes of the 2D-model and the calculation of the hydrodynamic model is started. At the end of each time step, the model run is stopped, the preprocessing step is repeated and the hydraulic model calculation is continued. In view of the later use for the whole of Upper Austria (12.000 km²) a model grid of 25x25 m² was established using digital elevation data. Model parameters could be estimated for the small catchment of river Ach, which was hit by an intense rain event with up to 109 mm per hour

  10. Mutations in human C2CD3 cause skeletal dysplasia and provide new insights into phenotypic and cellular consequences of altered C2CD3 function.

    PubMed

    Cortés, Claudio R; McInerney-Leo, Aideen M; Vogel, Ida; Rondón Galeano, Maria C; Leo, Paul J; Harris, Jessica E; Anderson, Lisa K; Keith, Patricia A; Brown, Matthew A; Ramsing, Mette; Duncan, Emma L; Zankl, Andreas; Wicking, Carol

    2016-01-01

    Ciliopathies are a group of genetic disorders caused by defective assembly or dysfunction of the primary cilium, a microtubule-based cellular organelle that plays a key role in developmental signalling. Ciliopathies are clinically grouped in a large number of overlapping disorders, including the orofaciodigital syndromes (OFDS), the short rib polydactyly syndromes and Jeune asphyxiating thoracic dystrophy. Recently, mutations in the gene encoding the centriolar protein C2CD3 have been described in two families with a new sub-type of OFDS (OFD14), with microcephaly and cerebral malformations. Here we describe a third family with novel compound heterozygous C2CD3 mutations in two fetuses with a different clinical presentation, dominated by skeletal dysplasia with no microcephaly. Analysis of fibroblast cultures derived from one of these fetuses revealed a reduced ability to form cilia, consistent with previous studies in C2cd3-mutant mouse and chicken cells. More detailed analyses support a role for C2CD3 in basal body maturation; but in contrast to previous mouse studies the normal recruitment of the distal appendage protein CEP164 suggests that this protein is not sufficient for efficient basal body maturation and subsequent axonemal extension in a C2CD3-defective background. PMID:27094867

  11. Mutations in human C2CD3 cause skeletal dysplasia and provide new insights into phenotypic and cellular consequences of altered C2CD3 function

    PubMed Central

    Cortés, Claudio R.; McInerney-Leo, Aideen M.; Vogel, Ida; Rondón Galeano, Maria C.; Leo, Paul J.; Harris, Jessica E.; Anderson, Lisa K.; Keith, Patricia A.; Brown, Matthew A.; Ramsing, Mette; Duncan, Emma L.; Zankl, Andreas; Wicking, Carol

    2016-01-01

    Ciliopathies are a group of genetic disorders caused by defective assembly or dysfunction of the primary cilium, a microtubule-based cellular organelle that plays a key role in developmental signalling. Ciliopathies are clinically grouped in a large number of overlapping disorders, including the orofaciodigital syndromes (OFDS), the short rib polydactyly syndromes and Jeune asphyxiating thoracic dystrophy. Recently, mutations in the gene encoding the centriolar protein C2CD3 have been described in two families with a new sub-type of OFDS (OFD14), with microcephaly and cerebral malformations. Here we describe a third family with novel compound heterozygous C2CD3 mutations in two fetuses with a different clinical presentation, dominated by skeletal dysplasia with no microcephaly. Analysis of fibroblast cultures derived from one of these fetuses revealed a reduced ability to form cilia, consistent with previous studies in C2cd3-mutant mouse and chicken cells. More detailed analyses support a role for C2CD3 in basal body maturation; but in contrast to previous mouse studies the normal recruitment of the distal appendage protein CEP164 suggests that this protein is not sufficient for efficient basal body maturation and subsequent axonemal extension in a C2CD3-defective background. PMID:27094867

  12. A Genomic Study of DNA Alteration Events Caused by Ionizing Radiation in Human Embryonic Stem Cells via Next-Generation Sequencing.

    PubMed

    Nguyen, Van; Panyutin, Irina V; Panyutin, Igor G; Neumann, Ronald D

    2016-01-01

    Ionizing radiation (IR) is a known mutagen that is widely employed for medical diagnostic and therapeutic purposes. To study the extent of genetic variations in DNA caused by IR, we used IR-sensitive human embryonic stem cells (hESCs). Four hESC cell lines, H1, H7, H9, and H14, were subjected to IR at 0.2 or 1 Gy dose and then maintained in culture for four days before being harvested for DNA isolation. Irradiation with 1 Gy dose resulted in significant cell death, ranging from 60% to 90% reduction in cell population. Since IR is often implicated as a risk for inducing cancer, a primer pool targeting genomic "hotspot" regions that are frequently mutated in human cancer genes was used to generate libraries from irradiated and control samples. Using a semiconductor-based next-generation sequencing approach, we were able to consistently sequence these samples with deep coverage for reliable data analysis. A possible rare nucleotide variant was identified in the KIT gene (chr4:55593481) exclusively in H1 hESCs irradiated with 1 Gy dose. More extensive further studies are warranted to assess the extent and distribution of genetic changes in hESCs after IR exposure. PMID:26709353

  13. Mutation of the Myxoma virus SERP2 P1-site to prevent proteinase inhibition causes apoptosis in cultured RK-13 cells and attenuates disease in rabbits, but mutation to alter specificity causes apoptosis without reducing virulence.

    PubMed

    MacNeill, Amy L; Turner, Peter C; Moyer, Richard W

    Myxoma virus (MYX) prevents apoptosis in RK-13 cells and forms thick dermal lesions with 100% mortality in rabbits. MYX encodes the virulence factor SERP2, a serine proteinase inhibitor (serpin). SERP2 was mutated to evaluate SERP2 function during MYX infection. MYXDeltaSERP2::lacZ (deleted for SERP2) did not inhibit apoptosis in RK-13 cells; infected rabbits had thin dermal lesions and <10% mortality. MYX-SERP2-D294A, a P1-site aspartate to alanine mutant, inactivated the serpin; infection was indistinguishable from MYXDeltaSERP2::lacZ. SERP2-D294E prevented inhibition of caspase-8, caspase-10 and granzyme-B; and MYX-SERP2-D294E failed to block apoptosis in RK-13 cells, but was fully virulent in rabbits. MYXDeltaSERP2::crmA expressed crmA instead of SERP2 and inhibited apoptosis in cell culture, but caused thin lesions and only 70% mortality in rabbits, hence crmA cannot fully substitute for SERP2. Control of apoptosis in culture does not correlate with virulence in rabbits. Virulence may instead depend on inhibition of proinflammatory proteinases by SERP2. PMID:16959285

  14. Loss of Arabidopsis GAUT12/IRX8 causes anther indehiscence and leads to reduced G lignin associated with altered matrix polysaccharide deposition

    PubMed Central

    Hao, Zhangying; Avci, Utku; Tan, Li; Zhu, Xiang; Glushka, John; Pattathil, Sivakumar; Eberhard, Stefan; Sholes, Tipton; Rothstein, Grace E.; Lukowitz, Wolfgang; Orlando, Ron; Hahn, Michael G.; Mohnen, Debra

    2014-01-01

    GAlactUronosylTransferase12 (GAUT12)/IRregular Xylem8 (IRX8) is a putative glycosyltransferase involved in Arabidopsis secondary cell wall biosynthesis. Previous work showed that Arabidopsis irregular xylem8 (irx8) mutants have collapsed xylem due to a reduction in xylan and a lesser reduction in a subfraction of homogalacturonan (HG). We now show that male sterility in the irx8 mutant is due to indehiscent anthers caused by reduced deposition of xylan and lignin in the endothecium cell layer. The reduced lignin content was demonstrated by histochemical lignin staining and pyrolysis Molecular Beam Mass Spectrometry (pyMBMS) and is associated with reduced lignin biosynthesis in irx8 stems. Examination of sequential chemical extracts of stem walls using 2D 13C-1H Heteronuclear Single-Quantum Correlation (HSQC) NMR spectroscopy and antibody-based glycome profiling revealed a reduction in G lignin in the 1 M KOH extract and a concomitant loss of xylan, arabinogalactan and pectin epitopes in the ammonium oxalate, sodium carbonate, and 1 M KOH extracts from the irx8 walls compared with wild-type walls. Immunolabeling of stem sections using the monoclonal antibody CCRC-M138 reactive against an unsubstituted xylopentaose epitope revealed a bi-lamellate pattern in wild-type fiber cells and a collapsed bi-layer in irx8 cells, suggesting that at least in fiber cells, GAUT12 participates in the synthesis of a specific layer or type of xylan or helps to provide an architecture framework required for the native xylan deposition pattern. The results support the hypothesis that GAUT12 functions in the synthesis of a structure required for xylan and lignin deposition during secondary cell wall formation. PMID:25120548

  15. Altered expression of triadin 95 causes parallel changes in localized Ca2+ release events and global Ca2+ signals in skeletal muscle cells in culture

    PubMed Central

    Fodor, János; Gönczi, Monika; Sztretye, Monika; Dienes, Beatrix; Oláh, Tamás; Szabó, László; Csoma, Eszter; Szentesi, Péter; Szigeti, Gyula P; Marty, Isabelle; Csernoch, László

    2008-01-01

    The 95 kDa triadin (Trisk 95), an integral protein of the sarcoplasmic reticular membrane in skeletal muscle, interacts with both the ryanodine receptor (RyR) and calsequestrin. While its role in the regulation of calcium homeostasis has been extensively studied, data are not available on whether the overexpression or the interference with the expression of Trisk 95 would affect calcium sparks the localized events of calcium release (LCRE). In the present study LCRE and calcium transients were studied using laser scanning confocal microscopy on C2C12 cells and on primary cultures of skeletal muscle. Liposome- or adenovirus-mediated Trisk 95 overexpression and shRNA interference with triadin translation were used to modify the level of the protein. Stable overexpression in C2C12 cells significantly decreased the amplitude and frequency of calcium sparks, and the frequency of embers. In line with these observations, depolarization-evoked calcium transients were also suppressed. Similarly, adenoviral transfection of Trisk 95 into cultured mouse skeletal muscle cells significantly decreased both the frequency and amplitude of spontaneous global calcium transients. Inhibition of endogenous triadin expression by RNA interference caused opposite effects. Primary cultures of rat skeletal muscle cells expressing endogenous Trisk 95 readily generated spontaneous calcium transients but rarely produced calcium sparks. Their transfection with specific shRNA sequence significantly reduced the triadin-specific immunoreactivity. Functional experiments on these cells revealed that while caffeine-evoked calcium transients were reduced, LCRE appeared with higher frequency. These results suggest that Trisk 95 negatively regulates RyR function by suppressing localized calcium release events and global calcium signals in cultured muscle cells. PMID:18845610

  16. Mutations in a Partitioning Protein and Altered Chromatin Structure at the Partitioning Locus Prevent Cohesin Recruitment by the Saccharomyces cerevisiae Plasmid and Cause Plasmid Missegregation

    PubMed Central

    Yang, Xian-Mei; Mehta, Shwetal; Uzri, Dina; Jayaram, Makkuni; Velmurugan, Soundarapandian

    2004-01-01

    The 2μm circle is a highly persistent “selfish” DNA element resident in the Saccharomyces cerevisiae nucleus whose stability approaches that of the chromosomes. The plasmid partitioning system, consisting of two plasmid-encoded proteins, Rep1p and Rep2p, and a cis-acting locus, STB, apparently feeds into the chromosome segregation pathway. The Rep proteins assist the recruitment of the yeast cohesin complex to STB during the S phase, presumably to apportion the replicated plasmid molecules equally to daughter cells. The DNA-protein and protein-protein interactions of the partitioning system, as well as the chromatin organization at STB, are important for cohesin recruitment. Rep1p variants that are incompetent in binding to Rep2p, STB, or both fail to assist the assembly of the cohesin complex at STB and are nonfunctional in plasmid maintenance. Preventing the cohesin-STB association without impeding Rep1p-Rep2p-STB interactions also causes plasmid missegregation. During the yeast cell cycle, the Rep1p and Rep2p proteins are expelled from STB during a short interval between the late G1 and early S phases. This dissociation and reassociation event ensures that cohesin loading at STB is replication dependent and is coordinated with chromosomal cohesin recruitment. In an rsc2Δ yeast strain lacking a specific chromatin remodeling complex and exhibiting a high degree of plasmid loss, neither Rep1p nor the cohesin complex can be recruited to STB. The phenotypes of the Rep1p mutations and of the rsc2Δ mutant are consistent with the role of cohesin in plasmid partitioning being analogous to that in chromosome partitioning. PMID:15169893

  17. Disturbance Distance: Using a process based ecosystem model to estimate and map potential thresholds in disturbance rates that would give rise to fundamentally altered ecosystems

    NASA Astrophysics Data System (ADS)

    Dolan, K. A.; Hurtt, G. C.; Fisk, J.; Flanagan, S.; LePage, Y.; Sahajpal, R.

    2014-12-01

    Disturbance plays a critical role in shaping the structure and function of forested ecosystems as well as the ecosystem services they provide, including but not limited to: carbon storage, biodiversity habitat, water quality and flow, and land atmosphere exchanges of energy and water. As recent studies highlight novel disturbance regimes resulting from pollution, invasive pests and climate change, there is a need to include these alterations in predictions of future forest function and structure. The Ecosystem Demography (ED) model is a mechanistic model of forest ecosystem dynamics in which individual-based forest dynamics can be efficiently implemented over regional to global scales due to advanced scaling methods. We utilize ED to characterize the sensitivity of potential vegetation structure and function to changes in rates of density independent mortality. Disturbance rate within ED can either be altered directly or through the development of sub-models. Disturbance sub-models in ED currently include fire, land use and hurricanes. We use a tiered approach to understand the sensitivity of North American ecosystems to changes in background density independent mortality. Our first analyses were conducted at half-degree spatial resolution with a constant rate of disturbance in space and time, which was altered between runs. Annual climate was held constant at the site level and the land use and fire sub-models were turned off. Results showed an ~ 30% increase in non-forest area across the US when disturbance rates were changed from 0.6% a year to 1.2% a year and a more than 3.5 fold increase in non-forest area when disturbance rates doubled again from 1.2% to 2.4%. Continued runs altered natural background disturbance rates with the existing fire and hurricane sub models turned on as well as historic and future land use. By quantify differences between model outputs that characterize ecosystem structure and function related to the carbon cycle across the US, we

  18. Near-infrared reflectance of zunyite: implications for field mapping and remote-sensing detection of hydrothermally altered high alumina rocks.

    USGS Publications Warehouse

    Crowley, J.K.

    1984-01-01

    Several hydroxyl-bearing minerals have diagnostic absorption bands in the 2.0-2.4 mu m wave length range, and can be identified with an orbital radiometer and with high-resolution airborne and field portable spectrometers. Among such minerals, zunyite, 143Al13Si5O20(OH,F)18Cl, has distinctive spectral absorption characteristics and is notably restricted to, and thus an indicator mineral of, advanced argillic alteration. Although seldom noted because it visually resembles quartz, zunyite is probably not as rare as generally believed. Laboratory measurements and general considerations underlie suggestions favouring the feasibility of detecting zunyite, alone and in mixtures with other Al-OH minerals, using field portable spectrometers.-G.J.N.

  19. Map showing landslides in California that have caused fatalities or at least $1,000,000 in damages from 1906 to 1984

    USGS Publications Warehouse

    Taylor, Fred; Brabb, E.E.

    1986-01-01

    Understanding where landslide processes in California have been most severe is helpful in determining priorities for landslide mapping, mitigation measures, and preparedness planning. Although a few studies of landslide damage and fatalities have been published (see sources of data 12, 17, 34, 36, 40), and many more reports mention landslide damage and fatalities incidentally, our map is the first to show where the problem is most severe for the entire state.

  20. Linkage mapping in the oilseed crop Jatropha curcas L. reveals a locus controlling the biosynthesis of phorbol esters which cause seed toxicity.

    PubMed

    King, Andrew J; Montes, Luis R; Clarke, Jasper G; Affleck, Julie; Li, Yi; Witsenboer, Hanneke; van der Vossen, Edwin; van der Linde, Piet; Tripathi, Yogendra; Tavares, Evanilda; Shukla, Parul; Rajasekaran, Thirunavukkarasu; van Loo, Eibertus N; Graham, Ian A

    2013-10-01

    Current efforts to grow the tropical oilseed crop Jatropha curcas L. economically are hampered by the lack of cultivars and the presence of toxic phorbol esters (PE) within the seeds of most provenances. These PE restrict the conversion of seed cake into animal feed, although naturally occurring 'nontoxic' provenances exist which produce seed lacking PE. As an important step towards the development of genetically improved varieties of J. curcas, we constructed a linkage map from four F₂ mapping populations. The consensus linkage map contains 502 codominant markers, distributed over 11 linkage groups, with a mean marker density of 1.8 cM per unique locus. Analysis of the inheritance of PE biosynthesis indicated that this is a maternally controlled dominant monogenic trait. This maternal control is due to biosynthesis of the PE occurring only within maternal tissues. The trait segregated 3 : 1 within seeds collected from F₂ plants, and QTL analysis revealed that a locus on linkage group 8 was responsible for phorbol ester biosynthesis. By taking advantage of the draft genome assemblies of J. curcas and Ricinus communis (castor), a comparative mapping approach was used to develop additional markers to fine map this mutation within 2.3 cM. The linkage map provides a framework for the dissection of agronomic traits in J. curcas, and the development of improved varieties by marker-assisted breeding. The identification of the locus responsible for PE biosynthesis means that it is now possible to rapidly breed new nontoxic varieties. PMID:23898859

  1. Human and mouse chromosomal mapping of the myeloid cell leukemia-1 gene: MCL1 maps to human chromosome 1q21, a region that is frequently altered in preneoplastic and neoplastic disease

    SciTech Connect

    Craig, R.W.; Zhou, P.; Kozopas, K.M.

    1994-09-15

    The MCL1 gene, recently identified in a myeloid leukemia cell line, has sequence similarity to BCL2, the gene at the t(14;18) translocation in follicular lymphoma. The chromosomal location of MCL1 has now been determined. The human locus (MCL1) was mapped to the long arm of human chromosome 1q21, using the methods of in situ hybridization and somatic cell hybrid analysis. In the mouse, MCL1-related sequences were mapped to positions on two mouse chromosomes (chromosomes 3 and 5), using haplotype analysis of an interspecific cross. The location of the locus on mouse chromosome 3 (Mcl1) was homologous to that of MCL1 on human chromosome 1; the second locus (Mcl-rs on mouse chromosome 5) may represent a pseudogene. The proximal long arm of human chromosome 1, where MCL1 is located, is duplicated and/or rearranged in a variety of preneoplastic and neoplastic diseases including hematologic diseases and solid tumors. MCL1 is thus a candidate gene for involvement in cancer. 46 refs., 2 figs., 3 tabs.

  2. Both chronic treatments by epothilone D and fluoxetine increase the short-term memory and differentially alter the mood status of STOP/MAP6 KO mice.

    PubMed

    Fournet, Vincent; de Lavilléon, Gaetan; Schweitzer, Annie; Giros, Bruno; Andrieux, Annie; Martres, Marie-Pascale

    2012-12-01

    Recent evidence underlines the crucial role of neuronal cytoskeleton in the pathophysiology of psychiatric diseases. In this line, the deletion of STOP/MAP6 (Stable Tubule Only Polypeptide), a microtubule-stabilizing protein, triggers various neurotransmission and behavioral defects, suggesting that STOP knockout (KO) mice could be a relevant experimental model for schizoaffective symptoms. To establish the predictive validity of such a mouse line, in which the brain serotonergic tone is dramatically imbalanced, the effects of a chronic fluoxetine treatment on the mood status of STOP KO mice were characterized. Moreover, we determined the impact, on mood, of a chronic treatment by epothilone D, a taxol-like microtubule-stabilizing compound that has previously been shown to improve the synaptic plasticity deficits of STOP KO mice. We demonstrated that chronic fluoxetine was either antidepressive and anxiolytic, or pro-depressive and anxiogenic, depending on the paradigm used to test treated mutant mice. Furthermore, control-treated STOP KO mice exhibited paradoxical behaviors, compared with their clear-cut basal mood status. Paradoxical fluoxetine effects and control-treated STOP KO behaviors could be because of their hyper-reactivity to acute and chronic stress. Interestingly, both epothilone D and fluoxetine chronic treatments improved the short-term memory of STOP KO mice. Such treatments did not affect the serotonin and norepinephrine transporter densities in cerebral areas of mice. Altogether, these data demonstrated that STOP KO mice could represent a useful model to study the relationship between cytoskeleton, mood, and stress, and to test innovative mood treatments, such as microtubule-stabilizing compounds. PMID:23013328

  3. Linkage mapping in the oilseed crop Jatropha curcas L. reveals a locus controlling the biosynthesis of phorbol esters which cause seed toxicity

    PubMed Central

    King, Andrew J; Montes, Luis R; Clarke, Jasper G; Affleck, Julie; Li, Yi; Witsenboer, Hanneke; van der Vossen, Edwin; van der Linde, Piet; Tripathi, Yogendra; Tavares, Evanilda; Shukla, Parul; Rajasekaran, Thirunavukkarasu; van Loo, Eibertus N; Graham, Ian A

    2013-01-01

    Current efforts to grow the tropical oilseed crop Jatropha curcas L. economically are hampered by the lack of cultivars and the presence of toxic phorbol esters (PE) within the seeds of most provenances. These PE restrict the conversion of seed cake into animal feed, although naturally occurring ‘nontoxic’ provenances exist which produce seed lacking PE. As an important step towards the development of genetically improved varieties of J. curcas, we constructed a linkage map from four F2 mapping populations. The consensus linkage map contains 502 codominant markers, distributed over 11 linkage groups, with a mean marker density of 1.8 cM per unique locus. Analysis of the inheritance of PE biosynthesis indicated that this is a maternally controlled dominant monogenic trait. This maternal control is due to biosynthesis of the PE occurring only within maternal tissues. The trait segregated 3 : 1 within seeds collected from F2 plants, and QTL analysis revealed that a locus on linkage group 8 was responsible for phorbol ester biosynthesis. By taking advantage of the draft genome assemblies of J. curcas and Ricinus communis (castor), a comparative mapping approach was used to develop additional markers to fine map this mutation within 2.3 cM. The linkage map provides a framework for the dissection of agronomic traits in J. curcas, and the development of improved varieties by marker-assisted breeding. The identification of the locus responsible for PE biosynthesis means that it is now possible to rapidly breed new nontoxic varieties. PMID:23898859

  4. Gestational and Lactational Exposure to Atrazine via the Drinking Water Causes Specific Behavioral Deficits and Selectively Alters Monoaminergic Systems in C57BL/6 Mouse Dams, Juvenile and Adult Offspring

    PubMed Central

    Krishna, Saritha; Ye, Xiaoqin; Filipov, Nikolay M.

    2014-01-01

    Atrazine (ATR) is one of the most frequently detected pesticides in the U.S. water supply. This study aimed to investigate neurobehavioral and neurochemical effects of ATR in C57BL/6 mouse offspring and dams exposed to a relatively low (3 mg/l, estimated intake 1.4 mg/kg/day) concentration of ATR via the drinking water (DW) from gestational day 6 to postnatal day (PND) 23. Behavioral tests included open field, pole, grip strength, novel object recognition (NOR), forced swim, and marble burying tests. Maternal weight gain and offspring (PND21, 35, and 70) body or brain weights were not affected by ATR. However, ATR-treated dams exhibited decreased NOR performance and a trend toward hyperactivity. Juvenile offspring (PND35) from ATR-exposed dams were hyperactive (both sexes), spent less time swimming (males), and buried more marbles (females). In adult offspring (PND70), the only behavioral change was a sex-specific (females) decreased NOR performance by ATR. Neurochemically, a trend toward increased striatal dopamine (DA) in dams and a significant increase in juvenile offspring (both sexes) was observed. Additionally, ATR exposure decreased perirhinal cortex serotonin in the adult female offspring. These results suggest that perinatal DW exposure to ATR targets the nigrostriatal DA pathway in dams and, especially, juvenile offspring, alters dams’ cognitive performance, induces sex-selective changes involving motor and emotional functions in juvenile offspring, and decreases cognitive ability of adult female offspring, with the latter possibly associated with altered perirhinal cortex serotonin homeostasis. Overall, ATR exposure during gestation and lactation may cause adverse nervous system effects to both offspring and dams. PMID:24913803

  5. Mapping and characterization of land subsidence in Beijing Plain caused by groundwater pumping using the Small Baseline Subset (SBAS) InSAR technique

    NASA Astrophysics Data System (ADS)

    Gao, M. L.; Gong, H. L.; Chen, B. B.; Zhou, C. F.; Liu, K. S.; Shi, M.

    2015-11-01

    InSAR time series analysis is widely used for detection and monitoring of slow surface deformation. In this paper, 15 TerraSAR-X radar images acquired in stripmap mode between 2012 and 2013 are processed for land subsidence monitoring with the Small Baseline Subset (SBAS) approach in Beijing Plain in China. Mapping results produced by SBAS show that the subsidence rates in the area of Beijing Plain range from -97.5 (subsidence) and to +23.8 mm yr-1 (uplift), relative to a presumably stable benchmark. The mapping result also reveals that there are the five subsidence centers formed by surface deformation spreading north to south east of the downtown. An uneven subsidence patten was detected near the Beijing Capital International Airpor, which may be related to loading of buildings and the aircraft.

  6. Rapid Identification of a Natural Knockout Allele of ARMADILLO REPEAT-CONTAINING KINESIN1 That Causes Root Hair Branching by Mapping-By-Sequencing1[C][W

    PubMed Central

    Rishmawi, Louai; Sun, Hequan; Schneeberger, Korbinian; Hülskamp, Martin; Schrader, Andrea

    2014-01-01

    In Arabidopsis (Arabidopsis thaliana), branched root hairs are an indicator of defects in root hair tip growth. Among 62 accessions, one accession (Heiligkreuztal2 [HKT2.4]) displayed branched root hairs, suggesting that this accession carries a mutation in a gene of importance for tip growth. We determined 200- to 300-kb mapping intervals using a mapping-by-sequencing approach of F2 pools from crossings of HKT2.4 with three different accessions. The intersection of these mapping intervals was 80 kb in size featuring not more than 36 HKT2.4-specific single nucleotide polymorphisms, only two of which changed the coding potential of genes. Among them, we identified the causative single nucleotide polymorphism changing a splicing site in ARMADILLO REPEAT-CONTAINING KINESIN1. The applied strategies have the potential to complement statistical methods in high-throughput phenotyping studies using different natural accessions to identify causative genes for distinct phenotypes represented by only one or a few accessions. PMID:25248719

  7. Rapid identification of a natural knockout allele of ARMADILLO REPEAT-CONTAINING KINESIN1 that causes root hair branching by mapping-by-sequencing.

    PubMed

    Rishmawi, Louai; Sun, Hequan; Schneeberger, Korbinian; Hülskamp, Martin; Schrader, Andrea

    2014-11-01

    In Arabidopsis (Arabidopsis thaliana), branched root hairs are an indicator of defects in root hair tip growth. Among 62 accessions, one accession (Heiligkreuztal2 [HKT2.4]) displayed branched root hairs, suggesting that this accession carries a mutation in a gene of importance for tip growth. We determined 200- to 300-kb mapping intervals using a mapping-by-sequencing approach of F2 pools from crossings of HKT2.4 with three different accessions. The intersection of these mapping intervals was 80 kb in size featuring not more than 36 HKT2.4-specific single nucleotide polymorphisms, only two of which changed the coding potential of genes. Among them, we identified the causative single nucleotide polymorphism changing a splicing site in ARMADILLO REPEAT-CONTAINING KINESIN1. The applied strategies have the potential to complement statistical methods in high-throughput phenotyping studies using different natural accessions to identify causative genes for distinct phenotypes represented by only one or a few accessions. PMID:25248719

  8. DNA ALTERATIONS

    EPA Science Inventory

    The exposure of an organism to genotoxic chemicals may induce a cascade of genetic events. nitially, structural alterations to DNA are formed. ext, the DNA damage is processed and subsequently expressed in mutant gene products. inally, diseases result from the genetic damage. he ...

  9. Historical mapping reveals causes and temporal patterns of woodland contraction in Austur-Skaftafellssýsla from the 12th century AD to present

    NASA Astrophysics Data System (ADS)

    Sigurmundsson, Friðþór S.; Gísladóttir, Guðrún; Erlendsson, Egill; Þorbjarnarson, Höskuldur

    2016-04-01

    Land-cover changes in Iceland over the last millennium encompass birch (Betula pubescens) woodland depletion and extensive soil erosion. Yet few studies have focused on spatial change of birch woodland coverage in Iceland over centuries and why and how the woodland depletion took place. The main objectives of this study are: (1) to map the woodland distribution today in Austur-Skaftafellssýsla (3041 km2) in southern Iceland; (2) to map woodland holdings over a period of 900 years from eleventh. AD 1100 to the early 20th century; (3) explain the relative impacts of socio-economic and natural forces on woodland cover over this period. We use a combined approach of historical reconstruction from diverse written archives, GIS techniques and field work. The woodland in Austur-Skaftafellssýsla now covers 73.2 km2 (2.5% of the study area). The woodland holdings, 44 in total, are regularly listed in the church inventories from 1179 to 1570 and are owned by the church. In the first complete register for the district in 1641 the woodland holdings were 73, owned and used by 58 estates, and distributed across Austur-Skaftafellssýsla. All the main patches of woodland remain today, with the exception of four minor woodlands which were exhausted near the end of the 19th century. The woodland was used for firewood and charcoal making as well as grazing during the study period but, crucially, in most cases only one estate had authority over each holding, none were commons. The main driving force behind the development of woodlands was socio-economic, rather than natural, where the form of ownership was fundamental for the fate of the woodland. Harsh climate and volcanism were not directly responsible for woodland depletion. The latter half of the 19th century was the period of greatest woodland loss. This period coincides with considerable expansion in livestock numbers, especially sheep and associated all year around grazing, at a time when the Little Ice Age culminated in

  10. Precise mapping of Quantitative Trait Loci for Resistance to Southern Leaf Blight, caused by Cochliobolus heterostrophus race O, using an Advanced Intercross Maize Population.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The IBM population, an advanced intercross recombinant inbred line population derived from a cross between the maize lines Mo17 (resistant) and B73 (susceptible), was evaluated in four environments for resistance to southern leaf blight (SLB) disease caused by Cochliobolus heterostrophus race O. ...

  11. Mutations of GIPC3 cause nonsyndromic hearing loss DFNB72 but not DFNB81 that also maps to chromosome 19p

    PubMed Central

    Rehman, Atteeq U.; Gul, Khitab; Morell, Robert J.; Lee, Kwanghyuk; Ahmed, Zubair M.; Riazuddin, Saima; Ali, Rana A.; Shahzad, Mohsin; Jaleel, Ateeq-ul; Andrade, Paula B.; Khan, Shaheen N.; Khan, Saadullah; Brewer, Carmen C.; Ahmad, Wasim; Leal, Suzanne M.; Riazuddin, Sheikh

    2012-01-01

    A missense mutation of Gipc3 was previously reported to cause age-related hearing loss in mice. Point mutations of human GIPC3 were found in two small families, but association with hearing loss was not statistically significant. Here, we describe one frameshift and six missense mutations in GIPC3 cosegregating with DFNB72 hearing loss in six large families that support statistically significant evidence for genetic linkage. However, GIPC3 is not the only nonsyndromic hearing impairment gene in this region; no GIPC3 mutations were found in a family cosegregating hearing loss with markers of chromosome 19p. Haplotype analysis excluded GIPC3 from the obligate linkage interval in this family and defined a novel locus spanning 4.08 Mb and 104 genes. This closely linked but distinct nonsyndromic hearing loss locus was designated DFNB81. PMID:21660509

  12. Sixth-grade Indonesian student explanations of directions on flat maps and globes, of the Earth's rotation to cause night and day, and of the relative positions of the Earth, Moon, and Sun during an eclipse

    NASA Astrophysics Data System (ADS)

    Dimyati, Surachman

    The purpose of the study was to elicit and analyze sixth grade students' explanations concerning concepts taught in the national Indonesian sixth grade science curriculum. In this study, students were asked to identify the cardinal directions on flat maps and a globe, to describe what causes night and day on the earth, to identify the direction of the earth's rotation, and to identify the relative positions of the earth, sun, and moon during either a solar or lunar eclipse. The findings in the study can be summarized as follows (1) Eighty out of 88 students (91%) were able to explain what causes night and day. (2) Approximately 50% could identify the direction the earth rotates to cause night and day. (3) Using a solar system model, about 64% of the students could describe the relative position of the earth, sun, and moon during an eclipse. (4) Cultural differences affect student thinking. One student thought that Mecca had to be west of everywhere, not just west of Indonesia. (5) The way teachers teach seems to influence student thinking. It is easy for students to form the misconception that up is north. Most maps in classrooms are hung vertically. (6) Some students were confused by the globe. Teachers need to explain why the globe is tilted. Also, they need to help students understand how to determine the cardinal directions on a globe. More research is needed to determine what is needed to help students truly understand these concepts and to determine whether these concepts are best taught at the elementary level.

  13. [Alcohol, drugs and tobacco smoking causes much of the burden of disease--Trends in Sweden 1990-2010 mapped based DALY method].

    PubMed

    Agardh, Emilie; Boman, Ulrika; Allebeck, Peter

    2015-01-01

    Various attempts have been made to measure the burden of alcohol, drugs and tobacco smoking on population health, and mortality is an often used measure. As part of the governmental strategy to prevent use of alcohol, drugs, doping and tobacco (ANDT) in Sweden, we assessed disease burden measured by DALY (Disability Adjusted Life Years), attributed to alcohol, drugs and tobacco over time, as an overall indicator of problem level. DALY was developed within the Global Burden of Disease study (GBD), and combines life lost to premature death (YLL) and years lived with disability (YLD) in one measure. In 2010 tobacco contributed to 7.7% of the total disease burden in Sweden, followed by alcohol (3.4%) and drugs (1.3%). The disease burden caused by tobacco has decreased substantially since 1990, while small changes are observed for alcohol and drugs. Much of the disease burden specially related to drugs and alcohol was related to YLD, which can be captured with the DALY measure. PMID:25584599

  14. Investigation of purification process stresses on erythropoietin peptide mapping profile

    PubMed Central

    Sepahi, Mina; Kaghazian, Hooman; Hadadian, Shahin; Norouzian, Dariush

    2015-01-01

    Background: Full compliance of recombinant protein peptide mapping chromatogram with the standard reference material, is one of the most basic quality control tests of biopharmaceuticals. Changing a single amino acid substitution or side chain diversity for a given peptide changes protein hydrophobicity and causes peak shape or retention time alteration in a peptide mapping assay. In this work, the effect of different stresses during the recombinant erythropoietin (EPO) purification process, including pH 4, pH 5, and room temperature were checked on product peptide mapping results. Materials and Methods: Cell culture harvest was purified under stress by different chromatographic techniques consisting of gel filtration, anionic ion exchange, concentration by ultrafiltration, and high resolution size exclusion chromatography. To induce more pH stresses, the purified EPO was exposed to pH stress 4 and 5 by exchanging buffer by a 10 KDa dialysis sac overnight. The effects of temperature and partial deglycosylation (acid hydrolysis) on purified EPO were also studied by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and peptide mapping analysis. Removal of sialic acid by mild hydrolysis was performed by exposure to two molar acetic acid at 80°C for 3 h. Results: No significant effect was observed between intact and stressed erythropoietin peptide mapping profiles and SDS-PAGE results. To validate the sensibility of the technique, erythropoietin was partially acid hydrolyzed and significant changes in the chromatographic peptide map of the intact form and a reduction on its molecular weight were detected, which indicates some partial deglycosylation. Conclusions: Purification process does not alter the peptide mapping profile and purification process stresses are not the cause of peptide mapping noncompliance. PMID:26261816

  15. Chronic Exposure to Arsenic in Drinking Water Causes Alterations in Locomotor Activity and Decreases Striatal mRNA for the D2 Dopamine Receptor in CD1 Male Mice.

    PubMed

    Moreno Ávila, Claudia Leticia; Limón-Pacheco, Jorge H; Giordano, Magda; Rodríguez, Verónica M

    2016-01-01

    Arsenic exposure has been associated with sensory, motor, memory, and learning alterations in humans and alterations in locomotor activity, behavioral tasks, and neurotransmitters systems in rodents. In this study, CD1 mice were exposed to 0.5 or 5.0 mg As/L of drinking water for 6 months. Locomotor activity, aggression, interspecific behavior and physical appearance, monoamines levels, and expression of the messenger for dopamine receptors D1 and D2 were assessed. Arsenic exposure produced hypoactivity at six months and other behaviors such as rearing and on-wall rearing and barbering showed both increases and decreases. No alterations on aggressive behavior or monoamines levels in striatum or frontal cortex were observed. A significant decrease in the expression of mRNA for D2 receptors was found in striatum of mice exposed to 5.0 mg As/L. This study provides evidence for the use of dopamine receptor D2 as potential target of arsenic toxicity in the dopaminergic system. PMID:27375740

  16. Chronic Exposure to Arsenic in Drinking Water Causes Alterations in Locomotor Activity and Decreases Striatal mRNA for the D2 Dopamine Receptor in CD1 Male Mice

    PubMed Central

    Moreno Ávila, Claudia Leticia

    2016-01-01

    Arsenic exposure has been associated with sensory, motor, memory, and learning alterations in humans and alterations in locomotor activity, behavioral tasks, and neurotransmitters systems in rodents. In this study, CD1 mice were exposed to 0.5 or 5.0 mg As/L of drinking water for 6 months. Locomotor activity, aggression, interspecific behavior and physical appearance, monoamines levels, and expression of the messenger for dopamine receptors D1 and D2 were assessed. Arsenic exposure produced hypoactivity at six months and other behaviors such as rearing and on-wall rearing and barbering showed both increases and decreases. No alterations on aggressive behavior or monoamines levels in striatum or frontal cortex were observed. A significant decrease in the expression of mRNA for D2 receptors was found in striatum of mice exposed to 5.0 mg As/L. This study provides evidence for the use of dopamine receptor D2 as potential target of arsenic toxicity in the dopaminergic system. PMID:27375740

  17. Genetically Altered Plant Species

    NASA Technical Reports Server (NTRS)

    2003-01-01

    Researchers in Robert Ferl's lab at the University of Florida in Gainesville, genetically altered this Arabdopsis Thaliana (a brassica species) plant to learn how extreme environments, such as the low atmospheric pressure on Mars, affect plant genes. They inserted green fluorescent protein (GFP) near the on/off switches for anoxia and drought genes. When those genes were turned on after exposure to reduced atmospheric pressure, GFP was turned on as well, causing cells expressing those genes to glow green under a blue light. The natural fluorescence of chlorophyll accounts for the red glow.

  18. The effects of artificial alteration on sulfur in Arctica islandica shells

    NASA Astrophysics Data System (ADS)

    Fichtner, Vanessa; Huthwelker, Thomas; Borca, Camelia N.; Göttlicher, Jörg; Griesshaber, Erika; Yin, Xiaofei; Schmahl, Wolfgang W.; Mavromatis, Vasileios; Immenhauser, Adrian; Strauss, Harald

    2016-04-01

    Carbonate associated sulfate (CAS) is an important proxy for reconstructing redox conditions in former oceans. Especially for biogenic carbonates it is not fully understood where exactly the CAS is incorporated, how much is incorporated in respect to ambient sulfate concentrations, and how CAS is affected by diagenetic alteration. By combining sulfur K μ-XANES and μ-XRF analyses with geochemical methods (CAS-extraction, sulfur isotope measurements), this study aims at specifying the location of incorporation of CAS. Moreover, the effects of diagenetic alteration on sulfur abundance, speciation and distribution in shells of the marine bivalve Arctica islandica will be assessed through alteration experiments. Hereby, shell pieces were hydrothermally altered at two different temperatures (100°C and 175°C) for different times (one to twelve weeks) with sulfate-free artificial seawater. Our results show that the samples altered at 100°C retain the original/primary sulfur distribution and concentration, similar to a non-altered Arctica islandica shell. In contrast, μ-XRF maps of the shells altered at 175°C exhibit a significant change in the sulfur distribution and a decrease in sulfur concentration. The respective incubation solutions, in turn, show an increase in sulfate concentration with longer alteration times at 175°C. Furthermore, μ-XRF maps of sulfur not only record the growth of calcite crystals with longer alteration times at 175°C but also indicate that newly formed crystals are characterized by a near complete absence of sulfur. We propose that the process of recrystallization from aragonite to calcite between 100°C and 175°C causes the loss of sulfur from the bivalve shell. This is consistent with S K XANES analyses which indicate that the majority of sulfur in the Arctica islandica shell is present as sulfate integrated into the inorganic, aragonitic part, where the spectra resemble sulfate in aqueous solution.

  19. Whole Exome Sequencing and Segregation Analysis Confirms That a Mutation in COL17A1 Is the Cause of Epithelial Recurrent Erosion Dystrophy in a Large Dominant Pedigree Previously Mapped to Chromosome 10q23-q24

    PubMed Central

    Le, Derek J.; Chen, Yabin; Wang, Qiwei; Chung, D. Doug; Frausto, Ricardo F.; Croasdale, Christopher; Yee, Richard W.; Hejtmancik, Fielding J.; Aldave, Anthony J.

    2016-01-01

    Purpose To report identification of a COL17A1 mutation in a family with a corneal dystrophy previously mapped to chromosome 10q23-q24. Methods Whole-exome sequencing was performed on DNA samples from five affected family members and two unrelated, unaffected individuals. Identified variants were filtered for those that were: located in the linked interval on chromosome 10q23-q24; novel or rare (minor allele frequency ≤0.01); heterozygous; present in all affected individuals and not in controls; and present in genes that encode proteins expressed in human corneal epithelial cells (reads per kilobase per million ≥1). Sanger sequencing of identified variants (SNVs) was performed in additional family members. In silico analysis was used to predict the functional impact of non-synonymous variants. Results Three SNVs located in two genes were identified that met the filtering criteria: one rare synonymous c.3156C>T variant in the collagen, type XVII, alpha I (COL17A1) gene; and two rare variants, one synonymous and one missense, in the dynamin binding protein (DNMBP) gene. Sanger sequencing of additional family members determined that only the COL17A1 variant segregates with the affected phenotype. In silico analysis predicts that the missense variant in DNMBP would be tolerated. Conclusions The corneal dystrophy mapped to chromosome 10q23-q24 is associated with the c.3156C>T variant in COL17A1. As this variant has recently been identified in five other families with early onset recurrent corneal erosions, and has been shown in vitro to introduce a cryptic splice donor site, this dystrophy is likely caused by aberrant splicing of COL17A1 and should be classified as epithelial recurrent erosion dystrophy. PMID:27309958

  20. miR-155, identified as anti-metastatic by global miRNA profiling of a metastasis model, inhibits cancer cell extravasation and colonization in vivo and causes significant signaling alterations

    PubMed Central

    Lund, Rikke R.; Søkilde, Rolf; Elias, Daniel; Bak, Martin; Litman, Thomas; Beck, Hans C.; Lyng, Maria B.; Ditzel, Henrik J.

    2015-01-01

    To gain insight into miRNA regulation in metastasis formation, we used a metastasis cell line model that allows investigation of extravasation and colonization of circulating cancer cells to lungs in mice. Using global miRNA profiling, 28 miRNAs were found to exhibit significantly altered expression between isogenic metastasizing and non-metastasizing cancer cells, with miR-155 being the most differentially expressed. Highly metastatic mesenchymal-like CL16 cancer cells showed very low miR-155 expression, and miR-155 overexpression in these cells lead to significantly decreased tumor burden in lungs when injected intravenously in immunodeficient mice. Our experiments addressing the underlying mechanism of the altered tumor burden revealed that miR-155-overexpressing CL16 cells were less invasive than CL16 control cells in vitro, while miR-155 overexpression had no effect on cancer cell proliferation or apoptosis in established lung tumors. To identify proteins regulated by miR-155 and thus delineate its function in our cell model, we compared the proteome of xenograft tumors derived from miR-155-overexpressing CL16 cells and CL16 control cells using mass spectrometry-based proteomics. >4,000 proteins were identified, of which 92 were consistently differentially expressed. Network analysis revealed that the altered proteins were associated with cellular functions such as movement, growth and survival as well as cell-to-cell signaling and interaction. Downregulation of the three metastasis-associated proteins ALDH1A1, PIR and PDCD4 in miR-155-overexpressing tumors was validated by immunohistochemistry. Our results demonstrate that miR-155 inhibits the ability of cancer cells to extravasate and/or colonize at distant organs and brings additional insight into the complexity of miR-155 regulation in metastatic seeding. PMID:26317550

  1. Androgen and taxol cause cell type-specific alterations of centrosome and DNA organization in androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cells

    NASA Technical Reports Server (NTRS)

    Schatten, H.; Ripple, M.; Balczon, R.; Weindruch, R.; Chakrabarti, A.; Taylor, M.; Hueser, C. N.

    2000-01-01

    We investigated the effects of androgen and taxol on the androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cell lines. Cells were treated for 48 and 72 h with 0.05-1 nM of the synthetic androgen R1881 and with 100 nM taxol. Treatment of LNCaP cells with 0.05 nM R1881 led to increased cell proliferation, whereas treatment with 1 nM R1881 resulted in inhibited cell division, DNA cycle arrest, and altered centrosome organization. After treatment with 1 nM R1881, chromatin became clustered, nuclear envelopes convoluted, and mitochondria accumulated around the nucleus. Immunofluorescence microscopy with antibodies to centrosomes showed altered centrosome structure. Although centrosomes were closely associated with the nucleus in untreated cells, they dispersed into the cytoplasm after treatment with 1 nM R1881. Microtubules were only faintly detected in 1 nM R1881-treated LNCaP cells. The effects of taxol included microtubule bundling and altered mitochondria morphology, but not DNA organization. As expected, the androgen-independent prostate cancer cell line DU145 was not affected by R1881. Treatment with taxol resulted in bundling of microtubules in both cell lines. Additional taxol effects were seen in DU145 cells with micronucleation of DNA, an indication of apoptosis. Simultaneous treatment with R1881 and taxol had no additional effects on LNCaP or DU145 cells. These results suggest that LNCaP and DU145 prostate cancer cells show differences not only in androgen responsiveness but in sensitivity to taxol as well. Copyright 2000 Wiley-Liss, Inc.

  2. Human Herpesvirus 6A (HHV-6A) and HHV-6B Alter E2F1/Rb Pathways and E2F1 Localization and Cause Cell Cycle Arrest in Infected T Cells▿

    PubMed Central

    Mlechkovich, Guy; Frenkel, Niza

    2007-01-01

    E2F transcription factors play pivotal roles in controlling the expression of genes involved in cell viability as well as genes involved in cell death. E2F1 is an important constituent of this protein family, which thus far contains eight members. The interaction of E2F1 with its major regulator, retinoblastoma protein (Rb), has been studied extensively in the past two decades, concentrating on the role of E2F1 in transcriptional regulation and the role of Rb in cell replication and cancer formation. Additionally, the effect of viral infections on E2F1/Rb interactions has been analyzed for different viruses, concentrating on cell division, which is essential for viral replication. In the present study, we monitored E2F1-Rb interactions during human herpesvirus 6A (HHV-6A) and HHV-6B infections of SupT1 T cells. The results have shown the following dramatic alterations in E2F1-Rb pathways compared to the pathways of parallel mock-infected control cultures. (i) The E2F1 levels were elevated during viral infections. (ii) The cellular localization of E2F1 was dramatically altered, and it was found to accumulate both in the cytoplasmic and nuclear fractions, as opposed to the strict nuclear localization seen in the mock-infected cells. (iii) Although E2F1 expression was elevated, two exemplary target genes, cyclin E and MCM5, were not upregulated. (iv) The Rb protein was dephosphorylated early postinfection, a trait that also occurred with UV-inactivated virus. (v) Infection was associated with significant reduction of E2F1/Rb complexing. (vi) HHV-6 infections were accompanied by cell cycle arrest. The altered E2F1-Rb interactions and functions might contribute to the observed cell cycle arrest. PMID:17913805

  3. Nuclear gene causing multiple mtDNA deletions in autosomal dominant ophthalmoplegia maps to a distinct chromosomal region - involvement of both nuclear and mitochondrial DNA in a single disorder

    SciTech Connect

    Suomalainen, A.; Kaukonen, J.; Timonen, R.

    1994-09-01

    Autosomal dominant progressive external ophthalmoplegia (adPEO) is a mitochondrial disease characterized by muscle weakness, most prominent in ocular muscles. The symptoms are caused by accumulation of multiple large deletions of mitochondrial DNA (mtDNA) in the tissues of the patient, especially in those tissues that are most dependent on oxidative metabolism: brain, skeletal muscle and heart. However, the disorder shows autosomal dominant way of transmission, suggesting a primary defect in a nuclear encoded protein, which only secondarily results in mtDNA deletions. The candidate genes could be those actively participating in the mtDNA replication, or those associated with oxidative metabolism and e.g. via overproduction or inefficient elimination of fire oxygen radicals fragmenting mtDNA. We applied random mapping approach to localize the autosomal adPEO gene locus in a large Finnish family. The affected subjects were identified by detection of multiple mtDNA deletions in the Southern blot analysis of DNA extracted from the muscle biopsy specimens. All the family members underwent muscle biopsy. After analysis of 248 highly polymorphic dinucleotide repeat markets dispersed throughout the genome we were able to assign the adPEO gene locus to a distinct chromosomal region with the maximum pairwise lod score of 4.52, recombination fraction 0.0. This is the first evidence that a mutation in a nuclear gene may interfere mtDNA. The pathogenesis of adPEO involves both the genomes: the primary nuclear gene defect leads to secondary mtDNA mutations that cause the symptoms of the patients.

  4. Liver enzyme alteration: a guide for clinicians

    PubMed Central

    Giannini, Edoardo G.; Testa, Roberto; Savarino, Vincenzo

    2005-01-01

    ISOLATED ALTERATIONS OF BIOCHEMICAL MARKERS OF LIVER DAMAGE in a seemingly healthy patient can present a challenge for the clinician. In this review we provide a guide to interpreting alterations to liver enzyme levels. The functional anatomy of the liver and pathophysiology of liver enzyme alteration are briefly reviewed. Using a schematic approach that classifies enzyme alterations as predominantly hepatocellular or predominantly cholestatic, we review abnormal enzymatic activity within the 2 subgroups, the most common causes of enzyme alteration and suggested initial investigations. PMID:15684121

  5. Hyperspectral surface materials map of quadrangles 2964, 2966, 3064, and 3066, Shah-Esmail (617), Reg-Alaqadari (618), Samandkhan-Karez (713), Laki-Bander (611), Jahangir-Naweran (612), and Sreh-Chena (707) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

    Hoefen, Todd M.; Kokaly, Raymond F.; King, Trude V.V.; Livo, Keith E.; Giles, Stuart A.; Johnson, Michaela R.

    2013-01-01

    This map shows the spatial distribution of selected carbonates, phyllosilicates, sulfates, altered minerals, and other materials derived from analysis of airborne HyMap™ imaging spectrometer (hyperspectral) data of Afghanistan collected in late 2007. The map is one in a series of U.S. Geological Survey/Afghanistan Geological Survey quadrangle maps covering Afghanistan. Flown at an altitude of 50,000 feet (15,240 meters (m)), the HyMap™ imaging spectrometer measured reflected sunlight in 128 channels, covering wavelengths between 0.4 and 2.5 μm. The data were georeferenced, atmospherically corrected and converted to apparent surface reflectance, empirically adjusted using ground-based reflectance measurements, and combined into a mosaic with 23-m pixel spacing. Variations in water vapor and dust content of the atmosphere, in solar angle, and in surface elevation complicated correction; therefore, some classification differences may be present between adjacent flight lines. The reflectance spectrum of each pixel of HyMap™ imaging spectrometer data was compared to the reference materials in a spectral library of minerals, vegetation, water, and other materials. Minerals occurring abundantly at the surface and those having unique spectral features were easily detected and discriminated, while minerals having slightly different compositions but similar spectral features were less easily discriminated; thus, some map classes consist of several minerals having similar spectra, such as “Epidote or chlorite.” A designation of “Not classified” was assigned to the pixel when there was no match with reference spectra.

  6. The impact of auxins used in assisted phytoextraction of metals from the contaminated environment on the alterations caused by lead(II) ions in the organization of model lipid membranes.

    PubMed

    Hąc-Wydro, Katarzyna; Sroka, Aleksandra; Jabłońska, Klaudia

    2016-07-01

    Auxins are successfully used to improve phytoextraction efficiency of metal ions from the contaminated environment, however, the mechanism of their activity in this field is not explained. Auxins are known to exert various biochemical alterations in the plant membranes and cells, but their activity involves also direct interactions with lipids leading to changes in membrane organization. Following the suggestion that the auxins-induced modifications in membrane properties alleviate toxic effect of metal ions in this paper we have undertaken the comparative studies on the effect of metal ions and metal ions/auxins mixtures on model membrane systems. The experiments were done on lipid monolayers differing in their composition spread on water subphase and on Pb(2+), Indole-3-acetic acid (IAA), 1-Naphthaleneacetic acid (NAA) and Pb(2+)/IAA and Pb(2+)/NAA water solutions. The analysis of the collected data suggests that metal ions and auxins can change fluidity of the lipid systems and weaken the interactions between monolayer components. This manifested in the increase of the mean area per molecule and the excess area per molecule values for the films on Pb(2+), auxins as well as Pb(2+)/auxin solutions as compared to the values on pure water subphase. However, the presence of auxin in the mixture with lead(II) ions makes the alterations induced by sole metal ions weaker. This effect was more pronounced for the membranes of a higher packing. Thus it was proposed that auxins may enhance phytoextraction of metal ions by weakening their destabilizing effect on membrane. PMID:26998874

  7. Active Mapping.

    ERIC Educational Resources Information Center

    Day, Dennis

    1994-01-01

    Explains a social studies lesson for third graders that uses KidPix, a computer software graphics program to help students make maps and map keys. Advantages to using the computer versus hand drawing maps are discussed, and an example of map requirements for the lesson is included. (LRW)

  8. Concept Mapping.

    ERIC Educational Resources Information Center

    Callison, Daniel

    2001-01-01

    Explains concept mapping as a heuristic device that is helpful in visualizing the relationships between and among ideas. Highlights include how to begin a map; brainstorming; map applications, including document or information summaries and writing composition; and mind mapping to strengthen note-taking. (LRW)

  9. Contour Mapping

    NASA Technical Reports Server (NTRS)

    1995-01-01

    In the early 1990s, the Ohio State University Center for Mapping, a NASA Center for the Commercial Development of Space (CCDS), developed a system for mobile mapping called the GPSVan. While driving, the users can map an area from the sophisticated mapping van equipped with satellite signal receivers, video cameras and computer systems for collecting and storing mapping data. George J. Igel and Company and the Ohio State University Center for Mapping advanced the technology for use in determining the contours of a construction site. The new system reduces the time required for mapping and staking, and can monitor the amount of soil moved.

  10. Sensory experience modifies feature map relationships in visual cortex.

    PubMed

    Cloherty, Shaun L; Hughes, Nicholas J; Hietanen, Markus A; Bhagavatula, Partha S; Goodhill, Geoffrey J; Ibbotson, Michael R

    2016-01-01

    The extent to which brain structure is influenced by sensory input during development is a critical but controversial question. A paradigmatic system for studying this is the mammalian visual cortex. Maps of orientation preference (OP) and ocular dominance (OD) in the primary visual cortex of ferrets, cats and monkeys can be individually changed by altered visual input. However, the spatial relationship between OP and OD maps has appeared immutable. Using a computational model we predicted that biasing the visual input to orthogonal orientation in the two eyes should cause a shift of OP pinwheels towards the border of OD columns. We then confirmed this prediction by rearing cats wearing orthogonally oriented cylindrical lenses over each eye. Thus, the spatial relationship between OP and OD maps can be modified by visual experience, revealing a previously unknown degree of brain plasticity in response to sensory input. PMID:27310531

  11. Sensory experience modifies feature map relationships in visual cortex

    PubMed Central

    Cloherty, Shaun L; Hughes, Nicholas J; Hietanen, Markus A; Bhagavatula, Partha S

    2016-01-01

    The extent to which brain structure is influenced by sensory input during development is a critical but controversial question. A paradigmatic system for studying this is the mammalian visual cortex. Maps of orientation preference (OP) and ocular dominance (OD) in the primary visual cortex of ferrets, cats and monkeys can be individually changed by altered visual input. However, the spatial relationship between OP and OD maps has appeared immutable. Using a computational model we predicted that biasing the visual input to orthogonal orientation in the two eyes should cause a shift of OP pinwheels towards the border of OD columns. We then confirmed this prediction by rearing cats wearing orthogonally oriented cylindrical lenses over each eye. Thus, the spatial relationship between OP and OD maps can be modified by visual experience, revealing a previously unknown degree of brain plasticity in response to sensory input. DOI: http://dx.doi.org/10.7554/eLife.13911.001 PMID:27310531

  12. White matter alterations in temporal lobe epilepsy

    NASA Astrophysics Data System (ADS)

    Diniz, P. B.; Salmon, C. E.; Velasco, T. R.; Sakamoto, A. C.; Leite, J. P.; Santos, A. C.

    2011-03-01

    In This study, we used Fractional anisotropy (FA), mean diffusivity (D), parallel diffusivity (D//) and perpendicular diffusivity (D), to localize the regions where occur axonal lesion and demyelization. TBSS was applied to analyze the FA data. After, the regions with alteration were studied with D, D// and D maps. Patients exhibited widespread degradation of FA. With D, D// and D maps analysis we found alterations in corpus callosum, corticospinal tract, fornix, internal capsule, corona radiate, Sagittal stratum, cingulum, fronto-occipital fasciculus and uncinate fasciculus. Our results are consistent with the hypothesis that exist demyelization and axonal damage in patients with TLE.

  13. Genome-wide ChIP-seq mapping and analysis of butyrate-induced H3K9 and H3K27 acetylation and epigenomic landscape alteration in bovine cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Utilizing next-generation sequencing technology, combined with ChIP (Chromatin Immunoprecipitation) technology, we analyzed histone modification (acetylation) induced by butyrate and the large-scale mapping of the epigenomic landscape of normal histone H3 and acetylated histone H3K9 and H3K27. To d...

  14. Lactational exposure of phthalate causes long-term disruption in testicular architecture by altering tight junctional and apoptotic protein expression in Sertoli cells of first filial generation pubertal Wistar rats.

    PubMed

    Sekaran, S; Balaganapathy, P; Parsanathan, R; Elangovan, S; Gunashekar, J; Bhat, F A; Jagadeesan, A

    2015-06-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental contaminant and a well-known endocrine disruptor (ED) that interferes with the reproductive function in both humans and animals. This study aimed to find out the impact of lactational exposure of DEHP in testes of first filial generation (F1) progeny male rat postnatal day (PND)-60. Lactating dams were orally treated with DEHP (0, 1, 10 and 100 mg/kg body weight/day, respectively) from the PND-1 to PND-21. Rats were killed at PND 60. Testes were removed and used for histological analysis and for isolation of Sertoli cells (SCs). The histoarchitecture of DEHP-treated rats showed disturbed testicular structure. DEHP-treated rats also showed increased oxidative stress by decreasing antioxidant levels in the SCs; it disrupted SC tight junctional proteins occludin, claudin, junctional adhesion molecule, zona occludens protein-1 (ZO-1), zona occludens protein-2 (ZO-2), and afadin-6 (AF-6), increased apoptosis by altering the apoptotic genes Bax, cytochrome c, caspase-8, -9, -3 and antiapoptotic gene Bcl-2. It is concluded that early postnatal exposure to DEHP disturbs histoarchitecture of testis and SC function in pubertal Wistar rats. PMID:25352649

  15. RICH MAPS

    EPA Science Inventory

    Michael Goodchild recently gave eight reasons why traditional maps are limited as communication devices, and how interactive internet mapping can overcome these limitations. In the past, many authorities in cartography, from Jenks to Bertin, have emphasized the importance of sim...

  16. Kentucky map

    NASA Astrophysics Data System (ADS)

    A wall-sized geological map of Kentucky, the product of 18 years of work, has just been released. Produced by the U.S. Geological Survey (USGS) in cooperation with the Kentucky Geological Survey (KGS) at the University of Kentucky, the map is unique, according to state geologist Donald Haney, because it is the first and only state map ever produced in detailed form from geologic quadrangle maps already available from the KGS.At a scale of 1:250,000, the map shows the surface distribution of various types of rock throughout the state, as well as geologic structure, faults, and surface coal beds. Numerous geologic sections, stratigraphic diagrams, correlation charts, and structure sections accompany the map. Compiled by R. C. McDowell and S. L. Moore of the USGS and by G. J . Grabowski of the KGS, the map was made by photoreducing and generalizing the detailed geologic quadrangle maps.

  17. Map adventures

    USGS Publications Warehouse

    1994-01-01

    Map Adventures, with seven accompanying lessons, is appropriate for grades K-3. Students will learn basic concepts for visualizing objects from different perspectives and how to understand /and use maps.

  18. Stable learning of functional maps in self-organizing spiking neural networks with continuous synaptic plasticity

    PubMed Central

    Srinivasa, Narayan; Jiang, Qin

    2013-01-01

    This study describes a spiking model that self-organizes for stable formation and maintenance of orientation and ocular dominance maps in the visual cortex (V1). This self-organization process simulates three development phases: an early experience-independent phase, a late experience-independent phase and a subsequent refinement phase during which experience acts to shape the map properties. The ocular dominance maps that emerge accommodate the two sets of monocular inputs that arise from the lateral geniculate nucleus (LGN) to layer 4 of V1. The orientation selectivity maps that emerge feature well-developed iso-orientation domains and fractures. During the last two phases of development the orientation preferences at some locations appear to rotate continuously through ±180° along circular paths and referred to as pinwheel-like patterns but without any corresponding point discontinuities in the orientation gradient maps. The formation of these functional maps is driven by balanced excitatory and inhibitory currents that are established via synaptic plasticity based on spike timing for both excitatory and inhibitory synapses. The stability and maintenance of the formed maps with continuous synaptic plasticity is enabled by homeostasis caused by inhibitory plasticity. However, a prolonged exposure to repeated stimuli does alter the formed maps over time due to plasticity. The results from this study suggest that continuous synaptic plasticity in both excitatory neurons and interneurons could play a critical role in the formation, stability, and maintenance of functional maps in the cortex. PMID:23450808

  19. Activation of mouse macrophages causes no change in expression and function of phorbol diesters' receptors, but is accompanied by alterations in the activity and kinetic parameters of NADPH oxidase.

    PubMed Central

    Berton, G; Cassatella, M; Cabrini, G; Rossi, F

    1985-01-01

    Mouse peritoneal macrophages activated in vivo by the injection of Corynebacterium parvum release larger amounts of superoxide anion (O2-) than macrophages from control mice when stimulated with phorbol myristate acetate (PMA). The biochemical bases for this enhanced response of activated macrophages have been investigated by studying the expression and function of receptors for the stimulant, and the activity of the enzyme NADPH oxidase which is responsible for the production of O2- in leucocytes. Studies of binding of phorbol dibutyrate, an agent closely related to PMA, showed that the affinity constants (Kds) and the number of binding sites were the same in resident and activated peritoneal macrophages. The activity of the NADPH oxidase was, however, different in the two macrophage populations which differ in their capacity to release O2-. NADPH oxidase activity was studied in macrophage monolayers after lysis with deoxycholate. The main features of this activity were as follows: stimulation of macrophages with PMA or zymosan caused an increase in NADPH-dependent O2- production; NADPH oxidase activity in the lysates followed the same dose-response curve for different concentrations of PMA as O2- release by intact macrophages; O2- release by intact macrophages could be fully accounted for by NADPH-dependent O2- production by macrophage lysates; activity was strictly substrate-specific, in that NADH could not substitute for NADPH; after stimulation with PMA or zymosan, NADPH oxidase activity was higher in lysates of C. parvum-activated macrophages than in lysates of resident macrophages; NADPH oxidase activities of activated and resident macrophages differed markedly in their kinetic parameters. The NADPH oxidase of macrophages activated by C. parvum or trehalose dimycolate of mycobacterial origin displayed a five to seven times lower Km compared to the enzyme in resident macrophages. PMID:2981767

  20. Jaundice causes

    MedlinePlus

    ... liver is unable to properly move into the digestive tract. Conditions that can cause jaundice include: Infections of the liver from a virus ( hepatitis A , hepatitis B , hepatitis C , hepatitis D , ...

  1. Altered states: psychedelics and anesthetics.

    PubMed

    Icaza, Eduardo E; Mashour, George A

    2013-12-01

    The psychedelic experience has been reported since antiquity, but there is relatively little known about the underlying neural mechanisms. A recent neuroimaging study on psilocybin revealed a pattern of decreased cerebral blood flow and functional disconnections that is surprisingly similar to that caused by various anesthetics. In this article, the authors review historical examples of psychedelic experiences induced by general anesthetics and then contrast the mechanisms by which these two drug classes generate altered states of consciousness. PMID:24061599

  2. [Altered states of consciousness].

    PubMed

    Gora, E P

    2005-01-01

    The review of modern ideas concerning the altered states of consciousness is presented in this article. Various methods of entry into the altered states of consciousness are looked over. It is shown that the altered states of consciousness are insufficiently known, but important aspects of human being existence. The role of investigation of the altered states of consciousness for the creation of integrative scientific conception base is discussed. PMID:15810684

  3. Molecular cytogenetic characterization of cancer cell alterations.

    PubMed

    Popescu, N C; Zimonjic, D B

    1997-01-01

    Chromosomal abnormalities are the hallmark of cancer cells. Recurring and highly consistent structural and numerical alterations have been identified in a large number of leukemias, lymphomas, and solid tumors. The identification of recurrent genetic alterations and the isolation of molecular markers have clinical applications in the diagnosis and prognosis of neoplasia and in the detection of minimal residual disease that are essential for designing the most effective therapeutic approach. Polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) are powerful techniques for detection of genomic alterations. The battery of FISH methods and DNA probes that are available can resolve virtually any chromosomal alterations regardless of their complexity. Combined chromosome banding, multifluor or spectral karyotype, and comparative genomic hybridization (CGH) allow identification of structural and numerical alterations on a global basis, mapping of the DNA copy number on the entire tumor genome, complete derivation of complex rearrangements, and localization of the breakpoints of translocations and deletions. Regions of recurrent alterations can be microdisected, amplified, microclone libraries constructed and probes localized on extended chromosomes or chromatin fibers for construction of high resolution physical maps that are critical for positional cloning and gene identification. In this review we attempted to cover the current trends in cancer molecular cytogenetics, and to outline the importance of molecular chromosome analysis in the understanding of oncogenesis and its clinical applications. PMID:9062575

  4. The hydrothermal alteration of cooling lava domes

    NASA Astrophysics Data System (ADS)

    Ball, Jessica L.; Stauffer, Philip H.; Calder, Eliza S.; Valentine, Greg A.

    2015-12-01

    Hydrothermal alteration is a recognized cause of volcanic instability and edifice collapse, including that of lava domes or dome complexes. Alteration by percolating fluids transforms primary minerals in dome lavas to weaker secondary products such as clay minerals; moreover, secondary mineral precipitation can affect the porosity and permeability of dome lithologies. The location and intensity of alteration in a dome depend heavily on fluid pathways and availability in conjunction with heat supply. Here we investigate postemplacement lava dome weakening by hydrothermal alteration using a finite element numerical model of water migration in simplified dome geometries. This is combined with the rock alteration index (RAI) to predict zones of alteration and secondary mineral precipitation. Our results show that alteration potential is highest at the interface between the hot core of a lava dome and its clastic talus carapace. The longest lived alteration potential fields occur in domes with persistent heat sources and permeabilities that allow sufficient infiltration of water for alteration processes, but not so much that domes cool quickly. This leads us to conclude that alteration-induced collapses are most likely to be shallow seated and originate in the talus or talus/core interface in domes which have a sustained supply of magmatic heat. Mineral precipitation at these zones of permeability contrast could create barriers to fluid flow, potentially causing gas pressurization which might promote deeper seated and larger volume collapses. This study contributes to our knowledge of how hydrothermal alteration can affect lava domes and provides constraints on potential sites for alteration-related collapses, which can be used to target hazard monitoring.

  5. Color on emergency mapping

    NASA Astrophysics Data System (ADS)

    Jiang, Lili; Qi, Qingwen; Zhang, An

    2007-06-01

    There are so many emergency issues in our daily life. Such as typhoons, tsunamis, earthquake, fires, floods, epidemics, etc. These emergencies made people lose their lives and their belongings. Every day, every hour, even every minute people probably face the emergency, so how to handle it and how to decrease its hurt are the matters people care most. If we can map it exactly before or after the emergencies; it will be helpful to the emergency researchers and people who live in the emergency place. So , through the emergency map, before emergency is occurring we can predict the situation, such as when and where the emergency will be happen; where people can refuge, etc. After disaster, we can also easily assess the lost, discuss the cause and make the lost less. The primary effect of mapping is offering information to the people who care about the emergency and the researcher who want to study it. Mapping allows the viewers to get a spatial sense of hazard. It can also provide the clues to study the relationship of the phenomenon in emergency. Color, as the basic element of the map, it can simplify and clarify the phenomenon. Color can also affects the general perceptibility of the map, and elicits subjective reactions to the map. It is to say, structure, readability, and the reader's psychological reactions can be affected by the use of color.

  6. Mapping Van

    NASA Technical Reports Server (NTRS)

    1994-01-01

    A NASA Center for the Commercial Development of Space (CCDS) - developed system for satellite mapping has been commercialized for the first time. Global Visions, Inc. maps an area while driving along a road in a sophisticated mapping van equipped with satellite signal receivers, video cameras and computer systems for collecting and storing mapping data. Data is fed into a computerized geographic information system (GIS). The resulting amps can be used for tax assessment purposes, emergency dispatch vehicles and fleet delivery companies as well as other applications.

  7. Hirsutinolide Series Inhibit Stat3 Activity, Alter GCN1, MAP1B, Hsp105, G6PD, Vimentin, TrxR1, and Importin α-2 Expression, and Induce Antitumor Effects against Human Glioma.

    PubMed

    Miklossy, Gabriella; Youn, Ui Joung; Yue, Peibin; Zhang, Mingming; Chen, Chih-Hong; Hilliard, Tyvette S; Paladino, David; Li, Yifei; Choi, Justin; Sarkaria, Jann N; Kawakami, Joel K; Wongwiwatthananukit, Supakit; Chen, Yuan; Sun, Dianqing; Chang, Leng Chee; Turkson, James

    2015-10-01

    We report that hirsutinolide series, 6, 7, 10, 11, 20, and 22, and the semisynthetic analogues, 30, 31, 33, and 36, inhibit constitutively active signal transducer and activator of transcription (Stat)3 and malignant glioma phenotype. A position 13 lipophilic ester group is required for activity. Molecular modeling and nuclear magnetic resonance structural analyses reveal direct hirsutinolide:Stat3 binding. One-hour treatment of cells with 6 and 22 also upregulated importin subunit α-2 levels and repressed translational activator GCN1, microtubule-associated protein (MAP)1B, thioredoxin reductase (TrxR)1 cytoplasmic isoform 3, glucose-6-phosphate 1-dehydrogenase isoform a, Hsp105, vimentin, and tumor necrosis factor α-induced protein (TNAP)2 expression. Active hirsutinolides inhibited anchorage-dependent and three-dimensional spheroid growth, survival, and migration of human glioma lines and glioma patients' tumor-derived xenograft cells harboring constitutively active Stat3. Oral gavage delivery of 6 or 22 inhibited human glioma tumor growth in subcutaneous mouse xenografts. The inhibition of Stat3 signaling represents part of the hirsutinolide-mediated mechanisms to induce antitumor effects. PMID:26331426

  8. The Loss and Gain of Functional Amino Acid Residues Is a Common Mechanism Causing Human Inherited Disease

    PubMed Central

    Lugo-Martinez, Jose; Pejaver, Vikas; Pagel, Kymberleigh A.; Mort, Matthew; Cooper, David N.; Mooney, Sean D.; Radivojac, Predrag

    2016-01-01

    Elucidating the precise molecular events altered by disease-causing genetic variants represents a major challenge in translational bioinformatics. To this end, many studies have investigated the structural and functional impact of amino acid substitutions. Most of these studies were however limited in scope to either individual molecular functions or were concerned with functional effects (e.g. deleterious vs. neutral) without specifically considering possible molecular alterations. The recent growth of structural, molecular and genetic data presents an opportunity for more comprehensive studies to consider the structural environment of a residue of interest, to hypothesize specific molecular effects of sequence variants and to statistically associate these effects with genetic disease. In this study, we analyzed data sets of disease-causing and putatively neutral human variants mapped to protein 3D structures as part of a systematic study of the loss and gain of various types of functional attribute potentially underlying pathogenic molecular alterations. We first propose a formal model to assess probabilistically function-impacting variants. We then develop an array of structure-based functional residue predictors, evaluate their performance, and use them to quantify the impact of disease-causing amino acid substitutions on catalytic activity, metal binding, macromolecular binding, ligand binding, allosteric regulation and post-translational modifications. We show that our methodology generates actionable biological hypotheses for up to 41% of disease-causing genetic variants mapped to protein structures suggesting that it can be reliably used to guide experimental validation. Our results suggest that a significant fraction of disease-causing human variants mapping to protein structures are function-altering both in the presence and absence of stability disruption. PMID:27564311

  9. Epigenetic Alterations in Alzheimer's Disease.

    PubMed

    Sanchez-Mut, Jose V; Gräff, Johannes

    2015-01-01

    Alzheimer's disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD. PMID:26734709

  10. Dietary turmeric modulates DMBA-induced p21{sup ras}, MAP kinases and AP-1/NF-{kappa}B pathway to alter cellular responses during hamster buccal pouch carcinogenesis

    SciTech Connect

    Garg, Rachana; Ingle, Arvind; Maru, Girish

    2008-11-01

    The chemopreventive efficacy of turmeric has been established in experimental systems. However, its mechanism(s) of action are not fully elucidated in vivo. The present study investigates the mechanism of turmeric-mediated chemoprevention in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis at 2, 4, 6, 10 and 12 weeks. Dietary turmeric (1%) led to decrease in DMBA-induced tumor burden and multiplicity, and enhanced the latency period in parallel, to its modulatory effects on oncogene products and various cellular responses during HBP tumorigenesis. DMBA-induced expression of ras oncogene product, p21 and downstream target, the mitogen-activated protein kinases were significantly decreased by turmeric during HBP carcinogenesis. Turmeric also diminished the DMBA-induced mRNA expression of proto-oncogenes (c-jun, c-fos) and NF-{kappa}B, leading to decreased protein levels and in further attenuation of DMBA-induced AP-1/NF-{kappa}B DNA-binding in the buccal pouch nuclear extracts. Besides, buccal pouch of hamsters receiving turmeric diet showed significant alterations in DMBA-induced effects: (a) decrease in cell proliferation (diminished PCNA and Bcl2 expression), (b) enhanced apoptosis (increased expression of Bax, caspase-3 and apoptotic index), (c) decrease in inflammation (levels of Cox-2, the downstream target of AP-1/NF-{kappa}B, and PGE2) and (d) aberrant expression of differentiation markers, the cytokeratins (1, 5, 8, and 18). Together, the protective effects of dietary turmeric converge on augmenting apoptosis of the initiated cells and decreasing cell proliferation in DMBA-treated animals, which in turn, is reflected in decreased tumor burden, multiplicity and enhanced latency period. Some of these biomarkers are likely to be helpful in monitoring clinical trials and evaluating drug effect measurements.

  11. Undersea Mapping.

    ERIC Educational Resources Information Center

    DiSpezio, Michael A.

    1991-01-01

    Presented is a cooperative learning activity in which students assume different roles in an effort to produce a relief map of the ocean floor. Materials, procedures, definitions, student roles, and questions are discussed. A reproducible map for the activity is provided. (CW)

  12. Question Mapping

    ERIC Educational Resources Information Center

    Martin, Josh

    2012-01-01

    After accepting the principal position at Farmersville (TX) Junior High, the author decided to increase instructional rigor through question mapping because of the success he saw using this instructional practice at his prior campus. Teachers are the number one influence on student achievement (Marzano, 2003), so question mapping provides a…

  13. Map Adventures.

    ERIC Educational Resources Information Center

    Geological Survey (Dept. of Interior), Reston, VA.

    This curriculum packet about maps, with seven accompanying lessons, is appropriate for students in grades K-3. Students learn basic concepts for visualizing objects from different perspectives and how to understand and use maps. Lessons in the packet center on a story about a little girl, Nikki, who rides in a hot-air balloon that gives her, and…

  14. Developmental exposure to paracetamol causes biochemical alterations in medulla oblongata.

    PubMed

    Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Jawna, Katarzyna; Pyrzanowska, Justyna; Piechal, Agnieszka; Wawer, Adriana; Widy-Tyszkiewicz, Ewa

    2015-09-01

    The effect and safety of prenatal and early life administration of paracetamol - routinely used over-the-counter antipyretic and analgesic medication on monoamines content and balance of amino acids in the medulla oblongata is still unknown. In this study we have determined the level of neurotransmitters in this structure in two-month old Wistar male rats exposed to paracetamol in the dose of 5 (P5, n=10) or 15mg/kg b.w. (P15, n=10) during prenatal period, lactation and till the end of the second month of life. Control group received drinking water (Con, n=10). Monoamines, their metabolites and amino acids concentration in medulla oblongata of rats were determined using high performance liquid chromatography (HPLC) in 60 postnatal day (PND60). This experiment shows that prenatal and early life paracetamol exposure modulates neurotransmission associated with serotonergic, noradrenergic and dopaminergic system in medulla oblongata. Reduction of alanine and taurine levels has also been established. PMID:26233562

  15. Altered motility causes the early gastrointestinal toxicity of irradiation

    SciTech Connect

    Erickson, B.A.; Moulder, J.E.; Otterson, M.F.; Sarna, S.K. )

    1994-03-01

    This article reviews studies of large and small intestinal contractile activity following radiation exposure. Studies of motility utilize strain gauge transducers surgically implanted on the seromuscular layer of the small intestine. All studies were performed in mixed breed dogs to record the occurrence of normal contractions, giant migrating contractions (GMCs) and retrograde giant contractions (RGCs) before, during and after irradiation (22.5 Gy in 9 fractions at 3 fractions/week). Giant migrating contractions and retrograde giant contractions are infrequent in the healthy state. However, in diseased states, GMCs are associated with abdominal cramps and diarrhea, and RGCs precede vomiting. In fasted animals, fractionated abdominal irradiation dramatically increased the frequency of GMCs, with the incidence peaking after the second dose. The increased frequency of GMCS occurred as early as a few hours after the first radiation fraction, and returned to normal within days of cessation of radiation. RGCs were also significantly increased after abdominal irradiation. The frequency of RGCs was greatest on the first and sixth dose of radiation. Clinically, the dogs developed nausea, vomiting and diarrhea as early as the first day of irradiation. In dogs studied in the fed state, decreased amplitude, duration, and frequency of postprandial contractions occurred. These changes may slow intestinal transit during irradiation. Radiation also produced a striking increase in the frequency of colonic GMCs; these changes in colonic motor activity were associated with diarrhea as early as the second irradiation. Changes in GI motility during fractionated irradiation precede the appearance of histopathological lesions in the GI tract. Thus, the symptoms of nausea, vomiting, and diarrhea experienced during radiotherapy (particularly those within the first week) are directly related to changes in bowel motility. 41 refs., 7 figs., 1 tab.

  16. Rare causes of osteoporosis

    PubMed Central

    Marcucci, Gemma; Brandi, Maria Luisa

    2015-01-01

    Summary Osteoporosis is a metabolic bone disease characterized by loss of bone mass and strength, resulting in increased risk of fractures. It is classically divided into primary (post-menopausal or senile), secondary and idiopathic forms. There are many rare diseases, that cause directly or indirectly osteoporosis. The identification and classification of most of these rare causes of osteoporosis is crucial for the specialists in endocrinology and not, in order to prevent this bone complication and to provide for an early therapy. Several pathogenic mechanisms are involved, including various aspects of bone metabolism such as: decreased bone formation, increased bone resorption, altered calcium, phosphorus and/or vitamin D homeostasis, and abnormal collagen synthesis. In this review, less common forms of primary and secondary osteoporosis are described, specifying, if applicable: genetic causes, epidemiology, clinical features, and pathogenic mechanisms causing osteoporosis. A greater awareness of all rare causes of osteoporosis could reduce the number of cases classified as idiopathic osteoporosis and allow the introduction of appropriate and timely treatments. PMID:26604941

  17. Amazing Altered Books

    ERIC Educational Resources Information Center

    Kieling, Linda W.

    2006-01-01

    Linda Kieling, an art teacher at Rosemont Ridge Middle school in West Linn, Oregon, describes an altered book art project she introduced to her students. Alteration of books is a form of recycling that started in the eleventh century when Italian monks recycled old manuscripts written on vellum by scraping off the ink and adding new text and…

  18. Semantic Mapping.

    ERIC Educational Resources Information Center

    Johnson, Dale D.; And Others

    1986-01-01

    Describes semantic mapping, an effective strategy for vocabulary instruction that involves the categorical structuring of information in graphic form and requires students to relate new words to their own experience and prior knowledge. (HOD)

  19. Mapping Biodiversity.

    ERIC Educational Resources Information Center

    World Wildlife Fund, Washington, DC.

    This document features a lesson plan that examines how maps help scientists protect biodiversity and how plants and animals are adapted to specific ecoregions by comparing biome, ecoregion, and habitat. Samples of instruction and assessment are included. (KHR)

  20. Map Separates

    USGS Publications Warehouse

    U.S. Geological Survey

    2001-01-01

    U.S. Geological Survey (USGS) topographic maps are printed using up to six colors (black, blue, green, red, brown, and purple). To prepare your own maps or artwork based on maps, you can order separate black-and-white film positives or negatives for any color printed on a USGS topographic map, or for one or more of the groups of related features printed in the same color on the map (such as drainage and drainage names from the blue plate.) In this document, examples are shown with appropriate ink color to illustrate the various separates. When purchased, separates are black-and-white film negatives or positives. After you receive a film separate or composite from the USGS, you can crop, enlarge or reduce, and edit to add or remove details to suit your special needs. For example, you can adapt the separates for making regional and local planning maps or for doing many kinds of studies or promotions by using the features you select and then printing them in colors of your choice.

  1. Venus mapping

    NASA Technical Reports Server (NTRS)

    Batson, R. M.; Morgan, H. F.; Sucharski, Robert

    1991-01-01

    Semicontrolled image mosaics of Venus, based on Magellan data, are being compiled at 1:50,000,000, 1:10,000,000, 1:5,000,000, and 1:1,000,000 scales to support the Magellan Radar Investigator (RADIG) team. The mosaics are semicontrolled in the sense that data gaps were not filled and significant cosmetic inconsistencies exist. Contours are based on preliminary radar altimetry data that is subjected to revision and improvement. Final maps to support geologic mapping and other scientific investigations, to be compiled as the dataset becomes complete, will be sponsored by the Planetary Geology and Geophysics Program and/or the Venus Data Analysis Program. All maps, both semicontrolled and final, will be published as I-maps by the United States Geological Survey. All of the mapping is based on existing knowledge of the spacecraft orbit; photogrammetric triangulation, a traditional basis for geodetic control on planets where framing cameras were used, is not feasible with the radar images of Venus, although an eventual shift of coordinate system to a revised spin-axis location is anticipated. This is expected to be small enough that it will affect only large-scale maps.

  2. Altered Mental Status and Delirium.

    PubMed

    Wilber, Scott T; Ondrejka, Jason E

    2016-08-01

    Older patients who present to the emergency department frequently have acute or chronic alterations of their mental status, including their level of consciousness and cognition. Recognizing both acute and chronic changes in cognition are important for emergency physicians. Delirium is an acute change in attention, awareness, and cognition. Numerous life-threatening conditions can cause delirium; therefore, prompt recognition and treatment are critical. The authors discuss an organized approach that can lead to a prompt diagnosis within the time constraints of the emergency department. PMID:27475019

  3. Concept Maps and Language: A Turkish Experience

    ERIC Educational Resources Information Center

    Kilic, Gulsen Bagci

    2003-01-01

    Concept maps are being used by an increasing number of educators in Europe and the US. This paper has four goals. First, it discusses problems in developing Novak's style concept maps in Turkish caused by linguistic differences between Turkish and English. Second, it reports the findings of a research study conducted to adapt concept maps to…

  4. Computer-Based Concept Mapping: Active Studying for Active Learners.

    ERIC Educational Resources Information Center

    Anderson-Inman, Lynne; Zeitz, Leigh

    1993-01-01

    Describes the use of computer-generated concept maps using a new genre of graphics programs that allows students to create, alter and expand maps as they acquire more subject matter knowledge. Four examples of increasingly complex concept maps developed by a high school student studying cellular biology are discussed and illustrated. (Contains 19…

  5. Acoustic trauma caused by lightning.

    PubMed

    Mora-Magaña, I; Collado-Corona, M A; Toral-Martiñòn, R; Cano, A

    1996-03-01

    Lesions produced by exposure to noise are frequent in everyday life. Injuries may be found in all systems of the human body, from the digestive to the endocrine, from the cardiovascular to the nervous system. Many organs may be damaged, the ear being one of them. It is known that noise produced by factories, airports, musical instruments and even toys can cause auditory loss. Noises in nature can also cause acoustic trauma. This report is the case history of acoustic trauma caused by lightning. The patient was studied with CAT scan, electroencephalogram, and brain mapping, impedance audiometry with tympanogram and acoustic reflex, audiometry and evoked otoacoustics emissions: distortion products and transients. PMID:8882110

  6. Parametric mapping

    NASA Astrophysics Data System (ADS)

    Branch, Allan C.

    1998-01-01

    Parametric mapping (PM) lies midway between older and proven artificial landmark based guidance systems and yet to be realized vision based guidance systems. It is a simple yet effective natural landmark recognition system offering freedom from the need for enhancements to the environment. Development of PM systems can be inexpensive and rapid and they are starting to appear in commercial and industrial applications. Together with a description of the structural framework developed to generically describe robot mobility, this paper illustrates clearly the parts of any mobile robot navigation and guidance system and their interrelationships. Among other things, the importance of the richness of the reference map, and not necessarily the sensor map, is introduced, the benefits of dynamic path planners to alleviate the need for separate object avoidance, and the independence of the PM system to the type of sensor input is shown.

  7. Brain injury causes loss of cardiovascular response to hemorrhagic shock.

    PubMed

    Fulton, R L; Flynn, W J; Mancino, M; Bowles, D; Cryer, H M

    1993-01-01

    The combined cardiovascular effects of hemorrhagic shock and mechanical brain injury were modeled in five groups of pigs. Standard and hypertonic saline resuscitation of hypotension were evaluated. Changes in mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), intracranial pressure (ICP), and brain water were measured. Brain injury (BI) was produced with a fluid percussion device that generated an extradural pressure of 3.5 x 10(5) N/m2 for 400 msec. Shock was caused by bleeding to a MAP of 60 mm Hg for 60 minutes and then resuscitated with shed blood only or shed blood plus 0.9% or 1.8% saline. Brain-injured only and shocked-only pigs served as controls. We found that brain injury alone caused refractory hypotension. Less shed blood was required to produce shock in brain injured animals (p < .05). Shock accompanied by brain injury was not reversed with crystalloid solutions. Volumes of saline required to restore blood pressure were large (> 6 L in 3 hours). 1.8% saline produced less rise in ICP than 0.9% saline but was less effective in restoring blood pressure. Brain edema was not decreased with 1.8% saline. Brain injury altered vascular compensation to hemorrhage and made accepted resuscitative measures ineffective. PMID:8512886

  8. Memphis Maps.

    ERIC Educational Resources Information Center

    Hyland, Stanley; Cox, David; Martin, Cindy

    1998-01-01

    The Memphis Maps program, a collaborative effort of Memphis (Tennessee) educational institutions, public agencies, a bank, and community programs, trains local students in Geographic Information Systems technology and provides the community with valuable demographic and assessment information. The program is described, and factors contributing to…

  9. Psychobiology of Altered States of Consciousness

    ERIC Educational Resources Information Center

    Vaitl, Dieter; Birbaumer, Niels; Gruzelier, John; Jamieson, Graham A.; Kotchoubey, Boris; Kubler, Andrea; Lehmann, Dietrich; Miltner, Wolfgang H. R.; Ott, Ulrich; Sammer, Gebhard; Strauch, Inge; Strehl, Ute; Wackermann, Jiri; Weiss, Thomas

    2005-01-01

    The article reviews the current knowledge regarding altered states of consciousness (ASC) (a) occurring spontaneously, (b) evoked by physical and physiological stimulation, (c) induced by psychological means, and (d) caused by diseases. The emphasis is laid on psychological and neurobiological approaches. The phenomenological analysis of the…

  10. Nicotinic alteration of functional thalamocortical topography.

    PubMed

    Lee, Charles C; Yanagawa, Yuchio; Imaizumi, Kazuo

    2015-08-19

    The thalamocortical pathways form highly topographic connections from the primary sensory thalamic nuclei to the primary cortical areas. The synaptic properties of these thalamocortical connections are modifiable by activation from various neuromodulators, such as acetylcholine. Cholinergic activation can alter functional properties in both the developing and the mature nervous system. Moreover, environmental factors, such as nicotine, can activate these receptors, although the circuit-level alterations resulting from such nicotinic activation of sensory neural circuits remain largely unexplored. Therefore, we examined alterations to the functional topography of thalamocortical circuits in the developing sensory pathways of the mouse. Photostimulation by uncaging of glutamate was used to map these functional thalamocortical alterations in response to nicotinic receptor activation. As a result, we found that activation of forebrain nicotinic acetylcholine receptors results in an expansion and enhancement of functional thalamocortical topographies as assessed in brain slice preparations using laser-scanning photostimulation by uncaging of glutamate. These physiological changes were correlated with the neuroanatomical expression of nicotinic acetylcholine receptor subtypes (α7 and β2). These circuit-level alterations may provide a neural substrate underlying the plastic development and reshaping of thalamocortical circuitry in response to nicotinic receptor activation. PMID:26164456

  11. Thermal maturity patterns (conodont color alteration index and vitrinite reflectance) in Upper Ordovician and Devonian rocks of the Appalachian basin: a major revision of USGS Map I-917-E using new subsurface collections: Chapter F.1 in Coal and petroleum resources in the Appalachian basin: distribution, geologic framework, and geochemical character

    USGS Publications Warehouse

    Repetski, John E.; Ryder, Robert T.; Weary, David J.; Harris, Anita G.; Trippi, Michael H.

    2014-01-01

    The conodont color alteration index (CAI) introduced by Epstein and others (1977) and Harris and others (1978) is an important criterion for estimating the thermal maturity of Ordovician to Mississippian rocks in the Appalachian basin. Consequently, the CAI isograd maps of Harris and others (1978) are commonly used by geologists to characterize the thermal and burial history of the Appalachian basin and to better understand the origin and distribution of oil and gas resources in the basin. The main objectives of this report are to present revised CAI isograd maps for Ordovician and Devonian rocks in the Appalachian basin and to interpret the geologic and petroleum resource implications of these maps. The CAI isograd maps presented herein complement, and in some areas replace, the CAI-based isograd maps of Harris and others (1978) for the Appalachian basin. The CAI data presented in this report were derived almost entirely from subsurface samples, whereas the CAI data used by Harris and others (1978) were derived almost entirely from outcrop samples. Because of the different sampling methods, there is little geographic overlap of the two data sets. The new data set is mostly from the Allegheny Plateau structural province and most of the data set of Harris and others (1978) is from the Valley and Ridge structural province, east of the Allegheny structural front (fig. 1). Vitrinite reflectance, based on dispersed vitrinite in Devonian black shale, is another important parameter for estimating the thermal maturity in pre-Pennsylvanian-age rocks of the Appalachian basin (Streib, 1981; Cole and others, 1987; Gerlach and Cercone, 1993; Rimmer and others, 1993; Curtis and Faure, 1997). This chapter also presents a revised percent vitrinite reflectance (%R0) isograd map based on dispersed vitrinite recovered from selected Devonian black shales. The Devonian black shales used for the vitrinite studies reported herein also were analyzed by RockEval pyrolysis and total organic

  12. Chemical and Mechanical Alteration of Fractures: Micro-Scale Simulations and Comparison to Experimental Results

    NASA Astrophysics Data System (ADS)

    Ameli, P.; Detwiler, R. L.; Elkhoury, J. E.; Morris, J. P.

    2012-12-01

    Fractures are often the main pathways for subsurface fluid flow especially in rocks with low matrix porosity. Therefore, the hydro-mechanical properties of fractures are of fundamental concern for subsurface CO2 sequestration, enhanced geothermal energy production, enhanced oil recovery, and nuclear waste disposal. Chemical and mechanical stresses induced during these applications may lead to significant alteration of the hydro-mechanical properties of fractures. Laboratory experiments aimed at understanding the chemo-hydro-mechanical response of fractures have shown a range of results that contradict simple conceptual models. For example, under conditions favoring mineral dissolution, where one would expect an overall increase in permeability and fracture aperture, permeability increases under some conditions and decreases under others. Recent experiments have attempted to link these core-scale observations to the relevant small-scale processes occurring within fractures. Results suggest that the loss of mechanical strength in asperities due to chemical alteration may cause non-uniform deformation and alteration of fracture apertures. However, it remains difficult to directly measure the coupled chemical and mechanical processes that lead to alteration of contacting fracture surfaces, which challenges our ability to predict the long-term evolution of the hydro-mechanical properties of fractures. Here, we present a computational model that uses micro-scale surface roughness and explicitly couples dissolution and elastic deformation to calculate local alterations in fracture aperture under chemical and mechanical stresses. Chemical alteration of the fracture surfaces is modeled using a depth-averaged algorithm of fracture flow and reactive transport. Then, we deform the resulting altered fracture-surfaces using an algorithm that calculates the elastic deformation. Nonuniform dissolution may cause the location of the resultant force between the two contacting

  13. Attention Alters Perceived Attractiveness.

    PubMed

    Störmer, Viola S; Alvarez, George A

    2016-04-01

    Can attention alter the impression of a face? Previous studies showed that attention modulates the appearance of lower-level visual features. For instance, attention can make a simple stimulus appear to have higher contrast than it actually does. We tested whether attention can also alter the perception of a higher-order property-namely, facial attractiveness. We asked participants to judge the relative attractiveness of two faces after summoning their attention to one of the faces using a briefly presented visual cue. Across trials, participants judged the attended face to be more attractive than the same face when it was unattended. This effect was not due to decision or response biases, but rather was due to changes in perceptual processing of the faces. These results show that attention alters perceived facial attractiveness, and broadly demonstrate that attention can influence higher-level perception and may affect people's initial impressions of one another. PMID:26966228

  14. Meiotic Mutants That Cause a Polar Decrease in Recombination on the X Chromosome in Caenorhabditis Elegans

    PubMed Central

    Broverman, S. A.; Meneely, P. M.

    1994-01-01

    Recessive mutations in three autosomal genes, him-1, him-5 and him-8, cause high levels of X chromosome nondisjunction in hermaphrodites of Caenorhabditis elegans, with no comparable effect on autosomal disjunction. Each of the mutants has reduced levels of X chromosome recombination, correlating with the increase in nondisjunction. However, normal or elevated levels of recombination occur at the end of the X chromosome hypothesized to contain the pairing region (the left end), with recombination levels decreasing in regions approaching the right end. Thus, both the number and the distribution of X chromosome exchange events are altered in these mutants. As a result, the genetic map of the X chromosome in the him mutants exhibits a clustering of genes due to reduced recombination, a feature characteristic of the genetic map of the autosomes in non-mutant animals. We hypothesize that these him genes are needed for some processive event that initiates near the left end of the X chromosome. PMID:8138150

  15. Meiotic mutants that cause a polar decrease in recombination on the X chromosome in Caenorhabditis elegans.

    PubMed

    Broverman, S A; Meneely, P M

    1994-01-01

    Recessive mutations in three autosomal genes, him-1, him-5 and him-8, cause high levels of X chromosome nondisjunction in hermaphrodites of Caenorhabditis elegans, with no comparable effect on autosomal disjunction. Each of the mutants has reduced levels of X chromosome recombination, correlating with the increase in nondisjunction. However, normal or elevated levels of recombination occur at the end of the X chromosome hypothesized to contain the pairing region (the left end), with recombination levels decreasing in regions approaching the right end. Thus, both the number and the distribution of X chromosome exchange events are altered in these mutants. As a result, the genetic map of the X chromosome in the him mutants exhibits a clustering of genes due to reduced recombination, a feature characteristic of the genetic map of the autosomes in non-mutant animals. We hypothesize that these him genes are needed for some processive event that initiates near the left end of the X chromosome. PMID:8138150

  16. How Misinformation Alters Memories.

    ERIC Educational Resources Information Center

    Wright, Daniel B.; Loftus, Elizabeth F.

    1998-01-01

    Notes that a multitude of studies have demonstrated that misleading postevent information affects people's memories. Contents that the fuzzy-trace theory is a positive step toward understanding the malleability of memory. Discusses fuzzy-trace theory in terms of three primary areas of study: altered response format, maximized misinformation…

  17. Immunization alters body odor.

    PubMed

    Kimball, Bruce A; Opiekun, Maryanne; Yamazaki, Kunio; Beauchamp, Gary K

    2014-04-10

    Infections have been shown to alter body odor. Because immune activation accompanies both infection and immunization, we tested the hypothesis that classical immunization might similarly result in the alteration of body odors detectable by trained biosensor mice. Using a Y-maze, we trained biosensor mice to distinguish between urine odors from rabies-vaccinated (RV) and unvaccinated control mice. RV-trained mice generalized this training to mice immunized with the equine West Nile virus (WNV) vaccine compared with urine of corresponding controls. These results suggest that there are similarities between body odors of mice immunized with these two vaccines. This conclusion was reinforced when mice could not be trained to directly discriminate between urine odors of RV- versus WNV-treated mice. Next, we trained biosensor mice to discriminate the urine odors of mice treated with lipopolysaccharide (LPS; a general elicitor of innate immunological responses) from the urine of control mice. These LPS-trained biosensors could distinguish between the odors of LPS-treated mouse urine and RV-treated mouse urine. Finally, biosensor mice trained to distinguish between the odors of RV-treated mouse urine and control mouse urine did not generalize this training to discriminate between the odors of LPS-treated mouse urine and control mouse urine. From these experiments, we conclude that: (1) immunization alters urine odor in similar ways for RV and WNV immunizations; and (2) immune activation with LPS also alters urine odor but in ways different from those of RV and WNV. PMID:24524972

  18. Towards a global land subsidence map

    NASA Astrophysics Data System (ADS)

    Erkens, G.; Sutanudjaja, E. H.

    2015-11-01

    Land subsidence is a global problem, but a global land subsidence map is not available yet. Such map is crucial to raise global awareness of land subsidence, as land subsidence causes extensive damage (probably in the order of billions of dollars annually). With the global land subsidence map relative sea level rise predictions may be improved, contributing to global flood risk calculations. In this paper, we discuss the approach and progress we have made so far in making a global land subsidence map. Initial results will be presented and discussed, and we give an outlook on the work needed to derive a global land subsidence map.

  19. Violent Video Games Alter Brain Function in Young Men

    MedlinePlus

    ... and Updates News from the RSNA Annual Meeting Violent Video Games Alter Brain Function in Young Men ... Using functional MRI, researchers have found that playing violent video games for one week causes changes in ...

  20. Distortions of glacial landform sizes by manual mapping

    NASA Astrophysics Data System (ADS)

    Hillier, John K.; Smith, Mike J.

    2016-04-01

    Mapped topographic features are important for understanding processes that sculpt the Earth's surface. Subjective manual techniques are commonly used for mapping, yet how effective they are in quantitative terms is poorly constrained. Here 12,121 outlines drawn by 25 interpreters searching for a total of 21,625 drumlins in 5 synthetic DEMs are interpreted in terms of how the manual mapping process distorts the height (H), width (W) and length (L) of the reported features. Bias in the size-frequency distributions is caused by the sub-set of the forms 'found', even assuming perfect extraction of sizes, and is governed by H driving detectability. Bias is then compounded in sizes that are extracted using the mapped outlines but, remarkably, the size-frequency distribution is not altered further when mappers' incorrect guesses (i.e. outline corresponds to no input synthetic drumlin) are then included; it seems possible that, once mappers have their 'eye in' based on the most clearly defined features, they are very effective at identifying similar morphologies. Of the metrics available to quantify the size of a population, maximum size and λ, the exponent of its tail, are the most robust to these distortions. The drumlins in the study area resemble UK drumlins, permitting extrapolation of the conclusions. These are the first results to give such granular insights into the impacts of the various stages in manually mapping glacial landforms, permitted by the development of the synthetic DEMs. Arguments will always exist about how realistic any synthetic is, but this work demonstrates another use of synthetic DEMs that may be applied more widely in geomorphology.

  1. Distribution of hydrothermally altered rocks in the Reko Diq, Pakistan mineralized area based on spectral analysis of ASTER data

    USGS Publications Warehouse

    Rowan, L.C.; Schmidt, R.G.; Mars, J.C.

    2006-01-01

    The Reko Diq, Pakistan mineralized study area, approximately 10??km in diameter, is underlain by a central zone of hydrothermally altered rocks associated with Cu-Au mineralization. The surrounding country rocks are a variable mixture of unaltered volcanic rocks, fluvial deposits, and eolian quartz sand. Analysis of 15-band Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data of the study area, aided by laboratory spectral reflectance and spectral emittance measurements of field samples, shows that phyllically altered rocks are laterally extensive, and contain localized areas of argillically altered rocks. In the visible through shortwave-infrared (VNIR + SWIR) phyllically altered rocks are characterized by Al-OH absorption in ASTER band 6 because of molecular vibrations in muscovite, whereas argillically altered rocks have an absorption feature in band 5 resulting from alunite. Propylitically altered rocks form a peripheral zone and are present in scattered exposures within the main altered area. Chlorite and muscovite cause distinctive absorption features at 2.33 and 2.20????m, respectively, although less intense 2.33????m absorption is also present in image spectra of country rocks. Important complementary lithologic information was derived by analysis of the spectral emittance data in the 5 thermal-infrared (TIR) bands. Silicified rocks were not distinguished in the 9 VNIR + SWIR bands because of the lack of diagnostic spectral absorption features in quartz in this wavelength region. Quartz-bearing surficial deposits, as well as hydrothermally silicified rocks, were mapped in the TIR bands by using a band 13/band 12 ratio image, which is sensitive to the intensity of the quartz reststrahlen feature. Improved distinction between the quartzose surficial deposits and silicified bedrock was achieved by using matched-filter processing with TIR image spectra for reference. ?? 2006 Elsevier Inc. All rights reserved.

  2. The impacts of altered tropical cyclone activity on climate mitigation strategies

    NASA Astrophysics Data System (ADS)

    Fisk, J. P.; Hurtt, G. C.; LePage, Y.; Patel, P.; Chini, L. P.; Thomson, A. M.; Clarke, L.; Calvin, K. V.; Wise, M.; Chambers, J. Q.; Negron Juarez, R. I.

    2012-12-01

    There is growing evidence that anthropogenic climate change may alter patterns of tropical cyclone frequency, intensity and spatial distribution, which in turn will alter the carbon balance of terrestrial systems in the large regions impacted by these storms. Recent studies project up to a doubling of major storms (Saffir-Simpson Scale 3-5) over the next century. Single large storms have been shown to be capable of causing committed carbon emissions equivalent to the annual U.S. carbon sink. These changes have the potential to affect climate mitigation strategies, most of which rely on maintaining or enhancing the terrestrial carbon sink to restrain the accumulation of atmospheric greenhouse gases. Altered patterns of disturbances and the resulting changes to the carbon balance of terrestrial systems could impact the magnitude of emissions to mitigate, the economic value of ecosystem carbon storage, and thus future land-use patterns, food prices and energy technology. Here we investigate the potential consequences of altered tropical cyclone activity on climate mitigation strategies using a fully integrated model (iED) that links advanced ecological and socio-economic models. The model combines the regional integrated assessment algorithms of the Global Change Assessment Model (GCAM), with the climate- sensitive ecosystem and carbon modeling in the Ecosystem Demography (ED) model, and the land-use mapping algorithms of the Global Land-use Model (GLM). We explore a range of scenarios of altered future tropical cyclone frequency, intensity and spatial pattern, the resulting effects on the terrestrial carbon balance, and the coupled effects on the food and energy sector under a range of future climate mitigation goals.

  3. Airborne infrared mineral mapping survey of Marysvale, Utah

    NASA Technical Reports Server (NTRS)

    Collins, W.; Chang, S. H.

    1982-01-01

    Infrared spectroradiometer survey results from flights over the Marysvale, Utah district show that hydrothermal alteration mineralogy can be mapped using very rapid and effective airborne techniques. The system detects alteration mineral absorption band intensities in the infrared spectral region with high sensitivity. The higher resolution spectral features and high spectral differences characteristic of the various clay and carbonate minerals are also readily identified by the instrument allowing the mineralogy to be mapped as well as the mineralization intensity.

  4. Body Maps in the Infant Brain

    PubMed Central

    Marshall, Peter J.; Meltzoff, Andrew N.

    2015-01-01

    Researchers have examined representations of the body in the adult brain, but relatively little attention has been paid to ontogenetic aspects of neural body maps in human infants. Novel applications of methods for recording brain activity in infants are delineating cortical body maps in the first months of life. Body maps may facilitate infants’ registration of similarities between self and other—an ability that is foundational to developing social cognition. Alterations in interpersonal aspects of body representations might also contribute to social deficits in certain neurodevelopmental disorders. PMID:26231760

  5. Multispectral thermal infrared mapping of the 1 October 1988 Kupaianaha flow field, Kilauea volcano, Hawaii

    USGS Publications Warehouse

    Realmuto, V.J.; Hon, K.; Kahle, A.B.; Abbott, E.A.; Pieri, D.C.

    1992-01-01

    Multispectral thermal infrared radiance measurements of the Kupaianaha flow field were acquired with the NASA airborne Thermal Infrared Multispectral Scanner (TIMS) on the morning of 1 October 1988. The TIMS data were used to map both the temperature and emissivity of the surface of the flow field. The temperature map depicted the underground storage and transport of lava. The presence of molten lava in a tube or tumulus resulted in surface temperatures that were at least 10?? C above ambient. The temperature map also clearly defined the boundaries of hydrothermal plumes which resulted from the entry of lava into the ocean. The emissivity map revealed the boundaries between individual flow units within the Kupaianaha field. In general, the emissivity of the flows varied systematically with age but the relationship between age and emissivity was not unique. Distinct spectral anomalies, indicative of silica-rich surface materials, were mapped near fumaroles and ocean entry sites. This apparent enrichment in silica may have resulted from an acid-induced leaching of cations from the surfaces of glassy flows. Such incipient alteration may have been the cause for virtually all of the emissivity variations observed on the flow field, the spectral anomalies representing areas where the acid attack was most intense. ?? 1992 Springer-Verlag.

  6. When Reasoning Modifies Memory: Schematic Assimilation Triggered by Analogical Mapping

    ERIC Educational Resources Information Center

    Vendetti, Michael S.; Wu, Aaron; Rowshanshad, Ebi; Knowlton, Barbara J.; Holyoak, Keith J.

    2014-01-01

    Analogical mapping highlights shared relations that link 2 situations, potentially at the expense of information that does not fit the dominant pattern of correspondences. To investigate whether analogical mapping can alter subsequent recognition memory for features of a source analog, we performed 2 experiments with 4-term proportional analogies…

  7. Application of hyperspectral infrared analysis of hydrothermal alteration on Earth and Mars.

    PubMed

    Thomas, Matilda; Walter, Malcolm R

    2002-01-01

    An integrated analysis of both airborne and field short-wave infrared hyperspectral measurements was used in conjunction with conventional field mapping techniques to map hydrothermal alteration in the central portion of the Mount Painter Inlier in the Flinders Ranges, South Australia. The airborne hyperspectral data show the spatial distribution of spectrally distinct minerals occurring as primary minerals and as weathering and alteration products. Field spectral measurements, taken with a portable infrared mineral analyzer spectrometer and supported by thin-section analyses, were used to verify the mineral maps and enhance the level of information obtainable from the airborne data. Hydrothermal alteration zones were identified and mapped separately from the background weathering signals. A main zone of alteration, coinciding with the Paralana Fault zone, was recognized, and found to contain kaolinite, muscovite, biotite, and K-feldspar. A small spectral variation associated with a ring-like feature around Mount Painter was tentatively determined to be halloysite and interpreted to represent a separate hydrothermal fluid and fluid source, and probably a separate system. The older parts of the alteration system are tentatively dated as Permo-Carboniferous. The remote sensing of alteration at Mount Painter confirms that hyperspectral imaging techniques can produce accurate mineralogical maps with significant details that can be used to identify and map hydrothermal activity. Application of hyperspectral surveys such as that conducted at Mount Painter would be likely to provide similar detail about putative hydrothermal deposits on Mars. PMID:12530243

  8. Updating Maps Using High Resolution Satellite Imagery

    NASA Astrophysics Data System (ADS)

    Alrajhi, Muhamad; Shahzad Janjua, Khurram; Afroz Khan, Mohammad; Alobeid, Abdalla

    2016-06-01

    Kingdom of Saudi Arabia is one of the most dynamic countries of the world. We have witnessed a very rapid urban development's which are altering Kingdom's landscape on daily basis. In recent years a substantial increase in urban populations is observed which results in the formation of large cities. Considering this fast paced growth, it has become necessary to monitor these changes, in consideration with challenges faced by aerial photography projects. It has been observed that data obtained through aerial photography has a lifecycle of 5-years because of delay caused by extreme weather conditions and dust storms which acts as hindrances or barriers during aerial imagery acquisition, which has increased the costs of aerial survey projects. All of these circumstances require that we must consider some alternatives that can provide us easy and better ways of image acquisition in short span of time for achieving reliable accuracy and cost effectiveness. The approach of this study is to conduct an extensive comparison between different resolutions of data sets which include: Orthophoto of (10 cm) GSD, Stereo images of (50 cm) GSD and Stereo images of (1 m) GSD, for map updating. Different approaches have been applied for digitizing buildings, roads, tracks, airport, roof level changes, filling stations, buildings under construction, property boundaries, mosques buildings and parking places.

  9. Human Mind Maps

    ERIC Educational Resources Information Center

    Glass, Tom

    2016-01-01

    When students generate mind maps, or concept maps, the maps are usually on paper, computer screens, or a blackboard. Human Mind Maps require few resources and little preparation. The main requirements are space where students can move around and a little creativity and imagination. Mind maps can be used for a variety of purposes, and Human Mind…

  10. Molecular analysis of radiation-induced albino (c)-locus mutations that cause death at preimplantation stages of development

    SciTech Connect

    Rinchik, E.M. ); Toenjes, R.R.; Paul, D. ); Potter, M.D. )

    1993-12-01

    Deletion mutations at the albino (c) locus have been useful for continuing the development of fine-structure physical and functional maps of the Fes-Hbb region of mouse chromosome 7. This report describes the molecular analysis of a number of radiation-induced c deletions that, when homozygous, cause death of the embryo during preimplantation stages. The distal extent of these deletions defines a locus, pid, (preimplantation development) genetically associated with this phenotype. The proximal breakpoints of eight of these deletions were mapped with respect to the Tyr (tyrosinase; albino) gene as well as to anonymous loci within the Fah-Tyr region that are defined by the Pmv-31 viral integration site and by chromosome-microdissection clones. Rearrangements corresponding to the proximal breakpoints of two of these deletions were detected by Southern blot analysis, and a size-altered restriction fragment carrying the breakpoint of one of them was cloned. A probe derived from this deletion fusion fragment defines a locus, D7Rn6, which maps within (or distal to) the pid region, and which discriminates among the distal extents of deletions eliciting the pid phenotype. Extension of physical maps from D7Rn6 should provide access both to the pid region and to loci mapping distal to pid that are defined by N-ethyl-N-nitrosourea-induced lethal mutations. 36 refs., 10 figs.

  11. Concept Mapping

    PubMed Central

    Brennan, Laura K.; Brownson, Ross C.; Kelly, Cheryl; Ivey, Melissa K.; Leviton, Laura C.

    2016-01-01

    Background From 2003 to 2008, 25 cross-sector, multidisciplinary community partnerships funded through the Active Living by Design (ALbD) national program designed, planned, and implemented policy and environmental changes, with complementary programs and promotions. This paper describes the use of concept-mapping methods to gain insights into promising active living intervention strategies based on the collective experience of community representatives implementing ALbD initiatives. Methods Using Concept Systems software, community representatives (n=43) anonymously generated actions and changes in their communities to support active living (183 original statements, 79 condensed statements). Next, respondents (n=26, from 23 partnerships) sorted the 79 statements into self-created categories, or active living intervention approaches. Respondents then rated statements based on their perceptions of the most important strategies for creating community changes (n=25, from 22 partnerships) and increasing community rates of physical activity (n=23, from 20 partnerships). Cluster analysis and multidimensional scaling were used to describe data patterns. Results ALbD community partnerships identified three active living intervention approaches with the greatest perceived importance to create community change and increase population levels of physical activity: changes to the built and natural environment, partnership and collaboration efforts, and land-use and transportation policies. The relative importance of intervention approaches varied according to subgroups of partnerships working with different populations. Conclusions Decision makers, practitioners, and community residents can incorporate what has been learned from the 25 community partnerships to prioritize active living policy, physical project, promotional, and programmatic strategies for work in different populations and settings. PMID:23079266

  12. Maps & minds : mapping through the ages

    USGS Publications Warehouse

    U.S. Geological Survey

    1984-01-01

    Throughout time, maps have expressed our understanding of our world. Human affairs have been influenced strongly by the quality of maps available to us at the major turning points in our history. "Maps & Minds" traces the ebb and flow of a few central ideas in the mainstream of mapping. Our expanding knowledge of our cosmic neighborhood stems largely from a small number of simple but grand ideas, vigorously pursued.

  13. Retinal Remodeling and Metabolic Alterations in Human AMD

    PubMed Central

    Jones, Bryan W.; Pfeiffer, Rebecca L.; Ferrell, William D.; Watt, Carl B.; Tucker, James; Marc, Robert E.

    2016-01-01

    Age-related macular degeneration (AMD) is a progressive retinal degeneration resulting in central visual field loss, ultimately causing debilitating blindness. AMD affects 18% of Americans from 65 to 74, 30% older than 74 years of age and is the leading cause of severe vision loss and blindness in Western populations. While many genetic and environmental risk factors are known for AMD, we currently know less about the mechanisms mediating disease progression. The pathways and mechanisms through which genetic and non-genetic risk factors modulate development of AMD pathogenesis remain largely unexplored. Moreover, current treatment for AMD is palliative and limited to wet/exudative forms. Retina is a complex, heterocellular tissue and most retinal cell classes are impacted or altered in AMD. Defining disease and stage-specific cytoarchitectural and metabolic responses in AMD is critical for highlighting targets for intervention. The goal of this article is to illustrate cell types impacted in AMD and demonstrate the implications of those changes, likely beginning in the retinal pigment epithelium (RPE), for remodeling of the the neural retina. Tracking heterocellular responses in disease progression is best achieved with computational molecular phenotyping (CMP), a tool that enables acquisition of a small molecule fingerprint for every cell in the retina. CMP uncovered critical cellular and molecular pathologies (remodeling and reprogramming) in progressive retinal degenerations such as retinitis pigmentosa (RP). We now applied these approaches to normal human and AMD tissues mapping progression of cellular and molecular changes in AMD retinas, including late-stage forms of the disease. PMID:27199657

  14. Mapping: A Course.

    ERIC Educational Resources Information Center

    Whitmore, Paul M.

    1988-01-01

    Reviews the history of cartography. Describes the contributions of Strabo and Ptolemy in early maps. Identifies the work of Gerhard Mercator as the most important advancement in mapping. Discusses present mapping standards from history. (CW)

  15. Protamine alterations in human spermatozoa.

    PubMed

    Jodar, Meritxell; Oliva, Rafael

    2014-01-01

    Protamines are the major nuclear proteins in sperm cells, having a crucial role in the correct packaging of the paternal DNA. The fact that protamine haploinsufficiency in mice resulted in abnormal chromatin packaging and male infertility suggested that the protamines could also be important candidates in explaining some of the idiopathic male infertility cases in humans. The first clinical studies focused on analyzing protamines at the protein level. Various studies have found the presence of an altered amount of protamines in some infertile patients, in contrast to the normal situation in fertile individuals where the two protamines, protamine 1 and protamine 2, are both present in approximately equal quantities. Subsequently, the protamine genes were the subject of various mutational genetic screening studies in search of variants that could be associated with deregulation in the protamine expression observed. The results of these protamine mutational studies showed that the presence of high penetrant mutations is a very rare cause of male infertility. However, some variants and some haplotypes described may behave as risk factors for male infertility. More recently, the presence of RNA in the mature sperm cell has also been investigated. The present chapter will introduce the basic aspects of protamine evolution and function and review the various articles published to date on the relationship between the protamines studied at the DNA, RNA, and protein levels and male infertility. PMID:23955674

  16. Altered fingerprints: analysis and detection.

    PubMed

    Yoon, Soweon; Feng, Jianjiang; Jain, Anil K

    2012-03-01

    The widespread deployment of Automated Fingerprint Identification Systems (AFIS) in law enforcement and border control applications has heightened the need for ensuring that these systems are not compromised. While several issues related to fingerprint system security have been investigated, including the use of fake fingerprints for masquerading identity, the problem of fingerprint alteration or obfuscation has received very little attention. Fingerprint obfuscation refers to the deliberate alteration of the fingerprint pattern by an individual for the purpose of masking his identity. Several cases of fingerprint obfuscation have been reported in the press. Fingerprint image quality assessment software (e.g., NFIQ) cannot always detect altered fingerprints since the implicit image quality due to alteration may not change significantly. The main contributions of this paper are: 1) compiling case studies of incidents where individuals were found to have altered their fingerprints for circumventing AFIS, 2) investigating the impact of fingerprint alteration on the accuracy of a commercial fingerprint matcher, 3) classifying the alterations into three major categories and suggesting possible countermeasures, 4) developing a technique to automatically detect altered fingerprints based on analyzing orientation field and minutiae distribution, and 5) evaluating the proposed technique and the NFIQ algorithm on a large database of altered fingerprints provided by a law enforcement agency. Experimental results show the feasibility of the proposed approach in detecting altered fingerprints and highlight the need to further pursue this problem. PMID:21808092

  17. Epigenetic Alterations in Alzheimer’s Disease

    PubMed Central

    Sanchez-Mut, Jose V.; Gräff, Johannes

    2015-01-01

    Alzheimer’s disease (AD) is the major cause of dementia in Western societies. It progresses asymptomatically during decades before being belatedly diagnosed when therapeutic strategies have become unviable. Although several genetic alterations have been associated with AD, the vast majority of AD cases do not show strong genetic underpinnings and are thus considered a consequence of non-genetic factors. Epigenetic mechanisms allow for the integration of long-lasting non-genetic inputs on specific genetic backgrounds, and recently, a growing number of epigenetic alterations in AD have been described. For instance, an accumulation of dysregulated epigenetic mechanisms in aging, the predominant risk factor of AD, might facilitate the onset of the disease. Likewise, mutations in several enzymes of the epigenetic machinery have been associated with neurodegenerative processes that are altered in AD such as impaired learning and memory formation. Genome-wide and locus-specific epigenetic alterations have also been reported, and several epigenetically dysregulated genes validated by independent groups. From these studies, a picture emerges of AD as being associated with DNA hypermethylation and histone deacetylation, suggesting a general repressed chromatin state and epigenetically reduced plasticity in AD. Here we review these recent findings and discuss several technical and methodological considerations that are imperative for their correct interpretation. We also pay particular focus on potential implementations and theoretical frameworks that we expect will help to better direct future studies aimed to unravel the epigenetic participation in AD. PMID:26734709

  18. Aerogeophysical measurements of collapse-prone hydrothermally altered zones at Mount Rainier volcano

    USGS Publications Warehouse

    Finn, C.A.; Sisson, T.W.; Deszcz-Pan, M.

    2001-01-01

    Hydrothermally altered rocks can weaken volcanoes, increasing the potential for catastrophic sector collapses that can lead to destructive debris flows1. Evaluating the hazards associated with such alteration is difficult because alteration has been mapped on few active volcanoes1-4 and the distribution and severity of subsurface alteration is largely unknown on any active volcano. At Mount Rainier volcano (Washington, USA), collapses of hydrothermally altered edifice flanks have generated numerous extensive debris flows5,6 and future collapses could threaten areas that are now densely populated7. Preliminary geological mapping and remote-sensing data indicated that exposed alteration is contained in a dyke-controlled belt trending east-west that passes through the volcano's summit3-5,8. But here we present helicopter-borne electromagnetic and magnetic data, combined with detailed geological mapping, to show that appreciable thicknesses of mostly buried hydrothermally altered rock lie mainly in the upper west flank of Mount Rainier. We identify this as the likely source for future large debris flows. But as negligible amounts of highly altered rock lie in the volcano's core, this might impede collapse retrogression and so limit the volumes and inundation areas of future debris flows. Our results demonstrate that high-resolution geophysical and geological observations can yield unprecedented views of the three-dimensional distribution of altered rock.

  19. Parasites alter community structure.

    PubMed

    Wood, Chelsea L; Byers, James E; Cottingham, Kathryn L; Altman, Irit; Donahue, Megan J; Blakeslee, April M H

    2007-05-29

    Parasites often play an important role in modifying the physiology and behavior of their hosts and may, consequently, mediate the influence hosts have on other components of an ecological community. Along the northern Atlantic coast of North America, the dominant herbivorous snail Littorina littorea structures rocky intertidal communities through strong grazing pressure and is frequently parasitized by the digenean trematode Cryptocotyle lingua. We hypothesized that the effects of parasitism on host physiology would induce behavioral changes in L. littorea, which in turn would modulate L. littorea's influence on intertidal community composition. Specifically, we hypothesized that C. lingua infection would alter the grazing rate of L. littorea and, consequently, macroalgal communities would develop differently in the presence of infected versus uninfected snails. Our results show that uninfected snails consumed 40% more ephemeral macroalgal biomass than infected snails in the laboratory, probably because the digestive system of infected snails is compromised by C. lingua infection. In the field, this weaker grazing by infected snails resulted in significantly greater expansion of ephemeral macroalgal cover relative to grazing by uninfected snails. By decreasing the per-capita grazing rate of the dominant herbivore, C. lingua indirectly affects the composition of the macroalgal community and may in turn affect other species that depend on macroalgae for resources or habitat structure. In light of the abundance of parasites across systems, we suggest that, through trait-mediated indirect effects, parasites may be a common determinant of structure in ecological communities. PMID:17517667

  20. What Causes Cardiomyopathy?

    MedlinePlus

    ... and can damage the organs, including the heart. Sarcoidosis : A disease that causes inflammation and can affect ... believe that an abnormal immune response may cause sarcoidosis. This abnormal response causes tiny lumps of cells ...

  1. Common Cause Failure Modeling

    NASA Technical Reports Server (NTRS)

    Hark, Frank; Britton, Paul; Ring, Robert; Novack, Steven

    2015-01-01

    Space Launch System (SLS) Agenda: Objective; Key Definitions; Calculating Common Cause; Examples; Defense against Common Cause; Impact of varied Common Cause Failure (CCF) and abortability; Response Surface for various CCF Beta; Takeaways.

  2. What Causes Pericarditis?

    MedlinePlus

    ... this page from the NHLBI on Twitter. What Causes Pericarditis? In many cases, the cause of pericarditis (both acute and chronic) is unknown. Viral infections are likely a common cause of pericarditis, although the virus may never be ...

  3. Graphene mobility mapping

    PubMed Central

    Buron, Jonas D.; Pizzocchero, Filippo; Jepsen, Peter U.; Petersen, Dirch H.; Caridad, José M.; Jessen, Bjarke S.; Booth, Timothy J.; Bøggild, Peter

    2015-01-01

    Carrier mobility and chemical doping level are essential figures of merit for graphene, and large-scale characterization of these properties and their uniformity is a prerequisite for commercialization of graphene for electronics and electrodes. However, existing mapping techniques cannot directly assess these vital parameters in a non-destructive way. By deconvoluting carrier mobility and density from non-contact terahertz spectroscopic measurements of conductance in graphene samples with terahertz-transparent backgates, we are able to present maps of the spatial variation of both quantities over large areas. The demonstrated non-contact approach provides a drastically more efficient alternative to measurements in contacted devices, with potential for aggressive scaling towards wafers/minute. The observed linear relation between conductance and carrier density in chemical vapour deposition graphene indicates dominance by charged scatterers. Unexpectedly, significant variations in mobility rather than doping are the cause of large conductance inhomogeneities, highlighting the importance of statistical approaches when assessing large-area graphene transport properties. PMID:26204815

  4. Graphene mobility mapping

    NASA Astrophysics Data System (ADS)

    Buron, Jonas D.; Pizzocchero, Filippo; Jepsen, Peter U.; Petersen, Dirch H.; Caridad, José M.; Jessen, Bjarke S.; Booth, Timothy J.; Bøggild, Peter

    2015-07-01

    Carrier mobility and chemical doping level are essential figures of merit for graphene, and large-scale characterization of these properties and their uniformity is a prerequisite for commercialization of graphene for electronics and electrodes. However, existing mapping techniques cannot directly assess these vital parameters in a non-destructive way. By deconvoluting carrier mobility and density from non-contact terahertz spectroscopic measurements of conductance in graphene samples with terahertz-transparent backgates, we are able to present maps of the spatial variation of both quantities over large areas. The demonstrated non-contact approach provides a drastically more efficient alternative to measurements in contacted devices, with potential for aggressive scaling towards wafers/minute. The observed linear relation between conductance and carrier density in chemical vapour deposition graphene indicates dominance by charged scatterers. Unexpectedly, significant variations in mobility rather than doping are the cause of large conductance inhomogeneities, highlighting the importance of statistical approaches when assessing large-area graphene transport properties.

  5. Graphene mobility mapping.

    PubMed

    Buron, Jonas D; Pizzocchero, Filippo; Jepsen, Peter U; Petersen, Dirch H; Caridad, José M; Jessen, Bjarke S; Booth, Timothy J; Bøggild, Peter

    2015-01-01

    Carrier mobility and chemical doping level are essential figures of merit for graphene, and large-scale characterization of these properties and their uniformity is a prerequisite for commercialization of graphene for electronics and electrodes. However, existing mapping techniques cannot directly assess these vital parameters in a non-destructive way. By deconvoluting carrier mobility and density from non-contact terahertz spectroscopic measurements of conductance in graphene samples with terahertz-transparent backgates, we are able to present maps of the spatial variation of both quantities over large areas. The demonstrated non-contact approach provides a drastically more efficient alternative to measurements in contacted devices, with potential for aggressive scaling towards wafers/minute. The observed linear relation between conductance and carrier density in chemical vapour deposition graphene indicates dominance by charged scatterers. Unexpectedly, significant variations in mobility rather than doping are the cause of large conductance inhomogeneities, highlighting the importance of statistical approaches when assessing large-area graphene transport properties. PMID:26204815

  6. Visual Space Constructed by Saccade Motor Maps

    PubMed Central

    Zimmermann, Eckart; Lappe, Markus

    2016-01-01

    How visual space is represented in the brain is an open question in neuroscience. Embodiment theories propose that spatial perception is structured by neural motor maps. Especially, maps which code the targets for saccadic eye movements contain a precise representation of external space. In this review article, we examine how modifications in saccade maps are accompanied by changes in visual space perception. Saccade adaptation, a method which systematically modifies saccade amplitudes, alters the localization of visual objects in space. We illustrate how information about saccade amplitudes is transferred from the cerebellum (CB) to the frontal eye field (FEF). We argue that changes in visual localization after adaptation of saccade maps provide evidence for a shared representation of visual and motor space. PMID:27242488

  7. Mapping the Heart

    ERIC Educational Resources Information Center

    Hulse, Grace

    2012-01-01

    In this article, the author describes how her fourth graders made ceramic heart maps. The impetus for this project came from reading "My Map Book" by Sara Fanelli. This book is a collection of quirky, hand-drawn and collaged maps that diagram a child's world. There are maps of her stomach, her day, her family, and her heart, among others. The…