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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. 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

  3. 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.

  4. Altering spatial priority maps via reward-based learning.

    PubMed

    Chelazzi, Leonardo; Eštočinová, Jana; Calletti, Riccardo; Lo Gerfo, Emanuele; Sani, Ilaria; Della Libera, Chiara; Santandrea, Elisa

    2014-06-18

    Spatial priority maps are real-time representations of the behavioral salience of locations in the visual field, resulting from the combined influence of stimulus driven activity and top-down signals related to the current goals of the individual. They arbitrate which of a number of (potential) targets in the visual scene will win the competition for attentional resources. As a result, deployment of visual attention to a specific spatial location is determined by the current peak of activation (corresponding to the highest behavioral salience) across the map. Here we report a behavioral study performed on healthy human volunteers, where we demonstrate that spatial priority maps can be shaped via reward-based learning, reflecting long-lasting alterations (biases) in the behavioral salience of specific spatial locations. These biases exert an especially strong influence on performance under conditions where multiple potential targets compete for selection, conferring competitive advantage to targets presented in spatial locations associated with greater reward during learning relative to targets presented in locations associated with lesser reward. Such acquired biases of spatial attention are persistent, are nonstrategic in nature, and generalize across stimuli and task contexts. These results suggest that reward-based attentional learning can induce plastic changes in spatial priority maps, endowing these representations with the "intelligent" capacity to learn from experience.

  5. Causes and consequences of nuclear envelope alterations in tumour progression.

    PubMed

    Bell, Emily S; Lammerding, Jan

    2016-11-01

    Morphological changes in the size and shape of the nucleus are highly prevalent in cancer, but the underlying molecular mechanisms and the functional relevance remain poorly understood. Nuclear envelope proteins, which can modulate nuclear shape and organization, have emerged as key components in a variety of signalling pathways long implicated in tumourigenesis and metastasis. The expression of nuclear envelope proteins is altered in many cancers, and changes in levels of nuclear envelope proteins lamins A and C are associated with poor prognosis in multiple human cancers. In this review we highlight the role of the nuclear envelope in different processes important for tumour initiation and cancer progression, with a focus on lamins A and C. Lamin A/C controls many cellular processes with key roles in cancer, including cell invasion, stemness, genomic stability, signal transduction, transcriptional regulation, and resistance to mechanical stress. In addition, we discuss potential mechanisms mediating the changes in lamin levels observed in many cancers. A better understanding of cause-and-effect relationships between lamin expression and tumour progression could reveal important mechanisms for coordinated regulation of oncogenic processes, and indicate therapeutic vulnerabilities that could be exploited for improved patient outcome.

  6. 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.

  7. The Causes and Consequences of Altered Glucose Metabolism in Cancer

    DTIC Science & Technology

    2007-10-05

    Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B ...diagram). B . Diagram of the Warburg Effect. Even in the presence of normal oxygen conditions, many cancer cells convert pyruvate to lactate. The...mitochondria of these cells often appear to be functional, so it remains uncertain why this altered metabolism occurs. A. B . 5 conditions. Based on

  8. Disease causing mutations of troponin alter regulated actin state distributions.

    PubMed

    Chalovich, Joseph M

    2012-12-01

    Striated muscle contraction is regulated primarily through the action of tropomyosin and troponin that are bound to actin. Activation requires Ca(2+) binding to troponin and/or binding of high affinity myosin complexes to actin. Mutations within components of the regulatory complex may lead to familial cardiomyopathies and myopathies. In several cases examined, either physiological or pathological changes in troponin alter the distribution among states of actin-tropomyosin-troponin that differ in their abilities to stimulate myosin ATPase activity. These observations open possibilities for managing disorders of the troponin complex. Furthermore, analyses of mutant forms of troponin give insights into the regulation of striated muscle contraction.

  9. 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.

  10. Altered sensation caused by peri-implantitis: a case report.

    PubMed

    Kim, Jong-Eun; Shim, Ji-Suk; Huh, Jung-Bo; Rim, Jae-Suk; Lee, Jeong-Yol; Shin, Sang-Wan

    2013-07-01

    Frequently reported is a case wherein a lesion caused by periodontitis or periapical lesion in a natural tooth enlarged, invaded the inferior alveolar nerve canal, and induced paresthesia. Cases wherein paresthesia occurred because of peri-implantitis have been rarely reported. The patient in this case report had experienced transient paresthesia after implant placement and recovered normal sensation 3 months later. Thirteen years later, this patient visited the authors' hospital with paresthesia in the same region because the peri-implantitis progressed to the apex of the implant. One week after removal of the implant, sense recovery and pain relief started, and 15 days after removal, the paresthesia and pain completely disappeared. For patients who experience transient paresthesia and recovery owing to nerve damage caused by the placement of an implant in the mandibular molar or premolar area, or in patients in whom the implant is close to the inferior alveolar nerve canal or the mental nerve, the spread of inflammation caused by peri-implantitis can induce paresthesia.

  11. [Alteration of biological rhythms causes metabolic diseases and obesity].

    PubMed

    Saderi, Nadia; Escobar, Carolina; Salgado-Delgado, Roberto

    2013-07-16

    The incidence of obesity worldwide has become a serious, constantly growing public health issue that reaches alarming proportions in some countries. To date none of the strategies developed to combat obesity have proved to be decisive, and hence there is an urgent need to address the problem with new approaches. Today, studies in the field of chronobiology have shown that our physiology continually adapts itself to the cyclical changes in the environment, regard-less of whether they are daily or seasonal. This is possible thanks to the existence of a biological clock in our hypothalamus which regulates the expression and/or activity of enzymes and hormones involved in regulating our metabolism, as well as all the homeostatic functions. It has been observed that this clock can be upset as a result of today's modern lifestyle, which involves a drop in physical activity during the day and the abundant ingestion of food during the night, among other factors, which together promote metabolic syndrome and obesity. Hence, the aim of this review is to summarise the recent findings that show the effect that altering the circadian rhythms has on the metabolism and how this can play a part in the development of metabolic diseases.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. Chaos Caused by a Transitive Map in Information

    NASA Astrophysics Data System (ADS)

    Wang, Lidong; Peng, Jiao; Liu, Heng

    In this paper, the chaotic phenomena have been discussed in an information system design process. Let (X, d 1) (Y, d 2) be compact metric spaces without isolated point and h : X →Y be a semi-conjugacy between f and g, where f : X →X g : Y →Y are continuous maps. In this paper, we investigated the expanding maps with transitivity. And we gave a sufficient condition about expanding maps are chaotic in the sense of Wiggins and Kato.

  17. Use of airborne multispectral scanner data to map alteration related to roll-front uranium migration

    SciTech Connect

    Peters, D.C.

    1983-06-01

    Computer-enhanced airborne multispectral scanner (MSS) images have been used to detect and map red oxidized alteration related to roll-front uranium migration in the southern Powder River basin, Wyoming. Information in the 0.4- to 1.1-..mu..m spectral region was used to produce a color ratio composite image, upon which the red-altered areas can be differentiated. The red-altered and incipiently altered sandstones result from the migration of a roll-front (or geochemical cell) through the sandstone in the direction of the hydrologic gradient. Most uranium deposits in the Powder River basin occur at the boundary between this oxidized sandstone and reduced sandstone. Therefore, the ability to detect and map this alteration reliably can provide important information about the potential for uranium mineralization down gradient from the altered areas, at the surface in an area of interest. Spectral reflectance studies indicate that a shift in the absorption band edge from 0.52 ..mu..m (for goethitic sandstone) to 0.58 ..mu..m (for hematitic sandstone) and an intensification of an absorption band at 0.85 ..mu..m (for hematitic sandstone) are the bases for identifying the red-altered sandstone as green anomalous areas on the color ratio composite image. Some of the incipiently altered sandstone also appears green, whereas unaltered material and white-altered sandstone appear as blue to cyan colors. Therefore, the composite image is useful in discriminating hematitic sandstone from goethitic sandstone. At high densities (>65%), vegetation masks the sandstones on the color ratio composite image. Artemisia tridentata (sage) and Stipa comata (grass) are the species that have the greatest individual effect on the image.

  18. 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.

  19. 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).

  20. 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.

  1. 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.

  2. 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.

  3. Low-dose, Chronic Exposure to Silver Nanoparticles Causes Mild Mitochondrial Alterations in the Liver of Sprague-Dawley Rat

    DTIC Science & Technology

    2014-05-10

    AFRL-AFOSR-UK-TR-2014-0032 Low-dose, chronic exposure to silver nanoparticles causes mild mitochondrial alterations in the liver ...TITLE AND SUBTITLE Low-dose, chronic exposure to silver nanoparticles causes mild mitochondrial alterations in the liver of Sprague-Dawley rat 5a...alterations were found in heart and kidney levels, and despite the fact that the alterations found in liver mitochondria did not appear to compromise ATP

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. Hyperspectral mapping of alteration assemblages within a hydrothermal vug at the Haughton impact structure, Canada

    NASA Astrophysics Data System (ADS)

    Greenberger, Rebecca N.; Mustard, John F.; Osinski, Gordon R.; Tornabene, Livio L.; Pontefract, Alexandra J.; Marion, Cassandra L.; Flemming, Roberta L.; Wilson, Janette H.; Cloutis, Edward A.

    2016-12-01

    Meteorite impacts on Earth and Mars can generate hydrothermal systems that alter the primary mineralogies of rocks and provide suitable environments for microbial colonization. We investigate a calcite-marcasite-bearing vug at the 23 km diameter Haughton impact structure, Devon Island, Nunavut, Canada, using imaging spectroscopy of the outcrop in the field (0.65-1.1 μm) and samples in the laboratory (0.4-2.5 μm), point spectroscopy (0.35-2.5 μm), major element chemistry, and X-ray diffraction analyses. The mineral assemblages mapped at the outcrop include marcasite; marcasite with minor gypsum and jarosite; fibroferrite and copiapite with minor gypsum and melanterite; gypsum, Fe3+ oxides, and jarosite; and calcite, gypsum, clay, microcline, and quartz. Hyperspectral mapping of alteration phases shows spatial patterns that illuminate changes in alteration conditions and formation of specific mineral phases. Marcasite formed from the postimpact hydrothermal system under reducing conditions, while subsequent weathering oxidized the marcasite at low temperatures and water/rock ratios. The acidic fluids resulting from the oxidation collected on flat-lying portions of the outcrop, precipitating fibroferrite + copiapite. That assemblage then likely dissolved, and the changing chemistry and pH resulting from interaction with the calcite-rich host rock formed gypsum-bearing red coatings. These results have implications for understanding water-rock interactions and habitabilities at this site and on Mars.

  14. 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.

  15. 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.

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

    PubMed

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

    2012-03-20

    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.

  17. 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

  18. Alteration in Taste Perception in Cancer: Causes and Strategies of Treatment

    PubMed Central

    Murtaza, Babar; Hichami, Aziz; Khan, Amira S.; Ghiringhelli, François; Khan, Naim A.

    2017-01-01

    The sense of taste is responsible for the detection and ingestion of food to cover energetic requirements in health and disease. The change in taste perception might lead to malnutrition that is usually one of the frequent causes of morbidity and mortality in patients with cancer. In this review, we summarize the mechanisms of taste perception and how they are altered in cancer. We also address the question of the implication of inflammation, responsible for the alterations in taste modalities. We highlight the role of radio- and chemotherapy in the modulation of taste physiology. Other several factors like damage to taste progenitor cells and disruption of gut microbiota are also dealt with relation to taste perception in cancer. We further shed light on how to restore taste acuity, by using different preventive methods, dietary modifications and pharmacotherapy in subjects with advanced cancer state. PMID:28337150

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

    PubMed

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

    2015-10-26

    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.

  20. 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

  1. Phenotypic alterations in Arabidopsis thaliana plants caused by Rhodococcus fascians infection.

    PubMed

    de O Manes, Carmem-Lara; Beeckman, Tom; Ritsema, Tita; Van Montagu, Marc; Goethals, Koen; Holsters, Marcelle

    2004-04-01

    Arabidopsis thaliana (L.) Heynh. plants were challenged with Rhodococcus fascians at several developmental stages and using different inoculation procedures. A variety of morphological alterations was scored on the infected plants; some of them resembled phenotypes of A. thaliana mutants in their shoot apical meristem (SAM) organization. Infection with R. fascians did not affect SAM organization in wild type nor in SAM mutants. Anatomical studies on the new organs formed after infection with R. fascians demonstrated extensive bacterial colonization. Colonization and concomitant production of specific signals are the likely cause of malformations.

  2. The Effectiveness of Hydrothermal Alteration Mapping based on Hyperspectral Data in Tropical Region

    NASA Astrophysics Data System (ADS)

    Muhammad, R. R. D.; Saepuloh, A.

    2016-09-01

    Hyperspectral remote sensing could be used to characterize targets at earth's surface based on their spectra. This capability is useful for mapping and characterizing the distribution of host rocks, alteration assemblages, and minerals. Contrary to the multispectral sensors, the hyperspectral identifies targets with high spectral resolution. The Wayang Windu Geothermal field in West Java, Indonesia was selected as the study area due to the existence of surface manifestation and dense vegetation environment. Therefore, the effectiveness of hyperspectral remote sensing in tropical region was targeted as the study objective. The Spectral Angle Mapper (SAM) method was used to detect the occurrence of clay minerals spatially from Hyperion data. The SAM references of reflectance spectra were obtained from field observation at altered materials. To calculate the effectiveness of hyperspectral data, we used multispectral data from Landsat-8. The comparison method was conducted by comparing the SAM's rule images from Hyperion and Landsat-8, resulting that hyperspectral was more accurate than multispectral data. Hyperion SAM's rule images showed lower value compared to Landsat-8, the significant number derived from using Hyperion was about 24% better. This inferred that the hyperspectral remote sensing is preferable for mineral mapping even though vegetation covered study area.

  3. 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

  4. Alteration of CFTR transmembrane span integration by disease-causing mutations.

    PubMed

    Patrick, Anna E; Karamyshev, Andrey L; Millen, Linda; Thomas, Philip J

    2011-12-01

    Many missense mutations in the cystic fibrosis transmembrane conductance regulator protein (CFTR) result in its misfolding, endoplasmic reticulum (ER) accumulation, and, thus, cystic fibrosis. A number of these mutations are located in the predicted CFTR transmembrane (TM) spans and have been projected to alter span integration. However, the boundaries of the spans have not been precisely defined experimentally. In this study, the ER luminal integration profiles of TM1 and TM2 were determined using the ER glycosylation machinery, and the effects of the CF-causing mutations G85E and G91R thereon were assessed. The mutations either destabilize the integrated conformation or alter the TM1 ER integration profile. G85E misfolding is based in TM1 destabilization by glutamic acid and loss of glycine and correlates with the temperature-insensitive ER accumulation of immature full-length CFTR harboring the mutation. By contrast, temperature-dependent misfolding owing to the G91R mutation depends on the introduction of the basic side chain rather than the loss of the glycine. This work demonstrates that CF-causing mutations predicted to have similar effects on CFTR structure actually result in disparate molecular perturbations that underlie ER accumulation and the pathology of CF.

  5. Spinocerebellar ataxia type 13 mutant potassium channel alters neuronal excitability and causes locomotor deficits in zebrafish.

    PubMed

    Issa, Fadi A; Mazzochi, Christopher; Mock, Allan F; Papazian, Diane M

    2011-05-04

    Whether changes in neuronal excitability can cause neurodegenerative disease in the absence of other factors such as protein aggregation is unknown. Mutations in the Kv3.3 voltage-gated K(+) channel cause spinocerebellar ataxia type 13 (SCA13), a human autosomal-dominant disease characterized by locomotor impairment and the death of cerebellar neurons. Kv3.3 channels facilitate repetitive, high-frequency firing of action potentials, suggesting that pathogenesis in SCA13 is triggered by changes in electrical activity in neurons. To investigate whether SCA13 mutations alter excitability in vivo, we expressed the human dominant-negative R420H mutant subunit in zebrafish. The disease-causing mutation specifically suppressed the excitability of Kv3.3-expressing, fast-spiking motor neurons during evoked firing and fictive swimming and, in parallel, decreased the precision and amplitude of the startle response. The dominant-negative effect of the mutant subunit on K(+) current amplitude was directly responsible for the reduced excitability and locomotor phenotype. Our data provide strong evidence that changes in excitability initiate pathogenesis in SCA13 and establish zebrafish as an excellent model system for investigating how changes in neuronal activity impair locomotor control and cause cell death.

  6. Mapping of Gold Mineralization Alteration Zones in Central Eastern Desert Egypt using Spectral Angular Mapper and Aeromagnetic Data

    NASA Astrophysics Data System (ADS)

    Hasan, E.; Fagin, T.; El Alfy, Z.

    2014-12-01

    Central Eastern Desert (CED), Egypt has long history of gold exploration and exploitation. In this study, we integrated Spectral Angular Mapper (SAM) technique and aeromagnetic data to map the gold mineralization associated within alteration zones in CED. The spectral reflectance curves of five main alteration minerals (Hematite, Illite, Kaolinite, Chlorite, and Quartz) were utilized as end members in the SAM supervised classification of ETM+ data. Each alteration mineral type was represented as a binary image that overlaid together to obtain single primary alteration map in CED. The possible pathways for the alteration migration was defined based on the subsurface and surface lineation features. For the subsurface lineation, Euler deconvolution filter was applied on the aeromagnetic data to locate the deep-seated faults. The surface lineation and shear zones were extracted from ETM+ data and used together with the subsurface lineation map to obtain a structural map. Layer intersection and fuzzy membership operation were applied for the entire datasets to identify the possible sites of alteration zones. Several GPS readings were taken from the field areas around the gold mine sites, and used as validation points for our primary results.

  7. 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.

  8. Structural and functional alteration of blood vessels caused by cigarette smoking: an overview of molecular mechanisms.

    PubMed

    Rahman, Mohammad M; Laher, Ismail

    2007-10-01

    Smoking is a significant independent risk factor for cardiovascular disease and is a leading cause of structural and functional alterations of the cardiovascular system. Most clinical and experimental investigations of the pathophysiology of cigarette smoking have studied the effects of smoke as a whole, while a few studies focused on specific components of cigarette smoke, e.g. nicotine and carbon monoxide, which are only 2 of the more than 4,000 different chemicals present in cigarette smoke. The findings point to some discrepancies when the effects of whole smoke are compared to nicotine alone, while there is almost uniform agreement that both active and passive smoking have detrimental effects on the cardiovascular system, although a milder effect was suggested for the latter. This review focuses on findings from clinical and experimental studies on the vascular effects of active and passive cigarette smoking and nicotine exposure. The findings are discussed in terms of tissue (conduit vs. resistance arteries and veins), species, age, gender and dosage. Although the exact pathophysiology of cigarette smoking has not been unveiled, cigarette smoking causes injury to the vascular endothelium, produces superoxide anions, reduces production and bioavailability of nitric oxide (NO), increases production and release of endothelin, causes endothelial dysfunction, thrombosis, atherosclerosis, infarction, coronary artery disease (CAD), stroke and death.

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

    PubMed

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

    2015-11-06

    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.

  10. FOXA1 deletion in luminal epithelium causes prostatic hyperplasia and alteration of differentiated phenotype.

    PubMed

    DeGraff, David J; Grabowska, Magdalena M; Case, Tom C; Yu, Xiuping; Herrick, Mary K; Hayward, William J; Strand, Douglas W; Cates, Justin M; Hayward, Simon W; Gao, Nan; Walter, Michael A; Buttyan, Ralph; Yi, Yajun; Kaestner, Klaus H; Matusik, Robert J

    2014-07-01

    The forkhead box (Fox) superfamily of transcription factors has essential roles in organogenesis and tissue differentiation. Foxa1 and Foxa2 are expressed during prostate budding and ductal morphogenesis, whereas Foxa1 expression is retained in adult prostate epithelium. Previous characterization of prostatic tissue rescued from embryonic Foxa1 knockout mice revealed Foxa1 to be essential for ductal morphogenesis and epithelial maturation. However, it is unknown whether Foxa1 is required to maintain the differentiated status in adult prostate epithelium. Here, we employed the PBCre4 transgenic system and determined the impact of prostate-specific Foxa1 deletion in adult murine epithelium. PBCre4/Foxa1(loxp/loxp) mouse prostates showed progressive florid hyperplasia with extensive cribriform patterning, with the anterior prostate being most affected. Immunohistochemistry studies show mosaic Foxa1 KO consistent with PBCre4 activity, with Foxa1 KO epithelial cells specifically exhibiting altered cell morphology, increased proliferation, and elevated expression of basal cell markers. Castration studies showed that, while PBCre4/Foxa1(loxp/loxp) prostates did not exhibit altered sensitivity in response to hormone ablation compared with control prostates, the number of Foxa1-positive cells in mosaic Foxa1 KO prostates was significantly reduced compared with Foxa1-negative cells following castration. Unexpectedly, gene expression profile analyses revealed that Foxa1 deletion caused abnormal expression of seminal vesicle-associated genes in KO prostates. In summary, these results indicate Foxa1 expression is required for the maintenance of prostatic cellular differentiation.

  11. Structural and functional alterations of catalase induced by acriflavine, a compound causing apoptosis and necrosis.

    PubMed

    Attar, Farnoosh; Khavari-Nejad, Sarah; Keyhani, Jacqueline; Keyhani, Ezzatollah

    2009-08-01

    Acriflavine is an antiseptic agent causing both apoptosis and necrosis in yeast. In this work, its effect on the structure and function of catalase, a vital enzyme actively involved in protection against oxidative stress, was investigated. In vitro kinetic studies showed that acriflavine inhibited the enzymatic activity in a competitive manner. The residual activity detectable after preincubation of catalase (1.5 nmol/L) with various concentrations of acriflavine went from 50% to 20% of the control value as the acriflavine concentration increased from 30 to 90 micromol/L. Correlatively with the decrease in activity, alterations in the enzyme's conformation were observed as indicated by fluorescence spectroscopy, circular dichroism spectroscopy, and electronic absorption spectroscopy. The enzyme's intrinsic fluorescence obtained upon excitation at either 297 nm (tryptophan residues) or 280 nm (tyrosine and tryptophan residues) decreased as a function of acriflavine concentration. Circular dichroism studies showed alterations of the protein structure by acriflavine with up to 13% decrease in alpha helix, 16% increase in beta-sheet content, 17% increase in random coil, and 4% increase in beta turns. Spectrophotometric studies showed a blueshift and modifications in the chromicity of catalase at 405 nm, corresponding to an absorbance band due to the enzyme's prosthetic group. Thus, acriflavine induced in vitro a profound change in the structure of catalase so that the enzyme could no longer function. Our results showed that acriflavine, a compound producing apoptosis and necrosis, can have a direct effect on vital functions in cells by disabling key enzymes.

  12. Altered gravity causes the changes in the proteins NoA100 in plant cell nucleoli

    NASA Astrophysics Data System (ADS)

    Sobol, Margarita A.; Gonzalez-Camacho, Fernando; Kordyum, Elizabeth L.; Medina, Francisco Javier

    2005-08-01

    A nucleolar protein homologous to the mammalian nucleolin and to the onion nucleolin-like protein NopA100 was detected in nuclear soluble protein fraction from Lepidium sativum root meristematic cells, using the specific silver staining method and the cross-reaction with the anti-NopA100 antibody. In 2D Western blots of soluble nuclear fraction, NopA100 was revealed as a smear extending through a certain range of pI. In extracts obtained from seedlings grown under clinorotation, the extension of the pI range was shorter than in the stationary control indicating a lower phosphorylation of the protein. This suggests that altered gravity causes a decrease in the rate of nucleolar activity.

  13. 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.

  14. Low dose chronic treatment of human keratinocytes with inorganic arsenic causes hyperproliferation and altered protein phosphorylation

    SciTech Connect

    Steinberg, M.L.; Su, L.; Snow, E.T. |

    1997-10-01

    Chronic exposure to arsenate [As(V)] or arsenite [As(III)] causes hyperproliferation of normal and SV40-transformed human epidermal keratinocytes. Line 327 SV40-infected human keratinocytes were grown in the presence of either As(III) or As(V) (0.01 to 10 {mu}M) in complete medium for seven days prior to harvesting and counting. Both As(III) and As(V) were cytotoxic at micromolar concentrations, however submicromolar arsenic caused a significant increase in cell growth. Cell numbers in cultures exposed to As(V) were increased more than 186% relative to controls, and an even larger stimulation in cell growth was observed after treatment with 50 nM As(III). Normal non-SV40 T-antigen. Preliminary cell cycle analysis using unselected, log-phase cultures of arsenic-treated keratinocytes shows an increased proportion of cells in S- and G2/M-phase. Isoelectric focusing of phosphotyrosine-containing proteins from cells labeled with {sup 32}P-inorganic phosphate showed that the hyperproliferation of keratinocytes grown in low concentrations of arsenic is accompanied by altered tyrosine-specific protein phosphorylation. A number of phosphorylated proteins were observed in As-treated cells that were not observed in the controls; and minor bands at IEPs of 3.0, 4.2, 7.2, 7.5 and 8.2. These results, together with the lack of direct enzyme inhibition by arsenic shown by Su et al., this volume, suggest that arsenic-induced skin lesions and carcinogenesis may be the result of altered cell cycle control rather than DNA damage or reduced DNA repair.

  15. Resolution of Genetic Map Expansion Caused by Excess Heterozygosity in Plant Recombinant Inbred Populations

    PubMed Central

    Truong, Sandra K.; McCormick, Ryan F.; Morishige, Daryl T.; Mullet, John E.

    2014-01-01

    Recombinant inbred populations of many plant species exhibit more heterozygosity than expected under the Mendelian model of segregation. This segregation distortion causes the overestimation of recombination frequencies and consequent genetic map expansion. Here we build upon existing genetic models of differential zygotic viability to model a heterozygote fitness term and calculate expected genotypic proportions in recombinant inbred populations propagated by selfing. We implement this model using the existing open-source genetic map construction code base for R/qtl to estimate recombination fractions. Finally, we show that accounting for excess heterozygosity in a sorghum recombinant inbred mapping population shrinks the genetic map by 213 cM (a 13% decrease corresponding to 4.26 fewer recombinations per meiosis). More accurate estimates of linkage benefit linkage-based analyses used in the identification and utilization of causal genetic variation. PMID:25128435

  16. UBIAD1 Mutation Alters a Mitochondrial Prenyltransferase to Cause Schnyder Corneal Dystrophy

    PubMed Central

    Nickerson, Michael L.; Kostiha, Brittany N.; Brandt, Wolfgang; Fredericks, William; Xu, Ke-Ping; Yu, Fu-Shin; Gold, Bert; Chodosh, James; Goldberg, Marc; Lu, Da Wen; Yamada, Masakazu; Tervo, Timo M.; Grutzmacher, Richard; Croasdale, Chris; Hoeltzenbein, Maria; Sutphin, John; Malkowicz, S. Bruce; Wessjohann, Ludger; Kruth, Howard S.; Dean, Michael; Weiss, Jayne S.

    2010-01-01

    Background Mutations in a novel gene, UBIAD1, were recently found to cause the autosomal dominant eye disease Schnyder corneal dystrophy (SCD). SCD is characterized by an abnormal deposition of cholesterol and phospholipids in the cornea resulting in progressive corneal opacification and visual loss. We characterized lesions in the UBIAD1 gene in new SCD families and examined protein homology, localization, and structure. Methodology/Principal Findings We characterized five novel mutations in the UBIAD1 gene in ten SCD families, including a first SCD family of Native American ethnicity. Examination of protein homology revealed that SCD altered amino acids which were highly conserved across species. Cell lines were established from patients including keratocytes obtained after corneal transplant surgery and lymphoblastoid cell lines from Epstein-Barr virus immortalized peripheral blood mononuclear cells. These were used to determine the subcellular localization of mutant and wild type protein, and to examine cholesterol metabolite ratios. Immunohistochemistry using antibodies specific for UBIAD1 protein in keratocytes revealed that both wild type and N102S protein were localized sub-cellularly to mitochondria. Analysis of cholesterol metabolites in patient cell line extracts showed no significant alteration in the presence of mutant protein indicating a potentially novel function of the UBIAD1 protein in cholesterol biochemistry. Molecular modeling was used to develop a model of human UBIAD1 protein in a membrane and revealed potentially critical roles for amino acids mutated in SCD. Potential primary and secondary substrate binding sites were identified and docking simulations indicated likely substrates including prenyl and phenolic molecules. Conclusions/Significance Accumulating evidence from the SCD familial mutation spectrum, protein homology across species, and molecular modeling suggest that protein function is likely down-regulated by SCD mutations

  17. 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.

  18. 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.

  19. 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

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

    NASA Astrophysics Data System (ADS)

    Finn, Carol A.; Deszcz-Pan, Maryla; Anderson, Eric D.; John, David A.

    2007-10-01

    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.

  1. 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.

  2. Olanzapine Treatment of Adolescent Rats Causes Enduring Specific Memory Impairments and Alters Cortical Development and Function

    PubMed Central

    Swanson, Thomas; Enos, Jennifer K.; Bailey, Aileen M.; Kolb, Bryan; Frost, Douglas O.

    2013-01-01

    Antipsychotic drugs are increasingly used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of early life antipsychotic drug treatment. Most antipsychotic drugs are potent antagonists or partial agonists of dopamine D2 receptors; atypical antipsychotic drugs also antagonize type 2A serotonin receptors. Dopamine and serotonin regulate many neurodevelopmental processes. Thus, early life antipsychotic drug treatment can, potentially, perturb these processes, causing long-term behavioral- and neurobiological impairments. Here, we treated adolescent, male rats with olanzapine on post-natal days 28–49. As adults, they exhibited impaired working memory, but normal spatial memory, as compared to vehicle-treated control rats. They also showed a deficit in extinction of fear conditioning. Measures of motor activity and skill, habituation to an open field, and affect were normal. In the orbital- and medial prefrontal cortices, parietal cortex, nucleus accumbens core and dentate gyrus, adolescent olanzapine treatment altered the developmental dynamics and mature values of dendritic spine density in a region-specific manner. Measures of motor activity and skill, habituation to an open field, and affect were normal. In the orbital- and medial prefrontal cortices, D1 binding was reduced and binding of GABAA receptors with open Cl− channels was increased. In medial prefrontal cortex, D2 binding was also increased. The persistence of these changes underscores the importance of improved understanding of the enduring sequelae of pediatric APD treatment as a basis for weighing the benefits and risks of adolescent antipsychotic drug therapy, especially prophylactic treatment in high risk, asymptomatic patients. The long-term changes in neurotransmitter receptor binding and neural circuitry induced by adolescent APD treatment may also cause enduring changes in behavioral- and neurobiological responses to

  3. Exposure to sorbitol during lactation causes metabolic alterations and genotoxic effects in rat offspring.

    PubMed

    Cardoso, Felipe S; Araujo-Lima, Carlos F; Aiub, Claudia A F; Felzenszwalb, Israel

    2016-10-17

    Sorbitol is a polyol used by the food industry as a sweetener. Women are consuming diet and light products containing sorbitol during pregnancy and in the postnatal period to prevent themselves from excessive weight gain and maintain a slim body. Although there is no evidence for the genotoxicity of sorbitol in the perinatal period, this study focused on evaluating the effects of the maternal intake of sorbitol on the biochemical and toxicological parameters of lactating Wistar rat offspring after 14days of mother-to-offspring exposure. A dose-dependent reduction of offspring length was observed. An increase in sorbitol levels determined in the milk was also observed. However, we detected an inverse relationship between the exposition dose in milk fructose and triacylglycerols concentrations. There was an increase in the plasmatic levels of ALT, AST and LDLc and a decrease in proteins, cholesterol and glucose levels in the offspring. Sorbitol exposure caused hepatocyte genotoxicity, including micronuclei induction. Maternal sorbitol intake induced myelotoxicity and myelosuppression in their offspring. The Comet assay of the blood cells detected a dose-dependent genotoxic response within the sorbitol-exposed offspring. According to our results, sorbitol is able to induce important metabolic alterations and genotoxic responses in the exposed offspring.

  4. Ceramide synthase 4 deficiency in mice causes lipid alterations in sebum and results in alopecia.

    PubMed

    Ebel, Philipp; Imgrund, Silke; Vom Dorp, Katharina; Hofmann, Kristina; Maier, Helena; Drake, Helena; Degen, Joachim; Dörmann, Peter; Eckhardt, Matthias; Franz, Thomas; Willecke, Klaus

    2014-07-01

    Five ceramide synthases (CerS2-CerS6) are expressed in mouse skin. Although CerS3 has been shown to fulfill an essential function during skin development, neither CerS6- nor CerS2-deficient mice show an obvious skin phenotype. In order to study the role of CerS4, we generated CerS4-deficient mice (Cers4-/-) and CerS4-specific antibodies. With these biological tools we analysed the tissue distribution and determined the cell-type specific expression of CerS4 in suprabasal epidermal layers of footpads as well as in sebaceous glands of the dorsal skin. Loss of CerS4 protein leads to an altered lipid composition of the sebum, which is more solidified and therefore might cause progressive hair loss due to physical blocking of the hair canal. We also noticed a strong decrease in C20 1,2-alkane diols consistent with the decrease of wax diesters in the sebum of Cers4-/- mice. Cers4-/- mice at 12 months old display additional epidermal tissue destruction due to dilated and obstructed pilary canals. Mass spectrometric analyses additionally show a strong decrease in C20-containing sphingolipids.

  5. Morphological and functional alteration of erythrocyte ghosts and giant unilamellar vesicles caused by Vipera latifi venom.

    PubMed

    Kirakosyan, Gayane; Mohamadvarzi, Maryam; Ghulikyan, Lusine; Zaqaryan, Naira; Kishmiryan, Arsen; Ayvazyan, Naira

    2016-12-01

    Snake bites are an endemic public health problem in Iran, both in rural and urban area. Viper venom as a hemolytic biochemical "cocktail" of toxins, primarily cause to the systemic alteration of blood cells. In the sixties and seventies, human erythrocytes were extensively studied, but the mechanical and chemical stresses commonly exerted on red blood cells continue to attract interest of scientists for the study of membrane structure and function. Here, we monitor the effect of Vipera latifi venom on human erythrocytes ghost membranes using phase contrast and fluorescent microscopy and changes in ATPase activity under snake venom influence in vitro. The ion pumps [Na(+),K(+)]-ATPase and (Ca(2+)+Mg(2+))-ATPase plays a pivotal role in the active transport of certain cations and maintenance of intracellular electrolyte homeostasis. We also describe the interaction of Vipera latifi (VL) venom with giant unilamellar vesicles (GUVs) composed of the native phospholipid mixtures visualized by the membrane fluorescence probe, ANS, used to assess the state of membrane and specifically mark the phospholipid domains.

  6. Mapping the basal ganglia alterations in children chronically exposed to manganese

    PubMed Central

    Lao, Yi; Dion, Laurie-Anne; Gilbert, Guillaume; Bouchard, Maryse F.; Rocha, Gabriel; Wang, Yalin; Leporé, Natasha; Saint-Amour, Dave

    2017-01-01

    Chronic manganese (Mn) exposure is associated with neuromotor and neurocognitive deficits, but the exact mechanism of Mn neurotoxicity is still unclear. With the advent of magnetic resonance imaging (MRI), in-vivo analysis of brain structures has become possible. Among different sub-cortical structures, the basal ganglia (BG) has been investigated as a putative anatomical biomarker in MR-based studies of Mn toxicity. However, previous investigations have yielded inconsistent results in terms of regional MR signal intensity changes. These discrepancies may be due to the subtlety of brain alterations caused by Mn toxicity, coupled to analysis techniques that lack the requisite detection power. Here, based on brain MRI, we apply a 3D surface-based morphometry method on 3 bilateral basal ganglia structures in school-age children chronically exposed to Mn through drinking water to investigate the effect of Mn exposure on brain anatomy. Our method successfully pinpointed significant enlargement of many areas of the basal ganglia structures, preferentially affecting the putamen. Moreover, these areas showed significant correlations with fine motor performance, indicating a possible link between altered basal ganglia neurodevelopment and declined motor performance in high Mn exposed children. PMID:28155922

  7. Mapping the basal ganglia alterations in children chronically exposed to manganese.

    PubMed

    Lao, Yi; Dion, Laurie-Anne; Gilbert, Guillaume; Bouchard, Maryse F; Rocha, Gabriel; Wang, Yalin; Leporé, Natasha; Saint-Amour, Dave

    2017-02-03

    Chronic manganese (Mn) exposure is associated with neuromotor and neurocognitive deficits, but the exact mechanism of Mn neurotoxicity is still unclear. With the advent of magnetic resonance imaging (MRI), in-vivo analysis of brain structures has become possible. Among different sub-cortical structures, the basal ganglia (BG) has been investigated as a putative anatomical biomarker in MR-based studies of Mn toxicity. However, previous investigations have yielded inconsistent results in terms of regional MR signal intensity changes. These discrepancies may be due to the subtlety of brain alterations caused by Mn toxicity, coupled to analysis techniques that lack the requisite detection power. Here, based on brain MRI, we apply a 3D surface-based morphometry method on 3 bilateral basal ganglia structures in school-age children chronically exposed to Mn through drinking water to investigate the effect of Mn exposure on brain anatomy. Our method successfully pinpointed significant enlargement of many areas of the basal ganglia structures, preferentially affecting the putamen. Moreover, these areas showed significant correlations with fine motor performance, indicating a possible link between altered basal ganglia neurodevelopment and declined motor performance in high Mn exposed children.

  8. Neonatal overnutrition causes early alterations in the central response to peripheral ghrelin

    PubMed Central

    Collden, Gustav; Balland, Eglantine; Parkash, Jyoti; Caron, Emilie; Langlet, Fanny; Prevot, Vincent; Bouret, Sebastien G.

    2014-01-01

    Objective Excess nutrient supply and rapid weight gain during early life are risk factors for the development of obesity during adulthood. This metabolic malprogramming may be mediated by endocrine disturbances during critical periods of development. Ghrelin is a metabolic hormone secreted from the stomach that acts centrally to promote feeding behavior by binding to growth hormone secretagogue receptors in the arcuate nucleus of the hypothalamus. Here, we examined whether neonatal overnutrition causes changes in the ghrelin system. Methods We used a well-described mouse model of divergent litter sizes to study the effects of postnatal overfeeding on the central and peripheral ghrelin systems during postnatal development. Results Mice raised in small litters became overweight during lactation and remained overweight with increased adiposity as adults. Neonatally overnourished mice showed attenuated levels of total and acyl ghrelin in serum and decreased levels of Ghrelin mRNA expression in the stomach during the third week of postnatal life. Normalization of hypoghrelinemia in overnourished pups was relatively ineffective at ameliorating metabolic outcomes, suggesting that small litter pups may present ghrelin resistance. Consistent with this idea, neonatally overnourished pups displayed an impaired central response to peripheral ghrelin. The mechanisms underlying this ghrelin resistance appear to include diminished ghrelin transport into the hypothalamus. Conclusions Early postnatal overnutrition results in central resistance to peripheral ghrelin during important periods of hypothalamic development. Because ghrelin signaling has recently been implicated in the neonatal programming of metabolism, these alterations in the ghrelin system may contribute to the metabolic defects observed in postnatally overnourished mice. PMID:25685686

  9. Altered cellular metabolism of HepG2 cells caused by microcystin-LR.

    PubMed

    Ma, Junguo; Feng, Yiyi; Jiang, Siyu; Li, Xiaoyu

    2017-03-21

    This study aimed to evaluate the possible effects of microcystin-LR (MC-LR) exposure on the metabolism and drug resistance of human hepatocellular carcinoma (HepG2) cells. For this purpose, we first conducted an experiment to make sure that MC-LR could penetrate the HepG2 cell membrane effectively. The transcriptional levels of phase I (such as CYP2E1, CYP3A4, and CYP26B1) and phase II (such as EPHX1, SULTs, and GSTM) enzymes and export pump genes (such as MRP1 and MDR1) were altered by MC-LR-exposure for 24 h, indicating that MC-LR treatment may destabilize the metabolism of HepG2 cells. Further research showed that the CYP inducers omeprazole, ethanol, and rifampicin inhibited cell viability, in particular, ethanol, a CYP2E1 inducer, induced ROS generation, lipid peroxidation, and apoptosis in HepG2 cells treated with MC-LR. The CYP2E1 inhibitor chlormethiazole inhibited ROS generation, mitochondrial membrane potential loss, caspase-3 activity, and cytotoxicity caused by MC-LR. Meanwhile, the results also showed that co-incubation with the ROS scavenger l-ascorbic acid and MC-LR decreased ROS levels and effectively prevented apoptosis. These findings provide an interesting mechanistic explanation of cellular metabolism associated with MC-LR, i.e., MC-LR-exposure exerted toxicity on HepG2 cells and induced apoptosis of HepG2 cells via promoting CYP2E1 expression and inducing excessive ROS in HepG2 cells.

  10. 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

  11. Is altered nutritional status the root cause of your clients' negative outcomes?

    PubMed

    Cole, C; Bigando, K; DeSutter, S

    2000-01-01

    The impact of altered nutritional status is costly. Surgical patients have 2-3 times the risk of complications, length of stay is extended by 90%, and charges are 35-75% higher. Risk factors are numerous; therefore, collaboration among all members of the health care team is required to impact patient outcomes positively. The purpose of this article is to review the significance of alteration in nutrition and its impact on patient outcomes. The article demonstrates two approaches to improve the quality of care given to clients with an identified alteration in nutritional status: a clinical research project and a quality improvement project.

  12. Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers.

    PubMed

    Lønning, P E; Knappskog, S

    2013-11-14

    Although new agents are implemented to cancer therapy, we lack fundamental understandings of the mechanisms of chemoresistance, the main obstacle to cure in cancer. Here we review clinical evidence linking molecular defects to drug resistance across different tumour forms and discuss contemporary experimental evidence exploring these mechanisms. Although evidence, in general, is sparse and fragmentary, merging knowledge links drug resistance, and also sensitivity, to defects in functional pathways having a key role in cell growth arrest or death and DNA repair. As these pathways may act in concert, there is a need to explore multiple mechanisms in parallel. Taking advantage of massive parallel sequencing and other novel high-throughput technologies and base research on biological hypotheses, we now have the possibility to characterize functional defects related to these key pathways and to design a new generation of studies identifying the mechanisms controlling resistance to different treatment regimens in different tumour forms.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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

    ... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 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...

  19. 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...

  20. 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

    ... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 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...

  1. 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

    ... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 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...

  2. 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...

  3. 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

  4. 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.

  5. 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

  6. Ultrastructural Study on Tissue Alterations Caused by Trypanosomatids in Experimental Murine Infections

    PubMed Central

    Finol, Héctor J.; Roschman-González, Antonio

    2014-01-01

    The ultrastructural study in different tissues of mice experimentally infected with isolates of Trypanosoma evansi, Trypanosoma cruzi, and Leishmania mexicana reveals changes in cardiac myocytes, skeletal muscle fibers, and hepatic, adrenal, kidney, and spleen cells. Some of these changes were cytoarchitectural and others consisted of necrosis. Alterations in the microvasculature were also found. The mononuclear cell infiltrate included neutrophils, eosinophils, and macrophages. This work shows that diverse mice tissues are important target for trypanosomatids. PMID:25072046

  7. Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients

    PubMed Central

    Sauer, Aisha V.; Hernandez, Raisa Jofra; Fumagalli, Francesca; Bianchi, Veronica; Poliani, Pietro L.; Dallatomasina, Chiara; Riboni, Elisa; Politi, Letterio S.; Tabucchi, Antonella; Carlucci, Filippo; Casiraghi, Miriam; Carriglio, Nicola; Cominelli, Manuela; Forcellini, Carlo Alberto; Barzaghi, Federica; Ferrua, Francesca; Minicucci, Fabio; Medaglini, Stefania; Leocani, Letizia; la Marca, Giancarlo; Notarangelo, Lucia D.; Azzari, Chiara; Comi, Giancarlo; Baldoli, Cristina; Canale, Sabrina; Sessa, Maria; D’Adamo, Patrizia; Aiuti, Alessandro

    2017-01-01

    Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA. These included motor dysfunction, EEG alterations, sensorineural hypoacusia, white matter and ventricular alterations in MRI as well as a low mental development index or IQ. Ada-deficient mice were significantly less active and showed anxiety-like behavior. Molecular and metabolic analyses showed that this phenotype coincides with metabolic alterations and aberrant adenosine receptor signaling. PEG-ADA treatment corrected metabolic adenosine-based alterations, but not cellular and signaling defects, indicating an intrinsic nature of the neurological and behavioral phenotype in ADA deficiency. PMID:28074903

  8. Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients.

    PubMed

    Sauer, Aisha V; Hernandez, Raisa Jofra; Fumagalli, Francesca; Bianchi, Veronica; Poliani, Pietro L; Dallatomasina, Chiara; Riboni, Elisa; Politi, Letterio S; Tabucchi, Antonella; Carlucci, Filippo; Casiraghi, Miriam; Carriglio, Nicola; Cominelli, Manuela; Forcellini, Carlo Alberto; Barzaghi, Federica; Ferrua, Francesca; Minicucci, Fabio; Medaglini, Stefania; Leocani, Letizia; la Marca, Giancarlo; Notarangelo, Lucia D; Azzari, Chiara; Comi, Giancarlo; Baldoli, Cristina; Canale, Sabrina; Sessa, Maria; D'Adamo, Patrizia; Aiuti, Alessandro

    2017-01-11

    Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA. These included motor dysfunction, EEG alterations, sensorineural hypoacusia, white matter and ventricular alterations in MRI as well as a low mental development index or IQ. Ada-deficient mice were significantly less active and showed anxiety-like behavior. Molecular and metabolic analyses showed that this phenotype coincides with metabolic alterations and aberrant adenosine receptor signaling. PEG-ADA treatment corrected metabolic adenosine-based alterations, but not cellular and signaling defects, indicating an intrinsic nature of the neurological and behavioral phenotype in ADA deficiency.

  9. Epigenetic alterations caused by nutritional stress during fetal programming of the endocrine pancreas.

    PubMed

    Sosa-Larios, Tonantzin C; Cerbón, Marco A; Morimoto, Sumiko

    2015-02-01

    Nutrition during critical periods of development is one of the pivotal factors in establishing a lifelong healthy metabolism. Different nutritional deficiencies such as a low availability of proteins in the maternal diet produce alterations in offspring that include changes in insulin and glucose metabolism, a decrease in the size and number of cells of pancreatic islets of Langerhans, and premature ageing of the secretory function of pancreatic β cells. Moreover, it has been reported that chronic nutritional stress is associated with epigenetic alterations in mechanisms of gene regulation during pancreatic development and function. These alterations can lead to dysfunctional states in pancreatic β cells, which in the long run are responsible for the onset of metabolic diseases like type 2 diabetes. The present review summarizes the most important evidence in relation to the participation of epigenetic mechanisms in the regulation of gene expression during the intrauterine programming of the endocrine pancreas in animal models. Such mechanisms include DNA methylation as well as modifications of histones and microRNAs (miRNAs).

  10. Changes in bone Pb accumulation: cause and effect of altered bone turnover.

    PubMed

    Brito, José A A; Costa, Isabel M; E Silva, Alexandra Maia; Marques, José M S; Zagalo, Carlos M; Cavaleiro, Inês I B; Fernandes, Tânia A P; Gonçalves, Luísa L

    2014-07-01

    This paper assesses the magnitude of Pb uptake in cortical and trabecular bones in healthy animals and animals with altered balance in bone turnover, and the impact of exposure to Pb on serum markers of bone formation and resorption. The results reported herein provide physiological evidence that Pb distributes differently in central compartments in Pb metabolism, such as cortical and trabecular bones, in healthy animals and animals with altered balance in bone turnover, and that exposure to Pb does have an impact on bone resorption resulting in OC-dependent osteopenia. These findings show that Pb may play a role in the etiology of osteoporosis and that its concentration in bones varies as a result of altered bone turnover characteristic of this disease, a long standing question in the field. In addition, data collected in this study are consistent with previous observations of increased half-life of Pb in bone at higher exposures. This evidence is relevant for the necessary revision of current physiologically based kinetic models for Pb in humans.

  11. Bifenthrin causes trophic cascades and alters insect emergence in mesocosms: implication for small streams

    USGS Publications Warehouse

    Rogers, Holly; Schmidt, Travis S.; Dabney, Brittanie L.; Hladik, Michelle; Mahler, Barbara J.; VanMetre, Peter

    2016-01-01

    Direct and indirect ecological effects of the widely used insecticide bifenthrin on stream ecosystems are largely unknown. To investigate such effects, a manipulative experiment was conducted in stream mesocosms that were colonized by aquatic insect communities and exposed to bifenthrin-contaminated sediment; implications for natural streams were interpreted through comparison of mesocosm results to a survey of 100 Midwestern streams, USA. In the mesocosm experiment, direct effects of bifenthrin exposure included reduced larval macroinvertebrate abundance, richness, and biomass at concentrations (EC50s ranged 197.6 – 233.5 ng bifenthrin/ g organic carbon) previously thought safe for aquatic life. Indirect effects included a trophic cascade in which periphyton abundance increased after macroinvertebrate scrapers decreased. Adult emergence dynamics and corresponding terrestrial subsidies were altered at all bifenthrin concentrations tested. Extrapolating these results to the Midwestern stream assessment suggests pervasive ecological effects, with altered emergence dynamics likely in 40% of streams and a trophic cascade in 7% of streams. This study provides new evidence that a common pyrethroid might alter aquatic and terrestrial ecosystem function at the regional scale.

  12. 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.

  13. Cause of exercise associated muscle cramps (EAMC)--altered neuromuscular control, dehydration or electrolyte depletion?

    PubMed

    Schwellnus, M P

    2009-06-01

    Exercise Associated Muscle Cramps (EAMC) is one of the most common conditions that require medical attention during or immediately after sports events. Despite the high prevalence of this condition the aetiology of EAMC in athletes is still not well understood. The purpose of this review is to examine current scientific evidence in support of (1) the "electrolyte depletion" and "dehydration" hypotheses and (2) the "altered neuromuscular control" hypothesis in the aetiology of EAMC. In this review, scientific evidence will, as far as possible, be presented using evidence-based medicine criteria. This is particularly relevant in this field, as the quality of experimental methodology varies considerably among studies that are commonly cited in support of hypotheses to explain the aetiology of EAMC. Scientific evidence in support of the "electrolyte depletion" and "dehydration" hypotheses for the aetiology of EAMC comes mainly from anecdotal clinical observations, case series totalling 18 cases, and one small (n = 10) case-control study. Results from four prospective cohort studies do not support these hypotheses. In addition, the "electrolyte depletion" and "dehydration" hypotheses do not offer plausible pathophysiological mechanisms with supporting scientific evidence that could adequately explain the clinical presentation and management of EAMC. Scientific evidence for the "altered neuromuscular control" hypothesis is based on evidence from research studies in human models of muscle cramping, epidemiological studies in cramping athletes, and animal experimental data. Whilst it is clear that further evidence to support the "altered neuromuscular control" hypothesis is also required, research data are accumulating that support this as the principal pathophysiological mechanism for the aetiology of EAMC.

  14. Epigenetic Alterations May Regulate Temporary Reversal of CD4+ T Cell Activation Caused by Trichloroethylene Exposure

    PubMed Central

    Gilbert, Kathleen M.; Nelson, Ashley R.; Cooney, Craig A.; Reisfeld, Brad; Blossom, Sarah J.

    2012-01-01

    Previous studies have shown that short-term (4 weeks) or chronic (32 weeks) exposure to trichloroethylene (TCE) in drinking water of female MRL+/+ mice generated CD4+ T cells that secreted increased levels of interferon (IFN)-γ and expressed an activated (CD44hiCD62Llo) phenotype. In contrast, the current study of subchronic TCE exposure showed that midway in the disease process both of these parameters of CD4+ T cell activation were reversed. This phase of the disease process may represent an attempt by the body to counteract the inflammatory effects of TCE. The decrease in CD4+ T cell production of IFN-γ following subchronic TCE exposure could not be attributed to skewing toward a Th2 or Th17 phenotype or to an increase in Treg cells. Instead, the suppression corresponded to alterations in markers used to assess DNA methylation, namely increased expression of retrotransposons Iap (intracisternal A particle) and Muerv (murine endogenous retrovirus). Also observed was an increase in the expression of Dnmt1 (DNA methyltransferase-1) and decreased expression of several genes known to be downregulated by DNA methylation, namely Ifng, Il2, and Cdkn1a. CD4+ T cells from a second study in which MRL+/+ mice were treated for 17 weeks with TCE showed a similar increase in Iap and decrease in Cdkn1a. In addition, DNA collected from the CD4+ T cells in the second study showed TCE-decreased global DNA methylation. Thus, these results described the biphasic nature of TCE-induced alterations in CD4+ T cell function and suggested that these changes represented potentially reversible alterations in epigenetic processes. PMID:22407948

  15. Deer herbivory alters forest response to canopy decline caused by an exotic insect pest.

    PubMed

    Eschtruth, Anne K; Battles, John J

    2008-03-01

    Hemlock woolly adelgid (HWA; Adelges tsugae) infestations have resulted in the continuing decline of eastern hemlock (Tsuga canadensis) throughout much of the eastern United States. While the initial impacts of HWA infestations have been documented, our understanding of forest response to this disturbance remains incomplete. HWA infestation is not occurring in isolation but within a complex ecological context. The role of potentially important interacting factors, such as elevated levels of white-tailed deer herbivory, is poorly understood. Despite the potential for herbivory to alter forest successional trajectories following a canopy disturbance, little is known about herbivory-disturbance interactions, and herbivory is rarely considered in assessing forest response to a co-occurring disturbance. We used repeated censuses of deer exclosures and paired controls (400 paired plots) to quantify the impact of deer herbivory on tree seedling species abundance in 10 eastern hemlock ravines that span a gradient in HWA-induced canopy decline severity. Use of a maximum likelihood estimation framework and information theoretics allowed us to quantify the strength of evidence for alternative models developed to estimate the impacts of herbivory on tree seedling abundance as a function of varying herbivore density and canopy decline severity. The exclusion of deer herbivory had marked impacts on the abundance of the studied seedling species: Acer rubrum, Acer saccharum, Betula lenta, Nyssa sylvatica, Quercus montana, and Tsuga canadensis. For all six species, the relationship between seedling abundance and deer density was either exponential or saturating. Although the functional form of the response varied among seedling species, the inclusion of both deer density and canopy decline severity measures consistently resulted in models with substantially greater support. Canopy decline resulted in higher proportional herbivory impacts and altered the ranking of herbivory impacts

  16. 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.

  17. Herbivores cause a rapid increase in hereditary symbiosis and alter plant community composition

    PubMed Central

    Clay, Keith; Holah, Jenny; Rudgers, Jennifer A.

    2005-01-01

    Microbial symbioses are ubiquitous in nature. Hereditary symbionts warrant particular attention because of their direct effects on the evolutionary potential of their hosts. In plants, hereditary fungal endophytes can increase the competitive ability, drought tolerance, and herbivore resistance of their host, although it is unclear whether or how these ecological benefits may alter the dynamics of the endophyte symbiosis over time. Here, we demonstrate that herbivores alter the dynamics of a hereditary symbiont under field conditions. Also, we show that changes in symbiont frequency were accompanied by shifts in the overall structure of the plant community. Replicated 25-m2 plots were enriched with seed of the introduced grass, Lolium arundinaceum at an initial frequency of 50% infection by the systemic, seed-transmitted endophyte Neotyphodium coenophialum. Over 54 months, there was a significantly greater increase in endophyte-infection frequency in the presence of herbivores (30% increase) than where mammalian and insect herbivory were experimentally reduced by fencing and insecticide application (12% increase). Under ambient mammalian herbivory, the above-ground biomass of nonhost plant species was reduced compared with the mammal-exclusion treatment, and plant composition shifted toward greater relative biomass of infected, tall fescue grass. These results demonstrate that herbivores can drive plant–microbe dynamics and, in doing so, modify plant community structure directly and indirectly. PMID:16116093

  18. Herbivores cause a rapid increase in hereditary symbiosis and alter plant community composition.

    PubMed

    Clay, Keith; Holah, Jenny; Rudgers, Jennifer A

    2005-08-30

    Microbial symbioses are ubiquitous in nature. Hereditary symbionts warrant particular attention because of their direct effects on the evolutionary potential of their hosts. In plants, hereditary fungal endophytes can increase the competitive ability, drought tolerance, and herbivore resistance of their host, although it is unclear whether or how these ecological benefits may alter the dynamics of the endophyte symbiosis over time. Here, we demonstrate that herbivores alter the dynamics of a hereditary symbiont under field conditions. Also, we show that changes in symbiont frequency were accompanied by shifts in the overall structure of the plant community. Replicated 25-m2 plots were enriched with seed of the introduced grass, Lolium arundinaceum at an initial frequency of 50% infection by the systemic, seed-transmitted endophyte Neotyphodium coenophialum. Over 54 months, there was a significantly greater increase in endophyte-infection frequency in the presence of herbivores (30% increase) than where mammalian and insect herbivory were experimentally reduced by fencing and insecticide application (12% increase). Under ambient mammalian herbivory, the above-ground biomass of nonhost plant species was reduced compared with the mammal-exclusion treatment, and plant composition shifted toward greater relative biomass of infected, tall fescue grass. These results demonstrate that herbivores can drive plant-microbe dynamics and, in doing so, modify plant community structure directly and indirectly.

  19. Podocyte-Specific Deletion of Dicer Alters Cytoskeletal Dynamics and Causes Glomerular Disease

    PubMed Central

    Harvey, Scott J.; Jarad, George; Cunningham, Jeanette; Goldberg, Seth; Schermer, Bernhard; Harfe, Brian D.; McManus, Michael T.; Benzing, Thomas; Miner, Jeffrey H.

    2008-01-01

    MicroRNAs (miRNAs) regulate gene expression by binding the 3′ untranslated region of mRNAs. To define their role in glomerular function, miRNA biogenesis was disrupted in mouse podocytes using a conditional Dicer allele. Mutant mice developed proteinuria by 3 wk after birth and progressed rapidly to end-stage kidney disease. Podocyte pathology included effacement, vacuolization, and hypertrophy with crescent formation. Despite normal expression of WT1, podocytes underwent dedifferentiation, exemplified by cytoskeletal disruption with early transcriptional downregulation of synaptopodin. These abnormalities differed from Cd2ap−/− mice, indicating they were not a general consequence of glomerular disease. Glomerular labeling of ezrin, moesin, and gelsolin was altered at 3 wk, but expression of nestin and α-actinin was unchanged. Abnormal cell proliferation or apoptosis was not responsible for the glomerular injury. Mutant podocytes were incapable of synthesizing mature miRNA, as revealed by their loss of miR-30a. In contrast, expression of glomerular endothelial and mesangial cell miRNAs (miR-126 and miR-145, respectively) was unchanged. These findings demonstrate a critical role for miRNA in glomerular function and suggest a pathway that may participate in the pathogenesis of kidney diseases of podocyte origin. The unique architecture of podocytes may make them especially susceptible to cytoskeletal alterations initiated by aberrant miRNA dynamics. PMID:18776121

  20. The self-incompatibility response in Papaver rhoeas pollen causes early and striking alterations to organelles.

    PubMed

    Geitmann, A; Franklin-Tong, V E; Emons, A C

    2004-08-01

    Self-incompatibility (SI) in Papaver rhoeas is accompanied by a cascade of signalling events that result in the rapid arrest and eventual death of the pollen tube. We have used rapid freeze fixation, freeze substitution and transmission electron microscopy to provide the first description of changes to pollen at the ultrastructural level during SI in this species. Our studies reveal that dramatic alterations to the morphology of mitochondria, Golgi bodies and ER occur within 1 h of SI induction. Similar symptoms have also been observed during programmed cell death (PCD) in some cell types. These include: the conspicuous condensation of the vegetative and generative nuclei, the swelling and loss of cristae in mitochondria and the disappearance of Golgi bodies. Some of the early alterations to the mitochondria and Golgi bodies observed at 1 h, almost certainly occur when cells are still alive. Other events, such as nuclear condensation, occur later and coincide with DNA fragmentation and the loss of cell viability. Our observations suggest that the SI response in P. rhoeas pollen may potentially involve a type of PCD.

  1. 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.

  2. Aging causes morphological alterations in astrocytes and microglia in human substantia nigra pars compacta.

    PubMed

    Jyothi, H J; Vidyadhara, D J; Mahadevan, Anita; Philip, Mariamma; Parmar, Suresh Kumar; Manohari, S Gowri; Shankar, S K; Raju, Trichur R; Alladi, Phalguni Anand

    2015-12-01

    Age being a risk factor for Parkinson's disease, assessment of age-related changes in the human substantia nigra may elucidate its pathogenesis. Increase in Marinesco bodies, α-synuclein, free radicals and so forth in the aging nigral neurons are clear indicators of neurodegeneration. Here, we report the glial responses in aging human nigra. The glial numbers were determined on Nissl-stained sections. The expression of glial fibrillary acidic protein, S100β, 2', 3'-cyclic nucleotide 3' phosphodiesterase, and Iba1 was assessed on cryosections of autopsied midbrains by immunohistochemistry and densitometry. The glial counts showed a biphasic increase, of which, the first prominent phase from fetal age to birth could be physiological gliogenesis whereas the second one after middle age may reflect mild age-related gliosis. Astrocytic morphology was altered, but glial fibrillary acidic protein expression increased only mildly. Presence of type-4 microglia suggests possibility of neuroinflammation. Mild reduction in 2', 3'-cyclic nucleotide 3' phosphodiesterase-labeled area denotes subtle demyelination. Stable age-related S100β expression indicates absence of calcium overload. Against the expected prominent gliosis, subtle age-related morphological alterations in human nigral glia attribute them a participatory role in aging.

  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. Off-the-Vine Ripening of Tomato Fruit Causes Alteration in the Primary Metabolite Composition.

    PubMed

    Sorrequieta, Augusto; Abriata, Luciano A; Boggio, Silvana B; Valle, Estela M

    2013-10-16

    The influence of postharvest fruit ripening in the composition of metabolites, transcripts and enzymes in tomato (Solanum lycopersicum L.) is poorly understood. The goal of this work was to study the changes in the metabolite composition of the tomato fruit ripened off-the-vine using the cultivar Micro-Tom as model system. Proton nuclear magnetic resonance (1H NMR) was used for analysis of the metabolic profile of tomato fruits ripened on- and off-the-vine. Significant differences under both ripening conditions were observed principally in the contents of fructose, glucose, aspartate and glutamate. Transcript levels and enzyme activities of -amino butyrate transaminase (EC 2.6.1.19) and glutamate decarboxylase (EC 4.1.1.15) showed differences in fruits ripened under these two conditions. These data indicate that the contents of metabolites involved in primary metabolism, and conferring the palatable properties of fruits, are altered when fruits are ripened off-the-vine.

  5. Mitochondrial proteomic alterations caused by long-term low-dose copper exposure in mouse cortex.

    PubMed

    Lin, Xuemei; Wei, Gang; Huang, Zhijun; Qu, Zhongsen; Huang, Xinfeng; Xu, Hua; Liu, Jianjun; Zhuang, Zhixiong; Yang, Xifei

    2016-11-30

    Mitochondrial dysfunction is involved in neurotoxicity caused by exposure of various chemicals such as copper. However, the effects of long-term low-dose copper exposure on mitochondrial proteome remain unclear. In this study, we found the treatment of copper (0.13ppm copper sulfate in drinking water) for 12 months caused abnormal expression of a total of 13 mitochondrial proteins (7 up-regulated and 6 down-regulated) as revealed by two-dimensional electrophoresis coupled with mass spectrometry in mouse cortex. Protein functional analysis revealed that these differentially expressed proteins mainly included apoptosis-associated proteins, axon guidance-associated proteins, axonogenesis-associated proteins and mitochondrial respiratory chain complex. Among these differentially expressed mitochondrial proteins, GRP75 (75kDa glucose-regulated protein) and GRP78 (78kDa glucose-regulated protein) were found to be significantly down-regulated as confirmed by Western-blot analysis. The down-regulation of GRP75 was shown to promote apoptosis. The down-regulation of GRP78/BiP could up-regulate endoplasmic reticulum (ER) stress mediators and thus cause apoptosis. Our study suggested that these differentially expressed mitochondrial proteins such as GRP75 and GRP78 could be involved in neurotoxicity caused by long-term low-dose copper exposure and serve as potential molecular targets for the treatment of copper neurotoxicity.

  6. 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.

  7. 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

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

    PubMed

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

    2014-06-01

    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.

  9. Alterations in seizure mechanisms caused by oxygen high pressure, 1,1-dimethylhydrazine, and pyridoxine.

    PubMed

    Segerbo, B E

    1979-06-01

    High pressure oxygen (HBO) and 1,1-dimethylhydrazine (UDMH) both cause grand mal seizures, brain glycogen degradation, and inhibition of glutamic acid decarboxylase (GAD). Brain glycogen degradation is a sudden process that is perhaps initiated by convulsions in the case of UDMH-poisoning, but a gradual decrease in glycogen is detectable before the onset of hyperbaric oxygen toxicity symptoms. UDMH injection causes consecutive convulsions that follow a predictable sequence. (Time to convulsions is referred to as the induction period, and time between convulsions as the interictal period.) After a single injection of UDMH, there is a gradual decrease in resistance to HBO during the induction period, measured as time to convulsions breathing 100% oxygen at 6 ATA; in the first interictal period, this time is only 4 1/2 min in comparison with a control value of 26 min for untreated rats. Administration of pyridoxine, a B6-vitamin, 2 h after UDMH injection in the first interictal period, resulted in an immediate tenfold increase in resistance to oxygen toxicity, from 4 1/2 to 48 min. Pyridoxine may reverse the inhibitary effect of UDMH on GAD, and there is perhaps an accumulation of substrate, which is made available when GAD inhibition is diminishing. Simultaneous injection of pyridoxine and UDMH causes no convulsions, no change in brain glycogen levels, and an unchanged or increased resistance to HBO, measured two and three hours after injection.

  10. Prenatal exposure to urban air nanoparticles in mice causes altered neuronal differentiation and depression-like responses.

    PubMed

    Davis, David A; Bortolato, Marco; Godar, Sean C; Sander, Thomas K; Iwata, Nahoko; Pakbin, Payam; Shih, Jean C; Berhane, Kiros; McConnell, Rob; Sioutas, Constantinos; Finch, Caleb E; Morgan, Todd E

    2013-01-01

    Emerging evidence suggests that excessive exposure to traffic-derived air pollution during pregnancy may increase the vulnerability to neurodevelopmental alterations that underlie a broad array of neuropsychiatric disorders. We present a mouse model for prenatal exposure to urban freeway nanoparticulate matter (nPM). In prior studies, we developed a model for adult rodent exposure to re-aerosolized urban nPM which caused inflammatory brain responses with altered neuronal glutamatergic functions. nPMs are collected continuously for one month from a local freeway and stored as an aqueous suspension, prior to re-aerosolization for exposure of mice under controlled dose and duration. This paradigm was used for a pilot study of prenatal nPM impact on neonatal neurons and adult behaviors. Adult C57BL/6J female mice were exposed to re-aerosolized nPM (350 µg/m(3)) or control filtered ambient air for 10 weeks (3×5 hour exposures per week), encompassing gestation and oocyte maturation prior to mating. Prenatal nPM did not alter litter size, pup weight, or postnatal growth. Neonatal cerebral cortex neurons at 24 hours in vitro showed impaired differentiation, with 50% reduction of stage 3 neurons with long neurites and correspondingly more undifferentiated neurons at Stages 0 and 1. Neuron number after 24 hours of culture was not altered by prenatal nPM exposure. Addition of exogenous nPM (2 µg/ml) to the cultures impaired pyramidal neuron Stage 3 differentiation by 60%. Adult males showed increased depression-like responses in the tail-suspension test, but not anxiety-related behaviors. These pilot data suggest that prenatal exposure to nPM can alter neuronal differentiation with gender-specific behavioral sequelae that may be relevant to human prenatal exposure to urban vehicular aerosols.

  11. 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

  12. TFIIH subunit alterations causing xeroderma pigmentosum and trichothiodystrophy specifically disturb several steps during transcription.

    PubMed

    Singh, Amita; Compe, Emanuel; Le May, Nicolas; Egly, Jean-Marc

    2015-02-05

    Mutations in genes encoding the ERCC3 (XPB), ERCC2 (XPD), and GTF2H5 (p8 or TTD-A) subunits of the transcription and DNA-repair factor TFIIH lead to three autosomal-recessive disorders: xeroderma pigmentosum (XP), XP associated with Cockayne syndrome (XP/CS), and trichothiodystrophy (TTD). Although these diseases were originally associated with defects in DNA repair, transcription deficiencies might be also implicated. By using retinoic acid receptor beta isoform 2 (RARB2) as a model in several cells bearing mutations in genes encoding TFIIH subunits, we observed that (1) the recruitment of the TFIIH complex was altered at the activated RARB2 promoter, (2) TFIIH participated in the recruitment of nucleotide excision repair (NER) factors during transcription in a manner different from that observed during NER, and (3) the different TFIIH variants disturbed transcription by having distinct consequences on post-translational modifications of histones, DNA-break induction, DNA demethylation, and gene-loop formation. The transition from heterochromatin to euchromatin was disrupted depending on the variant, illustrating the fact that TFIIH, by contributing to NER factor recruitment, orchestrates chromatin remodeling. The subtle transcriptional differences found between various TFIIH variants thus participate in the phenotypic variability observed among XP, XP/CS, and TTD individuals.

  13. Alterations of the mitochondrial proteome caused by the absence of mitochondrial DNA: A proteomic view

    PubMed Central

    Chevallet, Mireille; Lescuyer, Pierre; Diemer, Hélène; van Dorsselaer, Alain; Leize-Wagner, Emmanuelle; Rabilloud, Thierry

    2006-01-01

    The proper functioning of mitochondria requires that both the mitochondrial and the nuclear genome are functional. To investigate the importance of the mitochondrial genome, which encodes only 13 subunits of the respiratory complexes, the mitochondrial rRNAs and a few tRNAs, we performed a comparative study on the 143B cell line and on its Rho-0 counterpart, i.e. devoid of mitochondrial DNA. Quantitative differences were found, of course in the respiratory complexes subunits, but also in the mitochondrial translation apparatus, mainly mitochondrial ribosomal proteins, and in the ion and protein import system, i.e. including membrane proteins. Various mitochondrial metabolic processes were also altered, especially electron transfer proteins and some dehydrogenases, but quite often on a few proteins for each pathway. This study also showed variations in some hypothetical or poorly characterized proteins, suggesting a mitochondrial localization for these proteins. Examples include a stomatin-like protein and a protein sharing homologies with bacterial proteins implicated in tyrosine catabolism. Proteins involved in apoptosis control are also found modulated in Rho-0 mitochondria. PMID:16548050

  14. Defective histone supply causes condensin-dependent chromatin alterations, SAC activation and chromosome decatenation impairment

    PubMed Central

    Murillo-Pineda, Marina; Cabello-Lobato, María J.; Clemente-Ruiz, Marta; Monje-Casas, Fernando; Prado, Félix

    2014-01-01

    The structural organization of chromosomes is essential for their correct function and dynamics during the cell cycle. The assembly of DNA into chromatin provides the substrate for topoisomerases and condensins, which introduce the different levels of superhelical torsion required for DNA metabolism. In particular, Top2 and condensin are directly involved in both the resolution of precatenanes that form during replication and the formation of the intramolecular loop that detects tension at the centromeric chromatin during chromosome biorientation. Here we show that histone depletion activates the spindle assembly checkpoint (SAC) and impairs sister chromatid decatenation, leading to chromosome mis-segregation and lethality in the absence of the SAC. We demonstrate that histone depletion impairs chromosome biorientation and activates the Aurora-dependent pathway, which detects tension problems at the kinetochore. Interestingly, SAC activation is suppressed by the absence of Top2 and Smc2, an essential component of condensin. Indeed, smc2-8 suppresses catenanes accumulation, mitotic arrest and growth defects induced by histone depletion at semi-permissive temperature. Remarkably, SAC activation by histone depletion is associated with condensin-mediated alterations of the centromeric chromatin. Therefore, our results reveal the importance of a precise interplay between histone supply and condensin/Top2 for pericentric chromatin structure, precatenanes resolution and centromere biorientation. PMID:25300489

  15. 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

  16. Mapping and detecting bark beetle-caused tree mortality in the western United States

    NASA Astrophysics Data System (ADS)

    Meddens, Arjan J. H.

    Recently, insect outbreaks across North America have dramatically increased and the forest area affected by bark beetles is similar to that affected by fire. Remote sensing offers the potential to detect insect outbreaks with high accuracy. Chapter one involved detection of insect-caused tree mortality on the tree level for a 90km2 area in northcentral Colorado. Classes of interest included green trees, multiple stages of post-insect attack tree mortality including dead trees with red needles ("red-attack") and dead trees without needles ("gray-attack"), and non-forest. The results illustrated that classification of an image with a spatial resolution similar to the area of a tree crown outperformed that from finer and coarser resolution imagery for mapping tree mortality and non-forest classes. I also demonstrated that multispectral imagery could be used to separate multiple postoutbreak attack stages (i.e., red-attack and gray-attack) from other classes in the image. In Chapter 2, I compared and improved methods for detecting bark beetle-caused tree mortality using medium-resolution satellite data. I found that overall classification accuracy was similar between single-date and multi-date classification methods. I developed regression models to predict percent red attack within a 30-m grid cell and these models explained >75% of the variance using three Landsat spectral explanatory variables. Results of the final product showed that approximately 24% of the forest within the Landsat scene was comprised of tree mortality caused by bark beetles. In Chapter 3, I developed a gridded data set with 1-km2 resolution using aerial survey data and improved estimates of tree mortality across the western US and British Columbia. In the US, I also produced an upper estimate by forcing the mortality area to match that from high-resolution imagery in Idaho, Colorado, and New Mexico. Cumulative mortality area from all bark beetles was 5.46 Mha in British Columbia in 2001-2010 and

  17. Effects of interleukins 2 and 12 on TBT-induced alterations of MAP kinases p38 and p44/42 in human natural killer cells.

    PubMed

    Aluoch, Aloice O; Whalen, Margaret M

    2006-01-01

    NK cells are lymphocytes in the non-adaptive immune system that protect the body against intracellular pathogens and eliminate tumor cells. Tributyltin (TBT) is a toxic chemical that has been detected in human foods as well as in human blood. The role of TBT in immunosuppression has been described, including inhibition of the human NK-cell cytotoxic function. Previous studies indicated that exposure of NK cells to TBT for 1 h induced progressive and irreversible inhibition of cytotoxic function. However, it was found that if NK cells were incubated in TBT-free media with either IL-2 or IL-12, loss of cytotoxic function was prevented/reversed within 24 h. Molecular studies established that loss of cytotoxic function is accompanied by alteration of MAP kinases (MAPKs) p38 and p44/42 phosphorylation. This study examined whether interleukin-mediated recovery of cytotoxicity involved reversal of tributyltin-altered p38 and p44/42 phosphorylation. The results indicated that there was no substantial IL-2 prevention/reversal of the TBT-induced alteration of phosphorylation of either p38 or p44/42 after either a 24 or 48 h recovery period. Additionally, IL-12 caused no substantial prevention/reversal of the TBT-induced alteration of phosphorylation of the MAPKs seen after either 24 or 48 h. These data suggest that IL-2 and/or IL-12-mediated recovery of NK cytotoxic function is not a result of prevention/reversal of TBT-induced phosphorylation of p38 and p44/42 MAPKs at the 24 or 48 h time points.

  18. Possible cause for altered spatial cognition of prepubescent rats exposed to chronic radiofrequency electromagnetic radiation.

    PubMed

    Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Karun, Kalesh M; Nayak, Satheesha B; Bhat, P Gopalakrishna

    2015-10-01

    The effects of chronic and repeated radiofrequency electromagnetic radiation (RFEMR) exposure on spatial cognition and hippocampal architecture were investigated in prepubescent rats. Four weeks old male Wistar rats were exposed to RF-EMR (900 MHz; SAR-1.15 W/kg with peak power density of 146.60 μW/cm(2)) for 1 h/day, for 28 days. Followed by this, spatial cognition was evaluated by Morris water maze test. To evaluate the hippocampal morphology; H&E staining, cresyl violet staining, and Golgi-Cox staining were performed on hippocampal sections. CA3 pyramidal neuron morphology and surviving neuron count (in CA3 region) were studied using H&E and cresyl violet stained sections. Dendritic arborization pattern of CA3 pyramidal neuron was investigated by concentric circle method. Progressive learning abilities were found to be decreased in RF-EMR exposed rats. Memory retention test performed 24 h after the last training revealed minor spatial memory deficit in RF-EMR exposed group. However, RF-EMR exposed rats exhibited poor spatial memory retention when tested 48 h after the final trial. Hirano bodies and Granulovacuolar bodies were absent in the CA3 pyramidal neurons of different groups studied. Nevertheless, RF-EMR exposure affected the viable cell count in dorsal hippocampal CA3 region. RF-EMR exposure influenced dendritic arborization pattern of both apical and basal dendritic trees in RF-EMR exposed rats. Structural changes found in the hippocampus of RF-EMR exposed rats could be one of the possible reasons for altered cognition.

  19. 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.

  20. 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.

  1. Iron overload alters glucose homeostasis, causes liver steatosis, and increases serum triacylglycerols in rats.

    PubMed

    Silva, Maísa; Silva, Marcelo E; de Paula, Heberth; Carneiro, Cláudia Martins; Pedrosa, Maria Lucia

    2008-06-01

    The objective of this study was to investigate the effect of iron overload with a hyperlipidemic diet on the histologic feature of hepatic tissue, the lipid and glycemic serum profiles, and the markers of oxidative damage and stress in a rat model. Twenty-four male Fischer rats, purchased from Experimental Nutrition Laboratory, Federal University of Ouro Preto, were assigned to 4 equal groups, 2 were fed a standard cholesterol-free diet (group C or control and CI or control with iron) containing 8.0% soybean oil and 2 were fed a hyperlipidemic diet (group H or hyperlipidemic and HI or hyperlipidemic with iron) containing 1.0% cholesterol and 25.0% soybean oil. A total of 50 mg of iron was administered to rats in groups CI and HI in 5 equal doses (1 every 3 weeks for a 16-week period) by intraperitoneal injections of 0.1 mL of iron dextran solution (100 g Fe(2+)/L; Sigma, St Louis, Mo). The other rats in groups C and H were treated in a similar manner but with sterile saline (0.1 mL). Irrespective of the diet, iron excess enhanced serum triacylglycerols (P < .05) and reduced serum glucose and glycated hemoglobin levels (P < .05) but did not affect serum cholesterol concentration. Histologic analysis showed steatosis in groups H and to a lesser extent in HI. No significant differences (P > .05) were observed in paraoxonase activities or in serum levels of free or total sulfhydryl radicals, malondialdehyde, or total antioxidants. The findings suggest that iron excess in the rat probably modifies lipid metabolism and, as a consequence, alters glucose homeostasis and increases the level of serum triacylglycerols but not of cholesterol.

  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.

  3. 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

  4. 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

  5. Acrolein Inhalation Alters Myocardial Synchrony and Performance at and Below Exposure Concentrations that Cause Ventilatory Responses.

    PubMed

    Thompson, Leslie C; Ledbetter, Allen D; Haykal-Coates, Najwa; Cascio, Wayne E; Hazari, Mehdi S; Farraj, Aimen K

    2017-04-01

    Acrolein is an irritating aldehyde generated during combustion of organic compounds. Altered autonomic activity has been documented following acrolein inhalation, possibly impacting myocardial synchrony and function. Given the ubiquitous nature of acrolein in the environment, we sought to better define the immediate and delayed functional cardiac effects of acrolein inhalation in vivo. We hypothesized that acrolein inhalation would increase markers of cardiac mechanical dysfunction, i.e., myocardial dyssynchrony and performance index in mice. Male C57Bl/6J mice were exposed to filtered air (FA) or acrolein (0.3 or 3.0 ppm) for 3 h in whole-body plethysmography chambers (n = 6). Echocardiographic analyses were performed 1 day before exposure and at 1 and 24 h post-exposure. Speckle tracking echocardiography revealed that circumferential strain delay (i.e., dyssynchrony) was increased at 1 and 24 h following exposure to 3.0 ppm, but not 0.3 ppm, when compared to pre-exposure and/or FA exposure. Pulsed wave Doppler of transmitral blood flow revealed that acrolein exposure at 0.3 ppm, but not 3.0 ppm, increased the Tei index of myocardial performance (i.e., decreased global heart performance) at 1 and 24 h post-exposure compared to pre-exposure and/or FA exposure. We conclude that short-term inhalation of acrolein can acutely modify cardiac function in vivo and that echocardiographic evaluation of myocardial synchrony and performance following exposure to other inhaled pollutants could provide broader insight into the health effects of air pollution.

  6. 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.

  7. Diabetes causes multiple genetic alterations and downregulates expression of DNA repair genes in the prostate.

    PubMed

    Ye, Chunwei; Li, Xiaojuan; Wang, Yu; Zhang, Yuying; Cai, Mengyin; Zhu, Baoyi; Mu, Panwei; Xia, Xuan; Zhao, Yi; Weng, Jianping; Gao, Xin; Wen, Xingqiao

    2011-09-01

    The molecular impact of diabetes mellitus on prostate gland has not been elucidated. In this study, we performed a whole-genome cDNA microarray analysis using a streptozotocin-induced diabetic rat model to identify the effects of diabetes on the gene expression profiles in prostate. Our study shows that diabetes causes changes in the expression of multiple genes, particularly those related to cell proliferation and differentiation, oxidative stress, DNA damage repair, cell cycle checkpoints, angiogenesis and apoptosis. These findings were confirmed by real-time polymerase chain reaction and immunohistochemical staining using rat and human prostate tissue. We also used a cell culture model (human normal prostatic RWPE-1 cell line) to study the direct effect of high glucose. We found that high glucose caused increased intracellular oxidative stress and DNA damage, as well as downregulation of anti-oxidative enzymes and DNA damage repair genes MRE11 and XRCC3. Our findings provide important insights into understanding the pathogenesis of the diabetes-induced changes in prostate as well as identifying potential therapeutic targets for future studies.

  8. Could zinc prevent reproductive alterations caused by cigarette smoke in male rats?

    PubMed

    Garcia, Patrícia Carvalho; Piffer, Renata Carolina; Gerardin, Daniela Cristina Cecatto; Sankako, Michele Kimie; Alves de Lima, Rodrigo Otávio; Pereira, Oduvaldo Câmara Marques

    2012-01-01

    The aim of the present study was to evaluate the effects of zinc on fertility through semen parameters, testosterone level and oxidative DNA damage to spermatozoa of rats exposed to cigarette smoke. Male Wistar rats (60 days old) were divided into four groups (n = 10 per group): control, cigarette-smoking (20 cigarettes per day), zinc (zinc chloride 20 mg kg⁻¹ day⁻¹) and zinc plus cigarette-smoking (zinc chloride 20 mg kg⁻¹ day⁻¹; 20 cigarettes per day). The treatment was applied for nine weeks and the following parameters were analysed: bodyweight, wet weights of the reproductive organs and the adrenal gland, plasma testosterone concentration, testicular function (seminal analysis and daily sperm production) and sperm DNA oxidative damage. The exposure to cigarette smoke decreased testosterone concentration, the percentage of normal morphology and the motility of spermatozoa. In addition, this exposure increased sperm DNA oxidative damage. Zinc treatment protected against the toxic damage that smoking caused to spermatozoa. This study showed a correlation between smoking and possible male infertility and subfertility, and also that the majority of smoking-induced changes in spermatozoa were prevented by zinc treatment. In conclusion, zinc, an antioxidant and stimulant of cell division, can be indicated as a promising treatment in men with infertility caused by the toxic components of cigarette smoke.

  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).

  10. 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.

  11. Fine mapping of meiotic NAHR-associated crossovers causing large NF1 deletions.

    PubMed

    Hillmer, Morten; Wagner, David; Summerer, Anna; Daiber, Michaela; Mautner, Victor-Felix; Messiaen, Ludwine; Cooper, David N; Kehrer-Sawatzki, Hildegard

    2016-02-01

    Large deletions encompassing the NF1 gene and its flanking regions belong to the group of genomic disorders caused by copy number changes that are mediated by the local genomic architecture. Although nonallelic homologous recombination (NAHR) is known to be a major mutational mechanism underlying such genomic copy number changes, the sequence determinants of NAHR location and frequency are still poorly understood since few high-resolution mapping studies of NAHR hotspots have been performed to date. Here, we have characterized two NAHR hotspots, PRS1 and PRS2, separated by 20 kb and located within the low-copy repeats NF1-REPa and NF1-REPc, which flank the human NF1 gene region. High-resolution mapping of the crossover sites identified in 78 type 1 NF1 deletions mediated by NAHR indicated that PRS2 is a much stronger NAHR hotspot than PRS1 since 80% of these deletions exhibited crossovers within PRS2, whereas 20% had crossovers within PRS1. The identification of the most common strand exchange regions of these 78 deletions served to demarcate the cores of the PRS1 and PRS2 hotspots encompassing 1026 and 1976 bp, respectively. Several sequence features were identified that may influence hotspot intensity and direct the positional preference of NAHR to the hotspot cores. These features include regions of perfect sequence identity encompassing 700 bp at the hotspot core, the presence of PRDM9 binding sites perfectly matching the consensus motif for the most common PRDM9 variant, specific pre-existing patterns of histone modification and open chromatin conformations that are likely to facilitate PRDM9 binding.

  12. Genetic mapping of a mutation that causes ribonucleases III deficiency in Escherichia coli.

    PubMed Central

    Studier, F W

    1975-01-01

    the mutation that causes ribonuclease III (RNase III) deficiency in strain AB301-105 of Kindler et al. (1973) has been mapped by use of F' merodiploids, Hfr matings, and P1 transduction. This mutation, rnc-105, lies close to nadB, near 49 min on the genetic map of Escherichia coli. The rnc-105 mutation has been transferred from its original genetic background by transduction and conjugation, and these new strains have the same defects in ribonucleic acid processing reported previously for AB301-105. Strains that carry rnc-105 grow more slowly than parental rnc+ strains, but the difference in growth rate seems to depend on the genetic background of each strain. Bacteriophage T7 grows about equally well in RNase III+ and III- female strains of E. coli, even though the specific cuts that RNase III makes in T7 ribonucleic acid are not made in the RNase III- strains. A low-phosphate defined medium in which most E. coli strains seem to grow well was developed. This medium is equally useful for labeling ribonucleic acids with 32PO4 and as a selective medium for genetic manipulations. It was used to determine the growth requirements of strain AB301-105, which are biotin and succinate in addition to the methionine and histidine requirements of the parental strain. The biotin mutation lies near the position expected from known mutations of E. coli, but the succinate mutation apparently does not. The possibility that the succinate requirement could be due to the RNase III deficiency is discussed. A uraP mutation was isolated for use in transferring rnc-105 between strains by conjugation. It lies near 47 min, somewhat removed from the commonly accepted position for uraP. PMID:1100605

  13. 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

  14. 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

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

    PubMed Central

    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 release 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

  16. 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

  17. Micromolar changes in lysophosphatidylcholine concentration cause minor effects on mitochondrial permeability but major alterations in function.

    PubMed

    Hollie, Norris I; Cash, James G; Matlib, M Abdul; Wortman, Matthew; Basford, Joshua E; Abplanalp, William; Hui, David Y

    2014-06-01

    Mice deficient in group 1b phospholipase A2 have decreased plasma lysophosphatidylcholine and increased hepatic oxidation that is inhibited by intraperitoneal lysophosphatidylcholine injection. This study sought to identify a mechanism for lysophosphatidylcholine-mediated inhibition of hepatic oxidative function. Results showed that in vitro incubation of isolated mitochondria with 40-200μM lysophosphatidylcholine caused cyclosporine A-resistant swelling in a concentration-dependent manner. However, when mitochondria were challenged with 220μM CaCl2, cyclosporine A protected against permeability transition induced by 40μM, but not 80μM lysophosphatidylcholine. Incubation with 40-120μM lysophosphatidylcholine also increased mitochondrial permeability to 75μM CaCl2 in a concentration-dependent manner. Interestingly, despite incubation with 80μM lysophosphatidylcholine, the mitochondrial membrane potential was steady in the presence of succinate, and oxidation rates and respiratory control indices were similar to controls in the presence of succinate, glutamate/malate, and palmitoyl-carnitine. However, mitochondrial oxidation rates were inhibited by 30-50% at 100μM lysophosphatidylcholine. Finally, while 40μM lysophosphatidylcholine has no effect on fatty acid oxidation and mitochondria remained impermeable in intact hepatocytes, 100μM lysophosphatidylcholine inhibited fatty acid stimulated oxidation and caused intracellular mitochondrial permeability. Taken together, these present data demonstrated that LPC concentration dependently modulates mitochondrial microenvironment, with low micromolar concentrations of lysophosphatidylcholine sufficient to change hepatic oxidation rate whereas higher concentrations are required to disrupt mitochondrial integrity.

  18. Altered transport of lindane caused by the retention of natural particles in saturated porous media

    NASA Astrophysics Data System (ADS)

    Ngueleu, Stéphane K.; Grathwohl, Peter; Cirpka, Olaf A.

    2014-07-01

    Attachment and straining of colloidal particles in porous media result in their reversible and irreversible retention. The retained particles may either increase the retention of hydrophobic pollutants by sorption onto the particles, or enhance pollutant transport when particles, loaded with the pollutants, are remobilized. The present study examines the effects of retained particles on the transport of the hydrophobic pesticide lindane (gamma-hexachlorocyclohexane) in saturated porous media. The lignite particles used have median diameters of about 3 μm, 1 μm, 0.8 μm, and 0.2 μm, respectively. Laboratory column experiments were analyzed by numerical modeling in order to identify and understand the processes involved in the transport of the particles and of lindane. Four scenarios were considered in which the solution containing lindane is injected either during or after the elution of the particles. The results show that lignite particles retained in a sandy porous medium alter the transport of the invading lindane. Particle retention was high in all scenarios and increased with increasing particle size. Remobilization of particles occurred due to a change in solution chemistry, and continuous particle detachment was observed over time. Numerical modeling of particle transport suggests that both reversible attachment and irreversible straining affected the transport of the particles. Lindane was retarded in all scenarios due to the strong particle retention in conjunction with the sorption of lindane onto the sand and onto retained particles, and the limited number of mobile particles carrying lindane. Moreover, it was found that intra-particle diffusion limited adsorption/desorption of lindane onto/from both limestone fragments of the sand and lignite particles. We assume that retention of lindane is reversible even though lindane recovery was incomplete over the duration of the experiments. The analysis of the effluent concentration suggests that retained

  19. 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.

  20. 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.

  1. Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia

    PubMed Central

    El-Osta, Assam; Brasacchio, Daniella; Yao, Dachun; Pocai, Alessandro; Jones, Peter L.; Roeder, Robert G.; Cooper, Mark E.; Brownlee, Michael

    2008-01-01

    The current goal of diabetes therapy is to reduce time-averaged mean levels of glycemia, measured as HbA1c, to prevent diabetic complications. However, HbA1c only explains <25% of the variation in risk of developing complications. Because HbA1c does not correlate with glycemic variability when adjusted for mean blood glucose, we hypothesized that transient spikes of hyperglycemia may be an HbA1c–independent risk factor for diabetic complications. We show that transient hyperglycemia induces long-lasting activating epigenetic changes in the promoter of the nuclear factor κB (NF-κB) subunit p65 in aortic endothelial cells both in vitro and in nondiabetic mice, which cause increased p65 gene expression. Both the epigenetic changes and the gene expression changes persist for at least 6 d of subsequent normal glycemia, as do NF-κB–induced increases in monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 expression. Hyperglycemia-induced epigenetic changes and increased p65 expression are prevented by reducing mitochondrial superoxide production or superoxide-induced α-oxoaldehydes. These results highlight the dramatic and long-lasting effects that short-term hyperglycemic spikes can have on vascular cells and suggest that transient spikes of hyperglycemia may be an HbA1c–independent risk factor for diabetic complications. PMID:18809715

  2. Central nervous system alterations caused by infection with the human respiratory syncytial virus.

    PubMed

    Bohmwald, Karen; Espinoza, Janyra A; González, Pablo A; Bueno, Susan M; Riedel, Claudia A; Kalergis, Alexis M

    2014-11-01

    Worldwide, the human respiratory syncytial virus (hRSV) is the leading cause of infant hospitalization because of acute respiratory tract infections, including severe bronchiolitis and pneumonia. Despite intense research, to date there is neither vaccine nor treatment available to control hRSV disease burden globally. After infection, an incubation period of 3-5 days is usually followed by symptoms, such as cough and low-grade fever. However, hRSV infection can also produce a larger variety of symptoms, some of which relate to the individual's age at infection. Indeed, infants can display severe symptoms, such as dyspnea and chest wall retractions. Upon examination, crackles and wheezes are also common features that suggest infection by hRSV. Additionally, infection in infants younger than 1 year is associated with several non-specific symptoms, such as failure to thrive, periodic breathing or apnea, and feeding difficulties that usually require hospitalization. Recently, neurological symptoms have also been associated with hRSV respiratory infection and include seizures, central apnea, lethargy, feeding or swallowing difficulties, abnormalities in muscle tone, strabismus, abnormalities in the CSF, and encephalopathy. Here, we discuss recent findings linking the neurological, extrapulmonary effects of hRSV with infection and functional impairment of the CNS.

  3. Acetabular cartilage defects cause altered hip and knee joint coordination variability during gait

    PubMed Central

    Samaan, Michael A.; Teng, Hsiang-Ling; Kumar, Deepak; Lee, Sonia; Link, Thomas; Majumdar, Sharmila; Souza, Richard B.

    2015-01-01

    Background Patients with acetabular cartilage defects reported increased pain and disability compared to those without acetabular cartilage defects. The specific effects of acetabular cartilage defects on lower extremity coordination patterns are unclear. The purpose of this study was to determine hip and knee joint coordination variability during gait in those with and without acetabular cartilage defects. Methods A combined approach, consisting of a semi-quantitative MRI-based quantification method and vector coding, was used to assess hip and knee joint coordination variability during gait in those with and without acetabular cartilage lesions. Findings The coordination variability of the hip flexion-extension/knee rotation, hip abduction-adduction/knee rotation and hip rotation/knee rotation joint couplings were reduced in the acetabular lesion group compared to the control group during loading response of the gait cycle. The lesion group demonstrated increased variability in the hip flexion-extension/knee rotation and hip abduction-adduction/knee rotation joint couplings, compared to the control group, during the terminal stance/pre-swing phase of gait. Interpretation Reduced variability during loading response in the lesion group may suggest reduced movement strategies and a possible compensation mechanism for lower extremity instability during this phase of the gait cycle. During terminal stance/pre-swing, a larger variability in the lesion group may suggest increased movement strategies and represent a compensation or pain avoidance mechanism caused by the load applied to the hip joint. PMID:26298706

  4. The Baroque monuments of Modica (Eastern Sicily): assessment of causes of chromatic alteration of stone building materials

    NASA Astrophysics Data System (ADS)

    Belfiore, Cristina M.; La Russa, Mauro F.; Pezzino, Antonino; Campani, Elisa; Casoli, Antonella

    2010-09-01

    The Baroque monuments of several cities in eastern Sicily, built of local calcarenitic stone, are often subjected to conservation treatments, since they undergo many forms of alteration and degradation which can cause significant damage. However, a recent study of these building materials (Barone et al. in Environ. Geol. 54:1501, 2008) has demonstrated that some protective products, once applied, cause irreversible chromatic alterations. The façades of the monuments of the historic city centre of Modica are typically creamy yellow in colour, sometimes varying slightly due to the use of various pigments, such as clayey and gypseous earths (La Russa et al. in Appl. Phys. A 92:185, 2008). However, in some cases, these nuances are lost due to the application of protective products. This work provides a petrographic and colorimetric characterisation of the calcarenitic stone used to create the façades of the churches of S. Pietro, S. Maria del Soccorso and S. Maria dell’Annunziata in Modica, also by comparisons with locally quarried samples. In addition, it aims to identify protective substances which may have been used during previous restoration work. Analytical techniques included polarising optical microscopy, spectrophotometric colorimetric tests, Fourier-transform infrared spectroscopy (FTIR) and gas chromatography coupled with mass spectrometry (GC-MS).

  5. 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.

  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. Darkfield reflection visible microspectroscopy equipped with a color mapping system of a brown altered granite.

    PubMed

    Onga, Chie; Nakashima, Satoru

    2014-01-01

    Visible darkfield reflectance spectroscopy equipped with a color mapping system has been developed and applied to a brown-colored Rokko granite sample. Sample reflectance spectra converted to Kubelka-Munk (KM) spectra show similar features to goethite and lepidocrocite. Raman microspectroscopy on the granite sample surface confirms the presence of these minerals. Here, L*a*b* color values (second Commission Internationale d'Eclairage [CIELab] 1976 color space) were determined from the sample reflection spectra. Grey, yellow, and brown zones of the granite show different L*, a*, and b* values. In the a*-b* diagram, a* and b* values in the grey and brown zones are on the lepidocrocite/ferrihydrite trends, but their values in the brown zone are larger than those in the grey zone. The yellow zone shows data points close to the goethite trend. Iron (hydr)oxide-rich areas can be visualized by means of large a* and b* values in the L*, a*, and b* maps. Although the present method has some problems and limitations, the visible darkfield reflectance spectroscopy can be a useful method for colored-material characterization.

  8. Refined mapping of the gene causing Familial Mediterranean fever, by linkage and homozygosity studies

    SciTech Connect

    Aksentijevich, I.; Pras, E.; Gruberg, L.; Helling, S.; Prosen, L.; Pras, M.; Kastner, D.L. ); Shen, Y.; Holman, K.; Sutherland, G.R.; Richards, R.I. ); Ramsburg, M.; Dean, M. ); Amos, C.I. )

    1993-08-01

    Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by attacks of fever and serosal inflammation; the biochemical basis is unknown. The authors recently reported linkage of the gene causing FMF (designated [open quotes]MEF[close quotes]) to two markers on chromosome 16p. To map MEF more precisely, they 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. They 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 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. 30 refs., 6 figs., 2 tabs.

  9. 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

  10. MAP kinase pathway gene copy alterations in NRAS/BRAF wild-type advanced melanoma.

    PubMed

    Orouji, Elias; Orouji, Azadeh; Gaiser, Timo; Larribère, Lionel; Gebhardt, Christoffer; Utikal, Jochen

    2016-05-01

    Recent therapeutic advances have improved melanoma patientś clinical outcome. Novel therapeutics targeting BRAF, NRAS and cKit mutant melanomas are widely used in clinical practice. However therapeutic options in NRAS(wild-type) /BRAF(wild-type) /cKit(wild-type) melanoma patients are limited. Our study shows that gene copy numbers of members of the MAPK signaling pathway vary in different melanoma subgroups. NRAS(wild-type) /BRAF(wild-type) melanoma metastases are characterized by significant gains of MAP2K1 (MEK1) and MAPK3 (ERK1) gene loci. These additional gene copies could lead to an activation of the MAPK signaling pathway via a gene-dosage effect. Our results suggest that downstream analyses of the pMEK and pERK expression status in NRAS(wild-type) /BRAF(wild-type) melanoma patients identify patients that could benefit from targeted therapies with MEK and ERK inhibitors.

  11. Application of hydrothermal alteration mineral mapping using airborne hyperspectral remote sensing: data taken in the Baixianishan region of Gansu Province as an example

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

    Hyperspectral remote sensing, featured by integrated images and spectra, is now a frontier of the remote sensing. Using meticulous spectra, hyperspectral remote sensing technology can depict spectral features of objects in detail and are capable of identifying objects rather than simply discriminating them. This study took the Baixianishan region in Gansu Province as an example, and CASI/SASI airborne hyperspectral data were utilized to extract and map alteration minerals by MTMF mapping method. Six hydrothermal alteration minerals were mapped, which contained limonite, sericite and epidote. In addition, we analyzed the types, combinations and distribution of the alteration minerals and divided three stages of hydrothermal activity. It is considered that the favorable ore-forming elements for gold deposits are middle Hercynian porphyraceous granite, fracture and veined distribution of sericite and limonite. The application of CASI/SASI airborne hyperspectral remote sensing data in the Baixianishan area has achieved ideal results, indicative of their wide application potential in the geological research.

  12. Distinct laterality alterations distinguish mild cognitive impairment and Alzheimer's disease from healthy aging: statistical parametric mapping with high resolution MRI.

    PubMed

    Long, Xiaojing; Zhang, Lijuan; Liao, Weiqi; Jiang, Chunxiang; Qiu, Bensheng

    2013-12-01

    Laterality of human brain varies under healthy aging and diseased conditions. The alterations in hemispheric asymmetry may embed distinct biomarkers linked to the disease dynamics. Statistical parametric mapping based on high-resolution magnetic resonance imaging (MRI) and image processing techniques have allowed automated characterization of morphological features across the entire brain. In this study, 149 subjects grouped in healthy young, healthy elderly, mild cognitive impairment (MCI), and Alzheimer's disease (AD) were investigated using multivariate analysis for regional cerebral laterality indexed by surface area, curvature index, cortical thickness, and subjacent white matter volume measured on high-resolution MR images. Asymmetry alteration of MCI and AD were characterized by marked region-specific reduction, while healthy elderly featured a distinct laterality shift in the limbic system in addition to regional asymmetry loss. Lack of the laterality shift in limbic system and early loss of asymmetry in entorhinal cortex may be biomarkers to identify preclinical AD among other dementia. Multivariate analysis of hemispheric asymmetry may provide information helpful for monitoring the disease progress and improving the management of MCI and AD.

  13. Ectopic lipid accumulation: A potential cause for metabolic disturbances and a contributor to the alteration of kidney function.

    PubMed

    Guebre-Egziabher, Fitsum; Alix, Pascaline M; Koppe, Laetitia; Pelletier, Caroline C; Kalbacher, Emilie; Fouque, Denis; Soulage, Christophe O

    2013-11-01

    Ectopic lipid accumulation is now known to be a mechanism that contributes to organ injury in the context of metabolic diseases. In muscle and liver, accumulation of lipids impairs insulin signaling. This hypothesis accounts for the mechanism of insulin resistance in obesity, type 2 diabetes, aging and lipodystrophy. Increasing data suggest that lipid accumulation in the kidneys could also contribute to the alteration of kidney function in the context of metabolic syndrome and obesity. Furthermore and more unexpectedly, animal models of kidney disease exhibit a decreased adiposity and ectopic lipid redistribution suggesting that kidney disease may be a state of lipodystrophy. However, whether this abnormal lipid partitioning during chronic kidney disease (CKD) may have any functional impact in these tissues needs to be investigated. Here, we provide a perspective by defining the problem and analyzing the possible causes and consequences. Further human studies are required to strengthen these observations, and provide novel therapeutic approaches.

  14. Alteration of cytoskeletal molecules in a human T cell line caused by continuous exposure to chrysotile asbestos.

    PubMed

    Maeda, Megumi; Chen, Ying; Kumagai-Takei, Naoko; Hayashi, Hiroaki; Matsuzaki, Hidenori; Lee, Suni; Hiratsuka, Jun-Ichi; Nishimura, Yasumitsu; Kimura, Yoshinobu; Otsuki, Takemi

    2013-09-01

    Among the various biological effects of asbestos such as fibrogenesis and carcinogenesis, we have been focusing on the immunological effects becausesilica (SiO(2)) and asbestos chemically is a mineral silicate of silica. Observations of the effects of asbestos on CD4+ T cells showed reduction of CXCR3 chemokine receptor and reduced capacity of interferon γ production. In particular, use of theHTLV-1 immortalized human T cell line, MT-2, and cDNA array analysis have helped to identify the modification of CXCR3. We investigated alteration of protein expression among MT-2 original cells that had no contact with asbestos, and six chrysotile-continuously exposed independent sublines using ProteinChip and two-dimensional gel electrophoresis (2DGE) assays. Further confirmation of the changes in protein expression due to asbestos exposure was obtained after the 2DGE method indicated protein modification of β-actin. β-actin was upregulated in mRNA, as were the levels of protein expression and phosphorylation. Moreover, a binding assay between cells and chrysotile showed that various molecules related to the cytoskeleton such as vimentin, myosin-9 and tubulin-β2, as well as β-actin, exhibited enhanced bindings in asbestos-exposed cells. The overall findings indicate that the cell surface cytoskeleton may play an important role in inducing the cellular changes caused by asbestos in immune cells, since fibers are not incorporated to the cells and how the alterations of cytoskeleton determined cell destiny to cause the reduction of tumor immunity is important to consider the biological effects of asbestos. Further studies to target several cytoskeleton-related molecules associated with the effects of asbestos will result in a better understanding of the immunological effects of asbestos and support the development of chemo-prevention to recover anti-tumor immunity in asbestos-exposed patients.

  15. A Novel FC116/BC10 Mutation Distinctively Causes Alteration in the Expression of the Genes for Cell Wall Polymer Synthesis in Rice

    PubMed Central

    Zhang, Mingliang; Wei, Feng; Guo, Kai; Hu, Zhen; Li, Yuyang; Xie, Guosheng; Wang, Yanting; Cai, Xiwen; Peng, Liangcai; Wang, Lingqiang

    2016-01-01

    We report isolation and characterization of a fragile culm mutant fc116 that displays reduced mechanical strength caused by decreased cellulose content and altered cell wall structure in rice. Map-based cloning revealed that fc116 was a base substitution mutant (G to A) in a putative beta-1,6-N-acetylglucosaminyltransferase (C2GnT) gene (LOC_Os05g07790, allelic to BC10). This mutation resulted in one amino acid missing within a newly-identified protein motif “R, RXG, RA.” The FC116/BC10 gene was lowly but ubiquitously expressed in the all tissues examined across the whole life cycle of rice, and slightly down-regulated during secondary growth. This mutant also exhibited a significant increase in the content of hemicelluloses and lignins, as well as the content of pentoses (xylose and arabinose). But the content of hexoses (glucose, mannose, and galactose) was decreased in both cellulosic and non-cellulosic (pectins and hemicelluloses) fractions of the mutant. Transcriptomic analysis indicated that the typical genes in the fc116 mutant were up-regulated corresponding to xylan biosynthesis, as well as lignin biosynthesis including p-hydroxyphenyl (H), syringyl (S), and guaiacyl (G). Our results indicate that FC116 has universal function in regulation of the cell wall polymers in rice. PMID:27708650

  16. Graphical function mapping as a new way to explore cause-and-effect chains

    USGS Publications Warehouse

    Evans, Mary Anne

    2016-01-01

    Graphical function mapping provides a simple method for improving communication within interdisciplinary research teams and between scientists and nonscientists. This article introduces graphical function mapping using two examples and discusses its usefulness. Function mapping projects the outcome of one function into another to show the combined effect. Using this mathematical property in a simpler, even cartoon-like, graphical way allows the rapid combination of multiple information sources (models, empirical data, expert judgment, and guesses) in an intuitive visual to promote further discussion, scenario development, and clear communication.

  17. 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

    2015-10-28

    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.

  18. 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.

  19. 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

  20. 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.

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

    PubMed Central

    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. PMID:24407431

  2. Lethality and histopathological alterations caused by Phoneutria nigriventer spider venom from Argentina: Neutralization of lethality by experimental and therapeutic antivenoms.

    PubMed

    de Roodt, Adolfo Rafael; Lago, Néstor Rubén; Lanari, Laura Cecilia; Laskowicz, Rodrigo Daniel; Costa de Oliveira, Vanessa; Neder de Román, Estela; de Titto, Ernesto Horacio; Damin, Carlos Fabián

    2017-01-01

    Although the spiders of the genus Phoneutria cause envenomation and their presence has been described in several provinces of the north of Argentina, they are not as common as other spiders of sanitary importance. In the present work, we studied the toxicity of samples of venom of Phoneutria spiders from the provinces of Misiones (where severe envenomation and deaths by Phoneutria have been recorded) and Jujuy (where no deaths have been recorded and severe envenomations are not frequent). To this end, we assessed the lethal potency in mice and guinea pigs and the histopathological alterations caused by both venoms, as well as the neutralization by the commonly used therapeutic antivenom produced by the Butantan Institute in Brazil and by an experimental antivenom developed with venom of P. nigriventer from Misiones. There were no differences in the lethality of the venoms of spiders from both regions. Post mortem examination showed that the heart and lungs were the most affected organs, while important pulmonary edema was seen macroscopically. Histological analysis showed edema, atelectasis, emphysema and cardiac lesion in both experimental models. The antivenoms assayed showed good neutralization of the venoms in the two experimental models. Despite the different geographic origins, the venoms showed similar toxicity and both the experimental antivenom and therapeutic antivenmos were able to neutralize the venoms of Argentinean P. nigriventer.

  3. New insight into the Delia platura Meigen caused alteration in nutrient content of soybean (Glycine max L. Merill).

    PubMed

    Bosnyákné, Helga Egri; Kerepesi, Ildikó; Keszthelyi, Sándor

    2016-09-01

    Climate change has brought about an increasing level of seedcorn maggot (Delia platura Meigen, 1826) (Diptera: Anthomyiidae) damage in Hungary. In order to have a more accurate understanding of the effects of these plant injuries induced by the larvae of D. platura, the nutrient content of soybean (Glycine max L. Merill.) was studied. Our results show that the moisture, raw fat, raw fibre, and raw ash content of the batches damaged by D. platura were significantly less in comparison with that of the control samples. In response to the deleterious effect of the insect, the infected soybean plants showed forced ripening (P = 0.004) (P > 0.05). The difference of moisture content between damaged and control samples was 2.30% on average. The fact of nutritional value loss was also reflected by the alteration of sugar mobilisation. As the result of this experiment the sucrose breakdown to glucose and fructose during the germination was significantly slower in the damaged seeds than that of the control ones. Overall, this late and surprising damage caused by D. platura led to the forced ripening of the affected soybean plants and a significant change in their nutritional values. Based on the herein reported results, it is presumable that in cases when the current climatic extremities, which are envisaged to occur more frequently in the future, and effects of agricultural practices will be coincided in the future a qualitative change of the produced soybean batches can be expected through the damage caused by this fly species.

  4. Methamphetamine causes differential alterations in gene expression and patterns of histone acetylation/hypoacetylation in the rat nucleus accumbens.

    PubMed

    Martin, Tracey A; Jayanthi, Subramaniam; McCoy, Michael T; Brannock, Christie; Ladenheim, Bruce; Garrett, Tiffany; Lehrmann, Elin; Becker, Kevin G; Cadet, Jean Lud

    2012-01-01

    Methamphetamine (METH) addiction is associated with several neuropsychiatric symptoms. Little is known about the effects of METH on gene expression and epigenetic modifications in the rat nucleus accumbens (NAC). Our study investigated the effects of a non-toxic METH injection (20 mg/kg) on gene expression, histone acetylation, and the expression of the histone acetyltransferase (HAT), ATF2, and of the histone deacetylases (HDACs), HDAC1 and HDAC2, in that structure. Microarray analyses done at 1, 8, 16 and 24 hrs after the METH injection identified METH-induced changes in the expression of genes previously implicated in the acute and longterm effects of psychostimulants, including immediate early genes and corticotropin-releasing factor (Crf). In contrast, the METH injection caused time-dependent decreases in the expression of other genes including Npas4 and cholecystokinin (Cck). Pathway analyses showed that genes with altered expression participated in behavioral performance, cell-to-cell signaling, and regulation of gene expression. PCR analyses confirmed the changes in the expression of c-fos, fosB, Crf, Cck, and Npas4 transcripts. To determine if the METH injection caused post-translational changes in histone markers, we used western blot analyses and identified METH-mediated decreases in histone H3 acetylated at lysine 9 (H3K9ac) and lysine 18 (H3K18ac) in nuclear sub-fractions. In contrast, the METH injection caused time-dependent increases in acetylated H4K5 and H4K8. The changes in histone acetylation were accompanied by decreased expression of HDAC1 but increased expression of HDAC2 protein levels. The histone acetyltransferase, ATF2, showed significant METH-induced increased in protein expression. These results suggest that METH-induced alterations in global gene expression seen in rat NAC might be related, in part, to METH-induced changes in histone acetylation secondary to changes in HAT and HDAC expression. The causal role that HATs and HDACs might

  5. 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

  6. [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.

  7. 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.

  8. 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.

  9. Histological alterations in the intestinal epithelium caused by the inclusion of full-fat sunflower kernels in broiler chicken diets.

    PubMed

    Arija, I; Viveros, A; Brenes, A; Canales, R; Pizarro, M; Castaño, M

    2000-09-01

    Changes in small intestinal morphology (jejunum) were examined at 28 d of age in chicks fed with full-fat sunflower kernels (FFSK)-based diets. Jejunal mucosa of chicks (six chicks per treatment) were embedded in Epon-812 for examination by a conventional electron microscope procedure. A portion of the tissues was also sectioned and embedded in paraffin for examination by light microscopy. Brush border, goblet cells, and intraepithelial lymphocytes, on the one hand, and fibroblast and mononuclear cells (lymphocytes, plasma cells, macrophages) were observed in the enterocytes and lamina propria, respectively. The results showed that the birds fed 150 g kg(-1) of FFSK showed a shortening and thickening of the villi, hyperplasia and vacuolar degeneration of enterocytes, and hypertrophy and hyperplasia of goblet cells. Likewise, an increment of intraepithelial lymphoid cells and hypercellularity of the lamina propria was observed. In addition, electron microscopy showed large vacuoles in the enterocytes, which could be dilations of agranular and granular endoplasmic reticulum or Golgi. There were many dark granules within the vacuoles that could be triglyceride-rich lipoproteins (portomicrons). These lesions could have been due to the presence of chlorogenic acid or to the greater concentration of oil in the FFSK diet. Our observations demonstrated that addition of 150 g kg(-1) FFSK to broiler chicken diets caused alterations in jejunal mucosa that could explain the decrease in fat digestibility observed in a previous experiment in which we incorporated FFSK into broiler diets.

  10. Exposure to crude oil micro-droplets causes reduced food uptake in copepods associated with alteration in their metabolic profiles.

    PubMed

    Hansen, Bjørn Henrik; Altin, Dag; Nordtug, Trond; Øverjordet, Ida Beathe; Olsen, Anders J; Krause, Dan; Størdal, Ingvild; Størseth, Trond R

    2017-03-01

    Acute oil spills and produced water discharges may cause exposure of filter-feeding pelagic organisms to micron-sized dispersed oil droplets. The dissolved oil components are expected to be the main driver for oil dispersion toxicity; however, very few studies have investigated the specific contribution of oil droplets to toxicity. In the present work, the contribution of oil micro-droplet toxicity in dispersions was isolated by comparing exposures to oil dispersions (water soluble fraction with droplets) to concurrent exposure to filtered dispersions (water-soluble fractions without droplets). Physical (coloration) and behavioral (feeding activity) as well as molecular (metabolite profiling) responses to oil exposures in the copepod Calanus finmarchicus were studied. At high dispersion concentrations (4.1-5.6mg oil/L), copepods displayed carapace discoloration and reduced swimming activity. Reduced feeding activity, measured as algae uptake, gut filling and fecal pellet production, was evident also for lower concentrations (0.08mg oil/L). Alterations in metabolic profiles were also observed following exposure to oil dispersions. The pattern of responses were similar between two comparable experiments with different oil types, suggesting responses to be non-oil type specific. Furthermore, oil micro-droplets appear to contribute to some of the observed effects triggering a starvation-type response, manifested as a reduction in metabolite (homarine, acetylcholine, creatine and lactate) concentrations in copepods. Our work clearly displays a relationship between crude oil micro-droplet exposure and reduced uptake of algae in copepods.

  11. Defects in MAP1S-mediated autophagy cause reduction in mouse lifespans especially when fibronectin is overexpressed.

    PubMed

    Li, Wenjiao; Zou, Jing; Yue, Fei; Song, Kun; Chen, Qi; McKeehan, Wallace L; Wang, Fen; Xu, Guibin; Huang, Hai; Yi, Jinglin; Liu, Leyuan

    2016-04-01

    Autophagy is a cellular process that executes the turnover of dysfunctional organelles and misfolded or abnormally aggregated proteins. Microtubule-associated protein MAP1S interacts with autophagy marker LC3 and positively regulates autophagy flux. LC3 binds with fibronectinmRNA and facilitates its translation. The synthesized fibronectin protein is exported to cell surface to initiate the assembly of fibronectin extracellular matrix. Fibronectin is degraded in lysosomes after it is engulfed into cytosol via endocytosis. Here, we show that defects in MAP1S-mediated autophagy trigger oxidative stress, sinusoidal dilation, and lifespan reduction. Overexpression of LC3 in wild-type mice increases the levels of fibronectin and γ-H2 AX, a marker of DNA double-strand breakage. LC3-induced fibronectin is efficiently degraded in lysosomes to maintain a balance of fibronectin levels in wild-type mice so that the mice live a normal term of lifespan. In the LC3 transgenic mice with MAP1S deleted, LC3 enhances the synthesis of fibronectin but the MAP1S depletion causes an impairment of the lysosomal degradation of fibronectin. The accumulation of fibronectin protein promotes liver fibrosis, induces an accumulation of cell population at the G0/G1 stage, and further intensifies oxidative stress and sinusoidal dilatation. The LC3-induced overexpression of fibronectin imposes stresses on MAP1S-deficient mice and dramatically reduces their lifespans. Therefore, MAP1S-mediated autophagy plays an important role in maintaining mouse lifespan especially in the presence of extra amount of fibronectin.

  12. 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...

  13. Calsequestrin 2 deletion causes sinoatrial node dysfunction and atrial arrhythmias associated with altered sarcoplasmic reticulum calcium cycling and degenerative fibrosis within the mouse atrial pacemaker complex1

    PubMed Central

    Glukhov, Alexey V.; Kalyanasundaram, Anuradha; Lou, Qing; Hage, Lori T.; Hansen, Brian J.; Belevych, Andriy E.; Mohler, Peter J.; Knollmann, Björn C.; Periasamy, Muthu; Györke, Sandor; Fedorov, Vadim V.

    2015-01-01

    Aims Loss-of-function mutations in Calsequestrin 2 (CASQ2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT patients also exhibit bradycardia and atrial arrhythmias for which the underlying mechanism remains unknown. We aimed to study the sinoatrial node (SAN) dysfunction due to loss of CASQ2. Methods and results In vivo electrocardiogram (ECG) monitoring, in vitro high-resolution optical mapping, confocal imaging of intracellular Ca2+ cycling, and 3D atrial immunohistology were performed in wild-type (WT) and Casq2 null (Casq2−/−) mice. Casq2−/− mice exhibited bradycardia, SAN conduction abnormalities, and beat-to-beat heart rate variability due to enhanced atrial ectopic activity both at baseline and with autonomic stimulation. Loss of CASQ2 increased fibrosis within the pacemaker complex, depressed primary SAN activity, and conduction, but enhanced atrial ectopic activity and atrial fibrillation (AF) associated with macro- and micro-reentry during autonomic stimulation. In SAN myocytes, CASQ2 deficiency induced perturbations in intracellular Ca2+ cycling, including abnormal Ca2+ release, periods of significantly elevated diastolic Ca2+ levels leading to pauses and unstable pacemaker rate. Importantly, Ca2+ cycling dysfunction occurred not only at the SAN cellular level but was also globally manifested as an increased delay between action potential (AP) and Ca2+ transient upstrokes throughout the atrial pacemaker complex. Conclusions Loss of CASQ2 causes abnormal sarcoplasmic reticulum Ca2+ release and selective interstitial fibrosis in the atrial pacemaker complex, which disrupt SAN pacemaking but enhance latent pacemaker activity, create conduction abnormalities and increase susceptibility to AF. These functional and extensive structural alterations could contribute to SAN dysfunction as well as AF in CPVT patients. PMID:24216388

  14. 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.

  15. Increased expression of the frontotemporal dementia risk factor TMEM106B causes C9orf72-dependent alterations in lysosomes.

    PubMed

    Busch, Johanna I; Unger, Travis L; Jain, Nimansha; Tyler Skrinak, R; Charan, Rakshita A; Chen-Plotkin, Alice S

    2016-07-01

    Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is an important cause of dementia in individuals under age 65. Common variants in the TMEM106B gene were previously discovered by genome-wide association to confer genetic risk for FTLD-TDP (p = 1 × 10(-)(11), OR = 1.6). Furthermore, TMEM106B may act as a genetic modifier affecting age at onset and age at death in the Mendelian subgoup of FTLD-TDP due to expansions of the C9orf72 gene. Evidence suggests that TMEM106B variants increase risk for developing FTLD-TDP by increasing expression of Transmembrane Protein 106B (TMEM106B), a lysosomal protein. To further understand the functional role of TMEM106B in disease pathogenesis, we investigated the cell biological effects of increased TMEM106B expression. Here, we report that increased TMEM106B expression results in the appearance of a vacuolar phenotype in multiple cell types, including neurons. Concomitant with the development of this vacuolar phenotype, cells over-expressing TMEM106B exhibit impaired lysosomal acidification and degradative function, as well as increased cytotoxicity. We further identify a potential lysosomal sorting motif for TMEM106B and demonstrate that abrogation of sorting to lysosomes rescues TMEM106B-induced defects. Finally, we show that TMEM106B-induced defects are dependent on the presence of C9orf72, as knockdown of C9orf72 also rescues these defects. In sum, our results suggest that TMEM106B exerts its effects on FTLD-TDP disease risk through alterations in lysosomal pathways. Furthermore, TMEM106B and C9orf72 may interact in FTLD-TDP pathophysiology.

  16. 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.

  17. 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.

  18. Early lingual frenectomy assisted by CO2 laser helps prevention and treatment of functional alterations caused by ankyloglossia.

    PubMed

    Fiorotti, Renata C; Bertolini, Milene M; Nicola, Jorge H; Nicola, Ester M D

    2004-11-01

    Incorrectly produced speech sounds, the presence of dentofacial alterations and acquired functional adaptations may be due to a short and inadequate lingual frenum. When frenectomy is indicated, it should be performed as early as possible to prevent functional alterations. This study presents a literature review on correct lingual positioning in relation to orthodontic and phonetic function as well as an assessment of 15 patients who underwent frenectomy utilizing the carbon dioxide laser. The results demonstrated that this technique is safe, effective and perfect for use in young children and can be performed in an outpatient unit.

  19. 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

  20. 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.

  1. Perinatal exposure to delta-9-tetrahydrocannabinol causes enduring cognitive deficits associated with alteration of cortical gene expression and neurotransmission in rats.

    PubMed

    Campolongo, Patrizia; Trezza, Viviana; Cassano, Tommaso; Gaetani, Silvana; Morgese, Maria Grazia; Ubaldi, Massimo; Soverchia, Laura; Antonelli, Tiziana; Ferraro, Luca; Massi, Maurizio; Ciccocioppo, Roberto; Cuomo, Vincenzo

    2007-09-01

    The aim of the present study was to investigate whether perinatal exposure to a moderate dose of delta-9-tetrahydrocannabinol (THC) alters cortical gene expression and neurotransmission, leading to enduring cognitive dysfunctions in rat offspring. To this purpose, rat dams were treated, from gestational day 15 to postnatal day 9, with THC at a daily dose (5 mg/kg, per os) devoid of overt signs of toxicity. THC did not influence reproduction parameters, whereas it caused subtle neurofunctional deficits in the adult offspring. Particularly, perinatal THC induced long-lasting alterations of cortical genes related to glutamatergic and noradrenergic systems, associated with a decrease in the cortical extracellular levels of both neurotransmitters. These alterations may account, at least in part, for the enduring cognitive impairment displayed by THC-exposed offspring. Taken together, the present results highlight how exposure to cannabinoids during early stages of brain development can lead to irreversible, subtle dysfunctions in the offspring.

  2. Automated detection and mapping of crown discolouration caused by jack pine budworm with 2.5 m resolution multispectral imagery

    NASA Astrophysics Data System (ADS)

    Leckie, Donald G.; Cloney, Ed; Joyce, Steve P.

    2005-05-01

    Jack pine budworm ( Choristoneura pinus pinus (Free.)) is a native insect defoliator of mainly jack pine ( Pinus banksiana Lamb.) in North America east of the Rocky Mountains. Periodic outbreaks of this insect, which generally last two to three years, can cause growth loss and mortality and have an important impact ecologically and economically in terms of timber production and harvest. The jack pine budworm prefers to feed on current year needles. Their characteristic feeding habits cause discolouration or reddening of the canopy. This red colouration is used to map the distribution and intensity of defoliation that has taken place that year (current defoliation). An accurate and consistent map of the distribution and intensity of budworm defoliation (as represented by the red discolouration) at the stand and within stand level is desirable. Automated classification of multispectral imagery, such as is available from airborne and new high resolution satellite systems, was explored as a viable tool for objectively classifying current discolouration. Airborne multispectral imagery was acquired at a 2.5 m resolution with the Multispectral Electro-optical Imaging Sensor (MEIS). It recorded imagery in six nadir looking spectral bands specifically designed to detect discolouration caused by budworm and a near-infrared band viewing forward at 35° was also used. A 2200 nm middle infrared image was acquired with a Daedalus scanner. Training and test areas of different levels of discolouration were created based on field observations and a maximum likelihood supervized classification was used to estimate four classes of discolouration (nil-trace, light, moderate and severe). Good discrimination was achieved with an overall accuracy of 84% for the four discolouration levels. The moderate discolouration class was the poorest at 73%, because of confusion with both the severe and light classes. Accuracy on a stand basis was also good, and regional and within stand

  3. 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.

  4. High magnetic gradient environment causes alterations of cytoskeleton and cytoskeleton-associated genes in human osteoblasts cultured in vitro

    NASA Astrophysics Data System (ADS)

    Qian, A. R.; Yang, P. F.; Hu, L. F.; Zhang, W.; Di, S. M.; Wang, Z.; Han, J.; Gao, X.; Shang, P.

    2010-09-01

    The effects of a high magnetic gradient environment (HMGE) on the cytoskeletal architecture and genes associated with the cytoskeleton in osteoblasts (MC3T3-E1 and MG-63 cells) were investigated using confocal microscopy, real-time polymerase chain reaction (PCR) and atomic force microscopy (AFM). The findings showed that, under diamagnetic levitation conditions, the architecture and average height of the cytoskeleton and surface roughness in osteoblasts were dramatically altered. HMGE affects cytoskeleton arrangement and cytoskeleton-associated gene expression.

  5. Seed Germination and Seedling Growth under Simulated Microgravity Causes Alterations in Plant Cell Proliferation and Ribosome Biogenesis

    NASA Astrophysics Data System (ADS)

    Matía, Isabel; van Loon, Jack W. A.; Carnero-Díaz, Eugénie; Marco, Roberto; Medina, Francisco Javier

    2009-01-01

    The study of the modifications induced by altered gravity in functions of plant cells is a valuable tool for the objective of the survival of terrestrial organisms in conditions different from those of the Earth. We have used the system "cell proliferation-ribosome biogenesis", two inter-related essential cellular processes, with the purpose of studying these modifications. Arabidopsis seedlings belonging to a transformed line containing the reporter gene GUS under the control of the promoter of the cyclin gene CYCB1, a cell cycle regulator, were grown in a Random Positioning Machine, a device known to accurately simulate microgravity. Samples were taken at 2, 4 and 8 days after germination and subjected to biometrical analysis and cellular morphometrical, ultrastructural and immunocytochemical studies in order to know the rates of cell proliferation and ribosome biogenesis, plus the estimation of the expression of the cyclin gene, as an indication of the state of cell cycle regulation. Our results show that cells divide more in simulated microgravity in a Random Positioning Machine than in control gravity, but the cell cycle appears significantly altered as early as 2 days after germination. Furthermore, higher proliferation is not accompanied by an increase in ribosome synthesis, as is the rule on Earth, but the functional markers of this process appear depleted in simulated microgravity-grown samples. Therefore, the alteration of the gravitational environmental conditions results in a considerable stress for plant cells, including those not specialized in gravity perception.

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

    SciTech Connect

    Levin, M.; Ernst, S.G.

    1995-09-01

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

  7. 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.

  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 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  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 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. ECK, a human EPH-related gene, maps to 1p36.1, a common region of alteration in human cancers

    SciTech Connect

    Sulman, E.P.; Brodeur, G.M.; Ikegaki, N.

    1997-03-01

    Mouse eck, a member of the EPH gene family, has been mapped to mouse chromosome 4. The syntenic relationship between this chromosome and human chromosome 1 suggests that the human ECK gene maps to the distal short arm of human chromosome 1 (1p). Since this region is frequently deleted or altered in certain tumors of neuroectodermal origin, it is important to define the specific chromosomal localization of the human ECK gene. PCR screening of a rodent-human somatic cell hybrid panel by ECK-specific primers showed that ECK is indeed localized to human chromosome 1. Additional PCR screening of a regional screening panel for chromosome 1p indicated that ECK is localized to 1p36, distal to FUCA1. Furthermore, fluorescence in situ hybridization analysis with an ECK-specific P1 clone showed that ECK maps proximal to genetic marker D1S228. Taken together, the data suggest that ECK maps to 1p36.1, a region that is frequently deleted in neuroblastoma, melanoma, and other neuroectodermal tumors. 23 refs., 3 figs.

  11. Airborne Magnetic and Electromagnetic Data map Rock Alteration and Water Content at Mount Adams, Mount Baker and Mount Rainier, Washington: Implications for Lahar Hazards and Hydrothermal Systems

    NASA Astrophysics Data System (ADS)

    Finn, C. A.; Deszcz-Pan, M.; Horton, R.; Breit, G.; John, D.

    2007-12-01

    High resolution helicopter-borne magnetic and electromagnetic (EM) data flown over the rugged, ice-covered, highly magnetic and mostly resistive volcanoes of Mount Rainier, Mount Adams and Mount Baker, along with rock property measurements, reveal the distribution of alteration, water and hydrothermal fluids that are essential to evaluating volcanic landslide hazards and understanding hydrothermal systems. 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. Intense hydrothermal alteration significantly reduces the magnetization and resistivity of volcanic rock resulting in clear recognition of altered rock by helicopter magnetic and EM measurements. Magnetic and EM data, combined with geological mapping and rock property measurements, indicate the presence of appreciable thicknesses of hydrothermally altered rock west of the modern summit of Mount Rainier in the Sunset Amphitheater region, in the central core of Mount Adams north of the summit, and in much of the central cone of Mount Baker. We identify the Sunset Amphitheater region and steep cliffs at the western edge of the central altered zone at Mount Adams as likely sources for future debris flows. In addition, the EM data identified water-saturated rocks in the upper 100-200 m of the three volcanoes. The water-saturated zone could extend deeper, but is beyond the detection limits of the EM data. Water in hydrothermal fluids reacts with the volcanic rock to produce clay minerals. The formation of clay minerals and presence of free water 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. Finally, modeling requires extremely low

  12. 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

  13. 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.

  14. 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

  15. Homozygosity mapping and whole exome sequencing reveal a novel homozygous COL18A1 mutation causing Knobloch syndrome.

    PubMed

    Haghighi, Alireza; Tiwari, Amit; 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.

  16. 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

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

    USGS Publications Warehouse

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

    1979-01-01

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

  18. Mitochondrial defects and neuromuscular degeneration caused by altered expression of Drosophila Gdap1: implications for the Charcot-Marie-Tooth neuropathy.

    PubMed

    López Del Amo, Víctor; Seco-Cervera, Marta; García-Giménez, José Luís; Whitworth, Alexander J; Pallardó, Federico V; Galindo, Máximo Ibo

    2015-01-01

    One of the genes involved in Charcot-Marie-Tooth (CMT) disease, an inherited peripheral neuropathy, is GDAP1. In this work, we show that there is a true ortholog of this gene in Drosophila, which we have named Gdap1. By up- and down-regulation of Gdap1 in a tissue-specific manner, we show that altering its levels of expression produces changes in mitochondrial size, morphology and distribution, and neuronal and muscular degeneration. Interestingly, muscular degeneration is tissue-autonomous and not dependent on innervation. Metabolic analyses of our experimental genotypes suggest that alterations in oxidative stress are not a primary cause of the neuromuscular degeneration but a long-term consequence of the underlying mitochondrial dysfunction. Our results contribute to a better understanding of the role of mitochondria in CMT disease and pave the way to generate clinically relevant disease models to study the relationship between mitochondrial dynamics and peripheral neurodegeneration.

  19. Perinatal exposure to glyphosate-based herbicide alters the thyrotrophic axis and causes thyroid hormone homeostasis imbalance in male rats.

    PubMed

    de Souza, Janaina Sena; Kizys, Marina Malta Letro; da Conceição, Rodrigo Rodrigues; Glebocki, Gabriel; Romano, Renata Marino; Ortiga-Carvalho, Tania Maria; Giannocco, Gisele; da Silva, Ismael Dale Cotrim Guerreiro; Dias da Silva, Magnus Regios; Romano, Marco Aurélio; Chiamolera, Maria Izabel

    2017-02-15

    Glyphosate-based herbicides (GBHs) are widely used in agriculture. Recently, several animal and epidemiological studies have been conducted to understand the effects of these chemicals as an endocrine disruptor for the gonadal system. The aim of the present study was to determine whether GBHs could also disrupt the hypothalamic-pituitary-thyroid (HPT) axis. Female pregnant Wistar rats were exposed to a solution containing GBH Roundup(®)Transorb (Monsanto). The animals were divided into three groups (control, 5mg/kg/day or 50mg/kg/day) and exposed from gestation day 18 (GD18) to post-natal day 5 (PND5). Male offspring were euthanized at PND 90, and blood and tissues samples from the hypothalamus, pituitary, liver and heart were collected for hormonal evaluation (TSH-Thyroid stimulating hormone, T3-triiodothyronine and T4-thyroxine), metabolomic and mRNA analyses of genes related to thyroid hormone metabolism and function. The hormonal profiles showed decreased concentrations of TSH in the exposed groups, with no variation in the levels of the thyroid hormones (THs) T3 and T4 between the groups. Hypothalamus gene expression analysis of the exposed groups revealed a reduction in the expression of genes encoding deiodinases 2 (Dio2) and 3 (Dio3) and TH transporters Slco1c1 (former Oatp1c1) and Slc16a2 (former Mct8). In the pituitary, Dio2, thyroid hormone receptor genes (Thra1 and Thrb1), and Slc16a2 showed higher expression levels in the exposed groups than in the control group. Interestingly, Tshb gene expression did not show any difference in expression profile between the control and exposed groups. Liver Thra1 and Thrb1 showed increased mRNA expression in both GBH-exposed groups, and in the heart, Dio2, Mb, Myh6 (former Mhca) and Slc2a4 (former Glut4) showed higher mRNA expression in the exposed groups. Additionally, correlation analysis between gene expression and metabolomic data showed similar alterations as detected in hypothyroid rats. Perinatal exposure to

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

    USGS Publications Warehouse

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

    2003-01-01

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

  1. Human congenital myopathy actin mutants cause myopathy and alter Z-disc structure in Drosophila flight muscle.

    PubMed

    Sevdali, Maria; Kumar, Vikash; Peckham, Michelle; Sparrow, John

    2013-03-01

    Over 190 mutations in the human skeletal muscle α-actin gene, ACTA1 cause congenital actin myopathies. We transgenically expressed six different mutant actins, G15R, I136M, D154N, V163L, V163M and D292V in Drosophila indirect flight muscles and investigated their effects in flies that express one wild type and one mutant actin copy. All the flies were flightless, and the IFMs showed incomplete Z-discs, disorganised actin filaments and 'zebra bodies'. No differences in levels of sarcomeric protein expression were observed, but tropomodulin staining was somewhat disrupted in D164N, V163L, G15R and V163M heterozygotes. A single copy of D292V mutant actin rescued the hypercontractile phenotypes caused by TnI and TnT mutants, suggesting that the D292V mutation interferes with thin filament regulation. Our results show that expression of actin mutations homologous to those in humans in the indirect flight muscles of Drosophila disrupt sarcomere organisation, with somewhat similar phenotypes to those observed in humans. Using Drosophila to study actin mutations may help aid our understanding of congential myopathies caused by actin mutations.

  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. Structural Mutants of the Spindle Pole Body Cause Distinct Alteration of Cytoplasmic Microtubules and Nuclear Dynamics in Multinucleated Hyphae

    PubMed Central

    Lang, Claudia; Grava, Sandrine; Finlayson, Mark; Trimble, Rhonda; Philippsen, Peter

    2010-01-01

    In the multinucleate fungus Ashbya gossypii, cytoplasmic microtubules (cMTs) emerge from the spindle pole body outer plaque (OP) in perpendicular and tangential directions. To elucidate the role of cMTs in forward/backward movements (oscillations) and bypassing of nuclei, we constructed mutants potentially affecting cMT nucleation or stability. Hyphae lacking the OP components AgSpc72, AgNud1, AgCnm67, or the microtubule-stabilizing factor AgStu2 grew like wild- type but showed substantial alterations in the number, length, and/or nucleation sites of cMTs. These mutants differently influenced nuclear oscillation and bypassing. In Agspc72Δ, only long cMTs were observed, which emanate tangentially from reduced OPs; nuclei mainly moved with the cytoplasmic stream but some performed rapid bypassing. Agnud1Δ and Agcnm67Δ lack OPs; short and long cMTs emerged from the spindle pole body bridge/half-bridge structures, explaining nuclear oscillation and bypassing in these mutants. In Agstu2Δ only very short cMTs emanated from structurally intact OPs; all nuclei moved with the cytoplasmic stream. Therefore, long tangential cMTs promote nuclear bypassing and short cMTs are important for nuclear oscillation. Our electron microscopy ultrastructural analysis also indicated that assembly of the OP occurs in a stepwise manner, starting with AgCnm67, followed by AgNud1 and lastly AgSpc72. PMID:20053682

  4. 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

  5. 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

  6. A mutation in the FZL gene of Arabidopsis causing alteration in chloroplast morphology results in a lesion mimic phenotype

    PubMed Central

    Landoni, Michela

    2013-01-01

    Lesion mimic mutants (LMMs) are a class of mutants in which hypersensitive cell death and defence responses are constitutively activated in the absence of pathogen attack. Various signalling molecules, such as salicylic acid (SA), reactive oxygen species (ROS), nitric oxide (NO), Ca2+, ethylene, and jasmonate, are involved in the regulation of multiple pathways controlling hypersensitive response (HR) activation, and LMMs are considered useful tools to understand the role played by the key elements of the HR cell death signalling cascade. Here the characterization of an Arabidopsis LMM lacking the function of the FZL gene is reported. This gene encodes a membrane-remodelling GTPase playing an essential role in the determination of thylakoid and chloroplast morphology. The mutant displayed alteration in chloroplast number, size, and shape, and the typical characteristics of an LMM, namely development of chlorotic lesions on rosette leaves and constitutive expression of genetic and biochemical markers associated with defence responses. The chloroplasts are a major source of ROS, and the characterization of this mutant suggests that their accumulation, triggered by damage to the chloroplast membranes, is a signal sufficient to start the HR signalling cascade, thus confirming the central role of the chloroplast in HR activation. PMID:23963675

  7. Behavioral alterations in adolescent and adult rats caused by a brief subtoxic exposure to chlorpyrifos during neurulation.

    PubMed

    Icenogle, Laura M; Christopher, N Channelle; Blackwelder, W Paul; Caldwell, D Patrick; Qiao, Dan; Seidler, Frederic J; Slotkin, Theodore A; Levin, Edward D

    2004-01-01

    The widely used organophosphate insecticide, chlorpyrifos (CPF), elicits neurobehavioral abnormalities after apparently subtoxic neonatal exposures. In the current study, we administered 1 or 5 mg/kg/day of CPF to pregnant rats on gestational days 9-12, the embryonic phase spanning formation and closure of the neural tube. Although there were no effects on growth or viability, offspring showed behavioral abnormalities when tested in adolescence and adulthood. In the CPF-exposed groups, locomotor hyperactivity was noted in early T-maze trials, and in the elevated plus-maze; alterations in the rate of habituation were also identified. Learning and memory were adversely affected, as assessed using the 16-arm radial maze. Although all CPF-exposed animals eventually learned the task, reference and working memory were impaired in the early training sessions. After training, rats in the CPF group did not show the characteristic amnestic effect of scopolamine, a muscarinic acetylcholine antagonist, suggesting that, unlike the situation in the control group, muscarinic pathways were not used to solve the maze. These results indicate that apparently subtoxic CPF exposure during neurulation adversely affects brain development, leading to behavioral anomalies that selectively include impairment of cholinergic circuits used in learning and memory. The resemblance of these findings to those of late gestational or neonatal CPF exposure indicates a prolonged window of vulnerability of brain development to CPF.

  8. Cardiovascular alterations caused by the administration of 2% mepivacaine HCl with 1:20,000 levonordefrin (Carbocain) in dogs.

    PubMed

    Simone, J L; Tortamano, N; Armonia, P L; Rocha, R G

    1997-01-01

    We studied possible cardiovascular effects (systolic, diastolic, mean arterial blood pressures, and heart rate) caused by intraoral infiltrative administration of 2% mepivacaine HCl with 1:20,000 levonordefrin in dogs (Canis familiaris), using a Beckman electrophysiograph. Doses used were 0.514 and 1.542 mg/kg body weight corresponding to one and three 1.8-ml cartridges, respectively, in 70-kg average weight adult men. A statistically significant increase was observed in the systolic and the mean arterial blood pressures.

  9. 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.

  10. Female Putty-Nosed Monkeys Use Experimentally Altered Contextual Information to Disambiguate the Cause of Male Alarm Calls

    PubMed Central

    Arnold, Kate; Zuberbühler, Klaus

    2013-01-01

    Many animal vocal signals are given in a wide range of contexts which can sometimes have little in common. Yet, to respond adaptively, listeners must find ways to identify the cause of a signal, or at least rule out alternatives. Here, we investigate the nature of this process in putty-nosed monkeys, a forest primate. In this species, adult males have a very restricted repertoire of vocalizations which are given in response to a wide variety of events occurring under conditions of limited visibility. We carried out a series of field playback experiments on females (N = 6) in a habituated group in Gashaka Gumti National Park, Nigeria, in which male alarm/loud calls were presented either alone, or following acoustic information that simulated the occurrence of natural disturbances. We demonstrate that listeners appear to integrate contextual information in order to distinguish among possible causes of calls. We conclude that, in many cases, pragmatic aspects of communication play a crucial role in call interpretation and place a premium on listeners' abilities to integrate information from different sources. PMID:23755265

  11. Haematological and biochemical alterations caused by epidural and intramuscular administration of xylazine hydrochloride in dromedary camels (Camelus dromedarius).

    PubMed

    Azari, Omid; Molaei, Mohammad Mahdi; Emadi, Ladan; Sakhaee, Ehsanollah; Sharifi, Hamid; Mehdizadeh, Sara

    2012-01-01

    This study was conducted in 16 healthy immature dromedary camels weighing 120-150 kg to evaluate and compare the effects of epidural and intramuscular injections of xylazine administered at 0.1 mg/kg and 0.2 mg/kg. Haematological parameters included haemoglobin, packed cell volume, total erythrocyte count and total leukocyte count. Biochemical parameters included alkaline phosphates, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine and glucose. Parameters were measured at different intervals before (baseline) and after the administration of drugs. Our study showed that the effect of xylazine on haematological and biochemical parameters is dose-dependant and is also related to the route of administration. The low dose of xylazine administered using both intramuscular and epidural methods showed minimal effects, whereas high doses of the drug, especially when injected intramuscularly, caused greater changes in haematological and biochemical parameters.

  12. Altered phosphorylation of Bacillus subtilis DegU caused by single amino acid changes in DegS.

    PubMed Central

    Tanaka, T; Kawata, M; Mukai, K

    1991-01-01

    The Bacillus subtilis sacU locus consists of the degS and degU genes, which play a major role in controlling the production of degradative enzymes including extracellular proteases. DegS has been shown to be autophosphorylated and to transfer the phosphoryl group to DegU. In this study, we partially purified the DegS proteins which carry amino acid changes resulting from various mutations and examined the phosphorylation reaction. The mutations used were degS42, causing a reduction in exoprotease production, and degS100(Hy) and degS200(Hy), causing overproduction of the enzymes. The following results were obtained. The DegS protein derived from degS42 was deficient in both autophosphorylation and subsequent phosphate transfer to DegU. Compared with wild-type DegS, the DegS proteins derived from the overproduction mutations, degS100(Hy) and degS200(Hy), were less active in the autophosphorylation and phosphorylation of DegU. However, the DegU phosphates produced by the mutant DegS proteins were more stable than that produced by the wild-type DegS. These results suggest that phosphorylation is tightly linked to exoprotease production and that the prolonged retention of the phosphoryl moiety on DegU activates the genes for the extracellular proteases. It was also shown that the rate of dephosphorylation of DegU-phosphate was increased as the amount of DegS was increased. All of these results suggest that DegS is involved in the dephosphorylation of DegU-phosphate. Images PMID:1909319

  13. Intermittent ethanol exposure induces inflammatory brain damage and causes long-term behavioural alterations in adolescent rats.

    PubMed

    Pascual, Maria; Blanco, Ana M; Cauli, Omar; Miñarro, Jose; Guerri, Consuelo

    2007-01-01

    Adolescent brain development seems to be important for the maturation of brain structures and behaviour. Intermittent binge ethanol drinking is common among adolescents, and this type of drinking can induce brain damage. Because we have demonstrated that chronic ethanol treatment induces inflammatory processes in the brain, we investigate whether intermittent ethanol intoxication enhances cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in adolescent rats, and whether these mediators induce brain damage and cause permanent cognitive dysfunctions. Adolescent rats were exposed to ethanol (3.0 g/kg) for two consecutive days at 48-h intervals over 14 days. Levels of COX-2, iNOS and cell death were assessed in the neocortex, hippocampus and cerebellum 24 h after the final ethanol administration. The following day or 20 days after the final injection (adult stage), animals were tested for different behavioural tests (conditional discrimination learning, rotarod, object recognition, beam-walking performance) to assess cognitive and motor functions. Our results show that intermittent ethanol intoxication upregulates COX-2 and iNOS levels, and increases cell death in the neocortex, hippocampus and cerebellum. Furthermore, animals treated with ethanol during adolescence exhibited behavioural deficits that were evident at the end of ethanol treatments and at the adult stage. Administration of indomethacin, a COX-2 inhibitor, abolishes the induction of COX-2 and iNOS expression and cell death, preventing ethanol-induced behavioural deficits. These findings indicate that binge pattern exposure to ethanol during adolescence induces brain damage by inflammatory processes and causes long-lasting neurobehavioural consequences. Accordingly, administering indomethacin protects against ethanol-induced brain damage and prevents detrimental ethanol effects on cognitive and motor processes.

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

    PubMed Central

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

    2009-01-01

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

  15. BLT2 expression improves skin integrity and protects from alterations caused by hyperglycemia in type 2 diabetes

    PubMed Central

    2017-01-01

    ABSTRACT Type 2 diabetes (T2D) can go undiagnosed for years, leading to a stage where chronic high blood sugar produces complications such as delayed wound healing. Reports have shown that BLT2 activation improves keratinocyte migration and wound healing, as well as protecting the epidermal barrier through the promotion of actin polymerization. The goal of this study was to elucidate the role of BLT2 expression in skin epithelial integrity in T2D. For this purpose, we used both wild type (WT) and BLT2 knockout mice in a model, in which a T2D-like phenotype was induced by keeping the animals on a high fat (HF) diet over 5 weeks. In a parallel in vitro approach, we cultured BLT2-transfected HaCaT cells at both low and high glucose concentrations for 48 h. Structure, transepithelial resistance (TEER), IL-1ß, IL-8 or CXCL2, MMP9, Filaggrin, Loricrin and Keratin 10 (K10) were evaluated ex vivo and in vitro. Additionally, wound healing (WH) was studied in vitro. The skin from T2D and BLT2 knockout mice showed a reduction in TEER and the expression of IL-1ß, and in increase in CXCL2, MMP9, Filaggrin, Loricrin and K10 expression. The structure suggested an atrophic epidermis; however, the skin was dramatically affected in the BLT2 knockout mice kept on a HF diet. HaCaT-BLT2 cells presented as an organized monolayer and showed higher TEER and wound healing compared with vector only-transfected HaCaT-Mock cells. Likewise, alterations in the expression of skin inflammatory, matrix degradation and differentiation markers under low and high glucose conditions were less severe than in HaCaT-Mock cells. Our results suggest that BLT2 improves epithelial integrity and function by regulating differentiation markers, cytokines and MMP9. Furthermore, BLT2 attenuates the damaging effects of high glucose levels, thereby accelerating wound healing.

  16. Evaluation of surface properties and atmospheric disturbances caused by post-dam alterations of land-use/land-cover

    NASA Astrophysics Data System (ADS)

    Woldemichael, A. T.; Hossain, F.; Pielke, R., Sr.

    2014-05-01

    This study adopted a differential land-use/land-cover (LULC) analysis to evaluate dam-triggered land-atmosphere interactions for a number of LULC scenarios. Two specific questions were addressed: (1) can dam-triggered LULC heterogeneities modify surface and energy budget which, in turn, change regional convergence and precipitation patterns? and (2) how extensive is the modification in surface moisture and energy budget altered by dam-triggered LULC changes occurring in different climate and terrain features? The Regional Atmospheric Modeling System (RAMS, version 6.0) was set up for two climatologically and topographically contrasting regions: the American River Watershed (ARW) located in California and the Owyhee River Watershed (ORW) located in eastern Oregon. For the selected atmospheric river precipitation event of 29 December 1996 to 3 January 1997, simulations of three pre-defined LULC scenarios are performed. The definition of the scenarios are: (1) the control scenario representing the contemporary land-use, (2) the pre-dam scenario representing the natural landscape before the construction of the dams and (3) the non-irrigation scenario representing the condition where previously irrigated landscape in the control is transformed to the nearby land-use type. Results indicated that the ARW energy and moisture fluxes were more extensively affected by dam-induced changes in LULC than the ORW. Both regions, however, displayed commonalities in the modification of land-atmosphere processes due to LULC changes, with the control-non-irrigation scenario creating more change than the control-pre-dam scenarios. These commonalities were: (1) the combination of a decrease in temperature (up to 0.15 °C) and an increase in dewpoint (up to 0.25 °C) was observed, (2) there was a larger fraction of energy partitioned to latent heat flux (up to 10 W m-2) that increased the amount of water vapor to the atmosphere and resulted in a larger convective available potential

  17. Evaluation of surface properties and atmospheric disturbances caused by post-dam alterations of land use/land cover

    NASA Astrophysics Data System (ADS)

    Woldemichael, A. T.; Hossain, F.; Pielke, R., Sr.

    2014-09-01

    This study adopted a differential land-use/land-cover (LULC) analysis to evaluate dam-triggered land-atmosphere interactions for a number of LULC scenarios. Two specific questions were addressed: (1) can dam-triggered LULC heterogeneities modify surface and energy budget, which, in turn, change regional convergence and precipitation patterns? (2) How extensive is the modification in surface moisture and energy budget altered by dam-triggered LULC changes occurring in different climate and terrain features? The Regional Atmospheric Modeling System (RAMS, version 6.0) was set up for two climatologically and topographically contrasting regions: the American River watershed (ARW), located in California, and the Owyhee River watershed (ORW), located in eastern Oregon. For the selected atmospheric river precipitation event of 29 December 1996 to 3 January 1997, simulations of three pre-defined LULC scenarios are performed. The definition of the scenarios are (1) the "control" scenario, representing the contemporary land use, (2) the "pre-dam" scenario, representing the natural landscape before the construction of the dams and (3) the "non-irrigation" scenario, representing the condition where previously irrigated landscape in the control is transformed to the nearby land-use type. Results indicated that the ARW energy and moisture fluxes were more extensively affected by dam-induced changes in LULC than the ORW. Both regions, however, displayed commonalities in the modification of land-atmosphere processes due to LULC changes, with the control-non-irrigation scenario creating more change than the control-pre-dam scenarios. These commonalities were: (1) the combination of a decrease in temperature (up to 0.15 °C) and an increase at dew point (up to 0.25 °C) was observed; (2) there was a larger fraction of energy partitioned to latent heat flux (up to 10 W m-2) that increased the amount of water vapor in the atmosphere and resulted in a larger convective available

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

    PubMed

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

    2012-02-09

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

  19. More signs of neurotoxicity of surfactants and flame retardants - Neonatal PFOS and PBDE 99 cause transcriptional alterations in cholinergic genes in the mouse CNS.

    PubMed

    Hallgren, Stefan; Fredriksson, Anders; Viberg, Henrik

    2015-09-01

    Maternally and lactionally transferred persistent organic pollutants may interfere with CNS development. Here, 10-day-old male mice were exposed to single oral doses of PFOS (perflourooctanosulphonate) or PBDE 99 (2,2',4,4',5-penta-bromodiphenyl ether), and examined for changes in cholinergic gene transcription in the CNS 24h and 7 weeks later. 24h after exposure qPCR analyses revealed decreased transcription of nAChR-β2 and AChE in cortex, and increased mAChR-5 in hippocampus of PFOS treated mice. Neonatal PFOS treatment altered spontaneous behaviour at 2 months of age but did not affect gene transcription in adults. At 2 months of age neonatally PBDE 99 treated mice had altered spontaneous behaviour, and cortical transcription of AChE, nAChR-α4, nAChR-β2 and mAChR-5 were elevated. Our results indicate that PFOS and PBDE 99 affects the developing central cholinergic system by altering gene transcription in cortex and hippocampus, which may in part account for mechanisms causing changes in spontaneous behaviour.

  20. Temporal radiative heat flux estimation and alteration mapping of Tendürek volcano (eastern Turkey) using ASTER imagery

    NASA Astrophysics Data System (ADS)

    Ulusoy, İnan

    2016-11-01

    Tendürek volcano is a polygenetic, basaltic shield volcano formed by successive alkaline basalt flows. It is one of the youngest volcanoes of Turkey; both historical and Holocene activities have been reported for the volcano. Continuous hydrothermal and fumarole activity has been observed on the twin summit craters located 4.5 km apart. ASTER daytime and nighttime satellite imagery acquired between 2001 and 2014 are used to calculate surface temperature, surface temperature anomaly and relative radiative heat flux from the craters to determine a base value for the current thermal emission. Surface temperature and surface temperature anomaly calculations yield a heat flux between 14.4 and 35.5 W/m2 at the western crater and between 7.72 and 28.3 W/m2 at the eastern crater. These values are well-correlated with other known low-level activity volcanoes. The annual and long term consistency of the thermal pattern is investigated. The location and extent of surficial hydrothermal alteration within and surrounding the Tendürek craters is identified by band ratioing and indexing using ASTER visible through shortwave infrared bands. Spectral identification of gypsum, hydroxides, sulfates, hydrated sulfates and clay mineralisation indicates pervasive acid-sulfate alteration due to the activity of fumarole vents around Tendürek craters.

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

    SciTech Connect

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

    1993-01-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2010-04-09

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

  5. Dysregulation of autoimmunity caused by silica exposure and alteration of Fas-mediated apoptosis in T lymphocytes derived from silicosis patients.

    PubMed

    Otsuki, T; Hayashi, H; Nishimura, Y; Hyodo, F; Maeda, M; Kumagai, N; Miura, Y; Kusaka, M; Uragami, K

    2011-01-01

    Silicosis patients suffer from pulmonary fibrosis caused by silica inhalation, as well as autoimmune diseases known as the adjuvant effects of silica. Caplan syndrome complicated with rheumatoid arthritis (RA) is well known epidemiologically, and the incidence of complicated systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and antineutrophilic cytoplasmic antibody (ANCA)-related nephritis have been reported frequently in silicosis patients. To explore the detailed mechanisms of silica-induced dysregulation of autoimmunity, we had focused on Fas/CD95 and Fas-mediated apoptosis because Fas is one of the most important molecules regarding apoptosis of lymphocytes and its alteration makes some T cells survive longer. Additionally, if the long-survived T cells include the self-recognizing T-cell clones, it is easily thought that autoimmune diseases will appear in this situation. Furthermore, regulatory T cells (Treg) showing CD4+25+ and forkhead box P3 (FoxP3)-positive have been a central player in regulating activation of self- and foreign-antigen recognizing T cells, and it has been reported that activation of Treg causes its higher expression of Fas/CD95. Thus, in this review, we introduce the alteration of Fas and related molecules as found in silicosis and also present the Treg function of the CD4+25+ fraction in peripheral blood mononuclear cells derived from silicosis patients.

  6. IL-6 loss causes ventricular dysfunction, fibrosis, reduced capillary density, and dramatically alters the cell populations of the developing and adult heart

    PubMed Central

    Banerjee, Indroneal; Fuseler, John W.; Intwala, Arti R.; Baudino, Troy A.

    2009-01-01

    Interleukin-6 (IL-6) is a pleiotropic cytokine responsible for many different processes including the regulation of cell growth, apoptosis, differentiation, and survival in various cell types and organs, including the heart. Recent studies have indicated that IL-6 is a critical component in the cell-cell communication between myocytes and cardiac fibroblasts. In this study, we examined the effects of IL-6 deficiency on the cardiac cell populations, cardiac function, and interactions between the cells of the heart, specifically cardiac fibroblasts and myocytes. To examine the effects of IL-6 loss on cardiac function, we used the IL-6−/− mouse. IL-6 deficiency caused severe cardiac dilatation, increased accumulation of interstitial collagen, and altered expression of the adhesion protein periostin. In addition, flow cytometric analyses demonstrated dramatic alterations in the cardiac cell populations of IL-6−/− mice compared with wild-type littermates. We observed a marked increase in the cardiac fibroblast population in IL-6−/− mice, whereas a concomitant decrease was observed in the other cardiac cell populations examined. Moreover, we observed increased cell proliferation and apoptosis in the developing IL-6−/− heart. Additionally, we observed a significant decrease in the capillary density of IL-6−/− hearts. To elucidate the role of IL-6 in the interactions between cardiac fibroblasts and myocytes, we performed in vitro studies and demonstrated that IL-6 deficiency attenuated the activation of the STAT3 pathway and VEGF production. Taken together, these data demonstrate that a loss of IL-6 causes cardiac dysfunction by shifting the cardiac cell populations, altering the extracellular matrix, and disrupting critical cell-cell interactions. PMID:19234091

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

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

    2010-09-24

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

  10. Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice.

    PubMed

    Buratovic, Sonja; Stenerlöw, Bo; Fredriksson, Anders; Sundell-Bergman, Synnöve; Viberg, Henrik; Eriksson, Per

    2014-12-01

    Medical use of ionizing radiation (IR) has great benefits for treatment and diagnostic imaging, but procedures as computerized tomography (CT) may deliver a significant radiation dose to the patient. Recently, awareness has been raised about possible non-cancer consequences from low dose exposure to IR during critical phases of perinatal and/or neonatal brain development. In the present study neonatal NMRI mice were whole body irradiated with a single dose of gamma radiation (0; 350 and 500 mGy) on postnatal day 10 (PND 10). At 2 and 4 months of age, mice of both sexes were observed for spontaneous behaviour in a novel home environment. The neuroproteins CaMKII, GAP-43, synaptophysin and total tau in male mouse cerebral cortex and hippocampus were analysed 24h post-irradiation and in adults at 6 months of age exposed to 0 or 500 mGy on PND 10. A significantly dose-response related deranged spontaneous behaviour in 2- and 4-month-old mice was observed, where both males and females displayed a modified habituation, indicating reduced cognitive function. The dose of 350 mGy seems to be a tentative threshold. Six-month-old male mice showed a significantly increased level of total tau in cerebral cortex after irradiation to 500 mGy compared to controls. This demonstrates that a single moderate dose of IR, given during a defined critical period of brain development, is sufficient to cause persistently reduced cognitive function. Moreover, an elevation of tau protein was observed in male mice displaying reduced cognitive function.

  11. Absence of substrate inhibition and freezing-inactivation of the mosquito acetylcholinesterase are caused by alterations of hydrophobic interactions.

    PubMed

    Dary, O; Wedding, R T

    1990-05-31

    Membrane-bound acetylcholinesterase (AChE) from mosquito showed the characteristic substrate inhibition of this enzyme, but 105,000 x g supernatants of freshly extracted enzyme did not. Addition of chaotropic anions, a freeze-thaw cycle and autolysis of the amphiphilic acetylcholinesterase to its non-amphiphilic derivatives resulted in return of the substrate inhibition feature along with an apparent increment in the enzyme activity. These results suggested that the lipidic environment of the mosquito AChE is temporarily perturbed when extracted. The enzyme is probably trapped in non-sedimenting mixtures composed of endogenous amphiphilic molecules. The occurrence of this phenomenon was not affected by the presence of Triton X-100 and other detergents, either alone or in combination with sodium chloride. Freezing in the presence of strong chaotropic anions (perchlorate, iodide and thiocyanate) caused the irreversible inactivation of the mosquito AChE. Crude and incomplete purified fractions of the enzyme were more sensitive than a more purified preparation. With both the purified AChE and the non-purified AChE, amphiphilic AChE was more freeze labile. Freezing at -10 degrees C enhanced inactivation of non-purified fractions. At this temperature, even weak chaotropic anions (fluoride, chloride and nitrate), while in combination with non-ionic detergents that solubilized mosquito AChE efficiently, reduced the enzyme activity of these fractions. In this case, recovery of the enzyme activity by incubation at 25 degrees C was inversely correlated with the effectiveness of the chaotropic anion. Gel filtration failed to show any change in the hydrodynamic radius of the freezing-inactivated AChE. Therefore, this phenomenon is explained as different degrees of denaturation of the enzyme in direct association with the chaotropic strength. Thus, antichaotropic anions, such as sulfate, should improve the stability of the mosquito acetylcholinesterase during extraction

  12. Photosynthetic and antioxidative alterations in coffee leaves caused by epoxiconazole and pyraclostrobin sprays and Hemileia vastatrix infection.

    PubMed

    Honorato Júnior, J; Zambolim, L; Aucique-Pérez, C E; Resende, R S; Rodrigues, F A

    2015-09-01

    Coffee leaf rust (CLR), caused by Hemileia vastatrix, is a major disease affecting coffee production worldwide. In this study, an in-depth analysis of the photosynthetic performance of coffee leaves challenged or not with H. vastatrix and sprayed with either epoxiconazole (EPO) or pyraclostrobin (PYR) was performed by combining chlorophyll a fluorescence images, photosynthetic pigment pools and the activities of chitinase (CHI), β-1,3-glucanase (GLU), peroxidase (POX) and catalase (CAT). The CLR severity was higher in the control plants, but reduced in plants sprayed with both PYR and EPO. Also, the CLR severity was reduced in plants sprayed with PYR compared with plants sprayed with EPO. Plants sprayed with either EPO or PYR showed maximal photosystem II quantum efficiency (Fv/Fm) values ranging from 0.78 to 0.80, which were quite similar to those obtained with inoculated plants (values ranging from 0.74 to 0.77). The decreases in the Fv/Fm ratio values and parallel increases in the F0 values in the inoculated plants, which were not observed in the control plants (sprayed with water) and were confirmed by images of the initial fluorescence (F0) and Fv/Fm parameters in the regions of the leaf tissue containing pustules and in the asymptomatic leaf tissue, indicated that photosynthesis was negatively impacted. When effective photosystem II quantum yield (Y(II)) values approached zero with a high photosynthetic photon flux density, high values of quantum yield of regulated energy dissipation (Y(NPQ)) in association with a high carotenoid concentration were noted in the inoculated plants sprayed either with PYR or EPO. The increased CLR severity in inoculated plants in contrast to inoculated plants sprayed with either PYR or EPO was associated with greater POX activity and a reduced photosynthetic pigment concentration. POX and CAT activities were increased in inoculated plants sprayed with either EPO or PYR when compared with control plants. CHI and GLU activities

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

    PubMed Central

    Ho, Chao-Yi; Berridge, Kent C.

    2014-01-01

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

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

    SciTech Connect

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

    2012-04-15

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

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

    NASA Technical Reports Server (NTRS)

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

    1979-01-01

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

  16. Surgical removal of right-to-left cardiac shunt in the American alligator (Alligator mississippiensis) causes ventricular enlargement but does not alter apnoea or metabolism during diving.

    PubMed

    Eme, John; Gwalthney, June; Blank, Jason M; Owerkowicz, Tomasz; Barron, Gildardo; Hicks, James W

    2009-11-01

    Crocodilians have complete anatomical separation between the ventricles, similar to birds and mammals, but retain the dual aortic arch system found in all non-avian reptiles. This cardiac anatomy allows surgical modification that prevents right-to-left (R-L) cardiac shunt. A R-L shunt is a bypass of the pulmonary circulation and recirculation of oxygen-poor blood back to the systemic circulation and has often been observed during the frequent apnoeic periods of non-avian reptiles, particularly during diving in aquatic species. We eliminated R-L shunt in American alligators (Alligator mississippiensis) by surgically occluding the left aorta (LAo; arising from right ventricle) upstream and downstream of the foramen of Panizza (FoP), and we tested the hypotheses that this removal of R-L shunt would cause afterload-induced cardiac remodelling and adversely affect diving performance. Occlusion of the LAo both upstream and downstream of the FoP for approximately 21 months caused a doubling of RV pressure and significant ventricular enlargement (average approximately 65%) compared with age-matched, sham-operated animals. In a separate group of recovered, surgically altered alligators allowed to dive freely in a dive chamber at 23 degrees C, occlusion of the LAo did not alter oxygen consumption or voluntary apnoeic periods relative to sham animals. While surgical removal of R-L shunt causes considerable changes in cardiac morphology similar to aortic banding in mammals, its removal does not affect the respiratory pattern or metabolism of alligators. It appears probable that the low metabolic rate of reptiles, rather than pulmonary circulatory bypass, allows for normal aerobic dives.

  17. Surgical removal of right-to-left cardiac shunt in the American alligator (Alligator mississippiensis) causes ventricular enlargement but does not alter apnoea or metabolism during diving

    PubMed Central

    Eme, John; Gwalthney, June; Blank, Jason M.; Owerkowicz, Tomasz; Barron, Gildardo; Hicks, James W.

    2009-01-01

    SUMMARY Crocodilians have complete anatomical separation between the ventricles, similar to birds and mammals, but retain the dual aortic arch system found in all non-avian reptiles. This cardiac anatomy allows surgical modification that prevents right-to-left (R–L) cardiac shunt. A R–L shunt is a bypass of the pulmonary circulation and recirculation of oxygen-poor blood back to the systemic circulation and has often been observed during the frequent apnoeic periods of non-avian reptiles, particularly during diving in aquatic species. We eliminated R–L shunt in American alligators (Alligator mississippiensis) by surgically occluding the left aorta (LAo; arising from right ventricle) upstream and downstream of the foramen of Panizza (FoP), and we tested the hypotheses that this removal of R–L shunt would cause afterload-induced cardiac remodelling and adversely affect diving performance. Occlusion of the LAo both upstream and downstream of the FoP for ∼21 months caused a doubling of RV pressure and significant ventricular enlargement (average ∼65%) compared with age-matched, sham-operated animals. In a separate group of recovered, surgically altered alligators allowed to dive freely in a dive chamber at 23°C, occlusion of the LAo did not alter oxygen consumption or voluntary apnoeic periods relative to sham animals. While surgical removal of R–L shunt causes considerable changes in cardiac morphology similar to aortic banding in mammals, its removal does not affect the respiratory pattern or metabolism of alligators. It appears probable that the low metabolic rate of reptiles, rather than pulmonary circulatory bypass, allows for normal aerobic dives. PMID:19837897

  18. Combination of Methamphetamine and HIV-1 gp120 causes distinct long-term alterations of behavior, gene expression, and injury in the central nervous system

    PubMed Central

    Hoefer, Melanie M.; Sanchez, Ana B.; Maung, Ricky; de Rozieres, Cyrus M.; Catalan, Irene C.; Dowling, Cari C.; Thaney, Victoria E.; Piña-Crespo, Juan; Zhang, Dongxian; Roberts, Amanda J.; Kaul, Marcus

    2014-01-01

    Methamphetamine (METH) abuse is frequent in individuals infected with human immunodeficiency virus type-1 (HIV-1) and is suspected to aggravate HIV-associated neurocognitive disorders (HAND). METH is a psychostimulant that compromises several neurotransmitter systems and HIV proteins trigger neuronal injury but the combined effects of viral infection and METH abuse are incompletely understood. In this study we treated transgenic mice expressing the HIV envelope protein gp120 in the brain (HIV/gp120tg) at 3–4 months of age with an escalating-dose, multiple-binge METH regimen. The long-term effects were analyzed after 6–7 months of drug abstinence employing behavioral tests and analysis of neuropathology, electrophysiology and gene expression. Behavioral testing showed that both HIV/gp120tg and WT animals treated with METH displayed impaired learning and memory. Neuropathological analysis revealed that METH similar to HIV/gp120 caused a significant loss of neuronal dendrites and pre-synaptic terminals in hippocampus and cerebral cortex of WT animals. Electrophysiological studies in hippocampal slices showed that METH exposed HIV/gp120tg animals displayed reduced post-tetanic potentiation, whereas both gp120 expression and METH lead to reduced long-term potentiation. A quantitative reverse transcription-polymerase chain reaction array showed that gp120 expression, METH and their combination each caused a significant dysregulation of specific components of GABAergic and glutamatergic neurotransmission systems, providing a possible mechanism for synaptic dysfunction and behavioral impairment. In conclusion, both HIV-1/gp120 and METH caused lasting behavioral impairment in association with neuropathology and altered gene expression. However, combined METH exposure and HIV-1/gp120 expression resulted in the most pronounced, long lasting pre-and post-synaptic alterations coinciding with impaired learning and memory. PMID:25246228

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

    PubMed Central

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

    2013-01-01

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

  20. Conodont color alteration index (CAI) map and conodont-based age determinations for the Winchester 30' x 60' Quadrangle and adjacent area, Virginia, West Virginia, and Maryland

    USGS Publications Warehouse

    Harris, Anita G.; Stamm, Nancy R.; Weary, David J.; Repetski, John E.; Stamm, Robert G.; Parker, Ronald A.

    1994-01-01

    Most of the conodont data presented in this report (table 1) were acquired to support 1:100,000-scale geologic mapping of the Winchester 30' X 60' quadrangle by the U.S. Geological Survey (USGS). Conodonts were chosen to provide a biostratigraphic framework for the Upper Cambrian to Mississippian marine carbonate rocks that make up about 25 percent of the Paleozoic strata exposed in the quadrangle (~2,130 m of the approximately 9,450 m) of Paleozoic strata exposed in the quadrangle). Thickness of stratigraphic units are from McDowell (1991), our own measurements, and from many of the stratigraphic reports and geologic maps listed in the references cited. Conodont biostratigraphic and color alteration index (CAI) analyses help identify stratigraphic units and structural discontinuities, particularly in the Upper Cambrian to Middle Ordovician chiefly carbonate rocks of the Shenandoah Valley and North Mountain fault zone. Conodont biofacies analyses provide additional information about the provincial affinities of the conodonts and the depositional environment of the rocks that contain them. Lithostratigraphic, biostratigraphic, paleoenvironmental, and CAI data for all conodont samples are given in table 1.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  4. Altered gut microbiome in a mouse model of Gulf War Illness causes neuroinflammation and intestinal injury via leaky gut and TLR4 activation

    PubMed Central

    Dattaroy, Diptadip; Chandrashekaran, Varun; Ryan, Caitlin N.; Chan, Luisa S.; Testerman, Traci; Burch, James; Hofseth, Lorne J.; Horner, Ronnie; Nagarkatti, Mitzi; Nagarkatti, Prakash; Lasley, Stephen M.; Chatterjee, Saurabh

    2017-01-01

    Many of the symptoms of Gulf War Illness (GWI) that include neurological abnormalities, neuroinflammation, chronic fatigue and gastrointestinal disturbances have been traced to Gulf War chemical exposure. Though the association and subsequent evidences are strong, the mechanisms that connect exposure to intestinal and neurological abnormalities remain unclear. Using an established rodent model of Gulf War Illness, we show that chemical exposure caused significant dysbiosis in the gut that included increased abundance of phylum Firmicutes and Tenericutes, and decreased abundance of Bacteroidetes. Several gram negative bacterial genera were enriched in the GWI-model that included Allobaculum sp. Altered microbiome caused significant decrease in tight junction protein Occludin with a concomitant increase in Claudin-2, a signature of a leaky gut. Resultant leaching of gut caused portal endotoxemia that led to upregulation of toll like receptor 4 (TLR4) activation in the small intestine and the brain. TLR4 knock out mice and mice that had gut decontamination showed significant decrease in tyrosine nitration and inflammatory mediators IL1β and MCP-1 in both the small intestine and frontal cortex. These events signified that gut dysbiosis with simultaneous leaky gut and systemic endotoxemia-induced TLR4 activation contributes to GW chemical-induced neuroinflammation and gastrointestinal disturbances. PMID:28328972

  5. Altered neuronal mitochondrial coenzyme A synthesis in neurodegeneration with brain iron accumulation caused by abnormal processing, stability, and catalytic activity of mutant pantothenate kinase 2.

    PubMed

    Kotzbauer, Paul T; Truax, Adam C; Trojanowski, John Q; Lee, Virginia M-Y

    2005-01-19

    Mutations in the pantothenate kinase 2 (PANK2) gene have been identified in patients with neurodegeneration with brain iron accumulation (NBIA; formerly Hallervorden-Spatz disease). However, the mechanisms by which these mutations cause neurodegeneration are unclear, especially given the existence of multiple pantothenate kinase genes in humans and multiple PanK2 transcripts with potentially different subcellular localizations. We demonstrate that PanK2 protein is localized to mitochondria of neurons in human brain, distinguishing it from other pantothenate kinases that do not possess mitochondrial-targeting sequences. PanK2 protein translated from the most 5' start site is sequentially cleaved at two sites by the mitochondrial processing peptidase, generating a long-lived 48 kDa mature protein identical to that found in human brain extracts. The mature protein catalyzes the initial step in coenzyme A (CoA) synthesis but displays feedback inhibition in response to species of acyl CoA rather than CoA itself. Some, but not all disease-associated point mutations result in significantly reduced catalytic activity. The most common mutation, G521R, results in marked instability of the intermediate PanK2 isoform and reduced production of the mature isoform. These results suggest that NBIA is caused by altered neuronal mitochondrial lipid metabolism caused by mutations disrupting PanK2 protein levels and catalytic activity.

  6. Altered gut microbiome in a mouse model of Gulf War Illness causes neuroinflammation and intestinal injury via leaky gut and TLR4 activation.

    PubMed

    Alhasson, Firas; Das, Suvarthi; Seth, Ratanesh; Dattaroy, Diptadip; Chandrashekaran, Varun; Ryan, Caitlin N; Chan, Luisa S; Testerman, Traci; Burch, James; Hofseth, Lorne J; Horner, Ronnie; Nagarkatti, Mitzi; Nagarkatti, Prakash; Lasley, Stephen M; Chatterjee, Saurabh

    2017-01-01

    Many of the symptoms of Gulf War Illness (GWI) that include neurological abnormalities, neuroinflammation, chronic fatigue and gastrointestinal disturbances have been traced to Gulf War chemical exposure. Though the association and subsequent evidences are strong, the mechanisms that connect exposure to intestinal and neurological abnormalities remain unclear. Using an established rodent model of Gulf War Illness, we show that chemical exposure caused significant dysbiosis in the gut that included increased abundance of phylum Firmicutes and Tenericutes, and decreased abundance of Bacteroidetes. Several gram negative bacterial genera were enriched in the GWI-model that included Allobaculum sp. Altered microbiome caused significant decrease in tight junction protein Occludin with a concomitant increase in Claudin-2, a signature of a leaky gut. Resultant leaching of gut caused portal endotoxemia that led to upregulation of toll like receptor 4 (TLR4) activation in the small intestine and the brain. TLR4 knock out mice and mice that had gut decontamination showed significant decrease in tyrosine nitration and inflammatory mediators IL1β and MCP-1 in both the small intestine and frontal cortex. These events signified that gut dysbiosis with simultaneous leaky gut and systemic endotoxemia-induced TLR4 activation contributes to GW chemical-induced neuroinflammation and gastrointestinal disturbances.

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

    USGS Publications Warehouse

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

    2011-01-01

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

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

    SciTech Connect

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

    2013-12-06

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

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

    USGS Publications Warehouse

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

    2003-01-01

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

  10. Disruption of the microtubule network alters cellulose deposition and causes major changes in pectin distribution in the cell wall of the green alga, Penium margaritaceum

    PubMed Central

    Domozych, David S.

    2014-01-01

    Application of the dintroaniline compound, oryzalin, which inhibits microtubule formation, to the unicellular green alga Penium margaritaceum caused major perturbations to its cell morphology, such as swelling at the wall expansion zone in the central isthmus region. Cell wall structure was also notably altered, including a thinning of the inner cellulosic wall layer and a major disruption of the homogalacturonan (HG)-rich outer wall layer lattice. Polysaccharide microarray analysis indicated that the oryzalin treatment resulted in an increase in HG abundance in treated cells but a decrease in other cell wall components, specifically the pectin rhamnogalacturonan I (RG-I) and arabinogalactan proteins (AGPs). The ring of microtubules that characterizes the cortical area of the cell isthmus zone was significantly disrupted by oryzalin, as was the extensive peripheral network of actin microfilaments. It is proposed that the disruption of the microtubule network altered cellulose production, the main load-bearing component of the cell wall, which in turn affected the incorporation of HG in the two outer wall layers, suggesting coordinated mechanisms of wall polymer deposition. PMID:24285826

  11. Host knockout of E-prostanoid 2 receptors reduces tumor growth and causes major alterations of gene expression in prostaglandin E2-producing tumors

    PubMed Central

    Asting, Annika Gustafsson; Iresjö, Britt-Marie; Nilsberth, Camilla; Smedh, Ulrika; Lundholm, Kent

    2017-01-01

    Prostaglandin E2 (PGE2) is elevated in a variety of malignant tumors and has been shown to affect several hallmarks of cancer. Accordingly, the PGE2 receptor, E-prostanoid 2 (EP2), has been reported to be associated with patient survival and reduced tumor growth in EP2-knockout mice. Thus, the aim of the present study was to screen for major gene expression alterations in tumor tissue growing in EP2-knockout mice. EP2-knockout mice were bred and implanted with EP2 receptor-expressing and PGE2-producing epithelial-like tumors. Tumor tissue and plasma were collected and used for analyses with gene expression microarrays and multiplex enzyme-linked immunosorbent assays. Tumor growth, acute phase reactions/systemic inflammation and the expression of interleukin-6 were reduced in EP2-knockout tumor-bearing mice. Several hundreds of genes displayed major changes of expression in the tumor tissue when grown in EP2-knockout mice. Such gene alterations involved several different cellular functions, including stemness, migration and cell signaling. Besides gene expression, several long non-coding RNAs were downregulated in the tumors from the EP2-knockout mice. Overall, PGE2 signaling via host EP2 receptors affected a large number of different genes involved in tumor progression based on signaling between host stroma and tumor cells, which caused reduced tumor growth. PMID:28123585

  12. Loss of mitochondrial protease OMA1 alters processing of the GTPase OPA1 and causes obesity and defective thermogenesis in mice

    PubMed Central

    Quirós, Pedro M; Ramsay, Andrew J; Sala, David; Fernández-Vizarra, Erika; Rodríguez, Francisco; Peinado, Juan R; Fernández-García, Maria Soledad; Vega, José A; Enríquez, José A; Zorzano, Antonio; López-Otín, Carlos

    2012-01-01

    Mitochondria are dynamic subcellular organelles that convert nutrient intermediates into readily available energy equivalents. Optimal mitochondrial function is ensured by a highly evolved quality control system, coordinated by protein machinery that regulates a process of continual fusion and fission. In this work, we provide in vivo evidence that the ATP-independent metalloprotease OMA1 plays an essential role in the proteolytic inactivation of the dynamin-related GTPase OPA1 (optic atrophy 1). We also show that OMA1 deficiency causes a profound perturbation of the mitochondrial fusion–fission equilibrium that has important implications for metabolic homeostasis. Thus, ablation of OMA1 in mice results in marked transcriptional changes in genes of lipid and glucose metabolic pathways and substantial alterations in circulating blood parameters. Additionally, Oma1-mutant mice exhibit an increase in body weight due to increased adipose mass, hepatic steatosis, decreased energy expenditure and impaired thermogenenesis. These alterations are especially significant under metabolic stress conditions, indicating that an intact OMA1-OPA1 system is essential for developing the appropriate adaptive response to different metabolic stressors such as a high-fat diet or cold-shock. This study provides the first description of an unexpected role in energy metabolism for the metalloprotease OMA1 and reinforces the importance of mitochondrial quality control for normal metabolic function. PMID:22433842

  13. Genetic polymorphism of human cytochrome P-450 (S)-mephenytoin 4-hydroxylase. Studies with human autoantibodies suggest a functionally altered cytochrome P-450 isozyme as cause of the genetic deficiency

    SciTech Connect

    Meier, U.T.; Meyer, U.A.

    1987-12-15

    The metabolism of the anticonvulsant mephenytoin is subject to a genetic polymorphism. In 2-5% of Caucasians and 18-23% of Japanese subjects a specific cytochrome P-450 isozyme, P-450 meph, is functionally deficient or missing. The authors have accumulated evidence that autoimmune antibodies observed in sera of patients with tienilic acid induced hepatitis (anti-liver kidney microsome 2 or anti-LKM2 antibodies) specifically recognize the cytochrome P-450 involved in the mephrenytoin hydroxylation polymorphism. This is demonstrated by immunoinhibition and immunoprecipitation of microsomal (S)-mephenytoin 4-hydroxylation activity and by the recognition by anti-LKM2 antibodies of a single (/sup 125/I)-protein band on immunoblots of human liver microsomes after sodium dodecyl sulfate-polyacrylamide gel electrophoresis or isoelectric focusing. The cytochrome P-450 recognized by anti-LKM2 antibodies was immunopurified from microsomes derived from livers of extensive (EM) or poor metabolizers (PM) of (S)-mephenytoin. Comparison of the EM-type cytochrome P-450 to that isolated from PM livers revealed no difference in regard to immuno-cross-reactivity, molecular weight, isoelectric point, relative content in microsomes, two-dimensional tryptic peptide maps, one-dimensional peptide maps with three proteases, amino acid composition, and amino-terminal protein sequence. Finally, the same protein was precipitated from microsomes prepared from the liver biopsy of a subject phenotyped in vivo as a poor metabolizer of mephenytoin. These data strongly suggest that the mephenytoin hydroxylation deficiency is caused by a minor structural change leading to a functionally altered cytochrome P-450 isozyme.

  14. Confusion and altered behaviour? Cause

    PubMed Central

    Lobo, Ronstan; Pillay, Isweri; Kennedy, Barry; Watts, Michael

    2013-01-01

    We describe the case of a 65-year-old man who presented with confusion and change in behaviour, and describe the investigative steps that were taken before a diagnosis was made. This patient was eventually diagnosed with leptomeningeal carcinomatosis secondary to a previously undiagnosed oesophageal carcinoma. PMID:23341584

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

    USGS Publications Warehouse

    Mars, John L.; Zientek, M.L.; Hammarstrom, J.M.; Johnson, K.M.; Pierce, F.W.

    2014-01-01

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

  16. Novel Gal3 proteins showing altered Gal80p binding cause constitutive transcription of Gal4p-activated genes in Saccharomyces cerevisiae.

    PubMed Central

    Blank, T E; Woods, M P; Lebo, C M; Xin, P; Hopper, J E

    1997-01-01

    Gal4p-mediated activation of galactose gene expression in Saccharomyces cerevisiae normally requires both galactose and the activity of Gal3p. Recent evidence suggests that in cells exposed to galactose, Gal3p binds to and inhibits Ga180p, an inhibitor of the transcriptional activator Gal4p. Here, we report on the isolation and characterization of novel mutant forms of Gal3p that can induce Gal4p activity independently of galactose. Five mutant GAL3(c) alleles were isolated by using a selection demanding constitutive expression of a GAL1 promoter-driven HIS3 gene. This constitutive effect is not due to overproduction of Gal3p. The level of constitutive GAL gene expression in cells bearing different GAL3(c) alleles varies over more than a fourfold range and increases in response to galactose. Utilizing glutathione S-transferase-Gal3p fusions, we determined that the mutant Gal3p proteins show altered Gal80p-binding characteristics. The Gal3p mutant proteins differ in their requirements for galactose and ATP for their Gal80p-binding ability. The behavior of the novel Gal3p proteins provides strong support for a model wherein galactose causes an alteration in Gal3p that increases either its ability to bind to Gal80p or its access to Gal80p. With the Gal3p-Gal80p interaction being a critical step in the induction process, the Gal3p proteins constitute an important new reagent for studying the induction mechanism through both in vivo and in vitro methods. PMID:9111326

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

    PubMed

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

    2015-07-01

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

  18. Aging alterations in whole-brain networks during adulthood mapped with the minimum spanning tree indices: the interplay of density, connectivity cost and life-time trajectory.

    PubMed

    Otte, Willem M; van Diessen, Eric; Paul, Subhadip; Ramaswamy, Rajiv; Subramanyam Rallabandi, V P; Stam, Cornelis J; Roy, Prasun K

    2015-04-01

    The organizational network changes in the human brain across the lifespan have been mapped using functional and structural connectivity data. Brain network changes provide valuable insights into the processes underlying senescence. Nonetheless, the altered network density in the elderly severely compromises the usefulness of network analysis to study the aging brain. We successfully circumvented this problem by focusing on the critical structural network backbone, using a robust tree representation. Whole-brain networks' minimum spanning trees were determined in a dataset of diffusion-weighted images from 382 healthy subjects, ranging in age from 20.2 to 86.2 years. Tree-based metrics were compared with classical network metrics. In contrast to the tree-based metrics, classical metrics were highly influenced by age-related changes in network density. Tree-based metrics showed linear and non-linear correlation across adulthood and are in close accordance with results from previous histopathological characterizations of the changes in white matter integrity in the aging brain.

  19. Mapping the critical gestational age at birth that alters brain development in preterm-born infants using multi-modal MRI.

    PubMed

    Wu, Dan; Chang, Linda; Akazawa, Kentaro; Oishi, Kumiko; Skranes, Jon; Ernst, Thomas; Oishi, Kenichi

    2017-04-01

    Preterm birth adversely affects postnatal brain development. In order to investigate the critical gestational age at birth (GAB) that alters the developmental trajectory of gray and white matter structures in the brain, we investigated diffusion tensor and quantitative T2 mapping data in 43 term-born and 43 preterm-born infants. A novel multivariate linear model-the change point model, was applied to detect change points in fractional anisotropy, mean diffusivity, and T2 relaxation time. Change points captured the "critical" GAB value associated with a change in the linear relation between GAB and MRI measures. The analysis was performed in 126 regions across the whole brain using an atlas-based image quantification approach to investigate the spatial pattern of the critical GAB. Our results demonstrate that the critical GABs are region- and modality-specific, generally following a central-to-peripheral and bottom-to-top order of structural development. This study may offer unique insights into the postnatal neurological development associated with differential degrees of preterm birth.

  20. Genomewide mapping reveals a combination of different genetic effects causing the genetic basis of heterosis in two elite rice hybrids.

    PubMed

    Li, Lanzhi; He, Xiaohong; Zhang, Hongyan; Wang, Zhiming; Sun, Congwei; Mou, Tongmin; Li, Xinqi; Zhang, Yuanming; Hu, Zhongli

    2015-06-01

    North Carolina design III (NCIII) is one of the most powerful and widely used mating designs for understanding the genetic basis of heterosis. However, the quantitative trait mapping (QTL) conducted in previous studies with this design was mainly based on analysis of variance (ANOVA), composite interval or multiple interval mapping methods. These methodologies could not investigate all kinds of genetic effects, especially epistatic effects, simultaneously on the whole genome. In this study, with a statistical method for mapping epistatic QTL associated with heterosis using the recombinant inbred line (RIL)-based NCIII design, we conducted QTL mapping for nine agronomic traits of two elite hybrids to characterize the mode of gene action contributing to heterosis on a whole genomewide scale. In total, 23 main-effect QTL (M-QTL) and 23 digenic interactions in IJ (indica x japonica) hybrids, 11 M-QTL and 82 digenic interactions in II (indica x indica) hybrid QTLs were identified in the present study. The variation explained by individual M-QTL or interactions ranged from 2.3 to 11.0%. The number of digenic interactions and the total variation explained by interactions of each trait were larger than those of M-QTL. The augmented genetic effect ratio of most M-QTL and digenic interactions in (L1 - L2) data of two backcross populations (L1 and L2) showed complete dominance or overdominance, and in (L1 + L2) data showed an additive effect. Our results indicated that the dominance, overdominance and epistatic effect were important in conditioning the genetic basis of heterosis of the two elite hybrids. The relative contributions of the genetic components varied with traits and the genetic basis of the two hybrids was different.

  1. Postnatal ethanol exposure alters levels of 2-arachidonylglycerol-metabolizing enzymes and pharmacological inhibition of monoacylglycerol does not cause neurodegeneration in neonatal mice

    PubMed Central

    Subbanna, Shivakumar; Psychoyos, Delphine; Xie, Shan; Basavarajappa, Balapal S.

    2015-01-01

    The consumption of ethanol by pregnant women may cause neurological abnormalities, affecting learning and memory processes in children, and are collectively described as fetal alcohol spectrum disorders (FASDs). However, the molecular mechanisms underlying these changes are still poorly understood. In our previous studies, we found that ethanol treatment of postnatal day 7 (P7) mice significantly enhances anandamide (AEA) levels but not 2-arachidonylglycerol (2-AG) levels and induces widespread neurodegeneration, but the reason for the lack of significant effects of ethanol on the 2-AG level is unknown. In this study, we examined developmental changes in diacylglycerol lipase-α, β (DAGL-α and β) and monoacylglycerol lipase (MAGL). We found that the levels of these proteins were significantly higher in adult brains compared to those detected early in brain development. Next, we examined the influence of P7 ethanol treatment on these enzymes, finding that it differentially altered the DAGL-α protein and mRNA levels but consistently enhanced those of the DAGL-β. Interestingly, the ethanol treatment enhanced MAGL protein and mRNA levels. Inhibition of MAGL with KML29 failed to induce neurodegeneration in P7 mice. Collectively, these findings suggest that ethanol significantly activates DAGL-β and MAGL in the neonatal brain, resulting in no net change in 2-AG levels. PMID:25857698

  2. Postnatal ethanol exposure alters levels of 2-arachidonylglycerol-metabolizing enzymes and pharmacological inhibition of monoacylglycerol lipase does not cause neurodegeneration in neonatal mice.

    PubMed

    Subbanna, Shivakumar; Psychoyos, Delphine; Xie, Shan; Basavarajappa, Balapal S

    2015-07-01

    The consumption of ethanol by pregnant women may cause neurological abnormalities, affecting learning and memory processes in children, and are collectively described as fetal alcohol spectrum disorders. However, the molecular mechanisms underlying these changes are still poorly understood. In our previous studies, we found that ethanol treatment of postnatal day 7 (P7) mice significantly enhances the anandamide levels but not the 2-arachidonylglycerol (2-AG) levels and induces widespread neurodegeneration, but the reason for the lack of significant effects of ethanol on the 2-AG level is unknown. In this study, we examined developmental changes in diacylglycerol lipase-α, β (DAGL-α and β) and monoacylglycerol lipase (MAGL). We found that the levels of these proteins were significantly higher in adult brains compared to those detected early in brain development. Next, we examined the influence of P7 ethanol treatment on these enzymes, finding that it differentially altered the DAGL-α protein and mRNA levels but consistently enhanced those of the DAGL-β. Interestingly, the ethanol treatment enhanced MAGL protein and mRNA levels. Inhibition of MAGL with KML29 failed to induce neurodegeneration in P7 mice. Collectively, these findings suggest that ethanol significantly activates DAGL-β and MAGL in the neonatal brain, resulting in no net change in 2-AG levels.

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

    PubMed

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

    2016-08-01

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

  4. Ciprofloxacin provokes SOS-dependent changes in respiration and membrane potential and causes alterations in the redox status of Escherichia coli.

    PubMed

    Smirnova, Galina V; Tyulenev, Aleksey V; Muzyka, Nadezda G; Peters, Mikhail A; Oktyabrsky, Oleg N

    2017-01-01

    An in-depth understanding of the physiological response of bacteria to antibiotic-induced stress is needed for development of new approaches to combatting microbial infections. Fluoroquinolone ciprofloxacin causes phase alterations in Escherichia coli respiration and membrane potential that strongly depend on its concentration. Concentrations lower than the optimal bactericidal concentration (OBC) do not inhibit respiration during the first phase. A dose higher than the OBC provokes immediate SOS-independent inhibition of respiration and growth that can contribute to a decreased SOS response and lowered susceptibility to high concentrations of ciprofloxacin. Cells retain their metabolic activity, membrane potential and accelerated K(+) uptake and produce low levels of superoxide and H2O2 during the first phase. The time before initiation of the second phase is inversely correlated with the ciprofloxacin concentration. The second phase is SOS-dependent and characterized by respiratory inhibition, membrane depolarization, K(+) and glutathione leakage and cessation of glucose consumption and may be considered as cell death. atpA, gshA and kefBkefC knockouts, which perturb fluxes of protons and K(+), can modify the degree and duration of respiratory inhibition and potassium retention. Loss of K(+) efflux channels KefB and KefC enhances the susceptibility of E. coli to ciprofloxacin.

  5. Mitochondrial protein alterations in a familial peripheral neuropathy caused by the V144D amino acid mutation in the sphingolipid protein, SPTLC1.

    PubMed

    Stimpson, Scott E; Coorssen, Jens R; Myers, Simon J

    2015-01-01

    Axonal degeneration is the final common path in many neurological disorders. Subsets of neuropathies involving the sensory neuron are known as hereditary sensory neuropathies (HSNs). Hereditary sensory neuropathy type I (HSN-I) is the most common subtype of HSN with autosomal dominant inheritance. It is characterized by the progressive degeneration of the dorsal root ganglion (DRG) with clinical symptom onset between the second or third decade of life. Heterozygous mutations in the serine palmitoyltransferase (SPT) long chain subunit 1 (SPTLC1) gene were identified as the pathogenic cause of HSN-I. Ultrastructural analysis of mitochondria from HSN-I patient cells has displayed unique morphological abnormalities that are clustered to the perinucleus where they are wrapped by the endoplasmic reticulum (ER). This investigation defines a small subset of proteins with major alterations in abundance in mitochondria harvested from HSN-I mutant SPTLC1 cells. Using mitochondrial protein isolates from control and patient lymphoblasts, and a combination of 2D gel electrophoresis, immunoblotting and mass spectrometry, we have shown the increased abundance of ubiquinol-cytochrome c reductase core protein 1, an electron transport chain protein, as well as the immunoglobulin, Ig kappa chain C. The regulation of these proteins may provide a new route to understanding the cellular and molecular mechanisms underlying HSN-I.

  6. Sodium nitrite-induced oxidative stress causes membrane damage, protein oxidation, lipid peroxidation and alters major metabolic pathways in human erythrocytes.

    PubMed

    Ansari, Fariheen Aisha; Ali, Shaikh Nisar; Mahmood, Riaz

    2015-10-01

    Nitrite salts are present as contaminants in drinking water and in the food and feed chain. In this work, the effect of sodium nitrite (NaNO2) on human erythrocytes was studied under in vitro conditions. Incubation of erythrocytes with 0.1-10.0 mM NaNO2 at 37 °C for 30 min resulted in dose dependent decrease in the levels of reduced glutathione, total sulfhydryl and amino groups. It was accompanied by increase in hemoglobin oxidation and aggregation, lipid peroxidation, protein oxidation and hydrogen peroxide levels suggesting the induction of oxidative stress. Activities of all major erythrocyte antioxidant defense enzymes were decreased in NaNO2-treated erythrocytes. The activities of enzymes of glycolytic and pentose phosphate pathways were also compromised. However, there was a significant increase in acid phosphatase and also AMP deaminase, a marker of erythrocyte oxidative stress. Thus, the major metabolic pathways of cell were altered. Erythrocyte membrane damage was suggested by lowered activities of membrane bound enzymes and confirmed by electron microscopic images. These results show that NaNO2-induced oxidative stress causes hemoglobin denaturation and aggregation, weakens the cellular antioxidant defense mechanism, damages the cell membrane and also perturbs normal energy metabolism in erythrocytes. This nitrite-induced damage can reduce erythrocyte life span in the blood.

  7. Altered Pre-mRNA Splicing Caused by a Novel Intronic Mutation c.1443+5G>A in the Dihydropyrimidinase (DPYS) Gene.

    PubMed

    Nakajima, Yoko; Meijer, Judith; Zhang, Chunhua; Wang, Xu; Kondo, Tomomi; Ito, Tetsuya; Dobritzsch, Doreen; Van Kuilenburg, André B P

    2016-01-12

    Dihydropyrimidinase (DHP) deficiency is an autosomal recessive disease caused by mutations in the DPYS gene. Patients present with highly elevated levels of dihydrouracil and dihydrothymine in their urine, blood and cerebrospinal fluid. The analysis of the effect of mutations in DPYS on pre-mRNA splicing is hampered by the fact that DHP is primarily expressed in liver and kidney cells. The minigene approach can detect mRNA splicing aberrations using cells that do not express the endogenous mRNA. We have used a minigene-based approach to analyze the effects of a presumptive pre-mRNA splicing mutation in two newly identified Chinese pediatric patients with DHP deficiency. Mutation analysis of DPYS showed that both patients were compound heterozygous for a novel intronic mutation c.1443+5G>A in intron 8 and a previously described missense mutation c.1001A>G (p.Q334R) in exon 6. Wild-type and the mutated minigene constructs, containing exons 7, 8 and 9 of DPYS, yielded different splicing products after expression in HEK293 cells. The c.1443+5G>A mutation resulted in altered pre-mRNA splicing of the DPYS minigene construct with full skipping of exon 8. Analysis of the DHP crystal structure showed that the deletion of exon 8 severely affects folding, stability and homooligomerization of the enzyme as well as disruption of the catalytic site. Thus, the analysis suggests that the c.1443+5G>A mutation results in aberrant splicing of the pre-mRNA encoding DHP, underlying the DHP deficiency in two unrelated Chinese patients.

  8. Single episode of mild murine malaria induces neuroinflammation, alters microglial profile, impairs adult neurogenesis, and causes deficits in social and anxiety-like behavior.

    PubMed

    Guha, Suman K; Tillu, Rucha; Sood, Ankit; Patgaonkar, Mandar; Nanavaty, Ishira N; Sengupta, Arjun; Sharma, Shobhona; Vaidya, Vidita A; Pathak, Sulabha

    2014-11-01

    Cerebral malaria is associated with cerebrovascular damage and neurological sequelae. However, the neurological consequences of uncomplicated malaria, the most prevalent form of the disease, remain uninvestigated. Here, using a mild malaria model, we show that a single Plasmodium chabaudi adami infection in adult mice induces neuroinflammation, neurogenic, and behavioral changes in the absence of a blood-brain barrier breach. Using cytokine arrays we show that the infection induces differential serum and brain cytokine profiles, both at peak parasitemia and 15days post-parasite clearance. At the peak of infection, along with the serum, the brain also exhibited a definitive pro-inflammatory cytokine profile, and gene expression analysis revealed that pro-inflammatory cytokines were also produced locally in the hippocampus, an adult neurogenic niche. Hippocampal microglia numbers were enhanced, and we noted a shift to an activated profile at this time point, accompanied by a striking redistribution of the microglia to the subgranular zone adjacent to hippocampal neuronal progenitors. In the hippocampus, a distinct decline in progenitor turnover and survival was observed at peak parasitemia, accompanied by a shift from neuronal to glial fate specification. Studies in transgenic Nestin-GFP reporter mice demonstrated a decline in the Nestin-GFP(+)/GFAP(+) quiescent neural stem cell pool at peak parasitemia. Although these cellular changes reverted to normal 15days post-parasite clearance, specific brain cytokines continued to exhibit dysregulation. Behavioral analysis revealed selective deficits in social and anxiety-like behaviors, with no change observed in locomotor, cognitive, and depression-like behaviors, with a return to baseline at recovery. Collectively, these findings indicate that even a single episode of mild malaria results in alterations of the brain cytokine profile, causes specific behavioral dysfunction, is accompanied by hippocampal microglial

  9. A mutation in GDP-mannose pyrophosphorylase causes conditional hypersensitivity to ammonium, resulting in Arabidopsis root growth inhibition, altered ammonium metabolism, and hormone homeostasis.

    PubMed

    Barth, Carina; Gouzd, Zachary A; Steele, Hilary P; Imperio, Ryan M

    2010-01-01

    Ascorbic acid (AA) is an antioxidant fulfilling a multitude of cellular functions. Given its pivotal role in maintaining the rate of cell growth and division in the quiescent centre of the root, it was hypothesized that the AA-deficient Arabidopsis thaliana mutants vtc1-1, vtc2-1, vtc3-1, and vtc4-1 have altered root growth. To test this hypothesis, root development was studied in the wild type and vtc mutants grown on Murashige and Skoog medium. It was discovered, however, that only the vtc1-1 mutant has strongly retarded root growth, while the other vtc mutants exhibit a wild-type root phenotype. It is demonstrated that the short-root phenotype in vtc1-1 is independent of AA deficiency and oxidative stress. Instead, vtc1-1 is conditionally hypersensitive to ammonium (NH(4)(+)). To provide new insights into the mechanism of NH(4)(+) sensitivity in vtc1-1, root development, NH(4)(+) content, glutamine synthetase (GS) activity, glutamate dehydrogenase activity, and glutamine content were assessed in wild-type and vtc1-1 mutant plants grown in the presence and absence of high NH(4)(+) and the GS inhibitor MSO. Since VTC1 encodes a GDP-mannose pyrophosphorylase, an enzyme generating GDP-mannose for AA biosynthesis and protein N-glycosylation, it was also tested whether protein N-glycosylation is affected in vtc1-1. Furthermore, since root development requires the action of a variety of hormones, it was investigated whether hormone homeostasis is linked to NH(4)(+) sensitivity in vtc1-1. Our data suggest that NH(4)(+) hypersensitivity in vtc1-1 is caused by disturbed N-glycosylation and that it is associated with auxin and ethylene homeostasis and/or nitric oxide signalling.

  10. A mutation in GDP-mannose pyrophosphorylase causes conditional hypersensitivity to ammonium, resulting in Arabidopsis root growth inhibition, altered ammonium metabolism, and hormone homeostasis

    PubMed Central

    Barth, Carina; Gouzd, Zachary A.; Steele, Hilary P.; Imperio, Ryan M.

    2010-01-01

    Ascorbic acid (AA) is an antioxidant fulfilling a multitude of cellular functions. Given its pivotal role in maintaining the rate of cell growth and division in the quiescent centre of the root, it was hypothesized that the AA-deficient Arabidopsis thaliana mutants vtc1-1, vtc2-1, vtc3-1, and vtc4-1 have altered root growth. To test this hypothesis, root development was studied in the wild type and vtc mutants grown on Murashige and Skoog medium. It was discovered, however, that only the vtc1-1 mutant has strongly retarded root growth, while the other vtc mutants exhibit a wild-type root phenotype. It is demonstrated that the short-root phenotype in vtc1-1 is independent of AA deficiency and oxidative stress. Instead, vtc1-1 is conditionally hypersensitive to ammonium (NH4+). To provide new insights into the mechanism of NH4+ sensitivity in vtc1-1, root development, NH4+ content, glutamine synthetase (GS) activity, glutamate dehydrogenase activity, and glutamine content were assessed in wild-type and vtc1-1 mutant plants grown in the presence and absence of high NH4+ and the GS inhibitor MSO. Since VTC1 encodes a GDP-mannose pyrophosphorylase, an enzyme generating GDP-mannose for AA biosynthesis and protein N-glycosylation, it was also tested whether protein N-glycosylation is affected in vtc1-1. Furthermore, since root development requires the action of a variety of hormones, it was investigated whether hormone homeostasis is linked to NH4+ sensitivity in vtc1-1. Our data suggest that NH4+ hypersensitivity in vtc1-1 is caused by disturbed N-glycosylation and that it is associated with auxin and ethylene homeostasis and/or nitric oxide signalling. PMID:20007685

  11. Early postnatal nicotine exposure causes hippocampus-dependent memory impairments in adolescent mice: Association with altered nicotinic cholinergic modulation of LTP, but not impaired LTP.

    PubMed

    Nakauchi, Sakura; Malvaez, Melissa; Su, Hailing; Kleeman, Elise; Dang, Richard; Wood, Marcelo A; Sumikawa, Katumi

    2015-02-01

    Fetal nicotine exposure from smoking during pregnancy causes long-lasting cognitive impairments in offspring, yet little is known about the mechanisms that underlie this effect. Here we demonstrate that early postnatal exposure of mouse pups to nicotine via maternal milk impairs long-term, but not short-term, hippocampus-dependent memory during adolescence. At the Schaffer collateral (SC) pathway, the most widely studied synapses for a cellular correlate of hippocampus-dependent memory, the induction of N-methyl-D-aspartate receptor-dependent transient long-term potentiation (LTP) and protein synthesis-dependent long-lasting LTP are not diminished by nicotine exposure, but rather unexpectedly the threshold for LTP induction becomes lower after nicotine treatment. Using voltage sensitive dye to visualize hippocampal activity, we found that early postnatal nicotine exposure also results in enhanced CA1 depolarization and hyperpolarization after SC stimulation. Furthermore, we show that postnatal nicotine exposure induces pervasive changes to the nicotinic modulation of CA1 activity: activation of nicotinic receptors no longer increases CA1 network depolarization, acute nicotine inhibits rather than facilitates the induction of LTP at the SC pathway by recruiting an additional nicotinic receptor subtype, and acute nicotine no longer blocks LTP induction at the temporoammonic pathway. These findings reflect the pervasive impact of nicotine exposure during hippocampal development, and demonstrate an association of hippocampal memory impairments with altered nicotinic cholinergic modulation of LTP, but not impaired LTP. The implication of our results is that nicotinic cholinergic-dependent plasticity is required for long-term memory formation and that postnatal nicotine exposure disrupts this form of plasticity.

  12. Modulation of the phenylacetic acid metabolic complex by quinic acid alters the disease-causing activity of Rhizoctonia solani on tomato.

    PubMed

    Bartz, Faith E; Glassbrook, Norman J; Danehower, David A; Cubeta, Marc A

    2013-05-01

    The metabolic control of plant growth regulator production by the plant pathogenic fungus Rhizoctonia solani Kühn (teleomorph=Thanatephorus cucumeris (A.B. Frank) Donk) and consequences associated with the parasitic and saprobic activity of the fungus were investigated. Fourteen genetically distinct isolates of the fungus belonging to anastomosis groups (AG) AG-3, AG-4, and AG-1-IA were grown on Vogel's minimal medium N with and without the addition of a 25 mM quinic acid (QA) source of carbon. The effect of QA on fungal biomass was determined by measuring the dry wt of mycelia produced under each growth condition. QA stimulated growth of 13 of 14 isolates of R. solani examined. The production of phenylacetic acid (PAA) and the chemically related derivatives 2-hydroxy-PAA, 3-hydroxy-PAA, 4-hydroxy-PAA, and 3-methoxy-PAA on the two different media was compared by gas chromatography coupled with mass spectrometry (GC-MS). The presence of QA in the growth medium of R. solani altered the PAA production profile, limiting the conversion of PAA to derivative forms. The effect of QA on the ability of R. solani to cause disease was examined by inoculating tomato (Solanum lycopersicum L.) plants with 11 isolates of R. solani AG-3 grown on media with and without the addition of 25 mM QA. Mean percent survival of tomato plants inoculated with R. solani was significantly higher when the fungal inoculum was generated on growth medium containing QA. The results of this study support the hypotheses that utilization of QA by R. solani leads to reduced production of the plant growth regulators belonging to the PAA metabolic complex which can suppress plant disease development.

  13. Dwarfism and Altered Craniofacial Development in Rabbits Is Caused by a 12.1 kb Deletion at the HMGA2 Locus.

    PubMed

    Carneiro, Miguel; Hu, Dou; Archer, John; Feng, Chungang; Afonso, Sandra; Chen, Congying; Blanco-Aguiar, José A; Garreau, Hervé; Boucher, Samuel; Ferreira, Paula G; Ferrand, Nuno; Rubin, Carl-Johan; Andersson, Leif

    2017-02-01

    The dwarf phenotype characterizes the smallest of rabbit breeds and is governed largely by the effects of a single dwarfing allele with an incompletely dominant effect on growth. Dwarf rabbits typically weigh under 1 kg and have altered craniofacial morphology. The dwarf allele is recessive lethal and dwarf homozygotes die within a few days of birth. The dwarf phenotype is expressed in heterozygous individuals and rabbits from dwarf breeds homozygous for the wild-type allele are normal, although smaller when compared to other breeds. Here, we show that the dwarf allele constitutes a ∼12.1 kb deletion overlapping the promoter region and first three exons of the HMGA2 gene leading to inactivation of this gene. HMGA2 has been frequently associated with variation in body size across species. Homozygotes for null alleles are viable in mice but not in rabbits and probably not in humans. RNA-sequencing analysis of rabbit embryos showed that very few genes (4-29 genes) were differentially expressed among the three HMGA2/dwarf genotypes, suggesting that dwarfism and inviability in rabbits are caused by modest changes in gene expression. Our results show that HMGA2 is critical for normal expression of IGF2BP2, which encodes an RNA-binding protein. Finally, we report a catalog of regions of elevated genetic differentiation between dwarf and normal-size rabbits, including LCORL-NCAPG, STC2, HOXD cluster, and IGF2BP2 Levels and patterns of genetic diversity at the LCORL-NCAPG locus further suggest that small size in dwarf breeds was enhanced by crosses with wild rabbits. Overall, our results imply that small size in dwarf rabbits results from a large effect, loss-of-function (LOF) mutation in HMGA2 combined with polygenic selection.

  14. Altered Pre-mRNA Splicing Caused by a Novel Intronic Mutation c.1443+5G>A in the Dihydropyrimidinase (DPYS) Gene

    PubMed Central

    Nakajima, Yoko; Meijer, Judith; Zhang, Chunhua; Wang, Xu; Kondo, Tomomi; Ito, Tetsuya; Dobritzsch, Doreen; Van Kuilenburg, André B. P.

    2016-01-01

    Dihydropyrimidinase (DHP) deficiency is an autosomal recessive disease caused by mutations in the DPYS gene. Patients present with highly elevated levels of dihydrouracil and dihydrothymine in their urine, blood and cerebrospinal fluid. The analysis of the effect of mutations in DPYS on pre-mRNA splicing is hampered by the fact that DHP is primarily expressed in liver and kidney cells. The minigene approach can detect mRNA splicing aberrations using cells that do not express the endogenous mRNA. We have used a minigene-based approach to analyze the effects of a presumptive pre-mRNA splicing mutation in two newly identified Chinese pediatric patients with DHP deficiency. Mutation analysis of DPYS showed that both patients were compound heterozygous for a novel intronic mutation c.1443+5G>A in intron 8 and a previously described missense mutation c.1001A>G (p.Q334R) in exon 6. Wild-type and the mutated minigene constructs, containing exons 7, 8 and 9 of DPYS, yielded different splicing products after expression in HEK293 cells. The c.1443+5G>A mutation resulted in altered pre-mRNA splicing of the DPYS minigene construct with full skipping of exon 8. Analysis of the DHP crystal structure showed that the deletion of exon 8 severely affects folding, stability and homooligomerization of the enzyme as well as disruption of the catalytic site. Thus, the analysis suggests that the c.1443+5G>A mutation results in aberrant splicing of the pre-mRNA encoding DHP, underlying the DHP deficiency in two unrelated Chinese patients. PMID:26771602

  15. Alterations caused to soil organic matter by post-fire rehabilitation actions in a pine forest from doñana national park (southwest Spain)

    NASA Astrophysics Data System (ADS)

    González-Pérez, José A.; Jiménez-Morillo, Nicasio T.; Jordán, Antonio; Zavala, Lorena M.; Granged, Arturo J. P.; González-Vila, Francisco J.

    2016-04-01

    Post-fire rehabilitation actions and recovery attempts of burned soils include a range of management practices (tillage, tree logging, reforestation …), in some cases producing an additional damage to that directly caused by fire. Among negative impacts derived from unappropriated rehab practices are the increase soil erosion, loss of soil fertility and alterations in the hydrological cycle. Analytical pyrolysis (Py-GC/MS) is an appropriate technique to study organic matter characteristics within complex matrices. Here this technique is used to study the alterations caused by burning and post-fire rehab plans to soil organic matter (SOM). Fire and post-fire rehab actions impact on SOM is studied in a sandy soil under pine (Pinus pinea) forest that was affected by a severe fire in August 2012 in Doñana National Park (SW Spain). Bulk samples as well as its sieved soil fractions (coarse, 1-2 mm, and fine, <0.05 mm) collected from an undisturbed burned area (B) and in an adjacent burned area after rehab practices (BR) (logging and extraction of burned trees) were studied. An additional adjacent unburned (UB) area was used as a control. Conspicuous differences among bulk samples from the B, BR and UB control areas were found in the relative proportions of the main molecular families obtained by analytical pyrolysis, including alkane/alkene pairs, unspecific aromatic compounds (UAC), peptides, methoxyphenols, fatty acids, carbohydrates, N-compounds and polycyclic aromatic hydrocarbons (PAH). The B site SOM showed lower proportion of lignin methoxyphenols and higher of UAC and PAH than the SOM from the UB site. This indicates that fire produced methoxyphenol de-functionalization, increasing the proportion of recalcitrant compounds. With respect to soil size fractions, in all cases, the coarse fraction showed a high content of carbohydrate-derived compounds and methoxyphenols followed by fatty acids, in line with inputs of new litter from stressed post-fire vegetation

  16. Map showing areas of visible land disturbances caused by two military training operations in the Mojave Desert, California

    USGS Publications Warehouse

    Prose, D.V.

    1986-01-01

    Land disturbances caused by these training exercises are still evident today throughout the designated training areas (Lathrop, 1983; Prose, 1985; Prose and Metzger, 1985). The World War II base-camp locations are easily identified because the networks of dirt roads are still used by campers, hunters, artifact seekers, and other visitors. Vehicle trails and single tracks remain on many relatively stable surfaces and are most conspicuous on surfaces composed of a veneer of stones (desert pavement).

  17. A gene defect causing a novel progressive epilepsy with mental retardation, EPMR, maps to chromosome 8p

    SciTech Connect

    Ranta, S.; Tahvanainen, E.; Karila, E.

    1994-09-01

    EPMR (progressive epilepsy with mental retardation) is a newly discovered autosomal recessively inherited disorder which occurs with high frequency in an isolated rural population in Finland. So far 25 patients have been identified, 21 of whom are alive. Twenty-three patients share a common ancestor from the 18th century. The main features of EPMR are: normal early development, tonic-clonic seizures with onset between ages 5 and 10, and mental retardation which begins approximately 2 years after the onset of epilepsy and soon leads to deepening mental retardation. Adult patients do not manage their daily life without help. The EEG is normal at the onset of epilepsy but later progressive slowing of the background activity occurs. The etiology and pathogenesis of EPMR remain known. As this is a novel disease entity without any definitive diagnostic marker we wished to begin its elucidation by first defining its gene locus. A random search for linkage in four multiplex families (only 20 individuals tested) resulted in the finding of linkage to marker D8S264 with a lod score of 4.45 at zero recombination. The EPMR gene resides in a 7 centimorgan interval between marker loci AFM185xb2 and D8S262 with a maximum multipoint lod score of 7.03 at 1.8 centimorgans proximal to D8S264. Physically this region is very distal on 8p. Of the sixteen EPMR chromosomes haplotyped 15 were identical or almost identical. One chromosome, however, had a distinctly different haplotype raising the possibility of there being two different mutations or one very old mutation. These findings are a starting point toward isolating and characterizing the gene and its protein product. Physical mapping has been initiated by isolating nine YACs from the region.

  18. A gene causing Hermansky-Pudlak syndrome in a Puerto Rican population maps to chromosome 10q2

    SciTech Connect

    Wildenberg, S.C.; Oetting, W.S.; King, R.A.

    1995-10-01

    Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that affects pigment production and platelet function and causes the deposition of a ceroid like material in various tissues. Variability in the phenotype and the presence of several potential mouse models suggest that HPS may be a heterogeneous disorder. In order to identify a gene responsible for HPS, we collected blood samples from a relatively homogeneous population in Puerto Rico where the HPS carrier frequency is estimated to be 1 in 21. Analysis of pooled DNA samples allowed us to rapidly screen the genome for candidate loci, and significant evidence for linkage was detected for a marker on chromosome 10q. This region of the human genome is conserved syntenically with the region on mouse chromosome 19 where two possible mouse models for HPS, pale ear and ruby eye, are located. This linkage result was verified with additional markers, and a maximum LOD score of 5.07 at {theta} = .001 was calculated for marker D10S198. Haplotype analysis places the HPS gene in a region of {approximately} 14 cM that contains the markers D10S198 and D10S1239. 41 refs., 3 figs., 4 tabs.

  19. Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy.

    PubMed

    Arndt, Anne-Karin; Schafer, Sebastian; Drenckhahn, Jorg-Detlef; Sabeh, M Khaled; Plovie, Eva R; Caliebe, Almuth; Klopocki, Eva; Musso, Gabriel; Werdich, Andreas A; Kalwa, Hermann; Heinig, Matthias; Padera, Robert F; Wassilew, Katharina; Bluhm, Julia; Harnack, Christine; Martitz, Janine; Barton, Paul J; Greutmann, Matthias; Berger, Felix; Hubner, Norbert; Siebert, Reiner; Kramer, Hans-Heiner; Cook, Stuart A; MacRae, Calum A; Klaassen, Sabine

    2013-07-11

    Deletion 1p36 syndrome is recognized as the most common terminal deletion syndrome. Here, we describe the loss of a gene within the deletion that is responsible for the cardiomyopathy associated with monosomy 1p36, and we confirm its role in nonsyndromic left ventricular noncompaction cardiomyopathy (LVNC) and dilated cardiomyopathy (DCM). With our own data and publically available data from array comparative genomic hybridization (aCGH), we identified a minimal deletion for the cardiomyopathy associated with 1p36del syndrome that included only the terminal 14 exons of the transcription factor PRDM16 (PR domain containing 16), a gene that had previously been shown to direct brown fat determination and differentiation. Resequencing of PRDM16 in a cohort of 75 nonsyndromic individuals with LVNC detected three mutations, including one truncation mutant, one frameshift null mutation, and a single missense mutant. In addition, in a series of cardiac biopsies from 131 individuals with DCM, we found 5 individuals with 4 previously unreported nonsynonymous variants in the coding region of PRDM16. None of the PRDM16 mutations identified were observed in more than 6,400 controls. PRDM16 has not previously been associated with cardiac disease but is localized in the nuclei of cardiomyocytes throughout murine and human development and in the adult heart. Modeling of PRDM16 haploinsufficiency and a human truncation mutant in zebrafish resulted in both contractile dysfunction and partial uncoupling of cardiomyocytes and also revealed evidence of impaired cardiomyocyte proliferative capacity. In conclusion, mutation of PRDM16 causes the cardiomyopathy in 1p36 deletion syndrome as well as a proportion of nonsyndromic LVNC and DCM.

  20. Maps Showing Locations of Damaging Landslides Caused by El Nino Rainstorms, Winter Season 1997-98, San Francisco Bay Region, California

    USGS Publications Warehouse

    Godt, Jonathan W.

    1999-01-01

    Heavy rainfall associated with a strong El Nino caused over $150 million in landslide damage in the 10-county San Francisco Bay region during the winter and spring of 1998. Reports of landsliding began in early January 1998 and continued throughout the winter and spring. On February 9, President Clinton declared all 10 counties eligible for Federal Emergency Management Agency (FEMA) disaster assistance. In April and May of 1998, personnel from the U.S. Geological Survey (USGS) conducted a field reconnaissance in the area to provide a general overview of landslide damage resulting from the 1997-98 sequence of El Nino-related storms. Seven scientists from the USGS Landslide Hazards Program based in Reston, Virginia; Golden, Colorado; and Menlo Park, California; and five scientists from the USGS Geologic Mapping Program?s San Francisco Bay Mapping Team based in Menlo Park, California, cooperated in the landslide-damage assessments. The assessments were done for 10 counties in the Bay area: Alameda, Contra Costa, Marin, Napa, San Francisco, Santa Clara, Santa Cruz, San Mateo, Solano, and Sonoma. USGS Maps in this series include: MF-2325-A (Napa County), MF-2325-B (Alameda County), MF-2325-C (Marin County), MF-2325-D (Santa Cruz County), MF-2325-E (Contra Costa County), MF-2325-F (Sonoma County), MF-2325-G (San Francisco City and County), MF-2325-H (San Mateo County), MF-2325-I (Solano County), MF-2325-J (Santa Clara County). In addition to USGS scientists providing data from the field evaluation, each of the counties, many consultants, and others cooperated fully in providing the landslide-damage information compiled here.

  1. A recurrent KCNQ2 pore mutation causing early onset epileptic encephalopathy has a moderate effect on M current but alters subcellular localization of Kv7 channels.

    PubMed

    Abidi, Affef; Devaux, Jérôme J; Molinari, Florence; Alcaraz, Gisèle; Michon, François-Xavier; Sutera-Sardo, Julie; Becq, Hélène; Lacoste, Caroline; Altuzarra, Cécilia; Afenjar, Alexandra; Mignot, Cyril; Doummar, Diane; Isidor, Bertrand; Guyen, Sylvie N; Colin, Estelle; De La Vaissière, Sabine; Haye, Damien; Trauffler, Adeline; Badens, Catherine; Prieur, Fabienne; Lesca, Gaetan; Villard, Laurent; Milh, Mathieu; Aniksztejn, Laurent

    2015-08-01

    Mutations in the KCNQ2 gene encoding the voltage-dependent potassium M channel Kv7.2 subunit cause either benign epilepsy or early onset epileptic encephalopathy (EOEE). It has been proposed that the disease severity rests on the inhibitory impact of mutations on M current density. Here, we have analyzed the phenotype of 7 patients carrying the p.A294V mutation located on the S6 segment of the Kv7.2 pore domain (Kv7.2(A294V)). We investigated the functional and subcellular consequences of this mutation and compared it to another mutation (Kv7.2(A294G)) associated with a benign epilepsy and affecting the same residue. We report that all the patients carrying the p.A294V mutation presented the clinical and EEG characteristics of EOEE. In CHO cells, the total expression of Kv7.2(A294V) alone, assessed by western blotting, was only 20% compared to wild-type. No measurable current was recorded in CHO cells expressing Kv7.2(A294V) channel alone. Although the total Kv7.2(A294V) expression was rescued to wild-type levels in cells co-expressing the Kv7.3 subunit, the global current density was still reduced by 83% compared to wild-type heteromeric channel. In a configuration mimicking the patients' heterozygous genotype i.e., Kv7.2(A294V)/Kv7.2/Kv7.3, the global current density was reduced by 30%. In contrast to Kv7.2(A294V), the current density of homomeric Kv7.2(A294G) was not significantly changed compared to wild-type Kv7.2. However, the current density of Kv7.2(A294G)/Kv7.2/Kv7.3 and Kv7.2(A294G)/Kv7.3 channels were reduced by 30% and 50% respectively, compared to wild-type Kv7.2/Kv7.3. In neurons, the p.A294V mutation induced a mislocalization of heteromeric mutant channels to the somato-dendritic compartment, while the p.A294G mutation did not affect the localization of the heteromeric channels to the axon initial segment. We conclude that this position is a hotspot of mutation that can give rise to a severe or a benign epilepsy. The p.A294V mutation does not exert a

  2. Cholera outbreaks caused by an altered Vibrio cholerae O1 El Tor biotype strain producing classical cholera toxin B in Vietnam in 2007 to 2008.

    PubMed

    Nguyen, Binh Minh; Lee, Je Hee; Cuong, Ngo Tuan; Choi, Seon Young; Hien, Nguyen Tran; Anh, Dang Duc; Lee, Hye Ri; Ansaruzzaman, M; Endtz, Hubert P; Chun, Jongsik; Lopez, Anna Lena; Czerkinsky, Cecil; Clemens, John D; Kim, Dong Wook

    2009-05-01

    Vibrio cholerae O1 isolates collected during cholera outbreaks occurring from late 2007 to early 2008 in northern Vietnam were revealed to represent an altered strain containing the RS1 element followed by a CTX prophage harboring El Tor type rstR and classical ctxB on the large chromosome.

  3. Cellular and metabolic alterations in the hippocampus caused by insulin signalling dysfunction and its association with cognitive impairment during aging and Alzheimer's disease: studies in animal models.

    PubMed

    Calvo-Ochoa, Erika; Arias, Clorinda

    2015-01-01

    A growing body of animal and epidemiological studies suggest that metabolic diseases such as obesity, insulin resistance, metabolic syndrome and type 2 diabetes mellitus are associated with the development of cognitive impairment, dementia and Alzheimer's disease, particularly in aging. Several lines of evidence suggest that insulin signalling dysfunction produces these metabolic alterations and underlie the development of these neurodegenerative diseases. In this article, we address normal insulin function in the synapse; we review and discuss the physiopathological hallmarks of synaptic insulin signalling dysfunction associated with metabolic alterations. Additionally, we describe and review the major animal models of obesity, insulin resistance, metabolic syndrome and type 2 diabetes mellitus. The comprehensive knowledge of the molecular mechanisms behind the association of metabolic alterations and cognitive impairment could facilitate the early detection of neurodegenerative diseases in patients with metabolic alterations, with treatment that focus on neuroprotection. It could also help in the development of metabolic-based therapies and drugs for using in dementia and Alzheimer's disease patients to alleviate their symptoms in a more efficient and comprehensive way.

  4. Ethylene Glycol Poisoning: An Unusual Cause of Altered Mental Status and the Lessons Learned from Management of the Disease in the Acute Setting

    PubMed Central

    Arain, E.; Buth, A.; Kado, J.; Soubani, A.

    2016-01-01

    Ethylene glycol is found in many household products and is a common toxic ingestion. Acute ingestions present with altered sensorium and an osmolal gap. The true toxicity of ethylene glycol is mediated by its metabolites, which are responsible for the increased anion gap metabolic acidosis, renal tubular damage, and crystalluria seen later in ingestions. Early intervention is key; however, diagnosis is often delayed, especially in elderly patients presenting with altered mental status. There are several laboratory tests which can be exploited for the diagnosis, quantification of ingestion, and monitoring of treatment, including the lactate and osmolal gaps. As methods of direct measurement of ethylene glycol are often not readily available, it is important to have a high degree of suspicion based on these indirect laboratory findings. Mainstay of treatment is bicarbonate, fomepizole or ethanol, and, often, hemodialysis. A validated equation can be used to estimate necessary duration of hemodialysis, and even if direct measurements of ethylene glycol are not available, monitoring for the closure of the anion, lactate, and osmolal gaps can guide treatment. We present the case of an elderly male with altered mental status, acute kidney injury, elevated anion gap metabolic acidosis, and profound lactate and osmolal gaps. PMID:27847651

  5. Homozygosity mapping on homozygosity haplotype analysis to detect recessive disease-causing genes from a small number of unrelated, outbred patients.

    PubMed

    Hagiwara, Koichi; Morino, Hiroyuki; Shiihara, Jun; Tanaka, Tomoaki; Miyazawa, Hitoshi; Suzuki, Tomoko; Kohda, Masakazu; Okazaki, Yasushi; Seyama, Kuniaki; Kawakami, Hideshi

    2011-01-01

    Genes involved in disease that are not common are often difficult to identify; a method that pinpoints them from a small number of unrelated patients will be of great help. In order to establish such a method that detects recessive genes identical-by-descent, we modified homozygosity mapping (HM) so that it is constructed on the basis of homozygosity haplotype (HM on HH) analysis. An analysis using 6 unrelated patients with Siiyama-type α1-antitrypsin deficiency, a disease caused by a founder gene, the correct gene locus was pinpointed from data of any 2 patients (length: 1.2-21.8 centimorgans, median: 1.6 centimorgans). For a test population in which these 6 patients and 54 healthy subjects were scrambled, the approach accurately identified these 6 patients and pinpointed the locus to a 1.4-centimorgan fragment. Analyses using synthetic data revealed that the analysis works well for IBD fragment derived from a most recent common ancestor (MRCA) who existed less than 60 generations ago. The analysis is unsuitable for the genes with a frequency in general population more than 0.1. Thus, HM on HH analysis is a powerful technique, applicable to a small number of patients not known to be related, and will accelerate the identification of disease-causing genes for recessive conditions.

  6. Chronic low-level arsenic exposure causes gender-specific alterations in locomotor activity, dopaminergic systems, and thioredoxin expression in mice

    SciTech Connect

    Bardullas, U.; Limon-Pacheco, J.H.; Giordano, M.; Carrizales, L.; Mendoza-Trejo, M.S.; Rodriguez, V.M.

    2009-09-01

    Arsenic (As) is a toxic metalloid widely present in the environment. Human exposure to As has been associated with the development of skin and internal organ cancers and cardiovascular disorders, among other diseases. A few studies report decreases in intelligence quotient (IQ), and sensory and motor alterations after chronic As exposure in humans. On the other hand, studies of rodents exposed to high doses of As have found alterations in locomotor activity, brain neurochemistry, behavioral tasks, and oxidative stress. In the present study both male and female C57Bl/6J mice were exposed to environmentally relevant doses of As such as 0.05, 0.5, 5.0, or 50 mg As/L of drinking water for 4 months, and locomotor activity was assessed every month. Male mice presented hyperactivity in the group exposed to 0.5 mg As/L and hypoactivity in the group exposed to 50 mg As/L after 4 months of As exposure, whereas female mice exposed to 0.05, 0.5, and 5.0 mg As/L exhibited hyperactivity in every monthly test during As exposure. Furthermore, striatal and hypothalamic dopamine content was decreased only in female mice. Also decreases in tyrosine hydroxylase (TH) and cytosolic thioredoxin (Trx-1) mRNA expression in striatum and nucleus accumbens were observed in male and female mice, respectively. These results indicate that chronic As exposure leads to gender-dependent alterations in dopaminergic markers and spontaneous locomotor activity, and down-regulation of the antioxidant capacity of the brain.

  7. Maternal influenza viral infection causes schizophrenia-like alterations of 5-HT₂A and mGlu₂ receptors in the adult offspring.

    PubMed

    Moreno, José L; Kurita, Mitsumasa; Holloway, Terrell; López, Javier; Cadagan, Richard; Martínez-Sobrido, Luis; García-Sastre, Adolfo; González-Maeso, Javier

    2011-02-02

    Epidemiological studies indicate that maternal influenza viral infection increases the risk for schizophrenia in the adult offspring. The serotonin and glutamate systems are suspected in the etiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. The effects of hallucinogens, such as psilocybin and mescaline, require the serotonin 5-HT(2A) receptor, and induce schizophrenia-like psychosis in humans. In addition, metabotropic glutamate receptor mGlu(2/3) agonists show promise as a new treatment for schizophrenia. Here, we investigated the level of expression and behavioral function of 5-HT(2A) and mGlu(2) receptors in a mouse model of maternal influenza viral infection. We show that spontaneous locomotor activity is diminished by maternal infection with the mouse-adapted influenza A/WSN/33 (H1N1) virus. The behavioral responses to hallucinogens and glutamate antipsychotics are both affected by maternal exposure to influenza virus, with increased head-twitch response to hallucinogens and diminished antipsychotic-like effect of the glutamate agonist. In frontal cortex of mice born to influenza virus-infected mothers, the 5-HT(2A) receptor is upregulated and the mGlu(2) receptor is downregulated, an alteration that may be involved in the behavioral changes observed. Additionally, we find that the cortical 5-HT(2A) receptor-dependent signaling pathways are significantly altered in the offspring of infected mothers, showing higher c-fos, egr-1, and egr-2 expression in response to the hallucinogenic drug DOI. Identifying a biochemical alteration that parallels the behavioral changes observed in a mouse model of prenatal viral infection may facilitate targeting therapies for treatment and prevention of schizophrenia.

  8. Postnatal disruption of the disintegrin/metalloproteinase ADAM10 in brain causes epileptic seizures, learning deficits, altered spine morphology, and defective synaptic functions.

    PubMed

    Prox, Johannes; Bernreuther, Christian; Altmeppen, Hermann; Grendel, Jasper; Glatzel, Markus; D'Hooge, Rudi; Stroobants, Stijn; Ahmed, Tariq; Balschun, Detlef; Willem, Michael; Lammich, Sven; Isbrandt, Dirk; Schweizer, Michaela; Horré, Katrien; De Strooper, Bart; Saftig, Paul

    2013-08-07

    The metalloproteinase ADAM10 is of importance for Notch-dependent cortical brain development. The protease is tightly linked with α-secretase activity toward the amyloid precursor protein (APP) substrate. Increasing ADAM10 activity is suggested as a therapy to prevent the production of the neurotoxic amyloid β (Aβ) peptide in Alzheimer's disease. To investigate the function of ADAM10 in postnatal brain, we generated Adam10 conditional knock-out (A10cKO) mice using a CaMKIIα-Cre deleter strain. The lack of ADAM10 protein expression was evident in the brain cortex leading to a reduced generation of sAPPα and increased levels of sAPPβ and endogenous Aβ peptides. The A10cKO mice are characterized by weight loss and increased mortality after weaning associated with seizures. Behavioral comparison of adult mice revealed that the loss of ADAM10 in the A10cKO mice resulted in decreased neuromotor abilities and reduced learning performance, which were associated with altered in vivo network activities in the hippocampal CA1 region and impaired synaptic function. Histological and ultrastructural analysis of ADAM10-depleted brain revealed astrogliosis, microglia activation, and impaired number and altered morphology of postsynaptic spine structures. A defect in spine morphology was further supported by a reduction of the expression of NMDA receptors subunit 2A and 2B. The reduced shedding of essential postsynaptic cell adhesion proteins such as N-Cadherin, Nectin-1, and APP may explain the postsynaptic defects and the impaired learning, altered network activity, and synaptic plasticity of the A10cKO mice. Our study reveals that ADAM10 is instrumental for synaptic and neuronal network function in the adult murine brain.

  9. Hyperspectral surface materials map of quadrangles 3664 and 3764, Char Shengo (123), Shibirghan (124), Jalajin (117), and Kham-Ab (118) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

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

    2013-01-01

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

  10. Hyperspectral surface materials map of quadrangles 3668 and 3768, Baghlan (221), Taluqan (222), Imam Sahib (215), and Rustaq (216) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

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

    2013-01-01

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

  11. Hyperspectral surface materials map of quadrangles 2962 and 3062, Gawdezereh (615), Galachah (616), Chahar Burjak (609), and Khan Neshin (610) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

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

    2013-01-01

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

  12. Hyperspectral surface materials map of quadrangles 3666 and 3766, Balkh (219), Mazar-e Sharif (220), Qarqin (213), and Hazara Toghai (214) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

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

    2013-01-01

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

  13. Hyperspectral surface materials map of quadrangles 3360 and 3460, Kawir-e Naizar (413), Kohe-Mahmudo-Esmailjan (414), Kol-e Namaksar (407), and Ghoriyan (408) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

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

    2013-01-01

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

  14. Hyperspectral surface materials map of quadrangle 3260, Dasht-e-Chah-e-Mazar (419) and Anar Darah (420) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

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

    2013-01-01

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

  15. Identification of altered microRNAs and mRNAs in the cumulus cells of PCOS patients: miRNA-509-3p promotes oestradiol secretion by targeting MAP3K8.

    PubMed

    Huang, Xin; Liu, Chang; Hao, Cuifang; Tang, Qianqing; Liu, Riming; Lin, Shaoxia; Zhang, Luping; Yan, Wei

    2016-06-01

    Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women and is characterised by polycystic ovaries, hyperandrogenism and chronic anovulation. Although the clinical and biochemical signs of PCOS are typically heterogeneous, abnormal folliculogenesis is considered a common characteristic of PCOS. Our aim is to identify the altered miRNA and mRNA expression profiles in the cumulus cells of PCOS patients to investigate their molecular function in the aetiology and pathophysiology of PCOS. In this study, the miRNA expression profiles of the cumulus cell samples isolated from five PCOS and five control patients were determined by an miRNA microarray. At the same time, the altered mRNA profiles of the same cumulus cell samples were also identified by a cDNA microarray. From the microarray data, 17 miRNAs and 1263 mRNAs showed significantly different expression in the PCOS cumulus cells. The differentially expressed miRNA-509-3p and its potential target gene (MAP3K8) were identified from the miRNA and mRNA microarrays respectively. The expression of miRNA-509-3p was up-regulated and MAP3K8 was down-regulated in the PCOS cumulus cells. The direct interaction between miRNA-509-3p and MAP3K8 was confirmed by a luciferase activity assay in KGN cells. In addition, miRNA-509-3p mimics or inhibitor transfection tests in KGN cells further confirmed that miRNA-509-3p improved oestradiol (E2) secretion by inhibiting the expression of MAP3K8 These results help to characterise the pathogenesis of anovulation in PCOS, especially the regulation of E2 production.

  16. Infection by a black spot-causing species of Uvulifer and associated opercular alterations in fishes from a high-desert stream in Wyoming

    USGS Publications Warehouse

    Quist, M.C.; Bower, M.R.; Hubert, W.A.

    2007-01-01

    Black spot is a common disease syndrome of freshwater fishes. This study provides information on the rank of density of the black spot agent and opercular bone alterations associated with at least one digenean, Uvulifer sp., infecting native and non-native catostomids and cyprinids of the Upper Colorado River Basin. We evaluated the density rank of pigmented metacercariae and associated alterations in the operculum of the bluehead sucker Catostomus discobolus, flannelmouth sucker C. latipinnis, white sucker C. commersoni, catostomid hybrids, roundtail chub Gila robusta, and creek chub Semotilus atromaculatus, sampled from Muddy Creek, Wyoming, USA in 2003 or 2004. All fish species contained individuals that exhibited gross signs of the black spot agent. Bluehead and flannelmouth suckers had 100% prevalence of infection. Although the other suckers and chubs contained encysted metacercariae in at least one individual, the presence of pigmented metacercariae was not apparent (i.e. based on gross observations) in many individuals. Catostomids had higher densities of metacercariae than cyprinids, as shown by frequency distributions of density ranks. Opercular holes (i.e. holes that completely penetrated the opercle and were in direct association with the pigment associated metacercariae) and pockets (depressions on the external surface of the opercle associated with metacercariae) were abundant among catostomids but rare among cyprinids. ?? Inter-Research 2007.

  17. Maternal obesity induced by a high fat diet causes altered cellular development in fetal brains suggestive of a predisposition of offspring to neurological disorders in later life.

    PubMed

    Stachowiak, Ewa K; Srinivasan, Malathi; Stachowiak, Michal K; Patel, Mulchand S

    2013-12-01

    Fetal development in an obese maternal intrauterine environment has been shown to predispose the offspring for a number of metabolic disorders in later life. The observation that a large percentage of women of child-bearing age in the US are overweight/obese during pregnancy is therefore a source of concern. A high fat (HF) diet-induced obesity in female rats has been used as a model for maternal obesity. The objective of this study was to determine cellular development in brains of term fetuses of obese rats fed a HF diet from the time of weaning. Fetal brains were dissected out on gestational day 21 and processed for immunohistochemical analysis in the hypothalamic as well as extra-hypothalamic regions. The major observation of this study is that fetal development in the obese HF female rat induced several alterations in the HF fetal brain. Marked increases were observed in orexigenic signaling and a significant decrease was observed for anorexigenic signaling in the vicinity of the 3rd ventricle in HF brains. Additionally, our results indicated diminished migration and maturation of stem-like cells in the 3rd ventricular region as well as in the brain cortex. The results from the present study indicate developmental alterations in the hypothalamic and extra-hypothalamic regions in the HF fetal brain suggestive of a predisposition for the development of obesity and possibly neurodevelopmental abnormalities in the offspring.

  18. The Fault Lies on the Other Side: Altered Brain Functional Connectivity in Psychiatric Disorders is Mainly Caused by Counterpart Regions in the Opposite Hemisphere.

    PubMed

    Zhang, Jie; Kendrick, Keith M; Lu, Guangming; Feng, Jianfeng

    2015-10-01

    Many psychiatric disorders are associated with abnormal resting-state functional connectivity between pairs of brain regions, although it remains unclear whether the fault resides within the pair of regions themselves or other regions connected to them. Identifying the source of dysfunction is crucial for understanding the etiology of different disorders. Using pathway- and network-based techniques to analyze resting-state functional magnetic imaging data from a large population of patients with attention deficit hyperactivity disorder (239 patients, 251 controls), major depression (39 patients, 37 controls), and schizophrenia (69 patients, 62 controls), we show for the first time that only network-based cross-correlation identifies significant functional connectivity changes in all 3 disorders which survive correction. This demonstrates that the primary source of dysfunction resides not in the regional pairs themselves but in their external connections. Combining pathway and network-based functional-connectivity analysis, we established that, in all 3 disorders, the counterparts of pairs of regions in the opposite hemisphere contribute 60-76% to altered functional connectivity, compared with only 17-21% from the regions themselves. Thus, a transdiagnostic feature is of abnormal functional connectivity between brain regions produced via their contralateral counterparts. Our results demonstrate an important role for contralateral counterpart regions in contributing to altered regional connectivity in psychiatric disorders.

  19. Magnolol causes alterations in the cell cycle in androgen insensitive human prostate cancer cells in vitro by affecting expression of key cell cycle regulatory proteins.

    PubMed

    McKeown, Brendan T; McDougall, Luke; Catalli, Adriana; Hurta, Robert A R

    2014-01-01

    Prostate cancer, one of the most common cancers in the Western world, affects many men worldwide. This study investigated the effects of magnolol, a compound found in the roots and bark of the magnolia tree Magnolia officinalis, on the behavior of 2 androgen insensitive human prostate cancer cell lines, DU145 and PC3, in vitro. Magnolol, in a 24-h exposure at 40 and 80 μM, was found to be cytotoxic to cells. Magnolol also affected cell cycle progression of DU145 and PC3 cells, resulting in alterations to the cell cycle and subsequently decreasing the proportion of cells entering the G2/M-phase of the cell cycle. Magnolol inhibited the expression of cell cycle regulatory proteins including cyclins A, B1, D1, and E, as well as CDK2 and CDK4. Protein expression levels of pRBp107 decreased and pRBp130 protein expression levels increased in response to magnolol exposure, whereas p16(INK4a), p21, and p27 protein expression levels were apparently unchanged post 24-h exposure. Magnolol exposure at 6 h did increase p27 protein expression levels. This study has demonstrated that magnolol can alter the behavior of androgen insensitive human prostate cancer cells in vitro and suggests that magnolol may have potential as a novel anti-prostate cancer agent.

  20. FGF-2 deficiency causes dysregulation of Arhgef6 and downstream targets in the cerebral cortex accompanied by altered neurite outgrowth and dendritic spine morphology.

    PubMed

    Baum, Philip; Vogt, Miriam A; Gass, Peter; Unsicker, Klaus; von Bohlen und Halbach, Oliver

    2016-05-01

    Fibroblast growth factor 2 (FGF-2) is an abundant growth factor in the brain and exerts multiple functions on neural cells ranging from cell division, cell fate determination to differentiation. However, many details of the molecular mechanisms underlying the diverse functions of FGF-2 are poorly understood. In a comparative microarray analysis of motor sensory cortex (MSC) tissue of adult knockout (FGF-2(-/-)) and control (FGF-2(+/+)) mice, we found a substantial number of regulated genes, which are implicated in cytoskeletal machinery dynamics. Specifically, we found a prominent downregulation of Arhgef6. Arhgef6 mRNA was significantly reduced in the FGF-2(-/-) cortex, and Arhgef6 protein virtually absent, while RhoA protein levels were massively increased and Cdc42 protein levels were reduced. Since Arhgef6 is localized to dendritic spines, we next analyzed dendritic spines of adult FGF2(-/-) and control mouse cortices. Spine densities were significantly increased, whereas mean length of spines on dendrites of layer V of MSC neurons in adult FGF-2(-/-) mice was significantly decreased as compared to respective controls. Furthermore, neurite length in dissociated cortical cultures from E18 FGF-2(-/-) mice was significantly reduced at DIV7 as compared to wildtype neurons. Despite the fact that altered neuronal morphology and alterations in dendritic spines were observed, FGF-2(-/-) mice behave relatively unsuspicious in several behavioral tasks. However, FGF-2(-/-) mice exhibited decreased thermal pain sensitivity in the hotplate-test.

  1. Thiol-redox antioxidants protect against lung vascular endothelial cytoskeletal alterations caused by pulmonary fibrosis inducer, bleomycin: comparison between classical thiol-protectant, N-acetyl-L-cysteine, and novel thiol antioxidant, N,N'-bis-2-mercaptoethyl isophthalamide.

    PubMed

    Patel, Rishi B; Kotha, Sainath R; Sauers, Lynn A; Malireddy, Smitha; Gurney, Travis O; Gupta, Niladri N; Elton, Terry S; Magalang, Ulysses J; Marsh, Clay B; Haley, Boyd E; Parinandi, Narasimham L

    2012-06-01

    Lung vascular alterations and pulmonary hypertension associated with oxidative stress have been reported to be involved in idiopathic lung fibrosis (ILF). Therefore, here, we hypothesize that the widely used lung fibrosis inducer, bleomycin, would cause cytoskeletal rearrangement through thiol-redox alterations in the cultured lung vascular endothelial cell (EC) monolayers. We exposed the monolayers of primary bovine pulmonary artery ECs to bleomycin (10 µg) and studied the cytotoxicity, cytoskeletal rearrangements, and the macromolecule (fluorescein isothiocyanate-dextran, 70,000 mol. wt.) paracellular transport in the absence and presence of two thiol-redox protectants, the classic water-soluble N-acetyl-L-cysteine (NAC) and the novel hydrophobic N,N'-bis-2-mercaptoethyl isophthalamide (NBMI). Our results revealed that bleomycin induced cytotoxicity (lactate dehydrogenase leak), morphological alterations (rounding of cells and filipodia formation), and cytoskeletal rearrangement (actin stress fiber formation and alterations of tight junction proteins, ZO-1 and occludin) in a dose-dependent fashion. Furthermore, our study demonstrated the formation of reactive oxygen species, loss of thiols (glutathione, GSH), EC barrier dysfunction (decrease of transendothelial electrical resistance), and enhanced paracellular transport (leak) of macromolecules. The observed bleomycin-induced EC alterations were attenuated by both NAC and NBMI, revealing that the novel hydrophobic thiol-protectant, NBMI, was more effective at µM concentrations as compared to the water-soluble NAC that was effective at mM concentrations in offering protection against the bleomycin-induced EC alterations. Overall, the results of the current study suggested the central role of thiol-redox in vascular EC dysfunction associated with ILF.

  2. Mapping argillic and advanced argillic alteration in volcanic rocks, quartzites, and quartz arenites in the western Richfield 1° x 2 ° quadrangle, southwestern Utah, using ASTER satellite data

    USGS Publications Warehouse

    Rockwell, Barnaby W.; Hofstra, Albert H.

    2012-01-01

    The Richfield quadrangle in southwestern Utah is known to contain a variety of porphyry Mo, skarn, polymetallic replacement and vein, alunite, and kaolin resources associated with 27-32 Ma calc-alkaline or 12-23 Ma bimodal volcano-plutonic centers in Neoproterozoic to Mesozoic carbonate and siliciclastic rocks. Four scenes of visible to shortwave-infrared image data acquired by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) sensor were analyzed to generate maps of exposed clay, sulfate, mica, and carbonate minerals, and ASTER thermal infrared data were analyzed to identify quartz and carbonate minerals. Argillic and advanced argillic alteration minerals including alunite, pyrophyllite, dickite, and kaolinite were identified in both undocumented (U) and known (K) areas, including in the southern Paradise Mtns. (U); in calc-alkaline volcanic rocks in the Wah Wah Mtns. between Broken Ridge and the NG area (U/K); at Wah Wah Summit in a small zone adjacent to 33.1 Ma diorite and marble (U); in fractures cutting quartzites surrounding the 20-22 Ma Pine Grove Mo deposit (U); in volcanic rocks in the Shauntie Hills (U/K); in quartzites in the west-central San Francisco Mtns. (U); in volcanic rocks in the Black Mtns. (K); and in mainly 12-13 Ma rhyolitic rocks along a 20 km E-W belt that includes the Bible Spring fault zone west of Broken Ridge, with several small centers in the Escalante Desert to the south (U/K). Argillized Navajo Sandstone with kaolinite and (or) dickite ± alunite was mapped adjacent to calc-alkaline intrusions in the Star Range (U). Intense quartz-sericite alteration (K) with local kaolinite was identified in andesite adjacent to calc-alkaline intrusions in the Beaver Lake Mountains. Mo-bearing phyllic alteration was identified in 22.2 Ma rhyolite plugs at the center of the NG alunite area. Limestones, dolomites, and marbles were differentiated, and quartz and sericite were identified in most unaltered quartzites. Halos of

  3. Alterations in fruit and vegetable beta-carotene and vitamin C content caused by open-sun drying, visqueen-covered and polyethylene-covered solar-dryers.

    PubMed

    Ndawula, J; Kabasa, J D; Byaruhanga, Y B

    2004-08-01

    This study investigated the effects of three drying methods (open sun drying, visqueen-covered solar dryer and polyethylene-covered solar dryer) on b-carotene and vitamin C content of edible portions of mango fruit (Mangifera indica) and cowpea leaves (Vigna unguiculata). Commercial samples were analysed for vitamin C by titrimetry and b-carotene by spectrophotometry at 450 nm. Differences in vitamin retention and loss associated with the three drying methods were assessed by analysis of variance and least significant difference (LSD) at (p<0.05. The fresh cowpea leaf b-carotene and vitamin C content was 140.9 and 164.3 mg / 100g DM respectively and decreased (p<0.05) with drying. Open sun drying method caused the greatest b-carotene and vitamin C loss (58% and 84% respectively), while the visqueen-covered solar dryer caused the least loss (34.5% and 71% respectively). Blanching cowpea leaves improved b-carotene and vitamin C retention by 15% and 7.5% respectively. The b-carotene and vitamin C content of fresh ripe mango fruit was 5.9 and 164.3 mg/100g DM respectively. Similar to effects on cowpea leaves, the mango micronutrient content decreased (p<0.05) with drying. The open sun drying method caused the greatest b-carotene (94.2%) and vitamin C (84.5%) loss, while the visqueen-covered solar dryer caused the least (73 and 53% respectively). These results show that the three solar drying methods cause significant loss of pro-vitamin A and vitamin C in dried fruits and vegetables. However, open sun drying causes the most loss and the visqueen-covered solar dryer the least, making the later a probable better drying technology for fruit and vegetable preservation. The drying technologies should be improved to enhance vitamin retention.

  4. Vru (Sub0144) controls expression of proven and putative virulence determinants and alters the ability of Streptococcus uberis to cause disease in dairy cattle

    PubMed Central

    Egan, Sharon A.; Ward, Philip N.; Watson, Michael; Field, Terence R.

    2012-01-01

    The regulation and control of gene expression in response to differing environmental stimuli is crucial for successful pathogen adaptation and persistence. The regulatory gene vru of Streptococcus uberis encodes a stand-alone response regulator with similarity to the Mga of group A Streptococcus. Mga controls expression of a number of important virulence determinants. Experimental intramammary challenge of dairy cattle with a mutant of S. uberis carrying an inactivating lesion in vru showed reduced ability to colonize the mammary gland and an inability to induce clinical signs of mastitis compared with the wild-type strain. Analysis of transcriptional differences of gene expression in the mutant, determined by microarray analysis, identified a number of coding sequences with altered expression in the absence of Vru. These consisted of known and putative virulence determinants, including Lbp (Sub0145), SclB (Sub1095), PauA (Sub1785) and hasA (Sub1696). PMID:22383474

  5. MAPK signaling pathway alters expression of midgut ALP and ABCC genes and causes resistance to Bacillus thuringiensis Cry1Ac toxin in diamondback moth.

    PubMed

    Guo, Zhaojiang; Kang, Shi; Chen, Defeng; Wu, Qingjun; Wang, Shaoli; Xie, Wen; Zhu, Xun; Baxter, Simon W; Zhou, Xuguo; Jurat-Fuentes, Juan Luis; Zhang, Youjun

    2015-04-01

    Insecticidal crystal toxins derived from the soil bacterium Bacillus thuringiensis (Bt) are widely used as biopesticide sprays or expressed in transgenic crops to control insect pests. However, large-scale use of Bt has led to field-evolved resistance in several lepidopteran pests. Resistance to Bt Cry1Ac toxin in the diamondback moth, Plutella xylostella (L.), was previously mapped to a multigenic resistance locus (BtR-1). Here, we assembled the 3.15 Mb BtR-1 locus and found high-level resistance to Cry1Ac and Bt biopesticide in four independent P. xylostella strains were all associated with differential expression of a midgut membrane-bound alkaline phosphatase (ALP) outside this locus and a suite of ATP-binding cassette transporter subfamily C (ABCC) genes inside this locus. The interplay between these resistance genes is controlled by a previously uncharacterized trans-regulatory mechanism via the mitogen-activated protein kinase (MAPK) signaling pathway. Molecular, biochemical, and functional analyses have established ALP as a functional Cry1Ac receptor. Phenotypic association experiments revealed that the recessive Cry1Ac resistance was tightly linked to down-regulation of ALP, ABCC2 and ABCC3, whereas it was not linked to up-regulation of ABCC1. Silencing of ABCC2 and ABCC3 in susceptible larvae reduced their susceptibility to Cry1Ac but did not affect the expression of ALP, whereas suppression of MAP4K4, a constitutively transcriptionally-activated MAPK upstream gene within the BtR-1 locus, led to a transient recovery of gene expression thereby restoring the susceptibility in resistant larvae. These results highlight a crucial role for ALP and ABCC genes in field-evolved resistance to Cry1Ac and reveal a novel trans-regulatory signaling mechanism responsible for modulating the expression of these pivotal genes in P. xylostella.

  6. Neurochemical and electrophysiological deficits in the ventral hippocampus and selective behavioral alterations caused by high-fat diet in female C57BL/6 mice.

    PubMed

    Krishna, S; Keralapurath, M M; Lin, Z; Wagner, J J; de La Serre, C B; Harn, D A; Filipov, N M

    2015-06-25

    Mounting experimental evidence, predominantly from male rodents, demonstrates that high-fat diet (HFD) consumption and ensuing obesity are detrimental to the brain. To shed additional light on the neurological consequences of HFD consumption in female rodents and to determine the relatively early impact of HFD in the likely continuum of neurological dysfunction in the context of chronic HFD intake, this study investigated effects of HFD feeding for up to 12weeks on selected behavioral, neurochemical, and electrophysiological parameters in adult female C57BL/6 mice; particular focus was placed on the ventral hippocampus (vHIP). Selected locomotor, emotional and cognitive functions were evaluated using behavioral tests after 5weeks on HFD or control (low-fat diet) diets. One week later, mice were sacrificed and brain regional neurochemical (monoamine) analysis was performed. Behaviorally naïve mice were maintained on their respective diets for an additional 5-6weeks at which time synaptic plasticity was determined in ex vivo slices from the vHIP. HFD-fed female mice exhibited increased: (i) locomotor activity in the open field testing, (ii) mean turn time on the pole test, (iii) swimming time in the forced swim test, and (iv) number of marbles buried in the marble burying test. In contrast, the novel object recognition memory was unaffected. Mice on HFD also had decreased norepinephrine and dopamine turnover, respectively, in the prefrontal cortex and the vHIP. HFD consumption for a total of 11-12weeks altered vHIP synaptic plasticity, evidenced by significant reductions in the paired-pulse ratio and long-term potentiation (LTP) magnitude. In summary, in female mice, HFD intake for several weeks induced multiple behavioral alterations of mainly anxiety-like nature and impaired monoamine pathways in a brain region-specific manner, suggesting that in the female, certain behavioral domains (anxiety) and associated brain regions, i.e., the vHIP, are preferentially

  7. Glycine Administration Alters MAPK Signaling Pathways and Causes Neuronal Damage in Rat Brain: Putative Mechanisms Involved in the Neurological Dysfunction in Nonketotic Hyperglycinemia.

    PubMed

    Moura, Alana Pimentel; Parmeggiani, Belisa; Gasparotto, Juciano; Grings, Mateus; Fernandez Cardoso, Gabriela Miranda; Seminotti, Bianca; Moreira, José Cláudio Fonseca; Gelain, Daniel Pens; Wajner, Moacir; Leipnitz, Guilhian

    2017-01-03

    High glycine (GLY) levels have been suggested to induce neurotoxic effects in the central nervous system of patients with nonketotic hyperglycinemia (NKH). Since the mechanisms involved in the neuropathophysiology of NKH are not totally established, we evaluated the effect of a single intracerebroventricular administration of GLY on the content of proteins involved in neuronal damage and inflammatory response, as well as on the phosphorylation of the MAPK p38, ERK1/2, and JNK in rat striatum and cerebral cortex. We also examined glial fibrillary acidic protein (GFAP) staining, a marker of glial reactivity. The parameters were analyzed 30 min or 24 h after GLY administration. GLY decreased Tau phosphorylation in striatum and cerebral cortex 30 min and 24 h after its administration. On the other hand, synaptophysin levels were decreased in striatum at 30 min and in cerebral cortex at 24 h after GLY injection. GLY also decreased the phosphorylation of p38, ERK1/2, and JNK 30 min after its administration in both brain structures. Moreover, GLY-induced decrease of p38 phosphorylation in striatum was attenuated by N-methyl-D-aspartate receptor antagonist MK-801. In contrast, synuclein, NF-κB, iκB, inducible nitric oxide synthase and nitrotyrosine content, and GFAP immunostaining were not altered by GLY infusion. It may be presumed that the decreased phosphorylation of MAPK associated with alterations of markers of neuronal injury induced by GLY may contribute to the neurological dysfunction observed in NKH.

  8. QUANTIFICATION OF LOCAL HEMODYNAMIC ALTERATIONS CAUSED BY VIRTUAL IMPLANTATION OF THREE COMMERCIALLY-AVAILABLE STENTS FOR THE TREATMENT OF AORTIC COARCTATION

    PubMed Central

    Kwon, Sung; Feinstein, Jeffrey A.; Dholakia, Ronak J.; LaDisa, John F.

    2014-01-01

    Patients with coarctation of the aorta (CoA) are prone to morbidity including atherosclerotic plaque that has been shown to correlate with altered wall shear stress (WSS) in the descending thoracic aorta (dAo). We created the first patient-specific computational fluid dynamics (CFD) model of a CoA patient treated by Palmaz stenting to date, and compared resulting WSS distributions to those from virtual implantation of GenesisXD and modified NumedCP stents also commonly used for CoA. CFD models were created from magnetic resonance imaging, fluoroscopy and blood pressure (BP) data. Simulations incorporated vessel deformation, downstream vascular resistance and compliance to match measured data and generate blood flow velocity and time-averaged WSS (TAWSS) results. TAWSS was quantified longitudinally and circumferentially in the stented region and dAo. While modest differences were seen in the distal portion of the stented region, marked differences were observed downstream along the posterior dAo and depended on stent type. The GenesisXD model had the least area of TAWSS values exceeding the threshold for platelet aggregation in vitro, followed by the Palmaz and NumedCP stents. Alterations in local blood flow patterns and WSS imparted on the dAo appear to depend on the type of stent implanted for CoA. Following confirmation in larger studies, these findings may aid pediatric interventional cardiologists in selecting the most appropriate stent for each patient, and ultimately reduce long-term morbidity following treatment for CoA by stenting. PMID:24259013

  9. Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): a Y210C mutation causes either altered protein handling or altered protein function of N-acetylgalactosamine 4-sulfatase at multiple points in the vacuolar network.

    PubMed

    Bradford, Tessa M; Litjens, Tom; Parkinson, Emma J; Hopwood, John J; Brooks, Doug A

    2002-04-16

    The lysosomal hydrolase N-acetylgalactosamine 4-sulfatase (4-sulfatase) is required for the degradation of the glycosaminoglycan substrates dermatan and chondroitin sulfate. A 4-sulfatase deficiency results in the accumulation of undegraded substrate and causes the severe lysosomal storage disorder mucopolysaccharidosis type VI (MPS VI) or Maroteaux-Lamy syndrome. A wide variation in clinical severity is observed between MPS VI patients and reflects the number of different 4-sulfatase mutations that can cause the disorder. The most common 4-sulfatase mutation, Y210C, was detected in approximately 10% of MPS VI patients and has been associated with an attenuated clinical phenotype when compared to the archetypical form of MPS VI. To define the molecular defect caused by this mutation, Y210C 4-sulfatase was expressed in Chinese hamster ovary (CHO-K1) cells for protein and cell biological analysis. Biosynthetic studies revealed that Y210C 4-sulfatase was synthesized at a comparable molecular size and amount to wild-type 4-sulfatase, but there was evidence of delayed processing, traffic, and stability of the mutant protein. Thirty-three percent of the intracellular Y210C 4-sulfatase remained as a precursor form, for at least 8 h post labeling and was not processed to the mature lysosomal form. However, unlike other 4-sulfatase mutations causing MPS VI, a significant amount of Y210C 4-sulfatase escaped the endoplasmic reticulum and was either secreted from the expression cells or underwent delayed intracellular traffic. Sixty-seven percent of the intracellular Y210C 4-sulfatase was processed to the mature form (43, 8, and 7 kDa molecular mass forms) by a proteolytic processing step known to occur in endosomes-lysosomes. Treatment of Y210C CHO-K1 cells with the protein stabilizer glycerol resulted in increased amounts of Y210C 4-sulfatase in endosomes, which was eventually trafficked to the lysosome after a long, 24 h chase time. This demonstrated delayed traffic of Y210

  10. Repeated social defeat causes increased anxiety-like behavior and alters splenocyte function in C57BL/6 and CD-1 mice.

    PubMed

    Kinsey, Steven G; Bailey, Michael T; Sheridan, John F; Padgett, David A; Avitsur, Ronit

    2007-05-01

    The experimental model, social disruption (SDR), is a model of social stress in which mice are repeatedly attacked and defeated in their home cage by an aggressive conspecific. In terms of the impact of this stressor on the immune response, SDR has been reported to cause hyperinflammation and glucocorticoid insensitivity. To this point however, the behavioral consequences of SDR have not been thoroughly characterized. Because social defeat has been reported to cause anxiety- and depressive-like behaviors, the current study was designed to assess whether SDR also causes anxiety- and depressive-like behaviors. Using the light/dark preference test and the open field test as tools to measure behaviors characteristic of anxiety, the data showed that C57BL/6 and CD-1 male mice subjected to SDR displayed increased anxiety-like behavior. The increase in anxiety-like behaviors persisted for at least 1 week after the cessation of the stressor. In contrast, depressive-like behaviors were not elicited by SDR as assessed by the forced swim test or the tail suspension test. These data indicate that social disruption stress causes an increase in anxiety-like behaviors, but not depressive-like behaviors.

  11. A MIXTURE OF AMMONIUM PERCHLORATE AND SODIUM CHLORATE ENHANCES ALTERATIONS OF THE PITUITARY-THYROID AXIS CAUSED BY THE INDIVIDUAL CHEMICALS IN ADULT MALE F344 RATS

    EPA Science Inventory

    Ammonium perchlorate (AP) and sodium chlorate (SC) have been detected in public drinking water supplies in many parts of the U.S. These chemicals cause perturbations in pituitary-thyroid homeostasis in animals by competitively inhibiting the iodide uptake, thus hindering the synt...

  12. Jasmonic acid causes short- and long-term alterations to the transcriptome and the expression of defense genes in sugarbeet roots

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Jasmonic acid (JA) induces native defense responses in plants and increases the resistance of postharvest sugarbeet roots to three common storage-rot causing organisms. To gain insight into the defense responses induced by JA in harvested sugarbeet roots, RNA was isolated from roots treated with wat...

  13. Repeated Social Defeat Causes Increased Anxiety-Like Behavior and Alters Splenocyte Function in C57BL/6 and CD-1 Mice

    PubMed Central

    Kinsey, Steven G.; Bailey, Michael T.; Sheridan, John F.; Padgett, David A.; Avitsur, Ronit

    2007-01-01

    The experimental model, social disruption (SDR), is a model of social stress in which mice are repeatedly attacked and defeated in their home cage by an aggressive conspecific. In terms of the impact of this stressor on the immune response, SDR has been reported to cause hyperinflammation and glucocorticoid insensitivity. To this point however, the behavioral consequences of SDR have not been thoroughly characterized. Because social defeat has been reported to cause anxiety- and depressive-like behaviors, the current study was designed to assess whether SDR also causes anxiety- and depressive-like behaviors. Using the light/dark preference test and the open field test as tools to measure behaviors characteristic of anxiety, the data showed that C57BL/6 and CD-1 male mice subjected to SDR displayed increased anxiety-like behavior. The increase in anxiety-like behaviors persisted for at least one week after the cessation of the stressor. In contrast, depressive-like behaviors were not elicited by SDR as assessed by the forced swim test or the tail suspension test. These data indicate that social disruption stress causes an increase in anxiety-like behaviors, but not depressive-like behaviors. PMID:17178210

  14. Exposure to atheroma-relevant 7-oxysterols causes proteomic alterations in cell death, cellular longevity, and lipid metabolism in THP-1 macrophages

    PubMed Central

    Ljunggren, Stefan A.; Karlsson, Helen; Li, Wei; Yuan, Xi-Ming

    2017-01-01

    The 7-oxysterols are recognised as strong enhancers of inflammatory processes in foamy macrophages. Atheroma-relevant 7-oxysterol mixtures induce a mixed type of cell death in macrophages, and trigger cellular oxidative stress responses, which mimic oxidative exposures observed in atherosclerotic lesions. However, the macrophage proteome has not previously been determined in the 7-oxysterol treated cell model. The aim of the present study was to determine the specific effects of an atheroma-relevant 7-oxysterol mixture on human macrophage proteome. Human THP-1 macrophages were exposed to an atheroma-relevant mixture of 7β-hydroxycholesterol and 7-ketocholesterol. Two-dimensional gel electrophoresis and mass spectrometry techniques were used to analyse the alterations in macrophage proteome, which resulted in the identification of 19 proteins with significant differential expression upon oxysterol loading; 8 increased and 11 decreased. The expression patterns of 11 out of 19 identified significant proteins were further confirmed by tandem-mass spectrometry, including further validation of increased histone deacetylase 2 and macrophage scavenger receptor types I and II expressions by western blot analysis. Identified proteins with differential expression in the cell model have been associated with i) signalling imbalance in cell death and cellular longevity; ii) lipid uptake and metabolism in foam cells; and iii) inflammatory proteins. The presented findings highlight a new proteomic platform for further studies into the functional roles of macrophages in atherosclerosis, and present a cell model for future studies to modulate the macrophage proteome by potential anti-atherosclerotic agents. PMID:28350877

  15. Exposure to the synthetic FXR agonist GW4064 causes alterations in gene expression and sublethal hepatotoxicity in eleutheroembryo medaka (Oryzias latipes)

    SciTech Connect

    Howarth, Deanna L.; Law, Sheran H.W.; Law, J. McHugh; Mondon, J.A.; Kullman, Seth W.; Hinton, David E.

    2010-02-15

    The small freshwater teleost, medaka (Oryzias latipes), has a history of usage in studies of chronic toxicity of liver and biliary system. Recent progress with this model has focused on defining the medaka hepatobiliary system. Here we investigate critical liver function and toxicity by examining the in vivo role and function of the farnesoid X receptor alpha (FXRalpha, NR1H4), a member of the nuclear receptor superfamily that plays an essential role in the regulation of bile acid homeostasis. Quantitative mRNA analysis of medaka FXRalpha demonstrates differential expression of two FXRalpha isoforms designated Fxralpha1 and Fxralpha2, in both free swimming medaka embryos with remaining yolk (eleutheroembryos, EEs) and adults. Activation of medaka Fxralpha in vivo with GW4064 (a strong FXRalpha agonist) resulted in modification of gene expression for defined FXRalpha gene targets including the bile salt export protein, small heterodimer partner, and cytochrome P450 7A1. Histological examination of medaka liver subsequent to GW4064 exposure demonstrated significant lipid accumulation, cellular and organelle alterations in both hepatocytes and biliary epithelial cells of the liver. This report of hepatobiliary injury following GW4064 exposure extends previous investigations of the intrahepatic biliary system in medaka, reveals sensitivity to toxicant exposure, and illustrates the need for added resolution in detection and interpretation of toxic responses in this vertebrate.

  16. A postnatal role for embryonic myosin revealed by MYH3 mutations that alter TGFβ signaling and cause autosomal dominant spondylocarpotarsal synostosis

    PubMed Central

    Zieba, Jennifer; Zhang, Wenjuan; Chong, Jessica X.; Forlenza, Kimberly N.; Martin, Jorge H.; Heard, Kelly; Grange, Dorothy K.; Butler, Merlin G.; Kleefstra, Tjitske; Lachman, Ralph S.; Nickerson, Deborah; Regnier, Michael; Cohn, Daniel H.; Bamshad, Michael; Krakow, Deborah

    2017-01-01

    Spondylocarpotarsal synostosis (SCT) is a skeletal disorder characterized by progressive vertebral, carpal and tarsal fusions, and mild short stature. The majority of affected individuals have an autosomal recessive form of SCT and are homozygous or compound heterozygous for nonsense mutations in the gene that encodes the cytoskeletal protein filamin B (FLNB), but a subset do not have FLNB mutations. Exome sequence analysis of three SCT patients negative for FLNB mutations identified an autosomal dominant form of the disease due to heterozygosity for missense or nonsense mutations in MYH3, which encodes embryonic myosin. Cells transfected with the MYH3 missense mutations had reduced TGFβ signaling, revealing a regulatory role for embryonic myosin in the TGFβ signaling pathway. In wild-type mice, there was persistent postnatal expression of embryonic myosin in the small muscles joining the neural arches of the spine suggesting that loss of myosin function in these muscles contribute to the disease. Our findings demonstrate that dominant mutations in MYH3 underlie autosomal dominant SCT, identify a postnatal role for embryonic myosin and suggest that altered regulation of signal transduction in the muscles within the spine may lead to the development of vertebral fusions. PMID:28205584

  17. A postnatal role for embryonic myosin revealed by MYH3 mutations that alter TGFβ signaling and cause autosomal dominant spondylocarpotarsal synostosis.

    PubMed

    Zieba, Jennifer; Zhang, Wenjuan; Chong, Jessica X; Forlenza, Kimberly N; Martin, Jorge H; Heard, Kelly; Grange, Dorothy K; Butler, Merlin G; Kleefstra, Tjitske; Lachman, Ralph S; Nickerson, Deborah; Regnier, Michael; Cohn, Daniel H; Bamshad, Michael; Krakow, Deborah

    2017-02-16

    Spondylocarpotarsal synostosis (SCT) is a skeletal disorder characterized by progressive vertebral, carpal and tarsal fusions, and mild short stature. The majority of affected individuals have an autosomal recessive form of SCT and are homozygous or compound heterozygous for nonsense mutations in the gene that encodes the cytoskeletal protein filamin B (FLNB), but a subset do not have FLNB mutations. Exome sequence analysis of three SCT patients negative for FLNB mutations identified an autosomal dominant form of the disease due to heterozygosity for missense or nonsense mutations in MYH3, which encodes embryonic myosin. Cells transfected with the MYH3 missense mutations had reduced TGFβ signaling, revealing a regulatory role for embryonic myosin in the TGFβ signaling pathway. In wild-type mice, there was persistent postnatal expression of embryonic myosin in the small muscles joining the neural arches of the spine suggesting that loss of myosin function in these muscles contribute to the disease. Our findings demonstrate that dominant mutations in MYH3 underlie autosomal dominant SCT, identify a postnatal role for embryonic myosin and suggest that altered regulation of signal transduction in the muscles within the spine may lead to the development of vertebral fusions.

  18. CADDIS Volume 2. Sources, Stressors and Responses: Flow Alteration

    EPA Pesticide Factsheets

    Introduction to the flow alteration module, when to list flow alteration as a candidate cause, ways to measure flow alteration, simple and detailed conceptual model diagrams for flow alteration, flow alteration module references and literature reviews.

  19. Alteration of cell cytoskeleton and functions of cell recovery of normal human osteoblast cells caused by factors associated with real space flight.

    PubMed

    Kapitonova, M Y; Salim, N; Othman, S; Muhd Kamauzaman, T M H T; Ali, A M; Nawawi, H M; Froemming, G R A

    2013-12-01

    Experiments involving short-term space flight have shown an adverse effect on the physiology, morphology and functions of cells investigated. The causes for this effect on cells are: microgravity, temperature fluctuations, mechanical stress, hypergravity, nutrient restriction and others. However, the extent to which these adverse effects can be repaired by short-term space flown cells when recultured in conditions of normal gravity remains unclear. Therefore this study aimed to investigate the effect of short-term spaceflight on cytoskeleton distribution and recovery of cell functions of normal human osteoblast cells. The ultrastructure was evaluated using ESEM. Fluorescent staining was done using Hoechst, Mito Tracker CMXRos and Tubulin Tracker Green for cytoskeleton. Gene expression of cell functions was quantified using qPCR. As a result, recovered cells did not show any apoptotic markers when compared with control. Tubulin volume density (p<0.001) was decreased significantly when compared to control, while mitochondria volume density was insignificantly elevated. Gene expression for IL-6 (p<0.05) and sVCAM-1 (p<0.001) was significantly decreased while alkaline phosphatase (p<0.001), osteocalcin and sICAM (p<0.05) were significantly increased in the recovered cells compared to the control ones. The changes in gene and protein expression of collagen 1A, osteonectin, osteoprotegerin and beta-actin, caused by short-term spaceflight, were statistically not significant. These data indicate that short term space flight causes morphological changes in osteoblast cells which are consistent with hypertrophy, reduced cell differentiation and increased release of monocyte attracting proteins. The long-term effect of these changes on bone density and remodeling requires more detailed studies.

  20. Electrical Stimuli Are Anti-Apoptotic in Skeletal Muscle via Extracellular ATP. Alteration of This Signal in Mdx Mice Is a Likely Cause of Dystrophy

    PubMed Central

    Valladares, Denisse; Almarza, Gonzalo; Contreras, Ariel; Pavez, Mario; Buvinic, Sonja; Jaimovich, Enrique; Casas, Mariana

    2013-01-01

    ATP signaling has been shown to regulate gene expression in skeletal muscle and to be altered in models of muscular dystrophy. We have previously shown that in normal muscle fibers, ATP released through Pannexin1 (Panx1) channels after electrical stimulation plays a role in activating some signaling pathways related to gene expression. We searched for a possible role of ATP signaling in the dystrophy phenotype. We used muscle fibers from flexor digitorum brevis isolated from normal and mdx mice. We demonstrated that low frequency electrical stimulation has an anti-apoptotic effect in normal muscle fibers repressing the expression of Bax, Bim and PUMA. Addition of exogenous ATP to the medium has a similar effect. In dystrophic fibers, the basal levels of extracellular ATP were higher compared to normal fibers, but unlike control fibers, they do not present any ATP release after low frequency electrical stimulation, suggesting an uncoupling between electrical stimulation and ATP release in this condition. Elevated levels of Panx1 and decreased levels of Cav1.1 (dihydropyridine receptors) were found in triads fractions prepared from mdx muscles. Moreover, decreased immunoprecipitation of Cav1.1 and Panx1, suggest uncoupling of the signaling machinery. Importantly, in dystrophic fibers, exogenous ATP was pro-apoptotic, inducing the transcription of Bax, Bim and PUMA and increasing the levels of activated Bax and cytosolic cytochrome c. These evidence points to an involvement of the ATP pathway in the activation of mechanisms related with cell death in muscular dystrophy, opening new perspectives towards possible targets for pharmacological therapies. PMID:24282497

  1. Electrical stimuli are anti-apoptotic in skeletal muscle via extracellular ATP. Alteration of this signal in Mdx mice is a likely cause of dystrophy.

    PubMed

    Valladares, Denisse; Almarza, Gonzalo; Contreras, Ariel; Pavez, Mario; Buvinic, Sonja; Jaimovich, Enrique; Casas, Mariana

    2013-01-01

    ATP signaling has been shown to regulate gene expression in skeletal muscle and to be altered in models of muscular dystrophy. We have previously shown that in normal muscle fibers, ATP released through Pannexin1 (Panx1) channels after electrical stimulation plays a role in activating some signaling pathways related to gene expression. We searched for a possible role of ATP signaling in the dystrophy phenotype. We used muscle fibers from flexor digitorum brevis isolated from normal and mdx mice. We demonstrated that low frequency electrical stimulation has an anti-apoptotic effect in normal muscle fibers repressing the expression of Bax, Bim and PUMA. Addition of exogenous ATP to the medium has a similar effect. In dystrophic fibers, the basal levels of extracellular ATP were higher compared to normal fibers, but unlike control fibers, they do not present any ATP release after low frequency electrical stimulation, suggesting an uncoupling between electrical stimulation and ATP release in this condition. Elevated levels of Panx1 and decreased levels of Cav1.1 (dihydropyridine receptors) were found in triads fractions prepared from mdx muscles. Moreover, decreased immunoprecipitation of Cav1.1 and Panx1, suggest uncoupling of the signaling machinery. Importantly, in dystrophic fibers, exogenous ATP was pro-apoptotic, inducing the transcription of Bax, Bim and PUMA and increasing the levels of activated Bax and cytosolic cytochrome c. These evidence points to an involvement of the ATP pathway in the activation of mechanisms related with cell death in muscular dystrophy, opening new perspectives towards possible targets for pharmacological therapies.

  2. Peripheral blood mononuclear cells as a source to detect markers of homeostatic alterations caused by the intake of diets with an unbalanced macronutrient composition.

    PubMed

    Díaz-Rúa, Rubén; Keijer, Jaap; Caimari, Antoni; van Schothorst, Evert M; Palou, Andreu; Oliver, Paula

    2015-04-01

    Peripheral blood mononuclear cells (PBMCs) are accessible in humans, and their gene expression pattern was shown to reflect overall physiological response of the body to a specific stimulus, such as diet. We aimed to study the impact of sustained intake (4months) of diets with an unbalanced macronutrient proportion (rich in fat or protein) administered isocalorically to a balanced control diet, as physiological stressors on PBMC whole-genome gene expression in rats, to better understand the effects of these diets on metabolism and health and to identify biomarkers of nutritional imbalance. Dietary macronutrient composition (mainly increased protein content) altered PBMC gene expression, with genes involved in immune response being the most affected. Intake of a high-fat (HF) diet decreased the expression of genes related to antigen recognition/presentation, whereas the high-protein (HP) diet increased the expression of these genes and of genes involved in cytokine signaling and immune system maturation/activation. Key energy homeostasis genes (mainly related to lipid metabolism) were also affected, reflecting an adaptive response to the diets. Moreover, HF diet feeding impaired expression of genes involved in redox balance regulation. Finally, we identified a common gene expression signature of 7 genes whose expression changed in the same direction in response to the intake of both diets. These genes, individually or together, constitute a potential risk marker of diet macronutrient imbalance. In conclusion, we newly show that gene expression analysis in PBMCs allows for detection of diet-induced physiological deviations that distinguish from a diet with a proper and equilibrated macronutrient composition.

  3. Deregulation of the OsmiR160 Target Gene OsARF18 Causes Growth and Developmental Defects with an Alteration of Auxin Signaling in Rice

    PubMed Central

    Huang, Jian; Li, Zhiyong; Zhao, Dazhong

    2016-01-01

    MicroRNAs (miRNAs) control gene expression as key negative regulators at the post-transcriptional level. MiR160 plays a pivotal role in Arabidopsis growth and development through repressing expression of its target AUXIN RESPONSE FACTOR (ARF) genes; however, the function of miR160 in monocots remains elusive. In this study, we found that the mature rice miR160 (OsmiR160) was mainly derived from OsMIR160a and OsMIR160b genes. Among four potential OsmiR160 target OsARF genes, the OsARF18 transcript was cleaved at the OsmiR160 target site. Rice transgenic plants (named mOsARF18) expressing an OsmiR160-resistant version of OsARF18 exhibited pleiotropic defects in growth and development, including dwarf stature, rolled leaves, and small seeds. mOsARF18 leaves were abnormal in bulliform cell differentiation and epidermal cell division. Starch accumulation in mOsARF18 seeds was also reduced. Moreover, auxin induced expression of OsMIR160a, OsMIR160b, and OsARF18, whereas expression of OsMIR160a and OsMIR160b as well as genes involved in auxin signaling was altered in mOsARF18 plants. Our results show that negative regulation of OsARF18 expression by OsmiR160 is critical for rice growth and development via affecting auxin signaling, which will advance future studies on the molecular mechanism by which miR160 fine-tunes auxin signaling in plants. PMID:27444058

  4. Exposure to ethinylestradiol during prenatal development and postnatal supplementation with testosterone causes morphophysiological alterations in the prostate of male and female adult gerbils

    PubMed Central

    Perez, Ana Paula Silva; Biancardi, Manoel Francisco; Góes, Rejane Maira; dos Santos, Fernanda Alcântara; Taboga, Sebastião Roberto

    2011-01-01

    Steroids perform significant functions in prostatic development and growth, so that interferences of this equilibrium may predispose the gland to the development of diseases during the life. Embryonic and neonatal exposure to xenoestrogens, many of them with endocrine-disrupting potential, has been related to the induction of disturbances in reproductive system organs. Thus, this study aimed to analyse morphological and immunocytochemical aspects of prostate in both male and female adult gerbils either exposed to ethinylestradiol during the prenatal phase (pregnant females received 10 μg/kg, by gavage) (EE group) or exposed to testosterone (1 mg/kg) during the postnatal period (EE/T group). Serological analysis revealed a rise in estradiol levels in adult males and females of the EE group. A higher incidence of prostatic intraepithelial neoplasia (PIN) was observed in the male and female prostate of the treated groups, besides an increase in collagen and reticular fibres. Immunocytochemistry showed an increase in prostatic epithelial cells immunoreactive to AR and a presence of a smooth muscle layer, evidenced by α actin, in injured regions this way absent in prostatic epithelial buds. These pieces of evidence suggest that the alterations verified in the prostate in adulthood of both sexes may be due to the high oestrogen levels. Either males or females of the EE/T group showed normalized estradiol levels, although prostatic lesions could be observed. While the prostatic gland of male gerbils was more affected than the female prostate, this study showed that the exposure to EE during this critical period of development disrupts the prostate of both sexes in terms of prostatic lesions. PMID:21314741

  5. Comparison of the duration and power spectral changes of monopolar and bipolar M waves caused by alterations in muscle fibre conduction velocity.

    PubMed

    Rodriguez-Falces, Javier; Navallas, Javier; Malanda, Armando; Rodriguez-Martin, Olivia

    2014-08-01

    The muscle compound action potential (M wave) recorded under monopolar configuration reflects both the propagation of the action potentials along the muscle fibres and their extinction at the tendon. M waves recorded under a bipolar configuration contain less cross talk and noise than monopolar M waves, but they do not contain the entire informative content of the propagating potential. The objective of this study was to compare the effect of changes in muscle fibre conduction velocity (MFCV) on monopolar and bipolar M waves and how this effect depends on the distance between the recording electrodes and tendon. The study was based on a simulation approach and on an experimental investigation of the characteristics of surface M waves evoked in the vastus lateralis during 4-s step-wise isometric contractions in knee extension at 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% MVC. The peak-to-peak duration (Durpp) and median frequency (Fmedian) of the M waves were calculated. For monopolar M waves, changes in Durpp and Fmedian produced by MFCV depended on the distance from the electrode to the tendon, whereas, for bipolar M waves, changes in Durpp and Fmedian were largely independent of the electrode-to-tendon distance. When the distance between the detection point and tendon lay between approximately 15 and 40mm, changes in Durpp of bipolar M waves were more pronounced than those of distal monopolar M waves but less marked than those of proximal monopolar M waves, and the opposite occurred for Fmedian. Since, for bipolar M waves, changes in duration and power spectral features produced by alterations in MFCV are not influenced by the electrode-to-tendon distance, the bipolar electrode configuration is a preferable choice over monopolar arrangements to estimate changes in conduction velocity.

  6. Chronic overload of SEPT4, a parkin substrate that aggregates in Parkinson’s disease, causes behavioral alterations but not neurodegeneration in mice

    PubMed Central

    2013-01-01

    Background In autosomal recessive early-onset Parkinsonism (PARK2), the pathogenetic process from the loss of function of a ubiquitin ligase parkin to the death of dopamine neurons remains unclear. A dominant hypothesis attributes the neurotoxicity to accumulated substrates that are exempt from parkin-mediated degradation. Parkin substrates include two septins; SEPT4/CDCrel-2 which coaggregates with α-synuclein as Lewy bodies in Parkinson’s disease, and its closest homolog SEPT5/CDCrel-1/PNUTL1 whose overload with viral vector can rapidly eliminate dopamine neurons in rats. However, chronic effects of pan-neural overload of septins have never been examined in mammals. To address this, we established a line of transgenic mice that express the largest gene product SEPT454kDa via the prion promoter in the entire brain. Results Histological examination and biochemical quantification of SEPT4-associated proteins including α-synuclein and the dopamine transporter in the nigrostriatal dopamine neurons found no significant difference between Sept4Tg/+ and wild-type littermates. Thus, the hypothetical pathogenicity by the chronic overload of SEPT4 alone, if any, is insufficient to trigger neurodegenerative process in the mouse brain. Intriguingly, however, a systematic battery of behavioral tests revealed unexpected abnormalities in Sept4Tg/+ mice that include consistent attenuation of voluntary activities in distinct behavioral paradigms and altered social behaviors. Conclusions Together, these data indicate that septin dysregulations commonly found in postmortem human brains with Parkinson’s disease, schizophrenia and bipolar disorders may be responsible for a subset of behavioral abnormalities in the patients. PMID:23938054

  7. Using an extended 2D hydrodynamic model for evaluating damage risk caused by extreme rain events: Flash-Flood-Risk-Map (FFRM) Upper Austria

    NASA Astrophysics Data System (ADS)

    Humer, Günter; Reithofer, Andreas

    2016-04-01

    Using an extended 2D hydrodynamic model for evaluating damage risk caused by extreme rain events: Flash-Flood-Risk-Map (FFRM) Upper Austria Considering the increase in flash flood events causing massive damage during the last years in urban but also rural areas [1-4], the requirement for hydrodynamic calculation of flash flood prone areas and possible countermeasures has arisen to many municipalities and local governments. Besides the German based URBAS project [1], also the EU-funded FP7 research project "SWITCH-ON" [5] addresses the damage risk caused by flash floods in the sub-project "FFRM" (Flash Flood Risk Map Upper Austria) by calculating damage risk for buildings and vulnerable infrastructure like schools and hospitals caused by flash-flood driven inundation. While danger zones in riverine flooding are established as an integral part of spatial planning, flash floods caused by overland runoff from extreme rain events have been for long an underrated safety hazard not only for buildings and infrastructure, but man and animals as well. Based on the widespread 2D-model "hydro_as-2D", an extension was developed, which calculates the runoff formation from a spatially and temporally variable precipitation and determines two dimensionally the land surface area runoff and its concentration. The conception of the model is to preprocess the precipitation data and calculate the effective runoff-volume for a short time step of e.g. five minutes. This volume is applied to the nodes of the 2D-model and the calculation of the hydrodynamic model is started. At the end of each time step, the model run is stopped, the preprocessing step is repeated and the hydraulic model calculation is continued. In view of the later use for the whole of Upper Austria (12.000 km²) a model grid of 25x25 m² was established using digital elevation data. Model parameters could be estimated for the small catchment of river Ach, which was hit by an intense rain event with up to 109 mm per hour

  8. Development of Spontaneous Mammary Tumors in BALB/c-p53+/-Mice: Detection of Early Genetic Alterations and the Mapping of BALB/c Susceptibility Genes

    DTIC Science & Technology

    2005-07-01

    the Mapping of BALB/c Susceptibility Genes PRINCIPAL INVESTIGATOR: Xiaoling Hill, Ph.D. Joseph Jerry, Ph.D. CONTRACTING ORGANIZATION: University of...0315 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Xiaoling Hill, Ph.D. 5e. TASK NUMBER Joseph Jerry, Ph.D. 5f. WORK UNIT NUMBER 7...E] R2I L L El El D E 9a 23 28 129 175 211 254 254 255 266 267 268 MTu MTu MTu MTu MTu MTu MTu Sar Lym Lip MTu Lu D11MIT71 (1.1) * LI L I I LI I I

  9. Disturbance Distance: Using a process based ecosystem model to estimate and map potential thresholds in disturbance rates that would give rise to fundamentally altered ecosystems

    NASA Astrophysics Data System (ADS)

    Dolan, K. A.; Hurtt, G. C.; Fisk, J.; Flanagan, S.; LePage, Y.; Sahajpal, R.

    2014-12-01

    Disturbance plays a critical role in shaping the structure and function of forested ecosystems as well as the ecosystem services they provide, including but not limited to: carbon storage, biodiversity habitat, water quality and flow, and land atmosphere exchanges of energy and water. As recent studies highlight novel disturbance regimes resulting from pollution, invasive pests and climate change, there is a need to include these alterations in predictions of future forest function and structure. The Ecosystem Demography (ED) model is a mechanistic model of forest ecosystem dynamics in which individual-based forest dynamics can be efficiently implemented over regional to global scales due to advanced scaling methods. We utilize ED to characterize the sensitivity of potential vegetation structure and function to changes in rates of density independent mortality. Disturbance rate within ED can either be altered directly or through the development of sub-models. Disturbance sub-models in ED currently include fire, land use and hurricanes. We use a tiered approach to understand the sensitivity of North American ecosystems to changes in background density independent mortality. Our first analyses were conducted at half-degree spatial resolution with a constant rate of disturbance in space and time, which was altered between runs. Annual climate was held constant at the site level and the land use and fire sub-models were turned off. Results showed an ~ 30% increase in non-forest area across the US when disturbance rates were changed from 0.6% a year to 1.2% a year and a more than 3.5 fold increase in non-forest area when disturbance rates doubled again from 1.2% to 2.4%. Continued runs altered natural background disturbance rates with the existing fire and hurricane sub models turned on as well as historic and future land use. By quantify differences between model outputs that characterize ecosystem structure and function related to the carbon cycle across the US, we

  10. Altered Wnt Signaling Pathway in Cognitive Impairment Caused by Chronic Intermittent Hypoxia: Focus on Glycogen Synthase Kinase-3β and β-catenin

    PubMed Central

    Pan, Yue-Ying; Deng, Yan; Xie, Sheng; Wang, Zhi-Hua; Wang, Yu; Ren, Jie; Liu, Hui-Guo

    2016-01-01

    Background: Cognitive impairment is a severe complication caused by obstructive sleep apnea (OSA). The mechanisms of causation are still unclear. The Wnt/β-catenin signaling pathway is involved in cognition, and abnormalities in it are implicated in neurological disorders. Here, we explored the Wnt/β-catenin signaling pathway abnormalities caused by chronic intermittent hypoxia (CIH), the most characteristic pathophysiological component of OSA. Methods: We divided 32 4-week-old male C57/BL mice into four groups of eight each: a CIH + normal saline (NS) group, CIH + LiCl group, sham CIH + NS group, and a sham CIH + LiCl group. The spatial learning performance of each group was assessed by using the Morris water maze (MWM). Protein expressions of glycogen synthase kinase-3β (GSK-3β) and β-catenin in the hippocampus were examined using the Western blotting test. EdU labeling and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining methods were used, respectively, to determine the proliferation and apoptosis of neurons in the hippocampal dentate gyrus region. Results: Mice exposed to CIH showed impaired spatial learning performance in the MWM, including increased mean escape latencies to reach the target platform, decreased mean times passing through the target platform and mean duration in the target quadrant. The GSK-3β activity increased, and expression of β-catenin decreased significantly in the hippocampus of the CIH-exposed mice. Besides, CIH significantly increased hippocampal neuronal apoptosis, with an elevated apoptosis index. Meanwhile, LiCl decreased the activity of GSK-3β and increased the expression of β-catenin and partially reversed the spatial memory deficits in MWM and the apoptosis caused by CIH. Conclusions: Wnt/β-catenin signaling pathway abnormalities possibly play an important role in the development of cognitive deficits among mice exposed to CIH and that LiCl might attenuate CIH-induced cognitive

  11. The pathogenicity determinant of Citrus tristeza virus causing the seedling yellows syndrome maps at the 3'-terminal region of the viral genome.

    PubMed

    Albiach-Marti, Maria R; Robertson, Cecile; Gowda, Siddarame; Tatineni, Satyanarayana; Belliure, Belén; Garnsey, Stephen M; Folimonova, Svetlana Y; Moreno, Pedro; Dawson, William O

    2010-01-01

    Citrus tristeza virus (CTV) (genus Closterovirus, family Closteroviridae) causes some of the more important viral diseases of citrus worldwide. The ability to map disease-inducing determinants of CTV is needed to develop better diagnostic and disease control procedures. A distinctive phenotype of some isolates of CTV is the ability to induce seedling yellows (SY) in sour orange, lemon and grapefruit seedlings. In Florida, the decline isolate of CTV, T36, induces SY, whereas a widely distributed mild isolate, T30, does not. To delimit the viral sequences associated with the SY syndrome, we created a number of T36/T30 hybrids by substituting T30 sequences into different regions of the 3' half of the genome of an infectious cDNA of T36. Eleven T36/T30 hybrids replicated in Nicotiana benthamiana protoplasts. Five of these hybrids formed viable virions that were mechanically transmitted to Citrus macrophylla, a permissive host for CTV. All induced systemic infections, similar to that of the parental T36 clone. Tissues from these C. macrophylla source plants were then used to graft inoculate sour orange and grapefruit seedlings. Inoculation with three of the T30/T36 hybrid constructs induced SY symptoms identical to those of T36; however, two hybrids with T30 substitutions in the p23-3' nontranslated region (NTR) (nucleotides 18 394-19 296) failed to induce SY. Sour orange seedlings infected with a recombinant non-SY p23-3' NTR hybrid also remained symptomless when challenged with the parental virus (T36), demonstrating the potential feasibility of using engineered constructs of CTV to mitigate disease.

  12. αB-Crystallin R120G variant causes cardiac arrhythmias and alterations in the expression of Ca(2+) -handling proteins and endoplasmic reticulum stress in mice.

    PubMed

    Jiao, Qibin; Sanbe, Atsushi; Zhang, Xingwei; Liu, Jun-Ping; Minamisawa, Susumu

    2014-08-01

    Mutations of αB-crystallin (CryαB), a small heat shock protein abundantly expressed in cardiac and skeletal muscles, are known to cause desmin-related myopathies. The CryαB R120G allele has been linked to a familial desminopathy and, in transgenic mice, causes a sudden death at about 28 weeks of age. To investigate the mechanisms of the sudden cardiac arrest of CryαB R120G transgenic mice, we prepared protein samples from left ventricular tissues of two different age groups (10 and 28 weeks) and examined Ca(2+) -handling proteins. Expression of sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) 2, phospholamban, ryanodine receptor 2 and calsequestrin 2 was significantly decreased in 28- versus 10-week-old CryαB R120G transgenic mice. In addition, low heart rate variability, including heart rate, total power and low frequency, was observed and continuous electrocardiogram monitoring revealed cardiac arrhythmias, such as ventricular tachycardia, atrioventricular block and atrial flutter, in 28-week-old CryαB R120G transgenic mice. In contrast, expression of endoplasmic reticulum (ER) degradation enhancing α-mannosidase-like protein, inositol requirement 1 and X-box binding protein 1 were increased significantly in 28- versus 10-week-old CryαBR120G transgenic mice, suggesting that the CryαBR120G transgenic mice exhibit increased ER stress compared with wild-type mice. Together, the data suggest that the CryαB R120G dominant variant induces ER stress and impairs Ca(2+) regulation, leading to ageing-related cardiac dysfunction, arrhythmias and decreased autonomic tone with shortened lifespan.

  13. Overexpression of OsRAA1 causes pleiotropic phenotypes in transgenic rice plants, including altered leaf, flower, and root development and root response to gravity.

    PubMed

    Ge, Lei; Chen, Hui; Jiang, Jia-Fu; Zhao, Yuan; Xu, Ming-Li; Xu, Yun-Yuan; Tan, Ke-hui; Xu, Zhi-Hong; Chong, Kang

    2004-07-01

    There are very few root genes that have been described in rice as a monocotyledonous model plant so far. Here, the OsRAA1 (Oryza sativa Root Architecture Associated 1) gene has been characterized molecularly. OsRAA1 encodes a 12.0-kD protein that has 58% homology to the AtFPF1 (Flowering Promoting Factor 1) in Arabidopsis, which has not been reported as modulating root development yet. Data of in situ hybridization and OsRAA1::GUS transgenic plant showed that OsRAA1 expressed specifically in the apical meristem, the elongation zone of root tip, steles of the branch zone, and the young lateral root. Constitutive expression of OsRAA1 under the control of maize (Zea mays) ubiquitin promoter resulted in phenotypes of reduced growth of primary root, increased number of adventitious roots and helix primary root, and delayed gravitropic response of roots in seedlings of rice (Oryza sativa), which are similar to the phenotypes of the wild-type plant treated with auxin. With overexpression of OsRAA1, initiation and growth of adventitious root were more sensitive to treatment of auxin than those of the control plants, while their responses to 9-hydroxyfluorene-9-carboxylic acid in both transgenic line and wild type showed similar results. OsRAA1 constitutive expression also caused longer leaves and sterile florets at the last stage of plant development. Analysis of northern blot and GUS activity staining of OsRAA1::GUS transgenic plants demonstrated that the OsRAA1 expression was induced by auxin. At the same time, overexpression of OsRAA1 also caused endogenous indole-3-acetic acid to increase. These data suggested that OsRAA1 as a new gene functions in the development of rice root systems, which are mediated by auxin. A positive feedback regulation mechanism of OsRAA1 to indole-3-acetic acid metabolism may be involved in rice root development in nature.

  14. Acute exposure to bisphenol A and cadmium causes changes in the morphology of gerbil ventral prostates and promotes alterations in androgen-dependent proliferation and cell death.

    PubMed

    Colleta, Simone J; Antoniassi, Julia Q; Zanatelli, Marianna; Santos, Fernanda C A; Góes, Rejane M; Vilamaior, Patricia S L; Taboga, Sebastião R

    2017-01-01

    Bisphenol A (BPA) and cadmium (Cd) are environmental pollutants that are implicated in potential reproductive effects, including damage to the prostate gland. Their action during puberty requires analysis to determine the relationship of these compounds with the testosterone peak that occurs during this phase. This study evaluated whether exposure to BPA and Cd during puberty can cause changes in the morphology, proliferation and cell death and androgen receptor (AR) immunostaining of the ventral prostates of normal and castrated male gerbils (Meriones unguiculatus), considering an acute exposure to the chemicals and evaluation after short (52d) and long (120d) periods. Generally, morphometric-stereological results demonstrated that administration of BPA and Cd (individually or in combination) increased epithelial height, smooth muscle layer (SML) thickness and nuclear area and perimeter, and that these parameters were reduced in castrated animals. In addition, these groups showed important inflammatory processes but not prostate lesions. The proliferation/death rates of prostatic cells obtained by PCNA and TUNEL immunostaining demonstrated increased cell death in the 52d groups; in contrast, the gland acquired a more proliferative nature in the 120d groups. AR immunostaining showed that BPA and Cd compounds interact with ARs in different ways depending on the evaluated period and the hormonal profile of the animal. We conclude that BPA and cadmium are important agents in changing the morphology, proliferation and death of prostatic cells, in addition to interacting with ARs in different patterns. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 48-61, 2017.

  15. Mutations in human C2CD3 cause skeletal dysplasia and provide new insights into phenotypic and cellular consequences of altered C2CD3 function

    PubMed Central

    Cortés, Claudio R.; McInerney-Leo, Aideen M.; Vogel, Ida; Rondón Galeano, Maria C.; Leo, Paul J.; Harris, Jessica E.; Anderson, Lisa K.; Keith, Patricia A.; Brown, Matthew A.; Ramsing, Mette; Duncan, Emma L.; Zankl, Andreas; Wicking, Carol

    2016-01-01

    Ciliopathies are a group of genetic disorders caused by defective assembly or dysfunction of the primary cilium, a microtubule-based cellular organelle that plays a key role in developmental signalling. Ciliopathies are clinically grouped in a large number of overlapping disorders, including the orofaciodigital syndromes (OFDS), the short rib polydactyly syndromes and Jeune asphyxiating thoracic dystrophy. Recently, mutations in the gene encoding the centriolar protein C2CD3 have been described in two families with a new sub-type of OFDS (OFD14), with microcephaly and cerebral malformations. Here we describe a third family with novel compound heterozygous C2CD3 mutations in two fetuses with a different clinical presentation, dominated by skeletal dysplasia with no microcephaly. Analysis of fibroblast cultures derived from one of these fetuses revealed a reduced ability to form cilia, consistent with previous studies in C2cd3-mutant mouse and chicken cells. More detailed analyses support a role for C2CD3 in basal body maturation; but in contrast to previous mouse studies the normal recruitment of the distal appendage protein CEP164 suggests that this protein is not sufficient for efficient basal body maturation and subsequent axonemal extension in a C2CD3-defective background. PMID:27094867

  16. Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signaling.

    PubMed

    Logan, Clare V; Szabadkai, György; Sharpe, Jenny A; Parry, David A; Torelli, Silvia; Childs, Anne-Marie; Kriek, Marjolein; Phadke, Rahul; Johnson, Colin A; Roberts, Nicola Y; Bonthron, David T; Pysden, Karen A; Whyte, Tamieka; Munteanu, Iulia; Foley, A Reghan; Wheway, Gabrielle; Szymanska, Katarzyna; Natarajan, Subaashini; Abdelhamed, Zakia A; Morgan, Joanne E; Roper, Helen; Santen, Gijs W E; Niks, Erik H; van der Pol, W Ludo; Lindhout, Dick; Raffaello, Anna; De Stefani, Diego; den Dunnen, Johan T; Sun, Yu; Ginjaar, Ieke; Sewry, Caroline A; Hurles, Matthew; Rizzuto, Rosario; Duchen, Michael R; Muntoni, Francesco; Sheridan, Eamonn

    2014-02-01

    Mitochondrial Ca(2+) uptake has key roles in cell life and death. Physiological Ca(2+) signaling regulates aerobic metabolism, whereas pathological Ca(2+) overload triggers cell death. Mitochondrial Ca(2+) uptake is mediated by the Ca(2+) uniporter complex in the inner mitochondrial membrane, which comprises MCU, a Ca(2+)-selective ion channel, and its regulator, MICU1. Here we report mutations of MICU1 in individuals with a disease phenotype characterized by proximal myopathy, learning difficulties and a progressive extrapyramidal movement disorder. In fibroblasts from subjects with MICU1 mutations, agonist-induced mitochondrial Ca(2+) uptake at low cytosolic Ca(2+) concentrations was increased, and cytosolic Ca(2+) signals were reduced. Although resting mitochondrial membrane potential was unchanged in MICU1-deficient cells, the mitochondrial network was severely fragmented. Whereas the pathophysiology of muscular dystrophy and the core myopathies involves abnormal mitochondrial Ca(2+) handling, the phenotype associated with MICU1 deficiency is caused by a primary defect in mitochondrial Ca(2+) signaling, demonstrating the crucial role of mitochondrial Ca(2+) uptake in humans.

  17. Near-infrared reflectance of zunyite: implications for field mapping and remote-sensing detection of hydrothermally altered high alumina rocks.

    USGS Publications Warehouse

    Crowley, J.K.

    1984-01-01

    Several hydroxyl-bearing minerals have diagnostic absorption bands in the 2.0-2.4 mu m wave length range, and can be identified with an orbital radiometer and with high-resolution airborne and field portable spectrometers. Among such minerals, zunyite, 143Al13Si5O20(OH,F)18Cl, has distinctive spectral absorption characteristics and is notably restricted to, and thus an indicator mineral of, advanced argillic alteration. Although seldom noted because it visually resembles quartz, zunyite is probably not as rare as generally believed. Laboratory measurements and general considerations underlie suggestions favouring the feasibility of detecting zunyite, alone and in mixtures with other Al-OH minerals, using field portable spectrometers.-G.J.N.

  18. The D50N mutation and syndromic deafness: altered Cx26 hemichannel properties caused by effects on the pore and intersubunit interactions.

    PubMed

    Sanchez, Helmuth A; Villone, Krista; Srinivas, Miduturu; Verselis, Vytas K

    2013-07-01

    Mutations in the GJB2 gene, which encodes Cx26, are the most common cause of sensorineural deafness. In syndromic cases, such as keratitis-ichthyosis-deafness (KID) syndrome, in which deafness is accompanied by corneal inflammation and hyperkeratotic skin, aberrant hemichannel function has emerged as the leading contributing factor. We found that D50N, the most frequent mutation associated with KID syndrome, produces multiple aberrant hemichannel properties, including loss of inhibition by extracellular Ca(2+), decreased unitary conductance, increased open hemichannel current rectification and voltage-shifted activation. We demonstrate that D50 is a pore-lining residue and that negative charge at this position strongly influences open hemichannel properties. Examination of two putative intersubunit interactions involving D50 suggested by the Cx26 crystal structure, K61-D50 and Q48-D50, showed no evidence of a K61-D50 interaction in hemichannels. However, our data suggest that Q48 and D50 interact and disruption of this interaction shifts hemichannel activation positive along the voltage axis. Additional shifts in activation by extracellular Ca(2+) remained in the absence of a D50-Q48 interaction but required an Asp or Glu at position 50, suggesting a separate electrostatic mechanism that critically involves this position. In gap junction (GJ) channels, D50 substitutions produced loss of function, whereas K61 substitutions functioned as GJ channels but not as hemichannels. These data demonstrate that D50 exerts effects on Cx26 hemichannel and GJ channel function as a result of its dual role as a pore residue and a component of an intersubunit complex in the extracellular region of the hemichannel. Differences in the effects of substitutions in GJ channels and hemichannels suggest that perturbations in structure occur upon hemichannel docking that significantly impact function. Collectively, these data provide insight into Cx26 structure-function and the underlying

  19. Neonatal exposure to mild hyperoxia causes persistent increases in oxidative stress and immune cells in the lungs of mice without altering lung structure.

    PubMed

    Bouch, Sheena; O'Reilly, Megan; Harding, Richard; Sozo, Foula

    2015-09-01

    Preterm infants often require supplemental oxygen due to lung immaturity, but hyperoxia can contribute to an increased risk of respiratory illness later in life. Our aim was to compare the effects of mild and moderate levels of neonatal hyperoxia on markers of pulmonary oxidative stress and inflammation and on lung architecture; both immediate and persistent effects were assessed. Neonatal mice (C57BL6/J) were raised in either room air (21% O2), mild (40% O2), or moderate (65% O2) hyperoxia from birth until postnatal day 7 (P7d). The mice were killed at either P7d (immediate effects) or lived in air until adulthood (P56d, persistent effects). We enumerated macrophages in lung tissue at P7d and immune cells in bronchoalveolar lavage fluid (BALF) at P56d. At P7d and P56d, we assessed pulmonary oxidative stress [heme oxygenase-1 (HO-1) and nitrotyrosine staining] and lung architecture. The data were interrogated for sex differences. At P7d, HO-1 gene expression was greater in the 65% O2 group than in the 21% O2 group. At P56d, the area of nitrotyrosine staining and number of immune cells were greater in the 40% O2 and 65% O2 groups relative to the 21% O2 group. Exposure to 65% O2, but not 40% O2, led to larger alveoli and lower tissue fraction in the short term and to persistently fewer bronchiolar-alveolar attachments. Exposure to 40% O2 or 65% O2 causes persistent increases in pulmonary oxidative stress and immune cells, suggesting chronic inflammation within the adult lung. Unlike 65% O2, 40% O2 does not affect lung architecture.

  20. Advanced maternal age causes adverse programming of mouse blastocysts leading to altered growth and impaired cardiometabolic health in post-natal life

    PubMed Central

    Velazquez, M.A.; Smith, C.G.C.; Smyth, N.R.; Osmond, C.; Fleming, T.P.

    2016-01-01

    aged mice was decreased (P < 0.05) relative to young mice due to a lower number of cells in the trophectoderm (mean ± SEM: 34.5 ± 2.1 versus 29.6 ± 1.0). Weekly body weight did not differ in male offspring, but an increase in body weight from Week 13 onwards was observed in Old-ET females (final body weight at post-natal Week 30: 38.5 ± 0.8 versus 33.4 ± 0.8 g, P < 0.05). Blood pressure was increased in Old-ET offspring at Weeks 9–15 in males (Week 9: 108.5 ± 3.13 versus 100.8 ± 1.5 mmHg, Week 15: 112.9 ± 3.2 versus 103.4 ± 2.1 mmHg) and Week 15 in females (115.9 ± 3.7 versus 102.8 ± 0.7 mmHg; all P < 0.05 versus Young-ET). The GTT results and organ allometry were not affected in male offspring. In contrast, Old-ET females displayed a greater (P < 0.05) peak glucose concentration at 30 min during the GTT (21.1 ± 0.4 versus 17.8 ± 1.16 mmol/l) and their spleen weight (88.2 ± 2.6 ± 105.1 ± 4.6 mg) and several organ:body weight ratios (g/g × 103) were decreased (P < 0.05 versus Young-ET), including the heart (3.7 ± 0.06 versus 4.4 ± 0.08), lungs (4.4 ± 0.1 versus 5.0 ± 0.1), spleen (2.4 ± 0.06 versus 3.2 ± 0.1) and liver (36.4 ± 0.6 versus 39.1 ± 0.9). LIMITATIONS, REASONS FOR CAUTION Results from experimental animal models cannot be extrapolated to humans. Nevertheless, they are valuable to develop conceptual models that can produce hypotheses for eventual testing in the target species (i.e. humans). WIDER IMPLICATIONS OF THE FINDINGS Our data show that offspring from mouse embryos from aged mothers can develop altered phenotypes during post-natal development compared with embryos from young mothers. Because all embryos were transferred into young mothers for the duration of pregnancy to normalize the maternal in vivo environment, our findings indicate that adverse programming via AMA is already established at the blastocyst stage. Whilst human embryos display increased aneuploidy compared with mouse, we believe our data have implications for

  1. Intractable paroxysmal tachycardia caused by a concealed retrogradely conducting Kent bundle. Demonstration by epicardial mapping and cure of tachycardias by surgical interruption of the His bundle.

    PubMed Central

    Denes, P; Wyndham, C R; Rosen, K M

    1976-01-01

    Electrophysiological and epicardial mapping studies are described in a patient without pre-excitation who had intractable recurrent paroxysmal supraventricular tachycardia. Electrophysiological studies revealed fixed VA conduction times during both rapid ventricular pacing and coupled ventricular stimulation. Catheter mapping of atrial activation during retrograde conduction and during induced paroxysmal supraventricular tachycardia revealed early distal coronary sinus activation (posterior left atrium) relative to the low septal, low lateral, and high lateral right atrium. These studies suggested the presence of a concealed left-sided bypass tract. The patient underwent surgical interruption of the His bundle for control of paroxysmal supraventricular tachycardia. Epicardial mapping of the atria (during ventricular pacing) confirmed the presence of a concealed left-sided bypass tract. Surgery produced antegrade av block (while retrograde conduction was maintained) and total cure of paroxysmal supraventricular tachycardia. This is the first reported case of a concealed retrograde extranodal pathway documented by epicardial mapping. Images PMID:973901

  2. Disturbance Distance: Combining a process based ecosystem model and remote sensing data to map the vulnerability of U.S. forested ecosystems to potentially altered disturbance rates

    NASA Astrophysics Data System (ADS)

    Dolan, K. A.

    2015-12-01

    Disturbance plays a critical role in shaping the structure and function of forested ecosystems as well as the ecosystem services they provide, including but not limited to: carbon storage, biodiversity habitat, water quality and flow, and land atmosphere exchanges of energy and water. In addition, recent studies suggest that disturbance rates may increase in the future under altered climate and land use scenarios. Thus understanding how vulnerable forested ecosystems are to potential changes in disturbance rates is of high importance. This study calculated the theoretical threshold rate of disturbance for which forest ecosystems could no longer be sustained (λ*) across the Coterminous U.S. using an advanced process based ecosystem model (ED). Published rates of disturbance (λ) in 50 study sites were obtained from the North American Forest Disturbance (NAFD) program. Disturbance distance (λ* - λ) was calculated for each site by differencing the model based threshold under current climate conditions and average observed rates of disturbance over the last quarter century. Preliminary results confirm all sample forest sites have current average rates of disturbance below λ*, but there were interesting patterns in the recorded disturbance distances. In general western sites had much smaller disturbance distances, suggesting higher vulnerability to change, while eastern sites showed larger buffers. Ongoing work is being conducted to assess the vulnerability of these sites in the context of potential future changes by propagating scenarios of future climate and land-use change through the analysis.

  3. Alteration of structure and function of ATP synthase and cytochrome c oxidase by lack of Fo-a and Cox3 subunits caused by mitochondrial DNA 9205delTA mutation.

    PubMed

    Hejzlarová, Kateřina; Kaplanová, Vilma; Nůsková, Hana; Kovářová, Nikola; Ješina, Pavel; Drahota, Zdeněk; Mráček, Tomáš; Seneca, Sara; Houštěk, Josef

    2015-03-15

    Mutations in the MT-ATP6 gene are frequent causes of severe mitochondrial disorders. Typically, these are missense mutations, but another type is represented by the 9205delTA microdeletion, which removes the stop codon of the MT-ATP6 gene and affects the cleavage site in the MT-ATP8/MT-ATP6/MT-CO3 polycistronic transcript. This interferes with the processing of mRNAs for the Atp6 (Fo-a) subunit of ATP synthase and the Cox3 subunit of cytochrome c oxidase (COX). Two cases described so far presented with strikingly different clinical phenotypes-mild transient lactic acidosis or fatal encephalopathy. To gain more insight into the pathogenic mechanism, we prepared 9205delTA cybrids with mutation load ranging between 52 and 99% and investigated changes in the structure and function of ATP synthase and the COX. We found that 9205delTA mutation strongly reduces the levels of both Fo-a and Cox3 proteins. Lack of Fo-a alters the structure but not the content of ATP synthase, which assembles into a labile, ∼60 kDa smaller, complex retaining ATP hydrolytic activity but which is unable to synthesize ATP. In contrast, lack of Cox3 limits the biosynthesis of COX but does not alter the structure of the enzyme. Consequently, the diminished mitochondrial content of COX and non-functional ATP synthase prevent most mitochondrial ATP production. The biochemical effects caused by the 9205delTA microdeletion displayed a pronounced threshold effect above ∼90% mutation heteroplasmy. We observed a linear relationship between the decrease in subunit Fo-a or Cox3 content and the functional presentation of the defect. Therefore we conclude that the threshold effect originated from a gene-protein level.

  4. Mapping and characterization of land subsidence in Beijing Plain caused by groundwater pumping using the Small Baseline Subset (SBAS) InSAR technique

    NASA Astrophysics Data System (ADS)

    Gao, M. L.; Gong, H. L.; Chen, B. B.; Zhou, C. F.; Liu, K. S.; Shi, M.

    2015-11-01

    InSAR time series analysis is widely used for detection and monitoring of slow surface deformation. In this paper, 15 TerraSAR-X radar images acquired in stripmap mode between 2012 and 2013 are processed for land subsidence monitoring with the Small Baseline Subset (SBAS) approach in Beijing Plain in China. Mapping results produced by SBAS show that the subsidence rates in the area of Beijing Plain range from -97.5 (subsidence) and to +23.8 mm yr-1 (uplift), relative to a presumably stable benchmark. The mapping result also reveals that there are the five subsidence centers formed by surface deformation spreading north to south east of the downtown. An uneven subsidence patten was detected near the Beijing Capital International Airpor, which may be related to loading of buildings and the aircraft.

  5. Rapid Identification of a Natural Knockout Allele of ARMADILLO REPEAT-CONTAINING KINESIN1 That Causes Root Hair Branching by Mapping-By-Sequencing1[C][W

    PubMed Central

    Rishmawi, Louai; Sun, Hequan; Schneeberger, Korbinian; Hülskamp, Martin; Schrader, Andrea

    2014-01-01

    In Arabidopsis (Arabidopsis thaliana), branched root hairs are an indicator of defects in root hair tip growth. Among 62 accessions, one accession (Heiligkreuztal2 [HKT2.4]) displayed branched root hairs, suggesting that this accession carries a mutation in a gene of importance for tip growth. We determined 200- to 300-kb mapping intervals using a mapping-by-sequencing approach of F2 pools from crossings of HKT2.4 with three different accessions. The intersection of these mapping intervals was 80 kb in size featuring not more than 36 HKT2.4-specific single nucleotide polymorphisms, only two of which changed the coding potential of genes. Among them, we identified the causative single nucleotide polymorphism changing a splicing site in ARMADILLO REPEAT-CONTAINING KINESIN1. The applied strategies have the potential to complement statistical methods in high-throughput phenotyping studies using different natural accessions to identify causative genes for distinct phenotypes represented by only one or a few accessions. PMID:25248719

  6. Gestational and lactational exposure to atrazine via the drinking water causes specific behavioral deficits and selectively alters monoaminergic systems in C57BL/6 mouse dams, juvenile and adult offspring.

    PubMed

    Lin, Zhoumeng; Dodd, Celia A; Xiao, Shuo; Krishna, Saritha; Ye, Xiaoqin; Filipov, Nikolay M

    2014-09-01

    Atrazine (ATR) is one of the most frequently detected pesticides in the U.S. water supply. This study aimed to investigate neurobehavioral and neurochemical effects of ATR in C57BL/6 mouse offspring and dams exposed to a relatively low (3 mg/l, estimated intake 1.4 mg/kg/day) concentration of ATR via the drinking water (DW) from gestational day 6 to postnatal day (PND) 23. Behavioral tests included open field, pole, grip strength, novel object recognition (NOR), forced swim, and marble burying tests. Maternal weight gain and offspring (PND21, 35, and 70) body or brain weights were not affected by ATR. However, ATR-treated dams exhibited decreased NOR performance and a trend toward hyperactivity. Juvenile offspring (PND35) from ATR-exposed dams were hyperactive (both sexes), spent less time swimming (males), and buried more marbles (females). In adult offspring (PND70), the only behavioral change was a sex-specific (females) decreased NOR performance by ATR. Neurochemically, a trend toward increased striatal dopamine (DA) in dams and a significant increase in juvenile offspring (both sexes) was observed. Additionally, ATR exposure decreased perirhinal cortex serotonin in the adult female offspring. These results suggest that perinatal DW exposure to ATR targets the nigrostriatal DA pathway in dams and, especially, juvenile offspring, alters dams' cognitive performance, induces sex-selective changes involving motor and emotional functions in juvenile offspring, and decreases cognitive ability of adult female offspring, with the latter possibly associated with altered perirhinal cortex serotonin homeostasis. Overall, ATR exposure during gestation and lactation may cause adverse nervous system effects to both offspring and dams.

  7. Trans-10,cis-12-CLA-caused lipodystrophy is associated with profound changes of fatty acid profiles of liver, white adipose tissue and erythrocytes in mice: possible link to tissue-specific alterations of fatty acid desaturation.

    PubMed

    Jaudszus, Anke; Moeckel, Peter; Hamelmann, Eckard; Jahreis, Gerhard

    2010-01-01

    Dietary supplementation with conjugated linoleic acid (CLA) has been shown to reduce body fat mass. To investigate the effects of individual CLA isomers on the fatty acid profiles of lipogenic (liver and white adipose) and lipid sensitive (erythrocyte) tissues, BALB/c mice were fed with 1 of 2 diets supplemented with either a c9,t11-CLA-enriched and t10,c12-CLA-free or a CLA-mixture containing both isomers in equal amounts (1% w/w of the diet) for 5 weeks. A control group was fed with a diet enriched in sunflower oil to energy balance the CLA. Compared to the t10,c12-CLA-free and the control diets, we observed a significant reduction of adipose tissue accompanied by fatty livers in the CLA-mix-fed group. These alterations in body fat distribution entailed a conspicuous shift of the fatty acid profiles of adipose tissue and livers. Liver enlargement was mainly caused by accumulation of C18 monoenes that accounted for 67 ± 1% of total fatty acid methyl esters. The significant reduction of the 18:0/18:1 desaturation index in the liver upon CLA-mix diet indicated high stearoyl-CoA desaturase activity. In contrast, reduction in white adipose tissue was largely driven by percental reduction of monounsaturated fatty acids (p ≤ 0.001). 16:0/ 16:1 and 18:0/18:1 desaturation indices for white adipose tissue significantly increased, suggesting an inhibition of stearoyl-CoA desaturase upon CLA-mix diet. The fatty acid profile of the erythrocytes widely reflected that of livers, depending on the supplemented diet. These profound changes in fatty acid composition of lipogenic organs due to t10,c12-CLA intake may be the consequence of functional alterations of lipid metabolism.

  8. Fine mapping of a gene causing hybrid pollen sterility between Yunnan weedy rice and cultivated rice (Oryza sativa L.) and phylogenetic analysis of Yunnan weedy rice.

    PubMed

    Wang, Yong; Zhong, Zheng Zheng; Zhao, Zhi Gang; Jiang, Ling; Bian, Xiao Feng; Zhang, Wen Wei; Liu, Ling Long; Ikehashi, H; Wan, Jian Min

    2010-02-01

    Weedy rice represents an important resource for rice improvement. The F(1) hybrid between the japonica wide compatibility rice cultivar 02428 and a weedy rice accession from Yunnan province (SW China) suffered from pollen sterility. Pollen abortion in the hybrid occurred at the early bicellular pollen stage, as a result of mitotic failure in the microspore, although the tapetum developed normally. Genetic mapping in a BC(1)F(1) population (02428//Yunnan weedy rice (YWR)/02428) showed that a major QTL for hybrid pollen sterility (qPS-1) was present on chromosome 1. qPS-1 was fine-mapped to a 110 kb region known to contain the hybrid pollen sterility gene Sa, making it likely that qPS-1 is either identical to, or allelic with Sa. Interestingly, F(1) hybrid indicated that Dular and IR36 were assumed to carry the sterility-neutral allele, Sa ( n ). Re-sequencing SaM and SaF, the two component genes present at Sa, suggested that variation for IR36 and Dular may be responsible for the loss of male sterility, and the qPS-1 sequence might be derived from wild rice or indica cultivars. A phylogenetic analysis based on microsatellite genotyping suggested that the YWR accession is more closely related to wild rice and indica type cultivars than to japonica types. Thus it is probable that the YWR accession evolved from a spontaneous hybrid between wild rice and an ancient cultivated strain of domesticated rice.

  9. Fine mapping of a major QTL for flag leaf width in rice, qFLW4, which might be caused by alternative splicing of NAL1.

    PubMed

    Chen, Mingliang; Luo, Ju; Shao, Gaoneng; Wei, Xiangjin; Tang, Shaoqing; Sheng, Zhonghua; Song, Jian; Hu, Peisong

    2012-05-01

    Leaf width is an important agricultural trait in rice. QTL mapping in a recombinant inbred line population derived from the cross between the javanica cultivar D50 (narrow-leaved) and the indica cultivar HB277 (wide-leaved) identified five QTLs controlling flag leaf width. Fine mapping of the major QTL qFLW4 narrowed its location to a 74.8 kb interval between the SSR loci RM17483 and RM17486, a region which also contains the gene NAL1 (Narrow leaf 1). There was no difference in the level of NAL1 expression between cvs. D50 and HB277, but an analysis of the NAL1 transcripts showed that while most (if not all) of those produced in cv. D50 were full-length, two-thirds of those in HB277 were non-functional due to either loss or gain of sequence. The inference was that NAL1 is probably synonymous with qFLW4, and that the functional difference between the two alleles was due to alternative splicing. The analysis of expression of other known genes involved in the determination of leaf width provided no evidence of their having any clear functional association with qFLW4/NAL1.

  10. Cerebral Arterial Stenoses and Stroke: Novel Features of Aicardi-Goutières Syndrome Caused by the Arg164X Mutation in SAMHD1 Are Associated with Altered Cytokine Expression

    PubMed Central

    Thiele, Holger; du Moulin, Marcel; Barczyk, Katarzyna; George, Christel; Schwindt, Wolfram; Nürnberg, Gudrun; Frosch, Michael; Kurlemann, Gerhard; Roth, Johannes; Nürnberg, Peter; Rutsch, Frank

    2010-01-01

    Aicardi-Goutières syndrome (AGS) is a rare inborn multisystemic disease, resembling intrauterine viral infection and resulting in psychomotor retardation, spasticity and chilblain-like skin lesions. Diagnostic criteria include intracerebral calcifications and elevated interferon-alpha and pterin levels in cerebrospinal fluid (CSF). We report on four adult siblings with unknown neurodegenerative disease presenting with cerebrovascular stenoses, stroke and glaucoma in childhood, two of whom died at the age of 40 and 29 years. Genome-wide homozygosity mapping identified 170 candidate genes embedded in a common haplotype of 8Mb on chromosome 20q11-13. Next generation sequencing of the entire region identified the c.490C>T (p.Arg164X) mutation in SAMHD1, a gene most recently described in AGS, on both alleles in all affected siblings. Clinical diagnosis of AGS was then confirmed by demonstrating intracerebral calcifications on cranial computed tomography in all siblings and elevated pterin levels in CSF in three of them. In patient fibroblasts, lack of SAMHD1 protein expression was associated with increased basal expression of IL8, while stimulated expression of IFNB1 was reduced. We conclude that cerebrovascular stenoses and stroke associated with the Arg164X mutation in SAMHD1 extend the phenotypic spectrum of AGS. The observed vascular changes most likely reflect a vasculitis caused by dysregulated inflammatory stress response. © 2010 Wiley-Liss, Inc. PMID:20842748

  11. Historical mapping reveals causes and temporal patterns of woodland contraction in Austur-Skaftafellssýsla from the 12th century AD to present

    NASA Astrophysics Data System (ADS)

    Sigurmundsson, Friðþór S.; Gísladóttir, Guðrún; Erlendsson, Egill; Þorbjarnarson, Höskuldur

    2016-04-01

    Land-cover changes in Iceland over the last millennium encompass birch (Betula pubescens) woodland depletion and extensive soil erosion. Yet few studies have focused on spatial change of birch woodland coverage in Iceland over centuries and why and how the woodland depletion took place. The main objectives of this study are: (1) to map the woodland distribution today in Austur-Skaftafellssýsla (3041 km2) in southern Iceland; (2) to map woodland holdings over a period of 900 years from eleventh. AD 1100 to the early 20th century; (3) explain the relative impacts of socio-economic and natural forces on woodland cover over this period. We use a combined approach of historical reconstruction from diverse written archives, GIS techniques and field work. The woodland in Austur-Skaftafellssýsla now covers 73.2 km2 (2.5% of the study area). The woodland holdings, 44 in total, are regularly listed in the church inventories from 1179 to 1570 and are owned by the church. In the first complete register for the district in 1641 the woodland holdings were 73, owned and used by 58 estates, and distributed across Austur-Skaftafellssýsla. All the main patches of woodland remain today, with the exception of four minor woodlands which were exhausted near the end of the 19th century. The woodland was used for firewood and charcoal making as well as grazing during the study period but, crucially, in most cases only one estate had authority over each holding, none were commons. The main driving force behind the development of woodlands was socio-economic, rather than natural, where the form of ownership was fundamental for the fate of the woodland. Harsh climate and volcanism were not directly responsible for woodland depletion. The latter half of the 19th century was the period of greatest woodland loss. This period coincides with considerable expansion in livestock numbers, especially sheep and associated all year around grazing, at a time when the Little Ice Age culminated in

  12. In vivo sodium salicylate causes tolerance to acute morphine exposure and alters the ability of high frequency stimulation to induce long-term potentiation in hippocampus area CA1.

    PubMed

    Hosseinmardi, Narges; Azimi, Lila; Fathollahi, Yaghoub; Javan, Mohammad; Naghdi, Naser

    2011-11-30

    Effects of morphine on synaptic transmission and plasticity in the hippocampus area CA1 following in vivo sodium salicylate and the potential molecular mechanism were investigated. Population spikes (PS) were recorded from stratum pylamidale of area CA1 following stimulation of Schaffer collaterals in slices taken from control and sodium salicylate injected rats. To induce long term potentiation (LTP), a 100Hz tetanic stimulation was used. Acute in vitro morphine increased baseline PS amplitude in control slices but not in slices taken from sodium salicylate treated rats. In vivo chronic salicylate did slightly decrease and/or destabilize LTP of CA1 synaptic transmission. We also found that mRNA of NR2A subunit of NMDA receptor was reduced in the hippocampus of sodium salicylate treated rats as compared to control ones. Following LTP induction, the mRNA of NR2A and PP1 (protein phosphatase 1) in slices taken from salicylate-treated rats were more than those of control ones. After long-term exposure to in vitro morphine, high frequency stimulation (HFS) decreased NR2A mRNA level significantly in sodium salicylate treated slices. It is concluded that in vivo sodium salicylate causes tolerance to excitatory effect of morphine and changes the ability of HFS to induce PS LTP in the hippocampus area CA1 in vitro. These changes in synaptic response may be due to alterations in NR2A and PP1 expression.

  13. CADDIS Volume 2. Sources, Stressors and Responses: Flow Alteration - Detailed Conceptual Diagram

    EPA Pesticide Factsheets

    Introduction to the flow alteration module, when to list flow alteration as a candidate cause, ways to measure flow alteration, simple and detailed conceptual model diagrams for flow alteration, flow alteration module references and literature reviews.

  14. CADDIS Volume 2. Sources, Stressors and Responses: Flow Alteration - Simple Conceptual Diagram

    EPA Pesticide Factsheets

    Introduction to the flow alteration module, when to list flow alteration as a candidate cause, ways to measure flow alteration, simple and detailed conceptual model diagrams for flow alteration, flow alteration module references and literature reviews.

  15. Genetic Mapping

    MedlinePlus

    ... Fact Sheets Fact Sheets En Español: Mapeo Genético Genetic Mapping What is genetic mapping? How do researchers ... genetic map? What are genetic markers? What is genetic mapping? Among the main goals of the Human ...

  16. Sixth-grade Indonesian student explanations of directions on flat maps and globes, of the Earth's rotation to cause night and day, and of the relative positions of the Earth, Moon, and Sun during an eclipse

    NASA Astrophysics Data System (ADS)

    Dimyati, Surachman

    The purpose of the study was to elicit and analyze sixth grade students' explanations concerning concepts taught in the national Indonesian sixth grade science curriculum. In this study, students were asked to identify the cardinal directions on flat maps and a globe, to describe what causes night and day on the earth, to identify the direction of the earth's rotation, and to identify the relative positions of the earth, sun, and moon during either a solar or lunar eclipse. The findings in the study can be summarized as follows (1) Eighty out of 88 students (91%) were able to explain what causes night and day. (2) Approximately 50% could identify the direction the earth rotates to cause night and day. (3) Using a solar system model, about 64% of the students could describe the relative position of the earth, sun, and moon during an eclipse. (4) Cultural differences affect student thinking. One student thought that Mecca had to be west of everywhere, not just west of Indonesia. (5) The way teachers teach seems to influence student thinking. It is easy for students to form the misconception that up is north. Most maps in classrooms are hung vertically. (6) Some students were confused by the globe. Teachers need to explain why the globe is tilted. Also, they need to help students understand how to determine the cardinal directions on a globe. More research is needed to determine what is needed to help students truly understand these concepts and to determine whether these concepts are best taught at the elementary level.

  17. Planetary maps

    USGS Publications Warehouse

    ,

    1992-01-01

    An important goal of the USGS planetary mapping program is to systematically map the geology of the Moon, Mars, Venus, and Mercury, and the satellites of the outer planets. These geologic maps are published in the USGS Miscellaneous Investigations (I) Series. Planetary maps on sale at the USGS include shaded-relief maps, topographic maps, geologic maps, and controlled photomosaics. Controlled photomosaics are assembled from two or more photographs or images using a network of points of known latitude and longitude. The images used for most of these planetary maps are electronic images, obtained from orbiting television cameras, various optical-mechanical systems. Photographic film was only used to map Earth's Moon.

  18. Whole Exome Sequencing and Segregation Analysis Confirms That a Mutation in COL17A1 Is the Cause of Epithelial Recurrent Erosion Dystrophy in a Large Dominant Pedigree Previously Mapped to Chromosome 10q23-q24

    PubMed Central

    Le, Derek J.; Chen, Yabin; Wang, Qiwei; Chung, D. Doug; Frausto, Ricardo F.; Croasdale, Christopher; Yee, Richard W.; Hejtmancik, Fielding J.; Aldave, Anthony J.

    2016-01-01

    Purpose To report identification of a COL17A1 mutation in a family with a corneal dystrophy previously mapped to chromosome 10q23-q24. Methods Whole-exome sequencing was performed on DNA samples from five affected family members and two unrelated, unaffected individuals. Identified variants were filtered for those that were: located in the linked interval on chromosome 10q23-q24; novel or rare (minor allele frequency ≤0.01); heterozygous; present in all affected individuals and not in controls; and present in genes that encode proteins expressed in human corneal epithelial cells (reads per kilobase per million ≥1). Sanger sequencing of identified variants (SNVs) was performed in additional family members. In silico analysis was used to predict the functional impact of non-synonymous variants. Results Three SNVs located in two genes were identified that met the filtering criteria: one rare synonymous c.3156C>T variant in the collagen, type XVII, alpha I (COL17A1) gene; and two rare variants, one synonymous and one missense, in the dynamin binding protein (DNMBP) gene. Sanger sequencing of additional family members determined that only the COL17A1 variant segregates with the affected phenotype. In silico analysis predicts that the missense variant in DNMBP would be tolerated. Conclusions The corneal dystrophy mapped to chromosome 10q23-q24 is associated with the c.3156C>T variant in COL17A1. As this variant has recently been identified in five other families with early onset recurrent corneal erosions, and has been shown in vitro to introduce a cryptic splice donor site, this dystrophy is likely caused by aberrant splicing of COL17A1 and should be classified as epithelial recurrent erosion dystrophy. PMID:27309958

  19. Genetically Altered Plant Species

    NASA Technical Reports Server (NTRS)

    2003-01-01

    Researchers in Robert Ferl's lab at the University of Florida in Gainesville, genetically altered this Arabdopsis Thaliana (a brassica species) plant to learn how extreme environments, such as the low atmospheric pressure on Mars, affect plant genes. They inserted green fluorescent protein (GFP) near the on/off switches for anoxia and drought genes. When those genes were turned on after exposure to reduced atmospheric pressure, GFP was turned on as well, causing cells expressing those genes to glow green under a blue light. The natural fluorescence of chlorophyll accounts for the red glow.

  20. Contour Mapping

    NASA Technical Reports Server (NTRS)

    1995-01-01

    In the early 1990s, the Ohio State University Center for Mapping, a NASA Center for the Commercial Development of Space (CCDS), developed a system for mobile mapping called the GPSVan. While driving, the users can map an area from the sophisticated mapping van equipped with satellite signal receivers, video cameras and computer systems for collecting and storing mapping data. George J. Igel and Company and the Ohio State University Center for Mapping advanced the technology for use in determining the contours of a construction site. The new system reduces the time required for mapping and staking, and can monitor the amount of soil moved.

  1. Chronic Exposure to Arsenic in Drinking Water Causes Alterations in Locomotor Activity and Decreases Striatal mRNA for the D2 Dopamine Receptor in CD1 Male Mice.

    PubMed

    Moreno Ávila, Claudia Leticia; Limón-Pacheco, Jorge H; Giordano, Magda; Rodríguez, Verónica M

    2016-01-01

    Arsenic exposure has been associated with sensory, motor, memory, and learning alterations in humans and alterations in locomotor activity, behavioral tasks, and neurotransmitters systems in rodents. In this study, CD1 mice were exposed to 0.5 or 5.0 mg As/L of drinking water for 6 months. Locomotor activity, aggression, interspecific behavior and physical appearance, monoamines levels, and expression of the messenger for dopamine receptors D1 and D2 were assessed. Arsenic exposure produced hypoactivity at six months and other behaviors such as rearing and on-wall rearing and barbering showed both increases and decreases. No alterations on aggressive behavior or monoamines levels in striatum or frontal cortex were observed. A significant decrease in the expression of mRNA for D2 receptors was found in striatum of mice exposed to 5.0 mg As/L. This study provides evidence for the use of dopamine receptor D2 as potential target of arsenic toxicity in the dopaminergic system.

  2. Chronic Exposure to Arsenic in Drinking Water Causes Alterations in Locomotor Activity and Decreases Striatal mRNA for the D2 Dopamine Receptor in CD1 Male Mice

    PubMed Central

    Moreno Ávila, Claudia Leticia

    2016-01-01

    Arsenic exposure has been associated with sensory, motor, memory, and learning alterations in humans and alterations in locomotor activity, behavioral tasks, and neurotransmitters systems in rodents. In this study, CD1 mice were exposed to 0.5 or 5.0 mg As/L of drinking water for 6 months. Locomotor activity, aggression, interspecific behavior and physical appearance, monoamines levels, and expression of the messenger for dopamine receptors D1 and D2 were assessed. Arsenic exposure produced hypoactivity at six months and other behaviors such as rearing and on-wall rearing and barbering showed both increases and decreases. No alterations on aggressive behavior or monoamines levels in striatum or frontal cortex were observed. A significant decrease in the expression of mRNA for D2 receptors was found in striatum of mice exposed to 5.0 mg As/L. This study provides evidence for the use of dopamine receptor D2 as potential target of arsenic toxicity in the dopaminergic system. PMID:27375740

  3. Hyperspectral surface materials map of quadrangles 2964, 2966, 3064, and 3066, Shah-Esmail (617), Reg-Alaqadari (618), Samandkhan-Karez (713), Laki-Bander (611), Jahangir-Naweran (612), and Sreh-Chena (707) quadrangles, Afghanistan, showing carbonates, phyllosilicates, sulfates, altered minerals, and other materials

    USGS Publications Warehouse

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

    2013-01-01

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

  4. Sensory experience modifies feature map relationships in visual cortex

    PubMed Central

    Cloherty, Shaun L; Hughes, Nicholas J; Hietanen, Markus A; Bhagavatula, Partha S

    2016-01-01

    The extent to which brain structure is influenced by sensory input during development is a critical but controversial question. A paradigmatic system for studying this is the mammalian visual cortex. Maps of orientation preference (OP) and ocular dominance (OD) in the primary visual cortex of ferrets, cats and monkeys can be individually changed by altered visual input. However, the spatial relationship between OP and OD maps has appeared immutable. Using a computational model we predicted that biasing the visual input to orthogonal orientation in the two eyes should cause a shift of OP pinwheels towards the border of OD columns. We then confirmed this prediction by rearing cats wearing orthogonally oriented cylindrical lenses over each eye. Thus, the spatial relationship between OP and OD maps can be modified by visual experience, revealing a previously unknown degree of brain plasticity in response to sensory input. DOI: http://dx.doi.org/10.7554/eLife.13911.001 PMID:27310531

  5. Androgen and taxol cause cell type-specific alterations of centrosome and DNA organization in androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cells

    NASA Technical Reports Server (NTRS)

    Schatten, H.; Ripple, M.; Balczon, R.; Weindruch, R.; Chakrabarti, A.; Taylor, M.; Hueser, C. N.

    2000-01-01

    We investigated the effects of androgen and taxol on the androgen-responsive LNCaP and androgen-independent DU145 prostate cancer cell lines. Cells were treated for 48 and 72 h with 0.05-1 nM of the synthetic androgen R1881 and with 100 nM taxol. Treatment of LNCaP cells with 0.05 nM R1881 led to increased cell proliferation, whereas treatment with 1 nM R1881 resulted in inhibited cell division, DNA cycle arrest, and altered centrosome organization. After treatment with 1 nM R1881, chromatin became clustered, nuclear envelopes convoluted, and mitochondria accumulated around the nucleus. Immunofluorescence microscopy with antibodies to centrosomes showed altered centrosome structure. Although centrosomes were closely associated with the nucleus in untreated cells, they dispersed into the cytoplasm after treatment with 1 nM R1881. Microtubules were only faintly detected in 1 nM R1881-treated LNCaP cells. The effects of taxol included microtubule bundling and altered mitochondria morphology, but not DNA organization. As expected, the androgen-independent prostate cancer cell line DU145 was not affected by R1881. Treatment with taxol resulted in bundling of microtubules in both cell lines. Additional taxol effects were seen in DU145 cells with micronucleation of DNA, an indication of apoptosis. Simultaneous treatment with R1881 and taxol had no additional effects on LNCaP or DU145 cells. These results suggest that LNCaP and DU145 prostate cancer cells show differences not only in androgen responsiveness but in sensitivity to taxol as well. Copyright 2000 Wiley-Liss, Inc.

  6. Genome-wide ChIP-seq mapping and analysis of butyrate-induced H3K9 and H3K27 acetylation and epigenomic landscape alteration in bovine cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Utilizing next-generation sequencing technology, combined with ChIP (Chromatin Immunoprecipitation) technology, we analyzed histone modification (acetylation) induced by butyrate and the large-scale mapping of the epigenomic landscape of normal histone H3 and acetylated histone H3K9 and H3K27. To d...

  7. USGS maps

    USGS Publications Warehouse

    ,

    2005-01-01

    Discover a small sample of the millions of maps produced by the U.S. Geological Survey (USGS) in its mission to map the Nation and survey its resources. This booklet gives a brief overview of the types of maps sold and distributed by the USGS through its Earth Science Information Centers (ESIC) and also available from business partners located in most States. The USGS provides a wide variety of maps, from topographic maps showing the geographic relief and thematic maps displaying the geology and water resources of the United States, to special studies of the moon and planets.

  8. Altered mental status and endocrine diseases.

    PubMed

    Park, Elizabeth; Abraham, Michael K

    2014-05-01

    Although the altered mental status is a common presentation in the emergency department, altered mental status caused by endocrine emergencies is rare. The altered patient could have an endocrine cause that can quickly improve with appropriate diagnosis and interventions. When dealing with limited information and an obtunded patient, it is important to have a broad differential diagnosis, pick up on the physical examination findings, and evaluate laboratory abnormalities that could suggest an underlying endocrine emergency. This article outlines the findings and provides a description of altered patients with endocrine emergencies to facilitate the diagnosis and treatment in the emergency department.

  9. RICH MAPS

    EPA Science Inventory

    Michael Goodchild recently gave eight reasons why traditional maps are limited as communication devices, and how interactive internet mapping can overcome these limitations. In the past, many authorities in cartography, from Jenks to Bertin, have emphasized the importance of sim...

  10. White matter alterations in temporal lobe epilepsy

    NASA Astrophysics Data System (ADS)

    Diniz, P. B.; Salmon, C. E.; Velasco, T. R.; Sakamoto, A. C.; Leite, J. P.; Santos, A. C.

    2011-03-01

    In This study, we used Fractional anisotropy (FA), mean diffusivity (D), parallel diffusivity (D//) and perpendicular diffusivity (D), to localize the regions where occur axonal lesion and demyelization. TBSS was applied to analyze the FA data. After, the regions with alteration were studied with D, D// and D maps. Patients exhibited widespread degradation of FA. With D, D// and D maps analysis we found alterations in corpus callosum, corticospinal tract, fornix, internal capsule, corona radiate, Sagittal stratum, cingulum, fronto-occipital fasciculus and uncinate fasciculus. Our results are consistent with the hypothesis that exist demyelization and axonal damage in patients with TLE.

  11. Historical Mapping

    USGS Publications Warehouse

    ,

    1999-01-01

    Maps become out of date over time. Maps that are out of date, however, can be useful to historians, attorneys, environmentalists, genealogists, and others interested in researching the background of a particular area. Local historians can compare a series of maps of the same area compiled over a long period of time to learn how the area developed. A succession of such maps can provide a vivid picture of how a place changed over time.

  12. THE ALTERATION OF INTRACELLULAR ENZYMES

    PubMed Central

    Kaplan, J. Gordin

    1954-01-01

    1. The ability of homologous series of alcohols, ketones, and aldehydes to cause alteration of intracellular catalase increases approximately threefold for each methylene group added, thus following Traube's rule. Equiactive concentrations of alcohols (methanol to octanol) varied over a 4,000-fold range, yet the average corresponding surface tension was 42 ± 2 dynes/cm., that for ketones 43 ± 2, and for aldehydes (above C1) 41 ± 3. 2. Above C8 the altering activity of alcohols ceased to follow Traube's rule, and at C18 was nil. Yet the surface activities of alcohols from nonanol to dodecanol did follow Traube's rule. These two facts show that the interface which is being affected by these agents is not the cell surface, for if it were, altering activity should not fall off between C9 and C12 where surface activity is undiminished; they show also that micelle formation by short range association of hydrocarbon "tails," usually invoked to explain decrease in biological activity of compounds above C8, is not responsible for this effect in these experiments, in which permeability of the cell membrane probably is involved. 3. The most soluble alcohols and aldehydes (alcohols C1 to C8; aldehydes C1, C2), but not ketones, cause, above optimal concentration, an irreversible inhibition of yeast catalase. 4. The critical concentration of altering agent (i.e., that concentration just sufficient to cause doubling of the catalase activity of the yeast suspension) was independent of the concentration of the yeast cells. 5. Viability studies show that the number of yeast cells killed by the altering agents was not related to the degree of activation of the catalase produced. While all the cells were invariably killed by concentrations of altering agent which produced complete activation, all the cells had been killed by concentrations which were insufficient to cause more than 50 per cent maximal activation. Further, the evidence suggested that the catalase may be partially

  13. Stable learning of functional maps in self-organizing spiking neural networks with continuous synaptic plasticity.

    PubMed

    Srinivasa, Narayan; Jiang, Qin

    2013-01-01

    This study describes a spiking model that self-organizes for stable formation and maintenance of orientation and ocular dominance maps in the visual cortex (V1). This self-organization process simulates three development phases: an early experience-independent phase, a late experience-independent phase and a subsequent refinement phase during which experience acts to shape the map properties. The ocular dominance maps that emerge accommodate the two sets of monocular inputs that arise from the lateral geniculate nucleus (LGN) to layer 4 of V1. The orientation selectivity maps that emerge feature well-developed iso-orientation domains and fractures. During the last two phases of development the orientation preferences at some locations appear to rotate continuously through ±180° along circular paths and referred to as pinwheel-like patterns but without any corresponding point discontinuities in the orientation gradient maps. The formation of these functional maps is driven by balanced excitatory and inhibitory currents that are established via synaptic plasticity based on spike timing for both excitatory and inhibitory synapses. The stability and maintenance of the formed maps with continuous synaptic plasticity is enabled by homeostasis caused by inhibitory plasticity. However, a prolonged exposure to repeated stimuli does alter the formed maps over time due to plasticity. The results from this study suggest that continuous synaptic plasticity in both excitatory neurons and interneurons could play a critical role in the formation, stability, and maintenance of functional maps in the cortex.

  14. Topographic mapping

    USGS Publications Warehouse

    ,

    2008-01-01

    The U.S. Geological Survey (USGS) produced its first topographic map in 1879, the same year it was established. Today, more than 100 years and millions of map copies later, topographic mapping is still a central activity for the USGS. The topographic map remains an indispensable tool for government, science, industry, and leisure. Much has changed since early topographers traveled the unsettled West and carefully plotted the first USGS maps by hand. Advances in survey techniques, instrumentation, and design and printing technologies, as well as the use of aerial photography and satellite data, have dramatically improved mapping coverage, accuracy, and efficiency. Yet cartography, the art and science of mapping, may never before have undergone change more profound than today.

  15. Microlaparoscopic Conscious Pain Mapping in the Evaluation of Chronic Pelvic Pain: A Case Report

    PubMed Central

    2002-01-01

    Chronic pelvic pain is a debilitating, life-altering syndrome that negatively affects a woman's quality of life and personal relationships. Many women continue to suffer with pelvic pain despite having undergone multiple medical and surgical treatments. Unfortunately, some women are incorrectly labeled as having psychological illness when organic disease may be present. I report a case of a woman who underwent multiple pelvic and abdominal surgeries before the cause of her pain was identified through microlaparoscopic conscious pain mapping. PMID:12004805

  16. Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons

    PubMed Central

    Oosterman, Johanneke E.; Belsham, Denise D.

    2016-01-01

    Specific neurons in the hypothalamus are regulated by peripheral hormones and nutrients to maintain proper metabolic control. It is unclear if nutrients can directly control clock gene expression. We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. Per2 and Bmal1 mRNAs were assessed every 3 hours over 36 hours. Incubation with 5.5 mM glucose significantly shortened the period and delayed the phase of Per2 mRNA levels, but had no effect on Bmal1. Glucose had no significant effect on phospho-GSK3β, whereas AMPK phosphorylation was altered. Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. Remarkably, Compound C dramatically reduced transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt. Because AMPK was not inhibited at the same time or concentrations as the clock genes, we suggest that the effect of Compound C on gene expression occurs through an AMPK-independent mechanism. The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. PMID:26784927

  17. Color on emergency mapping

    NASA Astrophysics Data System (ADS)

    Jiang, Lili; Qi, Qingwen; Zhang, An

    2007-06-01

    There are so many emergency issues in our daily life. Such as typhoons, tsunamis, earthquake, fires, floods, epidemics, etc. These emergencies made people lose their lives and their belongings. Every day, every hour, even every minute people probably face the emergency, so how to handle it and how to decrease its hurt are the matters people care most. If we can map it exactly before or after the emergencies; it will be helpful to the emergency researchers and people who live in the emergency place. So , through the emergency map, before emergency is occurring we can predict the situation, such as when and where the emergency will be happen; where people can refuge, etc. After disaster, we can also easily assess the lost, discuss the cause and make the lost less. The primary effect of mapping is offering information to the people who care about the emergency and the researcher who want to study it. Mapping allows the viewers to get a spatial sense of hazard. It can also provide the clues to study the relationship of the phenomenon in emergency. Color, as the basic element of the map, it can simplify and clarify the phenomenon. Color can also affects the general perceptibility of the map, and elicits subjective reactions to the map. It is to say, structure, readability, and the reader's psychological reactions can be affected by the use of color.

  18. Mapping Van

    NASA Technical Reports Server (NTRS)

    1994-01-01

    A NASA Center for the Commercial Development of Space (CCDS) - developed system for satellite mapping has been commercialized for the first time. Global Visions, Inc. maps an area while driving along a road in a sophisticated mapping van equipped with satellite signal receivers, video cameras and computer systems for collecting and storing mapping data. Data is fed into a computerized geographic information system (GIS). The resulting amps can be used for tax assessment purposes, emergency dispatch vehicles and fleet delivery companies as well as other applications.

  19. Genome mapping

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genome maps can be thought of much like road maps except that, instead of traversing across land, they traverse across the chromosomes of an organism. Genetic markers serve as landmarks along the chromosome and provide researchers information as to how close they may be to a gene or region of inter...

  20. Undersea Mapping.

    ERIC Educational Resources Information Center

    DiSpezio, Michael A.

    1991-01-01

    Presented is a cooperative learning activity in which students assume different roles in an effort to produce a relief map of the ocean floor. Materials, procedures, definitions, student roles, and questions are discussed. A reproducible map for the activity is provided. (CW)

  1. Question Mapping

    ERIC Educational Resources Information Center

    Martin, Josh

    2012-01-01

    After accepting the principal position at Farmersville (TX) Junior High, the author decided to increase instructional rigor through question mapping because of the success he saw using this instructional practice at his prior campus. Teachers are the number one influence on student achievement (Marzano, 2003), so question mapping provides a…

  2. Map Adventures.

    ERIC Educational Resources Information Center

    Geological Survey (Dept. of Interior), Reston, VA.

    This curriculum packet about maps, with seven accompanying lessons, is appropriate for students in grades K-3. Students learn basic concepts for visualizing objects from different perspectives and how to understand and use maps. Lessons in the packet center on a story about a little girl, Nikki, who rides in a hot-air balloon that gives her, and…

  3. Concept Mapping

    ERIC Educational Resources Information Center

    Technology & Learning, 2005

    2005-01-01

    Concept maps are graphical ways of working with ideas and presenting information. They reveal patterns and relationships and help students to clarify their thinking, and to process, organize and prioritize. Displaying information visually--in concept maps, word webs, or diagrams--stimulates creativity. Being able to think logically teaches…

  4. Collection Mapping.

    ERIC Educational Resources Information Center

    Harbour, Denise

    2002-01-01

    Explains collection mapping for library media collections. Discusses purposes for creating collection maps, including helping with selection and weeding decisions, showing how the collection supports the curriculum, and making budget decisions; and methods of data collection, including evaluating a collaboratively taught unit with the classroom…

  5. Epigenetic alterations in preneoplastic and neoplastic lesions of the cervix

    PubMed Central

    2012-01-01

    Cervical cancer (CC) is one of the most malignant tumors and the second or third most common type of cancer in women worldwide. The association between human papillomavirus (HPV) and CC is widely known and accepted (99.7% of cases). At present, the pathogenesis mechanisms of CC are not entirely clear. It has been shown that inactivation of tumor suppressor genes and activation of oncogenes play a significant role in carcinogenesis, caused by the genetic and epigenetic alterations. In the past, it was generally thought that genetic mutation was a key event of tumor pathogenesis, especially somatic mutation of tumor suppressor genes. With deeper understanding of tumors in recent years, increasing evidence has shown that epigenetic silencing of those genes, as a result of aberrant hypermethylation of CpG islands in promoters and histone modification, is essential to carcinogenesis and metastasis. The term epigenetics refers to heritable changes in gene expression caused by regulation mechanisms, other than changes in DNA sequence. Specific epigenetic processes include DNA methylation, chromotin remodeling, histone modification, and microRNA regulations. These alterations, in combination or individually, make it possible to establish the methylation profiles, histone modification maps, and expression profiles characteristic of this pathology, which become useful tools for screening, early detection, or prognostic markers in cervical cancer. This paper reviews recent epigenetics research progress in the CC study, and tries to depict the relationships between CC and DNA methylation, histone modification, as well as microRNA regulations. PMID:22938091

  6. Endovascular Infections Caused by Methicillin-Resistant Staphylococcus aureus Are Linked to Clonal Complex-Specific Alterations in Binding and Invasion Domains of Fibronectin-Binding Protein A as Well as the Occurrence of fnbB

    PubMed Central

    Xiong, Yan Q.; Sharma-Kuinkel, Batu K.; Casillas-Ituarte, Nadia N.; Fowler, Vance G.; Rude, Thomas; DiBartola, Alex C.; Lins, Roberto D.; Abdel-Hady, Wessam; Bayer, Arnold S.

    2015-01-01

    Endovascular infections caused by Staphylococcus aureus involve interactions with fibronectin present as extracellular matrix or surface ligand on host cells. We examined the expression, structure, and binding activity of the two major S. aureus fibronectin-binding proteins (FnBPA, FnBPB) in 10 distinct, methicillin-resistant clinical isolates from patients with either persistent or resolving bacteremia. The persistent bacteremia isolates (n = 5) formed significantly stronger bonds with immobilized fibronectin as determined by dynamic binding measurements performed with atomic force microscopy. Several notable differences were also observed when the results were grouped by clonal complex 5 (CC5) strains (n = 5) versus CC45 strains (n = 5). Fibronectin-binding receptors on CC5 formed stronger bonds with immobilized fibronectin (P < 0.001). The fnbA gene was expressed at higher levels in CC45, whereas fnbB was found in only CC5 isolates. The fnbB gene was not sequenced because all CC45 isolates lacked this gene. Instead, comparisons were made for fnbA, which was present in all 10 isolates. Sequencing of fnbA revealed discrete differences within high-affinity, fibronectin-binding repeats (FnBRs) of FnBPA that included (i) 5-amino-acid polymorphisms in FnBR-9, FnBR-10, and FnBR-11 involving charged or polar side chains, (ii) an extra, 38-amino-acid repeat inserted between FnBR-9 and FnBR-10 exclusively seen in CC45 isolates, and (iii) CC5 isolates had the SVDFEED epitope in FnBR-11 (a sequence shown to be essential for fibronectin binding), while this sequence was replaced in all CC45 isolates with GIDFVED (a motif known to favor host cell invasion at the cost of reduced fibronectin binding). These complementary sequence and binding data suggest that differences in fnbA and fnbB, particularly polymorphisms and duplications in FnBPA, give S. aureus two distinct advantages in human endovascular infections: (i) FnBPs similar to that of CC5 enhance ligand binding and

  7. Endovascular infections caused by methicillin-resistant Staphylococcus aureus are linked to clonal complex-specific alterations in binding and invasion domains of fibronectin-binding protein A as well as the occurrence of fnbB.

    PubMed

    Xiong, Yan Q; Sharma-Kuinkel, Batu K; Casillas-Ituarte, Nadia N; Fowler, Vance G; Rude, Thomas; DiBartola, Alex C; Lins, Roberto D; Abdel-Hady, Wessam; Lower, Steven K; Bayer, Arnold S

    2015-12-01

    Endovascular infections caused by Staphylococcus aureus involve interactions with fibronectin present as extracellular matrix or surface ligand on host cells. We examined the expression, structure, and binding activity of the two major S. aureus fibronectin-binding proteins (FnBPA, FnBPB) in 10 distinct, methicillin-resistant clinical isolates from patients with either persistent or resolving bacteremia. The persistent bacteremia isolates (n = 5) formed significantly stronger bonds with immobilized fibronectin as determined by dynamic binding measurements performed with atomic force microscopy. Several notable differences were also observed when the results were grouped by clonal complex 5 (CC5) strains (n = 5) versus CC45 strains (n = 5). Fibronectin-binding receptors on CC5 formed stronger bonds with immobilized fibronectin (P < 0.001). The fnbA gene was expressed at higher levels in CC45, whereas fnbB was found in only CC5 isolates. The fnbB gene was not sequenced because all CC45 isolates lacked this gene. Instead, comparisons were made for fnbA, which was present in all 10 isolates. Sequencing of fnbA revealed discrete differences within high-affinity, fibronectin-binding repeats (FnBRs) of FnBPA that included (i) 5-amino-acid polymorphisms in FnBR-9, FnBR-10, and FnBR-11 involving charged or polar side chains, (ii) an extra, 38-amino-acid repeat inserted between FnBR-9 and FnBR-10 exclusively seen in CC45 isolates, and (iii) CC5 isolates had the SVDFEED epitope in FnBR-11 (a sequence shown to be essential for fibronectin binding), while this sequence was replaced in all CC45 isolates with GIDFVED (a motif known to favor host cell invasion at the cost of reduced fibronectin binding). These complementary sequence and binding data suggest that differences in fnbA and fnbB, particularly polymorphisms and duplications in FnBPA, give S. aureus two distinct advantages in human endovascular infections: (i) FnBPs similar to that of CC5 enhance ligand binding and

  8. Mapping Children--Mapping Space.

    ERIC Educational Resources Information Center

    Pick, Herbert L., Jr.

    Research is underway concerning the way the perception, conception, and representation of spatial layout develops. Three concepts are important here--space itself, frame of reference, and cognitive map. Cognitive map refers to a form of representation of the behavioral space, not paired associate or serial response learning. Other criteria…

  9. The National Map - Orthoimagery

    USGS Publications Warehouse

    Mauck, James; Brown, Kim; Carswell, William J.

    2009-01-01

    Orthorectified digital aerial photographs and satellite images of 1-meter (m) pixel resolution or finer make up the orthoimagery component of The National Map. The process of orthorectification removes feature displacements and scale variations caused by terrain relief and sensor geometry. The result is a combination of the image characteristics of an aerial photograph or satellite image and the geometric qualities of a map. These attributes allow users to: *Measure distance *Calculate areas *Determine shapes of features *Calculate directions *Determine accurate coordinates *Determine land cover and use *Perform change detection *Update maps The standard digital orthoimage is a 1-m or finer resolution, natural color or color infra-red product. Most are now produced as GeoTIFFs and accompanied by a Federal Geographic Data Committee (FGDC)-compliant metadata file. The primary source for 1-m data is the National Agriculture Imagery Program (NAIP) leaf-on imagery. The U.S. Geological Survey (USGS) utilizes NAIP imagery as the image layer on its 'Digital- Map' - a new generation of USGS topographic maps (http://nationalmap.gov/digital_map). However, many Federal, State, and local governments and organizations require finer resolutions to meet a myriad of needs. Most of these images are leaf-off, natural-color products at resolutions of 1-foot (ft) or finer.

  10. Dietary turmeric modulates DMBA-induced p21{sup ras}, MAP kinases and AP-1/NF-{kappa}B pathway to alter cellular responses during hamster buccal pouch carcinogenesis

    SciTech Connect

    Garg, Rachana; Ingle, Arvind; Maru, Girish

    2008-11-01

    The chemopreventive efficacy of turmeric has been established in experimental systems. However, its mechanism(s) of action are not fully elucidated in vivo. The present study investigates the mechanism of turmeric-mediated chemoprevention in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis at 2, 4, 6, 10 and 12 weeks. Dietary turmeric (1%) led to decrease in DMBA-induced tumor burden and multiplicity, and enhanced the latency period in parallel, to its modulatory effects on oncogene products and various cellular responses during HBP tumorigenesis. DMBA-induced expression of ras oncogene product, p21 and downstream target, the mitogen-activated protein kinases were significantly decreased by turmeric during HBP carcinogenesis. Turmeric also diminished the DMBA-induced mRNA expression of proto-oncogenes (c-jun, c-fos) and NF-{kappa}B, leading to decreased protein levels and in further attenuation of DMBA-induced AP-1/NF-{kappa}B DNA-binding in the buccal pouch nuclear extracts. Besides, buccal pouch of hamsters receiving turmeric diet showed significant alterations in DMBA-induced effects: (a) decrease in cell proliferation (diminished PCNA and Bcl2 expression), (b) enhanced apoptosis (increased expression of Bax, caspase-3 and apoptotic index), (c) decrease in inflammation (levels of Cox-2, the downstream target of AP-1/NF-{kappa}B, and PGE2) and (d) aberrant expression of differentiation markers, the cytokeratins (1, 5, 8, and 18). Together, the protective effects of dietary turmeric converge on augmenting apoptosis of the initiated cells and decreasing cell proliferation in DMBA-treated animals, which in turn, is reflected in decreased tumor burden, multiplicity and enhanced latency period. Some of these biomarkers are likely to be helpful in monitoring clinical trials and evaluating drug effect measurements.

  11. Mapping Biodiversity.

    ERIC Educational Resources Information Center

    World Wildlife Fund, Washington, DC.

    This document features a lesson plan that examines how maps help scientists protect biodiversity and how plants and animals are adapted to specific ecoregions by comparing biome, ecoregion, and habitat. Samples of instruction and assessment are included. (KHR)

  12. Map Separates

    USGS Publications Warehouse

    ,

    2001-01-01

    U.S. Geological Survey (USGS) topographic maps are printed using up to six colors (black, blue, green, red, brown, and purple). To prepare your own maps or artwork based on maps, you can order separate black-and-white film positives or negatives for any color printed on a USGS topographic map, or for one or more of the groups of related features printed in the same color on the map (such as drainage and drainage names from the blue plate.) In this document, examples are shown with appropriate ink color to illustrate the various separates. When purchased, separates are black-and-white film negatives or positives. After you receive a film separate or composite from the USGS, you can crop, enlarge or reduce, and edit to add or remove details to suit your special needs. For example, you can adapt the separates for making regional and local planning maps or for doing many kinds of studies or promotions by using the features you select and then printing them in colors of your choice.

  13. Venus mapping

    NASA Technical Reports Server (NTRS)

    Batson, R. M.; Morgan, H. F.; Sucharski, Robert

    1991-01-01

    Semicontrolled image mosaics of Venus, based on Magellan data, are being compiled at 1:50,000,000, 1:10,000,000, 1:5,000,000, and 1:1,000,000 scales to support the Magellan Radar Investigator (RADIG) team. The mosaics are semicontrolled in the sense that data gaps were not filled and significant cosmetic inconsistencies exist. Contours are based on preliminary radar altimetry data that is subjected to revision and improvement. Final maps to support geologic mapping and other scientific investigations, to be compiled as the dataset becomes complete, will be sponsored by the Planetary Geology and Geophysics Program and/or the Venus Data Analysis Program. All maps, both semicontrolled and final, will be published as I-maps by the United States Geological Survey. All of the mapping is based on existing knowledge of the spacecraft orbit; photogrammetric triangulation, a traditional basis for geodetic control on planets where framing cameras were used, is not feasible with the radar images of Venus, although an eventual shift of coordinate system to a revised spin-axis location is anticipated. This is expected to be small enough that it will affect only large-scale maps.

  14. The Loss and Gain of Functional Amino Acid Residues Is a Common Mechanism Causing Human Inherited Disease

    PubMed Central

    Lugo-Martinez, Jose; Pejaver, Vikas; Pagel, Kymberleigh A.; Mort, Matthew; Cooper, David N.; Mooney, Sean D.; Radivojac, Predrag

    2016-01-01

    Elucidating the precise molecular events altered by disease-causing genetic variants represents a major challenge in translational bioinformatics. To this end, many studies have investigated the structural and functional impact of amino acid substitutions. Most of these studies were however limited in scope to either individual molecular functions or were concerned with functional effects (e.g. deleterious vs. neutral) without specifically considering possible molecular alterations. The recent growth of structural, molecular and genetic data presents an opportunity for more comprehensive studies to consider the structural environment of a residue of interest, to hypothesize specific molecular effects of sequence variants and to statistically associate these effects with genetic disease. In this study, we analyzed data sets of disease-causing and putatively neutral human variants mapped to protein 3D structures as part of a systematic study of the loss and gain of various types of functional attribute potentially underlying pathogenic molecular alterations. We first propose a formal model to assess probabilistically function-impacting variants. We then develop an array of structure-based functional residue predictors, evaluate their performance, and use them to quantify the impact of disease-causing amino acid substitutions on catalytic activity, metal binding, macromolecular binding, ligand binding, allosteric regulation and post-translational modifications. We show that our methodology generates actionable biological hypotheses for up to 41% of disease-causing genetic variants mapped to protein structures suggesting that it can be reliably used to guide experimental validation. Our results suggest that a significant fraction of disease-causing human variants mapping to protein structures are function-altering both in the presence and absence of stability disruption. PMID:27564311

  15. The oral-facial-digital syndrome type 1 (OFD1), a cause of polycystic kidney disease and associated malformations, maps to Xp22.2-Xp22.3.

    PubMed

    Feather, S A; Woolf, A S; Donnai, D; Malcolm, S; Winter, R M

    1997-07-01

    Key features of the oral-facial-digital syndrome type 1 (OFD1) include malformations of the face, oral cavity and digits. In addition, the clinical phenotype often includes mental retardation and renal functional impairment. Approximately 75% of cases of OFD1 are sporadic, and the condition occurs almost exclusively in females. In familial cases, the most likely mode of inheritance is considered to be X-linked dominant with prenatal lethality in affected males. Therefore, the OFD1 gene product appears to have widespread importance in organogenesis and is essential for fetal survival. We have studied two kindreds in which the clinical course was dominated by polycystic kidney disease requiring dialysis and transplantation. Using polymorphic chromosome markers spaced at approximately 10 cM intervals along the X chromosome, we mapped the disease to a region on the short arm of the X chromosome (Xp22.2-Xp22.3) spanning 19.8 cM and flanked by crossovers with the markers DXS996 and DX7S105. There was a maximum lod score of 3.32 in an 'affecteds only' analysis using a marker within the KAL gene (theta = 0.0 ), thereby confirming the location of the gene for OFD1 on the X chromosome. The remainder of the X chromosome was excluded by recombinants in affected individuals. The importance of our findings includes the definitive assignment of this male-lethal disease to the X chromosome and the mapping of a further locus for a human polycystic kidney disease. Furthermore, this mapping study suggests a possible mouse model for OFD1 as the X-linked dominant Xpl mutant, in which polydactyly and renal cystic disease occurs, maps to the homologous region of the mouse X chromosome.

  16. Primary blast injury causes cognitive impairments and hippocampal circuit alterations

    PubMed Central

    Beamer, Matthew; Tummala, Shanti R.; Gullotti, David; Kopil, Kathryn; Gorka, Samuel; Abel, Ted; “Dale” Bass, Cameron R.; Morrison, Barclay; Cohen, Akiva S.; Meaney, David F.

    2016-01-01

    Blast-induced traumatic brain injury (bTBI) and its long term consequences are a major health concern among veterans. Despite recent work enhancing our knowledge about bTBI, very little is known about the contribution of the blast wave alone to the observed sequelae. Herein, we isolated its contribution in a mouse model by constraining the animals' heads during exposure to a shockwave (primary blast). Our results show that exposure to primary blast alone results in changes in hippocampus-dependent behaviors that correspond with electro-physiological changes in area CA1 and are accompanied by reactive gliosis. Specifically, five days after exposure, behavior in an open field and performance in a spatial object recognition (SOR) task were significantly different from sham. Network electrophysiology, also performed five days after injury, demonstrated a significant decrease in excitability and increase in inhibitory tone. Immunohistochemistry for GFAP and Iba1 performed ten days after injury showed a significant increase in staining. Interestingly, a threefold increase in the impulse of the primary blast wave did not exacerbate these measures. However, we observed a significant reduction in the contribution of the NMDA receptors to the field EPSP at the highest blast exposure level. Our results emphasize the need to account for the effects of primary blast loading when studying the sequelae of bTBI. PMID:27246999

  17. Primary blast injury causes cognitive impairments and hippocampal circuit alterations.

    PubMed

    Beamer, Matthew; Tummala, Shanti R; Gullotti, David; Kopil, Catherine; Gorka, Samuel; Ted Abel; Bass, Cameron R Dale; Morrison, Barclay; Cohen, Akiva S; Meaney, David F

    2016-09-01

    Blast-induced traumatic brain injury (bTBI) and its long term consequences are a major health concern among veterans. Despite recent work enhancing our knowledge about bTBI, very little is known about the contribution of the blast wave alone to the observed sequelae. Herein, we isolated its contribution in a mouse model by constraining the animals' heads during exposure to a shockwave (primary blast). Our results show that exposure to primary blast alone results in changes in hippocampus-dependent behaviors that correspond with electrophysiological changes in area CA1 and are accompanied by reactive gliosis. Specifically, five days after exposure, behavior in an open field and performance in a spatial object recognition (SOR) task were significantly different from sham. Network electrophysiology, also performed five days after injury, demonstrated a significant decrease in excitability and increase in inhibitory tone. Immunohistochemistry for GFAP and Iba1 performed ten days after injury showed a significant increase in staining. Interestingly, a threefold increase in the impulse of the primary blast wave did not exacerbate these measures. However, we observed a significant reduction in the contribution of the NMDA receptors to the field EPSP at the highest blast exposure level. Our results emphasize the need to account for the effects of primary blast loading when studying the sequelae of bTBI.

  18. Altered motility causes the early gastrointestinal toxicity of irradiation

    SciTech Connect

    Erickson, B.A.; Moulder, J.E.; Otterson, M.F.; Sarna, S.K. )

    1994-03-01

    This article reviews studies of large and small intestinal contractile activity following radiation exposure. Studies of motility utilize strain gauge transducers surgically implanted on the seromuscular layer of the small intestine. All studies were performed in mixed breed dogs to record the occurrence of normal contractions, giant migrating contractions (GMCs) and retrograde giant contractions (RGCs) before, during and after irradiation (22.5 Gy in 9 fractions at 3 fractions/week). Giant migrating contractions and retrograde giant contractions are infrequent in the healthy state. However, in diseased states, GMCs are associated with abdominal cramps and diarrhea, and RGCs precede vomiting. In fasted animals, fractionated abdominal irradiation dramatically increased the frequency of GMCs, with the incidence peaking after the second dose. The increased frequency of GMCS occurred as early as a few hours after the first radiation fraction, and returned to normal within days of cessation of radiation. RGCs were also significantly increased after abdominal irradiation. The frequency of RGCs was greatest on the first and sixth dose of radiation. Clinically, the dogs developed nausea, vomiting and diarrhea as early as the first day of irradiation. In dogs studied in the fed state, decreased amplitude, duration, and frequency of postprandial contractions occurred. These changes may slow intestinal transit during irradiation. Radiation also produced a striking increase in the frequency of colonic GMCs; these changes in colonic motor activity were associated with diarrhea as early as the second irradiation. Changes in GI motility during fractionated irradiation precede the appearance of histopathological lesions in the GI tract. Thus, the symptoms of nausea, vomiting, and diarrhea experienced during radiotherapy (particularly those within the first week) are directly related to changes in bowel motility. 41 refs., 7 figs., 1 tab.

  19. Developmental exposure to paracetamol causes biochemical alterations in medulla oblongata.

    PubMed

    Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Jawna, Katarzyna; Pyrzanowska, Justyna; Piechal, Agnieszka; Wawer, Adriana; Widy-Tyszkiewicz, Ewa

    2015-09-01

    The effect and safety of prenatal and early life administration of paracetamol - routinely used over-the-counter antipyretic and analgesic medication on monoamines content and balance of amino acids in the medulla oblongata is still unknown. In this study we have determined the level of neurotransmitters in this structure in two-month old Wistar male rats exposed to paracetamol in the dose of 5 (P5, n=10) or 15mg/kg b.w. (P15, n=10) during prenatal period, lactation and till the end of the second month of life. Control group received drinking water (Con, n=10). Monoamines, their metabolites and amino acids concentration in medulla oblongata of rats were determined using high performance liquid chromatography (HPLC) in 60 postnatal day (PND60). This experiment shows that prenatal and early life paracetamol exposure modulates neurotransmission associated with serotonergic, noradrenergic and dopaminergic system in medulla oblongata. Reduction of alanine and taurine levels has also been established.

  20. Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations.

    PubMed

    Levin, Edward D; Addy, Nii; Baruah, Avanti; Elias, Alana; Christopher, N Channelle; Seidler, Frederic J; Slotkin, Theodore A

    2002-01-01

    Use of chlorpyrifos (CPF) has been curtailed due to its developmental neurotoxicity. In rats, postnatal CPF administration produces lasting changes in cognitive performance, but less information is available about the effects of prenatal exposure. We administered CPF to pregnant rats on gestational days (GD) 17-20, a peak period of neurogenesis, using doses (1 or 5 mg/kg/day) below the threshold for fetal growth impairment. We then evaluated performance in the T-maze, Figure-8 apparatus and 16-arm radial maze, beginning in adolescence and continuing into adulthood. CPF elicited initial locomotor hyperactivity in the T-maze. Females showed slower habituation in the Fig. 8 maze; no effects were seen in males. In the radial-arm maze, females showed impaired choice accuracy for both working and reference memory and again, males were unaffected. Despite the deficits, all animals eventually learned the maze with continued training. At that point, we challenged them with the muscarinic antagonist, scopolamine, to determine the dependence of behavioral performance on cholinergic function. Whereas control females showed impairment with scopolamine, CPF-exposed females did not, implying that the delayed acquisition of the task had been accomplished through alternative mechanisms. The differences were specific to muscarinic circuits, as control and CPF groups responded similarly to the nicotinic antagonist, mecamylamine. Surprisingly, adverse effects of CPF were greater in the group receiving 1 mg/kg as compared to 5 mg/kg. Promotional effects of acetylcholine (ACh) on cell differentiation may thus help to offset CPF-induced developmental damage that occurs through other noncholinergic mechanisms. Our results indicate that late prenatal exposure to CPF induces long-term changes in cognitive performance that are distinctly gender-selective. Additional defects may be revealed by similar strategies that subject the animals to acute challenges, thus, uncovering the adaptive mechanisms that maintain basal performance.

  1. Cloth Ballistic Vest Alters Response to Blast

    DTIC Science & Technology

    1988-01-01

    Detrick, Frederick, MD 21701-501 ELEMENT NO. NO. NO. jACCESSION NO. 11. TITLE (include Security Classification) CLOTH BALLSISTIC VEST ALTERS RESPONSE...Suppl. ’rintd in USA Cloth Ballistic Vest Alters Response to Blast YANCY Y. PHILLIPS, M.D., THOMAS G. MUNDIE, PH.D., JOHN T. YELVERTON, M.S., AND DONALD R...RICHMOND, PH.D. Ballistic wounds have been and will remain the principal cause of casualties in combat. Cloth ballistic vests (CBV) play an

  2. Rare causes of osteoporosis

    PubMed Central

    Marcucci, Gemma; Brandi, Maria Luisa

    2015-01-01

    Summary Osteoporosis is a metabolic bone disease characterized by loss of bone mass and strength, resulting in increased risk of fractures. It is classically divided into primary (post-menopausal or senile), secondary and idiopathic forms. There are many rare diseases, that cause directly or indirectly osteoporosis. The identification and classification of most of these rare causes of osteoporosis is crucial for the specialists in endocrinology and not, in order to prevent this bone complication and to provide for an early therapy. Several pathogenic mechanisms are involved, including various aspects of bone metabolism such as: decreased bone formation, increased bone resorption, altered calcium, phosphorus and/or vitamin D homeostasis, and abnormal collagen synthesis. In this review, less common forms of primary and secondary osteoporosis are described, specifying, if applicable: genetic causes, epidemiology, clinical features, and pathogenic mechanisms causing osteoporosis. A greater awareness of all rare causes of osteoporosis could reduce the number of cases classified as idiopathic osteoporosis and allow the introduction of appropriate and timely treatments. PMID:26604941

  3. Amazing Altered Books

    ERIC Educational Resources Information Center

    Kieling, Linda W.

    2006-01-01

    Linda Kieling, an art teacher at Rosemont Ridge Middle school in West Linn, Oregon, describes an altered book art project she introduced to her students. Alteration of books is a form of recycling that started in the eleventh century when Italian monks recycled old manuscripts written on vellum by scraping off the ink and adding new text and…

  4. Map projections

    USGS Publications Warehouse

    ,

    1993-01-01

    A map projection is used to portray all or part of the round Earth on a flat surface. This cannot be done without some distortion. Every projection has its own set of advantages and disadvantages. There is no "best" projection. The mapmaker must select the one best suited to the needs, reducing distortion of the most important features. Mapmakers and mathematicians have devised almost limitless ways to project the image of the globe onto paper. Scientists at the U. S. Geological Survey have designed projections for their specific needs—such as the Space Oblique Mercator, which allows mapping from satellites with little or no distortion. This document gives the key properties, characteristics, and preferred uses of many historically important projections and of those frequently used by mapmakers today.

  5. Acoustic trauma caused by lightning.

    PubMed

    Mora-Magaña, I; Collado-Corona, M A; Toral-Martiñòn, R; Cano, A

    1996-03-01

    Lesions produced by exposure to noise are frequent in everyday life. Injuries may be found in all systems of the human body, from the digestive to the endocrine, from the cardiovascular to the nervous system. Many organs may be damaged, the ear being one of them. It is known that noise produced by factories, airports, musical instruments and even toys can cause auditory loss. Noises in nature can also cause acoustic trauma. This report is the case history of acoustic trauma caused by lightning. The patient was studied with CAT scan, electroencephalogram, and brain mapping, impedance audiometry with tympanogram and acoustic reflex, audiometry and evoked otoacoustics emissions: distortion products and transients.

  6. Thermal maturity patterns (conodont color alteration index and vitrinite reflectance) in Upper Ordovician and Devonian rocks of the Appalachian basin: a major revision of USGS Map I-917-E using new subsurface collections: Chapter F.1 in Coal and petroleum resources in the Appalachian basin: distribution, geologic framework, and geochemical character

    USGS Publications Warehouse

    Repetski, John E.; Ryder, Robert T.; Weary, David J.; Harris, Anita G.; Trippi, Michael H.; Ruppert, Leslie F.; Ryder, Robert T.

    2014-01-01

    The conodont color alteration index (CAI) introduced by Epstein and others (1977) and Harris and others (1978) is an important criterion for estimating the thermal maturity of Ordovician to Mississippian rocks in the Appalachian basin. Consequently, the CAI isograd maps of Harris and others (1978) are commonly used by geologists to characterize the thermal and burial history of the Appalachian basin and to better understand the origin and distribution of oil and gas resources in the basin. The main objectives of this report are to present revised CAI isograd maps for Ordovician and Devonian rocks in the Appalachian basin and to interpret the geologic and petroleum resource implications of these maps. The CAI isograd maps presented herein complement, and in some areas replace, the CAI-based isograd maps of Harris and others (1978) for the Appalachian basin. The CAI data presented in this report were derived almost entirely from subsurface samples, whereas the CAI data used by Harris and others (1978) were derived almost entirely from outcrop samples. Because of the different sampling methods, there is little geographic overlap of the two data sets. The new data set is mostly from the Allegheny Plateau structural province and most of the data set of Harris and others (1978) is from the Valley and Ridge structural province, east of the Allegheny structural front (fig. 1). Vitrinite reflectance, based on dispersed vitrinite in Devonian black shale, is another important parameter for estimating the thermal maturity in pre-Pennsylvanian-age rocks of the Appalachian basin (Streib, 1981; Cole and others, 1987; Gerlach and Cercone, 1993; Rimmer and others, 1993; Curtis and Faure, 1997). This chapter also presents a revised percent vitrinite reflectance (%R0) isograd map based on dispersed vitrinite recovered from selected Devonian black shales. The Devonian black shales used for the vitrinite studies reported herein also were analyzed by RockEval pyrolysis and total organic

  7. A Toxicogenomic Comparison of Primary and Photochemically Altered Air Pollutant Mixtures

    PubMed Central

    Rager, Julia E.; Lichtveld, Kim; Ebersviller, Seth; Smeester, Lisa; Jaspers, Ilona; Sexton, Kenneth G.

    2011-01-01

    Background: Air pollution contributes significantly to global increases in mortality, particularly within urban environments. Limited knowledge exists on the mechanisms underlying health effects resulting from exposure to pollutant mixtures similar to those occurring in ambient air. In order to clarify the mechanisms underlying exposure effects, toxicogenomic analyses are used to evaluate genomewide transcript responses and map these responses to molecular networks. Objectives: We compared responses induced by exposure to primary pollutants and photochemically altered (PCA) pollutant mixtures representing urban atmospheres to test our hypothesis that exposures to PCA pollutants would show increased modulation of inflammation-associated genes and pathways relative to primary air pollutants. Methods: We used an outdoor environmental irradiation chamber to expose human lung epithelial cells to mixtures representing either primary or PCA pollutants for 4 hr. Transcriptional changes were assessed using microarrays and confirmed using quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) on a subset of genes. Results: We found a large difference in the cellular responses to the two pollutant exposures: Primary air pollutants altered the expression levels of 19 genes, whereas PCA pollutants altered 709 genes. Functional and molecular analyses of the altered genes revealed novel pathways, such as hepatocyte nuclear factor 4α, potentially regulating the pollutant responses. Chemical component analysis characterized and confirmed the photochemical transformation of primary air pollutants into PCA air pollutants. Conclusions: Our study shows that the photochemical transformation of primary air pollutants produces altered mixtures that cause significantly greater biological effects than the primary pollutants themselves. These findings suggest that studying individual air pollutants or primary pollutant mixtures may greatly underestimate the adverse

  8. Physical Parameter Eclipse Mapping

    NASA Astrophysics Data System (ADS)

    Vrielmann, S.

    The tomographic method Physical Parameter Eclipse Mapping is a tool to reconstruct spatial distributions of physical parameters (like temperatures and surface densities) in accretion discs of cataclysmic variables. After summarizing the method, we apply it to multi-colour eclipse light curves of various dwarf novae and nova-likes like VZ Scl, IP Peg in outburst, UU Aqr, V2051 Oph and HT Cas in order to derive the temperatures (and surface densities) in the disc, the white dwarf temperature, the disc size, the effective temperatures and the viscosities. The results allows us to establish or refine a physical model for the accretion disc. Our maps of HT Cas and V 2051Oph, for example, indicate that the (quiescent) disc must be structured into a cool, optically thick inner disc sandwiched by hot, optically thin chromospheres. In addition, the disc of HT Cas must be patchy with a covering factor of about 40% caused by magnetic activity in the disc.

  9. Retinal Remodeling and Metabolic Alterations in Human AMD.

    PubMed

    Jones, Bryan W; Pfeiffer, Rebecca L; Ferrell, William D; Watt, Carl B; Tucker, James; Marc, Robert E

    2016-01-01

    Age-related macular degeneration (AMD) is a progressive retinal degeneration resulting in central visual field loss, ultimately causing debilitating blindness. AMD affects 18% of Americans from 65 to 74, 30% older than 74 years of age and is the leading cause of severe vision loss and blindness in Western populations. While many genetic and environmental risk factors are known for AMD, we currently know less about the mechanisms mediating disease progression. The pathways and mechanisms through which genetic and non-genetic risk factors modulate development of AMD pathogenesis remain largely unexplored. Moreover, current treatment for AMD is palliative and limited to wet/exudative forms. Retina is a complex, heterocellular tissue and most retinal cell classes are impacted or altered in AMD. Defining disease and stage-specific cytoarchitectural and metabolic responses in AMD is critical for highlighting targets for intervention. The goal of this article is to illustrate cell types impacted in AMD and demonstrate the implications of those changes, likely beginning in the retinal pigment epithelium (RPE), for remodeling of the the neural retina. Tracking heterocellular responses in disease progression is best achieved with computational molecular phenotyping (CMP), a tool that enables acquisition of a small molecule fingerprint for every cell in the retina. CMP uncovered critical cellular and molecular pathologies (remodeling and reprogramming) in progressive retinal degenerations such as retinitis pigmentosa (RP). We now applied these approaches to normal human and AMD tissues mapping progression of cellular and molecular changes in AMD retinas, including late-stage forms of the disease.

  10. Psychobiology of Altered States of Consciousness

    ERIC Educational Resources Information Center

    Vaitl, Dieter; Birbaumer, Niels; Gruzelier, John; Jamieson, Graham A.; Kotchoubey, Boris; Kubler, Andrea; Lehmann, Dietrich; Miltner, Wolfgang H. R.; Ott, Ulrich; Sammer, Gebhard; Strauch, Inge; Strehl, Ute; Wackermann, Jiri; Weiss, Thomas

    2005-01-01

    The article reviews the current knowledge regarding altered states of consciousness (ASC) (a) occurring spontaneously, (b) evoked by physical and physiological stimulation, (c) induced by psychological means, and (d) caused by diseases. The emphasis is laid on psychological and neurobiological approaches. The phenomenological analysis of the…

  11. Alterations in Intestinal Permeability After Thermal Injury,

    DTIC Science & Technology

    1992-01-01

    disaccharide with a The cause of the altered intestinal permeability in our molecular weight of 342, and mannitol, a monosaccharide patients who...and linear regression analyses were used as indicated. Differences •P<.01 vs controls and uninfected patients by analysis of were considered

  12. Chemical and Mechanical Alteration of Fractures: Micro-Scale Simulations and Comparison to Experimental Results

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

    Fractures are often the main pathways for subsurface fluid flow especially in rocks with low matrix porosity. Therefore, the hydro-mechanical properties of fractures are of fundamental concern for subsurface CO2 sequestration, enhanced geothermal energy production, enhanced oil recovery, and nuclear waste disposal. Chemical and mechanical stresses induced during these applications may lead to significant alteration of the hydro-mechanical properties of fractures. Laboratory experiments aimed at understanding the chemo-hydro-mechanical response of fractures have shown a range of results that contradict simple conceptual models. For example, under conditions favoring mineral dissolution, where one would expect an overall increase in permeability and fracture aperture, permeability increases under some conditions and decreases under others. Recent experiments have attempted to link these core-scale observations to the relevant small-scale processes occurring within fractures. Results suggest that the loss of mechanical strength in asperities due to chemical alteration may cause non-uniform deformation and alteration of fracture apertures. However, it remains difficult to directly measure the coupled chemical and mechanical processes that lead to alteration of contacting fracture surfaces, which challenges our ability to predict the long-term evolution of the hydro-mechanical properties of fractures. Here, we present a computational model that uses micro-scale surface roughness and explicitly couples dissolution and elastic deformation to calculate local alterations in fracture aperture under chemical and mechanical stresses. Chemical alteration of the fracture surfaces is modeled using a depth-averaged algorithm of fracture flow and reactive transport. Then, we deform the resulting altered fracture-surfaces using an algorithm that calculates the elastic deformation. Nonuniform dissolution may cause the location of the resultant force between the two contacting

  13. Attention Alters Perceived Attractiveness.

    PubMed

    Störmer, Viola S; Alvarez, George A

    2016-04-01

    Can attention alter the impression of a face? Previous studies showed that attention modulates the appearance of lower-level visual features. For instance, attention can make a simple stimulus appear to have higher contrast than it actually does. We tested whether attention can also alter the perception of a higher-order property-namely, facial attractiveness. We asked participants to judge the relative attractiveness of two faces after summoning their attention to one of the faces using a briefly presented visual cue. Across trials, participants judged the attended face to be more attractive than the same face when it was unattended. This effect was not due to decision or response biases, but rather was due to changes in perceptual processing of the faces. These results show that attention alters perceived facial attractiveness, and broadly demonstrate that attention can influence higher-level perception and may affect people's initial impressions of one another.

  14. Distortions of glacial landform sizes by manual mapping

    NASA Astrophysics Data System (ADS)

    Hillier, John K.; Smith, Mike J.

    2016-04-01

    Mapped topographic features are important for understanding processes that sculpt the Earth's surface. Subjective manual techniques are commonly used for mapping, yet how effective they are in quantitative terms is poorly constrained. Here 12,121 outlines drawn by 25 interpreters searching for a total of 21,625 drumlins in 5 synthetic DEMs are interpreted in terms of how the manual mapping process distorts the height (H), width (W) and length (L) of the reported features. Bias in the size-frequency distributions is caused by the sub-set of the forms 'found', even assuming perfect extraction of sizes, and is governed by H driving detectability. Bias is then compounded in sizes that are extracted using the mapped outlines but, remarkably, the size-frequency distribution is not altered further when mappers' incorrect guesses (i.e. outline corresponds to no input synthetic drumlin) are then included; it seems possible that, once mappers have their 'eye in' based on the most clearly defined features, they are very effective at identifying similar morphologies. Of the metrics available to quantify the size of a population, maximum size and λ, the exponent of its tail, are the most robust to these distortions. The drumlins in the study area resemble UK drumlins, permitting extrapolation of the conclusions. These are the first results to give such granular insights into the impacts of the various stages in manually mapping glacial landforms, permitted by the development of the synthetic DEMs. Arguments will always exist about how realistic any synthetic is, but this work demonstrates another use of synthetic DEMs that may be applied more widely in geomorphology.

  15. Altering embryonic cardiac dynamics with optical pacing.

    PubMed

    Peterson, L M; McPheeters, M; Barwick, L; Gu, S; Rollins, A M; Jenkins, M W

    2012-01-01

    Several studies have shown that altering blood flow early in development leads to congenital heart defects. In these studies the perturbations to hemodynamics were very gross manipulations (vessel ligation, conotruncal banding, etc.) that would be inappropriate for probing the delicate mechanisms responsible for mechanically-transduced signaling. Also, these perturbations lacked feedback from a monitoring system to determine the exact degree of alteration and the location of its effect. Here, we employed optical pacing (OP) to alter the heart rate in quail embryos and optical coherence tomography (OCT) to measure the resultant shear forces on the endocardium. OP is a new technique utilizing pulsed 1.851 µm infrared laser light to noninvasively capture the heart rate to the pulse frequency of the laser without the use of exogenous agents. To measure shear stress on the endocardium, we extended our previous OCT algorithms to enable the production of 4-D shear maps. 4-D shear maps allowed observation of the spatial and temporal distribution of shear stress. Employing both OCT and OP, we were able to develop perturbation protocols that increase regurgitant flow and greatly modify the oscillatory shear index (OSI) in a region of the heart tube where future valves will develop. Regurgitant flow has been linked with valve development and precise perturbations may allow one to determine the role of hemodynamics in valvulogenesis.

  16. Body Maps in the Infant Brain

    PubMed Central

    Marshall, Peter J.; Meltzoff, Andrew N.

    2015-01-01

    Researchers have examined representations of the body in the adult brain, but relatively little attention has been paid to ontogenetic aspects of neural body maps in human infants. Novel applications of methods for recording brain activity in infants are delineating cortical body maps in the first months of life. Body maps may facilitate infants’ registration of similarities between self and other—an ability that is foundational to developing social cognition. Alterations in interpersonal aspects of body representations might also contribute to social deficits in certain neurodevelopmental disorders. PMID:26231760

  17. Remote Detection and Geochemical Studies for Finding and Understanding Hydrocarbon-induced Rock Alterations

    NASA Astrophysics Data System (ADS)

    Petrovic, Ana

    The main objective of this work was to determine if there are characteristic mineral assemblages and chemical changes in areas affected by hydrocarbon microseepages. For this purpose remote sensing was utilized for mapping surficial rock alterations, and geochemical tools were used to understand the alteration processes. The key area chosen for this type of work were altered and unaltered Wingate Sandstone outcrops in Lisbon Valley, Utah. The Spectral Angle Mapper method was applied on HyMap hyperspectral images to classify the extent of altered and unaltered outcrops, as well as to map the changes in mineral content within the outcrops. The Spectral Feature Fitting and Band Ratio methods were used to identify lithological changes in the area. The commonly used band ratios for identification of calcite and kaolinite were modified for future use with multispectral data. Reflectance spectroscopy, thin section studies, major, minor, and trace element analyses, and stable carbon and oxygen studies on both bleached (altered) and unbleached (unaltered) samples were successfully used to delineate areas of similar rock composition and relate changes due to hydrocarbons leaking from underlying petroleum reservoirs. Unbleached Wingate Sandstone samples had higher hematite and feldspar content than bleached Wingate samples, which were characterized by larger amounts of clay, calcite, and pyrite. Some bleached samples also had higher concentrations of elements (U, Mo) characteristic of hydrocarbon-related reducing environments, and were depleted in 13C when compared to the unbleached samples. Based on these results, the following model of chemical reactions is suggested for diagnostic changes within Wingate Sandstone. Hydrocarbon-induced reducing environment caused the transformation of sulfate ion (obtained from groundwater or from oxidation of H2S) to sulfide ion, resulting in the reduction of hematite to pyrite, The released hydrogen ion from this reaction reacted with

  18. Airborne infrared mineral mapping survey of Marysvale, Utah

    NASA Technical Reports Server (NTRS)

    Collins, W.; Chang, S. H.

    1982-01-01

    Infrared spectroradiometer survey results from flights over the Marysvale, Utah district show that hydrothermal alteration mineralogy can be mapped using very rapid and effective airborne techniques. The system detects alteration mineral absorption band intensities in the infrared spectral region with high sensitivity. The higher resolution spectral features and high spectral differences characteristic of the various clay and carbonate minerals are also readily identified by the instrument allowing the mineralogy to be mapped as well as the mineralization intensity.

  19. Seismotectonic Map of Afghanistan and Adjacent Areas

    USGS Publications Warehouse

    Wheeler, Russell L.; Rukstales, Kenneth S.

    2007-01-01

    Introduction This map is part of an assessment of Afghanistan's geology, natural resources, and natural hazards. One of the natural hazards is from earthquake shaking. One of the tools required to address the shaking hazard is a probabilistic seismic-hazard map, which was made separately. The information on this seismotectonic map has been used in the design and computation of the hazard map. A seismotectonic map like this one shows geological, seismological, and other information that previously had been scattered among many sources. The compilation can show spatial relations that might not have been seen by comparing the original sources, and it can suggest hypotheses that might not have occurred to persons who studied those scattered sources. The main map shows faults and earthquakes of Afghanistan. Plate convergence drives the deformations that cause the earthquakes. Accordingly, smaller maps and text explain the modern plate-tectonic setting of Afghanistan and its evolution, and relate both to patterns of faults and earthquakes.

  20. The Systems Mapping of Soils

    NASA Astrophysics Data System (ADS)

    Nikiforova, Alexandra; Fleis, Maria; Borisov, Mickail

    2013-04-01

    Soil, together with rocks, waters, air, and living organisms, is one of the natural elements, which make up landscapes. At the same time soil is a unique (derivative) natural element because only it originates from the interaction of all the other (basic) natural elements. Reasoning from this fact, soil maps must be unique too - fundamentally different from geological, geomorphological, natural vegetation, and other thematic maps of the basic natural elements. It is suggested creating conceptually new soil maps, namely the systems soil maps, which are derived from the systems landscape maps. Legends of such maps are based on hierarchical classification of natural landscapes-systems. The last-mentioned are regarded as elementary structural units of the Earth's landscape envelope comprised of interacting landscape elements. The landscapes-systems step by step are divided into divisions and subdivisions of different hierarchical levels unless reaching separate and isolated landscapes-systems, which can not be divided further because of their homogeneity. Criteria used to differentiate between landscapes-systems include the most prominent properties of natural landscape elements, for instance: sequence of the elements, range of altitudes and slopes, zonal vegetation types associated with effective heat sum and precipitation ratio, the main genetic soil horizons, genetic types and forms of relief, lithology of parent materials, depth of humus horizons, chemical composition of ground waters, and so forth. Levels at which criteria of classification are soil properties are named the "soil" one; they are the lowest one in each scale range. The systems soil maps are produced for "soil" levels and show certain soil properties in connection with those properties of the basic natural elements, which cause these soil properties. In GIS environment the systems soil maps are produced automatically from an integrated polygon layer created manually on the basis of expert analysis of

  1. Identifying associations between genomic alterations in tumors.

    PubMed

    George, Joshy; Gorringe, Kylie L; Smyth, Gordon K; Bowtell, David D L

    2013-01-01

    Single-nucleotide polymorphism (SNP) mapping arrays are a reliable method for identifying somatic copy number alterations in cancer samples. Though this is immensely useful to identify potential driver genes, it is not sufficient to identify genes acting in a concerted manner. In cancer cells, co-amplified genes have been shown to provide synergistic effects, and genomic alterations targeting a pathway have been shown to occur in a mutually exclusive manner. We therefore developed a bioinformatic method for detecting such gene pairs using an integrated analysis of genomic copy number and gene expression data. This approach allowed us to identify a gene pair that is co-amplified and co-expressed in high-grade serous ovarian cancer. This finding provided information about the interaction of specific genetic events that contribute to the development and progression of this disease.

  2. The origin of peak-offsets in weak-lensing maps

    NASA Astrophysics Data System (ADS)

    Dietrich, J. P.; Böhnert, A.; Lombardi, M.; Hilbert, S.; Hartlap, J.

    2012-02-01

    Centroid positions of peaks identified in weak-lensing mass maps often show offsets with respect to other means of identifying halo centres, such as position of the brightest cluster galaxy or X-ray emission centroid. Here we study the effect of projected large-scale structure (LSS), smoothing of mass maps, and shape noise on the weak-lensing peak positions. In addition, we compare the offsets in mass maps to those found in parametric model fits. Using ray-tracing simulations through the Millennium Run N-body simulation, we find that projected LSS does not alter the weak-lensing peak position within the limits of our simulations' spatial resolution, which exceeds the typical resolution of weak-lensing maps. We conclude that projected LSS, although a major contaminant for weak-lensing mass estimates, is not a source of confusion for identifying halo centres. The typically reported offsets in the literature are caused by a combination of shape noise and smoothing alone. This is true for centroid positions derived both from mass maps and model fits.

  3. Mycobacterium paratuberculosis as a cause of Crohn's disease.

    PubMed

    McNees, Adrienne L; Markesich, Diane; Zayyani, Najah R; Graham, David Y

    2015-01-01

    Crohn's disease is a chronic inflammatory bowel disease of unknown cause, affecting approximately 1.4 million North American people. Due to the similarities between Crohn's disease and Johne's disease, a chronic enteritis in ruminant animals caused by Mycobacterium avium paratuberculosis (MAP) infection, MAP has long been considered to be a potential cause of Crohn's disease. MAP is an obligate intracellular pathogen that cannot replicate outside of animal hosts. MAP is widespread in dairy cattle and because of environmental contamination and resistance to pasteurization and chlorination, humans are frequently exposed through contamination of food and water. MAP can be cultured from the peripheral mononuclear cells from 50-100% of patients with Crohn's disease, and less frequently from healthy individuals. Association does not prove causation. We discuss the current data regarding MAP as a potential cause of Crohn's disease and outline what data will be required to firmly prove or disprove the hypothesis.

  4. Mycobacterium paratuberculosis as a cause of Crohn's disease

    PubMed Central

    McNees, Adrienne L.; Markesich, Diane; Zayyani, Najah R.; Graham, David Y.

    2016-01-01

    SUMMARY Crohn's disease is a chronic inflammatory bowel disease of unknown cause, affecting approximately 1.4 million North American people. Due to the similarities between Crohn's disease and Johne’s disease, a chronic enteritis in ruminant animals caused by Mycobacterium avium paratuberculosis (MAP) infection, MAP has long been considered to be a potential cause of Crohn's disease. MAP is an obligate intracellular pathogen that cannot replicate outside of animal hosts. MAP is widespread in dairy cattle and because of environmental contamination and resistance to pasteurization and chlorination, humans are frequently exposed through contamination of food and water. MAP can be cultured from the peripheral mononuclear cells from 50 to 100% of patients with Crohn's disease, and less frequently from healthy individuals. Association does not prove causation. We discuss the current data regarding MAP as a potential cause of Crohn's disease and outline what data will be required to firmly prove or disprove the hypothesis. PMID:26474349

  5. Distribution of hydrothermally altered rocks in the Reko Diq, Pakistan mineralized area based on spectral analysis of ASTER data

    USGS Publications Warehouse

    Rowan, L.C.; Schmidt, R.G.; Mars, J.C.

    2006-01-01

    The Reko Diq, Pakistan mineralized study area, approximately 10??km in diameter, is underlain by a central zone of hydrothermally altered rocks associated with Cu-Au mineralization. The surrounding country rocks are a variable mixture of unaltered volcanic rocks, fluvial deposits, and eolian quartz sand. Analysis of 15-band Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data of the study area, aided by laboratory spectral reflectance and spectral emittance measurements of field samples, shows that phyllically altered rocks are laterally extensive, and contain localized areas of argillically altered rocks. In the visible through shortwave-infrared (VNIR + SWIR) phyllically altered rocks are characterized by Al-OH absorption in ASTER band 6 because of molecular vibrations in muscovite, whereas argillically altered rocks have an absorption feature in band 5 resulting from alunite. Propylitically altered rocks form a peripheral zone and are present in scattered exposures within the main altered area. Chlorite and muscovite cause distinctive absorption features at 2.33 and 2.20????m, respectively, although less intense 2.33????m absorption is also present in image spectra of country rocks. Important complementary lithologic information was derived by analysis of the spectral emittance data in the 5 thermal-infrared (TIR) bands. Silicified rocks were not distinguished in the 9 VNIR + SWIR bands because of the lack of diagnostic spectral absorption features in quartz in this wavelength region. Quartz-bearing surficial deposits, as well as hydrothermally silicified rocks, were mapped in the TIR bands by using a band 13/band 12 ratio image, which is sensitive to the intensity of the quartz reststrahlen feature. Improved distinction between the quartzose surficial deposits and silicified bedrock was achieved by using matched-filter processing with TIR image spectra for reference. ?? 2006 Elsevier Inc. All rights reserved.

  6. Human Mind Maps

    ERIC Educational Resources Information Center

    Glass, Tom

    2016-01-01

    When students generate mind maps, or concept maps, the maps are usually on paper, computer screens, or a blackboard. Human Mind Maps require few resources and little preparation. The main requirements are space where students can move around and a little creativity and imagination. Mind maps can be used for a variety of purposes, and Human Mind…

  7. Violent Video Games Alter Brain Function in Young Men

    MedlinePlus

    ... RSS feed News from the RSNA Annual Meeting Violent Video Games Alter Brain Function in Young Men ... Using functional MRI, researchers have found that playing violent video games for one week causes changes in ...

  8. Violent Video Games Alter Brain Function in Young Men

    MedlinePlus

    ... News from the RSNA Annual Meeting Violent Video Games Alter Brain Function in Young Men At A ... MRI, researchers have found that playing violent video games for one week causes changes in brain function. ...

  9. When Reasoning Modifies Memory: Schematic Assimilation Triggered by Analogical Mapping

    ERIC Educational Resources Information Center

    Vendetti, Michael S.; Wu, Aaron; Rowshanshad, Ebi; Knowlton, Barbara J.; Holyoak, Keith J.

    2014-01-01

    Analogical mapping highlights shared relations that link 2 situations, potentially at the expense of information that does not fit the dominant pattern of correspondences. To investigate whether analogical mapping can alter subsequent recognition memory for features of a source analog, we performed 2 experiments with 4-term proportional analogies…

  10. Comparing the Performance of Japan's Earthquake Hazard Maps to Uniform and Randomized Maps

    NASA Astrophysics Data System (ADS)

    Brooks, E. M.; Stein, S. A.; Spencer, B. D.

    2015-12-01

    The devastating 2011 magnitude 9.1 Tohoku earthquake and the resulting shaking and tsunami were much larger than anticipated in earthquake hazard maps. Because this and all other earthquakes that caused ten or more fatalities in Japan since 1979 occurred in places assigned a relatively low hazard, Geller (2011) argued that "all of Japan is at risk from earthquakes, and the present state of seismological science does not allow us to reliably differentiate the risk level in particular geographic areas," so a map showing uniform hazard would be preferable to the existing map. Defenders of the maps countered by arguing that these earthquakes are low-probability events allowed by the maps, which predict the levels of shaking that should expected with a certain probability over a given time. Although such maps are used worldwide in making costly policy decisions for earthquake-resistant construction, how well these maps actually perform is unknown. We explore this hotly-contested issue by comparing how well a 510-year-long record of earthquake shaking in Japan is described by the Japanese national hazard (JNH) maps, uniform maps, and randomized maps. Surprisingly, as measured by the metric implicit in the JNH maps, i.e. that during the chosen time interval the predicted ground motion should be exceeded only at a specific fraction of the sites, both uniform and randomized maps do better than the actual maps. However, using as a metric the squared misfit between maximum observed shaking and that predicted, the JNH maps do better than uniform or randomized maps. These r