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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. 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

  6. 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.

  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. 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.

  17. 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

  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 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

  12. 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.

  13. 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

  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. 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...

  16. 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...

  17. 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…

  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. 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

  20. 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

  1. 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

  2. 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

  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. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  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. 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

  20. 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

  1. 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

  2. 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

  3. 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

  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. 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

  7. 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

  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

    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

  12. 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

  13. 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

  14. 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

  15. 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

  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. 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

  19. 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

  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. 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

  7. 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

  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. 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

  2. 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

  3. 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

  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

    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.

  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

    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

  10. 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

  11. 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

  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. 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

  15. 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

  16. 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.

  17. 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

  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 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.

  1. 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)

  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. 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

  17. 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

  18. 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

  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. 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

  7. 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.

  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. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  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 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  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